Magnetic Particle Imaging Performance Research Articles

Post-synthesis Oxidation of Superparamagnetic Iron Oxide Nanoparticles to Enhance Magnetic Particle Imaging Performance.

This study investigates the impact of post-synthesis oxidation on the performance of superparamagnetic iron oxide nanoparticles (SPIONs) in magnetic particle imaging (MPI), an emerging technology with applications in diagnostic imaging and theranostics. SPIONs synthesized from iron oleate were subjected to a post-synthesis oxidation treatment with a 1% Oxygen in Argon mixture. MPI performance, gauged via signal intensity and resolution using a MOMENTUM™ scanner, was correlated to the nanoparticles' physical and magnetic properties. Post-synthesis oxidation did not alter physical attributes like size and shape, but significantly enhanced magnetic properties. Saturation magnetization increased from 52% to 93% of the bulk value for magnetite, leading to better MPI performance in terms of signal intensity and resolution. However, the observed MPI performance did not fully align with predictions based on the ideal Langevin model, indicating the need for considering factors like relaxation and shape anisotropy. The findings underscore the potential of post-synthesis oxidation as a method to fine-tune magnetic properties of SPIONs and improve MPI performance, and the need for reproducible synthesis methods that afford finely tuned control of nanoparticle size, shape, and magnetic properties.

Adhesion molecule-targeted magnetic particle imaging nanoprobe for visualization of inflammation in acute lung injury.

Uncontrolled intra-alveolar inflammation is a central pathogenic feature, and its severity translates into a valid prognostic indicator of acute lung injury (ALI). Unfortunately, current clinical imaging approaches are unsuitable for visualizing and quantifying intra-alveolar inflammation. This study aimed to construct a small-sized vascular cell adhesion molecule-1 (VCAM-1)-targeted magnetic particle imaging (MPI) nanoprobe (ESPVPN) to visualize and accurately quantify intra-alveolar inflammation at the molecular level. ESPVPN was engineered by conjugating a peptide (VHPKQHRGGSK(Cy7)GC) onto a polydopamine-functionalized superparamagnetic iron oxide core. The MPI performance, targeting, and biosafety of the ESPVPN were characterized. VCAM-1 expression in HUVECs and mouse models was evaluated by western blot. The degree of inflammation and distribution of VCAM-1 in the lungs were assessed using histopathology. The expression of pro-inflammatory markers and VCAM-1 in lung tissue lysates was measured using ELISA. After intravenous administration of ESPVPN, MPI and CT imaging were used to analyze the distribution of ESPVPN in the lungs of the LPS-induced ALI models. The small-sized (~10 nm) ESPVPN exhibited superior MPI performance compared to commercial MagImaging® and Vivotrax, and ESPVPN had effective targeting and biosafety. VCAM-1 was highly expressed in LPS-induced ALI mice. VCAM-1 expression was positively correlated with the LPS-induced dose (R = 0.9381). The in vivo MPI signal showed positive correlations with both VCAM-1 expression (R = 0.9186) and representative pro-inflammatory markers (MPO, TNF-α, IL-6, IL-8, and IL-1β, R > 0.7). ESPVPN effectively targeted inflammatory lungs and combined the advantages of MPI quantitative imaging to visualize and evaluate the degree of ALI inflammation.

Multi-scale dual domain network for nonlinear magnetization signal filtering in magnetic particle imaging

Magnetic particle imaging (MPI) realizes functional imaging by generating nonlinear response signals in the magnetic field through magnetic nanoparticles. MPI is a highly sensitive tracer-based imaging technology, which opens new possibilities for promising biomedical applications. However, in practice, the background signals, including random thermal noise from MPI receive chains and the harmonic interference caused by nonlinear components under a high-frequency excitation field, restrict the MPI performance. In this study, we propose a learning-based method by training a multi-scale dual-domain network to effectively filter the MPI signals. In the model, a multi-channel filtering module was designed to suppress the noise-related features in time and frequency domains. We constructed four different MPI signal datasets including simulated and measured noises acquired from a homemade MPI system to verify our method. The signal filtering tests were performed on synthetic and measured data. The experimental results indicated that our method can achieve the best performance among state-of-art signal filtering methods. Especially, on the dataset containing measured noise, our proposal improved the signal-to-noise ratio from 6.88 dB to 29.11 dB. Moreover, the percentage root means square difference was reduced from 51.26 to 3.96 and the root mean square error was reduced from 65.07×10-4 to 5.29×10-4.

