Molecular Imaging and Biology

, Volume 11, Issue 1, pp 31–38 | Cite as

An In Vivo Multimodal Imaging Study Using MRI and PET of Stem Cell Transplantation after Myocardial Infarction in Rats

  • Catherine Chapon
  • Johanna S. Jackson
  • Eric O. Aboagye
  • Amy H. Herlihy
  • William A. Jones
  • Kishore K. Bhakoo
Research Article



The purpose of the study is to track iron-oxide nanoparticle-labelled adult rat bone marrow-derived stem cells (IO-rBMSCs) by magnetic resonance imaging (MRI) and determine their effect in host cardiac tissue using 2-deoxy-2-[F-18]fluoro-d-glucose-positron emission tomography (FDG-PET).


Infarcted rats were randomised to receive (1) live IO-rBMSCs by direct local injection, or (2) dead IO-rBMSCs as controls; (3) sham-operated rats received live IO-rBMSCs. The rats were then imaged from 2 days to 6 weeks post-cell implantation using both MRI at 9.4T and FDG-PET.


Implanted IO-rBMSCs were visible in the heart by MRI for the duration of the study. Histological analysis confirmed that the implanted IO-rBMSCs were present for up to 6 weeks post-implantation. At 1 week post-IO-rBMSC transplantation, PET studies demonstrated an increase in FDG uptake in infarcted regions implanted with live IO-rBMSC compared to controls.


Noninvasive multimodality imaging allowed us to visualise IO-rBMSCs and establish their affect on cardiac function in a rat model of myocardial infarction (MI).

