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      Radiomics to predict the mortality of patients with rheumatoid arthritis-associated interstitial lung disease: A proof-of-concept study

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          Abstract

          Objectives

          Patients with rheumatoid arthritis (RA) and interstitial lung disease (ILD) have increased mortality compared to the general population and factors capable of predicting RA-ILD long-term clinical outcomes are lacking. In oncology, radiomics allows the quantification of tumour phenotype by analysing the characteristics of medical images. Using specific software, it is possible to segment organs on high-resolution computed tomography (HRCT) images and extract many features that may uncover disease characteristics that are not detected by the naked eye. We aimed to investigate whether features from whole lung radiomic analysis of HRCT may alone predict mortality in RA-ILD patients.

          Methods

          High-resolution computed tomographies of RA patients from January 2012 to March 2022 were analyzed. The time between the first available HRCT and the last follow-up visit or ILD-related death was recorded. We performed a volumetric analysis in 3D Slicer, automatically segmenting the whole lungs and trachea via the Lung CT Analyzer. A LASSO-Cox model was carried out by considering ILD-related death as the outcome variable and extracting radiomic features as exposure variables.

          Results

          We retrieved the HRCTs of 30 RA-ILD patients. The median survival time (interquartile range) was 48 months (36–120 months). Thirteen out of 30 (43.33%) patients died during the observation period. Whole line segmentation was fast and reliable. The model included either the median grey level intensity within the whole lung segmentation [high-resolution (HR) 9.35, 95% CI 1.56–55.86] as a positive predictor of death and the 10th percentile of the number of included voxels (HR 0.20, 95% CI 0.05–0.84), the voxel-based pre-processing information (HR 0.23, 95% CI 0.06–0.82) and the flatness (HR 0.42, 95% CI 0.18–0.98), negatively correlating to mortality. The correlation of grey level values to their respective voxels (HR 1.52 95% CI 0.82–2.83) was also retained as a confounder.

          Conclusion

          Radiomic analysis may predict RA-ILD patients’ mortality and may promote HRCT as a digital biomarker regardless of the clinical characteristics of the disease.

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          Most cited references20

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          Computational Radiomics System to Decode the Radiographic Phenotype

          Radiomics aims to quantify phenotypic characteristics on medical imaging through the use of automated algorithms. Radiomic artificial intelligence (AI) technology, either based on engineered hard-coded algorithms or deep learning methods, can be used to develop non-invasive imaging-based biomarkers. However, lack of standardized algorithm definitions and image processing severely hampers reproducibility and comparability of results. To address this issue, we developed PyRadiomics , a flexible open-source platform capable of extracting a large panel of engineered features from medical images. PyRadiomics is implemented in Python and can be used standalone or using 3D-Slicer. Here, we discuss the workflow and architecture of PyRadiomics and demonstrate its application in characterizing lung-lesions. Source code, documentation, and examples are publicly available at www.radiomics.io . With this platform, we aim to establish a reference standard for radiomic analyses, provide a tested and maintained resource, and to grow the community of radiomic developers addressing critical needs in cancer research.
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            2010 Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative.

            The 1987 American College of Rheumatology (ACR; formerly, the American Rheumatism Association) classification criteria for rheumatoid arthritis (RA) have been criticized for their lack of sensitivity in early disease. This work was undertaken to develop new classification criteria for RA. A joint working group from the ACR and the European League Against Rheumatism developed, in 3 phases, a new approach to classifying RA. The work focused on identifying, among patients newly presenting with undifferentiated inflammatory synovitis, factors that best discriminated between those who were and those who were not at high risk for persistent and/or erosive disease--this being the appropriate current paradigm underlying the disease construct "rheumatoid arthritis." In the new criteria set, classification as "definite RA" is based on the confirmed presence of synovitis in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1). This new classification system redefines the current paradigm of RA by focusing on features at earlier stages of disease that are associated with persistent and/or erosive disease, rather than defining the disease by its late-stage features. This will refocus attention on the important need for earlier diagnosis and institution of effective disease-suppressing therapy to prevent or minimize the occurrence of the undesirable sequelae that currently comprise the paradigm underlying the disease construct "rheumatoid arthritis."
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              3D Slicer as an image computing platform for the Quantitative Imaging Network.

              Quantitative analysis has tremendous but mostly unrealized potential in healthcare to support objective and accurate interpretation of the clinical imaging. In 2008, the National Cancer Institute began building the Quantitative Imaging Network (QIN) initiative with the goal of advancing quantitative imaging in the context of personalized therapy and evaluation of treatment response. Computerized analysis is an important component contributing to reproducibility and efficiency of the quantitative imaging techniques. The success of quantitative imaging is contingent on robust analysis methods and software tools to bring these methods from bench to bedside. 3D Slicer is a free open-source software application for medical image computing. As a clinical research tool, 3D Slicer is similar to a radiology workstation that supports versatile visualizations but also provides advanced functionality such as automated segmentation and registration for a variety of application domains. Unlike a typical radiology workstation, 3D Slicer is free and is not tied to specific hardware. As a programming platform, 3D Slicer facilitates translation and evaluation of the new quantitative methods by allowing the biomedical researcher to focus on the implementation of the algorithm and providing abstractions for the common tasks of data communication, visualization and user interface development. Compared to other tools that provide aspects of this functionality, 3D Slicer is fully open source and can be readily extended and redistributed. In addition, 3D Slicer is designed to facilitate the development of new functionality in the form of 3D Slicer extensions. In this paper, we present an overview of 3D Slicer as a platform for prototyping, development and evaluation of image analysis tools for clinical research applications. To illustrate the utility of the platform in the scope of QIN, we discuss several use cases of 3D Slicer by the existing QIN teams, and we elaborate on the future directions that can further facilitate development and validation of imaging biomarkers using 3D Slicer. Copyright © 2012 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Med (Lausanne)
                Front Med (Lausanne)
                Front. Med.
                Frontiers in Medicine
                Frontiers Media S.A.
                2296-858X
                09 January 2023
                2022
                : 9
                : 1069486
                Affiliations
                [1] 1Rheumatology Unit, Department of Emergency and Organ Transplantation, University of Bari Aldo Moro , Bari, Italy
                [2] 2Rheumatology Unit, Azienda Ospedaliera Policlinico di Modena, University of Modena and Reggio Emilia , Modena, Italy
                [3] 3Radiology Unit, Department of Interdisciplinary Medicine, University of Bari Aldo Moro , Bari, Italy
                Author notes

                Edited by: Peter Korsten, University Medical Center Göttingen, Germany

                Reviewed by: Emre Bilgin, Hacettepe University, Türkiye; Arnulfo Hernan Nava-Zavala, Mexican Social Security Institute (IMSS), Mexico

                *Correspondence: Florenzo Iannone, florenzo.iannone@ 123456uniba.it

                These authors share first authorship

                ORCID: Vincenzo Venerito, orcid.org/0000-0002-2573-5930; Andreina Manfredi, orcid.org/0000-0003-0474-5344

                This article was submitted to Rheumatology, a section of the journal Frontiers in Medicine

                Article
                10.3389/fmed.2022.1069486
                9870287
                36698825
                3c544081-28e2-488d-b87b-e777971f572b
                Copyright © 2023 Venerito, Manfredi, Lopalco, Lavista, Cassone, Scardapane, Sebastiani and Iannone.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 13 October 2022
                : 19 December 2022
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 20, Pages: 7, Words: 3756
                Categories
                Medicine
                Original Research

                radiomics,rheumatoid arthritis-associated interstitial lung disease,high-resolution computed tomography,biomarker,lasso

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