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Main Authors: Scheinfeld, Adina, Zhang, Haotan, Mu, Shang, van Herten, Rudolf L. M., Stoffl, Lucas, Erturk, Ali, Wu, Zhuhao, Paetzold, Johannes C.
Format: Preprint
Published: 2026
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Online Access:https://arxiv.org/abs/2605.26026
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author Scheinfeld, Adina
Zhang, Haotan
Mu, Shang
van Herten, Rudolf L. M.
Stoffl, Lucas
Erturk, Ali
Wu, Zhuhao
Paetzold, Johannes C.
author_facet Scheinfeld, Adina
Zhang, Haotan
Mu, Shang
van Herten, Rudolf L. M.
Stoffl, Lucas
Erturk, Ali
Wu, Zhuhao
Paetzold, Johannes C.
contents Light sheet fluorescence microscopy (LSM) enables high-resolution, three-dimensional (3D) imaging of biological specimens, providing rich volumetric data for studying cellular organization, pathology, and vascular networks. However, the size, dimensionality, and annotation burden of LSM data make supervised deep learning approaches costly and difficult to scale. Additionally, despite the abundance of unannotated LSM volumes, foundation models for this modality remain underexplored due to computational challenges and the complexity of volumetric representation learning. In this work, we introduce a 3D foundation model for LSM data, pretrained on a large curated collection of 3D images spanning multiple organisms, stains, and imaging protocols. We learn transferable volumetric representations by jointly optimizing for masked reconstruction and image-text alignment. The pretrained backbone drastically reduces the annotation burden, enabling efficient, few-shot adaptation for varied downstream tasks. We evaluate this approach on downstream segmentation, classification, and deblurring. Our results demonstrate consistent improvements over baselines, (1) when measured using standard evaluation metrics and (2) when rigorously assessed by domain experts. This highlights the potential of foundation model pretraining to reduce annotation requirements while improving performance across diverse LSM analysis tasks. Pretrained model weights and code for pretraining and finetuning are publicly available: https://github.com/AdinaScheinfeld/lsm_fm_public_repo.git.
format Preprint
id arxiv_https___arxiv_org_abs_2605_26026
institution arXiv
publishDate 2026
record_format arxiv
spellingShingle A Multimodal 3D Foundation Model for Light Sheet Fluorescence Microscopy Enables Few-Shot Segmentation, Classification, and Deblurring
Scheinfeld, Adina
Zhang, Haotan
Mu, Shang
van Herten, Rudolf L. M.
Stoffl, Lucas
Erturk, Ali
Wu, Zhuhao
Paetzold, Johannes C.
Computer Vision and Pattern Recognition
Artificial Intelligence
Machine Learning
Light sheet fluorescence microscopy (LSM) enables high-resolution, three-dimensional (3D) imaging of biological specimens, providing rich volumetric data for studying cellular organization, pathology, and vascular networks. However, the size, dimensionality, and annotation burden of LSM data make supervised deep learning approaches costly and difficult to scale. Additionally, despite the abundance of unannotated LSM volumes, foundation models for this modality remain underexplored due to computational challenges and the complexity of volumetric representation learning. In this work, we introduce a 3D foundation model for LSM data, pretrained on a large curated collection of 3D images spanning multiple organisms, stains, and imaging protocols. We learn transferable volumetric representations by jointly optimizing for masked reconstruction and image-text alignment. The pretrained backbone drastically reduces the annotation burden, enabling efficient, few-shot adaptation for varied downstream tasks. We evaluate this approach on downstream segmentation, classification, and deblurring. Our results demonstrate consistent improvements over baselines, (1) when measured using standard evaluation metrics and (2) when rigorously assessed by domain experts. This highlights the potential of foundation model pretraining to reduce annotation requirements while improving performance across diverse LSM analysis tasks. Pretrained model weights and code for pretraining and finetuning are publicly available: https://github.com/AdinaScheinfeld/lsm_fm_public_repo.git.
title A Multimodal 3D Foundation Model for Light Sheet Fluorescence Microscopy Enables Few-Shot Segmentation, Classification, and Deblurring
topic Computer Vision and Pattern Recognition
Artificial Intelligence
Machine Learning
url https://arxiv.org/abs/2605.26026