Off-resonance saturation MRI of superparamagnetic nanoprobes: Theoretical models and experimental validations

Chalermchai Khemtong, Osamu Togao, Jimin Ren, Chase W. Kessinger, Masaya Takahashi, A. Dean Sherry, Jinming Gao

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Off-resonance saturation (ORS) is a new magnetic resonance imaging (MRI) method that has shown greatly improved contrast sensitivity for the detection of cancer-specific biomarkers by superparamagnetic nanoprobes in vivo. However, quantitative understanding of the ORS contrast mechanism and its dependence on the structural parameters of superparamagnetic nanoprobes are still lacking. Here we propose a quantitative model of ORS contrast and its experimental validation by superparamagnetic polymeric micelles (SPPM) with precisely controlled structural properties. Size selected, monodisperse Fe 3O4 nanoparticles (6.1 ± 0.2 nm) were used to form a series of SPPM nanoprobes with specifically controlled corona thickness using 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxypoly(ethylene glycol) (DSPE-PEG) with different PEG molecular weights. Transmission electron microscopy and dynamic light scattering showed that SPPM were uniform in size. The average hydrodynamic diameters of SPPM with PEG lengths of 0.55, 1, 2, and 5 kD were 16.6 ± 2.8, 18.4 ± 2.9, 24.1 ± 3.4, and 28.9 ± 3.4 nm, respectively. MRI experiments at 7T determined that r 2 values of SPPM with 0.55, 1, 2, and 5 kD PEG as corona were 201 ± 3, 136 ± 8, 107 ± 5, and 108 ± 8 Fe mM -1 s-1, respectively. ORS intensity from Z-spectra of SPPM showed a significant correlation with the inverse of T2 relaxation rates (1/T2, s-1) of the SPPM nanoprobes regardless of the PEG corona thickness. These data provide the fundamental understanding of the structure-property relationships between the SPPM nanostructures and ORS sensitivity, which offers useful mechanistic insights for the future improvement of SPPM nanoprobes in cancer molecular imaging applications.

Original languageEnglish (US)
Pages (from-to)53-60
Number of pages8
JournalJournal of Magnetic Resonance
Volume209
Issue number1
DOIs
StatePublished - Mar 2011

Keywords

  • Magnetic resonance imaging
  • Nanoprobes
  • Off-resonance saturation
  • PEG corona length
  • Superparamagnetic polymeric micelles
  • Transverse relaxivity

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Nuclear and High Energy Physics
  • Condensed Matter Physics

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