This R21 grant proposal will develop a novel technology to explore changes in brain electrical properties. We will measure sodium concentrations noninvasively using sodium magnetic resonance imaging (S-MRI) and directly using a sodium-measuring devise. We will also measure diffusion tensor, DT-MRI. These studies will prepare this novel technology for translational human studies for localization of epileptogenic sources of activity. This advancement will increase the number epilepsy patients that can benefit from epilepsy surgery. Our long-term goal is to devise a system where MRI and electroencephalogram (EEG) data input is converted into a conductivity and localization map overlaid on anatomical MRI for presurgical planning. Successful development of this technology will provide cost-effective and noninvasive presurgical evaluation for a much larger population of epilepsy surgery candidates, and for other brain diseases. We will measure the electrical properties of the human brain immediately after they are surgically removed from epilepsy patients to treat their seizure disorders. We will then measure the sodium content of these tissues with S-MRI first, and compare that with directly-measured sodium content using inductively coupled plasma mass spectrometer (ICP-MS) which is a very sensitive and accurate device used as gold standard to measure elemental contents such as sodium. We will show that noninvasive S-MRI is equally accurate in measuring sodium content of the brain as the gold standard. We will then use these data along with DT-MRI and a mathematical model to calculate the electrical conductivities of the brain. We will show that the data obtained from non-invasive S-MRI and DT-MRI along with the mathematical model can predict the electrical conductivity of the brain tissues as accurately as the direct invasive measurements. We will also study the ability of S-MRI or its combination with DT-MRI to localize epileptogenic brain tissues in an animal model of epilepsy. We will first prepare animals with epilepsy. We will then measure S-MRI and DT-MRI in these animals to locate the brain regions that show changes in these scans when compared to scans acquired before they developed epilepsy. We will then implant EEG electrodes in the animal?s brains to measure their brains? electrical activities and locate the brain regions that cause epileptic seizures. We will show that the noninvasive MRI scans will locate the regions of seizure activity as well as invasive intracranial EEG measurements. The successful completion of this proposed research has tremendous clinical significance given the limitations of EEG source models and current methodologies to localize epileptogenic areas for surgical treatment.
PUBLIC HEALTH RELEVANCE: The current proposal directly deals with the following NIH benchmarks: 1) ?Understand epileptogenic processes associated with acquired forms of the epilepsies, including those associated with traumatic brain injury, stroke, brain tumor, infections, neurodegeneration, or other insults to the brain?, 2) ?Identify biomarkers that will aid in identifying, predicting, and monitoring epileptogenesis and disease progression, including markers early after injury/insult that identify those people at risk for epilepsy?. This grant proposal will introduce a novel technology to improve these tools by studying if electrical signals move through the brain differently in epilepsy patients, whether electrical signal changes can be estimated using new MRI techniques, and if the electrical and MRI changes can be used to locate the abnormal brain tissues for treatment.
