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Molecular Imaging of Left Ventricular Remodeling

  • Cardiac Nuclear Imaging (RJ Gropler, Section Editor)
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Abstract

Every year nearly 1 million Americans with myocardial infarction suffer from acute coronary syndromes. Despite advances in reperfusion therapy, these molecular events may often lead to ventricular adverse remodeling resulting in the heart failure. This observation became a driving force to develop noninvasive imaging strategies to evaluate remodeling using concepts of molecular imaging. As such, cardiovascular imaging plays an important role in shifting the paradigm from the disease treatment to early diagnosis, prognostication, and stratification, which has a tremendous potential to alleviate socioeconomic and health care costs associated with the treatment of heart failure patients. This review is intended to be a brief overview of recent nuclear imaging techniques and applications to assess molecular events associated with the process of left ventricular (LV) remodeling following myocardial infarction (MI). The specific approaches presented here will include imaging of perfusion, viability, metabolism, cardiac neuroreceptors, angiogenesis, proteases activity, and renin-angiotensin-aldosterone system activation. We will first describe basic concepts of molecular imaging, then we will provide an overview of recent advances in molecular imaging technology, and finally we will report current nuclear imaging strategies in assessment of LV remodeling. The emphasis will be put on radiotracer-based modalities including single photon emission computed tomography (SPECT) and positron emission tomography (PET) techniques, although other clinical imaging modalities will be also briefly discussed. We expect that in near future these targeted imaging approaches will complement standard physiological parameters and will play a crucial role in post-MI patients’ stratification and development of individual therapy regimes.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Dixon JA, Spinale FG. Pathophysiology of myocardial injury and remodeling: Implications for molecular imaging. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2010;51 Suppl 1:102S–6.

    Google Scholar 

  2. • Buxton DB, Antman M, Danthi N, Dilsizian V, Fayad ZA, Garcia MJ, Jaff MR, Klimas M, Libby P, Nahrendorf M, Sinusas AJ, Wickline SA, Wu JC, Bonow RO, Weissleder R. Report of the national heart, lung, and blood institute working group on the translation of cardiovascular molecular imaging. Circulation. 2011;123:2157–2163. The panel of experts under the auspices of the National Institutes of Health tried to identify the barriers and challenges to translate molecular imaging approaches to a wide clinical use.

    Article  PubMed  Google Scholar 

  3. Zaidi H, Prasad R. Advances in multimodality molecular imaging. J Med Phys. 2009;34:122–8.

    Article  PubMed  Google Scholar 

  4. Catana C, Procissi D, Wu Y, Judenhofer MS, Qi J, Pichler BJ, Jacobs RE, Cherry SR. Simultaneous in vivo positron emission tomography and magnetic resonance imaging. Proc Nat Acad Sci USA. 2008;105:3705–10.

    Article  PubMed  CAS  Google Scholar 

  5. Judenhofer MS, Wehrl HF, Newport DF, Catana C, Siegel SB, Becker M, Thielscher A, Kneilling M, Lichy MP, Eichner M, Klingel K, Reischl G, Widmaier S, Rocken M, Nutt RE, Machulla HJ, Uludag K, Cherry SR, Claussen CD, Pichler BJ. Simultaneous pet-mri: A new approach for functional and morphological imaging. Nature medicine. 2008;14:459–65.

    Article  PubMed  CAS  Google Scholar 

  6. Menjoge AR, Kannan RM, Tomalia DA. Dendrimer-based drug and imaging conjugates: Design considerations for nanomedical applications. Drug Discov Today. 2010;15:171–85.

    Article  PubMed  CAS  Google Scholar 

  7. Sutton MG, Sharpe N. Left ventricular remodeling after myocardial infarction: Pathophysiology and therapy. Circulation. 2000;101:2981–8.

    PubMed  CAS  Google Scholar 

  8. •• Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure: Current concepts in clinical significance and assessment. JACC. Cardiovascular imaging. 2011;4:98–108. An overview of possible mechanisms for left ventricular remodeling including characterization of potential molecular targets which can be used to develop molecular probes targeted at remodeling process.

    Article  PubMed  Google Scholar 

  9. Sun Y. Myocardial repair/remodelling following infarction: Roles of local factors. Cardiovasc Res. 2009;81:482–90.

    Article  PubMed  CAS  Google Scholar 

  10. Chareonthaitawee P, Christian TF, Hirose K, Gibbons RJ, Rumberger JA. Relation of initial infarct size to extent of left ventricular remodeling in the year after acute myocardial infarction. J Am Coll Cardiol. 1995;25:567–73.

