Magnetic Particle Imaging (MPI) is an emerging, whole body biomedical imaging technique, with sub-millimeter spatial resolution and high sensitivity to a biocompatible contrast agent consisting of an ...iron oxide nanoparticle core and a biofunctionalized shell. Successful application of MPI for imaging of cancer depends on the nanoparticles (NPs) accumulating at tumors at sufficient levels relative to other sites. NPs' physiochemical properties such as size, crystallographic structure and uniformity, surface coating, stability, blood circulation time and magnetization determine the efficacy of their tumor accumulation and MPI signal generation. Here, we address these criteria by presenting strategies for the synthesis and surface functionalization of efficient MPI tracers, that can target a typical murine brain cancer model and generate three dimensional images of these tumors with very high signal-to-noise ratios (SNR). Our results showed high contrast agent sensitivities that enabled us to detect 1.1 ng of iron (SNR ∼ 3.9) and enhance the spatial resolution to about 600 μm. The biodistribution of these NPs was also studied using near-infrared fluorescence (NIRF) and single-photon emission computed tomography (SPECT) imaging. NPs were mainly accumulated in the liver and spleen and did not show any renal clearance. This first pre-clinical study of cancer targeted NPs imaged using a tomographic MPI system in an animal model paves the way to explore new nanomedicine strategies for cancer diagnosis and therapy, using clinically safe magnetic iron oxide nanoparticles and MPI.
One quarter of all iodinated contrast X‐ray clinical imaging studies are now performed on Chronic Kidney Disease (CKD) patients. Unfortunately, the iodine contrast agent used in X‐ray is often toxic ...to CKD patients’ weak kidneys, leading to significant morbidity and mortality. Hence, we are pioneering a new medical imaging method, called Magnetic Particle Imaging (MPI), to replace X‐ray and CT iodinated angiography, especially for CKD patients. MPI uses magnetic nanoparticle contrast agents that are much safer than iodine for CKD patients. MPI already offers superb contrast and extraordinary sensitivity. The iron oxide nanoparticle tracers required for MPI are also used in MRI, and some are already approved for human use, but the contrast agents are far more effective at illuminating blood vessels when used in the MPI modality. We have recently developed a systems theoretic framework for MPI called x‐space MPI, which has already dramatically improved the speed and robustness of MPI image reconstruction. X‐space MPI has allowed us to optimize the hardware for five MPI scanners. Moreover, x‐space MPI provides a powerful framework for optimizing the size and magnetic properties of the iron oxide nanoparticle tracers used in MPI. Currently MPI nanoparticles have diameters in the 10‐20 nanometer range, enabling millimeter‐scale resolution in small animals. X‐space MPI theory predicts that larger nanoparticles could enable up to 250 micrometer resolution imaging, which would represent a major breakthrough in safe imaging for CKD patients.
Magnetic particle imaging (MPI) is an emerging medical imaging technique that could be a safer alternative to X‐ray and CT using iodinated contrast agents, especially for patients with chronic kidney disease. Here we describe the overall technique, detail the latest advances in MPI theory, and discuss the optimal nanoparticle characteristics for MPI. We also show images taken using our latest MPI hardware, demonstrating MPI's already superb contrast and high sensitivity.
Gastrointestinal (GI) bleeding causes more than 300 000 hospitalizations per year in the United States. Imaging plays a crucial role in accurately locating the source of the bleed for timely ...intervention. Magnetic particle imaging (MPI) is an emerging clinically translatable imaging modality that images superparamagnetic iron-oxide (SPIO) tracers with extraordinary contrast and sensitivity. This linearly quantitative modality has zero background tissue signal and zero signal depth attenuation. MPI is also safe: there is zero ionizing radiation exposure to the patient and clinically approved tracers can be used with MPI. In this study, we demonstrate the use of MPI along with long-circulating, PEG-stabilized SPIOs for rapid in vivo detection and quantification of GI bleed. A mouse model genetically predisposed to GI polyp development (Apc Min/+) was used for this study, and heparin was used as an anticoagulant to induce acute GI bleeding. We then injected MPI-tailored, long-circulating SPIOs through the tail vein, and tracked the tracer biodistribution over time using our custom-built high resolution field-free line (FFL) MPI scanner. Dynamic MPI projection images captured tracer accumulation in the lower GI tract with excellent contrast. Quantitative analysis of the MPI images show that the mice experienced GI bleed rates between 1 and 5 μL/min. Although there are currently no human scale MPI systems, and MPI-tailored SPIOs need to undergo further development and evaluation, clinical translation of the technique is achievable. The robust contrast, sensitivity, safety, ability to image anywhere in the body, along with long-circulating SPIOs lends MPI outstanding promise as a clinical diagnostic tool for GI bleeding.
