In vitro labeling of glioma cells with gadofluorine M enhances T1 visibility without affecting glioma cell growth or motility.

Gadofluorine is a novel macrocyclic, amphiphilic gadolinium-based contrast agent. We found that malignant glioma cells could be labeled in vitro using Gadofluorine without the need for transfection agents or any other additional means. Labeling with Gadofluorine enhanced the visualization of glioma cells in T(1)-weighted sequences, even if the cells had been cultured in medium without Gadofluorine over several days. The intracellular uptake of Gadofluorine was measured and the loss of relevant amounts of Gadofluorine into the cell culture medium was ruled out by MRI. Confocal laser fluorescence microscopy revealed Cy-5-labeled Gadofluorine in the perinuclear cytoplasmic region, but neither within the nucleus nor bound to the cell membrane. Adverse effects of cellular Gadofluorine uptake were ruled out by proliferation and migration assays. Finally, in vivo analyses provided good visibility of labeled glioma cells in T(1)-weighted sequences after intracerebral injection in mice for more than 2 weeks. We thus conclude that Gadofluorine can easily be used to label glioma cells in vitro without affecting glioma cell biology. Gadofluorine provides an interesting alternative for cellular labeling if iron oxide particles are incorporated insufficiently by target cells or if the vicinity of susceptibility artifacts prohibits the use of signal-decreasing contrast agents.     

Cell labeling with the positive MR contrast agent Gadofluorine M

The purpose of this study was to label human monocytes with Gadofluorine M by simple incubation for subsequent cell depiction at 1.5 and 3 T. Gadofluorine M displays a high r(1) relaxivity and is spontaneously phagocytosed by macrophages. Human monocytes were incubated with Gadofluorine M-Cy at varying concentrations and incubation times and underwent MR imaging at 1.5 and 3 T at increasing time intervals after the labeling procedure. R1-relaxation rates and r1 relaxivities of the labeled cells and non-labeled controls were determined. Cellular contrast agent uptake was examined by fluorescence microscopy and quantified by ICP-AES. Efficient cell labeling was achieved after incubation of the cells with 25 mM Gd Gadofluorine M for 12 h, resulting in a maximal uptake of 0.3 fmol Gd/cell without impairment of cell viability. Fluorescence microscopy confirmed internalization of the fluorescent contrast agent by monocytes. The r1 relaxivity of the labeled cells was 137 mM(-1)s(-1) at 1.5 T and 80.46 mM(-1)s(-1) at 3 T. Imaging studies showed stable labeling for at least 7 days. Human monocytes can be effectively labeled for MR imaging with Gadofluorine M. Potential in vivo cell-tracking applications include targeting of inflammatory processes with Gadofluorine-labeled leukocytes or monitoring of stem cell therapies for the treatment of arthritis.     

Interstitial T1-weighted MR lymphography: lipophilic perfluorinated gadolinium chelates in pigs.

PURPOSE: To investigate the enhancement of the regional lymph nodes, lymphatic vessels, and thoracic duct after interstitial administration of lymphotropic perfluorinated gadolinium chelates at magnetic resonance (MR) imaging. MATERIALS AND METHODS: Two perfluorinated gadolinium chelates, gadofluoramide and gadofluorine 8, were injected subcutaneously into the hind legs of 10 pigs, respectively. Both contrast media were studied at doses of 10 and 25 micromol per kilogram of body weight. T1-weighted three-dimensional gradient-echo and maximum intensity projection images were obtained at 1.5 T between 1 and 210 minutes and 24 hours after injection. The contrast agents were qualitatively compared regarding enhancement and depiction of the regional lymph nodes, lymphatic vessels, and thoracic duct. RESULTS: The inguinal and iliac lymph nodes and lymphatic vasculature enhanced substantially within 10 minutes after subcutaneous administration of both lymphotropic contrast agents. Gadofluorine 8 showed a lymphographic effect superior to that of gadofluoramide. The paraaortic lymph nodes and thoracic duct were best visualized 10--50 minutes after injection of 25 micromol/kg of gadofluorine 8. Lymphatic system enhancement diminished after 2 hours, and the liver and bowel tract enhanced within 24 hours. CONCLUSION: Interstitial administration of perfluorinated gadolinium chelates offers great potential for T1-weighted MR lymphography with positive enhancement of the lymph nodes and lymphatic vasculature.     

