Cerebral Stroke, Sickle Cell Disease
Conditions
Keywords
cerebrovascular reactivity, magnetic resonance imaging, High density diffuse optical tomography
Brief summary
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.
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.
Interventions
OTHERCarbon 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.
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
All arms will receive the same study conditions.
Eligibility
Sex/Gender
ALL
Age
6 Years to 70 Years
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HDDOT-Based Cerebrovascular Reactivity | ~15 minutes during the MRI scan and ~60 minutes during the HDDOT imaging. | Changes in relative concentration of deoxyhemoglobin with fluctuations of carbon dioxide as compared to gold standard measurement of MRI-based cerebrovascular reactivity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Oxygen Metabolism | From administration of carbon dioxide to end of inhalation of carbon dioxide -- 60 minutes during MRI and/or HDDOT imaging. | MRI-based cerebral based blood flow oxygen extraction fraction will be combined with laboratory data estimating arterial oxygen content to calculate cerebral oxygen metabolism. |
Countries
United States
Contacts
CONTACTKristin Guilliams, MD
Outcome results
None listed