Structural and Diffusion Weighted MR Imaging of the Brain for Regional Analysis of Specific Mechanisms Underlying Individual Differences in Cognitive Outcomes Across the Lifespan

Abstract

The overall aim of this dissertation is to characterize the macrostructural (i.e. anatomical) and microstructural correlates of healthy cognitive aging in a rat model using high-resolution T2-weighted MRI and diffusion MRI (DMRI) of the brain, respectively. The cohort of rats in this work is the largest to date measuring behavior and carrying out non-invasive MRI at three distinct adult age groups (6, 15 and 23-months-old) and three cognitive groups (low, average and high) at each age. High-resolution 3D T2-weighted MRI images were analyzed in two different ways, namely, atlas-based region-of-interest analysis (ABA) and voxel-wise deformation based morphometry (DBM). The DMRI images were also analyzed in two different ways in this study, namely, diffusion tensor imaging (DTI) and fixel based analysis (FBA). Both macrostructural and microstructural MRI data are used to quantify any differences in healthy cognitive aging within and across age and cognitive groups. Neither macrostructural nor microstructural differences were observed with respect to cognition. However, both macrostructural and microstructural differences were see with respect to age. Interestingly, ABA and DBM identified both expansions and contractions with respect to age, where the deep brain structures are expanding and the neocortex is contracting. Microstructural analysis measured decreases in the apparent diffusion coefficient (ADC), and both decreases and increases FA in different parts of the brain, along with increases in the apparent fiber density in deep white matter structures. When coupled with the volumetry data the implications are that deep brain structures are growing in size and becoming more organized across the lifespan with the majority differences found between 6 month and 15-month age groups. Interestingly, differences between 15-month and 23-month-old groups, do continue, suggesting plasticity into old age. The findings of this study will further advance research on aging and may contribute to the establishment of interventional approaches to preserve healthy cognition into advanced age.