Hypervascular hepatocellular carcinoma in the cirrhotic liver: diffusion-weighted imaging versus superparamagnetic iron oxide-enhanced MRI

Purpose

The purpose of the study was to validate diffusion-weighted imaging (DWI) in the assessment of hypervascular hepatocellular carcinoma (HCC) compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the cirrhotic liver.

Material and Methods

Forty-six consecutive patients with 106 hypervascular focal lesions in the cirrhotic liver who underwent DWI using three b factors and gadopentetate dimeglumine-enhanced dynamic MRI followed by SPIO-enhanced MRI were enrolled. Two independent radiologists evaluated two separated image sets (SPIO set, dynamic MRI and SPIO-enhanced T2*-weighted images; DWI set, DWI and dynamic MRI) and assigned confidence levels for diagnosis of HCC using a five-point scale for each lesion. Area under the receiver operating characteristic curve (A_z) was calculated for each image set.

Results

The A_z value of the DWI set was larger than the SPIO set by both readers (reader 1, 0.936 vs. 0.900, P=.050; reader 2, 0.938 vs. 0.905, P=.110). For the sensitivity (reader 1, 93.1% vs. 86.2%, P=.146; reader 2, 95.4% vs. 88.5%, P=.070) and specificity (reader 1, 89.5% vs. 73.7%, P=.250; reader 2, 79.0% vs. 73.7%, P=1.000) of HCC diagnosis, DWI sets were superior to SPIO sets without statistically significant differences.

Conclusion

For assessment of hypervascular HCC, DWI in combination with dynamic MRI provides comparable or slightly better information compared with the combination of dynamic and SPIO-enhanced MRI.     

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.     

Magnetic resonance imaging with superparamagnetic iron oxide particles for the detection of myocardial reperfusion

The effect of superparamagnetic iron oxide particles on magnetic resonance myocardial signal intensity was examined in order to define the ability of this agent to identify normal, ischemic, and reperfused myocardium. Data were obtained from 6 normal rats (group 1) and from 6 heterotopic isogenic rat heart transplants (group 2) at 4.7 T with a multislice spin-echo sequence. Images were acquired in (a) normal rats before and after the infusion of 36 μmol Fe/kg of AMI-25 (group 1) and (b) rat heart transplants during control, global myocardial ischemia (before and after the injection of 72 μmol Fe/kg of AMI-25), and following reperfusion (group 2). Myocardial signal intensity decreased by 36 ± 4%, p < 0.001, following contrast infusion in normal hearts (group 1). The intensity remained constant in the rat heart transplants (group 2) during coronary occlusion, both before and after the infusion of AMI-25 and decreased by 61 ± 7%, p < 0.001, upon reperfusion. The larger effect of AMI-25 in reperfused as compared to normal myocardium suggests the presence of ischemia-induced hyperemia. There was no significant difference (analysis of variance) among intensities from different myocardial regions in either group at any stage of the experiment. We conclude that the use of AMI-25 permits identification of normal, ischemic, and reperfused myocardium and may therefore be helpful for the early detection of reperfusion following thrombolytic therapy for acute myocardial infarction.     

One-pot synthesis of amphiphilic superparamagnetic FePt nanoparticles and magnetic resonance imaging in vitro

Monodispersed amphiphilic FePt nanoparticles with the diameter of about 4 nm were synthesized by high temperature pyrolysis of iron(III) acetylacetonate and platinum(II) acetylacetonate. Their amphiphilicity is contributed to the tetraethylene glycol (TEG) and oleic acid (OA) on the surface, which is confirmed by FTIR and XPS spectra. They provide a superparamagnetic property with the saturation magnetization (Ms) of about 25 emu/g and the transverse relaxivity (r₂) of about 122.6 mM⁻¹ s⁻¹ in aqueous solutions. Furthermore, FePt nanoparticles show low cytotoxicity in living cells. They can be uptaken by HeLa cells effectively and result in the obvious decrease of T₂ relaxation time after internalization.     

