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

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 ¹²⁹ Xe MRI, ¹ H 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 ¹²⁹ Xe MRI: Interleaved multiecho imaging of dissolved and gas phase, ventilation imaging, dissolved-phase spectroscopy, and chemical shift saturation recovery spectroscopy. ¹ H 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 ¹²⁹ Xe 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, ¹ H 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 ¹ H 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 ¹²⁹ Xe dissolved-phase MRI and ¹ H 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 ¹²⁹ Xe MRI together with ¹ H T₁ mapping adds value to sputum analysis.

Level of evidence: 1 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1669-1676.

Keywords: 129Xe MRI; T1 mapping; dissolved phase; inflammation; lipopolysaccharide.