title: Estimating Total Cerebral Microinfarct Burden From Diffusion-Weighted Imaging.
abstract: OBJECTIVE
  Cerebral microinfarcts (CMI) are important contributors to vascular cognitive impairment. Magnetic resonance imaging diffusion-weighted imaging (DWI) hyperintensities have been suggested to represent acute CMI. We aim to describe a mathematical method for estimating total number of CMI based on the presence of incidental DWI lesions.
  
  
  METHODS
  We reviewed magnetic resonance imaging scans of subjects with cognitive decline, cognitively normal subjects and previously reported subjects with past intracerebral hemorrhage (ICH). Based on temporal and spatial characteristics of DWI lesions, we estimated the annual rate of CMI needed to explain the observed rate of DWI lesion detection in each group. To confirm our estimates, we performed extensive sampling for CMI in the brain of a deceased subject with past lobar ICH who found to have a DWI lesion during life.
  
  
  RESULTS
  Clinically silent DWI lesions were present in 13 of 343 (3.8%) cognitively impaired and 10 of 199 (5%) cognitively intact normal non-ICH patients, both lower than the incidence in the past ICH patients (23 of 178; 12.9%; P<0.0006). The predicted annual incidence of CMI ranges from 16 to 1566 for non-ICH and 50 to 5041 for ICH individuals. Histological sampling revealed a total of 60 lesions in 32 sections. Based on previously reported methods, this density of CMI yields an estimated total brain burden maximum likelihood estimate of 9321 CMIs (95% confidence interval, 7255-11 990).
  
  
  CONCLUSIONS
  Detecting even a single DWI lesion suggests an annual incidence of hundreds of new CMI. The cumulative effects of these lesions may directly contribute to small-vessel-related vascular cognitive impairment.
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Eitan
authors.initials: E
authors.lastname: Auriel
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: M Brandon
authors.initials: MB
authors.lastname: Westover
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Matt T
authors.initials: MT
authors.lastname: Bianchi
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Yael
authors.initials: Y
authors.lastname: Reijmer
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Sergi
authors.initials: S
authors.lastname: Martinez-Ramirez
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Jun
authors.initials: J
authors.lastname: Ni
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Ellis
authors.initials: E
authors.lastname: Van Etten
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Frosch
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Fotiadis
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Kris
authors.initials: K
authors.lastname: Schwab
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Anastasia
authors.initials: A
authors.lastname: Vashkevich
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Grégoire
authors.initials: G
authors.lastname: Boulouis
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Alayna P
authors.initials: AP
authors.lastname: Younger
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Trey
authors.initials: T
authors.lastname: Hedden
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: M Edip
authors.initials: ME
authors.lastname: Gurol
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.).
authors.forename: Anand
authors.initials: A
authors.lastname: Viswanathan
authors.affiliation: From the Department of Neurology, J. Philip Kistler Stroke Research Center (E.A., M.B.W., M.T.B., Y.R., S.M.-R., J.N., E.V.E., P.F., K.S., A. Vashkevich, G.B., M.E.G., A. Viswanathan, S.M.G.) and Department of Pathology, Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Radiology, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown (A.P.Y., K.A.J., R.A.S., T.H.); and Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (R.A.S.). sgreenberg@partners.org.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Greenberg
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002544:Cerebral Infarction / Q000175:diagnosis* / Q000378:metabolism*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods* / Q000592:standards; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D011446:Prospective Studies; D012189:Retrospective Studies
keywords: brain; cerebral hemorrhage; cerebral infarction; diffusion magnetic resonance imaging; mild cognitive impairment