Use of PET-MR in Head and Neck Cancer Patients - Diagnostic and Therapeutic Applications
Phase: NA
Conditions: Head and Neck Cancer
Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

                                
                           
  
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Research Protocol 
Version 1.1 
04.02.2022 
 
The use of PET-MRI scans in radiotherapy planning of 
patients with head and neck cancer: A single centre pilot 
study 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                
                           
  
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Contents 
Abbreviations: ....................................................................................................................... 4 
Section 1 - Project details ..................................................................................................... 5 
Section 2 – Research question(s) ......................................................................................... 8 
Section 3 – Abstract .............................................................................................................. 9 
Section 4 – Aim of the study................................................................................................ 10 
Section 5 -Background ........................................................................................................ 11 
5.1 Clinical and Scientific Relevance: .............................................................................. 11 
5.2 Scientific Justification................................................................................................. 12 
5.3 Potential benefit to patients ....................................................................................... 13 
Section 6 – Plan of Investigation ......................................................................................... 14 
6.1 Methodology .............................................................................................................. 15 
6.2 Summary of Study Design ......................................................................................... 16 
6.3 Setting for the Project ................................................................................................ 16 
6.4 Participants ................................................................................................................ 17 
6.4.1 Inclusion criteria .................................................................................................. 17 
6.4.2 Exclusion criteria ................................................................................................. 17 
6.5 Sample size ............................................................................................................... 18 
6.6 Recruitment ............................................................................................................... 18 
6.7 Outcome Measures ................................................................................................... 19 
6.7.1 Objectives and measurement .............................................................................. 19 
6.8 Statistical/Qualitative analysis .................................................................................... 20 
6.9 Intervention ................................................................................................................ 22 
6.10 Safety Assessment .................................................................................................. 23 
6.10.1 Administration of Gadolinium............................................................................. 23 
6.10.2 Administration of 18F-2-deoxyglucose ................................................................ 23 
6.10.3 Additional radiation exposure from 18F-2-deoxyglucose ..................................... 24 
6.10.4 Adverse events ................................................................................................. 24 
6.10.5 Definitions of Adverse Events ............................................................................ 25 

                                
                           
  
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6.10.6 Recording and Reporting Adverse Events ......................................................... 26 
6.11 Pregnancy ............................................................................................................... 27 
6.13 Instruments .............................................................................................................. 27 
6.13.1 PET-MRI scanner : ............................................................................................ 27 
6.13.2 Patient questionnaire ........................................................................................ 27 
6.13.3 Screening and data collection tool ..................................................................... 28 
6.14 Quality control and Assurance ................................................................................. 28 
6.15 Project Plan ............................................................................................................. 29 
Section 7 – Statistical opinion ............................................................................................. 30 
Section 8 – Project Management ........................................................................................ 31 
Section 9 – Expertise of the Researcher and Associated Team .......................................... 32 
Section 10 – Ethical Issues ................................................................................................. 33 
Section 11 – Involvement of Service Users ......................................................................... 34 
Section 12 – Methods for Disseminating Research Results ................................................ 35 
Section 13 – Strategy for taking the work forward if the research project is productive ........ 36 
Section 14 – Intellectual Property Arrangements ................................................................. 37 
Section 15 – Costing the project ......................................................................................... 38 
Section 16 – Funding source ............................................................................................... 39 
Section 17 – References ..................................................................................................... 40 
 
 
 
 

                                
                           
  
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Abbreviations: 
AE – Adverse event 
CT – Computed Tomography 
CTV – Clinical Target Volume 
GCP – Good Clinical Practice 
GTV – Gross Tumour Volume 
IMRT – Intensity Modulated RadioTherapy 
MDT – Multi-Disciplinary Team 
MRI – Magnetic Resonance Imaging 
NCI – CTCAE-National Cancer Institute Common Terminology Criteria for Adverse 
Events  
NCRI – National Cancer Research Institute 
PET – Positron Emission Tomography 
RCR – Royal College of Radiologists 
SAE – Serious Adverse event 
STH – Sheffield Teaching Hospitals 
SUSAR – Suspected unexpected serious adverse event 
UKIO – The United Kingdom Imaging & Oncology 
 
 
                                                                                                                                       
 

                                
                           
  
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Section 1 - Project details 
 
1.1 
Investigator details: 
 
Principal Investigator & Grant holder: 
Dr Satya Garikipati, 
Consultant Clinical Oncologist 
Weston Park Hospital 
Email: s.garikipati@nhs.net 
Tel: 01142265000, bleep 3235 
 
Co-investigators: 
 
Dr James Lester, Consultant Clinical Oncologist 
Email: james.lester@nhs.net 
Tel: 0114-2265000 
 
Dr Lynne Dixon, Consultant Clinical Oncologist 
Email: lynne.dixon3@nhs.net 
Tel: 0114-2265000  
 
Dr Shabbir Khan Rawther, Consultant Clinical Oncologist 
Email: shabbir.rawther@nhs.net 
Tel: 0114-2265000 
 
Richard Harrison, Lead Technician brachytherapy and mould room 
Email: Richard.harrison19@nhs.net 
Tel: 0114-2265049 
 
Dr Amy Taylor, Principal Therapeutic Radiographer, Research and Development 
Email : amy.taylor50@nhs.net 
Tel : 07796940684 
 
Prof. Nigel Hoggard, Professor of Neuroradiology 
Email: N.Hoggard@sheffield.ac.uk 
Tel: 0114-2159607 
 
Dr David Andrew, Senior Clinical lecturer in Dental & Maxillofacial Radiology 
Email: D.Andrew@sheffield.ac.uk 
Tel: 0114-2159311 
 
Professor James Wild, Professor of Magnetic Resonance Physics 

                                
                           
  
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Email: J.M.Wild@sheffield.ac.uk 
Tel: 0114-2159141 
 
Dr Eleanor Lorenz, Consultant Clinical Radiologist & ARSAC licence holder 
Email: eleanor.lorenz1@nhs.net 
Tel: 0114-2265000 
 
Phillip Hillel, Clinical Scientist, Nuclear medicine 
Email: philip.hillel@nhs.net 
Tel: 0114-2713468 
 
Stephen Tozer-Loft, Head of Radiotherapy Physics 
Email: stephen.tozer-loft@nhs.net 
Tel: 0114-2265174 
 
Stephen Riley, Principal Physicist 
Email: stephenriley1@nhs.net 
Tel: 0114-2265000 
 
Natalie Foley, Lead dosimetrist 
Email: natalie.foley1@nhs.net 
Tel: 0114-2265000 
 
Dr Bilal Tahir, Senior Research Fellow in Oncological Imaging 
Email: b.tahir@sheffield.ac.uk 
Tel: 07908967116  
 
 
 
 
1.2 
Sponsor details 
 
Sheffield Teaching Hospitals NHS Foundation Trust, 
Trust Headquarters, 
8 Beech Hill Road 
Sheffield, 
S10 2SB. 
 
