Ultrahigh sensitive optical microangiography reveals depth-resolved microcirculation and its longitudinal response to prolonged ischemic event within skeletal muscles in mice

摘要

The primary pathophysiology of peripheral arterial disease is associated with impaired perfusion tonthe muscle tissue in the lower extremities. The lack of effective pharmacologic treatments that stimulate vesselncollateralization emphasizes the need for an imaging method that can be used to dynamically visualize depthresolvednmicrocirculation within muscle tissues. Optical microangiography (OMAG) is a recently developednlabel-free imaging method capable of producing three-dimensional images of dynamic blood perfusion withinnmicrocirculatory tissue beds at an imaging depth of up to ∼2 mm, with an unprecedented imaging sensitivity ofnblood flow at ∼4 μm/s. In this paper, we demonstrate the utility of OMAG in imaging the detailed blood flowndistributions, at a capillary-level resolution, within skeletal muscles of mice. By use of the mouse model of hindlimbnischemia, we show that OMAG can assess the time-dependent changes in muscle perfusion and perfusionnrestoration along tissue depth. These findings indicate that OMAG can represent a sensitive, consistent techniquento effectively study pharmacologic therapies aimed at promoting the growth and development of collateral vessels.