Noninvasive Monitoring of the Response of Human Lungs to Low‐Dose Lipopolysaccharide Inhalation Challenge Using MRI: A Feasibility Study

Background Development of antiinflammatory drugs for lung diseases demands novel methods for noninvasive assessment of inflammatory processes in the lung. Purpose To investigate the feasibility of hyperpolarized 129Xe MRI, 1H T1 time mapping, and dynamic contrast‐enhanced (DCE) perfusion MRI for mon...

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Veröffentlicht in:Journal of magnetic resonance imaging 2020-06, Vol.51 (6), p.1669-1676
Hauptverfasser: Kern, Agilo L., Biller, Heike, Klimeš, Filip, Voskrebenzev, Andreas, Gutberlet, Marcel, Renne, Julius, Müller, Meike, Holz, Olaf, Wacker, Frank, Hohlfeld, Jens M., Vogel‐Claussen, Jens
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container_end_page 1676
container_issue 6
container_start_page 1669
container_title Journal of magnetic resonance imaging
container_volume 51
creator Kern, Agilo L.
Biller, Heike
Klimeš, Filip
Voskrebenzev, Andreas
Gutberlet, Marcel
Renne, Julius
Müller, Meike
Holz, Olaf
Wacker, Frank
Hohlfeld, Jens M.
Vogel‐Claussen, Jens
description Background Development of antiinflammatory drugs for lung diseases demands novel methods for noninvasive assessment of inflammatory processes in the lung. Purpose To investigate the feasibility of hyperpolarized 129Xe MRI, 1H T1 time mapping, and dynamic contrast‐enhanced (DCE) perfusion MRI for monitoring the response of human lungs to low‐dose inhaled lipopolysaccharide (LPS) challenge compared to inflammatory cell counts from induced‐sputum analysis. Study Type Prospective feasibility study. Population Ten healthy volunteers underwent MRI before and 6 hours after inhaled LPS challenge with subsequent induced‐sputum collection. Field Strength/Sequences 1.5T/hyperpolarized 129Xe MRI: Interleaved multiecho imaging of dissolved and gas phase, ventilation imaging, dissolved‐phase spectroscopy, and chemical shift saturation recovery spectroscopy. 1H MRI: Inversion recovery fast low‐angle shot imaging for T1 mapping, time‐resolved angiography with stochastic trajectories for DCE MRI. Assessment Dissolved‐phase ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP) and gas phase (GP), ventilation defect percentage, septal wall thickness, surface‐to‐volume ratio, capillary transit time, lineshape parameters in dissolved‐phase spectroscopy, 1H T1 time, blood volume, flow, and mean transit time were determined and compared to cell counts. Statistical Tests Wilcoxon signed‐rank test, Pearson correlation. Results The percentage of neutrophils in sputum was markedly increased after LPS inhalation compared to baseline, P = 0.002. The group median RBC‐TP ratio was significantly reduced from 0.40 to 0.31, P = 0.004, and 1H T1 was significantly elevated from 1157.6 msec to 1187.8 msec after LPS challenge, P = 0.027. DCE MRI exhibited no significant changes in blood volume, P = 0.64, flow, P = 0.17, and mean transit time, P = 0.11. Data Conclusion Hyperpolarized 129Xe dissolved‐phase MRI and 1H T1 mapping may provide biomarkers for noninvasive assessment of the response of human lungs to LPS inhalation. By its specificity to the alveolar region, hyperpolarized 129Xe MRI together with 1H T1 mapping adds value to sputum analysis. Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1669–1676.
