Mesoscale Diffusion MRI of the Ex Vivo Human Hippocampus

modo cover image

McGowan Institute for Regenerative Medicine affiliated faculty member Michel Modo, PhD, Professor in the Department of Radiology at the University of Pittsburgh with secondary appointments in the Department of Bioengineering and the Center for Neural Basis of Cognition, and colleagues recently published a paper, titled “Mesoscale diffusion magnetic resonance imaging of the ex vivo human hippocampus,” in Human Brain Mapping where the authors anticipate that ex vivo mesoscale imaging will yield novel insights into human hippocampal connectivity. The paper was also the featured cover of the journal. The abstract of the paper reads:

Mesoscale diffusion magnetic resonance imaging (MRI) endeavors to bridge the gap between macroscopic white matter tractography and microscopic studies investigating the cytoarchitecture of human brain tissue. To ensure a robust measurement of diffusion at the mesoscale, acquisition parameters were arrayed to investigate their effects on scalar indices (mean, radial, axial diffusivity, and fractional anisotropy) and streamlines (i.e., graphical representation of axonal tracts) in hippocampal layers. A mesoscale resolution afforded segmentation of the pyramidal cell layer (CA1‐4), the dentate gyrus, as well as stratum moleculare, radiatum, and oriens. Using ex vivo samples, surgically excised from patients with intractable epilepsy (n = 3), we found that shorter diffusion times (23.7 ms) with a b‐value of 4,000 s/mm2 were advantageous at the mesoscale, providing a compromise between mean diffusivity and fractional anisotropy measurements. Spatial resolution and sample orientation exerted a major effect on tractography, whereas the number of diffusion gradient encoding directions minimally affected scalar indices and streamline density. A sample temperature of 15°C provided a compromise between increasing signal‐to‐noise ratio and increasing the diffusion properties of the tissue. Optimization of the acquisition afforded a system’s view of intra‐ and extra‐hippocampal connections. Tractography reflected histological boundaries of hippocampal layers. Individual layer connectivity was visualized, as well as streamlines emanating from individual sub‐fields. The perforant path, subiculum and angular bundle demonstrated extra‐hippocampal connections. Histology of the samples confirmed individual cell layers corresponding to ROIs defined on MR images. We anticipate that this ex vivo mesoscale imaging will yield novel insights into human hippocampal connectivity.

Illustration: Human Brain Mapping cover illustration, 09/20/20. Mesoscale diffusion MR‐based tractography bridges the knowledge gap between anatomical MRI and histology. Maria Ly, Lesley Foley, Ashwinee Manivannan, T. Kevin Hitchens, R. Mark Richardson, Michel Modo.