Patterns of regional hippocampal diffusion abnormalities and surgical outcomes in mesial temporal lobe epilepsy

Previous high-resolution diffusion tensor (DTI) studies demonstrated elevated regional mean diffusivity in Mesial Temporal Lobe Epilepsy patients with hippocampal sclerosis (MTLE-HS), which correlated with post-surgical histology. The purpose here was to apply novel segmentation and visualization software to hippocampal diffusion tensor image to better characterize the patterns of diffusion abnormalities in regional hippocampal subfields (Subiculum, CA1, CA2, CA3, CA4/DG) in MTLE-HS and determine whether these patterns correlate with surgical outcomes. 1-mm isotropic diffusion tensor image of the hippocampus was acquired at 3T in 59 mesial temporal lobe epilepsy patients (before surgery) and 56 controls. Mean diffusivity was mapped to the hippocampal surface using HippUnfold, a deep learning-based software which provides automatic hippocampal subfield segmentation and unfolded hippocampal surfaces. Hippocampi with hippocampal sclerosis demonstrated significantly elevated mean diffusivity for whole hippocampus and all subfields compared to controls (P < 0.001). Unfolded hippocampal maps showed regional heterogeneity across all groups, with hippocampi of temporal lobe epilepsy patients without hippocampal sclerosis closely matching controls. In the MTLE-HS group, hippocampal sclerosis was associated with elevated mean diffusivity with dramatic heterogeneity in the pattern of elevation between subjects and along the long axis of the hippocampus in individual subjects. While whole hippocampus and whole subfield measurements were not significantly different from controls for the contralateral hippocampus, regional patterns of mean diffusivity elevation were observed which were consistent with the hippocampus with hippocampal sclerosis, although at lower levels of intensity. For the seizure-free (n=16) patients, mean diffusivity of the resected hippocampus was significantly elevated for the head, body, and tail, while only the head demonstrated significant differences for the not-seizure-free (n=9) group. HippUnfold provided enhanced visualization of the pattern of regional diffusion abnormalities in mesial temporal lobe epilepsy patients with seizure-free surgical outcomes being associated with more extensive regional abnormalities of the resected hippocampus.