In vivo visualization of cells labeled with superparamagnetic iron oxides by a sub-millisecond gradient echo sequence

  • Xeni Deligianni
  • Daniel Jirák
  • Zuzana Berková
  • Milan Hájek
  • Klaus Scheffler
  • Oliver Bieri
Research Article

Abstract

Object

In vivo magnetic resonance imaging (MRI) of iron-labeled pancreatic islets (PIs) transplanted into the liver is still challenging in humans. The aim of this study was to develop and evaluate a double contrast method for the detection of PIs labeled with superparamagnetic iron oxide (SPIO) nanoparticles.

Materials and methods

A double-echo three-dimensional (3D) spoiled gradient echo sequence was adapted to yield a sub-millisecond first echo time using variable echo times and highly asymmetric Cartesian readout. Positive contrast was achieved by conventional and relative image subtraction. Experiments for cell detection efficiency were performed in vitro on gelatin phantoms, in vivo on a Lewis rat and on a patient 6 months after PI transplantation.

Results

It was demonstrated that the proposed method can be used for the detection of transplanted PIs with positive contrast in vitro and in vivo. For all experiments, relative subtraction yielded comparable and in some cases better contrast than conventional subtraction. For the first time, positive contrast imaging of transplanted human PIs was performed in vivo in patients.

Conclusion

The proposed method allows 3D data acquisition within a single breath-hold and yields enhanced contrast-to-noise ratios of transplanted SPIO labeled pancreatic islets relative to negative contrast images, therefore providing improved identification.

Keywords

Variable echo time 3T MRI SPIO Pancreatic islets Diabetes Positive contrast 

Notes

Acknowledgments

The study was supported by the grant project (Ministry of Health, Czech Republic) for development of research organization 00023001 (IKEM, Prague, Czech Republic)—Institutional support and by grant ENCITE—Seventh EU Framework Program, number 201842 and by the Ministry of education, youth and sports of the Czech Republic, IC 7E08102 and by the grant IGA NT/13099 from Ministry of Health of the Czech Republic. This work was supported by Bayer Schering Pharma, of Switzerland. The study sponsor played no role in matters of design, collection, analysis, interpretation of data, and writing of the report. We thank Nicolin Hainc for reading and commenting on the paper.

