To compare exercise-recovery muscle perfusion using gadolinium MRI between healthy subjects and peripheral arterial disease (PAD) patients and correlate the pattern of PAD muscle perfusion with hemodynamically significant vascular pathology.Surgical intervention in patients with peripheral arterial disease (PAD) has generally been based on measurement of ankle-brachial-index (ABI), vascular imaging, and quality of life assessments (1). More refined measurements of calf muscle physiology, such as muscle perfusion, may improve the assessment of prognosis, muscle viability, and/or appropriateness of endovascular or surgical intervention. Four PAD patients with claudication (3M; 1F; 62 yrs +/-5.4) and 8 healthy volunteers (3M; 5F; 29+/-11.3) were enrolled in this HIPAA compliant/IRB approved study. All PAD subjects had ABI<0.9 (range 0.56-0.84). All subjects were imaged during exercise-recovery immediately after 3 minutes of plantar flexion exercise at 1 Hz (2.7 watts in PAD patients; 2.7-10.8 watts in healthy subjects) in a 3T scanner (Siemens Trio). All PAD patients had prior three-station gadolinium MRA from the abdominal aorta to the pedal arteries. For exercise recovery muscle perfusion, gadolinium contrast (gadoteridol, 0.05 mmol/kg) was injected 5 seconds before the completion of the exercise. Dynamic axial imaging (1.5 sec per frame for 4 min) through the proximal calf was performed with a saturation-recovery prepared FLASH using a flex coil and the following parameter values: TR 527 ms, TE 1.42 ms, flip angle 15°, matrix 128×128, FOV 18×18 cm, slice thickness 10 mm. In post-processing, voxel-wise analysis was applied: signal intensities of each muscle voxel were first converted to gadolinium contrast concentration, which were further analyzed by tracer kinetic modeling to estimate muscle perfusion and bolus transit time (calculated as time from posterior tibial or peroneal artery enhancement to muscle enhancement in the same imaging slice) (2,3). From the map of perfusion, ROI was drawn over each muscle to estimate the mean parameter values for each muscle. Parameters were compared to the expected distribution of vascular pathology based on proximal (abdominopelvic or thigh) or distal (calf) hemodynamically significant stenosis (>50% stenosis or occlusion) of supplying arteries found on previously performed gadolinium MRA. Superficial posterior (soleus and gastrocnemius muscles) and anterior/lateral (anterior tibialis, extensor digitorum longus, and peroneus longus muscles) compartments were compared between PAD patients and healthy controls. Paired T-tests were used to compare average perfusion values and transit times between PAD and healthy subjects for each compartment and also compared between PAD patients with abdominopelvic/thigh or calf vascular pathology.The perfusion measurements for the healthy and PAD subjects are shown in Table 1. In both the superficial posterior and anterior/lateral compartments, the healthy subjects demonstrated significantly higher perfusion and shorter transit times than PAD patients. Within the PAD cases, patterns of muscle perfusion (Figure 1) demonstrate varied appearance, with some (PAD-Proximal; Fig. 1) similar to healthy controls and others (PAD-Distal; Fig. 1) markedly different. We found no relation between the degree of disease of a supplying artery in PAD patients and the perfusion of the associated muscle bed (Figure 2). Further analysis of PAD patients compared muscle perfusion in the two with proximal (>50% stenosis of common iliac and occlusion of superficial femoral artery) versus the two with distal (anterior tibial/tibioperoneal trunk/posterior tibial artery stenosis and/or occlusion) vascular pathology. Muscle perfusion in the superficial posterior compartment was significantly lower in the two patients with calf vascular disease compared the two with proximal vascular pathology (Table 2).Differences in muscle perfusion demonstrated here among PAD patients with proximal and distal vascular pathology could have important implications for prognosis and treatment of PAD patients. The differences in perfusion observed may be explained by more focal vascular abnormalities in the proximal vascular pathology group and more diffuse/severe disease in the distal pathology group. These data suggest that measuring muscle perfusion may help identify a subset of patients who will benefit from revascularization. Inability to correlate the pattern of muscle perfusion with specific vascular deficits may be influenced by both microvascular variation from subject to subject and collateral vessel growth in PAD patients. Limitations of this study include the small sample size and use of AIF within the same imaging slice to calculate transit times. Despite limitations, PAD muscle perfusion warrants further study to understand the relationship among vascular supply, muscle abnormalities, and severity of PAD. Calf muscle perfusion differences can be detected using first-pass gadolinium perfusion MRI in exercise-recovery. Muscle perfusion provides objective measures that may help determine which patients will benefit from selected therapies.