Ex vivo mesoscopic diffusion MRI correlates with seizure frequency in patients with uncontrolled mesial temporal lobe epilepsy

Abstract

The role of hippocampal connectivity in mesial temporal lobe epilepsy (mTLE) remains poorly understood. The use of ex vivo hippocampal samples excised from patients with mTLE affords mesoscale diffusion magnetic resonance imaging (MRI) to identify individual cell layers, such as the pyramidal (PCL) and granule cell layers (GCL), which are thought to be impacted by seizure activity. Diffusion tensor imaging (DTI) of control (n = 3) and mTLE (n = 7) hippocampi on an 11.7 T MRI scanner allowed us to reveal intra-hippocampal connectivity and evaluate how epilepsy affected mean (MD), axial (AD), and radial diffusivity (RD), as well as fractional anisotropy (FA). Regional measurements indicated a volume loss in the PCL of the cornu ammonis (CA) 1 subfield in mTLE patients compared to controls, which provided anatomical context. Diffusion measurements, as well as streamline density, were generally higher in mTLE patients compared to controls, potentially reflecting differences due to tissue fixation. mTLE measurements were more variable than controls. This variability was associated with disease severity, as indicated by a strong correlation (r = 0.87) between FA in the stratum radiatum and the frequency of seizures in patients. MD and RD of the PCL in subfields CA3 and CA4 also correlated strongly with disease severity. No correlation of MR measures with disease duration was evident. These results reveal the potential of mesoscale diffusion MRI to examine layer-specific diffusion changes and connectivity to determine how these relate to clinical measures. Improving the visualization of intra-hippocampal connectivity will advance the development of novel hypotheses about seizure networks.

Alterations in white matter integrity and asymmetry in patients with benign childhood epilepsy with centrotemporal spikes and childhood absence epilepsy: An automated fiber quantification tractography study

“…The precise correlation between WM integrity and seizure frequency remains unclear in BECTS. Interestingly, many other epilepsy syndromes, such as temporal lobe epilepsy and juvenile myoclonic epilepsy, have demonstrated that greater WM abnormalities are associated with the higher frequency of seizures [53,54]. These findings and ours raise the possibility that repetitive seizures could promote progressive WM impairment across epilepsy syndromes.…”

Layer‐specific microstructural patterns of anterior hippocampus in Alzheimer's disease with ex vivo diffusion MRI at 14.1 T

“…Previous ex vivo studies in hippocampus mostly focused on the hippocampal body or middle hippocampus (Ke et al, 2020 ; Ly et al, 2020 ), which has a dark band with a “C” or reversed “C” shape in T2‐weighted image as a hallmark for segmenting the subfields and layers (de Flores et al, 2020 ). The anterior part of hippocampus is more complex with more folds and larger individual variances than the middle part (de Flores et al, 2020 ; DeKraker et al, 2020 ).…”

“…A recent ex vivo study in hippocampal body using DTI found that patients with mesial temporal lobe epilepsy exhibited a larger variance in dMRI measures in hippocampal layers compared to controls (Ke et al, 2020 ). Authors explained that this difference might reflect the variability in clinical measures (i.e., seizure severity or frequency).…”

“…Considering the small sample size, no group comparison was performed in the current study. Instead, we compared the variability of the dMRI measurements among the three groups, as done in previous studies (Ke et al, 2020 ). The HC group was much younger than other two groups, and the volume of anterior hippocampus showed a significant negative correlation with age ( r = −0.71, p = .02) across all samples in the present study.…”

“…Recent ex vivo dMRI studies have characterized the DTI features of subfields and layers in middle hippocampus of mesial temporal lobe epilepsy (Ly et al, 2020 ). Ke et al ( 2020 ) reported that inter‐hippocampal connectivity and FA in several layers were correlated with seizure frequency in patients with epilepsy. Despite the high‐sensitivity of DTI‐based indices, the tensor model cannot handle scenarios of branching or crossing fibers (Crombe et al, 2018 ), which is common in complex microstructures such as the hippocampus, for example, the axons of the pyramidal neurons run across the Shaffer collateral, Mossy fiber, and prefrontal pathway.…”