{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T10:07:30Z","timestamp":1789380450978,"version":"build-2803163510"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100001003","name":"Boehringer Ingelheim","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001003","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010564","name":"Deutsches Zentrum f\u00fcr Lungenforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur Radiol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To evaluate the effects of tiotropium\/olodaterol (T\/O) on phase-resolved functional lung (PREFUL) MRI parameters in hyperinflated chronic obstructive pulmonary disease (COPD) patients and examine correlations with conventional cardiopulmonary and hyperpolarized\n                      <jats:sup>129<\/jats:sup>\n                      Xe MRI measures.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and methods<\/jats:title>\n                    <jats:p>Retrospective subanalysis of a prospective, randomized, placebo-controlled, crossover trial with open-label extension. Thirty-two patients with moderate-to-severe COPD (61.5\u2009\u00b1\u20097.7 years; 17 men); 30 completed the MRI extension at 1.5\u2009T. PREFUL analysis yielded regional ventilation (RVent), flow-volume loop correlation metric (FVL-CM), normalized perfusion (QN), ventilation defect percentage (VDP), perfusion defect percentage (QDP), V\/Q match metrics (VQM), and pulmonary pulse wave velocity (PWV; post-hoc parameter). Linear mixed-effects models tested treatment effects; correlations were evaluated with Spearman\u2019s rank and bootstrap 95% confidence intervals (95% CIs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      PREFUL parameters improved after T\/O single dose (SD) versus placebo, including improvements in FVL-CM by 4.1 percentage points (pp; 95% CI: 1.0 to 7.3 pp) and QN by 0.4 pp (95% CI: 0.2 to 0.6 pp) and reductions in VDP and QDP, with parallel gains in VQM(Non-Defect) (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). PWV decreased after multiple doses (\u22120.87\u2009m\/s, 95% CI: \u22121.26 to \u22120.48\u2009m\/s). PREFUL MRI baseline values showed significant correlations with pulmonary function tests, cardiac, dynamic contrast-enhanced and\n                      <jats:sup>129<\/jats:sup>\n                      Xe MRI. SD treatment-induced absolute changes in VDP(FVL-CM) correlated with reductions in residual volume (\n                      <jats:italic>\u03c1<\/jats:italic>\n                      \u2009=\u20090.41, 95% CI: 0.02 to 0.64). Further correlations were observed between PREFUL MRI and \u00b9\u00b2\u2079Xe-derived VDP, apparent diffusion coefficient, and compartment ratios.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PREFUL MRI sensitively captured immediate SD T\/O-induced improvements in V\/Q parameters and dose-dependent PWV responses after sustained bronchodilation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Question<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>Can phase-resolved functional lung (PREFUL) MRI sensitively capture immediate single-dose and sustain multi-dose effects of tiotropium\/olodaterol on ventilation-perfusion and vascular function in COPD patients?<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Findings<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>Tiotropium\/olodaterol improved PREFUL MRI-derived ventilation, perfusion, and V\/Q matching parameters after a single dose, with sustained pulmonary vascular improvements after repeated dosing.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      <jats:bold>\n                        <jats:italic>Clinical relevance<\/jats:italic>\n                      <\/jats:bold>\n                      <jats:italic>PREFUL MRI detected immediate and sustained functional improvements after tiotropium\/olodaterol and showed significant correlations with cardiopulmonary tests and hyperpolarized \u00b9\u00b2\u2079Xe MRI, supporting its role as a sensitive, radiation-free tool for monitoring COPD treatment response.