Longitudinal Assessment of Multiple Organs in Patients With Type 2 Diabetes
Conditions: Type 2 Diabetes
Sponsor: Perspectum

 
 
 
 
 
 
 
 
 
 
 
 
 
Title 
Longitudinal Assessment of Multiple Organs in Patients with Type 2 Diabetes 
(MODIFY study) 
Ethics Reference 
19/LO/1338 
Date and version no. 28 Jan 2021 9.0 
 
Chief Investigator 
Professor Dan Cuthbertson 
Investigators 
Dan Cuthbertson, Graham Kemp (University of Liverpool) 
Sudhir Singh, Gaya Thanabalasingham (Oxford University Hospitals NHS Foundation 
Trust)  
Sarah Ali (Royal Free London Hospitals NHS Foundation Trust) 
Helena Thomaides-Brears (Perspectum Ltd) 
Malcolm Burgess (Aintree University Hospital (Liverpool University Hospitals NHS 
Foundation Trust)  
 
Sponsor 
Perspectum Ltd 
Funder(s) 
Innovate UK and Perspectum Ltd  
 
 

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Table of Contents 
Title ........................................................................................................................................................ 1 
Ethics Reference ..................................................................................................................................... 1 
Date and version no. ............................................................................................................................... 1 
Chief Investigator ................................................................................................................................... 1 
Investigators .......................................................................................................................................... 1 
Sponsor .................................................................................................................................................. 1 
Funder(s) ................................................................................................................................................ 1 
ABBREVIATIONS ..................................................................................................................................... 8 
1. 
SYNOPSIS ....................................................................................................................................... 10 
2. 
INTRODUCTION ............................................................................................................................. 12 
2.1. 
Background and Rationale .................................................................................................................................................12 
3. 
STUDY OBJECTIVES ......................................................................................................................... 15 
4. 
STUDY DESIGN ............................................................................................................................... 16 
a. Study Description .............................................................................................................................................................................16 
b. Study Setting ....................................................................................................................................................................................18 
5. 
Study Participants .......................................................................................................................... 19 
5.1. 
Inclusion criteria .................................................................................................................................................................19 
5.2. 
Exclusion Criteria ................................................................................................................................................................19 
6. 
Sample size .................................................................................................................................... 19 
7. 
STUDY PROCEDURES ...................................................................................................................... 20 
7.1. 
Recruitment........................................................................................................................................................................20 
7.2. 
Informed Consent ...............................................................................................................................................................21 
7.3. 
Study Visits .........................................................................................................................................................................21 
7.3.1. 
Standard study visit – assessments...........................................................................................................................23 
7.3.2. 
Outcome data collection ...........................................................................................................................................24 
7.3.3. 
Withdrawing from the study.....................................................................................................................................25 
8. 
DEFINITION OF END OF STUDY ....................................................................................................... 25 

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9. 
INTERVENTIONS ............................................................................................................................. 25 
10. 
DATA .......................................................................................................................................... 25 
10.1. 
Data Collection and Management ................................................................................................................................25 
10.2. 
Analysis plan ..................................................................................................................................................................26 
11. 
SAFETY REPORTING .................................................................................................................... 27 
11.1. 
Definition of Serious Adverse Events .............................................................................................................................27 
11.2. 
Reporting Procedures for Serious Adverse Events .........................................................................................................28 
12. 
ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................ 28 
12.1. 
Declaration of Helsinki...................................................................................................................................................28 
12.2. 
Guidelines for Good Clinical Practice .............................................................................................................................28 
12.3. 
Approvals .......................................................................................................................................................................28 
12.4. 
Reporting .......................................................................................................................................................................28 
12.5. 
Participant Confidentiality .............................................................................................................................................28 
12.6. 
Potential Risks of Procedures ........................................................................................................................................29 
12.7. 
Expenses and Benefits ...................................................................................................................................................29 
13. 
OTHER ETHICAL CONSIDERATIONS .............................................................................................. 29 
13.1. 
Incidental findings .........................................................................................................................................................30 
13.2. 
Participant comfort and dignity ....................................................................................................................................30 
13.3. 
Pregnancy in participants ..............................................................................................................................................30 
14. 
DATA HANDLING AND RECORD KEEPING ..................................................................................... 31 
15. 
QUALITY ASSURANCE PROCEDURES ............................................................................................ 32 
16. 
FINANCING AND INSURANCE ...................................................................................................... 32 
Negligent Harm ...................................................................................................................................................................................32 
Non-Negligent Harm ...........................................................................................................................................................................32 
17. 
REFERENCES ............................................................................................................................... 32 
APPENDIX 1: EXAMPLE GUIDELINES FOR MRI IMAGING IN CONSIDERATION OF COVID-19 ..................... 35 
Personal Protective Equipment (PPE) ..................................................................................................................................................35 
Staff Management ..............................................................................................................................................................................36 
Participant Management ....................................................................................................................................................................36 

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Scanning procedure .............................................................................................................................................................................37 
Additional Notes ..................................................................................................................................................................................38 
 
 
 

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Approvals 
 
Job Title 
Name 
Signature 
Chief Executive Officer  
Rajarshi Banerjee 
 
Chief Innovation Officer 
Matt Kelly 
 
Principal Clinical Scientist 
Helena Thomaides-Brears 
 
Head of Clinical Affairs 
Darina Speke 
 
Data Protection Officer 
Mike Sinnott 
 
Chief Investigator 
Dan Cuthbertson 
 
Validity: Please ensure that the required digital signatures are valid prior to publication of a new issue. 
 
 
 
 

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Issue control 
Issue 
Paragraph 
Details 
Reason 
Date/Initial 
0.1 
All 
New document 
First draft for review 
17.10.2018 HTB 
0.2 
 
All 
Edits based on collaborator 
feedback 
Second draft for review 
10.11.2018 HTB 
0.3 
All 
Citation corrections 
Third draft for review 
24.02.2019 HTB 
0.4 
All 
Adding comments 
For review 
18/03/2019 SR 
0.5 
All 
Adding comments 
Further review 
01/04/2019 SR 
0.6 
All 
Incorporating collaborator 
feedback and editing 
Final draft review 
14/05/2019 LH 
0.7 
All 
 
Review 
14May19 MN 
0.8 
All 
Incorporating all feedback 
and editing 
Review 
17JUN2019 HTB 
0.9 
All 
 
Review 
10JUL2019 MN 
1.0 
All 
Incorporating insurance 
policy number 
Review 
10JUL2019 HTB 
1.1 
All 
Specification of 
questionnaires and 
recruitment 
Response to REC comments  
13SEP2019HTB 
1.2 
All 
 
Review 
23SEP2019AB 
2.0 
All 
 
Review 
24SEP2019MN 
3.0 
Pages 1, 18 
Changing name of NHS Trust 
in Liverpool 
Trust merger on 1st October 
2019 
19NOV2019JW 
4.0 
Page 1 & 
footer all pages 
Changing date and version  
New version and date to reflect 
change outlined below 
04Feb2020JW 
4.0 
Page 29 
Changing date and version 
Changing the number of years in 
a sentence (from 10 to 5) in 
section 11 which should (and 
now does) correspond with 
another in section 11 regarding 
enrolment log 
04Feb2020JW 
5.0 
All relevant 
pages 
Company name change, 
protocol date and version 
number 
Changing name of company to 
Perspectum Ltd./Perspectum 
and not Perspectum Diagnostics 
13Mar2020 JW 
5.0 
Pages 2, 4 
Updated page numbers in 
TOC 
Updated page numbers in TOC 
13Mar2020 JW 
5.0 
Pages 15, 16 
Amending Visit 2 to take 
place within 35 days of visit 
1, and not 21. Text page 15 
and Fig.4 page 16 
To accommodate local 
availability to undertake both 
MRI and ECHO 
13Mar2020 JW 
5.0 
Page 19 
Addition of Diabetes UK 
Online Patient Forum 
Addition of this organisation as 
an advertising platform for 
recruitment to the study 
13Mar2020 JW 
5.1 
Page 19 
Addition of precautionary 
measures for COVID-19 
relating to study visits 
To provide further guidance on 
how to reduce risk to staff and 
participants due to COVID-19 
02Jun2020 GG 

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Page 19, 22 
and 27 
Referral to additional 
imaging guidelines 
To provide guidance on research 
imaging whilst considering 
COVID-19 
Page 32-35 
Addition of Appendix 1 
To provide guidance on research 
imaging whilst considering 
COVID-19 
5.2 
Page 14, 15, 
18, 19 and 28 
Addition of information 
regarding e-consent 
To provide an alternative 
method for consent and how 
the data is managed 
09Jun2020 GG 
5.3 
Page 7 and 29 
Removal or PDPA 2012 and 
replace Edison with 
Perspectum Portal 
To comply with GDPR relevant 
to this study and renaming of 
Perspectum Portal 
01Jul2020 MS 
5.4 
All 
Incorporating all feedback 
and adding signatories 
Review 
02Jul2020 GG 
5.5 
Page 8, 9, 13-
16, 22 and 24 
Update of study timepoint 
and analysis 
To ensure timepoint is more 
reflective of patient follow up 
07Jul2020 AR/GG 
6.0 
All 
 Final review and update of 
version 
 
Finalised document 
14Jul2020 GG 
6.1 
Page 16 
Adding Perspectum as 
clinical site open for 
recruitment 
To make up deficit of slow 
recruitment at London clinical 
site 
23Apr2021 JW/RS 
6.2 
Page 18, 24 
and 32 
 
Pg 25 
 
Pages 25 and 
27 
Healthy Volunteers 
additional information 
 
 
Statistical analysis plan 
 
 
Revised Incidental Findings 
process and SAE reporting 
 
To include healthy individuals 
from other studies to ensure age 
and gender matching 
 
Clarification of wording and 
exploratory metrics  
 
SAE requires updating as this is 
an observational study. IF 
process has been revised within 
Perspectum. 
18May2021 JW/RS 
7.0 
All 
Final review and update of 
version 
Finalised document 
21May2021 JW/RS 
7.1 
Page 19 
Addition of wording to use 
the ATLAS short film 
To utilise the participant-
interview ATLAS short film to 
raise awareness of MODIFY and 
assist recruitment 
18Jun2021 JW 
8.0 
All 
Final review and update of 
version 
 
