Abstract Body:

Magnetic Particle Imaging (MPI) is an emerging positive-contrast imaging modality that directly images superparamagnetic iron oxide (SPIO) tracers in the body [1]. The magnetic properties of the MPI tracers govern spatial resolution and sensitivity. Current MPI applications include Cancer, Stroke, Cell Tracking, WBC-MPI, Pulmonary Embolism Imaging and GI bleeds. MPI’s only significant weakness is poor spatial resolution, now about 1.5 mm in a mouse [2]. All MPI studies to date assume non-interacting SPIOs.  Recently, our group has demonstrated that up to 28-fold boost in SNR and spatial resolution in each dimension is possible with interacting SPIOs [3].  Several experiments support the “chaining hypothesis”, that the resolution boost is due to the formation of linear SPIO particle chains, which locally amplify the applied magnetic fields [3, 4].  We call these new high-resolution tracers superferromagnetic, because they display both remanence and coercivity [5].

Objective: We do not yet know the fundamental resolution limits of superferromagnetic iron oxide (SFMIO) tracers and we do not yet have an effective encapsulation method for in vivo use. The resolution could be limited by Brownian relaxation (physical rotation of the entire SPIO) or Néel relaxation (electronic re-alignment) [6]. These mechanisms occur in parallel, and so the faster one dominates and they depend on SPIO core size, shape and field strength [7]. Brownian relaxation times scale linearly with viscosity.  Because encapsulation methods for synthesizing safe, in vivo SFMIO tracers could effectively block Brownian rotation, it is crucial to establish which mechanism dominates the rotation.

Methods: We performed arbitrary waveform relaxometry to determine the MPI point spread functions (PSFs) of SFMIOs before and after immobilization.  We also compared the immobilized SFMIO tracers’ resolution when oriented and perpendicular to the drive field. 

Aliquots of in-house synthesized SFMIOs were colloidally stabilized in hexanes. Samples were imaged in the Berkeley Arbitrary Waveform Relaxometer (AWR) [8] to ensure that superferromagnetic behaviour was observed. A control sample was stored at room temperature and two were selected for immobilization. Sample polarization was performed in a uniform permanent magnet Helmholtz configuration to ensure chain orientation parallel to the AWR transmit axis. One test sample was incubated with styrene and heated to 70ºC until complete polymerization took place, yielding a solid sample with embedded SFMIO chains. Another test sample was incubated with molten docosane at 80ºC and cooled until solid. The control and polymerized samples were imaged in the AWR to obtain PSFs, from which the relaxation mechanisms were gleaned.  

Results: Immobilized tracer samples displayed PSFs compatible with superferromagnetism, with coercivities nearly identical to the control sample. Signal strength and resolution loss in the superferromagnetic signal peak was minimal, indicating that magnetization reversal in superferromagnetic chains is consistent with the electronic Néel mechanism. When the immobilized SFMIO sample was imaged in an orientation perpendicular to the AWR transmit field axis, the MPI PSF was severely degraded. Unpolarized SFMIOs displayed no signal post-immobilization, indicating that polarization and chain formation are essential for maintaining high resolution and SNR. 

Conclusion: We have successfully demonstrated that magnetization reversal in linear chains of SPIOs is dominated by the Néel mechanism since the MPI PSF is not degraded post-immobilization. The significant signal degradation in unpolarized SFMIO chains and polarized chains oriented perpendicular to the transmit field direction indicates that, as expected, the chains must be oriented with the drive field to retain high resolution. This will provide crucial physico-chemical insight into SFMIO encapsulation techniques and also inform MPI pulse sequences and hardware to best optimize the SFMIO super-resolution. 

Image/Figure:

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Image/Figure Caption:

Figure 1. 2D MPI images obtained in the UC Berkeley MPI scanner of (A) commercial SPIOs and (B) Berkeley SFMIOs in identical phantoms shows the order-of-magnitude resolution improvements in SFMIOs over SPIOs; (C) MPI point spread functions (PSFs) of conventional SPIOs and high-resolution SFMIOs in a colloidal (freely rotating) solution. Note the coercivity present in SFMIOs but lacking in SPIOs; (D) PSFs of polystyrene-immobilized SFMIO chains show coercivity, high resolution and high signal strength in chains polarized parallel to the transmit field axis. Significant signal and resolution degradation was observed in perpendicularly polarized chains, while no observable MPI PSF was present for unpolarized SFMIOs; (E) PSF of docosane-immobilized SFMIOs shows coercivity, signal strength and resolution consistent with superferromagnetism.

Author

Chinmoy Saayujya
University of California, Berkeley