    Article  PubMed  CAS  Google Scholar 

  11. Orn S, Manhenke C, Anand IS, Squire I, Nagel E, Edvardsen T, Dickstein K. Effect of left ventricular scar size, location, and transmurality on left ventricular remodeling with healed myocardial infarction. Am J Cardiol. 2007;99:1109–14.

    Article  PubMed  Google Scholar 

  12. Berti V, Sciagra R, Acampa W, Ricci F, Cerisano G, Gallicchio R, Vigorito C, Pupi A, Cuocolo A. Relationship between infarct size and severity measured by gated spect and long-term left ventricular remodelling after acute myocardial infarction. Eur J Nucl Med Mol Imaging. 2011;38:1124–31.

    Article  PubMed  Google Scholar 

  13. Russell 3rd RR, Zaret BL. Nuclear cardiology: Present and future. Curr Probl Cardiol. 2006;31:557–629.

    Article  PubMed  Google Scholar 

  14. Hofstra L, Liem IH, Dumont EA, Boersma HH, van Heerde WL, Doevendans PA, De Muinck E, Wellens HJ, Kemerink GJ, Reutelingsperger CP, Heidendal GA. Visualisation of cell death in vivo in patients with acute myocardial infarction. Lancet. 2000;356:209–12.

    Article  PubMed  CAS  Google Scholar 

  15. Narula J, Petrov A, Pak K, Lister B, Khaw B. Very early noninvasive detection of acute experimental nonreperfused myocardial infarction with 99mtc-labeled glucarate. Circulation. 1997;95:1577–84.

    PubMed  CAS  Google Scholar 

  16. Teramoto N, Koshino K, Yokoyama I, Miyagawa S, Zeniya T, Hirano Y, Fukuda H, Enmi J, Sawa Y, Knuuti J, Iida H. Experimental pig model of old myocardial infarction with long survival leading to chronic left ventricular dysfunction and remodeling as evaluated by pet. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2011;52:761–8.

    Google Scholar 

  17. Bengel FM. Clinical cardiovascular molecular imaging. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2009;50:837–40.

    CAS  Google Scholar 

  18. Sinusas AJ. Molecular imaging in nuclear cardiology: Translating research concepts into clinical applications. Quarterly Journal of Nuclear Medicine and Molecular Imaging: Official Publication of the Italian Association of Nuclear Medicine. 2010;54:230–40.

    CAS  Google Scholar 

  19. Sinusas AJ, Thomas JD, Mills G. The future of molecular imaging. JACC Cardiovascular imaging. 2011;4:799–806.

    Article  PubMed  Google Scholar 

  20. Kontos MC, Dilsizian V, Weiland F, DePuey G, Mahmarian JJ, Iskandrian AE, Bateman TM, Heller GV, Ananthasubramaniam K, Li Y, Goldman JL, Armor T, Kacena KA, LaFrance ND, Garcia EV, Babich JW, Udelson JE. Iodofiltic acid i 123 (bmipp) fatty acid imaging improves initial diagnosis in emergency department patients with suspected acute coronary syndromes: A multicenter trial. J Am Coll Cardiol. 2010;56:290–9.

    Article  PubMed  Google Scholar 

  21. Naya M, Tsukamoto T, Morita K, Katoh C, Nishijima K, Komatsu H, Yamada S, Kuge Y, Tamaki N, Tsutsui H. Myocardial beta-adrenergic receptor density assessed by 11c-cgp12177 pet predicts improvement of cardiac function after carvedilol treatment in patients with idiopathic dilated cardiomyopathy. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2009;50:220–5.

    CAS  Google Scholar 

  22. de Jong RM, Willemsen AT, Slart RH, Blanksma PK, van Waarde A, Cornel JH, Vaalburg W, van Veldhuisen DJ, Elsinga PH. Myocardial beta-adrenoceptor downregulation in idiopathic dilated cardiomyopathy measured in vivo with pet using the new radioligand (s)-[11c]cgp12388. Eur J Nucl Med Mol Imaging. 2005;32:443–7.

    Article  PubMed  Google Scholar 

  23. Salinas C, Muzic Jr RF, Berridge M, Ernsberger P. Pet imaging of myocardial beta-adrenergic receptors with fluorocarazolol: Lack of interference by endogenous catecholamines. J Cardiovasc Pharmacol. 2005;46:222–31.

    Article  PubMed  CAS  Google Scholar 

  24. Jacobson AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, Agostini D, Weiland F, Chandna H, Narula J. Myocardial iodine-123 meta-iodobenzylguanidine imaging and cardiac events in heart failure. Results of the prospective admire-hf (adreview myocardial imaging for risk evaluation in heart failure) study. J Am Coll Cardiol. 2010;55:2212–21.

    Article  PubMed  Google Scholar 

  25. Sasano T, Abraham MR, Chang KC, Ashikaga H, Mills KJ, Holt DP, Hilton J, Nekolla SG, Dong J, Lardo AC, Halperin H, Dannals RF, Marban E, Bengel FM. Abnormal sympathetic innervation of viable myocardium and the substrate of ventricular tachycardia after myocardial infarction. J Am Coll Cardiol. 2008;51:2266–75.

    Article  PubMed  Google Scholar 

  26. Luisi Jr AJ, Suzuki G, Dekemp R, Haka MS, Toorongian SA, Canty Jr JM, Fallavollita JA. Regional 11c-hydroxyephedrine retention in hibernating myocardium: Chronic inhomogeneity of sympathetic innervation in the absence of infarction. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2005;46:1368–74.

    CAS  Google Scholar 

  27. Fallavollita JA, Banas MD, Suzuki G, de Kemp RA, Sajjad M, Canty Jr JM. 11c-meta-hydroxyephedrine defects persist despite functional improvement in hibernating myocardium. Journal of nuclear cardiology: official publication of the American Society of Nuclear Cardiology. 2010;17:85–96.

    Article  Google Scholar 

  28. Meoli DF, Sadeghi MM, Krassilnikova S, Bourke BN, Giordano FJ, Dione DP, Su H, Edwards DS, Liu S, Harris TD, Madri JA, Zaret BL, Sinusas AJ. Noninvasive imaging of myocardial angiogenesis following experimental myocardial infarction. J Clin Invest. 2004;113:1684–91.

    PubMed  CAS  Google Scholar 

  29. Shirani J, Narula J, Eckelman WC, Narula N, Dilsizian V. Early imaging in heart failure: Exploring novel molecular targets. Journal of nuclear cardiology: official publication of the American Society of Nuclear Cardiology. 2007;14:100–10.

    Article  Google Scholar 

  30. Asano Y, Ihn H, Yamane K, Jinnin M, Mimura Y, Tamaki K. Increased expression of integrin alpha(v)beta3 contributes to the establishment of autocrine tgf-beta signaling in scleroderma fibroblasts. J Immunol. 2005;175:7708–18.

    PubMed  CAS  Google Scholar 

  31. Dobrucki LW, Sinusas AJ. Imaging angiogenesis. Curr Opin Biotechnol. 2007;18:90–6.

    Article  PubMed  CAS  Google Scholar 

  32. •• Morrison M, Sinusas A. Molecular imaging approaches for evaluation of myocardial pathophysiology: Angiogenesis, ventricular remodeling, inflammation, and cell death. In: Zaret BL, Beller GA, eds. Clinical nuclear cardiology: State of the art and future directions. Elsevier; 2010:691–712. An excellent review about cardiovascular molecular imaging with emphasis on myocardial pathophysiology, including post-MI left ventricular remodeling, outlining recent applications.

  33. Nahrendorf M, Sosnovik DE, French BA, Swirski FK, Bengel F, Sadeghi MM, Lindner JR, Wu JC, Kraitchman DL, Fayad ZA, Sinusas AJ. Multimodality cardiovascular molecular imaging, part ii. Circ Cardiovasc Imaging. 2009;2:56–70.

    Article  PubMed  Google Scholar 

  34. Sinusas AJ. Imaging of angiogenesis. J Nucl Cardiol. 2004;11:617–33.

    Article  PubMed  Google Scholar 

  35. Sinusas AJ, Bengel F, Nahrendorf M, Epstein FH, Wu JC, Villanueva FS, Fayad ZA, Gropler RJ. Multimodality cardiovascular molecular imaging, part i. Circ Cardiovasc Imaging. 2008;1:244–56.

    Article  PubMed  Google Scholar 

  36. Sinusas A, Bengel F, Nahrendorf M, Epstein F, Wu J, Villanueva F, Fayad Z, Gropler R. Multimodality cardiovascular molecular imaging, part i. Circ Cardiovasc Imaging. 2008;1:244–56.

    Article  PubMed  Google Scholar 

  37. van den Borne SW, Isobe S, Verjans JW, Petrov A, Lovhaug D, Li P, Zandbergen HR, Ni Y, Frederik P, Zhou J, Arbo B, Rogstad A, Cuthbertson A, Chettibi S, Reutelingsperger C, Blankesteijn WM, Smits JF, Daemen MJ, Zannad F, Vannan MA, Narula N, Pitt B, Hofstra L, Narula J. Molecular imaging of interstitial alterations in remodeling myocardium after myocardial infarction. J Am Coll Cardiol. 2008;52:2017–28.

    Article  PubMed  Google Scholar 

  38. Mann DL. Molecular imaging and the failing heart: Through the looking glass. JACC Cardiovascular imaging. 2009;2:199–201.

    Article  PubMed  Google Scholar 

  39. Dobrucki LW, Meoli DF, Hu J, Sadeghi MM, Sinusas AJ. Regional hypoxia correlates with the uptake of a radiolabeled targeted marker of angiogenesis in rat model of myocardial hypertrophy and ischemic injury. J Physiol Pharmacol. 2009;60 Suppl 4:117–23.

    PubMed  Google Scholar 

  40. Kalinowski L, Dobrucki LW, Meoli DF, Dione DP, Sadeghi MM, Madri JA, Sinusas AJ. Targeted imaging of hypoxia-induced integrin activation in myocardium early after infarction. J Appl Physiol. 2008;104:1504–12.

    Article  PubMed  CAS  Google Scholar 

  41. Dobrucki LW, Tsutsumi Y, Kalinowski L, Dean J, Gavin M, Sen S, Mendizabal M, Sinusas AJ, Aikawa R. Analysis of angiogenesis induced by local igf-1 expression after myocardial infarction using microspect-ct imaging. J Mol Cell Cardiol. 2010;48:1071–9.

    Article  PubMed  CAS  Google Scholar 

  42. Lindsey ML, Escobar GP, Dobrucki LW, Goshorn DK, Bouges S, Mingoia JT, McClister Jr DM, Su H, Gannon J, MacGillivray C, Lee RT, Sinusas AJ, Spinale FG. Matrix metalloproteinase-9 gene deletion facilitates angiogenesis after myocardial infarction. Am J Physiol Heart Circ Physiol. 2006;290:H232–9.

    Article  PubMed  CAS  Google Scholar 

  43. Makowski MR, Ebersberger U, Nekolla S, Schwaiger M. In vivo molecular imaging of angiogenesis, targeting alphavbeta3 integrin expression, in a patient after acute myocardial infarction. Eur Hear J. 2008;29:2201.

    Article  Google Scholar 

  44. Lu E, Wagner W, Schellenberger U, Abraham J, Klibanov A, Woulfe S, Csikari M, Fischer D, Schreiner G, Brandenburger G, Villanueva F. Targeted in vivo labeling of receptors for vascular endothelial growth factor: Approach to identification of ischemic tissue. Circulation. 2003;108:97–103.

    Article  PubMed  CAS  Google Scholar 

  45. Rodriguez-Porcel M, Cai W, Gheysens O, Willmann J, Chen K, Wang H, Chen I, He L, Wu J, Li Z, Mohamedali K, Kim S, Rosenblum M, Chen X, Gambhir S. Imaging of vegf receptor in a rat myocardial infarction model using pet. J Nucl Med. 2008;49:667–73.

    Article  PubMed  Google Scholar 

  46. Spinale FG, Mukherjee R, Zavadzkas JA, Koval CN, Bouges S, Stroud RE, Dobrucki LW, Sinusas AJ. Cardiac restricted overexpression of membrane type-1 matrix metalloproteinase causes adverse myocardial remodeling following myocardial infarction. J Biol Chem. 2010;285:30316–27.

    Article  PubMed  CAS  Google Scholar 

  47. Chung G, Sinusas AJ. Imaging of matrix metalloproteinase activation and left ventricular remodeling. Current cardiology reports. 2007;9:136–42.

    Article  PubMed  Google Scholar 

  48. Su H, Spinale FG, Dobrucki LW, Song J, Hua J, Sweterlitsch S, Dione DP, Cavaliere P, Chow C, Bourke BN, Hu XY, Azure M, Yalamanchili P, Liu R, Cheesman EH, Robinson S, Edwards DS, Sinusas AJ. Noninvasive targeted imaging of matrix metalloproteinase activation in a murine model of postinfarction remodeling. Circulation. 2005;112:3157–67.

    Article  PubMed  CAS  Google Scholar 

  49. Liu YH, Sahul Z, Weyman CA, Dione DP, Dobrucki LW, Mekkaoui C, Brennan MP, Sinusas AJ. Accuracy and reproducibility of quantification of regional myocardial tracer uptake from molecular targeted spect-ct images: Experimental validation. European Heart Journal Supplements. 2009;11:S71–1.

