Development of a MR Scanner Capable of Being Sited in a Neonatal Intensive Care Unit
Phase: NA
Conditions: Neonatal Neuroimaging
Sponsor: GE Healthcare

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 1 of 95 
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Version Date: 25/Sep/2015 
 
Study Title: Development of a MR Scanner Capable of Being 
Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Revision/Amendment: 7.0 
Version Date: 25/Sep/2015 
Confidentiality Statement  
This protocol is provided for conducting a research study. The information contained in this document is 
confidential and, except to the extent necessary to obtain informed consent or EC/IRB approval, cannot be 
disclosed unless required by governmental regulation. Persons to whom any portion of the contents of this 
document is disclosed must be informed that the information is confidential and may not further be disclosed 
by them.  
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
Development of a MR Scanner Capable of Being Sited in a Neonatal Intensive 
Care Unit 
GEHC Study Number: 114-2014-GES-0035 
Revision/Amendment: 7.0 
Version Date: 25/Sep/2015 
 
Investigator’s Signature Page 
I hereby agree to: 
(i)   Conduct the investigation in accordance with the agreement, the investigational plan, applicable 
MHRA or applicable government regulations, and conditions of approval imposed by the reviewing 
Ethics Committee, IRB or governing regulatory body; 
(ii)  Supervise all testing of the device involving human subjects; and 
(iii) Ensure that the requirements for obtaining informed consent are met. 
 
 
 
Investigator Signature 
 
Date 
 
 
 
 
Print Name 
 
 
 
Site Name 
 
Site Address 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Table of Contents 
This document contains the following sections:  
Topic 
Page 
Investigator’s Signature Page ................................
................................
........ 2 
Table of Contents ................................
................................
.............................
 3 
Document and Version Control ................................
................................
..... 6 
Abbreviations and Terms ................................
................................
................ 7 
Study Synopsis ................................
................................
................................
.. 8 
1.1. 
Preliminary Investigations and Justification ............................................................. 10 
1.2. 
Literature Review .................................................................................................................. 10 
1.3. 
Pre-Clinical (animal) Trials and Previous Clinical (human) Experience .......... 11 
1.4. 
Device Risk Analysis ............................................................................................................. 11 
2. Research Device and/or Product ................................
...........................
 12 
2.1. 
Identification and Description of Research Device/Product ............................. 12 
2.2. 
Regulatory Status .................................................................................................................. 16 
2.3. 
Risk Category and Rationale ............................................................................................ 17 
2.4. 
Device Classification and Rationale .............................................................................. 18 
2.5. 
Device Issuance and Replacement ............................................................................... 18 
2.6. 
Disposition of the Device/Product ................................................................................. 20 
3. Objectives of Research Study ................................
................................
. 21 
3.1. 
Hypothesis ................................................................................................................................ 21 
3.2. 
Justification .............................................................................................................................. 21 
3.3. 
Study Objectives .................................................................................................................... 21 
3.4. 
Study Endpoints ..................................................................................................................... 21 
4. Design of Research Study ................................
................................
........ 22 
4.1. 
Type of Research Study ...................................................................................................... 22 
4.2. 
Controls and Minimization of Bias ................................................................................. 23 
5. Study Subjects ................................
................................
...........................
 24 
5.1. 
Number of Subjects .............................................................................................................. 24 
5.2. 
Subject Population ................................................................................................................ 25 
5.3. 
Protection of Vulnerable Subjects ................................................................................. 25 
5.4. 
Inclusion Criteria .................................................................................................................... 25 
5.5. 
Exclusion Criteria ................................................................................................................... 26 
5.6. 
Screening Subjects for Enrolment ................................................................................. 26 
5.7. 
Duration of Enrolment ........................................................................................................ 27 
6. Procedures for Research Study ................................
..............................
 27 
6.1. 
General Procedures ............................................................................................................. 27 
6.2. 
Phase 1 (Feasibility) and Phase 2 (Data Collection) ................................................ 28 
6.3. 
Per-Subject Procedures ...................................................................................................... 30 
6.4. 
Unexpected Findings ........................................................................................................... 40 
6.5. 
Withdrawal and Discontinuation Criteria ................................................................... 41 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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6.6. 
Study Flowchart ..................................................................................................................... 42 
7. Training Plan ................................
................................
..............................
 44 
7.1. 
Training Plan for Research Device/Product .............................................................. 44 
7.2. 
Training Plan for Protocol .................................................................................................. 45 
8. Data Analysis and Statistics ................................
................................
... 45 
8.1. 
Statistical Analysis Methods ............................................................................................. 45 
8.2. 
Interim Analysis ...................................................................................................................... 46 
8.3. 
Handling of Missing Data .................................................................................................. 46 
8.4. 
Pass/Fail Criteria of the Study ......................................................................................... 46 
9. Other Interim Activities (Qualitative Interim Summaries) ................ 47 
9.1. 
Phase 1 Qualitative Investigator Summary ............................................................... 47 
9.2. 
Phase 1 and Phase 2 End-of-Phase Interim Reports ............................................ 47 
10. 
Deviations ................................
................................
........................
 47 
10.1. 
Management of Protocol Deviations............................................................................ 47 
11. 
Complaint Handling and Adverse Event Reporting ................. 48 
11.1. 
Foreseeable Adverse Events and Device Effects .................................................... 48 
11.2. 
Adverse Event Definitions .................................................................................................. 49 
11.3. 
Management of Adverse Event Reporting ................................................................. 50 
11.4. 
Management of Serious Adverse Event and Unanticipated Adverse Device 
Effect Reporting ..................................................................................................................... 51 
11.5. 
Management of Device Complaints ............................................................................. 51 
12. 
Early Termination or Suspension ................................
................ 51 
12.1. 
Criteria for Early Termination or Suspension ............................................................ 51 
12.2. 
Withdrawal of EC Approval ............................................................................................... 52 
13. 
Ethics Committee (EC) and Regulatory Filings
 ..........................
 52 
13.1. 
Regulatory Authority Approval Requirements (Global) ........................................ 52 
13.2. 
Ethics Committee Approval Requirements ................................................................ 52 
13.3. 
Management of Protocol Revisions/Amendments ................................................ 52 
13.4. 
Informed Consent and Privacy Requirements ......................................................... 53 
14. 
Data and Quality Management ................................
................... 53 
14.1. 
Management of Data .......................................................................................................... 53 
14.2. 
Subject De-identification ................................................................................................... 54 
14.3. 
Subject Pseudonymisation................................................................................................ 54 
14.4. 
Completion of Case Report Forms (CRFs) ................................................................... 54 
14.5. 
Record Retention at the Site ............................................................................................ 55 
15. 
Monitoring Plan ................................
................................
.............. 55 
15.1. 
Brief Description .................................................................................................................... 55 
15.2. 
Reference to Approved Monitoring Plan ..................................................................... 55 
16. 
Publication Policy ................................
................................
........... 55 
17. 
ADDITIONAL COUNTRY
-SPECIFIC REGULATORY 
REQUIREMENTS
 ................................
................................
.........................
 55 
17. References ................................
................................
................................
. 56 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Appendix A – Example of Investigator Summary Document ................. 58 
Appendix B – Example of MR Procedure document ................................
. 59 
Appendix C – Example of Investigational Single-Use Disposable 
Swaddle Log ................................
................................
...............................
 61 
Appendix D – Example of Possible Software Components .....................
 62 
Appendix E – Example of MR Scan Log ................................
.......................
 64 
Appendix F – Example 3.0T Neonatal MRI Investigational Device User 
Experience Questionnaire ................................
................................
....... 65 
Appendix G – Example of Single-Use Disposable Swaddle User 
Experience Questionnaire ................................
................................
....... 67 
Appendix H: Amendment to Protocol Version 1.0 ................................
.... 69 
Appendix I: Amendment to Protocol Version 2.0 ................................
...... 70 
Appendix J: Amendment to Protocol Version 3.0 ................................
..... 76 
Appendix K: Amendment to Protocol Version 4.0 ................................
..... 80 
Appendix L: Amendment to Protocol Version 5.0 ................................
..... 84 
Appendix M: Amendment to Protocol Version 6.0 ................................
.... 89 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
Document and Version Control 
This section records all changes made to the protocol for a specific study. In the table below, record 
each and every relevant change by indicating what changes were made.  
Revision 
Date 
(DD/Mmm/YYYY) 
Revision Author 
Comments/Changes 
1.0 
28/Oct/2014 
Angela Johnson 
Clinical Writer - Initial draft.  
2.0 
03/Dec/2014 
Angela Johnson 
Updated name of medical monitor, as detailed in 
Appendix H: Amendment to Protocol Version 1.0
. 
3.0 
04/Mar/2015 
Angela Johnson 
Revised to clarify that the primary endpoint of the study 
is in accordance with Section 2.1 of Annex X of the EU 
Medical Devices Directive, which species that verificatio
of performance and safety across the study cohort is an 
essential requirement of the study; details local site feed 
and sleep procedures; and clarifies the duration of the 
study at planned for 24 months, as detailed in Appendix I:
Amendment to Protocol Version 2.0
. 
4.0 
26/Apr/2015 
Angela Johnson 
Revised to clarify per MHRA questions, as detailed in 
Appendix J: Amendment to Protocol Version 3.0
. 
5.0 
15/May/2015 
Angela Johnson 
Revised to clarify per MHRA questions, as detailed in 
Appendix K: Amendment to Protocol Version 4.0
. 
6.0 
13/Aug/2015 
Angela Johnson 
Yvonne Celestial 
Lisa Augustine 
Revised to clarify modifications made in prior version, as 
detailed in Appendix L: Amendment to Protocol Version 
5.0. 
7.0 
25/Sep/2015 
Angela Johnson 
 
Revised to clarify modifications made in prior version, as
detailed in Appendix L: Amendment to Protocol Version 
6.0. 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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ABBREVIATIONS 
AND TERMS 
CHF 
 
Clinical History File 
CRF 
 
Case Report Form 
DMP 
 
Data Management Plan 
EU 
 
European Union 
FDA 
 
US Food and Drug Administration 
ICF 
 
Informed Consent Form 
ISO 
 
International Organization for Standardization 
MHRA   
Medicines and Healthcare Products Regulatory Agency 
MR 
 
Magnetic resonance 
MRI 
 
Magnetic resonance imaging 
NICU 
 
Neonatal Intensive Care Unit 
PDU 
 
Power distribution unit 
PNS 
 
Peripheral nerve stimulation 
RF 
 
Radiofrequency 
SAR 
 
Specific Absorption Rate 
SNR 
 
Signal to noise ratio 
 
SPR 
 
System problem report 
SUS 
 
System Usability Scale 
TiP 
 
Training in Partnership 
TVA 
 
Tip Virtual Assist (Remote Connectivity) 
UK 
 
Unites Kingdom 
US 
 
United States 
UXS 
 
User Experience Scale 
 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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STUDY SYNOPSIS
 
Study Title: Development of a MR Scanner Capable of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Research Type:  
Clinical (human)  
 Viable neonate and infant populations 
Pre-Clinical (animal) 
 
External Bench  
 
Brief Description of Study Purpose:  
This study investigates a novel magnetic resonance imaging (MRI)
 system designed by GEHC 
for imaging 
viable neonate and infant populations. This MR system has a smaller size and design 
features that may 
make it more feasible to locate the system in close proximity to 
care areas for neonates (birth – 1 month) 
and infants (>1 month to two years), such as 
clinical neonatal intensive care units (NICUs)
 and other 
infant and neonatal care departments. 
This is a two-phase prospective clinical study evaluating the performance and safety of the 
investigational MRI device for neonates and infants
, including: 
• 
Phase 1 - Initial feasibility assessment and optimization study (Phase 1) which may include 
hardware and software modifications. These studies are guided by a series of MR scanning 
procedures defined in sequential Sponsor-provided MR Procedure Documents
 
• 
Phase 2 - Controlled image and data collection study based on Phase 1 results, in which 
optimized scan procedure(s) according to MR Procedure Document(s)
 will be provided at the 
start of Phase 2 scanning and a fixed hardware and integrated software configuration will be 
applied for all subjects. 
Investigator feedback on scanning conducted under each MR Procedure Document
 will be documented. 
Because the device is intended for use in viable neonate and infant populations, clinical data are 
required that cannot be conducted in any other populations or simulated on non-human models. 
Clinical images and associated data as well as assessments of image quality, workflow, and usability will 
be collected. 
Images, associated image data, and subject data collected in both phases of this study may be used for 
future engineering development and activities that support MR product development, including 
Sponsor-authorized scientific and marketing activities. Summary evaluation of safety and performance 
from Phase 1 and Phase 2 may be used in support of regulatory submission, including filings for 
European CE mark.  
Sponsor Name:   GE Healthcare (GEHC) 
Sponsor contact: Yvonne Celestial, Clinical Affairs 
Project Manager 
Address:  283 rue de la Miniere 
Buc, 78533, FR 
Telephone: +33 130709133 
E-mail:        MarieYvonne.Celestial@ge.com  
Investigator Name(s):  
Prof. Paul Griffiths, MB, ChB, PhD 
Academic Unit of Radiology 
University of Sheffield 
Floor C, Royal Hallamshire Hospital 
Address:  Glossop Road 
Sheffield, UK S10 2JF 
Telephone:  +44 (0) 114 271 2587 
E-mail:  
 p.griffiths@sheffield.ac.uk  
Device/Product GEHC Modality: MR 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Device/Product Description: Small-footprint 3.0T Neonatal MRI investigational device capable of being 
located in a NICU and its components, including a  single-use disposable swaddle, sizing ring, and 
transport devices. The device design is based on commercially available Optima MR430s 1.5T, Discovery 
MR750 3.0T, and SIGNA HDx MR technologies and commercial Sponsor-provided patient monitor (Invivo 
Corp) and site-owned protective devices (e.g. hearing protection and, if necessary, padding or blankets) 
will be used. 
Regulatory Status:  
Pre-Market 
  
3.0T Neonatal MRI investigational device, its components, and its 
accessories (Single-use disposable swaddle, Sizing ring, and Transport devices)  
Post-Market 
  
 
Duration: The study plans to enrol patients for approximately 24 months. 
Research Manager Name: Lisa Augustine Warren, 
Research Project Manager, Global MR Research 
 
Address:     3200 N Grandview Blvd 
      Waukesha, WI 53188-1678 
Telephone: +1-440-250-9488 
E-mail:        Lisa.Augustine@med.ge.com 
 
Medical Monitor Name: Jeff Hersh, MD 
Address:     3200 N Grandview Blvd 
      Waukesha, WI 53188-1678 
Telephone: +1-262-366-7295 
E-mail:  
 Jeff.Hersh@ge.com   
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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1.1. Preliminary Investigations and Justification  
1.2. Literature Review 
Demand for postnatal magnetic resonance imaging (MRI) examinations in clinical settings is 
growing rapidly, in part due to recent improvements in neonatal survival rates and antenatal 
diagnostic imaging. The US Food and Drug Administration (FDA) defines infants (>1 month to 
2 years) and neonates (birth to 1 month) by approximate age and weight. 1 In particular, 
neonatal MRI has become standard clinical care for neurological and orthopaedic 
applications at many clinical facilities. 2, 3, 4, 5 Despite this increasing application of MRI to very 
young subjects, MRI has not been specifically optimized for imaging infants and neonates 
outside of a few limited research settings. 6 The challenges of neonatal MRI imaging have 
been extensively documented, 5, 4, 6, 7 leaving significant room for improvement in MRI 
scanning of neonates to make MRI more practical and comfortable for these vulnerable 
subjects and their care providers.  
MRI is useful for examining neurological disease in the developing brain of young subjects, 
and MRI also serves a key diagnostic role for a variety of other conditions and abnormalities 
in developing neonate and infant anatomy. The clinical manifestations of neurological 
disease are more subtle during early neurological scanning in infants and neonates, and 
many neural structures that are central to the adult human brain cognitive function are 
functionally silent in the infant. 8 This poses unique challenges for applying MRI effectively in 
this population. MRI systems have also been used for orthopaedic, thoracic, and abdominal 
exams in the first hours of life with good results, though there remains significant room for 
improvement and optimization of these systems for neonates and infants. 9 In a variety of 
anatomical regions, high-quality images have been attained with good spatial resolution, 
signal-to-noise ratio, and tissue contrast using standard clinical MRI protocols in infant and 
neonate subjects housed in the NICU environment, but the logistics of transport and safety 
for these subjects remains challenging in most clinical facilities. 9 
In preterm neonates, there is an even more pronounced disconnect between adult and 
neonatal MR image characteristics, resulting in significant risks associated with 
misinterpreting MR images resulting from using scanning techniques optimized for adult or 
older paediatric subjects. 8 Advances in antenatal diagnosis of brain, spine, and body 
abnormalities as well as diagnostic imaging for specialized conditions, such as ischemic 
encephalopathy, that rely on MR imaging systems have increased demand for postnatal MRI. 
10, 8, 11 Thus, there is a growing need for high-resolution MR images of the neonatal and infant 
brain, along with numerous possible clinical and research applications of such imaging.  
For neonatal MRI, the vast majority of clinical care facilities use a conventional commercial 
whole-body MRI system with standard, commercially available coils, though custom-built 
systems and systems that integrate commercially available incubators have been 
documented. 12, 13, 14 Because of the advantage of neonatal MRI, a growing number of clinical 
facilities are considering installing dedicated neonatal imaging systems that are optimized 
both logistically, in terms of location relative to the NICU and other infant/neonatal care 
departments, and in terms of subject care. 15 Recently, a small profile 1.5T MR system has 
been built by Cincinnati Children’s Hospital Medical Center for neonatal MRI and is sited in the 
neonatal intensive care unit at that institution. 13 
In contemporary clinical practice, there is a growing unmet need for MRI imaging systems 
that are specifically designed for use in neonatal and infant populations. Though off-label use 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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of MRI systems approved for adults does occurs in some clinical settings, MRI is still not 
accessible to the majority of neonates and infants in the current paradigm, and the current 
trend is away from off-label use of adult devices on infants and neonates. 2 Furthermore, the 
hardware and software developed for adults is being applied to neonates, often in a 
suboptimal manner that could involve yet unknown risks and reduce performance in this 
vulnerable population. 2 There are also notable risks involved in transporting infants from a 
neonatal intensive care unit (NICU) to a radiology department for MRI, both logistically and 
medically. 16  
The development and regulatory approval of dedicated MRI systems for neonates and 
infants may make MRI more widely available to these populations in clinical care settings. 
The potential advantages of dedicated neonatal MRI systems may include overall reduced 
cost and site demands, lower acoustic noise, improved ease of access, and reduced medical 
risk to the neonate. 16 This study investigates a dedicated MRI system developed by the 
Sponsor for imaging viable neonate and infant subjects. 
1.3. Pre-Clinical (animal) Trials and Previous Clinical (human) Experience 
Research and clinical use of MR imaging has been widely documented in scientific literature 
over the past three decades, including research as early as the 1980s. 17, 18, 19, 20 
Recommendations have also been made by the American Academy of Neurology and Child 
Neurology Society 10 to help guide clinical practice when imaging preterm and term infants, 
stating that “MRI holds great promise; however, this imaging modality and others that may 
be soon developed must become more infant friendly, and imaging strategies should be 
developed to provide maximum information in minimum time.“ Extensive scientific literature 
exists to support the safety and effectiveness of MRI executed by properly trained operators 
for neonate and infant populations; 21, 22, 23, 24 however, the physiologic differences in the 
neonate and infant brain compared to adults leaves room for optimization of MR hardware 
and software to produce improved results in these populations. 25 
GEHC has not previously conducted clinical studies using the 3.0T Neonatal MRI 
investigational device under study. A second study using this device in the United States (US) 
is currently being planned. 
1.4. Device Risk Analysis 
1.4.1. Risks 
The 3.0T Neonatal MRI investigational device is intended for use in neonates and infants, and 
its components and accessories used in this study are based on similar commercial systems 
labelled for use in patients aged greater than 2 years of age and manufactured by the 
Sponsor, and these devices have undergone non-clinical qualification and risk assessments 
conducted by the Sponsor. Participating in this study involves some risks that are unique to 
the design of the scanner and population (neonates and infants), as described Section 11.1 
Foreseeable Adverse Events. This section lists possible foreseeable adverse events and device 
effects, but actual occurrences of these risks are uncommon and are not anticipated to 
occur frequently, if at all, in this study. While serious adverse events can occur in MRI exams 
in rare cases, typically with adverse events occurring as a result of failure to correctly follow 
routine site MR safety procedures for scanning, no serious adverse events are anticipated in 
this study. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Subjects participating in research MRI scanning in this study are not expected to be at 
increased discomfort or risk beyond that posed by other standard of care MRI devices. The 
investigational single-use disposable swaddle is a medical device that is expected to have 
risk comparable or less than routine MR padding, blanketing, and/or other transportation 
devices. During the study, the subject will be transported and cables or other devices may be 
disconnected or connected, which could cause discomfort or interruption of care. The 
investigator is responsible for ensuring minimal disruption of normal care during the study.  
1.4.2. Benefits 
Subjects are not expected to directly benefit from participating in this study, and no 
diagnostic or other care will be determined based on research MR scanning in this study. 
2. 
RESEARCH DEVICE AND/
OR PRODUCT
 
2.1. Identification and Description of Research Device/Product 
2.1.1. 3.0T Neonatal MRI Investigational Device  
The investigational device being studied is a 3.0T Neonatal MRI device intended for use in 
neonates and infants. The device has a small size profile that makes it capable of being sited 
in a NICU or other neonatal and infant care units. This device includes an MR system and its 
hardware and software components is a whole body magnetic resonance scanner designed 
to support high resolution, high signal-to-noise ratio and short scan times. It is indicated for 
use as a diagnostic imaging device to produce axial, sagittal, coronal, and oblique images 
and proton spectra of the body of neonates and infants.  It is specifically designed so that the 
system is able to be sited in or near NICUs, including having smaller overall dimensions and 
weight compared to conventional commercial whole-body MRI scanners. This reduces the 
structural and space requirements for housing the device. Many components of the device 
are based on engineering designs used in the commercially released Optima MR430s 1.5T, 
the Discovery MR750 3.0T, and the SIGNA HDx Family of MR systems.  
The device is also designed with accessories to make transport of the neonatal subject from 
the bedside to the MR scanner more efficient. Image data produced by the 3.0T Neonatal MRI 
investigational device is capable of reflecting the spatial distribution or molecular 
environment of nuclei exhibiting magnetic resonance. Due to the nature of this research 
study, the device will not be used diagnostically for the purpose of this study, and study scans 
are conducted for research purposes only. 
2.1.2. 3.0T Neonatal MRI Investigational  Device Components and Initial Configuration 
The configuration of the device at the beginning of the study includes the central hardware 
and software components, as follows:  
System Hardware Components 
1. 3.0T Magnet: The device uses a 3.0T magnet based on GEHC’s commercially released 
Optima MR430s 1.5T musculoskeletal MR system. The device’s 3.0T magnet, unlike 
predecessor 1.5T magnets, is designed to increase image signal-to-noise ratio which is 
important in imaging this subject population in order to maximize tissue contrast in the 
images.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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2. 17.86 cm (diameter) Bore: The bore is the opening in the center of the device in which 
the subject is placed during MR scanning. Color-coded landmarking controls are used to 
assist in positioning subject anatomy in the bore. 
3. Gradient Coils and Gradient Drivers (70 mT/m gradient strength and 300 T/m/s slew 
rate: The gradient system used in the device is based on the combined technologies of 
the Optima MR430s 1.5T and SIGNA HDx series MR systems with adapted HDx gradient 
driver technology. Magnetic gradients are slight changes in the main magnetic field due 
to three electrically controlled orthogonal coils oriented in the x, y, and z directions of the 
scanner. These gradients are involved in signal localization and imaging plane selection 
(axial, sagittal, coronal, and oblique).  
4. Radiofrequency (RF) System
: The RF transmitter consists of an exciter (synthesizer), 
power amplifier, and transmitting/receiving coil. The exciter design is based on the 
commercially released Discovery MR750 3.0T system, and the amplifier is a new design 
specifically made for this device. The RF device consists of a coil, pre-amplifier, and signal 
processing system. The transmitting and receiving coil is a single channel sixteen rung 
“birdcage” coil (inner surface accessible to the subject). The RF transmits proton-exciting 
energy into tissues, and subsequent proton relaxation energy emission is detected by 
receiver RF coils. This data is processed into MR images. The closer fit to specific neonate 
anatomy is intended to improve RF signal detection in order to improve image quality.  
Transport Cart (Table): The small profile transport cart docks to the MR scanner table for 
bedside-to-MR transport within space-limited care areas for neonates and infants, such 
as NICU environments. 
System Software Components 
All of the pulse sequences, post-processing, and visualization software are based on, and are 
similar in design and function to other commercially released software for GEHC MR 
scanners. Software components that may be variably used in this study are detailed in 
Appendix D – Example of Possible Software Components. These include the following primary 
software components: 
1. Pulse Sequences: Pulse sequences are software sets of RF (and/or gradient) magnetic 
field pulses and time spacing’s between these pulses that can be used in conjunction 
with magnetic field gradients and MR signal reception to produce MR images. These 
software sets are installed on the system and are thereafter available for use with 
specific operator-set parameters. The pulse sequences being studied are similar in design 
and function to commercially available pulse sequences. The type of pulse sequence and 
parameter settings that dictate the timing and shape of the pulses provide the operator 
control over the image contrast. In most clinical MR exams, images are acquired with 
multiple pulse sequences with various settings, allowing clinicians to compare and 
distinguish tissues and abnormalities. The site may also provide phantoms for study use. 
2. MR Post-Processing and Visualization Software: Post-processing and visualization 
software are software modules and/or algorithms that manipulate the images for 
purposes such as, but not limited to, changing the characteristics of the images and 
generating parametric maps and related reports. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Additionally, services and accessories that are intended to work with the device may be used 
in this study, as follows: 
System Accessories 
1. Straps: The straps secure the patient to the table during the scan. 
2. Sizing guide (sizing ring tool): The sizing ring tool is a horseshoe-shaped component 
used to ensure the patient (with all required accessories) will fit into the bore of the MR 
device. 
3. Neonate MR Padding: Special padding for neonates and infants has been designed to 
work with the investigational device. 
4. System Service Tools/Phantoms (Simulations): Phantom images are simulations of 
human scanning that can be completed without a real human subject in the magnet 
bore. During the study, the Sponsor and the investigator may generate and run phantom 
imaging procedures on the device. Phantoms may be provided for training, education, 
engineering, and optimization purposes. 
5. Remote Connectivity: The device is capable of remote connectivity through the Training 
in Partnership (TiP) Virtual Assist (TVA) program, which offers secure data connections 
between a Sponsor representative and the device user for use in training, trouble-
shooting, and real-time image quality optimization during scanning. 
2.1.3. Single-use Disposable Swaddle 
The single-use disposable swaddle is an investigational medical device that is a soft, pliable, 
blanket-type accessory with Velcro® closures intended for swaddling infant or neonate 
subjects on both sides and feet before, during, and immediately after MR scanning. The 
swaddle has been designed for patient transfer and positioning and allows the infant to be 
securely positioned and immobilized during the lift and transfer process.  The swaddle also 
provides line management for any gating wires and/or tubes that may be attached to the 
infant and to any devices.  The swaddle is disposable and intended for single-use only.  It is 
considered to be an accessory to the MRI system that contains the following key 
components: 
1. Velcro® closures: Internal and external closures secure the infant/neonate using 
Velcro® straps. 
2. Textile material: Swaddles are constructed of soft, dual-layer, pliable, blanket-type textile 
materials. 
3. Backboard: The backboard is a non-disposable component that can be optionally used 
with the single-use disposable swaddle to stabilize larger subjects. 

