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White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts
Jamie M Kawadler1, Fenella J Kirkham2, Jonathan D Clayden1
1From the Developmental Imaging and Biophysics Section (J.M.K., J.D.C., C.A.C.), Clinical Neurosciences Section (F.J.K.), and Cognitive Neuroscience and Neuropsychiatry Section (E.L.S., R.E.), UCL Institute of Child Health, London, United Kingdom; Department of Clinical Neuroscience, University of Cambridge, Cambridge, United Kingdom (M.J.H.); Department of Paediatric Haematology, Barts and The London Hospital NHS Trust, London, United Kingdom (P.T.); Department of Paediatrics, Whittington Hospital NHS Trust, London, United Kingdom (A.R.); Department of Paediatrics, North Middlesex University Hospital NHS Trust, London, United Kingdom (O.W.); Wessex Neurological Centre (S.B.), and Department of Child Health (F.J.K.), Southampton University Hospitals NHS Trust, Southampton, United Kingdom (S.B.); and Department of Radiology, Great Ormond Street Hospital, London, United Kingdom (T.C.S.C.).
Insights
Children with sickle cell anemia show brain white matter abnormalities, even without stroke. Lower oxygen saturation and hemoglobin levels correlate with white matter damage, suggesting diffusion tensor imaging as a potential biomarker.
Area of Science:
- Neurology
- Pediatrics
- Hematology
Background:
- Sickle cell anemia (SCA) impairs hemoglobin's oxygen-carrying capacity, leading to frequent strokes.
- Children with SCA exhibit altered brain morphometry, even without overt cerebral infarction, potentially due to chronic anemia and hypoxia.
Purpose of the Study:
- To investigate white matter injury in children with SCA using diffusion tensor imaging (DTI).
- To determine the relationship between white matter damage and disease severity markers like oxygen saturation and hemoglobin levels.
Main Methods:
- Whole-brain tract-based spatial statistics (TBSS) analysis was performed on 25 children with SCA and 14 controls.
- DTI metrics, including fractional anisotropy (FA) and diffusivity measures, were analyzed.
- Correlation analyses examined relationships between DTI metrics and peripheral oxygen saturation and hemoglobin levels.
Main Results:
- Patients with SCA showed significantly lower FA in subcortical white matter (corticospinal tract, cerebellum).
- Mean diffusivity and radial diffusivity were elevated in widespread brain areas in SCA patients.
- Radial diffusivity correlated negatively with oxygen saturation and showed a trend with hemoglobin levels in specific white matter tracts.
Conclusions:
- Widespread white matter abnormalities are present in asymptomatic children with SCA.
- This study provides the first direct evidence linking brain microstructure to SCA severity markers.
- DTI metrics may serve as biomarkers for future therapeutic trials aimed at reducing hypoxic exposure in SCA.
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.
