Imaging Atherosclerotic Plaque Calcification: Translating Biology

Current Atherosclerosis Reports

Volumn 18, Issue 8, 2016, Pages

  Bailey, Grant ^a,b   Meadows, Judith ^a,b   Morrison, Alan R ^c,d  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b VA CONNECTICUT HEALTHCARE SYSTEM   (United States)

^c BROWN UNIVERSITY   (United States)

^d VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Atherosclerosis; Calcification; Coronary artery disease; Molecular imaging; Sodium fluoride PET; Vulnerable plaque

Indexed keywords

C REACTIVE PROTEIN; CANAKINUMAB; FLUORODEOXYGLUCOSE F 18; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; SODIUM FLUORIDE F 18; ULTRASMALL SUPERPARAMAGNETIC IRON OXIDE;

ATHEROSCLEROTIC PLAQUE; AUTOFLUORESCENCE IMAGING; BLOOD VESSEL CALCIFICATION; BONE DEVELOPMENT; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; COMPUTER ASSISTED EMISSION TOMOGRAPHY; COMPUTER ASSISTED TOMOGRAPHY; CORONARY ARTERY ATHEROSCLEROSIS; CORONARY ARTERY CALCIFICATION; CORONARY ARTERY CALCIUM SCORE; CORONARY ARTERY DISEASE; HUMAN; INTRACELLULAR SIGNALING; INTRAVASCULAR ULTRASOUND; MESENCHYME CELL; MOLECULAR IMAGING; NUCLEAR MAGNETIC RESONANCE IMAGING; OPTICAL COHERENCE TOMOGRAPHY; PERSONALIZED MEDICINE; PROTEIN EXPRESSION; REVIEW; RISK ASSESSMENT; RISK REDUCTION; ANIMAL; CALCINOSIS; DIAGNOSTIC IMAGING; METABOLISM; PLAQUE, ATHEROSCLEROTIC;

ANIMALS; CALCINOSIS; HUMANS; MOLECULAR IMAGING; PLAQUE, ATHEROSCLEROTIC; PRECISION MEDICINE;

EID: 84976334420     PISSN: 15233804     EISSN: 15346242     Source Type: Journal    
DOI: 10.1007/s11883-016-0601-6     Document Type: Review

References (70)

