Important Considerations in the Design of Iron Oxide Nanoparticles as Contrast Agents for Tl-Weighted MRI and MRA

Abstract

Organically coated magnetic monocrystalline iron oxide nanoparticles are being considered as contrast agents for T1-weighted magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) ( 1 Frank H Weissleder R Brady TJ Enhancement of MR angiography with iron oxide: preliminary studies in whole blood phantoms and animals. AJR Am J Roentgenol. 1994; 162: 209-213 Crossref PubMed Scopus (86) Google Scholar , 2 Knollmann FD Böck JC Teltenkötter S et al. Evaluation of portal MR angiography using superparamagnetic iron oxide. J Magn Reson Imaging. 1997; 7: 191-196 Crossref PubMed Scopus (20) Google Scholar , 3 Anzai Y Prince MR Chenevert TL et al. MR angiography with an ultrasmall superparamagnetic iron oxide blood pool agent. J Magn Reson Imaging. 1997; 7: 209-214 Crossref PubMed Scopus (149) Google Scholar , 4 Tobe K Yoshikawa K Seno A et al. Good resolution of contrast-enhanced MRA using USPIO on coronal plane acquisition. Acad Radiol. 1998; 5: S116-S118 Abstract Full Text PDF PubMed Google Scholar ). For such Tl-weighted applications, imaging efficacy is strongly dependent on the physical characteristics of the individual nanoparticles ( 5 Kellar KE Fujii DK Gunther WHH Briley-Sæbø K Spiller M Koenig SH “NC100150,” a preparation of iron oxide nanoparticles ideal for positive-contrast MR angiography. MAGMA. 1999; 8: 207-213 PubMed Google Scholar ). In particular, three stringent physical requirements must be satisfied. First, the magnetic cores must be of an optimal size with essentially a monodisperse size distribution. If the cores are too small, rl (the Tl relaxivity) will be too small for practical applications as T1 agents; if the cores are too large, r2 (the T2 relaxivity) may be so large relative to rl that the T1 efficacy of the particles will be diminished. Second, the high-field magnetization of the cores, typically close to its saturation value, must be sufficient to relax water protons effectively, also implying that the organic coating must not compromise access of solvent to the core. This high-field limit is related to both the total iron content of the cores and their geometry. Third, the nanoparticles cannot become agglomerated in vivo. Given that r2 is very sensitive to agglomeration and rl is not, agglomeration preferentially increases r2, thereby diminishing the efficacy of the nanoparticles as Tl agents.