Finalised document 
21Jun2021 JW 
8.1 
Pages 18 text, 
Table 1 
pp22/23 and 
Addition to p18 text and  
table 1, pp22/23 and text on 
pp24/25 to, include potential 
supplementary telephone 
Review document 
27Jan2022 JW 

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text on pages 
24/25 
call to participant to clarify 
any data that may missing or 
unclear from medical record, 
or where medical record 
cannot be accessed by a 
approved non-NHS clinical 
study site such as 
Perspectum Ltd. 
Page 29 
Addition of text to include 
letter fo feedback to 
participant 
9.0 
All 
Approved update of version 
 
Finalised document 
28Jan2022 JW/HTB 
ABBREVIATIONS 
ALT 
Alanine Transaminase 
AST 
Aspartate Transaminase 
APR 
Annual Progress Report 
BMI 
Body Mass Index 
CI 
Chief Investigator 
CKD 
Chronic Kidney Disease 
CTRG 
Clinical Trials & Research Governance, University of Oxford 
CVD 
Cardiovascular Disease 
DPA 
Data Protection Act 2018 
ECG 
Electrocardiogram 
ECHO 
Transthoracic echocardiogram 
eGFR 
Estimated glomerular filtration rate 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 
GGT 
Gamma-glutamyl transferase 
HbA1c 
Glycosylated haemoglobin A1c 
HRA 
Health Research Authority 
ICF 
Informed Consent Form 
ISO 
International Organization for Standardization 
LFT 
Liver Function Test 
MRI 
Magnetic Resonance Imaging 
NAFLD 
Non-alcoholic Fatty Liver Disease 

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NASH 
Non-alcoholic Steatohepatitis  
NRES 
National Research Ethics Service  
NT-proBNP 
N-terminal pro b-type natriuretic peptide 
PI 
Principal Investigator 
P3NP 
N-terminal levels of type III procollagen (P3NP)  
PIL 
Participant/Patient Information Leaflet 
PREMs 
Patient Reported Experience Measures 
PROMs 
Patient Reported Outcome Measures 
R&D 
Research and Development (NHS) 
REC 
Research Ethics Committee 
SAE 
Serious Adverse Event 
SIN 
Study Identification Number 
SOP 
Standard Operating Procedure 
T2D 
Type 2 Diabetes 
 
 

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1. SYNOPSIS 
 
Study Title 
Longitudinal Assessment of Multiple Organs in Patients with Type 2 Diabetes 
(MODIFY) 
Internal Ref. No. 
EC-148 / CA064 
Study Design 
Multi-site, prospective, longitudinal, observational cohort study 
Study Participants 
Adult patients with type 2 diabetes recruited from community, primary care or 
secondary care settings  
Number of Participants 
150 
Planned Study Period 
84 months 
Primary Objective 
1. To determine the degree of liver fibroinflammation in a large cohort of 
patients with type 2 diabetes, using multi-parametric abdominal MRI. 
Secondary Objectives 
1. To determine the degree of other liver abnormalities (such as fat 
infiltration) in a large cohort of patients with type 2 diabetes, using 
multi-parametric abdominal MRI. 
2. To determine the degree of abnormality in other organs associated with 
type 2 diabetes and its comorbidities (pancreas, spleen, kidneys, aorta) 
using multi-parametric abdominal MRI. 
3. To assess whether multi-parametric abdominal MRI can quantify 
changes in multiple organs (liver, kidneys, pancreas, spleen and aorta) 
that occur over 6-9 months. 
4. To assess changes in multiple organs (liver, kidneys, pancreas, spleen 
and aorta) that occur over 6-9 months, with conventional biochemical 
biomarkers utilised in the clinical pathway for T2D, chronic kidney 
disease (CKD) and non-alcoholic fatty liver disease (NALFD). 
5. To evaluate the impact of multi-parametric abdominal MRI on type 2 
diabetes management. 
6. To determine the prognostic information provided by abdominal 
imaging for longer-term evaluation of clinical outcomes (after 1, 3 5 
years). 
 Primary Endpoint 
 
7. MRI metrics for liver fibroinflammation in patients with type 2 diabetes 
compared with the same metrics in healthy, non-diabetic individuals at 
baseline. 

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Secondary Endpoints 
1. Correlations between liver MRI metrics in patients with type 2 diabetes 
with the same metrics in healthy, non-diabetic individuals, at baseline 
for: 
• 
fat infiltration 
• 
organ volume 
• 
proportion of patients with evidence of non-alcoholic fatty liver 
disease (based on thresholds for liver fat or fibroinflammation) 
 
2. Correlations between MRI metrics in patients with type 2 diabetes with 
those in healthy, non-diabetic individuals, at baseline for:  
• 
organ volume, fat infiltration and fibroinflammation in abdominal 
organs affected by type 2 diabetes (spleen, pancreas, kidney)  
• 
aortic health (aortic distensibility, diameter)  
 
3. At 6-9 months: to assess the difference, from baseline, across the 
cohort in the following MRI metrics: 
• 
organ volume, fat infiltration and fibroinflammation in abdominal 
organs affected by type 2 diabetes (liver, spleen, pancreas, kidney)  
• 
aortic health (aortic distensibility, diameter) 
• 
proportion of patients with evidence of non-alcoholic fatty liver 
disease (based on thresholds for liver fat or fibroinflammation) 
 
4. At 6-9 months: to assess the difference, from baseline, across the 
cohort in the following metrics:  
• 
glycaemic control (HbA1c)  
• 
lipid profiles 
• 
 renal health (serum creatinine, eGFR, urine albumin-creatinine 
ratio)  
• 
liver health (FBC, LFT) 
 
5. To review and analyse the patient and clinician reported outcome 
measures collected from non-validated questionnaires. 
 
6. At 1, 3 and 5 years: to assess the odds ratio for developing 
cardiovascular, liver, pancreatic and kidney related events and/or 
death, including hospital admissions. 
 
 

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2. INTRODUCTION 
2.1. 
Background and Rationale  
There has been a surge in incidence of the metabolic syndrome; a cluster of conditions which increase the risk of: 
• type 2 diabetes (T2D) (90% of diabetes cases), 
• non-alcoholic fatty liver disease (NAFLD), 
• non-alcoholic steatohepatitis (NASH), 
• cardiovascular disease (including ischaemic heart disease and heart failure), 
• ischaemic or haemorrhagic stroke 
 
This project concentrates on T2D, a disease whose multiple pathophysiological defects include: 
• increased renal glucose reabsorption, 
• decreased peripheral glucose utilisation, 
• increased hepatic glucose production due to insulin resistance, 
• increased glucagon secretion, 
• reduced insulin secretion (pancreas), 
• and incretin secretion (gastrointestinal tract)   
 
Estimated UK prevalence of T2D is 5.26%.  This represents 3.3 million people (1) (comparatively in the US, 9.1% or 26.44 
million people (2)), which equates to £8.8bn in associated healthcare costs in UK (3).  
Type 2 diabetes is associated with a heterogeneity in its aetiology – this is observed in its clinical presentation and 
subsequent rate of progression. Further factors associated with T2D include micro-and macrovascular complications 
and an observed decline in multiple organs (end-organ damage). End-organ damage contributes to the clinical picture 
of individuals with T2D and is demonstrated when observing the high prevalence of co-morbidities in this patient cohort.  
For example, the presence of NAFLD is seen in  60% of T2D patients (4, 5), along with a 34.2-50.7% presence of chronic 
kidney disease (CKD)(6) and a 32.2% presence of cardiovascular disease (CVD)(7).  
Currently, T2D and its complications are monitored using circulating plasma and serum biomarkers (8). However, these 
lack sufficient sensitivity or specificity. An example of this is highlighted in one researcher’s preliminary data that 
suggests that 85% of obese people with T2D had NAFLD, detected by MRI.  However, a vast proportion of this patient 
cohort have recorded normal biochemical biomarkers, such as Alanine Transaminase (ALT).  
Metformin is typically the initially treatment for T2D (8). However, due to its progressive nature, metformin 
monotherapy proves to be inadequate in maintaining long-term glycaemic control (9). Metformin has been used safely 
and effectively for decades, but newer drugs are becoming available. Numerous recent studies have shown that newer 
drug classes, including the SGLT-2 inhibitors and GLP1 receptor agonists (GLP-1RA), have substantial beneficial effects 

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beyond modulation of glycaemic levels, and can confer protection against CVD and CKD (10–13). It is now recommended 
that use of these drugs is advocated for high risk populations with evidence of CKD or CVD (14–16). 
This study aims to develop an MRI-based method that is able to identify the individuals at high risk of disease 
complications, looking particularly at renal, hepatic and cardiovascular pathology, and further compare this to the 
conventional biochemical approach. This has future potential in assisting in the stratification of patients to the most 
appropriate tailored treatment for their disease.  We will further evaluate the additional synergistic value of 
incorporating MRI-metrics into patient pathways. 
There is a healthcare need to provide further decision-making support for clinicians in the care of patients at risk or 
diagnosed with T2D.  This would combine multi-modality approaches, an incorporation of biochemical evaluation and 
imaging techniques. There is also a pressing need for treatment stratification to identify the T2D patients who would 
benefit from being triaged to receive the newer, more expensive drugs.  This would also empower patients and aid in 
their engagement of the lifestyle changes often required for treatment.  This should have the added benefit of reducing 
associated NHS costs by minimising the pool of patients with severe disease, who would be highlighted through early 
detection and early medical management.  
To address this growing need, we propose adding a complementary imaging aspect to the currently used biomarkers. 
MRI, specifically, provides excellent soft-tissue contrast. Perspectum’s LiverMultiScan is a quantitative 
multiparametric MRI method, FDA-cleared and CE-marked, that is used to detect and stage early liver disease.  It is 
already widely used in pharmaceutical trials for NAFLD therapeutics.  The MRI metrics from LiverMultiScan can 
quantify changes to liver tissue characteristics, like fibro-inflammation and fat, as a result of intervention (for example, 
bariatric surgery - see Fig. 1). The accuracy and reproducibility of LiverMultiScan has been demonstrated in studies 
scanning patients within different MRI scanners.  It continues to be further supported by data from clinical trials in liver 
disease cohorts, from comparative studies that include healthy controls, as well as whole-population studies in the UK 
and US (17–24). 
 
