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.
Artificial intelligence (AI) holds strong potential for medical diagnostics, yet its clinical adoption is limited by a lack of interpretability and generalizability. This study introduces the Pathobiological Dictionary for Liver Cancer (LCP1.0), a practical framework designed to translate complex Pathomics and Radiomics Features (PF and RF) into clinically meaningful insights aligned with existing diagnostic workflows. QuPath and PyRadiomics, standardized according to IBSI guidelines, were used to extract 333 imaging features from hepatocellular carcinoma (HCC) tissue samples, including 240 PF-based-cell detection/intensity, 74 RF-based texture, and 19 RF-based first-order features. Expert-defined ROIs from the public dataset excluded artifact-prone areas, and features were aggregated at the case level. Their relevance to the WHO grading system was assessed using multiple classifiers linked with feature selectors. The resulting dictionary was validated by 8 experts in oncology and pathology. In collaboration with 10 domain experts, we developed a Pathobiological dictionary of imaging features such as PFs and RF. In our study, the Variable Threshold feature selection algorithm combined with the SVM model achieved the highest accuracy (0.80, P-value less than 0.05), selecting 20 key features, primarily clinical and pathomics traits such as Centroid, Cell Nucleus, and Cytoplasmic characteristics. These features, particularly nuclear and cytoplasmic, were strongly associated with tumor grading and prognosis, reflecting atypia indicators like pleomorphism, hyperchromasia, and cellular orientation.The LCP1.0 provides a clinically validated bridge between AI outputs and expert interpretation, enhancing model transparency and usability. Aligning AI-derived features with clinical semantics supports the development of interpretable, trustworthy diagnostic tools for liver cancer pathology.
In this study, we built an end-to-end tumor-infiltrating lymphocytes (TILs) assessment pipeline within QuPath, demonstrating the potential of easily accessible tools to perform complex tasks in a fully automatic fashion. First, we trained a pixel classifier to segment tumor, tumor-associated stroma, and other tissue compartments in breast cancer H&E-stained whole-slide images (WSI) to isolate tumor-associated stroma for subsequent analysis. Next, we applied a pre-trained StarDist deep learning model in QuPath for cell detection and used the extracted cell features to train a binary classifier distinguishing TILs from other cells. To evaluate our TILs assessment pipeline, we calculated the TIL density in each WSI and categorized them as low, medium, or high TIL levels. Our pipeline was evaluated against pathologist-assigned TIL scores, achieving a Cohen's kappa of 0.71 on the external test set, corroborating previous research findings. These results confirm that existing software can offer a practical solution for the assessment of TILs in H&E-stained WSIs of breast cancer.
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.
This paper presents a Patherea, a framework for point-based cell detection and classification that provides a complete solution for developing and evaluating state-of-the-art approaches. We introduce a large-scale dataset collected to directly replicate a clinical workflow for Ki-67 proliferation index estimation and use it to develop an efficient point-based approach that directly predicts point-based predictions, without the need for intermediate representations. The proposed approach effectively utilizes point proposal candidates with the hybrid Hungarian matching strategy and a flexible architecture that enables the usage of various backbones and (pre)training strategies. We report state-of-the-art results on existing public datasets - Lizard, BRCA-M2C, BCData, and the newly proposed Patherea dataset. We show that the performance on existing public datasets is saturated and that the newly proposed Patherea dataset represents a significantly harder challenge for the recently proposed approaches. We also demonstrate the effectiveness of recently proposed pathology foundational models that our proposed approach can natively utilize and benefit from. We also revisit the evaluation protocol that is used in the broader field of cell detection and classification and identify the erroneous calculation of performance metrics. Patherea provides a benchmarking utility that addresses the identified issues and enables a fair comparison of different approaches. The dataset and the code will be publicly released upon acceptance.