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Figure 1 – Image of swaddled neonate entering the 3.0T Neonatal MRI investigational device 
bore (top left) and views of soft, dual-layer textile swaddle showing Velcro® closures. 
2.1.4. Other MR Equipment 
The Sponsor may also provide other commercial MR equipment required to conduct the 
study, including: 
a. physiologic motion synchronization devices, 
b. protective padding, 
c. hand-held metal detector, 
d. patient monitoring equipment (i.e. Invivo Corp monitor), and 
e. other commercial MR accessories 
There may be other commercial equipment provided to the investigational site(s) as part of 
this study. All commercial equipment provided to the investigational site will be documented 
in the Sponsor’s Clinical History File (CHF) in the Device Accountability Log
 and communicated 
in writing to the investigational site. The intent to use any other commercial MR accessory 
devices that are not explicated described in the protocol procedures during clinical scanning 
procedures will be documented in the Sponsor-provided MR Procedure Document
 and 
records will be retained in the Device Accountability Log
. 

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Expression Patient Monitor (Invivo, Corp; Orlando, FL, USA) 
Expression Monitor (Invivo Corp) – This is an MR Conditional patient monitor system labelled 
for use in neonate and infant populations that can remain in the magnet room during 
scanning.  Depending on workflow, this can also be sited near the operator console for 
patient monitoring during the MR scan.  
Invivo Corp patient monitor will be used during study procedures to monitor subject vital 
signs, body temperature (on the Expression Monitor using a single-use sensor in the MRI scan 
room), and O2 saturation.  
2.1.5. Device Configuration Management 
Throughout Phase 1 (Feasibility and Optimization) part of this study, the configuration of the 
device, including hardware and software components, may be altered for engineering 
research and optimization purposes to gain 
in vivo human data about the optimal device 
configuration. For Phase 2, a
 single device configuration will be used. 
 
The Sponsor will ensure that changes in device configuration will: 
 
a. Not increase risk classification of the study;
 
b. Not increase subject and/or operator risk;
 
c. Be released internally by the Sponsor prior to release to the investigational site;
 
d. Be communicated in writing to the Principal Investigator (PI) and stored in the 
Sponsor’s Clinical History File (CHF); AND
 
e. Be accompanied by appropriate training materials 
related to changes in device 
configuration, if determined to be necessary by the Sponsor or upon request of the PI.
 
Note: No changes in device configuration will be implemented that are not communicated in 
writing by the Sponsor to the Principal Investigator and stored in the Sponsor’s Clinical History 
File (CHF) as part of the 
Device Accountability Log
 and maintained in the Site Regulatory Binder.  
For changes in device configuration, the Principal Investigator assumes responsibility for: 
 
a. Providing confirmation of device configuration changes and ensuring that these are 
stored in the Site Regulatory Binder; 
b. Ensuring that Sponsor-provided communications or electronic copies thereof are 
stored in the Site Regulatory Binder
; 
c. Ensuring that Study Staff are trained and documentation is retained of such training 
for Sponsor-provided training materials and, as necessary, changes in
 device 
configuration and records. 
Note: The PI may request additional training from the Sponsor if necessary, at his or her 
discretion. All training will be documented. In addition to Sponsor
-provided training, the PI and 
designated study staff may perform phantom scanning not using human subjects for the 
purpose of training and retraining staff members at any time during the study. 
 
2.2. Regulatory Status 
The 3.0T Neonatal MRI 
investigational device is a pre-market magnetic resonance diagnostic 
device and its accessories and components are not yet cleared for commercial use (pre
-

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market). In the United Kingdom (UK), the use of the device is subject to regulation by the 
Medicines and Healthcare Products Regulatory Agency (MHRA), in compliance with the 
Medical Devices Regulations of 2002 (transposition of European Medical Device Directive 
93/42/EEC concerning medical devices, including Articles 3, 15, Annexes VIII and X).  
The Expression MRI patient monitoring system (Invivo, Corp; Orlando, FL, USA) provided by the 
Sponsor for use in this have received CE mark for commercial use and are labelled for use in 
neonate and infant populations. All patient monitoring equipment will be used in accordance 
with its labelled indications, including meeting all conditions for MR scanning for MR 
Conditional devices. 
2.3. Risk Category and Rationale 
The MRI device used in this study uses static magnetic field strengths <4.0T, which are widely 
accepted to pose minimal risks to typical adults, children, and infants/neonates, as detailed in 
the US FDA Guidance 
Criteria for Significant Risk Investigations of Magnetic Resonance 
Diagnostic Devices and contemporary medical literature. 26, 27  During this study, subjects will 
encounter routine risks of transport outside of their regular care environment, which are 
considered mitigated to levels as low as reasonably 
practicable (ALARP) by design of the 
device and attendance of medical personnel throughout the subject’s transport and  study 
procedures. The 3.0T Neonatal MRI investigational device under study uses a 3.0T static 
magnetic field. The Sponsor’s Risk Management procedures demonstrate that risks have 
been appropriately mitigated according to ISO 14971, in 
compliance with regulatory 
requirements set forth by the Medicines and Healthcare Products Regulatory Agency (MHRA), 
in compliance with the European Medical Device Dire
ctive 93/42/EEC. 
2.3.1. MR Safe, Conditional, and Unsafe  
Some medical devices placed into surgically or naturally formed cavities of the human body 
(implants) or other device or objects outside of the body may be allowed into the MR 
environment; however, MRI examinations may be contraindicated in patients with some 
types of passive or active implants that cannot be safely allowed in the MR environment
. If 
these procedures and the site MR safety policy are followed, the risks associated with devices 
and objects within the MRI environment are considered to be no greater than routine clinical 
MRI scanning. 
ASTM F2503 Standard Practice for Marking Medical Devices and Other Items for Safety in the 
Magnetic Resonance Environment
 provides terminology for classifying whether implants pose 

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potential hazards to patients in the MR environment that is recognized in the European Union 
and United States Food and Drug Administration (FDA), [1],[2] as follows: 
Label 
Description (typical use) 
 
MR Safe 
 
MR Conditional 
 
 
 
MR Unsafe 
 
Note: If the level of MR compatibility of the device in question is not known (not presented on 
the device label) or the device identity is not able to be determined, then an implantable 
device 
should be considered MR Unsafe for the purposes of this study, with the exception of dental 
devices/fillings, surgical clips, and surgical staples determined to be safe for MRI scanning by a 
physician investigator. 
Special care should be taken in 
MRI with metal objects typically found on neonates and infants, 
such as umbilical cord clips and identification bands. The local site MR safety policy should be 
followed when determining if these devices are safe for MRI.
 
 
2.4. Device Classification and Rationale 
In the United Kingdom (UK), the investigational 3.0T Neonatal MRI investigational device and 
its components and accessories used in this study are considered a Class IIa medical device 
per the European Medical Device Directive Annex IX, Rule 10. The Single-use Disposable 
Swaddle and its components and accessories are considered to be a Class I medical device 
per the European Medical Device Directive Annex IX, Rule 10.   
In the UK, the Expression MRI patient monitoring systems (Invivo, Corp; Orlando, FL, USA) are 
considered Class IIa medical device per the European Medical Device Directive Annex IX, Rule 
10. 
2.5. Device Issuance and Replacement 
2.5.1. Issuance and Installation  
The Sponsor will ship to the study site and install the investigational 3.0T Neonatal MRI 
investigational device. The Sponsor will provide single-use disposable swaddles and 
                                                          
[1] Establishing Safety and Compatibility of Passive Implants in the Magnetic Resonance (MR) Environment. US Food and 
Drug Administration (FDA). August 21, 2008, updated April 6 2011. 
 
[2] European Union (EU) Directive 2004/40/EC and 2008/46/EC 

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necessary hardware and software components and accessories for the investigational 
system. 
If not already owned by the investigational site, the Sponsor may provide each site with 
Sponsor-owned Expression (Invivo Corp) patient monitoring systems labelled for use in 
neonate and infant populations according to MR Conditional labelling. Unique identifying 
information will be recorded for both Sponsor-provided and site-owned devices used in this 
study and a copy of this information will be stored in the Sponsor
’s Device Accountability Log 
stored in the Clinical History File (CHF).
 
2.5.2. Medicinal and Biologic Product Administration  and Delay 
No clinically indicated medical care will be additionally administered or delayed for any 
subject due to study participation. No medicinal agents (including sedatives), biologically 
active agents, or contrast agents not required for the subject’s clinical care outside of this 
study will be administered for the purpose of this study, with the exception of routine sweet 
solutions (‘sweeties’) which may be used during the study period if prescribed by a physician.  
Subjects that received sedatives or other clinically indicated medicinal or contrast agents as 
part of their regular clinical care may be included if there are no extensions of administration 
or delays to administration of clinically indicated medications (including treatments required 
to end sedation) as a result of study participation. Sedation may not be extended for the 
purpose of this study. 
2.5.3. Future and Concurrent Use of Devices 
This study is being conducted for engineering development and regulatory submission 
(including CE mark in the EU) of an investigational medical device and its components and 
accessories. After the device is CE marked, the device and/or its components may be used 
concurrently in other research activities in the EU under EC/IRB approved protocols, subject 
to, and required to adhere to, applicable local laws and regulations, and to the requirements 
of the Sponsor for device accountability. Any concurrent research activity will also be 
required to receive approval from the Sponsor and the institutional EC/IRB at the 
investigational site(s). This information may also be used for regulatory purposes in other 
countries outside of the EU. If the device is used in other countries, future and concurrent use 
will adhere to applicable laws and regulations. 
2.5.4. Research Device Labelling 
The device and related components will be labelled as an investigational device in 
accordance with local regulatory requirements in the UK. Labeling for investigational 
device(s) shall be provided by the Sponsor in a format approved by the Sponsor and 
consistent with local regulatory requirements at the investigational site. 
2.5.5. Maintenance and Replacement 
During this study, the Sponsor will be conducting engineering optimization and ensuring that 
the device(s) operate as intended, which may involve maintenance or replacement of 
hardware or software components of the device(s) and device accessories at the 
investigational site(s). To this end, Sponsor-authorized personnel may:  

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a. Access device(s) in-person or remotely (such as through TVA/TiP or other secure 
remote connection) for quality control, trouble-shooting, training, real-time image 
optimization, to collect system configuration and system log files, or other purposes 
required for device maintenance, installation, de-installation, and/or system data 
collection; 
b. Conduct phantoms (simulated non-human) scans; 
c. Repair or replace the device or any of its components; 
The Principal Investigator (PI) assumes responsibility for promptly reporting any device-
related adverse events or product complaints observed by the PI or study staff to the 
Sponsors Clinical Affairs Project Manager (CAPM). 
2.5.6. Security for Investigational Devices 
1. Single-use Disposable Swaddles: Single-use disposable swaddles and non-disposable 
backboards will be uniquely and sequentially numbered and stored in a locked cabinet 
accessible to study staff. The investigational site will log the use and disposal of each 
swaddle (Appendix B). Swaddles are intended for use with the investigational device under 
this protocol, and swaddles may not be used outside of a Sponsor- and EC/IRB-approved 
study protocol. Each swaddle may be used only once, and may only be used on a single 
subject. 
2. Power Distribution Unit : The Sponsor may lock the Power Distribution Unit (PDU) to secure 
the investigational device if changes are made to the device configuration requiring 
additional study staff training or maintenance.  
3. Host Computer: The host computer will accessible to authorized study staff, including the PI 
and trained scan operators, with a Sponsor-provided username and password. 
4. Security for the MR Environment: The investigational device will be housed in a secured 
environment that meets the Sponsor’s engineering specifications for device installation. This 
area and the entrance to the scan room will accessible only to the PI and trained study staff. 
The Principal Investigator assumes responsibility for meeting all investigational site and 
Sponsor requirements for securing the device.  
2.6. Disposition of the Device/Product  
When scanning under EC/IRB approved study protocols, the following actions will be 
conducted: 
a. The Sponsor will ensure that the device(s) and its components are dispositioned 
according to the contractual agreement reached between the investigational site 
and the Sponsor, in accordance with applicable local laws and regulations. 
b. The Investigator will ensure that used disposable components, such as used 
swaddles, will be handled according to the investigational site(s) standard procedures 
for disposal of biomedical waste. 
c. The Investigator will ensure that unused disposables and other non-disposable 
equipment provide by the Sponsor (including any Sponsor-provided Invivo Corp 
Expression patient monitor, hand-held metal detectors provided by the Sponsor, and 
the non-disposable backboard for the swaddles) are returned to the Sponsor.  

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3. OBJECTIVES OF RESEAR
CH STUDY 
3.1. Hypothesis 
There is no statistical hypothesis being tested in this study. Descriptive statistics will be used 
to provide summary evaluations of performance and safety data. 
3.2. Justification  
This study is being done in two parts to optimize and collect data from a new MRI device for 
use in neonates and infants, the 3.0T Neonatal MRI investigational device. The first part of this 
study is being conducted to demonstrate the feasibility and safety of attaining diagnostic 
quality images and data using the 3.0T Neonatal MRI investigational device in neonates and 
infants with various hardware and software configurations. The second part of this study is 
being conducted to collect images and associated data in neonates and infants from a fixed 
hardware and software configuration of the 3.0T Neonatal MRI investigational device in 
support of regulatory activities in the European Union (EU), including CE mark. MR system log 
files containing operating parameters relative to safety and performance calculations will be 
systematically collected throughout the study for all subjects. Summary performance and 
safety evaluations from both parts of the study may be disclosed to regulatory agencies as 
part of this study. 
3.3. Study Objectives 
3.3.1. Primary Objective(s):  
To evaluate the safety and performance of the device by collection of images and associated 
data using the 3.0T Neonatal MRI investigational device that demonstrates the feasibility of 
use in clinical neonate and infant populations. 
3.3.2. Secondary Objective(s):  
To collect per-subject image quality, usability, workflow, and transport data. 
To collect usability information for each device configuration (per
 MR Procedure Document
) 
To optimize device use and configurations, including
 software and hardware components, 
functionality with MR accessories, and performance factors. 
3.3.3. Exploratory Objectives:  
To record per-subject information, including clinical and demographic data.
 
To collect image data related to clinical follow
-up conducted (if applicable) for engineering 
and device optimization purposes. 
 
3.4. Study Endpoints 
3.4.1. Primary endpoints 
For both Phase 1 and Phase 2, primary endpoints will be recorded as:
 
• 
Collection of MR images and associated data per quotas (Section 5.1.1 - Quotas by 
Anatomic Region) 

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• 
Performance will be determined by summary proportions of images determined to be 
of evaluable or non-evaluable diagnostic quality  
• 
Safety will be determined by summary rates of adverse events 
3.4.2. Secondary endpoints 
• 
MR image quality evaluation(s), per-phase as follows: 
o Phase 1 and 2 (all subjects): Overall image qual
ity rated on a 1-5 Likert scale 
o Phase 1 - Qualitative evaluation and optimization (Summary Report) provided 
by PI, as per applicable 
MR Procedure Document
 
o Phase 2 – Evaluations as described in the 
MR Procedure Document
 
• 
Per-subject Transport and swaddling times and data 
• 
Per-subject workflow and transport information 
• 
Per-subject formative and summative usability information (Appendix F – Example 
3.0T Neonatal MRI Investigational Device User Experience Questionnaire
; Appendix G 
– Example of Single-Use Disposable Swaddle System User Experience Questionnaire
)  
o Phase 1 – Collected as on-site Sponsor or study staff observations 
(may be completed by Sponsor staff trained on the study 
protocol and/or 
onsite study staff) 
o Phase 2 – Collected by on-site assessments by the scan operator 
(must be completed by trained site study staff)
 
• 
Number and type (as determined by Sponsor engineering 
representative based on 
investigator device complaint reports) of device issues, as follows: 
o Technical Issues (cause
d by operator error) 
o Malfunctions (device did not perform as intended)
 
3.4.3. Exploratory endpoints 
• 
Per-patient medical conditions, information, and demographics, as described in the 
procedure sections 
• 
Phase 1 only – Engineering/optimization images and associated image data from 
clinically indicated MRI follow-up for unexpected findings 
4. DESIGN OF RESEARCH S
TUDY 
4.1. Type of Research Study 
4.1.1. Study Type 
This is a two-phase, single-site, open-label, prospective research study involving human 
neonate and infant subjects. This study is designed as a two
-phase clinical trial with a 
feasibility and optimization phase (Phase 1) and controlled image collection study (Phase 2)
.  

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Phase 1 is being conducted to optimize and calibrate the device for subsequent data 
collection in Phase 2 of this study. Both parts may be used for regulatory submission 
purposes, including CE mark and submissions to other global regulatory authorities in other 
countries.  
 
Open-Label 
 
All MR scan configurations are known to researchers and 
subjects 
Blinded 
 
 
Double-Blinded 
 
 
 
Single-site  
 
There is one investigational site
 
Multi-site 
 
 
Randomization 
Procedure:  
 
 
Not randomized:  
 
Randomization is not required, as there 
is no comparative hypothesis 
testing 
Single arm 
 
There are no comparison or control groups 
Comparator 
 
 
 
Parallel 
 
 
Crossover 
 
 
Prospective 
 
Subjects are enrolled and then undergo study procedures
 
4.1.2. Rationale for Two-Phase Study Design 
This study is being conducted in two phases, as follows: 
Phase 1: The first phase (Phase 1) is a feasibility and optimization assessment that cannot be 
conducted in any other population and is designed to allow collection of clinical image and 
associated data as well as to assess image quality, workflow, and usability in human 
subjects. The results from Phase 1 will be considered in deciding whether to continue to 
Phase 2 and, if Phase 2 is conducted, the most appropriate device configuration. Phase 1 
data is not primarily intended for regulatory submission but may, if determined necessary by 
the Sponsor, be disclosed to regulatory authorities in support of regulatory submission.  
Phase 2: Phase 1 will be followed by a sequential second phase (Phase 2) to collect human 
images and data intended to as sample images and associated per-subject data for use in 
regulatory submissions. 
Images and data from both Phase 1 and Phase 2 may be used to support future engineering 
activities.  
4.2. Controls and Minimization of Bias 
The following bias control methods are being employed in this study:  
a. Selection bias will be limited by consecutively enrolling subjects meeting the 
inclusion/exclusion criteria  

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b. Spectrum bias will be limited by using a population expected to be representative of 
the general population at the investigational site, without regard for gender, race, or 
ethnicity.  
c. Reader bias will be limited by ensuring that evaluators and readers making 
performance assessments are separate radiologists (not the PI or neonatologist). 
5. STUDY SUBJECTS
 
5.1. Number of Subjects 
Subjects will be enrolled in two phases, to achieve thirty (30) datasets in Phase 1 (Feasibility 
and Optimization) and up to five (5) datasets in Phase 2 (Data Collection) for a total of thirty-
five (35) total evaluable datasets in both phases. 
To achieve the target of 35 datasets, a total maximum of 60 subjects may be enrolled per the 
sample size calculation shown in Section 8.1.1 – Sample Size Determination. The minimum 
number of patients possible will be used to achieve the target number of evaluable datasets.   
5.1.1. Quotas by Anatomic Region 
The expected 35 evaluable datasets required for this study are set forth in the quota detailed 
in Table 2 by anatomical region. There is only one anatomical region for this study.  
 
Table 2 - Number of evaluable image datasets  
Anatomic Region 
Approximate number of evaluable datasets required 
(n) 
Phase 1 
(Feasibility and 
Optimization) 
Phase 2 
(Data Collection) 
Neurological (Head/Neck/Spine) 
30 
5 
*n = approximate total number of evaluable datasets 
 
The Sponsor may choose to end either Phase of the Study when adequate datasets are 
achieved, based on determination made by the Sponsor
. Any such determination that would 
limit enrolment within a phase and/or individual quota group will be communicated in writing 
to the investigational site. Any such limitations that apply only within a single quota group do 
not constitute termination of the study. 
5.1.2. Special Considerations for Enrolment 
The following special considerations apply to 
subject enrolment in both Phase 1 and Phase 2
.  
1. Incomplete Datasets: Datasets may be incomplete due to factors such as noise, 
sequence failure, or patient movement. 
Datasets determined to be incomplete or 
non-evaluable by the investigator will not be counted towards the total required 
datasets for the purposes of determining quota fulfilment (per protocol population), 
but these will be reported in the total patient enrolment in the study final report 

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(intent-to-treat population). Both complete and incomplete images and data will be 
stored and provided to the Sponsor for engineering purposes.  
2. Changes to Quota Requirements during the Study: The Sponsor reserves the right 
to change quota or Phase dataset number requirements at its discretion and for any 
reason within the set patient enrolment maximum. The Sponsor will notify the 
investigational site in writing of any changes in enrolment quotas.  
5.2. Subject Population 
Viable neonate and/or infant subjects that meet the inclusion and do not meet the exclusion 
criteria will be enrolled.  
5.3. Protection of Vulnerable Subjects 
5.3.1. Vulnerable Subjects 
This study involves a vulnerable population (viable neonates and infants), per ISO 14155:2011 
that defines a vulnerable subject as any individual whose willingness to volunteer in a clinical 
investigation could be unduly influenced by the expectation, whether justified or not, of 
benefits associated with participation or of retaliatory response from senior members of a 
hierarchy in case of refusal to participate. This definition includes children, such as the 
neonates and infants included in this study, which would otherwise require consent from a 
legally authorized representative acting in their best interests. 
This study is being conducted to collect images and data on a device intended for use in 
neonates and infants that could not be otherwise conducted without using this vulnerable 
population. The Sponsor has conducted previous internal testing using phantoms to evaluate 
the safety of the device for use on humans. 
Protection of these vulnerable subjects is imperative and the following safeguards will be 
employed:  
a. Only viable, living neonates and infants will be included in this study; 
b. No neonates of uncertain viability or nonviable neonates will be included in this 
research; 
c. Individuals engaged in the research will have no part in determining the viability of a 
neonate, and all such determinations will be made according to the standard clinical 
practice at the investigational site.  
5.4. Inclusion Criteria  
Subjects will be included that are:  
1. Currently admitted for treatment or observation at the investigational site at the time 
of enrolment; 
2. In the weight range less than 5.0 kg (<5.0 kg1) and more than 0.5 kg (>0.5 kg2); 
3. Viable neonates (birth to 1 month of age) or infants (>1 month to two years of age);3 
4. Able to safely undergo an MRI scan, as determined by medically qualified personnel; 
                                                          
1 <5.0 kg is considered equivalent to <5000.00 g 
2 >0.5 kg is considered equivalent to <500.00 g 
3 1 month is considered equivalent to 30 days; 2 year is considered equivalent to 729 days or less   