 
With this study we aim to develop a new MRI image analysis technique, “ATLAS”, that builds on LiverMultiScan  
technology.  We also plan to gather clinical evidence that will demonstrate the potential added value to the NHS, as well 
as support future regulatory clearance. The phenotypical information that ATLAS delivers, combined with information 
from circulating biomarkers, will form the basis of a future clinical decision support tool for T2D (Fig. 2).   
Pre-operative: March 2011
PDFF: 20.4%
Normal range: <5.6%
cT1: 996.1ms
Reference range: 633-794ms
Post-operative: March 2012
PDFF: 1.7%
Normal range: <5.6%
cT1: 783.5ms
Reference range: 633-794ms
cT1 (ms)
cT1 (ms)
Figure 1 - Example of MRI metrics and images from LiverMultiScan before and after bariatric surgery 

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Perspectum has pilot data showing that LiverMultiScan can:  
• estimate portal hypertension (spleen), 
• detect pancreatitis, 
• characterise the tissue of the kidneys   
 
This study looks at the potential to extend LiverMultiScan to each of the other relevant organs – pancreas, kidneys and 
spleen.  The technical development of “ATLAS” will be complemented by the accumulation and analysis of clinical data, 
circulating biomarkers and imaging.  This information will be obtained from three diverse UK clinical centres (Liverpool, 
Oxford and London). 
The innovation comes from combining a number of quantitative MRI metrics to achieve this (Fig. 3):  
• volumes - for liver, spleen, kidneys, pancreas (25–27); 
• fibroinflammation: cT1 and/or T1 – for liver, spleen, kidneys, pancreas (25); 
• fat infiltration: PDFF – for liver, kidneys, pancreas (28); 
• aortic distensibility and diameter (29). 
 
We will also incorporate kidney diffusion and renal flow (25). There will be strong patient and clinician involvement in 
the collection of patient-reported experience and outcome measures throughout the study (PREMs and PROMs), both 
qualitative and quantitative, to reflect the patients’ experience of the clinical care pathway. 
The resulting MRI diagnostic solution will enable rapid and comprehensive stratification of T2D and affiliated diseases 
(NAFLD, CKD, CVD), allowing clinicians to facilitate personalised medicine. It is anticipated that adopting a clinical 
approach which utilises ATLAS will result in substantial cost savings for the NHS and will help improve patient experience 
by providing access to advanced treatments to those patients most at risk. 
Adult with type 2 diabetes (T2D)
HbA1c measurement & threshold
Metformin
Lifestyle management
Current UK 
clinical pathway
Treatment 
intensification
GLP1-RA or SGLT2i
Other treatments
T2D & CVD/CKD
Higher risk
T2D no comorbidities
Lesser risk
T2D & NAFLD 
Higher risk
First line 
treatment
Figure 2 – An example schematic of the impact of ATLAS in the clinical pathway of T2D, based on MRI metrics of liver and cardiovascular system health 

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Figure 3 – Example MRI images and metrics that are generated with ATLAS. Left panel shows liver (red), kidneys (yellow), pancreas (blue) and spleen 
(green) volume images within the thorax. Right panel shows single MRI slices with associated organ volume, fat infiltration or fibroinflammation 
metric values. 
 
3. STUDY OBJECTIVES  
The main objective of this study is to assess the health of multiple organs over a period of 6 to 9 months, using 
multiparametric abdominal MRI, in patients with type 2 diabetes who have been prescribed glucose lowering therapy 
(as per their standard of care). 
Primary Objective 
Primary Outcome Measure 
1. To 
determine 
the 
degree 
of 
liver 
fibroinflammation in a large cohort of patients 
with type 2 diabetes, using multi-parametric 
abdominal MRI. 
MRI metrics for liver fibroinflammation in patients with type 
2 diabetes vs. the same metrics in healthy, non-diabetic 
individuals at baseline. 
Secondary Objectives 
Secondary Outcome Measures 
1. To determine the degree of other liver 
abnormalities (such as fat infiltration) in a large 
cohort of patients with type 2 diabetes, using 
multi-parametric abdominal MRI. 
1. Liver MRI metrics in patients with type 2 diabetes vs. the 
same metrics in healthy, non-diabetic individuals, at baseline 
for: 
• fat infiltration 
• organ volume 
• proportion of patients with evidence of non-alcoholic 
fatty liver disease (based on thresholds for liver fat or 
fibroinflammation). 
2. To determine the degree of abnormality in other 
organs associated with type 2 diabetes and its 
2. MRI metrics in patients in patients with type 2 diabetes vs.  
those in healthy, non-diabetic individuals, at baseline for: 
 
AA
PDA
VC
Pancreas T1
Liver cT1
Liver PDFF
Pancreas
T1: 577 ms
Volume: 80 ml
Kidneys
Volume (R): 198 ml
Volume (L): 181 ml
Liver
Iron: 0.96 mg/g
cT1: 716 ms
PDFF: 4.5%
Volume: 1711 ml
Spleen
Volume: 206 ml

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comorbidities (pancreas, spleen, kidneys, aorta) 
using multi-parametric abdominal MRI 
• organ volume, fat infiltration and fibroinflammation in 
abdominal organs affected by type 2 diabetes (spleen, 
pancreas, kidney)  
• aortic health (aortic distensibility, diameter). 
3. To assess whether multi-parametric abdominal 
MRI can quantify changes in multiple organs (liver, 
kidneys, pancreas, spleen and aorta) that occur 
over 6-9 months. 
3. At 6-9 months: difference from baseline across the cohort 
in the following MRI metrics:  
• organ volume, fat infiltration and fibroinflammation in 
abdominal organs affected by type 2 diabetes (liver, 
spleen, pancreas, kidney)  
• aortic health (aortic distensibility, diameter) 
• proportion of patients with evidence of non-alcoholic 
fatty liver disease (based on thresholds for liver fat or 
fibroinflammation). 
4. To assess changes in multiple organs (liver, 
kidneys, pancreas, spleen and aorta) that occur 
over 6-9 months, with conventional biochemical 
biomarkers utilised in the clinical pathway for T2D, 
chronic kidney disease (CKD) and non-alcoholic 
fatty liver disease (NALFD). 
4. 6-9 months: difference from baseline across the cohort in 
the following metrics:  
• glycaemic control (HbA1c)  
• lipid profiles 
•  renal health (serum creatinine, eGFR, urine albumin-
creatinine ratio)  
• liver health (FBC, LFT). 
5. To evaluate the impact of multi-parametric 
abdominal MRI on type 2 diabetes management. 
5. Review/analysis of patient and clinician reported 
outcome measures collected from non-validated 
questionnaires. 
6. To determine the prognostic information provided 
by abdominal imaging for longer-term evaluation 
of clinical outcomes (after 1, 3 5 years). 
6. At 1, 3 and 5 years: odds ratio for developing 
cardiovascular, liver, pancreatic and kidney related events 
and/or death, including hospital admissions. 
 
4. STUDY DESIGN 
a. Study Description 
This will be a multi-site study adopting a prospective, observational, longitudinal, cohort study design. There will be no 
intervention to the standard of care. Participants will be required to attend a screening visit and additional study visits 
on up to three time points – baseline (visit 1), a visit within 35 days of baseline (visit 2) and at 6-9 months (visit 3). The 
second and third visit will involve having a multiparametric MRI scan. Where possible some visits (the screening visit 1 
or visit 1 /visit 2) may be on the same day or within standard of care, depending on patient and MRI scanner availability. 
The screening visit may be able to take place remotely over the phone, depending on the preference of the participant 
and the study team, facilitated by the use of an online platform to obtain Informed Consent. In consideration of the 
COVID-19 pandemic, prior to each study visit, participants will be asked to confirm whether they have experienced any 

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of the documented symptoms. Participants may also undergo a temperature measurement at the discretion of the local 
clinical care team. 
Patients with type 2 diabetes and prescribed with glucose lowering therapy (as per standard of care) will be recruited 
from community settings, primary care centres and diabetes clinics within secondary care settings (see Fig. 3). We aim 
to recruit patients who have been newly prescribed medication; also, those patients undergoing treatment 
intensification (when an additional treatment is being considered due to evidence of poor glycaemic control), as per 
their standard of care HbA1c level results.  Clinical outcome measurements, blood samples and urine samples will be 
collected to assess the response to standard of care treatment. There will be an optional thoracic echocardiogram 
(ECHO) included at visit 2. This is a non-invasive way in which we can capture data to enable us to assess cardiovascular 
disease. 
Study participants will be enrolled in this study for a total of 5-years.  During this time, consented participants will be 
asked to attend for up to 3 study visits: Visit 1 (baseline), Visit 2 and Visit 3.  
Visit 
Time 
Visit Details 
Screening visit 
0 weeks 
• Informed Consent 
• Medical Record Review  
Visit 1 - Baseline, Day 0 
0 weeks 
• Medical Hx 
• Blood Tests 
• Basic measurements (incl. height, 
weight, 
BMI, 
hip 
& 
waist 
circumference) 
• Urine Sample 
• Questionnaire 
Visit 2 
Within 35-days of Visit 1 
• MRI Scan 
• BP (optional) 
• ECHO (optional) 
• Questionnaire 
Visit 3 
6-9 months 
• Medical Hx 
• Blood Tests 
• Basic measurements (incl. height, 
weight, BMI, BP) 
• Urine Sample 
• Questionnaire 

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Visit 
Time 
Visit Details 
• MRI 
• Medical Record Review 
 
Further to this, participants will be asked to give consent to the review of their medical records at 3 time points - years 
1, 3, and 5, following baseline assessment. This review will be conducted by authorised study investigators who will 
obtain clinical outcome measures relating to the study objectives, for example, measures of liver or kidney function.    
In the majority of cases, follow-up data at years 1,3,5 will be entered from participants’ medical records. However, some 
participants may receive a short telephone call at years 1,3,5 to clarify any data which may be unclear or, to supply data 
which may be missing from their medical record. All participants recruited and scanned at Perspectum Ltd. in Oxford (a 
non-NHS clinical study site) will complete their years 1,3,5 follow-up medical history over the telephone: although all 
participants have consented to a medical records review during the study, medical records are not available to staff 
outwith the NHS. Thus self-reported data will be collected from these participants. 
 
