We have developed a new analytical method that uses nuclear magnetic resonance (NMR) imaging data to quantify lung water content and distribution. This new method generates a distribution of lung water density in which the fraction of voxels corresponding to a given water density is plotted on the vertical axis as a function of water density on the horizontal axis, thereby complementing the spatial information provided by the NMR image. We obtained reproducible lung water distribution data at comparable lung volumes in normal excised lungs and in intact living rats. In normal excised unperfused rat lungs, the distribution varied with the degree of inflation, but the changes were small compared with those associated with lung edema. The lung water density distribution changed markedly after induction of lung edema by intrabronchial saline instillation, intravenous oleic acid injection, and rapid intravenous saline infusion. Lung water density distribution data were well correlated (correlation coefficient = 0.948 for the excised lungs and 0.823 for the intact living rats) with gravimetric lung water measurements. The new analytical method is noninvasive, provides easily repeatable measurements, and is as sensitive as the gravimetric technique to lung water changes.

Certain biomarkers predict death due to acute respiratory distress syndrome in COVID-19 patients. We retrospectively analyzed biomarkers associated with time to mechanical ventilation for respiratory failure due to COVID-19 (time-to-mechanical ventilation) in 135 consecutive patients in our hospital. We analyzed biomarkers that were elevated immediately (at admission) and later (3 days after admission) using Cox proportional hazards regression analysis. Independent biomarkers of time-to-mechanical ventilation were high C-reactive protein (CRP), interleukin (IL)-6, and Krebs von den Lungen-6 (KL-6) concentrations at admission and elevated CRP, high-mobility group box-1 protein (HMGB-1), and d-dimer levels and low platelets 3 days after admission. Receiver operating characteristic analysis for detecting the association between independent biomarkers associated with time-to-event in multivariate analyses and the start of mechanical ventilation revealed that these biomarkers had area under the curve values higher than 0.700. The present study suggests that CRP was the only biomarker associated with time-to-mechanical ventilation both at admission and 3 days after admission. Moreover, IL-6 (an inflammatory cytokine), HMGB-1 (a late inflammatory mediator), and KL-6 (reflecting injury and/or remodeling of type II pneumocytes) were associated with outcomes in COVID-19 as reported previously. In conclusion, increased CRP, IL-6, KL-6, HMGB-1, and d-dimer levels and decreased platelet counts were associated with the start of mechanical ventilation due to COVID-19.

It is well known that pulmonary edema is, in general, spatially nonuniform. Since the NMR spin-lattice relaxation time (T1) is increased by lung edema, the spatial distribution of T1 will be nonuniform. When the repetition time (TR) is short relative to the T1 of edematous lung, lung water content will be underestimated and this underestimation will be spatially nonuniform as well. Therefore, technical artifacts which are a complex function of lung edema and its spatial distribution are expected. We compared overall and regional (topographic) lung water density measurements obtained from living rats (with normal or edematous lungs) using repetition times of 2.0 and 6.2 s (at a magnetic field of 1 T), to quantify this uneven T1 effect for normal and edematous lungs. NMR measurements at TR = 2.0 s underestimated whole lung water density (-rho H2O) TR = 6.2 s) by an average of 7.2% in normal rats and 22.5% in rats with pulmonary edema. Regional -rho H2O underestimation (%delta-rho H2O) varied from 2.2 to 8.8% (groups means) in normal lungs and from 7.3 to 30.8% in edematous lungs. As a result, the interquartile range (of the voxel distribution as a function of rho H2O) underestimated the spatial nonuniformity of lung water density by 28.0% in edematous lungs, likely because of greater loss of NMR signal from high-water-density, long-T1 lung regions. Both %delta-rho H2O and T1 were significantly correlated with -rho H2O at TR = 6.2 s.(ABSTRACT TRUNCATED AT 250 WORDS)

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