• Emphysema

• Humans
• Male
• Female
• Pulmonary Emphysema/physiopathology
• Pulmonary Emphysema/diagnostic imaging
• Pulmonary Emphysema/ethnology
• Tomography, X-Ray Computed/methods
• Aged
• Middle Aged
• Blood Volume/physiology
• Lung/blood supply
• Lung/diagnostic imaging
• Microvessels/physiopathology
• Microvessels/diagnostic imaging
• United States/epidemiology
• Aged, 80 and over

• 75N92020D00002 NHLBI NIH HHS
• 75N92020D00005 NHLBI NIH HHS
• N01HC95163 NHLBI NIH HHS
• R01 HL077612 NHLBI NIH HHS
• N01HC95164 NHLBI NIH HHS
• R01 HL121270 NHLBI NIH HHS
• N01HC95165 NHLBI NIH HHS
• 75N92020D00007 NHLBI NIH HHS
• N01HC95167 NHLBI NIH HHS
• N01HC95160 NHLBI NIH HHS
• R01 HL071759 NHLBI NIH HHS
• 75N92020D00001 NHLBI NIH HHS
• N01HC95169 NHLBI NIH HHS
• N01HC95162 NHLBI NIH HHS
• 75N92020D00003 NHLBI NIH HHS
• R01 HL093081 NHLBI NIH HHS
• N01HC95168 NHLBI NIH HHS
• R01 HL155816 NHLBI NIH HHS
• N01HC95159 NHLBI NIH HHS
• N01HC95161 NHLBI NIH HHS
• 75N92020D00004 NHLBI NIH HHS
• 75N92020D00006 NHLBI NIH HHS
• N01HC95166 NHLBI NIH HHS

• chronic obstructive pulmonary disease
• computed tomography
• pulmonary vascular structure
• quantitative analysis
• smoking

• Humans
• Pulmonary Disease, Chronic Obstructive/diagnostic imaging
• Pulmonary Disease, Chronic Obstructive/etiology
• Smokers
• Analysis of Variance
• Smoking Cessation
• Tomography, X-Ray Computed
• Vascular Remodeling

• This work was supported by the National Natural Science Foundation of China (grant numbers: 82171926, 81930049); National Key R&D Program of China (grant number: 2022YFC2010000, 2022YFC2010002, 2022YFC2010005); the program of Science and Technology Commission of Shanghai Municipality (grant number 21DZ2202600); the construction of CT standardized database for chronic obstructive pulmonary disease (grant number: YXFSC2022JJSJ002); Clinical Innovation Project of Shanghai Changzheng Hospital (grant number: 2020YLCYJ-Y24)

To explore optimal threshold of FEV1% predicted value (FEV1%pre) for high-risk chronic obstructive pulmonary disease (COPD) using the parameter response mapping (PRM) based on machine learning classification model.

A total of 561 consecutive non-COPD subjects who were screened for chest diseases in our hospital between August and October 2018 and who had complete questionnaire surveys, pulmonary function tests (PFT), and paired respiratory chest CT scans were enrolled retrospectively. The CT quantitative parameter for small airway remodeling was PRM, and 72 parameters were obtained at the levels of whole lung, left and right lung, and five lobes. To identify a more reasonable thresholds of FEV1% predicted value for distinguishing high-risk COPD patients from the normal, 80 thresholds from 50% to 129% were taken with a partition of 1% to establish a random forest classification model under each threshold, such that novel PFT-parameter-based high-risk criteria would be more consistent with the PRM-based machine learning classification model.

Machine learning-based PRM showed that consistency between PRM parameters and PFT was better able to distinguish high-risk COPD from the normal, with an AUC of 0.84 when the threshold was 72%. When the threshold was 80%, the AUC was 0.72 and when the threshold was 95%, the AUC was 0.64.

Machine learning-based PRM is feasible for redefining high-risk COPD, and setting the optimal FEV1% predicted value lays the foundation for redefining high-risk COPD diagnosis.

