Approximately 2.5 million Americans live with epilepsy and epilepsy-related deficits today, more than disabled by Parkinson disease or brain tumors. The impact of epilepsy in the US is significant with a total cost to the nation for seizures and epilepsy of approximately $12.5 billion. Epilepsy consists of more than 40 clinical syndromes affecting 40 million people worldwide. Approximately 25 percent of individuals receiving antiepileptic medication have inadequate seizure control;however, 80% individuals with medication resistant epilepsy might be cured through surgery if one were able to precisely localize the seizure focus. The proposed research will significantly advance our ability to localize such foci, and thereby offer curative epilepsy surgery for this devastating disease. We hypothesize that diffuse optical tomography (DOT) provides a new functional and cellular neuroimaging modality for non-invasively tracking dynamical changes during seizure occurrence. DOT has the ability to image tissue functions including oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), cerebral blood volume (CBV), cerebral blood flow (CBF) and rate of cerebral oxygen metabolism (CMRO2). In addition, we show that DOT can also provide cerebral cellular morphology that is derived from tissue scattering spectra. Given the high temporal and spatial resolution for optical modalities, the proposed hemodynamic and cellular imaging will offer unprecedented localization of both ictal and interictal seizure activities, a feature that is unavailable from any of the existing neuroimaging techniques. While the primary goal of this project is to develop a DOT system for accurate localization of epileptic focus, we also propose to study the neuro-vascular and neuro-cellular coupling between neuronal activity and hemodynamic/cellular response using concurrent electroencephalography (EEG) and DOT noninvasively in animal models of seizure. Such coupling study is becoming increasingly important for interpreting functional/cellular imaging results, and may be useful in predicting seizure onset. To test the hypothesis, we propose to complete the following specific aims: (1) To design, construct and test a fast multispectral optical system for functional/cellular DOT imaging;(2) To develop a set of image enhancement schemes for improved DOT imaging of small animals, and To develop both linear and nonlinear models that couple the electrophysiological recordings with the hemodynamic/cellular response measured by DOT;(3) To evaluate and optimize the integrated functioning of the hardware and software components of the multispectral DOT system, using simulation and phantom experiments;(4) To test and evaluate the proposed DOT system and neuro-vascular/neuro-cellular coupling models using animal models.

Public Health Relevance

Many individuals with medication resistant epilepsy might be cured through surgery if one were able to precisely localize the seizure focus. The proposed research will significantly advance our ability to localize such foci by developing a new imaging technology, and thereby offer curative epilepsy surgery for this devastating disease. Both technological development and in vivo animal studies are proposed in this application.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS069848-02
Application #
8020033
Study Section
Neurotechnology Study Section (NT)
Program Officer
Fureman, Brandy E
Project Start
2010-02-15
Project End
2014-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
2
Fiscal Year
2011
Total Cost
$266,410
Indirect Cost
Name
University of Florida
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611
Yang, Hao; Zhang, Tao; Zhou, Junli et al. (2015) In vivo imaging of epileptic foci in rats using a miniature probe integrating diffuse optical tomography and electroencephalographic source localization. Epilepsia 56:94-100
Zhang, Tao; Zhou, Junli; Carney, Paul R et al. (2015) Towards real-time detection of seizures in awake rats with GPU-accelerated diffuse optical tomography. J Neurosci Methods 240:28-36
Zhang, Tao; Zhou, Junli; Jiang, Ruixin et al. (2014) Pre-seizure state identified by diffuse optical tomography. Sci Rep 4:3798
Hajihashemi, M Reza; Zhang, Tao; Ormerod, Brandi K et al. (2014) Non-invasive detection of optical changes elicited by seizure activity using time-series analysis of light scattering images in a rat model of generalized seizure. J Neurosci Methods 227:18-28
Hajihashemi, M Reza; Jiang, Huabei (2013) Gaussian random ellipsoid geometry-based morphometric recovery of irregular particles using light scattering spectroscopy. J Quant Spectrosc Radiat Transf 118:86-95
Hajihashemi, M Reza; Jiang, Huabei (2012) An inverse light scattering technique for morphological characterization of irregular particles based on the Gaussian-random-sphere model. J Opt Soc Am A Opt Image Sci Vis 29:1124-31
Yuan, Zhen; Jiang, Huabei (2012) A calibration-free, one-step method for quantitative photoacoustic tomography. Med Phys 39:6895-9
Hajihashemi, Mohammad Reza; Grobmyer, Stephen R; Al-Quran, Samer Z et al. (2012) Noninvasive evaluation of nuclear morphometry in breast lesions using multispectral diffuse optical tomography. PLoS One 7:e45714
Yang, Jianjun; Zhang, Tao; Yang, Hao et al. (2012) Fast multispectral diffuse optical tomography system for in vivo three-dimensional imaging of seizure dynamics. Appl Opt 51:3461-9
Hajihashemi, Mohammad Reza; Li, Xiaoqi; Jiang, Huabei (2012) Morphological characterization of cells in concentrated suspensions using multispectral diffuse optical tomography. Opt Commun 285:4632-4637

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