# Cerebral oxygen extraction efficiency in patients with sickle cell anemia

> **NIH NIH F31** · VANDERBILT UNIVERSITY · 2024 · $34,370

## Abstract

PROJECT SUMMARY
This work proposes to refine novel non-invasive magnetic resonance imaging (MRI) methods to quantify
cerebral oxygen extraction and to apply these methods in persons with sickle cell anemia (SCA) to
elucidate potential mechanisms for cerebral infarct development.
SCA, caused by homozygous inheritance of mutant hemoglobin S (HbS), is the most severe and yet common
form of sickle cell disease affecting approximately 1 in every 500 African Americans in the United States. The
disease is characterized by the sickling of erythrocytes following deoxygenation of mutant HbS, which manifests
in patients as chronic hemolytic anemia and possible vascular occlusion. More than half of individuals with SCA
will have a silent cerebral infarct (SCI) by age 30 years; while largely asymptomatic at the time of injury, these
SCIs can lead to progressive infarctions and cognitive deficits. Despite the high risk of infarction in these
patients, few patients exhibit traditional risk factors for stroke such as macrovascular steno-occlusion
and as such it has been difficult to develop biomarkers that can be used to triage patients for
conservative versus more aggressive disease-modifying or curative therapies. Cerebral infarctions in
persons with SCA are likely due to alternative vascular and metabolic changes at the tissue level secondary to
the disease. It is well-established that cerebral blood flow (CBF) is elevated in SCA to compensate for reduced
hemoglobin, but CBF is an incomplete predictor of ischemic risk by itself. Prior work in our lab has shown reduced
capillary transit times in the presence of elevated CBF in individuals with SCA may lead to inefficient cerebral
oxygen extraction at the capillary level. It is critical to accurately characterize these and possibly related changes
in tissue physiology to establish functional biomarkers that can be used to triage patients with SCA to risk-
appropriate treatments, or rather, to use these biomarkers as end-points in clinical trials.
To address these needs, non-invasive imaging methods such as the asymmetric spin echo (ASE) MRI sequence
have been developed to characterize cerebral oxygen extraction in humans. However, current methodological
variants underestimate cerebral oxygen extraction metrics due to technical shortcomings of isolating
extravascular water signal in the sequence. The goals of this proposal are (1) to refine and evaluate MRI
methods to accurately quantify regional cerebral oxygen extraction and (2) to understand relationships
between regional changes in oxygen extraction and blood transit times in adults with SCA before and
after blood transfusions that modulate hemoglobin and flow velocities. Successful completion should
provide new methods to monitor tissue health in SCA and to improve our understanding of how tissue subserves
oxygen in the setting of anemia and in response to treatments.

## Key facts

- **NIH application ID:** 10901203
- **Project number:** 1F31HL174137-01
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Alexander K Song
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $34,370
- **Award type:** 1
- **Project period:** 2024-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901203

## Citation

> US National Institutes of Health, RePORTER application 10901203, Cerebral oxygen extraction efficiency in patients with sickle cell anemia (1F31HL174137-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10901203. Licensed CC0.

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