Physicians use biopsies to distinguish between different but histologically similar enteropathies. The range of syndromes and pathologies that could cause different gastrointestinal conditions makes this a difficult problem. Recently, deep learning has been used successfully in helping diagnose cancerous tissues in histopathological images. These successes motivated the research presented in this paper, which describes a deep learning approach that distinguishes between Celiac Disease (CD) and Environmental Enteropathy (EE) and normal tissue from digitized duodenal biopsies. Experimental results show accuracies of over 90% for this approach. We also look into interpreting the neural network model using Gradientweighted Class Activation Mappings and filter activations on input images to understand the visual explanations for the decisions made by the model.

Objectives: Striking histopathological overlap between distinct but related conditions poses a disease diagnostic challenge. There is a major clinical need to develop computational methods enabling clinicians to translate heterogeneous biomedical images into accurate and quantitative diagnostics. This need is particularly salient with small bowel enteropathies; environmental enteropathy (EE) and celiac disease (CD). We built upon our preliminary analysis by developing an artificial intelligence (AI)-based image analysis platform utilizing deep learning convolutional neural networks (CNNs) for these enteropathies. Methods: Data for the secondary analysis was obtained from three primary studies at different sites. The image analysis platform for EE and CD was developed using CNNs including one with multizoom architecture. Gradient-weighted class activation mappings (Grad-CAMs) were used to visualize the models' decision-making process for classifying each disease. A team of medical experts simultaneously reviewed the stain color normalized images done for bias reduction and Grad-CAMs to confirm structural preservation and biomedical relevance, respectively. Results: Four hundred and sixty-one high-resolution biopsy images from 150 children were acquired. Median age (interquartile range) was 37.5 (19.0-121.5) months with a roughly equal sex distribution; 77 males (51.3%). ResNet50 and shallow CNN demonstrated 98% and 96% casedetection accuracy, respectively, which increased to 98.3% with an ensemble. Grad-CAMs demonstrated models' ability to learn different microscopic morphological features for EE, CD, and controls. Conclusions: Our AI-based image analysis platform demonstrated high classification accuracy for small bowel enteropathies which was capable of identifying biologically relevant microscopic features and emulating human pathologist decision-making process. Grad-CAMs illuminated the otherwise ''black box'' of deep learning in medicine, allowing for increased physician confidence in adopting these new technologies in clinical practice.

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Objectives: Striking histopathological overlap between distinct but related conditions poses a significant disease diagnostic challenge. There is a major clinical need to develop computational methods enabling clinicians to translate heterogeneous biomedical images into accurate and quantitative diagnostics. This need is particularly salient with small bowel enteropathies; Environmental Enteropathy (EE) and Celiac Disease (CD). We built upon our preliminary analysis by developing an artificial intelligence (AI)-based image analysis platform utilizing deep learning convolutional neural networks (CNNs) for these enteropathies. Methods: Data for secondary analysis was obtained from three primary studies at different sites. The image analysis platform for EE and CD was developed using convolutional neural networks (CNNs: ResNet and custom Shallow CNN). Gradient-weighted Class Activation Mappings (Grad-CAMs) were used to visualize the decision making process of the models. A team of medical experts simultaneously reviewed the stain color normalized images done for bias reduction and Grad-CAM visualizations to confirm structural preservation and biological relevance, respectively. Results: 461 high-resolution biopsy images from 150 children were acquired. Median age (interquartile range) was 37.5 (19.0 to 121.5) months with a roughly equal sex distribution; 77 males (51.3%). ResNet50 and Shallow CNN demonstrated 98% and 96% case-detection accuracy, respectively, which increased to 98.3% with an ensemble. Grad-CAMs demonstrated ability of the models to learn distinct microscopic morphological features. Conclusion: Our AI-based image analysis platform demonstrated high classification accuracy for small bowel enteropathies which was capable of identifying biologically relevant microscopic features, emulating human pathologist decision making process, performing in the case of suboptimal computational environment, and being modified for improving disease classification accuracy. Grad-CAMs that were employed illuminated the otherwise black box of deep learning in medicine, allowing for increased physician confidence in adopting these new technologies in clinical practice.