Homogeneous-resolution photoacoustic microscopy for ultrawide field-of-view neurovascular imaging in Alzheimer's disease.

Neurovascular imaging is essential for investigating neurodegenerative diseases. However, the existing neurovascular imaging technology suffers from a trade-off between a field of view (FOV) and resolution in the whole brain, resulting in an inhomogeneous resolution and lack of information. Here, homogeneous-resolution arched-scanning photoacoustic microscopy (AS-PAM), which has an ultrawide FOV to cover the entire mouse cerebral cortex, was developed. Imaging of the neurovasculature was performed with a homogenous resolution of 6.9 µm from the superior sagittal sinus to the middle cerebral artery and caudal rhinal vein in an FOV of 12 × 12 mm. Moreover, using AS-PAM, vascular features of the meninges and cortex were quantified in early Alzheimer's disease (AD) and wild-type (WT) mice. The results demonstrated high sensitivity to the pathological progression of AD on tortuosity and branch index. The high-fidelity imaging capability in large FOV enables AS-PAM to be a promising tool for precise brain neurovascular visualization and quantification.