Pathology Report Generation and Multimodal Representation Learning for Cutaneous Melanocytic Lesions

Millions of melanocytic skin lesions are examined by pathologists each year, the majority of which concern common nevi (i.e., ordinary moles). While most of these lesions can be diagnosed in seconds, writing the corresponding pathology report is much more time-consuming. Automating part of the report writing could, therefore, alleviate the increasing workload of pathologists. In this work, we develop a vision-language model specifically for the pathology domain of cutaneous melanocytic lesions. The model follows the Contrastive Captioner framework and was trained and evaluated using a melanocytic lesion dataset of 42,512 H&E-stained whole slide images and 19,645 corresponding pathology reports. Our results show that the quality scores of model-generated reports were on par with pathologist-written reports for common nevi, assessed by an expert pathologist in a reader study. While report generation revealed to be more difficult for rare melanocytic lesion subtypes, the cross-modal retrieval performance for these cases was considerably better.

On the Importance of Text Preprocessing for Multimodal Representation Learning and Pathology Report Generation

Vision-language models in pathology enable multimodal case retrieval and automated report generation. Many of the models developed so far, however, have been trained on pathology reports that include information which cannot be inferred from paired whole slide images (e.g., patient history), potentially leading to hallucinated sentences in generated reports. To this end, we investigate how the selection of information from pathology reports for vision-language modeling affects the quality of the multimodal representations and generated reports. More concretely, we compare a model trained on full reports against a model trained on preprocessed reports that only include sentences describing the cell and tissue appearances based on the H&E-stained slides. For the experiments, we built upon the BLIP-2 framework and used a cutaneous melanocytic lesion dataset of 42,433 H&E-stained whole slide images and 19,636 corresponding pathology reports. Model performance was assessed using image-to-text and text-to-image retrieval, as well as qualitative evaluation of the generated reports by an expert pathologist. Our results demonstrate that text preprocessing prevents hallucination in report generation. Despite the improvement in the quality of the generated reports, training the vision-language model on full reports showed better cross-modal retrieval performance.

Artificial Intelligence-Based Triaging of Cutaneous Melanocytic Lesions

Pathologists are facing an increasing workload due to a growing volume of cases and the need for more comprehensive diagnoses. Aiming to facilitate workload reduction and faster turnaround times, we developed an artificial intelligence (AI) model for triaging cutaneous melanocytic lesions based on whole slide images. The AI model was developed and validated using a retrospective cohort from the UMC Utrecht. The dataset consisted of 52,202 whole slide images from 27,167 unique specimens, acquired from 20,707 patients. Specimens with only common nevi were assigned to the low complexity category (86.6%). In contrast, specimens with any other melanocytic lesion subtype, including non-common nevi, melanocytomas, and melanomas, were assigned to the high complexity category (13.4%). The dataset was split on patient level into a development set (80%) and test sets (20%) for independent evaluation. Predictive performance was primarily measured using the area under the receiver operating characteristic curve (AUROC) and the area under the precision-recall curve (AUPRC). A simulation experiment was performed to study the effect of implementing AI-based triaging in the clinic. The AI model reached an AUROC of 0.966 (95% CI, 0.960-0.972) and an AUPRC of 0.857 (95% CI, 0.836-0.877) on the in-distribution test set, and an AUROC of 0.899 (95% CI, 0.860-0.934) and an AUPRC of 0.498 (95% CI, 0.360-0.639) on the out-of-distribution test set. In the simulation experiment, using random case assignment as baseline, AI-based triaging prevented an average of 43.9 (95% CI, 36-55) initial examinations of high complexity cases by general pathologists for every 500 cases. In conclusion, the AI model achieved a strong predictive performance in differentiating between cutaneous melanocytic lesions of high and low complexity. The improvement in workflow efficiency due to AI-based triaging could be substantial.

