Microscopic fractional anisotropy asymmetry in unilateral temporal lobe epilepsy

Abstract

Objectives: Surgical resection is the method of choice for treating medically refractory unilateral temporal lobe epilepsy (TLE), but postsurgical prognosis depends on magnetic resonance imaging (MRI) findings. Seizure freedom is more often achieved after resection in MRI-positive patients (those with MRI abnormalities such as mesial temporal sclerosis) than in MRI-negative patients. Diffusion MRI shows promise as a marker of neuronal abnormalities due to its sensitivity to cellular changes such as axon damage, indexed by fractional anisotropy. However, fractional anisotropy is not specific to axon integrity in grey matter where axon orientation is not uniform. In contrast, microscopic fractional anisotropy is a recently introduced dMRI technique that is sensitive to axon integrity regardless of axon orientation. This work investigated whether microscopic fractional anisotropy may be sensitive to hippocampal abnormalities in unilateral TLE. Methods: Diffusion MRI was performed on a 3T scanner in 9 patients (age = 33 +/- 12 years) with unilateral TLE and 9 healthy volunteers (age = 26 +/- 6). A deep learning method was employed to segment the hippocampus into smaller subfields corresponding to the subiculum, cornu ammonis (CA) 1, CA2/3, and CA4 plus dentate gyrus (DG). Mean ipsilateral and contralateral measurements of subregion volume, diffusivity, fractional anisotropy, and microscopic fractional anisotropy were compared to investigate asymmetry in each subfield. Results: Microscopic fractional anisotropy was reduced, and diffusivity was elevated in the ipsilateral CA4/DG region relative to the contralateral side in all 9 patients. Asymmetries in diffusion metrics between the left and right sides of the hippocampus subfields were not observed in the healthy volunteers. Significance: Diffusion MRI may complement standard imaging procedures by detecting abnormalities in MRI-negative patients. Due to its insensitivity to axon orientation, microscopic fractional anisotropy may yield a more robust measurement than fractional anisotropy and may improve epileptic focus localization in surgical candidates.