 
 
 
 
 
1.3 
Project title 
 

                                
                           
  
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The use of PET-MRI scans in radiotherapy planning of patients with head and neck 
cancer: A single centre pilot study 
 
This is a pilot study to assess whether patients with head and neck cancer can 
tolerate a PET-MRI scan whilst immobilised in a thermoplastic shell that replicates 
their treatment position during radiotherapy and to assess whether it can improve 
accuracy in radiotherapy planning. 
 
1.4 
STH Project Reference number 
 
STH 21185 
 
1.5 
Protocol version number and date 
 
Version 1.1, 04.02.2022 
 
1.6 
Signatures of chief investigator and sponsor 
 
 
 
……………………………………….. 
 
 
…………………… 
Dr Satya Garikipati  
                           05.07.2021 
Principal Investigator 
 
 
 
………….. 
 
 
 
 
 
 
…………………… 
Professor Simon Heller                                  04/02/2022          
R&D Director 
 
1.7 
IRAS number: 286722 
 
 
1.8 
Phase of trial 
 
Not applicable. 
 
1.9 
STH Directorate affiliation 
 
Specialised cancer services directorate 
 
 

                                
                           
  
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Section 2 – Research question(s) 
 
The primary research question to be answered in this project is “Are patients with 
locally-advanced head and neck cancer able to tolerate a PET-MRI scan when they 
are immobilised in a radiotherapy treatment shell?” This will be assessed by 
measuring the proportion of patients that complete the full scanning protocol and by 
obtaining participant feedback on their experience of completing the scan. 
The secondary question is “Can a PET-MRI scan fused with a planning CT scan 
improve the accuracy in radiotherapy planning of patients with head and neck 
cancer?  Accuracy will be assessed by:  
1. Comparing the radiotherapy target volumes and radiotherapy plans with and 
without the use of a PET-MRI scan.  
2. Comparing inter- and intra-observer variability in treatment contours with and 
without the use of a PET-MRI scan within and between oncologists and implications 
of that. 
 
 
 

                                
                           
  
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Section 3 – Abstract 
 
Patients with head and neck cancers are often treated with radiotherapy. The overall 
aim of treatment is to cure the cancer whilst minimizing its side effects. These 
cancers are usually close to the surrounding vital organs which are often affected by 
the radiotherapy.  This can cause side effects such as a dry mouth or swallowing 
difficulties.  Improving the accuracy of radiotherapy planning could help reduce side 
effects and improve quality of life post-treatment.  
To design this treatment, patients undergo a “planning CT scan”, a computed 
tomography scan. This is obtained while the patient’s head and shoulders are held in 
position by a custom-made thermoplastic shell. The shell is necessary to ensure that 
the patient is in exactly the same position every time a dose of radiation is given.  
The most important step in planning this treatment is accurately identifying the 
cancer and the surrounding normal tissues. This is to work out exactly which areas 
need to be treated and which areas need to be avoided. This is done on the planning 
CT scan. During diagnosis of cancer, patients undergo other imaging  including an 
MRI (Magnetic Resonance Imaging) scan and a PET-CT(Positron Emission 
Tomography CT)  scan . These are the best imaging modalities for head and neck 
cancer and feed into the process of identifying cancer accurately. It would be better 
from a radiotherapy planning perspective if these scans are acquired in the same 
position as the ‘planning CT scan’. 
A PET-MRI scan is a combined MRI and PET scan, which is a new technology 
available in Sheffield. The current project aims to determine whether patients with 
head and neck cancers can tolerate an additional ‘PET-MRI’ scan with 
immobilisation similar to that used during the radiotherapy planning process and to 
assess if this additional scan helps in improving accuracy in radiotherapy planning. 
 
 
 

                                
                           
  
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Section 4 – Aim of the study 
 
This is a pilot study to investigate the use of PET-MRI scanning in patients with 
locally-advanced head and neck cancer in radiotherapy treatment planning. The 
specific objectives are: 
 
Primary objective: 
To assess the proportion of patients completing the full PET-MRI scans when they 
are immobilised in a radiotherapy treatment shell. For patients that do not complete 
the full scanning protocol, we would determine how long they remain within the 
scanner.  
Subjective assessment of tolerability to the scan, will be determined using a patient 
tolerability questionnaire (Appendix 1). 
 
Secondary objective: 
The secondary objective is to obtain pilot data on assessing the impact of the 
additional PET-MRI scan on the precision of radiotherapy planning. This will be 
assessed by comparing the radiotherapy target volumes and treatment plans with 
and without the use of PET-MRI scan. These tests will be conducted retrospectively 
and thus will not have any impact on patients’ flow through to treatment or their 
standard care.  
 
Exploratory objective: 
To assess whether PET-MRI scanning adds benefit to cancer patient’s diagnostic 
investigations. 
 
 

                                
                           
  
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Section 5 –Background 
 
5.1 Clinical and Scientific Relevance: 
Over the last 20 years, curative treatment of cancers of the head and neck has 
gradually evolved, particularly for cancers that arise in the pharynx/throat. There has 
been a progressive reduction in the proportion of patients that have surgery, and a 
concomitant 
increase 
in 
the 
proportion 
receiving 
radical 
(curative) 
chemo/radiotherapy (radiotherapy with or without concurrent chemotherapy). This is 
because function (speech and swallowing) is generally better preserved for 
chemo/radiotherapy compared to surgery and surgery and chemo/radiotherapy have 
similar cure rates1. 
The overall aim of chemo/radiotherapy treatment is to maintain a high chance of 
curing a patient’s cancer, while at the same time minimising side-effects and 
maximising longer-term function. All locally-advanced head and neck cancers are in 
close proximity to vital structures (‘organs at risk’), and these structures are often 
affected by radiotherapy. Frequent long-term side-effects include dry mouth, when 
the salivary glands are in the radiotherapy treatment fields, and difficulty swallowing 
due to scarring of the muscles of the pharynx/oesophagus. Technological 
developments, including Intensity Modulated Radiotherapy (IMRT), have improved 
the precision of radiotherapy treatment planning, leading to significantly reduced 
long-term side effects2. Further research strategies to improve outcomes are based 
on improving the accuracy of ‘target delineation’ which is a critical step in 
radiotherapy planning. This step includes identifying the gross tumour as well as the 
surrounding normal structures on scans with high accuracy. Interventions that can 
improve precision in this process could lead to changes in the overall volume of 
tissue treated and reduce the overall dose of radiation to surrounding normal 
structures which could translate to reduced side effects.  
Radiotherapy involves delivering high energy X-rays to the primary tumour, nodal 
metastases as well as the draining lymph nodes which may be at risk of microscopic 
i.e. subclinical disease, with the objective of killing all of the cancer cells. For patients 
with head and neck cancers, this treatment is generally given as fractions (doses) of 
radiation five days a week for six to seven weeks. In order to deliver the radiotherapy 

