Translational Development of Photon-Counting CT Imaging
Phase: NA
Conditions: Cancer, Inflammatory Disease, Vascular Diseases, Metabolic Bone Disease
Sponsor: National Institutes of Health Clinical Center (CC)

                      Translational Development of Photon counting CT-Imaging 
 
 
 
 
             Date 4/23/2019 
 
 
 
 
 
NCT03878134

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Protocol # 19-CC-0070
“Photon-counting CT”
CLINICAL RESEARCH PROTOCOL 
NATIONAL INSTITUTES OF HEALTH CLINICAL CENTER
PROTOCOL NUMBER: 19-CC-0070
PROTOCOL VERSION: 4.23.2019
TITLE: Translational Development of Photon-counting CT imaging 
SHORT TITLE: Photon-counting CT
IDENTIFYING WORDS: photon counting CT, photon counting detectors, computed tomography
PRINCIPAL INVESTIGATOR:
Elizabeth C. Jones, M.D.*
Chief
Radiology & Imaging Sciences, CC/NIH 
Building 10, Room 1C352
Phone: 301-402-5606
Email: ejones@cc.nih.gov
MEDICAL ADVISORY INVESTIGATOR:
Elizabeth C. Jones, M.D.*
Chief
Radiology & Imaging Sciences, CC/NIH 
Building 10, Room 1C352
Phone: 301-402-5606
Email: ejones@cc.nih.gov
NIH ASOCIATE INVESTIGATORS:
Brad Wood, M.D.*
RAD&IS, CC, NIH/Employee 
Phone: 301-496-7700
Email: bwood@cc.nih.gov
Marcus Chen, M.D.* 
NHLBI, NIH/Employee 
Phone: 301-496-0077
Email: marcus.chen@nih.gov
Marc Ahlman, M.D.* 
RAD&IS, CC, NIH/Employee 
Phone: 301-451-3995
Email: mark.ahlmann@nih.gov
William Pritchard, M.D., Ph.D. 
RAD&IS, CC NIH/Employee 
Phone: 301-496-3593
Email: william.pritchard@nih.gov
Haydar Celik, Ph.D. 
RAD&IS, CC, NIH/Contractor 
Phone: 240-271-3065
Email: haydar.celik@nih.gov
Tracy Cropper, R.N., B.S.N* 
RAD&IS, CC, NIH/Employee 
Phone: 301-402-6132
Email: tcropper@nih.gov
Jayasai Rajagopal
RAD&IS, CC, NIH/GPP Student 
Phone: 330-409-5051
Email: jayasai.rajagopal@nih.gov
Huong Tran, M.S.E., M.D. 
RAD&IS, CC, NIH/Fellow 
Phone:301-451-9405
Email: huong.tran2@nih.gov
Charisse Garcia, R.N., B.S.N., CCRP* 
RAD&IS, CC, NIH/Employee
Research Contact/AI:
Tracy Cropper, R.N., B.S.N*

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Protocol # 19-CC-0070
“Photon-counting CT”
Phone: 301-594-4511
Email: garciacr@nih.gov
Caroline (Carole) Webb, RN, MSN, 
CCRP, CCRC*
ORSC, CC NIH/Contractor 
Phone: 301-451-9462
Email:caroline.webb@nih.gov
RAD&IS, CC, NIH/Employee 
Phone: 301-402-6132
Email: tcropper@nih.gov 
And:
Caroline (Carole) Webb, RN, MSN * 
ORSC, CC NIH/Contractor
Phone: 301-451-9462
Email:caroline.webb@nih.gov
*Can obtain informed consent 
NON-NIH COLLABORATOR :
ESTIMATED DURATION OF STUDY:
5 Years
START DATE: 05/06/2019
END DATE: 10/21/2023 
NUMBER AND TYPE OF PATIENTS:
ACCRUAL CEILING: 750
Number
Sex
Age Range
Patients
750
Males or Females
18 and above
PROJECT USES IONIZING RADIATION:
 
None
 
X
Medically indicated:
 
X
Research indicated:
RSC Approval Number: 
2701_Expiration Date: 10/30/21  
PROJECT USES DURABLE POWER OF ATTORNEY: No 
OFF-SITE PROJECT: No
MULTI-SITE PROJECT: No
DATA SAFETY MONITORING BOARD (DSMB) INVOLVEMENT: No 
TECHNOLOGY TRANSFER: Yes (CRADA, MTA/SLA)
Institution
Primary Contact
Duke University
Ehsan Samei, Ph.D., Advisor

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Protocol # 19-CC-0070
“Photon-counting CT”
ABBREVIATIONS:
CD
Clinical Director
CFR:
Code of Federal Regulations 
Cr
Creatinine
CRADA;
Cooperative Research and Development Agreement 
CRIS:
Clinical Research Information System
CT:
Computed Tomography
DM
Diabetes Mellitus
eGFR
Estimated glomerular filtration rate 
HRPP
Human Research Protection Program 
IRB
Institutional Review Board
IV:
Intravenous
rem:
Unit of radiation dosage  
MTA:
Materials Transfer Agreement
PACS:
Picture Archiving and Communication System 
PCCT:
Photon Counting Computed Tomography
PI
Principal Investigator
PII
Personally identifiable information 
RAD&IS:
Radiology and Imaging Sciences 
SLA:
Simple Letter of Agreement
SOP
Standard operating procedure
UP
Unanticipated Problems (
UADE
Unanticipated Adverse Device Effect

