Effect Of Superparamagnetic Iron Oxide Research Articles

Superparamagnetic Iron Oxide-Erastin-Polyethylene Glycol Nanotherapeutic Platform: A Ferroptosis-Based Approach for the Integrated Diagnosis and Treatment of Nasopharyngeal Cancer.

Erastin can induce ferroptosis in tumor cells as an effective small molecule inhibitor. However, its application is hampered by a lack of water solubility. This study investigated the effects of superparamagnetic iron oxide (SPIO)-erastin-polyethylene glycol (PEG) nanoparticles prepared by loading SPIO-PEG nanoparticles with erastin on ferroptosis. SPIO-erastin-PEG nanoparticles exhibited square and spherical shapes with good dispersibility. The zeta potential and hydrodynamic size of SPIO-erastin-PEG were measured as (-37.68 ± 2.706) mV and (45.75 ± 18.88) nm, respectively. On T2-weighted imaging, the nanosystem showed significant contrast enhancement compared to no-enhancement magnetic resonance imaging (MRI). SPIO-erastin-PEG induced ferroptosis by increasing reactive oxygen species and iron content and promoting the accumulation of lipid peroxides and the degradation of glutathione peroxidase 4. Pharmacokinetic experiments revealed a half-life of 1.25 ± 0.05 h for the SPIO-erastin-PEG solution in circulation. Moreover, significant antitumorigenic effects of SPIO-erastin-PEG have been demonstrated in 5-8F cells and mouse-bearing tumors. These results indicated that the synthesized SPIO-erastin-PEG nanoplatform could induce ferroptosis effects in vitro and in vivo while exhibiting favorable physical characteristics. This approach may provide a new strategy for theranostic nanoplatform for nasopharyngeal cancer.

The effect of iron oxide nanoparticles on Bacillus subtilis biofilm, growth and viability

Abstract Bacillus subtilis is one of the key microorganisms for the industrial production of many value added products. The fermentation of this bacterium is associated with biofilm formation that results in major process and operational issues. The study of the effect of magnetic nanoparticles on the bacterial cells can immensely contribute to designing intensified bioprocess methods Present study was aimed at understanding the effect of superparamagnetic iron oxide (naked IONs) and 3-aminopropyltriethoxy silane coated IONs (IONs@APTES) on biofilm formation, growth and viability of Bacillus subtilis. Both IONs were successfully prepared and characterised by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction patterns (XRD) and vibrating sample magnetometry (VSM). IONs@APTES at 100 μg/mL were found to significantly reduce the total biofilm biomass without affecting the cell viability compared with the behavior of naked IONS, which significantly affected the viability of B. subtilis at high concentrations without any significant redution in biofilm biomass. This suggests an active role of IONs@APTES in eliminating the biofilm formation as compared to the naked IONs. This work suggests the possibility of using IONs@APTES coated bacteria for a range of applications for future industrial fermentation with Bacillus subtilis .

Effect of superparamagnetic iron oxide on differentiation of rat bone marrow stem cells into chondrocytes in vitro

To observe the effect of superparamagnetic iron oxide (SPIO) on the differentiation of rat bone marrow stem cells (BMSCs) into chondrocytes in vitro and explore the possible mechanism. CCK8 assay was performed to examine the cytotoxicity of SPIO (1 and 5 µg/mL) on cultured SD rat BMSCs. Prussian blue staining and fluorescence excitation assay were used to assess the binding of the SPIO to BMSCs after the cells had been cultured in chondrocytes-induced medium in the presence of SPIO (1 and 5 µg/mL) for 9 days. The mRNA levels of COL2 α2, aggrecan and MMP13 in the cell culture were examined using Q-PCR, and the chondrogenic differentiation of the BMSCs was analyzed using alcian blue staining and immunofluorescence staining for COL2 α2. The protein levels of COL2 α2, aggrecan, MMP13, Ihh and PTHrP in the cells were examined using Western blotting. CCK8 assay showed no significant toxicity of SPIO on BMSCs. Compared with the control cells, the cells cultured in the presence of SPIO showed increased expressions of COL2 α2 and aggrecan and decreased expression of MMP13 at both mRNA and protein levels with also significantly increased expressions of Ihh and PTHrP proteins. SPIO can promote the differentiation of rat BMSCs into chondrocytes and up-regulate the Ihh/PTHrP signal pathway, suggesting the potential of SPIO as a new therapeutic agent for chondrocyte-related diseases.

