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.     

Detection of synovial macrophages in an experimental rabbit model of antigen-induced arthritis: ultrasmall superparamagnetic iron oxide-enhanced MR imaging

PURPOSE: To evaluate intravenously administered ultrasmall superparamagnetic iron oxide (USPIO) as a marker of macrophage activity in an experimental rabbit model of antigen-induced arthritis. MATERIALS AND METHODS: Unilateral arthritis was induced by means of intraarticular injection of methylated bovine serum albumin in 10 knees of 10 rabbits that had been presensitized to the same antigen. The contralateral knees in these rabbits, as well as six knees in three other rabbits, served as controls. After onset of arthritis, all knees were imaged prior to and 24 hours after administration of USPIO. The magnetic resonance (MR) imaging protocol included T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo, and short inversion time inversion-recovery sequences. Images were analyzed quantitatively and qualitatively with regard to signal characteristics and pattern. MR findings were correlated with histopathologic findings. Wilcoxon signed rank test was used to compare results of signal-to-noise ratio calculations before and after USPIO administration. RESULTS: All knees with intraarticular injection of antigen suspension developed unilateral arthritis, whereas no signs of arthritis occurred in the control knees. On USPIO-enhanced images obtained 24 hours after contrast agent administration, significant T1 (P =.03) and more predominantly T2* (P =.02) and T2 effects (P =.01) were evident in the synovium of all 10 arthritic knees, which reflected USPIO uptake by macrophages in the synovial tissue. To a lesser extent, T2* effects were present also within the joint effusion (P =.01). No significant changes in signal characteristics were detected in the 10 nonarthritic knees in the antigen-injected group or the six knees in the control group (P =.06-.91). Histologic examination confirmed uptake of iron in the macrophages of arthritic knees. Changes in MR signal characteristics within the arthritic synovium and synovial effusion were visually detectable after intravenous administration of USPIO. CONCLUSION: MR imaging at 1.5 T can depict USPIO uptake in phagocytic-active macrophages in an antigen-induced arthritis animal model.     

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.     

MR imaging with ultrasmall superparamagnetic iron oxide particles in experimental soft-tissue infections in rats

PURPOSE: To investigate the feasibility of macrophage magnetic resonance (MR) imaging in rats by using an experimental soft-tissue infection model. MATERIALS AND METHODS: Thirteen rats with unilateral calf-muscle infection were imaged with a 4.7-T MR imager at an early chronic stage of infection (day 4 before contrast material injection, days 4-7 after injection). Eleven animals were imaged before and 3 and 24 hours after intravenous application of ultrasmall superparamagnetic iron oxide (USPIO), and eight animals were additionally imaged 48 hours and three animals 72 hours after USPIO application. Two infected rats served as controls. T1- and T2-weighted spin-echo and T2*-weighted gradient-echo sequences were applied. All animals were sacrificed, and histopathologic findings were correlated with findings on MR images. Electron microscopy was performed in two rats. For quantitative analysis, signal intensities on T2*-weighted images and T2 values on T2 maps were measured within regions of interest, and the temporal variation was analyzed by using the signed rank test. RESULTS: Visualization of USPIO-loaded macrophages was most sensitive with a T2*-weighted sequence. USPIO distribution pattern and quantitative analysis of T2 and T2* effects 3 hours after USPIO application were significantly different (P <.05) from those at 24 and 48 hours, reflecting the dynamic transit of the particle accumulation from the intravascular to the intracellular compartment by means of macrophage phagocytosis. Local signal intensity alterations could be correlated with iron-loaded macrophages at histopathologic examination. CONCLUSION: Activated macrophages in acute soft-tissue infection can be labeled with USPIOs and detected with MR imaging because of susceptibility effects.     

