PROTON NMR SPECTROSCOPY OF HUMAN FOCAL EPILEPSY AT 4 1 T

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DESCRIPTION: (Applicant's Abstract) Intractable epilepsy often beginning in childhood affects approximately 250,000 people in the United States despite optimal medical therapy. Surgical treatment of epilepsy is an effective procedure in selected patients. However, despite being highly effective, fewer than 600 patients are surgically treated in the U.S. each year. Presurgical investigations in candidates include scalp EEG, MRI, PET and intracranial EEG studies in some patients. However the sensitivity of scalp EEG is approximately 50 percent and that of PET and MRI approximately 70 percent in patients with partial seizures. This indicates that other noninvasive and highly sensitive localizing tests are needed. Recent technological advances in particular magnetic resonance spectroscopy (MRS) has been shown to noninvasively detect metabolic abnormalities in the epileptogenic focus. Preliminary experience with single voxel proton MRS suggests N-acetylaspartate (NAA) and creatine (Cr) ratio abnormalities in the site of the epileptic focus. Our recent experience using proton MR spectroscopic imaging suggest a 100 percent sensitivity and indicates bilateral metabolic abnormalities when other techniques indicated unilateral changes. The reasons for the metabolic changes are unclear but it has been postulated that they are related to neuronal cell loss. We propose to investigate the sensitivity and specificity of proton MRS in 150 patients with partial seizures of temporal and extratemporal lobe origin. Comparisons with neuronal cell loss by quantitative analysis of tissue resected at surgery and correlations with in vitro MRS studies will be carried out to permit a rational explanation of the findings detected by in vivo proton MRS. In addition the sensitivity and specificity of this technique will be compared to other methods including EEG, PET, and MRI. Finally the prognostic significance of the proton NMR based abnormalities will be studied through correlations with the surgical outcome. The availability of a 4.1T MR instrument providing improved sensitivity and small voxel size permits the construction of spectroscopic images based on these metabolic ratios. These maps may permit accurate localization of the epileptogenic focus in patients with partial seizures and may allow the noninvasive selection of patients for surgery. This in turn may allow cost effective interventions and may increase the number of surgeries with the consequent socioeconomic gains.