Metabolic and Hemodynamic Reserve in Pediatric SCA

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. SCA participants and healthy controls are age and sex-matched for comparison. Within the SCA cohort, children with infarcts may have thinner cortices than those without, reflecting a greater loss. The investigators 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 may vary by age. The brain's blood flow changes in small ways during everyday activities, such exercise, deep concentration, or normal brain growth. 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 a full oxygen supply may cause the brain to grow and develop more slowly than when it has a full supply. 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, cognitive assessments, and brief questionnaires. The study team will use a special mask to control the amount of carbon dioxide the participants breathe in.

Official Title
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The Role of Metabolic and Hemodynamic Reserve in Age-Related Brain Vulnerability in Pediatric Sickle Cell Anemia

Conditions
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Child, Only, Brain Diseases, Sickle Cell Disease, Anemia, Sickle Cell

Intervention / Treatment
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* Drug: Carbon Dioxide


Participation Criteria
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Eligibility Criteria
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Healthy Controls: Healthy controls ages 4-21 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 4-21 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 No known vasculopathy

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 21 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Healthy Control<br> | Drug: Carbon Dioxide<br>* Participants inhale carbon dioxide while in magnetic resonance imaging scan to measure cerebrovascular reactivity<br>|
| Active Comparator: Sickle Cell Anemia<br> | Drug: 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 |
| --- | --- | --- |
| Gray Matter cortical thickness | Mean whole brain cortical thickness on high resolution T1 images | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Brain volume | Total brain volume (gray matter and white matter) on high resolution T1 image | 3 years | 
| Cerebrovascular Reactivity | Change in blood flow as measured by MRI in response to 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 anemia, cerebrovascular reactivity, cerebral oxygen metabolism, cortical thickness, gray matter, carbon dioxide, magnetic resonance imaging, brain development