Ultrasound in Medicine and Biology
Volume 36, Issue 2 , Pages 181-191 , February 2010

Critical Appraisal of Targeted Ultrasound Contrast Agents for Molecular Imaging in Large Arteries

  • Liselotte M. Kornmann

      Affiliations

    • Department of Biophysics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
  • ,
  • Koen D. Reesink

      Affiliations

    • Department of Biophysics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
  • ,
  • Robert S. Reneman

      Affiliations

    • Department of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
  • ,
  • Arnold P.G. Hoeks

      Affiliations

    • Department of Biophysics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
    • Corresponding Author InformationAddress correspondence to: Prof. Dr. Arnold P. G. Hoeks, Department of Biomedical Engineering/Biophysics, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.

Received 23 June 2009 ,Revised 26 August 2009 ,Accepted 21 September 2009.

References 

  1. Alkan-Onyuksel H, Demos SM, Lanza GM, Vonesh MJ, Klegerman ME, Kane BJ, et al. Development of inherently echogenic liposomes as an ultrasonic contrast agent. J Pharm Sci. 1996;85:486–490
  2. Alon R, Hammer DA, Springer TA. Lifetime of the P-selectin-carbohydrate bond and its response to tensile force in hydrodynamic flow. Nature. 1995;374:539–542
  3. Barnard S, Leen E, Cooke T, Angerson W. A contrast-enhanced ultrasound study of benign and malignant breast tissue. S Afr Med J. 2008;98:386–391
  4. Basu S, Zhuang H, Torigian DA, Rosenbaum J, Chen W, Alavi A. Functional imaging of inflammatory diseases using nuclear medicine techniques. Semin Nucl Med. 2009;39:124–145
  5. Behm CZ, Lindner JR. Cellular and molecular imaging with targeted contrast ultrasound. Ultrasound Q. 2006;22:67–72
  6. Bharadvaj BK, Mabon RF, Giddens DP. Steady flow in a model of the human carotid bifurcation. Part I-Flow visualization. J Biomech. 1982;15:349–362
  7. Bharadvaj BK, Mabon RF, Giddens DP. Steady flow in a model of the human carotid bifurcation. Part II-Laser-Doppler anemometer measurements. J Biomech. 1982;15:363–378
  8. Bokor D. Diagnostic efficacy of SonoVue. Am J Cardiol. 2000;86:19G–24G
  9. Bruce M, Averkiou M, Tiemann K, Lohmaier S, Powers J, Beach K. Vascular flow and perfusion imaging with ultrasound contrast agents. Ultrasound Med Biol. 2004;30:735–743
  10. Chan JR, Hyduk SJ, Cybulsky MI. Chemoattractants induce a rapid and transient upregulation of monocyte alpha4 integrin affinity for vascular cell adhesion molecule 1 which mediates arrest: An early step in the process of emigration. J Exp Med. 2001;193:1149–1158
  11. Chappell JC, Price RJ. Targeted therapeutic applications of acoustically active microspheres in the microcirculation. Microcirculation. 2006;13:57–70
  12. Cheng C, Helderman F, Tempel D, Segers D, Hierck B, Poelmann R, et al. Large variations in absolute wall shear stress levels within one species and between species. Atherosclerosis. 2007;195:225–235
  13. Christiansen C, Kryvi H, Sontum PC, Skotland T. Physical and biochemical characterization of Albunex, a new ultrasound contrast agent consisting of air-filled albumin microspheres suspended in a solution of human albumin. Biotechnol Appl Biochem. 1994;19(Pt 3):307–320
  14. Cohen JL, Cheirif J, Segar DS, Gillam LD, Gottdiener JS, Hausnerova E, et al. Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial. J Am Coll Cardiol. 1998;32:746–752
  15. Couture O, Bevan PD, Cherin E, Cheung K, Burns PN, Foster FS. Investigating perfluorohexane particles with high-frequency ultrasound. Ultrasound Med Biol. 2006;32:73–82
