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 ∼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 ∼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.

Quantitative assessment of carotid plaque morphology (geometry and tissue composition) using computed tomography angiography.

OBJECTIVE: Quantification of carotid plaque morphology (geometry and tissue composition) may help stratify risk for future stroke and assess plaque progression or regression in response to medical risk factor modification. We assessed the feasibility and reliability of morphologic measurements of carotid plaques using computed tomography angiography (CTA) and determined the minimum detectable change in plaque features by this approach. METHODS: CTA images of both carotid arteries in 50 patients were analyzed by two observers using a semiautomatic image analysis program, yielding 93 observations per user (seven arteries were excluded because of prior stenting). One observer repeated the analyses 4 weeks later. Measurements included total plaque volume; percentage stenosis (by diameter and area); and tissue composition for calcium, lipid-rich necrotic core (LRNC), and intraplaque hemorrhage (IPH). Reliability of measurements was assessed by intraclass and interclass correlation and Bland-Altman plots. Dice similarity coefficient (DSC) and modified Hausdorff distance (MHD) assessed reliability of geometric shape measurements. We additionally computed the minimum amount of change in these features detectable by our approach. RESULTS: The cohort was 51% male (mean age, 70.1 years), and 56% had a prior stroke. The mean (± standard deviation) plaque volume was 837.3 ± 431.3 mm3, stenosis diameter was 44.5% ± 25.6%, and stenosis area was 58.1% ± 29.0%. These measurements showed high reliability. Intraclass correlation coefficients for plaque volume, percentage stenosis by diameter, and percentage stenosis by area were 0.96, 0.87, and 0.83, respectively; interclass correlation coefficients were 0.88, 0.84, and 0.78. Intraclass correlations for tissue composition were 0.99, 0.96, and 0.86 (calcium, LRNC, and IPH, respectively), and interclass correlations were 0.99, 0.92, and 0.92. Shape measurements showed high intraobserver (DSC, 0.95 ± 0.04; MHD, 0.16 ± 0.10 mm) and interobserver (DSC, 0.94 ± 0.05; MHD, 0.19 ± 0.12 mm) luminal agreement. This approach can detect a change of at least 3.9% in total plaque volume, 1.2 mm3 in calcium, 4.3 mm3 in LRNC, and 8.6 mm3 in IPH with the same observer repeating measurements and 9.9% in plaque volume, 1.9 mm3 in calcium, 7.9 mm3 in LRNC, and 6.8 mm3 in IPH for two different observers. CONCLUSIONS: Carotid plaque geometry (total volume, diameter stenosis, and area stenosis) and tissue composition (calcium, LRNC, and IPH) are measured reliably from clinical CTA images using a semiautomatic image analysis program. The minimum change in plaque volume detectable is ∼4% if the same observer makes both measurements and ∼10% for different observers. Small changes in plaque composition can also be detected reliably. This approach can facilitate longitudinal studies for identifying high-risk plaque features and for quantifying plaque progression or regression after treatment.