Dushan N. Wadduwage

Leonidas Zimianitis, Pasindu Thenahandi, Kai Buckhalter et al.

Tracking the dynamics of non-canonical biological systems in microscopy videos remains a persistent challenge. Both classical and learning-based trackers depend on expert-reviewed data to be evaluated and adapted, yet exhaustive manual annotation rarely scales to the videos where these tools are needed most. We developed RIPPLE (Refinement Interpolation Platform for Point Location Estimation), which recasts annotation as sparse correction: a user clicks a starting point, RIPPLE proposes a full trajectory, and the user intervenes only where the trajectory drifts. We tested RIPPLE on five challenging microscopy datasets from our laboratories, four from the transparent jellyfish Clytia hemisphaerica and one tracking landmarks on rapidly moving sperm. Across these, RIPPLE matched the quality of exhaustive manual annotation while reducing manual clicks by 3 to 25 times across datasets. RIPPLE thereby fills a missing layer between manual annotation and fully automated tracking, enabling immediate quantification of biological dynamics, method benchmarking, and the production of the gold-standard data needed to adapt future automated microscopy trackers.

Henry Arguello, Jorge Bacca, Hasindu Kariyawasam et al. · cmu

Computational optical imaging (COI) systems leverage optical coding elements (CE) in their setups to encode a high-dimensional scene in a single or multiple snapshots and decode it by using computational algorithms. The performance of COI systems highly depends on the design of its main components: the CE pattern and the computational method used to perform a given task. Conventional approaches rely on random patterns or analytical designs to set the distribution of the CE. However, the available data and algorithm capabilities of deep neural networks (DNNs) have opened a new horizon in CE data-driven designs that jointly consider the optical encoder and computational decoder. Specifically, by modeling the COI measurements through a fully differentiable image formation model that considers the physics-based propagation of light and its interaction with the CEs, the parameters that define the CE and the computational decoder can be optimized in an end-to-end (E2E) manner. Moreover, by optimizing just CEs in the same framework, inference tasks can be performed from pure optics. This work surveys the recent advances on CE data-driven design and provides guidelines on how to parametrize different optical elements to include them in the E2E framework. Since the E2E framework can handle different inference applications by changing the loss function and the DNN, we present low-level tasks such as spectral imaging reconstruction or high-level tasks such as pose estimation with privacy preserving enhanced by using optimal task-based optical architectures. Finally, we illustrate classification and 3D object recognition applications performed at the speed of the light using all-optics DNN.

Udith Haputhanthri, Kithmini Herath, Ramith Hettiarachchi et al. · cmu

With applications ranging from metabolomics to histopathology, quantitative phase microscopy (QPM) is a powerful label-free imaging modality. Despite significant advances in fast multiplexed imaging sensors and deep-learning-based inverse solvers, the throughput of QPM is currently limited by the speed of electronic hardware. Complementarily, to improve throughput further, here we propose to acquire images in a compressed form such that more information can be transferred beyond the existing electronic hardware bottleneck. To this end, we present a learnable optical compression-decompression framework that learns content-specific features. The proposed differentiable quantitative phase microscopy ($\partial μ$) first uses learnable optical feature extractors as image compressors. The intensity representation produced by these networks is then captured by the imaging sensor. Finally, a reconstruction network running on electronic hardware decompresses the QPM images. In numerical experiments, the proposed system achieves compression of $\times$ 64 while maintaining the SSIM of $\sim 0.90$ and PSNR of $\sim 30$ dB on cells. The results demonstrated by our experiments open up a new pathway for achieving end-to-end optimized (i.e., optics and electronic) compact QPM systems that may provide unprecedented throughput improvements.

Kithmini Herath, Udith Haputhanthri, Ramith Hettiarachchi et al. · cmu

Since the late 16th century, scientists have continuously innovated and developed new microscope types for various applications. Creating a new architecture from the ground up requires substantial scientific expertise and creativity, often spanning years or even decades. In this study, we propose an alternative approach called "Differentiable Microscopy," which introduces a top-down design paradigm for optical microscopes. Using all-optical phase retrieval as an illustrative example, we demonstrate the effectiveness of data-driven microscopy design through $\partialμ$. Furthermore, we conduct comprehensive comparisons with competing methods, showcasing the consistent superiority of our learned designs across multiple datasets, including biological samples. To substantiate our ideas, we experimentally validate the functionality of one of the learned designs, providing a proof of concept. The proposed differentiable microscopy framework supplements the creative process of designing new optical systems and would perhaps lead to unconventional but better optical designs.

Navodini Wijethilake, Mithunjha Anandakumar, Cheng Zheng et al.

Limited throughput is a key challenge in in-vivo deep-tissue imaging using nonlinear optical microscopy. Point scanning multiphoton microscopy, the current gold standard, is slow especially compared to the wide-field imaging modalities used for optically cleared or thin specimens. We recently introduced 'De-scattering with Excitation Patterning or DEEP', as a widefield alternative to point-scanning geometries. Using patterned multiphoton excitation, DEEP encodes spatial information inside tissue before scattering. However, to de-scatter at typical depths, hundreds of such patterned excitations are needed. In this work, we present DEEP$^2$, a deep learning based model, that can de-scatter images from just tens of patterned excitations instead of hundreds. Consequently, we improve DEEP's throughput by almost an order of magnitude. We demonstrate our method in multiple numerical and physical experiments including in-vivo cortical vasculature imaging up to four scattering lengths deep, in alive mice.