Gadofluorine-enhanced magnetic resonance imaging of carotid atherosclerosis in Yucatan miniswine

OBJECTIVE: The aim of this study was to determine whether gadofluorine, a paramagnetic magnetic resonance imaging (MRI) contrast agent, selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. METHODS: Atherosclerotic plaques were induced in the left carotid arteries (LCA) of Yucatan miniswine (n=3) by balloon denudation and high cholesterol diet. T1-weighted MRI was performed before and 24 hours after gadofluorine injection (at a dose of 100 micromol/kg) to assess the enhancement of the balloon-injured LCA wall relative to healthy, uninjured right carotid artery (RCA) wall. Histopathology was performed to verify the presence and composition of the atherosclerotic plaques imaged with MRI. RESULTS: Gadofluorine was found to enhance LCA atherosclerotic lesions relative to RCA wall by 21% (P<0.025) 24 hours after contrast injection. Enhancement of healthy LCA wall relative to healthy RCA wall was not observed. CONCLUSION: Gadofluorine selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. Gadofluorine appears to be a promising MR contrast agent for detection of atherosclerotic plaques in vivo.     

MR imaging of relapsing multiple sclerosis patients using ultra-small-particle iron oxide and compared with gadolinium

BACKGROUND AND PURPOSE: Inflammatory multiple sclerosis (MS) lesions are characterized by microglia activation and infiltration of T cells, B cells, and macrophages across the blood-brain barrier (BBB). In the experimental autoimmune encephalomyelitis (EAE) rat model of MS, previous MR imaging investigations with a new contrast agent ultra-small-particle iron oxide (USPIO) that accumulates in phagocytic cells revealed in vivo the presence of macrophage brain infiltration. The goal of this study was to characterize MS lesions with the use of this contrast agent. METHODS: A prospective MR imaging study of 10 patients with MS in acute relapses was achieved by using USPIO and gadolinium. RESULTS: Twenty-four hours after USPIO injection, 33 acute MS lesions in 9 patients showed USPIO uptake. Lesions were seen as high signal intensities on T1-weighted images and low signal intensities on T2-weighted images. Gadolinium enhancement was seen in 31 of these lesions in 7 patients. These 7 patients presented 24 gadolinium-enhanced lesions that did not enhance with USPIO. Two patients showed USPIO-enhanced lesions but no gadolinium-enhanced lesions. CONCLUSION: Taken together with earlier findings obtained in experimental models or in human stroke, the visualization of macrophage activity in vivo with USPIO characterize a distinct cellular and inflammatory event of the dynamic process of MS lesion formation. The macrophage activity information obtained with USPIO is distinct and complementary to the increased BBB permeability seen with gadolinium.     

Targeted contrast agent helps to monitor advanced plaque during progression: a magnetic resonance imaging study in rabbits

