A Two Site Pilot Study of Functional and Microstructural Imaging Using Magnetic Resonance Imaging in Patients With Renal Tumours
Phase: NA
Conditions: Renal Cancer, MRI, Small Renal Mass, Kidney Cancers
Sponsor: University College, London

1 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Full title of trial 
 
A 
two 
site 
pilot 
study 
of 
functional 
and 
microstructural imaging using magnetic resonance 
imaging in patients with renal tumours 
Short title 
 
Renal tumour Imaging using MRI. 
Version and date of protocol 
 
V1.1  21/03/2024 
  
Sponsor: 
 
University College London (UCL) 
 
Sponsor reference number: 
 
Funder (s): 
162190 
 
UCL/UCLH Biomedical Research Centre (NIHR) 
 
IRAS Number: 
 
323984 
 
 
UCL Data Protection Number: 
Z6364106/2023/11/12 
 
Intervention: 
 
MRI of renal tumours 
 
Chief investigator: 
Dr Richard Hesketh, 
r.hesketh@ucl.ac.uk  
Centre of Medical Imaging, 
2nd Floor, Charles Bell House,  
43-45 Foley Street,  
London, W1W 7TS. 
 
 
 
 
 
Sponsor Representative: 
Pushpsen Joshi 
uclh.randd@nhs.net 
UCLH/UCL Joint Research Office, 
4th Floor, West 
250 Euston Road 
London ,NW1 2PG 
 
 
 
 

2 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

3 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
PROTOCOL VERSION HISTORY 
Version Stage 
Versions Number 
Version Date 
Protocol updated & 
finalised by; 
Reasons for Update 
Former 
1.0 
24/11/2023 
Richard Hesketh 
 
Current 
1.1 
21/03/2024 
Richard Hesketh 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

4 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
 
DECLARATIONS 
The undersigned confirm that the following protocol has been agreed and accepted and that the 
investigator agrees to conduct the study in compliance with the approved protocol and will adhere to 
the U.K. Policy Framework for Health and Social Care Research 2017 (3rd edition) (as amended 
thereafter), the EU General Data Protection Regulation (2016/679) and the UK Data Protection Act 
(2018), Sponsor SOPs and applicable Trust policies and legal frameworks. 
I (investigator) agree to ensure that the confidential information contained in this document will not 
be used for any other purposes other than the evaluation or conduct of the research investigation 
without the prior written consent of the Sponsor. 
I (investigator) agree to ensure that no research activity or recruitment will commence at participating 
research sites until the appropriate regulatory approvals and NHS confirmations of Capacity and 
Capability have been issued, and Sponsor green light confirmed. 
I (investigator) also confirm that I will make the findings of the study publicly available through 
publication or other dissemination tools without any unnecessary delay and that an honest, accurate 
and transparent account of the study will be given.  Any deviations from the study as planned in this 
protocol will be explained and reported accordingly. 
Chief Investigator:  
Signature: ....................................................................................      Date 21/03/2024 
Print Name (in full): Richard Hesketh 
Position: UCL Clinical Lecturer 
On behalf of the Study Sponsor: 
Signature: ........................................ 
.............        Date.22./.03./.2024 
Print Name (in full): .....Pushpsen Joshi................................. 
Position: ...........Research Governance Manager .......................... 
 
 
 
 
 

5 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
 
 
 
 

6 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
IDENTIFIERS 
IRAS Number 
323984 
REC Reference No. 
 
Sponsor Reference No. 
162190 
Other research reference 
number(s) (if applicable) 
UCL Data protection: Z6364106/2023/11/12 
Full (Scientific) title 
A two site pilot study of functional and microstructural imaging using 
magnetic resonance imaging in patients with renal tumours 
Health 
condition(s) 
or 
problem(s) studied 
Cancer 
Study Type i.e. Cohort etc 
Interventional study 
Type of trial: 
Prospective pilot study 
Trial design and methods: 
Patients with known renal tumours will be identified from clinic and 
MDTs at the Royal Free.  
Study 1: 20 patients - histological analysis of renal tumours retrieved 
from the RFH tissue biobank. 
Study 2: 10 patients – Comparison between MRI and co-registered 
tumour histology in patients undergoing nephrectomy. Patients 
undergo a single MRI scan prior to standard of care surgery.  
Study 3: 10 patients – Repeatability study of microstructural renal 
MRI. Patients undergo two MRI’s within 14 days.  
Trial duration per 
participant: 
Single visit (study 2), two visits (study 3) 
Key Study milestones  
 
3 months: ethics and R&D approvals completed 
4 months: CRF training completed and first patient recruited 
12 months: Last prospective patient recruited 
18 months: Data analysis complete 
Planned trial sites: 
Two sites: Royal Free London Hospital and University College London 
Hospital 
Total number of 
participants planned: 
20 participants: Study 1.    
10 participants: Study 2.  
10 participants: Study 3.  

7 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
Main inclusion/exclusion 
criteria: 
Inclusion criteria:  
1) Aged 18 and over 
2) Confirmed renal tumour ≤ 7 cm planned for surgical resection 
3) Willing and able to provide written informed consent 
4) Able to lie supine for the duration of an MRI 
 
Exclusion criteria: 
1) Contraindication to MRI e.g., cardiac pacemaker 
2) Contraindication to MR contrast agents 
3) Pregnancy 
4) Breastfeeding 
5) Deranged renal function (eGFR <30) in the last three months.  
6) Previous treatment of the renal tumour e.g., ablation, 
radiotherapy 
Statistical methodology 
and analysis: 
Prospective pilot study, no specific statistical methodology 
FUNDING & OTHER 
 
Funding  
NIHR UCLH BRC: BRC1125/HEI/RH/110410: £48,712 
Other support  
. 
STORAGE of SAMPLES / 
DATA (if applicable) 
 
Human tissue samples 
All human tissue samples will remain stored in NHS hospitals as per 
clinical practice. Only pseudo-anonymised digital scans will be 
stored in UCL computers. 
KEY STUDY CONTACTS 
Full contact details 
including phone, email 
and fax numbers 
 
Chief Investigator 
Dr Richard Hesketh, r.hesketh@ucl.ac.uk, 07979510466 
Co-investigators 
Professor Maxine Tran, m.tran@ucl.ac.uk (PI: Royal Free Hospital) 
Professor Shonit Punwani s.punwani@ucl.ac.uk 
Dr Eleftheria Panagiotaki e.panagiotaki@.ucl.ac.uk 
Dr Timothy Bray, t.bray@ucl.ac.uk 
Dr Soha El- Sheikh, s.elsheikh@nhs.net 

8 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
Miss Fiona Gong, f.gong@ucl.ac.uk 
Dr Magdalena Sokolska, magdalena.sokolska@nhs.net 
Professor David Atkinson, d.atkinson@ucl.ac.uk 
Professor Geoff Parker, geoff.parker@ucl.ac.uk 
Dr Lorna Smith, lorna.smith@ucl.ac.uk 
 
 
 
 
 
 
 
 

9 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
KEY ROLES AND RESPONSIBILITIES 
SPONSOR: The sponsor is responsible for ensuring before a study begins that arrangements are in 
place for the research team to access resources and support to deliver the research as proposed and 
allocate responsibilities for the management, monitoring and reporting of the research. The Sponsor 
also must be satisfied there is agreement on appropriate arrangements to record, report and review 
significant developments as the research proceeds, and approve any modifications to the design.  
 