                                
                           
  
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to the same site over 30-35 treatment sessions, the patient position must be 
consistent and accurately reproduced at each treatment session. This is achieved by 
using a thermoplastic shell that holds the  patient’s head and shoulders in position 
and is secured to the treatment table. Patients undergo a computed tomography 
(CT) scan wearing the thermoplastic shell which enables a virtual simulation of the 
treatment. Critically, the planning CT scan is obtained in the same position and using 
similar immobilisation as the radiotherapy treatment itself.  
 
The most important step in radiotherapt planning is ‘target delineation’, the process 
of accurately defining the cancer and nearby normal organs on this planning scan. 
This dictates the volume of tissue that receives radiation. Other diagnostic scans 
such as magnetic resonance imaging (MRI) and positron emission tomography CT 
(PET-CT) scans feed into the target delineation process as oncologists use these 
images as a guide, but ultimately the contouring and treatment planning is done on 
the CT planning scan.  
Once the gross tumour is contoured, oncologists use a margin to create a clinical 
target volume. This margin is to account for microscopic spread of cancer cells. 
Using a smaller margin to set the clinical target volume will reduce the radiation to 
the surrounding normal structures and eventually can translate into reduced side 
effects. But the gross tumour volume must be identified accurately to avoid the risk 
of under-dosing the tumour3. 
 
5.2 Scientific Justification 
MRI is the imaging modality of choice for staging of malignant tumours of the head 
and neck because of its superior soft tissue detail compared to other modalities4. 
Patients with advanced-stage disease (e.g. T4 tumours or N3 nodal disease) should 
also have a PET-CT to exclude distant metastatic disease and help guide the 
decision-making process regarding treatment intent, resectability etc5. These scans 
are performed without patients being in the radiotherapy treatment position, which 
can then cause difficulties in localisation and using this information to aid target 
delineation. There is evidence that fusion of the planning CT scan with MRI or PET-
CT images can improve the accuracy of radiotherapy planning/contouring and this 

                                
                           
  
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accuracy is enhanced if the MRI or PET-CT scans are acquired in the radiotherapy 
treatment position6,7. 
Combining the superior anatomical image quality of an MRI scan with the functional 
images of a PET scan in a single scanner is a recent development in imaging 
technology that may provide a more accurate delineation of locally-advanced head 
and neck cancers. PET-MRI is superior to PET-CT for local staging of 
nasopharyngeal cancer and differentiated thyroid cancer8,9, with several small 
studies demonstrating the added value of PET-MRI in head and neck squamous 
cancer10,11. PET-MRI is not currently in routine clinical use, in part because of 
access, but it has the potential to transform future patient care. A new University of 
Sheffield PET-MRI scanner has been installed in 2020. Weston Park Cancer Centre 
has a national reputation of providing high quality clinical care for patients with head 
and neck cancer and is one of the top recruiters to UK-wide clinical trials (PET-Neck, 
De-Escalate, ART-DECO, DARS NIMRAD, COMPARE). The service is enhanced by 
wider multidisciplinary expertise: excellence in diagnostic radiology and state-of-the-
art multimodality image co-registration techniques that have been tested and applied 
in numerous structural and functional MRI and CT studies12,13. Using PET-MRI to aid 
radiotherapy planning has not been evaluated anywhere in the world. Therefore, the 
new PET-MRI scanner in Sheffield represents a ‘window of opportunity’ to exploit 
such technology and would place Sheffield at the forefront of UK research in this 
area. 
The current study will test the feasibility of PET-MRI in the setting of radiotherapy 
planning. Pilot data to assess and measure the variance in radiotherapy planning will 
also be obtained, and would be used to design a larger study if the feasibility was 
confirmed. 
 
5.3 Potential benefit to patients 
The current project is a feasibility study to confirm that PET-MRI scans with 
immobilisation in a radiotherapy shell are tolerated by head and neck cancer 
patients. At this stage, it is of no direct benefit to patients enrolled on the study, but, if 
successful, will provide important pilot data that could be used to plan a larger study 
in the future.  

                                
                           
  
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We do not anticipate that the PET-MRI scan will add any new diagnostic information 
as all recruited patients would have had similar imaging (MRI and PET-CT) already 
at the time of diagnosis.  However, this is an additional and advanced imaging 
technique where the PET-MR images are reported by an appropriately-trained 
radiologist. If there is any significant change that could have an impact on a patient’s 
cancer treatment, this will be communicated to the patient by their Oncologist. 
Gaining qualitative perspectives of the participant’s experience of undertaking a 
PET-MRI scan will allow the project team to gain valuable insight into potential 
barriers that could influence the implementation of this imaging modality into 
standard clinical practice. This will help the team to develop supportive services 
which will help future patients to successfully complete the scan as part of their 
routine standard care. Subsequently, this could provide a long term benefit to future 
patients by providing them with access to a technology that can potentially aid in 
improving the precision of radiotherapy planning. This can, in turn, have a positive 
impact on overall outcomes from cancer treatment; in terms of curing cancer as well 
as reducing side effects.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

                                
                           
  
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Section 6 – Plan of Investigation 
 