OBJECTIVE: Gadofluorine M has been reported to enhance early atherosclerotic plaque signals in magnetic resonance imaging (MRI). The aim of this study was to examine the use of Gadofluorine M to monitor the progression of advanced plaques in a rabbit model. METHODS: Focal advanced atherosclerosis was induced in the right femoral arteries of 6 New Zealand white rabbits using a combination of cholesterol-enriched diet, and sequential air-desiccation, and balloon-overstretch injury. MRI with conventional 3 contrasts (T1, T2, and proton density [PD]) was performed to monitor the progression of the atherosclerotic plaques with 2 MRI scans separated by 4 to 8 weeks. Gadofluorine M was given intravenously to the rabbits 24 hours before the first MRI scans, and before (n = 3) or during (n = 3) the second MRI scan. The left femoral arteries were used as a control. Histopathologic images localized individual plaque components. RESULTS: The advanced plaque displayed multilayered neointima that included foam cells, smooth muscle cells, and extracellular matrix. The separate image contrasts offered similar T1-weighted enhancement patterns, but the combination of all 3 contrasts helped to delineate plaque and lumen boundaries. Gadofluorine M strongly enhanced neointima areas with an image contrast (contrast-to-noise ratio [CNR]) of approximately 15, versus 2 in the control femoral arterial wall. With improved images, significant changes in neointima and total plaque volumes over the 4 to 8 weeks between scans could be identified. Gadofluorine M remained within the plaques with significant image enhancements (contrast-to-noise ratio = 5.8) for 2 months after a single injection. CONCLUSION: This preliminary study in rabbits indicated that Gadofluorine M provides specific enhancements of components associated with advanced atherosclerotic plaques and may help to monitor the progression of the plaque in a rabbit model of atherogenesis.     

Tissue-specific MR contrast agents

The purpose of this review is to outline recent trends in contrast agent development for magnetic resonance imaging. Up to now, small molecular weight gadolinium chelates are the workhorse in contrast enhanced MRI. These first generation MR contrast agents distribute into the intravascular and interstitial space, thus allowing the evaluation of physiological parameters, such as the status or existence of the blood-brain-barrier or the renal function. Shortly after the first clinical use of paramagnetic metallochelates in 1983, compounds were suggested for liver imaging and enhancing a cardiac infarct. Meanwhile, liver specific contrast agents based on gadolinium, manganese or iron become reality. Dedicated blood pool agents will be available within the next years. These gadolinium or iron agents will be beneficial for longer lasting MRA procedures, such as cardiac imaging. Contrast enhanced lymphography after interstitial or intravenous injection will be another major step forward in diagnostic imaging. Metastatic involvement will be seen either after the injection of ultrasmall superparamagnetic iron oxides or dedicated gadolinium chelates. The accumulation of both compound classes is triggered by an uptake into macrophages. It is likely that similar agents will augment MRI of atheriosclerotic plaques, a systemic inflammatory disease of the arterial wall. Thrombus-specific agents based on small gadolinium labeled peptides are on the horizon. It is very obvious that the future of cardiovascular MRI will benefit from the development of new paramagnetic and superparamagnetic substances. The expectations for new tumor-, pathology- or receptor-specific agents are high. However, is not likely that such a compound will be available for daily routine MRI within the next decade.     

Placental perfusion MR imaging with contrast agents in a mouse model

PURPOSE: To quantitatively analyze placental perfusion by using magnetic resonance (MR) imaging with contrast agents in a mouse model. MATERIALS AND METHODS: Study was conducted according to French law and in full compliance with National Institutes of Health recommendations for animal care. Thirty-six pregnant Balb/c mice at 16 days of gestation were injected intravenously with either a conventional or macromolecular gadolinium chelate, and 1.5-T single-section T1-weighted two-dimensional fast spoiled gradient-echo sequential MR imaging was then performed for 14 minutes. Images were analyzed qualitatively, and parametric map analysis was performed in the resultant 25 mice included in the study. Signal intensity was measured in maternal left ventricle (input function), placenta, and fetus on all images. After converting signal intensity into contrast agent tissue concentrations, a three-compartment model was developed with compartmental and numeric modeling software. Placental perfusion was calculated for conventional (n = 12) and macromolecular (n = 13) gadolinium chelates. Finally, placental and fetal gadolinium concentrations were assayed by means of atomic emission spectrophotometry (n = 15). Perfusion values and placental and fetal gadolinium concentrations for conventional and macromolecular chelates were compared by using an unpaired t test. RESULTS: Based on a constant transfer parameter, estimated placental perfusion did not differ between procedures with conventional and macromolecular gadolinium chelates (0.99 mL/min/g +/- 0.5 [standard deviation] and 1.28 mL/min/g +/- 0.6, respectively, P = .22). Likewise, mean placental gadolinium concentrations did not differ after injection of conventional and macromolecular chelates. In contrast, mean fetal gadolinium concentration was 9.83 micromol/L after conventional chelate injection and below detection limit after macromolecular chelate injection. CONCLUSION: Placental perfusion can be calculated by using dynamic contrast-enhanced MR imaging, as shown in this mouse model.     

