Advancing Digital Pathology through Novel Machine Learning Methodologies

项目摘要/摘要 病理学侧重于根据实验室方法提供医学诊断和预后，以指导 病人的治疗和管理。显微镜是病理学家检查组织和细胞的基础。 尽管取得了许多进步，但在上个世纪，在如何 显微镜图像用于病理学。目前的解剖病理学方法缺乏标准化。 并依赖于强加给病理学家的认知负担来手动评估数百个细胞中的数百万个 一个典型工作日的幻灯片数量。基于深度学习的方法最近显示出令人鼓舞的结果 分析显微镜图像。然而，它们依赖于标准的计算机视觉体系结构和管道， 由于幻灯片数字化所需的时间和成本以及 分析巨大的高分辨率图像。此外，开发准确的深度学习模型需要具备 访问标记的显微镜图像的大型数据库，这是具有挑战性的。在此应用程序中，新的 提出了利用组织病理学数据集的独特特征和 组织学显微镜图像中的一系列特征，以解决这些限制。这个项目展示了一部小说 基于生成对抗性网络的难度翻译生成扩充数据的方法 现实的、罕见的和难以分类的组织病理学模式。此方法将缓解以下方面的数据失衡 注释的组织学数据集并改进用于组织学分类的深度学习模型的性能， 特别是对于不常见和难以分类的案件。此外，一种新颖的课程学习方法 组织学图像分类将根据分类难度的范围来制定 组织病理学模式和多注释器标记的数据集。这种方法训练得越来越难-- 对由注释器协议确定的图像进行分类，并显著提高 所产生的深度学习模型不需要额外的数据或计算资源。此外，一个自我- 为了提高组织学图像的检索效率，将开发有监督的知识提取方法 分类。由于标注的大型数据集很少，因此该方法使用自监督方法来提取要素 将高分辨率提取到以较低分辨率操作的学生模型中的能力 未标记的数据集。由此提取的学生模型可以在较低的分类精度上达到较高的分类精度。 分辨率组织学图像，同时节省大量数字化工作的时间和资源 所需的计算资源。该应用程序中提出的方法消除了当前的瓶颈 数字病理学的学习应用。因此，这个项目的结果可能会对 在临床工作流程中使用深度学习技术并整合组织病理学的新机遇 与其他临床和分子数据一起提供信息，以改善患者的诊断、预后和治疗。

PROJECT SUMMARY/ABSTRACT Pathology is focused on providing medical diagnoses and prognoses based on laboratory methods to guide patient treatment and management. Microscopy is fundamental for pathologists to examine tissues and cells. Despite numerous advancements, there have not been many changes in the last century in terms of how microscopy images are used in pathology. The current approach in anatomic pathology lacks standardization and relies on the cognitive burden imposed on pathologists to manually evaluate millions of cells across hundreds of slides in a typical workday. Deep learning-based methods have recently shown encouraging results for analyzing microscopy images. However, they rely on standard computer vision architectures and pipelines, which are limited due to the required time and cost of slide digitization and the computational constraints of analyzing huge high-resolution images. Furthermore, developing accurate deep learning models requires having access to large databases of labeled microscopy images, which is challenging. In this application, new methodologies are proposed to take advantage of the unique characteristics of histopathology datasets and the range of features in histology microscopy images to address these limitations. This project presents a novel approach based on generative adversarial networks for difficulty translation to generate augmented data with realistic, rare, and hard-to-classify histopathological patterns. This approach will mitigate data imbalances in annotated histology datasets and improve the performance of deep learning models for histological classification, particularly for uncommon and difficult-to-classify cases. Furthermore, a novel curriculum learning approach for histology image classification will be developed based on the range of classification difficulty among histopathological patterns and multi-annotator labeled datasets. This approach trains on progressively harder- to-classify images, as determined by annotator agreement, and significantly improves the performance of the resulting deep learning models without requiring additional data or computational resources. In addition, a self- supervised knowledge distillation method will be developed to enhance the efficiency of histology image classification. As large, labeled datasets are scarce, this method uses a self-supervised approach to distill feature extraction capabilities at a high resolution into a student model operating at a lower resolution by leveraging unlabeled datasets. The resulting distilled student models can achieve high classification accuracy on low- resolution histology images while saving a significant amount of time and resources on digitization efforts and required computational resources. The proposed methods in this application remove current bottlenecks in deep learning applications for digital pathology. Therefore, the results from this project could have a major impact on new opportunities that use deep learning technology in clinical workflows and integrate histopathological information with other clinical and molecular data to improve patients' diagnoses, prognoses, and treatments.