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00330-026-12604-6","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T15:02:34Z","timestamp":1779289354000},"page":"7731-7746","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phase-resolved functional lung MRI detects single-dose and sustained bronchodilator responses in COPD in a randomized crossover trial"],"prefix":"10.1007","volume":"36","author":[{"given":"Andreas","family":"Voskrebenzev","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Till F.","family":"Kaireit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius M.","family":"Klein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agilo L.","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Behrendt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Filip","family":"Klime\u0161","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin A.","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Kayser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Wacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens","family":"Vogel-Claussen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5595-6948","authenticated-orcid":false,"given":"Jens M.","family":"Hohlfeld","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"12604_CR1","doi-asserted-by":"publisher","DOI":"10.7189\/jogh.05.020415","volume":"5","author":"D Adeloye","year":"2015","unstructured":"Adeloye D, Chua S, Lee C et al (2015) Global and regional estimates of COPD prevalence: Systematic review and meta-analysis. J Glob Health 5:020415. https:\/\/doi.org\/10.7189\/jogh.05.020415","journal-title":"J Glob Health"},{"key":"12604_CR2","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1097\/01.NPR.0000000000000180","volume":"49","author":"N Patel","year":"2024","unstructured":"Patel N (2024) An update on COPD prevention, diagnosis, and management: The 2024 GOLD Report. Nurse Pract 49:29\u201336. https:\/\/doi.org\/10.1097\/01.NPR.0000000000000180","journal-title":"Nurse Pract"},{"key":"12604_CR3","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1378\/chest.09-2810","volume":"138","author":"H Watz","year":"2010","unstructured":"Watz H, Waschki B, Meyer T et al (2010) Decreasing cardiac chamber sizes and associated heart dysfunction in COPD: role of hyperinflation. Chest 138:32\u201338. https:\/\/doi.org\/10.1378\/chest.09-2810","journal-title":"Chest"},{"key":"12604_CR4","doi-asserted-by":"publisher","first-page":"187","DOI":"10.2147\/COPD.S38934","volume":"9","author":"P Gagnon","year":"2014","unstructured":"Gagnon P, Guenette JA, Langer D et al (2014) Pathogenesis of hyperinflation in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 9:187\u2013201. https:\/\/doi.org\/10.2147\/COPD.S38934","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"key":"12604_CR5","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1016\/j.pupt.2010.03.003","volume":"23","author":"M Cazzola","year":"2010","unstructured":"Cazzola M, Molimard M (2010) The scientific rationale for combining long-acting beta2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther 23:257\u2013267. https:\/\/doi.org\/10.1016\/j.pupt.2010.03.003","journal-title":"Pulm Pharmacol Ther"},{"key":"12604_CR6","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4104\/pcrj.2011.00102","volume":"21","author":"T van der Molen","year":"2012","unstructured":"van der Molen T, Cazzola M (2012) Beyond lung function in COPD management: effectiveness of LABA\/LAMA combination therapy on patient-centred outcomes. Prim Care Respir J J Gen Pract Airw Group 21:101\u2013108. https:\/\/doi.org\/10.4104\/pcrj.2011.00102","journal-title":"Prim Care Respir J J Gen Pract Airw Group"},{"key":"12604_CR7","doi-asserted-by":"publisher","first-page":"1700214","DOI":"10.1183\/13993003.00214-2017","volume":"49","author":"CF Vogelmeier","year":"2017","unstructured":"Vogelmeier CF, Criner GJ, Martinez FJ et al (2017) Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease 2017 Report: GOLD executive summary. Eur Respir J 49:1700214. https:\/\/doi.org\/10.1183\/13993003.00214-2017","journal-title":"Eur Respir J"},{"key":"12604_CR8","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1016\/j.rmed.2015.08.002","volume":"109","author":"D Singh","year":"2015","unstructured":"Singh D, Ferguson GT, Bolitschek J et al (2015) Tiotropium + olodaterol shows clinically meaningful improvements in quality of life. Respir Med 109:1312\u20131319. https:\/\/doi.org\/10.1016\/j.rmed.2015.08.002","journal-title":"Respir Med"},{"key":"12604_CR9","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.rmed.2019.09.006","volume":"157","author":"DC