Abstracts

Rationale: Subcortical band heterotopia (SBH) is a disorder of neuronal migration most commonly due to mutations of the Doublecortin (DCX) gene [1]. A range of phenotypes is seen, with most patients having some degree of epilepsy and intellectual disability. Advanced structural and functional magnetic resonance imaging (MRI) may be useful in identifying heterotopias and dysplasias of different sizes in drug-resistant epilepsy. We describe a patient with SBH and drug-resistant epilepsy and investigate neurite density, neurite dispersion, and glutamate concentrations as compared to a healthy control through the use of multiple advanced MRI modalities. Methods: Multiple MR imaging modalities were acquired as part of a research epilepsy imaging protocol on a 3.0 T Siemens TrioTim Magnetom system and a 7.0 T multi-transmit Siemens MRI system. T1-weighted MP-RAGE, high-resolution T2 weighted imaging, and diffusion tensor imaging were collected on the 3.0 T scanner. GluCEST [2] maps were collected on a 7.0 T using a novel glutamate imaging sequence and corrected for B0 inhomogeneity. NODDI maps were derived using the NODDI MATLAB toolbox [3]. Results: Neurite density and dispersion in heterotopia was found to be more similar to white matter than gray matter. Figure 1 shows the patient (top row) and age-matched healthy control (bottom row). First two columns show T1-Weighted MPRAGE and Orientation Dispersion Index (ODI) derived from NODDI imaging. Band heterotopia (arrows) clearly delineated in a bilateral band located between the ventricular wall and cortical mantle. ODI map shows aberrant neurite dispersionin white matter regions as compared to healthy control ODI map. The third column shows tractography obtained by seeding the normal location of the superior longitudinal fasciculus. The fourth column shows tractography obtained by seeding the genu, body and splenium of the corpus callosum. Most large tracts, such as callosal fibers, could be followed through the heterotopic tissue, however the superior longitudinal fasciculus was attenuated compared to the control. Figure 2 shows patient MPRAGE along with a GluCEST map. Increased glutamate concentration is seen concordant with heterotopia on T1 imaging. Conclusions: Neurite density and dispersion maps obtained using diffusion imaging may be able to better characterize different subtypes of heterotopia. Advanced diffusion and metabolic imaging methods can provide novel information about abnormal gray matter in SBH beyond what is detected on structural MRI. These parameters may further enhance our understanding of the pathophysiologic mechanisms of malformations of cortical development as well as guiding targeted therapies. Funding: 1U24-NS-063930 NIH/ NINDS The International Epilepsy Electrophysiology Database, P20-NS-080181/P20-NS12006 NIH/NINDS The Epilepsy Bioinformatics Study (EpiBioS), McCabe Pilot Award (University of Pennsylvania), Center for Biomedical Image Computing and Analytics Seed Award (University of Pennsylvania), and the Thornton Foundation. Additional grant funding provided by NIH 1-T32-NS-091006-01 (Training Program in Neuroengineering and Medicine).