磁标记大鼠骨髓间充质干细胞活体内移植后向肝癌细胞趋向性迁移的研究

目的 探讨磁标记大鼠骨髓间充质干细胞(BMSCs)活体内移植后对大鼠肝细胞癌的趋向性迁移及其机制.方法 培养大鼠BMSCs,超顺磁性氧化铁粒子标记.制备大鼠肝癌模型24只,数字表法随机分为3组:实验组(n=12)经脾植入磁标记的BMSCs;对照组A(n=6)移植未标记的BMSCs;对照组B(n=6)不作任何处理.分别于移植前及移植后1、3、7和14 d行MR扫描,选用T_2*WI序列进行移植细胞的示踪并测量肿瘤组织与正常肝组织的信号强度的比值(SI/SI*),结果行单因素方差分析;取肿瘤组织、瘤旁正常肝组织行普鲁士蓝染色,分析BMSCs在体内的分布并与MR对照.结果 BMSCs的磁标记率为90%以上.移植后实验组T_2*WI显示肿瘤信号强度值明显减低,移植前及移植后1、3、7和14 d的SI/SI*值分别为3.18±0.21、1.98±0.20、2.38±0.28、2.70±0.25及3.16±0.24,差异有统计学意义(F=56.65,P<0.05);与移植前相比,1、3、7 d肿瘤信号强度的减低有统计学意义(t值分别为1.20、0.79、0.48,P值均<0.05).对照组移植前后各SI/SI*值差异无统计学意义(P>0.05).免疫组织化学显示实验组肿瘤边缘及内部有大量监染的普鲁士蓝阳性细胞分布,标记细胞在肿瘤内的分布与MR信号改变基本一致.对照组肿瘤组织普鲁士蓝染色均为阴性结果.结论 BMSCs在活体内对肝癌细胞有明显的趋向迁移特性,有望成为基因治疗肝细胞癌的载体.     

肾功能衰竭大鼠超顺磁性氧化铁标记骨髓间充质干细胞肾脏移植MR活体示踪的研究

目的应用磁性氧化铁纳米粒子和多聚左旋赖氨酸（poly-L-lysine，PLL）的偶联物Fe2O3-PLL标记大鼠骨髓间充质干细胞（MSCs），MR活体示踪经肾动脉移植入肾功能衰竭（简称肾衰）大鼠肾脏的标记细胞。方法制备Fe2O3-PLL，分离、纯化并培养大鼠骨髓MSCs，Fe2O3-PLL标记细胞，普鲁士蓝染色显示细胞内铁。肌内注射甘油所致肾衰的大鼠分为2组，分别经左肾动脉移植入标记细胞（6只）和未标记细胞（5只），移植后即刻及第1、3、5、8天应用MRI对移植细胞进行活体示踪，并与肾脏组织切片普鲁士蓝染色和HE染色对照。结果MSCs的Fe2O3-PLL标记率近100％，普鲁士蓝染色显示蓝色铁颗粒位于MSCs胞质内。标记细胞移植后肾衰大鼠肾脏皮质区信号强度明显下降，T2＊WI信号改变最明显，而肾髓质及肾盂信号较细胞移植前无明显变化，信号改变随着时间的延长逐渐减轻一直持续到移植后第8天。组织学分析见绝大多数标记细胞分布于肾皮质肾小球内，与MRI信号改变区域基本一致。未标记细胞移植后未见肾脏信号改变。结论Fe2O3-PLL可以有效标记大鼠骨髓MSCs，临床应用型1．5T磁共振仪可对经肾动脉移植入肾衰大鼠肾脏的标记细胞进行初步活体示踪。     

