This proposal is a competitive renewal of R01NS045879 "Stroke Imaging of Conscious Rats." In the previous grant cycle, we reported over two dozen peer-reviewed publications and leveraged multiple foundation grants to expand stroke research. Stroke remains to be the third leading cause of death and the leading cause of long-term disability. Our previous goals were to establish a rat stroke model with reproducible perfusion-diffusion mismatch (which approximates the ischemic penumbra), and to develop and apply quantitative perfusion, diffusion MRI and analysis methods to characterize pixel-by-pixel the spatiotemporal progression of diffusion and perfusion characteristics under different middle cerebral artery occlusion (MCAO) durations in the acute phase. Imaging measures were compared with histology. Gratifying progress was made on all previously proposed aims. In this competitive renewal, we seek to develop novel multimodal MRI approaches to probe the "physiological" and "functional" characteristics of the ischemic tissue at risk in stroke rats. These studies will focus on using blood-oxygenation-level dependent (BOLD) and cerebral blood flow (CBF) fMRI of physiologic (hypercapnic and oxygen) challenge and functional (stimulation and resting state) activity to probe perfusion and diffusion abnormality at 7 Tesla.
We aim to apply these methodologies to study both acute and chronic stroke. Together, through an artificial neural-network predictive model, we will examine different MRI measures to accurately predict acute infarction and chronic recovery. Our central hypothesis is - through improved understanding of the physiological and functional profiles of ischemic tissue at risk and their spatiotemporal characteristics - tissue viability and functional recovery can be accurately predicted using only acute MRI data.

Public Health Relevance

This proposal aims to develop novel multimodal MRI approaches to probe the "physiological" and "functional" characteristics of the ischemic tissue at risk in stroke rats. These non-invasive translational methodologies will provide a comprehensive anatomical, physiological and functional profile of ischemic tissue at risk and their spatiotemporal characteristics in a reproducible rat stroke model. These findings have the potential to positively impact stroke research, including testing of novel therapeutic strategies, as well as enhance clinical decision making in the treatment of acute stroke.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS045879-10
Application #
8518475
Study Section
Biomedical Imaging Technology Study Section (BMIT)
Program Officer
Babcock, Debra J
Project Start
2003-04-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
10
Fiscal Year
2013
Total Cost
$309,274
Indirect Cost
$102,402
Name
University of Texas Health Science Center San Antonio
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Long, Justin Alexander; Watts, Lora Talley; Chemello, Jonathan et al. (2015) Multiparametric and longitudinal MRI characterization of mild traumatic brain injury in rats. J Neurotrauma 32:598-607
Bresnen, Andrew; Duong, Timothy Q (2015) Brain high-energy phosphates and creatine kinase synthesis rate under graded isoflurane anesthesia: An in vivo (31) P magnetization transfer study at 11.7 tesla. Magn Reson Med 73:726-30
Muir, Eric R; Watts, Lora Talley; Tiwari, Yash Vardhan et al. (2014) Quantitative cerebral blood flow measurements using MRI. Methods Mol Biol 1135:205-11
Shih, Yen-Yu Ian; Huang, Shiliang; Chen, You-Yin et al. (2014) Imaging neurovascular function and functional recovery after stroke in the rat striatum using forepaw stimulation. J Cereb Blood Flow Metab 34:1483-92
Shen, Qiang; Du, Fang; Huang, Shiliang et al. (2014) Effects of cerebral ischemic and reperfusion on T2*-weighted MRI responses to brief oxygen challenge. J Cereb Blood Flow Metab 34:169-75
Shih, Yen-Yu Ian; Yash, Tiwari V; Rogers, Bill et al. (2014) FMRI of deep brain stimulation at the rat ventral posteromedial thalamus. Brain Stimul 7:190-3
Duong, Timothy Q (2014) Magnetic resonance imaging of the retina: from mice to men. Magn Reson Med 71:1526-30
Duong, Timothy Q (2013) Magnetic resonance imaging of perfusion-diffusion mismatch in rodent and non-human primate stroke models. Neurol Res 35:465-9
Yin, Biwei; Kuranov, Roman V; McElroy, Austin B et al. (2013) Dual-wavelength photothermal optical coherence tomography for imaging microvasculature blood oxygen saturation. J Biomed Opt 18:56005
Huang, Shiliang; Du, Fang; Shih, Yen-Yu I et al. (2013) Methylene blue potentiates stimulus-evoked fMRI responses and cerebral oxygen consumption during normoxia and hypoxia. Neuroimage 72:237-42

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