Abstract
Atherosclerotic plaque rupture is the main cause of acute cardiac events. The detection of these unstable plaques before rupture is clinically very important, and recently there have been considerable efforts to develop imaging methods for plaque visualization and characterization. It is likely that multiple approaches are needed, from simple screening tests to advanced invasive imaging studies. The strength of nuclear imaging techniques is the outstanding sensitivity. Although the spatial resolution of clinical nuclear imaging does not allow anatomical characterization of plaques, the recent hybrid imaging techniques offer possibility for combined anatomical and molecular imaging. We discuss the current progress on nuclear imaging techniques in assessing unstable plaques.
Similar content being viewed by others
References and Recommended Reading
Naghavi M, Libby P, Falk E, et al.: From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part II. Circulation 2003, 108:1772–1778.
Stamper D, Weissman NJ, Brezinski M: Plaque characterization with optical coherence tomography. J Am Coll Cardiol 2006, 47:C69–C79.
Stein PD, Yaekoub AY, Matta F, et al.: 64-slice CT for diagnosis of coronary artery disease: a systematic review. Am J Med 2008, 121:715–725.
Schaar JA, Mastik F, Regar E, et al.: Current diagnostic modalities for vulnerable plaque detection. Curr Pharm Des 2007, 13:995–1001.
Naghavi M, Libby P, Falk E, et al.: From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Circulation 2003, 108:1664–1672.
Narula J, Garg P, Achenbach S, et al.: Arithmetic of vulnerable plaques for noninvasive imaging. Nat Clin Pract Cardiovasc Med 2008, 5(Suppl 2):S2–S10.
Falk E: Pathogenesis of atherosclerosis. J Am Coll Cardiol 2006, 47:C7–C12.
Pletcher MJ, Tice JA, Pignone M, et al.: Using the coronary artery calcium score to predict coronary heart disease events: a systematic review and meta-analysis. Arch Intern Med 2004, 164:1285–1292.
Goldstein JA, Demetriou D, Grines CL, et al.: Multiple complex coronary plaques in patients with acute myocardial infarction. N Engl J Med 2000, 343:915–922.
Naghavi M, Falk E, Hecht HS, et al.: From vulnerable plaque to vulnerable patient—part III: executive summary of the Screening for Heart Attack Prevention and Education (SHAPE) Task Force report. Am J Cardiol 2006, 98:2H–15H.
Dalager S, Falk E, Kristensen IB, et al.: Plaque in superficial femoral arteries indicates generalized atherosclerosis and vulnerability to coronary death: an autopsy study. J Vasc Surg 2008, 47:296–302.
Rudd JH, Warburton EA, Fryer TD, et al.: Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 2002, 105:2708–2711.
Tawakol A, Migrino RQ, Bashian GG, et al.: In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients. J Am Coll Cardiol 2006, 48:1818–1824.
Tahara N, Kai H, Ishibashi M, et al.: Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol 2006, 48:1825–1831.
Lee SJ, On YK, Lee EJ, et al.: Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein elevation by atherogenic risk reduction. J Nucl Med 2008, 49:1277–1282.
Rudd JH, Myers KS, Bansilal S, et al.: (18)Fluorodeoxyglucose positron emission tomography imaging of atherosclerotic plaque inflammation is highly reproducible: implications for atherosclerosis therapy trials. J Am Coll Cardiol 2007, 50:892–896.
Rudd JH, Myers KS, Bansilal S, et al.: Atherosclerosis inflammation imaging with 18F-FDG PET: carotid, iliac, and femoral uptake reproducibility, quantification methods, and recommendations. J Nucl Med 2008, 49:871–878.
Laitinen I, Marjamäki P, Haaparanta M, et al.: Non-specific binding of [(18)F]FDG to calcifications in atherosclerotic plaques: experimental study of mouse and human arteries. Eur J Nucl Med Mol Imaging 2006, 33:1461–1467.