6.1 Methodology 
The current study is a feasibility study of whether patients with locally-advanced 
head and neck cancer can tolerate PET-MRI scanning whilst being immobilised in a 
radiotherapy shell. The primary objective will be the assessment of the proportion of 
patients that complete the full scanning protocol (estimated duration 20-30 minutes). 
For patients that fail to tolerate the full scan, their duration within the scanning 
environment will be determined as it may be possible to shorten the MRI component 
of the scan, thus reducing the scan duration. All recruited patients will have had a 
staging MRI scan, a CT scan of the chest and upper abdomen as well as PET-CT as 
part of their investigations for cancer diagnosis which means they have successfully 
completed the standard scanning protocols for MRI or PET, including the standard 
contrast agents used for these scans. 
Patients that participate in the current study will have an extra PET-MRI scan, which 
will expose them to a small amount (4 – 6 mSv) of extra radiation.  
This PET-MRI scan will be obtained while they are wearing the immobilisation shell. 
Enrolled patients would have had a trial run of wearing the same shell for their 
planning CT scan required as part of their standard care for radiotherapy planning. 
Planning CT scan is generally well tolerated and typically lasts 20 minutes which is 
relatively shorter compared to the time in the shell for a PET-MRI scan. 
Potential obstacles to individual patients are their size (the magnet bore is 60cm 
which is further narrowed down due to the immobilisation equipment required and 
may influence who can be recruited), their comfort during the scan, as large upper 
aerodigestive tract tumours affect swallowing and cause coughing, all of which 
degrade the quality of the images as well as claustrophobia which may be worsened 
by the thermoplastic shell. A PET-MRI scan with immobilisation has not been tested 
before. However, researchers are aware that an MRI scan with similar immobilisation 
is tolerated by head and neck cancer patients and is in routine use in some 
radiotherapy centres in the UK to aid radiotherapy planning. Likewise, proton beam 
therapy which involves radiotherapy treatment with protons requires patients to 
remain in the immobilisation shell for a significantly longer period than the 

                                
                           
  
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conventional linac based planning and treatment. This reassures the study team that 
a PET-MRI scan with immobilisation in patients with head and neck cancer may be 
feasible despite the longer duration of the scan. 
A subjective qualitative assessment of patient tolerability will be obtained using a 
patient  questionnaire. On completion of the PET-MRI, participants will be asked to 
complete a bespoke questionnaire about their scan. The questionnaire has been 
developed by members of the project team and lay representatives (Appendix 1). It 
explores key elements of the scan process (e.g. patient positioning, the use of 
contrast agents etc.) identified by the literature base as areas which can act as 
barriers to successful completion by participants. The questionnaire is composed of 
a mix of binary (yes/no) Likert-scale and open-ended exploratory questions. 
 
6.2 Summary of Study Design 
This is a prospective study that aims to determine the feasibility of PET-MRI 
scanning of head and neck cancer patients that are immobilised in a radiotherapy 
treatment shell. It is estimated that ten patients will be recruited to the study. Patients 
will be registered into the study once they have given informed written consent. All 
patients who consent to study entry will undergo study screening to confirm eligibility. 
Patients who are ineligible following screening will not be considered as enrolled in 
the study and will receive treatment as per their usual clinical care. 
 
6.3 Setting for the Project 
Patients will initially have their management discussed through the STH central head 
and neck  MDT. The study will be introduced to potentially eligible patients by 
oncologists when radical radiotherapy is recommended and recruitment to the study 
will be at Weston Park Cancer Centre, Sheffield. PET-MRI scans will be performed 
in the dedicated PET-MRI facility in Academic Radiology, Royal Hallamshire 
Hospital, Sheffield. 
 

                                
                           
  
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6.4 Participants 
Patients with locally-advanced head and neck cancers who are fit for radical 
(curative) treatment. This is a single-centre study and we expect to recruit ten 
patients. 
6.4.1 Inclusion criteria 
To be eligible for inclusion, participants must meet the following criteria: 
1. Aged 18 years or over 
2. Able to give informed written consent. 
3. New diagnosis of biopsy-proven head and neck cancer. 
4. WHO performance status ≤ 2. 
5. MDT-recommended treatment with radical radiotherapy, with or without 
concurrent systemic therapy. 
6. MRI and PET-CT staging scans for diagnosis. 
6.4.2 Exclusion criteria 
1. Known intolerance/sensitivity to 18F-2-deoxyglucose or gadolinium-containing 
contrast agents. 
2. Claustrophobia or other contraindications to MRI. 
3.  Unable to pass through a 55 cm hula hoop. 
4. Female patients that are pregnant or breastfeeding. 
5. Unable to understand written or spoken English. 
6. Patients not undergoing radical intent radiotherapy.  
7. Patients with stage 4 or 5 chronic kidney disease or other biochemical 
abnormalities e.g. uncontrolled blood glucose levels which can have an 
impact on PET-MRI imaging or contrast administration. 
 
In the last 12 months, 104 patients have been treated with radical radiotherapy 
(curative intent) for a newly-diagnosed head and neck cancer at Weston Park 
Cancer Centre, Sheffield. This equates to 8 new patients per month that are 
potentially eligible for recruitment. We anticipate 1 or 2 patients per month to 
participate in the study.  

                                
                           
  
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The patient population would include Sheffield as well as the peripheral cancer units 
of  Chesterfield, Rotherham, Doncaster and Barnsley. Radiotherapy is planned and 
delivered centrally at Weston Park Cancer Centre for all patients.  
 
6.5 Sample size 
The current study is a feasibility study. We estimate that ten patients will be sufficient 
to determine whether PET-MRI in a radiotherapy immobilisation shell is tolerable to 
patients with locally-advanced head and neck cancer. A patient tolerability 
questionnaire obtained from the ten patients will provide subjective qualitative data 
from a patient’s perspective. The retrospective analysis to achieve the secondary 
objective for patients who tolerate the scan will be used as pilot data to inform larger 
studies in the future if feasibility is successful.  
 
6.6 Recruitment 
Patients newly-diagnosed with head and neck cancer who had a PET-CT scan along 
with a staging MRI scan and CT chest/upper abdomen scans as part of their 
diagnosis and were recommended radical radiotherapy will be identified in the 
weekly central Sheffield Head and Neck MDT. Potentially eligible patients will be 
approached by their oncologist during an out-patient clinic prior to the radiotherapy 
planning process and the study discussed with them. Interested patients will be 
given a verbal explantion of the study and a Patient Information Sheet by an 
authorised trial clinician or research nurse (an individual on the delegation log). 
Following this, the patient will be given sufficient time (minimum 24 hours) before 
they are contacted and asked whether they wish to be considered for the study. If 
they wish to proceed, then they will be seen on their next hospital visit to give 
informed, written consent. The Principal Investigator or an authorised clinician on the 
delegation log will witness the patient’s signature and countersign the consent form. 
Patients are free to withdraw their consent at any time without reason; this will not 
adversely affect their treatment. One copy of the signed consent form will be given to 
the patient, one kept in the hospital notes and one in the site file. 
All staff involved in the consent procedure will have current Good Clinical Practice 
(GCP) training. In the unlikely event that the patient loses capacity after informed 

                                
                           
  
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consent and before the PET-MRI scan, then the patient will be withdrawn from the 
study in the interest of safety.  
Screening logs will be kept for those patients who are given the patient information 
sheet and were eligible. This data will be considered by the Trial Management Group 
if there are difficulties in recruiting to the study.  
 
