An interpretable machine learning system for colorectal cancer diagnosis from pathology slides.

Considering the profound transformation affecting pathology practice, we aimed to develop a scalable artificial intelligence (AI) system to diagnose colorectal cancer from whole-slide images (WSI). For this, we propose a deep learning (DL) system that learns from weak labels, a sampling strategy that reduces the number of training samples by a factor of six without compromising performance, an approach to leverage a small subset of fully annotated samples, and a prototype with explainable predictions, active learning features and parallelisation. Noting some problems in the literature, this study is conducted with one of the largest WSI colorectal samples dataset with approximately 10,500 WSIs. Of these samples, 900 are testing samples. Furthermore, the robustness of the proposed method is assessed with two additional external datasets (TCGA and PAIP) and a dataset of samples collected directly from the proposed prototype. Our proposed method predicts, for the patch-based tiles, a class based on the severity of the dysplasia and uses that information to classify the whole slide. It is trained with an interpretable mixed-supervision scheme to leverage the domain knowledge introduced by pathologists through spatial annotations. The mixed-supervision scheme allowed for an intelligent sampling strategy effectively evaluated in several different scenarios without compromising the performance. On the internal dataset, the method shows an accuracy of 93.44% and a sensitivity between positive (low-grade and high-grade dysplasia) and non-neoplastic samples of 0.996. On the external test samples varied with TCGA being the most challenging dataset with an overall accuracy of 84.91% and a sensitivity of 0.996.

A CAD system for automatic dysplasia grading on H&E cervical whole-slide images.

Cervical cancer is the fourth most common female cancer worldwide and the fourth leading cause of cancer-related death in women. Nonetheless, it is also among the most successfully preventable and treatable types of cancer, provided it is early identified and properly managed. As such, the detection of pre-cancerous lesions is crucial. These lesions are detected in the squamous epithelium of the uterine cervix and are graded as low- or high-grade intraepithelial squamous lesions, known as LSIL and HSIL, respectively. Due to their complex nature, this classification can become very subjective. Therefore, the development of machine learning models, particularly directly on whole-slide images (WSI), can assist pathologists in this task. In this work, we propose a weakly-supervised methodology for grading cervical dysplasia, using different levels of training supervision, in an effort to gather a bigger dataset without the need of having all samples fully annotated. The framework comprises an epithelium segmentation step followed by a dysplasia classifier (non-neoplastic, LSIL, HSIL), making the slide assessment completely automatic, without the need for manual identification of epithelial areas. The proposed classification approach achieved a balanced accuracy of 71.07% and sensitivity of 72.18%, at the slide-level testing on 600 independent samples, which are publicly available upon reasonable request.

Annotating for Artificial Intelligence Applications in Digital Pathology: A Practical Guide for Pathologists and Researchers.

Training machine learning models for artificial intelligence (AI) applications in pathology often requires extensive annotation by human experts, but there is little guidance on the subject. In this work, we aimed to describe our experience and provide a simple, useful, and practical guide addressing annotation strategies for AI development in computational pathology. Annotation methodology will vary significantly depending on the specific study's objectives, but common difficulties will be present across different settings. We summarize key aspects and issue guiding principles regarding team interaction, ground-truth quality assessment, different annotation types, and available software and hardware options and address common difficulties while annotating. This guide was specifically designed for pathology annotation, intending to help pathologists, other researchers, and AI developers with this process.

Quality Control in Digital Pathology: Automatic Fragment Detection and Counting.

Manual assessment of fragments during the pro-cessing of pathology specimens is critical to ensure that the material available for slide analysis matches that captured during grossing without losing valuable material during this process. However, this step is still performed manually, resulting in lost time and delays in making the complete case available for evaluation by the pathologist. To overcome this limitation, we developed an autonomous system that can detect and count the number of fragments contained on each slide. We applied and compared two different methods: conventional machine learning methods and deep convolutional network methods. For conventional machine learning methods, we tested a two-stage approach with a supervised classifier followed by unsupervised hierarchical clustering. In addition, Fast R-CNN and YOLOv5, two state-of-the-art deep learning models for detection, were used and compared. All experiments were performed on a dataset comprising 1276 images of colorec-tal biopsy and polypectomy specimens manually labeled for fragment/set detection. The best results were obtained with the YOLOv5 architecture with a map@0.5 of 0.977 for fragment/set detection.

iMIL4PATH: A Semi-Supervised Interpretable Approach for Colorectal Whole-Slide Images.

