LungVis 1.0: an automatic AI-powered 3D imaging ecosystem unveils spatial profiling of nanoparticle delivery and acinar migration of lung macrophages

Lin Yang; Qiongliang Liu; Pramod Kumar; Arunima Sengupta; Ali Farnoud; Ruolin Shen; Darya Trofimova; Sebastian Ziegler; Neda Davoudi; Ali Doryab; Ali Önder Yildirim; Markus E. Diefenbacher; Herbert B. Schiller; Daniel Razansky; Marie Piraud; Gerald Burgstaller; Wolfgang G. Kreyling; Fabian Isensee; Markus Rehberg; Tobias Stoeger; Otmar Schmid

doi:10.1038/s41467-024-54267-1

Nature Communications (Nov 2024)

LungVis 1.0: an automatic AI-powered 3D imaging ecosystem unveils spatial profiling of nanoparticle delivery and acinar migration of lung macrophages

Lin Yang,
Qiongliang Liu,
Pramod Kumar,
Arunima Sengupta,
Ali Farnoud,
Ruolin Shen,
Darya Trofimova,
Sebastian Ziegler,
Neda Davoudi,
Ali Doryab,
Ali Önder Yildirim,
Markus E. Diefenbacher,
Herbert B. Schiller,
Daniel Razansky,
Marie Piraud,
Gerald Burgstaller,
Wolfgang G. Kreyling,
Fabian Isensee,
Markus Rehberg,
Tobias Stoeger,
Otmar Schmid

Affiliations

Lin Yang: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Qiongliang Liu: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Pramod Kumar: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Arunima Sengupta: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Ali Farnoud: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Ruolin Shen: Helmholtz AI, Helmholtz Munich
Darya Trofimova: Helmholtz Imaging, German Cancer Research Center (DKFZ)
Sebastian Ziegler: Helmholtz Imaging, German Cancer Research Center (DKFZ)
Neda Davoudi: Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich
Ali Doryab: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Ali Önder Yildirim: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Markus E. Diefenbacher: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Herbert B. Schiller: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Daniel Razansky: Institute of Pharmacology and Toxicology and Institute for Biomedical Engineering, Faculty of Medicine, University of Zurich
Marie Piraud: Helmholtz AI, Helmholtz Munich
Gerald Burgstaller: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Wolfgang G. Kreyling: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Fabian Isensee: Helmholtz Imaging, German Cancer Research Center (DKFZ)
Markus Rehberg: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Tobias Stoeger: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)
Otmar Schmid: Institute of Lung Health and Immunity (LHI), Helmholtz Munich, Comprehensive Pneumology Center (CPC-M), Member of the German Center for Lung Research (DZL)

DOI: https://doi.org/10.1038/s41467-024-54267-1
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 22

Abstract

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Abstract Targeted (nano-)drug delivery is essential for treating respiratory diseases, which are often confined to distinct lung regions. However, spatio-temporal profiling of drugs or nanoparticles (NPs) and their interactions with lung macrophages remains unresolved. Here, we present LungVis 1.0, an AI-powered imaging ecosystem that integrates light sheet fluorescence microscopy with deep learning-based image analysis pipelines to map NP deposition and dosage holistically and quantitatively across bronchial and alveolar (acinar) regions in murine lungs for widely-used bulk-liquid and aerosol-based delivery methods. We demonstrate that bulk-liquid delivery results in patchy NP distribution with elevated bronchial doses, whereas aerosols achieve uniform deposition reaching distal alveoli. Furthermore, we reveal that lung tissue-resident macrophages (TRMs) are dynamic, actively patrolling and redistributing NPs within alveoli, contesting the conventional paradigm of TRMs as static entities. LungVis 1.0 provides an advanced framework for exploring pulmonary delivery dynamics and deepening insights into TRM-mediated lung immunity.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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