Skip to main content
SpringerLink
Log in

Intravascular Molecular Imaging of Proteolytic Activity

  • Chapter
  • First Online:
Cardiovascular Imaging

  • 1753 Accesses

Abstract

Atherosclerotic plaque disruption leads to myocardial infarction and stroke, but current clinical diagnostic tests lack the ability to predict which patients will suffer these complications. New strategies to define high-risk plaque biology in vivo hold promise to differentiate stable from vulnerable atherosclerotic plaques. Plaque proteolytic activity has emerged as a key target for identifying vulnerable plaques given its association with plaque inflammation and role in mechanical destabilization of plaques. Protease activity can now be evaluated in vivo with intravascular molecular imaging, a leading technology to identify inflammation in high-risk atherosclerotic plaques in coronary-sized arteries. In particular, hybrid catheters combining micrometer-resolution optical frequency domain structural imaging and high-sensitivity near-infrared fluorescence molecular imaging are proving to be powerful tools to investigate plaque biology in living subjects with clear translational potential for human use. Ultimately, through additional validation in human clinical trials, intravascular imaging of proteolytic activity and inflammation could inform new treatment strategies for atherosclerotic vascular disease that are likely to have significant impact on cardiovascular health.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, Subcommittee AHASCaSS. Heart disease and stroke statistics – 2013 update: a report from the American Heart Association. Circulation. 2013;127(1):e6–245. doi:10.1161/CIR.0b013e31828124ad.

    Article  PubMed  Google Scholar 

  2. Fleg JL, Stone GW, Fayad ZA, Granada JF, Hatsukami TS, Kolodgie FD, Ohayon J, Pettigrew R, Sabatine MS, Tearney GJ, Waxman S, Domanski MJ, Srinivas PR, Narula J. Detection of high-risk atherosclerotic plaque: report of the NHLBI Working Group on current status and future directions. JACC Cardiovasc Imaging. 2012;5(9):941–55. doi:10.1016/j.jcmg.2012.07.007.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Glagov S, Weisenberg E, Zarins CK, Stankunavicius R, Kolettis GJ. Compensatory enlargement of human atherosclerotic coronary arteries. N Engl J Med. 1987;316(22):1371–5. doi:10.1056/NEJM198705283162204.

    Article  CAS  PubMed  Google Scholar 

  4. Virmani R, Burke AP, Farb A, Kolodgie FD. Pathology of the vulnerable plaque. J Am Coll Cardiol. 2006;47(8 Suppl):C13–8. doi:10.1016/j.jacc.2005.10.065.

    Article  CAS  PubMed  Google Scholar 

  5. Osborn EA, Jaffer FA. Imaging atherosclerosis and risk of plaque rupture. Curr Atheroscler Rep. 2013;15(10):359. doi:10.1007/s11883-013-0359-z.

    Article  PubMed  Google Scholar 

  6. García-García HM, Mintz GS, Lerman A, Vince DG, Margolis MP, van Es G-A, Morel M-AM, Nair A, Virmani R, Burke AP, Stone GW, Serruys PW. Tissue characterisation using intravascular radiofrequency data analysis: recommendations for acquisition, analysis, interpretation and reporting. EuroIntervention. 2009;5(2):177–89.

    Article  PubMed  Google Scholar 

  7. Waxman S, Dixon SR, L’allier P, Moses JW, Petersen JL, Cutlip D, Tardif JC, Nesto RW, Muller JE, Hendricks MJ, Sum ST, Gardner CM, Goldstein JA, Stone GW, Krucoff MW. In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques. JCMG. 2011;2(7):858–68. doi:10.1016/j.jcmg.2009.05.001.

    Google Scholar 

  8. Jaffer F, Libby P, Weissleder R. Molecular imaging of cardiovascular disease. Circulation. 2007;116(9):1052–61.

    Article  PubMed  Google Scholar 

  9. Sanz J, Fayad Z. Imaging of atherosclerotic cardiovascular disease. Nature. 2008;451(7181):953–7.

    Article  CAS  PubMed  Google Scholar 

  10. Osborn EA, Jaffer FA. The advancing clinical impact of molecular imaging in CVD. JACC Cardiovasc Imaging. 2013;6(12):1327–41. doi:10.1016/j.jcmg.2013.09.014.

