Functional MRI of the Lower Extremities

Study Overview
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Brief Summary
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In this project, the investigators propose to use high-resolution magnetic resonance imaging (MRI) to measure blood perfusion in different groups of calf muscle. This imaging approach is standard of care for evaluation of coronary artery disease (CAD), and has never been successfully applied to PAD. Preliminary results show distinct patterns of muscle perfusion between healthy and PAD patients, and thus great promise of the technique. The investigators will first verify the reproducibility of the technique, and then compare the calf muscle perfusion measures in PAD patients against healthy age-matched controls. This comparison will test the feasibility of detecting functional abnormality in PAD patients. After the baseline scans, the PAD patients will opt to undergo a 12-week supervised exercise therapy, and then a post-therapy MRI scan. Comparison of the pre- and post-therapy measurements will indicate how the therapy improves the calf-muscle perfusion, and how this perfusion change correlates with increases in patient's walking ability. The long term goals of this project are to develop an improved diagnostic test for patients with PAD to predict who will benefit from therapeutic intervention. The MRI perfusion studies of calf muscle can be performed in conjunction with routine peripheral MR angiography to assess the functional significance of vascular stenosis.

Official Title
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Stress-rest Calf Muscle Perfusion: a Functional Diagnostic Test for Peripheral Arterial Disease (PAD)

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Behavioral: Supervised exercise therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: PAD patients with Intermittent claudication Ankle-brachial blood-pressure index (ABI) < 0.9 Exclusion Criteria: Estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73m2 Chronic pulmonary diseases Arthritis or other joint ailments

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy Controls<br> | |
| No Intervention: Age-Matched Controls<br>Subjects without PAD who have the same average age as the PAD patients | |
| Experimental: PAD Patients<br>Patients with PAD. Approximately 75% of PAD patients will be enrolled in the 12-week exercise therapy program. | Behavioral: Supervised exercise therapy<br>* The therapy will be conducted three times each week for 12 weeks. Each session takes 1 hour, consisting of 5 minutes of warmup activities, 50 minutes of intermittent exercise, and 5 minutes of cool-down activities. Exercise consists of walking on a treadmill initiated at 2 mph and 0% grade, until claudication pain becomes moderately severe. After claudication pain subsides, the subject will restart the walk. At the end of the session, the total exercise duration will be recorded. After a patient is able to walk 8-10 minutes at the initial workload, the grade is increased by 1-2%, or the speed is increased by 0.5 mph as tolerated.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Stress-rest calf-muscle perfusion | Perfusion in the different calf muscle groups following exercises of low (rest) and high (stress) intensities | Single visit ( 90 minutes) | 
| Perfusion changes following supervised exercise therapy | Change in stress-rest calf-muscle perfusion in PAD patients following the 12-week supervised exercise therapy | Before and after supervised exercise therapy (12 weeks) |