Daily Papers

Segmenting cells and tracking their motion over time is a common task in biomedical applications. However, predicting accurate instance-wise segmentation and cell motions from microscopy imagery remains a challenging task. Using microstructured environments for analyzing single cells in a constant flow of media adds additional complexity. While large-scale labeled microscopy datasets are available, we are not aware of any large-scale dataset, including both cells and microstructures. In this paper, we introduce the trapped yeast cell (TYC) dataset, a novel dataset for understanding instance-level semantics and motions of cells in microstructures. We release 105 dense annotated high-resolution brightfield microscopy images, including about 19k instance masks. We also release 261 curated video clips composed of 1293 high-resolution microscopy images to facilitate unsupervised understanding of cell motions and morphology. TYC offers ten times more instance annotations than the previously largest dataset, including cells and microstructures. Our effort also exceeds previous attempts in terms of microstructure variability, resolution, complexity, and capturing device (microscopy) variability. We facilitate a unified comparison on our novel dataset by introducing a standardized evaluation strategy. TYC and evaluation code are publicly available under CC BY 4.0 license.

Cell tracking is a subject of active research gathering great interest in medicine and biology. Positron emission tomography (PET) is well suited for tracking radio-labeled cells in vivo due to its exceptional sensitivity and whole-body capability. For validation, ground-truth data are desirable that realistically mimic the flow of cells in a clinical situation. This study develops a workflow (CeFloPS) for simulating moving radio-labeled cells in a human phantom. From the XCAT phantom, the blood vessels are reduced to nodal networks along which cells can move and distribute to organs and tissues. The movement is directed by the blood flow, which is calculated in each node using the Hagen-Pooiseuille equation and Kirchhoff's laws assuming laminar flow. Organs are voxelized and movement of cells from artery entry to vein exit is generated via a biased 3D random walk. The probabilities of cells moving or remaining in tissues are derived from rate constants of tracer kinetic-based compartment modeling. PET listmode data is generated using the Monte-Carlo simulation framework GATE based on the definition of a large-body PET scanner with cell paths as moving radioactive sources and the XCAT phantom providing attenuation data. From the flow simulation of 100,000 cells, 100 sample cells were further processed by GATE and listmode data was reconstructed into images for comparison. As demonstrated by comparisons of simulated and reconstructed cell distributions, CeFloPS is capable of simulating cell behavior in whole-body PET. It achieves this simulation in a way that is anatomically and physiologically reasonable, thereby providing valuable data for the development and validation of cell tracking algorithms.

We propose Beam Tree Recursive Cell (BT-Cell) - a backpropagation-friendly framework to extend Recursive Neural Networks (RvNNs) with beam search for latent structure induction. We further extend this framework by proposing a relaxation of the hard top-k operators in beam search for better propagation of gradient signals. We evaluate our proposed models in different out-of-distribution splits in both synthetic and realistic data. Our experiments show that BTCell achieves near-perfect performance on several challenging structure-sensitive synthetic tasks like ListOps and logical inference while maintaining comparable performance in realistic data against other RvNN-based models. Additionally, we identify a previously unknown failure case for neural models in generalization to unseen number of arguments in ListOps. The code is available at: https://github.com/JRC1995/BeamTreeRecursiveCells.

In this paper, we describe a design of a mixed signal circuit for a binary neuron (a.k.a perceptron, threshold logic gate) and a methodology for automatically embedding such cells in ASICs. The binary neuron, referred to as an FTL (flash threshold logic) uses floating gate or flash transistors whose threshold voltages serve as a proxy for the weights of the neuron. Algorithms for mapping the weights to the flash transistor threshold voltages are presented. The threshold voltages are determined to maximize both the robustness of the cell and its speed. The performance, power, and area of a single FTL cell are shown to be significantly smaller (79.4%), consume less power (61.6%), and operate faster (40.3%) compared to conventional CMOS logic equivalents. Also included are the architecture and the algorithms to program the flash devices of an FTL. The FTL cells are implemented as standard cells, and are designed to allow commercial synthesis and P&R tools to automatically use them in synthesis of ASICs. Substantial reductions in area and power without sacrificing performance are demonstrated on several ASIC benchmarks by the automatic embedding of FTL cells. The paper also demonstrates how FTL cells can be used for fixing timing errors after fabrication.