  16. Couture O, Bevan PD, Cherin E, Cheung K, Burns PN, Foster FS. A model for reflectivity enhancement due to surface bound submicrometer particles. Ultrasound Med Biol. 2006;32:1247–1255
  17. Couture O, Cherin E, Foster FS. Model for the ultrasound reflection from micro-beads and cells distributed in layers on a uniform surface. Phys Med Biol. 2007;52:4189–4204
  18. Crowder KC, Hughes MS, Marsh JN, Barbieri AM, Fuhrhop RW, Lanza GM, et al. Sonic activation of molecularly-targeted nanoparticles accelerates transmembrane lipid delivery to cancer cells through contact-mediated mechanisms: Implications for enhanced local drug delivery. Ultrasound Med Biol. 2005;31:1693–1700
  19. Dai G, Kaazempur-Mofrad MR, Natarajan S, Zhang Y, Vaughn S, Blackman BR, et al. Distinct endothelial phenotypes evoked by arterial waveforms derived from atherosclerosis-susceptible and -resistant regions of human vasculature. Proc Natl Acad Sci U S A. 2004;101:14871–14876
  20. Dayton PA, Rychak JJ. Molecular ultrasound imaging using microbubble contrast agents. Front Biosci. 2007;12:5124–5142
  21. de Jong N, Bouakaz A, Frinking P. Basic acoustic properties of microbubbles. Echocardiography. 2002;19:229–240
  22. de Jong N, Ten Cate FJ, Lancee CT, Roelandt JR, Bom N. Principles and recent developments in ultrasound contrast agents. Ultrasonics. 1991;29:324–330
  23. Demos SM, Alkan-Onyuksel H, Kane BJ, Ramani K, Nagaraj A, Greene R, et al. In vivo targeting of acoustically reflective liposomes for intravascular and transvascular ultrasonic enhancement. J Am Coll Cardiol. 1999;33:867–875
  24. Demos SM, Dagar S, Klegerman M, Nagaraj A, McPherson DD, Onyuksel H. In vitro targeting of acoustically reflective immunoliposomes to fibrin under various flow conditions. J Drug Target. 1998;5:507–518
  25. Demos SM, Onyuksel H, Gilbert J, Roth SI, Kane B, Jungblut P, et al. In vitro targeting of antibody-conjugated echogenic liposomes for site-specific ultrasonic image enhancement. J Pharm Sci. 1997;86:167–171
  26. Eniola AO, Willcox PJ, Hammer DA. Interplay between rolling and firm adhesion elucidated with a cell-free system engineered with two distinct receptor-ligand pairs. Biophys J. 2003;85:2720–2731
  27. Feigenbaum H, Stone JM, Lee DA, Nasser WK, Chang S. Identification of ultrasound echoes from the left ventricle by use of intracardiac injections of indocyanine green. Circulation. 1970;41:615–621
  28. Feinstein SB. Contrast ultrasound imaging of the carotid artery vasa vasorum and atherosclerotic plaque neovascularization. J Am Coll Cardiol. 2006;48:236–243
  29. Flaim SF. Pharmacokinetics and side effects of perfluorocarbon-based blood substitutes. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:1043–1054
  30. Freire MG, Dias AM, Coelho MA, Coutinho JA, Marrucho IM. Aging mechanisms of perfluorocarbon emulsions using image analysis. J Colloid Interface Sci. 2005;286:224–232
  31. Friedman MH, Deters OJ, Bargeron CB, Hutchins GM, Mark FF. Shear-dependent thickening of the human arterial intima. Atherosclerosis. 1986;60:161–171
  32. Gerszten RE, Lim YC, Ding HT, Snapp K, Kansas G, Dichek DA, et al. Adhesion of monocytes to vascular cell adhesion molecule-1-transduced human endothelial cells: Implications for atherogenesis. Circ Res. 1998;82:871–878
  33. Gimbrone MA, Topper JN, Nagel T, Anderson KR, Garcia-Cardena G. Endothelial dysfunction, hemodynamic forces, and atherogenesis. Ann N Y Acad Sci. 2000;902:230–239discussion 239–240
  34. Gramiak R, Shah PM. Echocardiography of the aortic root. Invest Radiol. 1968;3:356–366
  35. Greve JM, Les AS, Tang BT, Draney Blomme MT, Wilson NM, Dalman RL, et al. Allometric scaling of wall shear stress from mice to humans: Quantification using cine phase-contrast MRI and computational fluid dynamics. Am J Physiol Heart Circ Physiol. 2006;291:H1700–1708
