Summary:Purpose: Statistical parametric mapping (SPM) is an image-analysis tool that assesses the statistical significance of cerebral blood flow (CBF) changes on a voxel-by-voxel basis, thereby removing the subjectivity inherent in conventional region-of-interest (ROI) analysis. Our platform of single-photon emission computed tomography (SPECT) ictalinterictal difference imaging in clinical epilepsy has been validated for localizing seizure onset. We extend the tools of SPM by further applying statistical measures for the significance of perfusion changes in individual patients to localize epileptogenic foci in patients with defined temporal lobe epilepsy by using paired scans in this preliminary study.Methods: Twelve patients with pairs of periictal and interictal SPECT scans were analyzed in this comparison study between SPECT difference imaging and SPM difference analysis by using a reference database of paired normal healthy images. These 12 patients possessed seizure foci localized to the mesial temporal lobe as confirmed by surgical outcome and by hippocampal sclerosis on pathology. SPM was used to identify clusters of increased or decreased CBF in each patient in contrast to our control group. Results:The regions having the most significant increased or decreased CBF by SPM analysis were in agreement with regions identified by conventional difference imaging and visual analysis by viewers blinded to the results of the SPM analysis. Differentiated further by time of radiopharmaceutical injection, six of seven patients injected within 100 s of seizure onset displayed hyperperfusion changes localized to the corresponding epileptogenic temporal lobe by both techniques. Among patients receiving injections after 100 s, both techniques showed primarily regions of hypoperfusion, which again were similar between these two methods.Conclusions: The results provide strong evidence supporting SPM difference analysis in assessing regions of significant CBF change from baseline in concordance with our current clinically used technique of SPECT ictal-interictal difference imaging in epilepsy patients. Difference analysis using SPM could serve as a useful diagnostic tool in the evaluation of seizure focus in temporal lobe epilepsy. Key Words: Epilepsy-Periictal SPECT-CBF difference imaging-Statistical parametric mapping (SPM).Single-photon emission computed tomography (SPECT) provides important clinical information measuring regional cerebral blood flow changes in the evaluation of epileptic seizure foci. In general, SPECT has demonstrated hyperperfusion in the epileptogenic region periictally and hypoperfusion interictally. Zubal et al. (1) demonstrated improved localization using SPECT difference imaging, whereby interictal images are subtracted on a voxel-by-voxel basis following co-registration and normalization with ictal images. However, the limitation of this approach as with most others remains its degree of interobserver variability (1-3). Other methods of SPECT interpretation have increased diagnostic yield. Ca...

By digitally computing perfusion changes from ictal or postictal (peri-ictal) injections referenced to those acquired interictally, an enhanced method for localizing the epileptogenic area is reported. Computer-based image processing methods for quantifying regional percent change in the brain are applied to a group of 19 epilepsy patients after the injection of technetium-99m hexamethylpropylene amine oxime (HMPAO) and after acquiring single-photon emission tomography (SPET) data. Each patient's region of epileptogenesis was independently localized through pathology and/or successful surgery. The positive and negative quantitative perfusion changes were plotted as a function of the time of the 99mTc-HMPAO ictal injection. This time scale was normalized relative to the seizure duration and is referenced to the time of seizure termination. Eight patients, injected ictally, demonstrated perfusion increases of 25%-100% in the area of known epileptogenesis. Five patients, injected immediately after seizure cessation, demonstrated excessive perfusion decreases of 30%-92% associated with the region of seizure onset. Six patients, injected well after seizure termination, demonstrated hypoperfusion changes less than 30% at the epileptogenic area. Observations on perfusion changes calculated from 99mTc-HMPAO SPET scans, as a function of normalized time, support a progression from ictal hyper- to excessive hypo-, then finally to persistent interictal hypoperfusion. By applying this perfusion pattern model and by noting the time of injection for peri-ictal images, an improved method for localizing the epileptogenic area is demonstrated.

Nonepileptic seizures may represent difficult diagnostic problems. Identifying their presence and frequency is critical for determining appropriate treatment. The authors investigated the value of quantitative perfusion changes as measured by ictal single-photon emission tomography (SPECT) difference images in differentiating nonepileptic from epileptic seizures. Eleven patients with a clinical suspicion of nonepileptic events had ictal and interictal technetium-99m hexamethylpropylene amine SPECT scans during continuous audiovisual surface electroencephalogram (EEG) monitoring. The authors analyzed perfusion difference images based on registration, normalization, and subtraction of ictal and interictal SPECT images. The difference images were registered to each patient's magnetic resonance imaging scan to anatomically localize ictal perfusion changes. Three of 11 patients also carried the diagnosis of epilepsy and were taking antiepileptic medication. Five patients were taking antiepileptic drugs, but the diagnosis of epilepsy was not confirmed. In all patients, continuous video EEG monitoring revealed no ictal EEG findings. In nine of these patients, visual interpretation of ictal SPECT was suggestive of localized increased (n = 6) or decreased perfusion (n = 3). In all patients, however, no blood flow changes were noted on quantitative SPECT analysis with injections performed during the seizure-like event, suggesting the diagnosis of pseudoseizures. The authors' results suggest that quantitative ictal SPECT analysis is a useful tool in the diagnosis of nonepileptic seizures.

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