Top

Published in:

01-02-2010

Ultrasound Molecular Imaging of Cardiovascular Disease

Author: Beat A. Kaufmann

Published in: Current Cardiovascular Imaging Reports | Issue 1/2010

Abstract

Molecular imaging with ultrasound contrast agents relies on the detection of microbubbles within diseased tissue. Microbubbles produce an acoustic signal owing to their resonant properties in an ultrasound field. Microbubble targeting is accomplished by either manipulating the microbubble shell for attachment of microbubbles to activated leukocytes, or by conjugation of disease-specific ligands to the microbubble surface. Inflammation, angiogenesis, and thrombus formation are central pathophysiologic processes in many cardiovascular diseases and produce phenotypic changes in the vascular compartment that can be imaged with targeted ultrasound contrast agents. In the future, targeted contrast ultrasound could aid in the diagnosis of atherosclerosis, myocardial ischemia, transplant rejection, and thrombosis syndromes and could be used for assessing angiogenesis.

Kaufmann BA, Wei K, Lindner JR: Contrast echocardiography. Curr Probl Cardiol 2007, 32:51–96.CrossRefPubMed

Epstein PS, Plesset MS: On the stability of gas bubbles in liquid-gas solutions. J Chem Phys 1950, 18:1505–1509.CrossRef

Forsberg F, Shi WT: Physics of contrast microbubbles. In Ultrasound Contrast Agents. Edited by Goldberg BB, Raichlen JS, Forsberg F. London: Martin Dunitz Ltd; 2001:15–24.

De Jong N, Hoff L, Skotland T, Bom N: Absorption and scatter of encapsulated gas filled microspheres: theoretical considerations and some measurements. Ultrasonics 1992, 30:95–103.CrossRefPubMed

De Jong N, Bouakaz A, Frinking P: Basic acoustic properties of microbubbles. Echocardiography 2002, 19:229–240.CrossRefPubMed

De Jong N, Frinking PJ, Bouakaz A, et al.: Optical imaging of contrast agent microbubbles in an ultrasound field with a 100-MHz camera. Ultrasound Med Biol 2000, 26:487–492.CrossRefPubMed

Lindner JR, Song J, Jayaweera AR, et al.: Microvascular rheology of Definity microbubbles after intra-arterial and intravenous administration. J Am Soc Echocardiogr 2002, 15:396–403.CrossRefPubMed

Lanza GM, Abendschein DR, Hall CS, et al.: Molecular imaging of stretch-induced tissue factor expression in carotid arteries with intravascular ultrasound. Invest Radiol 2000, 35:227–234.CrossRefPubMed

Lindner JR, Song J, Xu F, et al.: Noninvasive ultrasound imaging of inflammation using microbubbles targeted to activated leukocytes. Circulation 2000, 102:2745–2750.PubMed

10.

Lindner JR, Dayton PA, Coggins MP, et al.: Noninvasive imaging of inflammation by ultrasound detection of phagocytosed microbubbles. Circulation 2000, 102:531–538.PubMed

11.

Lindner JR, Coggins MP, Kaul S, et al.: 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.PubMed

12.

Lankford M, Behm CZ, Yeh J, et al.: Effect of microbubble ligation to cells on ultrasound signal enhancement: implications for targeted imaging. Invest Radiol 2006, 41:721–728.CrossRefPubMed

13.

Yang J, Hirata T, Croce K, et al.: Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med 1999, 190:1769–1782.CrossRefPubMed

14.

Bevilacqua MP, Nelson RM: Selectins. J Clin Invest 1993, 91:379–387.CrossRefPubMed

15.

Dansky HM, Barlow CB, Lominska C, et al.: Adhesion of monocytes to arterial endothelium and initiation of atherosclerosis are critically dependent on vascular cell adhesion molecule-1 gene dosage. Arterioscler Thromb Vasc Biol 2001, 21:1662–1667.CrossRefPubMed

16.

Walpola PL, Gotlieb AI, Cybulsky MI, Langille BL: Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear stress. Arterioscler Thromb Vasc Biol 1995, 15:2–10.PubMed

17.

Christiansen JP, Leong-Poi H, Klibanov AL, et al.: Noninvasive imaging of myocardial reperfusion injury using leukocyte-targeted contrast echocardiography. Circulation 2002, 105:1764–1767.CrossRefPubMed

18.

Lindner JR, Song J, Christiansen J, et al.: Ultrasound assessment of inflammation and renal tissue injury with microbubbles targeted to P-selectin. Circulation 2001, 104:2107–2112.CrossRefPubMed

19.

Kaufmann BA, Lewis C, Xie A, et al.: Detection of recent myocardial ischaemia by molecular imaging of P-selectin with targeted contrast echocardiography. Eur Heart J 2007, 28:2011–2017.CrossRefPubMed

20.

• Villanueva FS, Lu E, Bowry S, et al.: Myocardial ischemic memory imaging with molecular echocardiography. Circulation 2007, 115:345–352. In this study, ultrasound molecular imaging is used for myocardial ischemic memory imaging. This application could be of significant clinical relevance given the high number of emergency unit visits for chest pain and the difficulties of diagnosing acute coronary syndromes with high accuracy in a short time.CrossRefPubMed

21.

Kondo I, Ohmori K, Oshita A, et al.: Leukocyte-targeted myocardial contrast echocardiography can assess the degree of acute allograft rejection in a rat cardiac transplantation model. Circulation 2004, 109:1056–1061.CrossRefPubMed

22.

Weller GE, Lu E, Csikari MM, et al.: Ultrasound imaging of acute cardiac transplant rejection with microbubbles targeted to intercellular adhesion molecule-1. Circulation 2003, 108:218–224.CrossRefPubMed

23.