Laurberg JM, Olsen AK, Hansen SB, et al.: Imaging of vulnerable atherosclerotic plaques with FDG-microPET: no FDG accumulation. Atherosclerosis 2007, 192:275–282.
Matter CM, Wyss MT, Meier P, et al.: 18F-choline images murine atherosclerotic plaques ex vivo. Arterioscler Thromb Vasc Biol 2006, 26:584–589.
Bucerius J, Schmaljohann J, Bohm I, et al.: Feasibility of 18F-fluoromethylcholine PET/CT for imaging of vessel wall alterations in humans—first results. Eur J Nucl Med Mol Imaging 2008, 35:815–820.
Tekabe Y, Li Q, Rosario R, et al.: Development of receptor for advanced glycation end products-directed imaging of atherosclerotic plaque in a murine model of spontaneous atherosclerosis. Circ Cardiovasc Imaging 2008, 1:212–219.
Hoppela E, Kankaanpää M, Parkkola R, et al.: Imaging of human inflammatory plaques using [11C]-PK11195 and [18F]-FDG [abstract]. J Nucl Cardiol 2007, 14:2.
Laitinen I, Marjamaki P, Nagren K, et al.: Uptake of inflammatory cell marker [(11)C]PK11195 into mouse atherosclerotic plaques. Eur J Nucl Med Mol Imaging 2009, 36:73–80.
Nahrendorf M, Zhang H, Hembrador S, et al.: Nanoparticle PET-CT imaging of macrophages in inflammatory atherosclerosis. Circulation 2008, 117:379–387.
Kircher MF, Grimm J, Swirski FK, et al.: Noninvasive in vivo imaging of monocyte trafficking to atherosclerotic lesions. Circulation 2008, 117:388–395.
Hartung D, Petrov A, Haider N, et al.: Radiolabeled monocyte chemotactic protein 1 for the detection of inflammation in experimental atherosclerosis. J Nucl Med 2007, 48:1816–1821.
Annovazzi A, Bonanno E, Arca M, et al.: 99mTc-interleukin-2 scintigraphy for the in vivo imaging of vulnerable atherosclerotic plaques. Eur J Nucl Med Mol Imaging 2006, 33:117–126.
Broisat A, Riou LM, Ardisson V, et al.: Molecular imaging of vascular cell adhesion molecule-1 expression in experimental atherosclerotic plaques with radiolabelled B2702-p. Eur J Nucl Med Mol Imaging 2007, 34:830–840.
Nahrendorf M, Keliher E, Panizzi P, et al.: VCAM-1 targeted PET-CT detects inflammatory atherosclerotic plaques [abstract 5788]. Circulation 2008, 118:S_102.
Schafers M, Riemann B, Kopka K, et al.: Scintigraphic imaging of matrix metalloproteinase activity in the arterial wall in vivo. Circulation 2004, 109:2554–2559.
Fujimoto S, Hartung D, Ohshima S, et al.: Molecular imaging of matrix metalloproteinase in atherosclerotic lesions: resolution with dietary modification and statin therapy. J Am Coll Cardiol 2008, 52:1847–1857.
Zhang J, Nie L, Razavian M, et al.: Molecular imaging of activated matrix metalloproteinases in vascular remodeling. Circulation 2008, 118:1953–1960.
Nahrendorf M, Sosnovik D, Chen JW, et al.: Activatable magnetic resonance imaging agent reports myeloperoxidase activity in healing infarcts and noninvasively detects the antiinflammatory effects of atorvastatin on ischemia-reperfusion injury. Circulation 2008, 117:1153–1160.
Isobe S, Tsimikas S, Zhou J, et al.: Noninvasive imaging of atherosclerotic lesions in apolipoprotein E-deficient and low-density-lipoprotein receptor-deficient mice with annexin A5. J Nucl Med 2006, 47:1497–1505.
Sarai M, Hartung D, Petrov A, et al.: Broad and specific caspase inhibitor-induced acute repression of apoptosis in atherosclerotic lesions evaluated by radiolabeled annexin A5 imaging. J Am Coll Cardiol 2007, 50:2305–2312.
