Thyroid cancer is the most common cancer in the endocrine system, and papillary thyroid carcinoma (PTC) is the most prevalent type of thyroid cancer, accounting for 70 to 80% of all thyroid cancer cases. In clinical practice, visual inspection of cytopathological slides is an essential initial method used by the pathologist to diagnose PTC. Manual visual assessment of the whole slide images is difficult, time consuming, and subjective, with a high inter-observer variability, which can sometimes lead to suboptimal patient management due to false-positive and false-negative. In this study, we present a fully automatic, efficient, and fast deep learning framework for fast screening of papanicolaou-stained thyroid fine needle aspiration (FNA) and ThinPrep (TP) cytological slides. To the authors’ best of knowledge, this work is the first study to build an automated deep learning framework for identification of PTC from both FNA and TP slides. The proposed deep learning framework is evaluated on a dataset of 131 WSIs, and the results show that the proposed method achieves an accuracy of 99%, precision of 85%, recall of 94% and F1-score of 87% in segmentation of PTC in FNA slides and an accuracy of 99%, precision of 97%, recall of 98%, F1-score of 98%, and Jaccard-Index of 96% in TP slides. In addition, the proposed method significantly outperforms the two state-of-the-art deep learning methods, i.e., U-Net and SegNet, in terms of accuracy, recall, F1-score, and Jaccard-Index (p<0.001). Furthermore, for run-time analysis, the proposed fast screening method takes 0.4 min to process a WSI and is 7.8 times faster than U-Net and 9.1 times faster than SegNet, respectively.
Breast cancer is the leading cause of death for women globally. In clinical practice, pathologists visually scan over enormous amounts of gigapixel microscopic tissue slide images, which is a tedious and challenging task. In breast cancer diagnosis, micro-metastases and especially isolated tumor cells are extremely difficult to detect and are easily neglected because tiny metastatic foci might be missed in visual examinations by medical doctors. However, the literature poorly explores the detection of isolated tumor cells, which could be recognized as a viable marker to determine the prognosis for T1NoMo breast cancer patients. To address these issues, we present a deep learning-based framework for efficient and robust lymph node metastasis segmentation in routinely used histopathological hematoxylin–eosin-stained (H–E) whole-slide images (WSI) in minutes, and a quantitative evaluation is conducted using 188 WSIs, containing 94 pairs of H–E-stained WSIs and immunohistochemical CK(AE1/AE3)-stained WSIs, which are used to produce a reliable and objective reference standard. The quantitative results demonstrate that the proposed method achieves 89.6% precision, 83.8% recall, 84.4% F1-score, and 74.9% mIoU, and that it performs significantly better than eight deep learning approaches, including two recently published models (v3_DCNN and Xception-65), and three variants of Deeplabv3+ with three different backbones, namely, U-Net, SegNet, and FCN, in precision, recall, F1-score, and mIoU (p<0.001). Importantly, the proposed system is shown to be capable of identifying tiny metastatic foci in challenging cases, for which there are high probabilities of misdiagnosis in visual inspection, while the baseline approaches tend to fail in detecting tiny metastatic foci. For computational time comparison, the proposed method takes 2.4 min for processing a WSI utilizing four NVIDIA Geforce GTX 1080Ti GPU cards and 9.6 min using a single NVIDIA Geforce GTX 1080Ti GPU card, and is notably faster than the baseline methods (4-times faster than U-Net and SegNet, 5-times faster than FCN, 2-times faster than the 3 different variants of Deeplabv3+, 1.4-times faster than v3_DCNN, and 41-times faster than Xception-65).
