High-resolution diffusion imaging of the hippocampus
Creators: Solar, Kevin Grant
Publisher: name: University of Alberta Library
Year: 2023

<p>The human hippocampus is difficult to image given its small size, location, shape, and complex internal architecture. Structural magnetic resonance imaging (MRI) has shown that typical age-related hippocampal volume changes vary along its anterior–posterior axis. Diffusion tensor imaging (DTI) provides complementary microstructural metrics, but there are few hippocampus DTI studies investigating typical age-related changes and all are limited by low spatial resolution. Structural MRI has also demonstrated smaller hippocampal volumes in individuals with prenatal alcohol exposure (PAE), which animal models suggest may result from microstructural changes due to cell loss and altered myelination; however, there are no PAE hippocampus DTI studies. Moreover, there are complex intra-hippocampal pathways with crossing fibers that DTI cannot resolve, hence there are few in vivo hippocampus DTI tractography studies and a more sophisticated approach is necessary and would be valuable for examining neurological/psychiatric disorders. Constrained spherical deconvolution (CSD) can disentangle complex fibers, however the only hippocampal CSD study used a low b value and low spatial resolution. <br>
Chapter 4 uses high spatial resolution 1 mm isotropic DTI of 153 healthy volunteers aged 5–74 years to investigate hippocampus diffusion and volume trajectories (whole-structure/head/body/tail) and memory correlations. Manually traced (on mean diffusion-weighted images, DWI) hippocampal volumes demonstrated age-related changes that varied across the head/body/tail. Fractional anisotropy (FA) and mean/axial/radial diffusivities (MD/AD/RD) yielded peaks or minima, respectively, at ~30–35 years across the hippocampus. Memory and FA and/or volume correlations were significant in younger volunteers (5–17 years), but not 18–49 or 50–74 year-olds. MD significantly correlated with memory in 18–49 year-olds, but not at other ages. Chapter 4 demonstrated regionally-specific age effects and cognitive correlations along the hippocampus anterior–posterior axis from 5-74 years. These findings form the basis of comparison to numerous neurological or psychiatric disorders.<br>
Chapter 5 comprises the first application of hippocampus DTI in PAE. Using the 1 mm isotropic DTI from Chapter 4, T1-weighted images, and cognitive testing, 36 healthy controls (8-24 years) and 19 participants with PAE (8-23 years) were studied. Whole-hippocampus volumes were 18% smaller in PAE than in controls on manually traced DTI, but automated T1-weighted image segmentations did not show group differences. Manual subregion DTI segmentation revealed reduced body/tail but not head volumes. There were no hippocampal diffusion metric group differences. Age and volume correlations were not significant in either group, whereas negative correlations between age and whole-hippocampus MD/AD/RD, and head/body (but not tail) MD/AD/RD were significant in both groups. In controls, seven positive linear correlations were found between hippocampal volume and episodic and working memory (left) and working memory and processing speed (right). In PAE, left tail MD positively correlated with executive functioning, and right head MD negatively correlated with episodic memory. Chapter 5 demonstrated hippocampal volume reductions and altered relationships with memory that suggest disrupted hippocampal development in PAE. <br>
Chapter 6 uses a multi-shell (64 b500s; 64 b2000s) version of the 1 mm isotropic diffusion protocol in Chapters 4/5. This qualitative pilot study included: 40 cross-sectional (scanned once) volunteers aged 5-90 years to demonstrate the feasibility of CSD tractography in comparison to DTI tractography across the lifespan, and six longitudinal (scanned twice) volunteers aged 23-40 years to demonstrate replicability. DTI ellipsoid maps and streamlines and CSD fiber orientation distribution function maps and streamlines demonstrated consistent anatomically-plausible fiber orientation patterns corresponding to polysynaptic and direct hippocampal pathways from 5-90 years and across the longitudinal data. CSD provided additional information in the form of anatomically-plausible crossing fibers that DTI could not resolve due to model limitations; the greatest portion of crossing fibers was in the hippocampal head. High spatial resolution diffusion data enables both DTI and CSD-based intrahippocampal tractography to provide anatomically-plausible results, but only CSD can resolve crossing fiber regions. Chapter 6 suggests that high spatial resolution diffusion tractography with DTI or CSD could be applied to study neurological and psychiatric disorders to identify potentially missing streamlines or differences in quantitative tract-based metrics that may relate to memory and other cognitive deficits.<br>
Altogether, this thesis demonstrates the applicability of clinically-relevant 1 mm isotropic hippocampus diffusion MRI protocols. These 3T MRI acquisitions allowed for novel studies of the hippocampus in humans across the typical life span (Chapters 4/6) and with PAE (Chapter 5). </p>