FUNDER: The funder is the entity that will provide the funds (financial support) for the conduction of 
the study. Funders are expected to provide assistance to any enquiry, audit or investigation related to 
the funded work.  
 
CHIEF INVESTIGATOR (CI): The person who takes overall responsibility for the design, conduct and 
reporting of a study. If the study involves researchers at more than once site, the CI takes on the 
primary responsibility whether he/she is an investigator at any particular site. 
 
The CI role is to complete and to ensure that all relevant regulatory approvals and confirmations of 
NHS Capacity and Capability are in place before the study begins. Ensure arrangements are in place 
for good study conduct, robust monitoring and reporting, including prompt reporting of incidents, this 
includes putting in place adequate training for study staff to conduct the study as per the protocol and 
relevant standards. 
 
The Chief Investigator is responsible for submission of annual reports as required. The Chief 
Investigator will notify the REC and JRO of the end of the study (including the reasons for  premature 
termination, where applicable). Within one year after the end of study, the Chief Investigator will 
submit a final report with the results, including any publications/abstracts to the REC and JRO.  
 
PRINCIPLE INVESTIGATOR (PI):  Individually or as leader of the researchers at a site; ensuring that 
the study is conducted as per the approved study protocol, and report/notify the relevant parties – 
this includes the CI of any breaches or incidents related to the study. 
 
 
 
 
 
 
 
 
 
 

10 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
 
KEY WORDS 
MRI, magnetic resonance imaging, renal cancer 
 
LIST OF ABBREVIATIONS 
AE 
Adverse event 
CI 
Chief investigator 
CRF 
Case report form 
CRO 
Contract research organisation 
DCE 
Dynamic contrast enhanced 
DWI 
Diffusion weighted imaging 
GCP 
Good Clinical Practice 
ICF 
Informed consent form 
ISF 
Investigator Site File 
IVIM 
Intravoxel incoherent motion 
MDT 
Multi-disciplinary team 
MRI 
Magnetic resonance imaging 
PIS 
Patient information sheet 
RCC 
Renal cell carcinoma 
REC 
Research ethics committee 
RFH 
Royal Free Hospital 
SAE 
Serious adverse event 
SAR 
Serious adverse reaction 
SOP 
Standard operating procedure 
UCL 
University College London 
UCLH 
University College London Hospital 
VERDICT 
Vascular, extracellular and restricted diffusion 
for cytometry in tumours 
 
 
 
 
 
 

11 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
Contents 
 
1. 
SUMMARY .................................................................................................... 13 
2. 
BACKGROUND AND RATIONALE ................................................................... 13 
OUTCOME MEASURES/ENDPOINTS ......................................................................... 16 
2.1 
Primary Objectives ....................................................................................... 16 
2.2 
Secondary Objective(s) ................................................................................. 16 
3. 
TRIAL DESIGN ............................................................................................... 16 
4. 
SAMPLING METHODS ................................................................................... 16 
4.1 
Inclusion criteria ........................................................................................... 16 
4.2 
Exclusion criteria .......................................................................................... 17 
4.4 
Informed Consent ......................................................................................... 18 
5. 
TRIAL PROCEDURES ...................................................................................... 18 
5.1 
Pre-MRI renal function testing ...................................................................... 18 
5.1.1 Intervention Procedures ............................................................................... 18 
5.2 
Material / Samples ....................................................................................... 22 
5.3 
Discontinuation/withdrawal of participants ................................................. 22 
5.4 
Definition of End of Trial ............................................................................... 22 
6. 
FINANCE AND SUPPLY OF EQUIPMENT ......................................................... 23 
7. 
DATA MANAGEMENT ................................................................................... 23 
7.1 
Confidentiality .............................................................................................. 23 
7.2 
Personal Data breaches ................................................................................ 23 
8. 
STATISTICAL CONSIDERATIONS ..................................................................... 24 
9. 
Planned recruitment rate ............................................................................. 24 
10. 
ASSESSMENT AND MANAGEMENT OF RISK ................................................... 24 
11. 
RECORDING AND REPORTING OF ADVERSE EVENTS ...................................... 25 
11.1 
Definitions .................................................................................................... 25 
11.2 
Assessments of Adverse Events .................................................................... 25 
11.2.1 Causality ....................................................................................................... 26 
11.2.2 Expectedness ................................................................................................ 27 
11.2.3 Recording of Adverse Events ........................................................................ 28 

12 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
11.3 
Incidental Findings in Research ..................................................................... 28 
11.4 
Reporting Urgent Safety Measures ............................................................... 28 
11.5 
NHS Serious Incidents and Near Misses ........................................................ 29 
11.6 
Complaints from research participants ......................................................... 29 
12. 
REGULATORY REVIEW AND PATIENT AND PUBLIC INVOLVEMENT ................ 29 
12.1 
Regulatory Review ........................................................................................ 29 
12.2 
Peer Review ................................................................................................. 30 
13. 
MONITORING AND AUDITING ....................................................................... 30 
14. 
TRAINING ..................................................................................................... 31 
15. 
INSURANCE AND INDEMNITY ....................................................................... 31 
16. 
RECORD KEEPING AND ARCHIVING ............................................................... 31 
17. 
INTELLECTUAL PROPERTY ............................................................................. 32 
18. 
PUBLICATION AND DISSEMINATION ............................................................. 32 
19. 
APPENDICES ................................................................................................. 32 
19.1 
APPENDIX 1: Schedule of Assessments ......................................................... 32 
19.2 
APPENDIX 2: Associated Documents ............................................................. 34 
20. 
REFERENCES ................................................................................................. 34 
 
 
 
 
 
 
 
 
 
 
 

13 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
1. SUMMARY 
Renal cancer has the highest mortality rate of any urological cancer. Despite the overall mortality rate 
renal tumours are diverse, presenting with a range of different histological subtypes and nuclear 
grade, ranging from the benign to the highly malignant. Current clinical imaging of renal tumours is 
heavily reliant on computed tomography (CT) which is an accurate technique for tumour detection 
and staging but cannot reliably differentiate tumour types or grade. Percutaneous biopsy is not 
routinely adopted due to concerns of tumour seeding, diagnostic uncertainty and sampling error due 
to intra-tumoral heterogeneity.  
An imaging test that can reliably differentiate between different tumour types and grades would result 
in improved personalised treatment decisions, benefiting patients with renal tumours and potentially 
delivering a considerable saving to the NHS by reducing unnecessary treatment of benign or indolent 
tumours.   
Magnetic resonance imaging (MRI) delivers unique soft tissue contrast and sequences can be designed 
to be sensitive to a wide range of microstructural tissue features. This project aims to develop 
magnetic resonance imaging (MRI) sequences and relate the imaging findings with the underlying 
histology of the tumour. In the future we aim that this will be the foundation of incorporating MRI 
into the clinical management algorithm of renal tumours.  
2. BACKGROUND AND RATIONALE 
Globally there are over 430,000 new cases of renal cancer each year and renal cancer has the highest 
mortality rate of any urological cancer. However, survival is dependent on stage – localised disease 
has a 5-year survival rate of 93% which falls to 12% for metastatic disease. The requirement to treat 
tumours early to maximise the chances of curative treatment meant radical nephrectomy was 
recommended for all solid renal tumours until relatively recently. However, though the increased the 
incidence of small renal tumours, largely as incidental findings on imaging, it has been recognised that 
only ~2% of these have metastatic potential(1). Thus, treatment algorithms have been refined and T1a 
stage renal tumours (≤4 cm) management options now include active surveillance and ablation as well 
as surgical resection. Management is currently decided by shared decision making between clinician 
and patient, informed by population rather than personalised risk of progression. With this approach 
~4% of nephrectomies are being performed with subsequent benign tumour pathology, with 
significant associated mortality, morbidity and expense(2).  
Surgical histology remains the gold standard diagnostic test for renal tumours(3) but imaging is the 
only way to non-invasively sample whole tumours, which is highly desirable in renal tumours which 
demonstrate considerable intra-lesional genetic, metabolic and morphological heterogeneity(4). This 
study aims to develop and apply novel MR methods that permit detailed characterisation of tissue 
function and microstructure to non-invasively characterise tumours.  
 