USPIO-enhanced MR imaging for visualization of synovial hyperperfusion and detection of synovial macrophages: preliminary results in an experimental model of antigen-induced arthritis

PURPOSE: To evaluate whether ultrasmall superparamagnetic iron particles (USPIO)-enhanced MRI is capable of assessing both synovial perfusion characteristics and the presence of synovial macrophages in a model of antigen-induced arthritis. MATERIALS AND METHODS: Unilateral arthritis was induced in six knees of six rabbits. The contralateral knees of the rabbits served as control knees. After onset of arthritis, all 12 knees were scanned prior to and immediately following intravenous administration of USPIO using a multiphase T1-weighted (T1w) fast gradient-echo (FGRE) sequence, and T1w spin-echo (SE), T2-weighted (T2w) FSE, T2*w GRE, and short-tau inversion recovery (STIR) sequences prior to and 24 hours following USPIO administration. SI-vs.-time curves (STCs) and the early enhancement rate during the first 56 seconds (REE(56)) were calculated from SI measurements within the synovial tissue of all knees on dynamic T1w images. MR findings were correlated to histopathology. RESULTS: REE(56) was significantly higher in the synovial tissue of arthritic knees than in the control knees (P < 0.01). Significant T1-, T2-, and T2* effects (P = 0.03-0.04) and multiple synovial vessels were visually detectable within the arthritic synovial tissue 24 hours after administration of USPIO, whereas no signal changes or synovial vessels were seen in the control knees. Histopathology revealed widened synovial blood vessels in the arthritic knees, and confirmed iron uptake by macrophages in the arthritic knees. CONCLUSION: USPIO-enhanced MRI is capable of both assessing synovial hyperperfusion and detecting macrophages in antigen-induced arthritis in rabbits.     

Characteristics of ultrasmall superparamagnetic iron oxides in patients with brain tumors

OBJECTIVE: The aim of this study was to evaluate the characteristics of an ultrasmall superparamagnetic iron oxides (USPIO) agent in patients with brain tumors and to correlate changes on MRI with histopathologic data collected systematically in all patients. SUBJECTS AND METHODS: Nine patients with brain tumors were imaged before and 24 hr after administration of a USPIO at a dose of 2.6 mg Fe/kg. Analysis of MR images included qualitative and quantitative comparison of the USPIO and gadolinium enhancement of brain tumors. Brain surgery was performed 25-112 hr after administration of the USPIO. The histopathologic workup included iron histochemistry with diaminobenzidine (DAB)-enhanced Perls stain. RESULTS: In seven of nine patients, USPIO-related changes of signal intensity were observed in gadolinium-enhancing brain tumors on T1- and T2*-weighted sequences. The difference in signal intensity on T1-weighted USPIO series was 40.1% +/- 26.7% (mean +/- SD). On T2*-weighted USPIO series, the difference in signal intensity was -33.1% +/- 18.4% in solid tumor parts. Areas of suspected radiation necrosis did not enhance in three patients with prior radiation therapy. Iron histochemistry revealed the presence of iron deposits in macrophages in two patients. CONCLUSION: USPIO agents will not replace gadolinium in the workup of patients with brain tumors. Our findings suggest that USPIO agents seem to offer complementary information and may help to differentiate between brain tumors and areas of radiation necrosis. Signal intensity changes on T2*-weighted images might be related to the blood pool properties of the agent, possibly reflecting steady-state susceptibility effects.     

Focal nodular hyperplasia of the liver on ferumoxides-enhanced MR imaging: features on conventional spin-echo, fast spin-echo and gradient-echo pulse sequences

The aim of this study was to assess the efficacy of a superparamagnetic iron oxide, ferumoxides, in the detection and characterization of focal nodular hyperplasia (FNH) on MR conventional spin-echo (SE), fast spin-echo (FSE) and gradient-echo (GRE) images. Fourteen adults with 27 FNHs were evaluated at 1.5 T before and after injection of ferumoxides. T1-weighted and T2-weighted SE, T2-weighted FSE and T2^*-weighted GRE sequences were used and analysed qualitatively and quantitatively. One hundred percent of FNHs showed a significant postcontrast decrease in signal intensity on T2- and T2*-weighted images. Heavily T2-weighted SE images showed the maximum decrease in FNH signal-to-noise ratio (S/N). Postcontrast GRE T2^*-weighted images improved the detection of the central scar and the delineation of FNHs and demonstrated the best lesion-to-liver contrast-to-noise ratio (C/N). Postcontrast T1-weighted SE images showed the least lesion-to-liver C/N. Ferumoxides-enhanced MR imaging can help detect and characterize FNH. Conventional pre- and postcontrast T2-weighted SE images and postcontrast GRE T2*-weighted images should be used preferentially. Received: 30 November 1998; Revised: 5 April 1999; Accepted: 6 April 1999     

