Histo-pathological diagnostics are an inherent part of the everyday work but are particularly laborious and associated with time-consuming manual analysis of image data. In order to cope with the increasing diagnostic case numbers due to the current growth and demographic change of the global population and the progress in personalized medicine, pathologists ask for assistance. Profiting from digital pathology and the use of artificial intelligence, individual solutions can be offered (e.g. detect labeled cancer tissue sections). The testing of the human epidermal growth factor receptor 2 (HER2) oncogene amplification status via fluorescence in situ hybridization (FISH) is recommended for breast and gastric cancer diagnostics and is regularly performed at clinics. Here, we develop an interpretable, deep learning (DL)-based pipeline which automates the evaluation of FISH images with respect to HER2 gene amplification testing. It mimics the pathological assessment and relies on the detection and localization of interphase nuclei based on instance segmentation networks. Furthermore, it localizes and classifies fluorescence signals within each nucleus with the help of image classification and object detection convolutional neural networks (CNNs). Finally, the pipeline classifies the whole image regarding its HER2 amplification status. The visualization of pixels on which the networks' decision occurs, complements an essential part to enable interpretability by pathologists.
Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Multi-parametric magnetic resonance (mpMR) imaging has emerged as a non-invasive diagnostic tool for detecting and localising prostate tumours by specialised radiologists. These radiological examinations, for example, for differentiating malignant lesions from benign prostatic hyperplasia in transition zones and for defining the boundaries of clinically significant cancer, remain challenging and highly skill-and-experience-dependent. We first investigate experimental results in developing object detection neural networks that are trained to predict the radiological assessment, using these high-variance labels. We further argue that such a computer-assisted diagnosis (CAD) system needs to have the ability to control the false-positive rate (FPR) or false-negative rate (FNR), in order to be usefully deployed in a clinical workflow, informing clinical decisions without further human intervention. This work proposes a novel PCa detection network that incorporates a lesion-level cost-sensitive loss and an additional slice-level loss based on a lesion-to-slice mapping function, to manage the lesion- and slice-level costs, respectively. Our experiments based on 290 clinical patients concludes that 1) The lesion-level FNR was effectively reduced from 0.19 to 0.10 and the lesion-level FPR was reduced from 1.03 to 0.66 by changing the lesion-level cost; 2) The slice-level FNR was reduced from 0.19 to 0.00 by taking into account the slice-level cost; (3) Both lesion-level and slice-level FNRs were reduced with lower FP/FPR by changing the lesion-level or slice-level costs, compared with post-training threshold adjustment using networks without the proposed cost-aware training.
Colorectal cancer (CRC) is one of the most common causes of cancer and cancer-related mortality worldwide. Performing colon cancer screening in a timely fashion is the key to early detection. Colonoscopy is the primary modality used to diagnose colon cancer. However, the miss rate of polyps, adenomas and advanced adenomas remains significantly high. Early detection of polyps at the precancerous stage can help reduce the mortality rate and the economic burden associated with colorectal cancer. Deep learning-based computer-aided diagnosis (CADx) system may help gastroenterologists to identify polyps that may otherwise be missed, thereby improving the polyp detection rate. Additionally, CADx system could prove to be a cost-effective system that improves long-term colorectal cancer prevention. In this study, we proposed a deep learning-based architecture for automatic polyp segmentation, called Transformer ResU-Net (TransResU-Net). Our proposed architecture is built upon residual blocks with ResNet-50 as the backbone and takes the advantage of transformer self-attention mechanism as well as dilated convolution(s). Our experimental results on two publicly available polyp segmentation benchmark datasets showed that TransResU-Net obtained a highly promising dice score and a real-time speed. With high efficacy in our performance metrics, we concluded that TransResU-Net could be a strong benchmark for building a real-time polyp detection system for the early diagnosis, treatment, and prevention of colorectal cancer. The source code of the proposed TransResU-Net is publicly available at https://github.com/nikhilroxtomar/TransResUNet.