 
VERDICT (Vascular, Extracellular, Restricted Diffusion for Cytometry in Tumours)  

14 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
The signal in diffusion-weighted MRI (DW-MRI) is generated by detection of the bulk movement of 
water molecules which is influenced by numerous factors including cell size and shape, cell density, 
extracellular volume and vascularity. Many of these tissue features are altered in tumours, particularly 
an increase in cellular density and reduction in the extracellular volume, therefore DW-MRI and a 
calculated apparent diffusion coefficient (ADC) have been used for tumour detection in many different 
organs. Renal tumours, along with most tumours in other organs, typically demonstrate a reduced 
apparent diffusion coefficient (ADC) indicating that water movement is more restricted compared to 
normal tissue and there is limited evidence that this can be useful to differentiate between tumour 
types and grade(5). However, the ADC is an over-simplification of the DWI signal and fails to discrimate 
between the underlying histological changes. The Vascular, Extracellular, Restricted Diffusion for 
Cytometry in Tumours model uses a 3-compartment tissue model designed to account of the main 
histological features of tumours that influence the DWI signal and can estimate specific tissue 
properties such as cell size, intracellular, extracellular – extravascular and intravascular space 
fractions.  
The VERDICT model was developed in colorectal xenograft models where it demonstrated superiority 
to ADC and the intravoxel incoherent motion (IVIM) models. It has since been translated to clinical 
studies of prostate cancer, where a high level of repeatability and particular usefulness in 
differentiating benign and clinically significant but low grade tumours(6, 7).  
Renal tumours are a diverse range of histological subtypes tumour type is important as well as grading. 
DW-MRI and ADC have demonstrated the ability to differentiate between many different types. 
However, one of the critical differentiations, distinguishing clear cell carcinomas from benign 
oncocytomas, is particularly challenging(8). We hypothesise that the improved characterisation of the 
tumour microstructure that VERDICT offers will be be able to differentiate between these two entities.   
Fat fraction and quantitative susceptibility mapping  
Imaging of fat is commonplace in clinical MRI studies, usually using in and out of phase Dixon imaging. 
This allows visual assessment of a loss of signal but inaccurate fat quantification. The modelling based 
on the Dixon method has evolved to account for some of the major confounders including B0 
inhomogeneity, T2* decay and the spectral complexity of the fat signal permitting accurate and 
reproducible fat quantification(9).  
The quantification of fat is an important diagnostic tool for the characterisation of renal tumours. 
Macroscopic fat, visible on CT or fat suppression MRI, is most frequently seen in angiomyolipomas, 
but occasionally RCCs may contain macroscopic fat. Different histological subtypes of RCC 
demonstrate different quantities of triglyceride, cholesterol and glycogen accumulation, for example 
clear cell RCCs are associated with a large lipid rich cytoplasm, which reduces at the higher tumour 
grades(10, 11).  
Fat fraction mapping is calculated using data from a gradient echo sequence. The same acquisition 
can also be used as the raw data for susceptibility mapping. Quantitative susceptibility mapping (QSM) 
is a post processing technique that uses the phase data of the gradient echo acquisition to generate 
maps of tissue magnetic susceptibility. This has the ability to quantitatively differentiate between 

15 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
diamagnetic calcifications and paramagnetic haemorrhage. The majority of QSM studies have been 
performed in the brain, but the feasibility of renal QSM has recently been demonstrated(12). 
Microhaemorrhage are common in papillary and clear cell RCC whilst calcification is most commonly 
associated with clear cell RCC(13).    
Perfusion MRI 
Vascularity is another important differentiator of renal tumour subtypes. Clear cell RCCs are usually 
hypervascular, enhance avidly in the corticomedullary phase before washing out on delayed images. 
Conversely, papillary RCCs are hypovascular and iso- or hypo-enhacing relative to normal renal 
parenchyma.  
 
Two methods are proposed to examine renal tumours. Dynamic contrast enhanced (DCE) MRI 
involves imaging before and after the injection of gadolinium contrast - gadoteridol (ProHance) or 
gadoterate meglumine (Dotarem) - at a dose of 0.1 mmol/kg. DCE MRI is used to identify and classify 
multiple different tumours, perhaps most notably in breast tumours where signal intensity curves are 
routinely used in clinical practice. Multi-timepoint pre- and post-contrast imaging of renal tumours is 
already standard-of-care. Small studies have demonstrated that analysis of the enhancement and 
washout characteristics can differentiate between RCC subtypes and that semi-quantitative 
measurements can be performed reproducibly(14, 15).  
Arterial spin labelling (ASL) is an alternative to DCE-MRI in which blood is magnetically labelled prior 
to entering the kidneys and provides endogenous contrast. It has several advantages in that it doesn’t 
require gadolinium injection and is a quantitative measure of tissue perfusion whereas DCE-MRI 
measurements are dependent on both blood flow and vascular permeability. However, labelling 
efficiency can be variable and the lower signal-to-noise ratio with ASL limits spatial resolution and 
makes detection of low levels of perfusion challenging.  
RCC subtype differentiation has been demonstrated with ASL, both were able to differentiate papillary 
cell RCCs from other subtypes(16). Furthermore, the volume transfer constant (Ktrans) and rate 
constant (Kep) positively correlate with perfusion (PASL) derived from ASL(17).  
The described imaging sequences have all been applied to renal imaging previously. However, with 
the aim being to differentiate between both tumour subtypes and grade, relying on a single sequence 
has produced limited results. For example, perfusion imaging (DCE and ASL MRI) are able to 
differentiate between hypervascular and hypovascular tumours, but can’t reliably subclassify these 
groups or differentiate between tumour grade(16). This is hardly surprising as tumours aren’t 
classified histologically based on a single feature but from a combination of features. For this reason 
this study aims to develop a multi-parametric imaging protocol that is able to identify multiple 
microstructural features of renal tumours.  
 