Quantification of superparamagnetic iron oxide using inversion recovery balanced steady-state free precession

Cellular and molecular MRI trafficking studies using superparamagnetic iron oxide (SPIO) have greatly improved non-invasive investigations of disease progression and drug efficacy, but thus far, these studies have largely been restricted to qualitative assessment of hypo- or hyperintense areas near SPIO. In this work, SPIO quantification using inversion recovery balanced steady-state free precession (IR-bSSFP) was demonstrated at 3 T by extracting R₂ values from a monoexponential model (P. Schmitt et al., 2004). A low flip angle was shown to reduce the apparent recovery rate of the IR-bSSFP time course, thus extending the dynamic range of quantification. However, low flip angle acquisitions preclude the use of traditional methods for combining RF phase-cycled images to reduce banding artifacts arising from off-resonance due to B₀ inhomogeneity. To achieve R₂ quantification of SPIO, we present a new algorithm applicable to low flip angle IR-bSSFP acquisitions that is specifically designed to identify on-resonance acquisitions. We demonstrate in this work, using both theoretical and empirical methods, that the smallest estimated R₂ from multiple RF phase-cycled acquisitions correspond well to the on-resonance time course. Using this novel minimum R₂ algorithm, homogeneous R₂ maps and linear R₂ calibration curves were created up to 100 μg(Fe)/mL with 20° flip angles, despite substantial B₀ inhomogeneity. In addition, we have shown this technique to be feasible for pre-clinical research: the minimum R₂ algorithm was resistant to off-resonance in a single slice mouse R₂ map, whereas maximum intensity projection resulted in banding artifacts and overestimated R₂ values. With the application of recent advances in accelerated acquisitions, IR-bSSFP has the potential to quantify SPIO in vivo, thus providing important information for oncology, immunology, and regenerative medicine MRI studies.     

Analysis of feasibility of in vitro nuclear magnetic resonance tracking human umbilical cord mesenchymal stem cells by Gd-DTPA labeled

Objective

Three different kinds of transfection reagents were used to mediate the transfection of gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) into human umbilical-cord-derived mesenchymal stem cells (hUCMSCs). The efficacy of different transfection reagents and the feasibility of NMR tracer in vitro of magnetized stem cells were estimated.

Methods

After purification by tissue explants adherent method, the biological characteristics of hUCMSCs in vitro were identified by subculture and amplification. Calcium phosphate, Effectene and liposome2000 were used to transfect Gd-DTPA-labeled hUCMSCs respectively, and cell counting was used to mediate the transfection of Gd-DTPA into hUCMSCs, which were then induced to lipoblast and osteoblast in vitro. The determination of the transfection activities of the transfection reagents was conducted by measuring the magnetic resonance imaging (MRI) signal intensity of the Gd-DTPA-labeled cells and the concentration of gadolinium ion in the cells. Furthermore, the relationship between the signal intensity of Gd-DTPA-labeled hUCMSCsMRI, cell subculture and generations was studied.

Results

Primary cells were obtained by tissue explants adherent for two weeks. The cells displayed a long spindle form and grew in swirl. After two passage generations, the cellular morphology became more homogeneous. The result detected by the flow cytometer showed that CD29C, D44, CD90, and CD105 were highly expressed, while no CD45, CD40, and HLA-DR expression was detected in the third generation cells. Directional induction in vitro caused the differentiation into lipoblast and osteoblast. After transfected by calcium phosphate, Effectene and liposome 2000, the signal intensity of stem cells was 2281.2 ± 118.8, 2031.9 ± 59.7 and 1887.4 ± 40.8 measured by MRI. Differences between these three groups were statistically significant (P < 0.05). The concentrations of gadolinium ion in three groups of stem cells were 0.178 ± 0.009 mg/L, 0.158 ± 0.003 mg/L and 0.120 ± 0.002 mg/L respectively, examined by inductively coupled plasma atomic emission spectrometry. No significant differences were found among these three groups (P < 0.05). The proliferation and differentiation abilities of the Gd-DTPA-labeled stem cells were not affected. A minimum 5 × 10⁴ Gd-DTPA-labeled stem cells could be traced with MRI in vitro and presented in high signal. The trace duration time in vitro was about 12 days.

Conclusions

Tissue explants adherent method can be availably applied to purify hUCMSCs. The Effectene method was proved to have the best transfection effect. The proliferation ability and differentiation potency of Gd-DTPA-labeled hUCMSCs were not affected, and the NMR of labeled stem cells in vitro was proved to be feasible.     

