Full exploitation of amyloid PET-MR data for dementia research

Simultaneous PET-MR data acquisition using amyloid radiotracers has utility for future clinical studies such as the development of novel therapeutic interventions for dementia. PET-MR as a new imaging modality suffers from some drawbacks such as inaccuracies in attenuation correction, but also offers significant advantages such as the simultaneity of data acquisition and the combined use of both imaging modalities to better understand the physiological measurements [1,2]. In the UK, there is a dementia platform UK (DPUK) network of 8 PET-MR scanners, a network that as part of a partnership grant conducted PET-MR test-retest scanning across these 8 scanners in 37 healthy elderly participants using two amyloid radiotracers, [18F]florbetaben and [18F]flutemetamol, a dataset which enables to precision of existing and new methods to be evaluated. Additionally, other PET-MR and PET-CT datasets are available or are currently being collected as part of multisite collaborations (ADNI, Amypad, Deep and Frequent Phenotyping).

Methods for the quantification of amyloid radiotracer uptake have been developed such as the calculation of standard uptake value ratios (SUVR) and their use to calculate centiloid values [3] or total brain load. However, such an approach has limitations in that: 1) it does not fully exploit the acquired data such evaluating temporal changes in radioactivity concentrations; 2) it does not exploit the simultaneously acquired MR data; and 3) it does not provide regional information on differential uptake within the brain. Likewise, functional MR data have utility as endpoints in clinical trials, but are often analysed in isolation of other MR sequences and PET data. It is therefore likely that alternative endpoints derived from PET-MR data to those previously proposed have greater value in future clinical trials. The Ph.D. research will therefore aim to develop and investigate novel methods of analysing amyloid PET-MR data in order to develop improved endpoints for use in future clinical studies.

Training/techniques to be provided

Quantitative skills – The proposed PhD project involves the analysis of imaging datasets from a clinical research study acquired on a combined PET-MR scanner. The student will thus develop their programming skills to process and combine the images from the two modalities. The student will also acquire skills in mathematical modelling when performing pharmacokinetic analyses of the advanced MR sequences and simultaneously acquired dynamic PET images to derive quantitative physiological parameters. Knowledge and understanding of statistics will be required to make comparisons between methods and within the brain.

Whole Organ/Organism Physiology – This brain imaging project aims to quantify amyloid deposition throughout the brain for which the student will learn about the anatomy and functioning of the brain, in health and when perturbed by neurodegeneration. The non-invasive in-vivo imaging biomarkers developed and validated in this project will be applicable to multiple neurodegenerative diseases other than dementia.

Entry requirements

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours BSc or MSc (or equivalent) in Physics, Biomedical Engineering or a related area. Candidates with experience in medical imaging or with an interest in neuroscience are encouraged to apply.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How To Apply

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. On the online application form select PhD Biomedical Imaging Sciences.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/programmes/integrated-teaching/

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered.

If you have any queries regarding making an application please contact our admissions team [email protected].

Equality, Diversity and 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/