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McCabe, Alastair (2025) Evaluation of Oxygen-Enhanced MRI for the identification of hypoxia induced treatment resistant tumours in patients with head and neck cancer. PhD thesis, University of Nottingham.

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Abstract

Tumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Although potential hypoxia modification therapeutic strategies exist, they are not widely used in clinical practice in part due to a lack of a readily available method to identify patients who may benefit from such treatments. Imaging of tumour hypoxia is an appealing solution to this issue due to its ability to repeatedly provide information on the spatial distribution of oxygen. This thesis evaluates the potential use of the hypoxia imaging technique of oxygen-enhanced MRI (OE-MRI) for the assessment of tumour hypoxia in HNSCC.

A scoping review of the use of OE-MRI for the assessment of tumour hypoxia revealed strong pre-clinical evidence of the utility of OEMRI in assessing tumour hypoxia but limited clinical translation of this work with no published clinical studies of the use of OE-MRI in HNSCC at the start of this research.

A volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was developed and implemented on 1.5T clinical scanners using only routinely available clinical equipment. Initial testing of the protocol yielded results that were considered adequate to proceed to a clinical study. 25 participants were scanned breathing room air and during high flow oxygen administration. Oxygen induced changes in T1 times (ΔT1) and R2* rates (ΔR2*) were measured in malignant tissue and healthy organs. Patients were surveyed on their experience of the OE-MRI protocol.

The developed OE-MRI sequence took only 10 mins to acquire and was well tolerated. A non-rigid image co-registration approach was applied and its effect on OE-MRI derived data evaluated. A total of 15 histologically confirmed primary tumours and 41 malignant nodal masses were identified in the scanned participants. The OE-MRI sequence was able to discern differing response of healthy tissues and tumours to oxygen challenge. Estimates of tumour hypoxic fractions were obtained in all patient participants with a statistically non-significant greater magnitude of hypoxic fractions present for radiotherapy treatment resistant tumours. Exploratory analysis was performed to investigate potential novel OE-MRI derived biomarkers and to explore the feasibility of using OE-MRI derived hypoxic maps to aid radiotherapy treatment planning contouring.

In summary, a well-tolerated clinical implementation of dynamic, volumetric OE-MRI of the head and neck region using only routinely available equipment that allows discernment of differing oxygen responses within biopsy confirmed HNSCC is presented. Novel OEMRI analysis methods are discussed and suggestions made for future work in order to fully translate this technique into a clinically utilised resource in the management of HNSCC.

Trial registration: ClinicalTrials.gov, NCT04724096.

Registered 26 January 2021.

https://www.clinicaltrials.gov/study/NCT04724096

Item Type:	Thesis (University of Nottingham only) (PhD)
Supervisors:	Martin, Stewart Storr, Sarah
Keywords:	Tumour hypoxia; Oxygen-enhanced MRI; Head and neck
Subjects:	W Medicine and related subjects (NLM Classification) > WE Muscoskeletal system
Faculties/Schools:	UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID:	81040
Depositing User:	McCabe, Alastair
Date Deposited:	23 Jul 2025 04:40
Last Modified:	23 Jul 2025 04:40
URI:	https://eprints.nottingham.ac.uk/id/eprint/81040

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