1. Mankoff DA. A definition of molecular imaging. J Nucl Med: Off Publ Soc Nucl Med. 2007;48:18N–21.
2. Hjortnaes J, New SE, Aikawa E. Visualizing novel concepts of cardiovascular calcification. Trends Cardiovasc Med. 2013;23:71–9.
3. Demer LL, Tintut Y. Vascular calcification: pathobiology of a multifaceted disease. Circulation. 2008;117:2938–48.
4. Morrison AR, Wu JC, Sadeghi MM. Cardiovascular molecular imaging. In: Iskandrian AE, Garcia EV, editors. Nuclear cardiac imaging. 5th ed. New York: Oxford University Press; 2016. p. 601–36.
5. New SE, Goettsch C, Aikawa M, Marchini JF, Shibasaki M, Yabusaki K, et al. Macrophage-derived matrix vesicles: an alternative novel mechanism for microcalcification in atherosclerotic plaques. Circ Res. 2013;113:72–7.
6. Otsuka F, Sakakura K, Yahagi K, Joner M, Virmani R. Has our understanding of calcification in human coronary atherosclerosis progressed? Arterioscler Thromb Vasc Biol. 2014;34:724–36.
7. Towler DA, Demer LL. Thematic series on the pathobiology of vascular calcification: an introduction. Circ Res. 2011;108:1378–80.
8. Aikawa E, Nahrendorf M, Figueiredo JL, Swirski FK, Shtatland T, Kohler RH, et al. Osteogenesis associates with inflammation in early-stage atherosclerosis evaluated by molecular imaging in vivo. Circulation. 2007;116:2841–50.
9. Radcliff K, Tang TB, Lim J, Zhang Z, Abedin M, Demer LL, et al. Insulin-like growth factor-I regulates proliferation and osteoblastic differentiation of calcifying vascular cells via extracellular signal-regulated protein kinase and phosphatidylinositol 3-kinase pathways. Circ Res. 2005;96:398–400.
10. Tintut Y, Patel J, Territo M, Saini T, Parhami F, Demer LL. Monocyte/macrophage regulation of vascular calcification in vitro. Circulation. 2002;105:650–5.
11. Al-Aly Z, Shao JS, Lai CF, Huang E, Cai J, Behrmann A, et al. Aortic Msx2-Wnt calcification cascade is regulated by TNF-alpha-dependent signals in diabetic Ldlr−/− mice. Arterioscler Thromb Vasc Biol. 2007;27:2589–96.
12. Li X, Yang HY, Giachelli CM. BMP-2 promotes phosphate uptake, phenotypic modulation, and calcification of human vascular smooth muscle cells. Atherosclerosis. 2008;199:271–7.
13. Sage AP, Tintut Y, Demer LL. Regulatory mechanisms in vascular calcification. Nat Rev Cardiol. 2010;7:528–36.
14. Panizo S, Cardus A, Encinas M, Parisi E, Valcheva P, Lopez-Ongil S, et al. RANKL increases vascular smooth muscle cell calcification through a RANK-BMP4-dependent pathway. Circ Res. 2009;104:1041–8.
15. Shanahan CM. Inflammation ushers in calcification: a cycle of damage and protection? Circulation. 2007;116:2782–5.
16. Goettsch C, Hutcheson JD, Aikawa M, Iwata H, Pham T, Nykjaer A, et al. Sortilin mediates vascular calcification via its recruitment into extracellular vesicles. J Clin Invest. 2016;126:1323–36.
17. Proudfoot D, Skepper JN, Hegyi L, Bennett MR, Shanahan CM, Weissberg PL. Apoptosis regulates human vascular calcification in vitro: evidence for initiation of vascular calcification by apoptotic bodies. Circ Res. 2000;87:1055–62.
18. Reynolds JL, Joannides AJ, Skepper JN, McNair R, Schurgers LJ, Proudfoot D, et al. Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: a potential mechanism for accelerated vascular calcification in ESRD. J Am Soc Nephrol. 2004;15:2857–67.
19. Kapustin AN, Davies JD, Reynolds JL, McNair R, Jones GT, Sidibe A, et al. Calcium regulates key components of vascular smooth muscle cell-derived matrix vesicles to enhance mineralization. Circ Res. 2011;109:e1–12.
20. Hecht HS. Coronary artery calcium scanning: past, present, and future. J Am Coll Cardiol Img. 2015;8:579–96.
21. Wexler L. Gaining perspective on the risks of ionizing radiation for cardiac imaging. J Am Coll Cardiol. 2014;63:1490–2.
22. Chen J, Einstein AJ, Fazel R, Krumholz HM, Wang Y, Ross JS, et al. Cumulative exposure to ionizing radiation from diagnostic and therapeutic cardiac imaging procedures: a population-based analysis. J Am Coll Cardiol. 2010;56:702–11.
23. Blaha MJ, Budoff MJ, DeFilippis AP, Blankstein R, Rivera JJ, Agatston A, et al. Associations between C-reactive protein, coronary artery calcium, and cardiovascular events: implications for the JUPITER population from MESA, a population-based cohort study. Lancet. 2011;378:684–92.
24. Study of Inherited Risk of Coronary A, Reilly MP, Wolfe ML, Localio AR, Rader DJ. C-reactive protein and coronary artery calcification. The Study of Inherited Risk of Coronary Atherosclerosis (SIRCA). Arterioscler Thromb Vasc Biol. 2003;23:1851–6.
25. Raggi P, Callister TQ, Shaw LJ. Progression of coronary artery calcium and risk of first myocardial infarction in patients receiving cholesterol-lowering therapy. Arterioscler Thromb Vasc Biol. 2004;24:1272–7.