Figure 4 - Schematic of patient recruitment and study pathway (participants will be asked to confirm an absence of COVID-19 symptoms prior to 
each visit and may undergo a temperature measurement if necessary) 
      b. Study Setting 
This is a multi-centre study conducted in 4 localities: 
1) Liverpool  
2) Oxford (Oxford University Hospitals NHS Foundation Trust - OUHNHSFT) 
n= 150
n= 50
Visit 1: Medical history, anthropometrics, bloods, urine, 
PROMs, medical record data collection. (Baseline-day 0) 
Visit 3: Anthropometrics, bloods, 
urine, MRI, PROMs, medical record 
data collection (6-9 months)
University of Liverpool
n= 50
Oxford University Hospitals NHSFT
n= 50
Royal Free London NHSFT
Follow Up: 1, 3 and 5 Years
End of study
Visit 2: MRI, BP, medical record data collection and 
optional Echo, PROMs. (within 35 days of Visit 1)
Recruitment
•
Community
•
Primary care
•
Secondary care
Screening visit: Informed consent, concomitant medication 
check, medical record review. (Before or at baseline)
Type 2 Diabetes
Visits 1 & 2
Visit 3
Screening visit
Type 2 Diabetes
Visits 1 & 2
Visit 3
Screening visit
Type 2 Diabetes
Visits 1 & 2
Visit 3
Screening visit

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3) London (in the catchment of the Royal Free NHS Foundation Trust) 
4) Oxford (Perspectum Ltd.) 
Site 1) and 2) to recruit 50 T2D patients each, with the remaining 50 patients to be recruited between sites 3) and 4). 
Recruitment will be carried out from various settings to include community, primary care and secondary care diabetes 
clinics. Imaging will be carried out at local imaging centres for each locality.  
5. Study Participants 
Adult participants, aged 18 years and over, with type 2 diabetes and prescribed with glucose lowering therapy as per 
their standard of care. 
5.1. 
Inclusion criteria 
• 
Male or female over 18 years of age and diagnosed with type 2 diabetes. 
• 
Participant currently taking glucose lowering therapy. 
• 
Participant willing and able to give informed consent for participation in the study. 
 
5.2. 
Exclusion Criteria 
• 
The participant may not enter the study if they have any contraindication to magnetic resonance imaging 
(standard MR exclusion criteria including pregnancy, extensive tattoos, pacemaker, shrapnel injury, severe 
claustrophobia). 
• 
Patients with known autoimmune hepatitis, viral hepatitis, Wilson’s disease, haemoglobinopathies or 
significant structural renal tract abnormality. 
• 
Patients with known excessive alcohol intake. 
• 
Any other cause, including a significant disease or disorder which, in the opinion of the investigator, may 
either put the participant at risk because of participation in the study, or may influence the participant’s ability 
to participate in the study. 
6. Sample size 
The primary endpoint of the study is to compare the MRI metrics for liver fibroinflammation in those patients with type 
2 diabetes at baseline vs. individuals who are healthy and non-diabetic.  Values for the healthy, non-diabetics will be 
provided from data from the UK Biobank (UKBB)(30) or from other studies (31). Healthy individuals will be matched to 
the diabetic population based on gender, age and ethnicity. Analysis will be based on a two-sample, two-sided t-test.  
The sample size required to perform a t-test with 90% power and alpha of 0.05 would require n=150. Based on MRI 
metric for liver fibroinflammation (cT1) this assumes: 
• 
Detection of a 24.87 ms difference in cT1 in liver (This represents 50% of the difference in cT1 between self-
reported diabetes vs healthy subgroups within the UK Biobank), based on unpublished data from Perspectum) 
• 
SD of 42ms (pooled SD from self-reported diabetes and healthy subgroups within UKBB, based on unpublished 
data from Perspectum)  
• 
20% drop-out rate. 
Secondary endpoints of the study include separate comparisons of MRI metrics for liver fat infiltration and volume in 
patients with type 2 diabetes vs. the same metrics in healthy, non-diabetic individuals. Values for the healthy, non-

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diabetics will be provided from data from the UK Biobank (30) or or from other studies (31) and will be selected based 
on the matching of gender, age, ethnicity to the patients from this study with type 2 diabetes. Analysis will be based on 
two-sample, two-sided t-tests.  
Based on MRI metric for liver fat infiltration (PDFF), the sample size required to perform the t-test with 90% power and 
alpha of 0.05 would require n=150. This assumes: 
• 
Detection of a 2.4% difference in PDFF [This represents 63% of the difference in PDFF between self-reported 
diabetes vs healthy subgroups within UK Biobank, unpublished Perspectum] 
• 
Measurement SD of 5.4% (Pooled SD from self-reported diabetes and healthy subgroups within UK Biobank, 
based on unpublished data from Perspectum) 
• 
20% drop-out rate. 
Based on MRI metric for liver volume, the sample size required to perform the t-test with 90% power and alpha of 
0.05 would require n=150. This assumes: 
• 
Detection of a 0.084 L difference in liver volume in liver (This represents 6% of the pooled mean from UK 
Biobank data, unpublished Perspectum) 
• 
Measurement SD of 0.289 L (pooled mean from UK Biobank data, unpublished Perspectum) 
• 
20% drop-out rate. 
7. STUDY PROCEDURES 
7.1. 
Recruitment 
Participants will be identified from the community, primary care and secondary care diabetes; appointments; 
specifically, those patients with type 2 diabetes who are prescribed glucose lowering treatment as per their standard of 
care. A member of the clinical care team will provide potential participants with a study invitation letter and an 
accompanying Participant Information Leaflet (PIL) in the following places: 
1) Liverpool Diabetes Partnership/ Aintree University Hospital (Liverpool University Hospitals NHS Foundation 
Trust) 
2) The Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM) based at the Churchill Hospital, the 
Horton Hospital and the John Radcliffe Hospital (Oxford University Hospitals NHS Foundation Trust)  
3) The Royal Free London NHS Foundation Trust - Diabetes Department 
4) Perspectum Ltd., Oxford 
At each locality (Oxford, Liverpool, London catchment area of Royal Free NHS Foundation Trust), posters will be 
displayed around the hospitals, University departmental buildings and GP practices so that potential participants can 
also self-refer into the study by contacting the study team directly. The study will also be advertised on social media 
platforms (for example, Twitter and Facebook), Perspectum Ltd.’s website, hospital websites, newspapers and the 
Diabetes UK Patient Online Forum (forum.diabetes.org.uk).  iWantGreatCare Ltd., a company that operates a patient 
experience data collection and analysis service, will also advertise the study by sharing the study poster via their website 
and will provide a website link to the Perspectum webpage for patients interested in participating in this research. The 
Perspectum webpage will provide a copy of the advertisement with details of how to contact us for further information. 

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A short film outlining the use of ATLAS in Perspectum’s research will also be made available on Perspectum’s MODIFY 
website and other social media platforms. We also plan to recruit through health awareness sessions in the local 
hospitals. Once a potential participant has been identified by any of these means and has expressed an interest in taking 
part in the study, they will be sent a Participant Information Leaflet (PIL) to read.  They will be allowed as much time as 
they require to understand the details of the study and what’s involved.  Further to this, they will be given the 
opportunity to discuss the study with a member of the research team as part of the informed consent process. 
7.2. 
Informed Consent 
The participant must personally sign and date the latest approved version of the Informed Consent Form (ICF) before 
any study specific procedures are performed. This can be obtained via a hard copy or via the online consent platform 
that will be available to further prevent the spread of COVID-19. 
Written and verbal versions of the Participant Information Leaflet (PIL) and Informed Consent Form (ICF) will be 
presented to the participants detailing no less than: the exact nature of the study; what it will involve for the participant; 
the implications and constraints of the protocol; and any risks involved in taking part. It will be clearly state that the 
participant is free to withdraw from the study at any time and for any reason without prejudice to future care, and with 
no obligation to give the reason for withdrawal. 
The participant will be allowed as much time as wished to consider the information, and the opportunity to question 
the Investigator, the research team, their GP or other independent parties to decide whether they will participate in the 
study. Written Informed Consent will then be obtained by means of participant dated signature using the paper version 
of the Informed Consent Form or by using the online platform for obtaining Informed Consent.  This will be followed by 
a dated signature of the person from the clinical study team who presented and obtained the Informed Consent.  
7.3. 
Study Visits  
In addition to the screening visit, there will be three dedicated study visits that are in addition to standard care for the 
participants. As far as possible we will endeavour to align study visits with clinic appointments or combine early visits, 
for the participants’ convenience. As a precautionary measure and in an effort to prevent the further spread of COVID-
19, participants will be asked to confirm whether they have experienced any of the documented symptoms prior to 
each study visit. Participants may also undergo a temperature measurement if necessary. 
Appointments will be allocated to specific time slots to ensure minimal contact between staff and participants and so 
social distancing measures can be adhered to where possible. Social distancing will not be possible during some study 
assessments, such as blood tests. 
Personal protective equipment (PPE) should be worn by all study staff in accordance with Public Health England 
guidance. This could include the use of items such as a plastic apron tied securely at the back, a surgical mask covering 
the nose, mouth and chin, and gloves. Suitable PPE can also be offered to participants, with special consideration for 
equipment used during imaging appointments. For example, ensure the metal strip is removed from the nose piece of 
surgical masks and replaced with tape, as per the guidance example in Appendix 1. 
Table 1 illustrates what will happen at each study visit.  Day 0 (Baseline) is defined as the day that the consented 
patient attends their diabetes clinic in order to participate in the study.  

