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      Evaluation of a commercial multi-dimensional echocardiography technique for ventricular volumetry in small animals

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          Abstract

          Background

          The assessment of ventricular volumes using conventional echocardiography methods is limited with regards to the need of geometrical assumptions. In the present study, we aimed to evaluate a novel commercial system for three-dimensional echocardiography (3DE) in preclinical models by direct comparison with conventional 1D- and 2D-echocardiography (1DE; 2DE) and the gold-standard technique magnetic resonance imaging (MRI). Further, we provide a standard operating protocol for image acquisition and analysis with 3DE.

          Methods

          3DE was carried out using a 30 MHz center frequency transducer coupled to a Vevo®3100 Imaging System. We evaluated under different experimental conditions: 1) in vitro phantom measurements served as controlled setting in which boundaries were clearly delineated; 2) a validation cohort composed of healthy C57BL/6 J mice and New Zealand Obese (NZO) mice was used in order to validate 3DE against cardiac MRI; 3) a standard mouse model of pressure overload induced-heart failure was investigated to estimate the value of 3DE.

          Results

          First, in vitro volumetry revealed good agreement between 3DE assessed volumes and the MRI-assessed volumes. Second, cardiac volume determination with 3DE showed smaller mean differences compared to cardiac MRI than conventional 1DE and 2DE. Third, 3DE was suitable to detect reduced ejection fractions in heart failure mice. Fourth, inter- and intra-observer variability of 3DE showed good to excellent agreement regarding absolute volumes in healthy mice, whereas agreement rates for the relative metrics ejection fraction and stroke volume demonstrated good to moderate observer variabilities.

          Conclusions

          3DE provides a novel method for accurate volumetry in small animals without the need for spatial assumptions, demonstrating a technique for an improved analysis of ventricular function. Further validation work and highly standardized image analyses are required to increase reproducibility of this approach.

          Electronic supplementary material

          The online version of this article (10.1186/s12947-018-0128-9) contains supplementary material, which is available to authorized users.

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          Most cited references24

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          Performance of 3-dimensional echocardiography in measuring left ventricular volumes and ejection fraction: a systematic review and meta-analysis.

          The primary aim of this systematic review is to objectively evaluate the test performance characteristics of three-dimensional echocardiography (3DE) in measuring left ventricular (LV) volumes and ejection fraction (EF). Despite its growing use in clinical laboratories, the accuracy of 3DE has not been studied on a large scale. It is unclear if this technology offers an advantage over traditional two-dimensional (2D) methods. We searched for studies that compared LV volumes and EF measured by 3DE and cardiac magnetic resonance (CMR) imaging. A subset of those also compared standard 2D methods with CMR. We used meta-analyses to determine the overall bias and limits of agreement of LV end-diastolic volume (EDV), end-systolic volume (ESV), and EF measured by 3DE and 2D echocardiography (2DE). Twenty-three studies (1,638 echocardiograms) were included. The pooled biases ± 2 SDs for 3DE were -19.1 ± 34.2 ml, -10.1 ± 29.7 ml, and - 0.6 ± 11.8% for EDV, ESV, and EF, respectively. Nine studies also included data from 2DE, where the pooled biases were -48.2 ± 55.9 ml, -27.7 ± 45.7 ml, and 0.1 ± 13.9% for EDV, ESV, and EF, respectively. In this subset, the difference in bias between 3DE and 2D volumes was statistically significant (p = 0.01 for both EDV and ESV). The difference in variance was statistically significant (p < 0.001) for all 3 measurements. Three-dimensional echocardiography underestimates volumes and has wide limits of agreement, but compared with traditional 2D methods in these carefully performed studies, 3DE is more accurate for volumes and more precise in all 3 measurements. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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            Left Ventricular Ejection Fraction and Volumes: It Depends on the Imaging Method

            Background and Methods In order to provide guidance for using measurements of left ventricular (LV) volume and ejection fraction (LVEF) from different echocardiographic methods a PubMed review was performed on studies that reported reference values in normal populations for two-dimensional (2D ECHO) and three-dimensional (3D ECHO) echocardiography, nuclear imaging, cardiac computed tomography, and cardiac magnetic resonance imaging (CMR). In addition all studies (2 multicenter, 16 single center) were reviewed, which included at least 30 patients, and the results compared of noncontrast and contrast 2D ECHO, and 3D ECHO with those of CMR. Results The lower limits for normal LVEF and the normal ranges for end-diastolic (EDV) and end-systolic (ESV) volumes were different in each method. Only minor differences in LVEF were found in studies comparing CMR and 2D contrast echocardiography or noncontrast 3D echocardiography. However, EDV and ESV measured with all echocardiographic methods were smaller and showed greater variability than those derived from CMR. Regarding agreement with CMR and reproducibility, all studies showed superiority of contrast 2D ECHO over noncontrast 2D ECHO and 3D ECHO over 2D ECHO. No final judgment can be made about the comparison between contrast 2D ECHO and noncontrast or contrast 3D ECHO. Conclusion Contrast 2D ECHO and noncontrast 3D ECHO show good reproducibility and good agreement with CMR measurements of LVEF. The agreement of volumes is worse. Further studies are required to assess the clinical value of contrast 3D ECHO as noncontrast 3D ECHO is only reliable in patients with good acoustic windows.
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              Validation of high-resolution echocardiography and magnetic resonance imaging vs. high-fidelity catheterization in experimental pulmonary hypertension.

