Regional hippocampal diffusion abnormalities associated with subfield-specific pathology in temporal lobe epilepsy

Sarah Treit; Graham Little; Trevor Steve; Tom Nowacki; Laura Schmitt; B Matt Wheatley; Christian Beaulieu; Donald W Gross

doi:10.1002/epi4.12357

Regional hippocampal diffusion abnormalities associated with subfield-specific pathology in temporal lobe epilepsy

Epilepsia Open. 2019 Sep 13;4(4):544-554. doi: 10.1002/epi4.12357. eCollection 2019 Dec.

Authors

Sarah Treit¹, Graham Little¹, Trevor Steve², Tom Nowacki², Laura Schmitt³, B Matt Wheatley⁴, Christian Beaulieu¹, Donald W Gross²

Affiliations

¹ Department of Biomedical Engineering Faculty of Medicine and Dentistry University of Alberta Edmonton Canada.
² Division of Neurology Faculty of Medicine & Dentistry University of Alberta Edmonton Canada.
³ Department of Laboratory Medicine and Pathology Faculty of Medicine and Dentistry University of Alberta Edmonton Canada.
⁴ Department of Surgery Faculty of Medicine and Dentistry University of Alberta Edmonton Canada.

Abstract

Objective: Hippocampal sclerosis (HS) is the most common pathology and best predictor of surgical outcome for medically refractory patients with temporal lobe epilepsy (TLE). Current clinical MRI methods can detect HS, but subfield pathology is poorly characterized, limiting accurate prediction of seizure-free outcomes after surgery. Diffusion tensor imaging (DTI) can probe regional microstructural changes associated with focal hippocampal pathology, but is typically limited by low-resolution whole-brain acquisitions.

Methods: High-resolution (1 × 1 × 1 mm³) DTI, T1, and quantitative T2 of the hippocampus was acquired in 18 preoperative TLE patients and 19 healthy controls. Diffusion images were qualitatively assessed for loss of internal architecture, and whole-hippocampus diffusion, volume, and quantitative T2 were compared across groups. Regional hippocampal diffusion abnormalities were examined in all subjects and compared to histology in four subjects who underwent anterior temporal lobectomy.

Results: High-resolution mean diffusion-weighted images enabled visualization of internal hippocampal architecture, used to visually identify HS with 86% specificity and 93% sensitivity. Mean diffusivity (MD) elevations were regionally heterogenous within the hippocampus and varied across TLE patients. The spatial location of diffusion abnormalities corresponded with the location of focal subfield neuron loss, gliosis, and reduced myelin staining abnormalities identified with postsurgical histology in four subjects who underwent anterior temporal lobectomy. Whole-hippocampus MD and T2 relaxation times were higher, and fractional anisotropy (FA) and volumes were lower in TLE patients relative to controls. Left hippocampus MD correlated with verbal memory in the TLE group.

Significance: Visualization of internal architecture and focal diffusion abnormalities on high-resolution diffusion imaging suggests potential clinical utility of diffusion imaging in TLE and may have significant implications for surgical planning and prediction of seizure-free outcomes in individual patients.

Keywords: hippocampal sclerosis; histology; mean diffusivity; memory; temporal lobe epilepsy.