Cell detection and segmentation are integral parts of automated systems in digital pathology. Encoder-decoder networks have emerged as a promising solution for these tasks. However, training of these networks has typically required full boundary annotations of cells, which are labor-intensive and difficult to obtain on a large scale. However, in many applications, such as cell counting, weaker forms of annotations--such as point annotations or approximate cell counts--can provide sufficient supervision for training. This study proposes a new mixed-supervision approach for training multitask networks in digital pathology by incorporating cell counts derived from the eyeballing process--a quick visual estimation method commonly used by pathologists. This study has two main contributions: (1) It proposes a mixed-supervision strategy for digital pathology that utilizes cell counts obtained by eyeballing as an auxiliary supervisory signal to train a multitask network for the first time. (2) This multitask network is designed to concurrently learn the tasks of cell counting and cell localization, and this study introduces a consistency loss that regularizes training by penalizing inconsistencies between the predictions of these two tasks. Our experiments on two datasets of hematoxylin-eosin stained tissue images demonstrate that the proposed approach effectively utilizes the weakest form of annotation, improving performance when stronger annotations are limited. These results highlight the potential of integrating eyeballing-derived ground truths into the network training, reducing the need for resource-intensive annotations.
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.
Detection and differentiation of circulating tumor cells (CTCs) and non-CTCs in blood draws of cancer patients pose multiple challenges. While the gold standard relies on tedious manual evaluation of an automatically generated selection of images, machine learning (ML) techniques offer the potential to automate these processes. However, human assessment remains indispensable when the ML system arrives at uncertain or wrong decisions due to an insufficient set of labeled training data. This study introduces a human-in-the-loop (HiL) strategy for improving ML-based CTC detection. We combine self-supervised deep learning and a conventional ML-based classifier and propose iterative targeted sampling and labeling of new unlabeled training samples by human experts. The sampling strategy is based on the classification performance of local latent space clusters. The advantages of the proposed approach compared to naive random sampling are demonstrated for liquid biopsy data from patients with metastatic breast cancer.
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.
Medical imaging is key in modern medicine. From magnetic resonance imaging (MRI) to microscopic imaging for blood cell detection, diagnostic medical imaging reveals vital insights into patient health. To predict diseases or provide individualized therapies, machine learning techniques like kernel methods have been widely used. Nevertheless, there are multiple challenges for implementing kernel methods. Medical image data often originates from various hospitals and cannot be combined due to privacy concerns, and the high dimensionality of image data presents another significant obstacle. While randomised encoding offers a promising direction, existing methods often struggle with a trade-off between accuracy and efficiency. Addressing the need for efficient privacy-preserving methods on distributed image data, we introduce OKRA (Orthonormal K-fRAmes), a novel randomized encoding-based approach for kernel-based machine learning. This technique, tailored for widely used kernel functions, significantly enhances scalability and speed compared to current state-of-the-art solutions. Through experiments conducted on various clinical image datasets, we evaluated model quality, computational performance, and resource overhead. Additionally, our method outperforms comparable approaches
Efficient detection and classification of blood cells are vital for accurate diagnosis and effective treatment of blood disorders. This study utilizes a YOLOv10 model trained on Roboflow data with images resized to 640x640 pixels across varying epochs. The results show that increased training epochs significantly enhance accuracy, precision, and recall, particularly in real-time blood cell detection & classification. The YOLOv10 model outperforms MobileNetV2, ShuffleNetV2, and DarkNet in real-time performance, though MobileNetV2 and ShuffleNetV2 are more computationally efficient, and DarkNet excels in feature extraction for blood cell classification. This research highlights the potential of integrating deep learning models like YOLOv10, MobileNetV2, ShuffleNetV2, and DarkNet into clinical workflows, promising improvements in diagnostic accuracy and efficiency. Additionally, a new, well-annotated blood cell dataset was created and will be open-sourced to support further advancements in automatic blood cell detection and classification. The findings demonstrate the transformative impact of these models in revolutionizing medical diagnostics and enhancing blood disorder management
Liquid biopsies (eg., blood draws) offer a less invasive and non-localized alternative to tissue biopsies for monitoring the progression of metastatic breast cancer (mBCa). Immunofluoresence (IF) microscopy is a tool to image and analyze millions of blood cells in a patient sample. By detecting and genetically sequencing circulating tumor cells (CTCs) in the blood, personalized treatment plans are achievable for various cancer subtypes. However, CTCs are rare (about 1 in 2M), making manual CTC detection very difficult. In addition, clinicians rely on quantitative cellular biomarkers to manually classify CTCs. This requires prior tasks of cell detection, segmentation and feature extraction. To assist clinicians, we have developed a fully automated machine learning-based production-level pipeline to efficiently detect, segment and classify CTCs in multi-channel IF images. We achieve over 99% sensitivity and 97% specificity on 9,533 cells from 15 mBCa patients. Our pipeline has been successfully deployed on real mBCa patients, reducing a patient average of 14M detected cells to only 335 CTC candidates for manual review.