Robotic systems operating in unstructured environments require the ability to switch between compliant and rigid states to perform diverse tasks such as adaptive grasping, high-force manipulation, shape holding, and navigation in constrained spaces, among others. However, many existing variable stiffness solutions rely on complex actuation schemes, continuous input power, or monolithic designs, limiting their modularity and scalability. This paper presents the Programmable Locking Cell (PLC)-a modular, tendon-driven unit that achieves discrete stiffness modulation through mechanically interlocked joints actuated by cable tension. Each unit transitions between compliant and firm states via structural engagement, and the assembled system exhibits high stiffness variation-up to 950% per unit-without susceptibility to damage under high payload in the firm state. Multiple PLC units can be assembled into reconfigurable robotic structures with spatially programmable stiffness. We validate the design through two functional prototypes: (1) a variable-stiffness gripper capable of adaptive grasping, firm holding, and in-hand manipulation; and (2) a pipe-traversing robot composed of serial PLC units that achieves shape adaptability and stiffness control in confined environments. These results demonstrate the PLC as a scalable, structure-centric mechanism for programmable stiffness and motion, enabling robotic systems with reconfigurable morphology and task-adaptive interaction.

Cell migration in vivo is often guided by chemical signals. Such chemotaxis, such as performed by immune cells migrating to a wound site, is complicated by the complex geometry inside living tissues. In this study, we extend our theoretical model of branched-cell migration on a network by introducing chemokine sources to explore the cellular response. The model predicts a speed-accuracy tradeoff, whereby slow cells are significantly more accurate and able to follow efficiently a weak chemoattractant signal. We then compare the model's predictions with experimental observations of neutrophils migrating to the site of laser-inflicted wound in a zebrafish larva fin, and migrating in-vitro inside a regular lattice of pillars. We find that the model captures the details of the sub-cellular response to the chemokine gradient, as well as the large-scale migration response. This comparison suggests that the neutrophils behave as fast cells, compromising their chemotaxis accuracy, which explains the functionality of these immune cells.

We introduce Latent Meaning Cells, a deep latent variable model which learns contextualized representations of words by combining local lexical context and metadata. Metadata can refer to granular context, such as section type, or to more global context, such as unique document ids. Reliance on metadata for contextualized representation learning is apropos in the clinical domain where text is semi-structured and expresses high variation in topics. We evaluate the LMC model on the task of zero-shot clinical acronym expansion across three datasets. The LMC significantly outperforms a diverse set of baselines at a fraction of the pre-training cost and learns clinically coherent representations. We demonstrate that not only is metadata itself very helpful for the task, but that the LMC inference algorithm provides an additional large benefit.

Digital pathology enables automatic analysis of histopathological sections using artificial intelligence (AI). Automatic evaluation could improve diagnostic efficiency and help find associations between morphological features and clinical outcome. For development of such prediction models, identifying invasive epithelial cells, and separating these from benign epithelial cells and in situ lesions would be the first step. In this study, we aimed to develop an AI model for segmentation of epithelial cells in sections from breast cancer. We generated epithelial ground truth masks by restaining hematoxylin and eosin (HE) sections with cytokeratin (CK) AE1/AE3, and by pathologists' annotations. HE/CK image pairs were used to train a convolutional neural network, and data augmentation was used to make the model more robust. Tissue microarrays (TMAs) from 839 patients, and whole slide images from two patients were used for training and evaluation of the models. The sections were derived from four cohorts of breast cancer patients. TMAs from 21 patients from a fifth cohort was used as a second test set. In quantitative evaluation, a mean Dice score of 0.70, 0.79, and 0.75 for invasive epithelial cells, benign epithelial cells, and in situ lesions, respectively, were achieved. In qualitative scoring (0-5) by pathologists, results were best for all epithelium and invasive epithelium, with scores of 4.7 and 4.4. Scores for benign epithelium and in situ lesions were 3.7 and 2.0. The proposed model segmented epithelial cells in HE stained breast cancer slides well, but further work is needed for accurate division between the classes. Immunohistochemistry, together with pathologists' annotations, enabled the creation of accurate ground truths. The model is made freely available in FastPathology and the code is available at https://github.com/AICAN-Research/breast-epithelium-segmentation

Despite significant research efforts, deep neural networks are still vulnerable to biases: this raises concerns about their fairness and limits their generalization. In this paper, we propose a bias-agnostic approach to mitigate the impact of bias in deep neural networks. Unlike traditional debiasing approaches, we rely on a metric to quantify ``bias alignment/misalignment'' on target classes, and use this information to discourage the propagation of bias-target alignment information through the network. We conduct experiments on several commonly used datasets for debiasing and compare our method to supervised and bias-specific approaches. Our results indicate that the proposed method achieves comparable performance to state-of-the-art supervised approaches, although it is bias-agnostic, even in presence of multiple biases in the same sample.