Mangafodipir trisodium‐enhanced MRI for the detection and characterization of focal hepatic lesions: Is delayed imaging useful?

PURPOSE: To investigate the usefulness of early and delayed hepatic MRI after mangafodipir trisodium (Mn-DPDP) administration for the detection and characterization of focal hepatic lesions. MATERIALS AND METHODS: Forty-five patients (31 males and 14 females, mean age = 61 years) with a total of 113 hepatic lesions (mean size = 3.5 cm) were included in this study (15 with hepatocellular carcinoma (HCC, N = 35), 20 with hepatic metastasis (N = 63), five with hemangioma (N = 10), three with cholangiocarcinoma (CC, N = 3), and two with liver abscess (N = 2)). T1-weighted gradient-echo MR images were obtained before and after Mn-DPDP administration, with a mean 18-hour delayed imaging. A qualitative analysis (including the size and signal intensity (SI)) and quantitative analysis (including enhancement and lesion-liver contrast-to-noise ratio (CNR)) were performed on pre- and postcontrast early and delayed MR images. RESULTS: Compared to postcontrast early imaging, 17 (48.6%) of 35 HCCs showed higher SI, 16 (45.7%) showed no SI change, and two (5.7%) showed lower SI on delayed imaging. All 63 metastases, 10 hemangiomas, three CCs, and two abscesses showed no SI change. On delayed imaging, ring enhancement was noted in 53 metastases (84.1%), three hemangiomas (30.0%), and one abscess (50.0%), but was not seen in HCCs or CCs. Eight metastases (12.7%) also showed ring enhancement on postcontrast early imaging. No newly detected hepatic lesions were revealed on postcontrast delayed MR images compared to postcontrast early images. Regarding CNR, the HCCs showed a significant increase in CNR from postcontrast early to delayed images after administration of Mn-DPDP (P < 0.01). However, none of the metastases, hemangiomas, CCs, and abscesses showed a significant increase of CNR from postcontrast early to delayed images. CONCLUSION: Postcontrast delayed MR images after Mn-DPDP administration were helpful in distinguishing hepatocellular from nonhepatocellular lesions, but were not useful for lesion detection and had limited utility for lesion characterization, since benign and malignant hepatic lesions looked the same.     

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.     

Comparison of ultrasmall particles of iron oxide (USPIO)-enhanced T2-weighted, conventional T2-weighted, and gadolinium-enhanced T1-weighted MR images in rats with experimental autoimmune encephalomyelitis

BACKGROUND AND PURPOSE: Ultrasmall particles of iron oxide (USPIO) constitute a contrast agent that accumulates in cells from the mononuclear phagocytic system. In the CNS they may accumulate in phagocytic cells such as macrophages. The goal of this study was to compare USPIO-enhanced MR images with conventional T2-weighted images and gadolinium-enhanced T1-weighted images in a model of experimental autoimmune encephalomyelitis (EAE). METHODS: Nine rats with EAE and four control rats were imaged at 4.7 T and 1.5 T with conventional T1- and T2-weighted sequences, gadolinium-enhanced T1-weighted sequences, and T2-weighted sequences obtained 24 hours after intravenous injection of a USPIO contrast agent, AMI-227. Histologic examination was performed with hematoxylin-eosin stain, Perls' stain for iron, and ED1 immunohistochemistry for macrophages. RESULTS: USPIO-enhanced images showed a high sensitivity (8/9) for detecting EAE lesions, whereas poor sensitivity was obtained with T2-weighted images (1/9) and gadolinium-enhanced T1-weighted images (0/9). All the MR findings in the control rats were negative. Histologic examination revealed the presence of macrophages at the site where abnormalities were seen on USPIO-enhanced images. CONCLUSION: The high sensitivity of USPIO for macrophage activity relative to other imaging techniques is explained by the histologic findings of numerous perivascular cell infiltrates, including macrophages, in EAE. This work supports the possibility of intracellular USPIO transport to the CNS by monocytes/macrophages, which may have future implications for imaging of human inflammatory diseases.     

