Papers for
microscopy imaging teams
Papers whose findings have a practical use for this group, as judged from the abstract. Open a paper to read what it means in practice.
Microscope software reconstructs missing live cell images over time
CellSplat4D: PSF-Aware 4D Gaussian Splatting for Sparse Robotic Live-Cell Imaging
Abstract: A robotic microscope watching living cells cannot afford to look as often as it would like. Every volume it acquires costs photons the specimen does not get back, and time owed to other wells. What such a platform exists to produce is a record of individual cells through time: which cell is which from one volume to the next, and which cell divided into which two. Sampling sparsely breaks that record exactly where it matters, and the fault lies in the acquisition schedule rather than in the analysis software. We fill the gaps by reconstructing them, fitting a 4D Gaussian model to whatever volumes the hardware could afford. The model is a cloud of light-emitting blobs, each carrying a position, a shape and a lifetime. Being continuous in time, it renders any missing volume on demand, decoupling how often the robot analyses from how often it can afford to look. The microscope's point-spread function is measured from the data rather than inherited from acquisition metadata or left to the optimizer, because metadata inflates it and the optimizer cannot recover it at all: a wider blur around a smaller blob fits the images equally well. Each blob's lifetime is stored in frames rather than as a fraction of the recording, so that it denotes a fixed duration on any sequence. Unmeasured timesteps are supervised at coarse scale by a 3D U-Net that predicts the intermediate volume directly and estimates no motion field, since a dividing cell becomes two and no motion describes that. On two Cell Tracking Challenge sequences, a C. elegans embryo and a Chinese Hamster Ovarian (CHO), with fidelity scored per cell nucleus, our reconstruction holds the highest nucleus fidelity at every distance from an acquired frame, has the flattest decay across the gap, and best recovers focal planes it was never shown with graceful degradation across the gap.
Digital toolkit generates realistic images for better microscopy denoising
A Digital Simulation Toolkit for Physics-Based Generation of Realistic Experimental Scanning Tunneling Microscopy Images
Abstract: Scanning Tunneling Microscopy (STM) is a widely used tool for characterizing surfaces of materials at the atomic scale, playing a crucial role in discoveries across condensed matter physics and materials science. Despite its extreme spatial resolution, STM is one of the most sensitive microscopy techniques and is highly prone to noise. While existing unsupervised denoising methods are very cheap to train, these are primarily focused on removing the noise with minimal recovery of key physical information. While supervised methods can offer superior performance, the major bottleneck is that a large amount of paired clean-noisy experimental images is required which are impractical to obtain. Thus, we developed a low-cost physics-driven digital toolkit to rapidly generate large volume of realistic STM images. Firstly, we simulate clean images from a chosen material system. Then, with prior knowledge of the physical characteristics of the artifacts and noise present in STM experiments, we formulate several artifact-noise functions such as Gaussian electronic noise, 1/f flicker noise, scan-line noise, background tilt and mechanical drift. These physically informed noise components are then added to the simulated clean images to generate realistic STM images. We demonstrated the capability of the proposed digital toolkit to generate AI-ready data for denoising images of the (111) surfaces of copper and lead, while preserving atoms, defects, and electron waves. We also validated the quality of the downstream image analysis of learning electron wave patterns induced by quantum interference from Cu(111) images. Results show that the supervised models trained on digitally generated AI-ready data can more effectively denoise and learn electron wave patterns on Cu(111) images than benchmarked unsupervised approaches, indicating that the proposed toolkit facilitate scientific discovery.
