Journal
STROKE
Volume 46, Issue 7, Pages 1793-1799Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/STROKEAHA.115.008721
Keywords
diffusion; pediatrics; sickle cell anemia
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Funding
- UCL Grand Challenges
- Great Ormond Street Hospital Childrens Charity [V4615] Funding Source: researchfish
- Medical Research Council [G1002276, G0300117] Funding Source: researchfish
- National Institute for Health Research [PB-PG-1112-29099] Funding Source: researchfish
- MRC [G0300117, G1002276] Funding Source: UKRI
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Background and Purpose Sickle cell anemia is associated with compromised oxygen-carrying capability of hemoglobin and a high incidence of overt and silent stroke. However, in children with no evidence of cerebral infarction, there are changes in brain morphometry relative to healthy controls, which may be related to chronic anemia and oxygen desaturation. Methods A whole-brain tract-based spatial statistics analysis was carried out in 25 children with sickle cell anemia with no evidence of abnormality on T2-weighted magnetic resonance imaging (13 male, age range: 8-18 years) and 14 age- and race-matched controls (7 male, age range: 10-19 years) to determine the extent of white matter injury. The hypotheses that white matter damage is related to daytime peripheral oxygen saturation and steady-state hemoglobin were tested. Results Fractional anisotropy was found to be significantly lower in patients in the subcortical white matter (corticospinal tract and cerebellum), whereas mean diffusivity and radial diffusivity were higher in patients in widespread areas. There was a significant negative relationship between radial diffusivity and oxygen saturation (P<0.05) in the anterior corpus callosum and a trend-level negative relationship between radial diffusivity and hemoglobin (P<0.1) in the midbody of the corpus callosum. Conclusions These data show widespread white matter abnormalities in a sample of asymptomatic children with sickle cell anemia, and provides for the first time direct evidence of a relationship between brain microstructure and markers of disease severity (eg, peripheral oxygen saturation and steady-state hemoglobin). This study suggests that diffusion tensor imaging metrics may serve as a biomarker for future trials of reducing hypoxic exposure.
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