I. George Zubal

Bio: I. George Zubal is an academic researcher from Yale University. The author has contributed to research in topics: Ictal & Epilepsy. The author has an hindex of 16, co-authored 24 publications receiving 2203 citations.

Computerized three‐dimensional segmented human anatomy

Abstract: 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 512×512 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.

Positive and Negative Network Correlations in Temporal Lobe Epilepsy

Abstract: Temporal lobe seizures are accompanied by complex behavioral phenomena including loss of consciousness, dystonic movements and neuroendocrine changes. These phenomena may arise from extended neural networks beyond the temporal lobe. To investigate this, we imaged cerebral blood flow (CBF) changes during human temporal lobe seizures with single photon emission computed tomography (SPECT) while performing continuous video/EEG monitoring. We found that temporal lobe seizures associated with loss of consciousness produced CBF increases in the temporal lobe, followed by increases in bilateral midline subcortical structures. These changes were accompanied by marked bilateral CBF decreases in the frontal and parietal association cortex. In contrast, temporal lobe seizures in which consciousness was spared were not accompanied by these widespread CBF changes. The CBF decreases in frontal and parietal association cortex were strongly correlated with increases in midline structures such as the mediodorsal thalamus. These results suggest that impaired consciousness in temporal lobe seizures may result from focal abnormal activity in temporal and subcortical networks linked to widespread impaired function of the association cortex.

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

Abstract: 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. Methods: Ictal or postictal SPECT scans were performed by using [99mTc]-labeled hexamethyl-propylene-amine-oxime (HMPAO), and images were analyzed by comparison with interictal scans for each patient. Forty-seven cases of localized epilepsy were studied. We used methods that can be implemented anywhere, based on freely downloadable software and normal SPECT databases (http://spect.yale.edu). Statistical parametric mapping (SPM) was used to localize a single region of seizure onset based on ictal (or postictal) versus interictal difference images for each patient. We refer to this method as ictal–interictal SPECT analyzed by SPM (ISAS). Results: With this approach, ictal SPECT identified a single unambiguous region of seizure onset in 71% of mesial temporal and 83% of neocortical epilepsy cases, even with late injections, and the localization was correct in all (100%) cases. Postictal SPECT, conversely, with injections performed soon after seizures, was very poor at localizing a single region based on either perfusion increases or decreases, often because changes were similar in multiple brain regions. However, measuring which hemisphere overall had more decreased perfusion with postictal SPECT, lateralized seizure onset to the correct side in ∼80% of cases. Conclusions: ISAS provides a validated and readily available method for epilepsy SPECT analysis and interpretation. The results also emphasize the need to obtain SPECT injections during seizures to achieve unambiguous localization.

Comparison of Statistical Parametric Mapping and SPECT Difference Imaging in Patients with Temporal Lobe Epilepsy

Abstract: 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. 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.

Sex differences in the functional organization of the brain for language

Abstract: A MUCH debated question is whether sex differences exist in the functional organization of the brain for language1–4. A long-held hypothesis posits that language functions are more likely to be highly lateralized in males and to be represented in both cerebral hemispheres in females5,6, but attempts to demonstrate this have been inconclusive7–17. Here we use echo-planar functional magnetic resonance imaging18–21 to study 38 right-handed subjects (19 males and 19 females) during orthographic (letter recognition), phonological (rhyme) and semantic (semantic category) tasks. During phonological tasks, brain activation in males is lateralized to the left inferior frontal gyrus regions; in females the pattern of activation is very different, engaging more diffuse neural systems that involve both the left and right inferior frontal gyrus. Our data provide clear evidence for a sex difference in the functional organization of the brain for language and indicate that these variations exist at the level of phonological processing.

A theoretically based index of consciousness independent of sensory processing and behavior

Abstract: One challenging aspect of the clinical assessment of brain-injured, unresponsive patients is the lack of an objective measure of consciousness that is independent of the subject's ability to interact with the external environment. Theoretical considerations suggest that consciousness depends on the brain's ability to support complex activity patterns that are, at once, distributed among interacting cortical areas (integrated) and differentiated in space and time (information-rich). We introduce and test a theory-driven index of the level of consciousness called the perturbational complexity index (PCI). PCI is calculated by (i) perturbing the cortex with transcranial magnetic stimulation (TMS) to engage distributed interactions in the brain (integration) and (ii) compressing the spatiotemporal pattern of these electrocortical responses to measure their algorithmic complexity (information). We test PCI on a large data set of TMS-evoked potentials recorded in healthy subjects during wakefulness, dreaming, nonrapid eye movement sleep, and different levels of sedation induced by anesthetic agents (midazolam, xenon, and propofol), as well as in patients who had emerged from coma (vegetative state, minimally conscious state, and locked-in syndrome). PCI reliably discriminated the level of consciousness in single individuals during wakefulness, sleep, and anesthesia, as well as in patients who had emerged from coma and recovered a minimal level of consciousness. PCI can potentially be used for objective determination of the level of consciousness at the bedside.

Implanted antennas inside a human body: simulations, designs, and characterizations

Abstract: Antennas implanted in a human body are largely applicable to hyperthermia and biotelemetry. To make practical use of antennas inside a human body, resonance characteristics of the implanted antennas and their radiation signature outside the body must be evaluated through numerical analysis and measurement setup. Most importantly, the antenna must be designed with an in-depth consideration given to its surrounding environment. In this paper, the spherical dyadic Green's function (DGF) expansions and finite-difference time-domain (FDTD) code are applied to analyze the electromagnetic characteristics of dipole antennas and low-profile patch antennas implanted in the human head and body. All studies to characterize and design the implanted antennas are performed at the biomedical frequency band of 402-405 MHz. By comparing the results from two numerical methodologies, the accuracy of the spherical DGF application for a dipole antenna at the center of the head is evaluated. We also consider how much impact a shoulder has on the performance of the dipole inside the head using FDTD. For the ease of the design of implanted low-profile antennas, simplified planar geometries based on a real human body are proposed. Two types of low-profile antennas, i.e., a spiral microstrip antenna and a planar inverted-F antenna, with superstrate dielectric layers are initially designed for medical devices implanted in the chest of the human body using FDTD simulations. The radiation performances of the designed low-profile antennas are estimated in terms of radiation patterns, radiation efficiency, and specific absorption rate. Maximum available power calculated to characterize the performance of a communication link between the designed antennas and an exterior antenna show how sensitive receivers are required to build a reliable telemetry link.