Exercise versus vasodilator stress limb perfusion imaging for the assessment of peripheral artery disease

Abstract

Purpose: Our aim was to determine whether pharmacologic vasodilation is an alternative to exercise stress during limb perfusion imaging for peripheral artery disease (PAD).

Methods: Quantitative contrast-enhanced ultrasound (CEU) perfusion imaging of the bilateral anterior thigh and calf was performed in nine control subjects and nine patients with moderate to severe PAD at rest and during vasodilator stress with dipyridamole. For those who were able, CEU of the calf was then performed during modest plantar flexion exercise (20 watts). CEU time-intensity data were analyzed to quantify microvascular blood flow (MBF) and its parametric components of microvascular blood volume and flux rate.

Results: Thigh and calf skeletal muscle MBF at rest was similar between control and PAD patients. During dipyridamole, MBF increased minimally (<twofold) for all groups and there were only nonsignificant trends for a reduction in calf MBF in those with PAD (13.5±6.9, 10.0±4.7, and 8.2±6.1 IU/s, for controls, moderate, and severe PAD, respectively; P=.11). In contrast, MBF during modest planar flexion exercise increased markedly in controls but not PAD patients (87.9±79.9 vs 15.2±12.9 IU/s, P<.05). In three moderate PAD patients restudied after undergoing surgical revascularization, MBF during dipyridamole did not change, whereas exercise MBF increased by an average of sevenfold.

Conclusions: Resting limb skeletal muscle MBF in patients with moderate to severe PAD is similar to that in normal subjects. However, differences in hyperemic flow during contractile exercise but not during dipyridamole allow evaluation of the degree of flow impairment from PAD and the degree of improvement with revascularization.

Keywords: contrast echocardiography; exercise; perfusion imaging; ultrasound contrast; vascular imaging.

Figure 1

Mean (±SEM) microvascular blood flow (Axβ) in the (A) thigh and the (B) calf at rest, during dipyridamole (DP) stress, and during plantar flexion exercise (Ex) (measured in calf alone). Data for PAD subjects are subdivided into those with moderate and severe symptoms and exercise data. * P< .05 vs. rest; † P< .05 vs. PAD

Figure 2

Examples of background-subtracted color-coded CEU images from the calf of a control subject at rest, during dipyridamole (DP), and during plantar flexion exercise (Ex); and corresponding time (pulsing interval) versus intensity curves. The images and data illustrate much greater flow reserve with exercise than dipyridamole, and that increased flow during exercise was attributable to increases in both microvascular blood volume (A-value or plateau intensity) and flux rate (β-value or rate constant of the curve). BG= background image obtained immediately after microbubble destruction; b= interval number of hearts beats after destruction.

Figure 3

Mean (±SEM) microvascular blood flow reserve from the different cohorts derived from the ratio of hyperemic (from dipyridamole [DP] or exercise) to resting MBF. *P<.05 versus PAD exercise and versus DP in controls.

Figure 4

Parametric CEU data (mean ±SEM) on (A) microvascular blood volume (A-value), and (B) microvascular blood flux rate (β-value) from the calf at rest, during dipyridamole (DP) stress, and during plantar flexion exercise (Ex). Data for PAD subjects are subdivided into those with moderate and severe symptoms and exercise data. * P< .05 vs. rest; † P< .05 vs. PAD.

Figure 5

Mean (±SEM) microvascular blood flow (Axβ) in the calf at rest, during dipyridamole (DP) stress, and during plantar flexion exercise pre- and post-revascularization for the three PAD patients undergoing surgical revascularization. Examples of CEU images from the calf only during exercise are also shown for a single subject undergoing revascularization. Statistical analysis was not performed due to the low number of subjects undergoing revascularization (n=3). BG= background image obtained immediately after microbubble destruction; b= interval number of hearts beats after destruction.