    Article  PubMed  Google Scholar 

  11. Dweck MR, Chow MWL, Joshi NV, Williams MC, Jones C, Fletcher AM, Richardson H, White A, McKillop G, van Beek EJR, Boon NA, Rudd JHF, Newby DE. Coronary arterial 18F-sodium fluoride uptake: a novel marker of plaque biology. J Am Coll Cardiol. 2012;59(17):1539–48. doi:10.1016/j.jacc.2011.12.037.

    Article  CAS  PubMed  Google Scholar 

  12. Rogers IS, Nasir K, Figueroa AL, Cury RC, Hoffmann U, Vermylen DA, Brady TJ, Tawakol A. Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina. JACC Cardiovasc Imaging. 2010;3(4):388–97. doi:10.1016/j.jcmg.2010.01.004.

    Article  PubMed  Google Scholar 

  13. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med. 2005;352(16):1685–95. doi:10.1056/NEJMra043430.

    Article  CAS  PubMed  Google Scholar 

  14. Naghavi M, Libby P, Falk E, Casscells SW, Litovsky S, Rumberger J, Badimon JJ, Stefanadis C, Moreno P, Pasterkamp G, Fayad Z, Stone PH, Waxman S, Raggi P, Madjid M, Zarrabi A, Burke A, Yuan C, Fitzgerald PJ, Siscovick DS, de Korte CL, Aikawa M, Juhani Airaksinen KE, Assmann G, Becker CR, Chesebro JH, Farb A, Galis ZS, Jackson C, Jang I-K, Koenig W, Lodder RA, March K, Demirovic J, Navab M, Priori SG, Rekhter MD, Bahr R, Grundy SM, Mehran R, Colombo A, Boerwinkle E, Ballantyne C, Insull W, Schwartz RS, Vogel R, Serruys PW, Hansson GK, Faxon DP, Kaul S, Drexler H, Greenland P, Muller JE, Virmani R, Ridker PM, Zipes DP, Shah PK, Willerson JT. From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: part I. Circulation. 2003;108(14):1664–72. doi:10.1161/01.CIR.0000087480.94275.97.

    Article  PubMed  Google Scholar 

  15. Narula J, Nakano M, Virmani R, Kolodgie FD, Petersen R, Newcomb R, Malik S, Fuster V, Finn AV. Histopathologic characteristics of atherosclerotic coronary disease and implications of the findings for the invasive and noninvasive detection of vulnerable plaques. J Am Coll Cardiol. 2013;61(10):1041–51. doi:10.1016/j.jacc.2012.10.054.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Arbab-Zadeh A, Nakano M, Virmani R, Fuster V. Acute coronary events. Circulation. 2012;125(9):1147–56. doi:10.1161/CIRCULATIONAHA.111.047431.

    Article  PubMed Central  PubMed  Google Scholar 

  17. Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32(9):2045–51. doi:10.1161/ATVBAHA.108.179705.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Galis ZS, Khatri JJ. Matrix metalloproteinases in vascular remodeling and atherogenesis: the good, the bad, and the ugly. Circ Res. 2002;90(3):251–62.

    CAS  PubMed  Google Scholar 

  19. Silvestre-Roig C, de Winther MP, Weber C, Daemen MJ, Lutgens E, Soehnlein O. Atherosclerotic plaque destabilization: mechanisms, models, and therapeutic strategies. Circ Res. 2014;114(1):214–26. doi:10.1161/CIRCRESAHA.114.302355.

    Article  CAS  PubMed  Google Scholar 

  20. Shah PK, Falk E, Badimon JJ, Fernandez-Ortiz A, Mailhac A, Villareal-Levy G, Fallon JT, Regnstrom J, Fuster V. Human monocyte-derived macrophages induce collagen breakdown in fibrous caps of atherosclerotic plaques. Potential role of matrix-degrading metalloproteinases and implications for plaque rupture. Circulation. 1995;92(6):1565–9.

    CAS  PubMed  Google Scholar 

  21. Falk E, Nakano M, Bentzon JF, Finn AV, Virmani R. Update on acute coronary syndromes: the pathologists’ view. Eur Heart J. 2013;34(10):719–28. doi:10.1093/eurheartj/ehs411.

    Article  CAS  PubMed  Google Scholar 

  22. Slager CJ, Wentzel JJ, Gijsen FJ, Schuurbiers JC, van der Wal AC, van der Steen AF, Serruys PW. The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat Clin Pract Cardiovasc Med. 2005;2(8):401–7.

    Article  CAS  PubMed  Google Scholar 

  23. Wentzel JJ, Chatzizisis YS, Gijsen FJ, Giannoglou GD, Feldman CL, Stone PH. Endothelial shear stress in the evolution of coronary atherosclerotic plaque and vascular remodelling: current understanding and remaining questions. Cardiovasc Res. 2012;96(2):234–43. doi:10.1093/cvr/cvs217.

    Article  CAS  PubMed  Google Scholar 

  24. Dollery CM, Libby P. Atherosclerosis and proteinase activation. Cardiovasc Res. 2006;69(3):625–35. doi:10.1016/j.cardiores.2005.11.003.

    Article  CAS  PubMed  Google Scholar 

  25. Liu J, Sukhova GK, Sun J-S, Xu W-H, Libby P, Shi G-P. Lysosomal cysteine proteases in atherosclerosis. Arterioscler Thromb Vasc Biol. 2004;24(8):1359–66. doi:10.1161/01.ATV.0000134530.27208.41.

    Article  CAS  PubMed  Google Scholar 

  26. Sukhova GK, Shi GP, Simon DI, Chapman HA, Libby P. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J Clin Invest. 1998;102(3):576–83. doi:10.1172/JCI181.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Jones CB, Sane DC, Herrington DM. Matrix metalloproteinases: a review of their structure and role in acute coronary syndrome. Cardiovasc Res. 2003;59(4):812–23.

    Article  CAS  PubMed  Google Scholar 

  28. Newby AC. Metalloproteinase expression in monocytes and macrophages and its relationship to atherosclerotic plaque instability. Arterioscler Thromb Vasc Biol. 2008;28(12):2108–14. doi:10.1161/ATVBAHA.108.173898.

    Article  CAS  PubMed  Google Scholar 

  29. Chen J, Tung C-H, Mahmood U, Ntziachristos V, Gyurko R, Fishman MC, Huang PL, Weissleder R. In vivo imaging of proteolytic activity in atherosclerosis. Circulation. 2002;105(23):2766–71.

    Article  PubMed  Google Scholar 

  30. Deguchi J-o, Aikawa M, Tung C-H, Aikawa E, Kim D-E, Ntziachristos V, Weissleder R, Libby P. Inflammation in atherosclerosis: visualizing matrix metalloproteinase action in macrophages in vivo. Circulation. 2006;114(1):55–62. doi:10.1161/CIRCULATIONAHA.106.619056.

    Article  PubMed  Google Scholar 

  31. Jaffer F, Kim D, Quinti L, Tung C, Aikawa E, Pande A, Kohler R, Shi G, Libby P, Weissleder R. Optical visualization of cathepsin K activity in atherosclerosis with a novel, protease-activatable fluorescence sensor. Circulation. 2007;115(17):2292–8.

    Article  CAS  PubMed  Google Scholar 

  32. Lancelot E, Amirbekian V, Brigger I, Raynaud J-S, Ballet S, David C, Rousseaux O, Le Greneur S, Port M, Lijnen HR, Bruneval P, Michel J-B, Ouimet T, Roques B, Amirbekian S, Hyafil F, Vucic E, Aguinaldo JGS, Corot C, Fayad ZA. Evaluation of matrix metalloproteinases in atherosclerosis using a novel noninvasive imaging approach. Arterioscler Thromb Vasc Biol. 2008;28(3):425–32. doi:10.1161/ATVBAHA.107.149666.

    Article  CAS  PubMed  Google Scholar 

  33. Quillard T, Croce K, Jaffer FA, Weissleder R, Libby P. Molecular imaging of macrophage protease activity in cardiovascular inflammation in vivo. Thromb Haemost. 2011;105(5):828–36. doi:10.1160/TH10-09-0589.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  34. Zhang J, Nie L, Razavian M, Ahmed M, Dobrucki LW, Asadi A, Edwards DS, Azure M, Sinusas AJ, Sadeghi MM. Molecular imaging of activated matrix metalloproteinases in vascular remodeling. Circulation. 2008;118(19):1953–60. doi:10.1161/CIRCULATIONAHA.108.789743.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Suter MJ, Nadkarni SK, Weisz G, Tanaka A, Jaffer FA, Bouma BE, Tearney GJ. Intravascular optical imaging technology for investigating the coronary artery. JACC Cardiovasc Imaging. 2011;4(9):1022–39. doi:10.1016/j.jcmg.2011.03.020.

