Anna K Bonkhoff1, Sungmin Hong2, Martin Bretzner2, Markus D Schirmer2, Robert W Regenhardt2, E Murat Arsava2, Kathleen Donahue2, Marco Nardin2, Adrian Dalca2, Anne-Katrin Giese2, Mark R Etherton2, Brandon L Hancock2, Steven J T Mocking2, Elissa McIntosh2, John Attia2, Oscar Benavente2, John W Cole2, Amanda Donatti2, Christoph Griessenauer2, Laura Heitsch2, Lukas Holmegaard2, Katarina Jood2, Jordi Jimenez-Conde2, Steven Kittner2, Robin Lemmens2, Christopher Levi2, Caitrin W McDonough2, James Meschia2, Chia-Ling Phuah2, Arndt Rolfs2, Stefan Ropele2, Jonathan Rosand2, Jaume Roquer2, Tatjana Rundek2, Ralph L Sacco2, Reinhold Schmidt2, Pankaj Sharma2, Agnieszka Slowik2, Martin Soederholm2, Alessandro Sousa2, Tara M Stanne2, Daniel Strbian2, Turgut Tatlisumak2, Vincent Thijs2, Achala Vagal2, Johan Wasselius2, Daniel Woo2, Ramin Zand2, Patrick McArdle2, Bradford B Worrall2, Christina Jern2, Arne G Lindgren2, Jane Maguire2, Polina Golland2, Danilo Bzdok2, Ona Wu2, Natalia S Rost2. 1. From the J. Philip Kistler Stroke Research Center (A.K.B., S.H., M.B., M.D.S., R.W.R., E.M.A., K.D., M.N., M.R.E., J. Rosand, N.S.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Univ. Lille (M.B.), Inserm, CHU Lille, U1171-LilNCog (JPARC)-Lille Neurosciences & Cognition, France; Clinic for Neuroradiology (M.D.S.), University Hospital Bonn, Germany; Computer Science and Artificial Intelligence Lab (A. Dalca, P.G.), Massachusetts Institute of Technology, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A. Dalca, B.L.H., S.J.T.M., E.M., J. Rosand, O.W.), Department of Radiology, Massachusetts General Hospital, Charlestown; Department of Neurology (A.-K.G.), University Medical Center Hamburg-Eppendorf, Germany; Hunter Medical Research Institute (J.A.), Newcastle; School of Medicine and Public Health, University of Newcastle, New South Wales, Australia; Department of Medicine (O.B.), Division of Neurology, University of British Columbia, Vancouver, Canada; Department of Neurology (J.W.C., S.K.), University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore; School of Medical Sciences (A. Donatti, A. Sousa), University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil; Department of Neurosurgery (C.G.), Geisinger, Danville, PA; Department of Neurosurgery (C.G.), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria; Department of Emergency Medicine (L. Heitsch), Washington University School of Medicine; Department of Neurology (L. Heitsch, C.-L.P.), Washington University School of Medicine & Barnes-Jewish Hospital, St. Louis, MO; Department of Clinical Neuroscience (L. Holmegaard, K.J., T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurology (J.J.-C., J. Roquer), Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona, Spain; KU Leuven-University of Leuven (R.L.), Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND); VIB, Vesalius Research Center, Laboratory of Neurobiology, University Hospitals Leuven, Department of Neurology, Belgium; School of Medicine and Public Health (C.L.), University of Newcastle; Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (C.W.M.), University of Florida, Gainesville; Department of Neurology (J. Meschia), Mayo Clinic, Jacksonville, FL; Centogene AG (A.R.), Rostock, Germany; Department of Neurology (S.R., R.S.), Clinical Division of Neurogeriatrics, Medical University Graz, Austria; Henry and Allison McCance Center for Brain Health (J. Rosand), Massachusetts General Hospital, Boston; Department of Neurology and Evelyn F. McKnight Brain Institute (T.R., R.L.S.), Miller School of Medicine, University