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5. Have parent(s), guardian(s), or legally authorized representative(s) willing and able to 
provide written informed consent for the subject’s participation; 
6. Are of appropriate size and shape to fit into the bore of the magnet, inclusive of all 
monitoring equipment, if any, necessary for the subject’s routine clinical care based 
on standard of care measurement methods, in accordance with site policies :  
a. Maximum width (shoulder-to-shoulder measurement) less than eighteen (18 
cm).  
b. Maximum length (head-to-foot measurement) less than sixty (60) cm.  
5.5. Exclusion Criteria  
Subjects will be excluded that:  
1. Have parent(s), guardian(s), or legally authorized representative(s) that require that 
they accompany the subject into the MR environment that have contraindications to 
the MR environment or would otherwise be put at undue risk or discomfort, as 
determined by  medically qualified personnel;4 
2. Have any ferrous or electrical items or non-removable medical devices that are not 
compatible with MR scanning (including devices labelled as MR Unsafe, MR 
conditional for which the scanning conditions are not met, or without MR safety 
labelling that does not satisfy site MR safety requirements) that may pose hazards in 
the MR scanning or MR environment, in the opinion of the Principal Investigator or 
medically qualified personnel in accordance with the site’s MR Safety policy; 
3. Have any contraindications or could otherwise be expected to experience 
detrimental effects to safety, well-being, or medical care, as determined by the 
Principal Investigator or medically qualified personnel in accordance with the site’s 
MR Safety policy; 
4. Require any scheduled standard of care procedures that are expected to be 
adversely impacted by participation in this study, in the opinion of the principal 
investigator or medically qualified  personnel; and 
5. Have been previously enrolled AND undergone any study procedures under the 
current study protocol (i.e. the same subject cannot undergo study procedures, 
including swaddling and/or MR scanning, more than once).  
5.6. Screening Subjects for Enrolment 
5.6.1. Subject Recruitment 
Subjects that are expected to meet the site’s MR Safety Policy criteria and any additional 
supplemental safety policies criteria recommended by the investigator (as per the exclusion 
criteria) and are otherwise eligible for inclusion will be recruited through a neonatologist, 
neonatologist fellow, or study staff authorized through written delegation at each 
investigational site, in accordance with EC/IRB policy. 
                                                          
4 If it is not safe for the parent or guardian that wishes to accompany the subject into the MR environment, the 
parent or guardian may opt not to accompany the subject. In this case, the subject would not be excluded.  
Subjects would be excluded if it is determined to be potentially unsafe for a parent or guardian to accompany a 
subject into the MR scan suite, and the parent or guardian is not willing to allow the subject to be scanned alone 
while he/she waits in another area of the hospital. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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5.6.2. Screening for Enrolment 
Potential subjects will be identified by the Principal Investigator or other qualified site staff.  
Informed consent will be obtained for those subjects who agree to participate in the study.  
Subjects will then be screened for enrolment to ensure the subject is eligible to participate 
per the inclusion/exclusion criteria, as per the judgement of medically qualified personnel.   
Subjects who do not qualify based on inclusion/exclusion criteria will be considered screen 
failures. 
Once a subject is determined to be eligible per the inclusion/exclusion criteria including 
providing written informed consent, the subject will be considered enrolled and assigned a 
subject number. 
5.7. Duration of Enrolment 
The study plans to enrol patients for approximately 24 months. 
6. PROCEDURES FOR RESEA
RCH STUDY
 
6.1. General Procedures 
6.1.1. Quality Control Scans 
The study staff conducting the investigational MR scans (scan operator) will conduct regular 
Quality Control scans using phantom imaging according to the MR system Operator Manual. 
The results of Quality Control scans will be stored at a secure location at the investigational 
site and may be reviewed by the Sponsor.  
Phantom Scanning 
The investigator and/or Sponsor representatives may execute phantom scans that simulate 
human scanning for the purposes of training, troubleshooting, or other engineering 
optimization purposes at any time during the study. 
Specific Absorption Rate (SAR)
 Scans 
The device is equipped with a predictive SAR model designed to conservatively limit actual 
SAR exposure in research subjects. The predictive SAR model used on the system is detailed 
in the technical documentation for the Neonatal MRI device. Each scan session will include 
sequences designed to generate a range of actual SAR data, which is stored in system logs 
and subsequently collected by Sponsor engineering representatives. Throughout the study, 
system log files containing experimentally generated SAR data will be routinely collected, 
along with relevant clinical data such as patient weight (as described in subsequent protocol 
sections), necessary for future evaluation of the system’s predictive SAR model versus actual 
clinical data in the infant/neonate population.  
MR Scan Session Log 
In order to account for all MR scan sessions using the investigational MR system
, the scan 
operator will maintain a daily MR Scan Session Log
. Because this investigational MR scanner 
may be used for concurrent research protocols, the MR Scan Session Log
 (Appendix E – 

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Example of MR Scan Log) may also contain entries from other approved studies. For this 
study, the log will include: 
a. the GEHC-issued study number, 
b. subject number,  
c. date of imaging 
d. MR Procedure Document version number, in applicable 
e. anatomy imaged 
f. 
comments, if applicable 
The log will continue as long as the investigational MR device is housed at the site, and will 
only be discontinued when all EC/IRB-approved studies are completed and the 
investigational MR device(s) is/are removed from the investigational site.  
Note: All human scans for this study, scans done for any other 
active EC/IRB-approved studies using 
this device, and other non-clinical scans (i.e. phantom scans
 for research, service/maintenance, or 
training) will be logged. This is done so that the log is consistent with the internal log inside of the 
system for engineering purposes. The log may contain other columns required by other concurrent 
protocols and some fields may be marked as not applicable (N/A) for other concurrent protocols.
 
6.2. Phase 1 (Feasibility) and Phase 2 (Data Collection) 
Phase 1 of the study will be conducted to collect feasibility data and optimize the MR system. 
Throughout the term of the Study, the Sponsor will communicate with the PI and Study Staff 
as required for device optimization. The Sponsor will provide 
MR Procedure Document
(s) to 
the site, and the PI or delegate will complete and return a qualitative Investigator Summary 
within approximately 3 business days after the procedures described in the current MR 
procedure document have been completed. The Sponsor may provide additional sequentially 
numbered MR Procedure Document
 versions (numbered as Version 1.0, 2.0, 3.0, etc.)
 to 
iterative adjustment the procedure for subsequent MR scanning.  
Phase 2 will be conducted to collect
 sample images and associated data for regulatory 
submission. While hardware and software may be modified throughout Phase 1, a fixed 
hardware and software configuration will be used for all Phase 2 scanning. 
Based on the 
results of Phase 1, MR Procedure Document(s)
 will be provided to the site and used 
consistently in all Phase 2 scanning.  
During both phases, remote TVA connectively feature will be available to scan operators for 
the purposes of training, troubleshooting, and real
-time image quality optimization during 
phantom and clinical procedures. The TVA feature limits remote connectivity so that no 
scanning can be initiated without scan operator confirmation.   
6.2.1. MR Procedure Documents 
At the beginning of the study (prior to initial scanning) the Sponsor will provide an initial 
MR 
Procedure Document to the site and, as determined necessary by the Sponsor, additional 
MR 
Procedure Documents will be provided.  Study procedures will continue under the 
documented MR Procedure Document
 until a new MR Procedure Document
 is provided by the 
Sponsor. During both Phase 1 and Phase 2, the MR Procedure Document 
Version used will be 
documented on each Subject’s Case Report Form (CRF).
 
Sponsor-prepared MR Procedure Documents 
will include the following items:  
• 
MR Procedure Document 
version 

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• 
Date of Document 
• 
Estimated number of subjects that will be subject to a particular MR Procedure 
Document.  
• 
Comments/Specific Instructions for procedures to be performed 
o Additional Sponsor-Requested Assessments of performance characteristics 
on a 1-5 Likert Scale 5, which may include: 
 
Assessments of performance 
 
Overall image quality 
 
Image contrast 
 
Artefacts 
 
Fat/water homogeneity 
 
Signal-to-noise ratio (SNR) 
 
Reconstruction software performance 
 
Optimization of application packs (pulse sequence and post-
processing software) 
 
Usability 
 
And/or other assessments 
Note: The investigator is responsible for completing only the assessments indicated by the 
current version of the MR Procedure Document
. The investigator should ensure that all study 
staff completing assessments are aware of any changes.  
• 
Effective Date that the specified study procedures should begin (i.e. begin on or after 
this date) 
• 
Name and signature of Sponsor Engineering Representative
 
• 
Name and signature of Sponsor Clinical Affairs Project Manager
 
Each MR Procedure Document will be assigned a unique, consecutive numerical, Version 
number (e.g. 1.0, 2.0, 3.0, etc.). 
 
No human MR scanning for this Study will be conducted outside of a Sponsor
-authorized MR 
Procedure Document. Phantom scanning may be conducted for traini
ng and maintenance 
purposes without a MR Procedure Document  Scanning that is not compliant with the 
MR 
Procedure Document will be considered a deviation and 
will be reported according to Section 
9.1 – Management of Protocol Deviations. 
                                        
                  
 
5 Likert Scale of 1-5, where: 
1 = Very Poor 
2 = Poor 
3 = Neutral 
4 = Good 
5 = Excellent 
Note: For image quality assessme
nt, scores of 3, 4, or 5 will be considered diagnostic quality, and scores of 1 and 2 will be 
considered non-diagnostic quality.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
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Protocol: 7.0 
 
 
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6.2.2. Qualitative Investigator Summary (Phase 1 only) 
The PI will complete on qualitative Investigator Summary (Appendix A – Example of 
Investigator Summary Document) documents within approximately 3 business days of 
completion MR Procedure Document
s. The Qualitative Investigator Summary will include:
 
• 
Consecutively numbered Investigator Summary Number 
• 
Version number of MR Procedure Document(s)
 being discussed 
• 
Qualitative Comments related to results 
• 
Comments/Suggestions for optimization of future study procedures (i.e., workflow, 
scanning, usability) 
• 
PI or delegate’s name, signature, and date completed 
All completed Investigator Summaries will be submitted by the PI or delegate to the Sponsor’s 
Clinical Affairs Project Manager, who will sign and date each document to confirm receipt and 
store a copy of the document in the Sponsor’s Clinical History File (CHF).   
6.3. Per-Subject Procedures 
6.3.1. Pre-MR Scanning Activities 
MR Pre-Screening 
To verify that subjects with necessary medical equipment present can safely fit into the study 
device bore with normal airflow and without contact, subjects will be verified to be of 
acceptable size for study MR scanning using the Sponsor-provided sizing tool (“horseshoe” 
shaped ring) with necessary attached medical equipment prior to removal from the normal 
clinical care environment. 
Note: The sizing tool is a study device that may only be used after written informed consent 
for participation has been attained. 
The study staff will then ensure that the subject and any person(s) accompanying him or her 
into the MR environment satisfy all applicable site MR Safety Screening requirements. 
If the subject is determined not be of appropriate size, not to meet MR Safety Screening 
policies at the site, or is discharged from clinical care at the investigational site prior to MR 
scanning, the subject will be withdrawn from the study. 
Duration of Active Enrolment (for AE/SAE reporting purposes) 
Subjects may be transported to the MR suite before or after removal from their incubator, 
crib, or other standard of care bedding. 
Subjects will be considered actively enrolled (for AE/SAE reporting purposes) in the study on a 
per-subject basis from the time that the Sponsor-provided horseshoe-shaped sizing tool is 
used to measure subject size (the first study procedure of MR Pre-Screening). It is mandatory 
that the sizing ring is used for all subjects before other study procedures to ensure that the 
subject is of proper size for the MR bore. 

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of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Active enrolment will be considered to end on a per-subject basis upon the later of: 
a. The time that the subject is returned to his or her standard of care clinical 
environment and all Sponsor provided devices are removed from the subject, 
including Sponsor-provided swaddle, protective padding, and all other study 
devices. 
b. After active enrolment ends, images and data about any standard of care follow-up 
or other medical care resulting from unexpected findings may still be accessed 
observationally and collected by the Sponsor for research purposes. 
Pre-Study Feed and Sleep Procedures
 
Per the applicable standard of care procedures required at the investigational site, each 
participating neonate or infant subject will be allowed adequate feed and sleep to ensure 
minimum disruption of care during MRI scanning, as follows: 
a. The subject will be either breast or bottle fed by or in the presence of the parent/legal 
guardian. 
b. The subject will be placed in a position that is relaxed and comfortable, with the 
expectation that it will be reasonably possible for the subject to sleep through the MRI 
scan. 
Swaddling Subjects and Use of Protective Padding 
If used, unique identification number of the Sponsor-provided single-use disposable swaddle 
will be documented and noted on the swaddle log (Appendix C – Example of Single-Use 
Disposable Swaddle Log), and the following data will be collected during swaddling:  
• 
Was a Sponsor-provided swaddle used (Y/N).  If no, explain why not. 
• 
Was other hospital-provided swaddling (e.g. , blankets) used (Y/N); explain why 
• 
Swaddle ID number 
• 
Time of subject placement in the swaddle (on 24 hour clock) 
• 
Swaddled shoulder circumference (in either swaddle or other padding) 
• 
Shoulder-shoulder length before swaddling 
• 
Description of when swaddling occurred (e.g. , diapering, bathing, feeding or 
changing, etc.) 
• 
Was backboard used (Y/N).  If yes, explain why used 
Subjects should be placed into the Sponsor-provided swaddles by trained study staff 
according to the instructions provided by the Sponsor. Subjects may be placed in the 
Sponsor-provided swaddles either immediately before transport to the MR suite or at an 
earlier time that will minimize subject discomfort, such as during routine feeding, bathing, or 
diapering. Efforts should be made to place subjects in the Sponsor-provided swaddles as 
close as possible to the time of MR scanning unless this presents a potential hazard or undue 
discomfort to subjects. If a swaddle is not used, the subject should be snuggly placed in 
blankets provided by the investigational site, as such to prevent direct contact between the 
subject and the walls of the 3.0T Neonatal MRI investigational device (the bore) during 
scanning. 

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of Being Sited in a Neonatal Intensive Care Unit 
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Protocol: 7.0 
 
 
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The site should follow the Sponsor’s operator manual for specifications and application of 
padding to the subject prior to scanning, and padding provided by the Sponsor should be 
utilized for all subjects. At the discretion of the Principal Investigator or medically qualified 
delegate, the site may also apply necessary additional site-provide padding along with 
Sponsor-provided padding. 
General Method for Recording Temperature 
Subject body temperature will be recorded at defined intervals before, during, and after 
scanning as detailed in the following sections. In the MR suite and during scanning, MR Safe 
Invivo Expression monitors should be used to determine temperature and other vital signs.  
Pre-Transport Subject Information  
The following pre-scan session subject information will be recorded for all subjects:  
• 
gender 
• 
age since birth (days for subjects aged ≤30 days and months for subjects aged >30 
days) 
• 
gestational age (for subjects ≤30 days old) 
• 
infant or neonate status (neonate = birth to ≤30 days; infant >30 days to <2 years) 
• 
Pre-transport temperature: body temperature just before leaving the incubator or 
crib, measured according to the standard clinical practice at the investigational site
, 
as follows: 
o temperature measurement value 
o device type (record standard of care device), and  
o anatomical area of measure (specific area of skin surface) 
• 
head circumference 
• 
weight on day of scan 
• 
Additional Sponsor-Requested Assessments: 
o Blank areas will be included for these assessments (10 blank “Assessment 
Title” lines with associated 1-5 Likert scales) will be provided on the CRF to 
accommodate Sponsor-requested elements that may be specified for each 
MR Procedure Document
. The investigator is responsible for being aware of 
any additional elements required by each MR Procedure Document
 Version 
number. The investigational site(s) will be notified of any additional 
instructions for completing comments, and will be responsible for completing 
the comments field as instructed after appropriate training and instruction 
has been provided by the Sponsor.  
• 
Investigator comments 
o The investigator is encouraged to make additional comments on any atypical 
or exceptional conditions of the subjects, including but not limited to pertinent 
medical history or known deformity.  
Pre-Scan Subject Transport  
The subject will be transported to the MR suite either before or after swaddling (whichever is 
less disruptive to the subject’s care, in the opinion of the study staff) from his or her standard 
clinical care environment. The following parameters will be recorded about subject transfer 
to the MR scanning location:  

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Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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• 
Transport mode into MR suite (subject moved by incubator/crib to MR suite or subject 
moved by transport cart/table) 
• 
Time of removal from incubator/crib (on 24 hour clock) 
• 
Number of staff required to transfer (departing incubator/crib; arriving MR) 
The transfer table will be docked to the MR scanner and advanced to centre the anatomy of 
interest (known as “land-marking”) relative to the MR scanner. Transport is considered to end 
when the table is docked and the subject is advanced into the magnet bore.  
Pre-scan Environmental Condition  
Immediately prior to the first scan series, the following environmental conditions in the MR 
scanning room will be recorded:  
• 
Scan room temperature 
• 
Number of personnel required to transport the MR table from the MRI preparation 
room into the scan room, dock the cart/table to the MR scanner and position, land-
mark, and advance the subject into the magnet bore 
Protective Devices/Procedures 
All subjects require mandatory hearing protection that provides a minimum of 22 dB 
attenuation prior to MR scanning (ear plugs or a combination of ear plugs and ear muffs, in 
accordance with site MR Safety Polices). 
Use of the horseshoe-shaped sizing ring to verify that subjects can safely fit into the bore of 
the MR device is mandatory immediately prior to scanning. 
The scan operator or delegate will ensure that the subject meets the criteria for MR scanning 
according to the site MR Safety Policy. In addition, the study staff may screen subjects and 
accompanying person(s) for presence of ferrous metallic objects using a hand-held metal 
detector, under the direction of the principal Investigator or delegate. If new information 
shows that the subject does not meet the site MR Safety Policy requirements, the subject will 
be withdrawn. 
In neonate and infant populations, special care should be taken to check umbilical or limb 
security devices that may have metal parts that are not safe for MRI scanning. Check if the 
infant or neonate has any umbilical clips or name bands with metal parts for MR safety 
before entering the MRI suite; remove them if deemed MR unsafe and it is safe to remove 
these per the standard clinical practice at the site. Special care should be taken to remove all 
metal objects from subjects and persons accompanying the subject prior to initiating MR 
scanning. If objects or devices that are not safe for MRI scanning are not able to be removed 
safely, the subject should be withdrawn from the study. 
Protective padding shall be used on all subjects according to the device’s operator manual 
and it is preferred that the Sponsor-provided protective padding is used. If the site uses site-
provided protective padding for a particular subject, the reason for not using the Sponsor-
provided protective padding will be documented. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Preparation for Scanning 
Immediately before initiating the scan, ensure that the Expression Monitor (Invivo) is 
connected and monitoring vital signs, including but not limited to body temperature and O2 
saturation. Once acclimated to the scan environment, the following scanning information 
shall be recorded by the scan operator, including the following: 
• 
Pre-scanning baseline temperature
: body temperature measurement made with 
Invivo Expression Monitor (Invivo)
, as follows: 
o the time (minutes) allowed for acclimation once in the magnet bore before 
taking the temperature measurement 
o temperature measurement value 
o anatomical area of measure (specific area of skin surface). 
The study staff will set the alarm level on the Expression Monitor (Invivo) to trigger at 0.5°C 
above the pre-scanning baseline temperature.  
6.3.2. MR Scanning Procedures 
Monitoring Subjects during MR Scanning 
During MRI scanning, subjects will be monitored in real-time using a properly functioning 
Expression MRI Patient Monitor (Invivo, Corp; Orlando, FL, USA). The subject will be observed 
all times during the MR scan by a qualified medical professional (nurse, neonatologist, and/or 
other medical doctor qualified for neonatal/infant care) on the study staff who shall remain in 
the magnet room with the subject during scanning. The observing staff should remain in a 
position where they can readily observe the subject and monitor and, if necessary, contact 
the scan operator during the scanning session.  
A conservative threshold for body temperature alarm is selected, as such that body 
temperature change is sufficient to trigger an alarm (0.5°C above the pre-scanning baseline 
temperature) is not in itself considered a clinically significant risk to patients; these patients 
will be evaluated by a medically qualified member of the study staff for any other possible 
signs or symptoms and they will determine whether an AE has occurred as per the standard 
procedures described in Section 11 – Complaint Handling and Adverse Event Reporting. 
If a body temperature alarm on the monitor is triggered at any time during scanning, the 
study staff should stop the scan series. Then, the following elements will be documented as 
part of study data for each such alarm occurrence: 
o the time of alarm 
o Alarm Temperature: the body temperature at time of alarm, based on body 
temperature measurement made with the Expression Monitor (Invivo), as follows: 
 
temperature measurement value 
 
anatomical area of measure (specific area of skin surface). 
o the time it takes to return to pre-scanning baseline temperature (minutes/seconds) 
Note: In the event that the baby’s body temperature does not return to a level at or below the pre-
scanning baseline temperature within the study 
scanning period (not to exceed 60 minutes from first 
localizer to end of scanning), patient scanning will be discontinued (if collected, the patient’s data 
collected up until this time may still be used for study purposes, and post
-scanning information may still 
be recorded about the patient). 

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Study Number: 114-2014-GES-0035 
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o any conditions observed that possibly contributed to temperature rise, such as 
swaddling, environmental conditions, distress, or scanning conditions? (Y/N, if yes 
explain) 
o decision to continue the scan session (do not continue after first alarm)? (Y/N) 
o Continuing Temperature: the body temperature at the time of scanning was 
continued using an Expression Monitor (Invivo)
, as follows: 
 
temperature measurement value 
 
anatomical area of measure (specific area of skin surface). 
A medically qualified investigator should evaluate each patient to determine if it is safe to 
continue scanning once the patient’s body temperature returns to pre-scanning baseline 
temperature or lower in the event of an alarm. If an alarm is triggered more than once during 
a single scan session, scanning will be discontinued. If collected, the patient’s data collected 
up until this time may still be used for study purposes, and post-scanning information may 
still be recorded about the patient. 
Subject MR Scanning Procedures 
The total time starting from the start of the first localizer to the time at the end of the last 
scan will not exceed sixty (60) minutes. Additional time may be required for setup and 
removal of the patient.  
The scan operator will: 
a. enter the subject’s anonymized ID number in the “Subject Name” and “Subject ID” 
field in the MR scanner’s user interface.  
b. enter the subject’s weight in the MR scanner’s user interface. 
In addition to the scan operator, a member of the study staff cleared to enter the MR magnet 
room will remain in the MR suite at all times when a subject is present in order to assist the 
scan operator should an emergency situation arise 
MR Scanning Information 
For each scanning session, the following scanning information shall be recorded by the scan 
operator, including the following:  
• 
MR Procedure Document
 Version Number  
• 
Phase of Scanning (Phase 1 or Phase 2) 
• 
Subject number 
• 
Date of scanning 
• 
Was the subject sedated for standard of care reasons prior to scanning (Y/N) 
• 
Time and type of clinically indicated sedative administration 
Note: No sedatives will be administered for the purpose of this study. Check yes only if the 
subject was previously administered clinically indicated sedative(s) within the last 24 hours 
prior to scanning. 
• 
Start and End time of scanning, determined by time just prior to first localizer and 
time at end of last scan (on 24 hour clock) 

Study Title: Development of a MR Scanner Capable 
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Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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• 
Scan operator name and signature 
• 
Anatomy scanned (i.e. neurological (head/neck/spine) Was subject fed before (<1 
hour) prior to scanning? (Y/N) 
• 
Did subject require pacifying during scan? (Y/N)Were there any repeat scans done 
due to motion artefacts caused by subject voluntary motion? (Y/N) 
• 
Were there any recoverable system errors or failures during the scanning session? 
(Y/N) If Yes, please describe.  
• 
Comment: Describe any image features which may have negatively affected the 
image quality including items such as, but not limited to, artefacts, tissue contrast, 
noise etc.  
• 
Additional Sponsor-Requested Assessments 
o Modifiable CRF fields (10 blank “Assessment Title” lines with associated 1-5 
Likert scales) will be provided on the CRF to accommodate Sponsor-
requested elements that may be specified for each 
MR Procedure Document
.  
 
The investigator is responsible for being aware of any additional 
elements required by each MR Procedure Document
 Version number.  
 
The investigational site(s) will be notified of any additional instructions 
for completing comments, and will be responsible for completing the 
comments field as instructed after appropriate training and 
instruction has been provided by the Sponsor.  
• 
Investigator Comments 
o The investigator is encouraged to make additional comments on any atypical 
or exceptional events that occur during subject scanning.  
o During the study, the Sponsor may provide additional instructions for 
recording specific types of conditions or information in the comments field at 
its discretion as part of an MR Procedure Document
.  
o The study staff will be responsible for completing the comments field as 
instructed in the applicable MR Procedure Document
 (indicated by version 
number) after appropriate training and instruction has been provided by the 
Sponsor.  
In Phase 1, the Sponsor’s engineering representative, if present, may optionally record any 
applicable comments on a dedicated CRF page. 
MR Scanner Issues 
Issues that occur during the scanning session: In the event of recoverable issues during the 
scan session: 
a. the scan operator will generate an issue report according to the instructions provided 
by the Sponsor, 
b. Data may be collected from the MR scanner by the Sponsor’s authorized engineering 
representative. 
Note: Any Sponsor engineer involved at the site will be trained on the clinical protocol. These 
Sponsor engineers are qualified to answer technical questions about the device, but 
will not 
be authorized to provide training, re-training, or answer study conduct questions raised by 

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study staff, such as issues with informed consent or other protocol issues/questions. Study 
conduct questions that are non-technical in nature should be referred to the Clinical Affairs 
Project Manager. Device use, installation, operation, maintenance, and other technical 
questions may be addressed with on-site engineers. 
 