Comparison of lymph node metastases assessment With the use of USPIO‐enhanced MR imaging at 1.5 T versus 3.0 T in a rabbit model

Purpose:

To prospectively compare the diagnostic performances of 1.5 T and 3.0 T ultrasmall superparamagnetic iron oxide (USPIO)‐enhanced magnetic resonance imaging (MRI) for the detection of lymph node (LN) metastases in a rabbit model.

Materials and Methods:

Experiments were approved by the animal care committee. VX2 carcinomas were implanted into the thighs of 18 rabbits 3 or 4 weeks before MRI examinations. T2*‐weighted 1.5 T and 3.0 T MRI was performed 24 hours after USPIO (2.6 mg/kg iron) administration. Two radiologists calculated signal intensity (SI) ratios (ie, the ratios of postcontrast to precontrast signal intensity) of each LN and also evaluated for the presence of a metastasis in the iliac and retroperitoneal LNs at 1.5 T and 3.0 T MRI. Student's t‐test, receiver operating characteristic (ROC) curve analysis, and a Z test were used for the statistical analysis.

Results:

Metastases were confirmed in 45 of 80 LNs by histopathology. For benign LNs the mean SI ratio at 1.5 T was higher (0.538) than at 3.0 T (0.463) (P = 0.004). In qualitative analysis, 1.5 T and 3.0 T USPIO‐enhanced MRI showed similar Az values (0.951 vs. 0.939; P = 0.296). The specificity of 3.0 T USPIO‐enhanced MRI was higher (91.4% [32 of 35]) than that of 1.5 T imaging (82.9% [29 of 35]) (P = 0.013); however, the sensitivities (88.9% [40 of 45]) were the same in the both modalities.

Conclusion:

3.0 T USPIO‐enhanced MRI shows a higher specificity as compared to 1.5 T imaging without a significant difference of sensitivity in a rabbit VX2 model. J. Magn. Reson. Imaging 2010;31:134–141. © 2009 Wiley‐Liss, Inc.     

MR angiography with an ultrasmall superparamagnetic iron oxide blood pool agent

The purpose of the study was to investigate the use of a dextran-coated ultrasmall superparamagnetic iron oxide (USPIO) as a blood pool contrast agent for thoracic and abdominal MR angiography. Abdominal and thoracic MR angiography was performed in six healthy volunteers using two-dimensional and three-dimensional spoiled gradient echo (SPGR) sequences before and after intravenous administration of USPIO. Doses ranged from 1.1 to 2.6 mg Fe/kg. Flip angle was varied from 20 to 60°. Subjective image quality, analysis of signal-to-noise ratio (SNR), and blood T1 relaxation times were measured. USPIO significantly lowered the T1 of blood (from 1,210 ms precontrast to 159 ms postcontrast at a dose of 2.6 mg Fe/kg) (P < .01). Image quality on coronal fast three-dimensional breath-hold SPGR images of the abdomen increased with increasing dose and was maximum at the highest dose, producing an aortic SNR of 9.6 compared to 1.8 precontrast. Axial two-dimensional time-of-flight (TOF) aortic SNR was reduced significantly from 13 on precontrast to 6 on the postcontrast images at the highest dose (P < .05) due to T2* shortening effects. There was little flip angle dependence on image quality. Due to the T1 shortening effect and long intravascular half-life, USPIO improved visualization of vascular anatomy using three-dimensional fast SPGR imaging. The echo time must be minimized to minimize signal loss from T2* shortening effects. The blood pool distribution of USPIO is useful for equilibriumphase MR angiography.     

