Dynamic signal intensity changes in liver with superparamagnetic MR contrast agents.

The dynamic effects of three different superparamagnetic magnetic resonance (MR) contrast agents on liver signal were evaluated with an echo-planar imaging technique. The contrast agents were (a) USPIO (ultrasmall superparamagnetic iron oxide), which has a long blood half-life and was developed for MR imaging of lymph nodes and bone marrow; (b) AG (arabinogalactan)-USPIO, an asialoglycoprotein receptor--directed iron oxide with hepatocyte uptake; and (c) AMI-25, a conventional reticuloendothelial iron oxide agent. Dynamic liver signal intensity (SI) curves reflect different uptake mechanisms for the different agents. Receptor blocking experiments indicate that intracellular redistribution or clustering of the AG-USPIO (known to occur from electron microscopy studies) does not contribute to the decrease in liver SI. Monitoring liver SI over time with echo-planar imaging may provide a better understanding of the kinetics of the growing number of MR contrast agents and allow optimization of imaging protocols to exploit peak enhancement.     

Receptor imaging: application to MR imaging of liver cancer

A new contrast agent for magnetic resonance (MR) imaging, directed to asialoglycoprotein (ASG) receptors on hepatocytes, was used for detection of liver cancer in rats. Ultrasmall superparamagnetic (mean size, 12 nm) particles of iron oxide (USPIOs) were targeted to ASG receptors by coating particles with arabinogalactan (AG). Liver T2 relaxation times decreased more effectively after a single intravenous administration of AG-USPIO than after an equal dose of a conventional superparamagnetic liver MR contrast agent (AMI-25; mean size, 72 nm). Receptor affinity studies demonstrated that receptor-mediated attachment and subsequent cellular endocytosis do not occur in primary malignant (hepatocellular carcinoma) or metastatic (adenocarcinoma) tumors, because the surface ASG receptors are lost during malignant dedifferentiation. In vitro relaxation and in vivo MR imaging experiments of liver tumors show that targeting USPIO to hepatocytes rather than to the mononuclear phagocytic system allows a considerable dose reduction, increases tumor-liver contrast, and potentially allows distinction of ASG-positive (benign hepatocellular) and ASG-negative (malignant hepatocellular) tumors.     

Asialoglycoprotein receptor function in benign liver disease: evaluation with MR imaging

An arabinogalactan-coated ultrasmall superparamagnetic iron oxide (AG-USPIO) preparation specific for asialoglycoprotein (ASG) receptors on hepatocytes was used as a magnetic resonance (MR) imaging contrast agent in the evaluation of a spectrum of benign liver diseases in animal models. The activity of hepatocyte ASG receptors, which directly reflects liver function, was directly assessed by measuring liver relaxation times in vitro and MR signal intensity in vivo. The following measurements allowed three-dimensional assessment of liver function: (a) liver relaxation time, (b) native MR signal intensities of liver, (c) response of liver to the AG-USPIO probe (percentage decrease of liver signal intensity after intravenous administration of 10 mumol/kg of AG-USPIO: normal liver 55%, fatty liver 57%, acute hepatitis 36%, chronic hepatitis 29%, and cirrhosis 46%), and (d) redistribution of hepatocyte-specific AG-USPIO to the spleen (present in hepatitis and cirrhosis but not in normal liver and fatty liver). The results of this study indicate that cellular hepatic abnormalities can be detected and quantitated with MR receptor imaging.     

MR imaging of intrarenal macrophage infiltration in an experimental model of nephrotic syndrome.

The objective of this study was to use MR imaging to detect macrophage infiltration of the kidney after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles in a rat model of experimental nephropathy. Ninety micromol of USPIO were injected intravenously in 10 rats with nephropathy secondary to intravenous injection of 5 mg of puromycin aminonucleoside (PAN), and in 10 control rats. The signal intensity was measured in each kidney compartment before and 24 h after injection of the contrast agent. FLASH sequences were performed on a spectrometer operating at 4.7 T. MR findings were compared with histological data. Twenty-four hours after injection of USPIO, a significant decrease (P < 0.0001) was observed in signal intensity in each kidney compartment in the PAN group. There was no variation in the control group. In the diseased kidneys, histological data revealed the presence of macrophages with iron oxide particles within their cytoplasm and lysosomes. Using USPIO, MR imaging can evidence infiltration of the rat kidney by macrophages.     

