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Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Intravital imaging of amyloid plaques in a transgenic mouse model using optical-resolution photoacoustic microscopy
Song Hu1, Ping Yan, Konstantin Maslov
1Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, Missouri, USA.
Abstract:
We report optical-resolution photoacoustic microscopy (OR-PAM) for in vivo imaging of amyloid plaques in an Alzheimer's disease mouse model. Validation using conventional fluorescence microscopy and multiphoton microscopy shows that OR-PAM has sufficient sensitivity and spatial resolution to identify amyloid plaques in living brains. In addition, with dual-wavelength OR-PAM, the three-dimensional morphology of amyloid plaques and the surrounding microvasculature are imaged simultaneously through a cranial window without angiographic contrast agents. OR-PAM, capable of providing both exogenous molecular contrast and endogenous hemoglobin contrast, has the potential to serve as a new technology for in vivo microscopic observations of cerebral plaque deposits.
Insights
Optical-resolution photoacoustic microscopy (OR-PAM) enables in vivo imaging of Alzheimer's disease amyloid plaques in mice. This technique visualizes plaque morphology and vasculature without contrast agents, offering a new tool for studying brain deposits.
Area of Science:
- Biomedical Optics
- Neuroimaging
- Molecular Imaging
Background:
- Alzheimer's disease is characterized by amyloid plaque accumulation in the brain.
- In vivo imaging of these plaques is crucial for understanding disease progression and testing therapeutics.
- Current imaging techniques have limitations in resolution, sensitivity, or require contrast agents.
Purpose of the Study:
- To demonstrate the capability of optical-resolution photoacoustic microscopy (OR-PAM) for in vivo imaging of amyloid plaques.
- To validate OR-PAM's performance against established microscopy techniques.
- To explore the potential of dual-wavelength OR-PAM for simultaneous imaging of plaques and vasculature.
Main Methods:
- Optical-resolution photoacoustic microscopy (OR-PAM) was employed for in vivo imaging in an Alzheimer's disease mouse model.
- Conventional fluorescence microscopy and multiphoton microscopy were used for validation.
- Dual-wavelength OR-PAM was utilized to assess simultaneous imaging capabilities.
Main Results:
- OR-PAM demonstrated sufficient sensitivity and spatial resolution for identifying amyloid plaques in living mouse brains.
- Validation confirmed OR-PAM's effectiveness compared to fluorescence and multiphoton microscopy.
- Dual-wavelength OR-PAM successfully imaged the 3D morphology of amyloid plaques and surrounding microvasculature concurrently without contrast agents.
Conclusions:
- OR-PAM is a viable technology for in vivo microscopic observation of cerebral amyloid deposits.
- The technique offers both exogenous molecular contrast and endogenous hemoglobin contrast.
- OR-PAM has significant potential for advancing Alzheimer's disease research and diagnostics.
