Studying neurodegeneration in humans using multidimensional diffusion-relaxation MRI

National Institute On Aging

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Abstract

In this project we combine pre-clinical and clinical MRI sequences that allows the simultaneous T1, T2, and diffusion encoding (i.e., diffusion-relaxation multidimensional MRI) with complementary histological methods, to investigate cellular processes that relate to function, microstructure, and chemical composition in normative aging, mild cognitive impairment, and dementia. The type of data acquisition and approach is novel and is only now starting to be used to investigate the human brain. We therefore established two foundational components to this research initiative: 1. Ex vivo studies: Identification of MRI markers of Alzheimers Disease (AD) pathology using combined post-mortem multidimensional MRI and histopathology studies that results in radiological-pathological integration. Given the prominent microscale chemical and structural alterations that accompany AD, such as Tau accumulation, beta-amyloid deposition, and TDP-43 proteinopaty, these advanced quantitative approaches are well suited to the discovery of new markers. Specifically, we scanned human brain samples from healthy and from donors with known AD pathology with a range of Braak stages, and from various regions including the superior frontal gyrus and the temporal lobe (hippocampus) using a 7 T Bruker MRI scanner. The analysis of these data and the neuropathological assessment is currently ongoing. 2. In vivo studies: Establish a pipeline to migrate ex vivo MRI methods to clinical MRI scanners. Develop clinical versions of AD-sensitive ex vivo multidimensional MRI pulse sequences we discovered and design appropriate imaging protocols. Then, develop pre-processing and post-processing procedures to handle the novel imaging data we acquire, and design a data analysis framework that provides diagnostic imaging biomarkers.