{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:57:39Z","timestamp":1792897059607,"version":"4.5.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows the assessment of pulmonary perfusion, which may play a key role in the development of muco-obstructive lung disease. One problem with quantifying pulmonary perfusion is the high variability of metrics. Quantifying the extent of abnormalities using unsupervised clustering algorithms in residue function maps leads to intrinsic normalization and could reduce variability.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>We investigated the reproducibility of perfusion defects in percent (QDP) in clinically stable patients with cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>15 CF (29.3 \u00b1 9.3y, FEV1%predicted = 66.6 \u00b1 15.8%) and 20 COPD (66.5 \u00b1 8.9y, FEV1%predicted = 42.0 \u00b1 13.3%) patients underwent DCE-MRI twice 1 month apart. QDP, pulmonary blood flow (PBF), and pulmonary blood volume (PBV) were computed from residue function maps using an in-house quantification pipeline. A previously validated MRI perfusion score was visually assessed by an expert reader.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall, mean QDP, PBF, and PBV did not change within 1 month, except for QDP in COPD (<jats:italic>p<\/jats:italic> &amp;lt; 0.05). We observed smaller limits of agreement (\u00b1 1.96 <jats:italic>SD<\/jats:italic>) related to the median for QDP (CF: \u00b1 38%, COPD: \u00b1 37%) compared to PBF (CF: \u00b1 89%, COPD: \u00b1 55%) and PBV (CF: \u00b1 55%, COPD: \u00b1 51%). QDP correlated moderately with the MRI perfusion score in CF (<jats:italic>r<\/jats:italic> = 0.46, <jats:italic>p<\/jats:italic> &amp;lt; 0.05) and COPD (<jats:italic>r<\/jats:italic> = 0.66, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). PBF and PBV correlated poorly with the MRI perfusion score in CF (<jats:italic>r<\/jats:italic> =\u22120.29, <jats:italic>p<\/jats:italic> = 0.132 and <jats:italic>r<\/jats:italic> =\u22120.35, <jats:italic>p<\/jats:italic> = 0.067, respectively) and moderately in COPD (<jats:italic>r<\/jats:italic> =\u22120.57 and <jats:italic>r<\/jats:italic> =\u22120.57, <jats:italic>p<\/jats:italic> &amp;lt; 0.001, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with muco-obstructive lung diseases, QDP was more robust and showed a higher correlation with the MRI perfusion score compared to the traditionally used perfusion metrics PBF and PBV.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.1022981","type":"journal-article","created":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T04:52:21Z","timestamp":1666587141000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Unsupervised clustering algorithms improve the reproducibility of dynamic contrast-enhanced magnetic resonance imaging pulmonary perfusion quantification in muco-obstructive lung diseases"],"prefix":"10.3389","volume":"9","author":[{"given":"Marilisa","family":"Konietzke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon M. F.","family":"Triphan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Eichinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Bossert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Heller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Wege","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Eberhardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael U.","family":"Puderbach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Ulrich","family":"Kauczor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudula","family":"Heu\u00dfel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claus P.","family":"Heu\u00dfel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Risse","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark O.","family":"Wielp\u00fctz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,10,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1016\/j.ejrad.2011.02.045","article-title":"Morphologic and functional scoring of cystic fibrosis lung disease using MRI.","volume":"81","author":"Eichinger","year":"2012","journal-title":"Eur J Radiol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1097\/rli.0b013e318074fd81","article-title":"Assessment of morphological mri for pulmonary changes in cystic fibrosis (CF) patients.","volume":"42","author":"Puderbach","year":"2007","journal-title":"Invest Radiol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1016\/j.jcf.2013.09.003","article-title":"HRCT and MRI of the lung in children with cystic fibrosis: comparison of different scoring systems.","volume":"13","author":"Sileo","year":"2014","journal-title":"J Cyst Fibros."