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Activities 
Screening visit 
Visit 1: 
Baseline,    
Day 0 
Visit 2: Within 
21-days of 
Visit 1 
Visit 3: 6-9 
months after 
Visit 1 
Follow Up 
phase at 1 
year, 3 years 
and 5 years 
Informed Consent 
X 
 
 
 
 
COVID-19 check 
X 
X 
X 
X 
X 
Medical Record Review 
X 
 
 
 
 
Concomitant Medication 
Check 
X 
 
 
 
 
Medical History 
 
X 
 
X 
 
Anthropometrics 
 
X 
 
X 
 
Blood Sample 
 
X 
 
X 
 
Urine Sample 
 
X 
 
X 
 
Multiparametric MRI Scan 
 
 
X 
X 
 
Echocardiogram (optional) 
 
 
X 
 
 
Medical Record Data 
Collection  
 
X 
X 
X 
X 
Potential supplememtary 
phone call to participant to:  
- clarify data that may not 
be clear from medical 
record  
-fill in missing data from 
medical record; 
-In case of Perspectum-
recruited participants who 
have consented to medical 
record check, to complete 
Yrs 1,3,5,follow-up data 
collection 
 
 
 
 
X 
Patient Reported 
Outcome/Experience 
 
X 
X 
X 
 

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Measures (PROMs)/ 
PREMs) 
Clinician Reported 
Experience Outcomes 
 
 
 
X 
 
 
 
7.3.1. 
Standard study visit – assessments  
Medical history (~10 min) 
We will obtain a full medical history including age, diabetes presentation, diabetes complications, diabetes duration, 
previous and current diabetes medication, current medication regime, family history, smoking history, alcohol history, 
ethnicity, history of cardiovascular disease, QRISK score, history of kidney disease, history of liver disease and record of 
any other co-morbidities the patient may have. 
We will confirm that the participant has no contraindications for MRI (e.g. pregnancy, pacemaker or other metallic 
unfixed implanted device, metallic fragments, extensive tattoos, severe claustrophobia, metal in clothing).  A resting 
blood pressure measurement will be taken. 
All measurements will be recorded on the study participant’s Case Report Form (CRF). 
Anthropometric measurements (5 min) 
We will measure the height and weight of the participant to calculate BMI and also take hip and waist circumference. 
 
Blood sample (10 min)  
Routine bloods will be performed as per standard-of-care for T2D or its complications and will include: HbA1c, serum 
creatinine, electrolytes, lipids, FBC (full blood count), LFT (liver function tests that include aspartate transaminase and 
alanine transaminase) and gamma glutamyl transferase (GGT). eGFR will also be calculated.  
 
A further blood sample of approximately 10 ml will be taken to measure additional circulating biomarkers [such as the 
enhanced liver fibrosis test (ELF), N-terminal levels of type III procollagen (P3NP), pancreatic lipase, cystatin C, serum 
albumin, high sensitivity C-reactive protein, NT-proBNP and uric acid] and optional genetic testing for NAFLD or T2D 
associated genetic variants.  Consent for genetic testing and to place blood samples in the biobank at Liverpool, Royal 
Free London or Oxford for future testing will be optional for all participants for up to 7 years after baseline to enable 
evaluation after full study completion. 
Biomarker 
Key organ(s) 
HbA1c 
Various/pancreas 
Lipids 
Various 
GGT 
Liver (various) 
Table 1 - Study visits and measurements 

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Full Blood Count 
Various 
LFT, including AST and 
ALT 
Liver 
Serum Creatinine 
Kidney 
Urine Albumin 
Creatinine Ratio 
Kidney 
Electrolytes 
Kidney 
 
 
Urine sample (10 min) 
Routine urine sample collection will be performed as per standard of care to measure urine dipstick and urine albumin 
creatinine ratio.  
MRI Scan (~30min) 
All participants will undergo a standardised imaging protocol (ATLAS) in an MRI scanner.  At the time of initial consent, 
participants will be asked for their consent to have their images de-identified and stored.  The MRI scan is not painful 
or risky, but a small minority of people feel claustrophobic. If this is apparent during screening, we will advise the 
patient to not participate. If this becomes apparent during a scan, we will stop the scan and take them out. 
The MRI scans will be performed exclusively for research purposes and are not routinely looked at by a clinician. If a 
study investigator suspects an incidental finding, then they will follow the Perspectum Ltd incidental findings standard 
operating procedure (please refer to section 13.1 of this protocol). Blood pressure measurement may be taken at the 
same visit. 
OPTIONAL Echocardiogram (~30min) 
Participants may undergo a standardised transthoracic echocardiogram (ECHO) protocol using an ultrasound machine 
at visit 2. Participants will be asked for their consent to have de-identified images stored at the time of initial consent. 
The ECHO scans will be performed exclusively for research purposes and are not routinely looked at by a clinician. If a 
study investigator suspects an incidental finding, then they will follow the University of Liverpool incidental findings 
standard operating procedure. 
Patient reported experience and outcome measures (~10min) 
All participants will be asked to complete a questionnaire on a hand-held tablet at the end of all active study visits (or 
on their mobile phone/online). They will be asked to describe their experience within the clinical care setting and the 
impact of their prescribed treatment course. 
7.3.2. 
Outcome data collection 
Participants will be asked to give written consent to allow the study team to access their primary care and hospital 
medical records. Data will be collected to assess outcome data pertaining to cardiovascular, kidney, liver and diabetes 
related clinical events, as well as any further complications and hospital admissions. Primary care medical records will 
be reviewed at 1, 3 and 5-year timepoints following the baseline visit. In the majority of cases, follow-up data at years 
Table 2 - Standard of care circulating biomarkers in study 

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1,3 and 5 will be entered from participants’ medical records. However, some participants may receive a short telephone 
call to clarify any data which may be unclear or, to supply data which may be missing, from their medical record. All 
participants recruited and scanned at Perspectum Ltd. in Oxford (an approved non-NHS clinical study site) will complete 
their years 1, 3 and 5 follow-up medical history over the telephone: although all participants have consented to a medical 
records review during the study, medical records are not available to staff outwith the NHS. Thus self-reported data will 
be collected from these participants. 
7.3.3. 
Withdrawing from the study 
Each participant has the right to withdraw from the study at any time. In addition, the Investigator may discontinue a 
participant from the study at any time if they deem it necessary for reasons that might include: 
• 
Ineligibility (arising during the study) 
• 
Significant protocol deviation 
• 
Significant non-compliance with study requirements 
• 
Withdrawal of consent 
• 
Loss to follow up 
Data already collected from the study participants will be included in the analysis. Withdrawn participants will be 
replaced. The reason for withdrawal (if provided) will be recorded in the CRF. 
8. DEFINITION OF END OF STUDY 
The end of the study will be the date that 5-year outcome data is obtained on the last recruited study participant.   Active 
participation will end when the last recruited participant attends their 6 to 9 month visit (Visit 3).  
9. INTERVENTIONS  
There will be no intervention to the standard of care these patients receive. However, consented participants will be 
asked to make two study visits where a multiparametric MRI scan will be performed – these visits will be defined as   
visit 2 and visit 3.  An optional echocardiogram may be included at Visit 2. The example guidelines provided in Appendix 
1 should be taken into consideration when imaging research participants to ensure the safety of both staff and 
participants, whilst helping to further prevent the spread of COVID-19. 
10. 
DATA  
10.1. Data Collection and Management 
All MRI imaging data will be pseudonymised before being uploaded to the custom-built data management system at 
Perspectum Ltd. No other parties will be able to access identifiable information (with the exception of the study team 
who will upload the data).  
Relevant medical history and demographics will be extracted from the patients’ medical notes by a local study 
investigator and subsequently entered into an eCRF.  The blood and urine samples will be processed at the local clinical 
site laboratory and the results entered into the eCRF by the local study team. 
All paper documents containing personal data (e.g. informed consent forms) will be stored securely and only accessible 
by local study staff and authorised personnel.  The study investigator is responsible for keeping these documents in a 
secure and accessible format to ensure that, in case of an emergency, patients can be identified and contacted. The 

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enrolment log that links a participant’s study ID to their personal information will be kept for 5 years after study 
completion or until ethical approval terminates, whichever is sooner (please refer to section 11). 
All study data will be stored for a minimum of five years after the end of the study in line with GCP recommendations. 
10.2. Analysis plan  
Descriptive statistics will be used to summarise subject characteristics. Summary data will be calculated for MRI metric 
values (Table 3). Normality will be determined by use of the Shapiro-Wilk test. Results will be expressed as means with 
standard deviation (SD) for continuous variables and as numbers and percentages for categorical variables. 
Analysis of variance will be used to test for differences between multiple groups. 
The primary endpoint will be a comparison of MRI metric values for fibro-inflammation in the liver compared to a 
matched non-diabetic control group from the UK Biobank(30) or from other studies (31) (Table 3). This will be assessed 
with a two-sample, two-sided t-test. Secondary endpoints include a comparison of individual MRI metric values 
[summarised in table 3 below] in individual organ associated with T2D and its comorbidities [summarised in table 3 
below] at baseline (visit 1/visit 2) compared to a matched non-diabetic control group from the UK Biobank or other 
studies. These will also be assessed with two sample, two-sided t-tests. Additionally, the prevalence of mean liver PDFF 
and / or mean liver cT1 above NAFLD thresholds in the study cohort will be compared to the matched non-diabetic 
control group, using a Chi-squared test. 
MRI metric 
Organ(s) or Location(s) 
Associated organ characteristic 
For primary endpoint 
cT1 
Liver 
Fibro-Inflammation 
For secondary endpoints 
Diameter of Aorta 
Heart 
Local Blood Flow 
Aortic Distensibility 
Heart 
Elasticity of Aorta  
T1 
Spleen, Kidney, Pancreas 
Fibro-Inflammation 
T2* 
Spleen 
Iron Level 
PDFF 
Liver, Spleen, Pancreas 
Fat content 
Volume 
Liver, Spleen, Kidney, Pancreas 
Size 
Optional exploratory endpoint metrics 
T2* Gradient 
Kidney 
Oxygenation 
D 
Kidney 
Glomerular Filtration 
PDFF 
Kidney 
Fat Content 