of Miami, FL; Institute of Cardiovascular Research (P.S.), Royal Holloway University of London (ICR2UL), Egham, UK St Peter's and Ashford Hospitals, United Kingdom; Department of Neurology (A. Slowik), Jagiellonian University Medical College, Krakow, Poland; Department of Clinical Sciences Malmö (M.S.), Lund University; Department of Neurology, Skåne University Hospital, Lund and Malmö; Department of Laboratory Medicine (T.M.S., C.J.), Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Neurology (D.S.), Helsinki University Hospital and University of Helsinki, Finland; Stroke Division (V.T.), Florey Institute of Neuroscience and Mental Health and Department of Neurology, Austin Health, Heidelberg, Australia; Department of Radiology (A.V.), University of Cincinnati College of Medicine, OH; Department of Clinical Sciences Lund (J.W.), Radiology, Lund University; Department of Radiology, Neuroradiology, Skåne University Hospital, Lund, Sweden; Department of Neurology and Rehabilitation Medicine (D.W.), University of Cincinnati College of Medicine, OH; Department of Neurology (R.Z.), Geisinger, Danville, PA; Division of Endocrinology (P.M.), Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore; Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville; Department of Clinical Genetics and Genomics (C.J.), Sahlgrenska University Hospital, Gothenburg; Department of Neurology (A.G.L.), Skåne University Hospital, Lund; Department of Clinical Sciences Lund, Neurology, Lund University, Sweden; University of Technology Sydney (J. Maguire), Australia; Department of Biomedical Engineering (D.B.), McConnell Brain Imaging Centre, Montreal Neurological Institute, Faculty of Medicine, School of Computer Science, McGill University; and Mila-Quebec Artificial Intelligence Institute (D.B.), Montreal, Canada. abonkhoff@mgh.harvard.edu. 2. From the J. Philip Kistler Stroke Research Center (A.K.B., S.H., M.B., M.D.S., R.W.R., E.M.A., K.D., M.N., M.R.E., J. Rosand, N.S.R.), Massachusetts General Hospital, Harvard Medical School, Boston; Univ. Lille (M.B.), Inserm, CHU Lille, U1171-LilNCog (JPARC)-Lille Neurosciences & Cognition, France; Clinic for Neuroradiology (M.D.S.), University Hospital Bonn, Germany; Computer Science and Artificial Intelligence Lab (A. Dalca, P.G.), Massachusetts Institute of Technology, Boston; Athinoula A. Martinos Center for Biomedical Imaging (A. Dalca, B.L.H., S.J.T.M., E.M., J. Rosand, O.W.), Department of Radiology, Massachusetts General Hospital, Charlestown; Department of Neurology (A.-K.G.), University Medical Center Hamburg-Eppendorf, Germany; Hunter Medical Research Institute (J.A.), Newcastle; School of Medicine and Public Health, University of Newcastle, New South Wales, Australia; Department of Medicine (O.B.), Division of Neurology, University of British Columbia, Vancouver, Canada; Department of Neurology (J.W.C., S.K.), University of Maryland School of Medicine and Veterans Affairs Maryland Health Care System, Baltimore; School of Medical Sciences (A. Donatti, A. Sousa), University of Campinas (UNICAMP) and the Brazilian Institute of Neuroscience and Neurotechnology (BRAINN), Campinas, SP, Brazil; Department of Neurosurgery (C.G.), Geisinger, Danville, PA; Department of Neurosurgery (C.G.), Christian Doppler Clinic, Paracelsus Medical University, Salzburg, Austria; Department of Emergency Medicine (L. Heitsch), Washington University School of Medicine; Department of Neurology (L. Heitsch, C.