Quantitative MR imaging of targeted SPIO particles on the cell surface and comparison to flow cytometry

Purpose

To detect anti-CEACAM5 targeted superparamagnetic iron oxide (SPIO) particles in vitro on the cell surface by quantitative magnetic resonance (MR) imaging and to compare with flow cytometry.

Materials and Methods

The monoclonal mouse antibody T84.1 and an appropriate IgG isotype antibody were conjugated to dextran-coated SPIO particles. HT29 cells expressing carcinoembryonic antigen (CEACAM5) were treated with antibody-conjugated SPIO particles. Purified cell samples were examined on a 3.0-T MR scanner using a multi-echo spin-echo sequence for MR relaxometry. Aliquots of the cell samples were further treated with a fluorescein isothiocyanate (FITC) anti-dextran antibody and an Alexa Fluor 488 anti-mouse antibody for the corresponding flow cytometry.

Results

MR relaxometry revealed a dose-dependent binding of T84.1-conjugated SPIO particles with a positive correlation between R₂ relaxation rate of cell samples and SPIO particle concentration during incubation (r=0.993, P<.01). Positive correlations were also observed between R₂ relaxation rate and flow cytometry (geometric mean) with both fluorescent antibodies (r=0.972 and r=0.953, both P<.01), respectively.

Conclusion

The study revealed the feasibility of quantitative MR imaging of targeted SPIO particles on the cell surface comparable to flow cytometry.     

Diffusion-weighted imaging versus superparamagnetic iron oxide (SPIO)-enhanced MRI: exclusive and combined values in the assessment of hepatic metastases

Purpose

The purpose was to validate diffusion-weighted imaging (DWI) in the assessment of hepatic metastases compared with superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging.

Materials and Methods

For 21 consecutive patients with 160 metastases from extrahepatic malignancy and 25 benign focal lesions, two radiologists evaluated four separate review sessions (I, SPIO-enhanced T2?-weighted images; II, precontrast DWI; III, SPIO-enhanced T2?-weighted images and precontrast DWI; IV, SPIO-enhanced T2?-weighted images plus precontrast and SPIO-enhanced DWI) and assigned confidence levels using a five-grade scale for each hepatic lesion.

Results

The A_z values after receiver operating characteristic curve analysis for Reader 1 and Reader 2 were 0.80 and 0.75 on session I, 0.91 and 0.91 on session II, 0.97 and 0.96 on session III and 0.96 and 0.96 on session IV, respectively. The A_z value of session II was significantly higher than that of session I (Reader 1, P=.004; Reader 2, P<.001), and that of session III was significantly higher than that of session I (P<.001 for each reader) or session II (Reader 1, P=.004; Reader 2, P=.003). Although there was no significant difference of A_z value between session III and session IV (Reader 1, P=.231; Reader 2, P=.878), the sensitivity improved for session IV compared with that for session III (Reader 1, P=.031; Reader 2, P=.039).

Conclusion

In the assessment of hepatic metastases, DWI can provide more accurate information than can SPIO-enhanced images. Diagnostic accuracy can be increased even more through the combination of both techniques.     

Gadolinium oxide: a protoype agent for contrast enhanced imaging of the liver and spleen with magnetic resonance

Gd2O3 particles (less than 2 microns) in suspension were evaluated as a potential contrast agent for liver-spleen imaging with magnetic resonance. The agent was administered IV to rabbits in doses ranging from 10 to 120 mumol/kg and the tissues removed after sacrifice for in vitro T1 and T2 analysis. The temporal response was determined in liver and spleen samples of rabbits given a fixed dose (60 mumol/kg) and sacrificed at intervals from 15 min to 60 hr later. Documentation of the subanatomic location of Gd2O3 particles in tissue was accomplished by electron microscopy and x-ray dispersion microanalysis. T1 weighted images were obtained at 0.12T on a prototype resistive scanner. The liver, spleen, and lung relaxation times are very responsive to Gd2O3 IV and the effect is dose related. A peak effect is observed between 3-7 hr after injection and relaxation times may normalize by 60 hr. By electron microscopic and x-ray analysis, Gd2O3 is most prominently found in the hepatic and splenic sinusoids. The images show marked enhancement of liver and splenic tissues, aiding in the clear delineation of these tissues from neighboring structures.     

