Ultrasmall Superparamagnetic Iron Oxide Nanoparticles Research Articles

Challenges towards MR imaging of the peripheral inflammatory response in the subacute and chronic stages of transient focal ischemia

Intravenous administration of iron oxide nanoparticles after experimental stroke has been shown to produce focal signal intensity changes in the ischemic boundary on MRI images. These changes have been attributed to the influx of iron-laden blood-borne macrophages, although it has been suggested that this effect might not always be completely specific to inflammatory cells. The aim of the present study was to investigate this phenomenon in a subacute time frame that is more relevant to the peripheral inflammatory response. Imaging experiments (T(2) -, T(2)*- and T(1) -weighted sequences) were acquired in Wistar rats 6 days after transient middle cerebral artery occlusion (MCAO). Animals were intravenously infused with different doses of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (300, 600 or 1000 µmol Fe/kg), or saline and gadolinium, and imaged again 24 h later. Tissue was immediately processed for immunohistochemistry with the macrophage marker ED-1, in combination with Prussian blue for iron. Ischemic tissue exhibited a large increase in T(2) values, and overall contrast enhancement was apparent in the brain and surrounding muscle. In contrast with previous reports, there were no regions of focal signal intensity changes in the ischemic territory in any of the images, although a region of interest analysis revealed a trend towards iron accumulation in the ischemic hemisphere, particularly in the cortex of T(2)* images. However, histological examination revealed that, despite extensive ED-1-positive macrophage accumulation in the entire ischemic territory, none of these cells were Prussian blue positive, except in the meninges of one animal that received a high dose of USPIO nanoparticles. These results imply that the observed trend is a result of the presence of contrast agent in the blood, or meninges, and not iron-containing inflammatory cells.

Combined off‐resonance imaging and T2 relaxation in the rotating frame for positive contrast MR imaging of infection in a murine burn model

To develop novel magnetic resonance (MR) imaging methods to monitor accumulation of macrophages in inflammation and infection. Positive-contrast MR imaging provides an alternative to negative-contrast MRI, exploiting the chemical shift induced by ultra-small superparamagnetic iron-oxide (USPIO) nanoparticles to nearby water molecules. We introduce a novel combination of off-resonance (ORI) positive-contrast MRI and T(2ρ) relaxation in the rotating frame (ORI-T(2ρ)) for positive-contrast MR imaging of USPIO. We tested ORI-T(2ρ) in phantoms and imaged in vivo the accumulation of USPIO-labeled macrophages at the infection site in a mouse model of burn trauma and infection with Pseudomonas aeruginosa (PA). PA infection is clinically important. The USPIO nanoparticles were injected directly in the animals in solution, and macrophage labeling occurred in vivo in the animal model. We observed a significant difference between ORI-T(2ρ) and ORI, which leads us to suggest that ORI-T(2ρ) is more sensitive in detecting USPIO signal. To this end, the ORI-T(2ρ) positive contrast method may prove to be of higher utility in future research. Our results may have direct implications in the longitudinal monitoring of infection, and open perspectives for testing novel anti-infective compounds.

Targeted Molecular Imaging of Antigen OC183B2 in Ovarian Cancers Using MR Molecular Probes

