Limb stress-rest perfusion imaging with contrast ultrasound for the assessment of peripheral arterial disease severity

Abstract

Objectives: We hypothesized that stress-rest perfusion imaging of skeletal muscle in the lower extremity with contrast-enhanced ultrasound (CEU) could evaluate the severity of peripheral arterial disease (PAD).

Background: Perfusion imaging may provide valuable quantitative information on PAD, particularly in patients with diabetes in whom microvascular functional abnormalities are common.

Methods: Study subjects included 26 control subjects and 39 patients with symptomatic PAD, 19 of whom had type 2 diabetes mellitus. A modified treadmill exercise test was performed to determine exercise time to development of claudication. Multilevel pulse-volume recordings and ankle-brachial index (ABI) at rest and post-exercise ABI were measured in both extremities. Microvascular blood flow in the gastrocnemius and soleus muscles was measured at rest and after 2 min of calibrated plantar-flexion exercise.

Results: During exercise, claudication did not occur in normal subjects and occurred earlier in PAD patients with diabetes than without (median time 1.2 min [95% confidence interval (CI) 0.6 to 2.5] vs. 3.0 min [95% CI 2.1 to 6.0], p < 0.01). Compared to control subjects, patients with PAD had lower skeletal muscle blood flow during plantar-flexion exercise and lower flow reserve on CEU. After adjusting for diabetes, the only diagnostic tests that predicted severity of disease by claudication threshold were CEU exercise blood flow and flow reserve (odds ratios 0.67 [95% CI 0.51 to 0.88; p = 0.003] and 0.64 [95% CI 0.46 to 0.89, p = 0.008], respectively). A quasi-likelihood information analysis incorporating all non-invasive diagnostic tests indicated that the best models for predicting severity of disease were the combination of diabetes and either exercise blood flow or flow-reserve on CEU.

Conclusions: Perfusion imaging of limb skeletal during exercise and measurement of absolute flow reserve can provide valuable information on the severity PAD. This strategy may be useful for evaluating the total impact of disease in patients with complex disease or those with coexisting functional abnormalities of flow regulation.

Figures

Figure 1

Examples of background-subtracted color-coded CEU images obtained at incremental pulsing intervals in seconds (s) and corresponding time versus intensity data from the calf plantar flexor muscles at rest and during exercise in a limb from a control subject (A) and a patient with PAD and claudication (B). For each panel, rest images are above and exercise images are below. Despite an identical workload for the two patients (38 Watts), exercise blood flow and flow reserve were markedly impaired in the patient with PAD. Color scale is shown at bottom of the first image. BG, background image obtained immediately after microbubble destruction.

Figure 2

Univariate predictors of disease severity defined as exercise treadmill time until the onset of claudication before (A), and after (B) stratification according to the presence of diabetes mellitus. Ex, exercise.

Figure 3

Multivariate model for best predictors of disease severity. A reduction in quasi-likelihood information coefficient (QICu) scores indicates improved predictive value for exercise time until claudication. Models are shown before (A), and after (B) stratification according to the presence of diabetes mellitus. MFR, muscle flow reserve; Ex Flow, blood flow at peak exercise.