Tongue abscesses: MR imaging findings

BACKGROUND AND PURPOSE: A lingual abscess is difficult to diagnose in the absence of physical signs. MR imaging may provide an excellent and invaluable adjunct to clinical examination, but the literature is incomplete in defining the various MR imaging findings of abscess. The objective of this study was to determine the MR imaging features of tongue abscesses. METHODS: Seven surgically proved tongue abscesses were evaluated with MR imaging. Four patients underwent MR imaging because of suspected tumor, and 3 patients, to show the extent and precise anatomic location of the lesion. Lesions were assessed with regard to the location, size, signal-intensity characteristics, and pattern of contrast enhancement. RESULTS: Five lesions were located in the anterior tongue and 2, in the posterior tongue. The central parts of 4 anterior tongue abscesses were hypointense, surrounded by a hyperintense wall on T1-weighted precontrast images. On postcontrast images, marked wall enhancement was detected. On T2-weighted images, a markedly hyperintense central part surrounded by a hypointense rim was seen. In 2 of these patients, there was a hypointense halo surrounding the wall (target sign). In 3 patients, a perilesional hyperintense area that enhanced diffusely after contrast administration was detected on T2-weighted images. The smallest lesion located in the anterior tongue was hypointense on T1-weighted images and enhanced diffusely on postcontrast images. On T2-weighted images, a markedly hyperintense central part surrounded by a mildly hyperintense peripheral part was depicted. Posterior tongue lesions appeared as polypoid ill-defined masses and were hypointense on T1-weighted images and heterogeneously hyperintense on T2-weighted images. On postcontrast images, the lesion in 1 patient showed diffuse and heterogeneous contrast enhancement, whereas the lesion in another patient enhanced peripherally. The lesions were totally excised in 4 patients and drained with surgical incisions in 3 patients. No recurrence was detected on follow-up. CONCLUSION: An abscess typically presents as a cystic lesion surrounded by an enhancing capsule formation, but lesions may also present as solid masses that enhance diffusely or peripherally.     

Decrease of signal intensity of myometrium and cervical stroma after ultrasmall superparamagnetic iron oxide (USPIO) particles administration: an MR finding with potential benefits in T staging of uterine neoplasms

OBJECTIVES: Following the empiric observation of a significant decrease of signal intensity of both myometrium and cervical stroma on ultrasmall superparamagnetic iron oxide (USPIO)-enhanced images, the aim of our study was to evaluate whether USPIO-enhanced T2*-weighted gradient echo (GRE) images might provide any potential advantage on T-staging of uterine malignancies having surgery and histology as standard of reference MATERIALS AND METHODS: Seventeen female patients with known uterine malignancies underwent magnetic resonance (MR) imaging before and 24 hours after the intravenous administration of the USPIO agent. Imaging protocol included proton density-weighted turbo spin echo and T2*-weighted GRE sequences. Each patient underwent surgery within 14 days from the first MR examination, and histologic confirmation of tumor T-stage was obtained. Quantitative (calculation of signal-to-noise and contrast-to-noise ratios) and qualitative (visual assessment of T staging) analyses were performed on unenhanced and USPIO-enhanced images. RESULTS: Quantitative analysis showed a significantly lower (P < 0.05) signal-to-noise ratio of myometrium and cervical stroma on USPIO-enhanced compared with unenhanced images. In 15 of 17 patients (88.2%), the contrast-to-noise ratio between tumor and myometrium and between tumor and cervical stroma was higher on USPIO-enhanced compared with unenhanced images (P < 0.001). Qualitative analysis demonstrated that the GRE T2* USPIO-enhanced MR offers a better definition of the depth of tumor infiltration rather than the unenhanced GRE T2* images. CONCLUSION: The decrease of signal intensity of myometrium and cervical stroma on T2*-weighted GRE images after the intravenous administration of USPIO should be considered a constant and physiologic finding that improves tumor conspicuity in the majority of the cases, allowing more accurate T-staging of neoplastic lesions.     

