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Visualization of immune cell infiltration in experimental viral myocarditis by 19F MRI in vivo

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Abstract

Objective

This paper introduces a new approach permitting for the first time a specific, non-invasive diagnosis of myocarditis by visualizing the infiltration of immune cells into the myocardium.

Materials and methods

The feasibility of this approach is shown in a murine model of viral myocarditis. Our study uses biochemically inert perfluorocarbons (PFCs) known to be taken up by circulating monocytes/macrophages after intravenous injection.

Results

In vivo 19F MRI at 9.4 T demonstrated that PFC-loaded immune cells infiltrate into inflamed myocardial areas. Because of the lack of any fluorine background in the body, detected 19F signals of PFCs are highly specific as confirmed ex vivo by flow cytometry and histology.

Conclusion

Since PFCs are a family of compounds previously used clinically as blood substitutes, the technique described in our paper holds the potential as a new imaging modality for the diagnosis of myocarditis in man.

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References

  1. Kawai C (1999) From myocarditis to cardiomyopathy: mechanisms of inflammation and cell death: learning from the past for the future. Circulation 99:1091–1100

    Article  CAS  PubMed  Google Scholar 

  2. Magnani JW, Dec GW (2006) Myocarditis: current trends in diagnosis and treatment. Circulation 113:876–890

    Article  PubMed  Google Scholar 

  3. Friedrich MG, Sechtem U, Schulz-Menger J, Holmvang G, Alakija P, Cooper LT, White JA, Abdel-Aty H, Gutberlet M, Prasad S, Aletras A, Laissy JP, Paterson I, Filipchuk NG, Kumar A, Pauschinger M, Liu P (2009) Cardiovascular magnetic resonance in myocarditis: a JACC white paper. J Am Coll Cardiol 53:1475–1487

    Article  PubMed Central  PubMed  Google Scholar 

  4. Hundley WG, Bluemke DA, Finn JP, Flamm SD, Fogel MA, Friedrich MG, Ho VB, Jerosch-Herold M, Kramer CM, Manning WJ, Patel M, Pohost GM, Stillman AE, White RD, Woodard PK (2010) ACCF/ACR/AHA/NASCI/SCMR 2010 expert consensus document on cardiovascular magnetic resonance: a report of the American college of cardiology foundation task force on expert consensus documents. Circulation 121:2462–2508

    Article  PubMed  Google Scholar 

  5. Weissleder R, Elizondo G, Wittenberg J, Rabito CA, Bengele HH, Josephson L (1990) Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging. Radiology 175:489–493

    CAS  PubMed  Google Scholar 

  6. Kleinschnitz C, Bendszus M, Frank M, Solymosi L, Toyka KV, Stoll G (2003) In vivo monitoring of macrophage infiltration in experimental ischemic brain lesions by magnetic resonance imaging. J Cereb Blood Flow Metab 23:1356–1361

    Article  CAS  PubMed  Google Scholar 

  7. Kok MB, Hak S, Mulder WJ, van der Schaft DW, Strijkers GJ, Nicolay K (2009) Cellular compartmentalization of internalized paramagnetic liposomes strongly influences both T1 and T2 relaxivity. Magn Reson Med 61:1022–1032

    Article  CAS  PubMed  Google Scholar 

  8. Flögel U, Ding Z, Hardung H, Jander S, Reichmann G, Jacoby C, Schubert R, Schrader J (2008) In vivo monitoring of inflammation after cardiac and cerebral ischemia by fluorine magnetic resonance imaging. Circulation 118:140–148

    Article  PubMed Central  PubMed  Google Scholar 

  9. Flögel U, Su S, Kreideweiss I, Ding Z, Galbarz L, Fu J, Jacoby C, Witzke O, Schrader J (2011) Noninvasive detection of graft rejection by in vivo 19F MRI in the early stage. Am J Transplant 11:235–244

    Article  PubMed  Google Scholar 

  10. Temme S, Bonner F, Schrader J, Flögel U (2012) 19F magnetic resonance imaging of endogenous macrophages in inflammation. Wiley Interdiscip Rev Nanomed Nanobiotechnol 4:329–343

