Machine learning methods for histopathological image analysis

Abundant accumulation of digital histopathological images has led to the increased demand for their analysis, such as computer-aided diagnosis using machine learning techniques. However, digital pathological images and related tasks have some issues to be considered. In this mini-review, we introduce the application of digital pathological image analysis using machine learning algorithms, address some problems specific to such analysis, and propose possible solutions.Comment: 23 pages, 4 figure

Joint and individual analysis of breast cancer histologic images and genomic covariates

A key challenge in modern data analysis is understanding connections between complex and differing modalities of data. For example, two of the main approaches to the study of breast cancer are histopathology (analyzing visual characteristics of tumors) and genetics. While histopathology is the gold standard for diagnostics and there have been many recent breakthroughs in genetics, there is little overlap between these two fields. We aim to bridge this gap by developing methods based on Angle-based Joint and Individual Variation Explained (AJIVE) to directly explore similarities and differences between these two modalities. Our approach exploits Convolutional Neural Networks (CNNs) as a powerful, automatic method for image feature extraction to address some of the challenges presented by statistical analysis of histopathology image data. CNNs raise issues of interpretability that we address by developing novel methods to explore visual modes of variation captured by statistical algorithms (e.g. PCA or AJIVE) applied to CNN features. Our results provide many interpretable connections and contrasts between histopathology and genetics

Context-aware stacked convolutional neural networks for classification of breast carcinomas in whole-slide histopathology images

Automated classification of histopathological whole-slide images (WSI) of breast tissue requires analysis at very high resolutions with a large contextual area. In this paper, we present context-aware stacked convolutional neural networks (CNN) for classification of breast WSIs into normal/benign, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We first train a CNN using high pixel resolution patches to capture cellular level information. The feature responses generated by this model are then fed as input to a second CNN, stacked on top of the first. Training of this stacked architecture with large input patches enables learning of fine-grained (cellular) details and global interdependence of tissue structures. Our system is trained and evaluated on a dataset containing 221 WSIs of H&E stained breast tissue specimens. The system achieves an AUC of 0.962 for the binary classification of non-malignant and malignant slides and obtains a three class accuracy of 81.3% for classification of WSIs into normal/benign, DCIS, and IDC, demonstrating its potentials for routine diagnostics

Machine-learning-based evaluation of intratumoral heterogeneity and tumor-stroma interface for clinical guidance

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Laurinavicius, A., Rasmusson, A., Plancoulaine, B., Shribak, M., & Levenson, R. Machine-learning-based evaluation of intratumoral heterogeneity and tumor-stroma interface for clinical guidance. American Journal of Pathology, 191(10), (2021): 1724–1731, https://doi.org/10.1016/j.ajpath.2021.04.008.Assessment of intratumoral heterogeneity and tumor-host interaction within the tumor microenvironment is becoming increasingly important for innovative cancer therapy decisions because of the unique information it can generate about the state of the disease. However, its assessment and quantification are limited by ambiguous definitions of the tumor-host interface and by human cognitive capacity in current pathology practice. Advances in machine learning and artificial intelligence have opened the field of digital pathology to novel tissue image analytics and feature extraction for generation of high-capacity computational disease management models. A particular benefit is expected from machine-learning applications that can perform extraction and quantification of subvisual features of both intratumoral heterogeneity and tumor microenvironment aspects. These methods generate information about cancer cell subpopulation heterogeneity, potential tumor-host interactions, and tissue microarchitecture, derived from morphologically resolved content using both explicit and implicit features. Several studies have achieved promising diagnostic, prognostic, and predictive artificial intelligence models that often outperform current clinical and pathology criteria. However, further effort is needed for clinical adoption of such methods through development of standardizable high-capacity workflows and proper validation studies.Supported by the European Social Fund grant 09.3.3-LMT-K-712

Learning to Segment Breast Biopsy Whole Slide Images

We trained and applied an encoder-decoder model to semantically segment breast biopsy images into biologically meaningful tissue labels. Since conventional encoder-decoder networks cannot be applied directly on large biopsy images and the different sized structures in biopsies present novel challenges, we propose four modifications: (1) an input-aware encoding block to compensate for information loss, (2) a new dense connection pattern between encoder and decoder, (3) dense and sparse decoders to combine multi-level features, (4) a multi-resolution network that fuses the results of encoder-decoders run on different resolutions. Our model outperforms a feature-based approach and conventional encoder-decoders from the literature. We use semantic segmentations produced with our model in an automated diagnosis task and obtain higher accuracies than a baseline approach that employs an SVM for feature-based segmentation, both using the same segmentation-based diagnostic features.Comment: Added more WSI images in appendi