title: White Matter Damage Relates to Oxygen Saturation in Children With Sickle Cell Anemia Without Silent Cerebral Infarcts.
abstract: OBJECTIVE
  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.
authors.affiliation: From 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.).
authors.forename: Jamie M
authors.initials: JM
authors.lastname: Kawadler
authors.affiliation: From 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.). fenella.kirkham@ucl.ac.uk.
authors.forename: Fenella J
authors.initials: FJ
authors.lastname: Kirkham
authors.affiliation: From 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.).
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Clayden
authors.affiliation: From 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.).
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Hollocks
authors.affiliation: From 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.).
authors.forename: Emma L
authors.initials: EL
authors.lastname: Seymour
authors.affiliation: From 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.).
authors.forename: Rosanna
authors.initials: R
authors.lastname: Edey
authors.affiliation: From 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.).
authors.forename: Paul
authors.initials: P
authors.lastname: Telfer
authors.affiliation: From 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.).
authors.forename: Andrew
authors.initials: A
authors.lastname: Robins
authors.affiliation: From 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.).
authors.forename: Olu
authors.initials: O
authors.lastname: Wilkey
authors.affiliation: From 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.).
authors.forename: Simon
authors.initials: S
authors.lastname: Barker
authors.affiliation: From 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.).
authors.forename: Tim C S
authors.initials: TC
authors.lastname: Cox
authors.affiliation: From 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.).
authors.forename: Chris A
authors.initials: CA
authors.lastname: Clark
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000175:diagnosis* / Q000378:metabolism*; D002544:Cerebral Infarction; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D066127:White Matter / Q000378:metabolism* / Q000473:pathology*; D055815:Young Adult
chemical_list: D010100:Oxygen
keywords: diffusion; pediatrics; sickle cell anemia