Berton","year":"2019","unstructured":"Berton DC, Marques RD, Palmer B et al (2019) Effects of lung deflation induced by tiotropium\/olodaterol on the cardiocirculatory responses to exertion in COPD. Respir Med 157:59\u201368. https:\/\/doi.org\/10.1016\/j.rmed.2019.09.006","journal-title":"Respir Med"},{"key":"12604_CR10","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/S2213-2600(18)30054-7","volume":"6","author":"JM Hohlfeld","year":"2018","unstructured":"Hohlfeld JM, Vogel-Claussen J, Biller H et al (2018) Effect of lung deflation with indacaterol plus glycopyrronium on ventricular filling in patients with hyperinflation and COPD (CLAIM): a double-blind, randomised, crossover, placebo-controlled, single-centre trial. Lancet Respir Med 6:368\u2013378. https:\/\/doi.org\/10.1016\/S2213-2600(18)30054-7","journal-title":"Lancet Respir Med"},{"key":"12604_CR11","doi-asserted-by":"publisher","first-page":"2937","DOI":"10.3390\/jcm13102937","volume":"13","author":"I Dimiene","year":"2024","unstructured":"Dimiene I, Hoppenot D, Vajauskas D et al (2024) Systemic manifestations of COPD and the impact of dual bronchodilation with tiotropium\/olodaterol on cardiac function and autonomic integrity. J Clin Med 13:2937. https:\/\/doi.org\/10.3390\/jcm13102937","journal-title":"J Clin Med"},{"key":"12604_CR12","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1378\/chest.06-2245","volume":"131","author":"K J\u00f6rgensen","year":"2007","unstructured":"J\u00f6rgensen K, M\u00fcller MF, Nel J et al (2007) Reduced intrathoracic blood volume and left and right ventricular dimensions in patients with severe emphysema: an MRI study. Chest 131:1050\u20131057. https:\/\/doi.org\/10.1378\/chest.06-2245","journal-title":"Chest"},{"key":"12604_CR13","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1164\/rccm.201508-1647OC","volume":"193","author":"IS Stone","year":"2016","unstructured":"Stone IS, Barnes NC, James W-Y et al (2016) Lung deflation and cardiovascular structure and function in chronic obstructive pulmonary disease. a randomized controlled trial. Am J Respir Crit Care Med 193:717\u2013726. https:\/\/doi.org\/10.1164\/rccm.201508-1647OC","journal-title":"Am J Respir Crit Care Med"},{"key":"12604_CR14","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1148\/radiology.200.2.8685356","volume":"200","author":"JR MacFall","year":"1996","unstructured":"MacFall JR, Charles HC, Black RD et al (1996) Human lung air spaces: potential for MR imaging with hyperpolarized He-3. Radiology 200:553\u2013558. https:\/\/doi.org\/10.1148\/radiology.200.2.8685356","journal-title":"Radiology"},{"key":"12604_CR15","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1002\/jmri.20154","volume":"20","author":"EJR van Beek","year":"2004","unstructured":"van Beek EJR, Wild JM, Kauczor H-U et al (2004) Functional MRI of the lung using hyperpolarized 3-helium gas. J Magn Reson Imaging 20:540\u2013554. https:\/\/doi.org\/10.1002\/jmri.20154","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/370199a0","volume":"370","author":"MS Albert","year":"1994","unstructured":"Albert MS, Cates GD, Driehuys B et al (1994) Biological magnetic resonance imaging using laser-polarized 129Xe. Nature 370:199\u2013201. https:\/\/doi.org\/10.1038\/370199a0","journal-title":"Nature"},{"key":"12604_CR17","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1002\/mrm.1910370602","volume":"37","author":"JP Mugler III","year":"1997","unstructured":"Mugler IIIJP, Driehuys B, Brookeman JR et al (1997) MR imaging and spectroscopy using hyperpolarized 129Xe gas: Preliminary human results. Magn Reson Med 37:809\u2013815. https:\/\/doi.org\/10.1002\/mrm.1910370602","journal-title":"Magn Reson Med"},{"key":"12604_CR18","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1002\/jmri.23844","volume":"37","author":"JP Mugler","year":"2013","unstructured":"Mugler JP, Altes TA (2013) Hyperpolarized 129Xe MRI of the human lung. J Magn Reson Imaging 37:313\u2013331. https:\/\/doi.org\/10.1002\/jmri.23844","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR19","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20170647","volume":"91","author":"AL Kern","year":"2018","unstructured":"Kern AL, Vogel-Claussen J (2018) Hyperpolarized gas MRI in pulmonology. Br J Radiol 91:20170647. https:\/\/doi.org\/10.1259\/bjr.20170647","journal-title":"Br J