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      Label Cleaning Multiple Instance Learning: Refining Coarse Annotations on Single Whole-Slide Images

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          Abstract

          Annotating cancerous regions in whole-slide images (WSIs) of pathology samples plays a critical role in clinical diagnosis, biomedical research, and machine learning algorithms development. However, generating exhaustive and accurate annotations is labor-intensive, challenging, and costly. Drawing only coarse and approximate annotations is a much easier task, less costly, and it alleviates pathologists’ workload. In this paper, we study the problem of refining these approximate annotations in digital pathology to obtain more accurate ones. Some previous works have explored obtaining machine learning models from these inaccurate annotations, but few of them tackle the refinement problem where the mislabeled regions should be explicitly identified and corrected, and all of them require a – often very large – number of training samples. We present a method, named Label Cleaning Multiple Instance Learning (LC-MIL), to refine coarse annotations on a single WSI without the need for external training data. Patches cropped from a WSI with inaccurate labels are processed jointly within a multiple instance learning framework, mitigating their impact on the predictive model and refining the segmentation. Our experiments on a heterogeneous WSI set with breast cancer lymph node metastasis, liver cancer, and colorectal cancer samples show that LC-MIL significantly refines the coarse annotations, out-performing state-of-the-art alternatives, even while learning from a single slide. Moreover, we demonstrate how real annotations drawn by pathologists can be efficiently refined and improved by the proposed approach. All these results demonstrate that LC-MIL is a promising, lightweight tool to provide fine-grained annotations from coarsely annotated pathology sets.

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          A Threshold Selection Method from Gray-Level Histograms

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            T cell exclusion, immune privilege, and the tumor microenvironment.

            Effective immunotherapy promotes the killing of cancer cells by cytotoxic T cells. This requires not only that cancer-specific T cells be generated, but also that these T cells physically contact cancer cells. The coexistence in some patients of cancer cells and T cells that recognize them indicates that tumors may exhibit the phenomenon of immune privilege, in which immunogenic tissue is protected from immune attack. Here, we review the evidence that stromal cells of the tumor microenvironment mediate this restriction by excluding T cells from the vicinity of cancer cells. Overcoming this T cell checkpoint may thus enable optimal immunotherapy.
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              Solving the multiple instance problem with axis-parallel rectangles

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                Author and article information

                Contributors
                Role: Member, IEEE
                Journal
                8310780
                20511
                IEEE Trans Med Imaging
                IEEE Trans Med Imaging
                IEEE transactions on medical imaging
                0278-0062
                1558-254X
                16 December 2022
                December 2022
                02 December 2022
                08 January 2023
                : 41
                : 12
                : 3952-3968
                Affiliations
                Department of Biomedical Engineering, Mathematical Institute of Data Science, Johns Hopkins University, Baltimore, MD 21218 USA
                Department of Pathology, Johns Hopkins Medicine, Baltimore, MD 21218 USA
                Department of Pathology, Johns Hopkins Medicine, Baltimore, MD 21218 USA
                Department of Pathology, Johns Hopkins Medicine, Baltimore, MD 21218 USA
                Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218 USA
                Department of Biomedical Engineering, Mathematical Institute of Data Science, Johns Hopkins University, Baltimore, MD 21218 USA
                Author notes
                (Corresponding author: Jeremias Sulam. jsulam1@ 123456jhu.edu )
                Author information
                http://orcid.org/0000-0002-0195-4362
                http://orcid.org/0000-0003-0946-1957
                Article
                NIHMS1854922
                10.1109/TMI.2022.3202759
                9825360
                36037454
                77d59537-44b3-473e-b4ea-f1766a3453f1

                This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/

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                whole-slide image segmentation,multiple instance learning,coarse annotations,label cleaning

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