Co-registration of histology to in vivo imaging  
 
A vital component of validation of functional and microstructural imaging findings is relating them to 
the underlying histological features. Renal tumours are often large and heterogeneous. Complex 

16 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
methods of co-registration have been described(18). For this pilot study we will perform imaging 
sequences in the same plane as the histological sectioning plane and provide coordinates from the 
MRI for targeted sampling of the tumour.  
OUTCOME MEASURES/ENDPOINTS 
2.1 Primary Objectives 
1. To develop novel MRI sequences and techniques for functional and microstructural 
characterisation of renal tumours.  
2.2 Secondary Objective(s) 
1. The biological validation of MR imaging biomarkers by correlation with histology.  
2. To demonstrate the repeatability of quantitative and qualitative MR imaging biomarkers of 
renal tumours.  
3. To use the pilot combined imaging and histological dataset to plan and power a subsequent 
clinical validation study. 
3. TRIAL DESIGN 
The study is a prospective cohort study in which participants will be scanned prior to surgery. Where 
possible scans will be performed as part of the patient’s routine clinical care to minimise the burden 
on participants in terms of additional hospital visits.  
The study duration will be 24 months.  
Imaging in this study will take place at University College London Hospital. Patients may be referred 
from MDTs and urology clinics from The Royal Free Hospital and all surgery and histopathology will be 
performed at Royal Free Hospital.  
4. SAMPLING METHODS 
4.1 Inclusion criteria 
Patient volunteers will be recruited if they meet the following inclusion criteria:  
1) Aged 18 and over 
2) Confirmed renal tumour ≤ 7 cm planned for surgical resection 
3) Willing and able to provide written informed consent 
4) Able to lie supine for the duration of an MRI 

17 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
4.2 Exclusion criteria 
1) Contraindication to MRI e.g., cardiac pacemaker 
2) Contraindication to MR contrast agents 
3) Pregnancy 
4) Breastfeeding 
5) Deranged renal function (eGFR <30) in the last three months.  
6) Previous treatment of the renal tumour e.g., ablation, radiotherapy 
 
4.3 Recruitment 
Patient volunteers will be recruited in one of the following ways:  
a. Identification at the relevant multidisciplinary team meeting 
i. 
Patients eligible for the study may be identified at the multidisciplinary meetings 
involving clinicians and radiology members of the research team.  
b. Direct referral from clinical colleagues 
i. 
Patients may be identified at outpatient clinics or as inpatients at Royal Free Hospital. 
A discussion between the research team and the clinical team will be held and the 
eligible patients’ suitability will be assessed. The MRI scan will only be booked after 
the patient has given his or her consent to participate in the study.  
 
Patient information sheet (PIS)  
 
Eligible participants would be identified by a trained member of the research team, clinical team from 
clinic or at relevant MDTs. Prospective study team members would be trained on the RIM study and 
would sign the study delegation log. They would then be able to approach participants and enrol them 
for the study. These study members would also be GCP trained and able to consent trial participants. 
Participants will be contacted by a member of the clinical team in person or on the telephone, or sent 
a letter inviting them to take part. The patient information sheet (appendix) will be sent to them by 
post or email. If agreeable, MRI appointment will be made by the research team (if not already been 
made as part of their routine investigation or standard of care). For new MRI bookings, patient consent 
would be sought before arranging this booking. When attending for the MRI, a member of the clinical 
team (radiographer, nurse, doctor or medial physicist) will confirm the desire of the patient to join the 
study and if agreeable, together they will sign the informed consent document. Participants may be 
asked to fast (for at least 8 h) before their scan. This information is already provided in the PIS and 
they would be given at least 24 h to decide before their enrolment in the study. Patient will usually be 
consented on the morning of the scan.  
 
Participant recruitment at a site will only commence when the trial has:  
1. Been confirmed by the Sponsor (or it’s delegated representative), and  
2. Been issued with Confirmation of Capacity and Capability from each participating site (where 
applicable). 

18 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
4.4 Informed Consent 
 
All participants will receive information more than 24 hours prior to inclusion in the study and signing 
the informed consent documents. Consent would be obtained by a member of the research team who 
has been trained in obtaining informed consent. He/she will go through the patient information sheet 
with the patient and provide an opportunity to ask questions and to opt in/out of the study. 
The Investigator or designee will explain that participants are under no obligation to enter the trial 
and that they can withdraw at any time during the trial, without having to give a reason and without 
prejudicing his/her further treatment. Data and samples collected up to the point of withdrawal can 
only be used after withdrawal if the participant has consented for this.  
A copy of the signed Informed Consent form will be given to the participant.  The original signed form 
will be retained in the Investigator Site File and a copy placed in the medical records. 
The PIS and consent form will be reviewed and updated if necessary throughout the trial (e.g., where 
new safety information becomes available) and participants will be re-consented as appropriate.  
5. TRIAL PROCEDURES 
5.1 Pre-MRI renal function testing 
Renal impairment with an eGFR <30 ml/min is a relative contraindication to many imaging contrast 
agents. Renal tests performed in the last 3 months as part of routine standard of care will be used to 
check renal function.   
5.1.1 Intervention Procedures 
Patients with renal tumours will undergo an MRI study which will last a maximum of one hour. 
5.1.2 Study 1: Histopathological validation of a renal VERDICT model 
 
5.1.2.1 
Primary objective:  
To define the histopathological tissue characteristics of renal tumours to adapt and 
optimise the VERDICT model. 
 
5.1.2.2 
Method 
Histology from a range of tumours from the major subtypes e.g., clear cell, papillary, chromophobe 
and oncocytoma, will be analysed to estimate the common differential tissue patterns. Key 
components to understand include determining mean cell diameter and shape, extracellular space 
area and anisotropy and vascular area. The VERDICT model is highly adaptable and adaptation to 
reflect the underlying histopathology is an important step of validation and improving its 

19 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
performance. Histopathological samples from 20 patients who have had renal tumours resected with 
known histopathology results will be accessed from the Royal Free Hospital Histology Biobank 
(Characterisation of the immunological and biological markers of Renal cancer progression REC 
reference: 16/WS/0039). New sections will be cut, and undergo staining ± immunohistochemistry e.g., 
haemotoxylin and eosin (H&E) staining and IHC with a vascular marker e.g., CD34. 
 
Slides will be pseudo-anonymised, digitised and the data analysed and stored on UCL computers.  
 
5.1.3 Study 2: Multi-parametric renal microstructural imaging 
 
5.1.3.1 
Primary objective 
• 
To develop and optimise multi-parametric microstructural and functional MRI to characterise 
renal tumours.  
 
5.1.3.2 
Secondary objectives 
• 
Spatial comparison of MRI and histology to pilot biological validation of quantitative and 
qualitative MRI biomarkers. 
 
5.1.3.3 
Method 
10 participants will be identified according to the study criteria and whom are planned for surgery at 
the Royal Free Hospital will be identified from weekly MDT meetings and urology clinics at Royal Free 
Hospital. Eligible participants will be contacted in person or by telephone and entered into a screening 
log kept on a secure NHS OneDrive account. Patients who satisfy the inclusion and exclusion criteria 
will be invited to have an MRI scan at University College Hospital University College London Hospital 
prior to their surgery and provided with an invitation letter, participant information sheet (PIS) and 
copy of the consent form a minimum of 24 h in advance by email or in person.   
Consent will be obtained for scans at the time of attendance for the MRI scan by the investigator or a 
designee. They will explain that participants are under no obligation to partake or provide a reason 
for declining to partake in the study. A copy of the signed consent form will be provided to the patient.  
MRI will be performed in a 3T MRI scanner at UCLH and routine clinical safety procedures followed. 
3D multi-parametric MRI of the kidney(s) will include the following sequences: 
• 
Localisation imaging 
• 
Anatomical T2-weighted imaging 
• 
Diffusion imaging with multiple b-values for VERDICT modelling. 
• 
3D gradient echo imaging (fat fraction, T2* and quantitative susceptibility mapping) 
• 
Perfusion imaging using dynamic contrast enhanced (DCE) MRI and/or arterial spin labelling 
(ASL).  