Jacobson TA, Griffiths GG, Varas C, et al.: Impact of evidence-based “clinical judgment” on the number of American adults requiring lipid-lowering therapy based on updated NHANES III data. National Health and Nutrition Examination Survey. Arch Intern Med 2000, 160:1361–1369.CrossRefPubMed

24.

Eriksson EE, Werr J, Guo Y, et al.: Direct observations in vivo on the role of endothelial selectins and alpha(4) integrin in cytokine-induced leukocyte-endothelium interactions in the mouse aorta. Circ Res 2000, 86:526–533.PubMed

25.

Greve JM, Les AS, Tang BT, 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–H1708.CrossRefPubMed

26.

Takalkar AM, Klibanov AL, Rychak JJ, et al.: Binding and detachment dynamics of microbubbles targeted to P-selectin under controlled shear flow. J Control Release 2004, 96:473–482.CrossRefPubMed

27.

Kaufmann BA, Sanders JM, Davis C, et al.: Molecular imaging of inflammation in atherosclerosis with targeted ultrasound detection of vascular cell adhesion molecule-1. Circulation 2007, 116:276–284.CrossRefPubMed

28.

Tsutsui JM, Xie F, Cano M, et al.: Detection of retained microbubbles in carotid arteries with real-time low mechanical index imaging in the setting of endothelial dysfunction. J Am Coll Cardiol 2004, 44:1036–1046.CrossRefPubMed

29.

Anderson DR, Tsutsui JM, Xie F, et al.: The role of complement in the adherence of microbubbles to dysfunctional arterial endothelium and atherosclerotic plaque. Cardiovasc Res 2007, 73:597–606.CrossRefPubMed

30.

Iiyama K, Hajra L, Iiyama M, et al.: Patterns of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 expression in rabbit and mouse atherosclerotic lesions and at sites predisposed to lesion formation. Circ Res 1999, 85:199–207.PubMed

31.

Nakashima Y, Raines EW, Plump AS, et al.: Upregulation of VCAM-1 and ICAM-1 at atherosclerosis-prone sites on the endothelium in the ApoE-deficient mouse. Arterioscler Thromb Vasc Biol 1998, 18:842–851.PubMed

32.

Hamilton AJ, Huang SL, Warnick D, et al.: Intravascular ultrasound molecular imaging of atheroma components in vivo. J Am Coll Cardiol 2004, 43:453–460.CrossRefPubMed

33.

• Kaufmann BA, Carr CL, Belcik JT, et al.: Molecular imaging of the initial inflammatory response in atherosclerosis. Implications for early detection of disease. Arterioscler Thromb Vasc Biol 2010, 30(1):54–59. This study establishes the feasibility of imaging vascular inflammatory phenotype prior to the development of atherosclerotic plaques. Such an approach could eventually prove viable in assessing the risk for atherosclerotic events at a very early stage, when preventive measures are most likely to offer the largest possible benefits.

34.

Brooks PC, Clark RA, Cheresh DA: Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 1994, 264:569–571.CrossRefPubMed

35.

Leong-Poi H, Christiansen J, Klibanov AL, et al.: Noninvasive assessment of angiogenesis by ultrasound and microbubbles targeted to alpha(v)-integrins. Circulation 2003, 107:455–460.CrossRefPubMed

36.

Leong-Poi H, Christiansen J, Heppner P, et al.: Assessment of endogenous and therapeutic arteriogenesis by contrast ultrasound molecular imaging of integrin expression. Circulation 2005, 111:3248–3254.CrossRefPubMed

37.

Behm CZ, Kaufmann BA, Carr C, et al.: Molecular imaging of endothelial vascular cell adhesion molecule-1 expression and inflammatory cell recruitment during vasculogenesis and ischemia-mediated arteriogenesis. Circulation 2008, 117:2902–2911.CrossRefPubMed

38.

Unger EC, McCreery TP, Sweitzer RH, et al.: In vitro studies of a new thrombus-specific ultrasound contrast agent. Am J Cardiol 1998, 81:58G–61G.CrossRefPubMed

39.

Schumann PA, Christiansen JP, Quigley RM, et al.: Targeted-microbubble binding selectively to GPIIb IIIa receptors of platelet thrombi. Invest Radiol 2002, 37:587–593.CrossRefPubMed

40.

Hamilton A, Huang SL, Warnick D, et al.: Left ventricular thrombus enhancement after intravenous injection of echogenic immunoliposomes: studies in a new experimental model. Circulation 2002, 105:2772–2778.CrossRefPubMed

41.

Lanza GM, Wallace KD, Scott MJ, et al.: A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation 1996, 94:3334–3340.PubMed

Title: Ultrasound Molecular Imaging of Cardiovascular Disease
Author: Beat A. Kaufmann
Publication date: 01-02-2010
Publisher: Current Science Inc.
Published in: Current Cardiovascular Imaging Reports / Issue 1/2010
Print ISSN: 1941-9066
Electronic ISSN: 1941-9074
DOI: https://doi.org/10.1007/s12410-009-9000-5

ACC 2024 Congress Coverage

Heart Failure Video

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Ultrasound Molecular Imaging of Cardiovascular Disease

Abstract

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 1/2010

Molecular and Microstructural Imaging of the Myocardium

Molecular Imaging of Thrombosis

Molecular MRI of Atherosclerosis

Optical Molecular Imaging of Inflammation and Calcification in Atherosclerosis

Nanomedicine and Cardiovascular Disease

The ATHEROMA Study: Rapid Anti-inflammatory Effects of High-Dose Statin Pharmacotherapy Illuminated by Molecular MRI

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page