Feature-driven whole-tissue imaging with subcellular resolution

Jinlong Lin¹, Zach Marin², Xiaoding Wang¹, Hazel M Borges¹, Qionghua Shen¹, Pierre-Emmanuel Y N'Guetta³, Xuemei Luo⁴, Baylee A Porter⁵, Yuanyuan Xue⁶, Md Torikul Islam⁶, Tai Ngo¹, Doreen Idonije¹, Seweryn Gałecki⁷, Arin B Aurora⁸, Hu Zhao⁹, Suzanne D Conzen⁵, Sean J Morrison¹⁰, Shuang Liang⁴, Zhenyu Zhong⁴, Lori L O'Brien³, Kevin M Dean¹¹

Affiliations

¹ Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
² Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Max Perutz Labs, Department of Structural and Computational Biology, University of Vienna, Vienna, VI 1030, Austria.
³ Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁵ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁶ Children's Medical Center Research Institute at University of Texas Southwestern, Dallas, TX 75390, USA.
⁷ Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland.
⁸ Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁹ Chinese Institute for Brain Research, Beijing 102206, China.
¹⁰ Children's Medical Center Research Institute at University of Texas Southwestern, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
¹¹ Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: kevin.dean@utsouthwestern.edu.

PMID: 40902591
DOI: 10.1016/j.crmeth.2025.101148

Feature-driven whole-tissue imaging with subcellular resolution

Jinlong Lin et al. Cell Rep Methods. 2025.

. 2025 Sep 15;5(9):101148.

doi: 10.1016/j.crmeth.2025.101148. Epub 2025 Sep 2.

Authors

Affiliations

¹ Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
² Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Max Perutz Labs, Department of Structural and Computational Biology, University of Vienna, Vienna, VI 1030, Austria.
³ Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Department of Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁵ Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁶ Children's Medical Center Research Institute at University of Texas Southwestern, Dallas, TX 75390, USA.
⁷ Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Department of Systems Biology and Engineering, Silesian University of Technology, Akademicka 16, 44-100 Gliwice, Poland.
⁸ Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
⁹ Chinese Institute for Brain Research, Beijing 102206, China.
¹⁰ Children's Medical Center Research Institute at University of Texas Southwestern, Dallas, TX 75390, USA; Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
¹¹ Lyda Hill Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA; Cecil H. and Ida Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Electronic address: kevin.dean@utsouthwestern.edu.

PMID: 40902591
DOI: 10.1016/j.crmeth.2025.101148

Abstract

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.

Keywords: CP: Imaging; LSFM; cancer; development; feature-driven cleared tissue imaging; multiscale ASLM; neuroscience.

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Conflict of interest statement

Declaration of interests K.M.D. is a founder of Discovery Imaging Systems, LLC, has a patent covering ASLM, and has consultancy agreements with 3i, Inc (Denver, CO, USA).

Update of

Feature-Driven Whole-Tissue Imaging with Subcellular Resolution.
Lin J, Marin Z, Wang X, Borges HM, N'Guetta PY, Luo X, Porter BA, Xue Y, Islam MT, Ngo T, Aurora AB, Zhao H, Conzen SD, Morrison SJ, Liang S, Zhong Z, O'Brien LL, Dean KM. Lin J, et al. bioRxiv [Preprint]. 2025 Jan 26:2025.01.23.634600. doi: 10.1101/2025.01.23.634600. bioRxiv. 2025. Update in: Cell Rep Methods. 2025 Sep 15;5(9):101148. doi: 10.1016/j.crmeth.2025.101148. PMID: 39896507 Free PMC article. Updated. Preprint.

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Feature-driven whole-tissue imaging with subcellular resolution

Affiliations

Feature-driven whole-tissue imaging with subcellular resolution

Authors

Affiliations

Abstract

Conflict of interest statement

Update of

MeSH terms

Grants and funding

LinkOut - more resources

Miscellaneous