MR tracking of magnetically labeled mesenchymal stem cells in rats with liver fibrosis

Purpose

In vivo magnetic resonance (MR) tracking of magnetically labeled bone marrow mesenchymal stem cells (BMSCs) administered via the mesenteric vein to rats with liver fibrosis.

Materials and Methods

Rat BMSCs were labeled with superparamagnetic iron oxide (SPIO) and the characteristics of the BMSCs after labeling were investigated. Eighteen rats with CCL4-induced liver fibrosis were randomized to three groups to receive SPIO-labeled BMSCs (BMSC-labeled group), cell-free SPIO (SPIO group), or unlabeled BMSCs (control group). MR imaging of the liver was performed at different time points, and signal-to-noise ratio (SNR) of the liver was measured. In vivo distribution of delivered BMSCs was assessed by histological analysis.

Results

Labeling of BMSCs with SPIO did not significantly alter cell viability and proliferation activity. In BMSC-labeled group, the liver SNR immediately decreased from 8.56±0.26 to 3.53±0.41 at 1 h post injection and remained at a significantly lower level till 12 days (P<.05 versus the level before). By contrast, the liver SNR of the SPIO group almost recovered to the preinjection level (P=.125) at 3 days after a transient decrease. In control group, the liver SNR demonstrated no significant difference at the tested time points. Additionally, Prussian blue-positive cells were mainly distributed in the liver parenchyma, especially in injured areas.

Conclusion

The magnetically labeled BMSCs infused through the mesenteric vein can be detected in the fibrotic liver of rats using in vivo MR imaging up to 12 days after injection.     

Are hepatic and muscle T2 values different at 0.5 and 1.5 Tesla?

In an effort to determine whether T2 values of liver and muscle change with increasing field strength, 144 abdominal MR examinations were retrospectively evaluated. These patients were evaluated with a dual echo T2-weighted spin-echo sequence. Eighty-two of the examinations were performed at 0.5 Tesla and 72 at 1.5 Tesla (T). Eleven of the patients were evaluated with both MR systems with the same sequences. T2 values were also obtained from a Fe NH4(SO4)2 12H2O phantom. The T2 values of liver decreased from 57.8 +/- 11.3 at 0.5 T to 43.7 +/- 8.3 at 1.5 T. The T2 values of muscle decreased from 44.2 +/- 9 at 0.5 T to 35.4 +/- 7.2 at 1.5 T. Patients who were examined on both systems also demonstrated a decrease in both liver and muscle T2 values. For concentrations in the range of hepatic T2's, the phantom demonstrated a decrease in T2 values from 0.5 to 1.5 T ranging from 20.3 to 23.4%. All the T2 changes were statistically significant (p less than .05). The findings suggest that T2 values may depend on field strength, or may vary due to other hardware-related differences.     

A comparison of T2*-weighted magnitude and phase imaging for measuring the arterial input function in the rat aorta following intravenous injection of gadolinium contrast agent

The arterial input function (AIF) is important for quantitative MR imaging perfusion experiments employing Gd contrast agents. This study compared the accuracy of T(2)*-weighted magnitude and phase imaging for noninvasive measurement of the AIF in the rat aorta. Twenty-eight in vivo experiments were performed involving simultaneous arterial blood sampling and MR imaging following Gd injection. In vitro experiments were also performed to confirm the in vivo results. At 1.89 T and TE=3 ms, the relationship between changes in 1/T(2)* in blood (estimated from MR signal magnitude) and Gd concentration ([Gd]) was measured to be approximately 19 s(-1) mM(-1), while that between phase and [Gd] was approximately 0.19 rad mM(-1). Both of these values are consistent with previously published results. The in vivo phase data had approximately half as much scatter with respect to [Gd] than the in vivo magnitude data (r(2)=.34 vs. r(2)=.17, respectively). This is likely due to the fact that the estimated change in 1/T(2)* is more sensitive than the phase to a variety of factors such as partial volume effects and T(1) weighting. Therefore, this study indicates that phase imaging may be a preferred method for measuring the AIF in the rat aorta compared to T(2)*-weighted magnitude imaging.     

