We propose that the site of seizure onset in epilepsy can be imaged by novel analysis of ictal and interictal nuclear medicine tomographic perfusion scans. The imaging techniques proposed here will yield data supporting the hypothesis that the epileptogenic region exhibits a hyperperfusion at seizure onset; and after a short time after seizure cessation, enters a state of excess hypoperfusion for a short time. WE believe that by analyzing EEG with SPECT difference images, we can support a physiological model which demonstrates the correlation between brain electrical activity and perfusion. By understanding the perfusion change characteristics at and near the epileptogenic region and by controlling the time of injection after seizure onset, we will be able to better localize seizure regions. This proposal outlines a prospective study in which a new image processing analysis will be applied to 60 epileptic patients. These patients will undergo SPECT imaging under a new protocol which localizes the epileptogenic region and strives to characterize the correlation between perfusion and synaptic activity. By registering the SPECT scans and applying our proposed processing algorithm, the location and size of perfusion alterations (both positive and negative) at the time of epileptic seizures can be shown in a functional image (difference-images). After appropriate normalization of the SPECT scan, a quantitative measure of change in regional brain blood flow can be calculated. These quantitative functional difference-images are superimposed on the anatomical detail provided by registered MRI. Careful analysis of this quantitative depiction of regions of positive and negative ictal blood flow changes during seizures may allow accurate definition of areas of spontaneous seizure onset and propagation. The patients in this study will undergo intracranial depth electrode implantation and surgery to localize and remove the area of seizure onset. Within the scope of this proposal we intend to accomplish the following tasks: Obtain perfusion images from ictal injection whose injection time vary from immediately after seizure onset to 5 minutes after seizure cessation. Update our model of perfusion changes correlated to synaptic activity during seizure based on these measurements. Create a model of the temporal evaluation of perfusion changes peri-ictally to establish an optimal imaging protocol.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS035674-02
Application #
2685750
Study Section
Neurology A Study Section (NEUA)
Program Officer
Jacobs, Margaret
Project Start
1997-04-01
Project End
2001-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
2
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Yale University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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Chelikani, Sudhakar; Gore, John; Zubal, George (2004) Optimizing Compton camera geometries. Phys Med Biol 49:1387-408
Chang, David J; Zubal, I George; Gottschalk, Chris et al. (2002) Comparison of statistical parametric mapping and SPECT difference imaging in patients with temporal lobe epilepsy. Epilepsia 43:68-74
Avery, R A; Zubal, I G; Studholme, C et al. (2001) Interictal 99mTc-HMPAO SPECT in temporal lobe epilepsy: relation to clinical variables. Epilepsia 42:869-74
Avery, R A; Zubal, I G; Stokking, R et al. (2000) Decreased cerebral blood flow during seizures with ictal SPECT injections. Epilepsy Res 40:53-61
Avery, R A; Spencer, S S; Studholme, C et al. (2000) Reproducibility of serial peri-ictal single-photon emission tomography difference images in epilepsy patients undergoing surgical resection. Eur J Nucl Med 27:50-5
Zubal, I G; Avery, R A; Stokking, R et al. (2000) Ratio-images calculated from interictal positron emission tomography and single-photon emission computed tomography for quantification of the uncoupling of brain metabolism and perfusion in epilepsy. Epilepsia 41:1560-6
Zubal, I G; Spanaki, M V; MacMullan, J et al. (1999) Influence of technetium-99m-hexamethylpropylene amine oxime injection time on single-photon emission tomography perfusion changes in epilepsy. Eur J Nucl Med 26:12-7
Avery, R A; Spencer, S S; Spanaki, M V et al. (1999) Effect of injection time on postictal SPET perfusion changes in medically refractory epilepsy. Eur J Nucl Med 26:830-6
Spanaki, M V; Spencer, S S; Corsi, M et al. (1999) Sensitivity and specificity of quantitative difference SPECT analysis in seizure localization. J Nucl Med 40:730-6

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