Negative Contrast Agent Research Articles

Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles

Development of a multifunctional nanoparticle (NP) system allowing for dual-contrast T 1- and T 2-weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, superparamagnetic silica-coated iron oxide core-shell nanoparticles (Fe 3O 4@SiO 2 NPs) with a diameter of approximately 21 nm were synthesized via a thermal decomposition approach and were aminated through silanization. The amine-functionalized Fe 3O 4@SiO 2 NPs enabled the covalent conjugation of a paramagnetic gadolinium complex (Gd-DTPA, DTPA: diethylenetriamine pentaacetic acid) and an arginine-glycine-aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed Fe 3O 4@SiO 2(Gd-DTPA)-RGD NPs are water-dispersible, stable, and biocompatible as confirmed by MTT cell viability assay. Relaxivity measurements show that they have a T 1 relaxivity ( r 1) of 4.2 m m −1 s −1 and T 2 relaxivity ( r 2) of 17.4 m m −1 s −1 at the Gd/Fe molar ratio of 0.3:1, suggesting a possibility to use them as both T 1 positive and T 2 negative contrast agents. In vitro and in vivo MR imaging experiments show that the developed multifunctional Fe 3O 4@SiO 2(Gd-DTPA)-RGD NPs enable targeted dual-contrast T 1- and T 2-weighted MR imaging of tumor cells over-expressing high-affinity α vβ 3 integrin in vitro and in vivo. Our results clearly indicate that the approach to forming multifunctional Fe 3O 4@SiO 2(Gd-DTPA)-RGD NPs could be extended for fabricating other biologically active NPs for T 1- and T 2-weighted MR imaging of other biological systems with high accuracy.

Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: Comparison of T1, T2*, and synergistic T1 − T2* contrast mechanisms

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T(1) shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T(2)*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T(1) and T(2)* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T(1) contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T(2)* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T(1) and T(2)* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor-targeted IONPs in vivo.

Design of water-based ferrofluids as contrast agents for magnetic resonance imaging

We report the synthesis, characterization and relaxometric study of ferrofluids based on iron oxide, with potential for use as magnetic resonance imaging (MRI) contrast agents (CAs). The effect of different cost-effective, water-based surface modification approaches which can be easily scaled-up for the large scale synthesis of the ferrofluids has been investigated. Surface modification was achieved by silanization, and/or coating with non-toxic commercial dispersants (a lauric polysorbate and a block copolymer with pigment affinic groups, namely Tween 20 and Disperbyk 190) which were added after or during iron oxide nanoparticle synthesis. It was observed that all the materials synthesized functioned as negative contrast agents at physiological temperature and at frequencies covered by clinical imagers. The relaxometric properties of the magnetic nanoparticles were significantly improved after surface coating with stabilizers compared to the original iron oxide nanoparticles, with particular reference to the silica-coated magnetic nanoparticles. The results indicate that the optimization of the preparation of colloidal magnetic ferrofluids by surface modification is effective in the design of novel contrast agents for MRI by enabling better or more effective interaction between the coated iron oxide nanoparticles and protons present in their aqueous environment.

Use of carbon dioxide as negative contrast agent for magnetic resonance cholangiopancreatography

To evaluate the effects of using CO(2) as negative contrast agent in decreasing the overlapping on the pancreaticobiliary system from intestinal fluids. We evaluated the magnetic resonance cholangiopancreatography (MRCP) images in 117 patients divided into two groups (group 1, without taking gas producing crystals to produce CO(2), n = 64; group 2, with CO(2), n = 53) in a 1.5T unit using MRCP sequence. Anatomic locations of intestinal fluids distribution, overlapping with common bile duct (CBD) and pancreatic duct (PD), were evaluated. In the group with CO(2), the decrease in distribution of intestinal fluids was significant in the gastric antrum (P = 0.001) and duodenal bulb (P < 0.001), but not in the gastric fundus and body and in the second portion of the duodenum (P = 1.000, P = 0.171, and P = 0.584 respectively). In the group with CO(2), the decrease in overlapping with CBD was significant (P < 0.001), but the decrease in overlapping with PD was not (P = 0.106). MRCP with carbon dioxide as negative contrast agent would decrease intestinal fluids in the gastric antrum and duodenal bulb, thereby decreasing overlapping with the CBD.

