Neoadjuvant treatment (NAT) of breast cancer (BCa) is an option for patients with the locally advanced disease. It has been compared with standard adjuvant therapy with the aim of improving prognosis and surgical outcome. Moreover, the response of the tumor to the therapy provides useful information for patient management. The pathological examination of the tissue sections after surgery is the gold-standard to estimate the residual tumor and the assessment of cellularity is an important component of tumor burden assessment. In the current clinical practice, tumor cellularity is manually estimated by pathologists on hematoxylin and eosin (H&E) stained slides, the quality, and reliability of which might be impaired by inter-observer variability which potentially affects prognostic power assessment in NAT trials. This procedure is also qualitative and time-consuming. In this paper, we describe a method of automatically assessing cellularity. A pipeline to automatically segment nuclei figures and estimate residual cancer cellularity from within patches and whole slide images (WSIs) of BCa was developed. We have compared the performance of our proposed pipeline in estimating residual cancer cellularity with that of two expert pathologists. We found an intra-class agreement coefficient (ICC) of 0.89 (95% CI of [0.70, 0.95]) between pathologists, 0.74 (95% CI of [0.70, 0.77]) between pathologist #1 and proposed method, and 0.75 (95% CI of [0.71, 0.79]) between pathologist #2 and proposed method. We have also successfully applied our proposed technique on a WSI to locate areas with high concentration of residual cancer. The main advantage of our approach is that it is fully automatic and can be used to find areas with high cellularity in WSIs. This provides a first step in developing an automatic technique for post-NAT tumor response assessment from pathology slides.
Completely labeled pathology datasets are often challenging and time-consuming to obtain. Semi-supervised learning (SSL) methods are able to learn from fewer labeled data points with the help of a large number of unlabeled data points. In this paper, we investigated the possibility of using clustering analysis to identify the underlying structure of the data space for SSL. A cluster-then-label method was proposed to identify high-density regions in the data space which were then used to help a supervised SVM in finding the decision boundary. We have compared our method with other supervised and semi-supervised state-of-the-art techniques using two different classification tasks applied to breast pathology datasets. We found that compared with other state-of-the-art supervised and semi-supervised methods, our SSL method is able to improve classification performance when a limited number of labeled data instances are made available. We also showed that it is important to examine the underlying distribution of the data space before applying SSL techniques to ensure semi-supervised learning assumptions are not violated by the data.
Texture features can be employed to triage clinically important areas within large WSIs.
The residual cancer burden index is an important quantitative measure used for assessing treatment response following neoadjuvant therapy for breast cancer. It has shown to be predictive of overall survival and is composed of two key metrics: qualitative assessment of lymph nodes and the percentage of invasive or in situ tumour cellularity (TC) in the tumour bed (TB). Currently, TC is assessed through eye-balling of routine histopathology slides estimating the proportion of tumour cells within the TB. With the advances in production of digitized slides and increasing availability of slide scanners in pathology laboratories, there is potential to measure TC using automated algorithms with greater precision and accuracy. We describe two methods for automated TC scoring: 1) a traditional approach to image analysis development whereby we mimic the pathologists’ workflow, and 2) a recent development in artificial intelligence in which features are learned automatically in deep neural networks using image data alone. We show strong agreements between automated and manual analysis of digital slides. Agreements between our trained deep neural networks and experts in this study (0.82) approach the inter-rater agreements between pathologists (0.89). We also reveal properties that are captured when we apply deep neural network to whole slide images, and discuss the potential of using such visualisations to improve upon TC assessment in the future.
The authors found properly adjusting the TRUS imaging settings to lower the ultrasound gain and power effectively minimized the appearance of elevation beamwidth artifacts and in turn reduced the localization errors of the needle tip.
Digital pathology has advanced substantially over the last decade however tumor localization continues to be a challenging problem due to highly complex patterns and textures in the underlying tissue bed. The use of convolutional neural networks (CNNs) to analyze such complex images has been well adopted in digital pathology. However in recent years, the architecture of CNNs have altered with the introduction of inception modules which have shown great promise for classification tasks. In this paper, we propose a modified "transition" module which learns global average pooling layers from filters of varying sizes to encourage class-specific filters at multiple spatial resolutions. We demonstrate the performance of the transition module in AlexNet and ZFNet, for classifying breast tumors in two independent datasets of scanned histology sections, of which the transition module was superior.
Purpose: Automatic cell segmentation plays an important role in reliable diagnosis and prognosis of patients. Most of the state-of-the-art cell detection and segmentation techniques focus on complicated methods to subtract foreground cells from the background. In this study, we introduce a preprocessing method which leads to a better detection and segmentation results compared to a well-known state-of-the-art work. Method: We transform the original red-green-blue (RGB) space into a new space defined by the top eigenvectors of the RGB space. Stretching is done by manipulating the contrast of each pixel value to equalize the color variances. New pixel values are then inverse transformed to the original RGB space. This altered RGB image is then used to segment cells. Result: The validation of our method with a well-known state-of-the-art technique revealed a statistically significant improvement on an identical validation set. We achieved a mean F1-score of 0.901. Conclusion: Preprocessing steps to decorrelate colorspaces may improve cell segmentation performances.
Abstract. Purpose: Completely labeled datasets of pathology slides are often difficult and time consuming to obtain. Semi-supervised learning methods are able to learn reliable models from small number of labeled instances and large quantities of unlabeled data. In this paper, we explored the potential of clustering analysis for semi-supervised support vector machine (SVM) classifier. Method: A clustering analysis method was proposed to find regions of high density prior to finding the decision boundary using a supervised SVM and was compared with another state-of-the-art semi-supervised technique. Different percentages of labeled instances were used to train supervised and semi-supervised SVM learners from an image dataset generated from 50 whole-mount images (8 patients) of breast specimen. Their cross-validated classification performances were compared with each other using the area under the ROC curve measure. Result: Our proposed clustering analysis for semisupervised learning was able to produce a reliable classification model from small amounts of labeled data. Comparing the proposed method in this study with a well-known implementation of semi-supervised SVM, our method performed much faster and produced better results.
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