Alzheimers Disease Project: Linking brain micro- and meso-structure with cognitive functioning

National Institute On Aging

Investigators

Linked publications & trials

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. Below, milestones from this project are summarized: 1. We have successfully developed and implemented a novel diffusion-relaxation multidimensional MRI acquisition protocol on a 3T clinical scanner, which simultaneously characterizes micro- and meso-structure and local chemical composition, and importantly, how these properties are coupled within complex tissue that contains multiple microenvironments. This 40 minute scan delivers 2 mm isotropic resolution and allows one to explore both the frequency-dependent and tensorial aspects of diffusion, enabling investigation of frequency/time-dependent changes of diffusion-relaxation correlations measures using a single framework. 2. We first scanned a well-defined physical phantom, demonstrating the robustness of this imaging protocol. We used these data, along with a few healthy volunteers, to design, implement and test a suitable pre-processing pipeline for multidimensional MRI data. 3. We performed a test-retest study scanning several healthy volunteers to establish repeatability and reproducibility. 4. We used the recently introduced mean apparent propagator (MAP) MRI framework to investigate existing large-scale cross-sectional and longitudinal neuroimaging studies. MAP-MRI comprehensively captures the micro- and mesoscopic complexity of cerebral tissue, encompassing various underlying structural and architectural characteristics. Initially, we explored age-related differences in a cross-sectional cohort of 58 cognitively unimpaired participants from the Baltimore Longitudinal Study of Aging (BLSA) and Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT). This study revealed that MAP-MRI derived parameters contain novel information related to cerebral aging, contributing to the biological interpretation of changes across the adult lifespan.