System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring

Abstract Three-dimensional subcellular imaging is essential for biomedical research, but the diffraction limit of optical microscopy compromises axial resolution, hindering accurate three-dimensional structural analysis. This challenge is particularly pronounced in label-free imaging of thick, heter...

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Main Authors: Jiashu Han, Kunzan Liu, Keith B. Isaacson, Kristina Monakhova, Linda G. Griffith, Sixian You
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56078-4
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author Jiashu Han
Kunzan Liu
Keith B. Isaacson
Kristina Monakhova
Linda G. Griffith
Sixian You
author_facet Jiashu Han
Kunzan Liu
Keith B. Isaacson
Kristina Monakhova
Linda G. Griffith
Sixian You
author_sort Jiashu Han
collection DOAJ
description Abstract Three-dimensional subcellular imaging is essential for biomedical research, but the diffraction limit of optical microscopy compromises axial resolution, hindering accurate three-dimensional structural analysis. This challenge is particularly pronounced in label-free imaging of thick, heterogeneous tissues, where assumptions about data distribution (e.g. sparsity, label-specific distribution, and lateral-axial similarity) and system priors (e.g. independent and identically distributed noise and linear shift-invariant point-spread functions are often invalid. Here, we introduce SSAI-3D, a weakly physics-informed, domain-shift-resistant framework for robust isotropic three-dimensional imaging. SSAI-3D enables robust axial deblurring by generating a diverse, noise-resilient, sample-informed training dataset and sparsely fine-tuning a large pre-trained blind deblurring network. SSAI-3D is applied to label-free nonlinear imaging of living organoids, freshly excised human endometrium tissue, and mouse whisker pads, and further validated in publicly available ground-truth-paired experimental datasets of three-dimensional heterogeneous biological tissues with unknown blurring and noise across different microscopy systems.
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institution Kabale University
issn 2041-1723
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publishDate 2025-01-01
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spelling doaj-art-9e02dfa8e0f8429c88f3a9f5be7781cc2025-01-19T12:31:42ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-025-56078-4System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurringJiashu Han0Kunzan Liu1Keith B. Isaacson2Kristina Monakhova3Linda G. Griffith4Sixian You5Research Laboratory of Electronics, MITResearch Laboratory of Electronics, MITNewton-Wellesley Hospital, Mass General BrighamResearch Laboratory of Electronics, MITDepartment of Biological Engineering, MITResearch Laboratory of Electronics, MITAbstract Three-dimensional subcellular imaging is essential for biomedical research, but the diffraction limit of optical microscopy compromises axial resolution, hindering accurate three-dimensional structural analysis. This challenge is particularly pronounced in label-free imaging of thick, heterogeneous tissues, where assumptions about data distribution (e.g. sparsity, label-specific distribution, and lateral-axial similarity) and system priors (e.g. independent and identically distributed noise and linear shift-invariant point-spread functions are often invalid. Here, we introduce SSAI-3D, a weakly physics-informed, domain-shift-resistant framework for robust isotropic three-dimensional imaging. SSAI-3D enables robust axial deblurring by generating a diverse, noise-resilient, sample-informed training dataset and sparsely fine-tuning a large pre-trained blind deblurring network. SSAI-3D is applied to label-free nonlinear imaging of living organoids, freshly excised human endometrium tissue, and mouse whisker pads, and further validated in publicly available ground-truth-paired experimental datasets of three-dimensional heterogeneous biological tissues with unknown blurring and noise across different microscopy systems.https://doi.org/10.1038/s41467-025-56078-4
spellingShingle Jiashu Han
Kunzan Liu
Keith B. Isaacson
Kristina Monakhova
Linda G. Griffith
Sixian You
System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring
Nature Communications
title System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring
title_full System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring
title_fullStr System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring
title_full_unstemmed System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring
title_short System- and sample-agnostic isotropic three-dimensional microscopy by weakly physics-informed, domain-shift-resistant axial deblurring
title_sort system and sample agnostic isotropic three dimensional microscopy by weakly physics informed domain shift resistant axial deblurring
url https://doi.org/10.1038/s41467-025-56078-4
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