    Article  CAS  PubMed  Google Scholar 

  11. Klingel K, Hohenadl C, Canu A, Albrecht M, Seemann M, Mall G, Kandolf R (1992) Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci USA 89:314–318

    Article  CAS  PubMed  Google Scholar 

  12. Ebner B, Behm P, Jacoby C, Burghoff S, French BA, Schrader J, Flögel U (2010) Early assessment of pulmonary inflammation by 19F MRI in vivo. Circ Cardiovasc Imaging 3:202–210

    Article  PubMed Central  PubMed  Google Scholar 

  13. Bönner F, Borg N, Burghoff S, Schrader J (2012) Resident cardiac immune cells and expression of the ectonucleotidase enzymes CD39 and CD73 after ischemic injury. PLoS One 7:e34730

    Article  PubMed Central  PubMed  Google Scholar 

  14. Mason RP, Shukla H, Antich PP (1993) In vivo oxygen tension and temperature: simultaneous determination using 19F NMR spectroscopy of perfluorocarbon. Magn Reson Med 29:296–302

    Article  CAS  PubMed  Google Scholar 

  15. Shukla HP, Mason RP, Bansal N, Antich PP (1996) Regional myocardial oxygen tension: 19F MRI of sequestered perfluorocarbon. Magn Reson Med 35:827–833

    Article  CAS  PubMed  Google Scholar 

  16. Ruiz-Cabello J, Barnett BP, Bottomley PA, Bulte JW (2011) Fluorine (19F) MRS and MRI in biomedicine. NMR Biomed 24:114–129

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Yu JX, Kodibagkar VD, Cui W, Mason RP (2005) 19F: a versatile reporter for non-invasive physiology and pharmacology using magnetic resonance. Curr Med Chem 12:819–848

    Article  CAS  PubMed  Google Scholar 

  18. Holland GN, Bottomley PA, Hinshaw WS (1977) 19F magnetic resonance imaging. J Magn Reson 28:133–136

    CAS  Google Scholar 

  19. Schwitter J (2008) Extending the frontiers of cardiac magnetic resonance. Circulation 118:109–112

    Article  PubMed  Google Scholar 

  20. van Heeswijk RB, De Blois J, Kania G, Gonzales C, Blyszczuk P, Stuber M, Eriksson U, Schwitter J (2013) Selective in vivo visualization of immune-cell infiltration in a mouse model of autoimmune myocarditis by fluorine-19 cardiac magnetic resonance. Circ Cardiovasc Imaging 6:277–284

    Google Scholar 

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Acknowledgments

This study was supported in part by the Sonderforschungsbereich 612 (JS, UF) and Transregio 19 (RK, KK), the Deutsche Forschungsgemeinschaft grant SCHR 154/13-1 (JS), and the BMBF grant 01EZ0817 (RK, KK).

Note added in proof

While this paper was under review, we became aware of an independent study by van Heeswijk et al. [20] which used a similar 19F MRI approach for in vivo visualization of immune cell infiltration in a murine model of autoimmune myocarditis.

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Correspondence to Ulrich Flögel.

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10334_2013_391_MOESM1_ESM.mpg

Supplemental Movie 1: Reconstruction of a murine heart from isotropic high resolution 3D 1H and 19F MR data sets (voxel size 0.125 nl) confirmed the prevalent confinement of the 19F signal to the left ventricular wall in CVB3-induced myocarditis. Contours of the heart and left/right chambers (green) were reconstructed from 1H MRI and overlayed by volume rendered anatomic corresponding 19F data (red). (MPG 7382 kb)

Supplementary material 2 (PPTX 972 kb)

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Jacoby, C., Borg, N., Heusch, P. et al. Visualization of immune cell infiltration in experimental viral myocarditis by 19F MRI in vivo. Magn Reson Mater Phy 27, 101–106 (2014). https://doi.org/10.1007/s10334-013-0391-6

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  • DOI: https://doi.org/10.1007/s10334-013-0391-6

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