Formation of multifunctional Fe_3O_4/Au composite nanoparticles for dual-mode MR/CT imaging applications

Recent advances with iron oxide/gold(Fe3O4/Au) composite nanoparticles(CNPs) in dual-modality magnetic resonance(MR) and computed tomography(CT) imaging applications are reviewed. The synthesis and assembly of "dumbbelllike" and "core/shell" Fe3O4/Au CNPs is introduced. Potential applications of some developed Fe3O4/Au CNPs as contrast agents for dual-mode MR/CT imaging applications are described in detail.     

Structure of iron phosphate glasses modified by alkali and alkaline earth additions: neutron and x-ray diffraction studies

The structure of iron phosphate glasses modified by additions of K(2)O and BaO, with nominal molar compositions [(1 - x)(0.6P(2)O(5)-0.4Fe(2)O(3))]xMe(y)O, where x = 0-0.4 in increments of 0.1; Me=K or Ba; and y = 1 or 2, has been investigated using neutron diffraction and x-ray diffraction techniques. Fitted coordination numbers for P-O and Fe-O showed a notable change in the P-O(NBO) and P-O(BO) contributions at greater than 20 mol% modifier addition, with barium producing a markedly larger increase in P-O(NBO) contribution than potassium. Fitting of T(N)(r) and T(X)(r) provided average n(BaO) = 9 and n(KO) = 6. Iron occurs in a range of coordination sites in these glasses: ([6])Fe(2+), ([4])Fe(3+), ([5])Fe(3+) and ([6])Fe(3+). The partitioning between these sites gives average n(FeO) = 5.2-5.8, with barium-doped glasses exhibiting higher average n(FeO) than potassium-doped glasses. The stronger depolymerizing effect of Ba(2+) than K(+) on the phosphate network, coupled with its greater ionic charge and higher Me-O, Fe-O and O···O coordination numbers, explain previously observed divergences in physical properties between the barium-doped and the potassium-doped glasses.     

Giant room-temperature magnetoresistance in polycrystalline Zn(0.41)Fe(2.59)O4 with alpha-Fe2O3 grain boundaries

A tunneling-type magnetoresistance (MR) as large as 158% is observed at T = 300 K in a polycrystalline Zn0.41Fe2.59O4 sample, in which the Zn0.41Fe2.59O4 grains are separated by insulating alpha-Fe2O3 boundaries. The huge room-temperature MR is attributed to the high spin polarization of Zn(0.41)Fe(2.59)O4 grains and antiferromagnetic correlations between magnetic domains on both sides of the insulating alpha-Fe2O3 boundary. The MR exhibits strong temperature dependence below 100 K and its magnitude is enhanced to reach 1280% at 4.2 K, which may arise from the Coulomb blockade effect.     

Artifacts caused by transcranial magnetic stimulation coils and EEG electrodes in T(2)*-weighted echo-planar imaging

We investigated the effects of transcranial magnetic stimulation (TMS) coils and electroencephalographic (EEG) electrodes on T(2)*-weighted echo-planar images (EPI) at 2.0 T (gradient-echo EPI, mean TE = 53 ms, 2x2x4 mm(3)). In comparison with anatomic gradient-echo images (3D FLASH, TE = 4 ms, 1x1x1 mm(3)), T(2)*-weighted EPI acquisitions of a water-filled spherical phantom revealed severe signal losses and geometric distortions in the vicinity of TMS coils. Even remote effects were observed for image orientations perpendicular to the coil plane. EEG electrodes and the fixation gel caused milder localized distortions. In humans, complications were avoided by the large distance between the TMS coil and the cortical surface and when using an EPI orientation parallel to the plane of the coil. It is concluded that T(2)*-weighted EPI studies of human brain function may be performed without distortions caused by TMS coils and EEG electrodes.     

