T1 Mapping in Stem Cell Therapy

  • Yoko Kato
  • Mohammad R. Ostovaneh
  • Bharath Ambale-VenkateshEmail author
  • Joao Lima


Cell therapy is increasingly seen as a viable technique to recover myocardial function by reverse remodeling. The goal of cell therapy is the functional recovery of the heart and consequently prognostic improvement, but the results of prior research has been inconsistent and controversial. Basic science experiments have also shown that cell therapy may improve myocardial function by reducing myocardial fibrosis and promoting the growth of active myocytes. From the aspect of imaging, late gadolinium enhancement imaging alone may not be sufficient to identify the effects of cell therapy. T1 mapping with its’ increased sensitivity to detect diffuse interstitial fibrosis may be seen as a viable and attractive endpoint, particularly, as it pertains to subtle changes in the structure of the underlying extracellular matrix. T1 mapping has also shown prognostic value in studies in participants with non-ischemic cardiomyopathy. The rationale to use T1 mapping in stem cell therapy exists on its utility to assess current disease status, as well as the assessment of future prognosis.


T1 mapping Stem cell therapy Ischemic heart disease Nonischemic cardiomyopathy Late gadolinium enhancement (LGE) Cardiac MRI Cellular cardiomyoplasty Myocardial scar Extracellular volume (ECV) 


  1. 1.
    Chiu RC, Zibaitis A, Kao RL. Cellular cardiomyoplasty: myocardial regeneration with satellite cell implantation. Ann Thorac Surg. 1995;60:12–8.CrossRefPubMedGoogle Scholar
  2. 2.
    Perin EC, Dohmann HFR, Borojevic R, et al. Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation. 2003;107(18):2294–302. Scholar
  3. 3.
    Psaltis PJ, Zannettino ACW, Gronthos S, Worthley SG. Intramyocardial navigation and mapping for stem cell delivery. J Cardiovasc Transl Res. 2010;3:135–46.CrossRefPubMedGoogle Scholar
  4. 4.
    Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarction: the BOOST randomised controlled clinical trial. Lancet. 2004;364:141–8.CrossRefPubMedGoogle Scholar
  5. 5.
    Lunde K, Solheim S, Aakhus S, et al. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med. 2006;355:1199–209.CrossRefPubMedGoogle Scholar
  6. 6.
    Hirsch A, Nijveldt R, van der Vleuten PA, et al. Intracoronary infusion of mononuclear cells from bone marrow or peripheral blood compared with standard therapy in patients after acute myocardial infarction treated by primary percutaneous coronary intervention: results of the randomized controlled HEBE. Eur Heart J. 2011;32:1736–47.CrossRefPubMedGoogle Scholar
  7. 7.
    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 (CArdiosphere-Derived aUtologous stem CElls to reverse ventricUlar dySfunction). J Am Coll Cardiol. 2014;63:110–22.CrossRefPubMedGoogle Scholar
  8. 8.
    Bolli R, Chugh AR, D’Amario D, et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet (London, England). 2011;378:1847–57.CrossRefGoogle Scholar
  9. 9.
    Heldman AW, DiFede DL, Fishman JE, et al. Transendocardial mesenchymal stem cells and mononuclear bone marrow cells for ischemic cardiomyopathy: the TAC-HFT randomized trial. JAMA. 2014;311:62–73.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Fischer-Rasokat U, Assmus B, Seeger FH, et al. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regenerat. Circ Heart Fail. 2009;2:417–23.CrossRefPubMedGoogle Scholar
  11. 11.
    Seth S, Bhargava B, Narang R, Ray R, Mohanty S, Gulati G, Kumar L, Airan B, Venugopal P, AIIMS Stem Cell Study Group. The ABCD (Autologous Bone Marrow Cells in Dilated Cardiomyopathy) trial a long-term follow-up study. J Am Coll Cardiol. 2010;55:1643–4.CrossRefPubMedGoogle Scholar
  12. 12.
    Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, Cernelc P, Torre-Amione G, Haddad F, Wu JC. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013;128:S42–9.CrossRefPubMedGoogle Scholar
  13. 13.
    Hare JM, DiFede DL, Rieger AC, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy. J Am Coll Cardiol. 2017;69:526–37.CrossRefPubMedGoogle Scholar
  14. 14.
    Lee J-W, Lee S-H, Youn Y-J, et al. A randomized, open-label, multicenter trial for the safety and efficacy of adult mesenchymal stem cells after acute myocardial infarction. J Korean Med Sci. 2014;29:23.CrossRefPubMedGoogle Scholar
  15. 15.
    Madonna R, Van Laake LW, Davidson SM, et al. Position paper of the European Society of Cardiology Working Group cellular biology of the heart: cell-based therapies for myocardial repair and regeneration in ischemic heart disease and heart failure. Eur Heart J. 2016;37:1789–98.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Hare JM, Fishman JE, Gerstenblith G, et al. Comparison of allogeneic vs autologous bone marrow–derived mesenchymal stem cells delivered by transendocardial injection in patients with ischemic cardiomyopathy. JAMA. 2012;308:2369.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Charoenpanichkit C, Hundley W. The 20 year evolution of dobutamine stress cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2010;12:59.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Meyer GP, Wollert KC, Lotz J, et al. Intracoronary bone marrow cell transfer after myocardial infarction: eighteen months’ follow-up data from the randomized, controlled BOOST (Bone marrow transfer to enhance ST-elevation infarct regeneration) trial. Circulation. 2006;113:1287–94.CrossRefPubMedGoogle Scholar
  19. 19.
    Fisher SA, Zhang H, Doree C, Mathur A, Martin-Rendon E. Stem cell treatment for acute myocardial infarction. Cochrane Database Syst Rev. 2015;(2):CD006536.Google Scholar
  20. 20.
    Afzal MR, Samanta A, Shah ZI, Jeevanantham V, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy for ischemic heart disease: evidence and insights from randomized controlled trials. Circ Res. 2015;117:558–75.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Henry TD, Moyé L, Traverse JH. Consistently inconsistent-bone marrow mononuclear stem cell therapy following acute myocardial infarction: a decade later. Circ Res. 2016;119:404–6.CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Suerder D, Manka R, Moccetti T, et al. The effect of bone marrow derived mononuclear cell treatment, early or late after acute myocardial infarction: twelve months CMR and long-term clinical results. Circ Res. 2016;119(3):481–90. Scholar
  23. 23.
    Solomon SD, Anavekar N, Skali H, et al. Influence of ejection fraction on cardiovascular outcomes in a broad spectrum of heart failure patients. Circulation. 2005;112:3738–44.CrossRefPubMedGoogle Scholar
  24. 24.
    Hsu JJ, Ziaeian B, Fonarow GC. Heart failure with mid-range (borderline) ejection fraction. JACC Hear Fail. 2017;5:763–71.CrossRefGoogle Scholar
  25. 25.
    Yan AT, Shayne AJ, Brown KA, Gupta SN, Chan CW, Luu TM, Di Carli MF, Reynolds HG, Stevenson WG, Kwong RY. Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality. Circulation. 2006;114:32–9.CrossRefPubMedGoogle Scholar
  26. 26.
    Avelar E, Strickland CR, Rosito G. Role of imaging in cardio-oncology. Curr Treat Options Cardiovasc Med. 2017;19(6):46. Scholar
  27. 27.
    Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, Klocke FJ, Bonow RO, Judd RM. The use of contrast-enhanced magnetic resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. 2000;343:1445–53.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Hamirani YS, Wong A, Kramer CM, Salerno M. Effect of microvascular obstruction and intramyocardial hemorrhage by CMR on LV remodeling and outcomes after myocardial infarction: a systematic review and meta-analysis. JACC Cardiovasc Imaging. 2014;7:940–52.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Gulati A, Jabbour A, Ismail TF, et al. Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA. 2013;309:896–908.CrossRefPubMedGoogle Scholar
  30. 30.
    Assomull RG, Prasad SK, Lyne J, Smith G, Burman ED, Khan M, Sheppard MN, Poole-Wilson PA, Pennell DJ. Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy. J Am Coll Cardiol. 2006;48:1977–85.CrossRefPubMedGoogle Scholar
  31. 31.
    Bruder O, Wagner A, Jensen CJ, et al. Myocardial scar visualized by cardiovascular magnetic resonance imaging predicts major adverse events in patients with hypertrophic cardiomyopathy. J Am Coll Cardiol. 2010;56:875–87.CrossRefPubMedGoogle Scholar
  32. 32.
    Greulich S, Deluigi CC, Gloekler S, et al. CMR imaging predicts death and other adverse events in suspected cardiac sarcoidosis. JACC Cardiovasc Imaging. 2013;6:501–11.CrossRefPubMedGoogle Scholar
  33. 33.
    Mahrholdt H, Wagner A, Judd RM, Sechtem U, Kim RJ. Delayed enhancement cardiovascular magnetic resonance assessment of non-ischaemic cardiomyopathies. Eur Heart J. 2005;26:1461–74.CrossRefPubMedGoogle Scholar
  34. 34.
    Puntmann VO, Carr-White G, Jabbour A, et al. T1-mapping and outcome in nonischemic cardiomyopathy. JACC Cardiovasc Imaging. 2016;9:40–50.CrossRefPubMedGoogle Scholar
  35. 35.
    Neilan TG, Coelho-Filho OR, Shah RV, et al. Myocardial extracellular volume by cardiac magnetic resonance imaging in patients treated with anthracycline-based chemotherapy. Am J Cardiol. 2013;111:717–22.CrossRefPubMedGoogle Scholar
  36. 36.
    Ambale-Venkatesh B, Lima JAC. Cardiac MRI: a central prognostic tool in myocardial fibrosis. Nat Rev Cardiol. 2015;12:18–29.CrossRefPubMedGoogle Scholar
  37. 37.
    Mewton N, Liu CY, Croisille P, Bluemke D, Lima JAC. Assessment of myocardial fibrosis with cardiovascular magnetic resonance. J Am Coll Cardiol. 2011;57:891–903.CrossRefPubMedGoogle Scholar
  38. 38.
    Maestrini V, Treibel TA, White SK, Fontana M, Moon JC. T1 mapping for characterization of intracellular and extracellular myocardial diseases in heart failure. Curr Cardiovasc Imaging Rep. 2014;7:1–7.CrossRefGoogle Scholar
  39. 39.
    Puntmann VO, Peker E, Chandrashekhar Y, Nagel E. T1 mapping in characterizing myocardial disease: a comprehensive review. Circ Res. 2016;119:277–99.CrossRefPubMedGoogle Scholar
  40. 40.
    Haaf P, Garg P, Messroghli DR, Broadbent DA, Greenwood JP, Plein S. Cardiac T1 mapping and extracellular volume (ECV) in clinical practice: a comprehensive review. J Cardiovasc Magn Reson. 2017;18:89.CrossRefGoogle Scholar
  41. 41.
    Liu C-Y, Liu Y-C, Wu C, et al. Evaluation of age-related interstitial myocardial fibrosis with cardiac magnetic resonance contrast-enhanced T1 mapping: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2013;62:1280–7.CrossRefPubMedGoogle Scholar
  42. 42.
    Donekal S, Venkatesh BA, Liu YC, et al. Interstitial fibrosis, left ventricular remodeling, and myocardial mechanical behavior in a population-based multiethnic cohort: the multi-ethnic study of atherosclerosis (mesa) study. Circ Cardiovasc Imaging. 2014;7:292–302.CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Inoue YY, Ambale-Venkatesh B, Mewton N, et al. Electrocardiographic impact of myocardial diffuse fibrosis and scar: MESA (Multi-Ethnic Study of Atherosclerosis). Radiology. 2017;282:690–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Yi CJ, Wu CO, Tee M, et al. The association between cardiovascular risk and cardiovascular magnetic resonance measures of fibrosis: the Multi-Ethnic Study of Atherosclerosis (MESA). J Cardiovasc Magn Reson. 2015;17(1):15.CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Reinstadler SJ, Stiermaier T, Liebetrau J, et al. 9Prognostic significance of remote myocardium alterations assessed by quantitative noncontrast T1 mapping in ST-segment elevation myocardial infarction. JACC Cardiovasc Imaging. 2017;11(3):411–9. Scholar
  46. 46.
    Biesbroek PS, Amier RP, Teunissen PFA, Hofman MBM, Robbers LFHJ, van de Ven PM, Beek AM, van Rossum AC, van Royen N, Nijveldt R. Changes in remote myocardial tissue after acute myocardial infarction and its relation to cardiac remodeling: a CMR T1 mapping study. PLoS One. 2017;12:1–13.CrossRefGoogle Scholar
  47. 47.
    Youn J-C, Hong YJ, Lee H-J, et al. Contrast-enhanced T1 mapping-based extracellular volume fraction independently predicts clinical outcome in patients with non-ischemic dilated cardiomyopathy: a prospective cohort study. Eur Radiol. 2017;27(9):3924–33. Scholar
  48. 48.
    Hamdy A, Kitagawa K, Ishida M, Sakuma H. Native myocardial T1 mapping, are we there yet? Int Heart J. 2016;57:400–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Venkatesh BA, Volpe GJ, Donekal S, et al. Association of longitudinal changes in left ventricular structure and function with myocardial fibrosis: the Multi-Ethnic Study of Atherosclerosis study. Hypertension. 2014;64:508–15.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Yoko Kato
    • 1
  • Mohammad R. Ostovaneh
    • 1
  • Bharath Ambale-Venkatesh
    • 2
    Email author
  • Joao Lima
    • 1
    • 2
  1. 1.Department of CardiologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of RadiologyJohns Hopkins University School of MedicineBaltimoreUSA

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