NaroNet: Discovery of tumor microenvironment elements from highly multiplexed images

Journal Article · 13 February 2022 · Medical Image Analysis

DOI: https://doi.org/10.1016/j.media.2022.102384 · OSTI ID:2470829

Jiménez-Sánchez, Daniel ^[1]; Ariz, Mikel  ^[2]; Chang, Hang ^[3]; Matias-Guiu, Xavier ^[4]; de Andrea, Carlos E. ^[2]; Ortiz-de-Solórzano, Carlos  ^[2]

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1. University of Navarra, Pamplona (Spain); Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
2. University of Navarra, Pamplona (Spain)
3. Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
4. Universities of Lleida and Barcelona (Spain)

Understanding the spatial interactions between the elements of the tumor microenvironment -i.e. tumor cells. fibroblasts, immune cells- and how these interactions relate to the diagnosis or prognosis of a tumor is one of the goals of computational pathology. We present NaroNet, a deep learning framework that models the multi-scale tumor microenvironment from multiplex-stained cancer tissue images and provides patient-level interpretable predictions using a seamless end-to-end learning pipeline. Trained only with multiplex-stained tissue images and their corresponding patient-level clinical labels, NaroNet unsupervisedly learns which cell phenotypes, cell neighborhoods, and neighborhood interactions have the highest influence to predict the correct label. To this end, NaroNet incorporates several novel and state-of-the-art deep learning techniques, such as patch-level contrastive learning, multi-level graph embeddings, a novel max-sum pooling operation, or a metric that quantifies the relevance that each microenvironment element has in the individual predictions. We validate NaroNet using synthetic data simulating multiplex-immunostained images where a patient label is artificially associated to the -adjustable- probabilistic incidence of different microenvironment elements. We then apply our model to two sets of images of human cancer tissues: 336 seven-color multiplex-immunostained images from 12 high-grade endometrial cancer patients; and 382 35-plex mass cytometry images from 215 breast cancer patients. In both synthetic and real datasets, NaroNet provides outstanding predictions of relevant clinical information while associating those predictions to the presence of specific microenvironment elements.

• Research Organization: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
• Sponsoring Organization: National Institutes of Health (NIH); Spanish Ministry of Science, Innovation and Universities; USDOE
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 2470829
• Journal Information: Medical Image Analysis, Journal Name: Medical Image Analysis Vol. 78; ISSN 1361-8415
• Publisher: ElsevierCopyright Statement
• Country of Publication: United States
• Language: English