Photoacoustic and fluorescence dual-modality imaging of cerebral biomarkers in Alzheimer's disease rodent model.

Significance: Alzheimer's disease (AD) is a predominant form of dementia that can lead to a decline in the quality of life and mortality. The understanding of the pathological changes requires monitoring of multiple cerebral biomarkers simultaneously with high resolution. Photoacoustic microscopy resolves single capillaries, allowing investigations into the most affected types of vessels. Combined with confocal fluorescence microscopy, the relationship between plaque deposition and small vessel pathology could be better understood.

Aim: We aim to introduce a dual-modality imaging system combining photoacoustic microscopy (PAM) and confocal fluorescence microscopy (CFM) to provide a comprehensive view of both cerebral cortical vessels and amyloid- $\beta$ ( $A\beta$ ) plaque in AD mouse model in vivo and to identify the pathological changes of these two biomarkers.

Approach: We developed a dual-modality imaging system to image both cerebral vessel structure and $A\beta$ plaque on groups of mice with different ages and phenotypes. Vessel imaging is enabled by PAM, whereas $A\beta$ plaque is imaged by CFM with the aid of fluorescent dye.

Results: The small vessel density in the AD group was significantly lower than in the control group, whereas the $A\beta$ plaque density in the AD group was not only higher but also increased with age.

Conclusions: This dual-modality system provides a powerful platform for biomarker monitoring of AD expressing multi-dimensional pathological changes.