Breast cancer is one of the main causes of death worldwide. Histopathological cellularity assessment of residual tumors in post-surgical tissues is used to analyze a tumor's response to a therapy. Correct cellularity assessment increases the chances of getting an appropriate treatment and facilitates the patient's survival. In current clinical practice, tumor cellularity is manually estimated by pathologists; this process is tedious and prone to errors or low agreement rates between assessors. In this work, we evaluated three strong novel Deep Learning-based approaches for automatic assessment of tumor cellularity from post-treated breast surgical specimens stained with hematoxylin and eosin. We validated the proposed methods on the BreastPathQ SPIE challenge dataset that consisted of 2395 image patches selected from whole slide images acquired from 64 patients. Compared to expert pathologist scoring, our best performing method yielded the Cohen's kappa coefficient of 0.70 (vs. 0.42 previously known in literature) and the intra-class correlation coefficient of 0.89 (vs. 0.83). Our results suggest that Deep Learning-based methods have a significant potential to alleviate the burden on pathologists, enhance the diagnostic workflow, and, thereby, facilitate better clinical outcomes in breast cancer treatment.
The conventional approach most relevant to our work is by Peikari @cite_21 who proposed an automated cellularity assesement protocol. First, they used smaller patches, or regions of interest (RoI), extracted from whole slide images to segment all present cell nuclei. Then they extracted a number of predefined features from segmented nuclei and used support vector machines to distinguish lymphocytes and normal epithelial nuclei from malignant ones. Cellularity estimation was done using distinguished malignant epithelial figures for every RoI.
@cite_21
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Background Automated segmentation of fluorescently-labeled cell nuclei in 3D confocal microscope images is essential to many studies involving morphological and functional analysis. A common source of segmentation error is tight clustering of nuclei. There is a compelling need to minimize these errors for constructing highly automated scoring systems. Methods A combination of two approaches is presented. First, an improved distance transform combining intensity gradients and geometric distance is used for the watershed step. Second, an explicit mathematical model for the anatomic characteristics of cell nuclei such as size and shape measures is incorporated. This model is constructed automatically from the data. Deliberate initial over-segmentation of the image data is performed, followed by statistical model-based merging. A confidence score is computed for each detected nucleus, measuring how well the nucleus fits the model. This is used in combination with the intensity gradient to control the merge decisions. Results Experimental validation on a set of rodent brain cell images showed 97 concordance with the human observer and significant improvement over prior methods. Conclusions Combining a gradient-weighted distance transform with a richer morphometric model significantly improves the accuracy of automated segmentation and FISH analysis. Cytometry Part A 56A:23–36, 2003. © 2003 Wiley-Liss, Inc. It is important to observe and study cancer cells' cycle progression in order to better understand drug effects on cancer cells. Time-lapse microscopy imaging serves as an important method to measure the cycle progression of individual cells in a large population. Since manual analysis is unreasonably time consuming for the large volumes of time-lapse image data, automated image analysis is proposed. Existing approaches dealing with time-lapse image data are rather limited and often give inaccurate analysis results, especially in segmenting and tracking individual cells in a cell population. In this paper, we present a new approach to segment and track cell nuclei in time-lapse fluorescence image sequence. First, we propose a novel marker-controlled watershed based on mathematical morphology, which can effectively segment clustered cells with less oversegmentation. To further segment undersegmented cells or to merge oversegmented cells, context information among neighboring frames is employed, which is proved to be an effective strategy. Then, we design a tracking method based on modified mean shift algorithm, in which several kernels with adaptive scale, shape, and direction are designed. Finally, we combine mean-shift and Kalman filter to achieve a more robust cell nuclei tracking method than existing ones. Experimental results show that our method can obtain 98.8 segmentation accuracy, 97.4 cell division tracking accuracy, and 97.6 cell tracking accuracy The residual cancer burden index is a powerful prognostic factor which is used to measure neoadjuvant therapy response in invasive breast cancers. Tumor cellularity is one component of the residual cancer burden index and is currently measured manually through eyeballing. As such it is subject to inter- and intra-variability and is currently restricted to discrete values. We propose a method for automatically determining tumor cellularity in digital slides using deep learning techniques. We train a series of ResNet architectures to output both discrete and continuous values and compare our outcomes with scores acquired manually by an expert pathologist. Our configurations were validated on a dataset of image patches extracted from digital slides, each containing various degrees of tumor cellularity. Results showed that, in the case of discrete values, our models were able to distinguish between regions-of-interest containing tumor and healthy cells with over 97 test accuracy rates. Overall, we achieved 76 accuracy over four predefined tumor cellularity classes (no tumor tumor; low, medium and high tumor cellularity). When computing tumor cellularity scores on a continuous scale, ResNet showed good correlations with manually-identified scores, showing potential for computing reproducible scores consistent with expert opinion using deep learning techniques. 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. © 2017 International Society for Advancement of Cytometry.