Radiol"},{"key":"12604_CR20","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1016\/j.acra.2018.05.025","volume":"26","author":"K Qing","year":"2019","unstructured":"Qing K, Tustison NJ, Mugler JP et al (2019) Probing changes in lung physiology in COPD using CT, perfusion MRI, and hyperpolarized Xenon-129 MRI. Acad Radiol 26:326\u2013334. https:\/\/doi.org\/10.1016\/j.acra.2018.05.025","journal-title":"Acad Radiol"},{"key":"12604_CR21","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1002\/nbm.2940","volume":"26","author":"SP Sourbron","year":"2013","unstructured":"Sourbron SP, Buckley DL (2013) Classic models for dynamic contrast-enhanced MRI. NMR Biomed 26:1004\u20131027. https:\/\/doi.org\/10.1002\/nbm.2940","journal-title":"NMR Biomed"},{"key":"12604_CR22","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1002\/jmri.26853","volume":"51","author":"HB Winther","year":"2020","unstructured":"Winther HB, Gutberlet M, Hundt C et al (2020) Deep semantic lung segmentation for tracking potential pulmonary perfusion biomarkers in chronic obstructive pulmonary disease (COPD): The multi-ethnic study of atherosclerosis COPD study. J Magn Reson Imaging 51:571\u2013579. https:\/\/doi.org\/10.1002\/jmri.26853","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR23","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1007\/s00330-021-08229-6","volume":"32","author":"M Schiwek","year":"2022","unstructured":"Schiwek M, Triphan SMF, Biederer J et al (2022) Quantification of pulmonary perfusion abnormalities using DCE-MRI in COPD: comparison with quantitative CT and pulmonary function. Eur Radiol 32:1879\u20131890. https:\/\/doi.org\/10.1007\/s00330-021-08229-6","journal-title":"Eur Radiol"},{"key":"12604_CR24","doi-asserted-by":"publisher","unstructured":"Edwards L, Waterton JC, Naish J et al (2023) Imaging human lung perfusion with contrast media: a meta-analysis. Eur J Radiol 164. https:\/\/doi.org\/10.1016\/j.ejrad.2023.110850","DOI":"10.1016\/j.ejrad.2023.110850"},{"key":"12604_CR25","doi-asserted-by":"publisher","first-page":"4071","DOI":"10.3390\/ijms25074071","volume":"25","author":"S Coimbra","year":"2024","unstructured":"Coimbra S, Rocha S, Sousa NR et al (2024) Toxicity mechanisms of gadolinium and gadolinium-based contrast agents-a review. Int J Mol Sci 25:4071. https:\/\/doi.org\/10.3390\/ijms25074071","journal-title":"Int J Mol Sci"},{"key":"12604_CR26","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1002\/mrm.22031","volume":"62","author":"G Bauman","year":"2009","unstructured":"Bauman G, Puderbach M, Deimling M et al (2009) Non-contrast-enhanced perfusion and ventilation assessment of the human lung by means of Fourier decomposition in proton MRI. Magn Reson Med 62:656\u2013664. https:\/\/doi.org\/10.1002\/mrm.22031","journal-title":"Magn Reson Med"},{"key":"12604_CR27","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1002\/nbm.3134","volume":"27","author":"A Fischer","year":"2014","unstructured":"Fischer A, Weick S, Ritter CO et al (2014) SElf-gated Non-Contrast-Enhanced FUnctional Lung imaging (SENCEFUL) using a quasi-random fast low-angle shot (FLASH) sequence and proton MRI. NMR Biomed 27:907\u2013917. https:\/\/doi.org\/10.1002\/nbm.3134","journal-title":"NMR Biomed"},{"key":"12604_CR28","doi-asserted-by":"publisher","first-page":"336","DOI":"10.1002\/mrm.26096","volume":"77","author":"G Bauman","year":"2017","unstructured":"Bauman G, Bieri O (2017) Matrix pencil decomposition of time-resolved proton MRI for robust and improved assessment of pulmonary ventilation and perfusion. Magn Reson Med 77:336\u2013342. https:\/\/doi.org\/10.1002\/mrm.26096","journal-title":"Magn Reson Med"},{"key":"12604_CR29","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.1002\/mrm.26893","volume":"79","author":"A Voskrebenzev","year":"2018","unstructured":"Voskrebenzev A, Gutberlet M, Klime\u0161 F et al (2018) Feasibility of quantitative regional ventilation and perfusion mapping with phase-resolved functional lung (PREFUL) MRI in healthy volunteers and COPD, CTEPH, and CF patients. Magn Reson Med 79:2306\u20132314. https:\/\/doi.org\/10.1002\/mrm.26893","journal-title":"Magn Reson Med"},{"key":"12604_CR30","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1002\/mrm.27803","volume":"82","author":"D Bondesson","year":"2019","unstructured":"Bondesson D, Schneider MJ, Gaass