Atypical focal nodular hyperplasia of the liver: imaging features of nonspecific and liver-specific MR contrast agents

OBJECTIVE: The objective of our study was to describe the functional and differential uptake features of atypical focal nodular hyperplasia using different MR contrast agents and to evaluate their potential role in the diagnosis and characterization of focal nodular hyperplasia. MATERIALS AND METHODS: Contrast-enhanced MR images of 45 patients with 85 focal nodular hyperplasia lesions were retrospectively reviewed. In these patients, sonographic findings were nonspecific (n = 37), or CT features were inconclusive (n = 8). Non-liver specific gadolinium chelates were used in 18 patients (48 lesions) suspected of having either focal nodular hyperplasia or hemangioma. The following liver-specific agents were used in patients with suspected focal nodular hyperplasia or metastases: mangafodipir trisodium, 30 patients (55 lesions); ferumoxides, six patients (16 lesions); and SHU 555 A, six patients (six lesions). Individual lesions were quantified by signal intensity and assessed qualitatively by homogeneity, contrast enhancement, and presence of a central scar. RESULTS: At unenhanced MR imaging, the triad of homogeneity, isointensity, and central scar was found in 22% of the focal nodular hyperplasia lesions. On mangafodipir trisodium-enhanced T1-weighted images, all focal nodular hyperplasia lesions showed contrast uptake: in 64% of the lesions, uptake was equal to parenchyma; 25%, greater than the parenchyma; and 11%, less than the parenchyma. On iron oxide-enhanced T2-weighted images, all focal nodular hyperplasia lesions showed uptake of the contrast agent, but contrast uptake in the lesions was less than in the surrounding parenchyma. Dynamic gadolinium chelate-enhanced MR imaging showed early and vigorous enhancement of focal nodular hyperplasia lesions with rapid washout in 88%. Atypical imaging features of the lesions included hyperintensity on T1-weighted images, necrosis and hemorrhage, and inhomogeneous or only minimal contrast uptake. CONCLUSION: For patients in whom the diagnosis of focal nodular hyperplasia cannot be established on unenhanced or gadolinium-enhanced MR imaging, homogeneous uptake of liver-specific contrast agent with better delineation of central scar may help to make a confident diagnosis of focal nodular hyperplasia.     

Dual contrast enhanced magnetic resonance imaging of the liver with superparamagnetic iron oxide followed by gadolinium for lesion detection and characterization

AIM: Iron oxide contrast agents are useful for lesion detection, and extracellular gadolinium chelates are advocated for lesion characterization. We undertook a study to determine if dual contrast enhanced liver imaging with sequential use of ferumoxides particles and gadolinium (Gd)-DTPA can be performed in the same imaging protocol. MATERIALS AND METHODS: Sixteen patients underwent dual contrast magnetic resonance imaging (MRI) of the liver for evaluation of known/suspected focal lesions which included, metastases (n = 5), hepatocellular carcinoma (HCC;n = 3), cholangiocharcinoma(n = 1) and focal nodular hyperplasia (FNH;n = 3). Pre- and post-iron oxide T1-weighted gradient recalled echo (GRE) and T2-weighted fast spin echo (FSE) sequences were obtained, followed by post-Gd-DTPA (0.1 mmol/kg) multi-phase dynamic T1-weighted out-of-phase GRE imaging. Images were analysed in a blinded fashion by three experts using a three-point scoring system for lesion conspicuity on pre- and post-iron oxide T1 images as well as for reader's confidence in characterizing liver lesions on post Gd-DTPA T1 images. RESULTS: No statistically significant difference in lesion conspicuity was observed on pre- and post-iron oxide T1-GRE images in this small study cohort. The presence of iron oxide did not appreciably diminish image quality of post-gadolinium sequences and did not prevent characterization of liver lesions. CONCLUSION: Our results suggest that characterization of focal liver lesion with Gd-enhanced liver MRI is still possible following iron oxide enhanced imaging.Kubaska, S.et al. (2001). Clinical Radiology, 56, 410-415 Copyright 2001 The Royal College of Radiology.     