• artificial intelligence
• chronic obstructive pulmonary disease
• computed tomography
• pulmonary function test
• quantitative imaging

Pulmonary perfusion abnormalities are prevalent in patients with chronic obstructive pulmonary disease (COPD), are potentially reversible, and may be associated with emphysema development. Therefore, we aimed to evaluate the clinical meaningfulness of perfusion defects in percent (QDP) using DCE-MRI.

We investigated a subset of baseline DCE-MRIs, paired inspiratory/expiratory CTs, and pulmonary function testing (PFT) of 83 subjects (age = 65.7 ± 9.0 years, patients-at-risk, and all GOLD groups) from one center of the “COSYCONET” COPD cohort. QDP was computed from DCE-MRI using an in-house developed quantification pipeline, including four different approaches: Otsu’s method, k-means clustering, texture analysis, and 80^th percentile threshold. QDP was compared with visual MRI perfusion scoring, CT parametric response mapping (PRM) indices of emphysema (PRM_Emph) and functional small airway disease (PRM_fSAD), and FEV1/FVC from PFT.

All QDP approaches showed high correlations with the MRI perfusion score (r = 0.67 to 0.72, p < 0.001), with the highest association based on Otsu’s method (r = 0.72, p < 0.001). QDP correlated significantly with all PRM indices (p < 0.001), with the strongest correlations with PRM_Emph (r = 0.70 to 0.75, p < 0.001). QDP was distinctly higher than PRM_Emph (mean difference = 35.85 to 40.40) and PRM_fSAD (mean difference = 15.12 to 19.68), but in close agreement when combining both PRM indices (mean difference = 1.47 to 6.03) for all QDP approaches. QDP correlated moderately with FEV1/FVC (r = − 0.54 to − 0.41, p < 0.001).

QDP is associated with established markers of disease severity and the extent corresponds to the CT-derived combined extent of PRM_Emph and PRM_fSAD. We propose to use QDP based on Otsu’s method for future clinical studies in COPD.

• QDP quantified from DCE-MRI is associated with visual MRI perfusion score, CT PRM indices, and PFT.

• The extent of QDP from DCE-MRI corresponds to the combined extent of PRM_Emph and PRM_fSAD from CT.

• Assessing pulmonary perfusion abnormalities using DCE-MRI with QDP improved the correlations with CT PRM indices and PFT compared to the quantification of pulmonary blood flow and volume.

The online version contains supplementary material available at 10.1007/s00330-021-08229-6.

• Biomarkers
• Chronic obstructive pulmonary disease
• Magnetic resonance imaging
• Perfusion imaging
• Pulmonary emphysema

Chronic obstructive lung disease (COPD) is responsible for substantial rates of mortality and economic burden, and is one of the most important public-health concerns. As the disease characteristics include irreversible airway obstruction and progressive lung function decline, there has been a great deal of interest in detection at the early stages of COPD during the “at risk” or undiagnosed preclinical stage to prevent the disease from progressing to the overt stage. Previous studies have used various definitions of early COPD, and the term mild COPD has also often been used. There has been a great deal of recent effort to establish a definition of early COPD, but comprehensive evaluation is still required, including identification of risk factors, various physiological and radiological tests, and clinical manifestations for diagnosis of early COPD, considering the heterogeneity of the disease. The treatment of early COPD should be considered from the perspective of prevention of disease progression and management of clinical deterioration. There has been a lack of studies on this topic as the definition of early COPD has been proposed only recently, and therefore further clinical studies are needed.

• COPD
• diagnostics
• early COPD
• therapy

• X-ray computed
• computational biology
• emphysema
• lung cancer screening
• tomography

• MR
• MR angiography
• MR perfusion
• Pulmonary embolus

Genome-wide association studies (GWASs) of a large cohort of subjects with chronic obstructive pulmonary disease (COPD) have successfully identified multiple risk genes, including fibroblast growth factor 7 (FGF7). However, the underlying molecular mechanism influencing function of FGF7 and risk of COPD remains further study.

