Cerebrovascular Reactivity Measurements With High-Density Diffuse Optical Tomography

Purpose

The purpose of the study protocol is to identify imaging biomarkers for brain tissue under high metabolic stress at risk for permanent injury. We will measure oxygen extraction fraction (OEF) and cerebrovascular reactivity (CVR) in participants with and without perturbations in cerebral oxygen delivery over time to determine each parameter's role in clinical and radiologic neurologic outcomes. Measuring OEF can be done with specialized MRI sequences. Measuring CVR requires a vasoactive response, such as carbon dioxide. In order to deliver carbon dioxide evenly and as safely as possible, we will use RespirACT, an MRI-compatible device, to prevent over-breathing carbon dioxide and allow rapid steady-state physiology to minimize total scan time. We will also use a high density diffuse optical tomography (HD-DOT) cap to assess the measurement of OEF and CVR. This study will investigate both regional OEF and CVR simultaneously to understand each marker's unique developmental trajectory and contribution to stroke risk in children. This work will expand insights into mechanisms of stroke in children and assess the feasibility of the HD-DOT cap for obtaining these insights by comparing a cohort of optical CVR and a cohort of MRI CVR. In addition to the MRI and/or HD-DOT cap with RespirAct, participants may also have their vitals measured, complete cognitive testing, and complete a blood draw with a study visit. Participants may be followed for up to three years and may complete both an MRI scan and an HD-DOT scan within 1 week-12 months of each other. Participants may be invited back to repeat MRI and/or HD-DOT scans 1-2 times over the next three years.

Conditions

  • Sickle Cell Disease
  • Cerebral Stroke

Eligibility

Eligible Ages
Between 6 Years and 70 Years
Eligible Sex
All
Accepts Healthy Volunteers
Yes

Inclusion Criteria

  • 6-70 Years Old - Able to participate in MRI scan without sedation - May or may not have HbSS or beta thalassemia null genotypes of sickle cell anemia

Exclusion Criteria

  • Significant craniofacial malformation or technical contraindications to DOT monitoring (for HDDOT imaging) - Metal in/on the body that is contraindicated for MRI safety (for MRI imaging)

Study Design

Phase
N/A
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Single Group Assignment
Intervention Model Description
All arms will receive the same study conditions.
Primary Purpose
Basic Science
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Healthy Controls
  • Other: Carbon Dioxide
    Participants inhale carbon dioxide, delivered by computer-controlled delivery system, to target specific levels of carbon dioxide while in magnetic resonance imaging scan and/or during HDDOT imaging to measure cerebrovascular reactivity.
Active Comparator
Sickle Cell Anemia Participants
  • Other: Carbon Dioxide
    Participants inhale carbon dioxide, delivered by computer-controlled delivery system, to target specific levels of carbon dioxide while in magnetic resonance imaging scan and/or during HDDOT imaging to measure cerebrovascular reactivity.

Recruiting Locations

Washington University in St. Louis
St Louis, Missouri 63110
Contact:
Kristin Guilliams, MD
3144546120
kristinguilliams@wustl.edu

More Details

Status
Recruiting
Sponsor
Washington University School of Medicine

Study Contact

Kristin Guilliams, MD
3144545436
kristinguilliams@wustl.edu

Detailed Description

The purpose of the study protocol is to identify imaging biomarkers for brain tissue under high metabolic stress at risk for permanent injury. We will measure OEF and CVR in participants with and without perturbations in cerebral oxygen delivery over time to determine each parameter's role in clinical and radiologic neurologic outcomes. Measuring OEF can be done with specialized MRI sequences. Measuring CVR requires a vasoactive response, such as carbon dioxide. In order to deliver carbon dioxide evenly and as safely as possible, we will use RespirACT, an MRI-compatible device, to prevent over-breathing carbon dioxide and allow rapid steady-state physiology to minimize total scan time. We will also use an HD-DOT cap to assess the measurement of OEF and CVR.