The goal of this study is to better understand how blood flows and how oxygen is utilized in the lower limbs of people who suffer from peripheral artery disease. This study will also assess how these factors affect treatment outcomes.

Specific aims include:

Aim 1: Utilize BB-NIR-DCS to differentiate PAD patients experiencing primary oxygen delivery limitations from those suffering from mitochondrial dysfunction.

Aim 2: Test the efficacy of BB-NIR-DCS at predicting individual responses to vascular intervention.

Subjects that do not have peripheral artery disease will complete the study procedures up to two times (baseline and follow-up at 1-2 months).

Subjects diagnosed with peripheral artery disease may be asked to complete the study procedures up to 4 separate times (baseline, follow-up at 1-2 weeks, 1-2 months, and 4-6 months). The investigators will work with them to schedule each visit.

All participants will provide informed consent prior to participating in the study. The screening procedures will include collecting information about health history, age, sex, race/ethnicity, height, weight, and reasons one should not undergo an MRI or exercise.

The laboratory procedures will include questionnaires about quality of life and walking ability, Ankle- Brachial Index, functional performance measures (treadmill walking and six minute walk distance), wearable activity monitor and activity log, and lower limb MRI with muscle perfusion and oxygenation measures at rest and in response to physiologic provocation (ischemia-reperfusion and exercise).

Investigators may ask subjects to return on a separate day to repeat part, or all, of the study procedures depending on image quality and/or equipment performance.

Inclusion Criteria:

• Cases, Aim 1

  1. 18 or older
  2. willing to participate under the conditions described in the informed consent form (ICF)
  3. eligible to sign the ICF
  4. established diagnosis of PAD confirmed by a physician
  5. able to comply with the study requirements

• Cases, Aim 2

  1) completed Aim 1

• Controls 1) asymptomatic, with no history or diagnosis of peripheral artery disease

Exclusion Criteria:

• Cases, Aim 1

  1. Ankle-Brachial Index >0.9 or <0.4
  2. isolated disease in aorta/iliac vessels
  3. unstable angina or myocardial infarction in past 12 months
  4. orthopedic or other physical limitations which would prevent data collection
  5. contraindications to MRI, including presence of a Pacemaker, presence of bone growth/ bone fusion stimulators, presence of tissue expander, presence of cochlear implants, unable to ambulate for 10 feet, receiving continuous Oxygen therapy, pregnancy, permanent Jewelry (screened using MRI safety screening form and verbal screening by MRI operator

• Cases, Aim 2

  1. unstable angina or myocardial infarction in past 12 months
  2. orthopedic or other physical limitations which would prevent data collection
  3. contraindications to MRI, including presence of a pacemaker, presence of bone growth/ bone fusion stimulators, presence of tissue expander, presence of cochlear implants, unable to ambulate for 10 feet, receiving continuous Oxygen therapy, pregnancy, permanent Jewelry (screened using MRI safety screening form and verbal screening by MRI operator).

• Controls 1) history of peripheral artery disease 2) overt cardiovascular disease (e.g. heart failure) 3) known pulmonary disease (excluding mild asthma) 4) current tobacco use 5) orthopedic or other physical limitations which would prevent data collection, 6) BP >150/90 mmHg at screening 7) contraindications to MRI, including presence of a pacemaker, presence of bone growth/ bone fusion stimulators, presence of tissue expander, presence of cochlear implants, unable to ambulate for 10 feet, receiving continuous Oxygen therapy, pregnancy, permanent Jewelry (screened using MRI safety screening form and verbal screening by MRI operator).

Cases- 80 individuals with PAD.

Controls- 40 healthy volunteers, of similar age, sex, and ethnicity as the PAD cases.