-L.P.), Washington University School of Medicine & Barnes-Jewish Hospital, St. Louis, MO; Department of Clinical Neuroscience (L. Holmegaard, K.J., T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg; Department of Neurology, Sahlgrenska University Hospital, Gothenburg, Sweden; Department of Neurology (J.J.-C., J. Roquer), Neurovascular Research Group (NEUVAS), IMIM-Hospital del Mar (Institut Hospital del Mar d'Investigacions Mèdiques), Universitat Autonoma de Barcelona, Spain; KU Leuven-University of Leuven (R.L.), Department of Neurosciences, Experimental Neurology and Leuven Research Institute for Neuroscience and Disease (LIND); VIB, Vesalius Research Center, Laboratory of Neurobiology, University Hospitals Leuven, Department of Neurology, Belgium; School of Medicine and Public Health (C.L.), University of Newcastle; Department of Neurology, John Hunter Hospital, Newcastle, New South Wales, Australia; Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics (C.W.M.), University of Florida, Gainesville; Department of Neurology (J. Meschia), Mayo Clinic, Jacksonville, FL; Centogene AG (A.R.), Rostock, Germany; Department of Neurology (S.R., R.S.), Clinical Division of Neurogeriatrics, Medical University Graz, Austria; Henry and Allison McCance Center for Brain Health (J. Rosand), Massachusetts General Hospital, Boston; Department of Neurology and Evelyn F. McKnight Brain Institute (T.R., R.L.S.), Miller School of Medicine, University of Miami, FL; Institute of Cardiovascular Research (P.S.), Royal Holloway University of London (ICR2UL), Egham, UK St Peter's and Ashford Hospitals, United Kingdom; Department of Neurology (A. Slowik), Jagiellonian University Medical College, Krakow, Poland; Department of Clinical Sciences Malmö (M.S.), Lund University; Department of Neurology, Skåne University Hospital, Lund and Malmö; Department of Laboratory Medicine (T.M.S., C.J.), Institute of Biomedicine, the Sahlgrenska Academy, University of Gothenburg, Sweden; Department of Neurology (D.S.), Helsinki University Hospital and University of Helsinki, Finland; Stroke Division (V.T.), Florey Institute of Neuroscience and Mental Health and Department of Neurology, Austin Health, Heidelberg, Australia; Department of Radiology (A.V.), University of Cincinnati College of Medicine, OH; Department of Clinical Sciences Lund (J.W.), Radiology, Lund University; Department of Radiology, Neuroradiology, Skåne University Hospital, Lund, Sweden; Department of Neurology and Rehabilitation Medicine (D.W.), University of Cincinnati College of Medicine, OH; Department of Neurology (R.Z.), Geisinger, Danville, PA; Division of Endocrinology (P.M.), Diabetes and Nutrition, Department of Medicine, University of Maryland School of Medicine, Baltimore; Departments of Neurology and Public Health Sciences (B.B.W.), University of Virginia, Charlottesville; Department of Clinical Genetics and Genomics (C.J.), Sahlgrenska University Hospital, Gothenburg; Department of Neurology (A.G.L.), Skåne University Hospital, Lund; Department of Clinical Sciences Lund, Neurology, Lund University, Sweden; University of Technology Sydney (J. Maguire), Australia; Department of Biomedical Engineering (D.B.), McConnell Brain Imaging Centre, Montreal Neurological Institute, Faculty of Medicine, School of Computer Science, McGill University; and Mila-Quebec Artificial Intelligence Institute (D.B.), Montreal, Canada.
Abstract
BACKGROUND AND OBJECTIVES: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. METHODS: MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. RESULTS: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. DISCUSSION: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.