20 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
Patients will receive an intravenous injection of gadolinium contrast at a dose of 0.1 mmol/kg via an 
intravenous cannula for DCE-MRI. This is standard-of-care for clinical MRI of the kidneys (and many 
other body parts).   
MRI images will be pseudo-anonymised and analysed offline. CT scans performed as part of the 
patients routine clinical care will be obtained from the local PACS (UCLH / RFH), pseudo-anonymised 
and analysed in conjunction with the MRI scans offline. 
Partial or radical nephrectomy will be performed as part of the patient’s clinical care. The sample will 
be bi-valved as part of routine histopathological procedure. From the MRI imaging the tumour position 
will be coordinated and sections taken of the tumour in the coronal plane. Where possible a coronal 
sections of the whole tumour will be taken. Where tumour size makes this impossible, blocks from a 
defined location will be taken. A fresh frozen tissue sample will be cryosectioned and stained with oil 
red O for lipid quantification. Haematoxylin and eosin (H&E) staining and CD34 immunohistochemistry 
for vascular endothelial cells will be performed on fixed tissue sections.  
5.1.3.4 
Patient pathway 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

21 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
5.1.4 Study 3: Repeatability of microstructural imaging 
5.1.4.1 
Primary objective:  
To determine the repeatability of microstructural imaging sequences.  
 
5.1.4.2 
Method 
10 patients who meet the study criteria will be identified from weekly MDT meetings and urology 
clinics at Royal Free and University College Hospitals. Eligible participants will be contacted in person 
or by telephone and entered into a screening log kept on a secure NHS computer within the NHS 
firewall. Patients will be invited to have two MRI scans repeated ≤ 14 d apart. All patients will be 
provided with a participant information sheet (PIS) and copy of the consent form a minimum of 24 h 
in advance.   
Consent will be obtained for scans at the time of attendance for the MRI scan by the investigator or a 
designee. They will explain that participants are under no obligation to partake or provide a reason 
for declining to partake in the study and are able to withdraw at any time. A copy of the signed consent 
form will be provided to the patient.  
MRI will be performed in a 3T MRI scanner at UCL/UCLH and routine clinical safety procedures 
followed. 3D multi-parametric MRI of the kidney(s) will include the following sequences: 
• 
Localisation imaging 
• 
Anatomical T2-weighted imaging 
• 
Diffusion imaging with multiple b-values for VERDICT modelling. 
• 
3D gradient echo imaging (fat fraction, T2* and quantitative susceptibility mapping) 
• 
Perfusion imaging using dynamic contrast enhanced (DCE) MRI and/or arterial spin labelling 
(ASL).  
Patients will receive an intravenous injection of gadolinium contrast at a dose of 0.1 mmol/kg via an 
intravenous cannula for DCE-MRI. Gadolinium is standard-of-care for clinical MRI of the kidneys (and 
many other body parts).   
Each patient will have a repeat scan performed with the same protocol ≤ 14 days.  
MRI images will be pseudo-anonymised and analysed offline. 

22 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
5.1.4.3 
Patient pathway 
5.2 Material / Samples 
Pseudo-anonymised data (MRIs, CTs, digitalised histopathology sections and patient information such 
as tumour type and grade) will be stored in university (UCL) computers.  
 
The Royal Free Hospital NHS Trust will process, store and dispose of histopathological sections from 
nephrectomy specimens as part of routine clinical practice in accordance with all applicable legal and 
regulatory requirements, including the Human Tissue Act 2004 and any amendments thereto. 
5.3 Discontinuation/withdrawal of participants 
Reasonable travel expenses will be covered and participants given a £10 Amazon voucher as a token 
of appreciation. Participants may withdraw from the study at any time and without giving a reason 
without this affecting their clinical care or legal rights.   
5.4 Definition of End of Trial 
For the prospective dataset collection we will consider the end of the study as the recruitment of the 
last patient. UCL BRC project funding ends 24 months after the project begins. Linked anonymised 

23 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
data will be securely stored on University computers for 20 years to enable potential long-term 
predictions of survival and tumour recurrence. 
6. FINANCE AND SUPPLY OF EQUIPMENT 
The research costs for the study have been supported by NIHR University College London Hospitals 
Biomedical Research Centre (BRC1125/HEI/RH/110410). Value: £48, 712.  
7. DATA MANAGEMENT 
7.1 Confidentiality 
The study is compliant with the requirements of the General Data Protection Regulation (2016/679) 
and the UK Data Protection Act (2018). All Investigators and study site staff will comply with the 
requirements of the General Data Protection Regulation (2016/679) with regards to the collection, 
storage, processing and disclosure of personal information, and will uphold the Act’s core principles. 
UCL is the data controller; the UCL Data Protection Officer -  data-protection@ucl.ac.uk The data 
processors are Richard Hesketh.  
 
Only clinicians involved in the direct care of the patient will have access to personal information. The 
clinician will enter pseudo-anonymised data on to a database which will only be accessible by 
researchers in the research team. The ‘key’ which will have study numbers associated with the 
patient’s hospital number will be stored on secure NHS computers at UCLH, only accessible by clinical 
fellows and the chief investigator using a password.  
 
Patient consent forms will be held in locked desks at UCLH. Only the Principal Investigator and the 
nominated Clinical Research Fellow(s) working on the project at RFH / UCLH will have access to this 
information. Patients on the pseudo-anonymised database will have a study number and relevant 
clinical information about their renal tumour. This information will include the patient’s age, clinical 
details about renal cancer (location, histopathology results, blood tests). The pseudo-anonymised 
database will be stored on UCL computers, which will also be password protected. Similarly, all data 
stored in UCL computers will be anonymised.  
7.2 Personal Data breaches 
Personal data breaches will be immediately reported to the UCL Information Security Group (ISG) and 
the UCL Data Protection Officer, and to the Sponsor via the UCL JRO research incident reporting form 
(as per form and guidance: https://www.ucl.ac.uk/legal-services/guidance/reporting-loss-personal-
data). The following information will be provided: full details as to the nature of the breach, an 
indication as to the volume of material involved, and the sensitivity of the breach (and any timeframes 
that apply). Sites will additionally follow their Trust incident reporting mechanisms, and will document 
this within their TMF/ISFs. 

24 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
8. STATISTICAL CONSIDERATIONS  
This study is developing novel imaging techniques at a pilot / proof of concept stage. At this stage 
there isn’t a significant statistical requirement and any statistical analysis required will be performed 
in house.  
As many of the imaging techniques have had limited use in renal imaging there are no data from which 
to reliably calculate a sample size. However, we will be developing the technology iteratively and will 
use the findings from this study to inform and power future studies.  
9. Planned recruitment rate 
We anticipate to be able to recruit two patients per month.  
10. ASSESSMENT AND MANAGEMENT OF RISK 
We do not anticipate significant risks for the participants associated to the study. The main risks are 
associated with the additional MRI acquired.  
 
MRI is a safe technique and the scans performed in this study will follow routine clinical procedures 
and using clinical equipment. Patients will be screened by a trained radiographer to ensure that no 
risks are introduced e.g., metallic objects being brought into the magnetic field of the scanner. Patients 
will wear earplugs and headphones during the MRI scan to protect from the loud noises generated.  
 
Patients may receive a gadolinium contrast injection which is routinely used in clinical MRI scans of 
multiple body sites including the kidneys. It is associated with a very low rate of immediate adverse 
events (0.06-0.09%) and most adverse events are mild e.g., nausea and vomiting. The incidence of 
acute, severe allergic reactions is estimated to be 0.0025-0.005%(19). Trained medical personnel will 
always be present to manage this situation. While the patient is in the MRI scanner regular contact 
will be made between the research team in the control room and the patient. Patients will hold an 
emergency call button to raise attention or terminate the scan if required.  
 
