Superparamagnetic Iron Oxide Nanoparticles Concentration Research Articles

Dual Nanoparticle Conjugates for Highly Sensitive and Versatile Sensing Using 19F Magnetic Resonance Imaging

AbstractFluorine magnetic resonance imaging (19F MRI) has emerged as an attractive alternative to conventional 1H MRI due to enhanced specificity deriving from negligible background signal in this modality. We report a dual nanoparticle conjugate (DNC) platform as an aptamer‐based sensor for use in 19F MRI. DNC consists of core–shell nanoparticles with a liquid perfluorocarbon core and a mesoporous silica shell (19F‐MSNs), which give a robust 19F MR signal, and superparamagnetic iron oxide nanoparticles (SPIONs) as magnetic quenchers. Due to the strong magnetic quenching effects of SPIONs, this platform is uniquely sensitive and functions with a low concentration of SPIONs (4 equivalents) relative to 19F‐MSNs. The probe functions as a “turn‐on” sensor using target‐induced dissociation of DNA aptamers. The thrombin binding aptamer was incorporated as a proof‐of‐concept (DNCThr), and we demonstrate a significant increase in 19F MR signal intensity when DNCThr is incubated with human α‐thrombin. This proof‐of‐concept probe is highly versatile and can be adapted to sense ATP and kanamycin as well. Importantly, DNCThr generates a robust 19F MRI “hot‐spot” signal in response to thrombin in live mice, establishing this platform as a practical, versatile, and biologically relevant molecular imaging probe.

Dual Nanoparticle Conjugates for Highly Sensitive and Versatile Sensing Using 19 F Magnetic Resonance Imaging.

Fluorine magnetic resonance imaging (19 F MRI) has emerged as an attractive alternative to conventional 1 H MRI due to enhanced specificity deriving from negligible background signal in this modality. We report a dual nanoparticle conjugate (DNC) platform as an aptamer-based sensor for use in 19 F MRI. DNC consists of core-shell nanoparticles with a liquid perfluorocarbon core and a mesoporous silica shell (19 F-MSNs), which give a robust 19 F MR signal, and superparamagnetic iron oxide nanoparticles (SPIONs) as magnetic quenchers. Due to the strong magnetic quenching effects of SPIONs, this platform is uniquely sensitive and functions with a low concentration of SPIONs (4 equivalents) relative to 19 F-MSNs. The probe functions as a "turn-on" sensor using target-induced dissociation of DNA aptamers. The thrombin binding aptamer was incorporated as a proof-of-concept (DNCThr ), and we demonstrate a significant increase in 19 F MR signal intensity when DNCThr is incubated with human α-thrombin. This proof-of-concept probe is highly versatile and can be adapted to sense ATP and kanamycin as well. Importantly, DNCThr generates a robust 19 F MRI "hot-spot" signal in response to thrombin in live mice, establishing this platform as a practical, versatile, and biologically relevant molecular imaging probe.

Simulation and experimental validation of magnetic nanoparticle accumulation in a bloodstream mimicking flow system

In this paper, a mathematical model for the dynamics of superparamagnetic iron oxide nanoparticles (SPIONs) in a laminar flow through a pipe under the influence of an external magnetic field of a single electromagnet is derived. The model consists of a convection–diffusion equation coupled with magnetostatic equations. The accumulation of particles along the boundary is modeled with the help of a surface concentration. Based on experimental data describing the retention of lauric acid coated SPIONs in a tubular flow under the influence of a magnetic field, the model is parametrized and finite element simulations are performed. With the exception of one outlier at low SPION concentration and high flowspeed, the simulation results agree very well with the experimental measurements within the bounds of the measurement error.

Multifunctional 3D-Printed Magnetic Polycaprolactone/Hydroxyapatite Scaffolds for Bone Tissue Engineering.