We present an interdisciplinary overview of material engineering and emerging applications of iron oxide nanoparticles. We discuss material engineering of nanoparticles in the broadest sense, ...emphasizing size and shape control, large-area self-assembly, composite/hybrid structures, and surface engineering. This is followed by a discussion of several nontraditional, emerging applications of iron oxide nanoparticles, including nanoparticle lithography, magnetic particle imaging, magnetic guided drug delivery, and positive contrast agents for magnetic resonance imaging. We conclude with a succinct discussion of the pharmacokinetics pathways of iron oxide nanoparticles in the human body—an important and required practical consideration for any in vivo biomedical application, followed by a brief outlook of the field.
Superparamagnetic iron oxide nanoparticles (SPIONs) are a foundational platform for a variety of biomedical applications. Of particular interest is Magnetic Particle Imaging (MPI), which is a growing ...area of research and development due to its advantages including high resolution and sensitivity with positive contrast. There has been significant work in the area of
in vivo
optimization of SPIONs for MPI as well as their biodistribution in and clearance from the body. However, little is known about the dynamics of SPIONs following cellular internalization which may limit their usefulness in a variety of potential imaging and treatment applications. This work shows a clear 20% decrease in magnetic performance of SPIONs, as observed by Magnetic Particle Spectroscopy (MPS), after internalization and systematic consideration of applicable factors that affect SPION signal generation, including microstructure, environment, and interparticle interactions. There is no observed change to SPION microstructure after internalization, and the surrounding environment plays little to no role in magnetic response for the SPIONs studied here. Interparticle interactions described by dipole-dipole coupling of SPIONs held close to one another after internalization are shown to be the dominant cause of decreased magnetic performance in cells. These conclusions were drawn from transmission electron microscopy (TEM) image analysis at relevant length scales, experimentally prepared and characterized SPIONs in varied environmental conditions, and theoretical modeling with Monte Carlo simulations.
An examination of the effects of intracellular environmental conditions on the dynamic magnetic response of superparamagnetic iron oxide nanoparticles.
Superparamagnetic iron oxide nanoparticles with highly nonlinear magnetic behavior are attractive for biomedical applications like magnetic particle imaging and magnetic fluid hyperthermia. Such ...particles display interesting magnetic properties in alternating magnetic fields and here we document experiments that show differences between the magnetization dynamics of certain particles in frozen and melted states. This effect goes beyond the small temperature difference (Δ
~ 20 °C) and we show the dynamics to be a mixture of Brownian alignment of the particles and Néel rotation of their moments occurring in liquid particle suspensions. These phenomena can be modeled in a stochastic differential equation approach by postulating log-normal distributions and partial Brownian alignment of an effective anisotropy axis. We emphasize that precise particle-specific characterization through experiments and nonlinear simulations is necessary to predict dynamics in solution and optimize their behavior for emerging biomedical applications including magnetic particle imaging.
•Particle heating measured for varying core sizes, field amplitudes and frequencies.•Stochastic Langevin simulations of particle heating verified by measurements.•Estimation of the effective ...anisotropy constant for iron oxide nanoparticles.•Simulating optimal particle and field parameters maximizing therapeutic heating.
