{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T21:42:59Z","timestamp":1790458979361,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"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":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Magnetic Resonance Imaging"],"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Long\u2010acting muscarinic antagonists\/long\u2010acting beta adrenoreceptor agonists lead to lung deflation and improved microvascular perfusion in hyperinflated chronic obstructive pulmonary disease (COPD), but with an unclear time course.<\/jats:p>\n <\/jats:sec>\n \n Purpose<\/jats:title>\n To investigate the effect of inhalation of tiotropium\/olodaterol (TIO\/OLO) on MRI measures of gas uptake and microvascular blood volume after single and multiple doses.<\/jats:p>\n <\/jats:sec>\n \n Study Type<\/jats:title>\n Prospective, randomized, investigator\u2010blinded, placebo\u2010controlled single\u2010dose crossover study with open\u2010label multiple\u2010dose extension.<\/jats:p>\n <\/jats:sec>\n \n Population<\/jats:title>\n 31 participants with COPD and lung hyperinflation (residual volume >\u2009135% predicted, \u2265\u200910 pack\u2010years smoking).<\/jats:p>\n <\/jats:sec>\n \n Fieldstrength\/Sequence<\/jats:title>\n 1.5\u2009T\/Interleaved 3D radial gas and dissolved\u2010phase MRI using multi\u2010echo FLASH, high\u2010resolution spectroscopy, chemical shift saturation recovery spectroscopy.<\/jats:p>\n <\/jats:sec>\n \n Assessment<\/jats:title>\n \n Ratios of\n 129<\/jats:sup>\n Xe in membrane tissues (M) to gas (M\u2010Gas), red blood cells (RBC) to gas (RBC\u2010Gas), RBC to M (RBC\u2010M) were calculated from dissolved\u2010phase imaging. Dissolved\u2010phase apparent transverse relaxation times (T\n 2<\/jats:sub>\n *) from high\u2010resolution spectra were also calculated, and septal wall thickness and surface\u2010volume ratio (S\/V) were assessed by fitting a model of xenon exchange functions. Parameters were compared for single\u2010dose (5\u2009\u03bcg\/5\u2009\u03bcg TIO\/OLO) versus placebo using saline, and single\u2010dose versus multiple\u2010dose (daily 5\u2009\u03bcg\/5\u2009\u03bcg TIO\/OLO for 14\u2009days) treatments.\n <\/jats:p>\n <\/jats:sec>\n \n Statistical Tests<\/jats:title>\n Linear mixed models with contrasts of estimated marginal means, significance level 0.05.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared with placebo, single\u2010dose treatment significantly increased RBC\u2010Gas and septal thickness but not RBC\u2010M (\n p<\/jats:italic>\n \u2009=\u20090.06), M\u2010Gas (\n p<\/jats:italic>\n \u2009=\u20090.16), RBC T\n 2<\/jats:sub>\n * (\n p<\/jats:italic>\n \u2009=\u20090.13), M T\n 2<\/jats:sub>\n * (\n p<\/jats:italic>\n \u2009=\u20090.09) and S\/V (\n p<\/jats:italic>\n \u2009=\u20090.47). Multiple\u2010dose treatment significantly increased RBC\u2010Gas, M\u2010Gas and M T\n 2<\/jats:sub>\n * compared with single\u2010dose treatment, but not RBC\u2010M (\n p<\/jats:italic>\n \u2009=\u20090.82), RBC T\n 2<\/jats:sub>\n * (\n p<\/jats:italic>\n \u2009=\u20090.48), septal thickness (\n p<\/jats:italic>\n \u2009=\u20090.61), and S\/V (\n p<\/jats:italic>\n \u2009=\u20090.49).\n <\/jats:p>\n <\/jats:sec>\n \n Data Conclusion<\/jats:title>\n \n Single\u2010dose TIO\/OLO increased\n 129<\/jats:sup>\n Xe in RBC\u2010Gas. Multiple\u2010dose treatment increased M\u2010Gas and further increased RBC\u2010Gas compared to single\u2010dose treatment.\n <\/jats:p>\n <\/jats:sec>\n \n Technical Efficacy<\/jats:title>\n Stage 4.<\/jats:p>\n <\/jats:sec>\n \n Evidence Level<\/jats:title>\n 2.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jmri.70558","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T03:42:36Z","timestamp":1790221356000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Single and Multiple Dose Tiotropium\/Olodaterol in Chronic Obstructive Pulmonary Disease on Alveolar Gas Exchange Measured by Hyperpolarized\n \n 129<\/sup>\n Xe MRI\n <\/scp>"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4157-9808","authenticated-orcid":false,"given":"Agilo L.","family":"Kern","sequence":"first","affiliation":[{"name":"Institute of Diagnostic and Interventional Radiology, 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Diagnostic and Interventional Radiology, Hannover Medical School Hannover Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL) Hannover Germany"},{"name":"Department of Radiology Charit\u00e9\u2014University Medical Center Berlin, Corporate Member of Freie Universit\u00e4t Berlin and Humboldt\u2010Universit\u00e4t zu Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6285-8403","authenticated-orcid":false,"given":"Frank","family":"Wacker","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic and Interventional Radiology, Hannover Medical School Hannover Germany"},{"name":"Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL) Hannover 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