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.
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.
|Davis, Mitchell A; Gagnon, Louis; Boas, David A et al. (2016) Sensitivity of laser speckle contrast imaging to flow perturbations in the cortex. Biomed Opt Express 7:759-75|
|Kazmi, S M Shams; Richards, Lisa M; Schrandt, Christian J et al. (2015) Expanding applications, accuracy, and interpretation of laser speckle contrast imaging of cerebral blood flow. J Cereb Blood Flow Metab 35:1076-84|
|Davis, Mitchell A; Dunn, Andrew K (2015) Dynamic light scattering Monte Carlo: a method for simulating time-varying dynamics for ordered motion in heterogeneous media. Opt Express 23:17145-55|
|Liu, C; Liu, Y-L; Perillo, E P et al. (2015) Improving z-tracking accuracy in the two-photon single-particle tracking microscope. Appl Phys Lett 107:153701|
|Kazmi, S M Shams; Faraji, Ehssan; Davis, Mitchell A et al. (2015) Flux or speed? Examining speckle contrast imaging of vascular flows. Biomed Opt Express 6:2588-608|
|Kazmi, S M Shams; Wu, Rebecca K; Dunn, Andrew K (2015) Evaluating multi-exposure speckle imaging estimates of absolute autocorrelation times. Opt Lett 40:3643-6|
|Perillo, Evan P; Liu, Yen-Liang; Huynh, Khang et al. (2015) Deep and high-resolution three-dimensional tracking of single particles using nonlinear and multiplexed illumination. Nat Commun 6:7874|
|Schrandt, Christian J; Kazmi, S M Shams; Jones, Theresa A et al. (2015) Chronic monitoring of vascular progression after ischemic stroke using multiexposure speckle imaging and two-photon fluorescence microscopy. J Cereb Blood Flow Metab 35:933-42|
|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|
|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|
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