Abnormal neurite density and orientation dispersion in unilateral temporal lobe epilepsy detected by advanced diffusion imaging

Abstract

Background: Despite recent advances in diffusion MRI (dMRI), there is still limited information on neurite orientation dispersion and density imaging (NODDI) in temporal lobe epilepsy (TLE). This study aimed to demonstrate neurite density and dispersion in TLE with and without hippocampal sclerosis (HS) using whole-brain voxel-wise analyses.

Material and methods: We recruited 33 patients with unilateral TLE (16 left, 17 right), including 14 patients with HS (TLE-HS) and 19 MRI-negative ¹⁸F-fluorodeoxyglucose positron emission tomography (FDG-PET)-positive patients (MRI-/PET+ TLE). The NODDI toolbox calculated the intracellular volume fraction (ICVF) and orientation dispersion index (ODI). Conventional dMRI metrics, that is, fractional anisotropy (FA) and mean diffusivity (MD), were also estimated. After spatial normalization, all dMRI parameters (ICVF, ODI, FA, and MD) of the patients were compared with those of age- and sex-matched healthy controls using Statistical Parametric Mapping 12 (SPM12). As a complementary analysis, we added an atlas-based region of interest (ROI) analysis of relevant white matter tracts using tract-based spatial statistics.

Results: We found decreased neurite density mainly in the ipsilateral temporal areas of both right and left TLE, with the right TLE showing more severe and widespread abnormalities. In addition, etiology-specific analyses revealed a localized reduction in ICVF (i.e., neurite density) in the ipsilateral temporal pole in MRI-/PET+ TLE, whereas TLE-HS presented greater abnormalities, including FA and MD, in addition to a localized hippocampal reduction in ODI. The results of the atlas-based ROI analysis were consistent with the results of the SPM12 analysis.

Conclusion: NODDI may provide clinically relevant information as well as novel insights into the field of TLE. Particularly, in MRI-/PET+ TLE, neurite density imaging may have higher sensitivity than other dMRI parameters. The results may also contribute to better understanding of the pathophysiology of TLE with HS.

Keywords: Diffusion MRI; Hippocampal sclerosis; MRI-negative focal epilepsy; Neurite orientation dispersion and density imaging; Temporal lobe epilepsy.