  36. Hall CS, Marsh JN, Scott MJ, Gaffney PJ, Wickline SA, Lanza GM. Time evolution of enhanced ultrasonic reflection using a fibrin-targeted nanoparticulate contrast agent. J Acoust Soc Am. 2000;108:3049–3057
  37. Hamilton A, Huang SL, Warnick D, Stein A, Rabbat M, Madhav T, et al. Left ventricular thrombus enhancement after intravenous injection of echogenic immunoliposomes: Studies in a new experimental model. Circulation. 2002;105:2772–2778
  38. Hamilton A, Rabbat M, Jain P, Belkind N, Huang SL, Nagaraj A, et al. A physiologic flow chamber model to define intravascular ultrasound enhancement of fibrin using echogenic liposomes. Invest Radiol. 2002;37:215–221
  39. Hamilton AJ, Huang SL, Warnick D, Rabbat M, Kane B, Nagaraj A, et al. Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol. 2004;43:453–460
  40. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352:1685–1695
  41. Huang SL, Hamilton AJ, Pozharski E, Nagaraj A, Klegerman ME, McPherson DD, et al. Physical correlates of the ultrasonic reflectivity of lipid dispersions suitable as diagnostic contrast agents. Ultrasound Med Biol. 2002;28:339–348
  42. Huang SL, MacDonald RC. Acoustically active liposomes for drug encapsulation and ultrasound-triggered release. Biochim Biophys Acta. 2004;1665:134–141
  43. Huo Y, Hafezi-Moghadam A, Ley K. Role of vascular cell adhesion molecule-1 and fibronectin connecting segment-1 in monocyte rolling and adhesion on early atherosclerotic lesions. Circ Res. 2000;87:153–159
  44. Ismail S, Jayaweera AR, Camarano G, Gimple LW, Powers ER, Kaul S. Relation between air-filled albumin microbubble and red blood cell rheology in the human myocardium. Influence of echocardiographic systems and chest wall attenuation. Circulation. 1996;94:445–451
  45. Jaffer FA, Libby P, Weissleder R. Molecular imaging of cardiovascular disease. Circulation. 2007;116:1052–1061
  46. Jayaweera AR, Edwards N, Glasheen WP, Villanueva FS, Abbott RD, Kaul S. In vivo myocardial kinetics of air-filled albumin microbubbles during myocardial contrast echocardiography. Comparison with radiolabeled red blood cells. Circ Res. 1994;74:1157–1165
  47. Kaufmann BA, Sanders JM, Davis C, Xie A, Aldred P, Sarembock IJ, et al. Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. Circulation. 2007;116:276–284
  48. Kheirolomoom A, Dayton PA, Lum AF, Little E, Paoli EE, Zheng H, et al. Acoustically-active microbubbles conjugated to liposomes: Characterization of a proposed drug delivery vehicle. J Control Release. 2007;118:275–284
  49. Klegerman ME, Huang S, Parikh D, Martinez J, Demos SM, Onyuksel HA, et al. Lipid contribution to the affinity of antigen association with specific antibodies conjugated to liposomes. Biochim Biophys Acta. 2007;1768:1703–1716
  50. Klibanov AL, Hughes MS, Marsh JN, Hall CS, Miller JG, Wible JH, et al. Targeting of ultrasound contrast material. An in vitro feasibility study. Acta Radiol Suppl. 1997;412:113–120
  51. Klibanov AL, Hughes MS, Villanueva FS, Jankowski RJ, Wagner WR, Wojdyla JK, et al. Targeting and ultrasound imaging of microbubble-based contrast agents. Magma. 1999;8:177–184
  52. Klibanov AL, Hughes MS, Wojdyla JK, Marsh JN, Hall CS, Miller JG, et al. Targeting of ultrasound contrast material: Selective imaging of microbubbles in vitro. Acad Radiol. 1998;5(Suppl.1):S243–S246
  53. Klibanov AL, Maruyama K, Torchilin VP, Huang L. Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 1990;268:235–237
  54. Klibanov AL, Rasche PT, Hughes MS, Wojdyla JK, Galen KP, Wible JH, et al. Detection of individual microbubbles of ultrasound contrast agents: Imaging of free-floating and targeted bubbles. Invest Radiol. 2004;39:187–195
