Noninvasive whole-brain imaging of glymphatic dynamics
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.
Authors
- Jonathan F. Lovell (ORCID: https://orcid.org/0000-0002-9052-884X)
- Junjie Yao (ORCID: https://orcid.org/0000-0002-2381-706X)
- Dean Ta (ORCID: https://orcid.org/0000-0001-6651-4491)
- Aidan J. Canning (ORCID: https://orcid.org/0000-0002-8001-6496)
- Wei Yang (ORCID: https://orcid.org/0000-0001-5719-4393)
- Yan Xu (ORCID: https://orcid.org/0000-0002-3319-4695)
- Matthew R. Lowerison (ORCID: https://orcid.org/0000-0002-1125-4554)
- X YU
- Brian E. Mace (ORCID: https://orcid.org/0000-0002-5478-6227)
- Xin Liu (ORCID: https://orcid.org/0000-0002-4783-9810)
- Dennis A. Turner (ORCID: https://orcid.org/0000-0001-7118-0764)
- Tuan Vo‐Dinh (ORCID: https://orcid.org/0000-0003-3701-3326)
- Peibang He (ORCID: https://orcid.org/0000-0002-6931-7722)
- Qinzhe Li
- Pengfei Song (ORCID: https://orcid.org/0000-0002-9103-6345)
- Nanchao Wang (ORCID: https://orcid.org/0000-0002-5037-4145)
- Wuwei Feng (ORCID: https://orcid.org/0000-0001-6230-4905)
- Simone Degan (ORCID: https://orcid.org/0000-0001-5417-1196)
- Lihong Dang
- Jingting Li (ORCID: https://orcid.org/0000-0001-8742-8488)
- Bing‐Ze Lin (ORCID: https://orcid.org/0000-0001-7323-4236)
- Tianhua Zhou (ORCID: https://orcid.org/0000-0002-3584-0785)
- Rui Yao (ORCID: https://orcid.org/0009-0000-3710-7387)
- Jinhuan Luo
Institutions
- Duke University (US)
- Fudan University (CN)
- Duke Medical Center (US)
- Duke University Hospital (US)
- University at Buffalo, State University of New York (US)
Publication Details
- Journal
- Science Advances
- Published
- 2026-06-17
- DOI
- https://doi.org/10.1126/sciadv.aee4926
- Primary Topic
- Cerebrospinal fluid and hydrocephalus
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- American Heart Association
- North Carolina Biotechnology Center
- National Institutes of Health