Dual imaging agent for magnetic particle imaging and computed tomography.

Magnetic particle imaging (MPI) is a novel biomedical imaging modality that allows non-invasive, tomographic, and quantitative tracking of the distribution of superparamagnetic iron oxide nanoparticle (SPION) tracers. While MPI possesses high sensitivity, detecting nanograms of iron, it does not provide anatomical information. Computed tomography (CT) is a widely used biomedical imaging modality that yields anatomical information at high resolution. A multimodal imaging agent combining the benefits of MPI and CT imaging would be of interest. Here we combine MPI-tailored SPIONs with CT-contrast hafnium oxide (hafnia) nanoparticles using flash nanoprecipitation to obtain dual-imaging MPI/CT agents. Co-encapsulation of iron oxide and hafnia in the composite nanoparticles was confirmed via transmission electron microscopy and elemental mapping. Equilibrium and dynamic magnetic characterization show a reduction in effective magnetic diameter and changes in dynamic magnetic susceptibility spectra at high oscillating field frequencies, suggesting magnetic interactions within the composite dual imaging tracers. The MPI performance of the dual imaging agent was evaluated and compared to the commercial tracer ferucarbotran. The dual-imaging agent has MPI sensitivity that is ∼3× better than this commercial tracer. However, worsening of MPI resolution was observed in the composite tracer when compared to individually coated SPIONs. This worsening resolution could result from magnetic dipolar interactions within the composite dual imaging tracer. The CT performance of the dual imaging agent was evaluated in a pre-clinical animal scanner and a clinical scanner, revealing better contrast compared to a commercial iodine-based contrast agent. We demonstrate that the dual imaging agent can be differentiated from the commercial iodine contrast agent using dual energy CT (DECT) imaging. Furthermore, the dual imaging agent displayed energy-dependent CT contrast arising from the combination of SPION and hafnia, making it potentially suitable for virtual monochromatic imaging of the contrast agent distribution using DECT.

Magnetic Particle Imaging of Magnetotactic Bacteria as Living Contrast Agents Is Improved by Altering Magnetosome Arrangement.

Superparamagnetic iron oxide nanoparticles (SPIONs) can be used as imaging agents to differentiate between normal and diseased tissue or track cell movement. Magnetic particle imaging (MPI) detects the magnetic properties of SPIONs, providing quantitative and sensitive image data. MPI performance depends on the size, structure, and composition of nanoparticles. Magnetotactic bacteria produce magnetosomes with properties similar to those of synthetic nanoparticles, and these can be modified by mutating biosynthetic genes. The use of Magnetospirillum gryphiswaldense, MSR-1 with a mamJ deletion, containing clustered magnetosomes instead of typical linear chains, resulted in improved MPI signal and resolution. Bioluminescent MSR-1 with the mamJ deletion were administered into tumor-bearing and healthy mice. In vivo bioluminescence imaging revealed the viability of MSR-1, and MPI detected signals in livers and tumors. The development of living contrast agents offers opportunities for imaging and therapy with multimodality imaging guiding development of these agents by tracking the location, viability, and resulting biological effects.

Bimodal Interventional Instrument Markers for Magnetic Particle Imaging and Magnetic Resonance Imaging-A Proof-of-Concept Study.