Multifunctional and resistant 3D structures represent a great promise and a great challenge in bone tissue engineering. This study addresses this problem by employing polycaprolactone (PCL)-based scaffolds added with hydroxyapatite (HAp) and superparamagnetic iron oxide nanoparticles (SPION), able to drive on demand the necessary cells and other bioagents for a high healing efficiency. PCL-HAp-SPION scaffolds with different concentrations of the superparamagnetic component were developed through the 3D-printing technology and the specific topographical features were detected by Atomic Force and Magnetic Force Microscopy (AFM-MFM). AFM-MFM measurements confirmed a homogenous distribution of HAp and SPION throughout the surface. The magnetically assisted seeding of cells in the scaffold resulted most efficient for the 1% SPION concentration, providing good cell entrapment and adhesion rates. Mesenchymal Stromal Cells (MSCs) seeded onto PCL-HAp-1% SPION showed a good cell proliferation and intrinsic osteogenic potential, indicating no toxic effects of the employed scaffold materials. The performed characterizations and the collected set of data point on the inherent osteogenic potential of the newly developed PCL-HAp-1% SPION scaffolds, endorsing them towards next steps of in vitro and in vivo studies and validations.

SPIONs self-assembly and magnetic sedimentation in quadrupole magnets: Gaining insight into the separation mechanisms

Superparamagnetic iron oxide nanoparticles (SPIONs) are currently popular materials experiencing rapid development with potential application value, especially in biomedical and chemical engineering fields. Examples include wastewater management, bio-detection, biological imaging, targeted drug delivery and biosensing. While not exclusive, magnetically driven isolation methods are typically required to separate the desired entity from the media in specific applications and in their manufacture and/or quality control. However, due to the nano-size of SPIONs, their magnetic manipulation is affected by Brownian motion, adding considerable complexities. The two most common methods for SPION magnetic separation are high and low gradient magnetic separation (HGMS and LGMS, respectively). Nevertheless, the effect of specific magnetic energy fields on SPIONs, such as horizontal (perpendicular to gravity), high fields and gradients (higher than LGMS) on the horizontal magnetophoresis and vertical sedimentation of SPIONs has only recently been suggested as a way to separate very small particles (5 nm). In this work, we continue those studies on the magnetic separation of 5–30 nm SPIONs by applying fields and gradients perpendicular to gravity. The magnetic field was generated by permanent magnets arranged in quadrupolar configurations (QMS). Different conditions were studied, and multiple variables were evaluated, including the particle size, the initial SPIONs concentration, the temperature, the magnetic field gradient and the magnetic exposure time. Our experimental data show that particles are subjected to horizontal magnetic forces, to particle agglomeration due to dipole–dipole interactions, and to vertical sedimentation due to gravity. The particle size and the type of separator employed (i.e. different gradient and field distribution acting on the particle suspension) have significant effects on the phenomena involved in the separation, whereas the temperature and particle concentration affect the separation to a lesser extent. Finally, the separation process was observed to occur in less than 3 mins for our experimental conditions, which is encouraging considering the long operation time (up to days) necessary to separate particles of similar sizes in LGMS columns that also employ permanent magnets.

Neutrophil Inflammatory Response Is Downregulated by Uptake of Superparamagnetic Iron Oxide Nanoparticle Therapeutics.