 
Non-recoverable malfunctions: Non-recoverable malfunctions will be considered those that 
are not resolved by the scan operator rebooting/resetting the system. In the event of a non-
recoverable MR system malfunction: 
a. the scan session will be stopped, 
b. the subject will be removed from the MR environment and returned to their standard 
of care environment,  
c. the equipment will be assessed by the Sponsor, and  
d. The Sponsor must authorize that the device may be used prior to scanning additional 
clinical subjects. 
6.3.3. Post-scanning MR Procedures 
Post-scanning Subject Information   
Post-scanning information will be recorded for all subjects:  
• 
Post-scanning temperature: Body temperature, immediately before removal from the 
MR scanner (post-scan body temperature), body temperature measurement made 
with an Expression Monitor (Invivo)
 and anatomical area of measure (specific area of 
skin surface). 
• 
Final temperature: Body temperature measured after transport and just before the 
subject is placed into the routine care environment, as follows: 
o temperature measurement value 
o device type ( record standard of care device), and  
o anatomical area of measure (specific area of skin surface) 
Note: It is preferred that the same method as used for the 
Pre-transport Temperature. 
• 
End of Enrolment Time: Time when the patient is returned to the clinical care 
area and all 
Sponsor-provided device components (i.e., Swaddle, Invivo monitor, pads, etc.) have been 
removed from the subject. 
• 
Additional Sponsor-Requested Assessments
 
o CRF fields (10 blank “Assessment Title” lines with associated 1
-5 Likert scales) 
will be provided on the CRF to accommodate Sponsor
-requested elements 
that may be specified for each MR Procedure Document
.  
 
The investigator is responsible for being aware of any additional 
elements required by each MR Procedure Document
 Version number.  
 
The investigational site(s) will be notified of any additional instructions 
for completing comments, and will be responsible for completing the 
comments field as instructed after appropriate training and 
instruction has been provided by the Sponsor.  
• 
Comments 
o The investigator is encouraged to make additional comments on any atypical 
or exceptional events that occur during subject scanning. During the study, 
the Sponsor may provide additional instructions for recording specific types 
of conditions or information in the comments field at its discretion as part of 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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an MR Procedure Document
. The study staff will be responsible for completing 
the comments field as instructed in the applicable 
MR Procedure Document
 
(indicated by version number) after appropriate training and instruction has 
been provided by the Sponsor.  
Post Scan Environmental Conditions 
At the end of the last scan series when the scan operator enters the scan room to remove 
the subject from the MR device, the scan operator will record:  
• 
Scan room temperature 
• 
Number of personnel required to remove subject from the scanner and undock the 
cart/table from the MR scanner and transport the MR table out of the scan room and 
into the MRI preparation room. 
Post Scan Operator Assessments 
For each subject, a designated study staff member present during the MR scan session will 
complete the usability survey for all applicable device components (Appendix F – Example of 
3.0T Neonatal MRI Investigational Device User Experience Questionnaire; Appendix G – 
Example of Single-Use Disposable Swaddle User Experience Questionnaire). More than one 
study staff may collaborate to complete these surveys, but only one survey form should be 
completed based on the consensus between all participating study staff. The Sponsor’s 
representative may also collect observational comments during human scanning. 
6.3.4. Evaluations 
Performance Evaluation 
Image sets will be labelled according to subject identification number. Images will be 
evaluated as evaluable (diagnostic) or non-evaluable (non-diagnostic) by two evaluators, and 
then evaluable images will be read for image quality by a separate reader, as shown in 
Figure 2. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Eligible participant 
consents and undergoes 
Neonatal MRI scan 
(Site)
Was an image dataset 
collected?
NO DATA
Document reason on CRF
(i.e. withdrawal, technical issue, 
scheduling, etc.)
No
(Evaluators)
Were images 
rated evaluable?
NON-DIAGNOSTIC DATA
Record reason as acquisition 
issue or image quality issue
Both evaluators agree image is Non-evaluable
NON-DIAGNOSTIC DUE TO IMAGE QUALITY 
ISSUE
(image quality is insufficient 
for diagnostic use)
NON-DIAGNOSTIC DUE TO ACQUISITION 
QUALITY ISSUE
(reasons such as withdrawal, technical issue, 
scheduling, etc. prevented acquisition of some 
or all target views necessary for diagnostic use)
One or both evaluators
indicate Evaluable
(Reader)
Complete Image Quality 
Assessments
(Reader)
Were images 
rated evaluable by
the reader?
Evaluable
Non-evaluable
 
Figure 2 – Flowchart of performance evaluation. Determination of evaluable/non-evaluable for diagnostic purposes 
will be used as the primary performance measure. All secondary Image Quality Assessments will be descriptively 
summarized.  
MR image datasets for each subject will be evaluated twice by two delegated radiologists 
serving as image evaluators (Evaluator 1 and Evaluator 2) as:  
• 
Evaluable (Diagnostic Quality) 6, or 
• 
Non-evaluable (Non-Diagnostic quality).  
The evaluations and printed name and signature of the image evaluator(s) will be recorded to 
an Evaluator CRF. In the event that the two evaluators (Evaluator 1 and Evaluator 2) disagree 
on whether an image is evaluable or non-evaluable, a third medically qualified reader 
(Reader 1) will arbitrate to provide an evaluable/non-evaluable decision, which will be 
recorded to the Reader CRF and treated as the final decision for the image set. 
Image Quality Assessments 
All evaluable images will be further examined by a single reader (Reader 1) that may be the PI 
or a qualified delegated radiologist for image quality on a 1-5 Likert Scale,7 as follows:  
• 
Overall image quality  
                                                          
6 An image set may be considered of diagnostic quality if it contains images suitable for diagnosis (not all images views are 
typically required to be diagnostic based on specific scanning circumstances, so long as applicable views necessary for 
diagnosis are present) 
7 Likert Scale of 1-5, where:  
1 = Very Poor 
2 = Poor 
3 = Neutral 
4 = Good 
5 = Excellent 
Note: For image quality assessment, scores of 3, 4, or 5 will be considered diagnostic quality, and scores of 1 and 2 will be 
considered non-diagnostic quality.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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• 
Image contrast 
• 
Presence of artefacts 
• 
Signal to noise ratio (SNR) 
• 
Tissue contrast 
• 
Fat/water homogeneity 
• 
Additional Sponsor-Requested Assessments 
o CRF fields (10 blank “Assessment Title” lines with associated 1-5 Likert scales) 
will be provided on the CRF to accommodate Sponsor-requested elements 
that may be specified for each MR Procedure Document
.  
• The investigator is responsible for being aware of any additional 
elements required by each MR Procedure Document
 Version number.  
• The investigational site(s) will be notified of any additional instructions 
for completing comments, and will be responsible for completing the 
comments field as instructed after appropriate training and 
instruction has been provided by the Sponsor. 
 
6.4. Unexpected Findings 
MR scanning in this study is for research purposes only, and is not intended to diagnose or 
treat any disease or condition. Furthermore, study images shall not be reviewed or provided 
for diagnostic or any other purposes which may affect patient care. Study images are not 
being evaluated for specific clinical findings. 
However, in the course of performing study procedures in any part of this study (Phase 1 or 
Phase 2), should the study staff observe  unexpected findings, the Principal Investigator may 
choose to communicate  such findings to the subject’s parent(s) or legally authorized 
representative(s) and/or other clinicians involved in the subjects routine clinical care.  A report 
of an unexpected finding should clearly state that the study MRI scans have been reviewed 
only for technical purposes as required by the study and are not meant to supplement or 
replace any clinical MRI exam or MRI report as would be provided for standard of care 
exams.  Further, it should be reported that the study scans were performed on an 
investigational device which is not yet approved for diagnostic imaging. Thus, any findings 
described cannot be guaranteed to be accurate or of clinical significance. The study Principal 
Investigator may note details of what is seen related to the unexpected finding to parent(s) or 
legally authorized representative(s) and/or, if necessary, to other clinician’s involved in the 
subject’s routine clinical care, but no diagnosis should be rendered based on study data. The 
study Principal Investigator may make recommendations for standard of care imaging 
follow-up, which, if necessary, will be conducted outside of this study. When an unexpected 
finding is reported, subjects in this study are then to be managed as patients with regard to 
standard of care in accordance with the site’s policies and procedures.  
The Principal Investigator shall complete the study Investigator’s Report form regarding 
unexpected findings, or the noted absence thereof, for every study scan session. The PI may 
use this form to communicate findings to the responsible clinicians. The form should be 
stored in the study file, and a copy of the completed form may also be stored in any other 
location required or recommended by the General Medical Council record keeping guidelines. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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6.4.1. Follow-up for Unexpected Findings 
In Phase 1 of this study, if unexpected findings identified during this study result in referral for 
further MRI diagnostic evaluation or other medical care according to the standard of care at 
the investigational site, de-identified images and associated image data from the standard of 
care MRI may be observationally collected and provided to the Sponsor for engineering 
development and device optimization purposes. The occurrence of unexpected findings will 
be reported on the case report form (CRF). This data is being collected for exploratory 
engineering development and device optimization purposes, to learn more about 
performance characteristics and potential artefacts in Neonatal MRI scans. Images and 
associated image data will be provided at the discretion of the Principal Investigator, and 
may not be available for all patients with unexpected findings.   
6.5. Withdrawal and Discontinuation Criteri a 
All subjects must be admitted for care in the NICU or other neonatal or infant care 
department or unit affiliated with the investigational site at the time of enrolment and 
scanning to be eligible to participate in this study. If a subject is discharged from clinical care 
at the investigational site prior to MR scanning, the subject will be withdrawn from the study.  
The subject’s medical care shall take precedence over any imaging or other procedures 
associated with the study.  
If it is determined during the exam that the study imaging will in any way negatively impact 
required clinical care, the subject shall be immediately withdrawn from the study.  
In the event the subject appears to be in pain or undue discomfort, if potentially destabilizing 
vital signs are observed by visual inspection or via monitoring equipment, or if the parent(s) or 
legally authorized representative requests to discontinue study procedures, the study 
procedures will be discontinued immediately and the subject will be removed from study, as 
determined necessary by the medically qualified staff at the investigational site. The subject 
shall be removed from the MR environment as soon as safely possible, and, if necessary, care 
will be provided to the subject to alleviate any discomfort according to the site’s standard of 
care. Data collected up until the time of withdrawal may still be used and disclosed to the 
Sponsor for research purposes. 
The subject’s parent or legal guardian may withdraw him or her from study participation at 
any time, for any reason without consequence.  
The study staff may withdraw a subject at any time for any reason.  
The reasons for withdrawal and discontinuation for any subject shall be recorded. These will 
be reported to the Sponsor.  
The EC/IRB should be notified per their notification of subject withdrawal policy.  
There shall be no negative repercussions to the subject, parent(s) or legally authorized 
representative, or Study Staff for deciding end any study procedures.  
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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6.6. Study Flowchart 
Table 3 – Flowchart detailing the data elements to be collected during each part of the study 
Procedure/ 
Data Element 
General 
Procedures 
(time interval) 
Recruitment
/ 
Screening 
Pre-Scan 
MR 
Scanning 
Post-Scan 
Reader/ 
Evaluator 
Assessments 
Quality Control Scan 
Sponsor-set 
interval(s)1 
 
 
 
 
 
Specific Absorption Rate 
(SAR) Scans 
 
 
 
X 
 
 
Running MR Scan 
Session Log 
Daily 
verification 
 
 
X 
 
 
MR Procedure 
Documents 
(Prepared by Sponsor) 
Prior to 
enrolling first 
subject, 
thereafter at 
Sponsor-set 
regular 
interval1 
 
 
 
 
 
Qualitative Investigator 
Summary  
(Prepared by PI) 
Within ~3 
business 
days of 
completing 
MR 
Procedure 
document 
activities 
 
 
 
X 
 
Inclusion/Exclusion 
 
X 
 
 
 
 
Collect subject 
Information 
 
 
X 
X 
X 
 
MR Safety 
(subject and any persons 
accompanying him or 
her into scan room) 
 
X 
X 
X 
X 
 
Application/Removal of 
Swaddling (if 
used)/Padding 
 
 
X 
 
X 
 
Transport 
 
 
X 
 
X 
 
Environmental 
conditions 
 
 
X 
 
X 
 
MR Procedure 
Document Identification 
(Version number) 
 
 
 
X 
 
 
MR Scanning 
Information 
 
 
 
X 
 
 
Software/Hardware 
components used 
 
 
 
X 
(Phase 1 
only)2 
 
 
MR Scanner Technical 
Issues/Malfunctions 
 
 
 
X 
 
 
Additional Sponsor-
Requested Assessments 
 
 
X 
X 
X 
X (reader only) 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 43 of 95 
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Version Date: 25/Sep/2015 
Procedure/ 
Data Element 
General 
Procedures 
(time interval) 
Recruitment
/ 
Screening 
Pre-Scan 
MR 
Scanning 
Post-Scan 
Reader/ 
Evaluator 
Assessments 
(defined in 
MR 
Procedure 
Doc) 
(defined 
in MR 
Procedur
e Doc) 
(defined in MR 
Procedure Doc) 
(defined in MR 
Procedure Doc) 
MR Images and Data 
 
 
 
X 
X 
X 
(access to) 
Evaluable 
(Diagnostic)/Non-
evaluable (Non-
diagnostic) Assessment 
 
 
 
 
 
X 
(reader and 
evaluators) 
Image Quality 
Assessments 
 
 
 
 
 
X  
(reader only) 
Overall image quality 
(based on 
investigator’s 
experience) 
 
 
 
 
 
X  
(reader only) 
Image contrast 
 
 
 
 
 
X  
(reader only) 
Presence of artefacts 
 
 
 
 
 
X  
(reader only) 
Signal to noise ratio 
(SNR) 
 
 
 
 
 
X  
(reader only) 
Tissue contrast 
 
 
 
 
 
X  
(reader only) 
Fat/water separation 
 
 
 
 
 
X  
(reader only) 
AEs/SAEs 
 
 
X 
(From 
placemen
t on 
swaddle, 
if used, or 
if not used 
from 
removal 
from 
clinical 
care 
environm
ent to MR) 
X 
X 
(to  removal 
from 
swaddle/paddin
g and return to 
clinical care 
environment) 
 
MR System 
Errors/Issues 
 
 
 
X 
 
 
MR 
Component/Accessori
es Errors/Issues 
 
 
X 
X 
X 
 
Usability Assessments 
 
 
 
 
 
 
System Usability Scale 
(SUS) 
Operator 
completes at 
end-of-
scanning for 
 
 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 44 of 95 
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Version Date: 25/Sep/2015 
Procedure/ 
Data Element 
General 
Procedures 
(time interval) 
Recruitment
/ 
Screening 
Pre-Scan 
MR 
Scanning 
Post-Scan 
Reader/ 
Evaluator 
Assessments 
each MR 
Procedure 
Doc in Phase 
1 and at end 
of Phase 2 
User Experience Scale 
(UXS) 
Operator 
completes 
end-of-
scanning for 
each MR 
Procedure 
Doc in Phase 
1 and at end 
of Phase 2 
 
 
 
 
 
Usability for Device 
Components 
 
 
 
 
X 
 
Qualitative Investigator 
Summary 
PI or 
designee 
completes 
for each 
Sponsor-
Investigator 
meeting in 
Phase 1 
 
 
 
 
 
End-of-Phase Summary 
Report 
PI or 
designee 
completes at 
end of Phase 
1 and Phase 
2 
 
 
 
 
 
Note: X = to be conducted in indicated part of the study 
1. Conducted at intervals set and determined by the study Sponsor. The PI may 
also complete additional 
general quality scans that do not use human subjects (i.e. phantoms)
 at any time during the study. 
2. For Phase 1 scanning only; In Phase 2 these components are fixe
d for all subjects by the applicable MR 
Procedure Document Version 
 
7. TRAINING PLAN
 
7.1. Training Plan for Research Device/Product 
Study Staff will be trained on the use of device system, its components, and Sponsor-
provided accessories such as the Sponsor-provided patient monitoring equipment. The 
Sponsor will provide initial instructions for use of the device and swaddles and, as necessary, 
subsequent training on any changes to the device, including any necessary storage and 
handling requirements, preparation for use, any pre-scan checks of safety and performance 
and any precautions to be taken after use, (e.g. disposal).  
No training will be conducted on human subjects. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
7.1.1. MR Procedure Documents 
The PI is responsible for ensuring that all MR scan operators that will be operating the 
research device will be made aware of and, if necessary, provided training on scanning 
procedures at the beginning of the study and after any new version of the 
MR Procedure 
Document is released by the Sponsor to the investigational site
. 
7.1.2. Configuration Changes 
The PI is responsible for ensuring that all MR 
scan operators that will be operating the 
research device will be made aware of and, if necessary, provided training on device
 
configuration changes released by the Sponsor to the investigational site.
 
7.2. Training Plan for Protocol 
Study staff will be trained on the Study protocol and Study procedures, including completion 
of Informed Consent Forms (ICFs), Case Report Forms (CRFs), 
MR Procedure Document
s, and 
other study documentation.  
Training will also be provided to ensure appropriate storage and handling of images and
 
data. All study staff will be required to be trained on 
Good Clinical Practice (GCP) guidelines 
per ISO 14155: 2011. 
A record of all formal training attendance and date conducted will be stored in the Site 
Regulatory Binder and provided to the Sponsor for inclusion in the Sponsor’s Clinical History 
File (CHF). 
  
 
8. DATA ANALYSIS 
AND STATISTICS
 
8.1. Statistical Analysis Methods 
8.1.1. Sample Size Determination 
Based on the literature, studies including low
-birth weight neonates commonly assume a 
20% dropout rate. 28 Compared to gold standard, approximately 82% of images attained 
from neonates/infants with MRI are diagnostically 
useful (evaluable), in part due to subject 
movement during scanning.
 29 The enrolment quota calls for 30 (Phase 1) and 5 (Phase 2) 
evaluable image sets. More than one image set may be collected from a single subject; 
however, this case is exceptional and may not be common.
 
This study requires a population (
N) such as that: 
0.82𝑁𝑁−(0.82 × 𝑁𝑁)(0.2) = (30 𝑝𝑝ℎ𝑎𝑎𝑎𝑎𝑎𝑎 1 + 5 𝑝𝑝ℎ𝑎𝑎𝑎𝑎𝑎𝑎 2) 
To satisfy this requirement, a minimum population size of
 N = 53 is required. This is 
approximated upwards to N = 60 to account for unforeseen contributions to dropout or 
evaluable image rates in sensitive neonate and infant
 populations. It is prospectively 
expected that Phase 1 of this study may be ended early if required data for engineering 
purposes is collected before the maximum number of subjects
 are enrolled; it is also 
prospectively expected that Phase 2 of this study
 may be ended early if required data for 
regulatory submission is collected before the maximum number of subjects are enrolled in 
this Phase. Any determination to end the study before the expected number of subjects has 
been enrolled will be provided by th
e Sponsor, in writing, to the investigational site.
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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8.1.2. Statistical Analysis Methods 
As necessary to support regulatory submission, continuous variables will be summarized with 
standard descriptive statistics including counts, means, standard deviations, medians, and 
minimum, maximum. Categorical variables will be summarized with frequencies and 
percentages. 
8.1.3. Other Analysis Methods 
Images and associated data being collected in this study are intended for use on a per-
subject basis for engineering purposes.  
Upon completion of this study, the Sponsor’s authorized research and engineering program 
may utilize data collected in this study in full or in part for authorized engineering purposes. 
The principal investigator (PI) at each site may be asked to provide electronically tabulated 
data summaries for subject demographics and other descriptive data summarizing study 
results. PI-prepared data tabulations will not be controlled or verified by the Sponsor. These 
results are collected for learning purposes only, and any PI-provided data tabulations will be 
summarized in the final study report for reference only. Any direct or derived results from PI-
prepared data tabulations will not be used by the Sponsor for regulatory submissions.   
8.2. Interim Analysis 
There are no interim cohort-based statistical analyses for this study. At the Sponsor’s 
discretion and per local EC/IRB requirements, the status of enrolment and other subject data 
may be summarized at any time determined by the Sponsor during this study. 
8.3. Handling of Missing Data 
The Sponsor may descriptively summarize the primary performance and safety endpoints 
from Phase 1 and Phase 2 of this study, including the descriptive statistical summary of 
patients that exhibit a body temperature rise of more than 0.5°C from acclimated pre-
scanning baseline body temperature (resulting in an Expression Monitor alarm during 
scanning). If the Sponsor observed that the dataset for any subject is incomplete, additional 
clarification from the investigator may be requested. The Sponsor may additionally request 
copies of any clinical imaging datasets (including MRI scan datasets and other clinically 
indicated imaging examinations) that are conducted as follow-up to unexpected findings 
observed in this study. 
8.4. Pass/Fail Criteria of the Study 
The study will be considered successful if sufficient evidence is collected to inform the 
performance and safety of the 3.0T Neonatal MRI investigational device in a representative 
population of neonates and/or infants, in accordance with Annex X of the European Medical 
Device Regulation.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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9. OTHER INTERIM ACTIVI
TIES (QUALITATIVE INTERI
M SUMMARIES)
 
9.1. Phase 1 Qualitative Investigator Summary 
For Phase 1 of this study, the PI is responsible for preparing qualitative Interim Summaries 
based on meetings between the Sponsor and investigator, as described in Section 9.1. Phase 
1 Qualitative Investigator Summary (Phase 1 only). 
These documents, along with images and data collected to date, will provide a basis for the 
Sponsor’s determination of MR Procedure Document
s.  
9.2. Phase 1 and Phase 2 End-of-Phase Interim Reports 
A total of two End-of-Phase Interim Reports will be prepared by
 the PI at the end of 
enrolment for Phase 1 and at the end of enrolment for Phase 2. The PI will
 descriptively 
summarize the subject population and imaging results collected to date
. This may include 
data tabulations, at the discretion of the PI.
 The Phase 1 End
-of-Phase Interim Report may be 
considered by the Sponsor in 
decision-making activities required for Phase 2, and may be 
summarized in the Sponsor’s final clinical study report
. PI-prepared data tabulations will not 
be controlled or verified by the Sponsor. These results are collected for learning purposes 
only, and any PI-provided data tabulations will be summarized in the final study report for 
reference only. Any direct or derived results from PI
-prepared data tabulations will not be 
used by the Sponsor for regulatory submissions.  
 
10. 
DEVIATIONS 
10.1. Management of Protocol Deviations 
All human MR scanning with the investigational device used in this study must be conducted 
under a current MR Procedure Document
 version. If any clinical scan procedu
re is conducted 
that is not compliant with the current MR Procedure Document
 version it will be considered a 
deviation and should be reported according to the following guidelines
: 
Deviations to the protocol may occur when necessary to protect the life or 
physical well-
being of a subject.  
Except in an emergency, prior approval by the 
Sponsor is required for changes in, or planned 
deviations from this protocol.  
If these changes affect the scientific soundness or the safety and welfare of the subject, prior
 
EC/IRB approval is also required.  
Planned Protocol Deviation documentation must be filed in the Site Study Regulatory Binder
.  
There are two types of unplanned protocol deviations, critical deviations and non
-critical 
deviations.  
All deviations must be documented and reported, the criticality of the deviation wil
l 
determine the reporting path.  
Critical Deviations:  
 
Deviations that significantly affect the safety, efficacy, integrity or conduct of the study
.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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These deviations must be reported to the Sponsor no later than 5 working days from 
awareness of occurrence and reported to the EC/IRB per the deviation reporting policy.  
If an Investigator uses a device without obtaining informed consent, the Investigator shall 
consider this a critical deviation and report the event to the Sponsor and the EC/IRB within 5 
working days of the occurrence.  
Non-Critical Deviations:  
Protocol deviations that DO NOT significantly affect the safety, efficacy, integrity or conduct 
of the trial.  
These deviations must be documented on the Case Report Form Protocol Deviation page and 
will be reviewed by the study monitor.  
11. 
COMPLAINT HANDLING 
AND ADVERSE EVENT REPOR
TING 
11.1. Foreseeable Adverse Events and Device Effects 
MRI is generally considered safe for adults and babies because it does not involve exposure 
to ionizing radiation, such as x-rays. MRI of 4T or less is considered non-significant risk for 
infants and neonates, and population-specific risks are well described. 26, 30, 31, 32, 33, 34, 35 The 
known risks typically associated with 3T MRI scans in this study are listed below and have 
been mitigated by the Sponsor to levels that are as low as reasonably practicable (ALARP), to 
levels equivalent or less than MRI using commercially released scanners: 
Movement of Metal Objects: Magnetic fields in MRI can cause internal or external ferrous 
metal (e.g. implants, umbilical cord clamps, oxygen tanks, infant security bands, scissors, 
paperclips, and pens) small enough to be innocuous to adults to move or become projectile, 
leading to minor injuries like cuts/bruises and, in rare cases, serious injury or death. 
 
Thermal Effects: Body temperature can change due to environmental cooling and/or MRI 
radiofrequency (RF) warming. Typical s
pecific absorption rates (SAR) during study MRI 
scanning are not expected to cause injury. In rare cases, serious burns can occur that are 
typically related metallic object presence or improper patient positioning. 
 
Semi-permanent Cable/Device Removal: Chest leads and other semi-permanent attached 
cables/devices can warm and electronics can function abnormally, potentially causing 
discomfort, injury, interruption of care, and, in rare cases, serious destabilization. Devices not 
known to be safe in the MRI environment may be removed or replaced when doing so wo
uld 
not detrimentally impact normal medical care, otherwise the subject will be
 withdrawn.  
Peripheral Nerve Stimulation: Transient skin sensations (‘tingling’) or peripheral nerve 
stimulation (PNS) is related to 
dB/dt and gradient rise time, and is expected to be rare in 
neonates and infants due to small skin surface area and conservative device thresholds.
 26 
Subjecting infants to sudden, rapidly changing gradient magnetic fields during imaging can, 
induce circulating currents in conductive tissues of the body that typically are not painful and 
resolve spontaneously, though, in theory, discomfort or pain from P
NS in infants is possible.
 26  
Acoustic Noise: High noise levels in the scan room and in the bore of the scanner 
during MRI 
scanning may cause discomfort but are not 
normally hazardous with proper hearing 
protection. Spontaneously resolving hearing loss
/tinnitus typically related to improper 
hearing protection can, in rare cases, become chronic or severe. Hearing protection
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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(combination of earplugs  or ear plugs combined with earmuffs to achieve noise reduction of 
≥22 dB is mandatory during MRI in this study) 
Adverse Effects due to Delay of care: Though discontinuation of study procedures for urgent 
medical care is not anticipated, unexpected 
urgent care may be delayed due to removal 
from the MRI or other study devices. The expected delay is only a few minutes, but there is a 
risk that any amount of delay could detrimentally impact urgent medical care.
 
