Fiber ball white matter modeling in focal epilepsy

Abstract

Multicompartment diffusion magnetic resonance imaging (MRI) approaches are increasingly being applied to estimate intra-axonal and extra-axonal diffusion characteristics in the human brain. Fiber ball imaging (FBI) and its extension fiber ball white matter modeling (FBWM) are such recently described multicompartment approaches.However, these particular approaches have yet to be applied in clinical cohorts. The modeling of several diffusion parameters with interpretable biological meaning may offer the development of new, noninvasive biomarkers of pharmacoresistance in epilepsy. In the present study, we used FBI and FBWM to evaluate intra-axonal and extra-axonal diffusion properties of white matter tracts in patients with longstanding focal epilepsy. FBI/FBWM diffusion parameters were calculated along the length of 50 white matter tract bundles and statistically compared between patients with refractory epilepsy, nonrefractory epilepsy and controls. We report that patients with chronic epilepsy had a widespread distribution of extra-axonal diffusivity relative to controls, particularly in circumscribed regions along white matter tracts projecting to cerebral cortex from thalamic, striatal, brainstem, and peduncular regions. Patients with refractory epilepsy had significantly greater markers of extra-axonal diffusivity compared to those with nonrefractory epilepsy. The extra-axonal diffusivity alterations in patients with epilepsy observed in the present study could be markers of neuroinflammatory processes or a reflection of reduced axonal density, both of which have been histologically demonstrated in focal epilepsy. FBI is a clinically feasible MRI approach that provides the basis for more interpretive conclusions about the microstructural environment of the brain and may represent a unique biomarker of pharmacoresistance in epilepsy.

High fidelity fiber orientation density functions from fiber ball imaging

“…These have proven valuable for both fiber tractography 4 and microstructural modeling. [5][6][7][8] Advancements in the measurement of fODFs now make it feasible to extract detailed information about fODF structure that go beyond identifying a few primary fiber bundle directions and supporting the calculation of compartmental diffusion parameters. However, systematic methods for exploiting this information are not currently well developed, which limits the application of fODF structure to the investigation and assessment of white matter disease.…”

“…An important step was the introduction of fODF approaches which focus on the main source of diffusion anisotropy, namely water confined inside axons. These have proven valuable for both fiber tractography 4 and microstructural modeling 5–8 . Advancements in the measurement of fODFs now make it feasible to extract detailed information about fODF structure that go beyond identifying a few primary fiber bundle directions and supporting the calculation of compartmental diffusion parameters.…”

“…Estimation of the fODF for individual imaging voxels is one of the more remarkable abilities of diffusion MRI (dMRI), providing a unique picture of the intricate details of brain tissue cytoarchitecture. Heretofore, fODFs have mainly been applied to support fiber tractography 4 and microstructural modeling 5–8 . In both cases, the fODF is essentially regarded as an input for the calculation of other physical quantities.…”

High b-value diffusion tractography: Abnormal axonal network organization associated with medication-refractory epilepsy

“…A key aspect of FBI, and some other high b -value diffusion imaging methods, is that the MRI signal originates predominately from intra-axonal water since the signal from the more mobile pool of extra-axonal water is suppressed by strong diffusion weighting ( Bryant et al, 2021 ; Jensen et al, 2016 ). As a consequence, FBI fiber tractography solely reflects the geometry of axons without contamination from the extra-axonal microenvironment, resulting in improved fidelity and robustness with respect to tissue changes (e.g., edema) that might otherwise impact the estimated axonal pathways.…”

“…In a recent epilepsy FBI study, we observed that refractory epilepsy is associated with abnormalities in white matter composition in comparison with patients with well controlled epilepsy and with healthy controls ( Bryant et al, 2021 ). Patients with epilepsy demonstrated intra- and extra-axonal abnormalities suggesting alterations in axonal projections and peri-axonal milieu changes, respectively.…”