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Investigating the in vivo Spatial Distribution of Hippocampal Microstructure and Macrostructure

The hippocampus is classically divided into mesoscopic subfields which contain varying microstructure that contribute to their unique functional roles. It has been challenging to characterize this microstructure with current MR based neuroimaging techniques. In this work, we used a novel surface-based approach in the hippocampus to show distinct microstructural distributions of myelin, neurite density and dispersion, fractional anisotropy, and mean diffusivity using diffusion MRI. To get at this issue we used the Neurite Orientation Dispersion and Density Imaging (NODDI) model optimized for gray matter diffusivity and diffusion tensor imaging (DTI). We found that neurite dispersion was highest in the Cornu Ammonis (CA) 1 and subiculum subfields which likely captures the large heterogeneity of tangential and radial fibers, such as the Schaffer collaterals, perforant path, and pyramidal neurites. Neurite density and myelin content were highest in the subiculum and lowest in CA1, which may reflect known myeloarchitecture differences between these subfields. We show macrostructural measures of gyrification, thickness, and curvature which were in line with ex vivo descriptions of hippocampal anatomy. We employed a multivariate orthogonal projective non-negative matrix factorization (OPNNMF) approach to capture co-varying regions of macro- and microstructure across the hippocampus. The clusters were highly variable along the medial-lateral (proximal-distal) direction, which is expected as there are known differences in morphology, cytoarchitectonic profiles, and connectivity. Long-axis (anterior-posterior) differences can also be seen in the OPNNMF components, where the body of the hippocampus has more parcellations than the head and tail. Finally, we show that by examining the main direction of diffusion relative to canonical hippocampal axes, we could identify microstructure that may map onto specific tangential fiber pathways, such as the Schaffer collaterals and perforant path. These results highlight the value of combining in vivo diffusion MRI with computational approaches for capturing hippocampal microstructure, which may provide useful features for understanding cognition and for diagnosis of disease states.