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Selective Enhancement of Swine Myocardium with a Novel Ultrasound Enhancing Agent During Transthoracic Echocardiography

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Abstract

Ultrasound enhancing agents are approved to delineate the endocardial border and opacify the left ventricle cavity (LVC). We present a nested phase change agent (NPCA) designed to enable selective myocardial enhancement without enhancing the LVC by employing a dual-activation mechanism dependent on sufficient ultrasound intensity and the microenvironment of the myocardium. Swine received bolus injections of NPCA while echocardiograms were collected and processed to determine background-subtracted acoustic intensities (AI) in the LVC and septal myocardium. At mechanical index (MI) ≥ 0.8, the NPCA enhanced the myocardium selectively (p < 0.001) while the LVC remained at baseline AI. A 5-mL bolus of NPCA enhanced swine myocardium and enhancement persisted for > 5 min at 1.4 MI, while hemodynamics and EKG remained normal. Our findings demonstrate that the NPCA enhances swine myocardium selectively without enhancing the LVC. The NPCA could have utility for functional and structural echocardiographic studies with clinical ultrasound using standard settings.

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Abbreviations

LVC:

Left ventricle cavity

NPCA:

Nested phase change agent

MI:

Mechanical index

AI:

Acoustic intensity

SER:

Selective enhancement ratio

EMA:

European Medicines Agency

FDA:

Food & Drug Administration

MPI:

Myocardial perfusion imaging

cMRI:

Cardiac magnetic resonance imaging

PET:

Positron emission tomography

SPECT:

Single-photon emission computed tomography

UEA:

Ultrasound enhancing agent

PCA:

Phase change agent

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Funding

This study was supported by the Coulter-Drexel Translational Research Partnership Program and the Department of Education (Award No. P200 A150240).

Author information

Authors and Affiliations

  1. Chemical and Biological Engineering, Drexel University, Philadelphia, PA, USA

    Michael Cimorelli, Michael A. Flynn, Benjamin Andrien, Aaron Fafarman & Steven Wrenn

  2. Cardiology, Drexel University College of Medicine, Philadelphia, PA, USA

    Brett Angel

  3. Cardiology, Tower Health, Phoenixville, PA, USA

    Brett Angel

  4. University Laboratory Animal Resources, Drexel University College of Medicine, Philadelphia, PA, USA

    Emily Reimold & Richard Huneke

  5. Cardiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Andrew Kohut

  6. Cardiology, Einstein Medical Center, Philadelphia, PA, USA

    Sahil S. Banka

  7. Chemical Engineering, Virginia Tech, Blacksburg, VA, USA

    Steven Wrenn

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  1. Michael Cimorelli
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Corresponding authors

Correspondence to Michael Cimorelli or Steven Wrenn.

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No human studies were carried out by the authors for this article.

Competing Interests

Drs. Angel, Cimorelli, Fafarman, Kohut, and Wrenn are co-inventors on an issued patent covering the voltage-sensitive nesting architecture described in this study. Drs. Angel, Cimorelli, Fafarman, Kohut, and Wrenn and Mr. Flynn are co-founders and own equity of Sonnest, Inc. Mr. Andrien, Dr. Cimorelli, and Mr. Flynn are employees at Sonnest, Inc., while Drs. Angel, Kohut, and Wrenn are consultants at Sonnest, Inc. All other authors declare no conflicts of interest.

Additional information

Communicated by Associate Editor Paul Jozine ter Maaten oversaw the review of this article.

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Supplementary Information

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Supplementary file1 (PDF 75 KB)

Supplemental video 2 Demonstrationof image processing to quantify acoustic intensity in regions of interest. The Brightness (B)-mode videos are loaded into custom software that was developed in Python 3.8.0 to quantify the average brightness in arbitrary units (a.u.) in the left ventricle cavity (LVC, red) and the septal myocardium (green) by digitizing the pixels from 0 (black) to 255 (white) in an ellipse with a predefined area of 2,000 pixels while tracking their movement throughout the cardiac cycle. The two ellipses are repositioned frame by frame to remain within the LVC and septal myocardium. The average brightness is determined for each 15-second increment and is shown above. (MP4 9088 KB)

Supplemental video 3 (MP4 34423 KB)

Supplementary file4 (DOCX 29 KB)

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Cimorelli, M., Flynn, M.A., Angel, B. et al. Selective Enhancement of Swine Myocardium with a Novel Ultrasound Enhancing Agent During Transthoracic Echocardiography. J. of Cardiovasc. Trans. Res. 15, 722–729 (2022). https://doi.org/10.1007/s12265-022-10207-2

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