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Register a new userPathologist-level classification of histologic patterns on resected lung adenocarcinoma slides with deep neural networks
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Jason Wei
Publication date
2019
fields
Informatics Engineering
and research's language is
English
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Classification of histologic patterns in lung adenocarcinoma is critical for determining tumor grade and treatment for patients. However, this task is often challenging due to the heterogeneous nature of lung adenocarcinoma and the subjective criteria for evaluation. In this study, we propose a deep learning model that automatically classifies the histologic patterns of lung adenocarcinoma on surgical resection slides. Our model uses a convolutional neural network to identify regions of neoplastic cells, then aggregates those classifications to infer predominant and minor histologic patterns for any given whole-slide image. We evaluated our model on an independent set of 143 whole-slide images. It achieved a kappa score of 0.525 and an agreement of 66.6% with three pathologists for classifying the predominant patterns, slightly higher than the inter-pathologist kappa score of 0.485 and agreement of 62.7% on this test set. All evaluation metrics for our model and the three pathologists were within 95% confidence intervals of agreement. If confirmed in clinical practice, our model can assist pathologists in improving classification of lung adenocarcinoma patterns by automatically pre-screening and highlighting cancerous regions prior to review. Our approach can be generalized to any whole-slide image classification task, and code is made publicly available at https://github.com/BMIRDS/deepslide.
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Renal cell carcinoma (RCC) is the most common renal cancer in adults. The histopathologic classification of RCC is essential for diagnosis, prognosis, and management of patients. Reorganization and classification of complex histologic patterns of RCC on biopsy and surgical resection slides under a microscope remains a heavily specialized, error-prone, and time-consuming task for pathologists. In this study, we developed a deep neural network model that can accurately classify digitized surgical resection slides and biopsy slides into five related classes: clear cell RCC, papillary RCC, chromophobe RCC, renal oncocytoma, and normal. In addition to the whole-slide classification pipeline, we visualized the identified indicative regions and features on slides for classification by reprocessing patch-level classification results to ensure the explainability of our diagnostic model. We evaluated our model on independent test sets of 78 surgical resection whole slides and 79 biopsy slides from our tertiary medical institution, and 69 randomly selected surgical resection slides from The Cancer Genome Atlas (TCGA) database. The average area under the curve (AUC) of our classifier on the internal resection slides, internal biopsy slides, and external TCGA slides is 0.98, 0.98 and 0.99, respectively. Our results suggest that the high generalizability of our approach across different data sources and specimen types. More importantly, our model has the potential to assist pathologists by (1) automatically pre-screening slides to reduce false-negative cases, (2) highlighting regions of importance on digitized slides to accelerate diagnosis, and (3) providing objective and accurate diagnosis as the second opinion.
The goal of this paper is to analyze the geometric properties of deep neural network classifiers in the input space. We specifically study the topology of classification regions created by deep networks, as well as their associated decision boundary. Through a systematic empirical investigation, we show that state-of-the-art deep nets learn connected classification regions, and that the decision boundary in the vicinity of datapoints is flat along most directions. We further draw an essential connection between two seemingly unrelated properties of deep networks: their sensitivity to additive perturbations in the inputs, and the curvature of their decision boundary. The directions where the decision boundary is curved in fact remarkably characterize the directions to which the classifier is the most vulnerable. We finally leverage a fundamental asymmetry in the curvature of the decision boundary of deep nets, and propose a method to discriminate between original images, and images perturbed with small adversarial examples. We show the effectiveness of this purely geometric approach for detecting small adversarial perturbations in images, and for recovering the labels of perturbed images.
Histological classification of colorectal polyps plays a critical role in both screening for colorectal cancer and care of affected patients. An accurate and automated algorithm for the classification of colorectal polyps on digitized histopathology slides could benefit clinicians and patients. Evaluate the performance and assess the generalizability of a deep neural network for colorectal polyp classification on histopathology slide images using a multi-institutional dataset. In this study, we developed a deep neural network for classification of four major colorectal polyp types, tubular adenoma, tubulovillous/villous adenoma, hyperplastic polyp, and sessile serrated adenoma, based on digitized histopathology slides from our institution, Dartmouth-Hitchcock Medical Center (DHMC), in New Hampshire. We evaluated the deep neural network on an internal dataset of 157 histopathology slide images from DHMC, as well as on an external dataset of 238 histopathology slide images from 24 different institutions spanning 13 states in the United States. We measured accuracy, sensitivity, and specificity of our model in this evaluation and compared its performance to local pathologists diagnoses at the point-of-care retrieved from corresponding pathology laboratories. For the internal evaluation, the deep neural network had a mean accuracy of 93.5% (95% CI 89.6%-97.4%), compared with local pathologists accuracy of 91.4% (95% CI 87.0%-95.8%). On the external test set, the deep neural network achieved an accuracy of 87.0% (95% CI 82.7%-91.3%), comparable with local pathologists accuracy of 86.6% (95% CI 82.3%-90.9%). If confirmed in clinical settings, our model could assist pathologists by improving the diagnostic efficiency, reproducibility, and accuracy of colorectal cancer screenings.
Background: An increasing volume of prostate biopsies and a world-wide shortage of uro-pathologists puts a strain on pathology departments. Additionally, the high intra- and inter-observer variability in grading can result in over- and undertreatment of prostate cancer. Artificial intelligence (AI) methods may alleviate these problems by assisting pathologists to reduce workload and harmonize grading. Methods: We digitized 6,682 needle biopsies from 976 participants in the population based STHLM3 diagnostic study to train deep neural networks for assessing prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test set comprising 1,631 biopsies from 245 men. We additionally evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics (ROC) and tumor extent predictions by correlating predicted millimeter cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI and the expert urological pathologists using Cohens kappa. Results: The performance of the AI to detect and grade cancer in prostate needle biopsy samples was comparable to that of international experts in prostate pathology. The AI achieved an area under the ROC curve of 0.997 for distinguishing between benign and malignant biopsy cores, and 0.999 for distinguishing between men with or without prostate cancer. The correlation between millimeter cancer predicted by the AI and assigned by the reporting pathologist was 0.96. For assigning Gleason grades, the AI achieved an average pairwise kappa of 0.62. This was within the range of the corresponding values for the expert pathologists (0.60 to 0.73).
We introduce QuasarNET, a deep convolutional neural network that performs classification and redshift estimation of astrophysical spectra with human-expert accuracy. We pose these two tasks as a emph{feature detection} problem: presence or absence of spectral features determines the class, and their wavelength determines the redshift, very much like human-experts proceed. When ran on BOSS data to identify quasars through their emission lines, QuasarNET defines a sample $99.51pm0.03$% pure and $99.52pm0.03$% complete, well above the requirements of many analyses using these data. QuasarNET significantly reduces the problem of line-confusion that induces catastrophic redshift failures to below 0.2%. We also extend QuasarNET to classify spectra with broad absorption line (BAL) features, achieving an accuracy of $98.0pm0.4$% for recognizing BAL and $97.0pm0.2$% for rejecting non-BAL quasars. QuasarNET is trained on data of low signal-to-noise and medium resolution, typical of current and future astrophysical surveys, and could be easily applied to classify spectra from current and upcoming surveys such as eBOSS, DESI and 4MOST.
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