Superparamagnetic colloidal nanocrystalclusters coated with polyethylene glycol fumarate: a possible novel theranostic agent

We report cell endocytosis, drug release, NMR relaxometry and in vitro MRI studies on a novel class of superparamagnetic colloidal nanocrystal clusters (CNCs) with various biocompatible coatings. It is shown that the transverse relaxivity r2, the parameter representing the MRI efficiency in negative contrast agents, for the PVA-coated, PEGF-coated, and crosslinked PEGF-coated CNCs, is high enough to contrast suitably the magnetic resonance images. The same samples have shown a good ability also in drug releasing (particularly the crosslinked PEGF-coated compound), thus finally allowing us to propose this class of compounds for future applications in theranostics.

Diffusion magnetic resonance imaging with gadofosveset trisodium as a negative contrast agent for lymph node metastases assessment

The aim of this study was to assess the feasibility of using intravenously administered gadofosveset trisodium as a negative contrast agent for lymph node (LN) assessment with diffusion-weighted imaging (DWI) using a VX2 tumor model in rabbits. VX2 cells were injected in the right hind limb of five Japanese white rabbits to induce ipsilateral popliteal LN metastasis. DWI was performed before and every 7.5 min (until 1 h) after intravenous gadofosveset trisodium administration, at 1.5 T. Signal intensities (SIs) of right (metastatic) and left (nonmetastatic) popliteal LNs at each time point were measured and compared to each other using two-sided unpaired t-tests. The SIs of metastatic lymph nodes were significantly higher (P < 0.05) than those of nonmetastatic LNs at each time point after intravenous gadofosveset trisodium administration. Although the SI of metastatic LNs was significantly higher (P = 0.0237) than that of nonmetastatic LNs before contrast injection, this difference became even more significant (P ≤ 0.0105) after gadofosveset trisodium administration. The SI of metastatic LNs at DWI is less suppressed than that of nonmetastatic LNs after the intravenous administration of gadofosveset trisodium. Therefore, intravenously administered gadofosveset trisodium shows promise for use as a negative contrast agent for discriminating metastatic from nonmetastatic LNs at DWI.

CT Enterography: Principles, Trends, and Interpretation of Findings

Computed tomographic (CT) enterography is an emerging alternative to traditional fluoroscopy for the assessment of disorders of the small bowel. The greatly improved spatial and temporal resolution provided by multidetector CT scanners, combined with good luminal distention provided by negative oral contrast agents and with good bowel wall visualization, have made CT enterography the main imaging modality not only for investigating proved or suspected inflammatory bowel disease but also for detecting occult gastrointestinal tract bleeding, small bowel neoplasms, and mesenteric ischemia. CT enterography is particularly useful for differentiating between active and fibrotic bowel strictures in patients with Crohn disease, thus enabling selection of the most appropriate treatment (medical management or intervention) for an improved outcome. CT enterography allows excellent visualization of the entire thickness of the bowel wall and depicts extraenteric involvement as well, providing more detailed and comprehensive information about the extent and severity of the disease process.