Image recovery improves using neural priors with Fourier phase data
Image Reconstruction from Phase with Untrained Neural Priors
Abstract: Fourier phase encodes important spatial image structure, but recovering an image without measured spectral magnitude requires additional constraints and leaves absolute intensity ambiguous. We propose a projection-based two-stage framework that combines Fourier-phase and spatial-support constraints with an image-specific neural prior. The first stage alternates constraint enforcement with regularized neural-prior updates, while the second performs phase/support refinement alone with guaranteed convergence. We evaluate two neural-prior implementations on the same 77 microscopy images and compare them with a constraint-only baseline. After 500 final refinement passes, the best-performing variant achieves 31.41 dB pooled PSNR, 35.75 dB mean PSNR, and 0.9531 mean SSIM, improving pooled PSNR by 1.51~dB and reducing pooled MSE by 29.3% relative to the baseline. The results demonstrate the benefit of combining neural guidance with explicit constraint refinement at the evaluated iteration budget, while showing that lower phase residual alone does not guarantee greater reconstruction accuracy.
Neural networks trained to improve dense emitter location accuracy
Training Neural Networks to Approach the Optimum Bayes Estimator in Dense Multi-Emitter Localization
Abstract: We train neural networks on synthesized frames to approach the optimum Bayes estimator for dense emitter localization. The result justifies the future work on training neural networks to achieve high-throughput large-FOV super spatiotemporal resolution SMLM.
Training data quality matters more than loss type in image denoising
Noise2Noise Revisited: Training Pair Distributions Dominate Loss Choice in Self-Supervised Denoising
Abstract: Noise2Noise (N2N) trains denoisers on pairs of independently corrupted observations, eliminating clean references. We stress-test two natural conjectures about why the L1 loss outperforms L2 here. First, the hypothesis that the L1 loss confers robustness via parameter sparsity confuses the loss with Lasso regularization: an explicit Lasso penalty produces the predicted sparsity yet fails to reproduce L1's cross-noise behavior, while L1- and L2-trained weight distributions are indistinguishable. Second, the population optima of the two losses coincide exactly for symmetric signal posteriors and nearly so for concentrated ones. Measured differences are therefore dominated by optimization dynamics (bounded-influence gradients), which we probe with gradient statistics and contaminated-target training. On Kodak24 with five synthetic noise families, the L1 loss holds a statistically significant edge over L2, below 1 dB PSNR, holding across three seeds on 13 of the 14 noise columns. On real camera noise the loss is not the decisive variable in distribution: on official SIDD validation blocks, synthetic-Gaussian-trained N2N models gain only 0.8 to 3.7 dB over the noisy input regardless of loss, while retraining on SIDD's own noisy pairs, never reading ground truth, gains 9.4 to 11.0 dB, far ahead of BM3D. All metrics are on raw network outputs, and the study makes no leaderboard claim. The training pair distribution, not the loss, carries the inductive bias. That design rule applies wherever clean references are unobtainable, from microscopy to industrial inspection sensors.
Physics aware AI improves identification of 2D quantum materials
QuPAINT: Physics-Aware Multimodal Reasoning for Quantum Material Characterization
Abstract: Characterizing two-dimensional (2D) quantum materials by optical microscopy requires localizing exfoliated flakes and determining their layer thickness from subtle optical contrast and interference color to select suitable flakes for device fabrication. However, models face synthetic-to-real domain shifts and variation across materials, substrates, laboratories, and imaging conditions. We present QuPAINT, a physics-aware multimodal framework for transferable quantum flake characterization. The Synthetic Materials Framework (Synthia) generates diverse synthetic microscopy images while preserving layer-dependent optical behavior. Using these images, we construct QMat-Instruct, a multimodal instruction dataset with image-specific reasoning traces generated from verified annotations and constrained to observable optical cues. QuPAINT integrates these signals through Physics-Informed Attention (PIA), which injects substrate-relative optical priors into the visual representation to support grounded multimodal reasoning. For evaluation, we introduce QF-Bench, to our knowledge, the largest real-world benchmark for this problem, spanning diverse microscopy and substrate conditions. Using its verified annotations, we study counting, visual grounding, reasoning quality, confidence calibration, and transfer to an unseen material. QuPAINT-8B substantially outperforms prior methods and establishes state-of-the-art performance for both general and monolayer flake detection. Additional experiments show that image-grounded supervision improves strict spatial grounding and confidence calibration while preserving robust general flake detection on the unseen material.