The purpose of this work was to develop instrument markers that are visible in both magnetic particle imaging (MPI) and magnetic resonance imaging (MRI). The instrument markers were based on two different magnetic nanoparticle types (synthesized in-house KLB and commercial Bayoxide E8706). Coatings containing one of both particle types were fabricated and measured with a magnetic particle spectrometer (MPS) to estimate their MPI performance. Coatings based on both particle types were then applied on a segment of a nonmetallic guidewire. Imaging experiments were conducted using a commercial, preclinical MPI scanner and a preclinical 1 tesla MRI system. MPI image reconstruction was performed based on system matrices measured with dried KLB and Bayoxide E8706 coatings. The bimodal markers were clearly visible in both methods. They caused circular signal voids in MRI and areas of high signal intensity in MPI. Both the signal voids as well as the areas of high signal intensity were larger than the real marker size. Images that were reconstructed with a Bayoxide E8706 system matrix did not show sufficient MPI signal. Instrument markers with bimodal visibility are essential for the perspective of monitoring cardiovascular interventions with MPI/MRI hybrid systems.

Mixed Metal Metal-Organic Frameworks Derived Carbon Supporting ZnFe2O4/C for High-Performance Magnetic Particle Imaging.

Recently, magnetic particle imaging (MPI) has shown diverse biomedical applications such as cell tracking, lung perfusion, image-guided hyperthermia, and so forth. However, the currently reported MPI agents cannot achieve the possible theoretical detection limit of MPI (20 nM). A previous theoretical study has shown that the MPI performance of superparamagnetic iron oxide nanoparticles (SPIONs) can be enhanced by carbon supporting and metal doping. In the current study, a series of mixed metal metal-organic framework-derived carbon supporting SPIONs were synthesized by pyrolysis. Among the synthesized SPIONs, the MPI signal intensity of ZnFe2O4/C@PDA was found to be 4.7 times higher than the commercial MPI contrast (Vivotrax) having the same Fe concentration. ZnFe2O4/C@PDA also showed the highest MPI intensity in tumor-bearing-mice among all tested samples. Furthermore, they were found highly biocompatible and showed linear cell quantification. This work can open new avenues for the design and development of novel and high-performance MPI agents.

Long circulating tracer tailored for magnetic particle imaging.

Superparamagnetic iron oxide nanoparticle (SPION) tracers possessing long blood circulation time and tailored for magnetic particle imaging (MPI) performance are crucial for the development of this emerging molecular imaging modality. Here, single-core SPION MPI tracers coated with covalently bonded polyethyelene glycol (PEG) brushes were obtained using a semi-batch thermal decomposition synthesis with controlled addition of molecular oxygen, followed by an optimized PEG-silane ligand exchange procedure. The physical and magnetic properties, MPI performance, and blood circulation time of these newly synthesized tracers were compared to those of two commercially available SPIONs that were not tailored for MPI but are used for MPI: ferucarbotran and PEG-coated Synomag®-D. The new tailored tracer has MPI sensitivity that is ~3-times better than the commercial tracer ferucarbotran and much longer circulation half-life than both commercial tracers (t1/2=6.99 h for the new tracer, vs t1/2=0.59 h for ferucarbotran, and t1/2=0.62 h for PEG-coated Synomag®-D).

Novel platform for the multidimensional analysis of magnetic nanoparticles

The success of Magnetic Particle Imaging (MPI) as a clinical imaging modality is inextricably linked to the availability of purpose-build magnetic nanoparticles (MNP). Attempts to develop MNP with tailored properties and predictable MPI-performance are underway and still of great debate. However, it is well-known that the MPI performance is hampered by the size distribution present in MNP systems. The hyphenation of asymmetric flow field-flow fractionation (AF4) with on-line detectors has proven to provide reliable multidimensional information of MNP size distributions in a quasi-closed system without additional preparation steps. We recently introduced a novel combination of AF4 with a magnetic detector. This detector is based on the same physical principle as MPI, called Magnetic Particle Spectroscopy (MPS), which has already proven a straightforward technique for MNP specific quantification and characterization. In this study we demonstrate that the AF4 multidetector approach, including our MPS detector, is feasible to assist the targeted development of MNP with optimized imaging capabilities in MPI by directly measuring the MNP size as well as the indispensable magnetic functionality. Furthermore, the new platform provides important insights into the physics of MNP and can be used for quality control of MNP in biomedical applications.