Magnetic nanoparticles (MNP) have been investigated for generating therapeutic heat when subjected to an alternating magnetic field (AMF) and applied for tumor-confined cancer therapy, so-called magnetic fluid hyperthermia (MFH). For application of MFH, a key requirement is the reduction of MNP dosing by maximizing the heat generation within medically safe limits of the applied AMF. Therefore, reliable and accurate predictions of particle heating are required for the advancement of therapy planning. In this study, we compare size-dependent particle heating data from calorimetric measurements to stochastic Néel-Brown Langevin equation Monte Carlo simulations, finding good agreement between them for various AMF amplitudes and frequencies. Within medical safety constraints of the AMF, our simulations predict maximum particle heating for magnetite particle core sizes above 25 nm with effective anisotropy constants K=4000 J/m3 at frequencies of ∼100 kHz and field amplitudes ∼10 mT/μ0. These simulations could help to predict the optimal combination of medically safe AMF parameters and MNP intrinsic properties, such as core size and effective anisotropy, to maximize heat generation and reduce MNP dosing in the application of MFH.
In the search for nonprecious metal catalysts for the hydrogen evolution reaction (HER), transition metal dichalcogenides (TMDCs) have been proposed as promising candidates. Here, we present a facile ...method for significantly decreasing the overpotential required for catalyzing the HER with colloidally synthesized WSe2. Solution phase deposition of 2H WSe2 nanoflowers (NFs) onto carbon fiber electrodes results in low catalytic activity in 0.5 M H2SO4 with an overpotential at −10 mA/cm2 of greater than 600 mV. However, two postdeposition electrode processing steps significantly reduce the overpotential. First, a room-temperature treatment of the prepared electrodes with a dilute solution of the alkylating agent Meerwein’s salt (Et3OBF4) results in a reduction in overpotential by approximately 130 mV at −10 mA/cm2. Second, we observe a decrease in overpotential of approximately 200–300 mV when the TMDC electrode is exposed to H+, Li+, Na+, or K+ ions under a reducing potential. The combined effect of ligand removal and electrochemical activation results in an improvement in overpotential by as much as 400 mV. Notably, the Li+ activated WSe2 NF deposited carbon fiber electrode requires an overpotential of only 243 mV to generate a current density of −10 mA/cm2. Measurement of changes in the material work function and charge transfer resistance ultimately provide rationale for the catalytic improvement.
We present a scalable thermolysis and high temperature oxidation procedure for synthesizing monodisperse magnetite nanoparticles with saturation magnetization of up to 80 emu g −1 (412 kA m −1 ), 92% ...of bulk magnetite. Diameters in the 15–30 nm size range are produced from iron oleate via the thermolysis method at 324 °C and varying oleic acid ratios for size control (6.7–7.6 equivalents per Fe). The influence of the iron oleate synthesis procedure on the quality of resulting nanoparticles is examined and the structure of the iron oleate is proposed to have a triironoxonium core Fe 3 O + based on magnetic susceptibility measurements. The thermolysis method is shown to initially give wüstite nanoparticles, which are oxidized in situ at 318 °C using 1% oxygen in argon to form highly magnetic magnetite nanoparticles. The use of 1% oxygen offers broad application as a safe and efficient reagent for the high temperature oxidation of nanoparticles. Special consideration to the reproducibility of nanoparticle diameter and monodispersity has uncovered critical factors. Additionally, the reduction of Fe( iii ) to Fe( ii ) is shown to occur during the heat up stage of thermolysis, beginning at less than 180 °C and being complete by 320 °C. Evidence for the reduction occurring by the oxidative decarboxylation of oleic acid is presented. Decomposition of the remaining oleic acid is shown to occur by a ketonization reaction producing oleone. The nucleation event and growth of particles is examined by TEM. Comparison of the solvents 1-octadecene and octadecane are presented demonstrating the effect on the reduction of Fe( iii ) during heat up, the large difference in particle size, and effects on the oxidation rate of iron oxide nanoparticles. Determination of Fe( ii ) content in magnetic iron oxide nanoparticles by titration is presented.
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