doi_str_mv 10.1002/jmri.27000
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Purpose To investigate the feasibility of hyperpolarized 129Xe MRI, 1H T1 time mapping, and dynamic contrast‐enhanced (DCE) perfusion MRI for monitoring the response of human lungs to low‐dose inhaled lipopolysaccharide (LPS) challenge compared to inflammatory cell counts from induced‐sputum analysis. Study Type Prospective feasibility study. Population Ten healthy volunteers underwent MRI before and 6 hours after inhaled LPS challenge with subsequent induced‐sputum collection. Field Strength/Sequences 1.5T/hyperpolarized 129Xe MRI: Interleaved multiecho imaging of dissolved and gas phase, ventilation imaging, dissolved‐phase spectroscopy, and chemical shift saturation recovery spectroscopy. 1H MRI: Inversion recovery fast low‐angle shot imaging for T1 mapping, time‐resolved angiography with stochastic trajectories for DCE MRI. Assessment Dissolved‐phase ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP) and gas phase (GP), ventilation defect percentage, septal wall thickness, surface‐to‐volume ratio, capillary transit time, lineshape parameters in dissolved‐phase spectroscopy, 1H T1 time, blood volume, flow, and mean transit time were determined and compared to cell counts. Statistical Tests Wilcoxon signed‐rank test, Pearson correlation. Results The percentage of neutrophils in sputum was markedly increased after LPS inhalation compared to baseline, P = 0.002. The group median RBC‐TP ratio was significantly reduced from 0.40 to 0.31, P = 0.004, and 1H T1 was significantly elevated from 1157.6 msec to 1187.8 msec after LPS challenge, P = 0.027. DCE MRI exhibited no significant changes in blood volume, P = 0.64, flow, P = 0.17, and mean transit time, P = 0.11. Data Conclusion Hyperpolarized 129Xe dissolved‐phase MRI and 1H T1 mapping may provide biomarkers for noninvasive assessment of the response of human lungs to LPS inhalation. By its specificity to the alveolar region, hyperpolarized 129Xe MRI together with 1H T1 mapping adds value to sputum analysis. Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1669–1676.</description><identifier>ISSN: 1053-1807</identifier><identifier>EISSN: 1522-2586</identifier><identifier>DOI: 10.1002/jmri.27000</identifier><identifier>PMID: 31729119</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley &amp; Sons, Inc</publisher><subject>129Xe MRI ; Administration, Inhalation ; Alveoli ; Angiography ; Anti-inflammatory agents ; Biomarkers ; Blood ; Blood volume ; Chemical equilibrium ; dissolved phase ; Drug development ; Erythrocytes ; Feasibility Studies ; Field strength ; Humans ; Inflammation ; Inhalation ; Leukocytes (neutrophilic) ; lipopolysaccharide ; Lipopolysaccharides ; Lung - diagnostic imaging ; Lung diseases ; Lungs ; Magnetic Resonance Imaging ; Mapping ; Medical imaging ; Monitoring ; Perfusion ; Population studies ; Prospective Studies ; Rank tests ; Recovery ; Respiration ; Spectroscopy ; Spectrum analysis ; Sputum ; Statistical analysis ; Statistical tests ; T1 mapping ; Trajectory analysis ; Transit time ; Vapor phases ; Ventilation ; Wall thickness ; Xenon 129 ; Xenon Isotopes</subject><ispartof>Journal of magnetic resonance imaging, 2020-06, Vol.51 (6), p.1669-1676</ispartof><rights>2019 The Authors. published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.</rights><rights>2019 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.</rights><rights>2019. This article is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). 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Purpose To investigate the feasibility of hyperpolarized 129Xe MRI, 1H T1 time mapping, and dynamic contrast‐enhanced (DCE) perfusion MRI for monitoring the response of human lungs to low‐dose inhaled lipopolysaccharide (LPS) challenge compared to inflammatory cell counts from induced‐sputum analysis. Study Type Prospective feasibility study. Population Ten healthy volunteers underwent MRI before and 6 hours after inhaled LPS challenge with subsequent induced‐sputum collection. Field Strength/Sequences 1.5T/hyperpolarized 129Xe MRI: Interleaved multiecho imaging of dissolved and gas phase, ventilation imaging, dissolved‐phase spectroscopy, and chemical shift saturation recovery spectroscopy. 1H MRI: Inversion recovery fast low‐angle shot imaging for T1 mapping, time‐resolved angiography with stochastic trajectories for DCE MRI. Assessment Dissolved‐phase ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP) and gas phase (GP), ventilation defect percentage, septal wall thickness, surface‐to‐volume ratio, capillary transit time, lineshape parameters in dissolved‐phase spectroscopy, 1H T1 time, blood volume, flow, and mean transit time were determined and compared to cell counts. Statistical Tests Wilcoxon signed‐rank test, Pearson correlation. Results The percentage of neutrophils in sputum was markedly increased after LPS inhalation compared to baseline, P = 0.002. The group median RBC‐TP ratio was significantly reduced from 0.40 to 0.31, P = 0.004, and 1H T1 was significantly elevated from 1157.6 msec to 1187.8 msec after LPS challenge, P = 0.027. DCE MRI exhibited no significant changes in blood volume, P = 0.64, flow, P = 0.17, and mean transit time, P = 0.11. Data Conclusion Hyperpolarized 129Xe dissolved‐phase MRI and 1H T1 mapping may provide biomarkers for noninvasive assessment of the response of human lungs to LPS inhalation. By its specificity to the alveolar region, hyperpolarized 129Xe MRI together with 1H T1 mapping adds value to sputum analysis. Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. 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Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Journal of magnetic resonance imaging</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kern, Agilo L.</au><au>Biller, Heike</au><au>Klimeš, Filip</au><au>Voskrebenzev, Andreas</au><au>Gutberlet, Marcel</au><au>Renne, Julius</au><au>Müller, Meike</au><au>Holz, Olaf</au><au>Wacker, Frank</au><au>Hohlfeld, Jens M.</au><au>Vogel‐Claussen, Jens</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Noninvasive Monitoring of the Response of Human Lungs to Low‐Dose Lipopolysaccharide Inhalation Challenge Using MRI: A Feasibility Study</atitle><jtitle>Journal of magnetic resonance imaging</jtitle><addtitle>J Magn Reson Imaging</addtitle><date>2020-06</date><risdate>2020</risdate><volume>51</volume><issue>6</issue><spage>1669</spage><epage>1676</epage><pages>1669-1676</pages><issn>1053-1807</issn><eissn>1522-2586</eissn><abstract>Background Development of antiinflammatory drugs for lung diseases demands novel methods for noninvasive assessment of inflammatory processes in the lung. Purpose To investigate the feasibility of hyperpolarized 129Xe MRI, 1H T1 time mapping, and dynamic contrast‐enhanced (DCE) perfusion MRI for monitoring the response of human lungs to low‐dose inhaled lipopolysaccharide (LPS) challenge compared to inflammatory cell counts from induced‐sputum analysis. Study Type Prospective feasibility study. Population Ten healthy volunteers underwent MRI before and 6 hours after inhaled LPS challenge with subsequent induced‐sputum collection. Field Strength/Sequences 1.5T/hyperpolarized 129Xe MRI: Interleaved multiecho imaging of dissolved and gas phase, ventilation imaging, dissolved‐phase spectroscopy, and chemical shift saturation recovery spectroscopy. 1H MRI: Inversion recovery fast low‐angle shot imaging for T1 mapping, time‐resolved angiography with stochastic trajectories for DCE MRI. Assessment Dissolved‐phase ratios of 129Xe in red blood cells (RBC), tissue/plasma (TP) and gas phase (GP), ventilation defect percentage, septal wall thickness, surface‐to‐volume ratio, capillary transit time, lineshape parameters in dissolved‐phase spectroscopy, 1H T1 time, blood volume, flow, and mean transit time were determined and compared to cell counts. Statistical Tests Wilcoxon signed‐rank test, Pearson correlation. Results The percentage of neutrophils in sputum was markedly increased after LPS inhalation compared to baseline, P = 0.002. The group median RBC‐TP ratio was significantly reduced from 0.40 to 0.31, P = 0.004, and 1H T1 was significantly elevated from 1157.6 msec to 1187.8 msec after LPS challenge, P = 0.027. DCE MRI exhibited no significant changes in blood volume, P = 0.64, flow, P = 0.17, and mean transit time, P = 0.11. Data Conclusion Hyperpolarized 129Xe dissolved‐phase MRI and 1H T1 mapping may provide biomarkers for noninvasive assessment of the response of human lungs to LPS inhalation. By its specificity to the alveolar region, hyperpolarized 129Xe MRI together with 1H T1 mapping adds value to sputum analysis. Level of Evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1669–1676.</abstract><cop>Hoboken, USA</cop><pub>John Wiley &amp; Sons, Inc</pub><pmid>31729119</pmid><doi>10.1002/jmri.27000</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0003-4157-9808</orcidid><orcidid>https://orcid.org/0000-0003-3727-8180</orcidid><orcidid>https://orcid.org/0000-0001-5595-6948</orcidid><oa>free_for_read</oa></addata></record>
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subjects 129Xe MRI
Administration, Inhalation
Alveoli
Angiography
Anti-inflammatory agents
Biomarkers
Blood
Blood volume
Chemical equilibrium
dissolved phase
Drug development
Erythrocytes
Feasibility Studies
Field strength
Humans
Inflammation
Inhalation
Leukocytes (neutrophilic)
lipopolysaccharide
Lipopolysaccharides
Lung - diagnostic imaging
Lung diseases
Lungs
Magnetic Resonance Imaging
Mapping
Medical imaging
Monitoring
Perfusion
Population studies
Prospective Studies
Rank tests
Recovery
Respiration
Spectroscopy
Spectrum analysis
Sputum
Statistical analysis
Statistical tests
T1 mapping
Trajectory analysis
Transit time
Vapor phases
Ventilation
Wall thickness
Xenon 129
Xenon Isotopes
title Noninvasive Monitoring of the Response of Human Lungs to Low‐Dose Lipopolysaccharide Inhalation Challenge Using MRI: A Feasibility Study
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