Comparison of iron oxide labeling properties of hematopoietic progenitor cells from umbilical cord blood and from peripheral blood for subsequent in vivo tracking in a xenotransplant mouse model XXX

RATIONALE AND OBJECTIVES: To compare and optimize ferumoxides labeling of human hematopoietic progenitor cells from umbilical cord blood and from peripheral blood for subsequent in vivo tracking with a clinical 1.5 T MR scanner. MATERIALS AND METHODS: Human hematopoietic progenitor cells, derived from umbilical cord blood or peripheral blood, were labeled with Ferumoxides by simple incubation or lipofection. Cellular iron uptake was quantified with spectrometry. Then, 3 x 10(7)-labeled cells were injected into the tail vein of 12 female nude Balb/c mice. The mice underwent magnetic resonance imaging before and 24 hours after injection. Precontrast and postcontrast signal intensities of liver, spleen, and bone marrow were measured and tested for significant differences with the t-test. Immunostains served as a histopathologic standard of reference. RESULTS: After labeling by simple incubation, only umbilical cord blood cells, but not peripheral blood cells, showed a significant iron uptake and could be tracked in vivo with magnetic resonance imaging. Using lipofection, both cell types could be tracked in vivo. A significant decline in signal intensity was observed in liver, spleen, and bone marrow at 24 hours after injection of efficiently labeled ferumoxides cells (P < .05). Histopathology proved the distribution of iron oxide-labeled cells to these organs. CONCLUSION: Hematopoietic progenitor cells from umbilical cord blood can be labeled by simple incubation with an Food and Drug Administration-approved magnetic resonance contrast agent with sufficient efficiency to provide an in vivo cell tracking at 1.5 T. Progenitor cells from peripheral blood need to be labeled with adjunctive transfection techniques to be depicted in vivo at 1.5 T.     

Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors

BACKGROUND AND PURPOSE: Ultrasmall superparamagnetic iron oxide particles result in shortening of T1 and T2 relaxation time constants and can be used as MR contrast agents. We tested four hypotheses by evaluating MR images of intracranial tumors after infusion of two iron oxide agents in comparison with a gadolinium chelate: 1) Ferumoxtran in contrast to ferumoxides can be used as an intravenous MR contrast agent in intracranial tumors; 2) ferumoxtran enhancement, albeit delayed, is similar to gadolinium enhancement; 3) ferumoxtran-enhanced MR images in contrast to gadolinium-enhanced MR images may be compared with histologic specimens showing the cellular location of iron oxide particles; 4) ferumoxtran can serve as a model for viral vector delivery. METHODS: In 20 patients, ferumoxides and ferumoxtran were intravenously administered at recommended clinical doses. MR imaging was performed 30 minutes and 4 hours after ferumoxides infusion (n = 3), whereas ferumoxtran-enhanced MR imaging (n = 17) was performed 6 and 24 hours after infusion in the first five patients and 24 hours after infusion in the remaining 12. MR sequences were spin-echo (SE) T1-weighted, fast SE T2- and proton density-weighted, gradient-recalled-echo T2*-weighted, and, in four cases, echo-planar T2-weighted sequences. Representative regions of interest were chosen on pre- and postcontrast images to compare each sequence and signal intensity. RESULTS: Despite some degree of gadolinium enhancement in all tumors, no significant T1 or T2 signal intensity changes were seen after ferumoxides administration at either examination time. Fifteen of 17 patients given ferumoxtrans had T1 and/or T2 shortening consistent with iron penetration into tumor. Histologic examination revealed minimal iron staining of the tumor with strong staining at the periphery of the tumors. CONCLUSION: 1) Ferumoxtran can be used as an intravenous MR contrast agent in intracranial tumors, mostly malignant tumors. 2) Enhancement with ferumoxtran is comparable to but more variable than that with the gadolinium chelate. 3) Histologic examination showed a distribution of ferumoxtran particles similar to that on MR images, but at histology the cellular uptake was primarily by parenchymal cells at the tumor margin. 4) Ferumoxtran may be used as a model for viral vector delivery in malignant brain tumors.     