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Table of Contents
ABBREVIATIONS:............................................................................................................2
Precis................................................................................................................................5
1.
Introduction, Background and Rationale ...................................................................7
2.
Study Objectives........................................................................................................8
3.
Study Design and Methods .......................................................................................8
3.1.
Study Implementation..........................................................................................9
3.2.
End of participation............................................................................................10
3.3.
Alternatives to participation ...............................................................................10
3.4.
Privacy...............................................................................................................10
4.
Subject Recruitment ................................................................................................10
4.1.
Recruitment plan ...............................................................................................10
4.2.
Recruitment materials and advertisements .......................................................11
5.
Eligibility Assessment and Enrollment.....................................................................11
5.1.
Inclusion Criteria................................................................................................11
5.2.
Exclusion Criteria...............................................................................................11
6.
Collection and Storage of Human Specimens or Data............................................11
6.1.
Collection practices ...........................................................................................11
6.2.
Image and data storage.....................................................................................12
6.3.
Tracking.............................................................................................................12
6.4.
End of study procedures....................................................................................12
6.5.
Loss or destructions of data ..............................................................................13
6.6.
Publication policy...............................................................................................13
7.
Statistical Analysis...................................................................................................13
7.1.
Sample Size ......................................................................................................13
7.2.
Analysis of Study...............................................................................................14
8.
Data Safety and Monitoring Plan.............................................................................14
8.1.
Data and Safety Monitoring...............................................................................14
8.2.
Reporting of Unanticipated Problems and Adverse Events...............................14
9.
Human Subjects Protection.....................................................................................16
9.1.
Rationale for Subject Selection .........................................................................16
9.2.
Participation of Children ....................................................................................16
9.3.
Participation of NIH Employees and Staff .........................................................17
9.4.
Evaluation of Benefits and Risks/Discomforts...................................................17
9.5.
Risks/Benefits Analysis .....................................................................................18
9.6.
Non-significant Risk Determination ...................................................................19
9.7.
Informed Consent Process and Procedures......................................................19
10.
Conflict of Interest.................................................................................................20
11.
Compensation.......................................................................................................20
12.
References ...........................................................................................................22

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“Photon-counting CT”
Precis
NIH develops new imaging techniques as one of its priorities for accelerating science, including 
methods for non-invasive patient assessments. Computed tomographic (CT) imaging is a 
mainstay of diagnostic imaging. The latest major technological advance is photon counting CT 
(PCCT) which uses a new x-ray detector that measures x-ray penetration of the body and the 
energy of each x-ray photon. NIH has one of three prototype Siemens PCCT CounT systems in 
the world for investigational use. The scanner can perform standard CT and PCCT imaging. In 
this protocol, NIH patients already enrolled in a clinical research protocol and who are referred 
to Radiology for diagnostic CT as part of that research may be enrolled in this study of PCCT. 
The diagnostic CT scan requested by their medical care team will be performed on the CounT 
scanner, providing the clinically indicated imaging, along with a single, brief PCCT exam to 
support PCCT development. The data will be used to characterize quality of the PCCT images 
and to develop testable hypotheses and new diagnostic applications using PCCT capabilities.
Current CT systems, such as the Siemens SOMATOM Flash, have two x-ray tubes, each 
paired with an x-ray detector that measures total x-ray penetration of the patient and uses that 
information to create the images. The CounT scanner is a modified version of the Flash in 
which one of the two standard detectors has been replaced with a PCCT detector. The two 
imaging modes for the CounT scanner are (i) standard detector study as in a Flash scanner and
(ii) PCCT scan. The patient scan will thus include clinically indicated radiation exposure with the 
standard detector and research radiation with the PCCT detector. The CounT system is sited at 
the Clinical Center under a CRADA with Siemens Medical Solutions.
Compared to current scanners, PCCT offers four major advantages:

lower radiation dose

greater spatial resolution

reduced imaging noise

x-ray energy discrimination
The primary objectives are to:

develop and characterize new medical imaging methods

facilitate translation of PCCT advantages into clinically useful applications.
As a translational development protocol, all imaging studies are open-label and data may be 
analyzed as they are collected. Bias is minimized using objective measurements. Observational 
data may be characterized using descriptive statistics. Simple comparisons between the 
standard CT and PCCT may use paired and unpaired parametric and non-parametric 
techniques. These studies will form the foundation to develop advanced clinical imaging 
capabilities and applications.

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1. Introduction, Background and Rationale
The NIH intramural program specifically includes developing novel imaging techniques as 
one of its priorities for accelerating science, including generating new methodologies for 
non-invasive patient assessments (https://irp.nih.gov/our-research/accelerating- 
science/developing-novel-imaging-techniques). Computed tomography (CT) is a core 
imaging modality in medicine. In CT imaging, an X-ray tube and an X-ray detector are 
rotated around the patient with the detector recording X-ray penetration continuously during 
exposure. That data is then used to reconstruct cross-sectional images of the patient for 
diagnostic purposes. There are myriad ways to structure the examination of a body area,
e.g. the system settings for the X-ray exposure, data collection and reconstruction and 
display of the images. Typical, optimized exam protocols have been developed for CT 
imaging for each area of the body and each organ as well as unique aspects of physiology, 
allowing for visualizing differences between normal and abnormal tissues and function.
The current clinical CT scanners at the NIH/RAD&IS have dual source capability with two X- 
ray tube/detector pairs that rotate around the patient simultaneously. Dual-source CT can be 
used to double the speed of acquisition or to perform dual energy scanning that may aid in 
determining tissue composition. These traditional CT systems detect X-rays using scintillator 
crystals and a photodiode array in an energy-integrating detector (EID) system that 
measures the total X-rays that pass through the patient and reach the detector. In these 
detectors, the individual imaging elements are separated by metal septae that limit the 
achievable spatial resolution.
In contrast, the photon-counting CT (PCCT) system utilizes very efficient semiconductor 
detectors that directly convert the X-ray energy of each individual photon into electric signal 
pulses. This not only allows detection of individual X-ray photons but also the energy 
associated with each photon. There are no metal septations between imaging elements in 
the detector, therefore much higher spatial resolution is possible. Altogether, the efficiency 
of the detector, the ability to discriminate between X-ray photon energies and the lack of 
septations in the detector permit higher spatial resolution, improved contrast to noise ratios 
and imaging with lower radiation dose.1,2 This may be of particular value in low-signal scans 
(i.e. obese patients or lung exams).3,4,5 Recent phantom studies and preliminary testing on 
humans demonstrate comparable image quality for both radiation dose-matched PCCT vs. 
current CT technology, notably in abdominal, cardiovascular, brain and lung scans, and 
improved contrast-to-noise ratio in renal tissue enhancement via iodine mapping in 
PCCT.6,7,8,9,10
Among its potential applications, PCCT provides spectral information for material 
decomposition analysis, which can help determine types of renal calculi11 and generate 
contrast material density maps (including that of water). The capability for material 
decomposition allows subtraction of calcium from extremity CT studies that may enhance 
detection or assessment of metastatic disease in cancer patients, particularly with clinical 
suspicion for metastases or new onset of pain, or new evaluation techniques in patients with 
metabolic musculoskeletal disease. High resolution imaging may generate a spatial map of 
radiopaque drug-eluting embolic beads used to treat liver cancer, leading to dose maps for 
therapy. Pre-clinical studies have evaluated multiple-contrast imaging in delineation of 
infarcted myocardial tissue, and biodistribution of gold nanoparticles, while postmortem