6.7 Outcome Measures 
6.7.1 Objectives and measurement 
Primary objective 
The primary outcome will be the proportion of patients that complete the PET-MRI 
scan as per protocol whilst immobilised in the radiotherapy treatment shell. For 
patients that do not complete the full scan, the duration of time in the scanner will be 
recorded as well as the reasons why they were unable to complete the scan. Patient 
tolerability questionnaire will provide this qualitative data. 
 
Secondary objective 
The secondary objective is to assess the impact of the additional PET-MRI scan on 
the precision of radiotherapy planning. These tests will be conducted retrospectively 
after conventional radiotherapy planning and do not interrupt a patient’s flow through 
to treatment or their standard  care.  
Co-registration of images for radiotherapy planning: 
A PET-MRI scan of each patient provides PET images that are inherently co-
registered with MRI images. In order to achieve the secondary objectives, three 
categories of images are obtained for radiotherapy planning purposes by 
superimposing images from the PET-MRI scan on to the planning CT scan, a 
technique termed ‘image registration’.  
Category 1: Planning CT scan (“CT”) with no fusion: this is standard practice  
Category 2: Planning CT fused with MRI images from the PET-MRI scan (‘CT-MRI’) 
Category 3: Planning CT fused with PET-MRI images (‘CT-PET-MRI’) 
 

                                
                           
  
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The secondary objectives are: 
1. To compare the radiotherapy target volumes (GTV (gross tumour volume) and 
CTV (clinical target volume)) contoured in the three categories above (CT, CT-MRI 
and CT-PET-MRI images). A quantitative assessment will be done by measuring the 
volumes  in three dimensions using Varian’s External Beam Planning software in 
Aria. A qualitative analysis of the 3D dose distribution, comparison of target 
coverage, conformity, homogeneity and examination of specific dose/volume 
objectives of organs at risk will be done.  
 
2. Assess inter- and intra-observer variability in treatment contours and precision of 
target delineation in the three categories above (CT, CT-MRI and CT-PET-MRI 
scans). This will be assessed using Dice Similarity Index and Hausdorff distance in 
the three categories. 
 
Exploratory objective: 
To assess whether PET-MRI scanning adds benefit to the cancer patient’s 
diagnostic investigations. Clinical reports of the PET-MRI scan will be compared to 
reports from staging MRI and PET-CT scans to determine if any new diagnostic 
information is brought to light by PET-MRI. 
 
6.8 Statistical/Qualitative analysis 
 The proportion of patients completing the PET-MRI scan will be recorded that 
will determine feasibility.  
 All recruited patients are expected to complete a questionnaire which will 
provide a qualitative assessment. Statistical analysis will be completed on the 
binary and Likert scale questions. This process will allow the study team to 
identify any issues faced during the PET-MRI scan  and thepercentage of 
participants who were affected by these. Thematic analysis will be completed 
on the open-ended questions. This will allow the project team to explore 
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patients may need to be supported during the scanning process if it is to 
become standard of care.  
 As this is a pilot study with ten patients, we do not anticipate this analysis for 
secondary objectives to provide any statistically significant outcomes. But this 
will help to specify the kinds of analysis that are possible in a larger study and 
will also be used to calculate sample sizes. 
 
 
 
 

                                
                           
  
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6.9 Intervention 
An illustration of the pathway of a patient that is enrolled in the study is shown in the 
following diagram. Study-specific events are indicated in red.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diagnostic tests 
Biopsy 
MRI Neck 
CT chest/abdomen 
PET-CT 
 
Consultation with Oncologist 
 
MDT discussion and treatment 
recommendation 
CT scan with immobilisation 
for Radiotherapy planning 
 
Potential participant identified 
Radiotherapy planning 
Radiotherapy treatment starts 
Retrospective analysis  
outside patient treatment 
pathway 
PET-MRI scan within a week 
of Planning CT scan 
Patient consents to study 
Study introduced to patient 

                                
                           
  
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6.10 Safety Assessment 
Patients that are enrolled in the study will have one additional diagnostic test 
compared to their normal standard of care, namely, a PET-MRI scan. Patients 
recruited to the study will have had a standard gadolinium-enhanced MRI scan of the 
neck as well as a whole-body PET-CT scan with radioactive glucose tracer during 
their diagnosis of cancer as standard of care a few weeks prior to recruitment into 
the study. Potential safety issues related to the additional PET-MRI scan are: (i) 
administration of the MRI contrast agent gadolinium; (ii) administration of radioactive 
18F-2-deoxyglucose; (iii) additional radiation exposure from 18F-2-deoxyglucose. 
 
6.10.1 Administration of Gadolinium 
Chelates of the rare earth element gadolinium are used as contrast agents in MRI 
scans. They improve the conspicuity of abnormal tissue and are considered 
mandatory in staging head and neck cancers14. The current Gadolinium-based 
contrast agents on the market are considered to be safe: they have a very low rate of 
immediate adverse events (0.06 – 0.09%) and the incidence of acute severe 
reactions such as anaphylaxis is very rare (0.0025 – 0.005%15;). A previous reaction 
to MRI contrast is an exclusion criterion (see section 6.4.2) and patients with a 
history of this will not be recruited. Gadolinium can be nephrotoxic when given in 
large volumes (30 mL) to patients with renal disease/renal impairment. For tumour 
enhancement in cancer staging 7.5 mL of the macrocylic chelate gadobutrol 
(Gadovist, Bayer; 1mmol/mL) is used in Sheffield Teaching Hospitals and this is 
safe. Linear chelate Gadolinium-containing agents have been associated with 
nephrogenic systemic fibrosis and there are also concerns regarding Gadolinium 
retention in the brain following repeated doses of linear chelates. These findings led 
the European Medicines Agency to suspend use of the linear chelates in 2017. The 
macrocyclic agents such as Gadobutrol are considered safe even in patients with 
severe chronic renal impairment16. Overall, there is considered to be no extra risk to 
patients from the MRI component of the PET-MRI scan. 
 
6.10.2 Administration of 18F-2-deoxyglucose 
PET imaging in oncology is based on the increased uptake of glucose by cancer 
cells, which have more cell surface glucose transporter proteins and increased 

                                
                           
  
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intracellular glycolytic enzyme levels than normal cells. The increased glycolytic rate 
of cancer cells enables their detection with the fluorine-labelled analogue of glucose, 
18F-2-deoxyglucose. There are no safety concerns with the use of 
18F-2-
deoxyglucose, which is in standard use for PET-CT scanning throughout the world. 
 
