Shaped Magnetogel Microparticles for Multispectral Magnetic Resonance Contrast and Sensing.

Multispectral magnetic resonance imaging (MRI) contrast agents are microfabricated three-dimensional magnetic structures that encode nearby water protons with discrete frequencies. The agents have a unique radiofrequency (RF) resonance that can be tuned by engineering the geometric parameters of these microstructures. Multispectral contrast agents can be used as sensors by incorporating a stimulus-driven shape-changing response into their structure. These geometrically encoded magnetic sensors (GEMS) enable MRI-based sensing via environmentally induced changes to their geometry and their corresponding RF resonance. Previously, GEMS have been made using thin-film lithography techniques in a cleanroom environment. While these approaches offer precise control of the microstructure, they can be a limitation for researchers who do not have cleanroom access or microfabrication expertise. Here, an alternative approach for GEMS fabrication based on soft lithography is introduced. The fabrication scheme uses cheap, accessible materials and simple chemistry to produce shaped magnetic hydrogel microparticles with multispectral MRI contrast properties. The microparticles can be used as sensors by fabricating them out of shape-reconfigurable, "smart" hydrogels. The change in shape causes a corresponding shift in the resonance of the GEMS, producing an MRI-addressable readout of the microenvironment. Proof-of-principle experiments showing a multispectral response to pH change with cylindrical shell-shaped magnetogel GEMS are presented.

Towards a barrier-free anthropomorphic brain phantom for quantitative magnetic resonance imaging: Design, first construction attempt, and challenges.

Existing magnetic resonance imaging (MRI) reference objects, or phantoms, are typically constructed from simple liquid or gel solutions in containers with specific geometric configurations to enable multi-year stability. However, there is a need for phantoms that better mimic the human anatomy without barriers between the tissues. Barriers result in regions without MRI signal between the different tissue mimics, which is an artificial image artifact. We created an anatomically representative 3D structure of the brain that mimicked the T1 and T2 relaxation properties of white and gray matter at 3 T. While the goal was to avoid barriers between tissues, the 3D printed barrier between white and gray matter and other flaws in the construction were visible at 3 T. Stability measurements were made using a portable MRI system operating at 64 mT, and T2 relaxation time was stable from 0 to 22 weeks. The phantom T1 relaxation properties did change from 0 to 10 weeks; however, they did not substantially change between 10 weeks and 22 weeks. The anthropomorphic phantom used a dissolvable mold construction method to better mimic anatomy, which worked in small test objects. The construction process, though, had many challenges. We share this work with the hope that the community can build on our experience.

Iron oxide nanoparticles as positive T1 contrast agents for low-field magnetic resonance imaging at 64 mT.

We have investigated the efficacy of superparamagnetic iron oxide nanoparticles (SPIONs) as positive T1 contrast agents for low-field magnetic resonance imaging (MRI) at 64 millitesla (mT). Iron oxide-based agents, such as the FDA-approved ferumoxytol, were measured using a variety of techniques to evaluate T1 contrast at 64 mT. Additionally, we characterized monodispersed carboxylic acid-coated SPIONs with a range of diameters (4.9-15.7 nm) in order to understand size-dependent properties of T1 contrast at low-field. MRI contrast properties were measured using 64 mT MRI, magnetometry, and nuclear magnetic resonance dispersion (NMRD). We also measured MRI contrast at 3 T to provide comparison to a standard clinical field strength. SPIONs have the capacity to perform well as T1 contrast agents at 64 mT, with measured longitudinal relaxivity (r1) values of up to 67 L mmol-1 s-1, more than an order of magnitude higher than corresponding r1 values at 3 T. The particles exhibit size-dependent longitudinal relaxivities and outperform a commercial Gd-based agent (gadobenate dimeglumine) by more than eight-fold at physiological temperatures. Additionally, we characterize the ratio of transverse to longitudinal relaxivity, r2/r1 and find that it is ~ 1 for the SPION based agents at 64 mT, indicating a favorable balance of relaxivities for T1-weighted contrast imaging. We also correlate the magnetic and structural properties of the particles with models of nanoparticle relaxivity to understand generation of T1 contrast. These experiments show that SPIONs, at low fields being targeted for point-of-care low-field MRI systems, have a unique combination of magnetic and structural properties that produce large T1 relaxivities.

Effects of fixatives on histomagnetic evaluation of iron in rodent spleen.

