Attention to detail: inter-resolution knowledge distillation

The development of computer vision solutions for gigapixel images in digital pathology is hampered by significant computational limitations due to the large size of whole slide images. In particular, digitizing biopsies at high resolutions is a time-consuming process, which is necessary due to the worsening results from the decrease in image detail. To alleviate this issue, recent literature has proposed using knowledge distillation to enhance the model performance at reduced image resolutions. In particular, soft labels and features extracted at the highest magnification level are distilled into a model that takes lower-magnification images as input. However, this approach fails to transfer knowledge about the most discriminative image regions in the classification process, which may be lost when the resolution is decreased. In this work, we propose to distill this information by incorporating attention maps during training. In particular, our formulation leverages saliency maps of the target class via grad-CAMs, which guides the lower-resolution Student model to match the Teacher distribution by minimizing the l2 distance between them. Comprehensive experiments on prostate histology image grading demonstrate that the proposed approach substantially improves the model performance across different image resolutions compared to previous literature.

HistoColAi: An Open-Source Web Platform for Collaborative Digital Histology Image Annotation with AI-Driven Predictive Integration

Digital pathology has become a standard in the pathology workflow due to its many benefits. These include the level of detail of the whole slide images generated and the potential immediate sharing of cases between hospitals. Recent advances in deep learning-based methods for image analysis make them of potential aid in digital pathology. However, a major limitation in developing computer-aided diagnostic systems for pathology is the lack of an intuitive and open web application for data annotation. This paper proposes a web service that efficiently provides a tool to visualize and annotate digitized histological images. In addition, to show and validate the tool, in this paper we include a use case centered on the diagnosis of spindle cell skin neoplasm for multiple annotators. A usability study of the tool is also presented, showing the feasibility of the developed tool.

Transductive few-shot adapters for medical image segmentation

With the recent raise of foundation models in computer vision and NLP, the pretrain-and-adapt strategy, where a large-scale model is fine-tuned on downstream tasks, is gaining popularity. However, traditional fine-tuning approaches may still require significant resources and yield sub-optimal results when the labeled data of the target task is scarce. This is especially the case in clinical settings. To address this challenge, we formalize few-shot efficient fine-tuning (FSEFT), a novel and realistic setting for medical image segmentation. Furthermore, we introduce a novel parameter-efficient fine-tuning strategy tailored to medical image segmentation, with (a) spatial adapter modules that are more appropriate for dense prediction tasks; and (b) a constrained transductive inference, which leverages task-specific prior knowledge. Our comprehensive experiments on a collection of public CT datasets for organ segmentation reveal the limitations of standard fine-tuning methods in few-shot scenarios, point to the potential of vision adapters and transductive inference, and confirm the suitability of foundation models.

Challenging mitosis detection algorithms: Global labels allow centroid localization

Mitotic activity is a crucial proliferation biomarker for the diagnosis and prognosis of different types of cancers. Nevertheless, mitosis counting is a cumbersome process for pathologists, prone to low reproducibility, due to the large size of augmented biopsy slides, the low density of mitotic cells, and pattern heterogeneity. To improve reproducibility, deep learning methods have been proposed in the last years using convolutional neural networks. However, these methods have been hindered by the process of data labelling, which usually solely consist of the mitosis centroids. Therefore, current literature proposes complex algorithms with multiple stages to refine the labels at pixel level, and to reduce the number of false positives. In this work, we propose to avoid complex scenarios, and we perform the localization task in a weakly supervised manner, using only image-level labels on patches. The results obtained on the publicly available TUPAC16 dataset are competitive with state-of-the-art methods, using only one training phase. Our method achieves an F1-score of 0.729 and challenges the efficiency of previous methods, which required multiple stages and strong mitosis location information.

Constrained unsupervised anomaly segmentation

Current unsupervised anomaly localization approaches rely on generative models to learn the distribution of normal images, which is later used to identify potential anomalous regions derived from errors on the reconstructed images. However, a main limitation of nearly all prior literature is the need of employing anomalous images to set a class-specific threshold to locate the anomalies. This limits their usability in realistic scenarios, where only normal data is typically accessible. Despite this major drawback, only a handful of works have addressed this limitation, by integrating supervision on attention maps during training. In this work, we propose a novel formulation that does not require accessing images with abnormalities to define the threshold. Furthermore, and in contrast to very recent work, the proposed constraint is formulated in a more principled manner, leveraging well-known knowledge in constrained optimization. In particular, the equality constraint on the attention maps in prior work is replaced by an inequality constraint, which allows more flexibility. In addition, to address the limitations of penalty-based functions we employ an extension of the popular log-barrier methods to handle the constraint. Last, we propose an alternative regularization term that maximizes the Shannon entropy of the attention maps, reducing the amount of hyperparameters of the proposed model. Comprehensive experiments on two publicly available datasets on brain lesion segmentation demonstrate that the proposed approach substantially outperforms relevant literature, establishing new state-of-the-art results for unsupervised lesion segmentation, and without the need to access anomalous images.

Looking at the whole picture: constrained unsupervised anomaly segmentation

Current unsupervised anomaly localization approaches rely on generative models to learn the distribution of normal images, which is later used to identify potential anomalous regions derived from errors on the reconstructed images. However, a main limitation of nearly all prior literature is the need of employing anomalous images to set a class-specific threshold to locate the anomalies. This limits their usability in realistic scenarios, where only normal data is typically accessible. Despite this major drawback, only a handful of works have addressed this limitation, by integrating supervision on attention maps during training. In this work, we propose a novel formulation that does not require accessing images with abnormalities to define the threshold. Furthermore, and in contrast to very recent work, the proposed constraint is formulated in a more principled manner, leveraging well-known knowledge in constrained optimization. In particular, the equality constraint on the attention maps in prior work is replaced by an inequality constraint, which allows more flexibility. In addition, to address the limitations of penalty-based functions we employ an extension of the popular log-barrier methods to handle the constraint. Comprehensive experiments on the popular BRATS'19 dataset demonstrate that the proposed approach substantially outperforms relevant literature, establishing new state-of-the-art results for unsupervised lesion segmentation.

