Celiac Disease (CD) and Environmental Enteropathy (EE) are common causes of malnutrition and adversely impact normal childhood development. CD is an autoimmune disorder that is prevalent worldwide and is caused by an increased sensitivity to gluten. Gluten exposure destructs the small intestinal epithelial barrier, resulting in nutrient mal-absorption and childhood under-nutrition. EE also results in barrier dysfunction but is thought to be caused by an increased vulnerability to infections. EE has been implicated as the predominant cause of under-nutrition, oral vaccine failure, and impaired cognitive development in low-and-middle-income countries. Both conditions require a tissue biopsy for diagnosis, and a major challenge of interpreting clinical biopsy images to differentiate between these gastrointestinal diseases is striking histopathologic overlap between them. In the current study, we propose a convolutional neural network (CNN) to classify duodenal biopsy images from subjects with CD, EE, and healthy controls. We evaluated the performance of our proposed model using a large cohort containing 1000 biopsy images. Our evaluations show that the proposed model achieves an area under ROC of 0.99, 1.00, and 0.97 for CD, EE, and healthy controls, respectively. These results demonstrate the discriminative power of the proposed model in duodenal biopsies classification.
Ström, Peter, Kartasalo, Kimmo, Olsson, Henrik, Solorzano, Leslie, Delahunt, Brett, Berney, Daniel M., Bostwick, David G., Evans, Andrew J., Grignon, David J., Humphrey, Peter A., Iczkowski, Kenneth A., Kench, James G., Kristiansen, Glen, van der Kwast, Theodorus H., Leite, Katia R. M., McKenney, Jesse K., Oxley, Jon, Pan, Chin-Chen, Samaratunga, Hemamali, Srigley, John R., Takahashi, Hiroyuki, Tsuzuki, Toyonori, Varma, Murali, Zhou, Ming, Lindberg, Johan, Bergström, Cecilia, Ruusuvuori, Pekka, Wählby, Carolina, Grönberg, Henrik, Rantalainen, Mattias, Egevad, Lars, Eklund, Martin
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 Cohen's 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).
Empirical evaluation of breast tissue biopsies for mitotic nuclei detection is considered an important prognostic biomarker in tumor grading and cancer progression. However, automated mitotic nuclei detection poses several challenges because of the unavailability of pixel-level annotations, different morphological configurations of mitotic nuclei, their sparse representation, and close resemblance with non-mitotic nuclei. These challenges undermine the precision of the automated detection model and thus make detection difficult in a single phase. This work proposes an end-to-end detection system for mitotic nuclei identification in breast cancer histopathological images. Deep object detection-based Mask R-CNN is adapted for mitotic nuclei detection that initially selects the candidate mitotic region with maximum recall. However, in the second phase, these candidate regions are refined by multi-object loss function to improve the precision. The performance of the proposed detection model shows improved discrimination ability (F-score of 0.86) for mitotic nuclei with significant precision (0.86) as compared to the two-stage detection models (F-score of 0.701) on TUPAC16 dataset. Promising results suggest that the deep object detection-based model has the potential to learn the characteristic features of mitotic nuclei from weakly annotated data and suggests that it can be adapted for the identification of other nuclear bodies in histopathological images.
Histopathology tissue samples are widely available in two states: paraffin-embedded unstained and non-paraffin-embedded stained whole slide RGB images (WSRI). Hematoxylin and eosin stain (H&E) is one of the principal stains in histology but suffers from several shortcomings related to tissue preparation, staining protocols, slowness and human error. We report two novel approaches for training machine learning models for the computational H&E staining and destaining of prostate core biopsy RGB images. The staining model uses a conditional generative adversarial network that learns hierarchical non-linear mappings between whole slide RGB image (WSRI) pairs of prostate core biopsy before and after H&E staining. The trained staining model can then generate computationally H&E-stained prostate core WSRIs using previously unseen non-stained biopsy images as input. The destaining model, by learning mappings between an H&E stained WSRI and a non-stained WSRI of the same biopsy, can computationally destain previously unseen H&E-stained images. Structural and anatomical details of prostate tissue and colors, shapes, geometries, locations of nuclei, stroma, vessels, glands and other cellular components were generated by both models with structural similarity indices of 0.68 (staining) and 0.84 (destaining). The proposed staining and destaining models can engender computational H&E staining and destaining of WSRI biopsies without additional equipment and devices.
Analysis of histopathology slides is a critical step for many diagnoses, and in particular in oncology where it defines the gold standard. In the case of digital histopathological analysis, highly trained pathologists must review vast whole-slide-images of extreme digital resolution ($100,000^2$ pixels) across multiple zoom levels in order to locate abnormal regions of cells, or in some cases single cells, out of millions. The application of deep learning to this problem is hampered not only by small sample sizes, as typical datasets contain only a few hundred samples, but also by the generation of ground-truth localized annotations for training interpretable classification and segmentation models. We propose a method for disease localization in the context of weakly supervised learning, where only image-level labels are available during training. Even without pixel-level annotations, we are able to demonstrate performance comparable with models trained with strong annotations on the Camelyon-16 lymph node metastases detection challenge. We accomplish this through the use of pre-trained deep convolutional networks, feature embedding, as well as learning via top instances and negative evidence, a multiple instance learning technique from the field of semantic segmentation and object detection.