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Ultrasound molecular imaging of cardiovascular disease

Abstract

Myocardial contrast echocardiography utilizes intravenously injected gas-filled microspheres as acoustically active red blood cell tracers. During ultrasound imaging, unimpeded microsphere transit through the intramyocardial microcirculation causes transient myocardial opacification, which can be mapped and quantified as myocardial perfusion. Ultrasound molecular imaging utilizes similar acoustically active microspheres, which are modified to bear a receptor-specific ligand on the surface, conferring microsphere binding to a disease-specific endothelial epitope. Because the microspheres adhere to the endothelium, ultrasound imaging reveals a persistent, rather than transient, contrast effect, indicating the presence and location of the molecule of interest in real time. Molecular contrast echocardiography has been developed to detect upregulated leukocyte adhesion molecules during microvascular inflammation, such as occurs in cardiac transplant rejection and ischemia–reperfusion. Principles of microsphere targeting and ultrasound imaging of microvascular epitopes have been extended to larger vessels to image molecular markers of atherosclerosis. This Article summarizes the current status of cardiovascular ultrasound molecular imaging. Experimental proofs of concept will be outlined and the clinical extension of these concepts to the molecular imaging of cardiovascular disease using clinical ultrasound technology will be discussed.

Key Points

  • Ultrasound molecular imaging is based on the use of gas-filled microspheres engineered to bind to function-specific endothelial markers of disease via specific ligand-receptor interactions and that can be detected using clinical ultrasound scanning

  • Targeted ultrasound imaging of leukocyte adhesion molecules can be used clinically to noninvasively identify myocardial ischemic memory, angiogenesis, and acute heart transplant rejection

  • Catheter-based intravascular ultrasound imaging of adhesion molecules might permit identification of atherosclerosis-prone endothelium before luminal stenosis, facilitating early-stage diagnosis, and hence preventative treatment

  • Optimization of microbubble and transducer design holds promise for the clinical translation of ultrasound molecular imaging to human populations in the foreseeable future

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Figure 1: Basis for molecular imaging with microbubbles.
Figure 2: Color-coded short axis ultrasound images and the corresponding myocardial specimen of the left ventricle demonstrating imaging of ischemic memory in a rat undergoing transient coronary artery occlusion.
Figure 3: Ultrasound molecular imaging of early atherosclerosis in atherosclerosis-prone mice (ApoE deficient) fed a high-cholesterol diet.

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Acknowledgements

FS Villanueva and WR Wagner are supported by grants from the NIH.

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Correspondence to Flordeliza S Villanueva.

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Villanueva, F., Wagner, W. Ultrasound molecular imaging of cardiovascular disease. Nat Rev Cardiol 5, S26–S32 (2008). https://doi.org/10.1038/ncpcardio1246

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