Deep learning-based tumor segmentation on digital images of histopathology slides for microdosimetry applications

L. Weishaupt, J. Torres, S. Camilleri-Broet, R. Rayes, J. Spicer, Sabrina Cot'e Maldonado, S. Unit, Department of Radiation Oncology, Faculty of Veterinary Medicine, M. University, Montr'eal, Qu'ebec, Canada, Departmentof Pathology, Cancer Research Program, the LD MacLean Surgical Research Laboratories, D. Surgery, GI DivisionofUpper, Thoracic Surgery, Research Center
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Abstract

The goal of this study was (i) to use artificial intelligence to automate the traditionally labor-intensive process of manual segmentation of tumor regions in pathology slides performed by a pathologist and (ii) to validate the use of a deep learning architecture. Automation will reduce the human error involved in the manual process, increase efficiency, and result in more accurate and reproducible segmentation. This advancement will alleviate the bottleneck in the workflow in clinical and research applications due to a lack of pathologist time. Our application is patient-specific microdosimetry and radiobiological modeling, which builds on the contoured pathology slides. A deep neural network named UNet was used to segment tumor regions in pathology core biopsies of lung tissue with adenocarcinoma stained using hematoxylin and eosin. A pathologist manually contoured the tumor regions in 56 images with binary masks for training. To overcome memory limitations overlapping and non-overlapping patch extraction with various patch sizes and image downsampling were investigated individually. Data augmentation was used to reduce overfitting and artificially create more data for training. Using this deep learning approach, the UNet achieved accuracy of 0.91±0.06, specificity of 0.90±0.08, sensitivity of 0.92±0.07, and precision of 0.8±0.1. The F1/DICE score was 0.85±0.07, with a segmentation time of 3.24±0.03 seconds per image, thus achieving a 370±3 times increased efficiency over manual segmentation, which took 20 minutes per image on average. In some cases, the neural network correctly delineated the tumor's stroma from its epithelial component in tumor regions that were classified as tumor by the pathologist. The UNet architecture can segment images with a level of efficiency and accuracy that makes it suitable for tumor segmentation of histopathological images in fields such as radiotherapy dosimetry, specifically in the subfields of microdosimetry.
基于深度学习的组织病理切片数字图像肿瘤分割,用于微剂量学应用
本研究的目标是:(i)使用人工智能来自动化传统的劳动密集型过程,即由病理学家在病理切片中手动分割肿瘤区域;(ii)验证深度学习架构的使用。自动化将减少人工过程中涉及的人为错误,提高效率,并导致更准确和可重复的分割。这一进步将缓解由于病理学家缺乏时间而在临床和研究应用工作流程中的瓶颈。我们的应用是患者特异性微剂量学和放射生物学建模,这建立在病理切片的轮廓上。在苏木精和伊红染色的肺组织病理核心活检中,使用深度神经网络UNet对肿瘤区域进行分割。病理学家用二值掩模对56张图像中的肿瘤区域进行人工轮廓化训练。为了克服内存限制,分别研究了不同大小的重叠和非重叠斑块提取以及图像降采样。数据增强用于减少过拟合,人为地为训练创造更多数据。采用这种深度学习方法,UNet的准确率为0.91±0.06,特异性为0.90±0.08,灵敏度为0.92±0.07,精密度为0.8±0.1。F1/DICE评分为0.85±0.07,每张图像的分割时间为3.24±0.03秒,与平均每张图像耗时20分钟的人工分割相比,分割效率提高了370±3倍。在某些情况下,神经网络正确地描绘了肿瘤区域的间质和上皮成分,这些肿瘤区域被病理学家归类为肿瘤。UNet架构可以以一定的效率和准确性分割图像,使其适用于放射治疗剂量学等领域的组织病理学图像的肿瘤分割,特别是在微剂量学的子领域。
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