MP11-19 MAGNETIC RESONANCE VISIBILITY OF IRON LABELED MESENCHYMAL STEM CELLS FOR ENDOSCOPIC INJECTION INTO THE PORCINE URETHRAL SPHINCTER

You have accessJournal of UrologyImaging/Radiology: Uroradiology II1 Apr 2015MP11-19 MAGNETIC RESONANCE VISIBILITY OF IRON LABELED MESENCHYMAL STEM CELLS FOR ENDOSCOPIC INJECTION INTO THE PORCINE URETHRAL SPHINCTER Susanne Will, Karl-Dietrich Sievert, Martin Vaegler, Petros Martirosian, Frank Eibofner, Fritz Schick, Jörg Schmehl, Gerd Grözinger, Rüdiger Bantleon, Konstantin Nikolaou, and Ulrich Kramer Susanne WillSusanne Will More articles by this author , Karl-Dietrich SievertKarl-Dietrich Sievert More articles by this author , Martin VaeglerMartin Vaegler More articles by this author , Petros MartirosianPetros Martirosian More articles by this author , Frank EibofnerFrank Eibofner More articles by this author , Fritz SchickFritz Schick More articles by this author , Jörg SchmehlJörg Schmehl More articles by this author , Gerd GrözingerGerd Grözinger More articles by this author , Rüdiger BantleonRüdiger Bantleon More articles by this author , Konstantin NikolaouKonstantin Nikolaou More articles by this author , and Ulrich KramerUlrich Kramer More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.400AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To improve the muscles of the urethral sphincter, different aspects of cell-based treatments should be investigated. Local injection of therapeutic mesenchymal stem cells (MSC) has been proved as a promising approach for tissue regeneration. The aim of this study was to evaluate the effects of superparamagnetic iron oxide (SPIO) cell labeling on the visualization of therapeutic MSC and validate in vitro and in vivo using mini-pig animal models. After injection into the porcine urethral sphincter, the labeled cells were monitored up to six months using MRI. METHODS MSC were labeled with SPIO particles for analysis of migration and viability. Phantom MR measurements were performed in order to evaluate labeling effects. For short and long term studies, iron labeled MSCs were endoscopically injected into the porcine urethral sphincter and monitored on a 3T MRI scanner. The animals were examined three weeks, three and six months after MSC injection. High resolution anatomical images of the urethral sphincter were measured to detect SPIO particles using a fast-spin-echo sequence. A gradient echo sequence with multiple echo times was utilized to visually identify and verify locations of iron particles. The distribution of injected cells was then correlated with histological findings (see Figure). RESULTS Functional analysis of cell parameters after iron labeling showed no effects on proliferation and differentiation of the cells. The adherence increased with a higher iron dose, and the ability to migrate decreased presumably the effect of iron labeling. Measurements of the sphincter muscle in the mini-pig clearly demonstrated visible iron deposits inside the sphincter muscle. Additionally, iron depositions could be verified in all time periods after stem cell injection. The comparison of MRI and tissue sections illustrated preeminent correlation of location and dilatation of iron depots. CONCLUSIONS SPIO-labeled MSC injection into the porcine urethral sphincter and subsequent evaluation with highly resolved MR data acquisition allows sensitive tracking of MSC for several months without any biological effects. Against common knowledge iron deposits within the cells were detectable and correlated histologically even six months after injection. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e126-e127 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Susanne Will More articles by this author Karl-Dietrich Sievert More articles by this author Martin Vaegler More articles by this author Petros Martirosian More articles by this author Frank Eibofner More articles by this author Fritz Schick More articles by this author Jörg Schmehl More articles by this author Gerd Grözinger More articles by this author Rüdiger Bantleon More articles by this author Konstantin Nikolaou More articles by this author Ulrich Kramer More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The effect of superparamagnetic iron oxide with iRGD peptide on the labeling of pancreatic cancer cells in vitro: a preliminary study.

