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Hyperpolarized 129Xe functional MR imaging to monitor the response of human lungs after segmental lipopolysaccharide challenge

: Kern, Agilo Luitger; Biller, Heike; Klimes, Filip; Voskrebenzev, Andreas; Gutberlet, Marcel; Rotärmel, Alexander; Schönfeld, Christian; Renne, Julius; Holz, Olaf; Wacker, Frank; Vogel-Claussen, Jens; Hohlfeld, Jens M.

American Journal of Respiratory and Critical Care Medicine 197 (2018), Abastract A4725
ISSN: 1073-449X
ISSN: 0003-0805
ISSN: 1535-4970
American Thoracic Society (ATS International Conference) <2018, San Diego/Calif.>
Fraunhofer ITEM ()

RATIONALE Hyperpolarized 129Xe MRI has been proven to be a highly sensitive probe for regional lung function and previous work has shown the sensitivity of 129Xe MRI-derived parameters for inflammatory changes after lung provocation by lipopolysaccharide (LPS) in an animal model [1]. Purpose of this work was to investigate the feasibility of monitoring changes in regional lung function parameters after segmental LPS challenge using hyperpolarized 129Xe MRI in humans. METHODS This study was approved by the institutional ethics review board and thirteen healthy volunteers were recruited. Hyperpolarized 129Xe MRI sessions were performed one week before (baseline) and 24h after segmental LPS challenge (provocation). Bronchoalveolar lavage was performed in the challenged segment and inflammatory cells (neutrophils, macrophages, lymphocytes and monocytes) were assessed. The MR protocol included dissolved-phase imaging and subsequent high-resolution 3D ventilation imaging during the same breath-hold after inhalation of 1L of hyperpolarized 129Xe and a variable amount of air to reach 1/3 of forced vital capacity [2]. 129Xe signals were separated into gaseous 129Xe (GP), 129Xe in aqueous solution (tissue and blood plasma, TP), and in red blood cells (RBC). A ratio map of ventilation after provocation compared to baseline imaging was derived. Using a region-growing algorithm regions of mildly decreased ventilation in the challenged segments were automatically identified and used as regions of interest (ROIs) for further data analysis. RESULTS Ten volunteers successfully completed the study protocol and were included for data analysis. The figure shows exemplary ventilation images from one volunteer along with the corresponding ventilation ratio map, the ROI used for data analysis and dissolved-phase imaging data (top row). The average RBC-TP ratio in the ROI applied to co-registered dissolved-phase imaging data was significantly lower after provocation (two-sided Wilcoxon signed-rank test, p = 0.0039), whereas the average TP-GP ratio was significantly elevated (p = 0.0488, bottom row). No significant correlation of imaging-derived parameters with the amount of inflammatory cells was found after LPS challenge. However, there was a trend of an inverse correlation of RBC-TP and number of neutrophilic granulocytes (Spearman’s ρ = -0.45, p = 0.18). CONCLUSIONS Lung areas with segmental LPS challenge show a local reduction in the gas-uptake parameter RBC-TP, likely due to pulmonary edema causing expansion of the interstitial space in the lung parenchyma. Hyperpolarized 129Xe dissolved-phase imaging may have added value to lavage fluid analysis. REFERENCES [1] Månsson et al., Magn Reson Med 2003;50:1170-1179 [2] Qing et al., NMR Biomed 2014;27:1490-1501