Superparamagnetic iron oxide nanoparticles (SPION) are employed as diagnostics and therapeutics following intravenous delivery for the treatment of iron deficiency anemia (IDA) in adult patients with chronic kidney failure. Neutrophils are the first defense against blood borne foreign insult and recruit to vascular sites of inflammation via a sequential process that is characterized by adhesive capture, rolling, and shear resistant arrest. A primary chemotactic agonist presented on the glycocalyx of inflamed endothelium is IL-8, which upon binding to its cognate membrane receptor (CXCR1/2) activates a suite of responses in neutrophils. An early response is degranulation with accompanying upregulation of β2-integrin (CD11/CD18) and shedding of L-selectin (CD62L) receptors, which exert differential effects on the efficiency of endothelial recruitment. Feraheme is an FDA approved SPION treatment for IDA, but its effect on the innate immune response of neutrophils during inflammation has not been reported. Here, we studied the immunomodulatory effects of Feraheme on neutrophils freshly isolated from healthy human subjects and stimulated in suspension or on inflammatory mimetic substrates with IL-8. Cells treated with Feraheme exhibited reduced sensitivity to stimulation with IL-8, indicated by reduced upregulation of membrane CD11b/CD18 receptors, high affinity (HA) CD18, and shedding of CD62L. Feraheme also inhibited N-formyl-Met-Leu-Phe (fMLP) induced reactive oxygen species production. Neutrophil rolling, arrest, and migration was assessed in vascular mimetic microfluidic channels coated with E-selectin and ICAM-1 to simulate inflamed endothelium. Neutrophils exposed to Feraheme rolled faster on E-selectin and arrested less frequently on ICAM-1, in a manner dependent upon SPION concentration. Subsequent neutrophil shape change, and migration were also significantly inhibited in the presence of Feraheme. Lastly, Feraheme accelerated clearance of cytosolic calcium flux following IL-8 stimulation. We conclude that uptake of Feraheme by neutrophils inhibits chemotactic activation and downregulates normal rolling to arrest under shear flow. The mechanism involves increased calcium clearance following chemotactic activation, which may diminish the efficiency of recruitment from the circulation at vascular sites of inflammation.

Nanoprecipitation preparation of low temperature-sensitive magnetoliposomes

Lysolipid-containing thermosensitive liposomes (LTSL) have gained attention for triggered release of chemotherapeutics. Superparamagnetic iron oxide nanoparticles (SPION) offers multimodal imaging and hyperthermia therapy opportunities as a promising theranostic agent. Combining LTSL with SPION may further enhance their performance and functionality of LTSL. However, a major challenge in clinical translation of nanomedicine is the poor scalability and complexity of their preparation process. Exploiting the nature of self-assembly, nanoprecipitation is a simple and scalable technique for preparing liposomes. Herein, we developed a novel SPION-incorporated lysolipid-containing thermosensitive liposome (mLTSL10) formulation using nanoprecipitation. The formulation and processing parameters were carefully designed to ensure high reproducibility and stability of mLTSL10. The effect of solvent, aqueous-to-organic volume ratio, SPION concentration on the mLTSL10 size and dispersity was investigated. mLTSL10 were successfully prepared with a small size (∼100 nm), phase transition temperature at around 42 °C, and high doxorubicin encapsulation efficiency. Indifferent from blank LTSL, we demonstrated that mLTSL10 combining the functionality of both LTSL and SPION can be successfully prepared using a scalable nanoprecipitation approach.

Self-assembly and sedimentation of 5 nm SPIONs using horizontal, high magnetic fields and gradients

Superparamagnetic iron oxide nanoparticles (SPIONs) are employed in multiple applications, especially within medical and chemical engineering fields. However, their magnetic separation is very challenging as the magnetophoretic motion is hindered by thermal energy and viscous drag. Recent studies have addressed the recovery of SPIONs by a combination of cooperative magnetophoresis and sedimentation. Nevertheless, the effect of horizontal, high fields and gradients on the vertical sedimentation of SPIONs has not been described. In this work, we report, for the first time, the magnetically facilitated sedimentation of 5 nm particles by applying fields and gradients perpendicular to gravity. The magnetic field was generated by quadrupole magnetic sorters and the process was measured with time by tracking the concentration along the length of a channel contacting the 5 nm SPIONs within the quadrupole field. Our experimental data suggest that aggregates of 60–90 particles are formed in the system; thus, particle agglomeration by dipole-dipole interactions was promoted, and these clusters settled down as a result of gravitational forces. Multiple variables and parameters were evaluated, including the initial SPION concentration, the temperature, the magnetic field and gradient and operation time. It was found that the process was improved by decreasing the initial concentration and the temperature, but the magnitude of the magnetic field and gradient did not significantly affect the sedimentation. Finally, the separation process was rapid, with the systems reaching the equilibrium in approximately 20 min, which is a significant advantage in comparison to other systems that require longer times and larger particle sizes.

