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      Visual vs Fully Automatic Histogram-Based Assessment of Idiopathic Pulmonary Fibrosis (IPF) Progression Using Sequential Multidetector Computed Tomography (MDCT)

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          Abstract

          Objectives

          To describe changes over time in extent of idiopathic pulmonary fibrosis (IPF) at multidetector computed tomography (MDCT) assessed by semi-quantitative visual scores (VSs) and fully automatic histogram-based quantitative evaluation and to test the relationship between these two methods of quantification.

          Methods

          Forty IPF patients (median age: 70 y, interquartile: 62-75 years; M:F, 33:7) that underwent 2 MDCT at different time points with a median interval of 13 months (interquartile: 10-17 months) were retrospectively evaluated. In-house software YACTA quantified automatically lung density histogram (10 th-90 th percentile in 5 th percentile steps). Longitudinal changes in VSs and in the percentiles of attenuation histogram were obtained in 20 untreated patients and 20 patients treated with pirfenidone. Pearson correlation analysis was used to test the relationship between VSs and selected percentiles.

          Results

          In follow-up MDCT, visual overall extent of parenchymal abnormalities (OE) increased in median by 5 %/year (interquartile: 0 %/y; +11 %/y). Substantial difference was found between treated and untreated patients in HU changes of the 40th and of the 80th percentiles of density histogram. Correlation analysis between VSs and selected percentiles showed higher correlation between the changes (Δ) in OE and Δ 40 th percentile ( r=0.69; p<0.001) as compared to Δ 80 th percentile ( r=0.58; p<0.001); closer correlation was found between Δ ground-glass extent and Δ 40 th percentile ( r=0.66, p<0.001) as compared to Δ 80 th percentile ( r=0.47, p=0.002), while the Δ reticulations correlated better with the Δ 80 th percentile ( r=0.56, p<0.001) in comparison to Δ 40 th percentile ( r=0.43, p=0.003).

          Conclusions

          There is a relevant and fully automatically measurable difference at MDCT in VSs and in histogram analysis at one year follow-up of IPF patients, whether treated or untreated: Δ 40 th percentile might reflect the change in overall extent of lung abnormalities, notably of ground-glass pattern; furthermore Δ 80 th percentile might reveal the course of reticular opacities.

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          Most cited references19

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          Ascertainment of individual risk of mortality for patients with idiopathic pulmonary fibrosis.

          Several predictors of mortality in patients with idiopathic pulmonary fibrosis have been described; however, there is a need for a practical and accurate method of quantifying the prognosis of individual patients. Develop a practical mortality risk scoring system for patients with idiopathic pulmonary fibrosis. We used a Cox proportional hazards model and data from two clinical trials (n = 1,099) to identify independent predictors of 1-year mortality among patients with idiopathic pulmonary fibrosis. From the comprehensive model, an abbreviated clinical model comprised of only those predictors that are readily and reliably ascertained by clinicians was derived. Beta coefficients for each predictor were then used to develop a practical mortality risk scoring system. Independent predictors of mortality included age, respiratory hospitalization, percent predicted FVC, 24-week change in FVC, percent predicted carbon monoxide diffusing capacity, 24-week change in percent predicted carbon monoxide diffusing capacity, and 24-week change in health-related quality of life. An abbreviated clinical model comprising only four predictors (age, respiratory hospitalization, percent predicted FVC, and 24-wk change in FVC), and the corresponding risk scoring system produced estimates of 1-year mortality risk consistent with observed data (9.9% vs. 9.7%; C statistic = 0.75; 95% confidence interval, 0.71–0.79). The prognosis for patients with idiopathic pulmonary fibrosis may be accurately determined using four readily ascertainable predictors. Our simplified scoring system may be a valuable tool for determining prognosis and guiding clinical management. Additional research is needed to validate the applicability and accuracy of the scoring system.
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            Idiopathic pulmonary fibrosis: physiologic tests, quantitative CT indexes, and CT visual scores as predictors of mortality.

            To retrospectively evaluate quantitative computed tomographic (CT) indexes, pulmonary function test results, and visual CT scoring as predictors of mortality and to describe serial changes in quantitative CT indexes over 12 months in patients with idiopathic pulmonary fibrosis (IPF). Institutional review board approval and informed consent were obtained at all participating institutions. One hundred sixty-seven patients (110 men, 57 women; mean age, 63 years +/- 9 [standard deviation]) with IPF were enrolled in a clinical trial. Patients underwent thin-section CT in the supine position at full inspiration at enrollment (baseline) and at 12-month follow-up. After segmentation of the lungs, mean lung attenuation (MLA), skewness, and kurtosis were measured. Extent of ground glass opacity and lung fibrosis were assessed visually. Forced vital capacity (FVC) and total lung capacity (TLC) were measured. Median duration of follow-up for mortality was 1.5 years. Univariate and multivariate survival analyses were used to determine the predictive value of baseline variables for survival. At univariate analysis, baseline variables predictive of death included TLC, fibrosis, skewness, and kurtosis. At multivariate analysis, FVC (P = .006) and fibrosis (P = .002) were predictors of short-term mortality. In 95 patients who had both baseline and follow-up CT scans, fibrosis (P = .030), MLA (P = .003), skewness (P < .001), and kurtosis (P < .001) all showed change indicating disease progression. Visually determined disease extent on CT images is a strong independent predictor of mortality in IPF. Serial evaluation of quantitative CT measures can show disease progression in these patients. (c) RSNA, 2008.
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              Quantitative CT indexes in idiopathic pulmonary fibrosis: relationship with physiologic impairment.