T et al (2019) Nonuniform Fourier-decomposition MRI for ventilation- and perfusion-weighted imaging of the lung. Magn Reson Med 82:1312\u20131321. https:\/\/doi.org\/10.1002\/mrm.27803","journal-title":"Magn Reson Med"},{"key":"12604_CR31","doi-asserted-by":"publisher","first-page":"1764","DOI":"10.1002\/mrm.29302","volume":"88","author":"E Ilicak","year":"2022","unstructured":"Ilicak E, Ozdemir S, Schad LR et al (2022) Phase-cycled balanced SSFP imaging for non-contrast-enhanced functional lung imaging. Magn Reson Med 88:1764\u20131774. https:\/\/doi.org\/10.1002\/mrm.29302","journal-title":"Magn Reson Med"},{"key":"12604_CR32","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1002\/jmri.29444","volume":"61","author":"ZJT Peggs","year":"2025","unstructured":"Peggs ZJT, Brooke JP, Bolton CE et al (2025) Free-breathing functional pulmonary proton MRI: a novel approach using voxel-wise lung ventilation (VOLVE) assessment in healthy volunteers and patients with chronic obstructive pulmonary disease. J Magn Reson Imaging 61:663\u2013675. https:\/\/doi.org\/10.1002\/jmri.29444","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR33","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/j.acra.2014.10.003","volume":"22","author":"DPI Capaldi","year":"2015","unstructured":"Capaldi DPI, Sheikh K, Guo F et al (2015) Free-breathing pulmonary 1H and hyperpolarized 3He MRI: comparison in COPD and Bronchiectasis. Acad Radiol 22:320\u2013329. https:\/\/doi.org\/10.1016\/j.acra.2014.10.003","journal-title":"Acad Radiol"},{"key":"12604_CR34","doi-asserted-by":"publisher","first-page":"026002","DOI":"10.1117\/1.JMI.5.2.026002","volume":"5","author":"F Guo","year":"2018","unstructured":"Guo F, Capaldi D, Kirby M et al (2018) Development of a pulmonary imaging biomarker pipeline for phenotyping of chronic lung disease. J Med Imaging 5:026002. https:\/\/doi.org\/10.1117\/1.JMI.5.2.026002","journal-title":"J Med Imaging"},{"key":"12604_CR35","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1002\/jmri.25902","volume":"47","author":"TF Kaireit","year":"2018","unstructured":"Kaireit TF, Gutberlet M, Voskrebenzev A et al (2018) Comparison of quantitative regional ventilation-weighted fourier decomposition MRI with dynamic fluorinated gas washout MRI and lung function testing in COPD patients. J Magn Reson Imaging 47:1534\u20131541. https:\/\/doi.org\/10.1002\/jmri.25902","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR36","doi-asserted-by":"publisher","first-page":"1122","DOI":"10.1002\/jmri.26342","volume":"49","author":"TF Kaireit","year":"2019","unstructured":"Kaireit TF, Voskrebenzev A, Gutberlet M et al (2019) Comparison of quantitative regional perfusion-weighted phase resolved functional lung (PREFUL) MRI with dynamic gadolinium-enhanced regional pulmonary perfusion MRI in COPD patients. J Magn Reson Imaging 49:1122\u20131132. https:\/\/doi.org\/10.1002\/jmri.26342","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR37","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1002\/jmri.27452","volume":"53","author":"TF Kaireit","year":"2021","unstructured":"Kaireit TF, Kern A, Voskrebenzev A et al (2021) Flow volume loop and regional ventilation assessment using phase-resolved functional lung (PREFUL) MRI: comparison with 129 xenon ventilation MRI and lung function testing. J Magn Reson Imaging 53:1092\u20131105. https:\/\/doi.org\/10.1002\/jmri.27452","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR38","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1002\/jmri.28016","volume":"56","author":"GH P\u00f6hler","year":"2022","unstructured":"P\u00f6hler GH, L\u00f6ffler F, Klime\u0161 F et al (2022) Validation of phase-resolved functional lung (preful) magnetic resonance imaging pulse wave transit time compared to echocardiography in chronic obstructive pulmonary disease. J Magn Reson Imaging 56:605\u2013615. https:\/\/doi.org\/10.1002\/jmri.28016","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR39","doi-asserted-by":"publisher","DOI":"10.3389\/fmed.2024.1418052","volume":"11","author":"A Voskrebenzev","year":"2024","unstructured":"Voskrebenzev A, Gutberlet M, Klime\u0161 F et al (2024) A synthetic lung model (ASYLUM) for validation of functional lung imaging methods shows significant differences between signal-based and deformation-field-based ventilation