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 and Otmar Schmid ()
Additional contact information
Lin Yang: Member of the German Center for Lung Research (DZL)
Qiongliang Liu: Member of the German Center for Lung Research (DZL)
Pramod Kumar: Member of the German Center for Lung Research (DZL)
Arunima Sengupta: Member of the German Center for Lung Research (DZL)
Ali Farnoud: Member of the German Center for Lung Research (DZL)
Ruolin Shen: Helmholtz Munich
Darya Trofimova: German Cancer Research Center (DKFZ)
Sebastian Ziegler: German Cancer Research Center (DKFZ)
Neda Davoudi: University of Zurich
Ali Doryab: Member of the German Center for Lung Research (DZL)
Ali Önder Yildirim: Member of the German Center for Lung Research (DZL)
Markus E. Diefenbacher: Member of the German Center for Lung Research (DZL)
Herbert B. Schiller: Member of the German Center for Lung Research (DZL)
Daniel Razansky: University of Zurich
Marie Piraud: Helmholtz Munich
Gerald Burgstaller: Member of the German Center for Lung Research (DZL)
Wolfgang G. Kreyling: Member of the German Center for Lung Research (DZL)
Fabian Isensee: German Cancer Research Center (DKFZ)
Markus Rehberg: Member of the German Center for Lung Research (DZL)
Tobias Stoeger: Member of the German Center for Lung Research (DZL)
Otmar Schmid: Member of the German Center for Lung Research (DZL)

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-54267-1

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