Positive contrast with therapeutic iron nanoparticles at 4.7 T

  • Monica SigovanEmail author
  • Misara Hamoudeh
  • Achraf Al Faraj
  • Delphine Charpigny
  • Hatem Fessi
  • Emmanuelle Canet-Soulas
Research Article



The purpose of the study was to show the feasibility of a positive contrast technique GRadient echo Acquisition for Superparamagnetic particles with Positive contrast (GRASP), for a specific type of magnetic particles, designed for tumor treatment under MRI monitoring.

Materials and methods

A simulation study was performed to estimate field inhomogeneity intensities induced by increasing concentrations of particles at different static fields. The GRASP sequence was setup on a 4.7 T Bruker system during an in vitro study. Six mice, included in the in vivo study received particles in the left calf muscle and contrast enhancement values, were measured over three time points, for both negative and positive contrast images.


Comparing values obtained by simulation at 1.5, 3, and 4.7 T, the strongest susceptibility effect was obtained at 4.7 T. Based on simulation and in vitro data, gradient settings were chosen for in vivo imaging. GRASP resulted in bright regions at and around the injection site, and higher enhancement values, compared to standard GRE imaging. Both contrasts were useful for longitudinal follow-up, with a faster decay over time for GRASP.


The magnetic nanoparticles for drug delivery can be detected using positive contrast. Combining imaging sequences, i.e., negative contrast and susceptibility methods, increased imaging specificity of large magnetic particles and enabled their follow-up for theranostic applications.