Comparison of multi-echo spiral and echo planar imaging in functional MRI

Multi-echo spiral and echo-planar (EPI) imaging sequences were compared in functional imaging experiments at 3 Tesla. Both sequence types allow calculation of the effective transversal relaxation time T(2)* and the initial signal intensity I(0). These parameters can be used in evaluation of the functional signal with respect to inflow effects and other vascular sources. Prior to functional magnetic resonance imaging (fMRI) experiments T(2)* measurements in the human brain were performed with single- and multi-echo FLASH (fast low angle shot) and compared with EPI und spiral imaging sequences. These experiments resulted in T(2)* values ranging from 42.9 to 53.8 ms in a ROI including white and gray matter and CSF in a prefrontal brain region, and allowed validation of the quantitative results of the fast single-shot techniques. In functional experiments with motor stimulation mean absolute T(2)* increases during stimulation of 1.1 +/- 0.6 ms and 1.4 +/- 0.9 ms were found with multi-echo EPI and spiral imaging, respectively, averaged over the activated pixels. In addition, absolute T(2)* values and the size of activated areas obtained with both sequences are comparable. In these investigations spiral imaging allowed higher spatial resolution due to more efficient use of available gradient performance.     

MR imaging of the her2/neu and 9.2.27 tumor antigens using immunospecific contrast agents

Molecular imaging of tumor antigens using immunospecific magnetic resonance (MR) contrast agents is a rapidly evolving field, which can potentially aid in early disease detection, monitoring of treatment efficacy, and drug development. In this study, we designed, synthetized, and tested in vitro two novel monocrystalline iron oxide nanoparticles (MION) conjugated to antibodies against the her2/neu tyrosine kinase receptor and the 9.2.27 proteoglycane sulfate. MION was synthetized by coprecipitation of iron II and iron III salts in 12-kD dextran solution; antibody coupling was performed by reductive amination. The relaxivity of the conjugates was 24.1-29.1 mM(-1) s(-1), with 1.8 to 2.1 antibody molecules per nanoparticle. A panel of cultured melanoma and mammary cell lines was used for testing. The cells were incubated with the particles at 16-32 microg Fe/ml in culture medium for 3 h at 37 degrees C, and investigated with immune fluorescence, transmission electron microscopy (TEM), MRI of cell suspensions in gelatine, and spectrophotometric iron determination. All receptor-positive cell lines, but not the controls, showed receptor-specific immune fluorescence, and strong changes in T(2) signal intensity at 1.5 T. The changes in 1/T(2) were between 1.5 and 4.6 s(-1) and correlated with the amount of cell-bound iron (R = 0.92). The relaxivity of cell-bound MION increased to 55.9 +/- 10.4 mM(-1) s(-1). TEM showed anti-9.2.27 conjugates binding to the plasma membrane, while the anti-her2/neu conjugates underwent receptor-mediated endocytosis. In conclusion, we obtained receptor-specific T(2) MR contrast with novel covalently bound, multivalent MION conjugates with anti-9.2.27 and anti-her2/neu to image tumor surface antigens. This concept can potentially be expanded to a large number of targets and to in vivo applications.     

Nuclear magnetic resonance study of iron overload in liver tissue

Whole-tissue and homogenized samples of human liver were studied in a NMR spectrometer, T1 and T2 relaxation times were measured as a function of added inorganic or organic iron. When inorganic iron (Fe+3) was added, pronounced T1 and T2 shortening was noted. However, when organic iron, in the form of ferritin, was added, the amount of T1 and T2 relaxation enhancement was much reduced for the same amount of added iron. The in vitro ferritin results model the situation found in clinical studies of hemochromatosis. Only in cases of severe iron overload were significant decreases in relaxation times observed. The T2 relaxation time was the more reliable indicator of excessive levels of iron in the liver. The large range of T1 and T2 values encountered in normal volunteers precludes the use of MR to quantitatively measure iron levels in the liver. The T1 and T2 relaxation times measured at intervals for one individual tend to fluctuate as well, making the use of MR to follow the course of treatment of iron overload disorders unreliable.