Abstract
BackgroundTraditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric and temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as the mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these geometric assumptions. New ECHO technology, including 4-dimensional ultrasound (4D-US), improves on these traditional models. This paper aims to compare commercially available 4D-US to M-mode and 2D-US in a mouse model of CAL.Methods37 mice underwent CAL surgery, of which 32 survived to a 4 week post-operative time point. ECHO was completed at baseline, 1 week, and 4 weeks after CAL. M-mode, 2D-US, and 4D-US were taken at each time point and evaluated by two separate echocardiographers. At 4 weeks, a subset (n = 12) of mice underwent cardiac magnetic resonance (CMR) imaging to serve as a reference standard. End systolic volume (ESV), end diastolic volume (EDV), and ejection fraction (EF) were compared among imaging modalities. Hearts were also collected for histologic evaluation of scar size (n = 16) and compared to ECHO-derived wall motion severity index (WMSI) and global longitudinal strain as well as gadolinium-enhanced CMR to compare scar assessment modalities.Results4D-US provides close agreement of ESV (Bias: -2.55%, LOA: − 61.55 to 66.66) and EF (US Bias: 11.23%, LOA − 43.10 to 102.8) 4 weeks after CAL when compared to CMR, outperforming 2D-US and M-mode estimations. 4D-US has lower inter-user variability as measured by intraclass correlation (ICC) in the evaluation of EDV (0.91) and ESV (0.93) when compared to other modalities. 4D-US also allows for rapid assessment of WMSI, which correlates strongly with infarct size by histology (r = 0.77).Conclusion4D-US outperforms M-Mode and 2D-US for volumetric analysis 4 weeks after CAL and has higher inter-user reliability. 4D-US allows for rapid calculation of WMSI, which correlates well with histologic scar size.
Highlights
Traditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric and temporal assumptions about the heart for volumetric measurements
Three-dimensional (3D) ECHO has gained favor recently in clinical and pre-clinical models, allowing full volume visualization of the heart by stacking concentric short-axis images to form a 3D representation at static time points [4, 11, 12]. 3D ECHO has been further improved by combining respiratory- and ECG-gated image acquisition to create 3D images throughout the cardiac cycle, referred to as 4-dimensional ultrasound (4D-US) [13, 14]. 4D-US has recently became commercially available for pre-clinical models and has already been validated against cardiac magnetic resonance (CMR) imaging in wild type mice and a mouse model of hypertrophy [15]
Subgroup analysis was performed between MHC (+) and MHC (−) groups and there was no significant difference noted in survival, scar size, baseline end diastolic volume (EDV), End systolic volume (ESV), or ejection fraction (EF), as well as 4-week EDV, ESV, or EF between groups by any ECHO modality (Supplemental Fig. 2, Supplemental Table 1)
Summary
Traditional preclinical echocardiography (ECHO) modalities, including 1-dimensional motion-mode (M-Mode) and 2-dimensional long axis (2D-US), rely on geometric and temporal assumptions about the heart for volumetric measurements. Surgical animal models, such as the mouse coronary artery ligation (CAL) model of myocardial infarction, result in morphologic changes that do not fit these geometric assumptions. Traditional ECHO modalities for evaluating ventricular size and function, including 1dimensional motion-mode (M-mode) and 2-dimensional (2D-US) long-axis analysis, make geometric assumptions about the heart that limit their accuracy, in the setting of heart disease, where regional ventricular shape abnormalities may exist [6,7,8]. While CMR imaging remains the gold standard for assessment of cardiac function in mice [16,17,18], recent studies in 3D ECHO and 4D-US have shown considerable advances in scanning time and reliability [13,14,15]
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