Restricted Spectrum Imaging Demonstrates Decreased Neurite Density in Patients with Mesial Temporal Lobe Epilepsy

Temporal lobe epilepsy (TLE) is a debilitating neurological condition that is physiologically characterized by pathological changes to the hippocampus and proximal tissues. Diffusion tensor imaging (DTI) has repeatedly shown that patients with TLE also have microstructural changes to temporal and extratemporal white matter unseen in traditional structural imaging. Previous DTI studies have shown decreased fractional anisotropy (FA), a measure representing directionality of diffusion, in patients with TLE compared to controls. The systematic decline of FA observed along major white matter tracts in TLE is often interpreted as a loss of integrity of white matter. However, FA is a nonspecific measure that is heavily influenced by not only axonal loss, but also by extracellular changes (i.e., edema, inflammation) and crossing fibers. In 21 patients with TLE and 11 age-matched controls, we aim to better characterize underlying white matter changes in TLE using a new diffusion model, Restricted Spectrum Imaging (RSI) that separates intracellular changes in diffusion (i.e., neurite density; ND) from extracellular changes (isotropic free water; IF) and crossing fibers (CF). Using both voxelwise and tract-based analysis, we demonstrate that both FA and ND measures have a high level of spatial correspondence, meaning the loss of directionality is primarily driven by the loss of diffusion derived from restricted neurite components, rather than increases in free water or the effects of CF. In addition, changes in ND, but not FA, were associated with disease duration, suggesting that ND may provide a more specific marker of white matter disease burden in refractory TLE