Multi-parametric longitudinal imaging of cerebral biomarkers in a rodent model of Alzheimer’s disease

This study introduces a method for longitudinally monitoring Alzheimer’s disease (AD)-related biomarkers in a rodent model utilizing a dual-modality imaging system combining photoacoustic microscopy (PAM) and confocal fluorescence microscopy (CFM). Using a cranial window transparent to both light and ultrasound, we examined cerebral vasculature, blood flow speed, oxygen saturation (sO 2 ), and amyloid-β (Aβ) deposition with single capillary resolution in genetically modified AD mice longitudinally over three months. Empowered by the high-resolution multimodal imaging, the analysis showed consistent changes of small vessel density decrease and Aβ deposition increase in AD mice compared to the control group. Meanwhile, a decrease in sO 2 was observed in AD group near the end of the observation period, highlighting the potential importance of functional imaging of hemodynamics that PAM facilitates. This multimodal system, with its longitudinal imaging capability, could provide valuable insight into the temporal dynamics and interrelationships of multiple biomarkers in neurodegenerative diseases.