Challenges such as the lack of high-quality annotations, long-tailed data distributions, and inconsistent staining styles pose significant obstacles to training neural networks to detect abnormal cells in cytopathology robustly. This paper proposes a style-aligned image composition (SAIC) method that composes high-fidelity and style-preserved pathological images to enhance the effectiveness and robustness of detection models. Without additional training, SAIC first selects an appropriate candidate from the abnormal cell bank based on attribute guidance. Then, it employs a high-frequency feature reconstruction to achieve a style-aligned and high-fidelity composition of abnormal cells and pathological backgrounds. Finally, it introduces a large vision-language model to filter high-quality synthesis images. Experimental results demonstrate that incorporating SAIC-synthesized images effectively enhances the performance and robustness of abnormal cell detection for tail categories and styles, thereby improving overall detection performance. The comprehensive quality evaluation further confirms the generalizability and practicality of SAIC in clinical application scenarios. Our code will be released at https://github.com/Joey-Qi/SAIC.
Accurate and efficient cell detection is crucial in many biomedical image analysis tasks. We evaluate the performance of several Deep Learning (DL) methods for cell detection in Papanicolaou-stained cytological Whole Slide Images (WSIs), focusing on accuracy of predictions and computational efficiency. We examine recentoff-the-shelf algorithms as well as custom-designed detectors, applying them to two datasets: the CNSeg Dataset and the Oral Cancer (OC) Dataset. Our comparison includes well-established segmentation methods such as StarDist, Cellpose, and the Segment Anything Model 2 (SAM2), alongside centroid-based Fully Convolutional Regression Network (FCRN) approaches. We introduce a suitable evaluation metric to assess the accuracy of predictions based on the distance from ground truth positions. We also explore the impact of dataset size and data augmentation techniques on model performance. Results show that centroid-based methods, particularly the Improved Fully Convolutional Regression Network (IFCRN) method, outperform segmentation-based methods in terms of both detection accuracy and computational efficiency. This study highlights the potential of centroid-based detectors as a preferred option for cell detection in resource-limited environments, offering faster processing times and lower GPU memory usage without compromising accuracy.
Precise cell classification is essential in biomedical diagnostics and therapeutic monitoring, particularly for identifying diverse cell types involved in various diseases. Traditional cell classification methods such as flow cytometry depend on molecular labeling which is often costly, time-intensive, and can alter cell integrity. To overcome these limitations, we present a label-free machine learning framework for cell classification, designed for real-time sorting applications using bright-field microscopy images. This approach leverages a teacher-student model architecture enhanced by knowledge distillation, achieving high efficiency and scalability across different cell types. Demonstrated through a use case of classifying lymphocyte subsets, our framework accurately classifies T4, T8, and B cell types with a dataset of 80,000 preprocessed images, accessible via an open-source Python package for easy adaptation. Our teacher model attained 98\% accuracy in differentiating T4 cells from B cells and 93\% accuracy in zero-shot classification between T8 and B cells. Remarkably, our student model operates with only 0.02\% of the teacher model's parameters, enabling field-programmable gate array (FPGA) deployment. Our FPGA-accelerated student model achieves an ultra-low inference latency of just 14.5~$\mu$s and a complete cell detection-to-sorting trigger time of 24.7~$\mu$s, delivering 12x and 40x improvements over the previous state-of-the-art real-time cell analysis algorithm in inference and total latency, respectively, while preserving accuracy comparable to the teacher model. This framework provides a scalable, cost-effective solution for lymphocyte classification, as well as a new SOTA real-time cell sorting implementation for rapid identification of subsets using in situ deep learning on off-the-shelf computing hardware.
Accurately modeling multi-class cell topology is crucial in digital pathology, as it provides critical insights into tissue structure and pathology. The synthetic generation of cell topology enables realistic simulations of complex tissue environments, enhances downstream tasks by augmenting training data, aligns more closely with pathologists' domain knowledge, and offers new opportunities for controlling and generalizing the tumor microenvironment. In this paper, we propose a novel approach that integrates topological constraints into a diffusion model to improve the generation of realistic, contextually accurate cell topologies. Our method refines the simulation of cell distributions and interactions, increasing the precision and interpretability of results in downstream tasks such as cell detection and classification. To assess the topological fidelity of generated layouts, we introduce a new metric, Topological Frechet Distance (TopoFD), which overcomes the limitations of traditional metrics like FID in evaluating topological structure. Experimental results demonstrate the effectiveness of our approach in generating multi-class cell layouts that capture intricate topological relationships. Code is available at https://github.com/Melon-Xu/TopoCellGen.