In this study, we replicated the genetic association of variants near the FGF7 gene in 258 Chinese Han patients with COPD and 311 healthy controls. Additionally, we functionally evaluated a candidate causal variant upstream of the FGF7 gene.

The most significant association was observed at rs12905203 (P = 5.9 × 10^− 3, odd ratio, OR = 1.516) that explains associations of previously reported variants at the FGF7 locus. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assays showed that the risk allele of the variant was bound to activator protein 1 transcription factors (c-Fos and c-Jun) with a significantly reduced affinity and associated with decreased mRNA expression of FGF7 in fibroblast cells at both resting and PMA/Ionomycin-stimulated conditions. Overexpression of c-Fos and c-Jun proteins or stimulation with PMA/Ionomycin significantly increases mRNA expression of FGF7 in fibroblast cells. Bioinformatic analysis showed that the variant overlaps with multiple genetic regulatory marks, suggesting the regulatory DNA element might function as an enhancer for the FGF7 gene. Luciferase enhancer activity assays demonstrated that the DNA sequences carrying the variant produce enhancer activity while the risk allele of the variant reduces its activity.

In this study, we demonstrated a consistent association of the FGF7 gene with COPD and mechanistically characterized a candidate functional variant upstream of the FGF7 gene. These data highlighted the important role of the risk variant and the FGF7 gene in influencing risk for COPD.

The online version of this article (10.1186/s12881-019-0761-7) contains supplementary material, which is available to authorized users.

• AP-1
• COPD
• FGF7

We aimed to evaluate the feasibility of simultaneous image acquisition of multiple instantaneous switchable scan (MISS) for prostate magnetic resonance imaging (MRI) on 3T. Fifty-three patients were scanned with MRI due to suspected prostate cancer. Twenty-eight of them got histological results. First, two readers assessed the structure delineation and image quality based on images of conventional T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) (CTD). Second, two readers identified the index lesion together, and then, reader one evaluated the contrast of index lesion on T2WI and signal ratio on apparent diffusion coefficient map. Third, they assigned Prostate Imaging Reporting and Data System (PI-RADS) score in consensus for the index lesion. After 4 weeks, the images of MISS were reviewed by the same readers following the same process. Finally, two readers gave preference for image interpretation, respectively. Kappa coefficient, Wilcoxon signed-rank test, paired-sample t-test, Bland–Altman analysis, and receiver operating characteristic (ROC) analysis were used for statistical analysis. The acquisition time of CTD was 6 min and 10 s, while the acquisition time of MISS was 4 min and 30 s. Interobserver agreements for image evaluation were κ = 0.65 and κ = 0.80 for CTD and MISS, respectively. MISS-T2WI showed better delineation for seminal vesicles than CTD-T2WI (reader 1: P < 0.001, reader 2: P = 0.001). The index lesion demonstrated higher contrast in MISS-T2WI (P < 0.001). The PI-RADS scores based on CTD and MISS exhibited high ability in predicting clinically significant cancer (area under curve [AUC] = 0.828 vs 0.854). Readers preferred to use MISS in 41.5%–47.2% of cases. MISS showed comparable performance to conventional technique with less acquisition time.

• diffusion-weighted imaging
• magnetic resonance imaging
• prostate cancer

• Lung volume reduction (LVR)
• computed tomography (CT)
• endobronchial procedure
• preinterventional imaging

The pathophysiology of chronic obstructive pulmonary disease (COPD) and Alpha one antitrypsin deficiency is increasingly recognised as complex such that lung function alone is insufficient for early detection, clinical categorisation and dictating management. Quantitative imaging techniques can detect disease earlier and more accurately, and provide an objective tool to help phenotype patients into predominant airways disease or emphysema. Computed tomography provides detailed information relating to structural and anatomical changes seen in COPD, and magnetic resonance imaging/nuclear imaging gives functional and regional information with regards to ventilation and perfusion. It is likely imaging will become part of routine clinical practice, and an understanding of the implications of the data is essential. This review discusses technical and clinical aspects of quantitative imaging in obstructive airways disease.