6.10.3 Additional radiation exposure from 18F-2-deoxyglucose 
The radioactive isotope 18F decays by positron emission, having a half-life of 110 
min. For ‘average’ patients, this isotope has an effective radiation dose of 19 
µSv/MBq14, resulting in an exposure of about 4 – 6mSv from the typical 200 - 300 
MBq of 18F that is used in PET oncology imaging.  
 
FDG dose reference levels 
Minimum ARSAC Dose Reference Level 
(DRL):  
100MBq 
SPC DRL for GE710 Discovery scanner 
Weight 
DRL 
min/bed 
Overlap 
<115Kg 
3.5MBq/Kg 
2 
  
23 
(~50%) 
115-140Kg 
400MBq 
2.5 
>140Kg 
3 
 
This is a standard dose for a diagnostic PET scanning and used widely. Patients will 
be required to follow radiation protection advice after the scan which includes staying 
away from pregnant women and young children for about 8 hours while the 
radioactive tracer can still be in their system.  
Patients have their contrast-enhanced radiotherapy planning CT scan as part of 
standard treatment before the PET-MRI scan. A minimum of 24 hours and maximum 
of 2 weeks will be maintained between the planning CT scan and the PET-MRI scan. 
 
6.10.4 Adverse events 
All Adverse Events (AEs), Serious Adverse Events (SAEs) and fatal or life-
threatening suspected / unexpected serious adverse reactions (SUSARs) that occur 
during the study, either observed by the investigator or reported by participants, 
whether or not attributed to the study, will be reported to the DMEC in accordance 
with current GCP standards. SAEs and SUSARs, and deaths should be reported 
within 24 hours of becoming aware of the event. 

                                
                           
  
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We do not expect any persistent or prolonged adverse effects from the intervention. 
Participants are monitored for 30 days from recruitment to the study. Standard care 
involves regular assessments and ongoing treatment of cancer over the next 6-8 
weeks and regular post treatment follow up thereafter. Any suspected adverse 
events from study intervention will be reported to the study team appropriately. 
 
6.10.5 Definitions of Adverse Events 
An adverse event(AE) is any untoward medical occurrence in a patient or clinical trial 
subject that does not necessarily have a causal relationship with this treatment and 
can include: 
 Any unintentional, unfavourable clinical sign or symptom. 
 Any new illness or disease or the deterioration of existing disease or illness. 
 Any clinically relevant deterioration in any laboratory assessments or clinical 
tests. 
All AEs judged by either the Investigator or the Sponsor as having a reasonable 
suspected causal relationship to the project will qualify as adverse reactions. The 
expression ‘reasonable causal relationship’ should convey that there are facts 
(evidence) or arguments to suggest a causal relationship. 
A Serious Adverse Event (SAE) is defined in general as any untoward medical 
occurrence or effect that: 
 Results in death. 
 Is life threatening. The term life threatening 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 that hypothetically might have caused death if it was more severe. 
 Requires inpatient hospitalisation or prolongation of existing hospitalisation. 
 Results in persistent or significant disability or incapacity. 
 May jeopardise the participant and may require medical or surgical 
intervention to prevent one of the outcomes listed above. 
Clinical judgement must be exercised in deciding whether an SAE is serious in other 
situations. Important SAEs that are not immediately life-threatening or do not result 
in death or hospitalisation but may jeopardise the participant may require 

                                
                           
  
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intervention to prevent one of the other outcomes listed in the definition above, must 
also be considered serious. 
A Suspected Unexpected Serious Adverse Reaction (SUSAR) is a Serious Adverse 
Reaction which also demonstrates the characteristics of being unexpected, the 
nature, seriousness, severity or outcome of which is not consistent with procedure. 
 
6.10.6 Recording and Reporting Adverse Events 
Information about adverse events, whether volunteered by the patient, discovered by 
investigator questioning or detected through physical examination, laboratory test or 
other investigation, will be collected and recorded on the relevant CRF. Adverse 
events will be collected for all participants from the time of written informed consent 
until 30 days after the PET-MRI scan. All AEs will be monitored until resolution, or if 
the AE is determined to be chronic, until a cause is identified. If an AE remains 
unresolved at the conclusion of the study, the investigator will make a clinical 
assessment about whether continued follow-up of the AE is warranted. The 
investigator will evaluate AEs for duration and intensity according to the National 
Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-
CTCAE). 
The investigator will determine the relationship of the study treatment to an AE 
based on the following definitions: 
 Not related - the AE is not related if the PET-MRI scan has not occurred or the 
occurrence of the AE is not reasonably related in time or the AE is considered 
unlikely to be related to the PET-MRI scan (i.e., there are no facts [evidence] 
or arguments to suggest a causal relationship).  
 Possibly related - the PET-MRI scan and the AE are reasonably related in 
time and the AE could be explained equally well by factors or causes other 
than the PET-MRI scan. 
 Probably related - the PET-MRI scan and the AE are reasonably related in 
time and the AE is more likely explained by the scan than by other factors or 
causes. 
All Serious Adverse Event (SAE) will be reported within 24 hours of discovery to the 
Research Department by a member of the Research Team using the form provided 
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6.11 Pregnancy 
Patients that are pregnant cannot be recruited to the study as per the exclusion 
criteria (section 6.4.2). 
 
6.12 
Subject 
withdrawal, 
breaking 
the 
blind 
and 
trial 
stopping/discontinuation rules 
Participants can withdraw from the study at any time. If a participant withdraws after 
giving written consent but before PET-MRI scanning, their scan will be cancelled. If a 
subject withdraws after the PET-MRI scan has been completed, their images will be 
retained and analysed for inclusion within the study. 
This study does not involve blinding, so breaking the blind rules are not applicable 
for this study. 
 
6.13 Instruments 
6.13.1 PET-MRI scanner :  
The new University of Sheffield PET-MRI scanner has been installed as per standard 
operating procedures. 
6.13.2 Patient questionnaire (Appendix 1) 
A Patient and public involvement(PPI) group was formed for the study at the time 
of applying for the SHC grant fund. Face validity was established by gaining 
feedback from key stake-holders including co-investigators and lay members of the 
project team. These experts were asked to evaluate whether the questions 
effectively captured and addressed the topic under investigation. The PPI group was 
consulted again and recommendations were incorporated.  
The questionnaire was pilot tested by a subset of the studies’ target population to 
explore any formatting or distribution issues which may influence the quality of 
returns and response rates.   
As this is a feasibility study recruiting  10 patients, the above steps to validate the the 
questionnaire were agreed as adequate by the study team. 
 