PET/MRI dual-modality tumor imaging using arginine-glycine-aspartic (RGD)-conjugated radiolabeled iron oxide nanoparticles

The purpose of this study was to develop a bifunctional iron oxide (IO) nanoparticle probe for PET and MRI scans of tumor integrin alphavbeta3 expression. METHODS: Polyaspartic acid (PASP)-coated IO (PASP-IO) nanoparticles were synthesized using a coprecipitation method, and particle size and magnetic properties were measured. A phantom study was used to assess the efficacy of PASP-IO as a T2-weighted MRI contrast agent. PASP-IO nanoparticles with surface amino groups were coupled to cyclic arginine-glycine-aspartic (RGD) peptides for integrin alphavbeta3 targeting and macrocyclic 1,4,7,10-tetraazacyclododecane-N,N',N',N',-tetraacetic acid (DOTA) chelators for PET after labeling with 64Cu. IO nanoparticle conjugates were further tested in vitro and in vivo to determine receptor targeting efficacy and feasibility for dual PET/MRI. RESULTS: PASP-IO nanoparticles made by single-step reaction have a core size of 5 nm with a hydrodynamic diameter of 45 +/- 10 nm. The saturation magnetization of PASP-IO nanoparticles is about 117 emu/g of iron, and the measured r2 and r2* are 105.5 and 165.5 (s.mM)(-1), respectively. A displacement competitive binding assay indicates that DOTA-IO-RGD conjugates bound specifically to integrin alphavbeta3 in vitro. Both small-animal PET and T2-weighted MRI show integrin-specific delivery of conjugated RGD-PASP-IO nanoparticles and prominent reticuloendothelial system uptake. CONCLUSION: We have successfully developed an IO-based nanoprobe for simultaneous dual PET and MRI of tumor integrin expression. The success of this bifunctional imaging approach may allow for earlier tumor detection with a high degree of accuracy and provide further insight into the molecular mechanisms of cancer.     

Gadolinium‐labeled quantum dots for molecular magnetic resonance imaging: R1 versus R2 mapping

Quantum dots labeled with paramagnetic gadolinium chelates can be applied as contrast agent for preclinical molecular MRI combined with fluorescence microscopy. Besides increasing the longitudinal relaxation rate, gadolinium‐labeled quantum dots may increase the transverse relaxation rate, which might be related to their magnetic properties. Furthermore, molecular MRI experiments are primarily conducted at high magnetic fields, where longitudinal relaxation rate becomes less effective, and the use of transverse relaxation rate as a source of contrast may become attractive. Consequently, the optimal method of contrast enhancement using gadolinium‐labeled quantum dots is a priori unknown. The objective of this study was to compare longitudinal relaxation rate– and transverse relaxation rate–based contrast enhancement, proton visibility, and changes thereof induced by gadolinium‐labeled quantum dots targeted to the angiogenic vasculature of murine tumors, using in vivo longitudinal and transverse relaxation rate mapping. At a field strength of 7 T, longitudinal relaxation rate–based measures were superior to transverse relaxation rate–based measures in detecting both the level and spatial extent of contrast agent–induced relaxation rate changes. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Characteristics of a new MRI contrast agent prepared from polypropyleneimine dendrimers, generation 2