  55. Klibanov AL, Rychak JJ, Yang WC, Alikhani S, Li B, Acton S, et al. Targeted ultrasound contrast agent for molecular imaging of inflammation in high-shear flow. Contrast Media Mol Imaging. 2006;1:259–266
  56. Kornmann LM, Curfs DM, Hermeling E, van der Made I, de Winther MP, Reneman RS, et al. Perfluorohexane-loaded macrophages as a novel ultrasound contrast agent: A feasibility study. Mol Imaging Biol. 2008;10:264–270
  57. Lankford M, Behm CZ, Yeh J, Klibanov AL, Robinson P, Lindner JR. Effect of microbubble ligation to cells on ultrasound signal enhancement: Implications for targeted imaging. Invest Radiol. 2006;41:721–728
  58. Lanza GM, Abendschein DR, Hall CS, Marsh JN, Scott MJ, Scherrer DE, et al. Molecular imaging of stretch-induced tissue factor expression in carotid arteries with intravascular ultrasound. Invest Radiol. 2000;35:227–234
  59. Lanza GM, Trousil RL, Wallace KD, Rose JH, Hall CS, Scott MJ, et al. In vitro characterization of a novel, tissue-targeted ultrasonic contrast system with acoustic microscopy. J Acoust Soc Am. 1998;104:3665–3672
  60. Lanza GM, Wallace KD, Fischer SE, Christy DH, Scott MJ, Trousil RL, et al. High-frequency ultrasonic detection of thrombi with a targeted contrast system. Ultrasound Med Biol. 1997;23:863–870
  61. Lanza GM, Wallace KD, Scott MJ, Cacheris WP, Abendschein DR, Christy DH, et al. A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation. 1996;94:3334–3340
  62. Lanza GM, Wickline SA. Targeted ultrasonic contrast agents for molecular imaging and therapy. Curr Probl Cardiol. 2003;28:625–653
  63. Laverman P, Zalipsky S, Oyen WJ, Dams ET, Storm G, Mullah N, et al. Improved imaging of infections by avidin-induced clearance of 99mTc-biotin-PEG liposomes. J Nucl Med. 2000;41:912–918
  64. Lawrence MB, Kansas GS, Kunkel EJ, Ley K. Threshold levels of fluid shear promote leukocyte adhesion through selectins (CD62L, P, E). J Cell Biol. 1997;136:717–727
  65. Ley K, Laudanna C, Cybulsky MI, Nourshargh S. Getting to the site of inflammation: The leukocyte adhesion cascade updated. Nat Rev Immunol. 2007;7:678–689
  66. Lindner JR. Assessment of inflammation with contrast ultrasound. Prog Cardiovasc Dis. 2001;44:111–120
  67. Lindner JR. Detection of inflamed plaques with contrast ultrasound. Am J Cardiol. 2002;90:32L–35L
  68. Lindner JR. Molecular imaging with contrast ultrasound and targeted microbubbles. J Nucl Cardiol. 2004;11:215–221
  69. Lindner JR, Coggins MP, Kaul S, Klibanov AL, Brandenburger GH, Ley K. Microbubble persistence in the microcirculation during ischemia/reperfusion and inflammation is caused by integrin- and complement-mediated adherence to activated leukocytes. Circulation. 2000;101:668–675
  70. Lindner JR, Dayton PA, Coggins MP, Ley K, Song J, Ferrara K, et al. Noninvasive imaging of inflammation by ultrasound detection of phagocytosed microbubbles. Circulation. 2000;102:531–538
  71. Lindner JR, Song J, Christiansen J, Klibanov AL, Xu F, Ley K. Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation. 2001;104:2107–2112
  72. Lindner JR, Song J, Jayaweera AR, Sklenar J, Kaul S. Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration. J Am Soc Echocardiogr. 2002;15:396–403
  73. Loughrey HC, Ferraretto A, Cannon AM, Acerbis G, Sudati F, Bottiroli G, et al. Characterisation of biotinylated liposomes for in vivo targeting applications. FEBS Lett. 1993;332:183–188
  74. Lusis AJ. Atherosclerosis. Nature. 2000;407:233–241