Extracting single-cell information from microscopy data requires accurate instance-wise segmentations. Obtaining pixel-wise segmentations from microscopy imagery remains a challenging task, especially with the added complexity of microstructured environments. This paper presents a novel dataset for segmenting yeast cells in microstructures. We offer pixel-wise instance segmentation labels for both cells and trap microstructures. In total, we release 493 densely annotated microscopy images. To facilitate a unified comparison between novel segmentation algorithms, we propose a standardized evaluation strategy for our dataset. The aim of the dataset and evaluation strategy is to facilitate the development of new cell segmentation approaches. The dataset is publicly available at https://christophreich1996.github.io/yeast_in_microstructures_dataset/ .

Context-sensitive two-point layer 5 pyramidal cells (L5PCs) were discovered as long ago as 1999. However, the potential of this discovery to provide useful neural computation has yet to be demonstrated. Here we show for the first time how a transformative L5PCs-driven deep neural network (DNN), termed the multisensory cooperative computing (MCC) architecture, can effectively process large amounts of heterogeneous real-world audio-visual (AV) data, using far less energy compared to best available 'point' neuron-driven DNNs. A novel highly-distributed parallel implementation on a Xilinx UltraScale+ MPSoC device estimates energy savings up to 245759 times 50000 muJ (i.e., 62% less than the baseline model in a semi-supervised learning setup) where a single synapse consumes 8e^{-5}muJ. In a supervised learning setup, the energy-saving can potentially reach up to 1250x less (per feedforward transmission) than the baseline model. The significantly reduced neural activity in MCC leads to inherently fast learning and resilience against sudden neural damage. This remarkable performance in pilot experiments demonstrates the embodied neuromorphic intelligence of our proposed cooperative L5PC that receives input from diverse neighbouring neurons as context to amplify the transmission of most salient and relevant information for onward transmission, from overwhelmingly large multimodal information utilised at the early stages of on-chip training. Our proposed approach opens new cross-disciplinary avenues for future on-chip DNN training implementations and posits a radical shift in current neuromorphic computing paradigms.

Detecting and segmenting object instances is a common task in biomedical applications. Examples range from detecting lesions on functional magnetic resonance images, to the detection of tumours in histopathological images and extracting quantitative single-cell information from microscopy imagery, where cell segmentation is a major bottleneck. Attention-based transformers are state-of-the-art in a range of deep learning fields. They have recently been proposed for segmentation tasks where they are beginning to outperforming other methods. We present a novel attention-based cell detection transformer (Cell-DETR) for direct end-to-end instance segmentation. While the segmentation performance is on par with a state-of-the-art instance segmentation method, Cell-DETR is simpler and faster. We showcase the method's contribution in a the typical use case of segmenting yeast in microstructured environments, commonly employed in systems or synthetic biology. For the specific use case, the proposed method surpasses the state-of-the-art tools for semantic segmentation and additionally predicts the individual object instances. The fast and accurate instance segmentation performance increases the experimental information yield for a posteriori data processing and makes online monitoring of experiments and closed-loop optimal experimental design feasible.

The simulation of the metabolism in mammalian cells becomes a severe problem if spatial distributions must be taken into account. Especially the cytoplasm has a very complex geometric structure which cannot be handled by standard discretization techniques. In the present paper we propose a homogenization technique for computing effective diffusion constants. This is accomplished by using a two-step strategy. The first step consists of an analytic homogenization from the smallest to an intermediate scale. The homogenization error is estimated by comparing the analytic diffusion constant with a numerical estimate obtained by using real cell geometries. The second step consists of a random homogenization. Since no analytical solution is known to this homogenization problem, a numerical approximation algorithm is proposed. Although rather expensive this algorithm provides a reasonable estimate of the homogenized diffusion constant.

Artificial Intelligence (AI) in healthcare, especially in white blood cell cancer diagnosis, is hindered by two primary challenges: the lack of large-scale labeled datasets for white blood cell (WBC) segmentation and outdated segmentation methods. These challenges inhibit the development of more accurate and modern techniques to diagnose cancer relating to white blood cells. To address the first challenge, a semi-supervised learning framework should be devised to efficiently capitalize on the scarcity of the dataset available. In this work, we address this issue by proposing a novel self-training pipeline with the incorporation of FixMatch. Self-training is a technique that utilizes the model trained on labeled data to generate pseudo-labels for the unlabeled data and then re-train on both of them. FixMatch is a consistency-regularization algorithm to enforce the model's robustness against variations in the input image. We discover that by incorporating FixMatch in the self-training pipeline, the performance improves in the majority of cases. Our performance achieved the best performance with the self-training scheme with consistency on DeepLab-V3 architecture and ResNet-50, reaching 90.69%, 87.37%, and 76.49% on Zheng 1, Zheng 2, and LISC datasets, respectively.