    Article  PubMed Central  PubMed  Google Scholar 

  36. Cheng VY, Slomka PJ, Le Meunier L, Tamarappoo BK, Nakazato R, Dey D, Berman DS. Coronary arterial 18F-FDG uptake by fusion of PET and coronary CT angiography at sites of percutaneous stenting for acute myocardial infarction and stable coronary artery disease. J Nucl Med. 2012;53(4):575–83. doi:10.2967/jnumed.111.097550.

    Article  CAS  PubMed  Google Scholar 

  37. Saam T, Rominger A, Wolpers S, Nikolaou K, Rist C, Greif M, Cumming P, Becker A, Foerster S, Reiser MF, Bartenstein P, Hacker M. Association of inflammation of the left anterior descending coronary artery with cardiovascular risk factors, plaque burden and pericardial fat volume: a PET/CT study. Eur J Nucl Med Mol Imaging. 2010;37(6):1203–12. doi:10.1007/s00259-010-1432-2.

    Article  PubMed  Google Scholar 

  38. Wykrzykowska J, Lehman S, Williams G, Parker JA, Palmer MR, Varkey S, Kolodny G, Laham R. Imaging of inflamed and vulnerable plaque in coronary arteries with 18F-FDG PET/CT in patients with suppression of myocardial uptake using a low-carbohydrate, high-fat preparation. J Nucl Med. 2009;50(4):563–8. doi:10.2967/jnumed.108.055616.

    Article  PubMed  Google Scholar 

  39. Howarth SPS, Tang TY, Trivedi R, Weerakkody R, U-King-Im J, Gaunt ME, Boyle JR, Li ZY, Miller SR, Graves MJ, Gillard JH. Utility of USPIO-enhanced MR imaging to identify inflammation and the fibrous cap: a comparison of symptomatic and asymptomatic individuals. Eur J Radiol. 2009;70(3):555–60. doi:10.1016/j.ejrad.2008.01.047.

    Article  CAS  PubMed  Google Scholar 

  40. Kooi ME, Cappendijk VC, Cleutjens KBJM, Kessels AGH, Kitslaar PJEHM, Borgers M, Frederik PM, Daemen MJAP, van Engelshoven JMA. Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging. Circulation. 2003;107(19):2453–8. doi:10.1161/01.CIR.0000068315.98705.CC.

    Article  CAS  PubMed  Google Scholar 

  41. Tang TY, Howarth SPS, Miller SR, Graves MJ, Patterson AJ, U-King-Im J-M, Li ZY, Walsh SR, Brown AP, Kirkpatrick PJ, Warburton EA, Hayes PD, Varty K, Boyle JR, Gaunt ME, Zalewski A, Gillard JH. The ATHEROMA (Atorvastatin Therapy: Effects on Reduction of Macrophage Activity) Study. Evaluation using ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging in carotid disease. J Am Coll Cardiol. 2009;53(22):2039–50. doi:10.1016/j.jacc.2009.03.018.

    Article  CAS  PubMed  Google Scholar 

  42. Calfon MA, Vinegoni C, Ntziachristos V, Jaffer FA. Intravascular near-infrared fluorescence molecular imaging of atherosclerosis: toward coronary arterial visualization of biologically high-risk plaques. J Biomed Opt. 2010;15(1):011107. doi:10.1117/1.3280282.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Thukkani AK, Jaffer FA. Intravascular near-infrared fluorescence molecular imaging of atherosclerosis. Am J Nucl Med Mol Imaging. 2013;3(3):217–31.

    PubMed Central  PubMed  Google Scholar 

  44. Jaffer FA, Libby P, Weissleder R. Optical and multimodality molecular imaging: insights into atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29(7):1017–24. doi:10.1161/ATVBAHA.108.165530.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  45. Weissleder R, Ntziachristos V. Shedding light onto live molecular targets. Nat Med. 2003;9(1):123–8. doi:10.1038/nm0103-123.

    Article  CAS  PubMed  Google Scholar 

  46. Jaffer FA, Calfon MA, Rosenthal A, Mallas G, Razansky RN, Mauskapf A, Weissleder R, Libby P, Ntziachristos V. Two-dimensional intravascular near-infrared fluorescence molecular imaging of inflammation in atherosclerosis and stent-induced vascular injury. J Am Coll Cardiol. 2011;57(25):2516–26. doi:10.1016/j.jacc.2011.02.036.

