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Molecular Imaging of Carotid Plaque with Targeted Ultrasound Contrast

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Ultrasound and Carotid Bifurcation Atherosclerosis

Abstract

Just about a decade ago, targeted or molecular1 imaging with ultrasound contrast agents was deemed impossible. However, with the advances of ultrasound imaging equipment and improved design of ultrasound contrast agents, the old point of view could be reconsidered. Currently, ultrasound contrast agents are widely investigated as the imaging tools for molecular imaging of the specific markers, mostly for the targets located within the vascular bed.2 Most of the studies are performed in vivo in the animal model setting and clinical trials are expected to follow in the near future.

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References

  1. Weissleder R, Mahmood U. Molecular imaging. Radiology. 2001;219(2):316–333.

    PubMed  CAS  Google Scholar 

  2. Villanueva FS. Molecular imaging of cardiovascular disease using ultrasound. J Nucl Cardiol. 2008;15(4):576–586.

    Article  PubMed  Google Scholar 

  3. Galkina E, Ley K. Leukocyte influx in atherosclerosis. Curr Drug Targets. 2007;8(12):1239–1248.

    Article  PubMed  CAS  Google Scholar 

  4. Hutter JC, Luu HM, Mehlhaff PM, Killam AL, Dittrich HC. Physiologically based pharmacokinetic model for fluorocarbon elimination after the administration of an octafluoropropane-albumin microsphere sonographic contrast agent. J Ultrasound Med. 1999;18(1):1–11.

    PubMed  CAS  Google Scholar 

  5. Harris JR, Depoix F, Urich K. The structure of gas-filled n-butyl-2-cyanoacrylate (BCA) polymer particles. Micron. 1995;26(2):103–111.

    Article  CAS  Google Scholar 

  6. Patrianakos AP, Hamilos MI. Drug evaluation: PB-127, a novel contrast agent for the detection of myocardial perfusion. Curr Opin Investig Drugs. 2007;8(3):248–255.

    PubMed  CAS  Google Scholar 

  7. Straub JA et al. Porous PLGA microparticles: AI-700, an intravenously administered ultrasound contrast agent for use in echocardiography. J Control Release. 2005;108(1):21–32.

    Article  PubMed  CAS  Google Scholar 

  8. Paradossi G, Cavalieri F, Chiessi E, Ponassi V, Martorana V. Tailoring of physical and chemical properties of macro- and microhydrogels based on telechelic PVA. Biomacromolecules. 2002;3(6):1255–1262.

    Article  PubMed  CAS  Google Scholar 

  9. Chlon C et al. Effect of molecular weight, crystallinity, and hydrophobicity on the acoustic activation of polymer-shelled ultrasound contrast agents. Biomacromolecules. 2009;10(5):1025–1031.

    Article  PubMed  CAS  Google Scholar 

  10. Lindner JR et al. Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes. Circulation. 2000;102(22):2745–2750.

    PubMed  CAS  Google Scholar 

  11. Korpanty G, Grayburn PA, Shohet RV, Brekken RA. Targeting vascular endothelium with avidin microbubbles. Ultrasound Med Biol. 2005;31(9):1279–1283.

    Article  PubMed  Google Scholar 

  12. Kim DH, Klibanov AL, Needham D. The influence of tiered layers of surface-grafted poly(ethylene glycol) on receptor-ligand-mediated adhesion between phospholipid monolayer-stabilized microbubbles and coated class beads. Langmuir. 2000;16(6):2808–2817.

    Article  CAS  Google Scholar 

  13. Ham AS, Klibanov AL, Lawrence MB. Action at a distance: lengthening adhesion bonds with poly(ethylene glycol) spacers enhances mechanically stressed affinity for improved vascular targeting of microparticles. Langmuir. 2009;25(17):10038–10044.

    Article  PubMed  CAS  Google Scholar 

  14. Klibanov AL et al. Detection of individual microbubbles of ultrasound contrast agents: imaging of free-floating and targeted bubbles. Invest Radiol. 2004;39(3):187–195.

    Article  PubMed  Google Scholar 

  15. Phillips P, Gardner E. Contrast-agent detection and quantification. Eur Radiol. 2004;14(suppl 8):P4–P10.

    PubMed  Google Scholar 

  16. Eckersley RJ, Chin CT, Burns PN. Optimising phase and amplitude modulation schemes for imaging microbubble contrast agents at low acoustic power. Ultrasound Med Biol. 2005;31(2):213–219.

    Article  PubMed  Google Scholar 

  17. Lindner JR et al. Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation. 2001;104(17):2107–2112.

    Article  PubMed  CAS  Google Scholar 

  18. Rychak JJ et al. Microultrasound molecular imaging of vascular endothelial growth factor receptor 2 in a mouse model of tumor angiogenesis. Mol Imaging. 2007;6(5):289–296.

    PubMed  Google Scholar 

  19. Christiansen JP, Leong-Poi H, Klibanov AL, Kaul S, Lindner JR. Noninvasive imaging of myocardial reperfusion injury using leukocyte-targeted contrast echocardiography. Circulation. 2002;105(15):1764–1767.

    Article  PubMed  Google Scholar 

  20. Dayton P, Klibanov A, Brandenburger G, Ferrara K. Acoustic radiation force in vivo: a mechanism to assist targeting of microbubbles. Ultrasound Med Biol. 1999;25(8):1195–1201.

    Article  PubMed  CAS  Google Scholar 

  21. Zhao S et al. Radiation-force assisted targeting facilitates ultrasonic molecular imaging. Mol Imaging. 2004;3(3):135–148.