Computational predictions of enhanced magnetic particle imaging performance by magnetic nanoparticle chains

The magnetic particle imaging (MPI) performance of collections of chains of magnetic nanoparticles with Néel and Brownian relaxation mechanisms was studied by carrying out simulations based on the Landau–Lifshitz–Gilbert equation and rotational Brownian dynamics, respectively. The effect of magnetic dipole–dipole interactions within chains on the time-domain average magnetic dipole moment and corresponding dynamic hysteresis loops, harmonic spectra, and point spread functions (PSFs) of the particle chains was evaluated. The results show that interactions within chains lead to ‘square-like’ dynamic hysteresis loops and enhanced MPI performance, compared to chains of non-interacting nanoparticles. For nanoparticles with the Brownian relaxation mechanism, subjected to a superimposed alternating and ramping magnetic field mimicking the magnetic field in MPI applications, we studied the dependence of x-space MPI performance of particle chains on parameters such as the amplitude of the alternating magnetic field, surface-to-surface separation between nanoparticles, solvent viscosity, and the number of nanoparticles in a chain. The results illustrate that magnetic dipole-dipole interactions within a chain contribute to enhanced MPI performance, and also suggest that there exist optimal values of the above parameters that lead to the best x-space MPI performance, i.e. maximum peak signal intensity and smallest full-width-at-half-maximum in PSFs.

Magnetic particle imaging performance of liposomes encapsulating iron oxide nanoparticles

Magnetic Particle Imaging (MPI) is a new imaging modality that quantifies spatial distribution of superparamagnetic iron oxide nanoparticles in a field of view through their non-linear magnetization response to an applied magnetic field. Liposomes loaded with magnetic nanoparticles (magnetoliposomes) are potential theranostic drug carriers that can combine magnetic properties with drug carrier ability. Prior work suggests that MPI signal can be affected by dipolar interactions between magnetic nanoparticles in close proximity – for instance, in a polymer matrix. Here we evaluate if encapsulating magnetic nanoparticles in liposomes has an impact in their MPI performance. For this purpose, magnetoliposomes were prepared using charge-stabilized iron oxide nanoparticles (IONPs) and their physical, magnetic and MPI properties were characterized. Interestingly, encapsulation of IONPs in magnetoliposomes led to an increase in MPI signal per unit mass.

Artificially Engineered Cubic Iron Oxide Nanoparticle as a High-Performance Magnetic Particle Imaging Tracer for Stem Cell Tracking.

Stem cell therapies are increasingly recognized as the future direction of regenerative medicine, but the biological fate of the administrated stem cells remains a major concern for clinical translation, which calls for an approach to efficiently monitoring the stem cell behaviors in vivo. Magnetic particle imaging (MPI) is an emerging technology for cell tracking; however, its utility has been largely restricted due to the lack of optimal magnetic nanoparticle tracers. Herein, by controlled engineering of the size and shape of magnetic nanoparticles tailored to MPI physics theory, a specialized MPI tracer, based on cubic iron oxide nanoparticles with an edge length of 22 nm (CIONs-22), is developed. Due to the inherent lower proportion of disordered surface spins, CIONs-22 exhibit significantly larger saturation magnetization than that of spherical ones, while they possess similar saturation magnetization but smaller coercivity compared to larger-sized CIONs. These magnetic properties of CIONs-22 warrant high sensitivity and resolution of MPI. With their efficient cellular uptake, CIONs-22 exhibit superior MPI performance for stem cell labeling and tracking compared to the commercialized tracer Vivotrax. By virtue of these advantages, CIONs-22 enable real-time and prolonged monitoring of the spatiotemporal trajectory of stem cells transplanted to hindlimb ischemia mice, which demonstrates the great potential of CIONs-22 as MPI tracers to advance stem cell therapies.