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.
Cytology screening from Papanicolaou (Pap) smears is a common and effective tool for the preventive clinical management of cervical cancer, where abnormal cell detection from whole slide images serves as the foundation for reporting cervical cytology. However, cervical cell detection remains challenging due to 1) hazily-defined cell types (e.g., ASC-US) with subtle morphological discrepancies caused by the dynamic cancerization process, i.e., cell class ambiguity, and 2) imbalanced class distributions of clinical data may cause missed detection, especially for minor categories, i.e., cell class imbalance. To this end, we propose a holistic and historical instance comparison approach for cervical cell detection. Specifically, we first develop a holistic instance comparison scheme enforcing both RoI-level and class-level cell discrimination. This coarse-to-fine cell comparison encourages the model to learn foreground-distinguishable and class-wise representations. To emphatically improve the distinguishability of minor classes, we then introduce a historical instance comparison scheme with a confident sample selection-based memory bank, which involves comparing current embeddings with historical embeddings for better cell instance discrimination. Extensive experiments and analysis on two large-scale cytology datasets including 42,592 and 114,513 cervical cells demonstrate the effectiveness of our method. The code is available at https://github.com/hjiangaz/HERO.
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.
Oral squamous cell carcinoma (OSCC) represents a significant global health concern, with increasing incidence rates and challenges in early diagnosis and treatment planning. Early detection is crucial for improving patient outcomes and survival rates. Deep learning, a subset of machine learning, has shown remarkable progress in extracting and analyzing crucial information from medical imaging data.EfficientNetB3, an advanced convolutional neural network architecture, has emerged as a leading model for image classification tasks, including medical imaging. Its superior performance, characterized by high accuracy, precision, and recall, makes it particularly promising for OSCC detection and diagnosis. EfficientNetB3 achieved an accuracy of 0.9833, precision of 0.9782, and recall of 0.9782 in our analysis. By leveraging EfficientNetB3 and other deep learning technologies, clinicians can potentially improve the accuracy and efficiency of OSCC diagnosis, leading to more timely interventions and better patient outcomes. This article also discusses the role of deep learning in advancing precision medicine for OSCC and provides insights into prospects and challenges in leveraging this technology for enhanced cancer care.
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
The precise segmentation and tracking of cells in microscopy image sequences play a pivotal role in biomedical research, facilitating the study of tissue, organ, and organism development. However, manual segmentation and tracking of cells is time-consuming and often require professional experiences. Besides, segmenting cells in the images with a low signal-to-noise ratio remains difficult. While deep learning (DL) has become a common method for cell segmentation, few DL- based methods address concurrent cell segmentation and tracking. In this paper, we propose a novel DL approach featuring graph-based tracking for cell segmentation and tracking in microscopy images. We combine Deeplabv3+ for semantic segmentation and ResNet50 for enhanced feature extraction, enabling comprehensive cell detection and instance segmentation. Post-processing, involving non-maxima suppression and outlier detection, refines predictions and produces final segmentation. The tracking method is based on the relative position of graph nodes to track segmented cells, encompassing cell division and apoptosis. We conduct our experiments on the induced pluripotent stem (iPS) cell datasets, and the results show that the segmentation and tracking performance of our method yields superior performance compared to the benchmark models. More specifically, our approach achieved DET values of 0.955 and 0.913, TRA values of 0.951 and 0.906, and SEG values of 0.690 and 0.665 on two iPS dataset videos, respectively. Additionally, the performance assessment encompasses four real microscopy datasets from the Cell Tracking Challenge (CTC). Our method greatly reduces the cost of manual labeling and labor-intensive costs.