The scanner software employs a series of safety checks to ensure that any specific set of scan 
parameters are safe to use. A local institutional quality control procedure is in place locally and will be 
used to approve any modifications to the pulse sequence software. Specifically, all code modifications 
are independently checked by two experienced physicists to ensure that:  
• 
All code modifications are fully documented 
• 
All software safety checks are still carried out 
• 
Code modifications do not affect the validity of these software checks 
• 
A risk assessment is produced for each approved set of code modifications to show that the 
manufacturer’s calculations of physiological effects remain valid. 
 
All RFH, UCLH and UCL individuals involved in this study will have received the adequate health and 
safety training regarding MRI and tissue handling. Therefore, we do not foresee any potential risk 
given that all protocols are followed accurately. Well established procedures are in place at RFH, UCLH 
and UCL to cope with the unlikely event of a breach of health and safety protocols.  

25 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
11. RECORDING AND REPORTING OF ADVERSE EVENTS 
11.1  Definitions 
Term 
Definition 
Adverse Event (AE) 
Any untoward medical occurrence in a patient or trial participant, 
which does not necessarily have a causal relationship with the 
intervention involved.  
Serious Adverse Event 
(SAE). 
Any adverse event that: 
• 
results in death, 
• 
is life-threatening*, 
• 
requires 
hospitalisation 
or 
prolongation 
of 
existing 
hospitalisation**, 
• 
results in persistent or significant disability or incapacity, or 
• 
consists of a congenital anomaly or birth defect. 
• 
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 
*     A life- threatening event, this refers to an event in which the participant was at risk of death 
at the time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe. 
** Hospitalisation is defined as an in-patient admission, regardless of length of stay. 
Hospitalisation for pre-existing conditions, including elective procedures do not constitute an SAE. 
 
11.2  Assessments of Adverse Events 
Each adverse event (AEs) will be assessed for severity, causality, seriousness and expectedness as 
described below. 
Category 
Definition 

26 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
Mild 
The adverse event does not interfere with the participant’s daily routine, and 
does not require further intervention; it causes slight discomfort 
Moderate 
The adverse event interferes with some aspects of the participant’s routine, or 
requires further intervention, but is not damaging to health; it causes 
moderate discomfort 
Severe 
The adverse event results in alteration, discomfort or disability which is clearly 
damaging to health 
 
11.2.1 Causality 
The assessment of relationship of adverse events to the intervention is a clinical decision made by 
the Investigator (or delegated medically qualified person) based on all available information at the 
time of the completion of the case report form.   
If a differentiated causality assessment which includes other factors in the trial is deemed 
appropriate, please add/amend the following wording to specify: 
It is of particular importance in this trial to capture events related to the MRI scan. The assessment 
of relationship of an adverse event to this/these additional safety issue(s) will also be carried out as 
part of the trial.  
The differentiated causality assessments will be captured in the study specific SAE form.   
The following categories will be used to define the causality of the adverse event: 
 
Category 
Definition 
Definitely 
There is clear evidence to suggest a causal relationship and other possible 
contributing factors can be ruled out. 

27 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
Probably 
There is evidence to suggest a causal relationship and the influence of other 
factors is unlikely. 
Possibly 
There is some evidence to suggest a causal relationship (e.g. the event 
occurred within a reasonable time after administration of the study 
procedure). However, the influence of other factors may have contributed to 
the event (e.g. the participant’s clinical condition, other concomitant events). 
Related 
A causal relationship between the intervention and an adverse event is at 
least a reasonable possibility, i.e., the relationship cannot be ruled out. 
Not related 
There is no reasonable possibility of a causal relationship between the 
intervention and an adverse event. 
Not Assessable 
Unable to assess on information available. 
 
11.2.2 Expectedness 
All SAEs assigned by the Investigator or delegate as suspected to be related to the intervention will 
be assessed for expectedness against the current SmPC or clearly defined in this protocol. 
Category 
Definition 
Expected 
An adverse event which is consistent with the information about the 
intervention listed in the section 10 of this protocol.  
Unexpected 
An adverse event which is not consistent with the information about the 
intervention listed in the MRI instruction manual or clearly defined in this 
protocol. 
* This includes listed events that are more frequently reported or more severe than previously 
reported. 

28 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
11.2.3 Recording of Adverse Events 
All adverse events within the first 24 h following an MRI scan will be recorded in the CRF following 
consent.  
Procedures for recording and reporting Serious Adverse Events (SAEs) 
All serious adverse events will be recorded in the medical records and the CRF, and the sponsor’s SAE 
log. The CI/PI or designated individual will complete an SAE form and the form will be preferably 
emailed to the Sponsor within 5 working days of becoming aware of the event. The Chief or Principal 
Investigator will respond to any SAE queries raised by the sponsor as soon as possible. Where the 
event is unexpected and thought to be related to the procedure this must be reported by the 
Investigator to the Health Research Authority within 15 days. 
All SAEs will be reported to the Sponsor within 24 hours of becoming aware. The CI/PI or designated 
individual 
will 
complete 
the 
Sponsor’s 
online 
Research 
Incident 
Reporting 
Form 
(https://redcap.slms.ucl.ac.uk/surveys/?s=NE5dypTdFo) within 24 hours of becoming aware of the 
event. The Chief or Principal Investigator will respond to any SAE queries raised by the Sponsor as soon 
as possible.  
Where the SAE is unexpected and thought to be related to the intervention, this must be reported by 
the Investigator to the main REC that approved the study within 15 days of the Investigator becoming 
aware of the event, using the non-CTIMP safety report to REC form. This form can be found on the 
HRA 
website: 
https://www.hra.nhs.uk/approvals-amendments/managing-your-approval/safety-
reporting/. The Sponsor should be copied into this, so they are aware. Discuss with the JRO Quality 
Assurance team in the first instance. 
Follow-up 
SAE 
reports 
(clearly 
marked 
as 
follow-up) 
will 
be 
completed 
via 
https://redcap.slms.ucl.ac.uk/surveys/?s=NE5dypTdFo and submitted to the JRO as further 
information becomes available.  
11.3 Incidental Findings in Research 
In the event that a clinically significant and unexpected finding is found on MRI e.g., 
unexpected cancer or suspicious lesion, the clinical team will be directly informed by the 
investigator. In addition, any such findings will be recorded on the standard clinical MRI report 
on the trust’s radiology reporting system.  
11.4 Reporting Urgent Safety Measures 
If any urgent safety measures are taken the CI/ PI shall immediately and in any event no later than 3 
days from the date the measures are taken, give written notice in the form of a substantial 
amendment to the relevant REC and Sponsor of the measures taken and the circumstances giving rise 
to those measures. 

