Localization of diagnostically relevant regions of interest in whole slide images

Whole slide imaging technology enables pathologists to screen biopsy images and make a diagnosis in a digital form. This creates an opportunity to understand the screening patterns of expert pathologists and extract the patterns that lead to accurate and efficient diagnoses. For this purpose, we are taking the first step to interpret the recorded actions of world-class expert pathologists on a set of digitized breast biopsy images. We propose an algorithm to extract regions of interest from the logs of image screenings using zoom levels, time and the magnitude of panning motion. Using diagnostically relevant regions marked by experts, we use the visual bag-of-words model with texture and color features to describe these regions and train probabilistic classifiers to predict similar regions of interest in new whole slide images. The proposed algorithm gives promising results for detecting diagnostically relevant regions. We hope this attempt to predict the regions that attract pathologists' attention will provide the first step in a more comprehensive study to understand the diagnostic patterns in histopathology. © 2014 IEEE

Localization of Diagnostically Relevant Regions of Interest in Whole Slide Images: a Comparative Study

Whole slide digital imaging technology enables researchers to study pathologists’ interpretive behavior as they view digital slides and gain new understanding of the diagnostic medical decision-making process. In this study, we propose a simple yet important analysis to extract diagnostically relevant regions of interest (ROIs) from tracking records using only pathologists’ actions as they viewed biopsy specimens in the whole slide digital imaging format (zooming, panning, and fixating). We use these extracted regions in a visual bag-of-words model based on color and texture features to predict diagnostically relevant ROIs on whole slide images. Using a logistic regression classifier in a cross-validation setting on 240 digital breast biopsy slides and viewport tracking logs of three expert pathologists, we produce probability maps that show 74 % overlap with the actual regions at which pathologists looked. We compare different bag-of-words models by changing dictionary size, visual word definition (patches vs. superpixels), and training data (automatically extracted ROIs vs. manually marked ROIs). This study is a first step in understanding the scanning behaviors of pathologists and the underlying reasons for diagnostic errors. © 2016, Society for Imaging Informatics in Medicine

Evaluation of Joint Multi-Instance Multi-Label Learning For Breast Cancer Diagnosis

Multi-instance multi-label (MIML) learning is a challenging problem in many aspects. Such learning approaches might be useful for many medical diagnosis applications including breast cancer detection and classification. In this study subset of digiPATH dataset (whole slide digital breast cancer histopathology images) are used for training and evaluation of six state-of-the-art MIML methods. At the end, performance comparison of these approaches are given by means of effective evaluation metrics. It is shown that MIML-kNN achieve the best performance that is %65.3 average precision, where most of other methods attain acceptable results as well

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

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

Capturing Global Spatial Context for Accurate Cell Classification in Skin Cancer Histology

The spectacular response observed in clinical trials of immunotherapy in patients with previously uncurable Melanoma, a highly aggressive form of skin cancer, calls for a better understanding of the cancer-immune interface. Computational pathology provides a unique opportunity to spatially dissect such interface on digitised pathological slides. Accurate cellular classification is a key to ensure meaningful results, but is often challenging even with state-of-art machine learning and deep learning methods. We propose a hierarchical framework, which mirrors the way pathologists perceive tumour architecture and define tumour heterogeneity to improve cell classification methods that rely solely on cell nuclei morphology. The SLIC superpixel algorithm was used to segment and classify tumour regions in low resolution H&E-stained histological images of melanoma skin cancer to provide a global context. Classification of superpixels into tumour, stroma, epidermis and lumen/white space, yielded a 97.7% training set accuracy and 95.7% testing set accuracy in 58 whole-tumour images of the TCGA melanoma dataset. The superpixel classification was projected down to high resolution images to enhance the performance of a single cell classifier, based on cell nuclear morphological features, and resulted in increasing its accuracy from 86.4% to 91.6%. Furthermore, a voting scheme was proposed to use global context as biological a priori knowledge, pushing the accuracy further to 92.8%. This study demonstrates how using the global spatial context can accurately characterise the tumour microenvironment and allow us to extend significantly beyond single-cell morphological classification.Comment: Accepted by MICCAI COMPAY 2018 worksho

Are you sure it's an artifact?:Artifact detection and uncertainty quantification in histological images

Modern cancer diagnostics involves extracting tissue specimens from suspicious areas and conducting histotechnical procedures to prepare a digitized glass slide, called Whole Slide Image (WSI), for further examination. These procedures frequently introduce different types of artifacts in the obtained WSI, and histological artifacts might influence Computational Pathology (CPATH) systems further down to a diagnostic pipeline if not excluded or handled. Deep Convolutional Neural Networks (DCNNs) have achieved promising results for the detection of some WSI artifacts, however, they do not incorporate uncertainty in their predictions. This paper proposes an uncertainty-aware Deep Kernel Learning (DKL) model to detect blurry areas and folded tissues, two types of artifacts that can appear in WSIs. The proposed probabilistic model combines a CNN feature extractor and a sparse Gaussian Processes (GPs) classifier, which improves the performance of current state-of-the-art artifact detection DCNNs and provides uncertainty estimates. We achieved 0.996 and 0.938 F1 scores for blur and folded tissue detection on unseen data, respectively. In extensive experiments, we validated the DKL model on unseen data from external independent cohorts with different staining and tissue types, where it outperformed DCNNs. Interestingly, the DKL model is more confident in the correct predictions and less in the wrong ones. The proposed DKL model can be integrated into the preprocessing pipeline of CPATH systems to provide reliable predictions and possibly serve as a quality control tool.</p

Are you sure it's an artifact?:Artifact detection and uncertainty quantification in histological images

Modern cancer diagnostics involves extracting tissue specimens from suspicious areas and conducting histotechnical procedures to prepare a digitized glass slide, called Whole Slide Image (WSI), for further examination. These procedures frequently introduce different types of artifacts in the obtained WSI, and histological artifacts might influence Computational Pathology (CPATH) systems further down to a diagnostic pipeline if not excluded or handled. Deep Convolutional Neural Networks (DCNNs) have achieved promising results for the detection of some WSI artifacts, however, they do not incorporate uncertainty in their predictions. This paper proposes an uncertainty-aware Deep Kernel Learning (DKL) model to detect blurry areas and folded tissues, two types of artifacts that can appear in WSIs. The proposed probabilistic model combines a CNN feature extractor and a sparse Gaussian Processes (GPs) classifier, which improves the performance of current state-of-the-art artifact detection DCNNs and provides uncertainty estimates. We achieved 0.996 and 0.938 F1 scores for blur and folded tissue detection on unseen data, respectively. In extensive experiments, we validated the DKL model on unseen data from external independent cohorts with different staining and tissue types, where it outperformed DCNNs. Interestingly, the DKL model is more confident in the correct predictions and less in the wrong ones. The proposed DKL model can be integrated into the preprocessing pipeline of CPATH systems to provide reliable predictions and possibly serve as a quality control tool.</p