Significance: Circulating tumor cells (CTCs) are important biomarkers for cancer management. Isolated CTCs from blood are stained to detect and enumerate CTCs. However, the staining process is laborious and moreover makes CTCs unsuitable for drug testing and molecular characterization.
Aim: The goal is to develop and test deep learning (DL) approaches to detect unstained breast cancer cells in bright-field microscopy images that contain white blood cells (WBCs).
Approach: We tested two convolutional neural network (CNN) approaches. The first approach allows investigation of the prominent features extracted by CNN to discriminate in vitro cancer cells from WBCs. The second approach is based on faster region-based convolutional neural network (Faster R-CNN).
Results: Both approaches detected cancer cells with higher than 95% sensitivity and 99% specificity with the Faster R-CNN being more efficient and suitable for deployment presenting an improvement of 4% in sensitivity. The distinctive feature that CNN uses for discrimination is cell size, however, in the absence of size difference, the CNN was found to be capable of learning other features. The Faster R-CNN was found to be robust with respect to intensity and contrast image transformations.
Conclusions: CNN-based DL approaches could be potentially applied to detect patient-derived CTCs from images of blood samples.
KEYWORDS: Image segmentation, Blood, Image processing algorithms and systems, Detection and tracking algorithms, Principal component analysis, Image processing, Medical research, RGB color model
Automated image analysis of slides of thin blood smears can assist with early diagnosis of many diseases. Automated detection and segmentation of red blood cells (RBCs) are prerequisites for any subsequent quantitative highthroughput screening analysis since the manual characterization of the cells is a time-consuming and error-prone task. Overlapping cell regions introduce considerable challenges to detection and segmentation techniques. We propose a novel algorithm that can successfully detect and segment overlapping cells in microscopic images of stained thin blood smears. The algorithm consists of three steps. In the first step, the input image is binarized to obtain the binary mask of the image. The second step accomplishes a reliable cell center localization that utilizes adaptive meanshift clustering. We employ a novel technique to choose an appropriate bandwidth for the meanshift algorithm. In the third step, the cell segmentation purpose is fulfilled by estimating the boundary of each cell through employing a Gradient Vector Flow (GVF) driven snake algorithm. We compare the experimental results of our methodology with the state-of-the-art and evaluate the performance of the cell segmentation results with those produced manually. The method is systematically tested on a dataset acquired at the Chittagong Medical College Hospital in Bangladesh. The overall evaluation of the proposed cell segmentation method based on a one-to-one cell matching on the aforementioned dataset resulted in 98% precision, 93% recall, and 95% F1-score index.
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