Earlier diagnosis of Leukemia can save thousands of lives annually. The prognosis of leukemia is challenging without the morphological information of White Blood Cells (WBC) and relies on the accessibility of expensive microscopes and the availability of hematologists to analyze Peripheral Blood Samples (PBS). Deep Learning based methods can be employed to assist hematologists. However, these algorithms require a large amount of labeled data, which is not readily available. To overcome this limitation, we have acquired a realistic, generalized, and large dataset. To collect this comprehensive dataset for real-world applications, two microscopes from two different cost spectrums (high-cost HCM and low-cost LCM) are used for dataset capturing at three magnifications (100x, 40x, 10x) through different sensors (high-end camera for HCM, middle-level camera for LCM and mobile-phone camera for both). The high-sensor camera is 47 times more expensive than the middle-level camera and HCM is 17 times more expensive than LCM. In this collection, using HCM at high resolution (100x), experienced hematologists annotated 10.3k WBC types (14) and artifacts, having 55k morphological labels (Cell Size, Nuclear Chromatin, Nuclear Shape, etc.) from 2.4k images of several PBS leukemia patients. Later on, these annotations are transferred to other 2 magnifications of HCM, and 3 magnifications of LCM, and on each camera captured images. Along with the LeukemiaAttri dataset, we provide baselines over multiple object detectors and Unsupervised Domain Adaptation (UDA) strategies, along with morphological information-based attribute prediction. The dataset will be publicly available after publication to facilitate the research in this direction.

This paper presents TULIP, a new architecture for a binary neural network (BNN) that uses an optimal schedule for executing the operations of an arbitrary BNN. It was constructed with the goal of maximizing energy efficiency per classification. At the top-level, TULIP consists of a collection of unique processing elements (TULIP-PEs) that are organized in a SIMD fashion. Each TULIP-PE consists of a small network of binary neurons, and a small amount of local memory per neuron. The unique aspect of the binary neuron is that it is implemented as a mixed-signal circuit that natively performs the inner-product and thresholding operation of an artificial binary neuron. Moreover, the binary neuron, which is implemented as a single CMOS standard cell, is reconfigurable, and with a change in a single parameter, can implement all standard operations involved in a BNN. We present novel algorithms for mapping arbitrary nodes of a BNN onto the TULIP-PEs. TULIP was implemented as an ASIC in TSMC 40nm-LP technology. To provide a fair comparison, a recently reported BNN that employs a conventional MAC-based arithmetic processor was also implemented in the same technology. The results show that TULIP is consistently 3X more energy-efficient than the conventional design, without any penalty in performance, area, or accuracy.

Learning-based multi-view stereo (MVS) methods deal with predicting accurate depth maps to achieve an accurate and complete 3D representation. Despite the excellent performance, existing methods ignore the fact that a suitable depth geometry is also critical in MVS. In this paper, we demonstrate that different depth geometries have significant performance gaps, even using the same depth prediction error. Therefore, we introduce an ideal depth geometry composed of Saddle-Shaped Cells, whose predicted depth map oscillates upward and downward around the ground-truth surface, rather than maintaining a continuous and smooth depth plane. To achieve it, we develop a coarse-to-fine framework called Dual-MVSNet (DMVSNet), which can produce an oscillating depth plane. Technically, we predict two depth values for each pixel (Dual-Depth), and propose a novel loss function and a checkerboard-shaped selecting strategy to constrain the predicted depth geometry. Compared to existing methods,DMVSNet achieves a high rank on the DTU benchmark and obtains the top performance on challenging scenes of Tanks and Temples, demonstrating its strong performance and generalization ability. Our method also points to a new research direction for considering depth geometry in MVS.

Fluorescence labeling is the standard approach to reveal cellular structures and other subcellular constituents for microscopy images. However, this invasive procedure may perturb or even kill the cells and the procedure itself is highly time-consuming and complex. Recently, in silico labeling has emerged as a promising alternative, aiming to use machine learning models to directly predict the fluorescently labeled images from label-free microscopy. In this paper, we propose a deep learning-based in silico labeling method for the Light My Cells challenge. Built upon pix2pix, our proposed method can be trained using the partially labeled datasets with an adaptive loss. Moreover, we explore the effectiveness of several training strategies to handle different input modalities, such as training them together or separately. The results show that our method achieves promising performance for in silico labeling. Our code is available at https://github.com/MedICL-VU/LightMyCells.