Hermann S, Kuhlmann M, Faust A, et al.: Imaging of intracellular caspase-3 to visualize apoptosis [presentation 0154]. Presented at the World Molecular Imaging Congress. Nice, France; September 10–13, 2008.
Waldeck J, Hager F, Holtke C, et al.: Fluorescence reflectance imaging of macrophage-rich atherosclerotic plaques using an {alpha}v{beta}3 integrin-targeted fluorochrome. J Nucl Med 2008, 49:1845–1851.
Burtea C, Laurent S, Murariu O, et al.: Molecular imaging of alpha v beta3 integrin expression in atherosclerotic plaques with a mimetic of RGD peptide grafted to Gd-DTPA. Cardiovasc Res 2008, 78:148–157.
Hua J, Dobrucki LW, Sadeghi MM, et al.: Noninvasive imaging of angiogenesis with a 99mTc-labeled peptide targeted at alphavbeta3 integrin after murine hindlimb ischemia. Circulation 2005, 111:3255–3260.
Saraste A, Laitinen I, Poethko T, et al.: Evaluation of [18F]-galacto-RGD, a PET tracer for imaging alpha(v)beta3 integrin, for detection of atherosclerotic plaques in mouse model [presentation 39]. Presented at the Annual Congress of the European Association of Nuclear Medicine. Munich, Germany; October 12–15, 2008. Eur J Nucl Med Mol Imaging 2008, 35 (Suppl 2):S131.
Ishino S, Mukai T, Kuge Y, et al.: Targeting of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1) with 99mTc-labeled anti-LOX-1 antibody: potential agent for imaging of vulnerable plaque. J Nucl Med 2008, 49:1677–1685.
Schulz C, Penz S, Hoffmann C, et al.: Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res Cardiol 2008, 103:356–367.
Elmaleh DR, Fischman AJ, Tawakol A, et al.: Detection of inflamed atherosclerotic lesions with diadenosine-5′,5‴-P1,P4-tetraphosphate (Ap4A) and positron-emission tomography. Proc Natl Acad Sci U S A 2006, 103:15992–15996.
von Lukowicz T, Silacci M, Wyss MT, et al.: Human antibody against C domain of tenascin-C visualizes murine atherosclerotic plaques ex vivo. J Nucl Med 2007, 48:582–587.
Mulder WJ, Cormode DP, Hak S, et al.: Multimodality nanotracers for cardiovascular applications. Nat Clin Pract Cardiovasc Med 2008, 5(Suppl 2):S103–S111.
Soret M, Bacharach SL, Buvat I: Partial-volume effect in PET tumor imaging. J Nucl Med 2007, 48:932–945.
Kokki T, Teräs M, Sipilä HT, et al.: Dual gating method for eliminating motion-related inaccuracies in cardiac PET [presentation M19–231]. Presented at the 2007 IEEE Medical Imaging Conference. Hawaii; October 27 to November 3, 2007.
Martinez-Möller A, Zikic D, Botnar RM, et al.: Dual cardiac-respiratory gated PET: implementation and results from a feasibility study. Eur J Nucl Med Mol Imaging 2007, 34:1447–1454.
Park SJ, Ionascu D, Killoran J, et al.: Evaluation of the combined effects of target size, respiratory motion and background activity on 3D and 4D PET/CT images. Phys Med Biol 2008, 53:3661–3679.
Ogawa M, Ishino S, Mukai T, et al.: (18)F-FDG accumulation in atherosclerotic plaques: immunohistochemical and PET imaging study. J Nucl Med 2004, 45:1245–1250.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Laitinen, I., Knuuti, J. Imaging of vulnerable plaque: Potential breakthrough or pipe dream?. curr cardiovasc imaging rep 2, 167–175 (2009). https://doi.org/10.1007/s12410-009-0021-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12410-009-0021-x