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.     

Iron oxide-enhanced MR lymphography: initial experience

The detection of nodal metastases is of utmost importance in oncologic imaging. Ultrasmall superparamagnetic iron oxide particles (USPIO) are novel contrast agents specifically developed for MR lymphography. After intravenous administration, they are taken up by the macrophages of the lymph nodes, where they accumulate. They reduce the signal intensity (SI) of normally functioning nodes on postcontrast T2-and T2*-weighted images through the magnetic susceptibility effects on iron oxide. Metastatic nodes, in which macrophages are replaced by tumor cells, show no significant change in SI on postcontrast T2-and T2*-weighted images. Early clinical experience suggests that USPIO-enhanced MR lymphography improves the sensitivity and specificity for the detection of nodal metastases. It also suggests that micrometastases could be detected in normal-sized nodes. This article reviews the physiochemical properties of USPIO contrast agents, their enhancement patterns, and early clinical experience.     

Improved delineation of human brain tumors on MR images using a long-circulating, superparamagnetic iron oxide agent

The purpose of this study was to corroborate experimental findings that long-circulating, superparamagnetic iron oxide contrast agents accumulate at the margins of human brain tumors, thereby improving their delineation on magnetic resonance (MR) images. This limited clinical study examined a total of four patients with brain tumors (three with primary gliomas and one with metastatic melanoma; n = 8 lesions) who were given a pharmaceutical formulation of a superparamagnetic, ultra-small-particulate iron oxide (USPIO, intravenous dose of 1.1 mg Fe/kg). The agent has a characteristically long plasma half-life and is currently undergoing Phase III clinical trials for liver disease (AMI-227, Advanced Magnetics, Cambridge, MA). MR (conventional spin-echo and gradient-echo) images of the brain were obtained before and 12, 24, and/or 36 hours after administration of the agent, with follow-up several weeks later. Twelve to 36 hours after IV administration of the USPIO, both primary and metastatic brain tumors showed readily detectable increases in signal intensity on T1-weighted spin-echo images. Unlike the pattern of enhancement with a gadolinium (Gd) chelate, which occurred immediately and decreased within hours, that with the USPIO occurred gradually, with a peak at 24 hours, and decreased over several days. Whereas the enhancing tumor margin with the Gd chelate blurred with time due to diffusion of the agent, the margin with the USPIO remained sharp, presumably due to the much lower diffusion coefficient (large size) of the particles and partly because of local endocytosis by tumor cells. Compared with Gd chelates, long-circulating, superparamagnetic iron oxide contrast agents can provide prolonged delineation of the margins of human brain tumors on MR images, which has implications for the targeting of diagnostic biopsies and the planning of surgical resections.     

Receptor-directed contrast agents for MR imaging: preclinical evaluation with affinity assays.

In this study, the target-specific behavior of magnetic resonance (MR) imaging contrast agents directed at human hepatic asialoglycoprotein (ASG) receptors was evaluated in vitro with use of two novel assays: relaxation time measurements of incubated human cell membrane solutions and iron staining of biopsy samples. Specific uptake of ASG receptor-directed agents was demonstrated in human samples of normal liver tissue, areas of hepatitis, regenerating nodules, areas of focal nodular hyperplasia, and hepatic adenomas. A conventional iron oxide preparation not directed at ASG receptors failed to demonstrate specific uptake in these tissues. Attachment of the ASG receptor-directed agents was competitively blocked with a receptor agonist (D(+)-galactose) in these tissues. No attachment of conventional or receptor agents was seen in areas of hepatocellular carcinoma, cholangiocarcinoma, or liver metastases. The studies indicate that in vitro receptor assays are useful in predicting the affinity of new receptor-directed MR imaging contrast agents in human tissue prior to clinical trials.     