measurements. Front Med 11:1418052. https:\/\/doi.org\/10.3389\/fmed.2024.1418052","journal-title":"Front Med"},{"key":"12604_CR40","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.1002\/jmri.26799","volume":"50","author":"TM Alsady","year":"2019","unstructured":"Alsady TM, Voskrebenzev A, Greer M et al (2019) MRI-derived regional flow-volume loop parameters detect early-stage chronic lung allograft dysfunction. J Magn Reson Imaging 50:1873\u20131882. https:\/\/doi.org\/10.1002\/jmri.26799","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR41","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.221958","volume":"307","author":"J Vogel-Claussen","year":"2023","unstructured":"Vogel-Claussen J, Kaireit TF, Voskrebenzev A et al (2023) Phase-resolved Functional Lung (PREFUL) MRI-derived Ventilation and Perfusion Parameters Predict Future Lung Transplant Loss. Radiology 307:e221958. https:\/\/doi.org\/10.1148\/radiol.221958","journal-title":"Radiology"},{"key":"12604_CR42","doi-asserted-by":"publisher","unstructured":"Voskrebenzev A, Kaireit T, Klime\u0161 F et al (2019) Effect of indacaterol\/glycopyrronium on ventilation\/perfusion match and ventilation dynamics in hyperinflated COPD patients: The CLAIM study. Eur Respir J 54. https:\/\/doi.org\/10.1183\/13993003.congress-2019.PA3381","DOI":"10.1183\/13993003.congress-2019.PA3381"},{"key":"12604_CR43","doi-asserted-by":"publisher","unstructured":"Marshall H, Voskrebenzev A, Biancardi A et al (2018) Comparison of 1H MRI and 3He MRI ventilation images in patients with cystic fibrosis and patients with lung cancer. Eur Respir J 52. https:\/\/doi.org\/10.1183\/13993003.congress-2018.PA387","DOI":"10.1183\/13993003.congress-2018.PA387"},{"key":"12604_CR44","doi-asserted-by":"publisher","first-page":"e209","DOI":"10.1016\/j.acra.2020.05.008","volume":"28","author":"MJ Couch","year":"2021","unstructured":"Couch MJ, Munidasa S, Rayment JH et al (2021) Comparison of functional free-breathing pulmonary 1H and hyperpolarized 129Xe magnetic resonance imaging in pediatric cystic fibrosis. Acad Radiol 28:e209\u2013e218. https:\/\/doi.org\/10.1016\/j.acra.2020.05.008","journal-title":"Acad Radiol"},{"key":"12604_CR45","doi-asserted-by":"publisher","first-page":"1908","DOI":"10.1002\/jmri.28470","volume":"57","author":"H Marshall","year":"2023","unstructured":"Marshall H, Voskrebenzev A, Smith LJ et al (2023) 129Xe and free-breathing 1H Ventilation MRI in patients with cystic fibrosis: a dual-center study. J Magn Reson Imaging 57:1908\u20131921. https:\/\/doi.org\/10.1002\/jmri.28470","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR46","doi-asserted-by":"publisher","unstructured":"Kayser T, Stru\u00df N, Pflock R et al (2026) Acute and 14-day effects of tiotropium\/olodaterol on cardiopulmonary function in COPD. ERJ Open Res. https:\/\/doi.org\/10.1183\/23120541.01282-2025","DOI":"10.1183\/23120541.01282-2025"},{"key":"12604_CR47","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1183\/09031936.05.00034805","volume":"26","author":"MR Miller","year":"2005","unstructured":"Miller MR, Hankinson J, Brusasco V et al (2005) Standardisation of spirometry. Eur Respir J 26:319\u2013338. https:\/\/doi.org\/10.1183\/09031936.05.00034805","journal-title":"Eur Respir J"},{"key":"12604_CR48","unstructured":"Smith HJ, Reinhold P, Goldman MD (2025) Forced oscillation technique and impulse oscillometry. In: Lung function testing. European Respiratory Society. pp. 72\u2013105"},{"key":"12604_CR49","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1183\/09031936.05.00035005","volume":"26","author":"J Wanger","year":"2005","unstructured":"Wanger J, Clausen JL, Coates A et al (2005) Standardisation of the measurement of lung volumes. Eur Respir J 26:511\u2013522. https:\/\/doi.org\/10.1183\/09031936.05.00035005","journal-title":"Eur Respir J"},{"key":"12604_CR50","doi-asserted-by":"publisher","unstructured":"Voskrebenzev A, Klime\u0161 F, Wacker F, Vogel-Claussen J (2024) Phase-resolved functional lung MRI for pulmonary ventilation and perfusion (V\/Q) assessment. J Vis Exp e66380. https:\/\/doi.org\/10.3791\/66380","DOI":"10.3791\/66380"},{"key":"12604_CR51","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1016\/j.neuroimage.2010.09.025","volume":"54","author":"BB Avants","year":"2011","unstructured":"Avants BB, Tustison NJ, Song G et al (2011) A