BACKGROUND AND OBJECTIVES: To examine whether high white matter hyperintensity (WMH) burden is associated with greater stroke severity and worse functional outcomes in lesion pattern-specific ways. METHODS: MR neuroimaging and NIH Stroke Scale data at index stroke and the modified Rankin Scale (mRS) score at 3-6 months after stroke were obtained from the MRI-Genetics Interface Exploration study of patients with acute ischemic stroke (AIS). Individual WMH volume was automatically derived from fluid-attenuated inversion recovery images. Stroke lesions were automatically segmented from diffusion-weighted imaging (DWI) images, parcellated into atlas-defined brain regions and further condensed to 10 lesion patterns via machine learning-based dimensionality reduction. Stroke lesion effects on AIS severity and unfavorable outcomes (mRS score >2) were modeled within purpose-built Bayesian linear and logistic regression frameworks. Interaction effects between stroke lesions and a high vs low WMH burden were integrated via hierarchical model structures. Models were adjusted for age, age2, sex, total DWI lesion and WMH volumes, and comorbidities. Data were split into derivation and validation cohorts. RESULTS: A total of 928 patients with AIS contributed to acute stroke severity analyses (age: 64.8 [14.5] years, 40% women) and 698 patients to long-term functional outcome analyses (age: 65.9 [14.7] years, 41% women). Stroke severity was mainly explained by lesions focused on bilateral subcortical and left hemispherically pronounced cortical regions across patients with both a high and low WMH burden. Lesions centered on left-hemispheric insular, opercular, and inferior frontal regions and lesions affecting right-hemispheric temporoparietal regions had more pronounced effects on stroke severity in case of high compared with low WMH burden. Unfavorable outcomes were predominantly explained by lesions in bilateral subcortical regions. In difference to the lesion location-specific WMH effects on stroke severity, higher WMH burden increased the odds of unfavorable outcomes independent of lesion location. DISCUSSION: Higher WMH burden may be associated with an increased stroke severity in case of stroke lesions involving left-hemispheric insular, opercular, and inferior frontal regions (potentially linked to language functions) and right-hemispheric temporoparietal regions (potentially linked to attention). Our findings suggest that patients with specific constellations of WMH burden and lesion locations may have greater benefits from acute recanalization treatments. Future clinical studies are warranted to systematically assess this assumption and guide more tailored treatment decisions.
Authors: Setsu Wakana; Hangyi Jiang; Lidia M Nagae-Poetscher; Peter C M van Zijl; Susumu Mori Journal: Radiology Date: 2003-11-26 Impact factor: 11.105
Authors: Robert W Regenhardt; Alvin S Das; Ryo Ohtomo; Eng H Lo; Cenk Ayata; Mahmut Edip Gurol Journal: J Stroke Cerebrovasc Dis Date: 2019-05-28 Impact factor: 2.136
Authors: Markus D Schirmer; Mark R Etherton Md PhD; Adrian V Dalca PhD; Anne-Katrin Giese Md; Lisa Cloonan MSc; Ona Wu PhD; Polina Golland PhD; Natalia S Rost Md Mph Faan Journal: J Stroke Cerebrovasc Dis Date: 2018-09-28 Impact factor: 2.136