    Article  PubMed Central  PubMed  Google Scholar 

  47. Osborn EA, Jaffer FA. The year in molecular imaging. JACC Cardiovasc Imaging. 2012;5(3):317–28. doi:10.1016/j.jcmg.2011.12.011.

    Article  PubMed Central  PubMed  Google Scholar 

  48. Bourantas CV, Garcia-Garcia HM, Naka KK, Michalis LK, Serruys PW. Hybrid intravascular imaging: current applications and prospective potential in the study of coronary atherosclerosis. J Am Coll Cardiol. 2013;61(13):1369–78. doi:10.1016/j.jacc.2012.10.057.

    Article  PubMed  Google Scholar 

  49. Suh WM, Seto AH, Margey RJP, Cruz-Gonzalez I, Jang I-K. Intravascular detection of the vulnerable plaque. Circ Cardiovasc Imaging. 2011;4(2):169–78. doi:10.1161/CIRCIMAGING.110.958777.

    Article  PubMed  Google Scholar 

  50. Tearney GJ, Regar E, Akasaka T, Adriaenssens T, Barlis P, Bezerra HG, Bouma B, Bruining N, Cho J-M, Chowdhary S, Costa MA, de Silva R, Dijkstra J, Di Mario C, Dudeck D, Falk E, Feldman MD, Fitzgerald P, Garcia H, Gonzalo N, Granada JF, Guagliumi G, Holm NR, Honda Y, Ikeno F, Kawasaki M, Kochman J, Koltowski L, Kubo T, Kume T, Kyono H, Lam CCS, Lamouche G, Lee DP, Leon MB, Maehara A, Manfrini O, Mintz GS, Mizuno K, Morel M-A, Nadkarni S, Okura H, Otake H, Pietrasik A, Prati F, Räber L, Radu MD, Rieber J, Riga M, Rollins A, Rosenberg M, Sirbu V, Serruys PWJC, Shimada K, Shinke T, Shite J, Siegel E, Sonada S, Suter M, Takarada S, Tanaka A, Terashima M, Troels T, Uemura S, Ughi GJ, van Beusekom HMM, van der Steen AFW, van Es G-A, van Soest G, Virmani R, Waxman S, Weissman NJ, Weisz G. Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies: a report from the international working group for intravascular optical coherence tomography standardization and validation. J Am Coll Cardiol. 2012;59(12):1058–72. doi:10.1016/j.jacc.2011.09.079.

    Article  PubMed  Google Scholar 

  51. Gardner CM, Tan H, Hull EL, Lisauskas JB, Sum ST, Meese TM, Jiang C, Madden SP, Caplan JD, Burke AP, Virmani R, Goldstein J, Muller JE. Detection of lipid core coronary plaques in autopsy specimens with a novel catheter-based near-infrared spectroscopy system. JACC Cardiovasc Imaging. 2008;1(5):638–48. doi:10.1016/j.jcmg.2008.06.001.

    Article  PubMed  Google Scholar 

  52. Garg S, Serruys PW, van der Ent M, Schultz C, Mastik F, van Soest G, van der Steen AFW, Wilder MA, Muller JE, Regar E. First use in patients of a combined near infra-red spectroscopy and intra-vascular ultrasound catheter to identify composition and structure of coronary plaque. EuroIntervention. 2010;5(6):755–6.

    Article  PubMed  Google Scholar 

  53. Madder RD, Smith JL, Dixon SR, Goldstein JA. Composition of target lesions by near-infrared spectroscopy in patients with acute coronary syndrome versus stable angina. Circ Cardiovasc Interv. 2012;5(1):55–61. doi:10.1161/CIRCINTERVENTIONS.111.963934.

    Article  PubMed  Google Scholar 

  54. Jaffer FA, Vinegoni C, John MC, Aikawa E, Gold HK, Finn AV, Ntziachristos V, Libby P, Weissleder R. Real-time catheter molecular sensing of inflammation in proteolytically active atherosclerosis. Circulation. 2008;118(18):1802–9. doi:10.1161/CIRCULATIONAHA.108.785881.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Yoo H, Kim JW, Shishkov M, Namati E, Morse T, Shubochkin R, Mccarthy JR, Ntziachristos V, Bouma BE, Jaffer FA, Tearney GJ. Intra-arterial catheter for simultaneous microstructural and molecular imaging in vivo. Nat Med. 2011;17(12):1680–4. doi:10.1038/nm.2555.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  56. McDaniel MC, Eshtehardi P, Sawaya FJ, Douglas JS, Samady H. Contemporary clinical applications of coronary intravascular ultrasound. JACC Cardiovasc Interv. 2011;4(11):1155–67. doi:10.1016/j.jcin.2011.07.013.