Size-isolation of superparamagnetic iron oxide nanoparticles improves MRI, MPI and hyperthermia performance

Superparamagnetic iron oxide nanoparticles (SPION) are extensively used for magnetic resonance imaging (MRI) and magnetic particle imaging (MPI), as well as for magnetic fluid hyperthermia (MFH). We here describe a sequential centrifugation protocol to obtain SPION with well-defined sizes from a polydisperse SPION starting formulation, synthesized using the routinely employed co-precipitation technique. Transmission electron microscopy, dynamic light scattering and nanoparticle tracking analyses show that the SPION fractions obtained upon size-isolation are well-defined and almost monodisperse. MRI, MPI and MFH analyses demonstrate improved imaging and hyperthermia performance for size-isolated SPION as compared to the polydisperse starting mixture, as well as to commercial and clinically used iron oxide nanoparticle formulations, such as Resovist® and Sinerem®. The size-isolation protocol presented here may help to identify SPION with optimal properties for diagnostic, therapeutic and theranostic applications.

Effects of particle diameter and magnetocrystalline anisotropy on magnetic relaxation and magnetic particle imaging performance of magnetic nanoparticles

The dynamic magnetization of immobilized spherical single-domain magnetic nanoparticles (MNPs) with uniaxial or cubic magnetocrystalline anisotropy was studied computationally by executing simulations based on the Landau–Lifshitz–Gilbert (LLG) equation. For situations when a static magnetic field was suddenly applied and then removed, the effects of particle diameter and anisotropy (considering both type of symmetry and characteristic energy) on the characteristic magnetic relaxation time were studied parametrically. The results, for both anisotropy symmetries, show that when a static magnetic field is suddenly turned on or off the MNPs undergo a successive two-step or combined one-step relaxation. Whether a MNP relaxes with one or two steps when the field is turned on is determined by the competition between the energy of the applied magnetic field, the magnetic anisotropy energy, and thermal energy. When the applied magnetic field is suddenly turned off, our results show good agreement with theoretical predictions for the cases of and , where represents the magnetic anisotropy energy barrier, is the Boltzmann constant and represents the absolute temperature. For the case of an applied alternating magnetic field (AMF) that is typical of magnetic particle imaging (MPI) applications, the effects of particle diameter and anisotropy symmetry were studied in terms of time-domain magnetization dynamics, dynamic hysteresis loops, harmonic spectra, and x-space point spread functions (PSFs). Results illustrate that the type of magnetocrystalline anisotropy (uniaxial versus cubic) has a significant effect on the MPI performance of the nanoparticles. These computational studies provide insight into the role of particle diameter and magnetic anisotropy on the performance of MNPs for applications in magnetorelaxometry and MPI.

Optimization of Iron Oxide Tracer Synthesis for Magnetic Particle Imaging.

The optimization of iron oxide nanoparticles as tracers for magnetic particle imaging (MPI) alongside the development of data acquisition equipment and image reconstruction techniques is crucial for the required improvements in image resolution and sensitivity of MPI scanners. We present a large-scale water-based synthesis of multicore superparamagnetic iron oxide nanoparticles stabilized with dextran (MC-SPIONs). We also demonstrate the preparation of single core superparamagnetic iron oxide nanoparticles in organic media, subsequently coated with a poly(ethylene glycol) gallic acid polymer and phase transferred to water (SC-SPIONs). Our aim was to obtain long-term stable particles in aqueous media with high MPI performance. We found that the amplitude of the third harmonic measured by magnetic particle spectroscopy (MPS) at 10 mT is 2.3- and 5.8-fold higher than Resovist for the MC-SPIONs and SC-SPIONs, respectively, revealing excellent MPI potential as compared to other reported MPI tracer particle preparations. We show that the reconstructed MPI images of phantoms using optimized multicore and specifically single-core particles are superior to that of commercially available Resovist, which we utilize as a reference standard, as predicted by MPS.

Novel magnetic multicore nanoparticles designed for MPI and other biomedical applications: From synthesis to first in vivo studies.