Effect of magnetic nanoparticles on partial discharges in transformer oil

We report on an experimental study of partial discharges (PD) in transformer oil with four different volume concentrations of superparamagnetic iron oxide nanoparticles (SPION) ranging from 0 to 0.0004 vol%. To investigate the PD, a specific high-voltage setup was designed. Thanks to the small amount of SPION in the oil (transparency), the PD events in the form of visible corona and streamer discharges were visualized by a CCD camera. Furthermore, the PD inception and extinction voltage, apparent charge and quantities derived from the PD recurrence, as pulse repetition rate and phase resolved patterns, were analyzed in dependence on SPION concentration. It was found that the PD inception voltage increases quasi linearly with increasing SPION concentration but the extinction voltage is practically unaffected. The pulse repetition rate decreases as a result of the increasing SPION concentration. The decreased PD activity is clearly concluded also from the reducing shape and growth of the visual corona discharge patterns. To interpret the observed suppression of PD in transformer oil-based magnetic nanofluids, the electric field modification and injected charge trapping by the dispersed nanoparticles is considered. Moreover, a possible effect of the local magnetic fields around the SPION on the space charge migration is taken into account, too.

A Multidisciplinary Approach Toward High Throughput Label-Free Cytotoxicity Monitoring of Superparamagnetic Iron Oxide Nanoparticles.

This paper focuses on cytotoxicity examination of superparamagnetic iron oxide nanoparticles (SPIONs) using different methods, including impedance spectroscopy. Recent advances of SPIONs for clinical and research applications have triggered the need to understand their effects in cells. Despite the great advances in adapting various biological and chemical methods to assess in-vitro toxicity of SPIONs, less attention has been paid on the development of a high throughput label-free screening platform to study the interaction between the cells and nanoparticles including SPIONs. In this paper, we have taken the first step toward this goal by proposing a label-free impedimetric method for monitoring living cells treated with SPIONs. We demonstrate the effect of SPIONs on the adhesion, growth, proliferation, and viability of neuroblastoma 2A (N2a) cells using impedance spectroscopy as a label-free method, along with other standard microscopic and cell viability testing methods as control methods. Our results have shown a decreased viability of the cells as the concentration of SPIONs increases with percentages of 59%, 47%, and 40% for 100 µg/mL (C4), 200 µg/mL (C5), 300 µg/mL (C6), respectively. Although all SPIONs concentrations have allowed the growth of cells within 72 h, C4, C5, and C6 showed slower growth compared to the control (C1). The growth and proliferation of N2a cells are faster in the absence or low concentration of SPIONS. The percent coefficient of variation (% CV) was used to compare cell concentrations obtained by TBDE assay and a Scepter cell counter. Results also showed that the lower the SPIONs concentration, the lower the impedance is expected to be in the sensing electrodes without the cells. Meanwhile, the variation of surface area (∆S) was affected by the concentration of SPIONs. It was observed that the double layer capacitance was almost constant because of the higher attachment of cells, the lower surface area coated by SPIONs. In conclusion, impedance changes of electrodes exposed to the mixture of cells and SPIONs offer a wide dynamic range (>1 MΩ using Electric Cell-substrate Impedance electrodes) suitable for cytotoxicity studies. Based on impedance based, viability testing and microscopic methods’ results, SPIONs concentrations higher than 100 ug/mL and 300 ug/mL cause minor and major effects, respectively. We propose that a high throughput impedance-based label-free platform provides great advantages for studying SPIONs in a cell-based context, opening a window of opportunity to design and test the next generation of SPIONs with reduced toxicity for biomedical or medical applications.

