Neurite Orientation Dispersion and Density Imaging (NODDI) and Immune System Response in Temporal Lobe Epilepsy
Jerzy Szaflarski1, Rodolphe Nenert1, Huixian Hong1, Christina Mueller1, Ayushe Sharma2, Hongwei Qin1, Etty Benveniste1
1University of Alabama At Birmingham, 2Yale University
Objective:
To examine the relationship between a noninvasive indirect neuroimaging of neuroinflammation (NODDI) and molecular and cellular biomarkers of peripheral inflammation in temporal lobe epilepsy (TLE). We hypothesized NODDI changes in the affected temporal lobe (aTL; ictal onset zone) will be associated with these biomarkers.
Background:
Studies have shown that neuroinflammation is a primary contributor to seizure initiation and maintenance in TLE. We used whole-brain diffusion magnetic resonance imaging to identify abnormalities in multicompartment NODDI measures (FISO (free water), FICVF (neurite density), and ODI (neurite dispersion)) as a non-invasive proxy of neuroinflammation in TLE.
Design/Methods:
18 TLE and 18 healthy participants underwent 3T MRI HARDI protocol. FISO, FICVF and ODI statistical maps were generated for each participant. Two-sample t-tests (FDR corrected, p<0.05) were conducted to compare the two groups across these maps, focusing on the temporal region using a binary mask. Peripheral venous blood was collected at the time of imaging for biomarker testing. For each significant cluster identified, FISO, FICVF and ODI values were extracted for the TLE group and correlated with molecular and cellular biomarkers of peripheral inflammation.
Results:
We observed, mostly in the aTL, significantly higher FICVF values in healthy compared to TLE participants and higher ODI and FISO values in TLE compared to healthy participants. Multiple significant correlations (Spearman, p<0.05) were found between significant NODDI clusters and molecular and cellular biomarkers mostly in the aTL.
Conclusions:
Developing non-invasive procedures to measure neuroinflammation has been a major focus of neuroimaging investigations in epilepsy. Such a technique would allow visualization of abnormal brain regions for possible surgical resection, and monitoring of disease course and treatment response. We report significant positive relationships between NODDI measures and peripheral molecular and cellular biomarkers of inflammation in the aTL, supporting NODDI as a possible measure of neuroinflammation in TLE.
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