Synthesis of novel magnetic multicore particles (MCP) in the nano range, involves alkaline precipitation of iron(II) chloride in the presence of atmospheric oxygen. This step yields green rust, which is oxidized to obtain magnetic nanoparticles, which probably consist of a magnetite/maghemite mixed-phase. Final growth and annealing at 90°C in the presence of a large excess of carboxymethyl dextran gives MCP very promising magnetic properties for magnetic particle imaging (MPI), an emerging medical imaging modality, and magnetic resonance imaging (MRI). The magnetic nanoparticles are biocompatible and thus potential candidates for future biomedical applications such as cardiovascular imaging, sentinel lymph node mapping in cancer patients, and stem cell tracking. The new MCP that we introduce here have three times higher magnetic particle spectroscopy performance at lower and middle harmonics and five times higher MPS signal strength at higher harmonics compared with Resovist®. In addition, the new MCP have also an improved in vivo MPI performance compared to Resovist®, and we here report the first in vivo MPI investigation of this new generation of magnetic nanoparticles.

Enhanced Methods to Estimate the Efficiency of Magnetic Nanoparticles in Imaging.

Magnetic resonance imaging (MRI) and magnetic particle imaging (MPI) are powerful methods in the early diagnosis of diseases. Both imaging techniques utilize magnetic nanoparticles that have high magnetic susceptibility, strong saturation magnetization, and no coercivity. FeraSpinTM R and its fractionated products have been studied for their imaging performances; however, a detailed magnetic characterization in their immobilized state is still lacking. This is particularly important for applications in MPI that require fixation of magnetic nanoparticles with the target cells or tissues. We examine the magnetic properties of immobilized FeraSpinTM R, its size fractions, and Resovist®, and use the findings to demonstrate which magnetic properties best predict performance. All samples show some degree of oxidation to hematite, and magnetic interaction between the particles, which impact negatively on image performance of the materials. MRI and MPI performance show a linear dependency on the slope of the magnetization curve, i.e., initial susceptibility, and average blocking temperature. The best performance of particles in immobilized state for MPI is found for particle sizes close to the boundary between superparamagnetic (SP) and magnetically ordered, in which only Néel relaxation is important. Initial susceptibility and bifurcation temperature are the best indicators to predict MRI and MPI performance.

Three-dimensional magnetic nanoparticle imaging using small field gradient and multiple pickup coils

We propose a magnetic particle imaging (MPI) method based on third harmonic signal detection using a small field gradient and multiple pickup coils. First, we developed a system using two pickup coils and performed three-dimensional detection of two magnetic nanoparticle (MNP) samples, which were spaced 15mm apart. In the experiments, an excitation field strength of 1.6 mT was used at an operating frequency of 3kHz. A DC gradient field with a typical value of 0.2T/m was also used to produce the so-called field-free line. A third harmonic signal generated by the MNP samples was detected using the two pickup coils, and the samples were then mechanically scanned to obtain field maps. The field maps were subsequently analyzed using the nonnegative least squares method to obtain three-dimensional position information for the MNP samples. The results show that the positions of the two MNP samples were estimated with good accuracy, despite the small field gradient used. Further improvement in MPI performance will be achieved by increasing the number of pickup coils used.

Developing Magnetic Particle Imaging (MPI) tracers for in vivo tissue-targeted applications

