Quantitative Assessment and Characterization of Microvascular Function Using Diffuse Optical Tomography
Condition: Atherosclerosis; Diabetes; Coronary Artery Disease
MeSH terms: Coronary Artery Disease; Atherosclerosis
Study type: Interventional

Summary: 
      Atherosclerosis is accompanied by microvascular dysfunction (an impairment of blood vessels
      to dilate or constrict in response to demand). The ability to reliably measure microvascular
      dysfunction would help identify patients at risk of myocardial infarction and test new
      treatments. All existing measures of microvascular dysfunction suffer significant
      limitations.

      Near Infrared Spectroscopy (NIRS) is an imaging method that uses an infrared light-source and
      detector (called optodes) to painlessly shines light into tissue and collect reflected light
      at different wavelengths. This data allows quantification of the amount of haemoglobin
      (blood) in the tissue and whether it is oxygenated or de-oxygenated.

      Diffuse optical tomography (DOT) is a powerful analysis technique for data collected from
      multiple NIRH optodes. Unlike most NIRS studies that use a single pair of optodes and
      collects a single datapoint for each wavelength over time, DOT allows three-dimensional
      spatial reconstruction of haemodynamic and anatomic changes in a large region of tissue over
      time.

      In preliminary work DOT had the potential to measure forearm reactive hyperaemia, a key
      indicator of microvascular function. Team will test whether DOT can detect differences
      between patients and healthy volunteers.

      In this work, 30 patients will be recruited with type 2 diabetes, 30 patients who have had a
      previous myocardial infarction and 30 healthy volunteers. The Investigator will also recruit
      50 patients who are on waiting lists for coronary angiography.

      The DOT will be used to measure participants' microvascular function after brachial artery
      occlusion by a blood pressure cuff. The Investigator will then examine whether DOT can detect
      differences between healthy volunteers, diabetics, and patients with a previous heart attack,
      and whether DOT is able to predict existence of coronary artery disease on angiography. If
      successful, DOT can be developed for assessment of microvascular function to the point where
      it could be applied to clinical studies.
    

Detailed description: 
      Previous pilot studies have shown ability to collect promising data safely. In the following
      studies, the same study as in the pilot will be performed to apply the array of optodes to
      the surface of the arm. These emit light painlessly into the tissue and collect scattered
      light from the tissue. Inflation of a blood pressure cuff around the arm for 5 minutes, then
      deflate the cuff to allow blood flow back into the tissue. From the data gathered before,
      during and after the cuff is inflated, 3D reconstructions can be performed of HbO, HbR, and
      HbT changes in the forearm during and after arterial occlusion.

      Study 1) Can DOT detect differences in vascular function between healthy volunteers and
      patients with proven heart disease or diabetes

      This study will measure vascular function in patients with known heart disease (previous
      myocardial infarction) or diabetes and compare this to matched healthy volunteers. This will
      establish whether DOT can detect differences in vascular response between these groups. If
      so, then the method has the potential to be useful diagnostically or prognostically.

      Potential participants will be approached by poster, or face to face in STH clinics and
      provided with the information sheet which participants will be asked to read at home.
      Participants will be given the opportunity to ask questions by email or telephone at any time
      afterwards. Participants will be asked to contact us if they are willing to participate.

      Participants will be booked with an appointment to attend the Clinical Research Facility at
      Sheffield Teaching Hospitals (at least 24hrs after receiving the information sheet and having
      the chance to ask questions) for a visit of 30-45 minutes. Visits will be arranged in advance
      at a convenient time.

      When participants attend, after agreeing to take part and signing a consent form,
      participants will take a seat in a private room. Participants will need to wear short
      sleeves, or roll their sleeves up. If necessary, the investigator can provide a gown to wear
      if the sleeves are too tight. The investigator will then do the following;

        1. Record some details about medical history, height/weight, whether they take medications,
           date of birth, whether male or female.

        2. Measure the blood pressure by briefly inflating a cuff around the upper arm.

        3. Place an array of fibre optics on the surface of the forearm. Some jelly will be placed
           on the skin first, and the array will be held in place by a strap or tape. This is not
           painful.

        4. After around 10 minutes of sitting quietly, the investigator will inflate a blood
           pressure cuff around the arm that the array is placed on. This will temporarily prevent
           blood entering or leaving the arm. This will feel tight and the arm may go numb. The
           investigator will keep the cuff inflated for five minutes, but the participant can ask
           for the cuff to be deflated at any time.

        5. The investigator will then deflate the cuff, allowing blood back into the arm. After
           around 10 more minutes, the investigator will remove the cuff and array and the
           participant will be free to leave.

      After the first assessment, the investigator will ask participants if they would be willing
      to attend for a second assessment where we would repeat the above measurements. This is to
      test how reproducible the measurements are in the same individual.

      Study 2) Can DOT predict presence or severity of coronary artery disease on angiography?

      This study will measure vascular function in patients awaiting diagnostic coronary
      angiography (either invasive or by CT), in whom it is not known whether or not coronary
      artery disease is present. Once the angiographic results are available the investigator will
      correlate vascular function measured by DOT with presence and severity of coronary artery
      disease to examine whether or not DOT identified

      Potential participants will be approached by poster, or face to face in STH clinics and
      provided with the information sheet which participants will be asked to read. Participants
      will be given the opportunity to ask questions by email or telephone at any time afterwards.
      Participants will be asked to contact us if they are willing to participate.

      Participants will be booked with an appointment to attend the Clinical Research Facility at
      Sheffield Teaching Hospitals (at least 24hrs after receiving the information sheet and having
      the chance to ask questions) for a visit of approximately 45 minutes. Visits will be arranged
      in advance at a convenient time.

      When participants attend, after agreeing to take part and signing a consent form, particpants
      will take a seat in a private room. Participants will need to wear short sleeves, or roll
      their sleeves up. If necessary, the investigator can provide a gown to wear if the sleeves
      are too tight. the investigator will then do the following;

        1. Record some details about medical history, whether they take medications, date of birth,
           whether male or female.

        2. Measure the blood pressure by briefly inflating a cuff around the upper arm.

        3. Place an array of fibre optics on the surface of the forearm. Some jelly will be placed
           on the skin first, and the array will be held in place by a strap or tape. This is not
           painful.

        4. After around 10 minutes of sitting quietly, the investigator will inflate a blood
           pressure cuff around the arm that the array is placed on. This will temporarily prevent
           blood entering or leaving the arm. This will feel tight and the arm may go numb. The
           investigator will keep the cuff inflated for five minutes, but the participant can ask
           for the cuff to be deflated at any time.

        5. The investigator will then deflate the cuff, allowing blood back into the arm. After
           around 10 more minutes, the investigator will remove the cuff and array and the
           participant will be free to leave.

      Once the angiogram is performed (as part of their routine clinical care) the results will be
      reviewed by a clinically trained researcher. This will then be correlated with their vascular
      function measured by DOT to determine whether this can predict angiographic findings.
    

Intervention name(s): diffuse optical tomography
Intervention type(s): Device
Intervention description(s): Optical tomography is a form of computed tomography that creates a digital volumetric model of an object by reconstructing images made from light transmitted and scattered through an object.
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science