Noninvasive quantification of postocclusive reactive hyperemia in mouse thigh muscle by near-infrared diffuse correlation spectroscopy

Abstract

Many vasculature-related diseases affecting skeletal muscle function have been studied in mouse models. Noninvasive quantification of muscle blood flow responses during postocclusive reactive hyperemia (PORH) is often used to evaluate vascular function in human skeletal muscles. However, blood flow measurements during PORH in small skeletal muscles of mice are rare due to the lack of appropriate technologies coupled with the challenge of measurement setup resulting from the lack of large enough test sites. In this study, we explored adapting diffuse correlation spectroscopy (DCS) for noninvasive measurement of the relative changes of blood flow (rBF) in mouse thigh muscles during PORH. A small fiber-optic probe was designed and glued on the mouse thigh to reduce the motion artifact induced by the occlusion procedure. Arterial occlusion was created by tying a polyvinyl chloride (PVC) tube around the mouse thigh while the muscle rBF was continuously monitored by DCS to ensure the success of the occlusion. After 5 min, the occlusion was rapidly released by severing the PVC tube using a cautery pen. Typical rBF responses during PORH were observed in all mice (n=7), which are consistent with those observed by arterial-spin-labeled magnetic resonance imaging (ASL-MRI) as reported in the literature. On average, rBF values from DCS during occlusion were lower than 10% (3.1±2.2%) of the baseline values (assigning 100%), indicating the success of arterial occlusion in all mice. Peak values of rBF during PORH measured by the DCS (357.6±36.3%) and ASL-MRI (387.5±150.0%) were also similar whereas the values of time-to-peak (the time duration from the end of occlusion to the peak rBF) were quite different (112.6±35.0 s versus 48.0±27.0 s). Simultaneous measurements by these two techniques are needed to identify the factors that may cause such discrepancy. This study highlights the utility of DCS technology to quantitatively evaluate tissue blood flow responses during PORH in mouse skeletal muscles. DCS holds promise as valuable tool to assess blood flow regulation in mouse models with a variety of vascular diseases (e.g., hypercholesterolemia, diabetes, peripheral artery disease).