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Protocol # 19-CC-0070
“Photon-counting CT”
studies demonstrate ability to characterize atherosclerotic plaque.12,13,14,15,16 Low dose 
imaging with PCCT may reduce cumulative radiation dose in the follow-up of patients who 
undergo repeated clinical CT.
Superior spatial resolution compared to standard CT provides greater detail in anatomic 
imaging.17 A major implication is the potential to advance radiogenomics, the correlation 
between imaging features and treatment outcomes or the genomics of a particular 
tumor.18,19 The NIH patient population is ideal for this component of the research, as there 
are significant populations with specific diseases, including uncommon and rare diseases. 
Furthermore, substantial longitudinal follow-up of patients is common, often with correlative 
information on treatment outcomes as well as genetics of specific tumors or other disorders.
High spatial resolution image acquisition at lower radiation exposure with added spectral 
capabilities has promising potential for more dose-efficient imaging, new applications and 
more widespread utility compared to conventional CT. One might think of PCCT is 
analogous to high resolution color film, whilst conventional CT is black and white film.
2. Study Objectives
Developmental studies in normal volunteers have been conducted at the NIH.2,6,7,8,10 This 
protocol serves to more conclusively evaluate and confirm the clinical performance of 
PCCT, optimize clinical protocols and develop clinical applications of this latest advance in 
CT technology. The primary objectives of this study include, but are not limited to:

Objective 1: To develop and characterize novel methods of evaluating patients using 
PCCT; and,

Objective 2: To facilitate the translation of PCCT technology and imaging methods 
into clinically useful applications for patients.
The applications being developed will take advantage of the potential for dose reduction, 
improved spatial resolution, noise reduction and x-ray energy discrimination. X-ray energy 
discrimination may be used for material decomposition wherein various materials such as 
iodine, gadolinium and calcium that all appear similar on conventional CT can be 
differentiated by PCCT imaging.
Because this is a translational development protocol for new technology, all imaging 
procedures are open-label and data may be analyzed as they are collected. Bias is 
minimized by defining and using objective measurements and recording them for review. 
Observational data may be characterized using descriptive statistics. Simple comparisons 
between the standard and PCCT images may use paired and unpaired parametric and non- 
parametric techniques as appropriate. New methods may be compared to the standard CT 
or computational models of the imaging studies. Objective quantitative measurements used 
in CT performance include, but are not limited to noise level and standard deviation, signal 
to noise ratio and variance, radiation dose and qualitative measures such as radiologist 
ratings of image quality, lesion conspicuity, image noise, beam hardening artifact, motion 
artifact.
3. Study Design and Methods

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“Photon-counting CT”
NIH patients referred to RAD&IS for diagnostic CT may be approached for participation in 
the study of PCCT The study team has shared information about the PCCT study with NIH 
researchers that frequently schedule their patients for diagnostic CT scans as part of their 
studies. Those researchers or other NIH research teams may refer patients for study 
participation in this PCCT study. Enrolled patients will undergo the requested clinical 
diagnostic CT study on the PCCT system using the standard detector, with or without IV 
and/or oral contrast as indicated for the diagnostic CT scan. If contrast is not indicated for 
the diagnostic scan, it will not be administered for the research PCCT study. They will also 
undergo a brief PCCT scan as part of the examination. The standard detector and PCCT 
scans may be performed in any order. The scan will thus include both clinically indicated 
radiation exposure with the standard detector and research radiation with the PCCT 
detector.
From the patient perspective, the experience is the same as with a standard CT study. The 
CT scans are accomplished by having the subject lie down on a patient table which slides 
into the gantry of the scanner, a hollow cylinder 78 cm in diameter. The scan is performed 
by a qualified person in an adjacent room; audible communication is by intercom. In 
addition, the patient can be observed directly through the window between the two rooms. 
The patient can be removed from the scanner immediately upon request or in case of 
emergency.
The study team may use standard monitoring equipment during the CT scan. This may 
include electrocardiogram, or pulse oximeter, adhesive beads or fiducial markers and x-ray 
dosimeters (to determine exposure to radiation). Densitometry phantoms or iodine reference 
standards may be included in the scan to serve as references for x-ray attenuation and 
material decomposition. During the scan, individuals may be asked to perform tasks such as 
breath holding to enhance CT scan quality. Iodinated contrast may be injected intravenously 
using a standard clinical CT injector system. Oral CT contrast may be administered.
The duration of the entire examination in the CT room including positioning, setting up the 
CT injector, scan planning and the scans including the PCCT component, will be 
approximately 20 minutes, comparable to a clinical CT scan duration. The PCCT component 
adds approximately 5 minutes beyond the standard study duration
3.1.Study Implementation
1. Potential subjects will be referred by research teams to the PCCT team. Patients will be 
given a copy of the informed consent form which describes the study protocol. Protocol 
staff (PI or AI) will review the consent form and answer any questions the subject may 
have. The PCCT research team may review the patient’s prior medical records and 
imaging to determine suitability for the PCCT scan. Patients will be registered on the 
protocol and the informed consent process will be documented in CRIS. CT scanning 
will occur on the PCCT scanner after confirmation that all standard of care CT scanning 
requirements are met by the study participant as required for any CT scan.
Since the study involves research radiation, women of child-bearing age who may be 
pregnant will undergo blood or urine pregnancy testing.

