Morphology-Preserving Holotomography: Quantitative Analysis of 3D Organoid Dynamics
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arXiv
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| Main Authors: | , , , , |
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| Format: | Preprint |
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2025
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| _version_ | 1866914221909868544 |
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| author | Oh, ChulMin Cho, Jimin Park, Juyeon Lee, Hoyeon Park, YongKeun |
| author_facet | Oh, ChulMin Cho, Jimin Park, Juyeon Lee, Hoyeon Park, YongKeun |
| contents | Organoids are three-dimensional (3D) in vitro models for studying tissue development, disease progression, and physiological responses. Holotomography (HT) enables long-term, label-free imaging of live organoids by reconstructing volumetric refractive-index (RI) maps, but quantitative analysis is limited by the missing-cone artifact, which introduces anisotropic resolution and axial distortion. Here, we present a quantitative analysis framework that addresses the missing-cone problem at the level of image representation rather than reconstruction. We introduce morphology-preserving holotomography (MP-HT), a torus-shaped spatial filtering strategy that emphasizes high-spatial-frequency RI texture while suppressing low-frequency components most susceptible to missing-cone-induced distortion. Based on MP-HT, we develop a 3D segmentation pipeline for robust separation of epithelial and luminal structures, together with a model-based RI quantification approach that incorporates the system point spread function to enable morphology-independent estimation of dry-mass density and total dry mass. We apply the framework to long-term imaging of live hepatic organoids undergoing expansion, collapse, and fusion. The results demonstrate consistent segmentation across diverse geometries and reveal coordinated epithelial-lumen remodeling, breakdown of morphometric homeostasis during collapse, and transient biophysical fluctuations during fusion. Overall, this work establishes a physically transparent and reproducible approach for quantitative, label-free analysis of organoid dynamics in three dimensions. |
| format | Preprint |
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arxiv_https___arxiv_org_abs_2512_22486 |
| institution | arXiv |
| publishDate | 2025 |
| record_format | arxiv |
| spellingShingle | Morphology-Preserving Holotomography: Quantitative Analysis of 3D Organoid Dynamics Oh, ChulMin Cho, Jimin Park, Juyeon Lee, Hoyeon Park, YongKeun Medical Physics Optics Organoids are three-dimensional (3D) in vitro models for studying tissue development, disease progression, and physiological responses. Holotomography (HT) enables long-term, label-free imaging of live organoids by reconstructing volumetric refractive-index (RI) maps, but quantitative analysis is limited by the missing-cone artifact, which introduces anisotropic resolution and axial distortion. Here, we present a quantitative analysis framework that addresses the missing-cone problem at the level of image representation rather than reconstruction. We introduce morphology-preserving holotomography (MP-HT), a torus-shaped spatial filtering strategy that emphasizes high-spatial-frequency RI texture while suppressing low-frequency components most susceptible to missing-cone-induced distortion. Based on MP-HT, we develop a 3D segmentation pipeline for robust separation of epithelial and luminal structures, together with a model-based RI quantification approach that incorporates the system point spread function to enable morphology-independent estimation of dry-mass density and total dry mass. We apply the framework to long-term imaging of live hepatic organoids undergoing expansion, collapse, and fusion. The results demonstrate consistent segmentation across diverse geometries and reveal coordinated epithelial-lumen remodeling, breakdown of morphometric homeostasis during collapse, and transient biophysical fluctuations during fusion. Overall, this work establishes a physically transparent and reproducible approach for quantitative, label-free analysis of organoid dynamics in three dimensions. |
| title | Morphology-Preserving Holotomography: Quantitative Analysis of 3D Organoid Dynamics |
| topic | Medical Physics Optics |
| url | https://arxiv.org/abs/2512.22486 |