ArticleAmerican journal of hematology2022
Cerebral oxygen metabolic stress is increased in children with sickle cell anemia compared to anemic controls.
Article in American journal of hematology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
- Effect of voxelotor on cerebral perfusion and cerebral oxygen metabolism and cardiac stress in adult patients with sickle cell disease.American journal of hematology · 2025Trial
- The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease.Blood · 2024Trial
- Reliability of diffuse optical spectroscopies for evaluation of cerebral hemometabolic stress in children with sickle cell anemia.Biomedical optics express · 2026Article
- Correlation between diffuse correlation spectroscopy and transcranial Doppler ultrasound in pediatric sickle cell disease.Biomedical optics express · 2026Article
- Accelerated drug approvals and patient trust: impact of voxelotor and crizanlizumab for sickle cell disease.Blood advances · 2025Article
- Cerebral Hemodynamic Responses to Disease-Modifying and Curative Sickle Cell Disease Therapies.Neurology · 2025Article
- Cerebral hemodynamics and oxygen metabolism in patients with milder and severe forms of sickle cell disease and thalassemia.HemaSphere · 2024Article
- Automatic Rejection based on Tissue Signal (ARTS) for motion-corrected quantification of cerebral venous oxygenation in neonates and older adults.Magnetic resonance imaging · 2024Article
- Molecular and environmental contributors to neurological complications in sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Anemia and brain hypoxia.Blood · 2023Article
- Article
- Grand challenges in pediatric stroke.Frontiers in stroke · 2023Article
- The Development of Neuroimaging Biomarkers for Cognitive Decline in Sickle Cell Disease.Hematology/oncology clinics of North America · 2022Review
- Magnetic resonance imaging metrics of oxygen extraction fraction: Contradictions or insight into pathophysiological mechanisms?American journal of hematology · 2022Article
- Chronic anemia: The effects on the connectivity of white matter.Frontiers in neurology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Patients with sickle cell anemia (SCA) experience cerebral metabolic stress with an increase in oxygen extraction fraction (OEF) to compensate for reduced oxygen carrying capacity due to anemia. It remains unclear if anemia alone drives this metabolic stress. Using MRI, we collected voxel-wise OEF measurements to test our hypothesis that OEF would be elevated in anemic controls without SCA (AC) compared to healthy controls (HC), but OEF would be even higher in SCA compared to AC. Brain MRIs (N = 159) were obtained in 120 participants (34 HC, 27 AC, 59 SCA). While hemoglobin was lower in AC versus HC (p < 0.001), hemoglobin was not different between AC and SCA cohorts (p = 0.459). Whole brain OEF was higher in AC compared to HC (p < 0.001), but lower compared to SCA (p = 0.001). Whole brain OEF remained significantly higher in SCA compared to HC (p = 0.001) while there was no longer a difference between AC versus HC (p = 0.935) in a multivariate model controlling for age and hemoglobin. OEF peaked within the border zone regions of the brain in both SCA and AC cohorts, but the volume of white matter with regionally elevated OEF in AC was smaller (1.8%) than SCA (58.0%). While infarcts colocalized within regions of elevated OEF, more SCA participants had infarcts than AC (p < 0.001). We conclude that children with SCA experience elevated OEF compared to AC and HC after controlling for the impact of anemia, suggesting that there are other pathophysiologic factors besides anemia contributing to cerebral metabolic stress in children with SCA.
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