# Age-Dependence of Cerebral Oxygen Metabolism and Stroke Risk in Pediatric Sickle Cell Disease

> **NIH NIH K23** · WASHINGTON UNIVERSITY · 2021 · $176,279

## Abstract

Pediatric stroke may occur because of an inadequate oxygen supply to meet the high energy
demands of a developing brain. The brain undergoes tremendous growth and development
throughout childhood. Brain tissues consume oxygen delivered by the blood, providing energy
for cellular processes. The brain’s demand for oxygen appears to peak between ages 5-9.
If regions of the brain do not get enough oxygen, either because the blood does not carry
enough oxygen, or because blood does not reach the tissue, a stroke can occur. The cerebral
metabolic rate of oxygen utilization (CMRO2), reflecting the energy demands of the brain, is a
product of amount of oxygen available in the blood, rate of blood delivery (cerebral blood flow,
or CBF) and the percentage of oxygen delivered taken up by the brain tissue (oxygen extraction
fraction, or OEF). CBF and OEF are dynamic processes, able to compensate for minor
perturbations or increased demand as needed to maintain a steady energy consumption rate. In
adults, an increased OEF demonstrates high metabolic compensation and signifies a high
stroke risk. Because the oxygen demand is higher in children than adults and changes
throughout childhood, it is unclear whether increased OEF and increased CBF also denote a
high stroke risk. One reason this is unknown is because previously OEF has required radiation
for tissue-level measurements; thus rendering OEF measurements unethical for pediatric
research. Our team has developed novel MR sequences to measure tissue-level OEF. Children
with sickle cell disease (SCD) have lower amounts of oxygen available in their blood due to
anemia. Children with SCD also have a high incidence of stroke, with 1 of 3 children
demonstrating stroke on MRI before reaching adulthood. This project seeks to understand
whether or not age-dependent increases in OEF and CBF predict stroke in children with SCD. I
hypothesize that age and oxygen metabolism predict stroke risk in children with SCD. The long-
term goal of this project is to develop these methods to assess stroke risk and mechanism
across pediatric stroke populations. Aim 1: To determine effects of age and SCD on oxygen
metabolism. I will examine the contribution of age, blood counts, and SCD on CBF and OEF.
Aim 2: To determine if age and oxygen metabolism predict individual stroke risk in subjects with
SCD. I will follow subjects with SCD for 4 years to determine the predictive value of global and
regional measures of age and oxygen metabolism, accounting blood counts, and disease
severity. Aim 3: To determine if oxygen metabolism response to therapeutic intervention is age-
dependent. I will examine how global and regional metabolism changes with transfusion.

## Key facts

- **NIH application ID:** 10071216
- **Project number:** 5K23NS099472-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Kristin Guilliams
- **Activity code:** K23 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $176,279
- **Award type:** 5
- **Project period:** 2017-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071216

## Citation

> US National Institutes of Health, RePORTER application 10071216, Age-Dependence of Cerebral Oxygen Metabolism and Stroke Risk in Pediatric Sickle Cell Disease (5K23NS099472-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071216. Licensed CC0.

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