reproducible evaluation of ANTs similarity metric performance in brain image registration. NeuroImage 54:2033\u20132044. https:\/\/doi.org\/10.1016\/j.neuroimage.2010.09.025","journal-title":"NeuroImage"},{"key":"12604_CR52","doi-asserted-by":"publisher","first-page":"1496","DOI":"10.1002\/mrm.26526","volume":"78","author":"A Voskrebenzev","year":"2017","unstructured":"Voskrebenzev A, Gutberlet M, Kaireit TF et al (2017) Low-pass imaging of dynamic acquisitions (LIDA) with a group-oriented registration (GOREG) for proton MR imaging of lung ventilation. Magn Reson Med 78:1496\u20131505. https:\/\/doi.org\/10.1002\/mrm.26526","journal-title":"Magn Reson Med"},{"key":"12604_CR53","doi-asserted-by":"publisher","first-page":"e0285378","DOI":"10.1371\/journal.pone.0285378","volume":"18","author":"C Crisosto","year":"2023","unstructured":"Crisosto C, Voskrebenzev A, Gutberlet M et al (2023) Artificially-generated consolidations and balanced augmentation increase performance of U-net for lung parenchyma segmentation on MR images. PloS One 18:e0285378. https:\/\/doi.org\/10.1371\/journal.pone.0285378","journal-title":"PloS One"},{"key":"12604_CR54","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1002\/jmri.27027","volume":"52","author":"L Behrendt","year":"2020","unstructured":"Behrendt L, Voskrebenzev A, Klime\u0161 F et al (2020) Validation of automated perfusion-weighted Phase-Resolved Functional Lung (PREFUL)-MRI in patients with pulmonary diseases. J Magn Reson Imaging 52:103\u2013114. https:\/\/doi.org\/10.1002\/jmri.27027","journal-title":"J Magn Reson Imaging"},{"key":"12604_CR55","doi-asserted-by":"publisher","unstructured":"Wernz MM, Voskrebenzev A, M\u00fcller RA et al (2024) Feasibility, repeatability, and correlation to lung function of Phase-Resolved Functional Lung (PREFUL) MRI-derived pulmonary artery pulse wave velocity measurements. J Magn Reson Imaging. https:\/\/doi.org\/10.1002\/jmri.29337","DOI":"10.1002\/jmri.29337"},{"key":"12604_CR56","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.4088","volume":"32","author":"F Klime\u0161","year":"2019","unstructured":"Klime\u0161 F, Voskrebenzev A, Gutberlet M et al (2019) Free-breathing quantification of regional ventilation derived by phase-resolved functional lung (PREFUL) MRI. NMR Biomed 32:e4088. https:\/\/doi.org\/10.1002\/nbm.4088","journal-title":"NMR Biomed"},{"key":"12604_CR57","doi-asserted-by":"publisher","unstructured":"Hahn JJ, Voskrebenzev A, Behrendt L et al (2024) Sequence comparison of spoiled gradient echo and balanced steady-state free precession for pulmonary free-breathing proton MRI in patients and healthy volunteers: Correspondence, repeatability, and validation with dynamic contrast-enhanced MRI. NMR Biomed e5209. https:\/\/doi.org\/10.1002\/nbm.5209","DOI":"10.1002\/nbm.5209"},{"key":"12604_CR58","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1080\/19466315.2020.1784780","volume":"13","author":"G Shan","year":"2021","unstructured":"Shan G, Bayram E, Caldwell JZK et al (2021) Partial correlation coefficient for a study with repeated measurements. Stat Biopharm Res 13:448\u2013454. https:\/\/doi.org\/10.1080\/19466315.2020.1784780","journal-title":"Stat Biopharm Res"},{"key":"12604_CR59","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1164\/rccm.201805-0995OC","volume":"199","author":"J Vogel-Claussen","year":"2019","unstructured":"Vogel-Claussen J, Sch\u00f6nfeld C-O, Kaireit TF et al (2019) Effect of indacaterol\/glycopyrronium on pulmonary perfusion and ventilation in hyperinflated patients with chronic obstructive pulmonary disease (CLAIM). A double-blind, randomized, crossover trial. Am J Respir Crit Care Med 199:1086\u20131096. https:\/\/doi.org\/10.1164\/rccm.201805-0995OC","journal-title":"Am J Respir Crit Care Med"},{"key":"12604_CR60","doi-asserted-by":"publisher","first-page":"e0176180","DOI":"10.1371\/journal.pone.0176180","volume":"12","author":"CP Aaron","year":"2017","unstructured":"Aaron CP, Hoffman EA, Lima JAC et al (2017) Pulmonary vascular volume, impaired left ventricular filling and dyspnea: The MESA Lung Study. PLOS One 12:e0176180. https:\/\/doi.org\/10.1371\/journal.pone.0176180","journal-title":"PLOS One"},{"key":"12604_CR61","doi-asserted-by":"publisher","DOI":"10.1002\/pul2.12054","volume":"12","author":"L Behrendt","year":"2022","unstructured":"Behrendt