Abstract

The ability to non-invasively monitor and quantify hemodynamic responses down to the capillary level is important for improved diagnosis, treatment and management of neurovascular disorders, including stroke. We developed an integrated multi-functional imaging system, in which synchronized dual wavelength laser speckle contrast imaging (DWLS) was used as a guiding tool for optical microangiography (OMAG) to test whether detailed vascular responses to experimental stroke in male mice can be evaluated with wide range sensitivity from arteries and veins down to the capillary level. DWLS enabled rapid identification of cerebral blood flow (CBF), prediction of infarct area and hemoglobin oxygenation over the whole mouse brain and was used to guide the OMAG system to hone in on depth information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density pertaining to defined regions of CBF in response to ischemia. OMAG-DWLS is a novel imaging platform technology to simultaneously evaluate multiple vascular responses to ischemic injury, which can be useful in improving our understanding of vascular responses under pathologic and physiological conditions, and ultimately facilitating clinical diagnosis, monitoring and therapeutic interventions of neurovascular diseases.

Highlights

  • Cortex since the imaging depth is only limited to 200 μm[3]

  • To evaluate microvascular responses to experimental stroke, we developed a multimodal imaging system by combing optical microangiography (OMAG) with dual wavelength laser speckle (DWLS) imaging systems

  • We used DWLS to rapidly evaluate the cerebral blood flow (CBF) and hemoglobin oxygenation over the whole mouse brain at a macroscopic scale, upon which to guide the OMAG to hone into the desired regions to provide depth-resolved information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density

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Summary

Introduction

Cortex since the imaging depth is only limited to 200 μm[3]. These techniques require injection of fluorescent tissue markers which may complicate the interpretation of the results. Laser speckle contrast imaging (LSCI) is a popular tool used for the non-invasive study of vascular dynamics in experimental stroke[16,17,18,19,20]. We used an integrated OMAG-DWLS to identify distinct blood flow regions corresponding to infarct, peri-infarct and mildly hypoperfused tissue, and to characterize the differences in vascular responses among these regions after middle cerebral artery occlusion (MCAO) in male mice. We used DWLS to rapidly evaluate the CBF and hemoglobin oxygenation over the whole mouse brain at a macroscopic scale, upon which to guide the OMAG to hone into the desired regions to provide depth-resolved information regarding blood volume, blood flow velocity and direction, vascular architecture, vessel diameter and capillary density. The integrated OMAG-DWLS provides a yet unparalleled tool to assess key dynamic information about cortical cerebral blood flow, which is necessary to understand the mechanisms relating to vascular injury and repair

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