title: Integrity of normal-appearing white matter and functional outcomes after acute ischemic stroke.
abstract: OBJECTIVE
  To characterize the effect of white matter microstructural integrity on cerebral tissue and long-term functional outcomes after acute ischemic stroke (AIS).
  
  
  METHODS
  Consecutive AIS patients with brain MRI acquired within 48 hours of symptom onset and 90-day modified Rankin Scale (mRS) score were included. Acute infarct volume on diffusion-weighted imaging (DWIv) and white matter hyperintensity volume (WMHv) on T2 fluid-attenuated inversion recovery MRI were measured. Median fractional anisotropy (FA), mean diffusivity, radial diffusivity, and axial diffusivity values were calculated within normal-appearing white matter (NAWM) in the hemisphere contralateral to the acute lesion. Regression models were used to assess the association between diffusivity metrics and acute cerebral tissue and long-term functional outcomes in AIS. Level of significance was set atp< 0.05 for all analyses.
  
  
  RESULTS
  Among 305 AIS patients with DWIv and mRS score, mean age was 64.4 ± 15.9 years, and 183 participants (60%) were male. Median NIH Stroke Scale (NIHSS) score was 3 (interquartile range [IQR] 1-8), and median normalized WMHv was 6.19 cm3(IQR 3.0-12.6 cm3). Admission stroke severity (β = 0.16,p< 0.0001) and small vessel stroke subtype (β = -1.53,p< 0.0001), but not diffusivity metrics, were independently associated with DWIv. However, median FA in contralesional NAWM was independently associated with mRS score (β = -9.74,p= 0.02), along with age, female sex, NIHSS score, and DWIv.
  
  
  CONCLUSIONS
  FA decrease in NAWM contralateral to the acute infarct is associated with worse mRS category at 90 days after stroke. These data suggest that white matter integrity may contribute to functional recovery after stroke.
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence. metherton@partners.org.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Etherton
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Ona
authors.initials: O
authors.lastname: Wu
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Pedro
authors.initials: P
authors.lastname: Cougo
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Anne-Katrin
authors.initials: AK
authors.lastname: Giese
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Lisa
authors.initials: L
authors.lastname: Cloonan
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Kaitlin M
authors.initials: KM
authors.lastname: Fitzpatrick
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Allison S
authors.initials: AS
authors.lastname: Kanakis
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Gregoire
authors.initials: G
authors.lastname: Boulouis
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Hasan H
authors.initials: HH
authors.lastname: Karadeli
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Arne
authors.initials: A
authors.lastname: Lauer
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Rosand
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Furie
authors.affiliation: From the J. Philip Kistler Stroke Research Center (M.R.E., O.W., P.C., A.-K.G., L.C., K.M.F., A.S.K., G.B., H.H.K., A.L., N.S.R.), Department of Neurology, and Athinoula A. Martinos Center for Biomedical Imaging (O.W.), Department of Radiology, Massachusetts General Hospital and Harvard Medical School; Division of Neurocritical Care and Emergency Neurology (J.R.), Department of Neurology and Center for Human Genetic Research, Massachusetts General Hospital, Boston; and Department of Neurology (K.L.F.), Rhode Island Hospital, Alpert Medical School of Brown University, Providence.
authors.forename: Natalia S
authors.initials: NS
authors.lastname: Rost
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging*; D002545:Brain Ischemia / Q000000981:diagnostic imaging* / Q000628:therapy*; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020127:Recovery of Function; D012720:Severity of Illness Index; D020521:Stroke / Q000000981:diagnostic imaging* / Q000628:therapy*; D016896:Treatment Outcome; D066127:White Matter / Q000000981:diagnostic imaging*