I. George Zubal

Computerized three-dimensional segmented human anatomy.

Manual segmentation of 129 x-ray CT transverse slices of a living male human has been done and a computerized 3-dimensional volume array modeling all major internal structures of the body has been created. Each voxel of the volume contains a index number designating it as belonging to a given organ or internal structure. The original x-ray CT images were reconstructed in a 512 x 512 matrix with a resolution of 1 mm in the x,y plane. The z-axis resolution is 1 cm from neck to midthigh and 0.5 cm from neck to crown of the head. This volume array represents a high resolution model of the human anatomy and can serve as a voxel-based anthropomorphic phantom suitable for many computer-based modeling and simulation calculations.

Localizing Value of Ictal–Interictal SPECT Analyzed by SPM (ISAS)

Summary:  Purpose: The goal of neuroimaging in epilepsy is to localize the region of seizure onset. Single‐photon emission computed tomography with tracer injection during seizures (ictal SPECT) is a promising tool for localizing seizures. However, much uncertainty exists about how to interpret late injections, or injections done after seizure end (postictal SPECT). A widely available and objective method is needed to interpret ambiguous ictal and postictal scans, with changes in multiple brain regions.

Voxel based Monte Carlo calculations of nuclear medicine images and applied variance reduction techniques

Due to the availability of digitally stored human anatomy images, 3-dimensional surfaces of internal structures of the body can be stored in computer volume arrays. Such a volume based software phantom delineates internal human organs with millimeter resolution and lends itself to fully 3-dimensional Monte Carlo simulations. Our simulation models 45 internal human organs (each with an associated radioisotope concentration and attenuation coefficient), calculates gamma radiation histories through these structures, and accepts gamma events onto a collimated planar camera. Variance reduction techniques are applied to decrease the time required to compute a given number of events at the detector. Stratification and two implementations of forced detection variance reduction techniques are compared to ”brute force” calculations for their efficiency speed-ups in this heterogeneous geometry. Simulated clinical images of the liver are shown.

Comparison of statistical parametric mapping and SPECT difference imaging in patients with temporal lobe epilepsy.

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) ictal–interictal 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.

Imaging Onset and Propagation of ECT‐induced Seizures

Summary:  Purpose: Regions of seizure onset and propagation in human generalized tonic–clonic seizures are not well understood. Cerebral blood flow (CBF) measurements with single photon emission computed tomography (SPECT) during electroconvulsive therapy (ECT)‐induced seizures provide a unique opportunity to investigate seizure onset and propagation under controlled conditions.

Optimized, Automated Striatal Uptake Analysis Applied to SPECT Brain Scans of Parkinson's Disease Patients

Reliable quantitative dopamine transporter imaging is critical for early and accurate diagnosis of Parkinsons disease (PD). Image quantitation is made difficult by the variability introduced by manual interventions during the quantitative processing steps. A fully automated objective striatal analysis (OSA) program was applied to dopamine transporter images acquired from PD subjects with early symptoms of suspected parkinsonism and compared with manual analysis by a trained image-processing technologist. Methods: A total of 101 123I-β-CIT SPECT scans were obtained of subjects recruited to participate in the Query-PD Study. Data were reconstructed and then analyzed according to a package of scripts (OSA) that reorients the SPECT brain volume to the standard geometry of an average scan, automatically locates the striata and occipital structures, locates the caudate and putamen, and calculates the background-subtracted striatal uptake ratio (V3″). The striatal uptake ratio calculated by OSA was compared with manual analysis by a trained image-processing technologist. Several parameters were varied in the automated analysis, including the number of summed transverse slices and the size and separation of the regions of interest applied to the caudate and putamen to determine the optimum OSA analysis. The parameters giving V3″ with the closest correlation to the manual analysis were accepted as optimal. Results: The optimal comparison between the V3″ obtained by the human analyst and that obtained by the automated OSA analysis yielded a correlation coefficient of 0.96. Conclusion: Our optimized OSA delivers V3″ evaluations that closely correlate with a similar evaluation manually applied by a highly trained image-processing technologist.

Opiate dependence and withdrawal: preliminary assessment using single photon emission computerized tomography (SPECT).

