Serial MR Imaging of Magnetically Labeled Humen Umbilical Vein Endothelial Cells in Acute Renal Failure Rat Model

PURPOSE: To evaluate the usefulness of in vivo magnetic resonance (MR) imaging for tracking intravenously injected superparamagnetic iron oxide (SPIO)-labeled human umbilical vein endothelial cells (HUVECs) in an acute renal failure (ARF) rat model. MATERIALS AND METHODS: HUVECs were labeled with SPIO and poly-L-lysine (PLL) complex. Relaxation rates at 1.5-T MR, cell viability, and labeling stability were assessed. HUVECs were injected into the tail vein of ARF rats (labeled cells in 10 rats, unlabeled cells in 2 rats). Follow-up serial T2*-weighted gradient-echo MR imaging was performed at 1, 3, 5 and 7 days after injection, and the MR findings were compared with histologic findings. RESULTS: There was an average of 98.4+/-2.4% Prussian blue stain-positive cells after labeling with SPIO-PLL complex. Relaxation rates (R2*) of all cultured HUVECs at day 3 and 5 were not markedly decreased compared with that at day 1. The stability of SPIO in HUVECs was maintained during the proliferation of HUVECs in culture media. In the presence of left unilateral renal artery ischemia, T2*-weighted MR imaging performed 1 day after the intravenous injection of labeled HUVECs revealed a significant signal intensity (SI) loss exclusively in the left renal outer medulla regions, but not in the right kidney. The MR imaging findings at days 3, 5 and 7 after intravenous injection of HUVECs showed a SI loss in the outer medulla regions of the ischemically injured kidney, but the SI progressively recovered with time and the right kidney did not have a significant change in SI in the same period. Upon histologic analysis, the SI loss on MR images was correspondent to the presence of Prussian blue stained cells, primarily in the renal outer medulla. CONCLUSION: MR imaging appears to be useful for in vivo monitoring of intravenously injected SPIO-labeled HUVECs in an ischemically injured rat kidney.

Diffusion-Weighted MR Imaging before and after Contrast Enhancement with Superparamagnetic Iron Oxide for Assessment of Hepatic Metastasis

PURPOSE: The purpose of our study was to validate diffusion-weighted MRI (DWI) before and after superparamagnetic iron oxide (SPIO) injection for assessment of hepatic metastases. MATERIALS AND METHODS: Eighty-six hepatic metastases (size range, 0.3-4.7 cm; mean, 1.5 cm) verified pathologically or by follow-up imaging studies in 22 consecutive patients (17 men and 5 women; 44-83 years; mean age, 60 years) during a 13-month period were enrolled. Hepatic MRI, including DWI (b-factors=50, 400, 800 s/mm2) with breath-holding technique of single-shot spin-echo echo-planar imaging (TR/TE=1000/69 ms, average=2) before and after SPIO administration, were retrospectively reviewed by two independent radiologists with a 5-point scale confidence score for each hepatic lesion on pre-contrast DWI (pre-DWI), SPIO-enhanced DWI (SPIO-DWI), and SPIO-enhanced T2*-weighted imaging (SPIO-T2*wI). RESULTS: For all lesions, SPIO-T2*wI showed significantly higher confidence score in the diagnosis of hepatic metastases than pre-contrast or SPIO-DWI regardless of the size of b-factors (p0.05). Pre-DWI using b-factor=50 sec/mm2 was also comparable with SPIO-T2*wI by observer 1 (p=0.060). CONCLUSION: Pre-DWI has a limited value for the assessment of hepatic metastases, however, the repetition of DWI after SPIO injection using small b-factors could complement SPIO-T2*wI, especially for subcentimeter lesions.