Status and development of new clinical contrast media for MR diagnosis of liver diseases]

MR contrast agents are developed for pharmaceutical manipulation of tissue signal intensities. Today it is widely recognized that MR contrast agents will play an increasingly important role in MR imaging of the liver. Contrast-enhanced MR-imaging allows to obtain simultaneously dynamic physiologic information and high anatomic detail. Up to now three major classes of MR contrast agents are available for clinical MR-imaging of the liver. These include paramagnetic perfusion agents, hepatobiliary agents, and super-paramagnetic RES-specific iron oxide particles. A fourth class of contrast agents now in use for animal experiments includes ultra-small super-paramagnetic particles which can be targeted to extra-reticuloendothelial structures such as asialoglycoprotein receptors of hepatocytes. In this article, we review recent advances in the development of MR contrast media and the clinical status of contrast-enhanced MR imaging of the liver.     

Transferrin receptor upregulation: in vitro labeling of rat mesenchymal stem cells with superparamagnetic iron oxide

PURPOSE: To prospectively evaluate the influence of superparamagnetic iron oxide (SPIO) or ultrasmall SPIO (USPIO) particles on the surface epitope pattern of adult mesenchymal stem cells (MSCs) by regulating the expression of transferrin receptor and to prospectively evaluate the influence of transfection agents (TAs) on the uptake of SPIO or USPIO particles in MSCs. MATERIALS AND METHODS: The study was approved by the institutional animal care committee of the University of Tübingen. MSCs were isolated from the bone marrow of four rats. To obtain highly homogeneous MSC populations, MSCs from one rat were single-cell cloned. One MSC clone was characterized and selected for the labeling experiments. The MSCs, which were characterized with flow cytometry and in vitro differentiation, were labeled with 200 microg/mL SPIO or USPIO or with 60 microg/mL SPIO or USPIO in combination with TAs. Aggregations of labeled cells were accommodated inside a defined volume in an agar gel matrix. Magnetic resonance (MR) imaging was performed to measure SPIO- or USPIO-induced signal voids. Quantification of cellular total iron load (TIL) (intracellular iron plus iron coating the cellular surface), determination of cellular viability, and electron microscopy were also performed. RESULTS: Labeling of MSCs with SPIO or USPIO was feasible without affecting cell viability (91.1%-94.7%) or differentiation potential. For MR imaging, SPIO plus a TA was most effective, depicting 5000 cells with an average TIL of 76.5 pg per cell. SPIO or USPIO particles in combination with TAs coated the cellular surface but were not incorporated into cells. In nontransfected cells, SPIO or USPIO was taken up. MSCs labeled with SPIO or USPIO but without a TA showed enhanced expression of transferrin receptor, in contrary to both MSCs labeled with SPIO or USPIO and a TA and control cells. CONCLUSION: SPIO or USPIO labeling without TAs has an influence on gene expression of MSCs upregulating transferrin receptor. Furthermore, SPIO labeling with a TA will coat the cellular surface.     

Bone marrow: ultrasmall superparamagnetic iron oxide for MR imaging

An ultrasmall superparamagnetic iron oxide (USPIO) preparation was evaluated as a potential intravenous contrast agent for magnetic resonance (MR) imaging of bone marrow. One hour after administration of USPIO (40, 80, and 160 mumols of iron per kilogram body weight) in rats and rabbits, T1 and T2 relaxation times were, respectively, approximately 30%, 50%, and 65% lower than precontrast relaxation times. Maximum decrease in relaxation times of marrow occurred within 1-24 hours after intravenous administration; thereafter, relaxation times slowly returned to normal within 7 days. In vivo MR imaging of rabbits and rats confirmed that USPIO decreases signal intensity of red and yellow marrow. The decrease was most marked with gradient echo pulse sequences. An animal model of intramedullary tumor demonstrated the potential of USPIO to enable differentiation between tumor and normal red marrow. USPIO-enhanced MR imaging improves detection of smaller tumors and allows differentiation of tumor deposits from islands of hyperplastic or normal red marrow.     