The iRGD peptide loaded with iron oxide nanoparticles for tumor targeting and tissue penetration was developed for targeted tumor therapy and ultrasensitive MR imaging. Binding of iRGD, a tumor homing peptide, is mediated by integrins, which are widely expressed on the surface of cells. Several types of small molecular drugs and nanoparticles can be transfected into cells with the help of iRGD peptide. Thus, we postulate that SPIO nanoparticles, which have good biocompatibility, can also be transfected into cells using iRGD. Despite the many kinds of cell labeling studies that have been performed with SPIO nanoparticles and RGD peptide or its analogues, only a few have applied SPIO nanoparticles with iRGD peptide in pancreatic cancer cells. This paper reports our preliminary findings regarding the effect of iRGD peptide (CRGDK/RGPD/EC) combined with SPIO on the labeling of pancreatic cancer cells. The results suggest that SPIO with iRGD peptide can enhance the positive labeling rate of cells and the uptake of SPIO. Optimal functionalization was achieved with the appropriate concentration or concentration range of SPIO and iRGD peptide. This study describes a simple and economical protocol to label panc-1 cells using SPIO in combination with iRGD peptide and may provide a useful method to improve the sensitivity of pancreatic cancer imaging.

In vitro labeling of endothelial progenitor cells isolated from peripheral blood with superparamagnetic iron oxide nanoparticles.

The transplantation of endothelial progenitor cells (EPCs) provides a novel method for the treatment of human tumors or vascular diseases. Magnetic resonance imaging (MRI) has proven to be effective in tracking transplanted stem cells by labeling the cells with superparamagnetic iron oxide (SPIO) nanoparticles. The SPIO has been used to label and track the EPCs; however, the effect of SPIO upon EPCs remains unclear on a cellular level. In the present study, EPCs were labeled with home-synthesized SPIO nanoparticles in vitro and the biological characteristics of the labeled EPCs were evaluated. The EPCs were isolated from the peripheral blood of New Zealand rabbits and cultured in fibronectin-coated culture flasks. The EPCs were labeled with home-synthesized SPIO nanoparticles at a final iron concentration of 20 μg/ml. Labeled EPCs were confirmed with transmission electron microscopy and Prussian blue staining. The quantity of iron/cell was detected by atomic absorption spectrometry. The membranous antigens of EPCs were detected by cytofluorimetric analysis. Cell viability and proliferative capability between the labeled and unlabeled EPCs were compared. The rabbit EPCs were effectively labeled and the labeling efficiency was approximately 95%. The SPIO nanoparticles were localized in the endosomal vesicles of the EPCs, which were confirmed by transmission electron microscopy. No significant differences were found in cell viability and proliferative capability between labeled and unlabeled EPCs (P>0.05). In conclusion, rabbit peripheral blood EPCs were effectively labeled by home-synthesized SPIO nanoparticles, without influencing their main biological characteristics.

Assessment of biological characteristics of mesenchymal stem cells labeled with superparamagnetic iron oxide particles in vitro

Mesenchymal stem cell (MSC) transplantation provides a novel strategy for the treatment of human disease. MR imaging (MRI) is able to track transplanted stem cells labeled with superparamagnetic iron oxide (SPIO) in vivo. However, the effect of SPIO upon labeled MSCs remains unclear on a cellular level. In this study, the biological characteristics of rat MSCs labeled with home-synthesized SPIO particles were evaluated. The MSCs were isolated from the bone marrow of 5 adult Sprague-Dawley rats and labeled with home-synthesized SPIO particles at a final iron concentration of 20 µg/ml. Labeled MSCs were confirmed with Prussian blue staining and transmission electron microscopy. The quantity of iron per cell was determined by atomic absorption spectrometry. Cell viability, proliferation, membranous antigen and multiple differentiation ability were compared between labeled and unlabeled MSCs. The rat MSCs were effectively labeled and the labeling efficiency was approximately 100%, as revealed by Prussian blue staining. The SPIO particles located in the endosomal vesicles of the MSCs were confirmed by transmission electron microscopy. No significant differences were observed in cell viability, proliferation, membranous antigen and multiple differentiation ability between the labeled and unlabeled MSCs (P>0.05). In conclusion, MSCs are able to be effectively labeled by home-synthesized SPIO particles without influencing their main biological characteristics.