Radiosensitization characteristic of superparamagnetic iron oxide nanoparticles in electron beam radiotherapy and brachytherapy

Superparamagnetic Iron Oxide Nanoparticles (SPIONs) has been the focus in medical imaging as MRI contrast agents. SPIONs demonstrate intriguing properties that not only advantageous in diagnostic imaging but also for therapeutic application. In this study, the radiosensitization characteristic of SPIONs in electron beam radiotherapy and brachytherapy were investigated. This study was conducted in-vitro using HeLa cells with SPIONs (15 nm) concentration of 1, 2 and 3 mMol/L. Irradiations were done at doses ranging from 0 to 10 Gy using electron beams of energy 6 and 12 MeV as well as 0.38 MeV 192Ir brachytherapy source. Cell survivals were determined from clonogenic assay. Radiosensitization characterization was performed by analyzing the sensitization enhancement ratio (SER) expolated from the survival curves. The results show SPIONs induce radiosensitization effects in electron beams especially at lower energy with SER value obtained up to 1.5. The radiosensitization is more prominent for brachytherapy with SER value around 2. Concentrations of SPIONs also play important roles in which higher SPIONs concentration are more likely to increase radiosensitization effects. In conclusion, radiosensitization are dependent on radiation energy and concentration of the SPIONs. Further characterization of the radiosensitization induced by SPIONs may enable clinical translation of SPIONs as radiosensitizer in radiotherapy.

Magnetic Particle Imaging–Guided Stenting

Purpose:To assess the feasibility of magnetic particle imaging (MPI) to guide stenting in a phantom model. Materials and Methods: MPI is a new tomographic imaging method based on the background-free magnetic field detection of a tracer agent composed of superparamagnetic iron oxide nanoparticles (SPIOs). All experiments were conducted on a custom-built MPI scanner (field of view: 29-mm diameter, 65-mm length; isotropic spatial resolution 1–1.5-mm). Stenosis phantoms (n=3) consisted of polyvinyl chloride (PVC) tubes (8-mm inner diameter) prepared with centrally aligned cable binders to form a ~50% stenosis. A dedicated image reconstruction algorithm allowed precise tracking of endovascular instruments at 8 frames/s with a latency time of ~115 ms. A custom-made MPI-visible lacquer was used to manually label conventional guidewires, balloon catheters, and stainless steel balloon-expandable stents. Vascular stenoses were visualized by injecting a diluted SPIO tracer (ferucarbotran, 10 mmol iron/L) into the vessel phantoms. Balloon angioplasty and stent placement were performed by inflating balloon catheters and stent delivery balloons with diluted ferucarbotran. Results: After deployment of the stent, the markers on its ends were clearly visible. The applied lacquer markers were thin enough to not relevantly alter gliding properties of the devices while withstanding friction during the experiments. Placing an optimized flexible lacquer formulation on the preexisting radiopaque stent markers provided enough stability to withstand stent expansion. Final MPA confirmed successful stenosis treatment, facilitated by the disappearance of the lacquer markers on the stent due to differences in SPIO concentration. Thus, the in-stent lumen could be visualized without interference by the signal from the markers. Conclusion: Near real-time visualization of MPI-guided stenting of stenoses in a phantom model is feasible. Optimized MPI-visible markers can withstand the expansion process of stents.

Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field

Magnetically guided cell delivery systems would be valuable to achieve effective macrophage-based cell therapy for colonic inflammatory diseases. In the current study, we developed a method for the efficient and simultaneous introduction of superparamagnetic iron oxide nanoparticles (SPIONs) and plasmid DNA (pDNA) into RAW264 murine macrophage-like cells using SPION-incorporated cationic liposome/pDNA complexes (magnetic lipoplexes). SPIONs and pDNA were introduced for magnetization and functionalization of the macrophages, respectively. We also evaluated the adhesive properties of magnetized RAW264 cells using magnetic lipoplexes in the murine colon under a magnetic field. Significant cellular association and gene expression without cytotoxicity were observed when magnetic cationic liposomes and pDNA were mixed at a weight ratio of 10:1, and SPION concentration and magnetic field exposure time was 0.1 mg/mL and 10 min, respectively. We also observed that cytokine production in magnetized RAW264 cells was similar to that in non-treated RAW264 cells, whereas nitric oxide production was significantly increased in magnetized RAW264 cells. Furthermore, magnetized RAW264 cells highly adhered to a Caco-2 cell monolayer and colon in mice, under a magnetic field. These results suggest that this magnetic cell delivery system can improve the colonic delivery of macrophages and its therapeutic efficacy against colonic inflammatory diseases.

