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Updated: Mar 25, 2026
Longitudinal In Vivo Imaging of the Cerebrovasculature: Relevance to CNS Diseases
Published on: December 6, 2016
Visualization of microbleeds with optical histology in mouse model of cerebral amyloid angiopathy
Patrick Lo1, Christian Crouzet1, Vitaly Vasilevko2
1Beckman Laser Institute and Medical Clinic, University of California, Irvine, 1002 Health Sciences Road East, Irvine, CA 92612, USA; Department of Biomedical Engineering, University of California, Irvine, 3120 Natural Sciences II, Irvine, CA 92697, USA.
Abstract:
Cerebral amyloid angiopathy (CAA) is a neurovascular disease that is strongly associated with an increase in the number and size of spontaneous microbleeds. Conventional methods of magnetic resonance imaging for detection of microbleeds, and positron emission tomography with Pittsburgh Compound B imaging for amyloid deposits, can separately demonstrate the presence of microbleeds and CAA in affected brains in vivo; however, there still is a critical need for strong evidence that shows involvement of CAA in microbleed formation. Here, we show in a Tg2576 mouse model of Alzheimer's disease, that the combination of histochemical staining and an optical clearing method called optical histology, enables simultaneous, co-registered three-dimensional visualization of cerebral microvasculature, microbleeds, and amyloid deposits. Our data suggest that microbleeds are localized within the brain regions affected by vascular amyloid deposits. All observed microhemorrhages (n=39) were in close proximity (0 to 144 μm) with vessels affected by CAA. Our data suggest that the predominant type of CAA-related microbleed is associated with leaky or ruptured hemorrhagic microvasculature. The proposed methodological and instrumental approach will allow future study of the relationship between CAA and microbleeds during disease development and in response to treatment strategies.
Insights
Cerebral amyloid angiopathy (CAA) is linked to brain microbleeds. This study used optical histology in a mouse model to visualize CAA and microbleeds together, showing microbleeds occur near amyloid deposits in cerebral vessels.
Area of Science:
- Neuroscience
- Pathology
- Biomedical Imaging
Background:
- Cerebral amyloid angiopathy (CAA) is a neurovascular disorder associated with increased microbleeds.
- Current imaging techniques can detect microbleeds and CAA separately but lack direct evidence linking them.
- A need exists to demonstrate the direct involvement of CAA in microbleed pathogenesis.
Purpose of the Study:
- To investigate the spatial relationship between cerebral microbleeds and vascular amyloid deposits in a mouse model.
- To develop and apply a novel imaging method for simultaneous visualization of microvasculature, microbleeds, and amyloid.
Main Methods:
- Utilized a Tg2576 mouse model of Alzheimer's disease.
- Combined histochemical staining with optical clearing (optical histology) for 3D visualization.
- Achieved simultaneous, co-registered imaging of cerebral microvasculature, microbleeds, and amyloid deposits.
Main Results:
- Demonstrated that microbleeds are localized within brain regions affected by vascular amyloid deposits.
- Found all observed microhemorrhages (n=39) were in close proximity (0-144 μm) to CAA-affected vessels.
- Indicated that CAA-related microbleeds predominantly stem from leaky or ruptured hemorrhagic microvasculature.
Conclusions:
- The developed optical histology method enables simultaneous 3D visualization of CAA and microbleeds.
- Data strongly suggest a direct link between vascular amyloid deposition and microbleed formation.
- This approach offers a powerful tool for future research on CAA-related microhemorrhages and therapeutic strategies.
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