Cerebral Oxygen Metabolism in Children

Study Overview
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Brief Summary
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The purpose of this research study is to better understand how blood flow and metabolism change can influence brain development in the early decades of life. We will examine brain blood flow and metabolism using magnetic resonance imaging (MRI). The brain's blood vessels expand and constrict to regulate blood flow based on the brain's needs. The amount of expanding and contracting the blood vessels can do varies by age. The brain's blood flow changes in small ways during everyday activities, such as normal brain growth, exercise, or deep concentration. Significant illness or psychological stress may increase the brain's metabolic demand or cause other bigger changes in blood flow. If blood vessels are not able to expand to give more blood flow when metabolic demand is high, the brain may not get all of the oxygen it needs. In extreme circumstances, if the brain is unable to get enough oxygen for a long time, a stroke may occur. Sometimes small strokes occur without other noticeable changes and are only detectable on an MRI. These are sometimes called silent strokes. In less extreme circumstances, not having as much oxygen as it wants may cause the brain to grow and develop more slowly than it should. One way to test the ability of blood vessels to expand is by measuring blood flow while breathing in carbon dioxide. Carbon dioxide causes blood vessels in the brain to dilate without increasing brain metabolism. During this study participants may be asked to undergo a blood draw, MRI, and potential neuropsychological assessments. It is also possible that the study team will use a special mask to control the amount of carbon dioxide the participants breathe in so they don't breathe in too much.

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

Official Title
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Cerebral Oxygen Metabolism in Children

Conditions
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Sickle Cell Disease, Cerebral Stroke

Intervention / Treatment
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* Other: Carbon Dioxide


Participation Criteria
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Eligibility Criteria
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Healthy Controls: Healthy controls ages 3-50 years of age Able to participate in MRI scan without sedation Not currently pregnant No significant psychiatric history, defined as having a severe psychiatric diagnosis, per PI discretion No history of epilepsy No history of stroke or cerebrovascular disease May have occasional headaches if not taking a daily preventative medication for headaches Not on vasodilatory medication, such as sildenafil or verapamil Sickle Cell Anemia Participants: Ages 3-50 years of age Hb SS or SBeta-thal Able to participate in MRI scan without sedation Not currently pregnant Not on vasodilatory medication, such as sildenafil or verapamil Extracorporeal Membrane Oxygenation (ECMO) Survivors: Ages 3-50 years of age History of cannulation for ECMO Able to participate in MRI scan without sedation Not currently pregnant Not on vasodilatory medication, such as sildenafil or verapamil

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 50 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: All arms will receive the same study conditions.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Controls<br> | Other: Carbon Dioxide<br>* Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity<br>|
| Active Comparator: Extracorporeal Membrane Oxygenation survivors<br> | Other: Carbon Dioxide<br>* Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity<br>|
| Active Comparator: Sickle Cell Anemia participants<br> | Other: Carbon Dioxide<br>* Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebral Oxygen Metabolism |  | From the beginning of the MRI scan to the completion of the MRI scan -- 75 minutes. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cerebrovascular Reactivity |  | From administration of carbon dioxide to end of inhalation of carbon dioxide -- 15 minutes. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sickle cell disease, healthy controls, magnetic resonance imaging, extracorporeal membrane oxygenation, cerebrovascular reactivity