Lung cancer is the biggest cause of cancer-related death worldwide. An accurate nodal staging is critical for the determination of treatment strategy for lung cancer patients. Endobronchial-ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) has revolutionized the field of pulmonology and is considered to be extremely sensitive, specific, and secure for lung cancer staging through rapid on-site evaluation (ROSE), but manual visual inspection on the entire slide of EBUS smears is challenging, time consuming, and worse, subjective, on a large interobserver scale. To satisfy ROSE’s needs, a rapid, automated, and accurate diagnosis system using EBUS-TBNA whole-slide images (WSIs) is highly desired to improve diagnosis accuracy and speed, minimize workload and labor costs, and ensure reproducibility. We present a fast, efficient, and fully automatic deep-convolutional-neural-network-based system for advanced lung cancer staging on gigapixel EBUS-TBNA cytological WSIs. Each WSI was converted into a patch-based hierarchical structure and examined by the proposed deep convolutional neural network, generating the segmentation of metastatic lesions in EBUS-TBNA WSIs. To the best of the authors’ knowledge, this is the first research on fully automated enlarged mediastinal lymph node analysis using EBUS-TBNA cytological WSIs. We evaluated the robustness of the proposed framework on a dataset of 122 WSIs, and the proposed method achieved a high precision of 93.4%, sensitivity of 89.8%, DSC of 82.2%, and IoU of 83.2% for the first experiment (37.7% training and 62.3% testing) and a high precision of 91.8 ± 1.2, sensitivity of 96.3 ± 0.8, DSC of 94.0 ± 1.0, and IoU of 88.7 ± 1.8 for the second experiment using a three-fold cross-validation, respectively. Furthermore, the proposed method significantly outperformed the three state-of-the-art baseline models, including U-Net, SegNet, and FCN, in terms of precision, sensitivity, DSC, and Jaccard index, based on Fisher’s least significant difference (LSD) test (p<0.001). For a computational time comparison on a WSI, the proposed method was 2.5 times faster than U-Net, 2.3 times faster than SegNet, and 3.4 times faster than FCN, using a single GeForce GTX 1080 Ti, respectively. With its high precision and sensitivity, the proposed method demonstrated that it manifested the potential to reduce the workload of pathologists in their routine clinical practice.
Joint analysis of multiple protein expressions and tissue morphology patterns is important for disease diagnosis, treatment planning, and drug development, requiring cross-staining alignment of multiple immunohistochemical and histopathological slides. However, cross-staining alignment of enormous gigapixel whole slide images (WSIs) at single cell precision is difficult. Apart from gigantic data dimensions of WSIs, there are large variations on the cell appearance and tissue morphology across different staining together with morphological deformations caused by slide preparation. The goal of this study is to build an image registration framework for cross-staining alignment of gigapixel WSIs of histopathological and immunohistochemical microscopic slides and assess its clinical applicability. To the authors’ best knowledge, this is the first study to perform real time fully automatic cross staining alignment of WSIs with 40× and 20× objective magnification. The proposed WSI registration framework consists of a rapid global image registration module, a real time interactive field of view (FOV) localization model and a real time propagated multi-level image registration module. In this study, the proposed method is evaluated on two kinds of cancer datasets from two hospitals using different digital scanners, including a dual staining breast cancer data set with 43 hematoxylin and eosin (H&E) WSIs and 43 immunohistochemical (IHC) CK(AE1/AE3) WSIs, and a triple staining prostate cancer data set containing 30 H&E WSIs, 30 IHC CK18 WSIs, and 30 IHC HMCK WSIs. In evaluation, the registration performance is measured by not only registration accuracy but also computational time. The results show that the proposed method achieves high accuracy of 0.833 ± 0.0674 for the triple-staining prostate cancer data set and 0.931 ± 0.0455 for the dual-staining breast cancer data set, respectively, and takes only 4.34 s per WSI registration on average. In addition, for 30.23% data, the proposed method takes less than 1 s for WSI registration. In comparison with the benchmark methods, the proposed method demonstrates superior performance in registration accuracy and computational time, which has great potentials for assisting medical doctors to identify cancerous tissues and determine the cancer stage in clinical practice.
Precision oncology, which ensures optimized cancer treatment tailored to the unique biology of a patient’s disease, has rapidly developed and is of great clinical importance. Deep learning has become the main method for precision oncology. This paper summarizes the recent deep-learning approaches relevant to precision oncology and reviews over 150 articles within the last six years. First, we survey the deep-learning approaches categorized by various precision oncology tasks, including the estimation of dose distribution for treatment planning, survival analysis and risk estimation after treatment, prediction of treatment response, and patient selection for treatment planning. Secondly, we provide an overview of the studies per anatomical area, including the brain, bladder, breast, bone, cervix, esophagus, gastric, head and neck, kidneys, liver, lung, pancreas, pelvis, prostate, and rectum. Finally, we highlight the challenges and discuss potential solutions for future research directions.
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