Nirhoshan Sivaroopan, Chamuditha Jayanga, Chalani Ekanayake et al.

Deep neural network models can learn clinically relevant features from millions of histopathology images. However generating high-quality annotations to train such models for each hospital, each cancer type, and each diagnostic task is prohibitively laborious. On the other hand, terabytes of training data -- while lacking reliable annotations -- are readily available in the public domain in some cases. In this work, we explore how these large datasets can be consciously utilized to pre-train deep networks to encode informative representations. We then fine-tune our pre-trained models on a fraction of annotated training data to perform specific downstream tasks. We show that our approach can reach the state-of-the-art (SOTA) for patch-level classification with only 1-10% randomly selected annotations compared to other SOTA approaches. Moreover, we propose an uncertainty-aware loss function, to quantify the model confidence during inference. Quantified uncertainty helps experts select the best instances to label for further training. Our uncertainty-aware labeling reaches the SOTA with significantly fewer annotations compared to random labeling. Last, we demonstrate how our pre-trained encoders can surpass current SOTA for whole-slide image classification with weak supervision. Our work lays the foundation for data and task-agnostic pre-trained deep networks with quantified uncertainty.

Pamuditha Somarathne, Tharindu Wickremasinghe, Amashi Niwarthana et al.

Compressive sensing (CS) reconstructs images from sub-Nyquist measurements by solving a sparsity-regularized inverse problem. Traditional CS solvers use iterative optimizers with hand crafted sparsifiers, while early data-driven methods directly learn an inverse mapping from the low-dimensional measurement space to the original image space. The latter outperforms the former, but is restrictive to a pre-defined measurement domain. More recent, deep unrolling methods combine traditional proximal gradient methods and data-driven approaches to iteratively refine an image approximation. To achieve higher accuracy, it has also been suggested to learn both the sampling matrix, and the choice of measurement vectors adaptively. Contrary to the current trend, in this work we hypothesize that a general inverse mapping from a random set of compressed measurements to the image domain exists for a given measurement basis, and can be learned. Such a model is single-shot, non-restrictive and does not parametrize the sampling process. To this end, we propose MOSAIC, a novel compressive sensing framework to reconstruct images given any random selection of measurements, sampled using a fixed basis. Motivated by the uneven distribution of information across measurements, MOSAIC incorporates an embedding technique to efficiently apply attention mechanisms on an encoded sequence of measurements, while dispensing the need to use unrolled deep networks. A range of experiments validate our proposed architecture as a promising alternative for existing CS reconstruction methods, by achieving the state-of-the-art for metrics of reconstruction accuracy on standard datasets.

Nirhoshan Sivaroopan, Chamuditha Jayanga Galappaththige, Chalani Ekanayake et al.

Machine-learning-assisted cancer subtyping is a promising avenue in digital pathology. Cancer subtyping models, however, require careful training using expert annotations so that they can be inferred with a degree of known certainty (or uncertainty). To this end, we introduce the concept of uncertainty awareness into a self-supervised contrastive learning model. This is achieved by computing an evidence vector at every epoch, which assesses the model's confidence in its predictions. The derived uncertainty score is then utilized as a metric to selectively label the most crucial images that require further annotation, thus iteratively refining the training process. With just 1-10% of strategically selected annotations, we attain state-of-the-art performance in cancer subtyping on benchmark datasets. Our method not only strategically guides the annotation process to minimize the need for extensive labeled datasets, but also improves the precision and efficiency of classifications. This development is particularly beneficial in settings where the availability of labeled data is limited, offering a promising direction for future research and application in digital pathology.

Yasith Jayawardana, Dineth Jayakody, Sampath Jayarathna et al.

Deep neural networks (DNNs) have the potential to power many biomedical workflows, but training them on truly representative, IID datasets is often infeasible. Most models instead rely on biased or incomplete data, making them prone to out-of-distribution (OoD) inputs that closely resemble in-distribution samples. Such near-OoD cases are harder to detect than standard OOD benchmarks and can cause unreliable, even catastrophic, predictions. Biomedical assays, however, offer a unique opportunity: they often generate multiple correlated measurements per specimen through biological or technical replicates. Exploiting this insight, we introduce Homogeneous OoD (HOoD), a novel OoD detection framework for correlated data. HOoD projects groups of correlated measurements through a trained model and uses permutation-based hypothesis tests to compare them with known subpopulations. Each test yields an interpretable p-value, quantifying how well a group matches a subpopulation. By aggregating these p-values, HOoD reliably identifies OoD groups. In evaluations, HOoD consistently outperforms point-wise and ensemble-based OoD detectors, demonstrating its promise for robust real-world deployment.