Naloxone (0.8 mg, s.c.) effects on opiate withdrawal signs and symptoms and regional brain function were assessed in 10 methadone-maintained patients and 10 healthy subjects in a double-blind, placebo-controlled study. Regional brain function was assessed using single photon emission computerized tomography (SPECT) by evaluating the uptake of [99mTc]d,l-hexamethylpropyleneamine oxime (HMPAO) in the brain, a process related to regional cerebral perfusion. Comparisons of patients and healthy subjects after saline infusion suggested that chronic opiate dependence was associated with lower corrected activity ratios (regional count density/whole brain count density) in frontal and parietal cortices and greater activity ratios in the thalamus. Opiate-dependent patients, but not healthy subjects, developed opiate withdrawal signs and symptoms after naloxone administration. Following naloxone administration, patients undergoing opiate withdrawal exhibited lower whole brain count density than healthy subjects. They also had lower activity ratios in frontal and parietal cortices and increased thalamic activity ratios relative to healthy subjects receiving naloxone. Naloxone administration in healthy subjects, but not opiate withdrawal in patients, was associated with decreased right parietal cortex and increased right temporal cortex and left basal ganglia activity ratios. Relative to naloxone effects in healthy subjects, opiate withdrawal was associated with decreased whole brain count density and a reduced right temporal cortex activity ratio. This preliminary study reports an initial evaluation of HMPAO-SPECT imaging for assessing regional alterations in brain function during opiate dependence and withdrawal. While group differences were reported, the small magnitude of regional alterations in patients undergoing opiate withdrawal raised concern that HMPAO-SPECT methods employed were inadequate for assessing human regional brain function during phases of opiate addiction. Other emerging functional brain imaging technologies should be evaluated relative to improved HMPAO-SPECT methods for this purpose.

Targeted prefrontal cortical activation with bifrontal ECT.

The anatomical brain regions involved in the therapeutic and adverse actions of electroconvulsive therapy (ECT) are unknown. Previous studies suggest that bifrontal vs. bitemporal ECT differ in therapeutic efficacy and cognitive side effects. We therefore performed cerebral blood flow (CBF) imaging during bitemporal vs. bifrontal ECT-induced seizures to identify regions crucial for the differences between these treatments. Patients with major depression, undergoing bitemporal or bifrontal ECT, were studied. Ictal-interictal SPECT images were analyzed with statistical parametric mapping for bitemporal (n=11 image pairs in 8 patients) and bifrontal (n=4 image pairs in 2 patients) ECT-induced seizures to identify regions of ictal CBF changes. Bifrontal ECT was found to cause increases in CBF in prefrontal and anterior cingulate regions. Bitemporal ECT, however, caused CBF increases in the lateral frontal cortex and in the anterior temporal lobes. In bifrontal ECT, a greater increase in prefrontal activation, while sparing the temporal lobes, may result in a better therapeutic response and fewer adverse effects on memory than bitemporal ECT.

Effect of injection time on postictal SPET perfusion changes in medically refractory epilepsy.

Abstract. Single-photon emission tomography (SPET) brain imaging in epilepsy has become an increasingly important noninvasive tool in localizing the epileptogenic site. Ictal SPET demonstrates the highest localization sensitivity as compared with postictal and interictal SPET. While ictal SPET consistently reveals hyperperfusion at the epileptogenic site, postictal SPET reveals either hyper- or hypoperfusion depending on the timing of radiopharmaceutical injection. Much discussion in the literature exists about exactly when the transition from hyper- to hypoperfusion occurs at the epileptogenic site in postictal SPET. The systematic examination of two clinical variables – time of injection from seizure onset and offset – was useful in understanding postictal perfusion changes. Twenty-seven patients with medically refractory epilepsy receiving postictal and interictal SPET scans were studied. Quantitative SPET difference imaging was used to evaluate perfusion changes in relationship to injection time. Perfusion changes were found to reflect the time of injection in relation to seizure onset, but to be somewhat independent of seizure offset. Thus, the majority of patients (8/12, 67%) receiving postictal injections within 100 s after seizure onset demonstrated hyperperfusion, while all patients (15/15, 100%) receiving postictal injections more than 100 s after seizure onset showed hypoperfusion. The explanation of this phenomenon is unknown but the findings appear to parallel known changes in cerebral lactate levels.

Periictal SPECT Localization Verified by Simultaneous Intracranial EEG

Summary: Purpose: We investigated whether blood‐flow changes measured by ictal or immediate postictal single photon emission computed tomography (SPECT) reflect with accuracy the actual location of ictal discharge as measured by simultaneous intracranial EEG. In addition, we evaluated the reliability of ictal SPECT obtained with implanted electrodes by comparing results with those of ictal SPECT performed during scalp EEG monitoring in selected patients.