                                
                           
  
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6.13.3 Screening and data collection tool (Appendix 2) 
See appendix 2. 
6.14 Quality control and Assurance 
Induction: Induction to all members in the delegation log assisting in conducting this 
research study will be provided at a setup meeting before commencing recruitment 
into the study. 
Quality assurance of documentation: The trial will be conducted in accordance with 
Good Clinical Practice standards.  
Immobilisation equipment and PET-MRI scanner: The intervention in this study is the 
extra PET-MRI scan with immobilisation of head, neck and shoulders. PET-MRI 
scanning is still relatively a new technology in the NHS; national standardised 
protocols and quality assurance procedures are not currently available.  
Immobilisation is achieved using a custom made thermoplastic shell and an MRI 
compatible board to secure the shell to the scanner couch. This equipment is quite 
similar to the standard immobilisation used in radiotherapy planning for head and 
neck cancer.  
Co-registration of PET-MRI images with planning CT images: Study team will use 
rigid registrations in Varian’s ™ Image Registration software.  A three point match 
will allow us to report an RMS value for each registration.  The match quality will be 
assessed qualitatively using split window and blended views, and then approved by 
a clinician before being used for contouring. 
Study QA team: This team includes co-investigators with expertise in multimodal 
image acquisition and co-registration of different imaging modalities. The team would 
facilitate transfer of confidential data between University of Sheffield Academic 
Radiology and Weston Park Cancer Centre radiotherapy departments. This team will 
also ensure accuracy of co-registration of PET-MRI scan images with the planning 
CT images. 
 
 
 

                                
                           
  
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6.15 Project Plan 
This study will recruit 10 patients over a period of  12 months.   
The project plan is: 
Dec  2021: Obtain NHS REC approval, HRA Approval and Confirmation of Capacity 
and Capability from STH NHS FT 
Obtain NHS REC approval and research governance approvals from NHS sites. 
Feb  2022: First patient recruited 
Feb 2023: Last patient recruited 
Mar 2023- Feb  2024 : Data analysis, report writing & dissemination of results 

                                
                           
  
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Section 7 – Statistical opinion 
 
With this type of feasibility study, it is not necessary to perform formal power 
calculations, and justification of the number of subjects to be enrolled is provided in 
section 6.5. 
 
 
 

                                
                           
  
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Section 8 – Project Management 
 
A Steering Committee will manage the study and ensure that the project proceeds in 
a timely manner. It will comprise: 
 Committee Chair  
 A Head and Neck Clinical Oncologist with expertise in head and neck cancers 
 A radiologist with expertise in reporting MRI scans  
 A radiologist with expertise in reporting PET scans 
 A medical physicist with expertise in engineering and clinical applications of 
MR imaging 
 A Nuclear medicine scientist 
 A radiotherapy dosimetrist with expertise in head and neck cancer 
radiotherapy planning 
 A radiotherapy physicist with expertise in head and neck cancer radiotherapy 
planning 
 
The Committee will: 
 Ensure, monitor and if necessary, revise the strategy of the project 
 Establish rules to run the project 
 Resolve problems and difficulties 
 Monitor costs 
 The principal investigator will supervise, monitor and holds overall 
responsibility of the study 
 
Communication between Committee members will be by email or telephone and 
face-to-face meetings will be held whenever needed at the following time-points: 
 At the start of the study 
 When the first participant has been scanned 
 2 monthly onthly until the study ends 
 Ad-hoc if required 
 
 

                                
                           
  
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Section 9 – Expertise of the Researcher and Associated Team 
 
The current project is a collaboration between Sheffield Teaching Hospitals and the 
University of Sheffield. The Principal applicant is Dr Satya Garikipati, who is a 
Consultant Clinical Oncologist at Weston Park Cancer Centre with a major clinical 
commitment to treating head and cancer patients. Dr Garikipati is the Site Lead for 
Head and Neck cancer services at Sheffield Teaching Hospitals, a member of the 
British Association of Head & Neck Oncologists and a Yorkshire Cancer Research 
connect NHS academy fellow. The wider head & neck oncology team at Weston 
Park Cancer Centre have a national reputation for providing high-quality clinical 
services to cancer patients and are one of the top UK recruiters to both national and 
international clinical trials in head & neck oncology (e.g. PET-Neck, De-Escalate, 
DARS, ART-DECO, NIMRAD, COMPARE). The Radiology team comprises a 
mixture of clinical consultants with expertise in head & neck imaging and PET 
imaging as well as expertise in imaging research, including translating basic science 
research into clinical use in the NHS. The combination of H&N specialist oncologists, 
radiologists, radiographers, dosimetrists and physicists (diagnostic/academic and 
radiotherapy) have participated in previous radiotherapy clinical trials in head & neck 
and are well versed in the practical issues of carrying out research projects that 
involve ionising radiation. 
 
 
 

                                
                           
  
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Section 10 – Ethical Issues 
 
The trial will be taken through the appropriate ethical and regulatory authorities prior 
to opening. All patients will provide informed, written consent and can refuse to 
participate at any stage without giving a reason. All information collected during the 
trial will be kept strictly confidential. Data protection will comply with the 1998 Data 
Protection Act. Data will be stored electronically on NHS servers within Sheffield 
Teaching Hospitals that are protected by firewalls. All clinical data will be identified 
only by the allocated study number; signed consent forms with patients’ names on 
will be stored securely separately. 
 
The only ethical issue raised by this study is that participants would receive an extra 
small dose of radiation (from the PET component of the PET-MRI scan) that, at this 
stage, would not be of clinical benefit. This is a standard dose of radiation used for 
diagnostic scans. In the future, if the addition of a PET-MRI scan could improve the 
accuracy of patients’ radiotherapy plans, the potential benefit in their overall cancer 
treatment is likely to outweigh the inconvenience from the small additional dose of 
radiation from a PET scan.  
 
 
 

                                
                           
  
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Section 11 – Involvement of Service Users 
 
A patient and public involvement (PPI) group was formed at the time of submission 
of this research proposal for the Sheffield Hospitals Charity fund. Members of this 
group have been contacted again and feedback was obtained about the patient 
information sheet  and patient tolerability questionnaire. Recommendations from 
feedback have been incorporated in these documents. 
We also aim to involve this group to discuss results from the study and obtain their 
comments and recommendations for future of this project. 
 
