The relaxation wall: experimental limits to improving MPI spatial resolution by increasing nanoparticle core size

Abstract

Magnetic Particle Imaging (MPI) is a promising new tracer modality with zero attenuation in tissue, high contrast and sensitivity, and an excellent safety profile. However, the spatial resolution of MPI is currently around 1 mm in small animal scanners. Especially considering tradeoffs when scaling up MPI scanning systems to human size, this resolution needs to be improved for clinical applications such as angiography and brain perfusion. One method to improve spatial resolution is to increase the magnetic core size of the superparamagnetic nanoparticle tracers. The Langevin model of superparamagnetism predicts a cubic improvement of spatial resolution with magnetic core diameter. However, prior work has shown that the finite temporal response, or magnetic relaxation, of the tracer increases with magnetic core diameter and eventually leads to blurring in the MPI image. Here we perform the first wide ranging study of 5 core sizes between 18–32 nm with experimental quantification of the spatial resolution of each. Our results show that increasing magnetic relaxation with core size eventually opposes the expected Langevin behavior, causing spatial resolution to stop improving after 25 nm. Different MPI excitation strategies were experimentally investigated to mitigate the effect of magnetic relaxation. The results show that magnetic relaxation could not be fully mitigated for the larger core sizes and the cubic resolution improvement predicted by the Langevin was not achieved. This suggests that magnetic relaxation is a significant and unsolved barrier to achieving the high spatial resolutions predicted by the Langevin model for large core size SPIOs.

Phase-sensitive small-angle neutron scattering experiment

“…High-resolution transmission electron microscopy and powder x-ray diffraction confirm that the cores consist of Fe 3 O 4 with no indications of other phases [14]. Magnetometry data shows that the magnetization of the cores is almost fully saturated at an applied magnetic field of 100 mT and reaches a saturation magnetization of about 70 Am 2 /kg Fe 3 O 4 [13][14][15] corresponding to · 3.6 10 5 A/m which is about 75% of the value for bulk magnetite.…”

In vivo tracking and quantification of inhaled aerosol using magnetic particle imaging towards inhaled therapeutic monitoring

“…The imaging performances of spatial resolution and sensitivity depend on the magnetic core. Attention should be given to phase purity 64 and the magnetic core size should be kept to ~25 nm for optimal imaging performance for single-core nanoparticles 53 . Multi-core nanoparticles should follow formulations similar to Resovist TM or recent multi-core SPION work 65 .…”

“…Individual cores within each multi-core cluster have average size ~5.5 ± 2 nm. The dynamic magnetization properties at MPI scanning parameters (20.225 kHz and 40 mTpp), which are more relevant to MPI performance than static magnetization, were measured by a custom-built magnetic particle spectrometer MPS as described previously 52 , 53 . The linearity of MPI signal with aerosol mass to validate MPI-based quantification of SPION-based aerosol is plotted in Figure 3 C .…”

Magnetic particle imaging for radiation-free, sensitive and high-contrast vascular imaging and cell tracking

“…Both theory and experiment have shown that 5–20 nm core sizes show poor resolution 47–49 . Larger core sizes ( > 27 nm) do not perform as well as the optimal range of 20–26 nm, due to relaxation blurring 50 . While 1–2 mm resolution is comparable to nuclear medicine’s resolution, a dramatic improvement in spatial resolution (100 microns) would obviate perhaps the last technical weakness of MPI.…”