• Chronic obstructive pulmonary disease
• Alpha one antitrypsin deficiency
• Computed tomography
• Densitometry
• Phenotype
• Spirometry
• Magnetic resonance imaging

• COPD
• dual energy CT
• phenotypes
• pulmonary MRI
• pulmonary ventilation and perfusion
• quantitative CT

• Animals
• Clinical Trials as Topic
• Disease Progression
• Fluorine/chemistry
• Gadolinium/chemistry
• Helium/chemistry
• Humans
• Inflammation
• Isotopes/chemistry
• Lung/diagnostic imaging
• Magnetic Resonance Imaging
• Perfusion
• Phenotype
• Pulmonary Disease, Chronic Obstructive/diagnostic imaging
• Pulmonary Disease, Chronic Obstructive/physiopathology
• Reproducibility of Results
• Swine
• Tomography, X-Ray Computed
• Treatment Outcome
• Xenon Isotopes/chemistry

• R01 HL112986 NHLBI NIH HHS
• P30 ES005605 NIEHS NIH HHS
• R01 HL077612 NHLBI NIH HHS
• R01 HL126838 NHLBI NIH HHS
• R01 HL093081 NHLBI NIH HHS
• R01 HL121270 NHLBI NIH HHS
• P30 DK054759 NIDDK NIH HHS

• chronic obstructive pulmonary disease (COPD)
• gadolinium-enhanced MRI
• lung emphysema
• pulmonary microvascular blood flow (PMBF)
• small airway disease

• chronic obstructive pulmonary disease
• haplotype
• osteoporosis
• polymorphism
• vitamin D receptor gene

Non-invasive end-points for interventional trials and tailored treatment regimes in chronic obstructive pulmonary disease (COPD) for monitoring regionally different manifestations of lung disease instead of global assessment of lung function with spirometry would be valuable. Proton nuclear magnetic resonance imaging (1H-MRI) allows for a radiation-free assessment of regional structure and function. The aim of this study was to evaluate the short-term reproducibility of a comprehensive morpho-functional lung MRI protocol in COPD.

20 prospectively enrolled COPD patients (GOLD I-IV) underwent 1H-MRI of the lung at 1.5T on two consecutive days, including sequences for morphology, 4D contrast-enhanced perfusion, and respiratory mechanics. Image quality and COPD-related morphological and functional changes were evaluated in consensus by three chest radiologists using a dedicated MRI-based visual scoring system. Test-retest reliability was calculated per each individual lung lobe for the extent of large airway (bronchiectasis, wall thickening, mucus plugging) and small airway abnormalities (tree in bud, peripheral bronchiectasis, mucus plugging), consolidations, nodules, parenchymal defects and perfusion defects. The presence of tracheal narrowing, dystelectasis, pleural effusion, pulmonary trunk ectasia, right ventricular enlargement and, finally, motion patterns of diaphragma and chest wall were addressed.

Median global scores [10(Q1:8.00;Q3:16.00) vs.11(Q1:6.00;Q3:15.00)] as well as category subscores were similar between both timepoints, and kappa statistics indicated “almost perfect” global agreement (ĸ = 0.86, 95%CI = 0.81–0.91). Most subscores showed at least “substantial” agreement of MRI1 and MRI2 (ĸ = 0.64–1.00), whereas the agreement for the diagnosis of dystelectasis/effusion (ĸ = 0.42, 95%CI = 0.00–0.93) was “moderate” and of tracheal abnormalities (ĸ = 0.21, 95%CI = 0.00–0.75) “fair”. Most MRI acquisitions showed at least diagnostic quality at MRI1 (276 of 278) and MRI2 (259 of 264).

Morpho-functional 1H-MRI can be obtained with reproducible image quality and high short-term test-retest reliability for COPD-related morphological and functional changes of the lung. This underlines its potential value for the monitoring of regional lung characteristics in COPD trials.