MRI monitoring superparamagnetic iron oxide (SPIO) particles labeling Schwann cells in vitro / 中华显微外科杂志

Objective To investigate the effects of labeling Schwann cells with different concentrations of SPIO, and to investigate the feasibility of in vitro MR imaging. Methods The C57BL/6 mices'Schwann cells were isolated, purified, and then 0.5 × 106, 1.0 × 106, 5.0 × 106 cells were labeled with 25.0 μg/ml, 50.0 μg/ml SPIO. Prussian blue stain and transmission electron microscope (TEM) were performed for showing intracellular iron. The signal intensity of cells were evaluated by 3.0 MRI with different sequences in vitro. Results Different cell population (0.5 × 106, 1.0 × 106,5.0 × 106) were cultured with different concentration SPIO about 24 hours. Dyeing degree of labeling cells stained by Prussion blue gradually deepened from 25.0 μg/ml to 50.0 μg/ml. Transmission electron microscope indicated that iron particles accumulated inendosomes/lysosomes. The MR signal intensity of labeling cells were inversely correlated with the concentration of SPIO groups in T2WI and GRE/30° imaging in vitro. Conclusion Schwann cells could be labeled effectively with SPIO, and MRI could be used to monitor these labeled cells in vitro.

Ferucarbotran-Enhanced Hepatic MRI at 3T Unit: Quantitative and Qualitative Comparison of Fast Breath-hold Imaging Sequences

PURPOSE: To compare the relative values of various fast breath-hold imaging sequences for superparamagnetic iron-oxide (SPIO)-enhanced hepatic MRI for the assessment of solid focal lesions with a 3T MRI unit. MATERIALS AND METHODS: 102 consecutive patients with one or more solid malignant hepatic lesions were evaluated by spoiled gradient echo (GRE) sequences with three different echo times (2.4 msec [GRE_2.4], 5.8 msec [GRE_5.8], and 10 msec [GRE_10]) for T2*-weighted imaging in addition to T2-weighted turbo spin echo (TSE) sequence following intravenous SPIO injection. Image qualities of the hepatic contour, vascular landmarks and artifacts were rated by two independent readers using a four-point scale. For quantitative analysis, contrast-to-noise ratio (CNR) was measured in 170 solid focal lesions larger than 1 cm (107 hepatocellular carcinomas, nine cholangiocarcinomas and 54 metastases). RESULTS: GRE_5.8 showed the highest mean points for hepatic contour, vascular anatomy and imaging artifact presence among all of the subjected sequences (p<0.001) and was comparable (p=0.414) with GRE_10 with regard to lesion conspicuity. The mean CNRs were significantly higher (p<0.001) in the following order: GRE_10 (24.4+/-14.5), GRE_5.8 (14.8+/-9.4), TSE (9.7+/-6.3), and GRE_2.4 (7.9+/-6.4). The mean CNRs of CCCs and metastases were higher than those of HCCs for all imaging sequences (p<0.05). CONCLUSION: Regarding overall performances, GRE using a moderate echo time of 5.8 msec can provide the most reliable data among the various fast breath-hold SPIO-enhanced hepatic MRI sequences at 3T unit despite the lower CNR of GRE_5.8 compared to that of GRE_10.

Ferucarbotran-Enhanced Hepatic MRI at 3T Unit: Quantitative and Qualitative Comparison of Fast Breath-hold Imaging Sequences

PURPOSE: To compare the relative values of various fast breath-hold imaging sequences for superparamagnetic iron-oxide (SPIO)-enhanced hepatic MRI for the assessment of solid focal lesions with a 3T MRI unit. MATERIALS AND METHODS: 102 consecutive patients with one or more solid malignant hepatic lesions were evaluated by spoiled gradient echo (GRE) sequences with three different echo times (2.4 msec [GRE_2.4], 5.8 msec [GRE_5.8], and 10 msec [GRE_10]) for T2*-weighted imaging in addition to T2-weighted turbo spin echo (TSE) sequence following intravenous SPIO injection. Image qualities of the hepatic contour, vascular landmarks and artifacts were rated by two independent readers using a four-point scale. For quantitative analysis, contrast-to-noise ratio (CNR) was measured in 170 solid focal lesions larger than 1 cm (107 hepatocellular carcinomas, nine cholangiocarcinomas and 54 metastases). RESULTS: GRE_5.8 showed the highest mean points for hepatic contour, vascular anatomy and imaging artifact presence among all of the subjected sequences (p<0.001) and was comparable (p=0.414) with GRE_10 with regard to lesion conspicuity. The mean CNRs were significantly higher (p<0.001) in the following order: GRE_10 (24.4+/-14.5), GRE_5.8 (14.8+/-9.4), TSE (9.7+/-6.3), and GRE_2.4 (7.9+/-6.4). The mean CNRs of CCCs and metastases were higher than those of HCCs for all imaging sequences (p<0.05). CONCLUSION: Regarding overall performances, GRE using a moderate echo time of 5.8 msec can provide the most reliable data among the various fast breath-hold SPIO-enhanced hepatic MRI sequences at 3T unit despite the lower CNR of GRE_5.8 compared to that of GRE_10.