Study on ASTC-a-1 cells labeled with superparamagnetic iron oxide and its magnetic resonance imaging

The aim of this preliminary study is to explore the feasibility of incorporating superparamagnetic iron oxide (SPIO) with poly-L-lysine (PLL) for labeling and magnetic resonance imaging (MRI) of human lung adenocarcinoma cells. Endorem (5-200 microg/mL) was incubated with ASTC-a-1 cells in the presence of PLL (1.5 microg/mL) for 0.5-24 h. The presence of SPIO in labeled cells was examined by Prussian blue stain. The effects of SPIO on cell proliferation, reactive oxygen species (ROS) generation and the mitochondria were also examined. In vitro MRI of SPIO-PLL-labeled cells was performed using a clinical 1.5 T MRI system. The labeling efficiency of >99% could be achieved after incubating for 0.5 h with 25 microg/mL of SPIO in the presence of PLL (1.5 microg/mL). Higher concentrations of SPIO (e.g. >50 microg/mL) could induce significant cell death, which might be mediated by changes in intracellular ROS level and mitochondrial membrane potential. In vitro MRI showed the decrease in MRI signal intensity on T(1)WI, T(2)WI and T(2)*WI sequences. In conclusion, MRI can trace SPIO-labeled cancer cells according to changes in T(1)WI, T(2)WI and T(2)*WI sequences. It should be noted that at higher concentrations, SPIO can cause cell damage.

HO-1 gene overexpression enhances the beneficial effects of superparamagnetic iron oxide labeled bone marrow stromal cells transplantation in swine hearts underwent ischemia/reperfusion: an MRI study

To determine the effect of intracoronary transfer of superparamagnetic iron oxide (SPIO) labeled heme oxygenase-1 (HO-1) overexpressed bone marrow stromal cells (BMSCs) in a porcine myocardial ischemia/reperfusion model. Cell apoptosis was assayed and supernatant cytokine concentrations were measured in BMSCs that underwent hypoxia/reoxygen in vitro. Female mini-swines that underwent 1 h LAD occlusion followed by 1 h reperfusion were randomly allocated to receive intracoronary saline (control), 1 x 10(7) SPIO-labeled BMSCs transfected with pcDNA3.1-Lacz plasmid (Lacz-BMSCs), pcDNA3.1-human HO-1 (HO-1-BMSCs), pcDNA3.1-hHO-1 pretreated with a HO inhibitor, tin protoporphyrin (SnPP, n = 10 each). MRI and postmortem histological analysis were made at 1 week or 3 months thereafter. Post hypoxia/reoxygen in vitro, apoptosis was significantly reduced, supernatant VEGF significantly increased while TNF-alpha and IL-6 significantly reduced in HO-1-BMSCs group compared with Lacz-BMSCs group (all p < 0.05). Myocardial expression of VEGF was significantly higher in HO-1-BMSCs than in Lacz-BMSCs group at 1 week post transplantation (all p < 0.05). Signal voids induced by the SPIO were detected in the peri-infarction region in all BMSC groups at 1 week but not at 3 months post transplantation and the extent of the hypointense signal was the highest in HO-1-BMSCs group, and histological analysis showed that signal voids represented cardiac macrophages that engulfed the SPIO-labeled BMSCs. Pretreatment with SnPP significantly attenuated the beneficial effects of HO-1-BMSCs. Transplantation of HO-1-overexpressed BMSCs significantly enhanced the beneficial effects of BMSCs on improving cardiac function in this model.

Effect of superparamagnetic iron oxide on tumor-to-liver contrast at T2*-weighted gradient-echo MRI: Comparison between 3.0T and 1.5T MR systems

To compare 3.0T and 1.5T MR systems in terms of the effect of superparamagnetic iron oxide (SPIO) on tumor-to-liver contrast in T2*-weighted gradient-echo MRI. SPIO-enhanced gradient-echo MR images of the liver with four different TEs (3, 5.3, 6.5, and 8.5 msec) were obtained by means of 1.5T and 3.0T systems. Quantitative analyses of relative signal intensities (SIs) and relative tumor contrast and qualitative analyses of image quality and lesion conspicuity of the liver were performed in 22 patients, 16 of whom had malignant liver tumors. With both 1.5T and 3.0T, at TE=8.4 msec, the relative SI of liver and relative tumor contrast were significantly (P<0.01) lower and higher, respectively, than that for any of the other TEs. There were no significant differences in the relative SI of the liver, relative tumor contrast, image quality, and tumor conspicuity for the same TE between the 1.5T and 3.0T systems. Our results showed that the effect of SPIO on tumor-to-liver contrast at T2*-weighted gradient-echo imaging was similar for the 1.5T and 3.0T systems, and that the 8.4-msec TE was optimal of the four TEs used in this study at 3.0T.