In addition, there are possible, but not anticipated risks that have been identified for the 
Neonatal MRI device during development. These risks have been
 identified and mitigated to 
levels ALARP 
by the Sponsor, and are described as follows: 
Airflow Interruption : In rare cases, blockage of the bore of the 
investigational 3.0T Neonatal 
MRI device, particularly at the head end of the scanner, can cause interruption of normal 
airflow in the bore of the scanner. Through proper measurement of the subject, combined 
with visual inspection of the bore of the scanner once the subject is placed in the scanne
r, 
the scan operator will ensure that no blockage of the bore of the MR scanner exists.
  
Swaddle risk: Compression by the swaddle can cause discomfort and, in rare cases 
more 
serious injury, usually due to study procedures not being followed. 
Fall: During transport or scanning, infants and neonates may be at increased risk of fall from 
the height of the MRI table or transport devices, typically due to improper use. The risk of fall 
is not expected to be greater than in routine transport and the heig
ht of all device 
components complies with regulatory requirements.
 
 
Like routine MRI scanning of <4.0T,
 MRI procedures conducted with the 3.0T Neonatal MRI 
investigational device rarely cause harm when performed as 
directed by trained staff using 
appropriate procedures, as described in this protocol, device documentation, and in Sponsor-
provided training. The risks of AEs and SAEs 
have been mitigated by the Sponsor to 
levels 
ALARP. If the Sponsor learns any new information that would increase risk 
to subjects in this 
study, the PI will be notified in writing.
 
11.2. Adverse Event Definitions 
Adverse Event (AE): As defined by EN ISO 14155-2011: any untoward medical occurrence, 
unintended disease or injury, or untoward clinical signs (including abnormal laboratory 
findings) in subjects, users or other persons, whether or not related to the investigational 
medical device.  
Serious Adverse Event (SAE)
: As defined by EN ISO 14155 – 2011: an adverse event that  
(a) led to death; 
(b) led to a serious deterioration in the health of the subject, that either resulted in:  
(1) a life-threatening illness or injury, or 
(2) a permanent impairment of a body structure or a body function, or 
(3) in-patient or prolonged hospitalization, or 
(4) medical or surgical intervention to prevent life-threatening illness or injury or 
permanent impairment to body structure or a body function; 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 50 of 95 
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(c) led to fetal distress, fetal death or a congenital abnormality or birth defect.  
Anticipated: Any adverse event and/or reaction, the specificity or severity of which is 
consistent with the EC/IRB approved informed consent, protocol, investigator brochure, or 
product labelling.  
Unanticipated adverse Device effect: Any serious adverse effect on health or safety or any 
life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence in 
the investigational plan or application (including a supplementary plan or application), or any 
other unanticipated serious problem associated with a device that relates to the rights, 
safety, or welfare of subjects.  
11.3. Management of Adverse Event Reporting 
Any adverse events will be recorded in the subjects study record and the Adverse Event Case 
Report Form. The following information should be obtained:  
 
Description of Event 
 
Date of onset and resolution  
 
Intensity (mild, moderate, severe) 
­ Mild: Symptom(s) barely noticeable to the subject or does not make the subject 
uncomfortable. The AE does not influence performance or functioning. Prescription 
drugs are not ordinarily needed for relief of symptom(s).  
­ Moderate: Symptom(s) of a sufficient severity to make the subject uncomfortable. 
Performance of daily activities is influenced. Treatment of symptom(s) may be 
needed.  
­ Severe: Symptom(s) of a sufficient severity to cause the subject severe discomfort. 
Treatment for symptom(s) may be given.  
 
Serious (yes/no)  
 
Relationship to device (unrelated, possibly related, probably related) 
­ Unrelated: The adverse event is reasonably expected to be related to (or caused by) a 
concurrent illness, effect of another device/drug or other cause, and is unlikely 
related to the investigational product 
­ Possibly related: The adverse event is reasonably expected to be related to the 
investigational product, and an alternative aetiology is equally or less likely compared 
to the potential relationship to investigational product 
­ Probably related: There is a strong relationship to investigational product, or recurs 
on re-challenge, and another aetiology is unlikely, or there is no other reasonable 
medical explanation for the event.  
 
Treatment given and/or action taken (procedure stopped, withdrawn from study, no 
action) 
 
Anticipated (yes/no) 
Adverse events that occur during a subject’s active enrolment (as described in Section 6.3.1. - 
Pre-MR Scanning Activities: Duration of Active Enrolment) will be reported to the local EC/IRB 
per their policy and, if applicable, to regulatory agencies. Medical events that occur outside of 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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the active study during observational data collection, such as during standard of care follow-
up conducted for any unexpected findings, will not be considered study adverse events. 
11.4. Management of Serious Adverse Event and Unanticipated Adverse 
Device Effect Reporting 
All SAEs and or UADEs will be documented as above and reported in writing to the Sponsor 
within 72 hours of knowledge of the event The Investigator shall submit the Adverse Event 
Case Report Form and GEHC_GQP_10. 07. 005_F002 Site Notification and Assessment of 
Serious and Unexpected Adverse Events (DOC0910335) with redacted supporting 
documentation to SAE mailbox.  
If the event resulted in the death of a subject, the event shall also be reported via telephone 
to the Sponsor within 24 hours of knowledge of the event. SAEs will be reported to the local 
EC/IRB per their policy and, if applicable, to regulatory authorities in accordance with their 
requirements.  
 
Sponsor contact for SAEs and/or UADEs:  
Jeff Hersh, MD 
+1-262-366-7295 
Fax: 800-888-3983 
E-mail: SAE@ge.com 
 
If additional information (i.e. outcome of event, date event resolved, additional treatments) is 
required to submit a follow-up report, the Investigator shall update the AE CRF and resubmit 
to Clinical Affairs.  
The Investigator shall submit the follow
-up SAE and/or UADE report to the local EC
/IRB per 
their policy.  
11.5. Management of Device Complaints 
Any complaints regarding the operation of the 
device or software or any malfunctions are to 
be reported to the Clinical Affair Project Manager
.  
 
Sponsor contact for Device complaints:  
Yvonne Celestial, Clinical Affairs Project Manager 
Phone: +33 130709133 
Email: MarieYvonne.CELESTIAL@ge.com
 
12. 
EARLY TERMINATION OR
 SUSPENSION
 
12.1. Criteria for Early Termination or Suspension 
The study may be terminated early if the 
Sponsor determines that unanticipated adverse 
event(s) presents an unreasonable risk to subjects or for any other reason as 
Sponsor 
determines to be appropriate.  

Study Title: Development of a MR Scanner Capable 
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Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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The Phase 1 Interim Report will be used by the Sponsor to determine if Phase 2 should be 
conducted and which version(s) of the MR Procedure Document
 will be applied in Phase 2. 
Consistent MR procedures will be used for all subjects throughout Phase 2.
 
Termination shall occur no later than 5 working days after the 
Sponsor makes the 
determination and no later than 15 working days after Sponsor first received notice of the 
effect.  
The Sponsor will promptly notify the Investigators of any determination to terminate the 
study outside of the protocol timeframe.  
The Sponsor will provide each Investigator with written guidelines/instructions on termination 
processes and timelines.  
The Investigator is responsible for reporting the early termination to their local EC
/IRB.  
In the event of early termination after Phase 1, the Investigator remains responsible
 for 
completing a descriptive report of the results
.  
12.2. Withdrawal of EC Approval 
The Investigator is to notify the Sponsor of any withdrawal of EC/IRB approval within 5 
working days of such occurrence.  
If the EC/IRB terminates or suspends its approval of the Study, the Investigator will promptly 
notify Sponsor and provide a detailed written explanation of the termination or suspension.  
Upon receipt, the Sponsor will provide written guidelines/instructions on subject 
withdrawal/termination processes and timelines.  
13. 
ETHICS COMMITTEE (EC
) AND REGULATORY FILINGS
 
13.1. Regulatory Authority Approval Requirements (Global) 
In the United Kingdom (UK) the use of the device is subject to regulation by the Medicines and 
Healthcare Products Regulatory Agency (MHRA), in compliance with the European Medical 
Device Directive 93/42/EEC. MHRA authorization is required prior to enrolling subjects.  The 
Sponsor will notify the PI in writing to authorize subject enrolment. 
13.2. Ethics Committee Approval Requirements 
This study is to be submitted to the EC/IRB for review and approval prior to enrolling subjects.  
The Investigator is responsible for keeping approval current and maintaining appropriate 
correspondence and reports.  
Copies of all EC/IRB applications, approval letters, Informed Consent Forms (ICF) and other 
correspondence are to be sent to the Sponsor, with originals kept in the Site Study Regulatory 
Binder.  
13.3. Management of Protocol Revisions/Amendments  
All protocol amendments will be approved and released by the Sponsor.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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13.4. Informed Consent and Privacy Requirements 
Per European Medical Device Directive 93/42/EEC, the following will be required for all 
neonate/infant subjects enrolled in this study:  
a. The parent(s), or guardian(s), or legally authorized representative(s) will be required to 
sign the informed consent form; 
b. If it is the determination of the EC/IRB that both parent(s) or guardian(s) sign the 
informed consent form, that will occur except in the case of deceased, unknown, 
incompetent, or not reasonably available parties, or when only one parent has legal 
responsibility for the care and custody of the child if consistent with (EU) law and any 
other applicable laws and/or regulations at the site where the study is being 
conducted.  
c. Permission by parents or legally authorized representative will be documented in 
accordance with, and to the extent required, by ISO 14155: 2011 (EU). 
Informed consent will be documented in each subject file.  
The Investigator or designee will consent the subject’s parent(s), or guardian(s), or legally 
authorized representative(s) per regulatory guidelines, which includes the right to have ample 
time to review the ICF and have all questions answered to their satisfaction. Subjects may 
sign the ICF at the time it is presented if all of his/her questions have been answered. In the 
event that a the parent(s), or guardian(s), or legally authorized representative(s) require 
additional time or wishes to discuss the ICF with others, he/she will be allowed to take the ICF 
home prior to signing to review with family members or others before making a decision.   
The parent(s), or guardian(s), or legally authorized representative(s); the person who 
consented the subject; and the investigator must sign and date the ICF document prior to a 
subject being included in the study.   
The subject’s parent(s), or guardian(s), or legally authorized representative(s) will be given a 
copy of the signed informed consent form and the original will be retained with subject files.  
13.4.1. Consent for International Transfer and Use of De-identified Data  
The informed consent form (ICF) will explain that some data collected as part of this study 
may be transferred outside of the European Union (EU), including to the United States (US) 
and to other countries which may not provide the same level of data protections as the EU. 
Steps will be taken in order to protect the confidentiality of the data subjects. Applicable local 
laws and regulations for the transfer and use of clinical study data will be followed.    
14. 
DATA AND QUALITY MANAGEMENT
 
14.1. Management of Data 
Images and data will be collected from subjects enrolled in this study and pseudonymised 
using subject identification designation (SID). The resulting data will be key-coded and will not 
contain any direct identifiable personal information (e.g. no name). 
GE Healthcare and authorized representatives may use image and associated data from this 
study for future technology development, marketing purposes, publications, regulatory use or 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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any other possible use. The images and associated image data collected from unexpected 
findings may be used for engineering development and device optimization purposes. Phase 
2 data is collected with the intent of use in regulatory submissions, such as CE mark. 
The approved Data Management Plan (DMP) will be located in the study’s clinical history file 
maintained by the Sponsor. 
14.1.1. International Transfer  and Use of De-identified Data  
In the case where personal data is transferred outside of the European Union (EU), it will be 
transferred to the United States (US) and other countries which may not provide the same 
level of data protections as the EU. Steps will be taken in order to protect the confidentiality 
of the data subjects. Applicable local laws and regulations for the transfer and use of clinical 
study data will be followed.    
14.2. Subject De-identification  
Not Applicable. This section is not applicable for studies conducted in this region
 and is 
superseded by Section 13.3 
- Subject Pseudonymisation. 
14.3. Subject Pseudonymisation  
All subject data that is submitted to the Sponsor will be identified by the use of a unique 
subject number assigned as an identification code to the Subject, without de
-identification. 
The scan operator will enter the identification number in the system
 to complete 
pseudonymisation. 
The assigned subject identification number 
according to the Sponsor’s Data Management 
Plan (DMP).  
Each participating site will maintain a subject identification log, which is a list of all subjects 
who are enrolled in the study, along with their address and medical record number in the 
event that they must be contacted in the future.  
The Sponsor will not receive a copy of the subject identification log
.  
14.4. Completion of Case Report Forms (CRFs)
 
Data will be collected using paper CRFs, and data file transfers
.  
GEHC will provide CRFs and the instructions for their completion.
 
To ensure the quality and integrity of the data, it is the responsibility of the 
Principal 
Investigator or designee in a timely manner,
 to complete a CRF for each subject who is 
enrolled to participate in this study. CRFs will be completed as information b
ecomes 
available.  
If errors or omissions are found in the course of a CRF audit, or data review, 
a Note to File 
(NTF) or Data Clarification Form (DCF) 
will be generated and the error, omissions or 
clarifications will be corrected on these forms
.  
The Principal Investigator will sign and date the indicated places on the CRF
.  
The Principal Investigator’s signature will indicate that a thorough inspection of the data has 
been made and will thereby certify the contents of the form
.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 55 of 95 
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14.5. Record Retention at the Site 
All records pertaining to the conduct of the study, including Case Report Forms, Informed 
Consent Forms, Ethics Committee correspondence, and other study documentation must be 
retained at the Site for inspection at any time by the GEHC Study Monitor or designee. These 
records will be maintained according to GEHC Retention Policies. Elements should include the 
following:  
 
Subject Files – containing the completed subject CRFs  
 
Regulatory Binder – containing the protocol and amendments, EC/IRB submissions and 
approvals, (blank and signed/dated) Informed Consent Form(s), and Site study logs 
 
Reference Manuals – containing the resource list, responsibilities of the Investigator, 
Sponsor, adverse event and informed consent guidelines, study aids (training material, 
device screen shots), and central supplier instructions.  
No records will be destroyed without GE Healthcare notification and approval.  
15. 
MONITORING PLAN
 
15.1. Brief Description 
In collaboration with the site, the Sponsor will ensure proper monitoring of the study to 
confirm that all the clinical requirements are met. Monitoring visits will ensure adherence to 
the protocol, completion of informed consents, EC/IRB review of the study, maintenance of 
records, primary outcomes review and review of the CRFs and source documentation for 
accuracy and completeness.  
15.2. Reference to Approved Monitoring Plan 
The approved monitoring plan will be located in the study’s clinical history file (CHF) 
maintained by the Sponsor.  
16. 
PUBLICATION PO
LICY 
The Sponsor and its authorized representative may also utilize the images and data, in a fully 
anonymized format, for scientific publication(s), presentation(s) at scientific meetings or trade 
shows, product development, marketing materials, educational and training, support of 
global regulatory submissions, or other purposes authorized by the Sponsor in accordance 
with applicable laws and regulations.  
Publications by investigators, study staff, and others involved with the study and/or 
investigational site will be governed by the contractual agreement between the Sponsor and 
site.  
17. 
ADDITIONAL COUNTRY
-SPECIFIC REGULATORY R
EQUIREMENTS
 
Applicable regulations in the UK will be followed in this study. 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 56 of 95 
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17. REFERENCES
 
1. US FDA. Guidance for Industry and FDA Staff: Premarket Assessment of Pediatric Medical D 
May 14, 2004. 
2. Malik S, Beqiri A, Price A, Teixeira J, Hand J, Hajnal J. Specific absorption rate in neonates 
undergoing magnetic resonance procedures at 1.5 T and 3 T. NMR Biomed. 2015;28(3):344-52. 
3. Glass H, Bonifacio S, Sullivan J, et al. MRI and Ultrasound Injury in Preterm Infants with Seizures. J 
Child Neurol. 2009;24(9):1105-1111. 
4. Arthur R. Magnetic Resonance Imaging in Preterm Infants. Pediatr Radiol;5:593–607. 
5. Barkovich A. R Imaging of the Neonatal Brain. Neuroimaging Clin. N. Am. 2006;16:117–35– viii–ix. 
Neuroimaging Clin N Am 2006
. 2006;16:117–35– viii–ix. 
6. Arthurs O, Edwards A, Austin T, Graves M, Lomas D. The challenges of neonatal magnetic 
resonance imaging. Pediatr Radiol. 2012;42(10):1183-94. 
7. Oishi K, Faria A, Mori S. Advanced Neonatal Neuro MRI. Magn Reson Imaging Clin N Am
. 
2012;20:81–91. 
8. Rutherford M, Biarge M, Allsop R. MRI of perinatal brain injury. Pediatr Radiol. 2010;40:819–833. 
9. Tkach J, Hillman N, Jobe A, et al. An MRI system for imaging neonates in the NICU: initial 
feasibility study. Pediatr Radiol. 2012;42(11):1347-56. 
10. Ment LR BHBPea. Practice parameter: Neuroimaging of the neonate: Report of the Quality 
Standards Subcommittee of the American Academy of Neurology and the Practice Committee of 
the Child Neurology Society. Neurology. 2002;58:1726–1738. 
11. Kilian A, Schaible T, Hofmann V. Congenital diaphragmatic hernia: Predictive value of MRI relative 
lung-tohead ration compared with MRI fetal lung volume and sonographic lung-to-head ratio. 
AJR;192:153–158. 
12. Dumoulin C, Rohling K, Piel J, et al. Magnetic Resonance Imaging Compatible Neonate Incubator. 
Concepts in Magnetic Resonance 2002;15:117
–128. 2002;15:117–128. 
13. Whitby E, Griffiths P, Lonneker-Lammers T, et al. Ultrafast Magnetic Resonance Imaging of the 
Neonate in a Magnetic Resonance-Compatible Incubator with a Built-in Coil. Pediatrics. 
2004;113:e150–2. 
14. Blüml S, Friedlich P, Erberich S, Wood J, Seri I, Nelson M. MR Imaging of Newborns by Using an 
MR-Compatible Incubator with Integrated Radiofrequency Coils: Initial Experience. Radiology. 
2004;231(594–601). 
15. Rutherford M. MRI of the neonatal brain. Saunders, UK. 2001. Available at: 
http://www.mrineonatalbrain.com. 
16. Tkach J, Hillman N, Jobe A, Loew W, Pratt R. An MRI system for imaging neonates in the NICU: 
initial feasibility study. Pediatr Radiol. 2012;42(11):1347-56. 
17. Barkovich A, Kjos B, Jackson D, Norman D. Normal Maturation of the Neonatal and Infant Brain: 
MR Imaging at 1.5 T. Radiology 1988. 1988;166:173–180. 
18. Johnson M, Pennock J, Bydder G, Dubowitz L, Thomas D, Young I. Serial MR Imaging in Neonatal 
Cerebral Injury. Am J Neuroradiol. 1987;8:83-92. 
19. McArdle C, Richardson C, Nicholas D, Mirfakhraee M, Hayden C, Amparo E. Developmental 
Features of the Neonatal Brain: MR Imaging Part I. Gray-White Matter Differentiation and 
Myelination. Radiology 1987. 1987;162:223–229. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 57 of 95 
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Version Date: 25/Sep/2015 
20. Dumoulin C, Rohling K, Piel J, et al. Magnetic Resonance Imaging Compatible Neonate Incubator. 
oncepts in Magnetic Resonance
. 2002;15:117–128. 
21. Stokowski L. Ensuring safety for infants undergoing magnetic resonance imaging. 
Adv Neonatal 
Care. 2005;5(1):14-27. 
22. Plaisier A, Raets M, van der Starre C, et al. Safety of routine early MRI in preterm infants. 
Pediatr 
Radiol. 2012;42(10):1205
-11. 
23. Benavente-Fernández I, Lubián-López P, Zuazo-Ojeda M, Jiménez-Gómez G, Lechuga
-Sancho A.
Safety of magnetic resonance imaging in preterm infants. 
Acta Paediatr. 2010;99(6):850
-3. 
24. Chaves A, Cava J, Simpson P, Hoffman G, Samyn M. Infant cardiac magnetic resonance im
using oscillatory ventilation: safe and effective. 
Pediatr Cardiol. 2013;34(5):1201
-5. 
25. Blüml S, Wisnowski J, Nelson M, Paquette L, Panigrahy A. Metabolic Matura
tion of White Matter Is
Altered in Preterm Infants. PLoS One. 2014;9(1):e85829.
 
26. Stokowski L. Ensuring Safety for Infants Undergoing Magnetic Resonance Imaging. 
Medscape 
Multispecialty: Advances in Neonatial Care
. 2005;5(1):14-27. 
27. Schenck J. Safety of Strong, Static Magnetic Fields. 
J Mag Res Img. 2000;12:2-19. 
28. Alibadi F, Askary R. Effects of Tactile
–Kinesthetic Stimulation on Low Birth Weight Neonates. 
Iran 
J Pediatr. 2013;23(3):289
–294. 
29. Anbeek P, Vincken K, Groenendaal F, Koeman A, van 
Osch M, van der Grond J. Probabilistic bra
tissue segmentation in neonatal magnetic resonance imaging. 
Pediatr Res. 2008;63(2):158
-63. 
30. Maalouf E, Counsell S. Imaging the preterm infant: practical issues. 
Rutherford MA, ed. MRI of th
Neonatal Brain. London, England: WB Saunders; 2002.
 
31. Groenendaal F, Leusink C, Nijenhuis M, Janssen M. Neonatal life support during magnetic 
resonance imaging. J Med Engin Technol
. 2002;26:71-74. 
32. ECRI. Hazard report: patient death illustrates the importance of a
dhering to safety precautions in 
magnetic resonance environments
 2004. 
33. Shellock F. Magnetic resonance safety update 2002: implants and devices. 
J Magn Reson 
Imaging. 2002;16:485- 496. 
34. Formica D, Silvestri S. Biological effects of exposure to magn
etic resonance imaging: an 
overview. BioMedical Engineering OnLine
. 2004;3(11). 
35. McJury M, Shellock F. Auditory noise associated with MR procedures: a review. 
J Magn Reson 
Imaging. 2000;12:37-45. 
 
 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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APPENDIX A 
– EXAMPLE OF 
INVESTIGATOR 
SUMMARY DOCUMENT 
This Investigator Summary will be completed by the PI or delegate within approximately three (3) days of 
the Sponsor-Investigator meeting conducted on: 
            ____________________    _________________
 
 
 
 
 
                        
      Date (DD/Mmm/YYYY)      Start Time 
– End Time 
Summary Number: ________ 
Applicable MR Procedure Document
 Version: ________ 
Subject Numbers (record subjects that completed these procedures): 
Comments on current workflow, usability, scanning per MR 
Procedure Document listed above (
attach 
additional pages, if necessary
): 
 
 
 
 
 
 
 
 
Comments/Suggestions for future Workflow, Usability, Scanning and/or 
optimization (attach additional 
pages, if necessary): 
 
 
 
 
 
 
 
 
_____________________________
___________ 
 
 ______________________________
 
Signature of Principal Investigator or delegate 
 
                  
Date Completed 
 
______________________________
__________ 
 
  
Printed Name of Principal Investigator or delegate 
 
________________________________________
 
 
 ______________________________
 
Signature of Clinical Affairs Project Manager 
                 
Date Received by Sponsor
 
 
________________________________
________ 
 
Printed Name of Sponsor Representative
 
Please submit the completed Investigator Summary within approximately 3 business days of each 
completing the activities described in the current MR Procedure Document. Submit to:  
Yvonne Celestial, Clinical
 Affairs Project Manager, Phone: +33 130709133,  
Email: MarieYvonne.CELESTIAL@ge.com
  
 
 
Sample Document – Not for Study Use 
(Please use most current Sponsor-provided 
document version) 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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APPENDIX B 
– EXAMPLE OF 
MR PROCEDURE DOCUMEN
T 
The Sponsor provided this MR Procedure document on
:       ____________________    
 
 
 
 
 
                                             
   Date (DD/Mmm/YYYY)      
 
MR Procedure Document
 Version: ____  Effective date (begin study procedures on or after): 
____________    
 
 
 
 
 
                                                                                                    
Date 
(DD/Mmm/YYYY)      
 
Specific Instructions for procedures to be performed 
(attach additional pages, if necessary
): 
 
 
 
 
 
 
 
 
 
Sponsor-Requested Assessments of performance on a 1
-5 Likert Scale (mark each assessment required
): 
 Overall Image Quality (required for all subjects) 
Other Assessments: 
Other Engineering Performance Measures 
 ___________________________(specify)
 
 Performance parameter ____________ (
specify)  
 ___________________________(specify)
 
 Performance parameter ____________ (
specify)  
 ___________________________(specify)
 
 Performance parameter ____________ (
specify)  
 ___________________________(specify)
 
Image contrast 
 ___________________________(specify)
 
Artefacts 
 ___________________________(specify)
 
Fat/water homogeneity 
 ___________________________(specify)
 
Signal-to-noise ratio 
 ___________________________(specify)
 
Reconstruction software performance 
 ___________________________(specify)
 
Signal-to-noise ratio 
 ___________________________(specify)
 
Reconstruction software performance 
 ___________________________(specify)
 
Sample Document – Not for Study Use 
(Please use most current Sponsor-provided 
document version) 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
 
 
____________________________________________ 
 
 
______________________________ 
Signature of Sponsor Engineering Representative                                                             Date  
 
_____________________________________________ 
  
Printed Name of Sponsor Engineering Representative 
 
 
____________________________________________ 
 
 
______________________________ 
Signature of Clinical Affairs Project Manager 
 
              
            Date 
 
_________________________________________ 
 
 
Printed Name of Clinical Affairs Project Manager 
 
 
 
___________________________________  
                                 
______________________________ 
Signature of Principal Investigator or delegate 
 
 
 
            Date Received 
 
___________________________________  
  
Printed Name of Principal Investigator or delegate 
 
 
 
Sample Document – Not for Study Use 
(Please use most current Sponsor-provided 
document version) 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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APPENDIX C – EXAMPLE OF 
INVESTIGATIONAL 
SINGLE-USE DISPOSABLE 
SWADDLE LOG 
Date of check-
out 
Swaddle 
Number 
Check-out 
Time 
Subject 
Number 
Print name of Study 
Staff checking out 
swaddle 
Study Staff Signature 
Date of 
disposal of 
swaddle 
Example :  
17/Jun/2013 
000 
08: 42 PM 
000 
Jane Smith 
  
17/Jun/13 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
 
 
 
Sample Document – Not for Study Use 
(Please use current
 Sponsor-provided 
document version) 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 62 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
APPENDIX D – EXAMPLE OF POSSIBLE 
SOFTWARE COMPONENTS
 
The software components listed below are an example of what may be used in subject scanning 
under an approved MR Procedure Document
 per the device configuration management and study 
protocol.  
   
