Classification in Histopathology: A unique deep embeddings extractor for multiple classification tasks

In biomedical imaging, deep learning-based methods are state-of-the-art for every modality (virtual slides, MRI, etc.) In histopathology, these methods can be used to detect certain biomarkers or classify lesions. However, such techniques require large amounts of data to train high-performing models which can be intrinsically difficult to acquire, especially when it comes to scarce biomarkers. To address this challenge, we use a single, pre-trained, deep embeddings extractor to convert images into deep features and train small, dedicated classification head on these embeddings for each classification task. This approach offers several benefits such as the ability to reuse a single pre-trained deep network for various tasks; reducing the amount of labeled data needed as classification heads have fewer parameters; and accelerating training time by up to 1000 times, which allows for much more tuning of the classification head. In this work, we perform an extensive comparison of various open-source backbones and assess their fit to the target histological image domain. This is achieved using a novel method based on a proxy classification task. We demonstrate that thanks to this selection method, an optimal feature extractor can be selected for different tasks on the target domain. We also introduce a feature space augmentation strategy which proves to substantially improve the final metrics computed for the different tasks considered. To demonstrate the benefit of such backbone selection and feature-space augmentation, our experiments are carried out on three separate classification tasks and show a clear improvement on each of them: microcalcifications (29.1% F1-score increase), lymph nodes metastasis (12.5% F1-score increase), mitosis (15.0% F1-score increase).

Standardized CycleGAN training for unsupervised stain adaptation in invasive carcinoma classification for breast histopathology

Generalization is one of the main challenges of computational pathology. Slide preparation heterogeneity and the diversity of scanners lead to poor model performance when used on data from medical centers not seen during training. In order to achieve stain invariance in breast invasive carcinoma patch classification, we implement a stain translation strategy using cycleGANs for unsupervised image-to-image translation. We compare three cycleGAN-based approaches to a baseline classification model obtained without any stain invariance strategy. Two of the proposed approaches use cycleGAN's translations at inference or training in order to build stain-specific classification models. The last method uses them for stain data augmentation during training. This constrains the classification model to learn stain-invariant features. Baseline metrics are set by training and testing the baseline classification model on a reference stain. We assessed performances using three medical centers with H&E and H&E&S staining. Every approach tested in this study improves baseline metrics without needing labels on target stains. The stain augmentation-based approach produced the best results on every stain. Each method's pros and cons are studied and discussed in this paper. However, training highly performing cycleGANs models in itself represents a challenge. In this work, we introduce a systematical method for optimizing cycleGAN training by setting a novel stopping criterion. This method has the benefit of not requiring any visual inspection of cycleGAN results and proves superiority to methods using a predefined number of training epochs. In addition, we also study the minimal amount of data required for cycleGAN training.

Multicenter automatic detection of invasive carcinoma on breast whole slide images

Breast cancer is one of the most prevalent cancers worldwide and pathologists are closely involved in establishing a diagnosis. Tools to assist in making a diagnosis are required to manage the increasing workload. In this context, artificial intelligence (AI) and deep-learning based tools may be used in daily pathology practice. However, it is challenging to develop fast and reliable algorithms that can be trusted by practitioners, whatever the medical center. We describe a patch-based algorithm that incorporates a convolutional neural network to detect and locate invasive carcinoma on breast whole-slide images. The network was trained on a dataset extracted from a reference acquisition center. We then performed a calibration step based on transfer learning to maintain the performance when translating on a new target acquisition center by using a limited amount of additional training data. Performance was evaluated using classical binary measures (accuracy, recall, precision) for both centers (referred to as test reference dataset and test target dataset) and at two levels: patch and slide level. At patch level, accuracy, recall, and precision of the model on the reference and target test sets were 92.1\% and 96.3\%, 95\% and 87.8\%, and 73.9\% and 70.6\%, respectively. At slide level, accuracy, recall, and precision were 97.6\% and 92.0\%, 90.9\% and 100\%, and 100\% and 70.8\% for test sets 1 and 2, respectively. The high performance of the algorithm at both centers shows that the calibration process is efficient. This is performed using limited training data from the new target acquisition center and requires that the model is trained beforehand on a large database from a reference center. This methodology allows the implementation of AI diagnostic tools to help in routine pathology practice.