Multi-head Attention-based Deep Multiple Instance Learning

This paper introduces MAD-MIL, a Multi-head Attention-based Deep Multiple Instance Learning model, designed for weakly supervised Whole Slide Images (WSIs) classification in digital pathology. Inspired by the multi-head attention mechanism of the Transformer, MAD-MIL simplifies model complexity while achieving competitive results against advanced models like CLAM and DS-MIL. Evaluated on the MNIST-BAGS and public datasets, including TUPAC16, TCGA BRCA, TCGA LUNG, and TCGA KIDNEY, MAD-MIL consistently outperforms ABMIL. This demonstrates enhanced information diversity, interpretability, and efficiency in slide representation. The model's effectiveness, coupled with fewer trainable parameters and lower computational complexity makes it a promising solution for automated pathology workflows. Our code is available at https://github.com/tueimage/MAD-MIL.

WSI-SAM: Multi-resolution Segment Anything Model (SAM) for histopathology whole-slide images

The Segment Anything Model (SAM) marks a significant advancement in segmentation models, offering robust zero-shot abilities and dynamic prompting. However, existing medical SAMs are not suitable for the multi-scale nature of whole-slide images (WSIs), restricting their effectiveness. To resolve this drawback, we present WSI-SAM, enhancing SAM with precise object segmentation capabilities for histopathology images using multi-resolution patches, while preserving its efficient, prompt-driven design, and zero-shot abilities. To fully exploit pretrained knowledge while minimizing training overhead, we keep SAM frozen, introducing only minimal extra parameters and computational overhead. In particular, we introduce High-Resolution (HR) token, Low-Resolution (LR) token and dual mask decoder. This decoder integrates the original SAM mask decoder with a lightweight fusion module that integrates features at multiple scales. Instead of predicting a mask independently, we integrate HR and LR token at intermediate layer to jointly learn features of the same object across multiple resolutions. Experiments show that our WSI-SAM outperforms state-of-the-art SAM and its variants. In particular, our model outperforms SAM by 4.1 and 2.5 percent points on a ductal carcinoma in situ (DCIS) segmentation tasks and breast cancer metastasis segmentation task (CAMELYON16 dataset). The code will be available at https://github.com/HongLiuuuuu/WSI-SAM.

Tissue Cross-Section and Pen Marking Segmentation in Whole Slide Images

Tissue segmentation is a routine preprocessing step to reduce the computational cost of whole slide image (WSI) analysis by excluding background regions. Traditional image processing techniques are commonly used for tissue segmentation, but often require manual adjustments to parameter values for atypical cases, fail to exclude all slide and scanning artifacts from the background, and are unable to segment adipose tissue. Pen marking artifacts in particular can be a potential source of bias for subsequent analyses if not removed. In addition, several applications require the separation of individual cross-sections, which can be challenging due to tissue fragmentation and adjacent positioning. To address these problems, we develop a convolutional neural network for tissue and pen marking segmentation using a dataset of 200 H&E stained WSIs. For separating tissue cross-sections, we propose a novel post-processing method based on clustering predicted centroid locations of the cross-sections in a 2D histogram. On an independent test set, the model achieved a mean Dice score of 0.981$\pm$0.033 for tissue segmentation and a mean Dice score of 0.912$\pm$0.090 for pen marking segmentation. The mean absolute difference between the number of annotated and separated cross-sections was 0.075$\pm$0.350. Our results demonstrate that the proposed model can accurately segment H&E stained tissue cross-sections and pen markings in WSIs while being robust to many common slide and scanning artifacts. The model with trained model parameters and post-processing method are made publicly available as a Python package called SlideSegmenter.

