OCEAN Study
Research type
Research Study
Full title
ONE-STOP-SHOP MICROSTRUCTURE-SENSITIVE PERFUSION/DIFFUSION MRI: APPLICATION TO VASCULAR COGNITIVE IMPAIRMENT (OCEAN)
IRAS ID
198267
Contact name
Paul Ince
Contact email
Sponsor organisation
University of Sheffield
Duration of Study in the UK
3 years, 0 months, 31 days
Research summary
This project aims to study the 3 dimensional microstructure and pathology of deep subcortical lesions (DSCL) of white matter, control non lesional and normal-appearing white matter in human brain. It will use diffusion-weighted magnetic resonance imaging and microscopy, representing a “nested” style study within CFAS.
Blocks of white matter of approximately 15mm×15mm×10mm will be cut from formalin-fixed brain. These will then be scanned in a 7T Brucker small-bore MRI system. For approximately 15 cases (5 each of control, DSCL and normal-appearing), an approximately 5mm×5mm×10mm “sub block” will be cut from the larger block and processed to resin for serial semithin section cutting with toluidine blue staining. The residual tissue will be processed to paraffin, from which 20 serial sections will be cut at at various thicknesses at 3 levels and mounted onto microscope slides.
Thus, three, 3 dimensional datasets will be available from each tissue block: diffusion weighted MR at high resolution, epoxy resin-based and paraffin-based. The toluidine blue sections will give data on 3dimensional aspects of tissue structure, such as axonal and vascular thickness, branching and tortuosity. The paraffin sections at each level will be stained either by immunohistochemistry or by conventional histology to show a different tissue element (e.g. myelin, axon, blood vessel, extracellular matrix).
The study is predominatly concerned with development of MRI phantoms that will allow development of an improved diagnostic imaging protocol for vascular white matter disease based on microstructural data and measurements made in human tissue samples. Whilst it will not fully exploit the population-representative power of the CFAS cohort this resource is an ideal sample from which to obtain the varying degree of white matter integrity required. The sample size needed and the amounts of tissue involved will not degrade the value of the CFAS cohort for future studies.
REC name
West Midlands - South Birmingham Research Ethics Committee
REC reference
16/WM/0187
Date of REC Opinion
15 Apr 2016
REC opinion
Favourable Opinion