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

Objective: Noninvasive 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.

Methods: In 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.

Results: All 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.

Conclusions: Peripheral 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.