},{"key":"B4","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/j.jcf.2018.05.003","article-title":"Multicentre standardisation of chest MRI as radiation-free outcome measure of lung disease in young children with cystic fibrosis.","volume":"17","author":"Wielp\u00fctz","year":"2018","journal-title":"J Cyst Fibros."},{"key":"B5","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1164\/rccm.201309-1659oc","article-title":"Magnetic resonance imaging detects changes in structure and perfusion, and response to therapy in early cystic fibrosis lung disease.","volume":"189","author":"Wielp\u00fctz","year":"2014","journal-title":"Am J Respir Crit Care Med."},{"key":"B6","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1164\/rccm.201604-0893oc","article-title":"Comparison of lung clearance index and magnetic resonance imaging for assessment of lung disease in children with cystic fibrosis.","volume":"195","author":"Stahl","year":"2017","journal-title":"Am J Resp Crit Care."},{"key":"B7","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1164\/rccm.201812-2356le","article-title":"Midterm reproducibility of chest magnetic resonance imaging in adults with clinically stable cystic fibrosis and chronic obstructive pulmonary disease.","volume":"200","author":"Wielp\u00fctz","year":"2019","journal-title":"Am J Resp Crit Care."},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1117\/12.911946","article-title":"Automated scoring of regional lung perfusion in children from contrast enhanced 3D MRI.","author":"Heimann","year":"","journal-title":"Proceedings of the SPIE 8315, Medical Imaging 2012: Computer-Aided Diagnosis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1002\/jmri.26342","article-title":"Comparison of quantitative regional perfusion-weighted phase resolved functional lung (PREFUL) MRI with dynamic gadolinium-enhanced regional pulmonary perfusion MRI in COPD patients.","volume":"49","author":"Kaireit","year":"2019","journal-title":"J Magn Reson Imaging."},{"key":"B10","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1097\/rli.0b013e318281057d","article-title":"Quantitative and semiquantitative measures of regional pulmonary microvascular perfusion by magnetic resonance imaging and their relationships to global lung perfusion and lung diffusing capacity: the multiethnic study of atherosclerosis chronic obstructive pulmonary disease study.","volume":"48","author":"Hueper","year":"2013","journal-title":"Invest Radiol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1164\/rccm.201411-2120oc","article-title":"Pulmonary microvascular blood flow in mild chronic obstructive pulmonary disease and emphysema. The MESA COPD study.","volume":"192","author":"Hueper","year":"2015","journal-title":"Am J Respir Crit Care Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1007\/s00330-021-08229-6","article-title":"Quantification of pulmonary perfusion abnormalities using DCE-MRI in COPD: comparison with quantitative CT and pulmonary function.","volume":"32","author":"Schiwek","year":"2021","journal-title":"Eur Radiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1002\/jmri.20137","article-title":"Quantitative assessment of regional pulmonary perfusion in the entire lung using three-dimensional ultrafast dynamic contrast-enhanced magnetic resonance imaging: preliminary experience in 40 subjects.","volume":"20","author":"Ohno","year":"2004","journal-title":"J Magn Reson Imaging."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02058-2021","article-title":"Dynamic contrast enhanced MRI for the evaluation of lung perfusion in idiopathic pulmonary fibrosis.","volume":"10","author":"Torres","year":"2022","journal-title":"Eur Respir J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1007\/s00330-008-0974-1","article-title":"In vivo Gd-DTPA concentration for MR lung perfusion measurements: assessment with computed tomography in a porcine model.","volume":"18","author":"Puderbach","year":"2008","journal-title":"Eur Radiol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1002\/mrm.22025","article-title":"Quantification of pulmonary blood flow (PBF): validation of perfusion MRI and nonlinear contrast agent (CA) dose correction with H?215O positron emission tomography (PET).","volume":"62","author":"Neeb","year":"2009","journal-title":"Magnet Reson Med."},{"key":"B17","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1097\/rti.0b013e3181e48c36","article-title":"Repeatability and reproducibility of quantitative whole-lung perfusion magnetic resonance imaging.","volume":"26","author":"Ley-Zaporozhan","year":"2011","journal-title":"J Thorac Imaging."