Assessment of peripheral skeletal muscle microperfusion in a porcine model of peripheral arterial stenosis by steady-state contrast-enhanced ultrasound and Doppler flow measurement

ObjectiveNoninvasive measurement of peripheral muscle microperfusion could potentially improve diagnosis, management, and treatment of peripheral arterial disease (PAD) and thus improve patient care. Contrast-enhanced ultrasound (CEUS) as a noninvasive diagnostic tool allows quantification of muscle perfusion. Increasing data on bolus technique CEUS reflecting microperfusion are becoming available, but only limited data on steady-state CEUS for assessment of muscle microperfusion are available. Therefore, the aim of this study was to evaluate steady-state CEUS for assessment of peripheral muscle microperfusion in a PAD animal model.MethodsIn a porcine animal model, peripheral muscle microperfusion was quantified by steady-state CEUS replenishment kinetics (mean transit time [mTT] and wash-in rate [WiR]) of the biceps femoris muscle during intravenous steady-state infusion of INN–sulfur hexafluoride (SonoVue; Bracco, Geneva, Switzerland). In addition, macroperfusion was quantified at the external femoral artery with a Doppler flow probe. Peripheral muscle microperfusion and Doppler flow measurements were performed bilaterally at rest and under adenosine stress (70 μg/kg body weight) before and after unilateral creation of a moderate external iliac artery stenosis.ResultsAll measurements could be performed completely in 10 pigs. Compared with baseline measurements, peripheral muscle microperfusion decreased significantly during adenosine stress (rest vs adenosine stress: mTT, 7.8 ± 3.3 vs 21.2 ± 17.8 s, P = .0006; WiR, 58.4 ± 38.1 vs 25.3 ± 15.6 arbitrary units [a.u.]/s, P < .0001; Doppler flow, 122.3 ± 31.4 vs 83.6 ± 28.1 mL/min, P = .0067) and after stenosis creation (no stenosis vs stenosis: mTT, 8.1 ± 3.1 vs 29.2 ± 18.0 s, P = .0469; WiR, 53.0 ± 22.7 vs 13.6 ± 8.4 a.u./s, P = .0156; Doppler flow, 124.2 ± 41.8 vs 65.9 ± 40.0 mL/min, P = .0313). After stenosis creation, adenosine stress led to a further significant decrease of peripheral muscle microperfusion but had no effect on macroperfusion (mTT, 29.2 ± 18.0 vs 56.3 ± 38.7 s, P = .0078; WiR, 13.6 ± 8.4 vs 6.0 ± 4.1 a.u./s, P = .0078; Doppler flow, 65.9 ± 40.0 vs 79.2 ± 29.6 mL/min, P = .8125). Receiver operating characteristic curves for the presence of inflow stenosis showed an excellent area under the curve of 0.93 for mTT at rest and 0.86 for Doppler flow.ConclusionsPeripheral muscle microperfusion measurement by steady-state CEUS with replenishment kinetics is feasible and allows detection of muscle microperfusion changes caused by vasodilative stress alone or in combination with a moderate inflow stenosis. Steady-state CEUS offers superior diagnostic performance compared with Doppler flow measurements. Therefore, steady-state CEUS may prove to be a useful tool in diagnosis of PAD and for evaluation of new therapies.

Clinical RelevanceNoninvasive imaging modalities currently used for the diagnosis of peripheral arterial disease (eg, Doppler ultrasound, magnetic resonance angiography, invasive angiography) cannot provide information on nutrient blood flow, limiting their ability to evaluate the influence of collateral perfusion in diffuse and small-vessel disease. Measurement of peripheral muscle microperfusion by contrast-enhanced ultrasound with replenishment kinetics is feasible and allows detection of microperfusion changes caused by vasodilative stress alone or a moderate inflow stenosis. In this regard, contrast-enhanced ultrasound may prove to be superior to Doppler flow measurements and therefore may evolve into a useful tool in diagnosis and therapy monitoring of peripheral arterial disease.