A Hybrid Intelligence Approach for Circulating Tumor Cell Enumeration in Digital Pathology by Using CNN and Weak Annotations

Counting the number of Circulating Tumor Cells (CTCs) for cancer screenings is currently done by cytopathologists with a heavy time and energy cost. AI, especially deep learning, has shown great potential in medical imaging domains. The aim of this paper is to develop a novel hybrid intelligence approach to automatically enumerate CTCs by combining cytopathologist expertise with the efficiency of deep learning convolutional neural networks (CNNs). This hybrid intelligence approach includes three major components: CNN based CTC detection/localization using weak annotations, CNN based CTC segmentation, and a classifier to ultimately determine CTCs. A support vector machine (SVM) was investigated for classification efficiency. The B-scale transform was also introduced to find the maximum sphericality of a given region. The SVM classifier was implemented to use a three-element vector as its input, including the B-scale (size), texture, and area values from the detection and segmentation results. We collected 466 fluoroscopic images for CTC detection/localization, 473 images for CTC segmentation and another 198 images with 323 CTCs as an independent data set for CTC enumeration. Precision and recall for CTC detection are 0.98 and 0.92, which is comparable with the state-of-the-art results that needed much larger and stricter training data sets. The counting error on an independent testing set was 2-3% and 9% (with/without B-scale) and performs much better than previous thresholding approaches with 30% of counting error rates. Recent publications prove facilitation of other types of research in object localization and segmentation are necessary.