Authors: Anna K Bonkhoff; Martin Bretzner; Sungmin Hong; Markus D Schirmer; Alexander Cohen; Robert W Regenhardt; Kathleen L Donahue; Marco J Nardin; Adrian V Dalca; Anne-Katrin Giese; Mark R Etherton; Brandon L Hancock; Steven J T Mocking; Elissa C McIntosh; John Attia; Oscar R Benavente; Stephen Bevan; John W Cole; Amanda Donatti; Christoph J Griessenauer; Laura Heitsch; Lukas Holmegaard; Katarina Jood; Jordi Jimenez-Conde; Steven J Kittner; Robin Lemmens; Christopher R Levi; Caitrin W McDonough; James F Meschia; Chia-Ling Phuah; Arndt Rolfs; Stefan Ropele; Jonathan Rosand; Jaume Roquer; Tatjana Rundek; Ralph L Sacco; Reinhold Schmidt; Pankaj Sharma; Agnieszka Slowik; Martin Söderholm; Alessandro Sousa; Tara M Stanne; Daniel Strbian; Turgut Tatlisumak; Vincent Thijs; Achala Vagal; Johan Wasselius; Daniel Woo; Ramin Zand; Patrick F McArdle; Bradford B Worrall; Christina Jern; Arne G Lindgren; Jane Maguire; Michael D Fox; Danilo Bzdok; Ona Wu; Natalia S Rost Journal: Brain Commun Date: 2022-02-02
Authors: Anna K Bonkhoff; Markus D Schirmer; Martin Bretzner; Sungmin Hong; Robert W Regenhardt; Mikael Brudfors; Kathleen L Donahue; Marco J Nardin; Adrian V Dalca; Anne-Katrin Giese; Mark R Etherton; Brandon L Hancock; Steven J T Mocking; Elissa C McIntosh; John Attia; Oscar R Benavente; Stephen Bevan; John W Cole; Amanda Donatti; Christoph J Griessenauer; Laura Heitsch; Lukas Holmegaard; Katarina Jood; Jordi Jimenez-Conde; Steven J Kittner; Robin Lemmens; Christopher R Levi; Caitrin W McDonough; James F Meschia; Chia-Ling Phuah; Arndt Rolfs; Stefan Ropele; Jonathan Rosand; Jaume Roquer; Tatjana Rundek; Ralph L Sacco; Reinhold Schmidt; Pankaj Sharma; Agnieszka Slowik; Martin Söderholm; Alessandro Sousa; Tara M Stanne; Daniel Strbian; Turgut Tatlisumak; Vincent Thijs; Achala Vagal; Johan Wasselius; Daniel Woo; Ramin Zand; Patrick F McArdle; Bradford B Worrall; Christina Jern; Arne G Lindgren; Jane Maguire; Danilo Bzdok; Ona Wu; Natalia S Rost Journal: Nat Commun Date: 2021-06-02 Impact factor: 14.919
Authors: Arne G Lindgren; Robynne G Braun; Jennifer Juhl Majersik; Philip Clatworthy; Shraddha Mainali; Colin P Derdeyn; Jane Maguire; Christina Jern; Jonathan Rosand; John W Cole; Jin-Moo Lee; Pooja Khatri; Paul Nyquist; Stéphanie Debette; Loo Keat Wei; Tatjana Rundek; Dana Leifer; Vincent Thijs; Robin Lemmens; Laura Heitsch; Kameshwar Prasad; Jordi Jimenez Conde; Martin Dichgans; Natalia S Rost; Steven C Cramer; Julie Bernhardt; Bradford B Worrall; Israel Fernandez-Cadenas Journal: Int J Stroke Date: 2021-04-26 Impact factor: 5.266
Authors: Anna K Bonkhoff; Teresa Ullberg; Martin Bretzner; Sungmin Hong; Markus D Schirmer; Robert W Regenhardt; Kathleen L Donahue; Marco J Nardin; Adrian V Dalca; Anne-Katrin Giese; Mark R Etherton; Brandon L Hancock; Steven J T Mocking; Elissa C McIntosh; John Attia; John W Cole; Amanda Donatti; Christoph J Griessenauer; Laura Heitsch; Lukas Holmegaard; Katarina Jood; Jordi Jimenez-Conde; Steven J Kittner; Robin Lemmens; Christopher R Levi; Caitrin W McDonough; James F Meschia; Chia-Ling Phuah; Stefan Ropele; Jonathan Rosand; Jaume Roquer; Tatjana Rundek; Ralph L Sacco; Reinhold Schmidt; Pankaj Sharma; Agnieszka Slowik; Alessandro Sousa; Tara M Stanne; Daniel Strbian; Turgut Tatlisumak; Vincent Thijs; Achala Vagal; Daniel Woo; Ramin Zand; Patrick F McArdle; Bradford B Worrall; Christina Jern; Arne G Lindgren; Jane Maguire; Ona Wu; Petrea Frid; Natalia S Rost; Johan Wasselius Journal: Front Neurosci Date: 2022-08-25 Impact factor: 5.152