Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonance

ABSTRACT: Background: Pathological extravascular lung water is a facet of decompensated congestive heart failure that current cardiovascular magnetic resonance (CMR) methods fail to quantify. CMR can measure total lung water density, but cannot distinguish between intravascular and extravascular fl...

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Main Authors: Felicia Seemann, Rim N. Halaby, Andrea Jaimes, Kendall O’Brien, Peter Kellman, Daniel A. Herzka, Robert J. Lederman, Adrienne E. Campbell-Washburn
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Journal of Cardiovascular Magnetic Resonance
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Online Access:http://www.sciencedirect.com/science/article/pii/S1097664725000456
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author Felicia Seemann
Rim N. Halaby
Andrea Jaimes
Kendall O’Brien
Peter Kellman
Daniel A. Herzka
Robert J. Lederman
Adrienne E. Campbell-Washburn
author_facet Felicia Seemann
Rim N. Halaby
Andrea Jaimes
Kendall O’Brien
Peter Kellman
Daniel A. Herzka
Robert J. Lederman
Adrienne E. Campbell-Washburn
author_sort Felicia Seemann
collection DOAJ
description ABSTRACT: Background: Pathological extravascular lung water is a facet of decompensated congestive heart failure that current cardiovascular magnetic resonance (CMR) methods fail to quantify. CMR can measure total lung water density, but cannot distinguish between intravascular and extravascular fluid, and thus is not diagnostic. Therefore, we develop and evaluate a novel method to measure extravascular lung water by distinguishing intravascular from extracellular fluid compartments using two different contrast agents, extracellular gadolinium chelates and iron-based intravascular ferumoxytol. Methods: We created two porcine models of pulmonary edema: reversible catheter-induced mitral regurgitation to induce extravascular lung water (n = 5); intravascular volume overload using rapid colloid infusion (n = 5); and compared to normal controls (n = 8). We sequentially acquired lung T1 maps and lung water density maps at 0.55T with native, gadolinium-based, and ferumoxytol contrast, from which we calculated the extracellular volume fraction (ECV) and blood plasma volume fraction in the pulmonary tissue, respectively. We computed extravascular ECV as the difference in ECV and plasma volume fractions. Extravascular lung water volumes were estimated. Results: In the mitral regurgitation model, baseline vs mitral regurgitation ECVextravascular increased from 27 ± 4.1% to 32 ± 1.9% (p = 0.006), and extravascular lung water volume increased from 105 ± 19 mL to 143 ± 15 mL (p = 0.048). Plasma volume fraction was similar at baseline vs mitral regurgitation (43 ± 4.2% vs 46 ± 5.4%, p = 0.26). Compared to naïve pigs, we measured higher plasma volume fractions in the intravascular volume-loaded model (42 ± 4.7% vs 51 ± 2.7%, p = 0.0054), but no differences in ECVextravascular (21 ± 4.6% vs 21 ± 3.6%, p = 0.99) or extravascular lung water volume (67 ± 13 mL vs 89 ± 24 mL, p = 0.11). Assessing the regional distribution, the plasma volume was higher posteriorly, indicating gravitational dependency, whereas, the extravascular lung water was higher anteriorly. Conclusion: Extravascular lung ECV measurements and derived lung water volumes corresponded well with predicted increases in extravascular and intravascular pulmonary fluid in animal models. This method may enable mechanistic studies of lung water in patients with dyspnea.
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spelling doaj-art-ea78fd7233774b45bcce52533c9cf4b72025-08-20T03:46:05ZengElsevierJournal of Cardiovascular Magnetic Resonance1097-66472025-01-0127110188310.1016/j.jocmr.2025.101883Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonanceFelicia Seemann0Rim N. Halaby1Andrea Jaimes2Kendall O’Brien3Peter Kellman4Daniel A. Herzka5Robert J. Lederman6Adrienne E. Campbell-Washburn7Cardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USACardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USACardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USACardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USACardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USACardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; Department of Radiology, Case Western Reserve School of Medicine, Cleveland, Ohio 44106, USACardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USACardiovascular Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA; Corresponding author.ABSTRACT: Background: Pathological extravascular lung water is a facet of decompensated congestive heart failure that current cardiovascular magnetic resonance (CMR) methods fail to quantify. CMR can measure total lung water density, but cannot distinguish between intravascular and extravascular fluid, and thus is not diagnostic. Therefore, we develop and evaluate a novel method to measure extravascular lung water by distinguishing intravascular from extracellular fluid compartments using two different contrast agents, extracellular gadolinium chelates and iron-based intravascular ferumoxytol. Methods: We created two porcine models of pulmonary edema: reversible catheter-induced mitral regurgitation to induce extravascular lung water (n = 5); intravascular volume overload using rapid colloid infusion (n = 5); and compared to normal controls (n = 8). We sequentially acquired lung T1 maps and lung water density maps at 0.55T with native, gadolinium-based, and ferumoxytol contrast, from which we calculated the extracellular volume fraction (ECV) and blood plasma volume fraction in the pulmonary tissue, respectively. We computed extravascular ECV as the difference in ECV and plasma volume fractions. Extravascular lung water volumes were estimated. Results: In the mitral regurgitation model, baseline vs mitral regurgitation ECVextravascular increased from 27 ± 4.1% to 32 ± 1.9% (p = 0.006), and extravascular lung water volume increased from 105 ± 19 mL to 143 ± 15 mL (p = 0.048). Plasma volume fraction was similar at baseline vs mitral regurgitation (43 ± 4.2% vs 46 ± 5.4%, p = 0.26). Compared to naïve pigs, we measured higher plasma volume fractions in the intravascular volume-loaded model (42 ± 4.7% vs 51 ± 2.7%, p = 0.0054), but no differences in ECVextravascular (21 ± 4.6% vs 21 ± 3.6%, p = 0.99) or extravascular lung water volume (67 ± 13 mL vs 89 ± 24 mL, p = 0.11). Assessing the regional distribution, the plasma volume was higher posteriorly, indicating gravitational dependency, whereas, the extravascular lung water was higher anteriorly. Conclusion: Extravascular lung ECV measurements and derived lung water volumes corresponded well with predicted increases in extravascular and intravascular pulmonary fluid in animal models. This method may enable mechanistic studies of lung water in patients with dyspnea.http://www.sciencedirect.com/science/article/pii/S1097664725000456Lung waterFerumoxytolExtracellular volumeDual-agent
spellingShingle Felicia Seemann
Rim N. Halaby
Andrea Jaimes
Kendall O’Brien
Peter Kellman
Daniel A. Herzka
Robert J. Lederman
Adrienne E. Campbell-Washburn
Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonance
Journal of Cardiovascular Magnetic Resonance
Lung water
Ferumoxytol
Extracellular volume
Dual-agent
title Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonance
title_full Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonance
title_fullStr Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonance
title_full_unstemmed Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonance
title_short Characterizing extravascular lung water—A dual-contrast agent extracellular volume approach by cardiovascular magnetic resonance
title_sort characterizing extravascular lung water a dual contrast agent extracellular volume approach by cardiovascular magnetic resonance
topic Lung water
Ferumoxytol
Extracellular volume
Dual-agent
url http://www.sciencedirect.com/science/article/pii/S1097664725000456
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