Event Abstract Back to Event Developing Magnetic Particle Imaging (MPI) tracers for in vivo tissue-targeted applications Hamed Arami1, Haydin Bradshaw1, Eric Teeman1, Alyssa Troksa1 and Kannan M. Krishnan1 1 University of Washington, Department of Materials Science and Engineering, United States Introduction: Magnetic particle imaging (MPI) is a real-time, quantitative and clinically safe imaging technique, potentially applicable for future clinical applications such as cancer imaging, cardiovascular imaging or stem cell labeling and tracking[1],[2]. MPI performance (i.e. spatial resolution and sensitivity) is highly dependent on nanoparticles (NPs) size distribution, magnetization and environment[3],[4]. Therefore, NPs MPI signal is different after distribution into tissues or binding to the cells. Here, using in vitro and in vivo studies, we present the potential capabilities of MPI for tissue targeted imaging applications such as cancer and atherosclerosis imaging. Materials and Methods: Monodispersed iron oxide nanoparticles (NPs) optimized for MPI were synthesized by thermal decomposition of iron oleate in the presence of oleic acid and transferred to water according to our previous reports[5]-[9]. Nanoparticles were functionalized using PMAO-PEG co-polymers and different PEG derivatives such as NH2-PEG-NH2 and NH2-PEG-SH (MWs: 2-20kDa). Cy5.5 near infra-red fluorescent (NIRF) molecules were conjugated to the NPs for multimodal (MPI/NIRF) imaging. For targeting experiments, the relevant targeting peptides (e.g. lactoferrin for targeting the C6 glioma xenografts in mice) were conjugated to the NPs[10]. All NPs formulations were characterized using dynamic light scattering (DLS), Zeta potential measurements, vibrating sample magnetometer (VSM) and transmission electron microscope (TEM). The biodistribution, pharmacokinetics and delivery of the NPs to organs and tissues (e.g. tumors and heart lesions) were evaluated using different groups of mice with brain or prostate cancers or aorta atherosclerosis. A home-built magnetic particle spectrometer (MPS) was used to evaluate the MPI performance of the NPs in tissues[4]. MPI, magnetic resonance imaging (MRI) and NIRF (IVIS) were used to monitor the biodistribution of the NPs in mice. Histology (H & E and Prussian Blue staining) were used to investigate tissue distribution and side-effects of the NPs. Results and Discussions: First, we used two preliminary experimental models to predict the MPI performance of the tracers in a tissue equivalent environment and an acidic lysosome-like solution[4],[7]. Then, for imaging of the reticuloendothelial system (RES) organs, cancers or heart lesions, we introduced functional groups (e.g. amine, -NH2) to the surface of the optimized NPs and used them as conjugation sites for bonding of the NIRF molecules (Cy5.5) and specific targeting peptides[8],[10]. We investigated the biodistribution (Fig. 1) of these NPs after their intravenous injection and evaluated their MPI performance after their accumulation in RES organs (e.g. liver and spleen) and other targeted tissues[5],[6]. Also, blood samples were collected by retro-orbital blood drawing and used for pharmacokinetic studies and evaluation of the NPs blood half-life. Our results show that MPI can be used as a potential whole-body imaging technique for a wide range of biomedical imaging applications. Also, NIRF has a high tracer mass sensitivity and reveals more details of microstructural distribution of these optimized MPI tracers in organs and tissues (e.g. cancers and heart lesions)[11]. Histology results showed no apparent side-effects due to accumulation of the NPs in organs. Fig.1. Multimodal MPI/NIRF/MRI imaging of the mice enabled us to map the biodistribution of the MPI tracers[5]. Conclusions: MPS and MPI enabled us to track our optimized MPI tracers in organs and targeted tissues effectively. Additional imaging modalities (NIRF and MRI) helped us to study the targeting ability, biodistribution and pharmacokinetics of the NPs in mice more accurately. These results pave the ways for future applications of MPI in pre-clinical tissue-targeted magnetic imaging and diagnostic applications. This work was supported by NIH grants 1RO1EB013689-01/NIBIB, 2R42EB013520-02A1 and 1R41EB013520-01.

High-performance iron oxide nanoparticles for magnetic particle imaging - guided hyperthermia (hMPI).

Magnetic particle imaging (MPI) is an emerging imaging modality that allows the direct and quantitative mapping of iron oxide nanoparticles. In MPI, the development of tailored iron oxide nanoparticle tracers is paramount to achieving high sensitivity and good spatial resolution. To date, most MPI tracers being developed for potential clinical applications are based on spherical undoped magnetite nanoparticles. For the first time, we report on the systematic investigation of the effects of changes in chemical composition and shape anisotropy on the MPI performance of iron oxide nanoparticle tracers. We observed a 2-fold enhancement in MPI signal through selective doping of magnetite nanoparticles with zinc. Moreover, we demonstrated focused magnetic hyperthermia heating by adapting the field gradient used in MPI. By saturating the iron oxide nanoparticles outside of a field free region (FFR) with an external static field, we can selectively heat a target region in our test sample. By comparing zinc-doped magnetite cubic nanoparticles with undoped spherical nanoparticles, we could show a 5-fold improvement in the specific absorption rate (SAR) in magnetic hyperthermia while providing good MPI signal, thereby demonstrating the potential for high-performance focused hyperthermia therapy through an MPI-guided approach (hMPI).