Cardiovascular aging and the microcirculation of skeletal muscle: using contrast-enhanced ultrasound

Skeletal muscle is the largest and most important site of capillary-tissue exchange, especially during high-energy demand tasks such as exercise; however, information regarding the role of the microcirculation in maintaining skeletal muscle health is limited. Changes in microcirculatory function, as observed with aging, chronic and cardiovascular diseases, and exercise, likely precede any alterations that arise in larger vessels, although further investigation into these changes is required. One of the main barriers to addressing this knowledge gap is the lack of methodologies for quantifying microvascular function in vivo; the utilization of valid and noninvasive quantification methods would allow the dynamic evaluation of microvascular flow during periods of clinical relevance such as during increased demand for flow (exercise) or decreased demand for flow (disuse). Contrast-enhanced ultrasound (CEUS) is a promising noninvasive technique that has been used for diagnostic medicine and more recently as a complementary research modality to investigate the response of the microcirculation in insulin resistance, diabetes, and aging. To improve the reproducibility of these measurements, our laboratory has optimized the quantification protocol associated with a bolus injection of the contrast agent for research purposes. This brief report outlines the assessment of microvascular flow using the raw time-intensity curve incorporated into gamma variate response modeling. CEUS could be used to compliment any macrovascular assessments to capture a more complete picture of the aging vasculature, and the modified methods presented here provide a template for the general analysis of CEUS within a research setting.