胎鼠神经干细胞超顺磁性氧化铁颗粒标记移植后MRI研究

目的:探讨超顺磁性氧化铁颗粒(SPIO)标记神经干细胞的方法,以及标记细胞正常大鼠脑内移植后MR成像的方法学研究。方法:多聚左旋赖氨酸介导的SPIO标记胎鼠神经干细胞,进行台盼兰染色和普鲁士兰染色分别检测标记细胞的存活率和标记率。选取SD大鼠15只,简单随机法分为3组:第1组于大鼠右侧尾状核移植未标记的NSCs,第2组于大鼠右侧尾状核移植标记的NSCs,第3组右侧尾状核移植游离的SPIO颗粒,移植后第1、4、8周进行MRI。8周后处死大鼠,行组织切片普鲁士兰染色。结果:体外标记的神经干细胞普鲁士兰染色发现铁颗粒聚集于细胞浆内,标记率为100%;标记细胞与未标记细胞的台盼兰染色结果无显著差异。移植后MRI,第1组注射点未见低信号影;第2组注射点T2WI及GRE序列均可见类圆形低信号影;第3组大鼠注射后1周注射点可见低信号影,4周后低信号影变淡且边缘变模糊,8周后低信号影T2WI已不明显。与T2WI序列比较,GRE序列显示标记细胞更清晰,但显示范围较扩散。脑组织切片的普鲁士兰染色显示,第1组大鼠脑组织切片未见异常蓝染细胞,第2组注射点可见蓝染细胞,第3组注射点可见稍许散在蓝色颗粒状物质。结论:多聚左旋赖氨酸介导下SPIO可用于标记神经干细胞,标记细胞移植后MRI可以无创性观察移植神经干细胞的位置及分布情况。     

MR evaluation of the glomerular homing of magnetically labeled mesenchymal stem cells in a rat model of nephropathy

PURPOSE: To assess renal glomerular homing of intravenously injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) at in vivo and ex vivo magnetic resonance (MR) imaging in an experimental rat model of mesangiolysis. MATERIALS AND METHODS: Animal procedures were performed in accordance with protocols approved by Institutional Animal Care and Use Committee. Fourteen rats were divided into two groups: one pathologic (n = 10), with persistent mesangiolysis following simultaneous injection of OX-7 monoclonal antibody and puromycin aminonucleoside in which 10(7) SPIO- and DiI-labeled MSCs were injected, and one control (n = 4). In vivo and ex vivo MR imaging examinations were performed with 4.7- and 9.4-T spectrometers, respectively, and T2*-weighted sequences. In vivo signal intensity variations were measured in the liver and kidney before and 6 days after MSC injection. Intrarenal signal intensity variations were correlated with histopathologic data by means of colocalization of DiI fluorescence, alpha-actin, and Prussian blue stain-positive cells. Histologic differences between the glomerular homing of MSCs in different kidney portions were correlated to the areas of MR signal intensity decrease with nonparametric statistical tests. RESULTS: On in vivo images, signal intensity measurements of pathologic kidneys following MSC injection did not show any signal intensity decrease (P = .7), whereas a 34% +/- 14 (mean +/- standard deviation) signal intensity decrease was observed in the liver (P < .01), where a substantial number of labeled cells were trapped. On ex vivo images, pathologic kidneys showed focal cortical (glomerular) areas of signal intensity loss, which was absent in controls. The areas of low signal intensity correlated well with alpha-actin and Prussian blue stain- and DiI-positive areas (P < .01), which indicates that MSCs specifically home to injured tissue. No MSCs were detected in the kidneys of control animals. CONCLUSION: Intravenously injected MSCs specifically home to focal areas of glomerular damage and can be detected at ex vivo MR imaging.     

An experimental study on MR imaging of atherosclerotic plaque with SPIO marked endothelial cells in a rabbit model

Purpose:

To investigate how to label macrophages in atherosclerotic plaques with superparamagnetic iron oxide (SPIO) nanoparticles and trace SPIO with MR imaging.

Materials and Methods:

Atherosclerotic lesions of a rabbit model were induced by a combination of high‐fat and high‐cholesterol diet and subsequent endothelial abrasion of the abdominal aorta. SPIO particles were pretreated with poly‐L‐lysine. SPIO nanoparticles and SPIO‐labeled human endothelial cells (ECV‐304) were IV injected into model animals, respectively. The MRI scans and histopathological examination were performed 12 h and 24 h after the injection. The imaging and histopathological data were analyzed.

Results:

Prussian blue staining of the vessel specimens indicated that SPIO particles were not found in the atheroma but in the Kupffer's cells of the liver after SPIO injection. However, the accumulation of SPIO particles in the atheroma was confirmed in animals received SPIO‐labeled endothelial cell transplantation. The best quality MR scan sequences of rabbit abdominal aorta were T₂WI fat suppression, T₁WI, and DIR series, on which of MR image had a higher quality. Signal loss of the original incrassate plaque in the vessel wall on T₂WI was found in 6 of 10 animals received SPIO‐labeled endothelial cell transplantation.

Conclusion:

SPIO‐labeled endothelial cells were superior to SPIO for MR imaging of atherosclerotic plaques. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.     