This study was designed to develop a novel magnetic resonance (MR) probe for the antigen OC183B2 in ovarian cancer cells and investigate its imaging features in vitro and in vivo. Molecular probes were achieved through ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) conjugated to ovarian cancer monoclonal antibodies 183B2 (OCMab183B2) using a chemical method. In the control group, USPIOs were coupled with murine immunoglobulin G (mIgG) and conjugated the same way. Native polyacrylamide gel electrophoresis was used to evaluate the conjugation reaction. The cytotoxicity of the probe was measured using the methyl thiazolyl tetrazolium assay, and its cell-labeling efficiency was evaluated by Prussian blue staining. In vitro cell MR imaging was performed to evaluate the targeting of the probe to the cells. After that, the OCMab183B2 USPIOs and mIgG USPIOs were injected intravenously into nude mice implanted with ovarian cancer xenograft tumors, respectively. T2-weighted imaging and T2 mapping were then performed on a 3.0-T MR imaging system equipped with an animal birdcage coil at different times. Finally, the nude mice were sacrificed for histologic examination to confirm the imaging results. Native polyacrylamide gel electrophoresis displayed an optimal conjugation of USPIOs to OCMab183B2 and mIgG. Various blue-staining particles were found in the cells labeled with the molecular probe at different iron concentrations, and the density of particles was positively related to the iron concentration. Its labeling rate was 96.06%, which was higher than that of USPIOs (62.5%) at the same iron concentration (20 μg/mL). The methyl thiazolyl tetrazolium assay showed that there was no difference in cellular bioactivity between OCMab183B2 USPIO-labeled and nonlabeled cells (P > .05). In vitro cell MR imaging showed that there was an obvious decrease in signal intensity for the probe-labeled cells compared to mIgG USPIO-labeled cells. For in vivo MR imaging, distinct changes of signal intensities and T2 values of ovarian cancers were detected after the injection of OCMab183B2 USPIOs compared to mIgG USPIOs. The histologic analysis showed that iron depositions were visualized in the experimental group but not in the control group. OCMab183B2 USPIO conjugates have the potential to be useful as OC183B2-targeted MR imaging agents for the early detection of ovarian cancers.

Interaction of Cationic Ultrasmall Superparamagnetic Iron Oxide Nanoparticles with Human Melanoma Cells

Ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) are currently under development for the intracellular delivery of therapeutics. However, the mechanisms of cellular uptake and the cellular reaction to this uptake, independent of therapeutics, are not well defined. The interactions of biocompatible cationic aminoUSPIONs with human cells was studied in 2D and 3D cultures using biochemical and electron microscopy techniques. AminoUSPIONs were internalized by human melanoma cells in 2D and 3D cultures. Uptake was clathrin mediated and the particles localized in lysosomes, inducing activation of the lysosomal cathepsin D and decreasing the expression of the transferrin receptor in human melanoma cells and/or skin fibroblasts. AminoUSPIONs deeply invaded 3D spheroids of human melanoma cells. Thus, aminoUSPIONs can invade tumors and their uptake by human cells induces cell reaction.

Preparation and characterization of a magnetic and optical dual-modality molecularprobe

Multi-modality imaging probes combine the advantages of individual imaging techniques toyield highly detailed anatomic and molecular information in living organisms. Herein, wereport the synthesis and characterization of a dual-modality nanoprobe that couples themagnetic properties of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs)with the near infrared fluorescence of Cy5.5. The fluorophore is encapsulated in abiocompatible shell of silica surrounding the iron oxide core for a final diameter of ∼ 17 nm. This silica-coated iron oxide nanoparticle (SCION) has been analyzed by transmissionelectron microscopy, dynamic light scattering, and superconducting quantum interferencedevice (SQUID). The particle demonstrates a strong negative surface charge and maintainscolloidal stability in the physiological pH range. Magnetic hysteresis analysis confirmssuperparamagnetic properties that could be manipulated for thermotherapy. The viabilityof primary human monocytes, T cells, and B cells incubated with the particlehas been examined in vitro. In vivo analysis of agent leakage into subcutaneousA431 tumors in mice was also conducted. This particle has been designed fordiagnostic application with magnetic resonance and fluorescence imaging, andhas future potential to serve as a heat-sensitive targeted drug delivery platform.

The ATHEROMA Study: Rapid Anti-inflammatory Effects of High-Dose Statin Pharmacotherapy Illuminated by Molecular MRI

Statins are thought to reduce inflammation in atherosclerotic plaques; however, to date, in vivo data in clinical subjects demonstrating this effect and statin-dose dependency are limited. Molecular MRI of carotid plaque macrophage activity is well-validated using ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles and offers a novel clinical approach to assess the effects of antiinflammatory therapies in human subjects. Aims

Lymphotropic nanoparticle enhanced MRI for the staging of genitourinary tumors

Nanotechnology is poised to have a substantial influence on biomedicine. A unique example of a nanotechnology that has progressed from proof-of-concept to human clinical trials is the use of ultrasmall superparamagnetic iron oxide nanoparticles as a cell-specific contrast agent for MRI. When injected systemically, these particles are taken up by macrophages of the reticuloendothelial system and accumulate in lymph nodes. This passive, cell-specific targeting of the iron oxide nanoparticles to lymph nodes, and the differential cellular content of benign versus malignantly infiltrated nodes make this method suitable for cancer staging. By using lymphotropic nanoparticle enhanced MRI, differences in benign versus malignant infiltration of lymph nodes can be visualized, which adds accuracy to standard MRI beyond criteria based solely upon the size and shape of lymph nodes. This technology has been used to assess lymph node metastases in a large number of human cancer types. In this Review, we focus on lymphotropic nanoparticle enhanced MRI and its application for the staging of genitourinary malignancies.

Detection sensitivity of lymph nodes of various sizes using USPIO nanoparticles in magnetic resonance imaging

Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles–based magnetic resonance imaging (MRI) have offered new promise for early detection of lymph nodes and their metastases. These nanoparticles are taken up by macrophages in normal lymph nodes and produce signal changes based on susceptibility artifact and dipolar relaxation. The effects of MR protocols and their parameters on artifact size and detection sensitivity have been studied before. In this study USPIO nanoparticles were used as MRI contrast agent, and their detection sensitivity in axillary lymph nodes was evaluated using earlier defined pulse sequences. The minimum amount (dose) of USPIO nanoparticles that delineates lymph nodes of various sizes using susceptibility-based gradient echo pulse sequences was also determined. It was found that a dose administration of as low as 0.028 mg iron (Fe)/kg for subcutaneous injection and 0.16 mg Fe/kg for intravenous injection can be used to visualize axillary lymph nodes when a sensitive MR protocol is employed. From the Clinical Editor Ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles are taken up by macrophages and have been shown to be promising negative contrast agents in the early detection of metastases in lymph nodes. In this study, their detection sensitivity in axillary lymph nodes was evaluated using previously defined MRI pulse sequences. The minimum dose of USPIO to delineate lymph nodes using gradient echo-based optimized pulse sequences was 0.028 mgFe/kg for subcutaneous and 0.16 mgFe/kg for intravenous injection.

Noninvasively characterizing the different αvβ3 expression patterns in lung cancers with RGD-USPIO using a clinical 3.0T MR scanner

The adhesion molecule alphavbeta3 integrin plays an important role in tumor development and metastases. We demonstrated the specificity of the probe to alphavbeta3 integrin with transmission electron microcopy (TEM) and magnetic resonance imaging (MRI). The in vivo targeting behavior of the probe was examined in 2 tumor models with different alphavbeta3 expression patterns by a 3.0T MRI scanner. MR imaging showed that R2* pseudo-color pictures of A549 lung cancer tumor was different from that of 3LL lung cancer. For A549 tumor, an homogeneous decrease of signal intensity was observed throughout the tumor, which was more evident in the periphery or central areas. Histological studies revealed that alphavbeta3 integrin was expressed both on the tumor vessel and tumor cells for A549 tumor. Our findings indicated that it was possible to noninvasively characterize the different alphavbeta3 expression pattern in lung cancers with arginine-glycine-aspartic acid (RGD) peptide conjugated ultra-small superparamagnetic iron oxide nanoparticles (RGD-USPIO) using a clinical 3.0T MR scanner. Nevertheless, the way of imaging targeting presentation of the probe differed in tumors with different alphavbeta3 expression patterns.

Quantitative effects of cell internalization of two types of ultrasmall superparamagnetic iron oxide nanoparticles at 4.7 T and 7 T

MRI coupled with the intravenous injection of ultrasmall superparamagnetic particles of iron oxides (USPIOs) is a promising tool for the study of neuroinflammation. Quantification of the approximate number of magnetically labelled macrophages may provide an effective and efficient method for monitoring inflammatory cells. The purpose of the present study was to characterise the relaxation properties of macrophages labelled with two types of USPIOs, at 4.7 T and 7 T. USPIO-labelled bone-marrow-derived macrophage phantoms were compared with phantoms of free dispersed USPIOs with the same global iron concentration, using multi-parametric (T1, T2 and T2) quantitative MRI. The same protocol was then evaluated in living mice after intracerebral injection of iron-labelled macrophages vs free iron oxide. A linear relationship was observed among R1, R2 and R2 values and iron concentration in vitro at 4.7 T and at 7 T. At a given field, T1 and T2 relaxivities of both types of USPIOs decreased following internalisation into macrophages, while T2 relaxivities increased. There was fair overall agreement between the theoretical number of injected cells and the number estimated from T2 quantification and in vitro calibration curves, supporting the validity of the present in vitro calibration curves for in vivo investigation.

