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Myocardial contrast echocardiography assessment of mouse myocardial infarction: comparison of kinetic parameters with conventional methods.

ABSTRACT: This study explores the use of a minimally invasive assessment of myocardial infarction (MI) in mice using myocardial contrast echocardiography (MCE). The technique uses existing equipment and software readily available to the average researcher. C57/BL6 mice were randomized to either MI or sham surgery and evaluated using MCE at 1- or 2-weeks post-surgery. Size-isolated microbubbles were injected via retro-orbital catheter where their non-linear characteristics were utilized to produce the two-dimensional parameters of Wash-in-Rate and the Peak Enhancement, indicative of relative myocardial perfusion and blood volume, respectively. Three-dimensional cardiac reconstructions allowed the calculation of the Percent Agent, interpreted as the vascularity of the entire myocardium. These MCE parameters were compared to conventional assessments including M-Mode, strain analysis, and 2,3,5-Triphenyltetrazolium chloride (TTC) staining. Except for the Wash-in-Rate 2-week cohort, all MCE parameters were able to differentiate sham-operated versus MI animals and correlated with TTC staining (P < 0.05). MCE parameters were also able to identify MI group animals which failed to develop infarctions as determined by TTC staining. This study provides basic validation of these MCE parameters to detect MI in mice complementary to conventional methods while providing additional hemodynamic information in vivo.

SUBMITTER: Thielen NT

PROVIDER: S-EPMC8176928 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The small size of the mouse heart frequently imparts technical challenges when applying conventional in vivo imaging methods for assessing heart function. Here, we describe the use of high-frequency ultrasound imaging in conjunction with a size-tuned blood pool contrast agent for quantitatively assessing myocardial perfusion in living mice. A perflurocarbon microbubble formulation exhibiting a narrow size distribution was developed, and echogenicity was assessed at 18 MHz in vitro. Adult mice were subjected to permanent ligation of the left anterior descending artery. Ultrasound imaging was performed on day 7, and a cohort of intact mice was used as a control. Parasternal long-axis cine clips were acquired at 18 MHz before and after contrast administration. Reduced ejection fraction and increased end-systolic volume were observed in infarcted compared with control mice. In control animals, washin of the contrast agent was visible in all myocardial segments. Reduced contrast enhancement was observed in apical-posterolateral regions of all infarcted mice. A novel method for reslicing of the imaging data through the time domain provided a two-dimensional presentation of regional contrast agent washin, enabling convenient identification of locations exhibiting altered perfusion. Myocardial segments exhibiting diminished contractility were observed to have correspondingly low relative myocardial perfusion. The contrast agent formulation and methods demonstrated here provide the basis for simplifying routine in vivo estimation of infarct size in mice and may be particularly useful in longitudinal evaluation of revascularization interventions and assessment of peri-infarct ischemia. NEW & NOTEWORTHY Murine myocardial contrast echocardiography frequently suffers from poor sensitivity to contrast. Here, we formulated a novel size-tuned microbubble contrast agent and validated it for use with ultra-high-frequency ultrasound. A novel data method for evaluating myocardial perfusion based on reslicing the imaging data through the time domain is presented.

Project description: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.

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Myocardial contrast echocardiography assessment of mouse myocardial infarction: comparison of kinetic parameters with conventional methods.

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