Yutaka Hatanaka works at Hokkaido University Hospital.

Posts

Evaluating Cellularity Estimation Methods: Comparing AI Counting with Pathologists’ Visual Estimates

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The development of next-generation sequencing (NGS) has enabled the discovery of cancer-specific driver gene alternations, making precision medicine possible. However, accurategenetic testing requires a sufficient amount of tumor cells in the specimen. The evaluation of tumor content ratio (TCR) from hematoxylin and eosin (H&E)-stained images has been found to vary between pathologists, making it an important challenge to obtain an accurate TCR. In this study, three pathologists exhaustively labeled all cells in 41 regions from 41 lung cancer cases as either tumor, non-tumor or indistinguishable, thus establishing a “gold standard” TCR. We then compared the accuracy of the TCR estimated by 13 pathologists based on visual assessment and the TCR calculated by an AI model that we have developed. It is a compact and fast model that follows a fully convolutional neural network architecture and produces cell detection maps which can be efficiently post-processed to obtain tumor and non-tumor cell counts from which TCR is calculated. Its raw cell detection accuracy is 92% while its classification accuracy is 84%. The results show that the error between the gold standard TCR and the AI calculation was significantly smaller than that between the gold standard TCR and the pathologist’s visual assessment (p < 0.05). Additionally, the robustness of AI models across institutions is a key issue and we demonstrate that the variation in AI was smallerthan that in the average of pathologists when evaluated by institution. These findings suggest that the accuracy of tumor cellularity assessments in clinical workflows is significantly improved by the introduction of robust AI models, leading to more efficient genetic testing and ultimately to better patient outcomes.

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A Multi-Scale Conditional Deep Model for Tumor Cell Ratio Counting

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We propose a method to accurately obtain the ratio of tumor cells over an entire histological slide. We use deep fully convolutional neural network models trained to detect and classify cells on images of H&E-stained tissue sections. Pathologists’ labels consisting of exhaustive nuclei locations and tumor regions were used to trained the model in a supervised fashion. We show that combining two models, each working at a different magnification allows the system to capture both cell-level details and surrounding context to enable successful detection and classification of cells as either tumor-cell or normal-cell. Indeed, by conditioning the classification of a single cell on a multi-scale context information, our models mimic the process used by pathologists who assess cell neoplasticity and tumor extent at different microscope magnifications. The ratio of tumor cells can then be readily obtained by counting the number of cells in each class. To analyze an entire slide, we split it into multiple tiles that can be processed in parallel. The overall tumor cell ratio can then be aggregated. We perform experiments on a dataset of 100 slides with lung tumor specimens from both resection and tissue micro-array (TMA). We train fully-convolutional models using heavy data augmentation and batch normalization. On an unseen test set, we obtain an average mean absolute error on predicting the tumor cell ratio of less than 6%, which is significantly better than the human average of 20% and is key in properly selecting tissue samples for recent genetic panel tests geared at prescribing targeted cancer drugs. We perform ablation studies to show the importance of training two models at different magnifications and to justify the choice of some parameters, such as the size of the receptive field.

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