Calf muscle perfusion at peak exercise in peripheral arterial disease: measurement by first-pass contrast-enhanced magnetic resonance imaging

Abstract

Purpose: To develop a contrast-enhanced magnetic resonance (MR) technique to measure skeletal muscle perfusion in peripheral arterial disease (PAD).

Materials and methods: A total of 11 patients (age = 61 +/- 11 years) with mild to moderate symptomatic PAD (ankle-brachial index [ABI] = 0.75 +/- 0.08) and 22 normals were studied using an MR-compatible ergometer. PAD and normal(max) (Nl(max); N = 11) exercised to exhaustion. Nl(low) (N = 11) exercised to the same workload achieved by PAD. At peak exercise, 0.1 mm/kg of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) was infused at 3-4 cm(3)/second followed by a saline flush at the same rate. A dual-contrast gradient echo (GRE) sequence enabled simultaneous acquisition of muscle perfusion and arterial input function (AIF). The perfusion index (PI) was defined as the slope of the time-intensity curve (TIC) in muscle divided by the arterial TIC slope.

Results: Median workload was 120 Joules in PAD, 210 Joules in Nl(low), and 698 Joules in Nl(max) (P < 0.001 vs. Nl(low) and PAD). Median PI was 0.29 in PAD (25th and 75th percentiles [%] = 0.20, 0.40), 0.48 in Nl(low) (25th, 75th % = 0.36, 0.62; P < 0.02 vs. PAD), and 0.69 in Nl(max) (25th, 75th % = 0.5, 0.77; P < 0.001 vs. PAD). Area under the ROC-curve for PI differentiating patients from Nl(max) was 0.95 (95% confidence interval [CI] = 0.77-0.99).

Conclusion: Peak-exercise measurement of lower limb perfusion with dual-contrast, first-pass MR distinguishes PAD from normals. This method may be useful in the study of novel therapies for PAD.

(c) 2007 Wiley-Liss, Inc.

Figures

Figure 1

MR compatible, two-pedal plantar flexion ergometer (Lode, Groningen, The Netherlands) affixed to the MR table. The patient is strapped into the ergometer and placed in the magnet with their calf at the isocenter. The ergometer was designed to have a low moment of inertia in order to compensate for the physical limitations imposed on patients supine in the magnet bore.

Figure 2

The scout image (left panel) shows the location of both the upper SR slice from which the AIF is derived and the lower IR slice, which yields the TF. Representative images from each slice are shown (right upper and lower panels) during contrast infusion in a normal subject at peak exercise with regions of interest delineated. Note the heterogenous pattern of enhancement (right lower panel) in the muscle groups of the lower leg. Also, note the differences in image contrast between the upper SR slice and lower IR slice, with nulling of nonenhanced muscle in the IR slice providing greater sensitivity to low concentrations of contrast agent.

Figure 3

Data from phantoms plotting gadolinium concentration against signal intensity, demonstrating the extended linear range of the SR slice compared to the IR slice, as well as the improved sensitivity of the IR slice for lower concentrations of gadolinium. The peak arterial concentration of gadolinium is estimated to be at most 9 mmol/liter, which is near the high end of the linear range for the SR slice. The peak concentration of gadolinium in muscle is approximately 2 mmol/liter, which is near the high end of the linear range for the IR slice. The estimates are made using previously published methods (11).

Figure 4

Quantitative analysis of first-pass perfusion in patient #9 from Table 1. Axial SR image (left upper panel) and IR image (left lower panel) during contrast infusion at the level of the midcalf with regions of interest drawn. Note regional enhancement in the anterior tibialis and soleus muscle regions (lower left panel). Time-intensity curves (right panel) from the soleus is shown and that of the AIF (labeled artery). The soleus and its arterial input have upslope values of 1.14 and 5.14, respectively, giving a PI of 0.22 in this example.

Figure 5

Workload (Joules) achieved between the three experimental groups. The central line represents the median, the outer borders of the box represents the 25th and 75th percentiles of the data. The Nlmax group achieved a higher workload than both the PAD and Nllow groups.

Figure 6

PI compared between the three experimental groups. The central line represents the median, the outer borders of the box the 25th and 75th percentiles of the data. PI discriminates PAD from normals, irrespective of the workload achieved. There is a strong trend towards increased PI in the Nlmax group compared to the Nllow group.

Figure 7

ROC curves. The upper solid line represents the discriminatory power of PI for distinguishing PAD from Nlmax. The area under the curve is 0.95 (95% CI = 0.77–0.99). The lower dashed line represents the discriminatory power of PI for distinguishing PAD when both normal groups are included. The area under the ROC curve is 0.88 (95% CI = 0.71–0.96). For both, the cutoff value used is a PI of 0.34.

Figure 8

Bland-Altman plot of intraobserver variability. Mean bias is 0.01 with 2SD = 0.24 and −0.25. Agreement between measurements was good.