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DOI: 10.1055/s-0039-1688492
Ultrasound Microbubbles for Diagnosis and Treatment of Cardiovascular Diseases
Publication History
Publication Date:
16 May 2019 (online)
Abstract
Ultrasound (US) imaging of heart and major arteries and veins is among the most frequently used diagnostic techniques applied in humans. Conventional cardiovascular US sessions include anatomical B-mode and functional M-, pulsed-wave- and Doppler mode, which have their limitations in both precise cardiac chambers' delineation and small vessel imaging. The introduction of contrast-enhanced US, employing microbubble suspensions as contrast agent, has enabled a better delineation of heart chambers, the visualization of myocardial microvasculature, and the atherosclerotic plaque neovascularization. Moreover, specific disease-related molecular tracers have been developed by modifying the microbubbles with targeting ligands directed to biological markers exposed to the luminal side of the blood vessels. Microbubble functionalization has enabled in vivo molecular US imaging of various stages of atherosclerosis, from plaque initiation to plaque vulnerability, and neointima formation following revascularization procedures. Furthermore, oscillating microbubbles have been used to mechanically dissolve thrombus material and may act as carriers of drugs and nucleic acids that are released locally by US pulses. This review article summarizes recent advances in functional and molecular US images and discusses therapeutic applications of microbubbles. The addressed topics include an overview on microbubble formats, microbubble detection methods, molecular targets of cardiovascular diseases, and the use of microbubbles for thrombolysis and drug delivery.
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References
- 1 Laslett LJ, Alagona Jr P, Clark III BA. , et al. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol 2012; 60 (25) , Suppl): S1 –S49
- 2 Mozaffarian D, Benjamin EJ, Go AS. , et al. Heart Disease and Stroke Statistics-2016 Update: A Report from the American Heart Association. Circulation 2016; 133: e38-e360
- 3 Monaghan M, Bhan A. New developments in echocardiography. In: Zamorano JL, Bax JJ, Rademakers FE, Knuuti J. , eds. The ESC Textbook of Cardiovascular Imaging. London: Springer; 2009: 39-72
- 4 Yong Y, Wu D, Fernandes V. , et al. Diagnostic accuracy and cost- effectiveness of contrast echocardiography on evaluation of cardiac function in technically very care unit. Am J Cardiol 2002; 89 (01) 711-718
- 5 Brinjikji W, Huston III J, Rabinstein AA, Kim G-M, Lerman A, Lanzino G. Contemporary carotid imaging: from degree of stenosis to plaque vulnerability. J Neurosurg 2016; 124 (01) 27-42
- 6 Shah BN, Chahal NS, Kooner JS, Senior R. Contrast-enhanced ultrasonography vs B-mode ultrasound for visualization of intima-media thickness and detection of plaques in human carotid arteries. Echocardiography 2017; 34 (05) 723-730
- 7 Rafailidis V, Charitanti A, Tegos T, Destanis E, Chryssogonidis I. Contrast-enhanced ultrasound of the carotid system: a review of the current literature. J Ultrasound 2017; 20 (02) 97-109
- 8 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 (03) 307-320
- 9 Kudo M. Properties of Levovist. In: Contrast Harmonic Imaging in the Diagnosis and Treatment of Hepatic Tumors. Tokyo: Springer Japan; 2003: 15-18
- 10 Sirsi S, Borden M. Microbubble compositions, properties and biomedical applications. Bubble Sci Eng Technol 2009; 1 (1-2): 3-17
- 11 Doinikov AA, Haac JF, Dayton PA. Resonance frequencies of lipid-shelled microbubbles in the regime of nonlinear oscillations. Ultrasonics 2009; 49 (02) 263-268