T1-weighted magnetic resonance imaging sequence appropriate for the evaluation of the longitudinal relaxation effect of superparamagnetic iron oxide: a phantom study.

The goal of this study was to determine a T1-weighted magnetic resonance (MR) imaging sequence appropriate for evaluating the longitudinal relaxation effect of superparamagnetic iron oxide (ferumoxides) in a phantom study. An agarose phantom that included various concentrations of ferumoxides (0 - 0.5 mmol/l in 0.05 mmol/l increments) was examined for six types of T1-weighted imaging sequences using a 1.5-T MR unit. Three-dimensional (3D) fast spoiled gradient-echo (SPGR) imaging with a short echo time showed a strong linear correlation between the concentration of ferumoxides and the enhancement ratio. Two-dimensional (2D) fast SPGR imaging showed a high signal-to-noise ratio of the phantom even at low ferumoxides concentrations. These results suggest that 3D fast SPGR imaging is an appropriate technique for the evaluation of the longitudinal relaxation effect of ferumoxides, and that 2D fast SPGR imaging can be useful for evaluating the longitudinal relaxation effect at lower ferumoxides concentrations.

Superparamagnetic iron oxide-enhanced magnetic resonance imaging of the liver in beagle dogs.

The role of superparamagnetic iron oxide as a tissue-specific contrast medium has been established in humans, especially for hepatic imaging. Superparamagnetic iron oxide particles exhibit a tissue-specific biodistribution to the reticuloendothelial system, where they predominantly shorten transverse T2 relaxation time. Most hepatic tumors lack Kupffer cells; therefore, the T2 of tumors remains virtually unchanged after administration of superparamagnetic iron oxide. The resulting loss of signal intensity from the liver, with unchanged tumor signal intensity, increases lesion-to-liver contrast. In this study, MR images were acquired with fast gradient echo recalled at steady state (FGRE) in five Beagle dogs before and after injection of superparamagnetic iron oxide. The effect of superparamagnetic iron oxide on signal intensity of the liver with time was assessed. A signal intensity decrease of 65.7+/-10.0% was detected at 20 minutes, and it continued to decrease until the last time point of MR scanning (200 minutes). The liver intensity of all dogs dropped to half its value after 20 minutes. The effect of motion was minimized by breath holding. Superparamagnetic iron oxide did not have any adverse effects on the dogs.

Effect of superparamagnetic iron oxide on bone marrow.

The goal of this study was to compare the effects of SPIO particles on the signal intensity of the bone marrow of the vertebra spine in patients with and without liver cirrhosis. Forty-eight patients with normal liver tissue and 56 patients with liver cirrhosis were examined before and after intravenous SPIO administration, using a 1.5-T system (Magnetom Vision, Siemens, Erlangen, Germany) with a semiflexible cp-array coil. Three different pulse sequences were applied: a T1-weighted gradient-echo sequence, a T2-weighted fast spin-echo sequence with spectral fat suppression and a T2*-weighted gradient-echo sequence. The signal-to-noise ratio (SNR) of the liver, vertebra bone and paraspinal muscle were obtained. The SNR value change in each patient group and the SNR value difference between the two groups were evaluated. For assessment of statistical significance, Student's t-test with a level of p < 0.05 was applied. No significant differences in the SNR values of the liver and bone marrow between the two groups could be seen with any of the three sequences precontrast. Using the T1-weighted gradient-echo sequence in the noncirrhotic liver group, pre- and postcontrast comparisons of the SNR values of the liver and bone marrow indicated a decrease of approximately -44.3% (p = 0.02) and increase of approximately 15.3% (p = 0.04), respectively. No significant change was seen in the cirrhotic liver group. With the T2-weighted fast spin-echo sequence, a significant decrease of the SNR value of the liver and the bone marrow in both groups was seen. With the T2*-weighted gradient-echo sequence, the signal intensity decrease of the normal liver tissue was approximately -65.6% (p = 0.00), in cirrhotic liver tissue the decrease was -29.9% (p = 0.02). The SNR values of the bone marrow showed a decrease of -27.8% (p = 0.04) in the noncirrhotic liver group, whereas in the cirrhotic liver group it was only -11.3% and statistically not significant. The effect of SPIO particles on the liver and bone marrow is significantly less in patients with liver cirrhosis.

