Microstructural imaging in temporal lobe epilepsy: Diffusion imaging changes relate to reduced neurite density

Gavin P Winston, Sjoerd B Vos, Benoit Caldairou, Seok-Jun Hong, Monika Czech, Tobias C Wood, Stephen J Wastling, Gareth J Barker, Boris C Bernhardt, Neda Bernasconi, John S Duncan, Andrea Bernasconi, Gavin P Winston, Sjoerd B Vos, Benoit Caldairou, Seok-Jun Hong, Monika Czech, Tobias C Wood, Stephen J Wastling, Gareth J Barker, Boris C Bernhardt, Neda Bernasconi, John S Duncan, Andrea Bernasconi

Abstract

Purpose: Previous imaging studies in patients with refractory temporal lobe epilepsy (TLE) have examined the spatial distribution of changes in imaging parameters such as diffusion tensor imaging (DTI) metrics and cortical thickness. Multi-compartment models offer greater specificity with parameters more directly related to known changes in TLE such as altered neuronal density and myelination. We studied the spatial distribution of conventional and novel metrics including neurite density derived from NODDI (Neurite Orientation Dispersion and Density Imaging) and myelin water fraction (MWF) derived from mcDESPOT (Multi-Compartment Driven Equilibrium Single Pulse Observation of T1/T2)] to infer the underlying neurobiology of changes in conventional metrics.

Methods: 20 patients with TLE and 20 matched controls underwent magnetic resonance imaging including a volumetric T1-weighted sequence, multi-shell diffusion from which DTI and NODDI metrics were derived and a protocol suitable for mcDESPOT fitting. Models of the grey matter-white matter and grey matter-CSF surfaces were automatically generated from the T1-weighted MRI. Conventional diffusion and novel metrics of neurite density and MWF were sampled from intracortical grey matter and subcortical white matter surfaces and cortical thickness was measured.

Results: In intracortical grey matter, diffusivity was increased in the ipsilateral temporal and frontopolar cortices with more restricted areas of reduced neurite density. Diffusivity increases were largely related to reductions in neurite density, and to a lesser extent CSF partial volume effects, but not MWF. In subcortical white matter, widespread bilateral reductions in fractional anisotropy and increases in radial diffusivity were seen. These were primarily related to reduced neurite density, with an additional relationship to reduced MWF in the temporal pole and anterolateral temporal neocortex. Changes were greater with increasing epilepsy duration. Bilaterally reduced cortical thickness in the mesial temporal lobe and centroparietal cortices was unrelated to neurite density and MWF.

Conclusions: Diffusivity changes in grey and white matter are primarily related to reduced neurite density with an additional relationship to reduced MWF in the temporal pole. Neurite density may represent a more sensitive and specific biomarker of progressive neuronal damage in refractory TLE that deserves further study.

Keywords: Diffusion imaging; Multi-compartment models; Myelination; Neurite density; Temporal lobe epilepsy.

Conflict of interest statement

Declarations of Competing Interest None.

Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.

Figures

Fig. 1
Fig. 1
Image processing framework. Grey matter-white matter and grey matter-CSF cortical surfaces were extracted from the T1-weighted image (top, cyan and blue respectively) and midcortical and 2 mm subcortical surfaces were generated using a Laplacian potential (top, red and green respectively). These surfaces were registered to diffusion and DESPOT space using the FA image (middle left) and IR-SPGR (middle right) respectively. Measurements from diffusion and DESPOT scans were sampled along these surfaces (bottom). Examples of mean values in patients on the two surfaces are shown for diffusion (FA, MD, ICVF) and DESPOT (MWF) scans.
Fig. 2
Fig. 2
Intracortical grey matter (main and regression findings). Group comparisons show that in patients mean diffusivity was increased in ipsilateral temporal and frontopolar regions (A) whilst reduced neurite density was more confined to mesial and basal temporal regions (B). Linear regression showed that increased mean diffusivity was related to both CSF fraction (C) and neurite density (D). Uncorrected p-values shown for significant clusters (defined by FWE 0.05, cluster threshold 0.01).
Fig. 3
Fig. 3
Subcortical white matter (main findings). Group comparisons show that in patients, bilateral reductions in FA were observed in temporal and frontopolar regions (A) with a similar distribution of increased RD (B) and reduced neurite density (C). Reduced myelin fraction (D) was more confined to the ipsilateral temporal lobe. Uncorrected p-values shown for significant clusters (defined by FWE 0.05, cluster threshold 0.01).
Fig. 4
Fig. 4
Subcortical white matter (regression findings). Linear regression showed that reduced FA in the ipsilateral temporal lobe is associated with axonal loss (A) with an additional relationship to altered myelination in the temporal pole and anterolateral temporal neocortex (B). A similar pattern was observed for the increase in RD (C,D). Neurite density in the temporal pole was more reduced with longer disease duration (E, shown with an outlier removed). Uncorrected p-values shown for significant clusters (defined by FWE 0.05, cluster threshold 0.01).

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