26. Raggi P, Cooil B, Shaw LJ, Aboulhson J, Takasu J, Budoff M, et al. Progression of coronary calcium on serial electron beam tomographic scanning is greater in patients with future myocardial infarction. Am J Cardiol. 2003;92:827–9.
27. Criqui MH, Denenberg JO, Ix JH, McClelland RL, Wassel CL, Rifkin DE, et al. Calcium density of coronary artery plaque and risk of incident cardiovascular events. JAMA: J Am Med Assoc. 2014;311:271–8. This article identifies calcium density as being inversely correlated to event risk, allowing for additional risk discrimination over traditional coronary calcium scores.
28. Vengrenyuk Y, Carlier S, Xanthos S, Cardoso L, Ganatos P, Virmani R, et al. A hypothesis for vulnerable plaque rupture due to stress-induced debonding around cellular microcalcifications in thin fibrous caps. Proc Natl Acad Sci U S A. 2006;103:14678–83.
29. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47:C13–8.
30. Motoyama S, Kondo T, Sarai M, Sugiura A, Harigaya H, Sato T, et al. Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes. J Am Coll Cardiol. 2007;50:319–26.
31. Motoyama S, Sarai M, Harigaya H, Anno H, Inoue K, Hara T, et al. Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome. J Am Coll Cardiol. 2009;54:49–57.
32. Puchner SB, Liu T, Mayrhofer T, Truong QA, Lee H, Fleg JL, et al. High-risk plaque detected on coronary CT angiography predicts acute coronary syndromes independent of significant stenosis in acute chest pain: results from the ROMICAT-II trial. J Am Coll Cardiol. 2014;64:684–92. This is a critical study that demonstrates individual plaque features associated with qualitative CT-based calcium measures have predictive value for ACS in patients presenting with acute chest pain.
33. Mintz GS. Intravascular imaging of coronary calcification and its clinical implications. J Am Coll Cardiol Img. 2015;8:461–71.
34. Liu L, Gardecki JA, Nadkarni SK, Toussaint JD, Yagi Y, Bouma BE, et al. Imaging the subcellular structure of human coronary atherosclerosis using micro-optical coherence tomography. Nat Med. 2011;17:1010–4.
35. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, et al. American College of Cardiology Clinical Expert Consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (IVUS). A report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2001;37:1478–92.
36. Puri R, Tuzcu EM, Nissen SE, Nicholls SJ. Exploring coronary atherosclerosis with intravascular imaging. Int J Cardiol. 2013;168:670–9.
37. Puri R, Nicholls SJ, Shao M, Kataoka Y, Uno K, Kapadia SR, et al. Impact of statins on serial coronary calcification during atheroma progression and regression. J Am Coll Cardiol. 2015;65:1273–82. This article provides a critical proof of principal for the role of serial intravascular ultrasound imaging in studying plaque biology. It demonstrates that statins promote coronary atheroma calcification, revealing potential insights into the plaque-stabilizing effects of statins.
38. Calfon MA, Rosenthal A, Mallas G, Mauskapf A, Nudelman RN, Ntziachristos V and Jaffer FA. In vivo near infrared fluorescence (NIRF) intravascular molecular imaging of inflammatory plaque, a multimodal approach to imaging of atherosclerosis. J Vis Exp. 2011.
39. Zaheer A, Murshed M, De Grand AM, Morgan TG, Karsenty G, Frangioni JV. Optical imaging of hydroxyapatite in the calcified vasculature of transgenic animals. Arterioscler Thromb Vasc Biol. 2006;26:1132–6.
40. Kooi ME, Cappendijk VC, Cleutjens KB, Kessels AG, Kitslaar PJ, Borgers M, et al. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003;107:2453–8.
41. Ruehm SG, Corot C, Vogt P, Kolb S, Debatin JF. Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits. Circulation. 2001;103:415–22.
42. Silvera SS, Aidi HE, Rudd JH, Mani V, Yang L, Farkouh M, et al. Multimodality imaging of atherosclerotic plaque activity and composition using FDG-PET/CT and MRI in carotid and femoral arteries. Atherosclerosis. 2009;207:139–43.
43. Henkelman RM, Watts JF, Kucharczyk W. High signal intensity in MR images of calcified brain tissue. Radiology. 1991;179:199–206.
44. Bitar R, Moody AR, Symons S, Leung G, Crisp S, Kiss A, et al. Carotid atherosclerotic calcification does not result in high signal intensity in MR imaging of intraplaque hemorrhage. AJNR Am J Neuroradiol. 2010;31:1403–7.
45. Hallock KJ, Hamilton JA. Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique. Magn Reson Med: Off J Soc Magn Reson Med/Soc Magn Reson Med. 2006;56:1380–3.
46. Turan TN, Rumboldt Z, Granholm AC, Columbo L, Welsh CT, Lopes-Virella MF, et al. Intracranial atherosclerosis: correlation between in-vivo 3T high resolution MRI and pathology. Atherosclerosis. 2014;237:460–3.
47. Tawakol A, Migrino RQ, Bashian GG, Bedri S, Vermylen D, Cury RC, 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;48:1818–24.