Ultrasmall supraparamagnetic iron oxide-enhanced magnetic resonance imaging of antigen-induced arthritis: a comparative study between SHU 555 C, ferumoxtran-10, and ferumoxytol

OBJECTIVES: We sought to compare the ability of 3 ultrasmall superparamagnetic iron oxides (USPIOs) to detect and characterize antigen-induced arthritis with MR imaging. MATERIALS AND METHODS: A monoarthritis was induced in the right knee of 18 rats. The left knee served as a normal control. Knees underwent magnetic resonance (MR) imaging before, up to 2 hours, and 24 hours after injection (p.i.) of 200 mumol Fe/kg SHU 555 C (n= 6), ferumoxtran-10 (n = 6), or ferumoxytol (n = 6), using T2-2D-SE 100/20,40,60,80/90 (TR/TE/flipangle), T2*-3D-spoiled gradient recalled (SPGR) 100/15/38, and T1-3D-SPGR 50/1,7/60 sequences. RESULTS: Quantitative signal to noise ratio and DeltaSI data of arthritic knees on T1- and T2*-weighted MR images showed no significant differences between the 3 USPIOs (P > 0.05). At 2 hours p.i., SNR and DeltaSI data were significantly increased from baseline on T1-weighted images and significantly decreased on T2*-weighted images (P < 0.001). At 24 hours p.i., the T1-enhancement returned to baseline, whereas the T2*-enhancement remained significantly elevated (P < 0.001). Immunostains demonstrated an USPIO compartmentalization in macrophages in the arthritic synovium. CONCLUSIONS: Based on the relatively small number of animals in our study group, inflammation in antigen-induced arthritis can be equally detected and characterized with any of the three USPIOs evaluated.     

USPIO-enhanced magnetic resonance imaging of the knee in asymptomatic volunteers

The aim of this study was to compare signal characteristics of the synovium in knees of asymptomatic volunteers before and after intravenous administration of ultrasmall superparamagnetic iron oxide particles (USPIO). Ten knees of 10 asymptomatic volunteers were examined before and 36 h after intravenous administration of USPIO on a 1.5-T MR system using T1-weighted spin-echo, T2-weighted fast spin-echo, T2*-weighted gradient-echo (GRE), and short inversion time inversion-recovery sequences. In addition, synovial perfusion was measured using Gd-enhanced GRE imaging during the first imaging session. Images were analyzed qualitatively for any visual changes before and after USPIO administration. Signal-to-noise ratios (SNR) of the synovium were determined on unenhanced and USPIO-enhanced sequences. All MR images were reviewed for presence of any degenerative changes. Qualitative image analysis revealed no visually detectable changes of any knee joint before and after USPIO administration. The SNR values of the synovium on T1w, T2w, and T2*w images before and after USPIO administration showed no significant difference (T1, P = 0.86; T2, P = 0.95; T2*, P = 0.86). None of the volunteers showed any relevant degenerative changes of the knee and synovial perfusion was within normal limits. In knees of asymptomatic volunteers without any relevant degenerative changes and normal synovial perfusion neither visual changes nor changes of SNR values of the synovium can be depicted after USPIO administration. This means that USPIO-enhanced MRI may be used for assessment of knee disorders with increased macrophage activity.     

