Mesoscopic Diffusion-based MRI Histology of Epileptic Human Hippocampi



 DESCRIPTION (provided by applicant): Epilepsy is the fourth most common neurological disorder in the United States with an approximate cost of $17.6 billion per year. Anti-epileptic medication is effective in most cases, but is insufficient to control seizures in as many as 40% of patients. Patients with focal epilepsy that can be shown to arise from a specific brain region, by noninvasive testing (EEG, imaging studies) or invasive intracranial recordings, are candidates for surgical resection. The most common type of resective epilepsy surgery is anterior temporal lobectomy, which includes removal of the hippocampus. There is good evidence that there is an ictal focus, a region where the seizure originates (typically defining the target for surgical intervention), but the functional anatomy of the seizure also affects regions downstream and is modulated by the input to the ictal focus. Understanding the seizure network, rather than merely the ictal focus (where aberrant processing converges to produce uncontrolled activity), will be an important advance to improve our surgical interventions and care for the affected individuals. Nevertheless current approaches such as clinical MRI or EEG, as well as neuropathology are inadequate to resolve the seizure network. We therefore here propose to investigate the use of mesoscale MRI on surgically-resected epileptic hippocampi to uncover anatomical changes that constitute a seizure network. Specificially, we here aim to: 1) further develop diffusion-based MR histology to better distinguish cell layer and axonal connectivity, as well as 2) implementing a 3 dimensional reconstruction of histological sections to validate tractographic reconstructions. The overarching goal is to provide a method that can lead to a better description of the seizure network to improve our understanding of mTLE with a tangible benefit to patients undergoing a hippocampectomy by improving the differential diagnosis, as well as pre-surgical planning