Acta Neuropathologica

, Volume 119, Issue 3, pp 291–302 | Cite as

Correlation of hypointensities in susceptibility-weighted images to tissue histology in dementia patients with cerebral amyloid angiopathy: a postmortem MRI study

  • Matthew Schrag
  • Grant McAuley
  • Justine Pomakian
  • Arshad Jiffry
  • Spencer Tung
  • Claudius Mueller
  • Harry V. Vinters
  • E. Mark Haacke
  • Barbara Holshouser
  • Daniel Kido
  • Wolff M. KirschEmail author
Original Paper


Neuroimaging with iron-sensitive MR sequences [gradient echo T2* and susceptibility-weighted imaging (SWI)] identifies small signal voids that are suspected brain microbleeds. Though the clinical significance of these lesions remains uncertain, their distribution and prevalence correlates with cerebral amyloid angiopathy (CAA), hypertension, smoking, and cognitive deficits. Investigation of the pathologies that produce signal voids is necessary to properly interpret these imaging findings. We conducted a systematic correlation of SWI-identified hypointensities to tissue pathology in postmortem brains with Alzheimer’s disease (AD) and varying degrees of CAA. Autopsied brains from eight AD patients, six of which showed advanced CAA, were imaged at 3T; foci corresponding to hypointensities were identified and studied histologically. A variety of lesions was detected; the most common lesions were acute microhemorrhage, hemosiderin residua of old hemorrhages, and small lacunes ringed by hemosiderin. In lesions where the bleeding vessel could be identified, β-amyloid immunohistochemistry confirmed the presence of β-amyloid in the vessel wall. Significant cellular apoptosis was noted in the perifocal region of recent bleeds along with heme oxygenase 1 activity and late complement activation. Acutely extravasated blood and hemosiderin were noted to migrate through enlarged Virchow–Robin spaces propagating an inflammatory reaction along the local microvasculature; a mechanism that may contribute to the formation of lacunar infarcts. Correlation of imaging findings to tissue pathology in our cases indicates that a variety of CAA-related pathologies produce MR-identified signal voids and further supports the use of SWI as a biomarker for this disease.


Alzheimer’s disease Cerebral amyloid angiopathy Microbleeds Microinfarcts Susceptibility-weighted imaging Blooming effect Complement C6 



Gradient echo T2*


Susceptibility-weighted imaging


Magnetic resonance


Brain microbleed


Cerebral amyloid angiopathy


Alzheimer’s disease


Heme oxygenase 1



This research was funded by the National Institutes of Health (AG20948). Harry V. Vinters is supported in part by P01 AG12435, P50 AG16570 and the Daljit S. and Elaine Sarkaria Chair in Diagnostic Medicine. E. Mark Haacke is a consultant to Siemens Corporation. None of the other authors have real or potential conflicts of interest related to this work. We thank Zachary Taylor who was an undergraduate summer researcher in our lab, as well as Cindy Dickson, April Dickson and Jackie Knecht for administrative assistance and for editing the manuscript.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Matthew Schrag
    • 1
  • Grant McAuley
    • 1
  • Justine Pomakian
    • 2
    • 3
  • Arshad Jiffry
    • 1
  • Spencer Tung
    • 2
    • 3
  • Claudius Mueller
    • 1
    • 4
  • Harry V. Vinters
    • 2
    • 3
  • E. Mark Haacke
    • 5
    • 6
    • 7
  • Barbara Holshouser
    • 5
  • Daniel Kido
    • 5
  • Wolff M. Kirsch
    • 1
    Email author
  1. 1.Neurosurgery Center for Research, Training and EducationLoma Linda UniversityLoma LindaUSA
  2. 2.Department of Pathology and Laboratory Medicine, David Geffen School of MedicineUniversity of California Los AngelesLos AngelesUSA
  3. 3.Department of Neurology, David Geffen School of MedicineUniversity of California Los AngelesLos AngelesUSA
  4. 4.Center for Applied Proteomics and Molecular MedicineGeorge Mason UniversityManassasUSA
  5. 5.The Magnetic Resonance Imaging Institute for Biomedical ResearchDetroitUSA
  6. 6.Department of RadiologyLoma Linda University School of MedicineLoma LindaUSA
  7. 7.Department of RadiologyWayne State UniversityDetroitUSA

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