Malignant lesions of the liver with high signal intensity on T1-Weighted MR images

Our purpose was to identify the histologic types of malignant liver lesions with high signal intensity (SI) on T1-weighted images and to describe the MR imaging features. Thirteen patients with malignant liver lesions high in SI on T1-weighted images were studied with a 1.5-T MR imager using pre- and serial postcontrast spoiled gradient-echo (SGE) sequences (all patients), T2-weighted fat-suppressed spin-echo sequences (all patients), precontrast T1-weighted fat-suppressed spin-echo sequences (five studies in five patients), and precontrast out-of-phase SGE sequences (seven studies in six patients). Images were reviewed retrospectively to determine number of lesions; lesion size; SI of lesions on T1-weighted, T2-weighted, and fat-attenuated T1-weighted images; distribution of high SI in lesions on T1-weighted images; and tumor enhancement pattern. Seven patients had multiple tumors high in SI on T1-weighted images and six patients had solitary tumors. Seventy-two lesions were less than 1.5 cm in diameter and 35 lesions were more than 1.5 cm in diameter. Nine patients had solid malignant lesions and four patients had cystic malignant lesions. All tumors more than 1.5 cm in diameter were heterogeneously high in SI on T1-weighted images, and all tumors less than 1.5 cm were completely homogeneous or homogeneous with a small central hypointense focus. All tumors were more conspicuous on T1-weighted fat-attenuated images, both on excitation spoiled fat-suppressed spin-echo or on out-of-phase SGE images with the exception of one fat-containing hepatocellular carcinoma (HCC). In one patient with melanoma metastases and one patient with multiple myeloma nodules, appreciably more lesions were detected on out-of-phase SGE images. Causes of hyperintensity were considered to be either fat, melanin, central hemorrhage, or high protein content, all of which may be seen in a variety of tumors. Fat-attenuation techniques are helpful in the detection of these lesions.     

Gadopentetate dimeglumine versus ultrasmall superparamagnetic iron oxide for dynamic contrast-enhanced MR imaging of tumor angiogenesis in human colon carcinoma in mice

PURPOSE: To compare the kinetic physiologic properties of a clinical contrast agent, gadopentetate dimeglumine, with those of ultrasmall superparamagnetic iron oxide (USPIO) particles for dynamic contrast material-enhanced magnetic resonance (MR) imaging of tumor angiogenesis in human colon carcinoma in mice with a clinical MR imaging unit. MATERIALS AND METHODS: Thirty-two mice with human colon carcinoma were injected with either gadopentetate dimeglumine (n = 16) or USPIO (n = 16) for dynamic contrast-enhanced MR imaging and pre- and postcontrast T2 and T2* measurements. Dynamic contrast-enhanced MR imaging measurements were analyzed by using a two-compartment model to calculate the endothelial transfer coefficient surface area product (KPS) for the tumor microvasculature, the reflux coefficient (k), and the fractional plasma volume (fPV). KPS, k, and fPV maps were compared with histologic microvessel density (MVD) and used to observe differences between core and rim regions of tumor. RESULTS: Results in 30 mice (15 in the gadopentetate dimeglumine group and 15 in the USPIO group) could be used. KPS values measured with both agents correlated well with MVD in hot spots (gadopentetate dimeglumine: r = 0.6, P =.02; USPIO: r = 0.6, P =.01). No significant difference (P =.4) in correlation was found between the two agents. Both USPIO and gadopentetate dimeglumine demonstrated higher MVD and KPS values in tumor rim than in tumor core (P <.01). Tumor k values correlated poorly with whole-tumor MVD for both gadopentetate dimeglumine (r = 0.3, P =.4) and USPIO (r = 0.2, P =.6), while fPV values correlated well with whole-tumor MVD for USPIO (r = 0.6, P =.02) but not gadopentetate dimeglumine (r = -0.01, P =.98). T2 and T2* measurements showed small differences between areas of high and low angiogenic activity with both agents. CONCLUSION: The kinetic physiologic properties of gadopentetate dimeglumine are as good as those of USPIO for dynamic contrast-enhanced MR imaging for calculating KPS as a measurement of angiogenesis in human colon carcinoma. Further studies with patients may reveal whether gadopentetate dimeglumine might be used for this purpose in clinical practice.     

