Abstract
Cardiomyocytes can die via necrosis, apoptosis, and autophagy. Although the molecular signals and pathways underlying these processes have been well elucidated, the pathophysiology of cardiomyocyte death remains incompletely understood. This review describes the development and application of novel imaging techniques to detect and characterize cardiomyocyte death noninvasively in vivo. It focuses on molecular and microstructural magnetic resonance images (MRIs) and their respective abilities to image cellular events such as apoptosis, inflammation, and myofiber architecture. These in vivo imaging techniques have the potential to provide novel insights into the mechanisms of cardiomyocyte death and to help guide the development of novel cardioprotective therapies.
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Amirbekian V, Lipinski MJ, Briley-Saebo KC, Amirbekian S, Aguinaldo JG, Weinreb DB, Vucic E, Frias JC, Hyafil F, Mani V, Fisher EA, Fayad ZA (2007) Detecting and assessing macrophages in vivo to evaluate atherosclerosis noninvasively using molecular MRI. Proc Natl Acad Sci USA 104:961–966
Botnar RM, Perez AS, Witte S, Wiethoff AJ, Laredo J, Hamilton J, Quist W, Parsons EC Jr, Vaidya A, Kolodziej A, Barrett JA, Graham PB, Weisskoff RM, Manning WJ, Johnstone MT (2004) In vivo molecular imaging of acute and subacute thrombosis using a fibrin-binding magnetic resonance imaging contrast agent. Circulation 109:2023–2029
Dumont EA, Reutelingsperger CP, Smits JF, Daemen MJ, Doevendans PA, Wellens HJ, Hofstra L (2001) Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart. Nat Med 7:1352–1355
Garanger E, Hilderbrand SA, Blois JT, Sosnovik DE, Weissleder R, Josephson L (2009) A DNA-binding Gd chelate for the detection of cell death by MRI. Chem Commun Camb 29:4444–4446
Hagmann P, Jonasson L, Maeder P, Thiran JP, Wedeen VJ, Meuli R (2006) Understanding diffusion MR imaging techniques: from scalar diffusion-weighted imaging to diffusion tensor imaging and beyond. Radiographics 26(Suppl 1):S205–S223
Hayakawa Y, Chandra M, Miao W, Shirani J, Brown JH, Dorn GW II, Armstrong RC, Kitsis RN (2003) Inhibition of cardiac myocyte apoptosis improves cardiac function and abolishes mortality in the peripartum cardiomyopathy of Galpha(q) transgenic mice. Circulation 108:3036–3041
Helm PA, Caravan P, French BA, Jacques V, Shen L, Xu Y, Beyers RJ, Roy RJ, Kramer CM, Epstein FH (2008) Postinfarction myocardial scarring in mice: molecular MR imaging with use of a collagen-targeting contrast agent. Radiology 247:788–796
Hotchkiss RS, Strasser A, McDunn JE, Swanson PE (2009) Cell death. N Engl J Med 361:1570–1583
Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, Reed JC, Olivetti G, Anversa P (1996) Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest 74:86–107
Nahrendorf M, Jaffer FA, Kelly KA, Sosnovik DE, Aikawa E, Libby P, Weissleder R (2006) Noninvasive vascular cell adhesion molecule-1 imaging identifies inflammatory activation of cells in atherosclerosis. Circulation 114:1504–1511
Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047
Nahrendorf M, Sosnovik D, Chen JW, Panizzi P, Figueiredo JL, Aikawa E, Libby P, Swirski FK, Weissleder R (2008) Activatable magnetic resonance imaging agent reports myeloperoxidase activity in healing infarcts and noninvasively detects the antiinflammatory effects of atorvastatin on ischemia-reperfusion injury. Circulation 117:1153–1160
Nahrendorf M, Sosnovik DE, French BA, Swirski FK, Bengel F, Sadeghi MM, Lindner JR, Wu JC, Kraitchman DL, Fayad ZA, Sinusas AJ (2009) Multimodality Cardiovascular Molecular Imaging, Part II. Circ Cardiovasc Imaging 2:56–70
Schellenberger EA, Sosnovik D, Weissleder R, Josephson L (2004) Magneto/optical annexin V, a multimodal protein. Bioconjug Chem 15:1062–1067
Sosnovik DE, Schellenberger EA, Nahrendorf M, Novikov MS, Matsui T, Dai G, Reynolds F, Grazette L, Rosenzweig A, Weissleder R, Josephson L (2005) Magnetic resonance imaging of cardiomyocyte apoptosis with a novel magneto-optical nanoparticle. Magn Reson Med 54:718–724
Sosnovik DE, Nahrendorf M, Deliolanis N, Novikov M, Aikawa E, Josephson L, Rosenzweig A, Weissleder R, Ntziachristos V (2007) Fluorescence tomography and magnetic resonance imaging of myocardial macrophage infiltration in infarcted myocardium in vivo. Circulation 115:1384–1391
Sosnovik DE, Nahrendorf M, Weissleder R (2007) Molecular magnetic resonance imaging in cardiovascular medicine. Circulation 115:2076–2086
Sosnovik DE, Nahrendorf M, Weissleder R (2008) Targeted imaging of myocardial damage. Nat Clin Pract Cardiovasc Med 5(Suppl 2):S63–S70
Sosnovik DE, Nahrendorf M, Weissleder R (2008) Magnetic nanoparticles for MR imaging: agents, techniques, and cardiovascular applications. Basic Res Cardiol 103:122–130
Sosnovik DE, Garanger E, Aikawa E, Nahrendorf M, Figuiredo JL, Dai G, Reynolds F, Rosenzweig A, Weissleder R, Josephson L (2009) Molecular MRI of cardiomyocyte apoptosis with simultaneous delayed-enhancement MRI distinguishes apoptotic and necrotic myocytes in vivo: potential for midmyocardial salvage in acute ischemia. Circ Cardiovasc Imaging 2:460–467
Sosnovik DE, Nahrendorf M, Panizzi P, Matsui T, Aikawa E, Dai G, Li L, Reynolds F, Dorn GW II, Weissleder R, Josephson L, Rosenzweig A (2009) Molecular MRI detects low levels of cardiomyocyte apoptosis in a transgenic model of chronic heart failure. Circ Cardiovasc Imaging 2:468–475
Sosnovik DE, Wang R, Dai G, Reese TG, Wedeen VJ (2009) Diffusion MR tractography of the heart. J Cardiovasc Magn Reson 11:47
Sosnovik DE, Wang R, Dai G, Wang T, Aikawa E, Novikov M, Rosenzweig A, Gilbert R, Wedeen VJ (2009) Diffusion spectrum MRI tractography reveals the presence of a complex network of residual myofibers in infarcted myocardium. Circ Cardiovasc Imaging 2:206–212
Streeter DD Jr, Spotnitz HM, Patel DP, Ross J Jr, Sonnenblick EH (1969) Fiber orientation in the canine left ventricle during diastole and systole. Circ Res 24:339–347
Winter PM, Neubauer AM, Caruthers SD, Harris TD, Robertson JD, Williams TA, Schmieder AH, Hu G, Allen JS, Lacy EK, Zhang H, Wickline SA, Lanza GM (2006) Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler Thromb Vasc Biol 26:2103–2109
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This study was funded in part by R01 HL093038 (DES).
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Berry, N.C., Sosnovik, D.E. Cardiomyocyte Death: Insights from Molecular and Microstructural Magnetic Resonance Imaging. Pediatr Cardiol 32, 290–296 (2011). https://doi.org/10.1007/s00246-011-9894-y
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DOI: https://doi.org/10.1007/s00246-011-9894-y