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Protocol # 19-CC-0070
“Photon-counting CT”
2. After the informed consent form is signed and suitability determined, volunteers will 
receive the clinically indicated CT study using the standard CT detector. Oral iodinated 
contrast will be administered as clinically indicated. Intravenous (IV) contrast will be 
administered as clinically indicated. This may require establishment of an IV access line. 
The PCCT scan may be performed before, during, or after the administration of IV 
contrast. The standard detector and PCCT scans may be performed in any order. The 
PCCT scan may or may not add additional diagnostic information related to the patient’s 
care. The patient’s active involvement in the study ends at the conclusion of the PCCT 
examination. However, future imaging studies may be reviewed (see #5 below). Repeat 
consent will be obtained in the event a patient is scanned on more than one occasion 
(see #4 below).
3. The CT scan acquired with the standard detector will be stored in the NIH Clinical Center 
Radiology PACS and CRIS systems. Those exams will be submitted for interpretation by 
a board certified and NIH CC credentialed RAD&IS physician. Reports of findings will be 
managed according to standard practices for diagnostic imaging studies within the 
Department.
4. If the subject is later referred to RAD&IS for another CT examination, they are eligible to 
participate in this study again, provided at least one year has passed since the prior 
PCCT scan. These subjects will be re-consented and "re-enrolled" in this study with the 
updated active Consent Form. However, patients may not undergo more than one PCCT 
examination within a one-year period.
5. Information within the patient’s medical record that was collected under other protocols 
may be collected as part of this study, including history and physical results, disease 
state and related diagnoses, treatment history and responses. Prior imaging data may be 
reviewed, analyzed and compared to the PCCT scan, as well as imaging data and 
information in the medical record generated after performance of the PCCT scan.
3.2.End of participation
Once a subject completes the clinical and PCCT scan their participation in the study is 
complete.
3.3.Alternatives to participation
Individuals will be allowed to withdraw from this protocol at any time and can also elect to 
not participate in this study. If they choose not to participate they will receive the standard 
CT study as ordered by their research team.
3.4.Privacy
All research activities will be conducted in as private a setting as possible.
4. Subject Recruitment
4.1.Recruitment plan
NIH patients currently on another NIH research protocol referred to RAD&IS for diagnostic 
CT may be approached for participation in the study of PCCT, subject to this study’s 
enrollment and exclusion criteria.

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Protocol # 19-CC-0070
“Photon-counting CT”
Potential subjects may be identified by study staff in RAD&IS who have routine access to 
the clinical CT scan schedule and patient orders. NIH clinicians and their staff may identify a 
patient on their study for this study of PCCT and may then contact personnel on the PCCT 
protocol. In either case, the potential enrollment would be discussed with the subject. This 
could be in RAD&IS or in the Outpatient Clinic/Inpatient wards, or by telephone depending 
on the circumstances.
4.2.Recruitment materials and advertisements
None
5. Eligibility Assessment and Enrollment
5.1.Inclusion Criteria

NIH patients currently on an NIH research protocol who are referred to RAD&IS for 
CT examination as part of that research protocol

18 years old or greater

Able to understand and sign informed consent
5.2.Exclusion Criteria

Studies that specifically require dual source CT scan capability or where dual source 
CT scan is requested

Studies ordered for an emergency indication

Pregnant women. When uncertain of pregnancy status, subjects of child-bearing 
potential will undergo serum or urine pregnancy testing on the day of examination. 
Post-menopausal and surgically sterilized subjects are automatically exempt from 
this testing

Lactating women who are unable to stop breast feeding for 24 hours following the 
administration of contrast

Body weight >500 lbs (227 kg) or a body circumference that prevents the study 
subject from lying flat in the scanner

Patients who have undergone PCCT examination within the past year.

Any contraindications that the research team identifies from the subject, RAD&IS CT 
questionnaires, and/or History and Assessment

Employees or staff supervised by the Principal Investigator or an Associate 
Investigator will not be recruited to participate
6. Collection and Storage of Human Specimens or Data
6.1.Collection practices
Data from the clinical history and from laboratory tests will be maintained in the NIH medical 
record. No tissue or body fluid samples are collected and stored under this protocol. Blood 
may be collected for assessment of renal function.  A pregnancy test may be ordered, as 
part of the screening process for the protocol. Clinical CT data acquired with the standard 
detector is transferred to the Diagnostic Radiology Department (DRD) for clinical 
interpretation. This CT data is archived per NIH Clinical Center and RAD&IS policy, on the 
radiology picture archiving and communication system (PACS). Access to the PACS is 
password protected and only provided through the Diagnostic Radiology Department.
Patient name and medical record number are associated with the images stored in the

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PACS and provide the means to retrieve this data. This is essential for continuity of the 
medical record, as these images provide clinically diagnostic information. The protocol 
number is retained in both Radiology Information System (RIS) and Clinical Research 
Information System (CRIS). Subjects may receive copies of the clinical portion of their CT 
examination from the film library in the DRD.
CT data (standard detector and PCCT detector) including personally identifiable information 
(PII) will be stored in Research PACS. Access will be limited to the Principal Investigator 
and Associate Investigators. CT data including PII may be transferred to individual 
investigator’s NIH computers for analysis. In addition to imaging data, data from the clinical 
history and laboratory tests retained by Investigators will include personally identifiable 
information. Reports, analyses and data with PII will be stored on secure computer systems 
and/or secured paper files according to NIH policy.
The PCCT detector data will be stored redundantly on hard drives within the scan room.
Photon-counting CT is being developed in collaboration with Siemens Medical Solutions, the 
scanner manufacturer. Siemens will provide proprietary software for the image 
reconstruction and data analysis techniques used in the study. In order to provide quality 
assurance, to “debug” problems with the system and to aid in Siemens’ development of new 
imaging capability for PCCT, de-identified image data may be provided to the manufacturer, 
Siemens Medical Solutions. All patients will be informed of the possibility of such data 
sharing
6.2.Image and data storage
While there are no plans to store and share de-identified imaging data by placing it into 
widely accessible scientific databases, the Informed Consent document provides for such 
sharing without further contact with the study subjects. In order to maximize the use of the 
data to advance PCCT imaging, de-identified data will be entered into an NIH-authorized 
and controlled research database with access restricted to scientists working to advance 
PCCT imaging. Any requests to use images in the database would be directed to the 
Principal Investigator of this study for approval. Data and images in this database will be 
identified only by a code number. The Principal Investigator or designated Associate 
Investigators will retain a list linking the code to specific patients.
The Informed Consent document stipulates that if a study subject does not wish for his or 
her stored data to be used for future research, he or she should inform the investigators. 
Any data that have not already been used or shared will be deleted and that data will not be 
used for future research. However, it may not be possible to withdraw or delete data once 
they have been shared with other researchers. Furthermore, the standard CT study 
obtained at the request of the health care team is a part of the patient’s medical record and 
cannot be deleted.
6.3.Tracking
The PI will be responsible for overseeing entry of data into an in-house password protected 
electronic system.

