Noninvasive whole-brain imaging of glymphatic dynamics
- NanChao Wang
- Xinyuan Yu
- Matthew Lowerison
- Qinzhe Li
- Aidan J. Canning
- Peibang He
- Lihong Dang
- Simone Degan
- Brian Mace
- Yirui Xu
- Rui Yao
- Jingting Li
- Tianhua Zhou
- Jinhuan Luo
- Bing-Ze Lin
- Denis A. Turner
- Xin Liu
- Dean Ta
- Jonathan Lovell
- Tuan Vo-Dinh
- Wuwei Feng
- Pengfei Song
- Wei Yang
- Junjie Yao
2026-06-17
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.