Nanorobots are a promising development in targeted drug delivery and the treatment of neurological disorders, with potential for crossing the blood-brain barrier (BBB). These small devices leverage advancements in nanotechnology and bioengineering for precise navigation and targeted payload delivery, particularly for conditions like brain tumors, Alzheimer's disease, and Parkinson's disease. Recent progress in artificial intelligence (AI) and machine learning (ML) has improved the navigation and effectiveness of nanorobots, allowing them to detect and interact with cancer cells through biomarker analysis. This study presents a new reinforcement learning (RL) framework for optimizing nanorobot navigation in complex biological environments, focusing on cancer cell detection by analyzing the concentration gradients of surrounding biomarkers. We utilize a computer simulation model to explore the behavior of nanorobots in a three-dimensional space with cancer cells and biological barriers. The proposed method uses Q-learning to refine movement strategies based on real-time biomarker concentration data, enabling nanorobots to autonomously navigate to cancerous tissues for targeted drug delivery. This research lays the groundwork for future laboratory experiments and clinical applications, with implications for personalized medicine and less invasive cancer treatments. The integration of intelligent nanorobots could revolutionize therapeutic strategies, reducing side effects and enhancing treatment effectiveness for cancer patients. Further research will investigate the practical deployment of these technologies in medical settings, aiming to unlock the full potential of nanorobotics in healthcare.
A global threshold (e.g., 0.5) is often applied to determine which bounding boxes should be included in the final results for an object detection task. A higher threshold reduces false positives but may result in missing a significant portion of true positives. A lower threshold can increase detection recall but may also result in more false positives. Because of this, using a preset global threshold (e.g., 0.5) applied to all the bounding box candidates may lead to suboptimal solutions. In this paper, we propose a Test-time Self-guided Bounding-box Propagation (TSBP) method, leveraging Earth Mover's Distance (EMD) to enhance object detection in histology images. TSBP utilizes bounding boxes with high confidence to influence those with low confidence, leveraging visual similarities between them. This propagation mechanism enables bounding boxes to be selected in a controllable, explainable, and robust manner, which surpasses the effectiveness of using simple thresholds and uncertainty calibration methods. Importantly, TSBP does not necessitate additional labeled samples for model training or parameter estimation, unlike calibration methods. We conduct experiments on gland detection and cell detection tasks in histology images. The results show that our proposed TSBP significantly improves detection outcomes when working in conjunction with state-of-the-art deep learning-based detection networks. Compared to other methods such as uncertainty calibration, TSBP yields more robust and accurate object detection predictions while using no additional labeled samples. The code is available at https://github.com/jwhgdeu/TSBP.
Generative models, such as GANs and diffusion models, have been used to augment training sets and boost performances in different tasks. We focus on generative models for cell detection instead, i.e., locating and classifying cells in given pathology images. One important information that has been largely overlooked is the spatial patterns of the cells. In this paper, we propose a spatial-pattern-guided generative model for cell layout generation. Specifically, a novel diffusion model guided by spatial features and generates realistic cell layouts has been proposed. We explore different density models as spatial features for the diffusion model. In downstream tasks, we show that the generated cell layouts can be used to guide the generation of high-quality pathology images. Augmenting with these images can significantly boost the performance of SOTA cell detection methods. The code is available at https://github.com/superlc1995/Diffusion-cell.
In existing medical Region of Interest (ROI) detection, there lacks an algorithm that can simultaneously satisfy both real-time performance and accuracy, not meeting the growing demand for automatic detection in medicine. Although the basic YOLO framework ensures real-time detection due to its fast speed, it still faces challenges in maintaining precision concurrently. To alleviate the above problems, we propose a novel model named Lightweight Shunt Matching-YOLO (LSM-YOLO), with Lightweight Adaptive Extraction (LAE) and Multipath Shunt Feature Matching (MSFM). Firstly, by using LAE to refine feature extraction, the model can obtain more contextual information and high-resolution details from multiscale feature maps, thereby extracting detailed features of ROI in medical images while reducing the influence of noise. Secondly, MSFM is utilized to further refine the fusion of high-level semantic features and low-level visual features, enabling better fusion between ROI features and neighboring features, thereby improving the detection rate for better diagnostic assistance. Experimental results demonstrate that LSM-YOLO achieves 48.6% AP on a private dataset of pancreatic tumors, 65.1% AP on the BCCD blood cell detection public dataset, and 73.0% AP on the Br35h brain tumor detection public dataset. Our model achieves state-of-the-art performance with minimal parameter cost on the above three datasets. The source codes are at: https://github.com/VincentYuuuuuu/LSM-YOLO.