3-Plane Pulse Sequence Family  
Spectroscopy PSD Family 
FGRE 
PROBE -PRESS CSI single voxel
 
FIESTA 
PROBE SVQ (PRESS and STEAM)
 
SSFSE 
Gradient Recalled Echo (GRE) Pulse Sequenc
Family 
SE Pulse Sequence Family 
2D FIESTA
 
Spin Echo 
2D Fat SAT FIESTA
 
IR 
3D FIESTA
 
Echo Planar Imaging (EPI) Pulse
 Sequence 
Family 
3D FIESTA with fat SAT
 
DW EPI including Focus
 
3D FIESTA
-C 
DW EPI Tensor
 
Fast GRE/SPGR (2D and 3D)
 
GRE EPI
 
2D GRE/SPGR (2D and 3D)
 
SE EPI 
FGRE Time Course
 
One-click applications 
2D FGRE with IR Prep 
(2DMDE) 
3DASL 
LAVA 
BRAVO 
2D MERGE
 
CineIR 
SWAN 
Silenz 
ASSET Calibration
 
Fast B1map 
Fast Spin Echo Pulse Sequence
 Family 
Vascular Pulse Sequence Family 
FRFSE-XL 
2D Fast Phase Contrast
 
FSE IR 
2D Phase Contrast with Cine Mode
 
FSE-XL 
3D Phase Contrast 
FSE-XL Double/Triple IR
 
2D TOF-GRE/SPGR
 
SSFSE 
2D Fast TOF-GRE/SPGR
 
3D TOF-GRE/SPGR
 
T1 FLAIR 
3D Fast TOF-GRE/SPGR
 
T2 FLAIR 
fAstCINE 
3D Cube 
FastCINE PC
 
3D Cube FLAIR
 
Inhance 3D Velocity 
3D FSE 
3D FRFSE
-XL 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 63 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
Visualization 
Imaging Options 
FuncTool DTI/FiberTrak 
ARC 
FuncTool DWI/eDWI 
ART 
FuncTool 3DASL 
ASSET 
FuncTool Fusion 
Blood Suppression 
FuncTool Spectro 
Bright Blood (ASL) 
FuncTool SER 
Cardiac Gating/Triggering 
FuncTool MR Standard 
Classic 
Volume Viewer: IVI 
DE Prepared 
Volume Viewer: Reformat 
Extended Dynamic Range 
Volume Viewer: 3D View 
Flow Compensation 
SAGE 
Fluoro Trigger 
SR Viewer 
fMRI 
Functool FMRI 
IR Prepared 
Viewer 
Mag Transfer 
Clariview 
Multi-Phase 
Add-Sub 
No Phase Wrap 
Flow Analysis 
Phase Sensitive 
Pasting 
Real Time 
Sequential 
Tailored RF 
ZIP 512 
ZIP 1024 
ZIP x2 
ZIP x 4 
Grad Warp 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 64 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
APPENDIX E 
– EXAMPLE OF 
MR SCAN LOG
 
The MR scan log will detail all scanning in this study and from other approved studies that use the 
same investigational MR device. Enter not applicable (“N/A”) for fields that do not apply. 
Scanner 
Generated 
Exam 
Number 
Date of 
Scanning 
(DD/Mmm/YYYY) 
GES/IIR 
study 
number 
(N/S for 
service, 
training, 
etc.) 
 
Subject 
Number 
MR Procedure 
Document Version 
(GES only, N/A for 
IIR/ service, 
training, etc.) 
Anatomy 
Imaged 
(N/A for 
phantoms) 
Comments 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Sample Document – Not for Study Use 
(Please most use current Sponsor-provided 
document version) 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 65 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
APPENDIX F 
– EXAMPLE 3.0T NEONATAL MRI INVESTIGATIONAL DEV
ICE USER 
EXPERIENCE QUESTIONN
AIRE 
 
This survey will be completed by an experienced scan operator once for each 
MR Procedure 
Document in Phase 1 and once at the end of Phase 2.
 
 
These survey questions will be completed by the scan operator for each patient on a scale of 
1 to 5 
or marked as ‘not applicable’ (N/A)
, as follows: 
1 = strongly disagree 
2 = disagree 
3 = neither agree nor disagree 
4 = agree 
5 = strongly agree 
 
Regarding your overall experience with the 
3.0T Neonatal MRI investigational device, please rate 
each of the following on a 1-5 scale: 
1. I think that I would like to use this system frequently
 
2. I found the system unnecessarily complex 
3. I thought the system was easy to use                      
 
 
4. I think that I would need the support of a technical person to be able to use this system
 
 
5. I found the various functions in this system were well integrated
 
6. I thought there was too much inconsistency in this system
 
7. I would imagine that most people would learn to
 use this system very quickly 
 
8. I found the system very cumbersome to use
 
9. I felt very confident using the system
 
10. I needed to learn a lot of things before I could get going with this system
 
11. I feel confident this system will meet my patient’s needs
 
 
 
12. How likely is it that you would recommend this product to other professionals in your 
field? 
 
 
Sample Document – Not for Study Use 
(Please use most current Sponsor-provided document version)
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 66 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
This survey will be completed by an experienced scan operator once for each 
MR Procedure 
Document in Phase 1 and once at the end of Phase 2. 
Responses should consider the user’s overall 
experience with the 3.0T Neonatal MRI
 investigational device. 
 
Questionnaire Instructions 
Please take your time and carefully indicate your responses in the following scales below.  
 
PAY ATTENTION TO THE FACT THAT THE SCALES CHANGE their anchor points in the left 
and right 
columns from one question to the next.  This is done in an effort to reduce bias in the results.
 
 
Based on your experiences interacting with the product how would you describe the product? 
 
 
 
 
 
1)   Learnable O--------- O--------- O--------- O--------- O--------- O--------- O 
Not Learnable  
 
2)   Inefficient  O--------- O--------- O--------- O--------- O--------- O--------- O 
Efficient 
 
 
 
3)   Resistant 
O--------- O--------- O------- --O--------- O--------- O--------- O 
Responsive 
 
4)   Annoying 
O--------- O--------- O--------- O--------- O--------- O--------- O 
Pleasing 
 
5)   Satisfying  O--------- O--------- O--------- O--------- O--------- O--------- O  
Dissatisfying  
 
6)   Ineffective O--------- O--------- O--------- O--------- O--------- O--------- O 
Effective 
 
7)   Fast 
O--------- O--------- O--------- O--------- O--------- O--------- O 
Slow 
 
 
8)   Unfamiliar O--------- O--------- O--------- O--------- O--------- O--------- O  
Familiar 
 
9)   Routine 
O--------- O--------- O--------- O--------- O--------- O--------- O  
Unusual 
 
10) Easy  
O--------- O--------- O--------- O--------- O--------- O--------- O  
Difficult  
 
11) Useful 
O--------- O--------- O--------- O--------- O--------- O--------- O 
Useless 
 
12) Bad  
O--------- O--------- O--------- O--------- O--------- O--------- O 
Good 
 
 
Sample Document – Not for Study Use 
(Please use most current Sponsor-provided document version)
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 67 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
APPENDIX G – EXAMPLE OF 
SINGLE-USE DISPOSABL
E SWADDLE USER 
EXPERIENCE QUESTIONN
AIRE 
These assessments are designed to assess the usability the single-use disposable swaddle 
component associated with the 3.0T Neonatal MRI investigational device on a per patient basis. This 
survey will be completed by the scan operator for each patient that uses a swaddle. 
 
These survey questions will be completed by the scan operator for each patient on a scale of 1 to 5 
or marked as ‘not applicable’ (N/A), as follows: 
1 = strongly disagree 
2 = disagree 
3 = neither agree nor disagree 
4 = agree 
5 = strongly agree 
 
Regarding your overall experience with the Single-use Disposable  Swaddle device, please rate each 
of the following on a 1-5 scale: 
1. I think that I would like to use this swaddle frequently 
2. I found the swaddle unnecessarily complex 
3. I thought the swaddle was easy to use                        
4. I think that I would need the support of a technical person to be able to use this swaddle 
 
5. I found the various functions in this swaddle were well integrated 
6. I thought there was too much inconsistency in this swaddle 
7. I would imagine that most people would learn to use this swaddle very quickly 
 
8. I found the swaddle very cumbersome to use 
9. I felt very confident using the swaddle 
10. I needed to learn a lot of things before I could get going with the swaddle 
11. I feel confident the swaddle will meet my patient’s needs  
 
12. How likely is it that you would recommend the swaddle to other professionals in your 
field? 
 
 
Sample Document – Not for Study Use 
(Please use most current Sponsor-provided document version)
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 68 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
Questionnaire Instructions 
Please take your time and carefully indicate your responses in the following scales below.   
PAY ATTENTION TO THE FACT THAT THE SCALES CHANGE their anchor points in the left and right 
columns from one question to the next.  This is done in an effort to reduce bias in the results. 
 
Based on your experiences interacting with the product how would you describe the product? 
 
 
 
 
 
 
1)   Routine 
O---------O---------O---------O---------O---------O---------O  
Unusual 
 
2)   Inefficient O---------O---------O---------O---------O---------O---------O 
Efficient 
 
 
 
3)   Irrelevant 
O---------O---------O---------O---------O---------O---------O 
Relevant 
 
4)   Annoying 
O---------O---------O---------O---------O---------O---------O 
Pleasing 
 
5)   Satisfying  O---------O---------O---------O---------O---------O---------O  
Dissatisfying  
 
6)   Ineffective   O---------O---------O---------O---------O---------O---------O 
Effective 
 
7)   Fast 
O---------O---------O---------O---------O---------O---------O 
Slow 
 
 
8)   Unfamiliar O---------O---------O---------O---------O---------O---------O  
Familiar  
 
9)   Learnable O---------O---------O---------O---------O---------O---------O 
Not Learnable 
 
10) Easy  
O---------O---------O---------O---------O---------O---------O  
Difficult  
 
11) Useful 
O---------O---------O---------O---------O---------O---------O 
Useless 
 
12) Bad  
O---------O---------O---------O---------O---------O---------O 
Good 
 
 
Sample Document – Not for Study Use 
(Please use current Sponsor
-provided document version)
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 69 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
APPENDIX H: AMENDMEN
T TO PROTOCOL VERSIO
N 1.0 
Purpose: This amendment document describes the changes from protocol version 1.0 to 2.0 to 
account for change in Sponsor medical monitor. 
The following amendments were made to version 1.0 to produce version 2.0. Point-by-point revisions are 
shown as additions in double-underline (double-underline) and deletions in strikethrough (strikethrough) for 
each change made in this amendment for the previous version. 
Item 
Section 
Revision or Clarification 
Justification  
1 
Study synopsis 
 
Medical Monitor Name: -
Roee Lazebnik 
Jeff Hersh, MD 
Address:     3200 N 
Grandview Blvd 
Waukesha, WI 53188-1678 
Telephone: +1-262-366-
7295262-312-1407 
E-mail: 
Roee.Lazebnik@ge.com
 
Jeff.Hersh@ge.com  
 
 
Updated amendment 
version to reflect 
change in Sponsor 
medical monitor. 
2 
Section 10.4. 
Management of Serious 
Adverse Event and 
Unanticipated Adverse 
Device Effect Reporting 
Sponsor contact for SAEs and/or UADEs:  
Roee Lazebnik Jeff Hersh, MD 
+1-262-422-5126 262-366-7295 
Fax: 800-888-3983 
E-mail: SAE@ge.com
 
 
Updated amendment 
version to reflect 
change in Sponsor 
medical monitor. 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 70 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
APPENDIX I: AMENDMEN
T TO PROTOCOL VERSIO
N 2.0 
Purpose: This amendment document describes the changes from protocol version 2.0 to 3.0, as follows: 
1. To clarify that the primary endpoint of the study is in accordance with Section 2.1 of Annex X of the EU 
Medical Devices Directive, which species that verification of performance across the study cohort is an 
essential requirement of the study. 
2. To clarify that the planned duration of the study is 24-months, in accordance with requirements of 
ISO14155. 
3. To add the feed and sleep procedure, as required by the local site IRB in accordance with the site 
standard of care requirements. 
The following amendments were made to version 2.0 to produce version 3.0. Point-by-point revisions are 
shown as additions in double-underline (double-underline) and deletions in strikethrough (strikethrough) for 
each change made in this amendment for the previous version. 
Item 
Section 
Revision or Clarification 
Justification  
3 
STUDY SYNOPSIS
 
This is a two-phase prospective clinical study evaluating the 
performance and safety of the investigational MRI device for 
neonates and infants, including: 
…. 
Images, associated image data, and subject data collected in bot
phases of this study may be used for future engineering 
development and activities that support MR product developmen
including Sponsor-authorized scientific and marketing activities. 
Images and associated data from Phase 2 are intended for use a
samples forSummary evaluation of safety and performance from 
Phase 1 and Phase 2 may be used in support of
 regulatory 
submission, including filings for European CE mark
. No cohort-
based analyses are planned for any phase of this study.
 
… 
Duration: The study plans to actively enrol patients for 
approximately 24 months. 
 
Per MHRA 
requirements in 
Annex 1 Section 2.1 o
EU Medical Device 
Directive, clarified 
that the primary 
objective of the study 
is analysis of 
performance and 
safety of the device. 
 
In accordance with 
ISO14155, the 24-
month planned 
duration of the study 
is specified. 
4 
Section 2.1.2. 3.0T 
Neonatal MRI 
Investigational Device 
Components and Initial 
Configuration 
System Service Tools
/Phantoms (Simulations):
 
 
Corrected 
typographical error of 
omitted punctuation 
(“/” mark). 
5 
Section 3.1. Hypothesis
 
There is no statistical hypothesis being tested in this study.
 
Descriptive statistics will be used to provide summary evaluation
of performance and safety data. 
 
Clarified that an 
evaluation summary 
using descriptive 
statistics is required 
for EU regulatory 
submission. 
6 
Section 3.2. Justification This study is being done in two parts to optimize and collect data 
from a new MRI device for use in neonates and infants, the 3.0T 
Neonatal MRI investigational device. The first part of this study is
being conducted to demonstrate the feasibility of attaining 
diagnostic quality images and data using the 3.0T Neonatal MRI 
Clarified that an 
evaluation summary 
using descriptive 
statistics is required 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 71 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
investigational device in neonates and infants with various 
hardware and software configurations. The second part of this 
study is being conducted to collect images and associated data i
neonates and infants from a fixed hardware and software 
configuration of the 3.0T Neonatal MRI investigational device in 
support of regulatory activities in the European Union (EU), 
including CE mark. Summary performance and safety evaluations 
from both parts of the study may be disclosed to regulatory 
agencies as part of this study. 
for EU regulatory 
submission. 
7 
Section 3.3.1. Primary 
Objective(s): 
To evaluate the safety and performance of the device by collectio
of collect images and associated data using the 3.0T Neonatal M
investigational device  that demonstrates the feasibility of use in 
clinical neonate and infant populations. 
Per MHRA 
requirements in 
Annex 1 Section 2.1 o
EU Medical Device 
Directive, clarified 
that the primary 
objective of the study 
is analysis of 
performance and 
safety of the device. 
8 
Section 3.4.1. Primary 
endpoints 
For both Phase 1 and Phase 2, primary endpoints will be r
ecorded 
as: 
• 
Collection of MR images and associated data per 
quotas (Section 5.1.1 - Quotas by Anatomic Region) 
• 
Performance will be determined by proportion of 
images determined to be of evaluable or non-
evaluable diagnostic quality 
• 
Safety will be determine by summary rates of 
adverse events  
 
Clarified the primary 
endpoint 
performance and 
safety measures, in 
accordance with 
revised objective 
described above. 
9 
Section 3.4.2. Secondary 
endpoints 
• 
MR image quality evaluation(s), per-phase as follows: 
o 
Phase 1 and 2 (all subjects): Overall imag
quality rated on a 1-5 Likert scale  
o 
Phase 1 - Qualitative evaluation and 
optimization (Summary Report) provided b
PI, as per applicable MR Procedure 
Document 
o 
Phase 2 – Evaluations as described in the 
MR Procedure Document
 
Clarified that 
engineering 
performance 
endpoints are 
secondary. Per EU 
Annex X 
requirements, a 
measure of overall 
quality is required for 
all subjects in the 
study. The appendix is
revised to clarify that 
this measure is 
required for all 
subjects in Phase 1 
and Phase 2. 
10 
Section 4.1.1. Study Typ This is a two-phase, single-site, open-label, prospective research 
study involving human neonate and infant subjects. 
There will be 
no comparative or cohort-based statistical analyses of efficacy or 
safety, and therefore no randomization. This study is designed as 
two-phase clinical trial with an adaptive feasibility and 
Clarified that an 
evaluation summary 
using descriptive 
statistics is required 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 72 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
optimization phase (Phase 1) and controlled image collection stu
(Phase 2).  
Phase 1 is being conducted to optimize and calibrate the device 
subsequent data collection in Phase 2 of this study. Both parts , 
which is being done formay be used for regulatory submission 
purposes, including CE mark and submissions to other global 
regulatory authorities in other countries.  
Not 
randomi
zed:  
 
Randomization is not required, as
there are is no comparative 
analyseshypothesis testing 
for EU regulatory 
submission. 
11 
Section 4.1.2. Rationale 
for Two-Phase Study 
Design 
Phase 2: Phase 1 will be followed by a sequential second phase 
(Phase 2) to collect human images and data intended to as samp
images and associated per-subject data for use in regulatory 
submissions. No comparative or cohort-based analyses will be 
conducted on this population as part of this study.
 
Clarified that an 
evaluation summary 
using descriptive 
statistics is required 
for EU regulatory 
submission. 
12 
Section 5.8 Duration of 
Enrolment 
5.8 Duration of Enrolment 
The study plans to actively enrol patients for approximately 24 
months. 
In accordance with 
ISO14155, the 24-
month planned 
duration of the study 
is specified. 
13 
Section 6.2. Phase 1 
(Adaptive Feasibility) an
Phase 2 (Data Collection 
Phase 2 will be conducted to collect sample images and 
associated data for regulatory submission. 
No cohort-based 
analysis is intended for this population, and data will only be 
recorded and stored on a per-subject basis. While hardware and 
software may be modified throughout Phase 1, a fixed hardware 
and software configuration will be used for all Phase 2 scanning.
Based on the results of Phase 1, 
MR Procedure Document(s)
 will be 
provided to the site and used consistently 
in all Phase 2 scanning. 
 
 
Clarified that an 
evaluation summary 
using descriptive 
statistics is required 
for EU regulatory 
submission. 
14 
Section 6.3.1. Pre
-MR 
Scanning Activities 
Pre-Study Feed and Sleep Procedures
 
Per the applicable standard of care procedures required at the 
investigational site, each participating neonate or infant subject 
will be allowed adequate feed and sleep to ensure minimum 
disruption of care during MRI scanning, as follows: 
c. 
The subject will be either breast or bottle fed by 
or in the presence of the parent/legal guardian. 
d. 
The subject will be placed in a position that is 
relaxed and comfortable, with the expectation 
that it will be reasonably possible for the subject 
to sleep through the MRI scan. 
 
Added site IRB-
required feed and 
sleep procedure, in 
accordance with local 
site standard of care 
requirements. 
15 
Section 6.3.4. 
Evaluations 
Image Assessments Evaluations 
Image Performance Evaluation 
Image sets will be labeledlabelled according to subject 
identification number. Images will be evaluated as shown in Figure 
2. 
Added figure to clarify 
that evaluable/non-
evaluable constitutes 
the primary 
performance 
measure. Added 
clarification that a 
third reader will 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 73 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
Eligible participant 
consents and undergoes 
Neonatal MRI scan 
Was an image dataset 
collected?
NO DATA
Document reason on CRF
(i.e. withdrawal, technical issue, 
scheduling, etc.)
No
Were images 
rated evaluable by PI
and co-investigator?
NON-DIAGNOSTIC DATA
Record reason as acquisition 
issue or image quality issue
Non-evaluable
NON-DIAGNOSTIC DUE TO IMAGE QUALITY 
ISSUE
(image quality is insufficient 
for diagnostic use)
NON-DIAGNOSTIC DUE TO IMAGE QUALITY 
ISSUE
(reasons such as withdrawal, technical issue, 
scheduling, etc. prevented acquisition of some 
or all target views necessary for diagnostic use)
Complete Image Quality 
Assessments (one reader)
Evaluable
 
Figure 2 – Flowchart of performance evaluation. Determination of evaluable/non-evaluable for diagnostic 
used as the primary performance measure. All secondary Image Quality Assessments will be descriptively 
MR image datasets for each subject will be evaluated twice, once 
by the Principal Investigator and once by the neonatologist co-
investigator or authorized designee as:  
• 
Evaluable (Diagnostic Quality), or 
• 
Non-evaluable (Non-Diagnostic quality).  
The printed name and signature of the image evaluator(s) will be 
recorded. In the event that the two readers disagree on whether 
an image is evaluable or non-evaluable, a third medically qualified 
reader will arbitrate to provide an evaluable/non-evaluable 
decision, which will be recorded to the CRF and treated as the final 
decision for the image set. 
arbitrate to produce 
final evaluable/non-
evaluable decision for 
inclusion in analyses, 
in the event of 
disagreement 
between the PI and 
neonatologist. This is 
required due to the 
addition of summary 
analysis of these data, 
as required for 
submission for CE 
mark of the device in 
accordance with the 
EU Medical Device 
Directive. 
16 
Section 8.1.2. Statistical 
Analysis Methods 
Images and associated data being collected in this study are 
intended for use on a per-subject basis. A summary evaluation of 
primary performance and safety endpoints and, if necessary, 
secondary image quality assessments will be prepared by the 
Sponsor and includes in the final clinical study report. Descriptive 
statistics may, as necessary, be used to summarize relevant 
results. This evaluation may be used for regulatory submission 
purposes. 
 No cohort-based analyses or descriptive summaries will be 
provided for any endpoint as part of this study. Upon completion of 
this study, the Sponsor’s authorized research and engineering 
program may utilize data collected in this study in full or in part for 
authorized engineering purposes. 
Clarified that an 
evaluation summary 
using descriptive 
statistics is required 
for EU regulatory 
submission. 
17 
Section 9.0 OTHER 
INTERIM ACTIVITIES 
(QUALITATIVE INTERIM 
SUMMARIES) 
8.5. 9.0 OTHER INTERIM ACTIVITIES (QUALITATIVE INTERIM 
SUMMARIES)
 
… 
8.5.1. 9.1 Phase 1 Qualitative Investigator Summary 
… 
8.5.2. 9.2 Phase 1 and Phase 2 End
-of-Phase Interim Reports 
 
Assigned separate 
numbering to this 
section to clearly 
indicate that these 
additional activities 
are not part of 
statistical analysis 
(Section 8 and its sub-
sections). 
Correspondingly, 
attached sub-sections 
assume headings 
beginning with 9.X. 
18 
Section 8.3. Handling of 
Missing Data 
8.4 8.3 Handling of Missing Data 
Clarified that an 
evaluation summary 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 74 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
There are no cohort-based analysesThe Sponsor may descriptively
summarize the primary performance and safety endpoints from 
Phase 1 and Phase 2 of this study
. If the Sponsor observed that the
dataset for any subject is incomplete, additional clarification from
the investigator may be requested. The Sponsor may additionally
request copies of any clinical imaging datasets (including MRI sc
datasets and other clinically indicated imaging examinations) tha
t 
are conducted as follow-up to unexpected findings observed in 
this study. 
 
using descriptive 
statistics is required 
for EU regulatory 
submission. The 
section is renumbered
due to above 
explained separation 
of statistical and non-
statistical and non-
statistical sections 
into separate Sections
8 and 9, respectively, 
for clarity of original 
protocol intent. 
18 
Section 8.4 Pass/Fail 
Criteria of the Study 
8.5 8.4. Pass/Fail Criteria of the Study 
The study will be considered successful if 
sufficient evidence is 
collected to inform the evaluable sample images are collected 
from the performance and safety of the 3.0T Neonatal MRI 
investigational device in a representative population of neonates 
and/or infants, in accordance with Annex X of the European 
Medical Device Regulation.  
 