In vitro characterization of two different ultrasmall iron oxide particles for magnetic resonance cell tracking

RATIONALE AND OBJECTIVES: Comparison of two different ultrasmall superparamagnetic iron oxide (USPIO) particles in terms of their intracellular cell-labeling properties of macrophages and subsequent visualization by MR imaging. MATERIALS AND METHODS: Cultures containing the macrophage cell line P-388D1 were incubated with a neutral carboxydextran-coated USPIO preparation (DDM 43/34/103) or an acidic citrate-coated USPIO (VSOP-C125). Experiments were performed in which incubation concentration and duration were varied and phagocytosis and pinocytosis suppressed by specific inhibitors. In cell culture specimens iron content was measured quantitatively and signal intensities determined by in vitro MR imaging. RESULTS: VSOP-C125 is incorporated by cells much faster than DDM 43/34/103 and produces significantly higher final intracellular iron concentrations per cell (3420 vs. 727 ng/million cells). Both preparations show similar signal-reducing effects at MR imaging relative to the Fe content per cell. Intracellular USPIO has a much lower detection threshold at MR imaging (50/80 micromol/L) than extracellular USPIO in free solution (300 micromol/L). CONCLUSIONS: Citrate-coated USPIO particles VSOP-C125 appear to have more favorable properties for magnetic labeling of macrophages than the carboxydextran-coated USPIO preparation DDM 43/34/103.     

Lymph nodes: microstructural anatomy at MR imaging

High-resolution microscopic magnetic resonance (MR) images of rodent lymph nodes were directly correlated with sections obtained for histologic study to determine the microstructural anatomy of lymph nodes seen at MR imaging and to evaluate signal intensity changes induced by a novel intravenous lymphotropic MR contrast agent (ultrasmall superparamagnetic iron oxide [USPIO]). High-resolution T2-weighted images of unenhanced lymph nodes demonstrated medullary sinus as regions of low signal intensity and follicles as high-intensity structures. After a single intravenous administration of USPIO (160 mumol/kg), both T1-weighted and T2-weighted images showed areas of focal signal intensity loss in medullary sinuses corresponding to the distribution of uptake by macrophages. Lymph follicles appeared unchanged in signal intensity, as they are largely devoid of macrophages. This model of microscopic MR imaging should provide the basis for (a) understanding differences between patterns of contrast-enhanced normal lymph nodes and those of diseased ones and (b) guiding the development of targeting strategies for novel pharmaceuticals at the cellular level.     

Nephrotoxic nephritis and obstructive nephropathy: evaluation with MR imaging enhanced with ultrasmall superparamagnetic iron oxide-preliminary findings in a rat model

PURPOSE: To evaluate the role of magnetic resonance (MR) imaging enhanced with ultrasmall superparamagnetic iron oxide (USPIO) in the evaluation and differentiation of different types of nephropathies. MATERIALS AND METHODS: Two experimental rat models of nephropathies were studied: a model of nephrotoxic nephritis induced by means of intravenous injection of sheep anti-rat glomerular basement membrane serum (n = 43) and a model of obstructive nephropathy (n = 6). Imaging sessions were performed with a spectrometer operating at 4.7 T with fast low-angle shot, or FLASH, sequences. Signal intensity was measured in each kidney compartment before and 24 hours after intravenous injection of USPIO (90 micromol of iron per kilogram of body weight). MR findings were compared with histologic data and urine protein levels. RESULTS: In the nephrotoxic nephritis model 24 hours after injection of USPIO, a significant signal intensity decrease (P: <.05) was present only in the cortex where the glomerular lesions were located. In the obstructive nephropathy model, the signal intensity decrease (P: <.05) was located in all kidney compartments in response to diffuse interstitial lesions. The decrease in signal intensity was due to iron uptake by either macrophages or mesangial cells gaining endocytic activity and was correlated, in the nephrotoxic nephritis model, to the degree of proteinuria. CONCLUSION: Twenty-four-hour delayed USPIO-enhanced MR imaging may help identify and differentiate various types of nephropathies.     