              High-frequency echocardiography and high-field-strength magnetic resonance imaging (MRI) are new noninvasive methods for quantifying pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy (RVH). We compared these noninvasive methods of assessing the pulmonary circulation to the gold standard, cardiac catheterization (micromanometer-tipped catheters), in rats with monocrotaline-induced PAH and normal controls. Closed-chest, Sprague-Dawley rats were anesthetized with inhaled isoflurane (25 monocrotaline, 6 age-matched controls). Noninvasive studies used 37.5-MHz ultrasound (Vevo 770; VisualSonics) or a 9.4-T MRI (Bruker BioSpin). Catheterization used a 1.4-F micromanometer-tipped Millar catheter and a thermodilution catheter to measure cardiac output (CO). We compared noninvasive measures of pulmonary artery (PA) pressure (PAP) using PA acceleration time (PAAT) and CO, using the geometric PA flow method and RV free wall (RVFW) thickness/mass with cardiac catheterization and/or autopsy. Blinded operators performed comparisons using each method within 2 days of another. In a subset of rats with monocrotaline PAH, weekly echocardiograms, catheterization, and autopsy data assessed disease progression. Heart rate was similar during all studies (>323 beats/min). PAAT shortened, and the PA flow envelope displayed systolic "notching," reflective of downstream vascular remodeling/stiffening, within 3 wk of monocrotaline. MRI and echocardiography measures of PAAT were highly correlated (r(2) = 0.87) and were inversely proportional to invasive mean PAP (r(2) = 0.72). Mean PAP by echocardiography was estimated as 58.7 - (1.21 x PAAT). Invasive and noninvasive CO measurement correlated well (r(2) >or= 0.75). Noninvasive measures of RVFW thickness/mass correlated well with postmortem measurements. We conclude that high-resolution echocardiography and MRI accurately determine CO, PAP, and RV thickness/mass, offering similar results as high-fidelity right heart catheterization and autopsy, and that PAAT accurately estimates PAP and permits serial monitoring of experimental PAH. These tools are useful for assessment of the rodent pulmonary circulation and RVH.
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                Author and article information

                Contributors
                +49 (0)30 450 525 276 , ulrich.kintscher@charite.de
                Journal
                Cardiovasc Ultrasound
                Cardiovasc Ultrasound
                Cardiovascular Ultrasound
                BioMed Central (London )
                1476-7120
                3 July 2018
                3 July 2018
                2018
                : 16
                : 10
                Affiliations
                [1 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Institute of Pharmacology, Center for Cardiovascular Research, , Charité -Universitaetsmedizin Berlin, ; Hessische Str. 3-4, 10115 Berlin, Germany
                [2 ]ISNI 0000 0004 5937 5237, GRID grid.452396.f, German Center for Cardiovascular Research (DZHK), ; partner site Berlin, 10117 Berlin, Germany
                [3 ]ISNI 0000 0004 0390 0098, GRID grid.418213.d, Department of Molecular Toxicology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), ; 14558 Nuthetal, Germany
                [4 ]GRID grid.452622.5, German Center for Diabetes Research (DZD), ; 85764 Muenchen-Neuherberg, Germany
                [5 ]ISNI 0000 0001 0000 0404, GRID grid.418209.6, Internal Medicine/Cardiology, Deutsches Herzzentrum Berlin, ; Augustenburger Platz 1, 13353 Berlin, Germany
                [6 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Department of Cardiology, , Charité University Medicine Berlin, ; Augustenburger Platz 1, 13353 Berlin, Germany
                [7 ]ISNI 0000 0001 2218 4662, GRID grid.6363.0, Institute of Physiology, , Charité University Medicine Berlin, ; Charitéplatz 1, 10117 Berlin, Germany
                Article
                128
                10.1186/s12947-018-0128-9
                6029342
                29966517
                d0a67a36-c507-472c-9ca3-c8bd51173d0b
                © The Author(s). 2018

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 January 2018
                : 13 June 2018
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100007537, Freie Universität Berlin;
                Funded by: Gesundheitscampus Brandenburg
                Funded by: FundRef http://dx.doi.org/10.13039/100010447, Deutsches Zentrum für Herz-Kreislaufforschung;
                Funded by: FundRef http://dx.doi.org/10.13039/501100005970, Deutsche Stiftung für Herzforschung;
                Funded by: FundRef http://dx.doi.org/10.13039/501100001659, Deutsche Forschungsgemeinschaft;
                Funded by: FundRef http://dx.doi.org/10.13039/501100003042, Else Kröner-Fresenius-Stiftung;
                Categories
                Technical Notes
                Custom metadata
                © The Author(s) 2018

                Cardiovascular Medicine
                3d echocardiography,heart failure,volumetry,preclinical imaging,small animals

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