Pediatrics

Epilepsy affects 3-5% of the population world-wide, affecting persons indiscriminately of age, sex, or race. The impact of epilepsy in the United States is significant with a total cost to the nation for seizures and epilepsy of approximately $12.5 billion. Approximately 2.5 million Americans live with epilepsy and epilepsy-related deficits today, more than disabled by Parkinson disease or brain tumors.

Epilepsy is the one of the greatest causes of disability in young people under 15 years old and older individuals over 65 years of age. Injury to hippocampal pyramidal cells and fiber tracts is a major component of status epilepticus. In the vast majority of cases, seizures arise from medial temporal structures that have been damaged months to years before onset of seizures. The proposed research will significantly advance our understanding of limbic system reorganization caused not only by prolonged seizures, but also the effects of recurrent seizures and further hippocampus damage. Insights into changes and structural connectivity in the injured brain will undoubtedly provide powerful insights into mechanisms underlying higher order functional interactions in the normal brain.

Our goal is to develop mathematical models, efficient algorithms and software to process high angular resolution diffusion weighted MRI (HARDI) data sets acquired from rat brains that have been imaged during the epileptogenetic period and derive structural signatures that can be used to predict the onset of epilepsy. HARDI data contain much more information than the traditional T1 or T2 weighted MRI, in that at each voxel, diffusion sensitized MR signal is acquired for several gradient directions. It is possible to compute the probability of water molecule diffusion over a sphere of directions at each voxel by using a fast diffusion orientation transform (DOT) recently introduced by our group or the proposed continuous domain multi-tensor model in this proposal.

Wilder Center for Epilepsy Research, National Institutes of Health Collaborative Research in Computational Neuroscience: Automatic Prediction of the Onset of Epilepsy via Analysis of High Angular Resolution Diffusion MRI, 2006-2010

An imaging modality, which could give a real time “read out” of the dynamic of seizures, would be valuable in determining the seizure onset and seizure propagation pathway.

It would be more valuable if this imaging modality could also provide functional mapping of brain that are involved in the generation of seizures. We have identified a novel laser-based modality, called photoacoustic tomography (PAT) as such a candidate for epilepsy imaging. PAT is sensitive to molecular signatures and able to provide functional information including blood oxygenation and blood volume. This cost-effective technology combines the high optical contrast and high acoustic resolution in a single modality which offers sufficient spatial and temporal resolution for functional epilepsy imaging. In this application, we have shown solid evidence using both tissue-like phantom and in vivo animal data that the proposed PAT technique has the potential to be a powerful tool for imaging the dynamic of seizures. Our specific aims are: