Jeanne Shen

Amirreza Mahbod, Ramona Woitek, Jeanne Shen

In computational pathology, nuclear instance segmentation is a fundamental task with many downstream clinical applications. With the advent of deep learning, many approaches, including convolutional neural networks (CNNs) and vision transformers (ViTs), have been proposed for this task, along with both machine learning-based and non-machine learning-based pre- and post-processing techniques to further boost performance. However, one fundamental aspect that has received less attention is the evaluation pipeline. In this study, we identify four key issues associated with nuclear instance segmentation evaluation and propose corresponding solutions. Our proposed modifications, namely handling vague regions, score normalization, overlapping instances, and border uncertainty, are integrated into a unified framework called NucEval, which enables robust evaluation of nuclear instance segmentation. We evaluate this pipeline using the NuInsSeg dataset, which provides unique characteristics that make it particularly suitable for this study, as well as two additional external datasets, with three CNN- and ViT-based nuclear instance segmentation models, to demonstrate the impact of these modifications on instance segmentation metrics. The code, along with complete guidelines and illustrative examples, is publicly available at: https://github.com/masih4/nuc_eval.

Sheng Wang, Ruiming Wu, Charles Herndon et al.

Diagnosing a whole-slide image is an interactive, multi-stage process of changing magnification and moving between fields. Although recent pathology foundation models demonstrated superior performances, practical agentic systems that decide what field to examine next, adjust magnification, and deliver explainable diagnoses are still lacking. Such limitation is largely bottlenecked by data: scalable, clinically aligned supervision of expert viewing behavior that is tacit and experience-based, not documented in textbooks or internet, and therefore absent from LLM training. Here we introduce a framework designed to address this challenge through three key breakthroughs. First, the AI Session Recorder seamlessly integrates with standard whole-slide image viewers to unobtrusively record routine navigation and convert the viewer logs into standardized behavioral commands and bounding boxes. Second, a lightweight human-in-the-loop review turns AI-drafted rationales for behavioral commands into the Pathology-CoT dataset, a form of paired "where to look" and "why it matters", enabling six-fold faster labeling compared to manual constructing such Chain-of-Thought dataset. Using this behavioral data, we build Pathology-o3, a two-stage agent that first proposes important ROIs and then performs behavior-guided reasoning. On the gastrointestinal lymph-node metastasis detection task, our method achieved 100 recall on the internal validation from Stanford Medicine and 97.6 recall on an independent external validation from Sweden, exceeding the state-of-the-art OpenAI o3 model and generalizing across backbones. To our knowledge, Pathology-CoT constitutes one of the first behavior-grounded agentic systems in pathology. Turning everyday viewer logs into scalable, expert-validated supervision, our framework makes agentic pathology practical and establishes a path to human-aligned, upgradeable clinical AI.

Jon Braatz, Pranav Rajpurkar, Stephanie Zhang et al.

In recent years, deep learning has successfully been applied to automate a wide variety of tasks in diagnostic histopathology. However, fast and reliable localization of small-scale regions-of-interest (ROI) has remained a key challenge, as discriminative morphologic features often occupy only a small fraction of a gigapixel-scale whole-slide image (WSI). In this paper, we propose a sparse WSI analysis method for the rapid identification of high-power ROI for WSI-level classification. We develop an evaluation framework inspired by the early classification literature, in order to quantify the tradeoff between diagnostic performance and inference time for sparse analytic approaches. We test our method on a common but time-consuming task in pathology - that of diagnosing gastric intestinal metaplasia (GIM) on hematoxylin and eosin (H&E)-stained slides from endoscopic biopsy specimens. GIM is a well-known precursor lesion along the pathway to development of gastric cancer. We performed a thorough evaluation of the performance and inference time of our approach on a test set of GIM-positive and GIM-negative WSI, finding that our method successfully detects GIM in all positive WSI, with a WSI-level classification area under the receiver operating characteristic curve (AUC) of 0.98 and an average precision (AP) of 0.95. Furthermore, we show that our method can attain these metrics in under one minute on a standard CPU. Our results are applicable toward the goal of developing neural networks that can easily be deployed in clinical settings to support pathologists in quickly localizing and diagnosing small-scale morphologic features in WSI.

Rikiya Yamashita, Jin Long, Snikitha Banda et al.

Suboptimal generalization of machine learning models on unseen data is a key challenge which hampers the clinical applicability of such models to medical imaging. Although various methods such as domain adaptation and domain generalization have evolved to combat this challenge, learning robust and generalizable representations is core to medical image understanding, and continues to be a problem. Here, we propose STRAP (Style TRansfer Augmentation for histoPathology), a form of data augmentation based on random style transfer from non-medical style source such as artistic paintings, for learning domain-agnostic visual representations in computational pathology. Style transfer replaces the low-level texture content of an image with the uninformative style of randomly selected style source image, while preserving the original high-level semantic content. This improves robustness to domain shift and can be used as a simple yet powerful tool for learning domain-agnostic representations. We demonstrate that STRAP leads to state-of-the-art performance, particularly in the presence of domain shifts, on two particular classification tasks in computational pathology.

Mehmet Burak Sayıcı, Rikiya Yamashita, Jeanne Shen

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide. Whole-slide imaging which is a method of scanning glass slides have been employed for diagnosis of HCC. Using high resolution Whole-slide images is infeasible for Convolutional Neural Network applications. Hence tiling the Whole-slide images is a common methodology for assigning Convolutional Neural Networks for classification and segmentation. Determination of the tile size affects the performance of the algorithms since small field of view can not capture the information on a larger scale and large field of view can not capture the information on a cellular scale. In this work, the effect of tile size on performance for classification problem is analysed. In addition, Multi Field of View CNN is assigned for taking advantage of the information provided by different tile sizes and Attention CNN is assigned for giving the capability of voting most contributing tile size. It is found that employing more than one tile size significantly increases the performance of the classification by 3.97% and both algorithms are found successful over the algorithm which uses only one tile size.

Okyaz Eminaga, Mahmoud Abbas, Christian Kunder et al.

Different convolutional neural network (CNN) models have been tested for their application in histological image analyses. However, these models are prone to overfitting due to their large parameter capacity, requiring more data or valuable computational resources for model training. Given these limitations, we introduced a novel architecture (termed PlexusNet). We utilized 310 Hematoxylin and Eosin stained (H&E) annotated histological images of prostate cancer cases from TCGA-PRAD and Stanford University and 398 H&E whole slides images from the Camelyon 2016 challenge. PlexusNet-architecture -derived models were compared to models derived from several existing "state of the art" architectures. We measured discrimination accuracy, calibration, and clinical utility. An ablation study was conducted to study the effect of each component of PlexusNet on model performance. A well-fitted PlexusNet-based model delivered comparable classification performance (AUC: 0.963) in distinguishing prostate cancer from healthy tissues, although it was at least 23 times smaller, had a better model calibration and clinical utility than the comparison models. A separate smaller PlexusNet model accurately detected slides with breast cancer metastases (AUC: 0.978); it helped reduce the slide number to examine by 43.8% without consequences, although its parameter capacity was 200 times smaller than ResNet18. We found that the partitioning of the development set influences the model calibration for all models. However, with PlexusNet architecture, we could achieve comparable well-calibrated models trained on different partitions. In conclusion, PlexusNet represents a novel model architecture for histological image analysis that achieves classification performance comparable to other models while providing orders-of-magnitude parameter reduction.