We present a novel multi-stage 3D computer-aided detection and diagnosis (CAD) model for automated localization of clinically significant prostate cancer (csPCa) in bi-parametric MR imaging (bpMRI). Deep attention mechanisms drive its detection network, targeting multi-resolution, salient structures and highly discriminative feature dimensions, in order to accurately identify csPCa lesions from indolent cancer and the wide range of benign pathology that can afflict the prostate gland. In parallel, a decoupled residual classifier is used to achieve consistent false positive reduction, without sacrificing high sensitivity or computational efficiency. Furthermore, a probabilistic anatomical prior, which captures the spatial prevalence of csPCa as well as its zonal distinction, is computed and encoded into the CNN architecture to guide model generalization with domain-specific clinical knowledge. For 486 institutional testing scans, the 3D CAD system achieves $83.69\pm5.22\%$ and $93.19\pm2.96\%$ detection sensitivity at 0.50 and 1.46 false positive(s) per patient, respectively, along with $0.882$ AUROC in patient-based diagnosis $-$significantly outperforming four state-of-the-art baseline architectures (U-SEResNet, UNet++, nnU-Net, Attention U-Net) from recent literature. For 296 external testing scans, the ensembled CAD system shares moderate agreement with a consensus of expert radiologists ($76.69\%$; $kappa=0.511$) and independent pathologists ($81.08\%$; $kappa=0.559$); demonstrating strong generalization to histologically-confirmed malignancies, despite using 1950 training-validation cases with radiologically-estimated annotations only.
We address the problem of supporting radiologists in the longitudinal management of lung cancer. Therefore, we proposed a deep learning pipeline, composed of four stages that completely automatized from the detection of nodules to the classification of cancer, through the detection of growth in the nodules. In addition, the pipeline integrated a novel approach for nodule growth detection, which relied on a recent hierarchical probabilistic U-Net adapted to report uncertainty estimates. Also, a second novel method was introduced for lung cancer nodule classification, integrating into a two stream 3D-CNN network the estimated nodule malignancy probabilities derived from a pretrained nodule malignancy network. The pipeline was evaluated in a longitudinal cohort and reported comparable performances to the state of art.
Early detection of pulmonary cancer is the most promising way to enhance a patient's chance for survival. Accurate pulmonary nodule detection in computed tomography (CT) images is a crucial step in diagnosing pulmonary cancer. In this paper, inspired by the successful use of deep convolutional neural networks (DCNNs) in natural image recognition, we propose a novel pulmonary nodule detection approach based on DCNNs. We first introduce a deconvolutional structure to Faster Region-based Convolutional Neural Network (Faster R-CNN) for candidate detection on axial slices. Then, a three-dimensional DCNN is presented for the subsequent false positive reduction. Experimental results of the LUng Nodule Analysis 2016 (LUNA16) Challenge demonstrate the superior detection performance of the proposed approach on nodule detection(average FROC-score of 0.891, ranking the 1st place over all submitted results).
Purpose: Colorectal cancer (CRC) is the second most common cause of cancer mortality worldwide. Colonoscopy is a widely used technique for colon screening and polyp lesions diagnosis. Nevertheless, manual screening using colonoscopy suffers from a substantial miss rate of polyps and is an overwhelming burden for endoscopists. Computer-aided diagnosis (CAD) for polyp detection has the potential to reduce human error and human burden. However, current polyp detection methods based on object detection framework need many handcrafted pre-processing and post-processing operations or user guidance that require domain-specific knowledge. Methods: In this paper, we propose a convolution in transformer (COTR) network for end-to-end polyp detection. Motivated by the detection transformer (DETR), COTR is constituted by a CNN for feature extraction, transformer encoder layers interleaved with convolutional layers for feature encoding and recalibration, transformer decoder layers for object querying, and a feed-forward network for detection prediction. Considering the slow convergence of DETR, COTR embeds convolution layers into transformer encoder for feature reconstruction and convergence acceleration. Results: Experimental results on two public polyp datasets show that COTR achieved 91.49\% precision, 82.69% sensitivity, and 86.87% F1-score on the ETIS-LARIB, and 91.67% precision, 93.54% sensitivity, and 92.60% F1-score on the CVC-ColonDB. Conclusion: This study proposed an end to end detection method based on detection transformer for colorectal polyp detection. Experimental results on ETIS-LARIB and CVC-ColonDB dataset demonstrated that the proposed model achieved comparable performance against state-of-the-art methods.