Monodisperse magnetite nanoparticles with high sensitivity as MRI contrast agents

The preparation of monodisperse and biocompatible water-soluble super-paramagnetic iron oxide nanoparticles (SPIONs) with high sensitivity in Magnetic Resonance Imaging (MRI) represents a challenge for the development of contrast agents. Here we report the synthesis of highly monodisperse citric acid (CA) coated SPIONs with an average diameter of 9 nm and spherical shape, prepared through a suitably optimized coprecipitation method. CA-SPIONs show a high solubility and stability in aqueous medium. Imaging of CA-SPIONs aqueous suspensions was performed in a clinical 1.5-T MRI scanner and different clinical acquisition sequences were exploited. Results show that image contrast can be effectively improved when concentrations of SPIONs lower than 1 ppm are present, and that the echo time is the main parameter influencing the image contrast of SPION-loaded solutions. Moreover, we found that CA-SPIONs show a high value of transverse relaxivity of 128 L mmol -1 s -1 (higher than the commercial contrast agents). Our results are encouraging for the further development of clinical application of SPIONs in MRI, and can represent a starting point for the optimization of clinical imaging exploiting the contrast enhancement of such agents. Namely, it seems possible to achieve an optimal image contrast with low concentration of SPIONs; this could lead to a lower probability of side effects.

Rodent Cerebral Blood Volume (CBV) changes during hypercapnia observed using Magnetic Particle Imaging (MPI) detection

Magnetic Particle Imaging (MPI) is a rapidly developing imaging modality that directly measures and maps the concentration of injected superparamagnetic iron oxide nanoparticles (SPIOs). Since the agent does not cross the blood-brain barrier, cerebral SPIO concentration provides a direct probe of Cerebral Blood Volume (CBV). Here we provide an initial demonstration of the ability of MPI to detect functional CBV changes (fCBV) by monitoring SPIO concentration during hypercapnic manipulation in a rat model. As a tracer detection method, MPI offers a more direct probe of agent concentration and therefore fCBV than MRI measurements in which the agent is indirectly detected through perturbation of water relaxation time constants such as T2∗. We found that MPI detection could measure CBV changes during hypercapnia with high CNR (CNR = 50) and potentially with high temporal resolution. Although the detection process more closely resembles a tracer method, we also identify evidence of physiological noise in the MPI time-series, with higher time-series variance at higher concentration levels. Our findings suggest that CBV-based MPI can provide a detection modality for hemodynamic changes. Further investigation with tomographic imaging is needed to assess tomographic ability of the method and further study the presence of time-series fluctuations which scale with signal level similar to physiological noise in resting fMRI time-courses.

Synthesis, characterization, and relaxometry studies of hydrophilic and hydrophobic superparamagnetic Fe3O4 nanoparticles for oil reservoir applications

Information acquisition and fluid characterization of oil reservoirs are one of the most challenging and scientifically demanding areas in the oil exploration industry. Herein, we report a single-step solvothermal method for the synthesis of highly-stable hydrophilic and hydrophobic superparamagnetic iron oxide nanoparticles (SPIONs). The functionalization of SPIONs was achieved using polyethylene glycol (PEG-400) and oleylamine (OLA) for water/oil phases of the reservoir, respectively. For comparison, uncoated SPIONs were also prepared by coprecipitation. Stability of hydrophilic SPIONs was monitored in deionized (DI) water and artificial seawater (ASW), while stability of hydrophobic SPIONs was investigated in model oil (cyclohexane-hexadecane 1:1). Several physicochemical techniques were utilized to characterize the phase and functionalization of SPIONs. Transmission electron microscopy (TEM) images display the spherical shape nanoparticles (NPs) having particle diameters 11.6 ± 1.4, 12.7 ± 2.2, and 9.1 ± 3.0 nm for PEG-Fe3O4, OLA-Fe3O4, and Fe3O4, respectively. Spin-spin (T2) relaxation measurements were performed by an Acorn Area analyzer to demonstrate contrasting ability of the contrast agents. The transverse relaxivity (r2) values for PEG-Fe3O4 (66.7 mM−1 s−1) and OLA-Fe3O4 (49.0 mM−1 s−1) were 2.07 and 1.53 times higher than Fe3O4 (32.2 mM−1 s−1) NPs, respectively. The (i) enhanced NMR T2-relaxation with optimum SPIONs concentration, (ii) excellent relaxivity properties due to their ultra-small size, and (iii) long-term stability in various continuous phases, suggest them to be promising T2-contrast agents for oil reservoir applications.

High-throughput Cell Screening for Spions Studies using Impedance Spectroscopy

Superparamagnetic Iron oxide nanoparticles (SPIONs) being clinically approved had elevated the optimism of majority in terms of its applicability in both research and clinical domain. Along with this optimism is the use of impedance spectroscopy which provides a non-invasive, fast, and convenient to use for wide range of biological and chemical applicability. This study focused on high-throughput test for SPION toxicity using impedance spectroscopy of mouse neuroblastoma cells (N2A). The platform consisted of an array of ITO microelectrode incorporated with microfluidics and connected to impedance spectroscopy system. Preliminary test included recording of impedance spectroscopy of the cell culture medium (CCM), 2.5X105 cells/ml concentration, and an increasing concentration of SPIONS (25, 50, 100, 200 and 300 µg/mL). In the experimental phase, impedance spectroscopy for CCM, mixture of 2.5X105 cells/ml and 25 µg/mL SPIONS, adhesion and spreading of cells were recorded every 2-hour interval within 8 hours for two days. The experimental phase was repeated using other mixtures of cells with an increasing concentration of SPIONs. Result showed that there was no significant difference on the impedance of CCM overtime. Meanwhile, there was a change in impedance for the concentration of cells, different SPIONs concentration and mixtures of cells and SPIONS overtime. Also, confirmatory and viability test were performed. The above findings substantiate the importance of thorough investigation of the interaction of SPIONS to the culture medium and high throughput screening of the toxicity effect of SPIONs to neuronal cells. The findings may be used to expand basic knowledge on the morphological characteristics of neuronal cells and physico-chemical aspect of SPIONs in the academe and research. Finally, this would also lead to further characterization of neuronal activities for the development of neuro-biosensors for early detection of neurological diseases and other clinical application.

Gaussian process classification of superparamagnetic relaxometry data: Phantom study.

Superparamagnetic relaxometry (SPMR) is an emerging technology that holds potential for use in early cancer detection. Measurement of the magnetic field after the excitation of cancer-bound superparamagnetic iron oxide nanoparticles (SPIONs) enables the reconstruction of SPIONs spatial distribution and hence tumor detection. However, image reconstruction often requires solving an ill-posed inverse problem that is computationally challenging and sensitive to measurement uncertainty. Moreover, an additional image processing module is required to automatically detect and localize the tumor in the reconstructed image. Our goal is to examine the use of data-driven machine learning technique to detect a weak signal induced by a small cluster of SPIONs (surrogate tumor) in presence of background signal and measurement uncertainty. We aim to investigate the performance of both data-driven and image reconstruction models to characterize situations that one can replace the computationally-challenging reconstruction technique by the data-driven model. We utilize Gaussian process (GP) classification model and a physics-based image reconstruction method, tailored to SPMR datasets that are obtained from (i) in silico simulations designed based on mouse cancer models and (ii) phantom experiments using MagSense system (Imagion Biosystems, Inc.). We investigate the performance of the GP classifier against the reconstruction technique, for different levels of measurement noise, different scenarios of SPIONs distribution, and different concentrations of SPIONs at the surrogate tumor. In our in silico source detection analysis, we were able to achieve high sensitivity results using GP model that outperformed the image reconstruction model for various choices of SPIONs concentration at the surrogate tumor and measurement noise levels. Moreover, in our phantom studies we were able to detect the surrogate tumor phantoms with 5% and 7.3% of the total used SPIONs, surrounded by 9 low-concentration phantoms with accuracies of 87.5% and 96.4%, respectively. The GP framework provides acceptable classification accuracies when dealing with in silico and phantom SPMR datasets and can outperform an image reconstruction method for binary classification of SPMR data.