    Article  PubMed  Google Scholar 

  57. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, Pinto FJ, Rosenfield K, Siegel RJ, Tuzcu EM, Yock PG. 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(5):1478–92.

    Article  CAS  PubMed  Google Scholar 

  58. Puri R, Kapadia SR, Nicholls SJ, Harvey JE, Kataoka Y, Tuzcu EM. Optimizing outcomes during left main percutaneous coronary intervention with intravascular ultrasound and fractional flow reserve: the current state of evidence. JACC Cardiovasc Interv. 2012;5(7):697–707. doi:10.1016/j.jcin.2012.02.018.

    Article  PubMed  Google Scholar 

  59. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368(21):2004–13. doi:10.1056/NEJMra1216063.

    Article  CAS  PubMed  Google Scholar 

  60. Cheng XW, Huang Z, Kuzuya M, Okumura K, Murohara T. Cysteine protease cathepsins in atherosclerosis-based vascular disease and its complications. Hypertension. 2011;58(6):978–86. doi:10.1161/HYPERTENSIONAHA.111.180935.

    Article  CAS  PubMed  Google Scholar 

  61. Kim D-E, Kim J-Y, Schellingerhout D, Kim E-J, Kim HK, Lee S, Kim K, Kwon IC, Shon S-M, Jeong S-W, Im S-H, Lee DK, Lee MM, Kim G-E. Protease imaging of human atheromata captures molecular information of atherosclerosis, complementing anatomic imaging. Arterioscler Thromb Vasc Biol. 2010;30(3):449–56. doi:10.1161/ATVBAHA.109.194613.

    Article  CAS  PubMed  Google Scholar 

  62. Lutgens SP, Cleutjens KB, Daemen MJ, Heeneman S. Cathepsin cysteine proteases in cardiovascular disease. FASEB J. 2007;21(12):3029–41. doi:10.1096/fj.06-7924com.

    Article  CAS  PubMed  Google Scholar 

  63. Papaspyridonos M, Smith A, Burnand KG, Taylor P, Padayachee S, Suckling KE, James CH, Greaves DR, Patel L. Novel candidate genes in unstable areas of human atherosclerotic plaques. Arterioscler Thromb Vasc Biol. 2006;26(8):1837–44. doi:10.1161/01.ATV.0000229695.68416.76.

    Article  CAS  PubMed  Google Scholar 

  64. Blum G, von Degenfeld G, Merchant MJ, Blau HM, Bogyo M. Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat Chem Biol. 2007;3(10):668–77. doi:10.1038/nchembio.2007.26.

    Article  CAS  PubMed  Google Scholar 

  65. Weissleder R, Tung CH, Mahmood U, Bogdanov A. In vivo imaging of tumors with protease-activated near-infrared fluorescent probes. Nat Biotechnol. 1999;17(4):375–8. doi:10.1038/7933.

    Article  CAS  PubMed  Google Scholar 

  66. Bogdanov Jr AA, Mazzanti M, Castillo G, Bolotin E. Protected Graft Copolymer (PGC) in imaging and therapy: a platform for the delivery of covalently and non-covalently bound drugs. Theranostics. 2012;2(6):553–76. doi:10.7150/thno.4070.

    Article  CAS  PubMed  Google Scholar 

  67. Tung CH, Bredow S, Mahmood U, Weissleder R. Preparation of a cathepsin D sensitive near-infrared fluorescence probe for imaging. Bioconjug Chem. 1999;10(5):892–6.

    Article  CAS  PubMed  Google Scholar 

  68. Bremer C, Tung CH, Weissleder R. In vivo molecular target assessment of matrix metalloproteinase inhibition. Nat Med. 2001;7(6):743–8. doi:10.1038/89126.

    Article  CAS  PubMed  Google Scholar 

  69. Tearney GJ, Yabushita H, Houser SL, Aretz HT, Jang I-K, Schlendorf KH, Kauffman CR, Shishkov M, Halpern EF, Bouma BE. Quantification of macrophage content in atherosclerotic plaques by optical coherence tomography. Circulation. 2003;107(1):113–9.