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Volume of Visceral Adipose 
Tissue (VAT) 
Abdomen 
Fat Content 
Abdominal 
Subcutaneous 
Adipose Tissue Volume (ASAT) 
Abdomen 
Fat Content 
Skeletal Muscle Index 
Abdomen 
Muscle Content 
 
Change from baseline in MRI metrics values at 6 to 9-months post-treatment will be assessed as secondary endpoints 
in each organ. These will be assessed with linear mixed effects model with an interaction variable of time. The change 
from baseline in proportion of patients at 6 to 9 months with mean PDFF and / or mean cT1 above NAFLD thresholds, 
across the whole study cohort, will be assessed using Chi-squared tests. Equivalent changes from baseline at 6 to 9 
months will be assessed for HbA1c (glycaemic control), and other circulating biomarkers utilised in the clinical pathway 
for T2D, NASH and CKD [serum creatinine and eGFR (kidney), urine albumin creatinine ratio (kidney), lipids (NALFD), LFT 
(liver)], using linear mixed effects to assess changes over time. Odds ratios will be calculated by logistic regression 
analysis in relation to cardiovascular, liver, pancreatic and kidney-related events and or death, including hospital 
admissions, at 1, 3 and 5 years from baseline.  
Exploratory endpoints will investigate the potential influence of glycaemic control/weight and of glucose/lowering 
therapies (oral/injectable agents) on prevalence of abnormality based on thresholds set from the healthy controls and 
on rate of progression for both biochemical and MRI-metrics, in subgroup analyses (including subgroups with 
abnormalities in multiple organs). Multiple testing will be corrected with Bonferroni correction. In addition, analysis of 
covariance will provide estimates of MRI metrics, adjusting for potential confounders such as baseline MRI metric, type 
of co-morbidity, type of therapeutic, HbA1c values, anthropometric measures and organ-specific circulating biomarker 
values as covariates. Similarly, additional associations of MRI metrics to biomarkers that are optional [for example left 
ventricular strain from the ECHO] or not in standard of care [for example pancreatic lipase] may be analysed, if evaluated 
locally or from stored, consented additional blood samples. Thresholds will be set based on Kaplan–Meier analysis to 
establish the proportions of patients in different MRI metric categories that remain free of diabetes-related events in 
the follow-up period. Differences between the curves will be compared using the log-rank test. 
The results will be expressed as effect sizes and 95% confidence intervals (95% CI). Spearman and/or Pearson’s 
correlations will be calculated to test associations between categorical and / or continuous variables, for example 
significant correlations between MRI metrics and weight, and between MRI metrics and biochemical metrics. To 
determine the diagnostic utility of MRI in these cohorts for assessing organ dysfunction, receiver-operating 
characteristic analyses will be carried out. 
11. 
SAFETY REPORTING 
11.1. Definition of Serious Adverse Events 
This study is an observational longitudinal study and there is no intervention. Therefore, the risk of the occurrence of a 
Serious Adverse Event is minimal.  
In relation to this study, a Serious Adverse Event would be any untoward medical occurrence immediately before, 
during or subsequent to the study visit. This would be classed as a Serious Adverse Event if it: 
Table 3 - MRI metrics in relevant organs 

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• 
results in death 
• 
is life-threatening 
• 
requires hospitalisation (outpatient and inpatient) 
• 
results in persistent or significant disability/incapacity 
Other ‘important medical events’ may also be considered serious if they jeopardise the participant or require an 
intervention to prevent one of the above consequences. 
11.2. Reporting Procedures for Serious Adverse Events 
A serious adverse event (SAE) occurring to a participant should be reported to the Research Ethics Committee (REC) that 
gave a favourable opinion for the study where in the opinion of the Chief Investigator the event was ‘related’ (resulted 
from administration of any of the research procedures) and ‘unexpected’ in relation to those procedures. Reports of 
related and unexpected SAEs should be submitted within 15 working days of the Chief Investigator becoming aware of 
the event, using the HRA report of serious adverse event form (see HRA website).   All SAEs must also be reported to 
local regulatory teams in line with local requirements. 
There are no anticipated ‘related’ serious adverse events from this study.  
12. 
ETHICAL AND REGULATORY CONSIDERATIONS 
12.1. Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the Declaration of Helsinki.  
12.2. Guidelines for Good Clinical Practice 
The Investigator will ensure that this study is conducted in full conformity with relevant regulations and with the 
Guidelines for Good Clinical Practice. 
12.3. Approvals 
The protocol, informed consent form, participant information sheet and any proposed advertising material will be 
submitted to an appropriate REC, HRA and host institution(s) for written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all substantial 
amendments to the original approved documents. 
Approval will also be sought locally by all participating sites. 
12.4. Reporting 
The CI shall submit once a year throughout the study, or on request, an Annual Progress Report (APR) to the REC 
Committee, host organisation and Sponsor.  In addition, an End of Study notification and final report will be submitted 
to the same parties. 
12.5. Participant Confidentiality 
The study staff will ensure that the participants’ privacy is maintained. Data shall be pseudonymised such that the 
participants will be identified only by a study ID number on the CRF and any electronic database.  All documents will be 
stored securely and only accessible by study staff and authorised personnel. The study will comply with the General 
Data Protection Regulation (GDPR). 

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The named investigators will have access to all pseudonymised data from the study. Students and collaborators may 
be given access to pseudonymised data under the supervision of the named investigators.  
12.6. Potential Risks of Procedures 
MRI 
MRI is a safe and non-invasive technique with no known risk when appropriately supervised. It does not involve ionising 
radiation (X-rays). Potential participants with ferromagnetic objects in their bodies or with implanted devices which can 
be damaged by the MRI magnet, cannot be scanned and so will be excluded. To minimise this risk, all participants before 
entering the scanner room complete a standard MRI safety screening interview and are screened for such objects. The 
MRI scanner is noisy and hence participants will be given earplugs and protective headphones. Some people find that 
being in the scanner is claustrophobic, and therefore participants will be given the opportunity to view the scanner prior 
to consenting to the study. The participant will be able to contact the operators throughout the scan via a microphone 
and hand buzzer. They will be able to indicate should they wish the scan to cease. All study sites are fully equipped for 
resuscitation (including defibrillation) in the unlikely event of a medical emergency during scanning.  
Phlebotomy 
Common risks associated with phlebotomy are pain during the procedure and bruising (with associated pain afterwards). 
These risks will be minimised by ensuring that all staff are fully trained in phlebotomy. Bruising after the event will also 
be reduced by promptly applying pressure on the puncture site after the needle is withdrawn. All participants will be 
fully informed about these risks in the Participant Information Leaflet (PIL). The worry associated with taking blood may 
cause some participants to feel unwell or faint before, during or after the procedure. The risk associated with this will 
be reduced by having an adequately equipped facility for performing the blood taking procedure and having a staff 
member trained in basic life support. Although phlebotomy is a very safe procedure, it does create a puncture wound 
on the skin which may very rarely lead to infection around the puncture site. The risk of this will be minimised by ensuring 
strict hygiene during the procedure and by not recruiting participants who are at increased risk of infection. In the event 
that a participant reports symptom of an infection (local redness, swelling, pain or discharge of pus), they should be 
referred to their GP or to A+E urgently.  
 
ECHO  
ECHO is a form of ultrasound assessment and there are no known risks associated with ultrasound scanning. 
 
12.7. Expenses and Benefits 
Reasonable travel expenses for all study specific visits (outside of standard of care) that are additional to normal care 
will be reimbursed on production of receipts, or a mileage allowance provided as appropriate. Expenses will also be 
provided for one companion, if applicable.   
Participants will receive a formal letter of thanks and study feedback after completion of their last face-to-face visit, 
and around the time of their 1-year follow-up. The letter will provide details on study progress, recent study 
publications and some basic healthy lifestyle guidance. A copy of a participant's LiverMultiScan Reports from baseline 
and 6-9-month follow-up MRI scans will also be included, with guidance on how to interpret the metrics of cT1 and 
PDFF. 

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13. 
OTHER ETHICAL CONSIDERATIONS 
13.1. Incidental findings 
Scans are carried out for research purposes only and are not a replacement for clinical diagnosis. In addition, existing 
disease may not be detected. If a suspected incidental finding is discovered, scans (MRI or optional ECHO) will be 
screened for technical artefacts by a relevantly trained specialist and where a perceived incidental finding is noted, it 
will be managed following the investigation-specific Incidental Findings Management Plan. If a site or local imaging 
facility has a bespoke Incidental Findings Management Standard Operating Procedure, this will be followed. In all other 
cases, Perspectum’s Incidental Findings Management Plan will be followed, and the scans will be reviewed by an expert 
reviewer (a radiologist) to assess for clinical significance. In the event that a potentially clinically significant incidental 
finding is discovered, this will be communicated to the relevant site’s Principal Investigator who will discuss this with the 
participant and, if appropriate, the finding will be referred to their GP and/or specialist consultant for further 
investigation as necessary. 
13.2. Participant comfort and dignity 
While most people do not experience discomfort in an MRI environment, the enclosed space of the scanner can 
potentially feel uncomfortable, especially for more elderly participants. Discomfort from lying still for a long period of 
time will be minimised with comfortable padding and positioning.  People with a history of claustrophobia will be 
excluded from participation in the study. Participants will be given a chance to see the scanner before the study starts. 
Whilst in the scanner, participants will be able to use the alarm button if they wish to communicate with the operator 
or to interrupt the scanning. All participants would be introduced carefully to the scanner and allowed to leave at any 
stage, should they wish to do so. Once in the scanner, participants would be able to indicate immediately if they wish 
the scanning to cease by squeezing a bulb placed in their hands, or by requesting it verbally. As the MRI scanner is noisy, 
participants would be given earplugs and acoustically shielded headphones to minimize the noise and aid 
communication between participants and investigators. 
Participants will be asked to wear a gown for the MRI scan. To help maintain participant dignity they will be asked to 
leave their underwear on, provided it is not made of synthetic material and has no metal parts (e.g. zips, bras clasps or 
studs).  The gowns are designed to cover participants and preserve their modesty while remaining loose in the scanner 
to avoid potential burns from synthetic clothing. Participants will be asked to change in a changing room near to the 
scanner and will be given a locker to securely store their belongings. If they are unable to change into the gown by 
themselves a member of staff will be on hand to offer assistance.  
The example guidance provided in Appendix 1 should be taken into consideration when imaging research participants 
and have been provided as a result of the COVID-19 pandemic. These guidelines provide details of further precautionary 
measures that could be put in place to ensure the comfort and safety of both staff and participants. Appendix 1 provides 
example guidance on additional PPE; study visit management and participant management. These guidelines are 
optional and can be considered alongside local protocols for imaging research participants. 
13.3. Pregnancy in participants 
Although there is no evidence that MRI scans cause harm to unborn babies, as a precaution clinical MRI scans are not 
usually recommended during pregnancy, particularly in the first three months. MRI for research purposes provides no 
benefit to the mother or unborn child and therefore research MRIs are not performed on women who may be pregnant. 
As part of screening for the MRI, women will be asked if they are pregnant, or if there is any chance that they could be. 
If there is any uncertainty, a urine test will be carried out prior to the MRI examination to rule out pregnancy. 

