Abstracts

Rationale: The majority of MRI studies in temporal lobe epilepsy (TLE) have utilized morphometry to map widespread cortical alterations. Morphological markers, such as cortical thickness or grey matter density, reflect combinations of biological events largely driven by overall cortical geometry rather than intracortical tissue properties.  Because of its sensitivity to intracortical myelin, quantitative measurement of longitudinal relaxation time (qT1) provides and an in vivo proxy for cortical microstructure.  Here, we mapped the regional distribution of alterations in qT1 in TLE compared to healthy controls. Methods: We studied a consecutive cohort of 24 patients with a unilateral drug-resistant TLE patients who underwent a research-dedicated 3T MRI examination including qT1 mapping.  The control group consisted of 20 healthy individuals.  MR images in all patients and controls were obtained on a 3 Tesla Siemens TrioTim using a 32-channel head coil. We acquired 3D-MPRAGE images for cortical and hippocampal surface extractions aand performed qT1 mapping using a 3D MP2RAGE sequence [1], which provides intrinsic bias field cancellation and T1 estimation.  Resting-state fMRI was acquired using a 2D echo-planar imaging sequence. To examine intracortical qT1, we positioned different surfaces between the inner (grey matter-white matter) and outer (grey matter–CSF) cortical interface to systematically sample the axis perpendicular to the cortical ribbon. Surface-based statistics mapped the topography of qT1 differences between patients and controls. We repeated the analysis after correcting qT1 for estimates of cortical thickness and interface blurring at each surface point. Using linear models, we assessed effects of duration of epilepsy and age at seizure onset on qT1 in patients. To study co-occurrence of qT1 changes and functional anomalies, we performed a resting-state functional connectivity analysis centered on the peak regions of between-group differences in qT1. Results: Compared to controls, patients presented with a strictly ipsilateral distribution of qT1 increases in temporopolar, parahippocampal and orbitofrontal cortices (Fig 1). Based on supervised statistical learning, qT1 maps could lateralize the seizure focus in 92% of patients. Intracortical profiling of qT1 along streamlines perpendicular to the cortical mantle revealed marked effects in upper levels that tapered off at the white matter interface (Fig 2). Findings remained robust after correction for cortical thickness and interface blurring, suggesting independence from previously reported morphological anomalies in this disorder.  Mapping qT1 along hippocampal subfield surfaces revealed marked increases in anterior portions of the ipsilateral CA1-3 and DG that were also robust against correction for atrophy. Notably, in operated patients, qualitative histopathological analysis of myelin stains in resected hippocampal specimens confirmed disrupted internal architecture and fiber organization. Hippocampal and neocortical qT1 anomalies were more severe in patients with early disease onset.  Finally, analysis of resting-state connectivity from regions of qT1 increases revealed altered network embedding in patients, particularly to prefrontal networks. Conclusions: Analysis of qT1 suggests preferential susceptibility of ipsilateral temporo-limbic cortices to microstructural damage, possibly related to disrupted myeloarchitecture.  These alterations may reflect atypical neurodevelopment and affect fronto-limbic functional network integrity. Funding: AB and NB are supported by CIHR. BB is funded by a SickKids/CIHR New Investigator Grant and an FRQS junior 1 salary award. References: [1] Marques & Gruetter, 2013, Neuroimage