Thermography has been used extensively as a complementary diagnostic tool in breast cancer detection. Among thermographic methods matrix factorization (MF) techniques show an unequivocal capability to detect thermal patterns corresponding to vasodilation in cancer cases. One of the biggest challenges in such techniques is selecting the best representation of the thermal basis. In this study, an embedding method is proposed to address this problem and Deep-semi-nonnegative matrix factorization (Deep-SemiNMF) for thermography is introduced, then tested for 208 breast cancer screening cases. First, we apply Deep-SemiNMF to infrared images to extract low-rank thermal representations for each case. Then, we embed low-rank bases to obtain one basis for each patient. After that, we extract 300 thermal imaging features, called thermomics, to decode imaging information for the automatic diagnostic model. We reduced the dimensionality of thermomics by spanning them onto Hilbert space using RBF kernel and select the three most efficient features using the block Hilbert Schmidt Independence Criterion Lasso (block HSIC Lasso). The preserved thermal heterogeneity successfully classified asymptomatic versus symptomatic patients applying a random forest model (cross-validated accuracy of 71.36% (69.42%-73.3%)).
Finding and identifying scatteredly-distributed, small, and critically important objects in 3D oncology images is very challenging. We focus on the detection and segmentation of oncology-significant (or suspicious cancer metastasized) lymph nodes (OSLNs), which has not been studied before as a computational task. Determining and delineating the spread of OSLNs is essential in defining the corresponding resection/irradiating regions for the downstream workflows of surgical resection and radiotherapy of various cancers. For patients who are treated with radiotherapy, this task is performed by experienced radiation oncologists that involves high-level reasoning on whether LNs are metastasized, which is subject to high inter-observer variations. In this work, we propose a divide-and-conquer decision stratification approach that divides OSLNs into tumor-proximal and tumor-distal categories. This is motivated by the observation that each category has its own different underlying distributions in appearance, size and other characteristics. Two separate detection-by-segmentation networks are trained per category and fused. To further reduce false positives (FP), we present a novel global-local network (GLNet) that combines high-level lesion characteristics with features learned from localized 3D image patches. Our method is evaluated on a dataset of 141 esophageal cancer patients with PET and CT modalities (the largest to-date). Our results significantly improve the recall from $45\%$ to $67\%$ at $3$ FPs per patient as compared to previous state-of-the-art methods. The highest achieved OSLN recall of $0.828$ is clinically relevant and valuable.
The gold standard for gastric cancer detection is gastric histopathological image analysis, but there are certain drawbacks in the existing histopathological detection and diagnosis. In this paper, based on the study of computer aided diagnosis system, graph based features are applied to gastric cancer histopathology microscopic image analysis, and a classifier is used to classify gastric cancer cells from benign cells. Firstly, image segmentation is performed, and after finding the region, cell nuclei are extracted using the k-means method, the minimum spanning tree (MST) is drawn, and graph based features of the MST are extracted. The graph based features are then put into the classifier for classification. In this study, different segmentation methods are compared in the tissue segmentation stage, among which are Level-Set, Otsu thresholding, watershed, SegNet, U-Net and Trans-U-Net segmentation; Graph based features, Red, Green, Blue features, Grey-Level Co-occurrence Matrix features, Histograms of Oriented Gradient features and Local Binary Patterns features are compared in the feature extraction stage; Radial Basis Function (RBF) Support Vector Machine (SVM), Linear SVM, Artificial Neural Network, Random Forests, k-NearestNeighbor, VGG16, and Inception-V3 are compared in the classifier stage. It is found that using U-Net to segment tissue areas, then extracting graph based features, and finally using RBF SVM classifier gives the optimal results with 94.29%.