- 12 Kiessling F, Fokong S, Bzyl J, Lederle W, Palmowski M, Lammers T. Recent advances in molecular, multimodal and theranostic ultrasound imaging. Adv Drug Deliv Rev 2014; 72: 15-27
- 13 Paul Sidhu AS, Cantisani V, Dietrich CF. , et al. The EFSUMB Guidelines and Recommendations for the Clinical Practice of Contrast-Enhanced Ultrasound (CEUS) in Non-Hepatic Applications: Update 2017 (Long Version) Die EFSUMB-Leitlinien und Empfehlungen für den klinischen Einsatz des kontrastverstärkten Ul. 2018 ;2017:154–180
- 14 Daeichin V, Van Rooij T, Skachkov I. , et al. Microbubble Composition and Preparation for Imaging: In Vitro and In Vivo Evaluation. 2017; 64 (03) 555-567
- 15 Gong Y, Cabodi M, Porter T. Pressure-dependent resonance frequency for lipid-coated microbubbles at lowacoustic pressures. Proc IEEE Ultrason Symp 2010; 1932-1935
- 16 Curaj A, Wu Z, Fokong S. , et al. Noninvasive molecular ultrasound monitoring of vessel healing after intravascular surgical procedures in a preclinical setup. Arterioscler Thromb Vasc Biol 2015; 35 (06) 1366-1373
- 17 Rix A, Fokong S, Heringer S. , et al. Molecular ultrasound imaging of αvβ3-integrin expression in carotid arteries of pigs after vessel injury. Invest Radiol 2016; 51 (12) 767-775
- 18 Moccetti F, Weinkauf CC, Davidson BP. , et al. Ultrasound Molecular Imaging of Atherosclerosis Using Small-Peptide Targeting Ligands Against Endothelial Markers of Inflammation and Oxidative Stress. Ultrasound Med Biol 2018; 44 (06) 1155-1163
- 19 Yan P, Chen K-J, Wu J. , et al. The use of MMP2 antibody-conjugated cationic microbubble to target the ischemic myocardium, enhance Timp3 gene transfection and improve cardiac function. Biomaterials 2014; 35 (03) 1063-1073
- 20 Wei K, Jayaweera AR, Firoozan S, Linka A, Skyba DM, Kaul S. Quantification of myocardial blood flow with ultrasound-induced destruction of microbubbles administered as a constant venous infusion. Circulation 1998; 97 (05) 473-483
- 21 Fokong S, Siepmann M, Liu Z, Schmitz G, Kiessling F, Gätjens J. Advanced characterization and refinement of poly N-butyl cyanoacrylate microbubbles for ultrasound imaging. Ultrasound Med Biol 2011; 37 (10) 1622-1634
- 22 Callot V, Canet E, Brochot J. , et al. Hyperpolarized helium3 encapsulated in microbubbles: a new class of blood pool MRI contrast agent. Acad Radiol 2002; 9 (Suppl (Suppl. 02) S501-S503
- 23 Qian L, Thapa B, Hong J. , et al. The present and future role of ultrasound targeted microbubble destruction in preclinical studies of cardiac gene therapy. J Thorac Dis 2018; 10 (Suppl. 02) 1099-1111
- 24 Brinjikji W, Huston III J, Rabinstein AA, Kim GM, Lerman A, Lanzino G. Contemporary carotid imaging: from degree of stenosis to plaque vulnerability. J Neurosurg 2016; 124 (01) 27-42
- 25 Partovi S, Loebe M, Aschwanden M. , et al. Contrast-enhanced ultrasound for assessing carotid atherosclerotic plaque lesions. AJR Am J Roentgenol 2012; 198 (01) W13-9
- 26 Saha SA, Gourineni V, Feinstein SB. The use of contrast-enhanced ultrasonography for imaging of carotid atherosclerotic plaques: current evidence, future directions. Neuroimaging Clin N Am 2016; 26 (01) 81-96
- 27 Wagenaar DJ, Weissleder R, Hengerer A. Glossary of molecular imaging terminology. Acad Radiol 2001; 8 (05) 409-420
- 28 Pope JH, Aufderheide TP, Ruthazer R. , et al. Missed diagnoses of acute cardiac ischemia in the emergency department. N Engl J Med 2000; 342 (16) 1163-1170
- 29 Lindner JR. Molecular imaging of cardiovascular disease with contrast-enhanced ultrasonography. Nat Rev Cardiol 2009; 6 (07) 475-481