L, Smith LJ, Voskrebenzev A et al (2022) A dual center and dual vendor comparison study of automated perfusion-weighted phase-resolved functional lung magnetic resonance imaging with dynamic contrast-enhanced magnetic resonance imaging in patients with cystic fibrosis. Pulm Circ 12:e12054. https:\/\/doi.org\/10.1002\/pul2.12054","journal-title":"Pulm Circ"},{"key":"12604_CR62","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1002\/mrm.28787","volume":"86","author":"J Glandorf","year":"2021","unstructured":"Glandorf J, Klime\u0161 F, Behrendt L et al (2021) Perfusion quantification using voxel-wise proton density and median signal decay in PREFUL MRI. Magn Reson Med 86:1482\u20131493. https:\/\/doi.org\/10.1002\/mrm.28787","journal-title":"Magn Reson Med"},{"key":"12604_CR63","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1136\/thoraxjnl-2020-214924","volume":"76","author":"L Myc","year":"2021","unstructured":"Myc L, Qing K, He M et al (2021) Characterisation of gas exchange in COPD with dissolved-phase hyperpolarised xenon-129 MRI. Thorax 76:178\u2013181. https:\/\/doi.org\/10.1136\/thoraxjnl-2020-214924","journal-title":"Thorax"},{"key":"12604_CR64","doi-asserted-by":"publisher","first-page":"3416","DOI":"10.1016\/j.acra.2024.01.039","volume":"31","author":"Y Friedlander","year":"2024","unstructured":"Friedlander Y, Munidasa S, Thakar A et al (2024) Phase-resolved functional lung (PREFUL) MRI to quantify ventilation: feasibility and physiological relevance in severe asthma. Acad Radiol 31:3416\u20133426. https:\/\/doi.org\/10.1016\/j.acra.2024.01.039","journal-title":"Acad Radiol"}],"container-title":["European Radiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-026-12604-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00330-026-12604-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00330-026-12604-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T09:53:45Z","timestamp":1789379625000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00330-026-12604-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":64,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["12604"],"URL":"https:\/\/doi.org\/10.1007\/s00330-026-12604-6","relation":{},"ISSN":["1432-1084"],"issn-type":[{"value":"1432-1084","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"assertion":[{"value":"26 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 March 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 April 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The scientific guarantor of this publication is Andreas Voskrebenzev.","order":1,"name":"Ethics","label":"Guarantor","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"F.K., A.V., and J.V.C. are shareholders of BioVisioneers GmbH, a company that has an interest in pulmonary magnetic resonance imaging methods. M.M. Klein is an employee of BioVisioners GmbH, a company that has an interest in pulmonary magnetic resonance imaging methods. J.M.H.\u2019s institution has received grant support from Boehringer Ingelheim for the conduct of this clinical trial. The remaining authors declare no relevant conflict of interest regarding this submission.","order":2,"name":"Ethics","label":"Conflict of interest","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"At least one of the authors has significant statistical expertise.","order":3,"name":"Ethics","label":"Statistics and biometry","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"Written informed consent was obtained from all subjects (patients) in this study.","order":4,"name":"Ethics","label":"Informed consent","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"All examinations were approved by the Ethics Committee of Hannover Medical School.","order":5,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"This study represents a retrospective subanalysis of a prospective, single-center clinical trial. The trial is registered at ClinicalTrials.gov (NCT04231214).","order":6,"name":"Ethics","label":"Study subjects or cohorts overlap","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"order":7,"name":"Ethics","label":"Methodology","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors meet the criteria for authorship as recommended by the ICMJE.","order":8,"name":"Ethics","label":"Further declarations","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}}]}}