MRS LOCALIZATION OF ADULTS/PEDIATRIC EPILEPTIC FOCI

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DESCRIPTION (Adapted from Applicant's Abstract): The proposal is designed to use proton magnetic resonance spectroscopic imaging (MRSI) in patients with drug-refractory surgically treatable focal temporal lobe epilepsy (TLE) to determine if MRSI spectra of localized abnormal brain metabolites are associated with: 1) the site(s) of maximal electroencephalographic (EEG) epileptiform activity, as determined by video-EEG monitoring of conventional scalp-sphenoidal or by depth-electrode recordings, 2) post-resection histopathologic tissue abnormalities in the MRSI abnormal region of interest (ROI); and 3) post-resection measurement of seizure control as predicted by the locations and extents of qualified anomalies in MSRI metabolites; 4) baseline of functional status of memory and the degree of post-surgery memory loss as determined by IAP and neuropsychological measures; 5) the study of the mechanism of correlations of MRS metabolite disturbances in hippocampal formation (HF) to the HF neuron cell loss (by histopathology) and HF atrophy (by MRI-volumetry). There is a history of using brain imaging in focal epilepsy, to lateralize temporal lobe epilepsy by fluoro-deoxyglucose positron emission tomography (18F-PET), and gross anatomic pathologies by magnetic resonance imaging (MRI). However, no imaging technique has yet actually tested if more subtle but well-established abnormalities in an epileptic focus can be reliably imaged, such as alterations in various neurochemicals and changes in their concentrations (e.g. glucose-lactate production, high-energy substrate creatine, or membrane substrate choline). Pediatric and adult patients with temporal lobe epilepsy (TLE) will be imaged interictally and early postictally by MRSI and MRS. Simultaneous acquisitions of two-dimensional double-spin echo (echo-time 135 msec.) MRSI and conventional MRI (T1, T2 and thin-slice Turbo-Flash) will provide feasibility of in situ metabolic maps for correlation to EEG seizure-onset profiles, and to the surgical regions, and pathoanatomic region(s) studied. Concentrations of and ratios between N-acetyl-aspertate (NAA), choline, (Cho), Creatine (Cr), and Lactate (Lac) will allow multivariate statistical tests with other variables to determine when MSRI of certain chemical substrates may be characteristic of epileptogenic areas of hippocampal sclerosis (neuronal loss and gliosis) and ultimately of seizure control after resection. This research is of great importance to the development of reliable and sensitive diagnostic methods for isolating surgically treatable focal epilepsies as well as the more difficult surgical treatment of childhood focal epilepsy, both of which afflict about 1% of Americans.