Dice similarity coefficient (DSC) and Hausdorff distance (HD) are widely used for evaluating medical image segmentation. They have also been criticised, when reported alone, for their unclear or even misleading clinical interpretation. DSCs may also differ substantially from HDs, due to boundary smoothness or multiple regions of interest (ROIs) within a subject. More importantly, either metric can also have a nonlinear, non-monotonic relationship with outcomes based on Type 1 and 2 errors, designed for specific clinical decisions that use the resulting segmentation. Whilst cases causing disagreement between these metrics are not difficult to postulate. This work first proposes a new asymmetric detection metric, adapting those used in object detection, for planning prostate cancer procedures. The lesion-level metrics is then compared with the voxel-level DSC and HD, whereas a 3D UNet is used for segmenting lesions from multiparametric MR (mpMR) images. Based on experimental results we report pairwise agreement and correlation 1) between DSC and HD, and 2) between voxel-level DSC and recall-controlled precision at lesion-level, with Cohen's [0.49, 0.61] and Pearson's [0.66, 0.76] (p-values}<0.001) at varying cut-offs. However, the differences in false-positives and false-negatives, between the actual errors and the perceived counterparts if DSC is used, can be as high as 152 and 154, respectively, out of the 357 test set lesions. We therefore carefully conclude that, despite of the significant correlations, voxel-level metrics such as DSC can misrepresent lesion-level detection accuracy for evaluating localisation of multifocal prostate cancer and should be interpreted with caution.
Whole slide images (WSIs) pose unique challenges when training deep learning models. They are very large which makes it necessary to break each image down into smaller patches for analysis, image features have to be extracted at multiple scales in order to capture both detail and context, and extreme class imbalances may exist. Significant progress has been made in the analysis of these images, thanks largely due to the availability of public annotated datasets. We postulate, however, that even if a method scores well on a challenge task, this success may not translate to good performance in a more clinically relevant workflow. Many datasets consist of image patches which may suffer from data curation bias; other datasets are only labelled at the whole slide level and the lack of annotations across an image may mask erroneous local predictions so long as the final decision is correct. In this paper, we outline the differences between patch or slide-level classification versus methods that need to localize or segment cancer accurately across the whole slide, and we experimentally verify that best practices differ in both cases. We apply a binary cancer detection network on post neoadjuvant therapy breast cancer WSIs to find the tumor bed outlining the extent of cancer, a task which requires sensitivity and precision across the whole slide. We extensively study multiple design choices and their effects on the outcome, including architectures and augmentations. Furthermore, we propose a negative data sampling strategy, which drastically reduces the false positive rate (7% on slide level) and improves each metric pertinent to our problem, with a 15% reduction in the error of tumor extent.
The Gleason scoring system is the primary diagnostic and prognostic tool for prostate cancer. In recent years, with the development of digitisation devices, the use of computer vision techniques for the analysis of biopsies has increased. However, to the best of the authors' knowledge, the development of algorithms to automatically detect individual cribriform patterns belonging to Gleason grade 4 has not yet been studied in the literature. The objective of the work presented in this paper is to develop a deep-learning-based system able to support pathologists in the daily analysis of prostate biopsies. The methodological core of this work is a patch-wise predictive model based on convolutional neural networks able to determine the presence of cancerous patterns. In particular, we train from scratch a simple self-design architecture. The cribriform pattern is detected by retraining the set of filters of the last convolutional layer in the network. From the reconstructed prediction map, we compute the percentage of each Gleason grade in the tissue to feed a multi-layer perceptron which provides a biopsy-level score.mIn our SICAPv2 database, composed of 182 annotated whole slide images, we obtained a Cohen's quadratic kappa of 0.77 in the test set for the patch-level Gleason grading with the proposed architecture trained from scratch. Our results outperform previous ones reported in the literature. Furthermore, this model reaches the level of fine-tuned state-of-the-art architectures in a patient-based four groups cross validation. In the cribriform pattern detection task, we obtained an area under ROC curve of 0.82. Regarding the biopsy Gleason scoring, we achieved a quadratic Cohen's Kappa of 0.81 in the test subset. Shallow CNN architectures trained from scratch outperform current state-of-the-art methods for Gleason grades classification.