  75. Marsh JN, Hall CS, Scott MJ, Fuhrhop RW, Gaffney PJ, Wickline SA, et al. Improvements in the ultrasonic contrast of targeted perfluorocarbon nanoparticles using an acoustic transmission line model. IEEE Trans Ultrason Ferroelectr Freq Control. 2002;49:29–38
  76. Marsh JN, Hall CS, Wickline SA, Lanza GM. Temperature dependence of acoustic impedance for specific fluorocarbon liquids. J Acoust Soc Am. 2002;112:2858–2862
  77. Marsh JN, Partlow KC, Abendschein DR, Scott MJ, Lanza GM, Wickline SA. Molecular imaging with targeted perfluorocarbon nanoparticles: Quantification of the concentration dependence of contrast enhancement for binding to sparse cellular epitopes. Ultrasound Med Biol. 2007;33:950–958
  78. Marshall BT, Long M, Piper JW, Yago T, McEver RP, Zhu C. Direct observation of catch bonds involving cell-adhesion molecules. Nature. 2003;423:190–193
  79. McGoron AJ, Pratt R, Zhang J, Shiferaw Y, Thomas S, Millard R. Perfluorocarbon distribution to liver, lung and spleen of emulsions of perfluorotributylamine (FTBA) in pigs and rats and perfluorooctyl bromide (PFOB) in rats and dogs by 19F NMR spectroscopy. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:1243–1250
  80. Narayan P, Marchant D, Wheatley MA. Optimization of spray drying by factorial design for production of hollow microspheres for ultrasound imaging. J Biomed Mater Res. 2001;56:333–341
  81. Ophir J, Parker KJ. Contrast agents in diagnostic ultrasound. Ultrasound Med Biol. 1989;15:319–333
  82. Peng CA, Hsu YC. Fluoroalkylated polyethylene glycol as potential surfactant for perfluorocarbon emulsion. Artif Cells Blood Substit Immobil Biotechnol. 2001;29:483–492
  83. Pozharski EV, McWilliams L, MacDonald RC. Relationship between turbidity of lipid vesicle suspensions and particle size. Anal Biochem. 2001;291:158–162
  84. Raisinghani A, DeMaria AN. Physical principles of microbubble ultrasound contrast agents. Am J Cardiol. 2002;90:3J–7J
  85. Reneman RS, Arts T, Hoeks AP. Wall shear stress—An important determinant of endothelial cell function and structure in the arterial system in vivo. Discrepancies with Theory. J Vasc Res. 2006;43:251–269
  86. Reneman RS, van Merode T, Hick P, Hoeks AP. Flow velocity patterns in and distensibility of the carotid artery bulb in subjects of various ages. Circulation. 1985;71:500–509
  87. Ridger V, Krams R, Carpi A, Evans PC. Hemodynamic parameters regulating vascular inflammation and atherosclerosis: A brief update. Biomed Pharmacother. 2008;62:536–540
  88. Rindt CC, Steenhoven AA. Unsteady flow in a rigid 3-D model of the carotid artery bifurcation. J Biomech Eng. 1996;118:90–96
  89. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med. 1999;340:115–126
  90. Rovai D, Morales MA, Amyot R, L'Abbate A. Clinical experience with SonoVue in myocardial perfusion imaging. Echocardiography. 2000;17:S17–23
  91. 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;52:421–433
  92. Rychak JJ, Klibanov AL, Ley KF, Hossack JA. Enhanced targeting of ultrasound contrast agents using acoustic radiation force. Ultrasound Med Biol. 2007;33:1132–1139
  93. Rychak JJ, Li B, Acton ST, Leppanen A, Cummings RD, Ley K, et al. Selectin ligands promote ultrasound contrast agent adhesion under shear flow. Mol Pharm. 2006;3:516–524
  94. Rychak JJ, Lindner JR, Ley K, Klibanov AL. Deformable gas-filled microbubbles targeted to P-selectin. J Control Release. 2006;114:288–299
  95. Samijo SK, Willigers JM, Barkhuysen R, Kitslaar PJ, Reneman RS, Brands PJ, et al. Wall shear stress in the human common carotid artery as function of age and gender. Cardiovasc Res. 1998;39:515–522
  96. Schwarz KQ, Becher H, Schimpfky C, Vorwerk D, Bogdahn U, Schlief R. Doppler enhancement with SH U 508A in multiple vascular regions. Radiology. 1994;193:195–201