Clarified that an 
evaluation summary 
using descriptive 
statistics is required 
for EU regulatory 
submission. The 
section is renumbered 
due to above 
explained separation 
of statistical and non-
statistical and non-
statistical sections 
into separate Sections
8 and 9, respectively, 
for clarity of original 
protocol intent. 
19 
APPENDIX B 
– EXAMPLE
OF MR PROCEDURE 
DOCUMENT
 
 Overall Image Quality (required for all subjects) 
Other Engineering Performance Measures Performance 
 
Per EU Annex X 
requirements, a 
measure of overall 
quality is required for 
all subjects in the 
study. The appendix is
revised to clarify that 
this measure is 
required for all 
subjects in Phase 1 
and Phase 2. 
20 
Throughout 
Updated US English spelling conventions to conventional UK En
spelling and MS word style throughout. No cha
nges other than 
spelling were made throughout as part of this amendment, other 
than those documented in this appendix.
 
Per UK best practice. 
21 
Throughout 
Removed the term “Adaptive” throughout. 
Per differences 
regarding 
implementation of 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Item 
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Revision or Clarification 
Justification  
adaptive trials in the 
EU, US, and other 
global regions, the 
term “adaptive” was 
determined to be 
misused in this 
context and could be 
misleading that the 
study is statistically 
adaptive (rather than 
adaption of iterative 
engineering 
parameters, as per 
protocol intent). This 
term is removed 
throughout to clarify 
the original protocol 
intent, and does not 
reflect a change in 
study design or risk 
level. 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
APPENDIX J: AMENDMENT TO PROTO
COL VERSION 3.0
 
Purpose: This amendment document describes the changes from protocol version 3.0 to 4.0, as follows: 
1. To clarify that MR system log files containing operating parameters relevant to device safety and 
performance models are being routinely collected for all study scanning. 
2. To update references, symbols, and terminology, as requested for clarification purposes by the MHRA. 
The following amendments were made to version 3.0 to produce version 4.0. Point-by-point revisions are 
shown as additions in double-underline (double-underline) and deletions in strikethrough (strikethrough) for 
each change made in this amendment for the previous version. 
Item 
Section 
Revision or Clarification 
Justification  
22 
Investigator’s Signature 
Page 
I hereby agree to: 
(i)   Conduct the investigation in accordance with the agreement,
the investigational plan, applicable MHRA or applicable 
government regulations, and conditions of approval imposed 
by the reviewing Ethics Committee, IRB or governing regulato
body; 
(ii)  Supervise all testing of the device involving human subjects; 
and 
(iii) Ensure that the requirements for obtaining informed consent 
are met. 
I have read this protocol and study related documents and agree
to conduct this study in full accordance with the stipulations of th
protocol described herein, and any subsequent amendments. 
 
Updated required 
language for 
investigator signature 
pages, as per current 
Sponsor global 
template 
requirements. These 
changes are 
applicable for all 
clinical trials 
conducted by the 
Sponsor. 
23 
Synopsis: 
Device/Product 
Description 
Small-footprint 3.0T Neonatal MRI investigational device capable o
being located in a NICU and its component
s, including a 
neonate/infant single-use disposable swaddle 
Updated language for 
consistency with the 
terminology found in 
the body of the 
protocol. 
24  
Section 1.2. Literature 
Review 
In particular, neonatal MRI has become standard clinical care for
neurological and orthopaedic applications at many clinical 
facilities. 2, 3, 4, 5 
Added citations to 
support this 
statement. 
25 
Section 1.4.1. Risks
 
While serious adverse events can occur in MRI exams in rare 
cases, typically with adverse events occurring as a result of 
when 
failure to correctly follow routine site MR safety 
procedures for 
scanning are not correctly followed, no serious adverse events are
anticipated in this study. 
Clarified the 
language, as per 
original intent of the 
statement. 
26 
Section 2.1.1. 3.0T 
Neonatal MRI 
Investigational Device 
This device includes and MR system 
Correction to spelling 
(typographical) 
27 
Section 2.1.2. 3.0T 
Neonatal MRI 
Investigational Device 
Components and Initial 
Configuration: 4. 
The transmitting and receiving coil is a single channel 
receive-only 
sixteen rung “birdcage” coil (inner surface accessible to the 
subject) 
Clarified that the coil 
is for both transmit 
and receive functions. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Item 
Section 
Revision or Clarification 
Justification  
Radiofrequency (RF) 
System 
28 
Section 2.3. Risk 
Category and Rationale 
The MRI device used in this study uses static magnetic field 
strengths <4.0T, which are widely accepted to pose minimal risks
to typical adults, children, and infants/neonates,
patients as 
detailed in the US FDA Guidance 
Criteria for Significant Risk 
Investigations of Magnetic Resonance Diagnostic Devices
 and 
contemporary medical literature, comparable with routine clinical 
MRI examination. 26, 27 
Clarified and added 
citation. 
29 
Section 2.3.1. MR Safe, 
Conditional, and Unsafe 
 
 
Updated symbols to 
current version of 
ASTM F2503.
 
30 
Section 2.5.5. 
Maintenance and 
Replacement: (a) 
a. Access device(s) in
-person or remotely (such as through TVA/Ti
or other secure remote connection) for quality control, trouble
-
shooting, training, real-time image optimization, to collect system 
configuration and system log files, or other purposes required for 
device maintenance, installation, or de-installation, and/or system 
data collection; 
 
Clarified that remote 
access is used as part
of routine data 
collection of MR 
system log files. 
31 
Section 3.2. Justification This study is being done in two parts to optimize and collect data
from a new MRI device for use in neonates and infants, the 3.0T 
Neonatal MRI investigational device. The first part of this study is
being conducted to demonstrate the feasibility and safety of 
attaining diagnostic quality images and data using the 3.0T 
Neonatal MRI investigational device in neonates and infants with
various hardware and software configurations. The second part o
this study is being conducted to collect images and associate
d 
data in neonates and infants from a fixed hardware and software
Clarified that 
operating parameters 
contained in system 
log files, such as SAR
data, will be routinely 
collected as part of 
this study. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Item 
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Revision or Clarification 
Justification  
configuration of the 3.0T Neonatal MRI investigational device in 
support of regulatory activities in the European Union (EU), 
including CE mark. MR system log files containing operating 
parameters relative to safety and performance calculations will b
systematically collected throughout the study for all subjects. 
Summary performance and safety evaluations from both parts of
the study may be disclosed to regulatory agencies as
 
32 
Section 3.4.1. Primary 
endpoints 
Safety will be determined by summary rates of adverse events 
 
Correction to spelling 
(typographical) 
33 
Section 5.3.1. Vulnerabl
Subjects 
The Sponsor has conducted previous internal testing using 
phantoms to confirm evaluate the safety of the device for use on 
humans. 
Updated terminology 
for consistency with 
internal Sponsor 
documentation. 
34 
Section 6.1.1. Quality 
Control Scans 
The device is equipped with a predictive SAR model designed to
conservatively limit actual SAR exposure in research subjects. T
predictive SAR model used on the system is detailed in the 
technical documentation for the Neonatal MRI device. Each scan 
session will include sequences designed to generate a range of 
actual SAR data, which is stored in may besystem logs and 
subsequently collected by the Sponsor’s engineering 
representatives from system data and logs of study procedures
. 
Throughout the study, system log files containing experimentally 
generated SAR data will be routinely collected, along with releva
clinical data such as patient weight (as described in subsequent 
protocol sections), necessary for future evaluation of the system’s
predictive SAR model versus actual clinical data in the 
infant/neonate population. SAR levels will not exceed levels of 4 
W/kg Whole Body, 3 W/kg 
 
Clarified that MR 
system log files 
containing operating 
parameter data, 
including SAR data, 
will be routinely 
collected. This data is 
intended for use in 
evaluating 
engineering modelling
of SAR in this 
population.  
35 
Section 6.3.2. MR 
Scanning Procedures: 
MR Scanning 
Information 
Anatomy scanned (i.e. neurological (head/neck/spine) , 
cardiac/thorax, or abdominal/pelvis) 
 
Corrected erroneous 
statement. All 
scanning in this 
protocol is of the 
neurological 
(head/neck/spine) 
anatomy. Other 
studies are being 
concurrently 
conducted by the 
Sponsor that examine 
additional anatomy 
types. 
36 
Section 11.1. 
Foreseeable Adverse 
Events and Device 
Effects 
Peripheral Nerve Stimulation: Transient skin sensations (‘tingling’
or peripheral nerve stimulation (PNS) is related to 
dB/dt and 
gradient rise time, and is expected to be rare in neonates and 
infants due to small skin surface area and conservative device 
thresholds. 26 Subjecting infants to sudden, rapidly changing 
gradient magnetic fields during imaging can, induce circulating 
currents in conductive tissues of the body that typically are not 
Clarified PNS risk as 
per current medical 
literature, including 
citations. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 79 of 95 
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Item 
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Revision or Clarification 
Justification  
painful and resolve Resolution is typically spontaneously, though, 
in theory, discomfort or pain rare cases can cause discomfort, 
or 
pain. injuryfrom PNS in infants is possible., 26 or death.  
37 
References 
2. Malik S, Beqiri A, Price A, Teixeira J, Hand J, Hajnal J. Specif
absorption rate in neonates undergoing magnetic resonance 
procedures at 1.5 T and 3 T. NMR Biomed. 2015;28(3):344
-52. 
3. Glass H, Bonifacio S, Sullivan J, et al. MRI and Ultrasound Inj
Preterm Infants with Seizures. J Child Neurol. 2009;24(9):1105
-1111. 
27. Schenck J. Safety of Strong, Static Magnetic Fields. J Mag Re
Img. 2000;12:2-19. 
28. Alibadi F, Askary R. Effects of Tactile
–Kinesthetic Stimulation on 
Low Birth Weight Neonates. Iran J Pediatr. 2013;23(3):289
–294. 
29. Anbeek P, Vincken K, Groenendaal F, Koe
man A, van Osch M, va
der Grond J. Probabilistic brain tissue segmentation in neonatal 
magnetic resonance imaging. Pediatr Res. 2008;63(2):158
-63. 
 
Added references to 
support the added 
citations in the 
document, and 
renumbered 
references 
appropriately in order 
of sequential 
appearance in the 
document. 
 
 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
APPENDIX K: AMENDMEN
T TO PROTOCOL VERSIO
N 4.0 
Purpose: This amendment document describes the changes from protocol version 4.0 to 5.0, as follows: 
1. To clarify body temperature measurement and associated procedures for setup and calibration of the 
Invivo Expression monitor for monitoring of body temperature during MRI scanning. 
The following amendments were made to version 4.0 to produce version 5.0. Point-by-point revisions are 
shown as additions in double-underline (double-underline) and deletions in strikethrough (strikethrough) for 
each change made in this amendment for the previous version. 
 
 
Item 
Section 
Revision or Clarification 
Justification  
38 
Section 2.1.4. Other MR
Equipment 
Invivo Corp patient monitors will be used during study 
procedures to monitor subject vital signs, body temperature
(on the Expression Monitor using a single
-use sensor), and 
O2 saturation.  
Added text to clarify the 
original intent that body 
temperature is measured 
during scanning using the 
MRI compatible Expression 
Monitor. 
39 
Section 6.3.1. Pre
-MR 
Scanning Activities 
Pre-scan Transport Subject Information 
The following pre-scan session subject information will be 
recorded for all subjects:  
• 
gender 
• 
age since birth (days for subjects aged ≤30
and months for subjects aged >30 days) 
• 
gestational age (for subjects ≤30 days old) 
• 
infant or neonate status (neonate = birth to ≤30 
days; infant >30 days to <2 years) 
• 
Pre-transport temperature: body temperature 
measured just before leaving the incubator or 
crib, measured according to the standard clinical 
practice at the investigational site, as follows: 
o 
temperature  measurement value 
o 
device type (Expression Monitor [Invivo] 
or standard of care device), and  
o 
anatomical area of measure (specific 
area of skin surface, i.e. axillary or 
specify; oesophageal; or other, specify) 
 
Differentiated between pre-
scanning and pre-transport 
procedures.  
 
Added specific requirements 
for capturing the value, 
device type, and anatomical 
area for temperature 
measures in the pre-
transport period. 
 
 
40 
Section 6.3.1. Pre-MR 
Scanning Activities 
Preparation for Scanning 
Immediately before initiating the scan, ensure that the 
Expression Monitor (Invivo) is connected and monitoring 
vital signs, including but not limited to body temperature 
and O2 saturation. Once acclimated to the scan 
environment, the following scanning information shall be 
recorded by the scan operator, including the following: 
• 
Pre-scanning baseline temperature
: body 
temperature measurement made with an Expression 
Monitor (Invivo), as follows: 
Added a new temperature 
measurement during the 
period in the MRI area 
immediately before 
scanning, This is collected as 
a baseline for confirmation 
that the subject’s body 
temperature does not 
exceed 0.5°C during 
scanning. All temperature 
measures during scanning 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Justification  
o 
the time (minutes) allowed for 
acclimation once in the magnet bore 
before taking the temperature 
measurement 
o 
temperature measurement value 
o 
anatomical area of measure (specific 
area of skin surface, i.e. axillary or 
specify; oesophageal; or other, specify). 
The study staff will set the alarm level on the Expression 
Monitor (Invivo) to trigger at 0.5°C above the pre-scanning 
baseline temperature.  
 
will be taken using the Invivo 
Expression Monitor that is 
MRI compatible. 
41 
Section 6.3.2. MR 
Scanning Procedures 
Monitoring Subjects During MRI Scanning 
During MRI scanning, subjects will be monitored in real-time 
using a properly functioning Expression MRI Patient Monitor 
(Invivo, Corp; Orlando, FL, USA). The subject will be observed 
all times during the MR scan by a qualified medical 
professional (nurse, neonatologist, and/or other medical 
doctor qualified for neonatal/infant care) on the study staff 
who shall remain in the magnet room with the subject 
during scanning. The observing staff should remain in a 
position where they can readily observe the subject and 
monitor and, if necessary, contact the scan operator during 
the scanning session.   
A conservative threshold for body temperature alarm is 
selected, as such that body temperature change is 
sufficient to trigger an alarm (0.5°C above the pre-scanning 
baseline temperature) is not in itself considered a clinically 
significant risk to patients; these patients will be evaluated 
by a medically qualified member of the study staff for any 
other possible signs or symptoms and they will determine 
whether an AE has occurred as per the standard 
procedures described in Section 11 – Complaint Handling 
and Adverse Event Reporting. 
If a body temperature alarm on the monitor is triggered at 
any time during scanning, the study staff should stop the 
scan series. Then, the following elements will be 
documented as part of study data for each such alarm 
occurrence: 
o 
the time of alarm 
o 
Alarm Temperature: the body temperature at time 
of alarm, based on body temperature 
measurement made with an Expression Monitor 
(Invivo), as follows: 
 
temperature measurement value 
 
anatomical area of measure 
(specific area of skin surface, i.e. 
axillary or specify; oesophageal; or 
other, specify). 
o 
the time it takes to return to pre-scanning 
baseline temperature (minutes/seconds) 
Describes that scanning will 
end if the temperature alarm 
indicates that body 
temperature rose more than 
0.5°C during MRI scanning, 
and documents applicable 
temperatures and if the scan 
was able to be successfully 
continued upon resolution of 
temperature rise. 
 
Added that the actual body 
temperature at alarm and, if 
applicable, upon continuing 
the scan will be captured. 
 
It is clarified that the 60 
minute scanning window 
only refers to the scanning 
time in the MR device, and 
not to setup or preparation 
time, 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Justification  
Note: In the event that the baby’s body 
temperature does not return to a level at or below
the pre-scanning baseline temperature within the
study scanning period (not to exceed 60 minutes
from first localizer to end of scanning), the patien
will be discontinued from the study. 
o 
any conditions observed that possibly contributed 
to temperature rise, such as swaddling, 
environmental conditions, distress, or scanning 
conditions? (Y/N, if yes explain) 
o 
decision to continue the scan session (do not 
continue after first alarm)? (Y/N) 
o 
Continuing Temperature: the body temperature at 
the time of scanning was continued using an 
Invivo Expression Monitor, as follows:
 
 
temperature measurement value 
 
anatomical area of measure 
(specific area of skin surface, i.e. 
axillary or specify; oesophageal; or 
other, specify). 
A medically qualified investigator should evaluate each 
patient to determine if it is safe to continue scanning 
once the patient’s body temperature returns to pre-
scanning baseline temperature or lower in the event of 
an alarm. If an alarm is triggered more than once during 
a single scan session, the patient will be discontinued. 
Subject MR Scanning Procedures 
The total time that the subject may be in the MR scanner, 
starting from the start of the first localizer to the time at the 
end of the last scan, will not exceed sixty (60) minutes. 
Additional time may be required for setup and removal of 
the patient.  
 
42 
Section 6.3.3. Post-
scanning MR Procedures Post-scanning Subject Information  
Post-scanning information will be recorded for all subjects:  
• 
Post-scanning temperature: Body temperature, 
immediately before removal from the MR scanner 
(post-scan body temperature), body temperature 
measurement made with an Invivo Expression 
Monitor and anatomical area of measure (specific 
area of skin surface, i.e. axillary or specify; 
oesophageal; or other, specify). 
• 
Time of removal from MR device (on 24 hour clock) 
• 
Final temperature: Body temperature  (measured 
after transport and just before the subject is 
moved placed back into theirthe routine care  
environmentincubator/crib by the same method 
used for previous body temperature recordings, 
as follows: 
o 
temperature measurement value 
Differentiated between post-
scanning and final 
temperature measurements.  
 
Added specific requirements 
for capturing the value, 
device type, and anatomical 
area for temperature 
measures in the post-
transport period. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
Item 
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Justification  
o 
device type (Expression Monitor [Invivo] 
or standard of care device), and  
o 
anatomical area of measure (specific 
area of skin surface, i.e. axillary or 
specify; oesophageal; or other, specify) 
Note: It is preferred that the same method as used 
for the Pre-transport Temperature.) 
43 
Section 8.3. Handling of 
Missing Data 
The Sponsor may descriptively summarize the primary 
performance and safety endpoints from Phase 1 and Phas 
2 of this study, including the descriptive statistical summary
of patients that exhibit a body temperature rise of more 
than 0.5°C from acclimated pre-scanning baseline body 
temperature (resulting in an Expression Monitor alarm 
during scanning). 
 
Describes intent to include 
the body temperature in 
descriptive statistic 
summary. 
44 
Signature Page 
 
Updated to per current 
Sponsor procedural 
requirements. 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
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Version Date: 25/Sep/2015 
APPENDIX L: AMENDMEN
T TO PROTOCOL VERSIO
N 5.0 
Purpose: This amendment document describes the changes from protocol version 5.0 to 6.0, as follows: 
1. To clarify temperature measurement procedures, including that only the MR Safe Invivo Expression 
monitor may be used during MR scanning and in the MR scan room; standard of care methods may be 
used for temperature determinations in the patient’s clinical care area.  
2. Clarified that InVivo Essential monitor is not a required patient transport monitoring system and that 
site will use their standard of care monitoring system during patient transport. All mention of InVivo 
Essential monitor is removed from the protocol. 
3. To clarify that if scanning is stopped due to alarm, the scanning will be discontinued, but patients may 
continue on in other parts of the study (i.e. transport) and that data from such subjects may still be 
used and disclosed to the Sponsor. 
The following amendments were made to version 5.0 to produce version 6.0. Point-by-point revisions are 
shown as additions in double-underline (double-underline) and deletions in strikethrough (strikethrough) for 
each change made in this amendment for the previous version. 
Item 
Section 
Revision or Clarification 
Justification  
45 
Section 2.1.4. Other MR
Equipment 
Invivo Corp patient monitor will be used during study procedures
to monitor subject vital signs, body temperature (on the Expressio
Monitor using a single-use sensor in the MRI scan room), and O2 
saturation.  
 
Essential Monitor (Invivo Corp) 
– This is a patient transport 
monitoring system. This is MR Conditional patient monitor system
labelled for use in neonate and infant populations that may remain
in the magnet room during scanning if conditions are met.  This is
a small monitor that attaches to the patient table for transport 
purposes. 
Clarification to when 
monitor may be used. 
 
Clarified that InVivo 
Essential Monitor will 
not be a required 
patient monitoring 
system during 
transport. Site will use
their own monitoring 
system as per their 
standard of care. 
46 
Section 6.3.1. Pre
-MR 
Scanning Activities 
General Method for Recording Temperature 
Subject body temperature will be recorded at defined intervals 
before, during, and after scanning as detailed in the following 
sections. In the MR suite and during scanning, MR Safe Invivo 
Expression monitor should be used to determine temperature an
other vital signs.  
Clarification to when 
monitor may be used 
for study temperature 
measurements. 
47 
Section 6.3.1. Pre
-MR 
Scanning Activities - 
Pre-Transport Subject 
Information 
• 
Pre-transport temperature: body temperature just before 
leaving the incubator or crib, measured according to the 
standard clinical practice at the investigational site, as 
follows: 
o 
temperature measurement value 
o 
device type (Expression monitor [Invivo] or 
record standard of care device), and  
o 
anatomical area of measure (specific area of 
skin surface, i.e. axillary or specify; oesophageal; 
or other, specify) 
 
Clarified that 
Expression monitor is 
used during MR 
scanning. 
Corrected that 
standard of care 
temperature 
measurements will be 
used (Expression is 
only used in the MR 
suite.  
48 
Section 6.3.1. Pre-MR 
Scanning Activities - 
Pre-scan Environmental 
Condition 
Immediately prior to the first scan series, the following 
environmental conditions in the MR scanning room will be 
recorded:  
• 
Scan room temperature 
• 
System temperature, per MR device console 
 
Clarified that the 
system console does 
not display this 
temperature and thus 
it cannot be recorded. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 85 of 95 
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Version Date: 25/Sep/2015 
Item 
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Revision or Clarification 
Justification  
49 
Section 6.3.1. Pre
-MR 
Scanning Activities - 
Preparation for 
Scanning 
• 
Pre-transport temperature: body temperature just before 
leaving the incubator or crib, measured according to the
standard clinical practice at the investigational site, as 
follows: 
o 
temperature measurement value 
o 
device type (Expression monitor [Invivo] or 
record standard of care device), and  
o 
anatomical area of measure (specific area of 
skin surface, i.e. axillary or specify; oesophageal; 
or other, specify) 
 
Clarified that the site 
will not perform 
oesophageal 
measurements.  
 
Corrected that 
standard of care 
temperature 
measurements will be 
used (Expression is 
only used in the MR 
suite.  
50 
Section 6.3.1. Pre-MR 
Scanning Activities –
Duration of Active 
Enrolment 
Active enrolment will be considered to end on a per-
subject basis upon the later of: 
a. 
The time that the subject is returned to his or 
her standard of care clinical environment and all Sponsor 
provided devices are removed from the subject, including 
Sponsor-provided swaddle, protective padding, and all 
other study devices 
OR 
b. 
The time that all Sponsor provided devices are 
removed from the subject, including Sponsor-provided 
swaddle, protective padding, and all other study devices. 
b. After active enrolment ends, images and data about 
any standard of care follow-up or other medical care 
resulting from unexpected findings may still be accessed 
observationally and collected by the Sponsor for research 
purposes. 
Clarified end of 
subject active 
enrolment in the 
study. 
51 
Section 6.3.1. Pre-MR 
Scanning Activities – 
General Method for 
Recording Temperature 
Subject body temperature will be recorded at defined intervals 
before, during, and after scanning as detailed in the following 
sections. In the MR suite and during scanning, MR Safe Invivo 
Expression monitors should be used to determine temperature and 
other vital signs. Outside of the MR suite, Invivo Essential monitors  
should be used to determine temperature and other vital signs. In 
the event that these monitors are not able to be used for any 
reason, study temperature measurements may be taken using 
alternative standard of care body temperature measurement 
methods, and the type of body temperature measurement method 
should be documents on the CRF . Temperature and vital signs 
measurement devices used during scanning or in the MR suite 
must be labeled as MR Safe or meet the conditions of MR 
Conditional labelling. 
Clarified and 
simplified the 
instruction of 
temperature 
collection. 
 