Effects of superparamagnetic iron oxide on radio-frequency-induced temperature distribution: in vitro measurements in polyacrylamide phantoms and in vivo results in a rabbit liver model.

To determine whether contrast medium containing superparamagnetic iron oxide (SPIO) alters radio-frequency (RF)-related temperature distribution in acrylamide phantoms and in an in vivo model. In nine acrylamide phantoms with increasing SPIO content, RF was applied with simultaneous measurement of temperature profile along the probe track. Additionally, magnetic resonance imaging-guided RF ablation was performed in the liver of six rabbits after the intravenous administration of SPIO (0.05 mL per kilogram of body weight) 40 minutes prior to ablation (SPIO group) and in another six rabbits without prior SPIO administration (control group). Coagulation diameter was evaluated on the basis of postprocedural imaging and subsequent gross pathologic findings. Statistical analysis was performed with the Student t test. In the phantoms, progressive increases in iron content resulted in higher temperatures along the RF electrode track (P < .05). In the in vivo model, however, SPIO at physiologic concentrations did not significantly increase the diameter of coagulation on the basis of either postprocedural imaging or subsequent gross pathologic findings. Additionally, no significant differences were seen in other RF-related parameters including impedance, voltage, current, and grounding pad temperature. Administration of SPIO in conjunction with RF ablation of focal liver lesions is feasible and safe, but no significant difference in the extent of induced coagulation can be expected.

Evaluation of portal MR angiography using superparamagnetic iron oxide.

The purpose of our research was to determine the effects of superparamagnetic iron oxide on MR imaging of the portal venous system. Eight piglets were examined in deep anaesthesia and respiratory arrest using a time-of-flight magnetic resonance fast low angle shot, two-dimensional angiography sequence at 1.5T, MR angiograms were acquired precontrast and after intravenous administration of a cumulative dose of 10, 20 and 40 mumol/kg SHU 555A, a superparamagnetic iron oxide contrast agent for MR imaging with a particle size of 60 nm. For each dose, two subsequent sets of scans were obtained and reconstructed by a maximum-intensity-projection algorithm. Hepatic parenchymal and portal venous signal intensities were measured, and portal vein contrast calculated for each set of scans. All examinations were visually rated as to portal vein contrast and homogeneity by two blinded observers. Receiver operating characteristics of both observers were analyzed. The contrast agent reduced hepatic parenchymal signal in a dose-dependent way. After a cumulative dose of 10 mumol iron oxide, hepatic parenchymal signal intensity decreased to 63 +/- 6% (average of measurements at 4 and 14 minutes, mean +/- standard error of the mean), after 20 mumol to 24 +/- 3%, and after 40 mumol to 12 +/- 1% of control. Intravascular signal in the left main portal vein branch increased to 117 +/- 6%, 127 +/- 10%, and 133 +/- 9% of control, respectively. The contrast-to-noise ratio of the portal vein improved (521 +/- 90%, 891 +/- 178%, and 995 +/- 201% of control in the left portal vein main branch). Intravascular signal intensities increased slightly. The combined effect improved contrast of the portal vein stem and its branches. Receiver operating characteristics analysis documented dose-dependency of contrast medium effects on portal venous contrast and intravascular homogeneity. Visual rating also indicated a positive effect on portal venous contrast. The superparamagnetic iron oxide agent improved portal venous contrast with surrounding hepatic parenchyma in this normal animal model, and could potentially result in more accurate diagnosis of portal venous pathology.

Effects of spatial distribution on proton relaxation enhancement by particulate iron oxide.