The 3D anatomy of the cervical articular process joints in the horse and their topographical relationship to the spinal cord

REASONS FOR STUDY: Detailed anatomy of the equine cervical articular process joints (APJs) has received little attention in the literature and yet disorders of this joint have been linked to spinal cord compression resulting in severe clinical signs such as ataxia and weakness. This study aimed to describe the 3D anatomy of the APJ in relation to the spinal cord in the horse. Artificial distension of the APJ causes the joint pouches to extend into the vertebral canal, with the potential for APJ effusion to cause spinal cord compressive disease. Six cadaveric necks (C1-C7) of clinically normal horses were used in this study. Computed tomography scans of the cervical APJ were acquired after injection of a negative contrast agent to maximal distension. The resulting images were semi-automatically segmented using greyscale thresholding and reconstructed in 3D by polygonal surface meshing. The 3D reconstructions were used to assess the topographic anatomy of the APJ in relation to the spinal cord and to measure joint volume at each cervical vertebra in relation to vertebrae size. Joint volume varied significantly between joint location (P<0.0001) and was positively correlated to the vertebral site (from cranial to caudal) (r = 0.781, P<0.0001). After distension, the medial outpouch of the APJ extended towards the vertebral canal from a dorsolateral location but in none of the 6 horses was there apparent compression of the dura mater surrounding the spinal cord. There was no significant difference in the extent of medial outpouch at any vertebral level (P = 0.104). Flexion of the neck resulted in minor changes to the shape of the APJ but did not result in the medial outpouch encroaching any closer to the spinal cord. From this study, it appears that in the absence of any other soft tissue or bony changes an effusion of the APJ is unlikely to cause spinal cord compression. However, given that the APJ and spinal cord are in close approximation, in the presence of other anatomical changes, an effusion may have the potential to cause compression. This study confirms that the APJ extend into the dorsolateral aspect of the vertebral canal in a ventromedial direction, suggesting that oblique myelographic views are recommended for the diagnosis of spinal cord compression when pathology of the APJ is suspected.

MRI Manifestation of Novel Superparamagnetic Iron Oxide Nanoparticles in The Rat Inner Ear

Superparamagnetic iron oxide nanoparticles hierarchically coated with oleic acid and Pluronic F127 copolymers (POA@SPION) have shown exceptional T2 contrast enhancement. The aim of the present work was to investigate the MRI manifestation of POA@SPION in the inner ear. A total of 26 male Wister rats were selected for testing POA@SPION administered through intracochlear, intratympanic and intravenous routes. MRI was performed with a 4.7 T MR scanner. POA@SPION can be introduced into the perilymph space, after which it becomes widely distributed and can demonstrate the integrity of the perilymph-endolymph barrier. Positive highlighting of the endolymph compartment against the darkened perilymph was visualized for the first time. POA@SPION passed through the middle-inner ear barriers in only small amounts, but stayed in the perilymph for 3 days. They did not traverse the blood-perilymph barrier or blood-endolymph barrier. The inner ear distribution of POA@SPION was confirmed by histology. POA@SPION is a promising T2 negative contrast agent.

Noninvasive visualization of in vivo release and intratumoral distribution of surrogate MR contrast agent using the dual MR contrast technique

A direct evaluation of the in vivo release profile of drugs from carriers is a clinical demand in drug delivery systems, because drug release characterized in vitro correlates poorly with in vivo release. The purpose of this study is to demonstrate the in vivo applicability of the dual MR contrast technique as a useful tool for noninvasive monitoring of the stability and the release profile of drug carriers, by visualizing in vivo release of the encapsulated surrogate MR contrast agent from carriers and its subsequent intratumoral distribution profile. The important aspect of this technique is that it incorporates both positive and negative contrast agents within a single carrier. GdDTPA, superparamagnetic iron oxide nanoparticles, and 5-fluorouracil were encapsulated in nano- and microspheres composed of poly( d,l-lactide- co-glycolide), which was used as a model carrier. In vivo studies were performed with orthotopic xenograft of human breast cancer. The MR-based technique demonstrated here has enabled visualization of the delivery of carriers, and release and intratumoral distribution of the encapsulated positive contrast agent. This study demonstrated proof-of-principle results for the noninvasive monitoring of in vivo release and distribution profiles of MR contrast agents, and thus, this technique will make a great contribution to the field.