Specific targeting of breast tumor by octreotide-conjugated ultrasmall superparamagnetic iron oxide particles using a clinical 3.0-tesla magnetic resonance scanner

Targeted magnetic resonance contrast agents have enabled the imaging of biological processes in vivo, and current insights have opened up new perspectives for the monitoring and diagnosis of many diseases. To develop a contrast agent for targeting somatostatin receptors (SSTRs) expressed on breast cancer cells, and to evaluate the detection capabilities of a molecular probe using magnetic resonance (MR) imaging in an in vivo mouse model of breast carcinoma. Octreotide (OCT) was conjugated with polyethylene glycol-coated ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles by an ethyl-3-(dimethylaminopropyl) carbodiimide (EDC)-mediated reaction. Prussian blue staining for intracellular iron, 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and cellular MR imaging in vitro were performed on labeled MCF-7 breast cancer cells. Twenty-four mice bearing tumors were divided into two groups: 1) study group with injection of OCT-USPIOs (n=12); 2) control group with injection of USPIOs (n=12). Tumors were monitored in vivo using a 3.0-Tesla MR scanner before and after injection of contrast agents, and the findings were correlated with the histopathological findings. OCT-USPIOs were shown to specifically bind to MCF-7 cells and did not affect proliferation and viability of the cells labeled. T(2) value of the cells labeled with OCT-USPIOs in vitro was 56.465+/-13.147 ms, while those of the cells cultured with USPIOs and gelatin/phosphate-buffered saline (PBS) gel alone were 75.435+/-16.171 ms and 85.950+/-22.352 ms, respectively (P<0.05). Signal intensity of the tumor gradually decreased, and its T(2) value reached a minimum of approximately 24.49% 6 hours after injection of OCT-USPIOs in vivo, compared to a minimum of 21.89% after 2 hours in the control group. Iron depositions were visualized as blue particles in tumor 6 hours after injection of OCT-USPIOs, while no blue particles were observed in the control group. SSTR expression in vitro and in vivo can be selectively and directly imaged with an MR molecular probe. OCT-conjugated PEG-coated USPIO is potentially suitable to be used as a magnetic resonance contrast agent for MR imaging in vivo and increases the sensitivity for the early detection of breast carcinoma.

Fast low-angle positive contrast steady-state free precession imaging of USPIO-labeled macrophages: theory and in vitro experiment

The feasibility of imaging macrophages labeled with ultrasmall superparamagnetic iron-oxide nanoparticles (USPIO) with fast low-angle positive contrast steady-state free precession (FLAPS) was investigated through theory and in vitro experiment. Human macrophage cells were labeled with USPIO and imaged at 1.5 T. The metric "visibility," which combines magnitude and spatial extent of positive contrast, was used to evaluate the images. Negative contrast steady-state free precession (SSFP) and gradient-echo (GRE) imaging were also evaluated. Positive contrast was observed for relatively high concentrations of labeled cells for flip angles less than alpha=25 degrees . Theoretical and experimental results indicate that positive visibility (VIS(POS)) was maximized at alpha=10 degrees and 15 degrees. Low flip angle SSFP also provided negative contrast comparable to standard SSFP and GRE imaging. Results suggest that USPIO-labeled macrophages are capable of producing the conditions necessary for positive contrast with FLAPS at clinical field strength (1.5 T) and resolution (0.8x0.8x3 mm(3)).

Surface‐Functionalized Ultrasmall Superparamagnetic Nanoparticles as Magnetic Delivery Vectors for Camptothecin

Drug-nanoparticle conjugates: The anticancer drug camptothecin (CPT) was covalently linked at the surface of ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) via a linker, allowing drug release by cellular esterases. Nanoparticles were hierarchically built to achieve magnetically-enhanced drug delivery to human cancer cells and antiproliferative activity.The linking of therapeutic drugs to ultrasmall superparamagnetic iron oxide nanoparticles (USPIOs) allowing intracellular release of the active drug via cell-specific mechanisms would achieve tumor-selective magnetically-enhanced drug delivery. To validate this concept, we covalently attached the anticancer drug camptothecin (CPT) to biocompatible USPIOs (iron oxide core, 9-10 nm; hydrodynamic diameter, 52 nm) coated with polyvinylalcohol/polyvinylamine (PVA/aminoPVA). A bifunctional, end-differentiated dicarboxylic acid linker allowed the attachment of CPT to the aminoPVA as a biologically labile ester substrate for cellular esterases at one end, and as an amide at the other end. These CPT-USPIO conjugates exhibited antiproliferative activity in vitro against human melanoma cells. The intracellular localization of CPT-USPIOs was confirmed by transmission electron microscopy (iron oxide core), suggesting localization in lipid vesicles, and by fluorescence microscopy (CPT). An external static magnetic field applied during exposure increased melanoma cell uptake of the CPT-USPIOs.

Comparison of Superparamagnetic and Ultrasmall Superparamagnetic Iron Oxide Cell Labeling for Tracking Green Fluorescent Protein Gene Marker with Negative and Positive Contrast Magnetic Resonance Imaging

The objectives of this study were to investigate the feasibility of imaging green fluorescent protein (GFP)-expressing cells labeled with iron oxide nanoparticles with the fast low-angle positive contrast steady-state free precession (FLAPS) method and to compare them with the traditional negative contrast technique. The GFP-R3230Ac cell line (GFP cell) was incubated for 24 hours using 20 microg Fe/mL concentration of superparamagnetic iron oxide (SPIO) and ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. Cell samples were prepared for iron content analysis and cell function evaluation. The labeled cells were imaged using positive contrast with FLAPS imaging, and FLAPS images were compared with negative contrast T2*-weighted images. The results demonstrated that SPIO and USPIO labeling of GFP cells had no effect on cell function or GFP expression. Labeled cells were successfully imaged with both positive and negative contrast magnetic resonance imaging (MRI). The labeled cells were observed as a narrow band of signal enhancement surrounding signal voids in FLAPS images and were visible as signal voids in T2*-weighted images. Positive contrast and negative contrast imaging were both valuable for visualizing labeled GFP cells. MRI of labeled cells with GFP expression holds potential promise for monitoring the temporal and spatial migration of gene markers and cells, thereby enhancing the understanding of cell- and gene-based therapeutic strategies.

Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)?

Gadolinium (Gd) based contrast agents (GBCAs) in magnetic resonance imaging (MRI) are used in daily clinical practice and appear safe in most patients; however, nephrogenic systemic fibrosis (NSF) is a recently recognized severe complication associated with GBCAs. It affects primarily patients with renal disease, such as stage 4 or 5 chronic kidney disease (CKD; glomerular filtration rate <30 ml/min per 1.73 m(2)), acute kidney injury, or kidney and liver transplant recipients with kidney dysfunction. Contrast-enhanced MRI and computed tomography (CT) scans provide important clinical information and influence patient management. An alternative contrast agent is needed to obtain adequate imaging results while avoiding the risk of NSF in this vulnerable patient group. One potential alternative is ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, which provide enhancement characteristics similar to GBCAs. We review our experience in approximately 150 patients on the potential benefits of the USPIOs ferumoxtran-10 and ferumoxytol. We focus on central nervous system (CNS) MRI but also review imaging of other vascular beds. Safety studies, including USPIO administration (ferumoxytol) as iron supplement therapy in CKD patients on and not on dialysis, suggest that decreased kidney function does not alter the safety profile. We conclude that for both CNS MR imaging and MR angiography, USPIO agents like ferumoxytol are a viable option for patients at risk for NSF.

How size evaluation of lymph node is protocol dependent in MRI when using ultrasmall superparamagnetic iron oxide nanoparticles

In this study, the volume of susceptibility artifact was evaluated in T1 and T2-weighted spin echo (SE) and gradient echo (GRE) images at various parameters using registration and subtraction methods. In order to state an important misinterpretation problem in lymphography, it was demonstrated that a lymph node size may be enlarged approximately 10 times when a T2*-weighted GRE protocol is used. To overcome this problem a technical consideration using multisequence (GRE and SE) paradigm was suggested to ensure both lymph node detection and metastasis identification in lymphatic system. The paradigm was also extended by post-processing manipulation of the SE images using a registration and subtraction approach for detection of lymphatic lesions.

