The relatively high success rates (~70%+) for 1 to 2 year seizure freedom in patients undergoing temporal lobe surgery for epilepsy indicate that with accurate localization of seizure onset, respective surgery works. While there are clearly uncertainties of longer term success, the 2 year timeframe argues clearly that the surgery successfully removed a key node of the seizure network, thus frequently enabling more effective medical therapy. However for localization-related epilepsies which are not clearly temporal lobe (or medial temporal lobe) in onset, the rates of success for the 1 year time frame are substantially less, e.g., at 25%. Given the understanding of the pathophysiological basis of localization related epilepsy, the key step in these more difficult cases remains adequate localization and network characterization MR spectroscopic imaging (MRSI) has been suggested to have the potential sensitivity to assist in this localization problem. In this projectwe will implement key steps originally developed at 7T to make MRSI clinically robust at a clinical field (3 Tesla) for epileptogenic locus and network localization. This will be performed at the University of Pittsburgh and New York University, both sites of which have the needed experience and collaborative interest in epilepsy and imaging.
Aim 1 will result in a robust dataset of pre-operative fronto-parietal-temporal and temporal-occipital MRSI from a large group (a total of n=60 each year, 240 total) of surgically treated patients. The MRSI-abnormal regions will define candidate regions of seizure onset, to be compared against the current clinical localization paradigm and clinical outcome of seizure control. This will be done in several subgroups of epilepsy patients segregated based on lesion types and semiology to evaluate this approach in adequate sampling of epilepsy types. In comparison with the MRSI, Aim 2 will evaluate structural imaging abnormalities with whole brain T1W and FLAIR MRI using quantitative maps of cortical thickness, white-gray matter contrast and FLAIR intensities between patients and controls.
This Aim will assess the extent to which these quantitative imaging abnormalities will be synchronous with MRSI-determined metabolic dysfunction. Finally in Aim 3, the conclusions of the MRSI and quantitative imaging analysis for localization of seizure onset will be correlated with region of seizure surgery and 2year post-surgical outcomes using ILAE classification. As a result of this project, we believe that we will have evaluated the role of extended volume brain metabolic MRSI evaluation for epilepsy localization and integrated its pathophysiological use with structural imaging. The health relatedness of this study: MRSI integrated with quantitative structural imaging analysis will be able to augment current seizure localization accuracy beyond the temporal lobe group. This may potentially improve outcome, reduce the cost of disease management, and hopefully make this complex yet highly effective treatment strategy more realistic and available to patients with medically refractory epilepsy.

Public Health Relevance

This project will implement and test high sensitivity MR imaging methods to help in the identification of seizure onset in patients with medically intractable epilepsy. The methods are based on imaging the biochemistry and metabolism of the brain in conjunction with quantitative high resolution imaging structural brain analysis. While the surgical resection plan will be clinically handled independent of this study, the accuracy of this identification will be assessed by whether there is agreement between the resection site and MR identified abnormal regions, in comparison to seizure control after surgery.

National Institute of Health (NIH)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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Fureman, Brandy E
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University of Pittsburgh
Schools of Medicine
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Meyer, E J; Kirov, I I; Tal, A et al. (2016) Metabolic Abnormalities in the Hippocampus of Patients with Schizophrenia: A 3D Multivoxel MR Spectroscopic Imaging Study at 3T. AJNR Am J Neuroradiol 37:2273-2279
Wu, Yijen; Pearce, Patrice S; Rapuano, Amedeo et al. (2015) Metabolic changes in early poststatus epilepticus measured by MR spectroscopy in rats. J Cereb Blood Flow Metab 35:1862-70
Hetherington, Hoby P; Hamid, Hamada; Kulas, Joseph et al. (2014) MRSI of the medial temporal lobe at 7 T in explosive blast mild traumatic brain injury. Magn Reson Med 71:1358-67
Pan, Jullie W; Duckrow, Robert B; Gerrard, Jason et al. (2013) 7T MR spectroscopic imaging in the localization of surgical epilepsy. Epilepsia 54:1668-78