References

  1. 1.
    Liu W, Frank JA (2009) Detection and quantification of magnetically labeled cells by cellular MRI. Eur J Radiol 70(2):258–264PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Langley J, Liu W, Jordan EK, Frank JA, Zhao Q (2011) Quantification of SPIO nanoparticles in vivo using the finite perturber method. Magn Reson Med 65(5):1461–1469PubMedCentralPubMedCrossRefGoogle Scholar
  3. 3.
    Bulte JWM, Kraitchman DL (2004) Iron oxide MR contrast agents for molecular and cellular imaging. NMR Biomed 17(7):484–499PubMedCrossRefGoogle Scholar
  4. 4.
    Robertson RP (2004) Islet transplantation as a treatment for diabetes—a work in progress. N Engl J Med 350(7):694–705PubMedCrossRefGoogle Scholar
  5. 5.
    Shapiro AMJ, Lakey JRT, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV (2000) Islet transplantation in seven patients with Type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343(4):230–238PubMedCrossRefGoogle Scholar
  6. 6.
    Jirák D, Kríz J, Herynek V, Andersson B, Girman P, Burian M, Saudek F, Hájek M (2004) MRI of transplanted pancreatic islets. Magn Reson Med 52:1228–1233PubMedCrossRefGoogle Scholar
  7. 7.
    Jirak D, Kriz J, Strzelecki M, Yang J, Hasilo C, White DJ, Foster PJ (2009) Monitoring the survival of islet transplants by MRI using a novel technique for their automated detection and quantification. Magn Reson Mater Phy 22(4):257–265CrossRefGoogle Scholar
  8. 8.
    Jiao Y, Peng Z-H, Xing T-H, Qin J, Zhong C-P (2008) Assessment of islet graft survival using a 3.0-Tesla magnetic resonance scanner. Anat Rec 291(12):1684–1692CrossRefGoogle Scholar
  9. 9.
    Evgenov NV, Medarova Z, Pratt J, Pantazopoulos P, Leyting S, Bonner-Weir S, Moore A (2006) In vivo imaging of immune rejection in transplanted pancreatic islets. Diabetes 55(9):2419–2428PubMedCrossRefGoogle Scholar
  10. 10.
    Toso C, Vallee J-P, Morel P, Ris F, Demuylder-Mischler S, Lepetit-Coiffe M, Marangon N, Saudek F, Shapiro AMJ, Bosco D, Berney T (2008) Clinical magnetic resonance imaging of pancreatic islet grafts after iron nanoparticle labeling. Am J Transplant 8(3):701–706PubMedCrossRefGoogle Scholar
  11. 11.
    Saudek F, Jirak D, Girman P, Herynek V, Dezortova M, Kriz J, Peregrin J, Berkova Z, Zacharova K, Hajek M (2010) Magnetic resonance imaging of pancreatic islets transplanted into the liver in humans. Transplantation 90(12):1602–1606PubMedCrossRefGoogle Scholar
  12. 12.
    Zacharova K, Berkova Z, Jirak D, Herynek V, Vancova M, Dovolilova E, Saudek F (2012) Processing of superparamagnetic iron contrast agent ferucarbotran in transplanted pancreatic islets. Contrast Media Mol Imaging 7(6):485–493CrossRefGoogle Scholar
  13. 13.
    Marzola P, Longoni B, Szilagyi E, Merigo F, Nicolato E, Fiorini S, Paoli GT, Benati D, Mosca F, Sbarbati A (2009) In vivo visualization of transplanted pancreatic islets by MRI: comparison between in vivo, histological and electron microscopy findings. Contrast Media Mol Imaging 4(3):135–142PubMedCrossRefGoogle Scholar
  14. 14.
    Wu S, Zhang L, Zhong J, Zhang Z (2010) Dual contrast magnetic resonance imaging tracking of iron-labeled cells in vivo. Cytotherapy 12(7):859–869PubMedCrossRefGoogle Scholar
  15. 15.
    Brisset J-C, Sigovan M, Chauveau F, Riou A, Devillard E, Desestret V, Touret M, Nataf S, Honnorat J, Canet-Soulas E, Nighoghossian N, Berthezene Y, Wiart M (2011) Quantification of iron-labeled cells with positive contrast in mouse brains. Mol Imaging Biol 13(4):672–678PubMedCrossRefGoogle Scholar
  16. 16.
    Cunningham CH, Arai T, Yang PC, McConnell MV, Pauly JM, Conolly SM (2005) Positive contrast magnetic resonance imaging of cells labeled with magnetic nanoparticles. Magn Reson Med 53(5):999–1005PubMedCrossRefGoogle Scholar
  17. 17.
    Eibofner F, Steidle G, Kehlbach R, Bantleon R, Schick F (2010) Positive contrast imaging of iron oxide nanoparticles with susceptibility-weighted imaging. Magn Reson Med 64(4):1027–1038PubMedCrossRefGoogle Scholar
  18. 18.
    Zhao Q, Langley J, Lee S, Liu W (2011) Positive contrast technique for the detection and quantification of superparamagnetic iron oxide nanoparticles in MRI. NMR Biomed 24(5):464–472PubMedCrossRefGoogle Scholar
  19. 19.
    Crowe LA, Ris F, Nielles-Vallespin S, Speier P, Masson S, Armanet M, Morel P, Toso C, Bosco D, Berney T, Vallee J-P (2011) A novel method for quantitative monitoring of transplanted islets of langerhans by positive contrast magnetic resonance imaging. Am J Transpl 11(6):1158–1168CrossRefGoogle Scholar
  20. 20.
    Bergin CJ, Pauly JM, Macovski A (1991) Lung parenchyma: projection reconstruction MR imaging. Radiology 179(3):777–781PubMedCrossRefGoogle Scholar
  21. 21.
    Robson MD, Gatehouse PD, Bydder M, Bydder GM (2003) Magnetic resonance: an introduction to ultrashort TE (UTE) imaging. J Comput Assist Tomogr 27(6):825–846PubMedCrossRefGoogle Scholar
  22. 22.
    Martirosian P, Schraml C, Springer F, Schwenzer NF, Würslin C, Schick F and Deimling M (2013), Positive contrast MR imaging of tendons, ligaments, and menisci by subtraction of signals from a double echo steady state sequence (Sub-DESS). Magn Reson Med. doi:10.1002/mrm.24651. [Epub ahead of print]
  23. 23.
    Deligianni X, Bär P, Scheffler K, Trattnig S, Bieri O (2012) High-resolution fourier-encoded sub-millisecond echo time musculoskeletal imaging at 3 Tesla and 7 Tesla. Magn Reson Med. doi:10.1002/mrm.24578. [Epub ahead of print]
  24. 24.
    McGibney G, Smith MR, Nichols ST, Crawley A (1993) Quantitative evaluation of several partial Fourier reconstruction algorithms used in MRI. Magn Reson Med 30(1):51–59PubMedCrossRefGoogle Scholar
  25. 25.
    Santini F, Patil S, Scheffler K (2011) IceLuva: a scripting framework for MR image reconstruction based on free software. Concepts Magn Reson B Magn Reson Eng 39B(1):1–10CrossRefGoogle Scholar
  26. 26.
    Ketkar-Atre A, Louchami K, Yin T, Struys T, Malaisse W, Himmelreich U (2013) Longitudinal follow up of pancreatic islets by MRI using labeling with magnetoliposomes. Proc Intl Soc Magn Reson Med 21:4059Google Scholar

Copyright information

© ESMRMB 2013

Authors and Affiliations

  • Xeni Deligianni
    • 1
    • 3
  • Daniel Jirák
    • 2
    • 5
  • Zuzana Berková
    • 2
  • Milan Hájek
    • 2
  • Klaus Scheffler
    • 3
    • 4
  • Oliver Bieri
    • 1
  1. 1.Division of Radiological Physics, Department of Radiology, Clinic of Radiology and Nuclear MedicineUniversity of Basel HospitalBaselSwitzerland
  2. 2.Institute for Clinical and Experimental MedicinePragueCzech Republic
  3. 3.High-Field Magnetic Resonance CenterMax-Planck Institute for Biological CyberneticsTübingenGermany
  4. 4.Department of Biomedical Magnetic ResonanceUniversity Hospital TübingenTübingenGermany
  5. 5.Institute of Biophysics and Informatics, 1st Medicine FacultyCharles UniversityPragueCzech Republic

Personalised recommendations