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14. 
DATA HANDLING AND RECORD KEEPING 
Direct access to study data will be granted to local research teams and authorised representatives from the Sponsor and 
host institution for the purposes of monitoring and/or audit of the study to ensure compliance with regulations. At the 
time of recruitment, each participant will be assigned a unique Study ID that contains no personal or identifying 
information about them. This will be how they are identified throughout the study and only the enrolment log will 
contain personal and identifiable data that links the Study ID to the study participant. 
The enrolment log for each site will be stored securely (password protected) with restricted access to authorised 
members of the study team only. Study data collected (measurements, outcomes etc.) will be stored in a pseudonymised 
format using the assigned Study ID only and kept on a separate database to the enrolment log in line with GCP guidelines.  
Only data outlined on the case report forms will be collected and entered into the electronic data capture study database 
by members of the research team.  Training on how to use the study database shall be provided by the Sponsor or 
another appropriately qualified member of the study team.  In addition to using strict version control of the study 
database to prevent duplication and errors, quality checks of data entered including consistency, missing data and 
unusual values, shall be performed by the study manager and a data manager from Perspectum Ltd. 
All collected study data will be carefully reviewed and ‘cleaned’ before any final analysis and database lock is undertaken. 
The reason for any excluded data or data changed after database lock will be described in detail in the end of study 
report. Study data collected (measurements, outcomes, etc.) will be stored in a pseudonymised format using the 
assigned Study ID only and kept on a separate platform to the link between Study ID and participant identifiable data, 
in line with GCP guidelines. 
Perspectum’s chosen on-line eConsent platform will be utilised to aid in the Informed Consent Process. This on-line 
platform allows potential participants to consider and engage remotely with the participant information leaflet and 
informed consent form. Reducing the exchange of paper documentation, in turn, reduces any risk of SARS-CoV-2 
transmission. The highly infectious nature of this new coronavirus is recognised and, therefore, all measures will be 
taken to lessen the risk of transmission. The link between the participant’s name and Study ID will be housed within the 
eConsent platform, which is compliant to ISO27001 and 21CFR11. This information will be stored securely (password 
protected) with restricted access only to authorised members of the study team. 
All paper documents containing personal data (e.g. informed consent forms) will be stored securely in a locked cabinet 
behind locked or ID accessed doors. Documents will be only accessible by study staff and authorised personnel. The 
local principal investigator is responsible for keeping these documents in a secure and accessible location to ensure that, 
in any case of an emergency, participants can be identified and contacted readily. The enrolment log containing the 
linking personal data to the study ID will be kept for up to 5 years after study completion or until ethical approval 
terminates, whichever is sooner. 
The study will comply with GDPR and relevant privacy legislation, please refer to section 12. As part of the informed 
consent process, participants will authorise the pseudonymous collection, use and disclosure of their study data by the 
study investigators and by those persons who need that information for the purposes of the study, including the 
commercial sponsor of the study, Perspectum. 
The pseudonymised MRI DICOM files will be uploaded to Perspectum data transfer system called Perspectum Portal. 
Perspectum Portal is compliant with GDPR laws. Our data security infrastructure is supported by an ISO 27001, ISO 9001 
and ISO 13485 compliant quality management system designed around a defence-in-depth approach with multiple 

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layers of redundancy, surveillance, physical access controls and audit logs. Access to the Perspectum Portal is controlled 
and secured by Secure Sockets Layer (SSL) encryption mandating a HTTPS protocol for web-based data transmissions to 
prevent eavesdropping, tampering and forgery. All data is encrypted while in storage in Perspectum Portal and routinely 
backed-up to an alternative secondary physical location to ensure service continuity. Perspectum Portal is hosted by 
Amazon Web Services (AWS), a market-leading provider of cloud platform solutions who employ rigorous and 
sophisticated security processes to safeguard data privacy from malicious or accidental incident. No project partner will 
be able to access identifiable information (with the exception of the study team who will upload the data).  
15. QUALITY ASSURANCE PROCEDURES 
The study will be monitored, and/or audited in accordance with the current approved protocol, GCP, relevant 
regulations and standard operating procedures.  Direct access to the study data will be granted to authorised 
representatives from the Sponsor and host institution(s) for the purposes of monitoring to ensure compliance with 
regulations.  A monitoring plan will be established for this study and circulated to the local study teams. 
16. FINANCING AND INSURANCE 
The study will be financed for 2-years by Innovate UK (grant reference: 26512).  The remaining study period will be 
funded by Perspectum Ltd. 
Perspectum has in place a specialist insurance policy which operates in the event of a participant suffering harm as a 
result of their involvement in the study (CNA Hardy Policy number 10351211). 
NHS indemnity operates in respect to the clinical treatment that is provided. 
Negligent Harm 
Indemnity and/or compensation for negligent harm arising specifically from an accidental injury for which the 
Perspectum is legally liable as the Research Sponsor will be covered by Perspectum.  
Non-Negligent Harm 
Indemnity and/or compensation for harm arising specifically from an accidental injury and occurring as a consequence 
of the Research Subjects' participation in the study may be covered by Perspectum. 
17. REFERENCES 
1. NCD Risk Factor Collaboration (NCD-RisC): Worldwide trends in diabetes since 1980: a pooled analysis of 751 
population-based studies with 4·4 million participants. Lancet 2016; 387:1513–1530. 
2. WHO: World Health Organization – Diabetes Country Profiles, United States of America. 2016. 
3. Hex N, Bartlett C, Wright D, Taylor M, Varley D: Estimating the current and future costs of Type 1 and Type 2 
diabetes in the UK, including direct health costs and indirect societal and productivity costs. Diabet Med 2012; 29:855–
862. 
4. Dai W, Ye L, Liu A, et al.: Prevalence of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: A 
meta-analysis. Med 2017; 96:e8179–e8179. 
5. Friedman S, Neuschwander-Tetri B, Rinella M, Sanyal A: Mechanisms of NAFLD development and therapeutic 
strategies. Nat Med 2018; 24:908–922. 
6. Lou Arnal L, Campos Gutiérrez B, Cuberes Izquierdo M, et al.: Prevalence of chronic kidney disease in patients with 
type 2 diabetes mellitus treated in primary care. Nefrologia 2010; 30:552–556. 
7. Einarson TR, Acs A, Ludwig C, Panton UH: Prevalence of cardiovascular disease in type 2 diabetes: a systematic 

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literature review of scientific evidence from across the world in 2007–2017. Cardiovasc Diabetol 2018; 17:83. 
8. NICE: Type 2 Diabetes in Adults: Management. 2017. 
9. Brown JB, Conner C, Nichols GA: Secondary failure of metformin monotherapy in clinical practice. Diabetes Care 
2010; 33:501–506. 
10. Cuthbertson DJ, Irwin A, Gardner CJ, et al.: Improved glycaemia correlates with liver fat reduction in obese, type 2 
diabetes, patients given glucagon-like peptide-1 (GLP-1) receptor agonists. PLoS One 2012; 7:e50117–e50117. 
11. Yan J, Yao B, Kuang H, et al.: Liraglutide, sitagliptin and insulin glargine added to metformin: the effect on body 
weight and intrahepatic lipid in patients with type 2 diabetes mellitus and NAFLD. Hepatology 2018. 
12. O’Neil P, Birkenfeld A, McGowan B, et al.: Efficacy and safety of semaglutide compared with liraglutide and placebo 
for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, 
phase 2 trial. Lancet 2018; 392:637–649. 
13. Fitchett D, Zinman B, Wanner C, et al.: Heart failure outcomes with empagliflozin in patients with type 2 diabetes 
at high cardiovascular risk: results of the EMPA-REG OUTCOME® trial. Eur Heart J 2016; 37:1526–1534. 
14. NHS: Https://Www.Sps.Nhs.Uk/Medicines/Semaglutide/. 2018. 
15. NICE: Resource Impact Report: Type 2 Diabetes in Adults: Management (NG28). 2015. 
16. Johansen P, Hakan-Bloch J, Liu A, Persson S, Toresson Grip E: Cost-Effectiveness of once-weekly semaglutide 1.0 
mg vs. dulaglutide 1.5 mg as add-on to metformin in the treatment of type 2 diabetes in Canada. Diabetes 2018; 
67(Supplement 1). 
17. Harrison S, Dennis A, Fiore M, et al.: Utility and variability of three non-invasive liver fibrosis imaging modalities to 
evaluate efficacy of GR-MD-02 in subjects with NASH and bridging fibrosis during a Phase 2 controlled study. PLoS One 
2018; 13:e0203054. 
18. McDonald N, Eddowes P, Hodson J, et al.: Multiparametric magnetic resonance imaging for quantitation of liver 
disease: a two-centre cross-sectional observational study. Sci Rep 2018; 8:9189. 
19. McKay A, Wilman HR, Dennis A, et al.: Measurement of liver iron by magnetic resonance imaging in the UK Biobank 
population. PLoS One 2018; 13:e0209340–e0209340. 
20. Mojtahed A, Kelly C, Herlihy A, et al.: Reference range of liver corrected T1 values in a population at low risk for 
fatty liver disease-a UK Biobank sub-study, with an appendix of interesting cases. Abdomimal Radiol 2019; 44:72–84. 
21. Wilman HR, Kelly M, Garratt S, et al.: Characterisation of liver fat in the UK Biobank cohort. PLoS One 2017; 
12:e0172921. 
22. Pavlides M, Banerjee R, Sellwood J, et al.: Multiparametric magnetic resonance imaging predicts clinical outcomes 
in patients with chronic liver disease. J Hepatol 2016; 64:308–315. 
23. Pavlides M, Banerjee R, Tunnicliffe EM, et al.: Multiparametric magnetic resonance imaging for the assessment of 
non‐alcoholic fatty liver disease severity. Liver Int 2017; 37:1065–1073. 
24. Banerjee R, Pavlides M, Tunnicliffe EM, et al.: Multiparametric magnetic resonance for the non-invasive diagnosis 
of liver disease. J Hepatol 2014; 60:69–77. 
25. Bradley CR, Cox EF, Scott RA, et al.: Multi organ assessment of compensated cirrhosis patients using quantitative 
magnetic resonance imaging. J Hepatol 2018; 69:1015–1024. 
26. Macauley M, Percival K, Thelwall PE, Hollingsworth KG, Taylor R: Altered volume, morphology and composition of 
the pancreas in type 2 diabetes. PLoS One 2015; 10:e0126825–e0126825. 
27. Perrone RD, Mouksassi M-S, Romero K, et al.: Total Kidney Volume Is a Prognostic Biomarker of Renal Function 
Decline and Progression to End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease. 
Kidney Int Reports 2017; 2:442–450. 
28. Pfeifer C, Schoennagel B, Grosse R, et al.: Pancreatic iron and fat assessment by MRI-R2* in patients with iron 
overload diseases. J Magn Reson Imaging 2015; 42:196–203. 
29. Ohyama Y, Teixido-Tura G, Ambale-Venkatesh B, et al.: Ten-year longitudinal change in aortic stiffness assessed by 
cardiac MRI in the second half of the human lifespan: the multi-ethnic study of atherosclerosis. Eur Heart J Cardiovasc 
Imaging 2016; 17:1044–1053. 
30. Sudlow C, Gallacher J, Allen N, et al.: UK biobank: an open access resource for identifying the causes of a wide 
range of complex diseases of middle and old age. PLoS Med 2015; 12:e1001779–e1001779. 
31. Dennis A, Wamil M, Alberts J, et al.: Multiorgan impairment in low-risk individuals with post-COVID-19 syndrome: a 

