Nanchao Wang, X YU, Matthew R. Lowerison, Qinzhe Li, Aidan J. Canning, Peibang He, Lihong Dang, Simone Degan, Brian E. Mace, Yan Xu, Rui Yao, Jingting Li, Tianhua Zhou, Jinhuan Luo, Bing‐Ze Lin, Dennis A. Turner, Xin Liu, Dean Ta, Jonathan F. Lovell, Tuan Vo‐Dinh, Wuwei Feng, Pengfei Song, Wei Yang, Junjie Yao
Cerebrospinal fluid circulation through the glymphatic system plays a crucial role in removing metabolic waste from the central nervous system. However, the mechanism underlying the brain-wide glymphatic dynamics is not yet fully understood, in part due to the lack of glymphatic imaging technologies on deep brains. Here, we report a hybrid imaging technology that integrates three-dimensional photoacoustic tomography and ultrasound localization microscopy (3D-PAULM), enhanced by a photoacoustic dye with strong optical absorption in the second near-infrared window (NIR-II). 3D-PAULM allows for continuous, noninvasive, whole-brain imaging in mice through intact skull, providing superresolution mapping of the brain vasculature and highly sensitive tracing of the NIR-II dye in the glymphatic system. Using 3D-PAULM, we investigated the glymphatic function impaired by ischemic stroke, aging, and anesthesia. Our results provide insights into glymphatic transport under various physiological as well as pathological conditions and establish 3D-PAULM as a valuable tool for preclinical glymphatic research.