48. Tahara N, Kai H, Ishibashi M, Nakaura H, Kaida H, Baba K, et al. Simvastatin attenuates plaque inflammation: evaluation by fluorodeoxyglucose positron emission tomography. J Am Coll Cardiol. 2006;48:1825–31.
49. Tawakol A, Fayad ZA, Mogg R, Alon A, Klimas MT, Dansky H, et al. Intensification of statin therapy results in a rapid reduction in atherosclerotic inflammation: results of a multicenter fluorodeoxyglucose-positron emission tomography/computed tomography feasibility study. J Am Coll Cardiol. 2013;62:909–17.
50. Demeure F, Hanin FX, Bol A, Vincent MF, Pouleur AC, Gerber B, et al. A randomized trial on the optimization of 18F-FDG myocardial uptake suppression: implications for vulnerable coronary plaque imaging. J Nucl Med: Off Publ Soc Nucl Med. 2014;55:1629–35.
51. Gaeta C, Fernandez Y, Pavia J, Flotats A, Artigas C, Deportos J, et al. Reduced myocardial 18F-FDG uptake after calcium channel blocker administration. Initial observation for a potential new method to improve plaque detection. Eur J Nucl Med Mol Imaging. 2011;38:2018–24.
52. Derlin T, Toth Z, Papp L, Wisotzki C, Apostolova I, Habermann CR, et al. Correlation of inflammation assessed by 18F-FDG PET, active mineral deposition assessed by 18F-fluoride PET, and vascular calcification in atherosclerotic plaque: a dual-tracer PET/CT study. J Nucl Med: Off Publ Soc Nucl Med. 2011;52:1020–7.
53. Dunphy MP, Freiman A, Larson SM, Strauss HW. Association of vascular 18F-FDG uptake with vascular calcification. J Nucl Med: Off Publ Soc Nucl Med. 2005;46:1278–84.
54. Meirelles GS, Gonen M, Strauss HW. 18F-FDG uptake and calcifications in the thoracic aorta on positron emission tomography/computed tomography examinations: frequency and stability on serial scans. J Thorac Imaging. 2011;26:54–62.
55. Tavakoli S, Zamora D, Ullevig S, Asmis R. Bioenergetic profiles diverge during macrophage polarization: implications for the interpretation of 18F-FDG PET imaging of atherosclerosis. J Nucl Med: Off Publ Soc Nucl Med. 2013;54:1661–7.
56. Czernin J, Satyamurthy N, Schiepers C. Molecular mechanisms of bone 18F-NaF deposition. J Nucl Med: Off Publ Soc Nucl Med. 2010;51:1826–9.
57. Irkle A, Vesey AT, Lewis DY, Skepper JN, Bird JL, Dweck MR, et al. Identifying active vascular microcalcification by (18)F-sodium fluoride positron emission tomography. Nat Commun. 2015;6:7495. This article demonstrates that 18F-NaF uptake is higher in sites of microcalcification relative to sites of macrocalcification, providing better discrimination high-risk plaque by calcium-based features.
58. Kelly-Arnold A, Maldonado N, Laudier D, Aikawa E, Cardoso L, Weinbaum S. Revised microcalcification hypothesis for fibrous cap rupture in human coronary arteries. Proc Natl Acad Sci U S A. 2013;110:10741–6.
59. Joshi NV, Vesey AT, Williams MC, Shah AS, Calvert PA, Craighead FH, et al. 18F-fluoride positron emission tomography for identification of ruptured and high-risk coronary atherosclerotic plaques: a prospective clinical trial. Lancet. 2014;383:705–13. This article is the first to demonstrate that 18F-NaF PET coupled to CT can effectively identify and localize ruptured and high risk-plaque at the time of symptomatic presentation.
60. American College of Cardiology/American Heart Association Task Force on Practice G., Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1–45.
61. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto Jr AM, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.
62. Ridker PM. The JUPITER trial: results, controversies, and implications for prevention. Circ Cardiovasc Qual Outcomes. 2009;2:279–85.
63. American College of Cardiology/American Heart Association Task Force on Practice G, Goff Jr DC, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S49–73.
64. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1489–99.
65. Open-Label Study of Long-Term Evaluation against LDLCI, Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500–9.
66. Wald DS, Morris JK, Wald NJ, Chase AJ, Edwards RJ, Hughes LO, et al. Randomized trial of preventive angioplasty in myocardial infarction. N Engl J Med. 2013;369:1115–23.
67. Ridker PM, Thuren T, Zalewski A, Libby P. Interleukin-1beta inhibition and the prevention of recurrent cardiovascular events: rationale and design of the Canakinumab Anti-inflammatory Thrombosis Outcomes Study (CANTOS). Am Heart J. 2011;162:597–605.
68. Collins FS, Varmus H. A new initiative on precision medicine. N Engl J Med. 2015;372:793–5.
69. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part II. Circulation. 2003;108:1772–8.
70. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, et al. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Circulation. 2003;108:1664–72.