29 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
11.5 NHS Serious Incidents and Near Misses 
A serious incident or near miss is any unintended or unexpected event that could have or did lead to 
harm, loss or damage that contains one or more of the following components: 
a. It is an accident or other incident which results in injury or ill health. 
b. It is contrary to specified or expected standard of patient care or service. 
c. It places patients, staff members, visitors, contractors or members of the public at unnecessary risk. 
d. It puts the Trust in an adverse position with potential loss of reputation. 
e. It puts Trust property or assets in an adverse position or at risk. 
Serious Incidents and near misses will be reported to the Sponsor and Trust Quality & Safety 
department as soon as the study team becomes aware of them.  
11.6 Complaints from research participants 
In the first instance, research participant complaints (patients or health volunteers) will be reported 
to the CI/PI to investigate, as documented in the patient information sheet(s), and to the Sponsor via 
research-incidents@ucl.ac.uk, following the UCL Complaints from Research Subjects about UCL 
Sponsored Studies and Trials policy. For participants who are NHS patients, complaints will be reported 
to the NHS Complaints Manager at the Trust where the recruitment and study procedures were 
undertaken. Complaints from NHS patients are handled under NHS complaints policies and 
procedures, with involvement from PALS and the Sponsor where necessary.  
12. REGULATORY REVIEW AND PATIENT AND PUBLIC INVOLVEMENT 
12.1 Regulatory Review 
The Sponsor will ensure that the trial protocol, participant information sheet, consent form, GP letter 
and submitted supporting documents have been approved by the appropriate research ethics 
committee, prior to any participant recruitment. The protocol, all other supporting documents 
including and agreed amendments, will be documented and submitted for ethical and regulatory 
approval as required. Amendments will not be implemented prior to receipt of the required 
approval(s).  
The study was deemed to require regulatory approval from the following bodies NHS REC Favourable 
Opinion and HRA Approval). Before any site can enrol patients into the study, the Chief 
Investigator/Principal Investigator or designee will ensure that the appropriate regulatory approvals 
have been issued, and NHS Confirmations of Capacity and Capability and Sponsor green lights are in 
place. 
 
For any amendments to the study, the Chief Investigator or designee, in agreement with the Sponsor, 
will submit information to the appropriate body in order for them to issue approval for the 
amendment. The Chief Investigator or designee will work with sites (R&D departments as well as the 
study delivery team) to confirm ongoing Capacity and Capability for the study. 
 

30 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
All correspondence with the Sponsor, REC and HRA will be retained.  The Chief Investigator will notify 
the Sponsor and REC of the end of the study. 
 
It is the Chief Investigator’s responsibility to produce the annual progress reports when required; an 
annual progress report (APR) will be submitted to the Sponsor and REC within 30 days of the 
anniversary date on which the favourable opinion was issued, and annually until the study is declared 
ended. 
 
Within 90 days after the end of the trial, the CI will ensure that the main REC is notified that the trial 
has finished.  If the trial is terminated prematurely, those reports will be made within 15 days after 
the end of the trial. 
 
Within one year after the end of the study, the Chief Investigator will submit a final report with the 
results, including any publications/abstracts, to the Sponsor and to the REC and HRA. 
 
12.2 Peer Review 
The study has been independently peer reviewed as part of the procedure for obtaining funding from 
(NIHR UCLH/UCL Biomedical Research Centre). 
13. MONITORING AND AUDITING 
A trial specific oversight and monitoring plan will be established for studies. The trial will be monitored 
in accordance with the agreed plan. The degree of monitoring will be proportionate to the risks 
associated with the trial.  Risk will be assessed on an ongoing basis by the Chief Investigator, and 
adjustments made accordingly (in conjunction with the Sponsor). 
 
The Chief Investigator will be responsible for the day to day monitoring and management of the study. 
The Chief Investigator will ensure there are adequate quality and number of monitoring activities 
conducted by the study team. This will include adherence to the protocol, procedures for consenting 
and ensure adequate data quality.  
 
The Chief Investigator will inform the Sponsor should he/she have concerns which have arisen from 
monitoring activities, and/or if there are problems with oversight/monitoring procedures. 
 
The UCLH/UCL Joint Research Office, on behalf of UCL as Sponsor, will conduct random audits on a 
selection of studies in its clinical research portfolio. Monitoring and auditing will be conducted in 
accordance with the UK Policy Framework for Health and Social Care Research, and in accordance with 
the Sponsor’s monitoring and audit policies and procedures.  
 

31 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
14. TRAINING 
The Chief Investigator will review and provide assurances of the training and experience of all staff 
working on this study.  Appropriate training records will be maintained in the study files. 
 
 
All site staff must be appropriately qualified by education, training and experience to perform the trial 
related duties allocated to them, which must be recorded on the site delegation log. CVs for all staff 
must be kept up-to-date, signed and dated copies held in the Investigator Site File (ISF).  
15. INSURANCE AND INDEMNITY 
University College London holds insurance against claims from participants for harm caused by their 
participation in this clinical study. Participants may be able to claim compensation if they can prove 
that UCL has been negligent. However, as this clinical study is being carried out in a hospital, the 
hospital continues to have a duty of care to the participant of the clinical study. University College 
London does not accept liability for any breach in the hospital’s duty of care, or any negligence on the 
part of hospital employees. This applies whether the hospital is an NHS Trust or otherwise.  
 
Participants may also be able to claim compensation for injury caused by participation in this clinical 
study without the need to prove negligence on the part of University College London or another party. 
Participants who sustain injury and wish to make a claim for compensation should be advised to do so 
in writing in the first instance to the Chief Investigator, who will pass the claim to the Sponsor’s 
Insurers, via the Sponsor’s office. 
 
Hospitals selected to participate in this clinical study shall provide clinical negligence insurance cover 
for harm caused by their employees and a copy of the relevant insurance policy or summary shall be 
provided to University College London upon request. 
 
Additionally, UCL does not accept liability for sites such as GP surgeries in primary care; 
investigators/collaborators based in these types of sites must ensure that their activity on the study is 
covered under their own professional indemnity. 
 
16. RECORD KEEPING AND ARCHIVING 
UCL and each participating site recognise that there is an obligation to archive study-related 
documents at the end of the study (as such end is defined within this protocol). The Chief Investigator 
confirms that he/she will archive the Trial Master File at University College London for the period 
stipulated in the protocol and in line with all relevant legal and statutory requirements. The Principal 
Investigator at each participating site agrees to archive his/her respective site’s study documents in 
line with all relevant legal and statutory requirements. Study documents will be archived for a 
minimum of 5 years from the study end, and no longer than 20 years from the study end. 
The Trial Master File will be archived at UCL, in accordance with the UCL Retentions Schedule. It will 
be archived for a minimum of 5 years from the study end, and no longer than 20 years from study end.  

32 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
17. INTELLECTUAL PROPERTY 
All background intellectual property rights (including licences) and know-how used in connection with 
the study shall remain the property of the party introducing the same and the exercise of such rights 
for purposes of the study shall not infringe any third party’s rights. 
 
All intellectual property rights and know-how in the protocol, the study data and in the results arising 
directly from the study, but excluding all improvements thereto or clinical procedures developed or 
used independently of the study by each participating site, shall belong to UCL. All intellectual 
property rights deriving or arising from the material or any derivations of the material provided to UCL 
by the participating site shall belong to UCL. Each participating site agrees that by giving approval to 
conduct the study at its respective site, it agrees hereby to effectively assign all such intellectual 
property rights (“IPR”) to UCL and to disclose all such know-how to UCL.  
 
Each participating site agrees to, at the request and expense of UCL execute all such documents and 
do all acts necessary to fully vest the IPR in UCL.  
 
Nothing in this section shall be construed so as to prevent or hinder the participating site from using 
know-how gained during the performance of the study in the furtherance of its normal activities of 
providing or commissioning clinical services, teaching and research to the extent that such use does 
not result in the disclosure or misuse of confidential information or the infringement of an intellectual 
property right of UCL or its funder.  This does not permit the disclosure of any of the results of the 
study, all of which remain confidential. 
18. PUBLICATION AND DISSEMINATION  
The analysis of results and dissemination of findings will be performed via:  
a) Technical conference presentations. Scientific developments and validation results will be 
presented regularly throughout the project at international conferences directed at the 
imaging and oncology scientific communities e.g., ISMRM, RSNA, ASCO and ECR.  
b) Technical journal publications. Major methodological developments will be published in 
technical journals e.g., Magnetic Resonance in Medicine.  
c) Public engagement (as detailed in section 12.3).  
 
