Contrast-enhanced ultrasound measurement of microvascular perfusion relevant to nutrient and hormone delivery in skeletal muscle: A model study in vitro

Abstract

Contrast-enhanced ultrasound (CEU) has been used to measure muscle microvascular perfusion in vivo in response to exercise and insulin. In the present study we address whether CEU measurement of capillary volume is influenced by bulk flow and if measured capillary filling rate allows discrimination of different flow pattern changes within muscle. Three in vitro models were used: (i) bulk flow rate was varied within a single length of capillary tubing; (ii) at constant bulk flow, capillary volume was increased 3-fold by joining lengths of capillary in series, and compared to a single length; and (iii) at constant bulk flow, capillary volume was increased by sharing flow between a number of lengths of identical capillaries in parallel. The contrast medium for CEU was gas-filled albumin microbubbles. Pulsing interval (time) versus acoustic-intensity curves were constructed and from these, capillary volume and capillary filling rate were calculated. CEU estimates of capillary volume were not affected by changes in bulk flow. Furthermore, as CEU estimates of capillary volume increased, measures of capillary filling rate decreased, regardless of whether capillaries were connected in series or parallel. Therefore, CEU can detect a change in filling rate of the microvascular volume under measurement, but it can not be used to discriminate between different flow patterns within muscle that might account for capillary recruitment in vivo.

A new method to study changes in microvascular blood volume in muscle and adipose tissue: real-time imaging in humans and rat

“…A major argument against this assumption is the model experiment in which an increase in flow rate in preexisting tubes did not lead to increased AI, whereas, when more tubes were perfused, the AI increased (29). These experiments clearly indicate that the increase in AI with insulin and exercise must be due to an increase in the number of microvessels perfused.…”

Impaired microvascular perfusion: a consequence of vascular dysfunction and a potential cause of insulin resistance in muscle

“…In contrast, in the second model, if flow is redistributed from a shorter into a longer, more tortuous route where capillary surface area increases, red cell velocity would not change. However, recent studies using CEU (135), which provides a measurement of both microvascular volume and the rate of fill of that volume, proved inconclusive. CEU estimates of capillary volume increased and measurements of capillary filling rate decreased, regardless of whether flow was switched from shorter to longer capillaries, or flow was recruited from one to many capillaries within a manifold.…”

Systematic method to assess microvascular recruitment using contrast-enhanced ultrasound. Application to insulin-induced capillary recruitment in subjects with T1DM

“…[20, 11, 21, 22]). Once a sequence is loaded, the software enables ROI selection for that sequence, computation of the mean signal intensity in the ROI for each image, and estimation of MBV by fitting an exponential function to the replenishment curve.…”

“…CEU has also been successfully used for measurement of tissue perfusion in the skeletal muscle [8, 9, 10, 11], skin [12], brain [13] and kidney [14]. We apply the proposed method to insulin-mediated changes of blood volume in capillaries of skeletal muscles in subjects with type 1 diabetes mellitus (T1DM).…”