MR assessment of iodinated contrast-medium-induced nephropathy in rats using ultrasmall particles of iron oxide

The purpose of this study was to determine the diagnostic value of ultrasmall particles of iron oxide (USPIO)-enhanced MR imaging at different concentrations to evaluate experimental nephropathy. This study was conducted in 23 uninephrectomized rats using a model of iodinated contrast media-induced renal failure. Eleven rats received selective intra-arterial renal administration of diatrizoate (370 mg I/m1) and were compared to two control groups, including five animals injected with isotonic saline and seven noninjected animals. MR imaging was performed 28 hours after the procedure, including T1- and T2-weighted images before and after intravenous administration of successively 5 μmol Fe/kg and 60 μmol/kg of USPIO. Results were interpreted qualitatively and quantitatively with respect to pathologic data, and differences were studied statistically. The maximal signal intensity decrease was noted in normal kidneys in cortex (?65 ± 4%) and medulla (?84 ± 5%) on T2-weighted images after injection of 60 μmol/kg of USPIO. At this dose, diseased kidneys displayed less signal intensity decrease than normal kidneys on T2-weighted images (p = .05). Moreover, qualitative analysis showed that the highest sensitivity and specificity to diagnose kidney involvement were obtained with T2-weighted MR images (75% and 91%, respectively) when 60 μmol/kg of USPIO were used (p < .01). USPIO should be useful for in vivo evaluation of the severity of experimentally induced iodinated contrast media renal impairment in animals.     

Pyogenic hepatic abscesses: MRI findings on T1- and T2-weighted and serial gadolinium-enhanced gradient-echo images

The purpose of this study was to determine the magnetic resonance imaging (MRI) features of pyogenic hepatic abscesses on T1-weighted, T2-weighted, and serial gadolinium (Gd)-enhanced T1-weighted spoiled gradient-echo (SGE) images including images acquired in the immediate, intermediate, and late phases of enhancement. The MRI studies of 20 patients with pyogenic liver abscesses were retrospectively reviewed. All patients were examined on 1.5 (n = 19) and 1.0 (n = 1) T MR scanners. MR studies included T1-weighted, T2-weighted, and serial Gd-enhanced SGE images. The following determinations were made: signal intensity of the abscess cavity and perilesional liver tissue, and the presence of internal septations, layering material, or air in the abscess cavity. The pattern of enhancement of the abscess wall, internal septae and peri-abscess liver were evaluated on serial Gd-enhanced SGE images. A total of 53 abscesses were observed in the 20 patients. Fortyeight abscesses were hypointense on T1-weighted and hyperintense on T2-weighted images. Internal septations were present in four abscesses. Lower signal intensity material was observed in a dependent location on T2-weighted images in one abscess. Signal void foci of air located on the nondependent surface was observed in two abscesses. Two other abscesses contained signal void air that occupied the entire abscess cavity, observed on all imaging sequences. On serial gadolinium-enhanced images, all abscesses revealed early enhancement of the wall, which persisted with negligible change in degree of enhancement or thickness on delayed images. Abscess walls ranged in thickness from 2 to 5 mm. Internal septations ranged in thickness from 2 to 3 mm. Abscess walls and septations were relatively uniform in thickness with no evidence of focal nodularity. Periabscess liver tissue was mildly hypointense on T1-weighted and mildly hyperintense on T2-weighted images in 20 lesions, which were either circumferential (n = 12) or wedge-shaped (n = 8). All these regions enhanced more than the remainder of the liver on immediate post-gadolinium images and remained relatively hyperintense on late phase images. Periabscess liver parenchyma was isointense on both T1- and T2-weighted images in 18 lesions, and in these lesions wedge-shaped subsegmental (n = 6) or segmental (n = 12) enhancement was observed on immediate gadolinium-enhanced images, which faded to isointensity on intermediate phase images. No perilesional signal changes and enhancement difference was observed in 15 lesions. Characteristic features of abscesses include: intense mural enhancement on early gadolinium-enhanced images, which persists with negligible change in thickness and intensity on later post-gadolinium images, and the presence of periabscess increased enhancement on immediate post-gadolinium images. These MRI features may help to distinguish abscesses from other focal liver lesions during differential diagnosis.