Ultrasmall superparamagnetic iron oxide: an intravenous contrast agent for assessing lymph nodes with MR imaging

An ultrasmall superparamagnetic iron oxide (USPIO) preparation was evaluated as a potential intravenous contrast agent for lymph nodes. Relaxation time measurements and magnetic resonance (MR) imaging were performed in rats with normal lymph nodes and in rats with lymph node metastases. In normal animals, lymph node relaxation times decreased maximally within 24-48 hours after intravenous administration of USPIO. Twenty-four hours after administration, the T2 of normal lymph nodes had decreased from 74 msec +/- 2.2 to 30 msec +/- 0.7 (USPIO, 40 mumol of iron per kilogram) or 15 msec +/- 0.0 (200 mumol Fe/kg), whereas the T2 of metastatic nodes did not change. MR imaging of the animal model of nodal metastases confirmed the hypothesis that intravenously administered USPIO decreases signal intensity of normal but not metastatic nodes. A single intravenous administration of USPIO may allow detection of nodal metastases on the basis of signal intensity characteristics rather than the currently used, insensitive size characteristics.     

Use of a blood-pool contrast agent for MR-guided vascular procedures: feasibility of ultrasmall superparamagnetic iron oxide particles

RATIONALE AND OBJECTIVES: The purpose of this study was to examine the dose dependency of the intravascular signal intensity after injection of ultrasmall superparamagnetic iron oxide (USPIO) particles (SH U 555 C) in a rabbit model studied with a low-field-strength magnetic resonance (MR) imaging system. The results were used to facilitate MR-guided vascular procedures in a pig. MATERIALS AND METHODS: All experiments were performed at 0.2 T. To determine the optimum USPIO (or SH U 555 C) dose for intravascular interventions, the authors acquired coronal three-dimensional MR angiographic images in 12 rabbits after injection of four dose levels (10, 20, 30, and 40 micromol of iron per kilogram body weight). The intraaortic signal intensities were measured in user-defined regions of interest. For numerical analysis, signal intensity enhancement was computed. Subsequently MR image-guided procedures were performed in USPIO-enhanced vessels in one pig. RESULTS: The signal intensity evaluation shows a clear-cut dose dependence in both early and late phases after administration of SH U 555 C. A high-spatial-resolution MR angiogram acquired 20 minutes after injection yielded the best results with the highest dose (40 micromol of iron per kilogram); at that dose, intravascular enhancement was sufficient for vascular procedures for 60 minutes after injection. CONCLUSION: SH U 555 C is a promising contrast agent for MR angiography and MR-guided vascular procedures in an open low-field-strength MR imager.     

Targeting of ultrasmall superparamagnetic iron oxide (USPIO) particles to tumor cells in Vivo by using transferrin receptor pathways

Human transferrin was covalently coupled to ultrasmall superparamagnetic iron oxide (USPIO) particles, and the trans-ferrin-USPIO obtained was investigated in vivo in experimental SMT/2A tumor-bearing rats (rat mammary carcinoma). Physicochemical characterization showed an overall size of 36 nm (DLS) with a core size of 5 nm (TEM). Relaxivities were R,₁ = 23.6 and R₂ = 52.1 liter/mmol · s (0.47 T). Bound transferrin was 280 μg/mg of iron. Pharmacokinetic investigations revealed a half-life of 17 min in normal rats. The MR evaluation of tumor signal intensity over time showed a 40% (range 25–55%) signal reduction 150 min after injection with the reduction persisting for at least 8 h. Control experiments using the parent USPIO compound or USPIO labeled with a nonspecific human serum albumin (HSA-USPIO) showed a change of only 10% (range 5–15%) in tumor signal intensity over time. The results demonstrate that a combination of the USPIO relaxivity properties with the specificity of transferrin-medi-ated endocytosis allows in vivo detection of tumors by MR imaging.     

Ultrasmall superparamagnetic iron oxide: characterization of a new class of contrast agents for MR imaging

An ultrasmall superparamagnetic iron oxide (USPIO) preparation was developed that is small enough to migrate across the capillary wall, a prerequisite in the design of targetable particulate pharmaceuticals. Seventy percent of particles were smaller than 10 nm; 26%, smaller than 5 nm. The blood half-life of USPIO in rats was 81 minutes, considerably longer than that of larger superparamagnetic iron oxide preparations such as AMI-25 (6 minutes). Electron microscopy demonstrated that USPIO particles transmigrate the capillary wall by means of vesicular transport and through interendothelial junctions. Twenty-four hours after intravenous administration, 3.6% of the injected dose per gram of tissue was found in lymph nodes, 2.9% per gram in bone marrow, 6.3% per gram in liver, and 7.1% per gram in spleen. The major potential applications for USPIO are as (a) an intravenous contrast agent for the lymphatic system, (b) a bone marrow contrast agent, (c) a long-half-life perfusion agent for brain and heart, and (d) the magnetic moiety in organ-targeted superparamagnetic contrast agents for magnetic resonance imaging.     

