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Updated: Jan 30, 2026
Assessing Cortical Cerebral Microinfarcts on High Resolution MR Images
Published on: November 20, 2015
Histopathology of diffusion imaging abnormalities in cerebral amyloid angiopathy
Susanne J van Veluw1, Yael D Reijmer2, Andre J van der Kouwe2
1From the J. Philip Kistler Stroke Research Center, Department of Neurology (S.J.v.V., Y.D.R., A.C., G.A.R., A.V., S.M.G.), and Neuropathology Service, C.S. Kubik Laboratory for Neuropathology (M.P.F.), Massachusetts General Hospital and Harvard Medical School, Boston; MassGeneral Institute for Neurodegenerative Disease (S.J.v.V., B.J.B., M.P.F.), Charlestown Navy Yard, MA; Department of Neurology, Brain Center Rudolf Magnus (Y.D.R.), and Image Sciences Institute (A.L.), University Medical Center Utrecht, Utrecht University, the Netherlands; and Athinoula A. Martinos Center for Biomedical Imaging (A.J.v.d.K.), Department of Radiology, Massachusetts General Hospital, Charlestown. svanveluw@mgh.harvard.edu.
Objective:
We sought to determine the underlying mechanism for altered white matter diffusion tensor imaging (DTI) measures at the histopathologic level in patients with cerebral amyloid angiopathy (CAA).
Methods:
Formalin-fixed intact hemispheres from 9 CAA cases and 2 elderly controls were scanned at 3-tesla MRI, including a diffusion-weighted sequence. DTI measures (i.e., fractional anisotropy [FA] and mean diffusivity [MD]) and histopathology measures were obtained from 2 tracts: the anterior thalamic radiation and inferior longitudinal fasciculus.
Results:
FA was reduced in both tracts and MD was increased in cases with CAA compared to controls. Regional FA was significantly correlated with tissue rarefaction, myelin density, axonal density, and white matter microinfarcts. MD correlated significantly with tissue rarefaction, myelin density, and white matter microinfarcts, but not axonal density. FA and MD did not correlate with oligodendrocytes, astrocytes, or gliosis. Multivariate analysis revealed that tissue rarefaction (β = -0.32 ± 0.12, p = 0.009) and axonal density (β = 0.25 ± 0.12, p = 0.04) were both independently associated with FA, whereas myelin density was independently associated with MD (β = -0.32 ± 0.12, p = 0.013). Finally, we found an association between increased MD in the frontal white matter and CAA severity in the frontal cortex (p = 0.035).
Conclusions:
These results suggest that overall tissue loss, and in particular axonal and myelin loss, are major components underlying CAA-related alterations in DTI properties observed in living patients. The findings allow for a more mechanistic interpretation of DTI parameters in small vessel disease and for mechanism-based selection of candidate treatments to prevent vascular cognitive impairment.
Insights
Cerebral amyloid angiopathy (CAA) alters white matter diffusion tensor imaging (DTI) measures due to tissue loss, including axons and myelin. This research clarifies DTI changes in CAA, aiding treatment development for vascular cognitive impairment.
Area of Science:
- Neurology
- Neuroimaging
- Pathology
Background:
- Cerebral amyloid angiopathy (CAA) is a common cause of small vessel disease, often leading to cognitive impairment.
- Diffusion tensor imaging (DTI) measures white matter integrity, but its histopathologic underpinnings in CAA are not fully understood.
Purpose of the Study:
- To elucidate the histopathologic mechanisms behind altered white matter DTI measures in patients with cerebral amyloid angiopathy (CAA).
Main Methods:
- Formalin-fixed brain hemispheres from 9 CAA cases and 2 controls underwent 3-tesla MRI with diffusion-weighted imaging.
- DTI measures (fractional anisotropy [FA] and mean diffusivity [MD]) and histopathology were analyzed in the anterior thalamic radiation and inferior longitudinal fasciculus.
Main Results:
- CAA cases showed reduced FA and increased MD compared to controls.
- FA correlated with tissue rarefaction, myelin, and microinfarcts; MD correlated with tissue rarefaction, myelin, and microinfarcts.
- Tissue rarefaction and axonal density independently associated with FA, while myelin density associated with MD. Increased MD linked to frontal cortex CAA severity.
Conclusions:
- Tissue loss, particularly axonal and myelin loss, underlies CAA-related DTI alterations in vivo.
- Findings provide mechanistic insights into DTI parameters in small vessel disease.
- Enables mechanism-based treatment selection for preventing vascular cognitive impairment.
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