Prostate cancer is the most prevalent cancer among men in Western countries, with 1.1 million new diagnoses every year. The gold standard for the diagnosis of prostate cancer is a pathologists' evaluation of prostate tissue. To potentially assist pathologists deep-learning-based cancer detection systems have been developed. Many of the state-of-the-art models are patch-based convolutional neural networks, as the use of entire scanned slides is hampered by memory limitations on accelerator cards. Patch-based systems typically require detailed, pixel-level annotations for effective training. However, such annotations are seldom readily available, in contrast to the clinical reports of pathologists, which contain slide-level labels. As such, developing algorithms which do not require manual pixel-wise annotations, but can learn using only the clinical report would be a significant advancement for the field. In this paper, we propose to use a streaming implementation of convolutional layers, to train a modern CNN (ResNet-34) with 21 million parameters end-to-end on 4712 prostate biopsies. The method enables the use of entire biopsy images at high-resolution directly by reducing the GPU memory requirements by 2.4 TB. We show that modern CNNs, trained using our streaming approach, can extract meaningful features from high-resolution images without additional heuristics, reaching similar performance as state-of-the-art patch-based and multiple-instance learning methods. By circumventing the need for manual annotations, this approach can function as a blueprint for other tasks in histopathological diagnosis. The source code to reproduce the streaming models is available at https://github.com/DIAGNijmegen/pathology-streaming-pipeline .
Analyzing Pap cytology slides is an important tasks in detecting and grading precancerous and cancerous cervical cancer stages. Processing cytology images usually involve segmenting nuclei and overlapping cells. We introduce a cervical cytology dataset that can be used to evaluate nucleus detection, as well as image classification methods in the cytology image processing area. This dataset contains 93 real image stacks with their grade labels and manually annotated nuclei within images. We also present two methods: a baseline method based on a previously proposed approach, and a deep learning method, and compare their results with other state-of-the-art methods. Both the baseline method and the deep learning method outperform other state-of-the-art methods by significant margins. Along with the dataset, we publicly make the evaluation code and the baseline method available to download for further benchmarking.
Screening mammography improves breast cancer outcomes by enabling early detection and treatment. However, false positive callbacks for additional imaging from screening exams cause unnecessary procedures, patient anxiety, and financial burden. This work demonstrates an AI algorithm that reduces false positives by identifying mammograms not suspicious for breast cancer. We trained the algorithm to determine the absence of cancer using 123,248 2D digital mammograms (6,161 cancers) and performed a retrospective study on 14,831 screening exams (1,026 cancers) from 15 US and 3 UK sites. Retrospective evaluation of the algorithm on the largest of the US sites (11,592 mammograms, 101 cancers) a) left the cancer detection rate unaffected (p=0.02, non-inferiority margin 0.25 cancers per 1000 exams), b) reduced callbacks for diagnostic exams by 31.1% compared to standard clinical readings, c) reduced benign needle biopsies by 7.4%, and d) reduced screening exams requiring radiologist interpretation by 41.6% in the simulated clinical workflow. This work lays the foundation for semi-autonomous breast cancer screening systems that could benefit patients and healthcare systems by reducing false positives, unnecessary procedures, patient anxiety, and expenses.
Melanoma is one of the ten most common cancers in the US. Early detection is crucial for survival, but often the cancer is diagnosed in the fatal stage. Deep learning has the potential to improve cancer detection rates, but its applicability to melanoma detection is compromised by the limitations of the available skin lesion databases, which are small, heavily imbalanced, and contain images with occlusions. We propose a complete deep learning system for lesion segmentation and classification that utilizes networks specialized in data purification and augmentation. It contains the processing unit for removing image occlusions and the data generation unit for populating scarce lesion classes, or equivalently creating virtual patients with pre-defined types of lesions. We empirically verify our approach and show superior performance over common baselines.
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