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Application of advanced MRI measurements to improve the management of brain tumours


   Faculty of Biology, Medicine and Health

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  Dr Owen Thomas, Dr L Parkes, Dr David Coope, Dr Ibrahim Djoukhadar  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Gliomas are the most common primary brain tumour and result in significant morbidly and mortality. Diffuse low-grade gliomas are a subset with a propensity for slow, insidious growth; they almost inevitably undergo transformation into high-grade gliomas with resultant neurological dysfunction and death. We will examine the feasibility of using two magnetic resonance imaging (MRI) techniques in the management of gliomas: 1) multi-delay arterial spin labelled (ASL) MRI to measure blood flow and 2) amide proton transfer-weighted (APT) MRI to measure cellular protein content. These imaging measurements should identify regions of altered tumour physiology which are invisible on conventional images.

The management of low-grade gliomas relies on MRI biomarkers of tumour micro-vascularity to identify regions of likely transformation. Conventional assessment requires the administration of a contrast agent and is therefore not ideal given that patients may undergo serial surveillance imaging. ASL MRI offers assessment of microvascular parameters without contrast administration (1). The use of multiple labelling delays offers more robust quantification of perfusion parameters particularly in tumours with abnormal blood flow patterns. We will assess whether multi-delay ASL could replace the use of contrast agents (2) and also compare it to a novel contrast-sparing technique (3).

For many years, the aim of high-grade glioma surgery was the complete resection of ‘enhancing’ tumour – the part that appears bright after contrast agent inject. More recently, studies have evaluated ‘supra-total’ resections that also include non-enhancing tumour – reliable identification of non-enhancing tumour is critical to this approach but biomarkers are lacking.  APT MRI is a novel technique that has been increasingly employed in glioma imaging to identify regions of active tumour. Initial studies have evaluated the role of APT imaging in glioma grading (4) and in differentiating tumour progression from treatment-related changes (5).  We will explore the role of APT MRI in identification of the non-enhancing tumour, thus facilitating supra-total resection. 

Entry Requirements:

Applicants are expected to hold (or about to obtain) a minimum upper second class undergraduate honours degree (or equivalent) in physics or engineering with a keen interest in biology and the brain. Research experience in imaging is desirable. A clinical radiology trainee with appropriate skills would also be considered. 

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. You MUST also submit an online application form - choose PhD Biomedical Imaging Sciences.

Equality, Diversity & Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/ 


Funding Notes

This project is jointly funded by the University of Manchester and Philips Healthcare. Studentship funding is for a duration of three years to commence in September 2021 and covers UK tuition fees and a UKRI stipend (£15609 per annum 21/22). The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a scholarship that will enable full studentship to be awarded to international applicants. This full studentship will only be awarded to exceptional quality candidates, due to the competitive nature of this funding.

References

(1) David C. Alsop, John A. Detre, Xavier Golay, Matthias Gunther, Jeroen Hendrikse, Luis Hernandez-Garcia, Hanzhang Lu, Bradley J. MacIntosh, Laura M. Parkes, Marion Smits, Matthias J. P. van Osch, Danny JJ Wang, Eric C. Wong, Greg Zaharchuk, ‘Recommended Implementation of Arterial Spin Labeled Perfusion MRI for Clinical Applications’ Mag Res Med 73(1):102-116 Jan [2015]. DOI: 10.1002/mrm.25197.
(2) Vidyasagar R, Abernethy L, Pizer B, Mallucci CL, Avula S, Parkes LM, ‘Quantitative measurement of blood flow in paediatric brain tumours – a comparative study of dynamic susceptibility contrast and multi time-point arterial spin labeled MRI.’ British Journal of Radiology 89:1062 April [2016] DOI: 10.1259/bjr.20150624
(3) Li KL, Djoukhadar I, Zhu X, Zhao S, Lloyd S, McCabe M, McBain C, Evans DG, Jackson A. ‘Vascular biomarkers derived from dynamic contrast-enhanced MRI predict response of vestibular schwannoma to antiangiogenic therapy in type 2 neurofibromatosis’. Neuro Oncol. 2016 Feb;18(2):275-82. doi: 10.1093/neuonc/nov168. Epub 2015 Aug 26. PMID: 26311690; PMCID: PMC4724182.
(4) Choi YS, Ahn SS, Lee SK, Chang JH, Kang SG, Kim SH, Zhou J. ‘Amide proton transfer imaging to discriminate between low- and high-grade gliomas: added value to apparent diffusion coefficient and relative cerebral blood volume’. Eur Radiol. 2017 Aug;27(8):3181-3189. doi: 10.1007/s00330-017-4732-0. Epub 2017 Jan 23. PMID: 28116517; PMCID: PMC5746027.
(5) Zhou J, Tryggestad E, Wen Z, Lal B, Zhou T, Grossman R, Wang S, Yan K, Fu DX, Ford E, Tyler B, Blakeley J, Laterra J, van Zijl PC. ‘Differentiation between glioma and radiation necrosis using molecular magnetic resonance imaging of endogenous proteins and peptides’. Nat Med. 2011 Jan;17(1):130-4. doi: 10.1038/nm.2268. Epub 2010 Dec 19. PMID: 21170048; PMCID: PMC3058561.
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