 
 

                                
                           
  
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Section 12 – Methods for Disseminating Research Results 
 
This is the first time such a feasibility study using PET-MRI is being conducted 
globally. If feasibility is demonstrated,  the results may  be disseminated by 
presentations and publication in a scientific/medical journal. We expect that the 
academic 
beneficiaries 
would 
include 
clinical 
oncologists, 
radiotherapy 
radiographers and radiotherapy physicists as well as diagnostic radiologists and 
physicists involved in head and neck cancer research. These groups will be engaged 
by presenting results obtained from this pilot study at national/international scientific 
conferences in Imaging and Oncology (e.g. NCRI, UKIO and RCR).  
 
 
 
 

                                
                           
  
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Section 13 – Strategy for taking the work forward if the research 
project is productive 
 
If technically-feasible, further funding will be required to collect data that will inform a 
definitive future study. Potential funders are  Yorkshire Cancer Research,  Medical 
Research Council (Confidence in Concept scheme) and The National Institute for 
Health Research (Efficacy and Mechanism Evaluation programme). 
 
 
 

                                
                           
  
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Section 14 – Intellectual Property Arrangements 
 
 
Sheffield Teaching Hospitals NHS Foundation Trust is the study sponsor. The 
University of Sheffield will have shared ownership of the intellectual property(IP) that 
results from the project. If commercially-exploitable findings result from the project, 
IP advice will be sought at an early stage. Intellectual property will be managed by 
Sheffield Teaching Hospitals NHS FT  and the University of Sheffield  Research 
departments as required by the project. 
 
 

                                
                           
  
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Section 15 – Costing the project 
 
The total costs for the project are £53,899. 
This is composed of the following: 
 
Staff costs : £32,832 
Non-staff costs: £6,642 
Scanning costs: 14,425 
 
 
 

                                
                           
  
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Section 16 – Funding source 
 
The project has been funded by Sheffield Hospitals Charity through the Specialised 
Cancer Services Research fund (2019 round; grant ref. 192035)  
 
 
 

                                
                           
  
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Section 17 – References 
 
1. Kim Y-J & Lee R (2018) Surgery vs. radiotherapy for locally advanced 
hypopharyngeal cancer in the contemporary era: A population based study. 
Cancer Med. 7: 5889-5900. 
 
2. Nutting CM, Morden JP, Harrington KJ, Guerro Urbano T, Bhide SA, Clark C 
et al. (2011) Parotid -sparing intensity modulated versus conventional 
radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre 
randomised controlled trial. Lancet Oncol. 12: 127-136. 
 
3. Grégoire V, Evans M, Le QT, Bourhis J, Budach V, Chen A et al. (2018) 
Delineation of the primary tumour clinical target volumes (CTV-P) in laryngeal, 
hypopharyngeal, oropharyngeal and oral cavity squamous cell carcinoma: 
AIRO, CACA, DAHANCA, EORTC, GEORCC, GORTEC, HKNPCSG, HNCIG, 
IAG-KHT, LPRHHT, NCIC CTG, NCRI, NRG Oncology, PHNS, SBRT, 
SOMERS, SRO, SSHNO, TROG consensus guidelines. Radiother Oncol. 
126: 3-24. 
 
4. iRefer: Making the best use of Clinical Radiology (2017). Royal College of 
Radiologists, London, 8th ed. 
 
5. Cancer of the upper aerodigestive tract: assessment and management in 
people aged 16 and over (NG36) NICE (2018). 
 
6. Chuter R, Prestwich R, Bird D, Scarsbrook A, Sykes J, Wislon D, Speight, R 
(2017). The use of deformable image registration to integrate diagnostic MRI 
into the radiotherapy planning pathway for head and neck cancer. Radiother 
Oncol. 122: 229-235. 
 
7. Paulino AC, Koshy M, Howell R, Schuster D, David LW (2005). Comparison of 
CT- and FDG-PET-defined gross tumor volume in intensity-modulated 

                                
                           
  
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radiotherapy for head-and-neck cancer. Int J Radiat Oncol Biol Phys 61: 
1385–92. 
 
8. Chan S-C, Yeh C-H, Yen T-C, Ng S-H, Chang JT-C, Lin C-Y et al. (2018) 
Clinical utility of simultaneous whole body 18F-FDG PET/MRI as a single-step 
imaging modality in the staging of primary nasopharyngeal carcinoma. Eur. J 
Nucl. Med. Mol. Imaging 45: 1297-1308. 
 
9. Binse I, Poeppel TD, Ruhlmann M, Gomez B, Umutlu L, Bockisch A, 
Rosenbaum-Krumme SJ (2016) Imaging with 124I in differentiated thyroid 
carcinoma: Is PET/MRI superior to PET/CT ? Eur. J Nucl. Med. Mol. Imaging 
43: 1011-11017. 
 
10. Partovi S, Kohan A, Vercher-Conejero JL, Rubbert C, Margevicius S, 
Schlucter MD et al. (2014) Qualitative and quantitative performance of 18F-
FDG-PET/MRI versus 18F-FDG-PET/CT in patients with head and neck 
cancer. Am J Neuroradiol 35: 1970–1975. 
 
11. Schaarschmidt BM, Heusch P, Buchbender C, Ruhlmann M, Bergmann C, 
Ruhlmann V et al. (2016) Locoregional tumour evaluation of squamous cell 
carcinoma in the head and neck area: a comparison between MRI, PET/CT 
and integrated PET/MRI. Eur J Nucl Med Mol Imaging 43: 92–102. 
 
12. B A Tahir, A J Swift, H Marshall et al(2014).  A method for quantitative 
analysis of regional lung ventilation using deformable image registration of CT 
and hybrid hyperpolarized gas/1H MRIPhysics in medicine and biology 2014 
Dec 7;59(23):7267-77.  
13. B H Tahir, P J Hughes. S Robinson, M Q Hatton, J M Wild, R H Ireland 
(2018). Spatial Comparison of CT-Based Surrogates of Lung Ventilation With 
Hyperpolarized Helium-3 and Xenon-129 Gas MRI in Patients Undergoing 
Radiation Therapy International journal of radiation oncology 2018 Nov 
15;102(4):1276-1286. 
 
 
 

                                
                           
  
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14. Olliff J, Richards P, Connor S, Wong WL, Beale T, Madani G. Head and Neck 
Cancers. In: Nicholoson T (ed). Recommendations for cross-sectional 
imaging in cancer management, Second edition. London: The Royal College 
of Radiologists, 2014. 
 
15. The Royal College of Radiologists. Guidance on gadolinium-based contrast 
agent administration to adult patients. London: The Royal College of 
Radiologists, 2019. 
 
16. The International Atomic Energy Agency. Radiation Protection in newer 
medical imaging techniques: PET/CT. Vienna: International Atomic Energy 
Agency, 2008.