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prospective, community-based study. BMJ Open 2021; 11:e048391. 
 
 

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APPENDIX 1: EXAMPLE GUIDELINES FOR MRI IMAGING IN CONSIDERATION OF 
COVID-19 
COVID-19 is the clinical syndrome resulting from infection with a novel coronavirus, the severe acute respiratory 
syndrome coronavirus 2 (SARS-CoV-2), which was first identified in December 2019. SARS-CoV-2 has since been 
declared a global pandemic by the World Health Organization. 
It is therefore necessary to consider the following safety aspects when imaging a research participant during the 
COVID-19 pandemic: 
• 
The virus is transmitted through contact with endothelium (mouth, nose, eyes) 
• 
Transmission occurs through droplets and contaminated surfaces 
• 
Aerosol transmission possible over longer distances (>1m) 
Whilst the MRI procedure itself is not aerosol generating, it is important to remember that: 
• 
In a pandemic, all participants should be considered carriers 
• 
Healthcare staff need efficient personal protective equipment (PPE) 
Personal Protective Equipment (PPE) 
To ensure both participant and staff safety, appropriate PPE should be worn during the imaging process. It is 
important to consider the type of PPE appropriate for MRI imaging specifically. 
An appropriate PPE kit would consist of: 
Staff (e.g. MRI operator) 
• 
Mask or respirator 
• 
Gloves (consider two pairs each time) 
• 
Face shield or googles 
• 
Long sleeved disposable surgical gown 
• 
Head caps 
• 
Shoe covering 
Research participant 
• 
Mask (ensuring the nasal metal band has been removed and adhesive tape is used across the bridge of the nose) 
• 
Gloves 
• 
Gown 
Options for PPE vary, depending on requirements. Table 1 provides alternative mask and respirator options. 
Table 1: Masks and respirators 
FFP3 (European standard) respirators filter 99% of particles. FFP2 respirators are specified to filter 94% of particles 
The N99 (American standard) respirator is an alternative to the FFP3 and filters 99% of particles 
An N95 respirator is specified to filter 95% of particles and is a close equivalent to the FFP2 
Other equivalents: 
• 
KN95 (China) 
• 
P2 (Australia/New Zealand) 
• 
DF FFR (Japan) 
The Type IIR (European Standard) fluid resistant surgical mask is the “regular” surgical mask often used in clinical settings 
The Level 2 (American standard) fluid resistant surgical mask is equivalent to the Type IIR 

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Availability may dictate the use of specific items however Table 2 provides recommendations for masks to use for both 
staff and participants during MRI imaging. 
Table 2: Mask/respirator recommendations for staff and participants 
Participant 
Staff (e.g. Operator) 
Type IIR/Level 2 Fluid Resistant Mask 
 
Respirators (N95 non-valved FFP3 valved) 
Loose fitting covers nose and mouth 
Tight fitting creates a facial seal 
One-way protection captures bodily fluid e.g. 
cough/sneeze leaving the wearer of the mask 
Non-valved provides two-way protection to filter inflow 
and outflow of air 
“R” denotes that the mask is fluid resistant 
Respirators may have additional letters (e.g. FFP3R FFP3D) 
to denote the following: 
“R” = reusable 
“NR” = Non-reusable 
“D” = passed the dolomite dust clogging test and is suitable 
for >8 hours use depending on surrounding conditions 
Staff Management  
Healthcare and office staff should be reduced to the minimum necessary.  
Scheduling for appointments should allocate enough time between scans to allow for proper cleaning of the MRI scan 
room and all tools/devices utilised. 
• 
Workstation area should be treated similarly; constant cleaning of desktops, phones, door handles, keyboards 
etc. should be performed between operators 
• 
Sufficient time should be allotted for surfaces to dry after disinfection 
Participant Management 
Prioritising participant study visits 
The usual clinical indications for the triage of imaging would be to defer elective exams, schedule imaging based on 
urgency and to have a tailored protocol to tailor to clinical indications whilst limiting time waste. 
For research scans during COVID-19, the above should be taken into account whilst also considering the following 
protocol: 
• 
Schedule non-active COVID-19 participants who are clear from symptoms and/or risk factors 
• 
Postpone non-active COVID-19 participants who have shown symptoms and/or risk factors for at least 14 
days; then re-assess symptoms and risk factors 
• 
Do not schedule imaging for active COVID-19 participants, unless it affects the direct management of their 
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Prior to study visit 
Screen participants for active COVID-19 prior to scheduling their study visit where possible. This could include asking 
the participant if they have recently developed or had any of the documented symptoms or have been exposed to 
certain risk factors (e.g. recent travels or recent close contact with active subjects). 
During study visit 
Screen participant again by confirming any changes in their health and if they have developed any symptoms or been 
exposed to any risk factors since the appointment was scheduled. It may be necessary to postpone the procedure 
based on the participants current health status. 
It is important to maintain social distancing where possible (in accordance with latest government guidelines). The 
following considerations are recommended to help comply with social distancing: 
• 
Reduce the capacity of the waiting rooms/research areas 
• 
Minimise time in waiting room by ensuring sufficient time between appointments/visits. 
• 
Schedule less participants per clinic to ensure sufficient time between scans to allow time for: 
o Participant to get ready for visit (e.g. getting changed into gown and appropriate PPE) 
o Participant to complete safety questionnaire and addressing any concerns (if any) 
o Participant time to prepare for departure after completing the scanning procedure 
o The scanning room, workstation and equipment to dry after disinfection 
Scanning procedure 
Participant 
Make sure that the participant is wearing PPE even during the MRI (mask, gown and glove), ensuring the surgical mask 
is fluid resistant (level 2 - type IIR) and that the nasal metal band has been removed and adhesive tape used across the 
bridge of the nose instead. 
Operator(s) 
Ideally two operators should be present during the MRI procedure: 
• 
One operator in full PPE would take care of managing the participant 
o preparation 
o safety questionnaire 
o positioning on the MR table 
• 
The other operator should be scanning 
o Potentially wearing a lower level of PPE but keeping in mind that, in case of emergency, should be able to 
be in full PPE in matter of seconds to help out the other operator sliding the participant out of the scanner 
and start any emergency procedure according to the standard operating procedure in place. This means 
that at least a clean full PPE kit should be available in the scanning room 
During the scanning session, the operator in full PPE managing the participant, should simply be able to wait at an 
adequate distance without touching the workstation or other common surfaces; particularly advised in case of 
claustrophobic participants. 
Post scanning 
The operator in full PPE appointed for the management of the participant will: 
• 
Escort the participant in the changing room 
• 
Disinfect the MR scan room, including everything that has been used during the scanning procedure, for example: 
o Scanner bore (MRI safe cleaning wands suggested) 
o Scanner table 
o All coils used 
o All pads/cushion used 

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o Headphones, emergency buzzer 
o Door handles 
o ECG/PPG devices 
o Infusion pumps 
• 
Allow enough time for the surfaces to dry after disinfection between participants 
o Thirty minutes should be sufficient, depending on the agent used (the bore fan may be Increased to 
maximum to accelerate the process) 
o Allow fresh air to flow into the MR scan room between participants (without compromising MR safety) 
Additional Notes 
• 
It is worth considering having hand sanitisers, gloves and surgical masks available in the reception area so that 
participants can be warned to use these safety precautions immediately at the entrance and without any 
particular interaction with the front-desk personnel 
• 
Signage with explanations and/or rules may be useful in all areas (e.g. how to sanitise your hand, how to wear 
gloves, how to wear a mask or “wearing the mask is a mandatory requirement for the entire length of your visit in 
these premises”) 
• 
It is worth considering avoiding scheduling Research participants with underlying severe medical conditions; any 
chances to avoid an emergency situation should be taken.