Feature-driven whole-tissue imaging with subcellular resolution
Existing microscopy approaches are often unable to identify and contextualize rare but biologically meaningful events due to limitations associated with simultaneously achieving both high-resolution imaging and a cm-scale field of view. Here, we present multiscale cleared tissue axially swept light-sheet microscopy (MCT-ASLM), a platform combining cm-scale imaging with targeted high-resolution interrogation of intact tissues in human-guided or autonomous modes. Capable of capturing fields of view up to 21 mm at micron-scale resolution, MCT-ASLM can seamlessly transition to a targeted imaging mode with an isotropic resolution that approaches ∼300 nm. This versatility enables detailed studies of hierarchical organization and spatially complex processes, including mapping neuronal circuits in rat brains, visualizing glomerular innervation in mouse kidneys, and examining metastatic tumor microenvironments. By bridging subcellular- to tissue-level scales, MCT-ASLM offers a powerful method for unraveling how local events contribute to global biological phenomena.
Authors
- Suzanne Daniela Conzen (ORCID: https://orcid.org/0000-0003-1750-5868)
- Md Torikul Islam (ORCID: https://orcid.org/0000-0001-8263-0628)
- Arin B. Aurora (ORCID: https://orcid.org/0009-0009-1909-256X)
- Zach Marin (ORCID: https://orcid.org/0000-0001-5341-9911)
- Seweryn Gałecki (ORCID: https://orcid.org/0000-0002-7020-0804)
- Qionghua Shen (ORCID: https://orcid.org/0000-0002-2808-4408)
- Baylee A. Porter (ORCID: https://orcid.org/0000-0002-9503-6537)
- Hu Zhao (ORCID: https://orcid.org/0000-0002-2961-0086)
- Shuang Liang (ORCID: https://orcid.org/0000-0001-6869-6049)
- Sean J. Morrison (ORCID: https://orcid.org/0000-0003-1587-8329)
- Lori L. O’Brien (ORCID: https://orcid.org/0000-0002-0741-181X)
- Yuanyuan Xue
- Tai Ngo
- Pierre-Emmanuel N'Guetta (ORCID: https://orcid.org/0000-0001-9163-855X)
- Kevin M. Dean (ORCID: https://orcid.org/0000-0003-0839-2320)
- Jinlong Lin
- Xiaoding Wang (ORCID: https://orcid.org/0000-0003-2333-2270)
- Zhenyu Zhong (ORCID: https://orcid.org/0000-0003-1379-6178)
- Xuemei Luo
- Hazel M. Borges (ORCID: https://orcid.org/0009-0006-5834-5310)
- Doreen Idonije
Institutions
- University of North Carolina at Chapel Hill (US)
- Southwestern Medical Center (US)
- Chinese Institute for Brain Research (CN)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- Cell Reports Methods
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.crmeth.2025.101148
- Citations
- 1
- Primary Topic
- Advanced Fluorescence Microscopy Techniques
- Type
- article
- Field-Weighted Citation Impact
- 1.63
Funders
- American Heart Association
- Cancer Prevention and Research Institute of Texas
- Lyda Hill Philanthropies
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke