Micrometer-sized Iron Oxide Particles Research Articles

The Magnetic Field of Magnetic Resonance Imaging Systems Does Not Affect Cells Labeled with Micrometer-Sized Iron Oxide Particles.

Labeling using iron oxide particles enables cell tracking through magnetic resonance imaging (MRI). However, the magnetic field can affect the particle-labeled cells. Here, we investigated the effects of a clinical MRI system on primary human hepatocytes labeled using micrometer-sized iron oxide particles (MPIOs). HuH7 tumor cells were incubated with increasing concentrations of biocompatible, silica-based, micrometer-sized iron oxide-containing particles (sMPIOs; 40-160 particles/cell). Primary human hepatocytes were incubated with 100 sMPIOs/cell. The particle-labeled cells and the native cells were imaged using a clinical 3.0 T MRI system, whereas the control groups of the labeled and unlabeled cells were kept at room temperature without exposure to a magnetic field. Viability, formation of reactive oxygen species (ROS), aspartate aminotransferase leakage, and urea and albumin synthesis were assessed for a culture period of 5 days. The dose finding study showed no adverse effects of the sMPIOs labeling on HuH7 cells. MRI had no adverse effects on the morphology of the sMPIO-labeled primary human hepatocytes. Imaging using the T1- and T2-weighted sequences did not affect the viability, transaminase leakage, formation of ROS, or metabolic activity of the sMPIO-labeled cells or the unlabeled, primary human hepatocytes. sMPIOs did not induce adverse effects on the labeled cells under the conditions of the magnetic field of a clinical MRI system.

Fouling of a Heated Rod in a Stirred Tank System

A batch stirred tank device has been developed for measuring fouling from oil samples. The unit consists of a baffled tank equipped with a centrally mounted long blade stirrer, and an electrically heated rod located at 40% of the radius of the tank. Heat transfer from the rod was first characterized. The velocity field was measured, from which the approach velocity to the probe was determined, which allowed the wall shear on the heating probe to be calculated from a literature equation. Fouling of a heavy oil fraction was studied in 1- to 2-day experiments with bulk oil temperatures typically at 320°C, initial probe surface temperatures to 536°C, and stirrer speeds of 100–900 rpm. Micrometer-sized iron oxide particles were added to the oil, such that fouling was due to a combination of particle deposition and coke formation. Deposition rates were measured thermally from the change in heat transfer coefficient when fouling was relatively heavy, and by thickness and mass accumulation when fouling was light. Effects of oil type, film temperature, stirrer rotation speed (or probe wall shear stress), and concentration of suspended particles on deposition rate and deposit composition are presented.

CARS microscopy for the visualization of micrometer-sized iron oxide MRI contrast agents in living cells

Micrometer-sized iron oxide particles (MPIOs) attract increasing interest as contrast agents for cellular tracking by clinical Magnetic Resonance Imaging (MRI). Despite the great potential of MPIOs for in vivo imaging of labeled cells, little is known on the intracellular localization of these particles following uptake due to the lack of techniques with the ability to monitor the particle uptake in vivo at single-cell level. Here, we show that coherent anti-Stokes Raman scattering (CARS) microscopy enables non-invasive, label-free imaging of MPIOs in living cells with sub-micron resolution in three dimensions. CARS allows simultaneous visualization of the cell framework and the MPIOs, where the particles can be readily distinguished from other cellular components of comparable dimensions, and localized inside the cell.

Assessment of cell infiltration in myocardial infarction: A dose-dependent study using micrometer-sized iron oxide particles

Myocardial infarction (MI) is a leading cause of death and disabilities. Inflammatory cells play a vital role in the process of postinfarction remodeling and repair. Inflammatory cell infiltration into the infarct site can be monitored using T 2-weighted MRI following an intravenous administration of iron oxide particles. In this study, various doses of micrometer-sized iron oxide particles (1.1-14.5 μg Fe/g body weight) were injected into the mouse blood stream before a surgical induction of MI. Cardiac MRIs were performed at 3, 7, 14, and 21 days postinfarction to monitor the signal attenuation at the infarct site. A dose-dependent phenomenon of signal attenuation was observed at the infarct site, with a higher dose leading to a darker signal. The study suggests an optimal temporal window for monitoring iron oxide particles-labeled inflammatory cell infiltration to the infarct site using MRI. The dose-dependent signal attenuation also indicates an optimal iron oxide dose of approximately 9.1-14.5 μg Fe/g body weight. A lower dose cannot differentiate the signal attenuation, whereas a higher dose would cause significant artifacts. This iron oxide-enhanced MRI technique can potentially be used to monitor cell migration and infiltration at the pathological site or to confirm any cellular response following some specific treatment strategies.

Monitoring bone marrow-originated mesenchymal stem cell traffic to myocardial infarction sites using magnetic resonance imaging

How stem cells promote myocardial repair in myocardial infarction (MI) is not well understood. The purpose of this study was to noninvasively monitor and quantify mesenchymal stem cells (MSC) from bone marrow to MI sites using magnetic resonance imaging (MRI). MSC were dual-labeled with an enhanced green fluorescent protein and micrometer-sized iron oxide particles prior to intra-bone marrow transplantation into the tibial medullary space of C57Bl/6 mice. Micrometer-sized iron oxide particles labeling caused signal attenuation in T(2)*-weighted MRI and thus allowed noninvasive cell tracking. Longitudinal MRI demonstrated MSC infiltration into MI sites over time. Fluorescence from both micrometer-sized iron oxide particles and enhanced green fluorescent protein in histology validated the presence of dual-labeled cells at MI sites. This study demonstrated that MSC traffic to MI sites can be noninvasively monitored in MRI by labeling cells with micrometer-sized iron oxide particles. The dual-labeled MSC at MI sites maintained their capability of proliferation and differentiation. The dual-labeling, intra-bone marrow transplantation, and MRI cell tracking provided a unique approach for investigating stem cells' roles in the post-MI healing process. This technique can potentially be applied to monitor possible effects on stem cell mobilization caused by given treatment strategies.

Micrometer-sized iron oxide particle labeling of mesenchymal stem cells for magnetic resonance imaging-based monitoring of cartilage tissue engineering

PurposeTo examine mesenchymal stem cell (MSC) labeling with micrometer-sized iron oxide particles (MPIOs) for magnetic resonance imaging (MRI)-based tracking and its application to monitoring articular cartilage regeneration. MethodsRabbit MSCs were labeled using commercial MPIOs. In vitro MRI was performed with gradient echo (GRE) and spin echo (SE) sequences at 3T and quantitatively characterized using line profile and region of interest analysis. Ex vivo MRI of hydrogel-encapsulated labeled MSCs implanted within a bovine knee was performed with spoiled GRE (SPGR) and T1ρ sequences. Fluorescence microscopy, labeling efficiency, and chondrogenesis of MPIO-labeled cells were also examined. ResultsMPIO labeling results in efficient contrast uptake and signal loss that can be visualized and quantitatively characterized via MRI. SPGR imaging of implanted cells results in ex vivo detection within native tissue, and T1ρ imaging is unaffected by the presence of labeled cells immediately following implantation. MPIO labeling does not affect quantitative glycosaminoglycan production during chondrogenesis, but iron aggregation hinders extracellular matrix visualization. This aggregation may result from excess unincorporated particles following labeling and is an issue that necessitates further investigation. ConclusionThis study demonstrates the promise of MPIO labeling for monitoring cartilage regeneration and highlights its potential in the development of cell-based tissue engineering strategies.

Temporal and noninvasive monitoring of inflammatory‐cell infiltration to myocardial infarction sites using micrometer‐sized iron oxide particles

Micrometer-sized iron oxide particles (MPIO) are a more sensitive MRI contrast agent for tracking cell migration compared to ultrasmall iron oxide particles. This study investigated the temporal relationship between inflammation and tissue remodeling due to myocardial infarction (MI) using MPIO-enhanced MRI. C57Bl/6 mice received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later (n=7). For controls, two groups underwent either sham-operated surgery without inducing an MI post-MPIO injection (n=7) or MI surgery without MPIO injection (n=6). The MRIs performed post-MI showed significant signal attenuation around the MI site for the mice that received an intravenous MPIO injection for cell labeling, followed by a surgically induced MI seven days later, compared to the two control groups (P<0.01). The findings suggested that the prelabeled inflammatory cells mobilized and infiltrated into the MI site. Furthermore, the linear regression of contrast-to-noise ratio at the MI site and left ventricular ejection function suggested a positive correlation between the labeled inflammatory cell infiltration and cardiac function attenuation during post-MI remodeling (r2=0.98). In conclusion, this study demonstrated an MRI technique for noninvasively and temporally monitoring inflammatory cell migration into the myocardium while potentially providing additional insight concerning the pathologic progression of a myocardial infarction.

MRI detection of single particles for cellular imaging.

There is rapid growth in the use of MRI for molecular and cellular imaging. Much of this work relies on the high relaxivity of nanometer-sized, ultrasmall dextran-coated iron oxide particles. Typically, millions of dextran-coated ultrasmall iron oxide particles must be loaded into cells for efficient detection. Here we show that single, micrometer-sized iron oxide particles (MPIOs) can be detected by MRI in vitro in agarose samples, in cultured cells, and in mouse embryos. Experiments studying effects of MRI resolution and particle size from 0.76 to 1.63 microm indicated that T(2)* effects can be readily detected from single MPIOs at 50-microm resolution and significant signal effects could be detected at resolutions as low as 200 microm. Cultured cells were labeled with fluorescent MPIOs such that single particles were present in individual cells. These single particles in single cells could be detected both by MRI and fluorescence microscopy. Finally, single particles injected into single-cell-stage mouse embryos could be detected at embryonic day 11.5, demonstrating that even after many cell divisions, daughter cells still carry individual particles. These results demonstrate that MRI can detect single particles and indicate that single-particle detection will be useful for cellular imaging.

Effect of the occurrence and composition of iron compounds on ash formation, composition, and size in pilot-scale combustion of pulverized coal and coal-water slurry fuels

Two coals, Beulah (North Dakota) lignite and Elk Creek (West Virginia) high-volatile A bituminous, were burned in both pulverized coal and coal-water slurry fuel forms to study the effect of the modes of occurrence and composition of iron compounds in the coal on the particle size distribution and composition of ash. The slurry preparation process appeared to cause a significant reduction in the particle size distribution of pyrite in the lignite, relative to the pulverized coal. This in turn caused a change in the dominant mechanism of ash formation. In the Beulah pulverized coal, pyrite fragmentation is the major process, forming submicrometer- or micrometer-sized iron oxide particles