A Multimodal Approach to Image the Human Spinal Cord with Simultaneous Positron Emission Tomography and functional Magnetic Resonance Imaging

Details

Background

PET-MRI is a novel hybrid imaging technique that combines the metabolic specificity of PET with anatomical, microstructural and functional information available through MRI. This promises to provide novel insights into the specific role of the spinal cord in the progression of a range of nervous system diseases, and potentially lead to new biomarkers or treatment targets. Unfortunately, the spinal cord has so far remained a blind spot in PET-MRI due to technical challenges such as severe image distortions caused by the attenuation of radiation in the bone around the spinal cord and physiological noise.

 Preliminary studies: In an ongoing PhD project led by the primary supervisor (SPS, physicist), solutions have been developed to address these technical problems using dedicated PET-MRI reconstruction methods. With support from the vendor, these solutions have been successfully implemented on the new PET-MRI system in Sheffield. Independently, the secondary supervisor (DS, clinician scientist ) has been awarded a training scholarship to visit the Systems Neuroscience and Pain Lab at Stanford University, where he will learn to apply functional MRI (fMRI, or BOLD-MRI) to investigate spinal cord neuronal function on PET-MRI scanners.

 The integration of these two cross-disciplinary perspectives now opens a unique opportunity to study metabolic activity, neuronal microstructure, and function of the spinal cord in range of nervous system diseases using combined PET and fMRI.

 Hypotheses

The combination of metabolic activity measured by PET with functional imaging measured with fMRI will generate novel insights into the role of the spinal cord in demyelinating, inflammatory and neurodegenerative disease of the nervous system. This will have implications in the diagnosis and prognosis of conditions such as multiple sclerosis, motor neuron disease and peripheral nerve diseases such as diabetic neuropathy.

Aims and objectives

The global aim of this PhD project is to advance the state-of-the-art of PET-MRI to quantify spinal cord metabolic activity, neuronal microstructural and functional integrity. Specifically, we will establish a joint PET and fMRI methodology in-vivo, on the hybrid PET-MRI scanner in Sheffield and test proof of concept in both health and disease.

Specific objectives:

 Year 1 (Technical developments). To set up and optimize joint microstructure, anatomical and functional (BOLD) MRI of the spinal cord on the PET-MRI system in Sheffield, and demonstrate feasibility in volunteers by performing acquisition and analysis of resting-state (task-free) fMRI data including motion correction, image denoising, and use of software analysis tools [Data Processing Assistant for Resting-State fMRI Advance Edition Toolbox, GraphVar software and the Brain Connectivity Toolbox].

 Year 2 (Healthy volunteer studies). To examine the relationship between the intensity of stimulation and the amplitude of the BOLD-fMRI response in human spinal cord during a controlled motor task (graded isometric force) and sensory task (nociceptive heat stimulation) with the dominant hand. In addition, we will study the structure and distribution of the vascular and neuronal network, which together contribute to the BOLD fMRI signal. This study will be performed in healthy volunteers across different age and sex strata and will serve as normative data for interpretation of results in patients in Year 3.

 Year 3 (Patient studies). Studies in carefully phenotyped patients with peripheral neuropathy [painless (n=10) and painful (n=10) diabetic neuropathy]. This will provide validation for the specificity of multimodal PET-MR metrics via comparison to healthy volunteer cohorts. The experiments require the implementation of PET-MR scans as well as complex analysis pipelines. We will also design and run computer simulations to aid with the interpretation of our in vivo findings. 

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Please see this link for information on how to apply: https://www.sheffield.ac.uk/postgraduate/phd/apply/applying. Please include the name of the first supervisor and the title of the PhD project within your application. Please state Division of Neuroscience as the division of your project, regardless of where your supervisor sits.

Interviews will be held late November/early December. Students must be able to start in February 2024.

Applications are open to home students only. We would expect applicants to have an excellent undergraduate degree in a relevant discipline. We would also expect applicants to have completed or be undertaking a relevant master’s degree to a similar very high standard (or have equivalent research experience).