Evaluation of Fibrosis in Liver Cirrhosis by Superparamagnetic Iron Oxide (SPIO)-Enhanced MR Imaging: Does the Radiological Non-Invasive Fibrosis Index Correlate with the Laboratory Non-Invasive Fibrosis Index?

PURPOSE: To evaluate the correlation between the radiological non-invasive hepatic fibrosis index (RNHFI), as determined by SPIO-enhanced MRI, and the laboratory non-invasive hepatic fibrosis index. MATERIALS AND METHODS: Patients (99 total: 61 men and 38 women; mean age: 58 years) who underwent SPIO-enhanced MRI (1.5T) during 5 years included. These patients were subdivided into a liver cirrhosis group (LCG) and a non-liver cirrhosis group (non-LCG). Using PACS view, we measured the RNHFI (mean standard deviation of hepatic signal intensity (SD), noise-corrected coefficient of variation (CV)) of three ROIs in the liver parenchyma by SPIO-enhanced MRI. The laboratory non-invasive hepatic fibrosis index (AST-platelet ratio index (APRI)) of all patients was calculated from the laboratory data. We compared the RNHFI and APRI of LCG with those of non-LC group using Student's t-test. A bivariate correlation was performed to investigate the relationship between the RNHFI and APRI in the LCG. RESULTS: For the LCG, mean values of SD and CV by SPIO-enhanced MRI were 10.3 +/-3.7 and 0.19+/-0.08, respectively. For the non-LCG, mean values of SD and CV were 6.5+/-1.6 and 0.08+/-0.05, respectively. The mean APRI of the LCG and the non-LCG were 2.04+/-1.7 and 0.32+/-0.32, respectively. The RNHFI and APRI were significantly different between both groups (p<05). For the LCG, the bivariate correlation between SD and APRI revealed a statistically significant positive correlation (r=0.5, p<0.001). In both groups, there was no statistically significant correlation between CV and APRI. CONCLUSION: A measurement of SD can be a simple and useful method for the evaluation of hepatic fibrosis.

Preparation and performance testing for super-paramagnetic contrast agent of magnetic resonance / 重庆医科大学学报

Objective:To explore the possibility as antisense gene carriers.Preparation of super paramagnetic iron oxide MR contrast agent Iron oxide nanoparticles and test their physical and Magnetic Properties.Methods:the iron oxide nanoparticles is obtained by means of Co-precipitation method,its structure is analyzed by X-ray powder diffraction method,its size and distribution is measured by transmission electron microscope,and its Susceptibility is measured by Vibrating Sample Magnetometer dollars.Results:Testing after dextran-coated particle diameter overall,the size is20～35nm,core diameter of around is 5nm,These particles possessed some characteristics of super paramagnetic.Relaxation rate Of the sample is 0.155?106/(mol?sec) and quality saturation magnetic intensity is 69.42162emu/g Fe.Conclusion:the sample possessed the advantages of small size,dispersed,super-paramagnetic,so it could be used as an anti-gene carriers.

Histologic Monitoring of the Transplanted Superparamagnetic Iron Oxide Labelled Human Mesenchymal Stem Cells in the Rat Bladder

PURPOSE: Molecular magnetic resonance(MR) imaging technique using the superparamagnetic iron oxide nanocrystals(SPIO) are developed for the monitoring the stem cells noninvasively. This study was performed to monitor the transplanted SPIO labelled human mesenchymal stem cells(hMSCs) with the molecular MR imaging and histologically in the rat bladder. MATERIALS AND METHODS: SPIO(Feridex; AMI, Cambridge, MA, USA) were labelled to hMSCs using GenePORTER. The labeling viability, efficiency of the SPIO labelled hMSCs were examined with tripan blue, prussian blue staining. SPIO labelled hMSCs are transplanted to the bladder in rats and MR images of them were examined using 1.5 T MR. Histologic examination of the SPIO labelled hMSCs transplanted bladder was performed with H&E and prussian blue staining. RESULTS: The viability, efficiency of the SPIO labelled hMSCs were good. MR signal intensity at the areas of the SPIO labelled hMSCs in the bladder decreased after transplantation of 1x10(6) SPIO labelled hMSCs and were confined locally. Intracellular SPIO were confirmed in the hMSCs transplanted bladder up to 5 weeks. CONCLUSION: The SPIO labelled hMSCs in the bladder can be monitored using the molecular MR imaging and SPIO labelled hMSCs were found in the transplanted bladder.