Domain generalization across tumor types, laboratories, and species -- insights from the 2022 edition of the Mitosis Domain Generalization Challenge

Recognition of mitotic figures in histologic tumor specimens is highly relevant to patient outcome assessment. This task is challenging for algorithms and human experts alike, with deterioration of algorithmic performance under shifts in image representations. Considerable covariate shifts occur when assessment is performed on different tumor types, images are acquired using different digitization devices, or specimens are produced in different laboratories. This observation motivated the inception of the 2022 challenge on MItosis Domain Generalization (MIDOG 2022). The challenge provided annotated histologic tumor images from six different domains and evaluated the algorithmic approaches for mitotic figure detection provided by nine challenge participants on ten independent domains. Ground truth for mitotic figure detection was established in two ways: a three-expert consensus and an independent, immunohistochemistry-assisted set of labels. This work represents an overview of the challenge tasks, the algorithmic strategies employed by the participants, and potential factors contributing to their success. With an $F_1$ score of 0.764 for the top-performing team, we summarize that domain generalization across various tumor domains is possible with today's deep learning-based recognition pipelines. When assessed against the immunohistochemistry-assisted reference standard, all methods resulted in reduced recall scores, but with only minor changes in the order of participants in the ranking.

A Deep Learning Approach Utilizing Covariance Matrix Analysis for the ISBI Edited MRS Reconstruction Challenge

This work proposes a method to accelerate the acquisition of high-quality edited magnetic resonance spectroscopy (MRS) scans using machine learning models taking the sample covariance matrix as input. The method is invariant to the number of transients and robust to noisy input data for both synthetic as well as in-vivo scenarios.

Deep Learning for Detection and Localization of B-Lines in Lung Ultrasound

Lung ultrasound (LUS) is an important imaging modality used by emergency physicians to assess pulmonary congestion at the patient bedside. B-line artifacts in LUS videos are key findings associated with pulmonary congestion. Not only can the interpretation of LUS be challenging for novice operators, but visual quantification of B-lines remains subject to observer variability. In this work, we investigate the strengths and weaknesses of multiple deep learning approaches for automated B-line detection and localization in LUS videos. We curate and publish, BEDLUS, a new ultrasound dataset comprising 1,419 videos from 113 patients with a total of 15,755 expert-annotated B-lines. Based on this dataset, we present a benchmark of established deep learning methods applied to the task of B-line detection. To pave the way for interpretable quantification of B-lines, we propose a novel "single-point" approach to B-line localization using only the point of origin. Our results show that (a) the area under the receiver operating characteristic curve ranges from 0.864 to 0.955 for the benchmarked detection methods, (b) within this range, the best performance is achieved by models that leverage multiple successive frames as input, and (c) the proposed single-point approach for B-line localization reaches an F1-score of 0.65, performing on par with the inter-observer agreement. The dataset and developed methods can facilitate further biomedical research on automated interpretation of lung ultrasound with the potential to expand the clinical utility.

LYSTO: The Lymphocyte Assessment Hackathon and Benchmark Dataset

We introduce LYSTO, the Lymphocyte Assessment Hackathon, which was held in conjunction with the MICCAI 2019 Conference in Shenzen (China). The competition required participants to automatically assess the number of lymphocytes, in particular T-cells, in histopathological images of colon, breast, and prostate cancer stained with CD3 and CD8 immunohistochemistry. Differently from other challenges setup in medical image analysis, LYSTO participants were solely given a few hours to address this problem. In this paper, we describe the goal and the multi-phase organization of the hackathon; we describe the proposed methods and the on-site results. Additionally, we present post-competition results where we show how the presented methods perform on an independent set of lung cancer slides, which was not part of the initial competition, as well as a comparison on lymphocyte assessment between presented methods and a panel of pathologists. We show that some of the participants were capable to achieve pathologist-level performance at lymphocyte assessment. After the hackathon, LYSTO was left as a lightweight plug-and-play benchmark dataset on grand-challenge website, together with an automatic evaluation platform. LYSTO has supported a number of research in lymphocyte assessment in oncology. LYSTO will be a long-lasting educational challenge for deep learning and digital pathology, it is available at https://lysto.grand-challenge.org/.