Many stroke therapies currently under development in animal models target the cerebral microcirculation. As a result, quantitative in vivo measurement of hemodynamic parameters such as blood flow and oxygenation are critical needs in these studies. Although several optical and MR based techniques are widely used in such experimental stroke studies, the existing techniques suffer from significant limitations. In particular, most techniques are limited to measurement of the relative change of a single hemodynamic parameter within a single animal during a single measurement period. As a result these methods cannot be used to determine absolute blood flow or oxygenation, or to assess chronic hemodynamic changes, which can hinder efforts to evaluate stroke therapies that attempt to gradually restore blood flow and oxygen delivery to ischemic tissue by stimulating angiogenesis or by enhancing nitric oxide synthesis. Therefore, the overall goal of this proposal is to develop an optical instrument capable of imaging baseline cerebral hemodynamics (blood flow and oxygenation) and to use this instrument to quantify the acute and chronic hemodynamic changes that occur following ischemia. To accomplish this goal we will advance two optical imaging techniques that have shown significant promise in stroke studies.
In Aim 1 we will advance laser speckle contrast imaging for imaging cerebral blood flow to enable imaging of baseline blood flow levels by developing multi-exposure speckle imaging. Our recent results have demonstrated that multi-exposure speckle imaging is capable of overcoming many of the limitations of traditional single exposure speckle imaging.
In Aim 2 we will develop an instrument for high resolution mapping of absolute cortical oxygenation levels by combining a digital micromirror device with phosphorescence quenching measurements. This approach will be combined with the multi-exposure speckle imaging for simultaneous imaging of absolute oxygenation and blood flow. We will then use this instrument to quantify the acute and chronic hemodynamic alterations following stroke in Aim 3. In particular we will map the absolute blood flow and oxygenation levels throughout the ischemic territory and compare the chronic hemodynamics with behavioral and anatomical stroke outcomes.

Public Health Relevance

The goal of this project is to develop new imaging technology designed to further the knowledge of the physiologic changes that occur during acute and chronic stroke. It is expected the results will advance current understanding of stroke physiology, resulting in better treatment of stroke patients.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB011556-03
Application #
8279207
Study Section
Neurotechnology Study Section (NT)
Program Officer
Conroy, Richard
Project Start
2010-08-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2013-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$311,937
Indirect Cost
$95,667
Name
University of Texas Austin
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
170230239
City
Austin
State
TX
Country
United States
Zip Code
78712
Davis, Mitchell A; Kazmi, S M Shams; Dunn, Andrew K (2014) Imaging depth and multiple scattering in laser speckle contrast imaging. J Biomed Opt 19:086001
Ranasinghesagara, Janaka C; Hayakawa, Carole K; Davis, Mitchell A et al. (2014) Rapid computation of the amplitude and phase of tightly focused optical fields distorted by scattering particles. J Opt Soc Am A Opt Image Sci Vis 31:1520-30
Kazmi, Syed Mohammad Shams; Parthasarthy, Ashwin B; Song, Nelly E et al. (2013) Chronic imaging of cortical blood flow using Multi-Exposure Speckle Imaging. J Cereb Blood Flow Metab 33:798-808
Dunn, Andrew K (2012) Laser speckle contrast imaging of cerebral blood flow. Ann Biomed Eng 40:367-77