19. APPENDICES 
19.1 APPENDIX 1: Schedule of Assessments 
Study schedule for RIM - Substudy 2 
  
  
  
  
Visit 1 
EoT 
  
Informed Consent 
x 
  
  

33 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
Inclusion/Exclusion Criteria 
x 
  
  
Medical History 
x 
  
  
Concomitant Medications review 
x 
  
  
mpMRI 
x 
  
  
Adverse Event assessment 
x 
x 
  
Study Data Collection 
x 
x 
  
  
  
  
  
Study schedule for RIM - Substudy 3 
  
  
  
  
Visit 1 (day 
0) 
Visit 2 (day ≤14) 
EoT 
Informed Consent 
x 
  
  
Inclusion/Exclusion Criteria 
x 
  
  
Medical History 
x 
x 
  
Concomitant Medications review 
x 
x 
  
mpMRI 
x 
x 
  
Adverse Event assessment 
x 
x 
x 
Study Data Collection 
x 
x 
x 
  
  
  
  
  
  
  
  
Abbreviations 
  
  
  
D - Day 
  
  
  
SoC - Standard of care 
  
  
  
EoT - End of Trial 
  
  
  
W - week 
  
  
  
t - Telephone call 
  
  
  
 
 
 
 
 
 

34 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
19.2 APPENDIX 2: Associated Documents 
 
Document Name 
Document Version 
Document Date 
 
 
 
ICF 
Draft 
03/10/2023 
 
PIS 
Draft 
03/10/2023 
GP Letter 
Draft 
03/10/2023 
Incidental findings 
letter 
 
Draft 
03/10/2023 
Schedule of Events 
Draft 
25/10/2023 
 
SOECAT 
Draft 
25/10/2023 
 
 
 
 
20. REFERENCES 
References 
 
1. 
Smaldone MC, Kutikov A, Egleston BL, Canter DJ, Viterbo R, Chen DY, et al. Small 
renal masses progressing to metastases under active surveillance: a systematic review and 
pooled analysis. Cancer. 2012;118(4):997-1006. 
2. 
Neves JB, Withington J, Fowler S, Patki P, Barod R, Mumtaz F, et al. Contemporary 
surgical management of renal oncocytoma: a nation's outcome. BJU Int. 2018;121(6):893-9. 
3. 
Fuhrman SA, Lasky LC, Limas C. Prognostic significance of morphologic parameters 
in renal cell carcinoma. Am J Surg Pathol. 1982;6(7):655-63. 
4. 
Beksac AT, Paulucci DJ, Blum KA, Yadav SS, Sfakianos JP, Badani KK. 
Heterogeneity in renal cell carcinoma. Urol Oncol. 2017;35(8):507-15. 
5. 
Sandrasegaran K, Sundaram CP, Ramaswamy R, Akisik FM, Rydberg MP, Lin C, 
Aisen AM. Usefulness of diffusion-weighted imaging in the evaluation of renal masses. AJR 
Am J Roentgenol. 2010;194(2):438-45. 
6. 
Panagiotaki E, Chan RW, Dikaios N, Ahmed HU, O'Callaghan J, Freeman A, et al. 
Microstructural characterization of normal and malignant human prostate tissue with 
vascular, extracellular, and restricted diffusion for cytometry in tumours magnetic resonance 
imaging. Invest Radiol. 2015;50(4):218-27. 
7. 
Singh S, Rogers H, Kanber B, Clemente J, Pye H, Johnston EW, et al. Avoiding 
Unnecessary Biopsy after Multiparametric Prostate MRI with VERDICT Analysis: The 
INNOVATE Study. Radiology. 2022;305(3):623-30. 
8. 
Hotker AM, Mazaheri Y, Wibmer A, Zheng J, Moskowitz CS, Tickoo SK, et al. Use 
of DWI in the Differentiation of Renal Cortical Tumors. AJR Am J Roentgenol. 
2016;206(1):100-5. 

35 
Renal tumour Imaging using MRI (RIM); EDGE (sponsor) number 162190; IRAS 
number 323984; Protocol v1.1, 21/03/2024   
  
 
9. 
Reeder SB, Pineda AR, Wen Z, Shimakawa A, Yu H, Brittain JH, et al. Iterative 
decomposition of water and fat with echo asymmetry and least-squares estimation (IDEAL): 
application with fast spin-echo imaging. Magn Reson Med. 2005;54(3):636-44. 
10. 
Zhang Y, Udayakumar D, Cai L, Hu Z, Kapur P, Kho EY, et al. Addressing metabolic 
heterogeneity in clear cell renal cell carcinoma with quantitative Dixon MRI. JCI Insight. 
2017;2(15). 
11. 
Sun J, Xing Z, Chen J, Zha T, Cao Y, Zhang D, et al. Fat status detection and 
histotypes differentiation in solid renal masses using Dixon technique. Clin Imaging. 
2018;51:12-22. 
12. 
Bechler E, Stabinska J, Thiel T, Jasse J, Zukovs R, Valentin B, et al. Feasibility of 
quantitative susceptibility mapping (QSM) of the human kidney. MAGMA. 2021;34(3):389-
97. 
13. 
Xing W, He X, Kassir MA, Chen J, Ding J, Sun J, et al. Evaluating hemorrhage in 
renal cell carcinoma using susceptibility weighted imaging. PLoS One. 2013;8(2):e57691. 
14. 
Wang H, Su Z, Ye H, Xu X, Sun Z, Li L, et al. Reproducibility of Dynamic Contrast-
Enhanced MRI in Renal Cell Carcinoma: A Prospective Analysis on Intra- and Interobserver 
and Scan-Rescan Performance of Pharmacokinetic Parameters. Medicine (Baltimore). 
2015;94(37):e1529. 
15. 
Sun MR, Ngo L, Genega EM, Atkins MB, Finn ME, Rofsky NM, Pedrosa I. Renal 
cell carcinoma: dynamic contrast-enhanced MR imaging for differentiation of tumor 
subtypes--correlation with pathologic findings. Radiology. 2009;250(3):793-802. 
16. 
Lanzman RS, Robson PM, Sun MR, Patel AD, Mentore K, Wagner AA, et al. Arterial 
spin-labeling MR imaging of renal masses: correlation with histopathologic findings. 
Radiology. 2012;265(3):799-808. 
17. 
Zhang Y, Kapur P, Yuan Q, Xi Y, Carvo I, Signoretti S, et al. Tumor Vascularity in 
Renal Masses: Correlation of Arterial Spin-Labeled and Dynamic Contrast-Enhanced 
Magnetic Resonance Imaging Assessments. Clin Genitourin Cancer. 2016;14(1):e25-36. 
18. 
Crispin-Ortuzar M, Gehrung M, Ursprung S, Gill AB, Warren AY, Beer L, et al. 
Three-Dimensional Printed Molds for Image-Guided Surgical Biopsies: An Open Source 
Computational Platform. JCO Clin Cancer Inform. 2020;4:736-48. 
19. 
Radiologists RCo. BFCR(19)4: Guidance on gadolinium-based contrast agent 
administration to adult patients. 2019.