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6.4.End of study procedures
The study will remain open so long as data analysis continues. Images from consenting 
subjects will be stored until they are no longer of scientific value or if a subject withdraws 
consent for their continued use, at which time study staff will destroy them. Standard CT 
study images and reports cannot be destroyed. The standard/clinical CT study results will be 
shared with the requesting provider/research team. PCCT image data will not be shared 
with the subject.
6.5.Loss or destructions of data
As all CT imaging data is digital in nature, data loss can occur due to scanner or computer 
failure. Since the imaging data is archived on a redundant system, it is unusual for data to 
be lost irrevocably. Any loss of data from the archive will be reported to the IRB.
6.6.Publication policy
A description of this clinical trial will be available on http://www.Clinicaltrials.gov, as required 
by U.S. Law. A summary of the study results will be posted incompliance with the 
requirements. No PII will be released.
Results of the research will be shared through public presentations and publication in 
scientific journals. No PII will be included in such presentations or publications.
7. Statistical Analysis
7.1.Sample Size
Due to the early stage of development of this technology and its significant clinical potential, 
a sample size up to 750 subjects is requested for the protocol. PCCT is a new technology 
that offers advantages and new imaging capabilities compared to current CT scanner 
technology. However, the clinical utility and clinical applications related to these features 
(dose reduction, improved spatial resolution, noise reduction and x-ray energy 
discrimination) are as yet undefined. While preliminary development of scan parameters in 
normal volunteers has been conducted at NIH as well as at the Mayo Clinic where the other 
Siemens PCCT scanner is sited in the U.S., applications in patient populations remain to be 
defined and characterized. The manufacturer continues to develop and refine the system as 
well as the software used to reconstruct the imaging data, introducing new areas for study. It 
is anticipated that technical developments will continue and the need for subjects will 
continue over the next 5 years. The protocol is of an exploratory, observational nature, and 
will serve to generate hypotheses thus a statistical sample size cannot be reliably gauged at 
the onset due to insufficient pre-existing data. Consultation with one of the Clinical Center 
statisticians has been obtained concurring with our initial approach. We will plan frequent 
meetings with the statistician and adjust statistical sample size as we accrue data and can 
better predict the type of analysis that will be performed. Based on workflow using the PCCT 
prototype during prior studies of volunteers at the Clinical Center and subject accrual at 
Mayo Clinic, annual accrual is likely to be no more than 150 patients. Studies under this 
protocol will be used to develop data for the formulation of future hypotheses for 
investigation, which may be the subjects of future protocols or protocol amendments. At this 
time, subjects will not be divided into cohorts until a future time where a more informed 
delineation of cohorts may be determined.

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7.2.Analysis of Study
Each patient will undergo a CT scan using the standard detector that will be submitted to the 
Radiology & Imaging Sciences Department for interpretation.
The PCCT scan will cover either identical volumes or, in many cases, a smaller volume. 
Often the smaller volume will be selected for study rather than the full clinically indicated 
body part(s) included in the standard detector scan. This allows direct comparison between 
the scans for image assessment. Objective quantitative measurements will include but are 
not limited to image noise level and standard deviation, signal to noise ratio and variance, 
radiation dose and qualitative measures such as radiologist’s ratings of image quality, lesion 
conspicuity, image noise, beam hardening artifact, motion artifact. Comparisons of these 
quantitative and qualitative measures in different PCCT protocols among similar patients 
may also be made. As observational experience is gained with PCCT capabilities, the data 
will be used to generate hypotheses that may be investigated by future amendments, future 
cohorts, or future protocols. Because this is a translational development protocol for new 
technology, all imaging procedures are open-label and data may be analyzed as they are 
collected.
This protocol provides data for technical development purposes. The results may be used to 
iteratively improve the PCCT software and hardware for application to patient care. The 
relationship with the industry partner (Siemens Medical Solutions) is governed by an 
approved and active NIH CRADA. The CRADA document is available for IRB Chair review, 
upon request.
8. Data Safety and Monitoring Plan
8.1.Data and Safety Monitoring
Accrual and safety data will be monitored by the principal investigator, who will provide 
oversight to the conduct of this study. The PI will continuously evaluate implementation of 
the protocol for any unusual or unpredicted complications that occur and will review the data 
for accuracy and completeness.
The NIH Clinical Center’s Quality Assurance Program will conduct study monitoring at least 
annually or more frequently as required for open studies unless studies are monitored by an 
outside organization or sponsor. Monitoring visits will include a review of patient consent 
documents, primary outcome and safety laboratory results and diagnostic test results will be 
monitored for accuracy, correct dating, and agreement between case report forms and 
source documents. All regulatory reports, reviews and amendments, adverse events and 
problem reports related to study, along with investigator credentials, training records, and 
the delegation of responsibility log will also be reviewed during monitoring visits. Any major 
findings will be summarized in writing and reported to the study PI who will be responsible 
for submitting the monitoring report to the IRB.
Monitoring will not apply to imaging data measurement, analysis and interpretation. An 
independent audit of these data is not planned.
8.2.Reporting of Unanticipated Problems and Adverse Events

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Adverse events, protocol deviations, unanticipated problems (UP), Unanticipated Adverse 
Device Effects (UADEs), serious adverse events, sponsor and serious, are defined as 
described in NIH HRPP SOP 16 (“Reporting Requirements for Unanticipated Problems, 
Adverse Events and Protocol Deviations.”). All adverse events occurring during the study, 
including those observed by or reported to the research team, will be recorded. Serious 
unanticipated problems, Unanticipated Adverse Device Effects and serious protocol 
deviations, will be reported to the IRB and Clinical Director (CD) as soon as possible but not 
more than 7 days after the PI first learns of the event. Not serious unanticipated problems 
will be reported to the IRB and CD as soon as possible but not more than 14 days after the 
PI first learns of the event.
Deaths will be reported to the Clinical Director and IRB within 7 days after the PI first learns 
of the event.
Non-serious protocol deviations will only be reported to the IRB (within 14 days after the PI 
first learns of the event) if they represent a departure from NIH policies for the conduct of 
human subjects research, adversely affect the health care of the subject(s) or compromise 
the interpretation or integrity of the research. Non-serious protocol deviations that result 
from normal subject scheduling variations or technical issues associated with sampling that 
does not impact the health of the subject or the interpretation of the study data will not be 
reported.
The PI is responsible for summarizing all serious adverse events and adverse events at 
least possibly related to the research procedure and interventions at the time of Continuing 
Review. If (at any time during the course of the study) the severity or frequency of these 
events exceeds that anticipated, the events should be classified and reported expeditiously 
as Unanticipated Problems
All adverse events will be reported to Siemens Medical Solutions as part of our collaboration 
with the manufacturer to develop this technology.
Reports to the IRB, participating investigators, Clinical Center management, or FDA will also 
comply with the reporting requirements under 21 CFR 812.150 Reports, as appropriate. 
(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=812.150)
Expected Adverse Events
Expected adverse events can be divided into non-serious events not requiring treatment 
which will not be reported and serious events requiring treatment which will be reported to 
the IRB. No adverse events are expected from the performance of the PCCT scan.
Potential adverse events related to the placement of the intravenous (IV) line and the 
intravenous injection of contrast are a part of the performance of the standard CT scan and 
are not reportable.. Adverse events related to incidental imaging findings of no clinical 
significance will not be reported.
All serious events related to the PCCT scan will be recorded in CRIS and in the research 
records maintained by the study team. Serious adverse events will be reported to the IRB,