},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0208587","article-title":"Towards quantitative perfusion MRI of the lung in COPD: the problem of short-term repeatability.","volume":"13","author":"Ter-Karapetyan","year":"2018","journal-title":"PLoS One."},{"key":"B19","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1097\/01.rli.0000149252.42679.78","article-title":"Effect of inspiratory and expiratory breathhold on pulmonary perfusion: assessment by pulmonary perfusion magnetic resonance imaging.","volume":"40","author":"Fink","year":"2005","journal-title":"Invest Radiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2269","DOI":"10.1001\/jama.2012.5214","article-title":"Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial.","volume":"307","author":"Rosenfeld","year":"2012","journal-title":"JAMA."},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00164-2019","article-title":"Global strategy for the diagnosis, management, and prevention of chronic obstructive lung disease: the GOLD science committee report 2019.","volume":"53","author":"Singh","year":"2019","journal-title":"Eur Respir J."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0199148","article-title":"Design and application of an MR reference phantom for multicentre lung imaging trials.","volume":"13","author":"Triphan","year":"2018","journal-title":"PLoS One."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0137282","article-title":"Morpho-functional 1H-MRI of the lung in COPD: short-term test-retest reliability.","volume":"10","author":"Jobst","year":"2015","journal-title":"PLoS One."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1645","DOI":"10.1002\/jmri.27271","article-title":"Echo time-dependence of observed lung T1 in patients with cystic fibrosis and correlation with clinical metrics.","volume":"52","author":"Triphan","year":"2020","journal-title":"J Magn Reson Imaging."},{"key":"B25","author":"Kohlmann","year":"2011","journal-title":"Fully-Automatic Determination of the Arterial Input Function for Dynamic Contrast-Enhanced Pulmonary MR Imaging."},{"key":"B26","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1007\/s11548-014-1090-0","article-title":"Automatic lung segmentation method for MRI-based lung perfusion studies of patients with chronic obstructive pulmonary disease.","volume":"10","author":"Kohlmann","year":"2015","journal-title":"Int J Comput Assist Radiol Surg."},{"key":"B27","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1088\/0031-9155\/52\/2\/009","article-title":"Pixel-by-pixel deconvolution of bolus-tracking data: optimization and implementation.","volume":"52","author":"Sourbron","year":"2006","journal-title":"Phys Med Biol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1164\/rccm.201908-1590st","article-title":"Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement.","volume":"200","author":"Graham","year":"2019","journal-title":"Am J Resp Crit Care."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.2307\/3001968","article-title":"Individual comparisons by ranking methods.","volume":"1","author":"Wilcoxon","year":"1945","journal-title":"Biometrics Bull."},{"key":"B30","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1001\/archpsyc.61.3.310","article-title":"Move over ANOVA: progress in analyzing repeated-measures data andits reflection in papers published in the archives of general psychiatry.","volume":"61","author":"Gueorguieva","year":"2004","journal-title":"Arch Gen Psychiatry."},{"key":"B31","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1080\/01621459.1952.10483441","article-title":"Use of ranks in one-criterion variance analysis.","volume":"47","author":"Kruskal","year":"1952","journal-title":"J Am Stat Assoc."},{"key":"B32","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1098\/rsta.1898.0007","article-title":"VII. Mathematical contributions to the theory of evolution.\u2014 IV. On the probable errors of frequency constants and on the influence of random selection on variation and correlation.","volume":"191","author":"Pearson","year":"1898","journal-title":"Philos Trans R Soc."},{"key":"B33","doi-asserted-by":"publisher","first-page":"307","DOI":"10.2307\/2987937","article-title":"Measurement in medicine: the analysis of method comparison studies.","volume":"32","author":"Altman","year":"1983","journal-title":"J R Stat Soc Ser D Stat."