Relationship of Skeletal Muscle Perfusion Measured by Contrast-Enhanced Ultrasonography to Histologic Microvascular Density

Abstract

The purpose of this study was to compare skeletal muscle perfusion measured by contrast-enhanced ultrasonography (CEUS) with microvascular density in muscle biopsies. Power Doppler sonography after intravenous bolus injection of Levovist (SH U 508A; Schering AG, Berlin, Germany) was used to examine perfusion of vastus lateralis muscle in 23 healthy volunteers. Local blood volume (B), blood flow velocity (v), and blood flow (f) were calculated by analyzing replenishment kinetics. CEUS perfusion was compared with vascularization of biopsy samples from vastus lateralis muscle. Subjects were selected such that their aerobic capacity (maximal oxygen uptake [VO(2)max]) per body weight ranged between 23 and 66 mL . min(-1) . kg(-1) to render a large variability of skeletal muscle capillarization. Moreover, subjects' venous blood hematocrit (Hkt) was determined to estimate the plasmatic intravascular volume fraction (1-Hkt=PVF) in which the microbubbles can distribute. Median capillary density was 331/mm(2) (range, 207-469/mm(2)), and median capillary fiber contacts (CFC) were 3.6 (range, 2.3-6.5). CFC was correlated with VO(2)max (r=0.59; P<.01). Among CEUS parameters, B showed the closest correlation to CFC (r=0.53; P<.01). When CFC was normalized for PVF, correlation of B to CFC was r=0.64 (P<.01). CEUS could depict the physiologic large variability of vastus lateralis muscle perfusion at rest (median [range]: B, 2.5 [0.1-12.3] approximately mL; v, 0.3 [0.1-3.7] mm/s; f, 0.7 [0.1-5.3] approximately mL . min(-1) . 100 g tissue(-1)). B is significantly related to fiber-adjacent capillarization and may represent physiologic capillary recruitment (eg, through metabolic fiber-related signals). CEUS is feasible for skeletal muscle perfusion quantification.