RATIONALE AND OBJECTIVES: Dendrimer-based magnetic resonance imaging (MRI) contrast agents offer many advantages including high levels of amplification. The objective of this research was to test the adequacy and viability of a new family of dendrimers for use as MRI contrast agents in vitro and in vivo. METHODS: Dendrimers based on 1,4-diaminobutane core polypropyleneimine (PPI) generation 2 and ammonia core polyamidoamine dendrimers had the free surface amines conjugated to a diethylenetriaminepentaacetic acid derivative followed by complex formation with gadolinium. Relaxivity measurements were made on an IBM Field Cycling Relaxometer. Biodistribution and pharmacokinetic studies were examined with the radiotracer 153Gd in rats and a counting window of 95 to 105 keV. MRI images were conducted at 4.7 T. RESULTS: The relaxivity of the PPI agent exceeded that of the corresponding generation polyamidoamine (PAMAM) agent. Uptake occurred in the liver, spleen, and kidney. Pharmacokinetic studies showed a biexponential decay with excretion half-lives of 3 hours and 33.6 days respectively. The agent increased the contrast enhancement, 1 hour after injection, of T1-weighted images by 52%. CONCLUSIONS: This PPI agent resulted in significant contrast signal enhancement. This family of agent may also provide a valuable contrast agent backbone.     

Cervical lymph node metastases: MR imaging of gadofluorine M and monocrystalline iron oxide nanoparticle-47 in a rabbit model of head and neck cancer

PURPOSE: To prospectively compare the accuracy of gadofluorine M with that of monocrystalline iron oxide nanoparticle (MION)-47 for the depiction of cervical lymph node metastases at magnetic resonance (MR) imaging in a rabbit model of head and neck cancer by using histologic analysis as the reference standard. MATERIALS AND METHODS: Experiments were approved by the animal care committee. VX2 carcinomas were implanted in both ears of 11 rabbits 4 weeks before MR imaging. T2-weighted, T2*-weighted, and T1-weighted MR images were acquired, and sequential T1-weighted MR imaging was performed immediately and 30 minutes after administration of gadofluorine M (0.05 mmol gadolinium per kilogram body weight). T2-weighted and T2*-weighted MR imaging were performed 24 hours after administration of MION-47 (2.6 mg iron per kilogram body weight). Gadofluorine M- and MION-47-enhanced MR imaging were performed separately and independently by two radiologists who had no knowledge of histopathologic results, and the presence of metastases in lymph nodes was evaluated. A receiver operating characteristic analysis was conducted to compare the diagnostic value of gadofluorine M- and MION-47-enhanced MR imaging. RESULTS: Metastases were confirmed in 20 of 77 lymph nodes at histopathologic analysis. The area under the curve was significantly greater for gadofluorine M-enhanced MR imaging (0.997 and 0.981 for readers 1 and 2, respectively) than for MION-47-enhanced MR imaging (0.889 and 0.846 for readers 1 and 2, respectively). For gadofluorine M-enhanced MR imaging, sensitivity was 100% for both readers and specificity was 89.5% for reader 1 and 87.7% for reader 2. For MION-47-enhanced MR imaging, sensitivity was 80.0% for both readers and specificity was 75.4% for reader 1 and 71.9% for reader 2. CONCLUSION: Gadofluorine M-enhanced MR imaging has higher accuracy for depicting lymph node metastases than does MION-47-enhanced MR imaging.     