The Clinical Usefulness of SPIO-MRI in Detection and Staging of Hepatocellular Carcinoma / 대한간학회지

BACKGROUND/AIMS: It is still unclear whether Super Paramagnetic Iron Oxide-Magnetic Resonance Imaging (SPIO-MRI) is a clinically useful imaging modality for patients with hepatocellular carcinoma (HCC). This study searched for the clinical usefulness and limitations of SPIO-MRI with respect to tumor detection capacity, false positive and negative rate, and early recurrence rate. METHODS: From December 1999 to February 2001, 218 patients who were surgical candidates by 3-phase dynamic helical CT (3dHCT) were enrolled. We reviewed the medical records and radiologic findings, retrospectively, and postulated the post-operative pathologic findings and the early recurrences within 3 months as the standards for the true positive lesion. RESULTS: The mean number of nodules detected by SPIO-MRI was significantly more numerous than that of 3dHCT (p<0.01). Modifications of treatment strategy due to the discordant findings between SPIO-MRI and 3dHCT for tumor resectability were observed in 22 (10.1%) out of 218 patients. Early recurrences were observed in 10 patients (7.8%). The false positive and negative rates of SPIO-MRI were 6.3% and 13.3%, respectively. CONCLUSIONS: We demonstrated that the tumor detection rate of SPIO-MRI was better than that of 3dHCT. Given the relatively acceptable false positive and negative rates, SPIO-MRI could be an appropriate preoperative imaging modality for patients with HCCs.

Usefulness of Superparamagnetic Iron Oxide (SPIO) as a Negative Oral Contrast Agent in MR Cholangiopancreatography

PURPOSE: To evaluate value of superparamagnetic iron oxide (SPIO) as a negative oral contrast agent in MR cholangiopancreatography (MRCP). MATERIALS AND METHODS: Forty-eight patients with suspected biliary tract or pancreatic diseases and six healthy volunteers were enrolled in this study. All MR images were obtained using a 1.5 T MR unit. MRCP using fat-suppressed half-Fourier acquisition single-shot turbo spin echo (HASTE) and turbo spin echo (TSE) techniques were performed and reconstructed with maximal intensity projection (MIP). To determine the most optimal concentration of SPIO to obliterate the high signal intensity of water, a phantom experiment was conducted with various concentrations of SPIO-water mixture. Two radiologists evaluated pre- and postcontrast MRCPs. The contrast enhancement was assessed on the basis of loss of signal intensity in the stomach and duodenum. RESULTS: In the phantom experiment, a significant increase of percentage of signal intensity loss (PSIL) occurred in concentration of 22.4 ugFe/ml (Feridex 1 ml diluted with water 500 ml). Postcontrast MRCP showed an improved image quality compared with precontrast images. The rate of improvement in the diagnosis of diseases of the common bile duct and pancreatic duct was 25% (12/48). CONCLUSION: In patients with suspected biliary tract and pancreatic diseases, the SPIO is useful as a negative oral contrast agent for MRCP and provides an improvement of image quality.

Evaluation of Feridex-enhanced MRI in the Diagnosis of Hepatic Lesions / 实用放射学杂志

Objective To evaluate Feridex(superparamagnetic iron oxide,SPIO)enhanced MRI in the diagnosis of hepatic lesions.Methods Feridex-enhanced MRI was performed in 31 patients with CT,or MRI proved or suspected hepatic lesions.T 2WI signal intensity of hepatic parenchyma,lesion and background noise was measured before and after enhancement separately.SNR and CNR of parenchyma and lesion before and after enhancement were calculated.The number of lesions on plain and enhanced scans were observed and alalyzed.Results Post-enhancement SNR of liver significantly decreased (?0.05).Post-enhancement lesion-liver CNR increased significantly (?

