Evaluation of Dynamic Contrast-Enhanced MRI Measures of Lung Congestion and Endothelial Permeability in Heart Failure: A Prospective Method Validation Study

Background Methods for accurate quantification of lung fluid in heart failure (HF) are needed. Dynamic contrast-enhanced (DCE)-MRI may be an appropriate modality. Purpose DCE-MRI evaluation of fraction of fluid volume in the interstitial lung space (v(e)) and vascular permeability (K-trans). Study Type Prospective, single-center method validation. Population Seventeen evaluable healthy volunteers (HVs), 12 participants with HF, and 3 with acute decompensated HF (ADHF). Field Strength/Sequence T-1 mapping (spoiled gradient echo variable flip angle acquisition) followed by dynamic series (three-dimensional spoiled gradient-recalled echo acquisitions [constant echo time, repetition time, and flip angle at 1.5 T]). Assessment Three whole-chest scans were acquired: baseline (Session 1), 1-week later (Session 2), following exercise (Session 3). Extended Tofts model quantified v(e) and K-trans (voxel-wise basis); total lung median measures were extracted and fitted via repeat measure analysis of variance (ANOVA) model. Patient tolerability of the scanning protocol was assessed. Statistical Tests This was constructed as an experimental medicine study. Primary endpoints: K-trans and v(e) at baseline (HV vs. HF), change in K-trans and v(e) following exercise, and following lung congestion resolution (ADHF). K-trans and v(e) were fitted separately using ANOVA. Secondary endpoint: repeatability, that is, within-participant variability in v(e) and K-trans between sessions (coefficient of variation estimated via mixed effects model). Results There was no significant difference in mean K-trans between HF and HV (P <= 0.17): 0.2216 minutes(-1) and 0.2353 minutes(-1) (Session 1), 0.2044 minutes(-1) and 0.2567 minutes(-1) (Session 2), 0.1841 minutes(-1) and 0.2108 minutes(-1) (Session 3), respectively. v(e) was greater in the HF group (all scans, P <= 0.02). Results were repeatable between Sessions 1 and 2; mean values for HF and HV were 0.4946 and 0.3346 (Session 1), 0.4353 and 0.3205 (Session 2), respectively. There was minimal difference in K-trans or v(e) between scans for participants with ADHF (small population precluded significance testing). Scanning was well tolerated. Data Conclusion While no differences were detected in K-trans, v(e) was greater in chronic HF patients vs. HV, augmented beyond plasma and intracellular volume. DCE-MRI is a valuable diagnostic and physiologic tool to evaluate changes in fluid volume in the interstitial lung space associated with symptomatic HF. Level of Evidence 2 Technical Efficacy Stage 2

Automated summary

This study aimed to evaluate lung fluid volume in HF patients using DCE-MRI, finding significantly higher v(e) in HF patients compared to healthy volunteers. The results showed good tolerability of the scanning protocol and repeatability of v(e) in HF patients.