2003 — 2004 |
Hochman, Daryl William |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
Optical Imaging of Seizure Activity in Adult Neocortex
DESCRIPTION (provided by applicant): Changes in the optical properties of brain tissue are associated with changes in the level of neuronal activity. The method of mapping these activity-evoked optical changes is known as 'imaging of intrinsic optical signals' (IIOS), and can provide high-resolution maps of functional and pathological activity in brain tissue. Intrinsic optical signals (lOS) are thought to be generated by a combination of at least three distinct physiological mechanisms: i) changes in blood volume, ii) changes in blood oxygenation, and iii) blood-independent light scattering changes resulting from ion fluxes associated with neuronal activity. Each of these components provides important and distinct types of physiological information. IIOS has several advantages over other imaging modalities that include its relative low cost, and its unique ability to map interictal and ictal epileptiform activity with high temporal and spatial resolution. Consequently, IIOS has the potential to become a powerful tool with broad applicability in the study and treatment of epilepsy. However, IIOS has remained of limited clinical and laboratory use for at least two reasons. First, incomplete knowledge about the physiological mechanisms that generate functionally- and seizure-evoked optical changes in brain tissue limits our ability to interpret IIOS data. Second, there has been relatively little rigorous effort in determining how well IIOS data correlates spatially and temporally to functional and epileptiform neuronal activity in primates and humans. The major goals of this project are to determine the physiological mechanisms that generate normal and seizure-evoked lOS, and to establish the spatial and temporal correlates between lOS and epileptiform neuronal activity. Once these goals are achieved, the first steps will be taken to develop IIOS as a practical method for the intraoperative localization of neocortical seizure foci in adult human patients. The specific aims of this project are to: i) develop optical imaging-based spectroscopic techniques that will enable IIOS to provide high-resolution maps of changes in blood oxygenation, blood volume, and blood-independent changes in primates and human patients; ii) combine IIOS and electrophysiological studies towards gaining a more complete understanding of the links between seizure activity and the epileptiform-evoked changes in cortical hemodynamics and metabolism; and iii) apply IIOS towards the high-resolution intraoperative localization of seizure activity in human patients.
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0.958 |
2009 — 2013 |
Hochman, Daryl William |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neocortical Hemodynamics During Epileptic Activity in Primates and Humans
DESCRIPTION (provided by applicant): Statement of work: How do cerebral blood flow (CBF), volume (CBV), and oxygenation (CBO) vary in response to normal and epileptic neuronal activity in the neocortex? The focus of this proposal is to investigate this question in primates in humans using optical imaging techniques combined with electrophysiological and pharmacological studies. Optical imaging of intrinsic optical signals (OI), a technique of focus in these studies, depends on the differential absorption of light by oxy- and deoxy-hemoglobin. OI can selectively measure changes in cortical tissue due to either blood volume or blood oxygenation. Further study of neocortical hemodynamics is important for at least three reasons. First, a better elucidation of the quantitative relationships between cerebral hemodynamics and neuronal activity represents basic knowledge required for a more complete understanding of in vivo brain physiology. Second, identifying the differences in the coupling of cerebral hemodynamics between normal and epileptic activity may shed light on how hemodynamic-related phenomena, such as abnormal changes in blood volume or deoxygenation of neocortical tissue elicited by seizure activity may contribute to tissue atrophy and other pathological aspects of the "epileptic brain". Third, quantifying the temporal and spatial relationships between neuronal activity and neocortical hemodynamics is a necessary step towards developing optical imaging as a practical clinical tool for localizing functional and epileptic neocortex in neurosurgical patients. To date, OI has been of limited use in epilepsy research for at least two reasons: i) The problem of interpreting optical signals acquired at the various optical wavelengths has not been fully resolved, and ii) ad hoc or qualitative methods have typically been used for the analysis of optical imaging data, with very little work devoted towards developing rigorous statistical methods necessary for making OI a quantitative technique. A major goal of this project is to resolve these issues. Three specific aims will be addressed in the proposal: Aim 1: To quantify relationships between changes in neuronal activity, CBF, CBV, CBO, and optical imaging;Aim 2: To develop practical statistical methods for modeling and analysis of OI data, and Aim 3: To elucidate the relationships between hemodymanic changes and optical signals in neocortex during ictal and interical activity . PUBLIC HEALTH RELEVANCE: Non-technical explanation: When areas of the brain become active, there are increases in the oxygenation and flow of blood to those active regions. These activity-dependent changes in blood result from both normal activity, as well as from pathological epileptic activity. This proposal will address two major goals which could have clinical implications in the treatment of epilepsy. First, it will study how epileptic activity alters blood flow and oxygenation changes in the brain in primates and in humans suffering from epilepsy. This information may be helpful in better understanding the basic mechanisms of epilepsy. Second, an experiment optical imaging technique will be further developed that is capable of mapping activity-evoked changes in blood oxygenation and blood flow with very high spatial resolution. This optical imaging technique has the potential to provide the neurosurgeon with a new and better method for identifying epileptic brain regions during the surgical treatment for medically intractable epilepsy.
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0.958 |