Migration of iron oxide-labeled human hematopoietic progenitor cells in a mouse model: in vivo monitoring with 1.5-T MR imaging equipment

PURPOSE: To evaluate the use of clinical 1.5-T magnetic resonance (MR) imaging equipment to depict the in vivo distribution of iron oxide-labeled human hematopoietic progenitor cells in athymic mice. MATERIALS AND METHODS: This study was approved by the ethical committee, and all women had given consent to donate umbilical cord blood for research. Twenty athymic female Balb/c mice underwent MR imaging before and 1, 4, 24, and 48 hours after intravenous injection of (1-3) x 10(7) human hematopoietic progenitor cells labeled with the superparamagnetic iron oxide particles ferumoxides through simple incubation (n = 10) or P7228 through lipofection (n = 10). Fifteen female Balb/c control mice were examined after intravenous injection of the pure contrast agents (n = 6 for both probes) or nonlabeled cells (n = 3). Signal intensities of liver, spleen, and bone marrow on MR images obtained before and after injection were measured and compared for significant differences by using the t test. MR imaging data were compared with the results of immunostaining against human CD31(+) cells and against the coating of the contrast agents; these results served as the standard of reference. RESULTS: Ferumoxides was internalized into more mature CD34(-) cells but not into CD34(+) stem cells, while P7228 liposomes were internalized into both CD34(-) and CD34(+) cells. After injection of iron oxide-labeled hematopoietic cells, a significant decrease in MR signal intensity was observed in liver and spleen at 1, 4, 24, and 48 hours after injection (P < .05) and in the bone marrow at 24 and 48 hours after injection (P < .05). The signal intensity decrease in bone marrow was significantly stronger after injection of iron oxide-labeled cells compared to controls that received injections of the pure contrast agent (P < .05). Results of histopathologic examination confirmed homing of iron oxide-labeled human progenitor cells in the murine recipient organs. CONCLUSION: The in vivo distribution of intravenously administered iron oxide-labeled hematopoietic progenitor cells can be monitored with 1.5-T MR imaging equipment.     

Iron oxide nanoparticle-labeled rat smooth muscle cells: cardiac MR imaging for cell graft monitoring and quantitation

PURPOSE: To perform a quantitative analysis of anionic maghemite nanoparticle-labeled cells in vitro and determine the effect of labeling on signal intensity at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study was approved by the institutional animal care and use committee at H?pital Bichat. In vitro cell proliferation, iron content per cell, and MR signal intensity of cells were measured in agarose phantoms for 0-14 days of culture after labeling of rat smooth muscle cells with anionic maghemite nanoparticles. Next, iron oxide-labeled smooth muscle cells were injected into healthy hearts and hearts with ischemic injury in seven live Fisher rats. Ex vivo MR imaging experiments in excised hearts 2 and 48 hours after injection were performed with a 1.5-T medical imaging system by using T2-weighted gradient-echo and spin-echo sequences. Histologic sections were obtained after MR imaging. Correlation analyses between division factor of iron load and cell amplification factor and between 1/T2 and number of labeled cells or number of days in culture were performed by using linear regression. RESULTS: Viability of smooth muscle cells was not affected by magnetic labeling. Transmission electron micrographs of cells revealed the presence of iron oxide nanoparticles in vesicles up to day 14 of culture. Intracellular iron concentration decreased in parallel with cell division (r2 = 0.99) and was correlated with MR signal intensity (r2 = 0.95). T2*-weighted MR images of excised rat hearts showed hypointense signal in myocardium at 2 and 48 hours after local injection of labeled cells. Subsequent histologic staining evidenced iron oxide nanoparticles within cells and confirmed the presence of the original cells at 2 and 48 hours after implantation. CONCLUSION: Magnetic labeling of smooth muscle cells with anionic maghemite nanoparticles allows detection of cells with MR imaging after local transplantation in the heart.     

In vivo MR imaging of intravascularly injected magnetically labeled mesenchymal stem cells in rat kidney and liver

