Project Summary

 

ONE-STOP-SHOP MICROSTRUCTURE-SENSITIVE PERFUSION/DIFFUSION MRI: APPLICATION TO VASCULAR COGNITIVE IMPAIRMENT (OCEAN)  is a project funded by EPSRC that aims to characterise and quantify early differential alterations in brain blood transport and subsequent microstructural tissue damage using one-stop-shop perfusion/diffusion Magnetic Resonance (MR) Gradient Sensitised Imaging (GSI).  incorporating novel MR signal models and optimal MR sequence design based on new human brain histomorphometric data in health and disease.


How will we achieve this:

MR GSI will be developed as a one-stop-shop approach that sees p/d as two extremes of the same phenomenon. This is exploited in the context of Vascular Cognitive Impairment (VCI) where we propose the novel concept of associating the two regimes to different stages of the condition. We will develop ultra-detailed models of myelinated axon fibres and neuroglia, and of white matter (WM) microcirculation in normal and VCI-affected brains.

Finally, we will progress the state of the art in IVIM not only by developing an integrated approach with  diffusion Magnetic Resonance Imaging (dMRI), but also by a substantial leap forward in the way that intravoxel incoherent motion (IVIM) is analysed.


Objectives:

Our overall aim is to characterise and quantify early differential alterations in brain blood transport and subsequent microstructural tissue damage using one-stop-shop perfusion/diffusion MR GSI incorporating novel MR signal models and optimal MR sequence design based on new human brain histomorphometric data in health and disease.

OCEAN will:

Develop the most comprehensive statistical computational models of tissue blocks of WM microstructure and microcirculation to date based on novel human brain histomorphometric data in health and disease state.

Deliver the most detailed signal models to date of simultaneous diffusion and perfusion weighted MR GSI and robust and consistent estimators to optimally identify these model parameters.

Design a set of optimal gradient-sensitising directions and pulse sequence that harmonise constraints on optimal sensing and hardware demands enabling use across the widest range of clinical MR scanners

Develop tissue biomimetic brain phantoms based on polymer materials with dimensions, p and barrier permeabilities in the range of axons in WM serving as gold-standard for both p/d MRI

Demonstrate the accuracy of the proposed technique in high-resolution imaging of brain tissue blocks and biomimetic brain phantoms; demonstrate feasibility and clinical potential in a small patient cohort

Pathways to impact

Towards a technology for differential and early diagnosis of VCI-related dementias.

Dementia already is one of society’s biggest medical challenges. No cures are so far available. Given the variety of causes and aetiologies of dementia, reliable identification of the underlying pathologies is a requisite for therapy effectiveness. Differential diagnosis is therefore key.

Effectiveness, also, is greatly modulated by the level of disease progression in individuals. Even where outright cure is unrealistic, evidence already suggests that lifestyle changes and other treatments can delay the progression of symptoms, provided these are identified sufficiently early. This is of enormous significance to sufferers and their families. Societal economic implications aside, the quality of life benefits for sufferers from prolonged independence, and the emotional and financial alleviation for families and carers are substantial. Early diagnosis is therefore key.

It is in the provision of differential and early diagnosis that the technologies developed within OCEAN can have a serious impact.

By working towards technological innovations in perfusion/diffusion MRI for VaD, OCEAN will also foster developments aimed at other WM diseases.