Comparison of the ${^{1}{\rm H}}$ NMR Relaxation Enhancement Produced by Bacterial Magnetosomes and Synthetic Iron Oxide Nanoparticles for Potential Use as MR Molecular Probes

Iron oxide nanoparticle, named synthetic magnetite, as contrast agent has been widely used in clinical MRI. Recently, a new magnetite nanocrystal, called magnetosome, has been found in magnetotactic bacteria. Physicochemical and magnetorelaxo-metric characterization of bacteria magnetosomes and iron oxide nanoparticles are investigated. Bacterial magnetosomes have the larger mean aggregate size, better dispersion and obviously stronger ferromagnetism compared to synthetic magnetites. The samples of several concentrations of magnetic nanoparticles were analyzed using a clinical 3.0 T MR-scanner. The signal decay in the Magnetic Resonance images is found to change proportionally to the nanoparticles concentration. Two kinds of nanoparticles can be though as a negative contrast agent and show slight effects on T1, but strong effects on T2 weighted images. Notice that at the same concentration the signal attenuation of bacterial magnetite samples is more obvious than that of synthetic magnetite samples.

Magnetic Iron Oxide Nanoparticles for Biomedical Applications

Due to their high magnetization, superparamagnetic iron oxide nanoparticles induce an important decrease in the transverse relaxation of water protons and are, therefore, very efficient negative MRI contrast agents. The knowledge and control of the chemical and physical characteristics of nanoparticles are of great importance. The choice of the synthesis method (microemulsions, sol-gel synthesis, laser pyrolysis, sonochemical synthesis or coprecipitation) determines the magnetic nanoparticle's size and shape, as well as its size distribution and surface chemistry. Nanoparticles can be used for numerous in vivo applications, such as MRI contrast enhancement and hyperthermia drug delivery. New developments focus on targeting through molecular imaging and cell tracking.

Prospective comparative study of negative oral contrast agents for magnetic resonance cholangiopancreatography

The aim of this study was to compare prospectively the image quality of magnetic resonance cholangiopancreatography (MRCP) using manganese chloride tetrahydrate (Bothdel Oral Solution 10) (MCT), a new negative oral contrast agent; ferric ammonium citrate (FerriSeltz powder 20%) (FAC); and no agent. MRCP images (TE 970 ms) of patients administered MCT (n = 19) or FAC (n = 20) at random, and 18 patients without an agent were evaluated. The subjective image quality of the overall, extrahepatic bile duct, and pancreatic duct and the degree of elimination of gastrointestinal fluid scored by two radiologists blinded to information regarding the agent were compared using Mann-Whitney's U-test. The degrees of elimination of gastroduodenal fluid of MCT and FAC were significantly better than those without an agent (P < 0.01 and P < 0.01). The subjective image quality of MCT of the overall and extrahepatic bile duct were significantly better, although no significant differences for FAC were observed compared with those without an agent (P < 0.01 and P = 0.21, P = 0.02 and P = 0.16). There were no significant differences for the pancreatic duct (P = 0.12 and P = 0.19), nor were there any significant differences in the evaluations between MCT and FAC (P = 0.19-0.98). MCT has shown performance comparable to that of conventional FAC in terms of pancreatic and biliary depiction and safety.

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.

Defining juxtapapillary diverticulum with 3D segmented trueFISP MRCP: comparison with conventional MRCP sequences with an oral negative contrast agent