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with a copy to the clinical director, as soon as possible, and no later than seven days in the 
case of death or life-threatening serious adverse events. Any additional unexpected serious 
adverse events will similarly be reported to the IRB as soon as possible and always within 
14 days.
Unexpected Adverse Events
Unexpected adverse events are those that are not described in the published medical 
literature, in this protocol, or in the informed consent, as being associated with routine CT 
scanning. If they are coincident with research procedures and are possibly related to the 
protocol they will be reported to the IRB according to NIH guidelines.
9. Human Subjects Protection
9.1.Rationale for Subject Selection
Study of PCCT in normal volunteers has been conducted at the NIH. In a report of first 
human experience, Pourmorteza et al., (2016) compared radiation dose-matched, contrast 
enhanced CT of the abdomen performed with the standard detector and the PCCT detector 
and found no statistically significant difference in image quality although the PCCT scan 
included spectral information which may be used for material decomposition.6 Pourmorteza 
et al., (2017) compared radiation dose-matched CT of the head performed with the standard 
detector and the PCCT detector and found greater gray-white matter contrast with PCCT, 
attributed to the higher soft-tissue contrast and lower image noise with the PCCT.8 Symons 
et al., (2017) reported initial data comparing reduced dose chest CT with the two detectors 
and found that the PCCT images had lower image noise with better diagnostic quality and 
lung nodule contrast to noise ratios.10 Symons et al., (2017), also reported first in vivo 
human results comparing vascular imaging of the head and neck with PCCT to the standard 
detector and found that image quality was greater with PCCT with lower image noise, less 
image artefact and improved iodine contrast to noise ratios.7 Finally, Pourmorteza et al., 
(2018) reported first in human results with high resolution PCCT imaging compared to dose- 
matched standard resolution PCCT images that demonstrated improved image spatial 
resolution with reduced noise in the high resolution PCCT imaging.2
Advancing PCCT technology requires imaging of patients to develop optimal protocols and 
define utility and new applications in disease states. NIH patients referred to RAD&IS for 
diagnostic CT may be enrolled in this study of PCCT. Since the diagnostic imaging 
requested by the referring physician would be performed whether on a RAD&IS clinical 
scanner or as part of the photon-counting CT protocol, that component of the photon- 
counting CT protocol is not adding to the experimental radiation exposure to each patient.
Subjects from all racial/ethnic groups and genders are eligible for this study, subject to the 
inclusion and exclusion criteria.
9.2.Participation of Children
Children are excluded from participation on the study due to possible radiation exposure 
risks. The technical developments and refinements likely to result from this protocol are 

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anticipated to be generalizable to imaging techniques at younger.

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9.3.Participation of NIH Employees and Staff
All employees/staff supervised by the Principal Investigator or an Associate Investigator are 
excluded from participation. Participation of employees/staff not supervised by a study 
investigator will follow the procedures outlined in SOP 14F (12).
Protection for employees and staff participating in this study include 1) assuring the 
participation or refusal to participate will have no effect, either beneficial or adverse, on the 
subject’s employment or position at NIH, 2) giving employees and staff who are interested in 
participating the “NIH Information Sheet on Employee Research Participation” prior to 
obtaining consent, and 3) assuring that there will be no direct solicitation of employees or 
staff.
This study collects sensitive information regarding medical history, pregnancy status, and 
clinical interpretations of collected radiology images. The PI will train study staff regarding 
obtaining and handling potentially sensitive and private information about co-workers 
through staff discussions and written branch/section procedure. Information on medical 
history, pregnancy status, and clinical interpretations will be in the participant’s NIH medical 
record.
9.4.Evaluation of Benefits and Risks/Discomforts
The risk related to participation in this study is limited to the radiation exposure from the 
single PCCT scan which is not required for their diagnostic scan. The diagnostic CT scan 
requested by the medical care team and related insertion of an IV line and the 
administration of oral and/or IV contrast would be performed, whether or not the subject is 
enrolled in this study of PCCT.  The risks related to the diagnostic CT scan, including 
medical radiation from the diagnostic CT scan, IV insertion, and IV and/or oral contrast 
administration, would occur whether or not the patient in enrolled in this protocol. Contrast is 
only administered if required by the ordered diagnostic CT scan.
Radiation exposure:
CT scans use ionizing radiation (X-rays) to generate the images. The study is limited to NIH 
patients who are referred to RAD&IS for performance of a medically indicated diagnostic CT 
scan. Since the diagnostic imaging requested by the referring physician would be performed 
whether on a RAD&IS clinical scanner or with the standard detector on this device as part of 
the Photon-counting CT protocol, that medically indicated component of the procedure is not 
adding experimental radiation exposure to each patient. The CT study acquired with the 
standard detector will be stored in the NIH Clinical Center Radiology PACS and CRIS 
systems. Those exams will be submitted for interpretation by a board certified and NIH CC 
credentialed Radiology & Imaging Science Department physician and reports of findings will 
be managed according to standard practices for diagnostic imaging studies within the 
Department.
The expected research radiation total effective dose from the scan with the PCCT detector 
will be less than or equal to 2.2 rem for the average study subject. The dosimetry 
calculations were performed assuming the entire scan would be repeated at the abdomen 
dose or the highest dose that might be administered to a study subject. For the PCCT scan, 
we expect to scan a more limited volume than the complete diagnostic CT scan. Further the