Colorectal cancer (CRC) diagnosis is based on samples obtained from biopsies, assessed in pathology laboratories. Due to population growth and ageing, as well as better screening programs, the CRC incidence rate has been increasing, leading to a higher workload for pathologists. In this sense, the application of AI for automatic CRC diagnosis, particularly on whole-slide images (WSI), is of utmost relevance, in order to assist professionals in case triage and case review. In this work, we propose an interpretable semi-supervised approach to detect lesions in colorectal biopsies with high sensitivity, based on multiple-instance learning and feature aggregation methods. The model was developed on an extended version of the recent, publicly available CRC dataset (the CRC+ dataset with 4433 WSI), using 3424 slides for training and 1009 slides for evaluation. The proposed method attained 90.19% classification ACC, 98.8% sensitivity, 85.7% specificity, and a quadratic weighted kappa of 0.888 at slide-based evaluation. Its generalisation capabilities are also studied on two publicly available external datasets.

CAD systems for colorectal cancer from WSI are still not ready for clinical acceptance.

Most oncological cases can be detected by imaging techniques, but diagnosis is based on pathological assessment of tissue samples. In recent years, the pathology field has evolved to a digital era where tissue samples are digitised and evaluated on screen. As a result, digital pathology opened up many research opportunities, allowing the development of more advanced image processing techniques, as well as artificial intelligence (AI) methodologies. Nevertheless, despite colorectal cancer (CRC) being the second deadliest cancer type worldwide, with increasing incidence rates, the application of AI for CRC diagnosis, particularly on whole-slide images (WSI), is still a young field. In this review, we analyse some relevant works published on this particular task and highlight the limitations that hinder the application of these works in clinical practice. We also empirically investigate the feasibility of using weakly annotated datasets to support the development of computer-aided diagnosis systems for CRC from WSI. Our study underscores the need for large datasets in this field and the use of an appropriate learning methodology to gain the most benefit from partially annotated datasets. The CRC WSI dataset used in this study, containing 1,133 colorectal biopsy and polypectomy samples, is available upon reasonable request.

A Regression Model for Predicting Shape Deformation after Breast Conserving Surgery.

Breast cancer treatments can have a negative impact on breast aesthetics, in case when surgery is intended to intersect tumor. For many years mastectomy was the only surgical option, but more recently breast conserving surgery (BCS) has been promoted as a liable alternative to treat cancer while preserving most part of the breast. However, there is still a significant number of BCS intervened patients who are unpleasant with the result of the treatment, which leads to self-image issues and emotional overloads. Surgeons recognize the value of a tool to predict the breast shape after BCS to facilitate surgeon/patient communication and allow more educated decisions; however, no such tool is available that is suited for clinical usage. These tools could serve as a way of visually sensing the aesthetic consequences of the treatment. In this research, it is intended to propose a methodology for predict the deformation after BCS by using machine learning techniques. Nonetheless, there is no appropriate dataset containing breast data before and after surgery in order to train a learning model. Therefore, an in-house semi-synthetic dataset is proposed to fulfill the requirement of this research. Using the proposed dataset, several learning methodologies were investigated, and promising outcomes are obtained.

Three-Dimensional Planning Tool for Breast Conserving Surgery: A Technological Review.

Breast cancer is one of the most common malignancies affecting women worldwide. However, despite its incidence trends have increased, the mortality rate has significantly decreased. The primary concern in any cancer treatment is the oncological outcome but, in the case of breast cancer, the surgery aesthetic result has become an important quality indicator for breast cancer patients. In this sense, an adequate surgical planning and prediction tool would empower the patient regarding the treatment decision process, enabling a better communication between the surgeon and the patient and a better understanding of the impact of each surgical option. To develop such tool, it is necessary to create complete 3D model of the breast, integrating both inner and outer breast data. In this review, we thoroughly explore and review the major existing works that address, directly or not, the technical challenges involved in the development of a 3D software planning tool in the field of breast conserving surgery.