Characterizing the iron distribution in tissue sections is important for several pathologies. Iron content in excised tissue is typically analyzed via histochemical stains, which are dependent on sample preparation and staining protocols. In our recent studies, we examined how magnetic properties of iron can also be exploited to characterize iron distribution in tissue sections in a label free manner. To enable a histomagnetic characterization of iron in a wide variety of available tissues, it is important to extend it to samples routinely prepared for histochemical staining, which often involve use of chemical fixatives. In this study, we took a systematic approach to determine differences between unfixed and formalin-fixed murine spleen tissues in histomagnetic characterization of iron. Superconducting quantum interference device (SQUID) magnetometry and magnetic force microscopy (MFM) were used for macro- and micro-scale histomagnetic characterization. Perl's stain was used for histochemical characterization of ferric (Fe3+) iron on adjacent sections as that used for MFM analysis. While histochemical analysis revealed a substantial difference in the dispersion of the stain between fixed versus unfixed samples, histomagnetic characterization was not dependent on chemical fixation of tissue. The results from this study reveal that histomagnetic characterization of iron is free from staining artifacts which can be present in histochemical analysis.

Observation of iron oxide nanoparticle synthesis in magnetogels using magnetic resonance imaging.

We show that magnetic resonance imaging (MRI) can be used to visualize the spatiotemporal dynamics of iron oxide nanoparticle growth within a hydrogel network during in situ coprecipitation. The synthesis creates a magnetic nanoparticle loaded polymer gel, or magnetogel. During in situ coprecipitation, iron oxide nanoparticles nucleate and grow due to diffusion of a precipitating agent throughout an iron precursor loaded polymer network. The creation of iron oxide particles changes the magnetic properties of the gel, allowing the synthesis to be monitored via magnetic measurements. Formation of iron oxide nanoparticles generates dark, or hypointense, contrast in gradient echo (GRE) images acquired by MRI, allowing nanoparticle nucleation to be tracked in both space and time. We show that the growth of iron oxide nanoparticles in the hydrogel scaffold is consistent with a simple reaction-diffusion model.

Patterned Surface Energy in Elastomeric Molds as a Generalized Approach to Polymer Particle Fabrication.

We present a generic fabrication scheme to produce polymer microparticles with engineerable, complex shapes. The polymer particles are made from polyethylene glycol based hydrogels using a poly(dimethylsiloxane) (PDMS) molding technique. A simple surface treatment is used to pattern the surface energy of the PDMS molds, engendering the recessed wells in the molds with a higher surface energy than that of the surface. The contrast in surface energy causes hydrogel precursor to wet only the inside of the molds, creating isolated particles after curing with UV light. This eliminates the formation of an interconnecting "scum" layer and allows for fabrication of well-defined, independent particles. We discuss resolution limits for the approach and present a simple strategy for releasing the particles. Finally, to show how the fabrication technique is inherently compatible with further particle modifications, we also demonstrate magnetic functionalization of particles.

Spin canting across core/shell Fe3O4/MnxFe3-xO4 nanoparticles.

Magnetic nanoparticles (MNPs) have become increasingly important in biomedical applications like magnetic imaging and hyperthermia based cancer treatment. Understanding their magnetic spin configurations is important for optimizing these applications. The measured magnetization of MNPs can be significantly lower than bulk counterparts, often due to canted spins. This has previously been presumed to be a surface effect, where reduced exchange allows spins closest to the nanoparticle surface to deviate locally from collinear structures. We demonstrate that intraparticle effects can induce spin canting throughout a MNP via the Dzyaloshinskii-Moriya interaction (DMI). We study ~7.4 nm diameter, core/shell Fe3O4/MnxFe3-xO4 MNPs with a 0.5 nm Mn-ferrite shell. Mössbauer spectroscopy, x-ray absorption spectroscopy and x-ray magnetic circular dichroism are used to determine chemical structure of core and shell. Polarized small angle neutron scattering shows parallel and perpendicular magnetic correlations, suggesting multiparticle coherent spin canting in an applied field. Atomistic simulations reveal the underlying mechanism of the observed spin canting. These show that strong DMI can lead to magnetic frustration within the shell and cause canting of the net particle moment. These results illuminate how core/shell nanoparticle systems can be engineered for spin canting across the whole of the particle, rather than solely at the surface.

Origin of reduced magnetization and domain formation in small magnetite nanoparticles.

The structural, chemical, and magnetic properties of magnetite nanoparticles are compared. Aberration corrected scanning transmission electron microscopy reveals the prevalence of antiphase boundaries in nanoparticles that have significantly reduced magnetization, relative to the bulk. Atomistic magnetic modelling of nanoparticles with and without these defects reveals the origin of the reduced moment. Strong antiferromagnetic interactions across antiphase boundaries support multiple magnetic domains even in particles as small as 12-14 nm.