In pathology, accurate and efficient analysis of Hematoxylin and Eosin (H\&E) slides is crucial for timely and effective cancer diagnosis. Although many deep learning solutions for nuclei instance segmentation and classification exist in the literature, they often entail high computational costs and resource requirements, thus limiting their practical usage in medical applications. To address this issue, we introduce a novel convolutional neural network, NuLite, a U-Net-like architecture designed explicitly on Fast-ViT, a state-of-the-art (SOTA) lightweight CNN. We obtained three versions of our model, NuLite-S, NuLite-M, and NuLite-H, trained on the PanNuke dataset. The experimental results prove that our models equal CellViT (SOTA) in terms of panoptic quality and detection. However, our lightest model, NuLite-S, is 40 times smaller in terms of parameters and about 8 times smaller in terms of GFlops, while our heaviest model is 17 times smaller in terms of parameters and about 7 times smaller in terms of GFlops. Moreover, our model is up to about 8 times faster than CellViT. Lastly, to prove the effectiveness of our solution, we provide a robust comparison of external datasets, namely CoNseP, MoNuSeg, and GlySAC. Our model is publicly available at https://github.com/CosmoIknosLab/NuLite
Recent advances in microscopy have enabled the rapid generation of terabytes of image data in cell biology and biomedical research. Vision-language models (VLMs) offer a promising solution for large-scale biological image analysis, enhancing researchers' efficiency, identifying new image biomarkers, and accelerating hypothesis generation and scientific discovery. However, there is a lack of standardized, diverse, and large-scale vision-language benchmarks to evaluate VLMs' perception and cognition capabilities in biological image understanding. To address this gap, we introduce {\mu}-Bench, an expert-curated benchmark encompassing 22 biomedical tasks across various scientific disciplines (biology, pathology), microscopy modalities (electron, fluorescence, light), scales (subcellular, cellular, tissue), and organisms in both normal and abnormal states. We evaluate state-of-the-art biomedical, pathology, and general VLMs on {\mu}-Bench and find that: i) current models struggle on all categories, even for basic tasks such as distinguishing microscopy modalities; ii) current specialist models fine-tuned on biomedical data often perform worse than generalist models; iii) fine-tuning in specific microscopy domains can cause catastrophic forgetting, eroding prior biomedical knowledge encoded in their base model. iv) weight interpolation between fine-tuned and pre-trained models offers one solution to forgetting and improves general performance across biomedical tasks. We release {\mu}-Bench under a permissive license to accelerate the research and development of microscopy foundation models.
Anterior uveitis, a common form of eye inflammation, can lead to permanent vision loss if not promptly diagnosed. Monitoring this condition involves quantifying inflammatory cells in the anterior chamber (AC) of the eye, which can be captured using Anterior Segment Optical Coherence Tomography (AS-OCT). However, manually identifying cells in AS-OCT images is time-consuming and subjective. Moreover, existing automated approaches may have limitations in both the effectiveness of detecting cells and the reliability of their detection results. To address these challenges, we propose an automated framework to detect cells in the AS-OCT images. This framework consists of a zero-shot chamber segmentation module and a cell detection module. The first module segments the AC area in the image without requiring human-annotated training data. Subsequently, the second module identifies individual cells within the segmented AC region. Through experiments, our framework demonstrates superior performance compared to current state-of-the-art methods for both AC segmentation and cell detection tasks. Notably, we find that previous cell detection approaches could suffer from low recall, potentially overlooking a significant number of cells. In contrast, our framework offers an improved solution, which could benefit the diagnosis and study of anterior uveitis. Our code for cell detection is publicly available at: https://github.com/joeybyc/cell_detection.