    Article  PubMed  Google Scholar 

  70. Dzurinko VL, Gurwood AS, Price JR. Intravenous and indocyanine green angiography. Optometry. 2004;75(12):743–55.

    Article  PubMed  Google Scholar 

  71. Polom K, Murawa D, Rho YS, Nowaczyk P, Hunerbein M, Murawa P. Current trends and emerging future of indocyanine green usage in surgery and oncology: a literature review. Cancer. 2011;117(21):4812–22. doi:10.1002/cncr.26087.

    Article  PubMed  Google Scholar 

  72. Yoneya S, Saito T, Komatsu Y, Koyama I, Takahashi K, Duvoll-Young J. Binding properties of indocyanine green in human blood. Invest Ophthalmol Vis Sci. 1998;39(7):1286–90.

    CAS  PubMed  Google Scholar 

  73. Fischer T, Gemeinhardt I, Wagner S, Stieglitz DV, Schnorr J, Hermann KG, Ebert B, Petzelt D, Macdonald R, Licha K, Schirner M, Krenn V, Kamradt T, Taupitz M. Assessment of unspecific near-infrared dyes in laser-induced fluorescence imaging of experimental arthritis. Acad Radiol. 2006;13(1):4–13. doi:10.1016/j.acra.2005.07.010.

    Article  PubMed  Google Scholar 

  74. Vinegoni C, Botnaru I, Aikawa E, Calfon MA, Iwamoto Y, Folco EJ, Ntziachristos V, Weissleder R, Libby P, Jaffer FA. Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques. Sci Transl Med. 2011;3(84):84ra45. doi:10.1126/scitranslmed.3001577.

    Article  PubMed Central  PubMed  Google Scholar 

  75. Bavry AA, Bhatt DL. Appropriate use of drug-eluting stents: balancing the reduction in restenosis with the concern of late thrombosis. Lancet. 2008;371(9630):2134–43. doi:10.1016/S0140-6736(08)60922-8.

    Article  CAS  PubMed  Google Scholar 

  76. Holmes DR, Kereiakes DJ, Garg S, Serruys PW, Dehmer GJ, Ellis SG, Williams DO, Kimura T, Moliterno DJ. Stent thrombosis. J Am Coll Cardiol. 2010;56(17):1357–65. doi:10.1016/j.jacc.2010.07.016.

    Article  PubMed  Google Scholar 

  77. Witzenbichler B, Mehran R, Guagliumi G, Dudek D, Huber K, Kornowski R, Stuckey TD, Fahy M, Parise H, Stone GW. Impact of diabetes mellitus on the safety and effectiveness of bivalirudin in patients with acute myocardial infarction undergoing primary angioplasty: analysis from the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial. JACC Cardiovasc Interv. 2011;4(7):760–8. doi:10.1016/j.jcin.2011.04.008.

    Article  PubMed  Google Scholar 

  78. Roffi M, Topol EJ. Percutaneous coronary intervention in diabetic patients with non-ST-segment elevation acute coronary syndromes. Eur Heart J. 2004;25(3):190–8. doi:10.1016/j.ehj.2003.10.027.

    Article  PubMed  Google Scholar 

  79. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med. 1994;331(8):489–95. doi:10.1056/NEJM199408253310801.

    Article  CAS  PubMed  Google Scholar 

  80. Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R. Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation. 2007;115(18):2435–41. doi:10.1161/CIRCULATIONAHA.107.693739.

    Article  PubMed  Google Scholar 

  81. Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol. 2006;48(1):193–202. doi:10.1016/j.jacc.2006.03.042.

    Article  PubMed  Google Scholar 

  82. Nakazawa G, Finn AV, Joner M, Ladich E, Kutys R, Mont EK, Gold HK, Burke AP, Kolodgie FD, Virmani R. Delayed arterial healing and increased late stent thrombosis at culprit sites after drug-eluting stent placement for acute myocardial infarction patients: an autopsy study. Circulation. 2008;118(11):1138–45. doi:10.1161/CIRCULATIONAHA.107.762047.

    Article  PubMed  Google Scholar 

  83. Lüscher TF, Steffel J, Eberli FR, Joner M, Nakazawa G, Tanner FC, Virmani R. Drug-eluting stent and coronary thrombosis: biological mechanisms and clinical implications. Circulation. 2007;115(8):1051–8. doi:10.1161/CIRCULATIONAHA.106.675934.