    Article  PubMed  CAS  Google Scholar 

  22. Rychak JJ, Klibanov AL, Hossack JA. Acoustic radiation force enhances targeted delivery of ultrasound contrast microbubbles: in vitro verification. IEEE Trans Ultrason Ferroelectr Freq Control. 2005;52(3):421–433.

    Article  PubMed  Google Scholar 

  23. Rychak JJ, Klibanov AL, Ley KF, Hossack JA. Enhanced targeting of ultrasound contrast agents using acoustic radiation force. Ultrasound Med Biol. 2007;33(7):1132–1139.

    Article  PubMed  Google Scholar 

  24. Patil AV, Rychak JJ, Allen JS, Klibanov AL, Hossack JA. Dual frequency method for simultaneous translation and real-time imaging of ultrasound contrast agents within large blood vessels. Ultrasound Med Biol. 2009;35(12):2021–2030.

    Article  PubMed  Google Scholar 

  25. Takalkar AM, Klibanov AL, Rychak JJ, Lindner JR, Ley K. Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow. J Control Release. 2004;96(3):473–482.

    Article  PubMed  CAS  Google Scholar 

  26. Ley K, Gaehtgens P, Spanel-Borowski K. Differential adhesion of granulocytes to five distinct phenotypes of cultured microvascular endothelial cells. Microvasc Res. 1992;43(2):119–133.

    Article  PubMed  CAS  Google Scholar 

  27. Watanabe R, Matsumura M, Munemasa T, Fujimaki M, Suematsu M. Mechanism of hepatic parenchyma-specific contrast of microbubble-based contrast agent for ultrasonography: microscopic studies in rat liver. Invest Radiol. 2007;42(9):643–651.

    Article  PubMed  CAS  Google Scholar 

  28. Klibanov AL et al. Targeting of ultrasound contrast material. An in vitro feasibility study. Acta Radiol Suppl. 1997;412:113–120.

    PubMed  CAS  Google Scholar 

  29. Villanueva FS et al. Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells. Circulation. 1998;98(1):1–5.

    PubMed  CAS  Google Scholar 

  30. Weller GE, Villanueva FS, Tom EM, Wagner WR. Targeted ultrasound contrast agents: in vitro assessment of endothelial dysfunction and multi-targeting to ICAM-1 and sialyl Lewisx. Biotechnol Bioeng. 2005;92(6):780–788.

    Article  PubMed  CAS  Google Scholar 

  31. Klibanov AL et al. Targeted ultrasound contrast agent for molecular imaging of inflammation in high-shear flow. Contrast Media Mol Imaging. 2006;1(6):259–266.

    Article  PubMed  CAS  Google Scholar 

  32. Ottoboni S et al. Characterization of the in vitro adherence behavior of ultrasound responsive double-shelled microspheres targeted to cellular adhesion molecules. Contrast Media Mol Imaging. 2006;1(6):279–290.

    Article  PubMed  CAS  Google Scholar 

  33. Kaufmann BA et al. Molecular imaging of the initial inflammatory response in atherosclerosis: implications for early detection of disease. Arterioscler Thromb Vasc Biol. 2009;30(1):54–59.

    Article  PubMed  Google Scholar 

  34. Ferrante EA, Pickard JE, Rychak J, Klibanov A, Ley K. Dual targeting improves microbubble contrast agent adhesion to VCAM-1 and P-selectin under flow. J Control Release. 2009;140(2):100–107.

    Article  PubMed  CAS  Google Scholar 

  35. Cho YK et al. Dual-targeted contrast enhanced ultrasound imaging of atherosclerosis in apolipoprotein e gene knockout mice. Circulation. 2006;114(18):759.

    Google Scholar 

  36. Guenther F, Klibanov AL, Ferrante E, Bode C, von zur Muhlen C. An ultrasound contrast agent targeted towards P-selectin detects activated platelets at supra-arterial shear flow ex-vivo. In: Contrast Media Research Symposium; Copenhagen; 2009:21–23.

    Google Scholar 

  37. Schumann PA et al. Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi. Invest Radiol. 2002;37(11):587–593.

    Article  PubMed  CAS  Google Scholar 

  38. Pochon S et al. BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis. Invest Radiol. 2010;45(2):89–95.

    Article  PubMed  CAS  Google Scholar 

  39. Staub D et al. Vasa vasorum and plaque neovascularization on contrast-enhanced carotid ultrasound imaging correlates with cardiovascular disease and past cardiovascular events. Stroke. 2010;41(1):41–47.

    Article  PubMed  Google Scholar 

  40. Fuster V, Badimon J, Chesebro JH, Fallon JT. Plaque rupture, thrombosis, and therapeutic implications. Haemostasis. 1996;26(suppl 4):269–284.

    PubMed  Google Scholar 

  41. Dunn S et al. The lectin-like oxidized low-density-lipoprotein receptor: a pro-inflammatory factor in vascular disease. Biochem J. 2008;409(2):349–355.

    Article  PubMed  CAS  Google Scholar 

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Rychak, J.J., Klibanov, A.L. (2011). Molecular Imaging of Carotid Plaque with Targeted Ultrasound Contrast. In: Nicolaides, A., Beach, K., Kyriacou, E., Pattichis, C. (eds) Ultrasound and Carotid Bifurcation Atherosclerosis. Springer, London. https://doi.org/10.1007/978-1-84882-688-5_9

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  • DOI: https://doi.org/10.1007/978-1-84882-688-5_9

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