Fined-grained anomalous cell detection from affected tissues is critical for clinical diagnosis and pathological research. Single-cell sequencing data provide unprecedented opportunities for this task. However, current anomaly detection methods struggle to handle domain shifts prevalent in multi-sample and multi-domain single-cell sequencing data, leading to suboptimal performance. Moreover, these methods fall short of distinguishing anomalous cells into pathologically distinct subtypes. In response, we propose ACSleuth, a novel, reconstruction deviation-guided generative framework that integrates the detection, domain adaptation, and fine-grained annotating of anomalous cells into a methodologically cohesive workflow. Notably, we present the first theoretical analysis of using reconstruction deviations output by generative models for anomaly detection in lieu of domain shifts. This analysis informs us to develop a novel and superior maximum mean discrepancy-based anomaly scorer in ACSleuth. Extensive benchmarks over various single-cell data and other types of tabular data demonstrate ACSleuth's superiority over the state-of-the-art methods in identifying and subtyping anomalies in multi-sample and multi-domain contexts. Our code is available at https://github.com/Catchxu/ACsleuth.
Detecting and classifying cells in histopathology H\&E stained whole-slide images is a core task in computational pathology, as it provides valuable insight into the tumor microenvironment. In this work we investigate the impact of ground truth formats on the models performance. Additionally, cell-tissue interactions are considered by providing tissue segmentation predictions as input to the cell detection model. We find that a "soft", probability-map instance segmentation ground truth leads to best model performance. Combined with cell-tissue interaction and test-time augmentation our Soft Cell-Tissue-Model (SoftCTM) achieves 0.7172 mean F1-Score on the Overlapped Cell On Tissue (OCELOT) test set, achieving the third best overall score in the OCELOT 2023 Challenge. The source code for our approach is made publicly available at https://github.com/lely475/ocelot23algo.
While model architectures and training strategies have become more generic and flexible with respect to different data modalities over the past years, a persistent limitation lies in the assumption of fixed quantities and arrangements of input features. This limitation becomes particularly relevant in scenarios where the attributes captured during data acquisition vary across different samples. In this work, we aim at effectively leveraging data with varying features, without the need to constrain the input space to the intersection of potential feature sets or to expand it to their union. We propose a novel architecture that can directly process data without the necessity of aligned feature modalities by learning a general embedding space that captures the relationship between features across data samples with varying sets of features. This is achieved via a set-transformer architecture augmented by feature-encoder layers, thereby enabling the learning of a shared latent feature space from data originating from heterogeneous feature spaces. The advantages of the model are demonstrated for automatic cancer cell detection in acute myeloid leukemia in flow cytometry data, where the features measured during acquisition often vary between samples. Our proposed architecture's capacity to operate seamlessly across incongruent feature spaces is particularly relevant in this context, where data scarcity arises from the low prevalence of the disease. The code is available for research purposes at https://github.com/lisaweijler/FATE.
Cell detection and tracking are paramount for bio-analysis. Recent approaches rely on the tracking-by-model evolution paradigm, which usually consists of training end-to-end deep learning models to detect and track the cells on the frames with promising results. However, such methods require extensive amounts of annotated data, which is time-consuming to obtain and often requires specialized annotators. This work proposes a new approach based on the classical tracking-by-detection paradigm that alleviates the requirement of annotated data. More precisely, it approximates the cell shapes as oriented ellipses and then uses generic-purpose oriented object detectors to identify the cells in each frame. We then rely on a global data association algorithm that explores temporal cell similarity using probability distance metrics, considering that the ellipses relate to two-dimensional Gaussian distributions. Our results show that our method can achieve detection and tracking results competitively with state-of-the-art techniques that require considerably more extensive data annotation. Our code is available at: https://github.com/LucasKirsten/Deep-Cell-Tracking-EBB.
In view of the recent paradigm shift in deep AI based image processing methods, medical image processing has advanced considerably. In this study, we propose a novel deep neural network (DNN), entitled InceptNet, in the scope of medical image processing, for early disease detection and segmentation of medical images in order to enhance precision and performance. We also investigate the interaction of users with the InceptNet application to present a comprehensive application including the background processes, and foreground interactions with users. Fast InceptNet is shaped by the prominent Unet architecture, and it seizes the power of an Inception module to be fast and cost effective while aiming to approximate an optimal local sparse structure. Adding Inception modules with various parallel kernel sizes can improve the network's ability to capture the variations in the scaled regions of interest. To experiment, the model is tested on four benchmark datasets, including retina blood vessel segmentation, lung nodule segmentation, skin lesion segmentation, and breast cancer cell detection. The improvement was more significant on images with small scale structures. The proposed method improved the accuracy from 0.9531, 0.8900, 0.9872, and 0.9881 to 0.9555, 0.9510, 0.9945, and 0.9945 on the mentioned datasets, respectively, which show outperforming of the proposed method over the previous works. Furthermore, by exploring the procedure from start to end, individuals who have utilized a trial edition of InceptNet, in the form of a complete application, are presented with thirteen multiple choice questions in order to assess the proposed method. The outcomes are evaluated through the means of Human Computer Interaction.