The proton relaxation effect of superparamagnetic iron oxide (SPIO) particles under varying conditions of spatial distribution was investigated with use of phantoms. Agar phantoms containing various concentrations of SPIO or gadopentetate dimeglumine, with and without Sephadex beads, were studied. Phantoms with Sephadex had a heterogeneous spatial distribution of iron oxide, comparable to liver tissue in vivo. Relaxometry at 0.47 T showed decreased T2 relaxivity of SPIO in Sephadex phantoms compared with that in agar phantoms without Sephadex. On T2-weighted images obtained at 1.5 T, the signal intensity of Sephadex phantoms showed less SPIO relaxation effect than that of plain agar phantoms. Unlike SPIO, gadopentetate dimeglumine showed the same relaxivities and signal intensity in plain agar and Sephadex phantoms. The results show that the T2 relaxation effect of iron oxide depends on its spatial distribution. A heterogeneous spatial distribution, as in intact liver tissue, diminishes the T2 relaxivity of iron oxide particles.

Effects of Superparamagnetic Iron Oxide (AMI-25) on Liver and Spleen Imaging Using Spin-Echo and Fast Spin-Echo Magnetic Resonance Pulse Sequences

Effects of Superparamagnetic Iron Oxide (AMI-25) on Liver and Spleen Imaging Using Spin-Echo and Fast Spin-Echo Magnetic Resonance Pulse Sequences

MR lymphography with iron oxide particles: dose-response studies and pulse sequence optimization in rabbits.

Superparamagnetic iron oxide (SPIO) particles are a promising contrast agent for MR lymphography. The effect of SPIO on MR imaging of normal lymph nodes and the impact of the size of the dose have not yet been investigated in detail. Therefore, we performed dose-response and pulse sequence optimization studies. MR images of the iliac lymph nodes of 15 normal rabbits were obtained at 1.5 T with 12 different spin-echo (SE) and gradient-echo (GRE) sequences before and after SPIO administration. The contrast agent was injected into a femoral lymph vessel at five different doses (0.02-2.0 mumol Fe/animal). The dose that reduced signal intensity by half (ED50) was determined for each sequence, and images were evaluated qualitatively. Doses of 0.2 and 1.0 mumol Fe caused a complete signal loss throughout the lymph node. In this dose range, proton density-weighted SE sequences showed a profound signal loss (ED50, 0.132 mumol Fe), and lymph nodes were sharply demarcated. The GRE sequences (ED50, 0.027-0.070 mumol Fe) and the T2-weighted SE sequence (ED50, 0.014 mumol Fe) showed an even more pronounced signal loss but insufficient anatomic resolution. Underdosing (less than or equal to 0.1 mumol Fe) caused only a focal signal loss in the lymph nodes. Oversaturation (2.0 mumol Fe for SE sequences, greater than or equal to 1.0 mumol Fe for GRE sequences) led to image distortion and did not allow assessment of lymph node morphology. Our results show that optimal contrast enhancement of normal lymph nodes with SPIO can be achieved in the dose range of 0.2-1.0 mumol Fe on proton density-weighted SE sequences. Our results may serve as a basis for further development of noninvasive MR lymphography.

Cardiovascular MR imaging with iron oxide particles: utility of a superparamagnetic contrast agent and the role of diffusion in signal loss.

This study describes the effect of superparamagnetic iron oxide on myocardial signal intensity and defines the mechanism of action of this agent. Magnetic resonance images of the heart and relaxation data were obtained in 19 rats, and another three rats were used for measurements of contrast material concentration in the heart, with the contrast agent enriched with iron-59. A dose of 36 mumols of iron per kilogram induced homogeneous signal loss in the myocardium with a gated spin-echo sequence with a repetition time of 1,500 msec and an echo time of 20 msec. The reduction in signal intensity was the result of a combination of diffusion-dependent and diffusion-independent T2 shortening. The diffusion effect results from dephasing of spins moving across magnetic field gradients generated in the tissue by the contrast agent. The relative contribution of the diffusion-induced signal loss observed in vivo was larger than that predicted from the in vitro relaxation measurements. The reduced in vitro effect is likely the result of loss of a portion of the intramyocardial blood volume during sample preparation, as assessed with the Fe-59 measurements.