Optimization of effective parameters in the synthesis of nanopore anodic aluminum oxide membrane and arsenic removal by prepared magnetic iron oxide nanoparicles in anodic aluminum oxide membrane via ultrasonic-hydrothermal method

In this study, a new anodized aluminum oxide (AAO) nanostructure membrane was synthesized by anodization process under a constant voltage, in oxalic acid solution that was improved with trace amounts of sulfuric acid at room temperature. The effect of various parameters on the morphology of the synthesized nanostructures such as voltage, electrolyte composition, anodization time and type of stripping solution were investigated. According to the results, corrosion of the walls, size regularity, diameter and number of the pores increased in the presence of sulfuric acid (0.018 mol.L⁻¹). Nitrogen adsorption-desorption analysis confirmed significant porosity, array and uniformity of the pore size in the synthesized nanoporous membrane. A new modification method was used based on ultrasonic-hydrothermal method to modify the synthesized AAO with Fe₃O₄/SiO₂ nanoparticles for metals and metalloids removal from aqueous solution. In this method, Fe₃O₄/SiO₂ nanoparticles were placed very regularly and uniformly on the surface and inside the pores. This modification was confirmed by characterization techniques. The modified AAO@Fe₃O₄/SiO₂ membrane showed excellent results for removing arsenic from aqueous media.     

Reproducibility of the quantitative assessment of cartilage morphology and trabecular bone structure with magnetic resonance imaging at 7 T

To assess the reproducibility of quantitative measurements of cartilage morphology and trabecular bone structure of the knee at 7 T, high-resolution sagittal spoiled gradient-echo images and high-resolution axial fully refocused steady-state free-precession (SSFP) images from six healthy volunteers were acquired with a 7-T scanner. The subjects were repositioned between repeated scans to test the reproducibility of the measurements. The reproducibility of each measurement was evaluated using the coefficient(s) of variation (CV). The computed CV were 1.13% and 1.55% for cartilage thickness and cartilage volume, respectively, and were 2.86%, 1.07%, 2.27% and 3.30% for apparent bone volume over total volume fraction (app.BV/TV), apparent trabecular number (app.Tb.N), apparent trabecular separation (app.Tb.Sp) and apparent trabecular thickness (app.Tb.Th), respectively. The results demonstrate that quantitative assessment of cartilage morphology and trabecular bone structure is reproducible at 7 T and motivates future musculoskeletal applications seeking the high-field strength's superior signal-to-noise ratio.     

Visualization of superior mesenteric lymph nodes by the combined oral and intravenous administration of the ultrasmall superparamagnetic iron oxide, AMI-227

Superior mesenteric lymph nodes which lie as a chain near the small intestine are difficult to visualize in the rat with MRI either with or without the use of contrast agents. We previously demonstrated that the oral administration of an ultrasmall superparamagnetic iron oxide (AMI-227) produces a brightening of the lumen of the GI tract with a T₁-weighted spin-echo pulse sequence. We have also shown that AMI-227 darkens abdominal lymph nodes. In the present study we show that the combined oral and intravenous administration of AMI-227 produces a brightening of the lumen of the GI tract and a darkening of the superior mesenteric lymph node chain. As a result of these combined and opposing effects on image signal intensity, a necessary contrast is established to reliably locate the superior mesenteric lymph nodes in vivo, which, to our knowledge, have been elusive by other techniques.     

Computer-assisted design of surface coils used in magnetic resonance imaging. II. Rotational discrimination nonlinear regression analysis and the design of surface coils

For a number of reasons, it is desirable to fabricate coils which, for a known current, shall produce predetermined values of the magnetic field intensity at a number of points within a nuclear magnetic resonance imager.

The calculation of the magnetic field intensity at a set of points involves the integration of the Biot-Savart equation for all components of the segments of conductor which make up the coil. This process in itself is a rather formidable task. When this process is parameterized in terms of coil diameter, coil spacing, etc. the problem is to determine the values of these parameters to match values of magnetic field intensities which are desired. The problem thereby increases in complexity to the point where, by ordinary methods, the problem becomes intractable.

A generalized solution technique has been developed on a digital computer to implement the rotational discrimination nonlinear regression techniques of Faris, Law and Letcher to find the best solution to this problem. The problem is posed by integrating the Biot-Savart equation. This produces algebraic expressions for incorporation into the optimization program which is executed on a computer in a conversational mode.

This technique was employed to specify the dimensions of a rectangular surface coil for the investigation of the whole human spine.