Contrast-Enhanced Ultrasound Reveals Exercise-Induced Perfusion Deficits in Claudicants

Abstract

Background: Contrast-Enhanced Ultrasonography (CEUS) is an imaging modality allowing perfusion quantification in targeted regions of interest of the lower extremity that has not been possible with color-flow imaging or with measurement of ankle brachial indices. We developed a protocol to quantify lower extremity muscle perfusion impairment in PAD patients in response to exercise.

Methods and findings: Thirteen patients with Rutherford Class I-III Peripheral Arterial Disease (PAD) and no prior revascularization procedures were recruited from the Baltimore Veterans Affairs Medical Center and compared with eight control patients without PAD. CEUS interrogation of the index limb gastrocnemius muscle was performed using an intravenous bolus of lipid-stabilized microsphere contrast before and after a standardized treadmill protocol. Peak perfusion (PEAK) and time to peak perfusion (TTP) were measured before and after exercise. Between and within group differences were assessed. Control subjects demonstrated a more rapid TTP (p<0.01) and an increase in peak perfusion (PEAK, p=0.02) after exercise, when compared to their baseline measures. Patients with PAD demonstrated TTP and PEAK measures equivalent to controls at baseline (p=0.39, p=0.71, respectively). However, they exhibited no significant exercise-induced changes in perfusion (TTP p=0.49 and PEAK 0.67, respectively compared to baseline). After exercise, normal subjects had significantly shorter TTP (p=0.04) and greater PEAK (p=0.02) than PAD patients.

Conclusion: Consistent with their lack of ischemic symptoms at rest, class I to III claudicant PAD patients showed similar perfusion measures (TTP and PEAK) at rest. PAD patients, however, were unable to increase perfusion in response to exercise, whereas controls increased perfusion significantly. This corresponds with claudication and limited walking capacity observed in PAD. CEUS with bolus injection offers a convenient, objective, quantitative and visual physiologic assessment of perfusion limitation in specific muscle groups of PAD patients. This has the potential for substantial clinical and research utility.

Keywords: Chronic peripheral ischemia; Claudication; Contrast ultrasound; Perfusion; Peripheral arterial disease; Vascular surgery.

Figure 1

Representative intensity versus time plots of gastrocnemius perfusion in normal subjects (a) and PAD patients (b) at rest (blue line) and after exercise (red line).

Figure 2

Representative contrast-enhanced ultrasound images at the time of exercise-induced peak gastrocnemius perfusion in normal subjects (a) and PAD patients (b).

Figure 3

Intensity of peak perfusion before and after exercise. At rest, no significant difference in perfusion is seen between Control and PAD subjects. After exercise, Control subjects demonstrate significantly greater perfusion. Data are means ± SEM. *Significant difference, p<0.05.

Figure 4

Time to peak perfusion before and after exercise. At rest, no significant difference in perfusion is seen between Control and PAD subjects. After exercise, Control subjects demonstrate significantly faster achievement of peak perfusion. Data are means ± SEM. *Significant difference, p<0.05.

Figure 5

Exercise-induced changes in intensity of perfusion (left) and time to peak perfusion (right) in Control and PAD subjects. Exercise had significantly greater effects on both measures in control subjects. “Data are means +/− SEM. *Significant difference, p:0.05.”