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Research ArticleBRAIN

MR Imaging Features of Amyloid-Related Imaging Abnormalities

J. Barakos, R. Sperling, S. Salloway, C. Jack, A. Gass, J.B. Fiebach, D. Tampieri, D. Melançon, Y. Miaux, G. Rippon, R. Black, Y. Lu, H.R. Brashear, H.M. Arrighi, K.A. Morris and M. Grundman
American Journal of Neuroradiology April 2013, DOI: https://doi.org/10.3174/ajnr.A3500
J. Barakos
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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R. Sperling
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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S. Salloway
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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C. Jack
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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A. Gass
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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J.B. Fiebach
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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D. Tampieri
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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D. Melançon
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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Y. Miaux
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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G. Rippon
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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R. Black
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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Y. Lu
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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H.R. Brashear
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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H.M. Arrighi
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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K.A. Morris
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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M. Grundman
From the California Pacific Medical Center (J.B.), San Francisco, California; Synarc (J.B., Y.M.), Newark, California; Brigham and Women’s Hospital (R.S.), Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Warren Alpert Medical School of Brown University (S.S.), Providence, Rhode Island; Mayo Clinic (C.J.), Rochester, Minnesota; University Hospital Mannheim (A.G.), University of Heidelberg, Mannheim, Germany; Center for Stroke Research (J.B.F.), Charité, Berlin, Germany; NeuroRx Research (D.T., D.M.), Montreal, Quebec, Canada; Pfizer Inc (G.R., R.B.), Collegeville, Pennsylvania; Janssen Alzheimer Immunotherapy Research & Development, LLC (H.R.B., H.M.A., K.A.M., M.G.), South San Francisco, California; and Global Partners Inc (M.G.), Cambridge, Massachusetts.
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Abstract

BACKGROUND AND PURPOSE: AD is one of the few leading causes of death without a disease-modifying drug; however, hopeful agents are in various phases of development. MR imaging abnormalities, collectively referred to as amyloid-related imaging abnormalities, have been reported for several agents that target cerebral Aβ burden. ARIA includes ARIA-E, parenchymal or sulcal hyperintensities on FLAIR indicative of parenchymal edema or sulcal effusions, and ARIA-H, hypointense regions on gradient recalled-echo/T2* indicative of hemosiderin deposition. This report describes imaging characteristics of ARIA-E and ARIA-H identified during studies of bapineuzumab, a humanized monoclonal antibody against Aβ.

MATERIALS AND METHODS: Two neuroradiologists with knowledge of imaging changes reflective of ARIA reviewed MR imaging scans from 210 bapineuzumab-treated patients derived from 3 phase 2 studies. Each central reader interpreted the studies independently, and discrepancies were resolved by consensus. The inter-reader κ was 0.76, with 94% agreement between neuroradiologists regarding the presence or absence of ARIA-E in individual patients.

RESULTS: Thirty-six patients were identified with incident ARIA-E (17.1%, 36/210) and 26 with incident ARIA-H (12.4%, 26/210); of those with incident ARIA-H, 24 had incident microhemorrhages and 2 had incident large superficial hemosiderin deposits.

CONCLUSIONS: In 49% of cases of ARIA-E, there was the associated appearance of ARIA-H. In treated patients without ARIA-E, the risk for incident blood products was 4%. This association between ARIA-E and ARIA-H may suggest a common pathophysiologic mechanism. Familiarity with ARIA should permit radiologists and clinicians to recognize and communicate ARIA findings more reliably for optimal patient management.

Abbreviations

Aβ
amyloid-β
AD
Alzheimer disease
ARIA
amyloid-related imaging abnormalities
ARIA-E
amyloid-related imaging abnormalities associated with edema or effusion/exudate
ARIA-H
amyloid-related imaging abnormalities associated with hemosiderin deposition
  • © 2013 American Society of Neuroradiology
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Cite this article
J. Barakos, R. Sperling, S. Salloway, C. Jack, A. Gass, J.B. Fiebach, D. Tampieri, D. Melançon, Y. Miaux, G. Rippon, R. Black, Y. Lu, H.R. Brashear, H.M. Arrighi, K.A. Morris, M. Grundman
MR Imaging Features of Amyloid-Related Imaging Abnormalities
American Journal of Neuroradiology Apr 2013, DOI: 10.3174/ajnr.A3500

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MR Imaging Features of Amyloid-Related Imaging Abnormalities
J. Barakos, R. Sperling, S. Salloway, C. Jack, A. Gass, J.B. Fiebach, D. Tampieri, D. Melançon, Y. Miaux, G. Rippon, R. Black, Y. Lu, H.R. Brashear, H.M. Arrighi, K.A. Morris, M. Grundman
American Journal of Neuroradiology Apr 2013, DOI: 10.3174/ajnr.A3500
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