- 30 Yan Y, Liao Y, Yang L. , et al. Late-phase detection of recent myocardial ischaemia using ultrasound molecular imaging targeted to intercellular adhesion molecule-1. Cardiovasc Res 2011; 89 (01) 175-183
- 31 Wu Z, Curaj A, Fokong S. , et al. Rhodamine-loaded intercellular adhesion molecule-1-targeted microbubbles for dual-modality imaging under controlled shear stresses. Circ Cardiovasc Imaging 2013; 6 (06) 974-981
- 32 Curaj A, Wu Z, Rix A. , et al. Molecular ultrasound imaging of junctional adhesion molecule a depicts acute alterations in blood flow and early endothelial dysregulation. Arterioscler Thromb Vasc Biol 2018; 38 (01) 40-48
- 33 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 (03) 276-284
- 34 Sun R, Tian J, Zhang J, Wang L, Guo J, Liu Y. Monitoring inflammation injuries in the progression of atherosclerosis with contrast enhanced ultrasound molecular imaging. PLoS One 2017; 12 (10) e0186155
- 35 Fotis L, Agrogiannis G, Vlachos IS. , et al. Intercellular adhesion molecule (ICAM) -1 and vascular cell adhesion molecule (VCAM) -1 at the early stages of atherosclerosis in a rat model. In Vivo 2012; 26: 243-250
- 36 Zhang YJ, Bai DN, Du JX. , et al. Ultrasound-guided imaging of junctional adhesion molecule-A-targeted microbubbles identifies vulnerable plaque in rabbits. Biomaterials 2016; 94: 20-30
- 37 Khanicheh E, Mitterhuber M, Xu L, Haeuselmann SP, Kuster GM, Kaufmann BA. Noninvasive ultrasound molecular imaging of the effect of statins on endothelial inflammatory phenotype in early atherosclerosis. PLoS One 2013; 8 (03) e58761
- 38 Yan F, Sun Y, Mao Y. , et al. Ultrasound molecular imaging of atherosclerosis for early diagnosis and therapeutic evaluation through leucocyte-like multiple targeted microbubbles. Theranostics 2018; 8 (07) 1879-1891
- 39 Lanza GM, Wallace KD, Scott MJ. , et al. A novel site-targeted ultrasonic contrast agent with broad biomedical application. Circulation 1996; 94 (12) 3334-3340
- 40 Wang X, Gkanatsas Y, Palasubramaniam J. , et al. Thrombus-targeted theranostic microbubbles: a new technology towards concurrent rapid ultrasound diagnosis and bleeding-free fibrinolytic treatment of thrombosis. Theranostics 2016; 6 (05) 726-738
- 41 Nederhoed JH, Ebben HP, Slikkerveer J. , et al. Intravenous targeted microbubbles carrying urokinase versus urokinase alone in acute peripheral arterial thrombosis in a porcine model. Ann Vasc Surg 2017; 44: 400-407
- 42 Ebben HP, Nederhoed JH, Lely RJ, Wisselink W, Yeung K. ; MUST collaborators. Microbubbles and UltraSound-accelerated Thrombolysis (MUST) for peripheral arterial occlusions: protocol for a phase II single-arm trial. BMJ Open 2017; 7 (08) e014365
- 43 Xie F, Gao S, Wu J. , et al. Diagnostic ultrasound induced inertial cavitation to non-invasively restore coronary and microvascular flow in acute myocardial infarction. PLoS One 2013; 8 (07) e69780
- 44 Roos ST, Juffermans LJM, van Royen N. , et al. Unexpected high incidence of coronary vasoconstriction in the Reduction of Microvascular Injury Using Sonolysis (ROMIUS) trial. Ultrasound Med Biol 2016; 42 (08) 1919-1928
- 45 Zhang L, Sun Z, Ren P. , et al. Localized delivery of shRNA against PHD2 protects the heart from acute myocardial infarction through ultrasound-targeted cationic microbubble destruction. Theranostics 2017; 7 (01) 51-66
- 46 He Y, Zhang B, Chen Y. , et al. Image-guided hydrogen gas delivery for protection from myocardial ischemia-reperfusion injury via microbubbles. ACS Appl Mater Interfaces 2017; 9 (25) 21190-21199
- 47 Chen G, Yang L, Zhong L. , et al. Delivery of hydrogen sulfide by ultrasound targeted microbubble destruction attenuates myocardial ischemia-reperfusion injury. Sci Rep 2016; 6: 30643