Intravital imaging of amyloid plaques in a transgenic mouse model using optical-resolution photoacoustic microscopy

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.

Figure 1

(Color online) Schematic of the optical-resolution photoacoustic microscope for amyloid plaque imaging. OR-PAM imaging and multiphoton imaging were performed through a cranial window preparation (inset).

Figure 2

(Color online) In vitro imaging of a Congo-red-stained brain section from a 10-month-old APP/PS1 mouse. (A) The entire hippocampus imaged using conventional fluorescence microscopy. (B) A region of interest selected from (A) (boxed area). (C) The same region of interest imaged by optical-sresolution photoacoustic microscopy for comparison. Arrows: plaques. Scale bar in (A) applies for (A–C).

Figure 3

(Color online) In vivo brain imaging of a Congo-red-injected 10-month-old APP/PS1 mouse through a cranial window. (A) The exposed cortical brain region imaged using conventional fluorescence microscopy through the cranial window. The region of interest marked by a red dashed box was imaged by (B) multiphoton microscopy, and optical-resolution photoacoustic microscopy at (C) 570 nm and (D) 523 nm, respectively. (E) The processed dual-contrast optical-resolution photoacoustic microscopic image, where amyloid plaques are colored green and blood vessels are colored red (volumetric visualization is available online as Media 1). Arrows: plaques. Scale bar in (B) applies for (B–E).