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chest exposure parameters will be less than what was used to estimate the dose. Even at 
this level, the research radiation dose from the PCCT scan will be below the maximum 
allowable research radiation dose guidelines established by the NIH Radiation Safety 
Committee for research participants. One possible effect that could occur as a result of 
using radiation is a slight increase in the risk of cancer. However, there has been no 
convincing epidemiological evidence that there is a risk of cancer development at these low 
levels. Unlike normal volunteers, there are no limits placed on medically indicated radiation 
exposures. Because patients will be selected from those already on clinical protocols at the 
Clinical Center and often receive many CT exams over the course of their treatment at NIH, 
the research radiation from the PCCT is likely to be only a small contribution to each 
patient’s overall radiation dose.
In order to mitigate any risk, the volume scanned for the experimental PCCT exposure will 
be reduced compared to the standard detector CT, if possible, in order to reduce the 
exposure and radiation dose. Only one PCCT scan will be performed. Patients may not 
have more than one PCCT scan over a one-year period.
Since the study involves research radiation exposure, women of child-bearing age who may 
be pregnant will undergo blood or urine pregnancy testing. This may not always be the case 
for medically indicated CT scans, particularly if the body part is far from the pelvis.
.
Possible Benefits:
The subject will undergo the clinically indicated CT scan as part of participation in this study. 
Those exams will be submitted for interpretation by a board certified and NIH CC 
credentialed RAD&IS physician and reports of findings will be managed according to 
standard practices for diagnostic imaging studies within RAD&IS.
The PCCT detector scan is unlikely to add additional diagnostic information with direct 
benefit to study subjects. The major expected benefit is to society, future patients, industry 
partners and the academic/scientific community as the result of the development and 
characterization of this new imaging technology. In particular, compared to current 
scanners, this new technology offers four major benefits to patients and medical imaging:

lower radiation dose to patients;

greater spatial resolution (the ability to distinguish between adjacent structures in the 
body);

reduced imaging noise (image degradation due to variations in x-ray detection); and,

advanced imaging applications based on the measured x-ray energies.
9.5.Risks/Benefits Analysis
The level of risk to the research participants is considered to be greater than minimal risk 
(45 CFR 46 102) without prospect of direct benefit. The primary expected benefit is to the 
public as a result of improved imaging techniques. There is no expectation of early detection 
of new or unknown disease process as an incidental finding with the use of PCCT.

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9.6.Non-significant Risk Determination
According to 21 CFR 812.3 (m) and FDA “Information Sheet Guidance for IRBs, Clinical 
Investigators, and Sponsors: Significant Risk and Nonsignificant Risk and Nonsignificant 
Risk Medical Device Studies January 2006 (accessible at 
http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM126418.pdf), the use 
of the Siemens CounT scanner is considered to be a Non-significant Risk medical device 
study which does not require an IDE application approved by the FDA. Specifically, 21 CFR 
812.3(m) enumerates four criteria for a significant risk device; none of these apply to this 
device.
1.
This device is not intended as an implant
2.
This device is not purported or represented to be for use supporting or sustaining 
human life.
3.
While it is for “a use of substantial importance in diagnosing … disease,” it does not 
“present a potential for serious risk to the health, safety, or welfare of a subject.” 
Specifically, as part of the imaging to be conducted under this proposal, the patient will 
receive a CT scan with the standard x-ray tube-detector pair similar to that which would 
be acquired on one of the Siemens SOMATOM Force CT scanners in clinical use in 
RAD&IS, thereby providing standard diagnostic imaging information. The use of the 
photon counting CT component has the potential to add additional and unique 
diagnostic information. The primary consideration would be the radiation dose for the 
patient. However, as we previously reported, the radiation dose from PCCT is 
comparable to or may be less than that for a standard scan. The radiation doses will be 
reviewed and approved by the NIH RSC prior to study commencement.
4.
The device does not otherwise present a potential for serious risk to the health, safety, 
or welfare of a subject.
The protocol will comply with the abbreviated IDE requirements under 21 CFR 812.2(b), 
available at: 
https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?fr=812.2
In accordance with Sec. 812.5 Labeling of investigational devices, the device is clearly 
labeled with the statement: "CAUTION--Investigational device. Limited by Federal (or United 
States) law to investigational use." and with the name and place of business of the 
manufacturer (Appendix C).
9.7.Informed Consent Process and Procedures
For outpatients:

When feasible, patients will be approached in the clinic at an earlier visit. If the 
patient felt they had all questions answered they could provide informed consent at 
that time. This may be up to one month before the scheduled scan. In that case, 
when they come for the scan they will be verbally asked to confirm they are still 
willing to participate and answer any additional questions. The research team will 
confirm that a properly executed informed consent document is on file prior to 
performing the research scan.

If we are not able to obtain consent in the clinic, we will contact patients by phone

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and or email close to the scan date (within one month) and send them information 
about the scan along with the informed consent for their review in advance of their 
scan appointment. Along with the email we will provide a phone number for contact 
and schedule a phone call with a research team member to answer questions 
beforehand or meet with a research team member the day of the scan to answer any 
questions. If all questions are answered and they agree to participate, they will be 
permitted to sign the consent ahead of time and mail the consent to us or provide the 
informed consent when they arrive for the scan. If they consent ahead of the scan 
date, they would be interviewed before the scan to be sure they still want to 
participate. If the consent is mailed in ahead of time, the research team will confirm 
that a properly executed informed consent document is on file prior to performing the 
research scan.
For inpatients:

They will be identified from the CT scanner schedule and the PI will be made aware 
of the study and asked if it is appropriate to enroll the participant. If the PI is 
agreeable, the patient will be approached the day before the scan and consent 
obtained in their room. They will be given time to consider the protocol and have 
questions answered. If they want to think about the protocol that day/evening and 
wait until the following day to ask additional questions and consent at that time, they 
will be provided the opportunity do so in Radiology when they come for their scan. 
The patients we would invite to participate will not be those who need urgent CT 
scans or are admitted for unexpected events/complications. Typically, these will only 
be patients who are here for routine evaluations such as cancer staging or natural 
history studies which include CT scans.
In Radiology, there is a private room just outside the CT scan waiting area that is used for 
consenting patients.
Each subject will receive an oral and written explanation of the purposes, procedures, and 
risks of this study in language appropriate for the individual's level of understanding. A copy 
of the signed consent form will be placed in the medical record.
We do not plan or anticipate the enrollment of non-English speaking subjects; however, they 
are not excluded from participation. Should we enroll a non-English speaking subject, we 
request IRB approval to use the short form consent processes as outlined in SOP 12 up to 
three times for each language before a full translation is required. The IRB will be notified at 
each continuing review the number of short form consents uses by language.
The following investigators are authorized to obtain informed consent from the study 
subjects and are marked with an asterisk (*) on page 1 of the protocol:

Elizabeth Jones, M.D.

