Project Summary In pediatric epilepsy patients with drug-resistant seizures, surgical resection is the most effective treatment option. The goal of resective surgery is to maximize removal of epileptic foci to attain seizure-freedom while minimizing damage to surrounding brain regions to avoid permanent post-surgical functional loss. Diffusion MRI enables rapid and non-invasive pre-surgical mapping of language, motor skills and other critical functional brain regions with high spatial resolution. However, excessive head motion presents a major limitation for acquiring high-quality diffusion MRI in pediatric patients with focal brain lesions, who usually have difficulty remaining still for long scan durations. Unfortunately, current retrospective and prospective approaches cannot adequately compensate for the complex effects of motion in diffusion MRI. As echo planar imaging (EPI) is highly susceptible to local magnetic field variations, motion-induced geometric distortions can lead to potentially significant mislocalization of important brain regions, even with accurate head motion tracking. The overarching goal of the research proposed under this application to the NIH is to dramatically improve the quality of diffusion MRI for pre-surgical mapping in pediatric epilepsy patients. We are proposing a solution based on a dual-echo EPI sequence, which was shown to produce high quality slice level distortion maps that can be used to correct motion related artifacts. We will generate a pipeline that produces motion and distortion free images on the scanner with the utilization of an online reacquisition and distortion correction strategy. We hypothesize that this improved diffusion MRI acquisition strategy will produce technically useful tractography in pediatric epilepsy patients evaluated for a resection surgery at a higher rate than previously thought possible. To achieve these ambitious goals, we will undertake the following specific aims: Specific Aim 1: Develop, optimize and evaluate a dual echo sequence for slice level geometric distortions correction; Specific Aim 2: Develop and evaluate a novel prospective motion correction technology that estimates and corrects geometric distortions at each position; Specific Aim 3: Develop and evaluate tools for on- scanner motion and distortion correction, reacquisition and diffusion parameter estimation; Specific Aim 4: Apply and evaluate motion and distortion compensation technologies in DW-MRI of pediatric candidates for epilepsy surgery: If successful, our project will facilitate widespread clinical adaptation of diffusion MRI for pre-surgical mapping in epilepsy, and enable high resolution diffusion MRI for research studies in incompliant patient populations.