Clarified that in the 
MR suite, if for some 
reason InVivo 
Expression monitor is 
not working, the 
subject cannot be 
scanned at all.Outside 
of the MR suite, other 
devices can be used 
to monitor/measure 
the subject 
temperature. 
52 
Section 6.3.2. MR 
Scanning Procedures - 
Monitoring Subjects 
during MR Scanning 
• 
Pre-scanning baseline temperature
: body temperature 
measurement made with Invivo Expression Monitor 
(Invivo), as follows: 
o 
the time (minutes) allowed for acclimation once 
in the magnet bore before taking the 
temperature measurement 
o 
temperature measurement value 
o 
anatomical area of measure (specific area of 
skin surface, i.e. axillary or specify; oesophageal; 
or other, specify). 
Clarified that the site 
will not perform 
oesophageal 
measurements. Also 
clarified that scanning 
is discontinued in the 
event of alarm 
(subject is not 
necessarily 
withdrawn or 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 86 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
 
If a body temperature alarm on the monitor is triggered at any 
time during scanning, the study staff should stop the scan series
Then, the following elements will be documented as part of study
data for each such alarm occurrence: 
o 
the time of alarm 
o 
Alarm Temperature: the body temperature at time of 
alarm, based on body temperature measurement made 
with the Expression Monitor (Invivo), as follows:
 
o 
temperature measurement value 
o 
anatomical area of measure (specific 
area of skin surface, i.e. axillary or 
specify; oesophageal; or other, 
specify). 
o 
the time it takes to return to pre-scanning baseline 
temperature (minutes/seconds) 
Note: In the event that the baby’s body temperature doe
not return to a level at or below the pre-scanning 
baseline temperature within the study scanning period 
(not to exceed 60 minutes from first localizer to end of 
scanning), the patient will be scanning will be 
discontinued from the study(if collected, the patient’s 
data collected up until this time may still be used for 
study purposes, and post-scanning information may still 
be recorded about the patient). 
o 
any conditions observed that possibly contributed
 to 
temperature rise, such as swaddling, environmental 
conditions, distress, or scanning conditions?
 (Y/N, if yes 
explain) 
o 
decision to continue the scan session (do not continue 
after first alarm)? (Y/N) 
o 
Continuing Temperature: the body temperature at the 
time of scanning was continued using an Expression 
Monitor (Invivo), as follows:
 
 
temperature measurement 
value 
 
anatomical area of measure 
(specific area of skin surface, 
i.e. axillary or specify; 
oesophageal; or other, 
specify). 
A medically qualified investigator should evaluate each patient to 
determine if it is safe to continue scanning once the patient’s body 
temperature returns to pre-scanning baseline temperature or 
lower in the event of an alarm. If an alarm is triggered more than 
once during a single scan session, the patient will be 
discontinuedscanning will be discontinued. If collected, the 
patient’s data collected up until this time may still be used for 
study purposes, and post-scanning information may still be 
recorded about the patient. 
discontinued from the 
study). 
 
Corrected that 
standard of care 
temperature 
measurements will be 
used (Expression is 
only used in the MR 
suite.  
53 
Section 6.3.3. Post-
scanning MR Procedures 
- Post-scanning Subject 
Information 
Post-scanning information will be recorded for all subjects:  
• 
Post-scanning temperature: Body temperature, 
immediately before removal from the MR scanner (post-
scan body temperature), body temperature 
measurement made with and Expression Monitor (Invivo) 
and anatomical area of measure (specific area of skin 
Clarified that the site 
will not perform 
oesophageal 
measurements. 
 
Clarified that 
Expression monitor is 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 87 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
surface, i.e. axillary or specify;
 oesophageal; or other, 
specify). 
• 
Time of removal from MR device (on 24 hour clock) 
• 
Final temperature: Body temperature measured after 
transport and just before the subject is placed into the 
routine care environment, as follows: 
o 
temperature measurement value 
o 
device type (Expression  Monitor [Invivo] or 
record standard of care device), and  
o 
anatomical area of measure (specific area of 
skin surface, i.e. axillary or specify; oesophageal; 
or other, specify) 
Note: It is preferred that the same method as used for 
the Pre-transport Temperature. 
• 
End of Enrolment Time: Time when the patient is 
returned to the clinical care area and all 
Sponsor-provided device components (i.e., 
Swaddle, Invivo monitor, pads, etc.) have been 
removed from the subject. 
 
used during MR 
scanning, and 
Essential Monitor is 
used during transport 
(temperature 
measurements during 
transport are made 
according to the 
standard of care). 
 
Corrected that 
standard of care 
temperature 
measurements will be 
used (Expression is 
only used in the MR 
suite. 
Removed Time of 
removal from MR 
device (on 24 hour 
clock)  and clarified 
end of enrolment time 
definition. 
 
54 
Section 6.3.3. Post-
scanning MR Procedures 
- Post Scan 
Environmental 
Conditions 
At the end of the last scan series when the scan operator enters 
the scan room to remove the subject from the MR device, the scan 
operator will record:  
• 
Scan room temperature 
• 
System temperature, per MR device console 
Clarified that the 
system console does 
not display this 
temperature and thus 
it cannot be recorded 
55 
Section 6.5 - Withdrawal 
and Discontinuation 
Criteria 
All subjects must be admitted for care in the NICU or other 
neonatal or infant care department or unit affiliated with the 
investigational site at the time of enrolment and scanning to be 
eligible to participate in this study. If a subject is discharged from 
clinical care at the investigational site prior to MR scanning, the 
subject will be withdrawn from the study.  
The subject’s medical care shall take precedence over any imaging 
or other procedures associated with the study.  
If it is determined during the exam that the study imaging will in 
any way negatively impact required clinical care, the subject shall 
be immediately withdrawn from the study.  
In the event the subject appears to be in pain or undue discomfort, 
if potentially destabilizing vital signs are observed by visual 
inspection or via monitoring equipment, or if the parent(s) or legally 
authorized representative requests to discontinue study 
procedures, the study procedures will be discontinued immediately 
and the subject will be removed from study , as determined 
necessary by the medically qualified staffas soon as possible 
according to the standard of care at the investigational site. The 
subject shall be removed from the MR environment as soon as 
safely possible, and, if necessary, care will be provided to the 
subject to alleviate any discomfort according to the site’s standard 
of care. Data collected up until the time of withdrawal may still be 
used and disclosed to the Sponsor for research purpose 
Clarified that data 
collected up until the 
time of withdrawal 
(even if scanning is 
discontinued) will be 
recorded. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 88 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
The subject’s parent or legal guardian may withdraw him or her 
from study participation at any time, for any reason without 
consequence.  
The study staff may withdraw a subject at any time for any reaso 
The reasons for withdrawal and discontinuation for
 any subject 
shall be recorded. These will be reported to the Sponsor. 
 
56 
Section 14.3 Subject 
Pseudonymisation 
All subject data that is submitted to the Sponsor will be identified 
by the use of a unique subject number assigned as an 
identification code to the Subject, without de-identification. The 
scan operator will enter the identification number in the system to
complete pseudonymisation. 
The assigned subject identification number 
will consist of a four 
digit number and be issued in consecutive order starting with 
0001.according to the Sponsor’s Data Management Plan (DMP).
  
Each participating site will maintain a subject identification log, 
which is a list of all subjects who are enrolled in the study, along 
with their address and medical record number in the event that 
they must be contacted in the future.  
 
Updated to reference 
this detailed 
description of 
numbering located in 
the DMP, as per 
standard Sponsor 
procedure. 
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 89 of 95 
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Version Date: 25/Sep/2015 
APPENDIX M: AMENDMEN
T TO PROTOCOL VERSIO
N 6.0 
Purpose: This amendment document describes the changes from protocol version 6.0 to 7.0, as follows: 
1. To clarify that the two (2) radiologists will act as image evaluators (rather than the PI and a 
neonatologist).  This is done to minimize bias, as the PI and neonatologist may be directly involved in 
study acquisitions based on specific site practices. 
2. Clarifies the responsibilities of evaluators and readers in this study in figures and flowcharts, for clarity 
only (this does not change the original intent or design of the study, other than as described in #1 
above). 
3. To clarify the roles of participating physicians and neonatologists in the study procedure and 
assessments. 
4. To clarify the procedures for screenings subjects for enrolment and verify MR safety prior to study 
procedures. 
The following amendments were made to version 6.0 to produce version 7.0. Point-by 
-point revisions are shown as additions in double-underline (double-underline) and deletions in strikethrough 
(strikethrough) for each change made in this amendment for the previous version. 
Item 
Section 
Revision or Clarification 
Justification  
57 
Study Synopsis 
Duration: The study plans to actively enrol patients for approximately 24
months. 
Removed the 
descriptor “active” 
describing the EC/IRB
-
approved protocol as 
this is not meant to 
correspond with the 
“active” enrolment 
period for AE 
reporting purposes. 
This term is removed 
to clarify this intent. 
58 
Section 2.6. 
Disposition of the 
Device/Product 
When scanning under all active EC/IRB approved study protocolss is 
completed, the following actions will be conducted:
 
 
Removed the 
descriptor “active” 
describing the EC/IRB
-
approved protocol as 
this is not meant to 
correspond with the 
“active” enrolment 
period for AE 
reporting purposes. 
This term is removed 
to clarify this intent. 
60 
Section 4.2. 
Controls and 
Minimization of 
Bias 
The following bias control methods are being employed in this study: 
 
d. 
Selection bias will be limited by consecutively enrolling 
subjects meeting the inclusion/exclusion criteria 
 
e. 
Spectrum bias will be limited by using a population expected 
to be representative of the general population at the 
investigational site, without regard for gender, race, or 
ethnicity. 
f. 
Reader bias will be limited by ensuring that evaluators and 
readers making performance assessments are separate 
radiologists (not the PI or neonatologist).
 
Described added 
protections for reader 
bias by ensuring that 
the evaluators 
making image 
assessments are 
separate from the 
principal investigator. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 90 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
 
61 
Section 5.4. 
Inclusion Criteria 
4. 
Able to safely undergo an MRI scan, as determined by 
the 
site’s co-investigator neonatologistmedically qualified 
personnel; 
 
6. 
Are of appropriate size and shape to fit into the bore of th
magnet, inclusive of all monitoring equipment, if any, 
necessary for the subject’s routine clinical care based on 
standard of care measurement methods, in accordance 
with site policies:  
 
Clarified that the site 
would delegate 
medically qualified 
personnel, but this wil
be done under the 
supervision of the PI 
and the Sponsor will 
not require that this 
be delegated to the 
site neonatologist. 
62 
Section 5.4. 
Exclusion Criteria 
6. 
Have parent(s), guardian(s), or legally authorized 
representative(s) that require that they accompany the 
subject into the MR environment that have 
contraindications to the MR environment or would 
otherwise be put at undue risk or discomfort, as 
determined by the investigators medically qualified 
personnel;8 
7. 
Have any ferrous or electrical items or non-removable 
medical devices that are not compatible with MR scanning 
(including devices labelled as MR Unsafe, MR conditional 
for which the scanning conditions are not met, or without 
MR safety labelling that does not satisfy site MR safety 
requirements) that may pose hazards in the MR scanning 
or MR environment, in the opinion of the Principal 
Investigator or medically qualified personnel neonatologist 
co-investigator in accordance with the site’s MR Safety 
policy; 
8. 
Have any contraindications or could otherwise be 
expected to experience detrimental effects to safety, well-
being, or medical care, as determined by the Principal 
Investigator or medically qualified personnel neonatologist 
co-investigator in accordance with the site’s MR Safety 
policy; 
9. 
Require any scheduled standard of care procedures that 
are expected to be adversely impacted by participation in 
this study, in the opinion of the principal investigator , 
neonatologist co-investigator, or medically qualified 
delegate personnel; and 
 
Clarified that the site 
would delegate 
medically qualified 
personnel, but this will 
be done under the 
supervision of the PI 
and the Sponsor will 
not require that this 
be delegated to the 
site neonatologist 
63 
Section 5.7 
Screening and 
Enrolment 
5.7 Screening and Enrolment 
5.6.2  Screening for Enrolment 
Potential subjects will be identified by the Principal Investigator or other 
qualified site staff.  Informed consent will be obtained for those subjects 
who agree to participate in the study.  Subjects will then be screened for 
enrolment to ensure the subject is eligible to participate per the 
inclusion/exclusion criteria, as per the judgement of medically qualified 
personnel.   
Subjects who do not qualify based on inclusion/exclusion criteria will be 
considered screen failures. 
Clarified screening 
requirements to 
specifically indicate 
that enrolment 
happens after 
consent is provided 
and before any study 
procedures are 
performed (including 
sizing ring). 
                                                          
8 If it is not safe for the parent or guardian that wishes to accompany the subject into the MR environment, the 
parent or guardian may opt not to accompany the subject. In this case, the subject would not be excluded.  
Subjects would be excluded if it is determined to be potentially unsafe for a parent or guardian to accompany a 
subject into the MR scan suite, and the parent or guardian is not willing to allow the subject to be scanned alone 
while he/she waits in another area of the hospital. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 91 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
Once a subject is determined to be eligible per the inclusion/exclusion 
criteria including providing written informed consent, the subject will be
considered enrolled and assigned a subject n
umber.Subjects will be 
screened to ensure that all of the following conditions are met prior to 
study enrolment: 
The subject meets the criteria for inclusion/exclusion, including size 
requirements, 
Note: At screening, the subject’s size will be determined 
according to the 
standard of care at the investigational site (e.g. using a tape measure 
other standard device). After informed consent is attained for the 
subject, the Sponsor-provided sizing tool will be used to confirm the 
subject’s size as part of MR safety screening. 
Parents(s) or legal guardian(s) provide written informed consent for the
subject’s participation, 
The subject and any person(s) accompanying him or her into the MR 
environment have been successfully screened according to the standa
of care MR safety screening procedures at the investigational site(s), 
including supplemental screening for patients that are suspected to 
have metal object on or implanted in their body (i.e. using hand
-held 
metal detectors), to ensure that both the subject
 and any person(s) who 
wish to accompany the subject into the MR scanning room are eligible
for MR scanning. Written documentation will be retained by the site for
MR safety screening. 
If the subject and/or parent or other person that will accompany the 
subject fail to meet screening criteria, the subject will be considered as
screen failure and will not be considered enrolled.
 
Subjects that meet the screening criteria will be enrolled and will be 
considered actively enrolled from the time the subject is 
placed on the 
swaddle, if used, or removed from his or her normal standard of care 
environment for transport until the subject is returned to his or her stan
of care situation and all MR equipment, such as swaddle or padding, is
removed. 
5.7.1 MR Safety Screening 
Screening will be completed for the subject and any person 
accompanying him or her into the magnet room prior to allowing 
entrance into the MR scan room. The scan operator will confirm 
completion of MR safety screening, per standard clinical prac
tice at the 
investigational site. In addition, subjects may be screened for the 
presence of ferrous metallic objects using a hand
-held metal detector, 
under the direction of the principal Investigator or delegate. The subjec
and anyone accompanying the subject into the MR scan room, will be 
provided with mandatory hearing protection, such as ear 
plugs or ear 
plugs combined with ear muffs and/or ear plugs, and other protective 
devices required by site MR safety policies.
 
Enrolled subjects must be confirmed
 to be of acceptable size for MR 
scanning in this study using the Sponsor
-provided sizing tool 
(“horseshoe” shaped ring) with all required attached medical equipmen
presentThis is conducted to verify that the subject and all necessary 
medical equipment can safely fit into the bore of the MR device with 
normal airflow and without contacting the bore., at the following 
intervals:Prior to removal from the normal clinical care environment
 
Immediately prior to MRI scanning (by the scan operator or qualified 
designee) 
Note: The sizing tool is a study device that may only be used after 
written informed consent for participation has been attained.
 
 
 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 92 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
64 
Section 5.7. 
Duration of 
Enrolment 
The study plans to actively enrol patients for approximately 24 months. 
 
Removed the 
descriptor “active” 
describing the EC/IRB
-
approved protocol as 
this is not meant to 
correspond with the 
“active” enrolment 
period for AE 
reporting purposes. 
This term is removed 
to clarify this intent. 
65 
Section 6.1.1. 
Quality Control 
Scans 
The log will continue as long as the investigational MR device is house
at the site, and will only be discontinued when all 
active EC/IRB-
approved studies are completed and the investigational MR device(s) 
is/are removed from the investigational site. 
 
Note: All human scans for this study, scans done for any other 
active 
EC/IRB-approved active studies using this device, and other non
-clinical 
scans (i.e. phantom scans for research, service/maintenance, or trainin
will be logged. This is done so that the 
log is consistent with the internal 
log inside of the system for engineering purposes. The log may contain
other columns required by other concurrent protocols and some fields 
may be marked as not applicable (N/A) for other concurrent protocols.
 
 
Removed the 
descriptor “active” 
describing the EC/IRB
-
approved protocol as 
this is not meant to 
correspond with the 
“active” enrolment 
period for AE 
reporting purposes. 
This term is removed 
to clarify this intent. 
66 
Section 6.3.1. Pre
-
MR Scanning 
Activities: MR Pre-
screeening 
MR Pre-Screening 
To verify that subjects with necessary medical equipment present can 
safely fit into the study device bore with normal airflow and without 
contact, subjects will be verified to be of acceptable size for study MR 
scanning using the Sponsor-provided sizing tool (“horseshoe” shaped 
ring) with necessary attached medical equipment prior to removal from
the normal clinical care environment. 
Note: The sizing tool is a study device that may only be used 
after written informed consent for participation has been 
attained. 
The study staff will then ensure that the subject and any person(s) 
accompanying him or her into the MR environment satisfy all applicabl
site MR Safety Screening requirements.
 
The study staff will verify that enrolled subjects can be expected to saf
undergo MR scanning according to the investigational site MR safety 
policy (which may include screening with hand
-held metal detectors, at 
the discretion of the PI). If the subjec
t or any persons required to 
accompany him or her into the MR scan room are determined to be 
ineligible for MR scanning or if, for any reason, MR scanning would 
detrimentally impact any medical care that may be required or present
undue discomfort to the subject or persons accompanying him or her 
into the scan room, the subject will be withdrawn from the study. 
 
If the subject is determined not be of appropriate size, not to meet MR 
Safety Screening policies at the site, or is
 discharged from clinical care at 
the investigational site prior to MR scanning, the subject will be 
withdrawn from the study. 
 
Clarified the 
difference between 
pre-screening that 
happens as a study 
procedure vs. 
screening for 
enrolment. 
67 
Section 6.3.1. Pre
-
MR Scanning 
Activities: Duration 
of Active 
Enrolment 
Duration of Active Enrolment (for AE/SAE reporting purposes) 
Subjects may be transported to the MR suite before or after removal 
from their incubator, crib, or other standard of care bedding.
 
Subjects will be considered activel
y enrolled (for AE/SAE reporting 
purposes) in the study on a per-subject basis from the time that the 
Removed the 
descriptor “active” 
describing the EC/IRB
-
approved protocol as 
this is not meant to 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 93 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
Sponsor-provided horseshoe-shaped sizing tool is used to measure 
subject size (the first study procedure of MR Pre
-Screening). It is 
mandatory that the sizing ring is used for all subjects before other study
procedures to ensure that the subject is of proper size for the MR bore
 
 
correspond with the 
“active” enrolment 
period for AE 
reporting purposes. 
This term is removed 
to clarify this intent. 
68 
Section 6.3.1. Pre
-
MR Scanning 
Activities: 
Protective 
Devices/Procedur
es 
All subjects require mandatory hearing protection that provides a 
minimum of 22 dB attenuation prior to MR scanning (ear plugs or a 
combination of ear plugs and ear muffs, in accordance with site MR 
Safety Polices)..  
Use of the horseshoe-shaped sizing ring to verify that subjects can safe
fit into the bore of the MR device is mandatory
 and should also be 
performed before transporting the subject out of their clinical care 
environment immediately prior to scanning.. 
The scan operator or delegate will ensure that 
 Athe subject meets the 
criteria for MR scanning according to the
pplicable site-specific MR safety 
site MR Safety Policy. 
procedures should be followed in addition to those
specified in this protocol.In addition, the study staff may screen subjects
and accompanying person(s) for presence of ferrous metallic objects 
using a hand-held metal detector, under the direction of the principal 
Investigator or delegate. If new information shows that the subject doe
not meet the site MR Safety Policy requirements, the subject will be 
withdrawn. 
 
Clarified that ear 
plugs or a 
combination of ear 
plugs+muffs is 
required. 
69 
Section 6.3.4. 
Evaluations: 
Performance 
Evaluation 
Performance Evaluation 
Image sets will be labelled according to subject identification number. 
Images will be evaluated as evaluable (diagnostic) or non
-evaluable 
(non-diagnostic) by two evaluators, and then evaluable images will be 
read for image quality by a separate reader, 
as shown in Figure 2. 
Original Figure 2] 
Eligible participant 
consents and undergoes 
Neonatal MRI scan 
Was an image dataset 
collected?
NO DATA
Document reason on CRF
(i.e. withdrawal, technical issue, 
scheduling, etc.)
No
Were images 
rated evaluable by PI
and co-investigator?
NON-DIAGNOSTIC DATA
Record reason as acquisition 
issue or image quality issue
Non-evaluable
NON-DIAGNOSTIC DUE TO IMAGE QUALITY 
ISSUE
(image quality is insufficient 
for diagnostic use)
NON-DIAGNOSTIC DUE TO ACQUISITION 
QUALITY ISSUE
(reasons such as withdrawal, technical issue, 
scheduling, etc. prevented acquisition of some 
or all target views necessary for diagnostic use)
Complete Image Quality 
Assessments (one reader)
Evaluable
[Revised Figure 2] 
Eligible participant 
consents and undergoes 
Neonatal MRI scan 
(Site)
Was an image dataset 
collected?
NO DATA
Document reason on CRF
(i.e. withdrawal, technical issue, 
scheduling, etc.)
No
(Evaluators)
Were images 
rated evaluable?
NON-DIAGNOSTIC DATA
Record reason as acquisition 
issue or image quality issue
Both evaluators agree image is Non-evaluable
NON-DIAGNOSTIC DUE TO IMAGE QUALITY 
ISSUE
(image quality is insufficient 
for diagnostic use)
NON-DIAGNOSTIC DUE TO ACQUISITION 
QUALITY ISSUE
(reasons such as withdrawal, technical issue, 
scheduling, etc. prevented acquisition of some 
or all target views necessary for diagnostic use)
One or both evaluators
indicate Evaluable
(Reader)
Complete Image Quality 
Assessments
(Reader)
Were images 
rated evaluable by
the reader?
Evaluable
Non-evaluable
Figure 2 – Flowchart of performance evaluation. Determination of evalua
the primary performance measure. All secondary Image Quality Assessm
Clarified text and 
Figure 2 to indicate 
that the PI will not be 
the study image 
evaluator, as an 
additional bias 
control. 

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 94 of 95 
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Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
MR image datasets for each subject will be evaluated twice by two 
delegated radiologists serving as image evaluators (Evaluator 1 and 
Evaluator 2), once by the Principal Investigator and once by the 
neonatologist co-investigator or authorized designee  as: 
• 
Evaluable (Diagnostic Quality) 9, or 
• 
Non-evaluable (Non-Diagnostic quality).  
The evaluations and printed name and signature of the image 
evaluator(s) will be recorded to an Evaluator CRF. In the event that the 
two readers evaluators (Evaluator 1 and Evaluator 2) disagree on 
whether an image is evaluable or non-evaluable, a third medically 
qualified reader (Reader 1) will arbitrate to provide an evaluable/non-
evaluable decision, which will be recorded to the Reader CRF and treated 
as the final decision for the image set. 
 
70 
Section 6.3.4. 
Evaluations: 
Image Quality 
Assessments 
All evaluable images will be further examined by a single reader (Reader 
1) that may be the PI or a qualified delegated radiologist for image 
quality on a 1-5 Likert Scale,10 as follows:  
 
Clarified reader roles. 
71 
Section 6.6. Study 
Flowchart (Table 3) 
… 
Post-
Scan 
Reader/ 
Evaluator 
Assessme
nts 
Additional 
Sponsor-
Requested 
Assessments 
… 
X (reader 
only) 
(defined 
in MR 
Procedure 
Doc) 
MR Images 
and Data 
 
X 
(access 
to) 
Evaluable 
(Diagnostic)/N
on-evaluable 
(Non-
diagnostic) 
Assessment 
 
X 
(reader 
and 
evaluator
s) 
Image Quality 
Assessments 
 
X  
(reader 
only) 
Overall 
image 
quality 
(based on 
investigator’
s 
experience) 
 
X 
(reader 
only) 
Clarified flowchart 
language around 
evaluators and 
readers. This is a 
clarification of the 
original intent, as 
described above. 
                                        
                  
 
9 An image set may be considered of diagnostic quality if it contains images suitable for diagnosis (not all images views are 
typically required to be diagnostic based on specific scanning circumstances, so long as applicable views necessary for 
diagnosis are present) 
10 Likert Scale of 1-5, where: 
1 = Very Poor 
2 = Poor 
3 = Neutral 
4 = Good 
5 = Excellent 
Note: For image quality assesment, scores of 3, 4, or 5 will be considered diagnostic quality, and scores of 1 and 2 will be 
considered non-diagnostic quality.  

Study Title: Development of a MR Scanner Capable 
of Being Sited in a Neonatal Intensive Care Unit 
Study Number: 114-2014-GES-0035 
Protocol: 7.0 
 
 
Page 95 of 95 
 DOC1547483 (Rev. 7.0) 
 
Version Date: 25/Sep/2015 
Item 
Section 
Revision or Clarification 
Justification  
Image 
contrast 
 
X 
(reader 
only) 
Presence of 
artefacts 
 
X 
(reader 
only) 
Signal to 
noise ratio 
(SNR) 
 
X 
(reader 
only) 
Tissue 
contrast 
 
X 
(reader 
only) 
Fat/water 
separation 
 
X 
(reader 
only) 
 
 
 
72 
Section 11.1. 
Foreseeable 
Adverse Events 
and Device Effects 
Acoustic Noise: High noise levels in the scan room and in the bo
re of the 
scanner during MRI scanning may cause discomfort but are not norma
hazardous with proper hearing protection. Spontaneously resolving 
hearing loss/tinnitus typically related to improper hearing protection ca
in rare cases, become chronic or s
evere. Hearing protection 
(combination of earplugs and/or  or ear plugs combined with earmuffs to 
achieve noise reduction of ≥22 dB is mandatory during MRI in  
 
Clarified that ear 
plugs or a 
combination of ear 
plugs+muffs is 
required 
 
 
End of Document