Dynamic MRI Using Iron Oxide Nanoparticles to Assess Early Vascular Effects of Antiangiogenic versus Corticosteroid Treatment in a Glioma Model

The vascular effects of antiangiogenic treatment may pose problems for evaluating brain tumor response based on contrast-enhanced magnetic resonance imaging (MRI). We used serial dynamic contrast-enhanced MRI at 12 T to assess vascular responses to antiangiogenic versus steroid therapy. Athymic rats with intracerebral U87MG human glioma (n=17) underwent susceptibility-weighted perfusion MRI with ferumoxytol, a solely intravascular ultrasmall superparamagnetic iron oxide (USPIO) nanoparticle, followed by T1-weighted dynamic gadodiamide-enhanced MRI to measure vascular permeability. Rats were imaged before and after 24, 48, and 72 h of treatment with the antiangiogenic agent bevacizumab or the corticosteroid dexamethasone. Contrast agent extravasation was seen rapidly after gadodiamide, but not with ferumoxytol administration. Bevacizumab significantly decreased the blood volume and decreased permeability in tumors as determined by increased time-to-peak enhancement. A single dose of 45 mg/kg bevacizumab resulted in changes analogous to dexamethasone given in an extremely high dose (12 mg/kg per day), and was significantly more effective than dexamethasone at 2 mg/kg per day. We conclude that dynamic perfusion MRI measurements with ferumoxytol USPIO to assess cerebral blood volume, along with dynamic gadodiamide-enhanced MR to assess vascular permeability, hold promise in more accurately detecting therapeutic responses to antiangiogenic therapy.

Pitfalls in employing superparamagnetic iron oxide particles for stem cell labelling andin vivoMRI tracking

Pitfalls in employing superparamagnetic iron oxide particles for stem cell labelling and<i>in vivo</i>MRI tracking

547 POSTER Effect of the extract of Taraxacum officinale on inflammation induced by anti-cancer treatment

Transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising approach for treatment of epilepsy. To our knowledge, there is little research on magnetic resonance imaging (MRI) tracking of BMSCs labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles in a rat model of temporal lobe epilepsy (TLE). In this study, BMSCs were pre-labeled with USPIO nanoparticles, and then the cell apoptosis, proliferation, surface antigens, and multipotency were investigated. Lithium chloride-pilocarpine induced TLE models were administered by USPIO-labeled BMSCs (U-BMSCs), BMSCs, and saline through lateral ventricle injection as the experimental group, control I group and control II group, respectively, followed by MRI examination, electroencephalography (EEG) and Prussian blue staining. The cell experimental results showed that the labeled USPIO did not affect the biological characteristics and multiple potential of BMSCs. The U-BMSCs can be detected using MRI in vitro and in vivo, and observed in the hippocampus and adjacent parahippocampal cortical areas of the epileptic model. Moreover, electroencephalographic results showed that transplanted U-BMSCs, as well as BMSCs, were capable of reducing the number of epileptiform waves significantly (P < 0.01) compared with control II group. All of these findings suggest that it is feasible to track transplanted BMSCs using MRI in a rat model of TLE, and support that USPIO labeling is a valuable tool for cell tracking in the study of seizure disorders.

Initial evaluation of the use of USPIO cell labeling and noninvasive MR monitoring of human tissue‐engineered vascular grafts in vivo

This pilot study examines noninvasive MR monitoring of tissue-engineered vascular grafts (TEVGs) in vivo using cells labeled with iron oxide nanoparticles. Human aortic smooth muscle cells (hASMCs) were labeled with ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles. The labeled hASMCs, along with human aortic endothelial cells, were incorporated into eight TEVGs and were then surgically implanted as aortic interposition grafts in a C.B-17 SCID/bg mouse host. USPIO-labeled hASMCs persisted in the grafts throughout a 3 wk observation period and allowed noninvasive MR imaging of the human TEVGs for real-time, serial monitoring of hASMC retention. This study demonstrates the feasibility of applying noninvasive imaging techniques for evaluation of in vivo TEVG performance.