    Article  PubMed  Google Scholar 

  84. Mintz GS, Nissen SE, Anderson WD, Bailey SR, Erbel R, Fitzgerald PJ, Pinto FJ, Rosenfield K, Siegel RJ, Tuzcu EM, Yock PG. J Am Coll Cardiol. 2001 Apr;37(5):1478–92.

    Google Scholar 

  85. Murata A, Wallace-Bradley D, Tellez A, Alviar C, Aboodi M, Sheehy A, Coleman L, Perkins L, Nakazawa G, Mintz G, Kaluza GL, Virmani R, Granada JF. Accuracy of optical coherence tomography in the evaluation of neointimal coverage after stent implantation. JACC Cardiovasc Imaging. 2010;3(1):76–84. doi:10.1016/j.jcmg.2009.09.018.

    Article  PubMed  Google Scholar 

  86. Nakano M, Vorpahl M, Otsuka F, Taniwaki M, Yazdani SK, Finn AV, Ladich ER, Kolodgie FD, Virmani R. Ex vivo assessment of vascular response to coronary stents by optical frequency domain imaging. JACC Cardiovasc Imaging. 2012;5(1):71–82. doi:10.1016/j.jcmg.2011.09.015.

    Article  PubMed  Google Scholar 

  87. Botnar RM, Buecker A, Wiethoff AJ, Parsons EC, Katoh M, Katsimaglis G, Weisskoff RM, Lauffer RB, Graham PB, Gunther RW, Manning WJ, Spuentrup E. In vivo magnetic resonance imaging of coronary thrombosis using a fibrin-binding molecular magnetic resonance contrast agent. Circulation. 2004;110(11):1463–6. doi:10.1161/01.CIR.0000134960.31304.87.

    Article  PubMed  Google Scholar 

  88. Hara T, Bhayana B, Thompson B, Kessinger CW, Khatri A, McCarthy JR, Weissleder R, Lin CP, Tearney GJ, Jaffer FA. Molecular imaging of fibrin deposition in deep vein thrombosis using fibrin-targeted near-infrared fluorescence. JACC Cardiovasc Imaging. 2012;5(6):607–15. doi:10.1016/j.jcmg.2012.01.017.

    Article  PubMed Central  PubMed  Google Scholar 

  89. Spuentrup E, Botnar RM, Wiethoff AJ, Ibrahim T, Kelle S, Katoh M, Ozgun M, Nagel E, Vymazal J, Graham PB, Günther RW, Maintz D. MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients. Eur Radiol. 2008;18(9):1995–2005. doi:10.1007/s00330-008-0965-2.

    Article  PubMed  Google Scholar 

  90. Vymazal J, Spuentrup E, Cardenas-Molina G, Wiethoff AJ, Hartmann MG, Caravan P, Parsons EC. Thrombus imaging with fibrin-specific gadolinium-based MR contrast agent EP-2104R: results of a phase II clinical study of feasibility. Invest Radiol. 2009;44(11):697–704. doi:10.1097/RLI.0b013e3181b092a7.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

NIH R01 HL 108229 and American Heart Association Scientist Development Grant #0830352N (FJ); Harvard Catalyst KL2/Medical Research Investigator Training Award NIH 1UL1 TR001102-01 and Beth Israel Deaconess Medical Center Cardiovascular Division (EO).

Author information

Authors and Affiliations

  1. Cardiology Division, Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Simches Research Building 3206, 185 Cambridge Street, Boston, MA, 02114, USA

    Eric A. Osborn & Farouc A. Jaffer MD, PhD

  2. Cardiology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    Eric A. Osborn

Authors
  1. Eric A. Osborn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Farouc A. Jaffer MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Farouc A. Jaffer MD, PhD .

Editor information

Editors and Affiliations

  1. Cardiovascular Medicine, Brigham and Women’s Hospital Harvard Medical School, Boston, Massachusetts, USA

    Elena Aikawa

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Osborn, E.A., Jaffer, F.A. (2015). Intravascular Molecular Imaging of Proteolytic Activity. In: Aikawa, E. (eds) Cardiovascular Imaging. Springer, Cham. https://doi.org/10.1007/978-3-319-09268-3_4

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-09268-3_4

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-09267-6

  • Online ISBN: 978-3-319-09268-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation