Magnetic Resonance Imaging of Myocardial Function Following Intracoronary and Intramyocardial Stem Cell Injection

András Mester 1 , 2 , Balázs Oltean-Péter 1 , 2 , Ioana Rodean 2 , Diana Opincariu 1 , 2 , Alexandra Stănescu 1 , 2 , Erzsébet Lázár 1 , 3 , István Benedek Jr 1 , 3 , Imre Benedek 1 , 2  and István Benedek 1 , 3
  • 1 University of Medicine and Pharmacy, Tîrgu Mureș, Romania
  • 2 Center of Advanced Research in Multimodality Cardiac Imaging, Tîrgu Mureș, Romania
  • 3 Clinic of Hematology and Bone Marrow Transplantation Unit, Tîrgu Mureș, Romania


Stem cell-based therapy is a new therapeutic option that can be used in patients with cardiac diseases caused by myocardial injury. Cardiac magnetic resonance imaging (MRI) is a new noninvasive imaging method with an increasingly widespread indication. The aim of this review was to evaluate the role of cardiac MRI in patients with myocardial infarction undergoing stem cell therapy. We studied the role of MRI in the assessment of myocardial viability, stem cell tracking, assessment of cell survival rate, and monitoring of the long-term effects of stem cell therapy. Based on the current knowledge in this field, this noninvasive, in vivo cardiac imaging technique has a large indication in this group of patients and plays an important role in all stages of stem cell therapy, from the indication to the long-term follow-up of patients.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. European Cardiovascular Disease Statistics 2017. Avaible at:

  • 2. Konstam MA, Kramer DG, Patel AR, et al. Left ventricular remodeling in heart failure current concepts in clinical significance and assessment. J Am Coll Cardiol Img. 2011;4:98-108.

  • 3. Abbate A, Biondi-Zoccai GG, Appleton DL, et al. Survival and cardiac remodeling benefits in patients undergoing late percutaneous coronary intervention of the infarct-related artery: evidence from a meta-analysis of randomized controlled clinical trials. J Am Coll Cardiol. 2008;21:956-964.

  • 4. David G, David AB. MRI determination of myocardial viability. Appl Radiol. 2006;35.

  • 5. Frangioni JV, Hajjar RJ. In vivo tracking of stem cells for clinical trials in cardiovascular disease. Circulation. 2004;110:3378-3383.

  • 6. Chen IY, Wu JC. Cardiovascular molecular imaging: focus on clinical translation. Circulation. 2011;123:425-443.

  • 7. Comella K, Griffeth J. Stem Cell Research in the Cardiac Field: Where Are We Now? World Stem Cell Report. 2009.

  • 8. Krishna KA, Krishna KS, Berrocal R, Rao KS, Sambasiva Rao KRS. Myocardial infarction and stem cells. Myocardial infarction and stem cells. J Pharm Bioallied Sci. 2011;3:182-188.

  • 9. Perin EC, López J. Methods of stem cell delivery in cardiac diseases. Nat Clin Pract Cardiovasc Med. 2006:Suppl1:110-113.

  • 10. Bodo-Eckehard S, Gustav S. 10 Years of Intracoronary and Intramyocardial Bone Marrow Stem Cell Therapy of the Heart. J Am Coll Cardiol. 2011;58:1095-1104.

  • 11. Whitney F, Rony A. Therapeutic use of stem cells for cardiovascular disease. Clin Transl Med. 2016;5:34.

  • 12. Donndorf P, Strauer BE. Stem cell therapy for the treatment of acute myocardial infarction and chronic ischemic heart disease. Curr Pharm Biotechnol. 2013;14:12-19.

  • 13. Lau JF, Anderson SA, Adler E, Frank JA. Imaging approaches for the study of cell-based cardiac therapies. Nat Rev Cardiol. 2009;7:97-105.

  • 14. Mahrholdt H, Wagner A, Holly TA, et al. Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging. Circulation. 2002;106: 2322-2327.

  • 15. Al Saadi N, Nagel E, Gross M, et al. Noninvasive detection of myocardial ischemia from perfusion reserve based on cardiovascular magnetic resonance. Circulation. 2000;101:1379-1383.

  • 16. Baer FM, Theissen P, Schneider CA, et al. Dobutamine magnetic resonance imaging predicts contractile recovery of chronically dysfunctional myocardium after successful revascularization. J Am Coll Cardiol. 1998;31:1040-1048.

  • 17. Hassan AA, Anja Z. Delayed Enhancement and T2-Weighted Cardiovascular Magnetic Resonance Imaging Differentiate Acute From Chronic Myocardial Infarction. Circulation. 2003;107:2290-2293.

  • 18. Wagner A, Mahrholdt H, Holly TA, et al. Contrast-enhanced MRI and routine single photon emission computed tomography (SPECT) perfusion imaging for detection of subendocardial myocardial infarcts: an imaging study. Lancet. 2003;361:374-379.

  • 19. Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. Eur Heart J. 2007;28:2525-2538.

  • 20. Dash R, Kim PJ, Matsuura Y, et al. Manganese-enhanced MRI enables in vivo confirmation of peri-infarct restoration following stem cell therapy in porcine ischemia-reperfusion model. J Am Heart Assoc. 2015;4:e002044.

  • 21. Choi KM, Kim RJ, Gubernikoff G, et al. Transmural extent of acute myocardial infarction predicts long-term improvement in contractile function. Circulation. 2001;104:1101-1107.

  • 22. Gerber BL, Garot J, Bluemke DA, Wu KC, Lima JAC. Accuracy of contrast-enhanced magnetic resonance imaging in predicting improvement of regional myocardial function in patients after acute myocardial infarction. Circulation. 2002;106:1083-1089.

  • 23. Kim RJ, Fieno DS, Parrish TB, et al. Relationship of MRI delayed contrast enhancement to irreversible injury, infarct age, and contractile function. Circulation.1999;100:1992-2002.

  • 24. van Assche LMR, Kim HW, Kim RJ. Cardiac Mr For The Assessment Of Myocardial Viability. Methodist Debakey Cardiovascular Journal. 2013;9:163-168.

  • 25. Romero J, Xue X, Gonzalez W, et al. CMR imaging assessing viability in patients with chronic ventricular dysfunction due to coronary artery disease: a meta-analysis of prospective trials. JACC Cardiovasc Imaging. 2012;5:494-508.

  • 26. Cwajg JM, Cwajg E, Nagueh SF, et al. End-diastolic wall thickness as a predictor of recovery of function in myocardial hibernation: relation to rest-redistribution T1-201 tomography and dobutamine stress echocardiography. J Am Coll Cardiol. 2000;35:1152-1161.

  • 27. Shah DJ, Kim HW, Elliott M, et al. Contrast MRI predicts reverse remodeling and contractile improvement in akinetic thinned myocardium. Circulation. 2003;108:697.

  • 28. Wu YW, Tadamura E, Yamamuro M, et al. Comparison of contrast-enhanced MRI with (18) F-FDG PET/201Tl SPECT in dysfunctional myocardium: relation to early functional outcome after surgical revascularization in chronic ischemic heart disease. J Nucl Med. 2007;48:1096-1103.

  • 29. Grover S, Srinivasan G, Selvanayagam JB. Myocardial viability imaging: does it still have a role in patient selection prior to coronary revascularisation? Heart Lung Circ. 2012;21:468-479.

  • 30. Xi L, Rui X, Zhang B, Gao F. MRI tracking stem cells transplantation for coronary heart disease. Pak J Med Sci. 2014;30:899-903.

  • 31. Sterenczak KA, Meier M, Glage S, et al. Longitudinal MRI contrast enhanced monitoring of early tumour development with manganese chloride (MnCl2) and superparamagnetic iron oxide nanoparticles (SPIOs) in a CT1258 based in vivo model of prostate cancer. BMC Cancer. 2012;12:284.

  • 32. Guenoun J, Koning GA, Doeswijk G, et al. Cationic Gd-DTPA liposomes for highly efficient labeling of mesenchymal stem cells and cell tracking with MRI. Cell Transplant. 2012;21:191-205.

  • 33. Mamani JB, Pavon LF, Miyaki LA, et al. Intracellular labeling and quantification process by magnetic resonance imaging using iron oxide magnetic nanoparticles in rat C6 glioma cell line. Einstein. 2012;10:216-221.

  • 34. Vuong QL, Van Doorslaer S, Bridot JL, et al. Paramagnetic nanoparticles as potential MRI contrast agents: characterization, NMR relaxation, simulations and theory. MAGMA. 2012; 25:467-478.

  • 35. Bowen CV, Zhang X, Saab G, Gareau PJ, Rutt BK. Application of the static dephasing regime theory to superparamagnetic iron-oxide loaded cells. Magn Reson Med. 2002;48:52-61.

  • 36. Moriel V. Cardiac Cell Tracking with MRI Reporter Genes: Welcoming a New Field. Curr Cardiovasc Imaging Rep. 2014;7:9250.

  • 37. Vandsburger MH, Radoul M, et al. MRI reporter genes: applications for imaging of cell survival, proliferation, migration and differentiation. NMR Biomed. 2013;26:872-84.

  • 38. Lee SW, Lee SH, et al. Magnetic resonance reporter gene imaging. Theranostics.2012;2:403-12.

  • 39. Naumova AV, Reinecke H, et al. Ferritin overexpression for noninvasive magnetic resonance imaging-based tracking of stem cells transplanted into the heart. Mol Imaging. 2010 Aug;9:201-210.

  • 40. Naumova AV, Yarnykh VL, Cohen B, Neeman M. Quantification of MRI signal of transgenic grafts overexpressing ferritin in murine myocardial infarcts. NMR Biomedicine. 2012;25:1187-1195.

  • 41. Moriel Vandsburger. Cardiac Cell Tracking with MRI Reporter Genes: Welcoming a New Field. Curr Cardiovasc Imaging Rep. 2014;7:9250.

  • 42. Patricia KN, Feng L, Wang Y, Wu JC. Imaging: Guiding the Clinical Translation of Cardiac Stem Cell Therapy. Circ Res. 2011;109:962-979.

  • 43. David E. Sosnovik. Seeing What We Build—The Need for New Imaging Techniques in Myocardial Regeneration. J Am Heart Assoc. 2015;4:e002306.

  • 44. Cao F, Lin S, Xie X, et al. In vivo visualization of embryonic stem cell survival, proliferation, and migration after cardiac delivery. Circulation. 2006;113:1005-1014.

  • 45. Terrovitis JV, Smith RR, Marbán E. Assessment and Optimization of Cell Engraftment after Transplantation into the Heart. Circ Res. 2010;106:479-494.

  • 46. Amsalem Y, Mardor Y, Feinberg MS, et al. Iron-oxide labeling and outcome of transplanted mesenchymal stem cells in the infarcted myocardium. Circulation. 2007;116:38-45.

  • 47. Terrovitis J, Stuber M, et al. Iron-labeled stem cells seen by magnetic resonance imaging: dead or alive? Circulation. 2006;114:264.

  • 48. Partlow KC, Chen J, Brant J, Wickline SA. 19F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. FASEB J. 2007;21:1647-1654.

  • 49. Berry MF, Engler AJ, Woo YJ, et al. Mesenchymal stem cell injection after myocardial infarction improves myocardial compliance. Am J Physiol Heart Circ Physiol. 2006;290:2196-2203.

  • 50. Nesteruk J, Voronina N, Kundt G, et al. Stem cell registry programme for patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting: what benefits does it derive? ESC Heart Fail. 2017;4:105-111.

  • 51. Traverse JH, Henry TD, Pepine CJ, Willerson JT, Ellis SG. One-Year Follow-up of Intracoronary Stem Cell Delivery on Left-Ventricular Function Following ST-Elevation Myocardial Infarction. JAMA. 2014;311:301-302.

  • 52. Malliaras K, Makkar RR, Smith RR, et al. Intracoronary Cardiosphere-Derived Cells After Myocardial Infarction: Evidence of Therapeutic Regeneration in the Final 1-Year Results of the CADUCEUS Trial. J Am Coll Cardiol. 2014;63(2):110-122.

  • 53. Lipinski MJ, Biondi-Zoccai GG, Abbate A, Vetrovec GW. Impact of intracoronary cell therapy on left ventricular function in the setting of acute myocardial infarction: a collaborative systematic review and meta-analysis of controlled clinical trials. J Am Coll Cardiol. 2007;50:1761-1767.

  • 54. Martin-Rendon E, Brunskill SJ, Hyde CJ, Stanworth SJ, Mathur A, Watt SM. Autologous bone marrow stem cells to treat acute myocardial infarction: a systematic review. Eur Heart J. 2008;29:1807-1818.

  • 55. Delewi R, Hirsch A, Tijssen JG, et al. Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis. Eur Heart J. 2014;35:989-998.

  • 56. Jeevanantham V, Butler M, Saad A, et al. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation. 2012;126:551-568.


Journal + Issues