Prostate cancer is among the most common cancer in males and its heterogeneity is well known. Its early detection helps making therapeutic decision. There is no standard technique or procedure yet which is full-proof in predicting cancer class. The genomic level changes can be detected in gene expression data and those changes may serve as standard model for any random cancer data for class prediction. Various techniques were implied on prostate cancer data set in order to accurately predict cancer class including machine learning techniques. Huge number of attributes and few number of sample in microarray data leads to poor machine learning, therefore the most challenging part is attribute reduction or non significant gene reduction. In this work we have compared several machine learning techniques for their accuracy in predicting the cancer class. Machine learning is effective when number of attributes (genes) are larger than the number of samples which is rarely possible with gene expression data. Attribute reduction or gene filtering is absolutely required in order to make the data more meaningful as most of the genes do not participate in tumor development and are irrelevant for cancer prediction. Here we have applied combination of statistical techniques such as inter-quartile range and t-test, which has been effective in filtering significant genes and minimizing noise from data. Further we have done a comprehensive evaluation of ten state-of-the-art machine learning techniques for their accuracy in class prediction of prostate cancer. Out of these techniques, Bayes Network out performed with an accuracy of 94.11% followed by Navie Bayes with an accuracy of 91.17%. To cross validate our results, we modified our training dataset in six different way and found that average sensitivity, specificity, precision and accuracy of Bayes Network is highest among all other techniques used.
Computer-aided detection systems based on deep learning have shown great potential in breast cancer detection. However, the lack of domain generalization of artificial neural networks is an important obstacle to their deployment in changing clinical environments. In this work, we explore the domain generalization of deep learning methods for mass detection in digital mammography and analyze in-depth the sources of domain shift in a large-scale multi-center setting. To this end, we compare the performance of eight state-of-the-art detection methods, including Transformer-based models, trained in a single domain and tested in five unseen domains. Moreover, a single-source mass detection training pipeline is designed to improve the domain generalization without requiring images from the new domain. The results show that our workflow generalizes better than state-of-the-art transfer learning-based approaches in four out of five domains while reducing the domain shift caused by the different acquisition protocols and scanner manufacturers. Subsequently, an extensive analysis is performed to identify the covariate shifts with bigger effects on the detection performance, such as due to differences in patient age, breast density, mass size, and mass malignancy. Ultimately, this comprehensive study provides key insights and best practices for future research on domain generalization in deep learning-based breast cancer detection.
Lung cancer is the leading cause of cancer death worldwide with early detection being the key to a positive patient prognosis. Although a multitude of studies have demonstrated that machine learning, and particularly deep learning, techniques are effective at automatically diagnosing lung cancer, these techniques have yet to be clinically approved and adopted by the medical community. Most research in this field is focused on the narrow task of nodule detection to provide an artificial radiological second reading. We instead focus on extracting, from chest X-ray images, a wider range of pathologies associated with lung cancer using a computer vision model trained on a large dataset. We then find the set of best fit decision trees against an independent, smaller dataset for which lung cancer malignancy metadata is provided. For this small inferencing dataset, our best model achieves sensitivity and specificity of 85% and 75% respectively with a positive predictive value of 85% which is comparable to the performance of human radiologists. Furthermore, the decision trees created by this method may be considered as a starting point for refinement by medical experts into clinically usable multi-variate lung cancer scoring and diagnostic models.