Superparamagnetic iron oxide Positive contrast GRASP 


  1. 1.
    Wang YX, Hussain SM, Krestin GP (2001) Superparamagnetic iron oxide contrast agents: physicochemical characteristics and applications in MR imaging. Eur Radiol 11(11): 2319–2331PubMedCrossRefGoogle Scholar
  2. 2.
    Hamoudeh M, Al Faraj A, Canet-Soulas E, Bessueille F, Leonard D, Fessi H (2007) Elaboration of PLLA-based superparamagnetic nanoparticles: Characterization, magnetic behaviour study and in vitro relaxivity evaluation. Int J Pharm 338(1–2): 248–257PubMedCrossRefGoogle Scholar
  3. 3.
    Yang QX, Williams GD, Demeure RJ, Mosher TJ, Smith MB (1998) Removal of local field gradient artifacts in T2*-weighted images at high fields by gradient-echo slice excitation profile imaging. Magn Reson Med 39(3): 402–409PubMedCrossRefGoogle Scholar
  4. 4.
    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
  5. 5.
    Dharmakumar R, Koktzoglou I, Li D (2006) Generating positive contrast from off-resonant spins with steady-state free precession magnetic resonance imaging: theory and proof-of-principle experiments. Phys Med Biol 51(17): 4201–4215PubMedCrossRefGoogle Scholar
  6. 6.
    Faber C, Heil C, Zahneisen B, Balla DZ, Bowtell R (2006) Sensitivity to local dipole fields in the CRAZED experiment: an approach to bright spot MRI. J Magn Reson 182(2): 315–324PubMedCrossRefGoogle Scholar
  7. 7.
    Mani V, Briley-Saebo KC, Hyafil F, Fayad ZA (2006) Feasibility of in vivo identification of endogenous ferritin with positive contrast MRI in rabbit carotid crush injury using GRASP. Magn Reson Med 56(5): 1096–1106PubMedCrossRefGoogle Scholar
  8. 8.
    Zurkiya O, Hu X (2006) Off-resonance saturation as a means of generating contrast with superparamagnetic nanoparticles. Magn Reson Med 56(4): 726–732PubMedCrossRefGoogle Scholar
  9. 9.
    Seppenwoolde JH, Viergever MA, Bakker CJ (2003) Passive tracking exploiting local signal conservation: the white marker phenomenon. Magn Reson Med 50(4): 784–790PubMedCrossRefGoogle Scholar
  10. 10.
    Mani V, Briley-Saebo KC, Itskovich VV, Samber DD, Fayad ZA (2006) Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): sequence characterization in membrane and gl ass superparamagnetic iron oxide phantoms at 1.5 and 3 T. Magn Reson Med 55(1): 126–135PubMedCrossRefGoogle Scholar
  11. 11.
    Mani V, Adler E, Briley-Saebo KC, Bystrup A, Fuster V, Keller G, Fayad ZA (2008) Serial in vivo positive contrast MRI of iron oxide-labeled embryonic stem cell-derived cardiac precursor cells in a mouse model of myocardial infarction. Magn Reson Med 60(1): 73–81PubMedCrossRefGoogle Scholar
  12. 12.
    Benoit-Cattin H, Collewet G, Belaroussi B, Saint-Jalmes H, Odet C (2005) The SIMRI project: a versatile and interactive MRI simulator. J Magn Reson 173(1): 97–115PubMedCrossRefGoogle Scholar
  13. 13.
    Derbyshire WDI (1974) NMR of agarose gel. Faraday discussions of the chemical society 57: 243–254CrossRefGoogle Scholar
  14. 14.
    Kanayama S, Kuhara S, Satoh K (1996) In vivo rapid magnetic field measurement and shimming using single scan differential phase mapping. Magn Reson Med 36(4): 637–642PubMedCrossRefGoogle Scholar
  15. 15.
    de Rochefort LNT, Brown R, Spincemaille P, Choi G, Weinsaft J, Prince MR, Wang Y (2008) In vivo quantification of contrast agent concentration using the induced magnetic field for time-resolved arterial input function measurement with MRI. Med Phys 35(12): 5328–5339PubMedCrossRefGoogle Scholar
  16. 16.
    Langley J, Liu W, Jordan EK, Frank JA, Zhao Q (2010) Quantification of SPIO nanoparticles in vivo using the finite perturber method. Magn Reson Med 65(5): 1461–1469PubMedCrossRefGoogle Scholar
  17. 17.
    Hamoudeh M, Fessi H, Mehier H, Faraj AA, Canet-Soulas E (2008) Dirhenium decacarbonyl-loaded PLLA nanoparticles: influence of neutron irradiation and preliminary in vivo administration by the TMT technique. Int J Pharm 348(1–2): 125–136PubMedCrossRefGoogle Scholar
  18. 18.
    Canet E, Revel D, Forrat R, Baldy-Porcher C, de Lorgeril M, Sebbag L, Vallee JP, Didier D, Amiel M (1993) Superparamagnetic iron oxide particles and positive enhancement for myocardial perfusion studies assessed by subsecond T1-weighted MRI. Magn Reson Imaging 11(8): 1139–1145PubMedCrossRefGoogle Scholar
  19. 19.
    Zhao Q, Langley J, Lee S, Liu W (2010) Positive contrast technique for the detection and quantification of superparamagnetic iron oxide nanoparticles in MRI. NMR Biomed. doi: 10.1002/nbm.1608
  20. 20.
    Dahnke H, Schaeffter T (2005) Limits of detection of SPIO at 3.0 T using T2 relaxometry. Magn Reson Med 53(5): 1202–1206PubMedCrossRefGoogle Scholar
  21. 21.
    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
  22. 22.
    Seppenwoolde JH, Oude Engberink R, van der Toorn A, Blezer EL, Bakker CJ (2006) Selective MRI of magnetically labeled cells—a comparative evaluation of positive contrast techniques. Proc Intl Soc Mag Reson Med, Seattle, Washington, USA, p 360Google Scholar
  23. 23.
    Briley-Saebo KC, Cho YS, Tsimikas S (2011) Imaging of oxidation-specific epitopes in atherosclerosis and macrophage-rich vulnerable plaques. Curr Cardiovasc Imaging Rep 4(1): 4–16PubMedCrossRefGoogle Scholar
  24. 24.
    Liu W, Dahnke H, Jordan EK, Schaeffter T, Frank JA (2008) In vivo MRI using positive-contrast techniques in detection of cells labeled with superparamagnetic iron oxide nanoparticles. NMR Biomed 21(3): 242–250PubMedCrossRefGoogle Scholar
  25. 25.
    Seppenwoolde JH, Vincken KL, Bakker CJ (2007) White-marker imaging—separating magnetic susceptibility effects from partial volume effects. Magn Reson Med 58(3): 605–609PubMedCrossRefGoogle Scholar
  26. 26.
    Brisset JC, 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 (2010) Quantification of iron-labeled cells with positive contrast in mouse brains. Mol Imaging Biol. doi: 10.1007/s11307-010-0402-1

Copyright information

© ESMRMB 2011

Authors and Affiliations

  • Monica Sigovan
    • 1
    Email author
  • Misara Hamoudeh
    • 2
  • Achraf Al Faraj
    • 1
  • Delphine Charpigny
    • 1
  • Hatem Fessi
    • 2
  • Emmanuelle Canet-Soulas
    • 1
  1. 1.CREATIS-LRMN, UMR CNRS 5220, U630 INSERMLyon-1 UniversityLyonFrance
  2. 2.Pharmaceutics and Pharmaceutical Technology Department, LAGEP, Laboratoire d’Automatique et de Génie de Procédés, UMR CNRS 5007, CPE-Lyon, Faculté de Pharmacie Lyon1Lyon-1 UniversityLyonFrance

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