We investigate volumetric reconstruction for compressive sensing light-sheet microscopy (CS-LSM), where fast volumetric imaging is achieved by encoding multiple axial planes into each camera exposure. To recover the underlying volume from highly multiplexed measurements, we propose a plug-and-play (PnP) framework that flexibly incorporates any user-specified denoiser into the reconstruction process. Building on a slice-based formulation, we further introduce an axial-coupled model that exploits correlations between adjacent slices to improve volumetric continuity. For efficient computation, we derive a Woodbury-based update for the data-consistency step in both the slice-based and axial-coupled formulations, and employ a Gauss-Seidel sweep for the denoising step in the axial-coupled model. Under a weakly convex regularization assumption, we establish subsequential convergence of the proposed algorithm. Experiments on synthetic and real zebrafish-heart data demonstrate that the proposed framework successfully recovers cellular structures from compressed measurements, and provide practical insights into the comparative performance of commonly used denoisers within the PnP framework under the CS-LSM setup.
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.
This work introduces Structured 3D-SVD as a practical framework for the reconstruction, compression, and analysis of biological volumetric data. Inspired by the logic of matrix singular value decomposition (SVD), the proposed approach represents third-order volumetric data in the spatial domain and supports progressive reconstruction through ordered quasi-singular coeffients. The experimental evaluation was carried out on two biological volumetric datasets: one full-volume scan of a fish and another of a brain. The results show that Structured 3D-SVD achieves reconstruction quality close to that of Tucker decomposition while requiring shorter computation times and outperforms canonical polyadic decomposition (CPD) in both accuracy and runtime. In addition, a progressive reconstruction analysis shows that relatively low truncation levels are sufficient to preserve the main volumetric structures, while higher truncation levels lead to more detailed reconstructions.
Laser line-scanning microscopy enables fast volumetric imaging but produces anisotropic lateral resolution. Orthogonal line scans provide complementary directional information that can recover near-isotropic resolution, yet existing deep-learning methods require a separate model for each optical configuration. We present a unified, resolution-conditioned fusion framework based on Rank Enhanced Linear Attention (RELA). Feature-wise Linear Modulation (FiLM) conditions the network continuously on the resolving-power ratio, enabling one model to adapt across slit widths. We further introduce Adaptive RELA, which replaces fixed-kernel rank enhancement with ratio-conditioned multi-scale depthwise convolutions and uses a learnable attention temperature to adjust selectivity with degradation severity. Training data spanning multiple slit configurations are generated using a physics-grounded separable point-spread-function model verified against measured optical data at 48.3 dB accuracy. The resulting model achieves 34-40 dB PSNR across configurations, whereas unconditioned multi-slit training collapses to 24.3 dB and per-slit specialists lose 4-9 dB outside their training setting. It also generalizes smoothly to unseen intermediate configurations without interpolation artifacts. Ablations show that FiLM resolves configuration ambiguity, global linear attention captures long-range directional correspondences, and adaptive temperature yields an additional 2 dB in the challenging near-isotropic regime, where complementary signals are weak.