Fat-suppressed three-dimensional dual echo Dixon technique for contrast agent enhanced MRI

PURPOSE: To develop a fast T1-weighted, fat-suppressed three-dimensional dual echo Dixon technique and to demonstrate its use in contrast agent enhanced MRI. MATERIALS AND METHODS: A product fast three-dimensional gradient echo pulse sequence was modified to acquire dual echoes after each RF excitation with water and fat signals in-phase (IP) and opposed-phase (OP), respectively. An on-line reconstruction algorithm was implemented to automatically generate separate water and fat images. The signal to noise ratio (SNR) of the new technique was compared to that of the product technique in phantom. In vivo abdomen and breast images of cancer patients were acquired at 1.5 Tesla using both techniques before and after intravenous administration of gadolinium contrast agent. RESULTS: In phantom, the new technique yields a close to the theoretically predicted 41% increase in SNR in comparison to the product technique without fat suppression (FS). In vivo images of the new technique show noticeably improved FS and image quality in comparison to the images acquired of the same patients using the product technique with FS. CONCLUSION: The three-dimensional dual echo Dixon technique provides excellent image quality and can be used for T1-weighted, fat-suppressed imaging with contrast agent injection.     

Targeted nanoparticles for quantitative imaging of sparse molecular epitopes with MRI.

Before molecular imaging with MRI can be applied clinically, certain problems, such as the potential sparseness of molecular epitopes on targeted cell surfaces, and the relative weakness of conventional targeted MR contrast agents, must be overcome. Accordingly, the conditions for diagnostic conspicuity that apply to any paramagnetic MRI contrast agent with known intrinsic relaxivity were examined in this study. A highly potent paramagnetic liquid perfluorocarbon nanoparticle contrast agent ( approximately 250 nm diameter, >90,000 Gd3+/particle) was imaged at 1.5 T and used to successfully predict a range of sparse concentrations in experimental phantoms with the use of standard MR signal models. Additionally, we cultured and targeted the smooth muscle cell (SMC) monolayers that express "tissue factor," a glycoprotein of crucial significance to hemostasis and response to vascular injury, by conjugating an anti-tissue factor antibody fragment to the nanoparticles to effect specific binding. Quantification of the signal from cell monolayers imaged at 1.5 T demonstrated, as predicted via modeling, that only picomolar concentrations of paramagnetic perfluorocarbon nanoparticles were required for the detection and quantification of tissue factor at clinical field strengths. Thus, for targeted paramagnetic agents carrying high payloads of gadolinium, it is possible to quantify molecular epitopes present in picomolar concentrations in single cells with routine MRI.     

Contrast agents for MR imaging of the liver

A variety of different categories of contrast agents, and within each category a number of individual agents, are currently available for clinical use in magnetic resonance (MR) imaging of the liver. In this review, the use of nonspecific extracellular gadolinium chelates, reticuloendothelial system-specific iron oxide particulate agents, hepatocyte-selective agents, and combined perfusion and hepatocyte-selective agents are described. Most clinical experience is with nonspecific extracellular gadolinium chelates. The relatively low cost, safety, good patient tolerance, and ability to help detect and characterize a wide range of liver diseases have rendered gadolinium chelates as commonly used agents. Reticuloendothelial system-specific agents improve lesion detection by decreasing the signal intensity of background liver on T2-weighted MR images, which increases the conspicuity of focal hepatic lesions with negligible reticuloendothelial cells (eg, metastases). Hepatocyte-selective agents increase the signal intensity of background liver on T1-weighted images, which increases the conspicuity of focal lesions that do not contain hepatocytes (eg, metastases). The clinical application of the different categories of contrast agents, techniques for their administration, sequences to be used, and appearances of common entities on contrast agent-enhanced studies are described.     

Kontrastmittel in der MRT

The use of intravenous contrast agents in magnetic resonance imaging (MRI) has become well established clinical practice. Contrast agents provide additional information in many applications. Gadolinium chelates constitute the largest group of MR contrast agents and are considered to be safe. Different groups of contrast agents are established for clinical application: low concentrated gadolinium chelates, high concentrated gadolinium chelates, superparamagnetic iron oxide particles and hepatobiliary contrast agents. The review discusses the clinical applications and the safety issues involved with administration of intravenous contrast agents in MR imaging. Several approaches of intravascular or blood pool agents are also presented.