Experimental Study :the Preparing of Targeted-directed Probe (Hab18-SPIO) and Testing of Its Phisichemical Characteristics / 实用放射学杂志

Objective To prepare the Target-directed probe(Hab18-SPIO) and to test its phisichemical characteristics. Methods The McAb Target-directed probe(Hab18-SPIO) was prepared through hepatocellular carcinoma(HCC) McAb(Hab18) conjugated toSPIO using chemical method,while negative McAb probe(SED-SPIO) was also prepared using the same method.These agents weretested by high-performance liquid chromatography(HPLC) and electron microscope. Results The results of HPLC and electronmicroscope proved that Hab18 was conjugated SPIO effectively.The diameter of particles was between 50 and 70 nm.The binding rate of Hab18 was 97.5%. Conclusion The probe targeted to membrane-associated antigen of HCC(Hab18g) has been successfully prepared,which has novel physiochemical property.It is of great value in specific MR diagnosis of early HCCs.

In vitro and in vivo MR imaging of SHU 555A-labelled swine bone marrow mesenchymal stem cells / 介入放射学杂志

Objective To detect the feasibility of magnetically labeled swine bone marrow mesenehymal stem cells(MSCs)with SHU 555A combined with poly-L-arginine(PLL),under MR imaging in vitro and in vivo.Methods Swine mesenehymal stem cells were isolated and culture-expanded 3 passages in vitro,then magnetically labeled by incubation with SHU 555A(25?g Fe/ml,Resovist,Schering)for 24 hours with 750 ng/mL poly-L-lysine(PLL;average MW_275 kDa)added 1 hour before incubation.Cellular iron incorporation and detention at 0 d,4 d,8 d,12 d,16 d,20 d after labeling was qualitatively assessed using Prussian blue and quantified at atomic absorption spectrometry.Cell viability was assessed by trypan-blue exclusion test.Cell suspensions underwent MR imaging with T_1-and T_2-weighted spin-echo and fast field-echo sequences on a clinical 1.5 T MR system.At last,1?10~6 SHU 555A labeled and unlabeled MSCs were transextracardially implanted into the infracted and normal myocardium approximately 2 week following the ligation of left anterior descending coronary artery in 1 swine respectively,and finally performed 1.5-T MRI within 1 week after infarction.Results①Intracytoplasmic particles stained with Prussian blue stain were detected for all cells with mean cellular iron content of(13.13?2.30)pg per cell.With division of stem cells, the stained particles decreased gradually with iron content(0.68?0.20)pg per cell.at 16 days after labeling, approximately to the prelabeled baseline values.(0.21?0.06)pg per cell(P＞0.05).The viability of the labeled cells at various time points were not significantly different with that of nonlabeled cells(P＞0.05).②MR images showed signal intensity changed most obviouly in T2*WI in vitro.The percentage change of signal intensity increased with increasing cell numbers,and decreased with the time.As few as 5?10~4-1?10~5 cells could be detected by using this approach.③Two injected sites containing MR-MSCs were detected in vivo,presentingas low signal intensity areas with the T_2*WI scanning sequence.Conclusion Swine bone marrow MSCs can be labeled with SHU555A-PLL and depicted with a standard 1.5-T MR imager in vitro and in vivo.(J lntervent Radiol,2007,16:115-121)

The Diagnostic Efficacy of SPIO in Patients with Known Liver Lesions / 实用放射学杂志

Objective:To evaluate the diagnostic efficacy of SPIO in known liver lesions.Methods:30 patients with known liver lesion were underwent MRI.The contrast noise rate(CNR)of lesion to liver and the relative enhancement rate(RE)of liver were measured at 10、30、45、70 min and 16 hour after SPIO was injected.The dynamic curve of signal-noise were made and analysed.Results:The study shown that the hepatic parenchyma had a significantly negative enhancement in T 2 weight of SE and GRE sequence.However,the signal intensity showed few changes in hepatic metastases and only a little positive or negative enhancement in angioma、HCC and FNH.Conclusion:SPIO,as a negative contrast media for liver,has a significantly efficacy to show liver lesions,and as liver lesion-specific contrast MR agent,is worth being explored. [