Key words

Myocardial infarction MRI PET Stem cell Rat 


  1. 1.
    Orlic D, Kajstura J, Chimenti S et al (2001) Bone marrow cells regenerate infarcted myocardium. Nature 410:701–705CrossRefPubMedGoogle Scholar
  2. 2.
    Tse HF, Kwong YL, Chan JK et al (2003) Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet 361:47–49CrossRefPubMedGoogle Scholar
  3. 3.
    Perin EC, Dohmann HF, Borojevic R et al (2003) Transendocardial, autologous bone marrow cell transplantation for severe, chronic ischemic heart failure. Circulation 107:2294–2302CrossRefPubMedGoogle Scholar
  4. 4.
    Stamm C, Westphal B, Kleine HD et al (2003) Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet 361:45–46CrossRefPubMedGoogle Scholar
  5. 5.
    Strauer BE, Brehm M, Zeus T et al (2002) Repair of infarcted myocardium by autologous intracoronary mononuclear bone marrow cell transplantation in humans. Circulation 106:1913–1918CrossRefPubMedGoogle Scholar
  6. 6.
    Reffelmann T, Kloner RA (2003) Cellular cardiomyoplasty–cardiomyocytes, skeletal myoblasts, or stem cells for regenerating myocardium and treatment of heart failure? Cardiovasc Res 58:358–368CrossRefPubMedGoogle Scholar
  7. 7.
    Kraitchman DL, Tatsumi M, Gilson WD et al (2005) Dynamic imaging of allogeneic mesenchymal stem cells trafficking to myocardial infarction. Circulation 112:1451–1461CrossRefPubMedGoogle Scholar
  8. 8.
    Hill JM, Dick AJ, Raman VK et al (2003) Serial cardiac magnetic resonance imaging of injected mesenchymal stem cells. Circulation 108:1009–1014CrossRefPubMedGoogle Scholar
  9. 9.
    Stuckey DJ, Carr CA, Martin-Rendon E et al (2006) Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment into, and isolation of viable engrafted donor cells from, the heart. Stem Cells 24:1968–1975CrossRefPubMedGoogle Scholar
  10. 10.
    Tossios P, Muller-Ehmsen J, Schmidt M et al (2006) No evidence of myocardial restoration following transplantation of mononuclear bone marrow cells in coronary bypass grafting surgery patients based upon cardiac SPECT and 18F-PET. BMC Med Imaging 6:7CrossRefPubMedGoogle Scholar
  11. 11.
    Depre C, Vanoverschelde JL, Melin JA et al (1995) Structural and metabolic correlates of the reversibility of chronic left ventricular ischemic dysfunction in humans. Am J Physiol 268:H1265–H1275PubMedGoogle Scholar
  12. 12.
    Pagano D, Townend JN, Parums DV et al (2000) Hibernating myocardium: morphological correlates of inotropic stimulation and glucose uptake. Heart 83:456–461CrossRefPubMedGoogle Scholar
  13. 13.
    Camici PG, Dutka DP (2001) Repetitive stunning, hibernation, and heart failure: contribution of PET to establishing a link. Am J Physiol Heart Circ Physiol 280:H929–H936PubMedGoogle Scholar
  14. 14.
    Knuesel PR, Nanz D, Wyss C et al (2003) Characterization of dysfunctional myocardium by positron emission tomography and magnetic resonance: relation to functional outcome after revascularization. Circulation 108:1095–1100CrossRefPubMedGoogle Scholar
  15. 15.
    Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284:143–147CrossRefPubMedGoogle Scholar
  16. 16.
    Josephson L, Tung CH, Moore A et al (1999) High-efficiency intracellular magnetic labeling with novel superparamagnetic-Tat peptide conjugates. Bioconjug Chem 10:186–191CrossRefPubMedGoogle Scholar
  17. 17.
    Himes N, Min JY, Lee R et al (2004) In vivo MRI of embryonic stem cells in a mouse model of myocardial infarction. Magn Reson Med 52:1214–1219CrossRefPubMedGoogle Scholar
  18. 18.
    Cahill KS, Germain S, Byrne BJ et al (2004) Non-invasive analysis of myoblast transplants in rodent cardiac muscle. Int J Cardiovasc Imaging 20:593–598CrossRefPubMedGoogle Scholar
  19. 19.
    Makino S, Fukuda K, Miyoshi S et al (1999) Cardiomyocytes can be generated from marrow stromal cells in vitro. J Clin Invest 103:697–705CrossRefPubMedGoogle Scholar
  20. 20.
    Nagaya N, Fujii T, Iwase T et al (2004) Intravenous administration of mesenchymal stem cells improves cardiac function in rats with acute myocardial infarction through angiogenesis and myogenesis. Am J Physiol Heart Circ Physiol 287:H2670–2676CrossRefPubMedGoogle Scholar
  21. 21.
    Jaquet K, Krause KT, Denschel J et al (2005) Reduction of myocardial scar size after implantation of mesenchymal stem cells in rats: what is the mechanism? Stem Cells Dev 14:299–309CrossRefPubMedGoogle Scholar
  22. 22.
    Amado LC, Saliaris AP, Schuleri KH et al (2005) Cardiac repair with intramyocardial injection of allogeneic mesenchymal stem cells after myocardial infarction. Proc Natl Acad Sci USA 102:11474–11479CrossRefPubMedGoogle Scholar
  23. 23.
    Dai W, Hale SL, Martin BJ et al (2005) Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardium: short- and long-term effects. Circulation 112:214–223CrossRefPubMedGoogle Scholar
  24. 24.
    Tomita S, Li RK, Weisel RD et al (1999) Autologous transplantation of bone marrow cells improves damaged heart function. Circulation 100:II247–II256PubMedGoogle Scholar
  25. 25.
    Miyahara Y, Nagaya N, Kataoka M et al (2006) Monolayered mesenchymal stem cells repair scarred myocardium after myocardial infarction. Nat Med 12:459–465CrossRefPubMedGoogle Scholar
  26. 26.
    Rudd JH, Warburton EA, Fryer TD et al (2002) Imaging atherosclerotic plaque inflammation with [18F]-fluorodeoxyglucose positron emission tomography. Circulation 105:2708–2711CrossRefPubMedGoogle Scholar
  27. 27.
    Zhang Z, Machac J, Helft G et al (2006) Non-invasive imaging of atherosclerotic plaque macrophage in a rabbit model with F-18 FDG PET: a histopathological correlation. BMC Nucl Med 6:3CrossRefPubMedGoogle Scholar

Copyright information

© Academy of Molecular Imaging 2008

Authors and Affiliations

  • Catherine Chapon
    • 1
  • Johanna S. Jackson
    • 1
  • Eric O. Aboagye
    • 2
  • Amy H. Herlihy
    • 3
  • William A. Jones
    • 1
  • Kishore K. Bhakoo
    • 1
  1. 1.Stem Cell ImagingMRC Clinical Sciences Centre, Imperial College LondonLondonUK
  2. 2.Molecular TherapyMRC Clinical Sciences Centre, Imperial College London, Hammersmith HospitalLondonUK
  3. 3.Biological Imaging Centre, Imaging Science DepartmentMRC Clinical Sciences Centre, Imperial College London, Hammersmith HospitalLondonUK

Personalised recommendations