    Google Scholar 

  50. Sahul ZH, Mukherjee R, Song J, McAteer J, Stroud RE, Dione DP, Staib L, Papademetris X, Dobrucki LW, Duncan JS, Spinale FG, Sinusas AJ. Targeted imaging of the spatial and temporal variation of matrix metalloproteinase activity in a porcine model of postinfarct remodeling: Relationship to myocardial dysfunction. Circulation Cardiovascular imaging. 2011;4:381–91.

    Article  PubMed  Google Scholar 

  51. Nahrendorf M. Imaging of infarct healing predicts left ventricular remodeling and evolution of heart failure: Focus on protease activity. Circulation Cardiovascular imaging. 2011;4:351–3.

    Article  PubMed  Google Scholar 

  52. Greenberg B. Molecular imaging of the remodeling heart: The next step forward. JACC Cardiovascular imaging. 2008;1:363–5.

    Article  PubMed  Google Scholar 

  53. Verjans JW, Lovhaug D, Narula N, Petrov AD, Indrevoll B, Bjurgert E, Krasieva TB, Petersen LB, Kindberg GM, Solbakken M, Cuthbertson A, Vannan MA, Reutelingsperger CP, Tromberg BJ, Hofstra L, Narula J. Noninvasive imaging of angiotensin receptors after myocardial infarction. JACC Cardiovascular imaging. 2008;1:354–62.

    Article  PubMed  Google Scholar 

  54. Iwata M, Cowling RT, Gurantz D, Moore C, Zhang S, Yuan JX, Greenberg BH. Angiotensin-(1–7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects. American journal of physiology. Heart and circulatory physiology. 2005;289:H2356–63.

    Article  PubMed  CAS  Google Scholar 

  55. Shirani J, Dilsizian V. Imaging left ventricular remodeling: Targeting the neurohumoral axis. Nature clinical practice. Cardiovascular medicine. 2008;5(2):S57–62.

    PubMed  CAS  Google Scholar 

  56. Dilsizian V, Eckelman WC, Loredo ML, Jagoda EM, Shirani J. Evidence for tissue angiotensin-converting enzyme in explanted hearts of ischemic cardiomyopathy using targeted radiotracer technique. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 2007;48:182–7.

    CAS  Google Scholar 

  57. Hua J, Dobrucki LW, Sadeghi MM, Zhang JS, Bourke BN, Cavaliere P, Song J, Chow C, Jahanshad N, van Royen N, Buschmann I, Madri JA, Mendizabal M, Sinusas AJ. Noninvasive imaging of angiogenesis with a tc-99 m-labeled peptide targeted at alpha(v)beta(3) integrin after murine hindlimb ischemia. Circulation. 2005;111:3255–60.

    Article  PubMed  CAS  Google Scholar 

  58. Raffel DM, Corbett JR, del Rosario RB, Gildersleeve DL, Chiao PC, Schwaiger M, Wieland DM. Clinical evaluation of carbon-11-phenylephrine: Mao-sensitive marker of cardiac sympathetic neurons. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 1996;37:1923–31.

    CAS  Google Scholar 

  59. Raffel DM, Corbett JR, del Rosario RB, Mukhopadhyay SK, Gildersleeve DL, Rose P, Wieland DM. Sensitivity of [11c]phenylephrine kinetics to monoamine oxidase activity in normal human heart. Journal of nuclear medicine: official publication, Society of Nuclear Medicine. 1999;40:232–8.

    CAS  Google Scholar 

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Acknowledgments

This work was supported in part by grants AHA 10SDG4180043 (LWD) and the Ministry of Science and Higher Education, the National Science Center, Poland, and the Foundation for Polish Science (LK).

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Authors and Affiliations

  1. Beckman Institute of Advanced Science and Technology, University of Illinois at Urbana-Champaign, 405 N. Mathews Ave., MC-251, Urbana, IL, 61801, USA

    Lawrence W. Dobrucki

  2. Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, IL, 61801, USA

    Lawrence W. Dobrucki

  3. Department of Medical Laboratory Diagnostics, Medical University of Gdansk, Gdansk, Poland

    Leszek Kalinowski

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  1. Lawrence W. Dobrucki
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Correspondence to Lawrence W. Dobrucki.

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Dobrucki, L.W., Kalinowski, L. Molecular Imaging of Left Ventricular Remodeling. Curr Cardiovasc Imaging Rep 5, 188–197 (2012). https://doi.org/10.1007/s12410-012-9137-5

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