              To determine whether measurements of skewness, kurtosis, and mean lung attenuation on thin-section computed tomographic (CT) histograms in patients with idiopathic pulmonary fibrosis (IPF) correlate with pulmonary physiologic abnormality in a nonspirometrically controlled multicenter study. The authors analyzed baseline digital thin-section CT data from 144 patients with IPF who enrolled in a double-blind placebo-controlled clinical effectiveness trial of interferon beta 1a in the treatment of IPF. All patients underwent thin-section CT in the supine position at full inspiration. The lungs were isolated by using a semiautomated thresholding technique, with an upper threshold of -200 HU. An attenuation correction algorithm was used. Pulmonary function tests (PFTs) included forced vital capacity, total lung capacity, forced expiratory volume in 1 second, and diffusing lung capacity. Univariate and multiple correlation and regression statistical analyses were used to determine relationships between histogram features and results of PFTs. Moderate correlations existed between histogram features and PFT results. Kurtosis showed the greatest degree of correlation with physiologic abnormality (r = 0.53, P <.01). Strength of correlation increased with exclusion of suboptimal scans but did not change significantly after application of an attenuation correction algorithm. Attenuations for lungs, gas, and soft tissue varied considerably between scanner manufacturers. Kurtosis alone provided predictions of pulmonary function that were virtually as good as those from all histogram features combined. Thin-section CT histograms of the lungs were found to correlate with results of PFTs in patients with IPF, which supports the claim that histogram features can be used as valid indexes of IPF in a multiinstitutional nonspirometrically controlled study. Copyright RSNA, 2003.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 June 2015
                2015
                : 10
                : 6
                : e0130653
                Affiliations
                [1 ]Department of Surgical Sciences, Section of Diagnostic Imaging at University of Parma, Parma, Italy
                [2 ]Translational Lung Research Centre (TLRC), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
                [3 ]Department of Diagnostic and Interventional Radiology, University of Heidelberg, Heidelberg, Germany
                [4 ]Department of Clinical Radiology, University of Munich, Munich, Germany
                [5 ]Department of Pneumology, Iuliu Hatieganu University of Medicine and Pharmacy in Cluj-Napoca, Cluj-Napoca, Romania
                [6 ]Division of Medical and Biological Informatics (E130), German Cancer Research Center (DFKZ), Heidelberg, Germany
                [7 ]Department of Pneumology and respiratory critical care medicine, Center for interstitial and rare lung diseases, Thoraxklinik at University of Heidelberg, Heidelberg, Germany
                University of Miami Miller School of Medicine, UNITED STATES
                Author notes

                Competing Interests: Colombi D received a support for travel to meetings for the study from Intermune. Oltmanns U received payment for educational presentation from European Respiratory Society and fees for both meetings and presentation at congresses from Intermune. Palmowski K received meetings expenses from Intermune. Herth F is board member of Novartis, Astra Zeneca, Grifols, Berlin Chemie, Chiesi, Pulmonx, and PneumRx; he also received fees for lectures from the same companies. Kauczor HU is board member of Siemens; he also received fees for lectures and educational presentations from Bracco, Novartis, Siemens, Boehringer, and Bayer. Sverzellati N received fees for lectures and educational presentation from Intermune, Boeringher, Astrazeneca, Pfizer, and Chiesi. Kreuter M received a grant from Dietmar Hopp Stiftung; he is also a consultant for Intermune and he received fees for lectures and educational presentations from Boehringer and Intermune. Heussel CP is a consultant of Pfizer, Boheringer Ingelheim, Gilead, Intermune, and Fresenius; he also received research funding from Siemens, Pfizer, and Boheringer Ingelheim as well as fees for lectures from Gilead, MSD, Pfizer, Intermune, Boheringer Ingelheim, and Novartis. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials. For the remaining authors no competing interests were declared.

                Conceived and designed the experiments: DC JD FH HUK MK CPH. Performed the experiments: DC JD OW DN UO KP. Analyzed the data: DC JD TB NS MK CPH BO. Contributed reagents/materials/analysis tools: OW TB. Wrote the paper: DC HUK NS MK CPH.

                Article
                PONE-D-15-00072
                10.1371/journal.pone.0130653
                4482435
                26110421
                9aaa9d2f-8905-4547-9433-6edfe15ffb73
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 2 January 2015
                : 22 May 2015
                Page count
                Figures: 5, Tables: 4, Pages: 17
                Funding
                This study was supported by grants from the Dietmar Hopp Stiftung, the Bundesministerium für Bildung und Forschung (BMBF) to the German Center for Lung Research (DZL) (82DZL00401, 82DZL00402, 82DZL00404), the Deutsche Forschungsgemeinschaft, and the Ruprecht-Karls-Universität Heidelberg within the funding program Open Access Publishing.
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