Rectal cancer: mesorectal lymph nodes at MR imaging with USPIO versus histopathologic findings--initial observations

PURPOSE: To compare histopathologic findings with appearances of mesorectal lymph nodes at magnetic resonance (MR) imaging with ultrasmall particles of iron oxide (USPIO) in rectal cancer. MATERIALS AND METHODS: Mesorectal lymph nodes in 12 patients with adenocarcinoma of the rectum were evaluated with USPIO and high-spatial-resolution MR imaging. Appearance and signal intensity of lymph nodes at T2- and T2*-weighted imaging were recorded before and after USPIO administration. Two radiologists visually assessed pattern of enhancement; interobserver agreement was tested with the kappa statistic. After total mesorectal excision, MR imaging of surgical specimens was performed, and it enabled node-by-node correlation with histopathologic findings. RESULTS: Appearances of 74 nodes at in vivo MR imaging were compared with histopathologic findings. Sixty-eight nodes were nonmalignant (34 were normal, 34 showed reactive changes); six nodes were malignant. Four patterns of USPIO uptake were demonstrated at T2*-weighted imaging: uniform low signal intensity, central low signal intensity, eccentric high signal intensity, and uniform high signal intensity. Two radiologists showed good interobserver agreement (kappa = 0.88, P <.01) in classification of nodes into these four categories. Sixty-five (96%) of 68 nonmalignant nodes showed uniform or central low-signal-intensity patterns; 16 (47%) of 34 reactive nodes showed central low-signal-intensity patterns. Compared with uniform low-signal-intensity pattern, central low-signal-intensity pattern was more commonly observed in reactive nodes (P <.01, chi(2) test; positive predictive value, 67%; 95% CI: 47%, 87%). Eccentric and uniform high-signal-intensity patterns were observed in lymph nodes that contained metastases larger than 1 mm in diameter. CONCLUSION: Mesorectal lymph nodes can be characterized by using USPIO and T2*-weighted MR imaging. Uniform and central low-signal-intensity patterns are features of nonmalignant nodes. Reactive nodes frequently show central low signal intensity at T2*-weighted imaging.     

MRI in focal liver disease: A comparison of small and ultra-small superparamagnetic iron oxide as hepatic contrast agents

The purpose of this study was to compare small and ultrasmall superparamagnetic iron oxide particles (SPIO and USPIO, respectively) as MR contrast agents for the evaluation of focal hepatic disease. In two different patient groups (SPIO [n = 53], USPIO [n = 27]), with focal liver disease (metastases, hepatocellular carcinoma [HCC], hepatocellular adenoma [HCA], and focal nodular hyperplasia [FNH]), spin-echo T1- and T2-weighted images (T1WI, T2WI) were obtained at 1.0T, before and after intravenous contrast administration. The percentage signal-to-noise ratio (SNR) change and lesion-to-liver contrast (LLC) were measured and statistically compared. The liver decreased in signal intensity (SI) after SPIO administration (?28%) and increased after USPIO administration (+16%) on T1WI. On T2WI, the liver decreased in SI on postcontrast images with both agents (?78% SPIO, ?73% USPIO). This difference was not statistically significantly different (P ? .07). Both SPIO and USPIO provided >500% improvement in LLC on T2WI. On T1WI, LLC was increased in metastases (120%) and HCC (325%) with SPIO. Post-USPIO, LLC was increased on T1WI only in metastases (>500%). Both SPIO and USPIO show excellent hepatic uptake, presumed secondary to reticuloendothelial activity, based on the degree of %SI change seen in the liver after administration of contrast on T2WI. However, USPIO preparations exhibit blood pool activity that may aid in further characterization of focal liver lesions, as is evidenced by their greater T1 effect in the liver and in some focal liver lesions.