Superparamagnetic Iron Oxide Nanoparticles-Complexed Cationic Amylose for In Vivo Magnetic Resonance Imaging Tracking of Transplanted Stem Cells in Stroke

Cell-based therapy with mesenchymal stem cells (MSCs) is a promising strategy for acute ischemic stroke. In vivo tracking of therapeutic stem cells with magnetic resonance imaging (MRI) is imperative for better understanding cellular survival and migrational dynamics over time. In this study, we develop a novel biocompatible nanocomplex (ASP-SPIONs) based on cationic amylose, by introducing spermine and the image label, ultrasmall superparamagnetic iron oxide nanoparticles (SPIONs), to label MSCs. The capacity, efficiency, and cytotoxicity of the nanocomplex in transferring SPIONs into green fluorescence protein-modified MSCs were tested; and the performance of in vivo MRI tracking of the transplanted cells in acute ischemic stroke was determined. The results demonstrated that the new class of SPIONs-complexed nanoparticles based on biodegradable amylose can serve as a highly effective and safe carrier to transfer magnetic label into stem cells. A reliable tracking of transplanted stem cells in stroke was achieved by MRI up to 6 weeks, with the desirable therapeutic benefit of stem cells on stroke retained. With the advantages of a relatively low SPIONs concentration and a short labeling period, the biocompatible complex of cationic amylose with SPIONs is highly translatable for clinical application. It holds great promise in efficient, rapid, and safe labeling of stem cells for subsequent cellular MRI tracking in regenerative medicine.

Magnetic Particle Imaging (MPI): Experimental Quantification of Vascular Stenosis Using Stationary Stenosis Phantoms.

Magnetic Particle Imaging (MPI) is able to provide high temporal and good spatial resolution, high signal-to-noise ratio and sensitivity. Furthermore, it is a truly quantitative method as its signal strength is proportional to the concentration of its tracer, superparamagnetic iron oxide nanoparticles (SPIOs). Because of that, MPI is proposed to be a promising future method for cardiovascular imaging. Here, an interesting application may be the quantification of vascular pathologies like stenosis by utilizing the proportionality of the SPIO concentration and the MPI signal strength. In this study, the feasibility of MPI based stenosis quantification is evaluated based on this application scenario. Nine different stenosis phantoms with a normal diameter of 10 mm each and different stenoses of 1–9 mm and ten reference phantoms with a straight diameter of 1–10 mm were filled with a 1% Resovist dilution and measured in a preclinical MPI-demonstrator. The MPI signal intensities of the reference phantoms were compared to each other and the change of signal intensity within each stenosis phantom was used to calculate the degree of stenosis. These values were then compared to the known diameters of each phantom. As a second measurement, the 5 mm stenosis phantom was used for a serial dilution measurement down to a Resovist dilution of 1:3200 (0.031%), which is lower than a first pass blood concentration of a Resovist bolus in the peripheral arteries of an average adult human of at least about 1:1000. The correlation of the stenosis values based on MPI signal intensity measurements and based on the known diameters showed a very good agreement, proving the high precision of quantitative MPI in this regard.