Title:
Size-dependent ferrohydrodynamic relaxometry of magnetic particle imaging tracers in different environments.

Abstract:
Magnetic particle imaging (MPI) is a recently developed imaging technique that seeks to provide ultrahigh resolution and tracer sensitivity with positive contrast directly originated from superparamagnetic iron oxide nanoparticles (NPs). MPI signals can be generated from a combination of Néel relaxation, Brownian rotational diffusion, and hysteretic reversal mechanisms of NPs in response to applied magnetic fields. When specific targeting of organs, such as carcinoma and endothelial cardiovascular cells, is needed, different behavior may be expected in immobilized NPs, due to complete or partial elimination of the Brownian motion. Here, the authors present an experimental investigation of the MPI spatial resolution and signal intensities as a function of a wide range of median core sizes of NPs under four representative conditions, including after immobilization in a tissue equivalent medium.
Monodisperse hydrophobic NPs with median core diameters (d0) ranging from 7 to 22 nm were synthesized in organic media and subsequently dispersed in aqueous solution after a facile surface modification. Morphology, median size, size distribution, and magnetic properties of the NPs were investigated. Hydrophobic and hydrophilic NPs with various core sizes were immobilized in trioctyl phosphine oxide and agarose gel, respectively. Their size-dependent performance as MPI tracers for system matrix and x-space image reconstruction was evaluated using magnetic particle spectrometry (MPS) and compared with the free rotating counterparts.
Immobilized NPs with core diameters smaller than ≈ 20 nm have similar spatial resolution, but lower signal intensities when compared with their free rotating counterparts. Compared to their performance in solution, spatial resolution was improved, but signal intensity was lower, when larger NPs with core size of 22 nm were immobilized in agarose. Same trends were observed in signal intensities, when considering either system matrix or x-space approaches. The harmonic and dm/dH signal intensities changed linearly and the spatial resolution did not change with decreasing NP concentration up to 15 μg/ml.
The results show that the MPI signal is very sensitive to both NP size and environment. The authors' calculations show that Brownian rotational diffusion is slower than the field switching cycle and, therefore, it has minimal influence on MPS signals. dm/dH analyses show that Néel relaxation is the dominant mechanism determining MPI response in smaller NPs (d0 < ≈ 20 nm). Larger NPs show hysteretic reversal when the applied field amplitude is large enough to overcome the coercivity. Linear variation of the MPS signal intensity with iron concentration but with uniform spatial resolution enables quantitative imaging for a range of applications, from high-concentration bolus chase imaging to low-concentration molecular imaging (while the authors' instrument is noise-limited to ≈ millimolar iron concentrations, nanomolar sensitivity is expected for MPI, theoretically). These results pave the way for future application of the authors' synthesized tracers for immobilized or in vivo targeted MPI of tissues.