  97. Shinde Patil VR, Campbell CJ, Yun YH, Slack SM, Goetz DJ. Particle diameter influences adhesion under flow. Biophys J. 2001;80:1733–1743
  98. Shung KK, Fei DY, Ballard JO. Further studies on ultrasonic properties of blood clots. J Clin Ultrasound. 1986;14:269–275
  99. Smith DA, Porter TM, Martinez J, Huang S, Macdonald RC, McPherson DD, et al. Destruction thresholds of echogenic liposomes with clinical diagnostic ultrasound. Ultrasound Med Biol. 2007;33:797–809
  100. Smith DJ, Kornbrust ES, Lane TA. Phagocytosis of a fluorescently labeled perflubron emulsion by a human monocyte cell line. Artif Cells Blood Substit Immobil Biotechnol. 1994;22:1215–1221
  101. Spahn DR, Kocian R. Artificial O2 carriers: Status in 2005. Curr Pharm Des. 2005;11:4099–4114
  102. Springer TA. Traffic signals for lymphocyte recirculation and leukocyte emigration: The multistep paradigm. Cell. 1994;76:301–314
  103. Suzuki R, Takizawa T, Negishi Y, Hagisawa K, Tanaka K, Sawamura K, et al. Gene delivery by combination of novel liposomal bubbles with perfluoropropane and ultrasound. J Control Release. 2007;117:130–136
  104. Suzuki R, Takizawa T, Negishi Y, Utoguchi N, Maruyama K. Effective gene delivery with novel liposomal bubbles and ultrasonic destruction technology. Int J Pharm. 2008;354:49–55
  105. 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;96:473–482
  106. Van Hemert FJ, Voermans C, Van Eck-Smit BL, Bennink RJ. Labeling monocytes for imaging chronic inflammation. Q J Nucl Med Mol Imaging. 2009;53:78–88
  107. Vicenzini E, Giannoni MF, Puccinelli F, Ricciardi MC, Altieri M, Di Piero V, et al. Detection of carotid adventitial vasa vasorum and plaque vascularization with ultrasound cadence contrast pulse sequencing technique and echo-contrast agent. Stroke. 2007;38:2841–2843
  108. Villanueva FS, Jankowski RJ, Klibanov S, Pina ML, Alber SM, Watkins SC, et al. Microbubbles targeted to intercellular adhesion molecule-1 bind to activated coronary artery endothelial cells. Circulation. 1998;98:1–5
  109. Villanueva FS, Jankowski RJ, Manaugh C, Wagner WR. Albumin microbubble adherence to human coronary endothelium: Implications for assessment of endothelial function using myocardial contrast echocardiography. J Am Coll Cardiol. 1997;30:689–693
  110. Weller GE, Villanueva FS, Klibanov AL, Wagner WR. Modulating targeted adhesion of an ultrasound contrast agent to dysfunctional endothelium. Ann Biomed Eng. 2002;30:1012–1019
  111. Weller GE, Villanueva FS, Tom EM, Wagner WR. Targeted ultrasound contrast agents: In vitro assessment of endothelial dysfunction and multitargeting to ICAM-1 and sialyl Lewisx. Biotechnol Bioeng. 2005;92:780–788
  112. Weller GE, Wong MK, Modzelewski RA, Lu E, Klibanov AL, Wagner WR, et al. Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. Cancer Res. 2005;65:533–539
  113. Wickline SA, Neubauer AM, Winter PM, Caruthers SD, Lanza GM. Molecular imaging and therapy of atherosclerosis with targeted nanoparticles. J Magn Reson Imaging. 2007;25:667–680
  114. Woodle MC, Matthay KK, Newman MS, Hidayat JE, Collins LR, Redemann C, et al. Versatility in lipid compositions showing prolonged circulation with sterically stabilized liposomes. Biochim Biophys Acta. 1992;1105:193–200
  115. Zarins CK, Giddens DP, Bharadvaj BK, Sottiurai VS, Mabon RF, Glagov S. Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res. 1983;53:502–514
  116. Zhao S, Kruse DE, Ferrara KW, Dayton PA. Selective imaging of adherent targeted ultrasound contrast agents. Phys Med Biol. 2007;52:2055–2072

PII: S0301-5629(09)01537-3

doi: 10.1016/j.ultrasmedbio.2009.09.009

Ultrasound in Medicine and Biology
Volume 36, Issue 2 , Pages 181-191 , February 2010