Magnetic Resonance Imaging and Histology Correlation in the Neocortex in Temporal Lobe Epilepsy

ObjectiveTo investigate the histopathological correlates of quantitative relaxometry and diffusion tensor imaging (DTI) and to determine their efficacy in epileptogenic lesion detection for preoperative evaluation of focal epilepsy. MethodsWe correlated quantitative relaxometry and DTI with histological features of neuronal density and morphology in 55 regions of the temporal lobe neocortex, selected from 13 patients who underwent epilepsy surgery. We made use of a validated nonrigid image registration protocol to obtain accurate correspondences between in vivo magnetic resonance imaging and histology images. ResultsWe found T1 to be a predictor of neuronal density in the neocortical gray matter (GM) using linear mixed effects models with random effects for subjects. Fractional anisotropy (FA) was a predictor of neuronal density of large-caliber neurons only (pyramidal cells, layers 3 and 5). Comparing multivariate to univariate mixed effects models with nested variables demonstrated that employing T1 and FA together provided a significantly better fit than T1 or FA alone in predicting density of large-caliber neurons. Correlations with clinical variables revealed significant positive correlations between neuronal density and age (r(s)=0.726, p(fwe)=0.021). This study is the first to relate in vivo T1 and FA values to the proportion of neurons in GM. InterpretationOur results suggest that quantitative T1 mapping and DTI may have a role in preoperative evaluation of focal epilepsy and can be extended to identify GM pathology in a variety of neurological disorders. Ann Neurol 2015;77:237-250