},{"key":"B34","doi-asserted-by":"publisher","first-page":"7485","DOI":"10.1073\/pnas.0913880107","article-title":"Heterogeneity of pulmonary perfusion as a mechanistic image-based phenotype in emphysema susceptible smokers.","volume":"107","author":"Alford","year":"2010","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1902","DOI":"10.1152\/japplphysiol.00085.2009","article-title":"Ventilation-perfusion imbalance and chronic obstructive pulmonary disease staging severity.","volume":"106","author":"Rodri\u00ecguez-Roisin","year":"2009","journal-title":"J Appl Physiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1378\/chest.08-0820","article-title":"Pulmonary vascular involvement in COPD.","volume":"134","author":"Peinado","year":"2008","journal-title":"Chest."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1164\/rccm.201805-0995oc","article-title":"Effect of indacaterol\/glycopyrronium on pulmonary perfusion and ventilation in hyperinflated patients with chronic obstructive pulmonary disease (CLAIM). A double-blind, randomized, crossover trial.","volume":"199","author":"Vogel-Claussen","year":"2019","journal-title":"Am J Resp Crit Care."},{"key":"B38","doi-asserted-by":"publisher","first-page":"344","DOI":"10.4261\/1305-3825.dir.5365-11.0","article-title":"MRI of the lung: state of the art.","volume":"18","author":"Wielp\u00fctz","year":"2012","journal-title":"Diagn Interv Radiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1152\/jappl.1954.6.12.731","article-title":"On the theory of the indicator-dilution method for measurement of blood flow and volume.","volume":"6","author":"Meier","year":"1954","journal-title":"J Appl Physiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1161\/01.res.10.3.393","article-title":"Theoretical basis of indicator-dilution methods for measuring flow and volume.","volume":"10","author":"Zierler","year":"1962","journal-title":"Circ Res."},{"key":"B41","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1002\/jmri.20290","article-title":"Combined helium-3\/proton magnetic resonance imaging measurement of ventilated lung volumes in smokers compared to never-smokers.","volume":"21","author":"Woodhouse","year":"2005","journal-title":"J Magn Reson Imaging."},{"key":"B42","doi-asserted-by":"publisher","first-page":"753","DOI":"10.1016\/j.acra.2007.10.019","article-title":"Evaluation of structure-function relationships in asthma using multidetector CT and hyperpolarized He-3 MRI.","volume":"15","author":"Fain","year":"2008","journal-title":"Acad Radiol."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01987-2019","article-title":"Pulmonary xenon-129 MRI: new opportunities to unravel enigmas in respiratory medicine.","volume":"55","author":"Eddy","year":"2020","journal-title":"Eur Respir J."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00324-2018","article-title":"What is the minimal clinically important difference for helium-3 magnetic resonance imaging ventilation defects?","volume":"51","author":"Eddy","year":"2018","journal-title":"Eur Respir J."},{"key":"B45","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1148\/radiol.2018171993","article-title":"Free-breathing pulmonary MR imaging to quantify regional ventilation.","volume":"287","author":"Capaldi","year":"2018","journal-title":"Radiology."},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.rmed.2021.106623","article-title":"Combined use of rheology and portable low-field NMR in cystic fibrosis patients.","volume":"189","author":"Abrami","year":"2021","journal-title":"Respir Med."},{"key":"B47","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1002\/mrm.28115","article-title":"Use of low field nuclear magnetic resonance to monitor lung inflammation and the amount of pathological components in the sputum of cystic fibrosis patients.","volume":"84","author":"Abrami","year":"2020","journal-title":"Magn Reson Med."},{"key":"B48","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1055\/s-2004-817624","article-title":"Quantitative analysis of pulmonary perfusion using time-resolved parallel 3D MRI \u2013 initial results.","volume":"176","author":"Fink","year":"2004","journal-title":"R\u00f6fo."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1022981\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T04:52:26Z","timestamp":1666587146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.1022981\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,24]]},"references-count":48,"alternative-id":["10.3389\/fmed.2022.1022981"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.1022981","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,24]]},"article-number":"1022981"}}