Molecular imaging of neurodegenerative pathology using deuterium MRI
Study Code / Acronym
MINDERAward Number
BB/X004260/1Status / Stage
ActiveDates
2 January 2023 -1 May 2024
Duration (calculated)
01 years 03 monthsFunder(s)
BBSRC (UKRI)Funding Amount
£179,543.00Funder/Grant study page
BBSRC UKRIContracted Centre
The University of ManchesterPrincipal Investigator
Dr Benjamin DickiePI ORCID
0000-0001-5018-2111WHO Catergories
Development of novel therapiesDisease Type
Alzheimer's Disease (AD)CPEC Review Info
| Reference ID | 380 |
|---|---|
| Researcher | Reside Team |
| Published | 12/06/2023 |
Data
| Study Code / Acronym | MINDER |
|---|---|
| Award Number | BB/X004260/1 |
| Status / Stage | Active |
| Start Date | 20230102 |
| End Date | 20240501 |
| Duration (calculated) | 01 years 03 months |
| Funder/Grant study page | BBSRC UKRI |
| Contracted Centre | The University of Manchester |
| Funding Amount | £179,543.00 |
Abstract
Problem: Alzheimer’s disease (AD) accounts for 60-70% of dementia cases, and is characterised by insidious accumulation of beta-amyloid and tau proteins in cortical regions. Current diagnosis of AD is led by clinical assessment of cognition/history, however such expert clinical estimates are wrong 30% of the time. In research studies, the precise contribution of AD relative to e.g. coexisting vascular pathology can be established using positron emission tomography (PET) scanning or cerebrospinal fluid analysis, however these tests are not in routine clinical use because of their high cost and limited availability. New imaging approaches that can detect molecular targets using clinically ubiquitous technologies such as magnetic resonance imaging (MRI) are urgently needed. However MRI currently lacks routine capability to detect proteins such as beta-amyloid, which are present in AD brain at concentrations between 1-10 microMolar (~1-10 nmol/g tissue). Proposed solution: Our objective is to make molecular imaging widely accessible by creating versatile ‘MRI detectable’ ligands. To demonstrate proof of concept, we will target beta-amyloid plaques by labelling existing beta-amyloid PET ligands with deuterium, then using deuterium-tuned MRI coils to detect the presence of the these ligands in the brain. We will optimise imaging protocols to maximise sensitivity to the ligand, including using ultra-short time-to-echo (UTE) spectroscopic imaging to capture rapidly decaying signal from bound ligand with short T2. Finally, we will obtain vital validatory data comparing detection of our deuterated ligand to florbetaben PET in 5xFAD mice, a commonly used mouse model of amyloidosis. Impact: The approach, if successful, could fundamentally transform clinical imaging capabilities both nationally and internationally by providing a means to perform molecular imaging in any hospital.
Aims
Our objective is to make molecular imaging widely accessible by creating versatile ‘MRI detectable’ ligands.