To compare three-dimensional segmented true fast imaging with steady-state precession magnetic resonance cholangiopancreatography (3D-trueFISP-MRCP) to conventional MRCP sequences with an oral negative contrast agent for diagnosing juxtapapillary diverticulum. A total of 42 patients with (n = 21) and without (n = 21) juxtapapillary diverticulum confirmed by endoscopic retrograde cholangiopancreatography (ERCP) were evaluated. Three MRCP sequences, 3D-trueFISP-MRCP, two-dimensional rapid acquisition with relaxation enhancement MRCP (2D-RARE-MRCP), and 3D T(2)-weighted turbo spin-echo MRCP (3D-TSE-MRCP), obtained after administering an oral negative contrast agent (FerriSeltz; Otsuka Pharmaceutical, Tokushima, Japan) were compared. Two radiologists independently and blindly interpreted the presence or absence of juxtapapillary diverticulum and its positional relationship against the papilla. The detectability of juxtapapillary diverticulum of each sequence as decided by consensus was then compared. Kappa statistics were used to measure interobserver agreement of the classifications. The sensitivity, specificity, and accuracy for detecting juxtapapillary diverticulum of 3D-trueFISPMRCP (61.9%, 85.7%, and 73.8%) were substantively higher than those of 2D-RARE-MRCP (0.0%, 100%, and 50.0%) and 3D-TSE-MRCP (9.5%, 100%, and 54.8%). Interobserver agreement of the position of juxtapapillary diverticulum by 3D-trueFISP-MRCP was good (kappa = 0.55). 3D-trueFISP-MRCP can define juxtapapillary diverticulum even with an oral negative contrast agent, whereas conventional MRCP sequences cannot.

Iron Oxide Based MR Contrast Agents: from Chemistry to Cell Labeling

Superparamagnetic iron oxide nanoparticles can be used for numerous applications such as MRI contrast enhancement, hyperthermia, detoxification of biological fluids, drug delivery, or cell separation. In this work, we will summarize the chemical routes for synthesis of iron oxide nanoparticles, the fluid stabilization, and the surface modification of superparamagnetic iron oxide nanoparticles. Some examples of the numerous applications of these particles in the biomedical field mainly as MRI negative contrast agents for tissue-specific imaging, cellular labeling, and molecular imaging will be given. Larger particles or particles displaying a non-neutral surface (thanks to their coating or to a cell transfection agent with which they are mixed) are very useful tools, although the cells to be labeled have no professional phagocytic function. Labeled cells can then be transplanted and monitored by MRI in a broad spectrum of applications. Direct in vivo magnetic labeling of cells is mainly performed by intravenous injection of long-circulating iron oxide-based MRI contrast agents, which can extravasate and/or undergo a cellular uptake in an amount sufficient to allow an MRI visualization of areas of interest such as inflamed regions or tumors. Particles with long circulation times, or able to induce a strong negative effect individually have been also modified by conjugation to a ligand, so that their cellular uptake, or at least their binding to the cell surface, could occur through a specific ligand-receptor interaction, in vivo as well as in vitro. Thus, experimentally as well as in a few trials on humans, iron oxide particles currently find promising applications.

Negative MR contrast caused by USPIO uptake in lymph nodes may lead to false positive observations with in vivo visualization of murine atherosclerotic plaque

ObjectiveUSPIOs are used clinically as contrast agent for magnetic resonance imaging (MRI) of lymph nodes, and in research settings for MRI of macrophages in atherosclerotic lesions. However, T2* weighted (T2*w) imaging can lead to “blooming” with overestimation of the area occupied by USPIOs. In this study, plaque uptake of USPIOs in atherosclerotic mice was investigated in the presence and absence of circulating monocytes. The influence of peri-aortic lymph node uptake on the interpretation of T2*w images of the aortic wall was studied. MethodsAtherosclerotic mice were fed an atherogenic diet and were randomized to total body irradiation or non-irradiation. After 2 days, T2*w MRI of the abdominal aorta was performed, followed by intravenous administration of 100μmol/kg USPIOs (t=0). At t=3 and 5 days MRI of the abdominal aorta was repeated. Animals were sacrificed and histological evidence for iron uptake by aortic wall and lymph nodes was compared with the degree of focal signal loss on in vivo MR images. ResultsAortic walls in irradiated and non-irradiated mice, but also in healthy wild-type mice, showed signal loss on T2*w MRI. Signal loss however did not correspond with histological evidence of USPIO uptake by aortic wall but by peri-aortic lymph nodes. ConclusionsThe versatility of USPIOs as a negative MR contrast agent for both lymph node staging and atherosclerosis may limit the use for detection of atherosclerotic lesions in vessels where lymph nodes are highly prevalent.