Brad Wood, M.D.

Marcus Chen, M.D.

Mark Ahlman, M.D.

Tracy L Cropper, R.N

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
Charisse Garcia, RN, BSN, CCRP

Caroline (Carole) Webb, RN, MSN, CCRP, CCRC
All employees/staff supervised by the Principal Investigator or an Associate Investigator are 
excluded from participation. If an NIH employee or staff member plans to enroll in the study 
and the individual obtaining consent is a nonsupervisory co-worker, the consent process will 
be independently monitored in accordance with the procedures outlined in SOP 14F.
10.Conflict of Interest
The PI assured that each AI listed on the protocol title page received a copy of the NIH’s
Guide to preventing conflict of interest. The National Institutes of Health reviews NIH staff
researchers at least yearly for conflicts of interest. The following link contains details on this
process https://ethics.od.nih.gov/forms/Protocol-Review-Guide.pdf. Neither the PI nor any AI
has any potential conflict of interest to report.
11.Compensation
Patients will not receive monetary compensation. Upon enrollment, participants will already
have clinical indications for conventional CT exam(s) as ordered by their NIH physicians.
With informed consent, photon-counting CT scans of the same body regions of interest will 
immediately follow the regular CT scan on the same scanner.

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12.References
1.
Kappler S, Hannemann T, Kraft E, Kreisler B, Niederloehner D. First results from a
hybrid prototype CT scanner for exploring benefits of quantum-counting in clinical CT.
Proc SPIE 2012; 8313(1): 83130X.
2.
Pourmorteza A, Symons R, Henning A, et al. Dose Efficiency of Quarter-Millimeter
Photon-Counting Computed Tomography: First-in-Human Results. Invest Radiol. 2018;
53(6):365-372.
3.
Yu Z, Leng S, Jorgensen SM, et al. Evaluation of conventional imaging performance in a
research whole-body CT system with a photon-counting detector array. Phys Med Biol
2016; 61(4): 1572-1595.
4.
Taguchi K, Iwanczyk JS. Vision 20/20: Single photon counting x-ray detectors in medical
imaging. Med Phys 2013; 40(10): 100901.
5.
Gutjahr R, Halaweish AF, Yu Z, et al. Human imaging with photon-counting-based CT at
clinical dose levels: Contrast-to-noise ratio and cadaver studies. Invest Radiol 2016;
51(7): 421-429.
6.
Pourmorteza A, Symons R, Sandfort V, et al. Abdominal imaging with contrast-enhanced
photon-counting CT: first human experience. Radiology 2016; 279(1): 239-245.
7.
Symons R, Reich DS, Bagheri M, et al. Photon-counting computed tomography for
vascular imaging of the head and neck: first in vivo human results. Investigative
Radiology 2017; 2018;53: 135–142).
8.
Pourmorteza A, Symons R, Reich DS, et al. Photon-Counting CT of the Brain: In Vivo
Human Results and Image-Quality Assessment. AJNR Am J Neuroradiol. 2017;
38(12):2257-2263.
9.
Symons R, Cork TE, Sahbaee P, et al. Low-dose lung cancer screening with photon- 
counting CT: feasibility study. Phys Med Biol. 2017; 62(1):202-213.
10.
Symons R, Pourmorteza A, Sandfort V, et al. Feasibility of Dose-reduced Chest CT with
Photon-counting Detectors: Initial Results in Humans. Radiology. 2017; 285(3):980-989.
11.
Ferrero A, Gutjahr R, Halaweish AR, et al., Characterization of Urinary Stone
Composition by Use of Whole-body, Photon-counting Detector CT. Acad Radiol 2018
Feb 14. pii: S1076-6332(18)30019-9. [Epub ahead of print]
12.
Symons R, Cork TE, Lakshmanan, et al. Dual-contrast agent photon-counting computed
tomography of the heart: initial experience. Int J Cardiovasc Imaging 2017; 33: 1253-
1261.

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13.
Symons R, Krauss, Sahbaee, et al. Photon-counting CT for simultaneous imaging of
multiple contrast agents in the abdomen: an in vivo study. Med Phys 2017; 44(10): 5120-
5127.
14.
Cormode DP, Si-Mohamad S, Bar-Ness D, et al. Multicolor spectral photon-counting
computed tomography: in vivo dual contrast imaging with a high count rate scanner.
Nature Scientific Reports 2017; 7: 4784-4795. https://doi.org/10.1038/s41598-017-
04659-9.
15.
Si-Mohamed S, Cormode DP, Bar-Ness D, et al. Evaluation of spectral photon counting
computed tomography K-edge imaging for determination of gold nanoparticle
biodistribution in vivo. Nanoscale 2017; 9: 18246-18257.
16.
Boussel L, Coulon P, Thran A, et al. Photon counting spectral CT component analysis of
coronary artery atherosclerotic plaque samples. BJR 2013; 87.
https://doi.org/10.1259/bjr20130798.
17.
Leng S, Gutjahr R, Ferrero A, et al. Ultra-high spatial resolution, multi-energy CT using
photon counting detector technology. Proc SPIE Int Soc Opt Eng 2017; 10132:
https://doi.org/10.1117/12.2255589.
18.
Bashir U, Siddique MM, Mclean E, Goh V, Cook GJ. Imaging heterogeneity in lung
cancer: techniques, applications, and challenges. AJR 2016: 207: 534-543.
19.
Zhou M, Leung A, Echegaray S, et al. Non-small cell lung cancer radiogenomics map
identifies relationships between molecular and imaging phenotypes with prognostic
implications. Radiology 2018; 0(0): 00-00.