Dataset Information

Quantitative CT-derived vessel metrics in idiopathic pulmonary fibrosis: A structure-function study.

ABSTRACT:

Background and objective

This study aimed to investigate whether quantitative lung vessel morphology determined by a new fully automated algorithm is associated with functional indices in idiopathic pulmonary fibrosis (IPF).

Methods

A total of 152 IPF patients had vessel volume, density, tortuosity and heterogeneity quantified from computed tomography (CT) images by a fully automated algorithm. Separate quantitation of vessel metrics in pulmonary arteries and veins was performed in 106 patients. Results were evaluated against readouts from lung function tests.

Results

Normalized vessel volume expressed as a percentage of total lung volume was moderately correlated with functional indices on univariable linear regression analysis: forced vital capacity (R² =?0.27, P -6 ), diffusion capacity for carbon monoxide (DL_CO ; R² =?0.12, P =?3?×?10^-5 ), total lung capacity (TLC; R² =?0.45, P -6 ) and composite physiologic index (CPI; R² =?0.28, P -6 ). Normalized vessel volume was correlated with vessel density but not with vessel heterogeneity. Quantitatively derived vessel metrics (and artery and vein subdivision scores) were not significantly linked with the transfer factor for carbon monoxide (K_CO ), and only weakly with DL_CO . On multivariable linear regression analysis, normalized vessel volume and vessel heterogeneity were independently linked with DL_CO , TLC and CPI indicating that they capture different aspects of lung damage. Artery-vein separation provided no additional information beyond that captured in the whole vasculature.

Conclusion

Our study confirms previous observations of links between vessel volume and functional measures of disease severity in IPF using a new vessel quantitation tool. Additionally, the new tool shows independent linkages of normalized vessel volume and vessel heterogeneity with functional indices. Quantitative vessel metrics do not appear to reflect vasculopathic damage in IPF.

SUBMITTER: Jacob J

PROVIDER: S-EPMC6519024 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Quantitative CT-derived vessel metrics in idiopathic pulmonary fibrosis: A structure-function study.

Jacob Joseph J Pienn Michael M Payer Christian C Urschler Martin M Kokosi Maria M Devaraj Anand A Wells Athol U AU Olschewski Horst H

Respirology (Carlton, Vic.) 20190220 5

<h4>Background and objective</h4>This study aimed to investigate whether quantitative lung vessel morphology determined by a new fully automated algorithm is associated with functional indices in idiopathic pulmonary fibrosis (IPF).<h4>Methods</h4>A total of 152 IPF patients had vessel volume, density, tortuosity and heterogeneity quantified from computed tomography (CT) images by a fully automated algorithm. Separate quantitation of vessel metrics in pulmonary arteries and veins was performed i ...[more]

PMID: 30786325

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Project description:ObjectivesTo quantify the heterogeneity of fibrosis boundaries in idiopathic pulmonary fibrosis (IPF) using the Gaussian curvature analysis for evaluating disease severity and predicting survival.MethodsWe retrospectively included 104 IPF patients and 52 controls who underwent baseline chest CT scans. Normal lungs below - 500 HU were segmented, and the boundary was three-dimensionally reconstructed using in-house software. Gaussian curvature analysis provided histogram features on the heterogeneity of the fibrosis boundary. We analyzed the correlations between histogram features and the gender-age-physiology (GAP) and CT fibrosis scores. We built a regression model to predict diffusing capacity of carbon monoxide (DLCO) using the histogram features and calculated the modified GAP (mGAP) score by replacing DLCO with the predicted DLCO. The performances of the GAP, CT-GAP, and mGAP scores were compared using 100 repeated random-split sets.ResultsPatients with moderate-to-severe IPF had more numerous Gaussian curvatures at the fibrosis boundary, lower uniformity, and lower 10th to 30th percentiles of Gaussian curvature than controls or patients with mild IPF (all p < 0.0033). The 20th percentile was most significantly correlated with the GAP score (r = - 0.357; p < 0.001) and the CT fibrosis score (r = - 0.343; p = 0.001). More numerous Gaussian curvatures, higher entropy, lower uniformity, and 10th to 30th percentiles (p < 0.001-0.041) were associated with mortality. The mGAP score was comparable to the GAP and CT-GAP scores for survival prediction (mean C-indices, 0.76 vs. 0.79 vs. 0.77, respectively).ConclusionsGaussian curvatures of fibrosis boundaries became more heterogeneous as the disease progressed, and heterogeneity was negatively associated with survival in IPF.Key points• Gaussian curvature of the fibrotic lung boundary was more heterogeneous in patients with moderate-to-severe IPF than those with mild IPF or normal controls. • The 20th percentile of the Gaussian curvature of the fibrosis boundary was linearly correlated with the GAP score and the CT fibrosis score. • A modified GAP score that replaced the diffusing capacity of carbon monoxide with a composite measure using histogram features of the Gaussian curvature of the fibrosis boundary showed a comparable ability to predict survival to both the GAP and the CT-GAP score.

Project description:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and progressive lung scarring. The pathogenesis of IPF and whether the ECM involved in the process remain unknown.MethodsTo identify potential treatment target and ECM associated proteins that may be involved in the development of IPF, we employed isobaric tag for relative and absolute quantitation (iTRAQ) combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to examine protein expression in lung tissues from IPF patients.ResultsA total of 662 proteins with altered expression (455 upregulated proteins and 207 downregulated proteins) were identified in lung tissue of IPF patients compared with control. KEGG pathway enrichment analysis showed that the altered proteins in lung tissue mainly belonged to the PI3K-Akt signaling, focal adhesion, ECM-receptor interaction, and carbon metabolism pathways. According to the bioinformatic definition of the matrisome, 229 matrisome proteins were identified in lung tissue. These proteins comprised the ECM of lung, of which 104 were core matrisome proteins, and 125 were matrisome-associated proteins. Of the 229 ECM quantified proteins, 56 significantly differentially expressed proteins (19 upregulated proteins and 37 downregulated proteins) were detected in IPF lung tissue samples. In addition to proteins with well-known functions such as COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, we identified several novel ECM proteins with unknown function deposited in IPF lung tissue including LGALS7, ASPN, HSP90AA1 and HSP90AB1. Some of these differentially expressed proteins were further verified using Western blot analysis and immunohistochemical staining.ConclusionsThis study provides a list of proteomes that were detected in IPF lung tissue by iTRAQ technology combined with LC-MS/MS. The findings of this study will contribute better understanding to the pathogenesis of IPF and facilitate the development of therapeutic targets.

Dataset Information

Quantitative CT-derived vessel metrics in idiopathic pulmonary fibrosis: A structure-function study.

Background and objective

Methods

Results

Conclusion

Publications

Quantitative CT-derived vessel metrics in idiopathic pulmonary fibrosis: A structure-function study.

Similar Datasets

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