The success of supervised deep learning models on cell recognition tasks relies on detailed annotations. Many previous works have managed to reduce the dependency on labels. However, considering the large number of cells contained in a patch, costly and inefficient labeling is still inevitable. To this end, we explored label-free methods for cell recognition. Prior self-activation maps (PSM) are proposed to generate pseudo masks as training targets. To be specific, an activation network is trained with self-supervised learning. The gradient information in the shallow layers of the network is aggregated to generate prior self-activation maps. Afterward, a semantic clustering module is then introduced as a pipeline to transform PSMs to pixel-level semantic pseudo masks for downstream tasks. We evaluated our method on two histological datasets: MoNuSeg (cell segmentation) and BCData (multi-class cell detection). Compared with other fully-supervised and weakly-supervised methods, our method can achieve competitive performance without any manual annotations. Our simple but effective framework can also achieve multi-class cell detection which can not be done by existing unsupervised methods. The results show the potential of PSMs that might inspire other research to deal with the hunger for labels in medical area.
Nuclei detection and segmentation in hematoxylin and eosin-stained (H&E) tissue images are important clinical tasks and crucial for a wide range of applications. However, it is a challenging task due to nuclei variances in staining and size, overlapping boundaries, and nuclei clustering. While convolutional neural networks have been extensively used for this task, we explore the potential of Transformer-based networks in this domain. Therefore, we introduce a new method for automated instance segmentation of cell nuclei in digitized tissue samples using a deep learning architecture based on Vision Transformer called CellViT. CellViT is trained and evaluated on the PanNuke dataset, which is one of the most challenging nuclei instance segmentation datasets, consisting of nearly 200,000 annotated Nuclei into 5 clinically important classes in 19 tissue types. We demonstrate the superiority of large-scale in-domain and out-of-domain pre-trained Vision Transformers by leveraging the recently published Segment Anything Model and a ViT-encoder pre-trained on 104 million histological image patches - achieving state-of-the-art nuclei detection and instance segmentation performance on the PanNuke dataset with a mean panoptic quality of 0.50 and an F1-detection score of 0.83. The code is publicly available at https://github.com/TIO-IKIM/CellViT
Blood cell detection is a typical small-scale object detection problem in computer vision. In this paper, we propose a CST-YOLO model for blood cell detection based on YOLOv7 architecture and enhance it with the CNN-Swin Transformer (CST), which is a new attempt at CNN-Transformer fusion. We also introduce three other useful modules: Weighted Efficient Layer Aggregation Networks (W-ELAN), Multiscale Channel Split (MCS), and Concatenate Convolutional Layers (CatConv) in our CST-YOLO to improve small-scale object detection precision. Experimental results show that the proposed CST-YOLO achieves 92.7%, 95.6%, and 91.1% [email omitted], respectively, on three blood cell datasets, outperforming state-of-the-art object detectors, e.g., RT-DETR, YOLOv5, and YOLOv7. Our code is available at https://github.com/mkang315/CST-YOLO.
Multi-class cell detection and counting is an essential task for many pathological diagnoses. Manual counting is tedious and often leads to inter-observer variations among pathologists. While there exist multiple, general-purpose, deep learning-based object detection and counting methods, they may not readily transfer to detecting and counting cells in medical images, due to the limited data, presence of tiny overlapping objects, multiple cell types, severe class-imbalance, minute differences in size/shape of cells, etc. In response, we propose guided posterior regularization (DeGPR), which assists an object detector by guiding it to exploit discriminative features among cells. The features may be pathologist-provided or inferred directly from visual data. We validate our model on two publicly available datasets (CoNSeP and MoNuSAC), and on MuCeD, a novel dataset that we contribute. MuCeD consists of 55 biopsy images of the human duodenum for predicting celiac disease. We perform extensive experimentation with three object detection baselines on three datasets to show that DeGPR is model-agnostic, and consistently improves baselines obtaining up to 9% (absolute) mAP gains.