Prostate Gland Segmentation in Histology Images via Residual and Multi-Resolution U-Net

Prostate cancer is one of the most prevalent cancers worldwide. One of the key factors in reducing its mortality is based on early detection. The computer-aided diagnosis systems for this task are based on the glandular structural analysis in histology images. Hence, accurate gland detection and segmentation is crucial for a successful prediction. The methodological basis of this work is a prostate gland segmentation based on U-Net convolutional neural network architectures modified with residual and multi-resolution blocks, trained using data augmentation techniques. The residual configuration outperforms in the test subset the previous state-of-the-art approaches in an image-level comparison, reaching an average Dice Index of 0.77.

Going Deeper through the Gleason Scoring Scale: An Automatic end-to-end System for Histology Prostate Grading and Cribriform Pattern Detection

The Gleason scoring system is the primary diagnostic and prognostic tool for prostate cancer. In recent years, with the development of digitisation devices, the use of computer vision techniques for the analysis of biopsies has increased. However, to the best of the authors' knowledge, the development of algorithms to automatically detect individual cribriform patterns belonging to Gleason grade 4 has not yet been studied in the literature. The objective of the work presented in this paper is to develop a deep-learning-based system able to support pathologists in the daily analysis of prostate biopsies. The methodological core of this work is a patch-wise predictive model based on convolutional neural networks able to determine the presence of cancerous patterns. In particular, we train from scratch a simple self-design architecture. The cribriform pattern is detected by retraining the set of filters of the last convolutional layer in the network. From the reconstructed prediction map, we compute the percentage of each Gleason grade in the tissue to feed a multi-layer perceptron which provides a biopsy-level score.mIn our SICAPv2 database, composed of 182 annotated whole slide images, we obtained a Cohen's quadratic kappa of 0.77 in the test set for the patch-level Gleason grading with the proposed architecture trained from scratch. Our results outperform previous ones reported in the literature. Furthermore, this model reaches the level of fine-tuned state-of-the-art architectures in a patient-based four groups cross validation. In the cribriform pattern detection task, we obtained an area under ROC curve of 0.82. Regarding the biopsy Gleason scoring, we achieved a quadratic Cohen's Kappa of 0.81 in the test subset. Shallow CNN architectures trained from scratch outperform current state-of-the-art methods for Gleason grades classification.

WeGleNet: A Weakly-Supervised Convolutional Neural Network for the Semantic Segmentation of Gleason Grades in Prostate Histology Images

Prostate cancer is one of the main diseases affecting men worldwide. The Gleason scoring system is the primary diagnostic tool for prostate cancer. This is obtained via the visual analysis of cancerous patterns in prostate biopsies performed by expert pathologists, and the aggregation of the main Gleason grades in a combined score. Computer-aided diagnosis systems allow to reduce the workload of pathologists and increase the objectivity. Recently, efforts have been made in the literature to develop algorithms aiming the direct estimation of the global Gleason score at biopsy/core level with global labels. However, these algorithms do not cover the accurate localization of the Gleason patterns into the tissue. In this work, we propose a deep-learning-based system able to detect local cancerous patterns in the prostate tissue using only the global-level Gleason score during training. The methodological core of this work is the proposed weakly-supervised-trained convolutional neural network, WeGleNet, based on a multi-class segmentation layer after the feature extraction module, a global-aggregation, and the slicing of the background class for the model loss estimation during training. We obtained a Cohen's quadratic kappa (k) of 0.67 for the pixel-level prediction of cancerous patterns in the validation cohort. We compared the model performance for semantic segmentation of Gleason grades with supervised state-of-the-art architectures in the test cohort. We obtained a pixel-level k of 0.61 and a macro-averaged f1-score of 0.58, at the same level as fully-supervised methods. Regarding the estimation of the core-level Gleason score, we obtained a k of 0.76 and 0.67 between the model and two different pathologists. WeGleNet is capable of performing the semantic segmentation of Gleason grades similarly to fully-supervised methods without requiring pixel-level annotations.

Self-learning for weakly supervised Gleason grading of local patterns

Prostate cancer is one of the main diseases affecting men worldwide. The gold standard for diagnosis and prognosis is the Gleason grading system. In this process, pathologists manually analyze prostate histology slides under microscope, in a high time-consuming and subjective task. In the last years, computer-aided-diagnosis (CAD) systems have emerged as a promising tool that could support pathologists in the daily clinical practice. Nevertheless, these systems are usually trained using tedious and prone-to-error pixel-level annotations of Gleason grades in the tissue. To alleviate the need of manual pixel-wise labeling, just a handful of works have been presented in the literature. Motivated by this, we propose a novel weakly-supervised deep-learning model, based on self-learning CNNs, that leverages only the global Gleason score of gigapixel whole slide images during training to accurately perform both, grading of patch-level patterns and biopsy-level scoring. To evaluate the performance of the proposed method, we perform extensive experiments on three different external datasets for the patch-level Gleason grading, and on two different test sets for global Grade Group prediction. We empirically demonstrate that our approach outperforms its supervised counterpart on patch-level Gleason grading by a large margin, as well as state-of-the-art methods on global biopsy-level scoring. Particularly, the proposed model brings an average improvement on the Cohen's quadratic kappa (k) score of nearly 18% compared to full-supervision for the patch-level Gleason grading task.