Korean Circ J.  2014 Jan;44(1):1-9. 10.4070/kcj.2014.44.1.1.

Cardiovascular Molecular Imaging with Contrast Ultrasound: Principles and Applications

  • 1Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA. lindnerj@ohsu.edu


Methods for imaging the molecular or cellular profile of tissue are being developed for all forms of non-invasive cardiovascular imaging. It is thought that these technologies will potentially improve patient outcomes by allowing diagnosis of disease at an early-stage, monitoring disease progression, providing important information on patient risk, and for tailoring therapy to the molecular basis of disease. Molecular imaging is also already assuming an important role in science by providing a better understanding of the molecular basis of cardiovascular pathology, for assessing response to new therapies, and for rapidly optimizing new or established therapies. Ultrasound-based molecular imaging is one of these new approaches. Contrast-enhanced ultrasound molecular imaging relies on the detection of novel site-targeted microbubbles (MB) or other acoustically active particles which are administered by intravenous injection, circulate throughout the vascular compartment, and are then retained and imaged within regions of disease by ligand-directed binding. The technique is thought to be advantageous in practical terms of cost, time, and ease of use. The aim of this review is to discuss the molecular participants of cardiovascular disease that have been targeted for ultrasound imaging, general features of site-targeted MB, imaging protocols, and potential roles of ultrasound molecular imaging in cardiovascular research and clinical medicine.


Molecular imaging; Contrast ultrasound; Microbubbles

MeSH Terms

Cardiovascular Diseases
Clinical Medicine
Disease Progression
Injections, Intravenous
Molecular Imaging*


  • Fig. 1 Schematic illustrating mechanisms of leukocyte recruitment during inflammation. Key adhesion molecules involved in rolling and adhesion are shown. PSGL-1: P-selectin glycoprotein ligand-1, VCAM-1: vascular cell adhesion molecule-1, ICAM: intercellular adhesion molecule, VLA-4: very late antigen-4, LFA-1: lymphocyte function-associated antigen-1.

  • Fig. 2 Schematic illustrating potential mechanisms of platelet adhesion in cardiovascular disease. PSGL-1: P-selectin glycoprotein ligand-1, ICAM: intercellular adhesion molecule, VWF: von Willebrand factor. GP1bα: glycoprotein Ib-alpha, GpIIb/IIIa: glycoprotein IIb/IIIa.

  • Fig. 3 Strategies used for targeting of microbubble contrast agents.

  • Fig. 4 Determinants of the success of ligand-directed targeting of microbubbles contrast agents.

  • Fig. 5 Schematic illustrating a common algorithm for molecular imaging with targeted MB contrast agents.

  • Fig. 6 CEU molecular imaging of endothelial activation and platelet adhesion in the aorta in a murine model of age-dependent atherosclerosis (LDL-/-, ApoBec-1-/-), and the effect of anti-oxidant therapy with the NADPH-oxidase-inhibitor apocynin at high or low dose. A-D: molecular imaging signal of P-selectin, VCAM-1, GP1bα, and control MBs in mice at 30 weeks of age and at 40 weeks of age with and without treatment with apocynin. Thoracic aorta images from a non-treated 40 weeks mouse are shown with high-frequency 2-D ultrasound (E) and CEU molecular imaging with GP1bα-targeted and control MBs (F and G).18) CEU: contrast-enhanced ultrasoud, NADPH: nicotinamide adenine dinucleotide phosphate, MB: microbubble, VCAM-1: vascular cell adhesion molecule-1, WT: wild-type mice, DKO: double knockout mice, LDL: low-density lipoprotein, 2-D: 2-dimensional.

  • Fig. 7 Ischemic memory imaging with CEU molecular imaging of P-selectin in mice. A: post-mortem microsphere-defined risk area during LAD occlusion. B and C: B-mode and P-selectin-targeted imaging several hours after producing brief (10 minutes) of transient ischemia of the LAD territory. D: P-selectin molecular imaging data using MBs bearing either PSGL-1 (MBYSPSL) or anti-P-selectin antibody (MBAb) from either the previously ischemic risk area or remote area. Data are shown for various reperfusion time intervals after 10 minutes of ischemia.*p<0.05 vs. remote region. Adapted from Davidson et al. J Am Coll Cardiol 2012;60:1690-7.41) MB: microbubble, CEU: contrast-enhanced ultrasoud, PSGL-1: P-selectin glycoprotein ligand-1.


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