Clinical Feasibility of Açai (Euterpe olerácea) Pulp as an Oral Contrast Agent for Magnetic Resonance Cholangiopancreatography

We evaluate the effectiveness of the Amazonian fruit pulp from Euterpe olerácea (popularly named Açaí) as a negative oral contrast agent applied to clinical routine. The use of such contrasts is particularly important in magnetic resonance cholangiopancreatography (MRCP) to reduce overlapping. We administered Açaí pulp to 5 nonsymptomatic subjects and 35 patients submitted to unspecific abdominal MR imaging, intending to set up optimal protocol. In 8 MRCP examinations, contrast and image effects were assessed and graded blindly by 2 independent radiologists. Quantitative analysis was performed by Wilcoxon test as to verify the potential of the Açaí to eliminate overlap signal over the pancreaticobiliary tract. Adverse effects and subject tolerance were also addressed. The Açaí pulp elicited a local brightness decrease in T2-weighted images. The depiction of gallbladder, common bile duct, ampulla of Vater, and pancreatic duct was markedly improved after Açaí ingestion because of the suppression of the overlapping from bowel loops and gastric content (P < 0.01). All patients considered Açaí palatable, and no side effect was registered. The Açaí pulp can be used routinely in MRCP studies as a natural, safe, and inexpensive negative oral contrast agent with high efficacy and patient acceptance.

Molecular Imaging With Targeted Contrast Agents

Molecular imaging with targeted contrast agents by magnetic resonance imaging (MRI) allows for the noninvasive detection and characterization of biological changes on a molecular level. In this article, the principles of molecular MRI and its applications in cardiovascular diseases are reviewed. First, basic properties of positive and negative contrast agents are introduced and their effect on signal generation in a magnetic field is described. In the next part, different types of MRI scanners and the influence of field strength on signal properties of contrast agents for molecular imaging are discussed. Additionally, the assessment, analysis, and quantification of the changes in T1 and T2* relaxation time induced by the different molecular contrast agents are reviewed. Finally, the basic mechanisms of targeting of imaging probes on a molecular level and recent applications of molecular MRI in cardiovascular disease are reviewed.

In Vivo Detection of Inflammation Using Pegylated Iron Oxide Particles Targeted at E-Selectin

Ultrasmall particles of iron oxide (USPIO) possess superparamagnetic properties and are used as negative contrast agent in magnetic resonance imaging (MRI) because of their strong T(2) and T(2)* effects. Besides this method, electron paramagnetic resonance (EPR) offers the unique capability to quantify these particles. The objective of this study was to evaluate a molecular marker for non invasive diagnosis and monitoring of inflammation. During inflammation cell adhesion molecules such as E-selectin are expressed on the endothelial cell surface. An E-selectin ligand was coupled to pegylated USPIO particles. Inflammation was induced by intramuscular injection of Freund's Complete Adjuvant in male NMRI mice. After intravenous injection of grafted or ungrafted USPIO particles, iron concentration in inflamed muscles was quantified ex vivo by X-band EPR. Particle accumulation was also assessed in vivo by L-Band EPR, as well as by T(2)-weighted MRI. We determined the mean iron oxide concentration in inflamed muscles after injection of grafted or ungrafted UPSIO particles, which was 0.8% and 0.4% of the initially injected dose, respectively. By L-band EPR, we observed that the concentration of the grafted USPIO particles in inflamed muscles was twice higher than for the ungrafted particles. Using MRI experiments, a higher signal loss was clearly observed in the inflamed muscle when grafted particles were injected in comparison with the ungrafted particles. Even taking into account a non specific accumulation of iron oxides, the targeting of USPIO particles with E-selectin ligands significantly improved the sensitivity of detection of inflamed tissues.