An exercise stress test for contrast-enhanced duplex ultrasound assessment of lower limb muscle perfusion in patients with peripheral arterial disease

Objective: The aim of the present study was to develop a standardized contrast-enhanced duplex ultrasound (CE-DUS) protocol to assess lower-extremity muscle perfusion before and after exercise and determine relationships of perfusion with clinical and functional measures. Methods: CE-DUS (EPIQ 5G, Philips) was used before and immediately after a 10-minute, standardized bout of treadmill walking to compare microvascular perfusion of the gastrocnemius muscle in older (55-82 years) patients with peripheral arterial disease (PAD) (n = 15, mean ankle-brachial index, 0.78 +/- 0.04) and controls (n = 13). Microvascular blood volume (MBV) and microvascular flow velocity (MFV) were measured at rest and immediately following treadmill exercise, and the Modified Physical Performance Test (MPPT) was used to assess mobility function. Results: In the resting state (pre-exercise), MBV in patients with PAD was not significantly different than normal controls (5.17 +/- 0.71 vs 6.20 +/- 0.83 arbitrary units (AU) respectively; P = .36); however, after exercise, MBV was similar to 40% lower in patients with PAD compared with normal controls (5.85 +/- 1.13 vs 9.53 +/- 1.31 AU, respectively; P = .04). Conversely, MFV was similar to 60% higher in patients with PAD compared with normal controls after exercise (0.180 +/- 0.016 vs 0.113 +/- 0.018 AU, respectively; P = .01). There was a significant between-group difference in the exercise-induced changes in both MBV and MFV (P <= .05). Both basal and exercise MBV directly correlated with MPPT score in the patients with PAD (r = 0.56-0.62; P < .05). Conclusions: This standardized protocol for exercise stress testing of the lower extremities quantifies calf muscle perfusion and elicits perfusion deficits in patients with PAD. This technique objectively quantifies microvascular perfusion deficits that are related to reduced mobility function and could be used to assess therapeutic efficacy in patients with PAD.