PURPOSE: To evaluate in vivo magnetic resonance (MR) imaging with a conventional 1.5-T system for depiction and tracking of intravascularly injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs). MATERIALS AND METHODS: This study was conducted in accordance with French law governing animal research and met guidelines for animal care and use. Rat MSCs were labeled with SPIO and transfection agent. Relaxation rates at 1.5 T, cell viability, proliferation, differentiation capacity, and labeling stability were assessed in vitro as a function of SPIO concentration. MSCs were injected into renal arteries of healthy rats (labeled cells in four, unlabeled cells in two) and portal veins of rats treated with carbon tetrachloride to induce centrolobular liver necrosis (labeled cells and unlabeled cells in two each). Follow-up serial T2*-weighted gradient-echo MR imaging and R2* mapping were performed. MR imaging findings were compared histologically. RESULTS: SPIO labeling caused a strong R2* effect that increased linearly with iron dose; R2* increase for cells labeled for 48 hours with 50 microg of iron per milliliter was 50 sec(-1) per million cells per milliliter. R2* was proportional to iron load of cells. SPIO labeling did not affect cell viability (P > .27). Labeled cells were able to differentiate into adipocytes and osteocytes. Proliferation was substantially limited for MSCs labeled with 100 microg Fe/mL or greater. Label half-life was longer than 11 days. In normal kidneys, labeled MSCs caused signal intensity loss in renal cortex. After labeled MSC injection, diseased liver had diffuse granular appearance. Cells were detected for up to 7 days in kidney and 12 days in liver. Signal intensity loss and fading over time were confirmed with serial R2* mapping. At histologic analysis, signal intensity loss correlated with iron-loaded cells, primarily in renal glomeruli and hepatic sinusoids; immunohistochemical analysis results confirmed these cells were MSCs. CONCLUSION: MR imaging can aid in monitoring of intravascularly administered SPIO-labeled MSCs in vivo in kidney and liver.     

MR Imaging–Based In Vivo Macrophage Imaging to Monitor Immune Response after Radiofrequency Ablation of the Liver

PurposeTo establish molecular magnetic resonance (MR) imaging instruments for in vivo characterization of the immune response to hepatic radiofrequency (RF) ablation using cell-specific immunoprobes.Materials and MethodsSeventy-two C57BL/6 wild-type mice underwent standardized hepatic RF ablation (70 °C for 5 minutes) to generate a coagulation area measuring 6–7 mm in diameter. CD68⁺ macrophage periablational infiltration was characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (n = 24). Twenty-one mice were subjected to a dose-escalation study with either 10, 15, 30, or 60 mg/kg of rhodamine-labeled superparamagnetic iron oxide nanoparticles (SPIONs) or 2.4, 1.2, or 0.6 mg/kg of gadolinium-160 (¹⁶⁰Gd)-labeled CD68 antibody for assessment of the optimal in vivo dose of contrast agent. MR imaging experiments included 9 mice, each receiving 10-mg/kg SPIONs to visualize phagocytes using T2¹-weighted imaging in a horizontal-bore 9.4-T MR imaging scanner, ¹⁶⁰Gd-CD68 for T1-weighted MR imaging of macrophages, or 0.1-mmol/kg intravenous gadoterate (control group). Radiological-pathological correlation included Prussian blue staining, rhodamine immunofluorescence, imaging mass cytometry, and immunohistochemistry.ResultsRF ablation–induced periablational infiltration (206.92 μm ± 12.2) of CD68⁺ macrophages peaked at 7 days after ablation (P < .01) compared with the untreated lobe. T2¹-weighted MR imaging with SPION contrast demonstrated curvilinear T2¹ signal in the transitional zone (TZ) (186 μm ± 16.9), corresponsing to Iron Prussian blue staining. T1-weighted MR imaging with ¹⁶⁰Gd-CD68 antibody showed curvilinear signal in the TZ (164 μm ± 3.6) corresponding to imaging mass cytometry.ConclusionsBoth SPION-enhanced T2¹-weighted and ¹⁶⁰Gd-enhanced T1-weighted MR imaging allow for in vivo monitoring of macrophages after RF ablation, demonstrating the feasibility of this model to investigate local immune responses.     

MR imaging with ultrasmall superparamagnetic iron oxide particles in experimental soft-tissue infections in rats

PURPOSE: To investigate the feasibility of macrophage magnetic resonance (MR) imaging in rats by using an experimental soft-tissue infection model. MATERIALS AND METHODS: Thirteen rats with unilateral calf-muscle infection were imaged with a 4.7-T MR imager at an early chronic stage of infection (day 4 before contrast material injection, days 4-7 after injection). Eleven animals were imaged before and 3 and 24 hours after intravenous application of ultrasmall superparamagnetic iron oxide (USPIO), and eight animals were additionally imaged 48 hours and three animals 72 hours after USPIO application. Two infected rats served as controls. T1- and T2-weighted spin-echo and T2*-weighted gradient-echo sequences were applied. All animals were sacrificed, and histopathologic findings were correlated with findings on MR images. Electron microscopy was performed in two rats. For quantitative analysis, signal intensities on T2*-weighted images and T2 values on T2 maps were measured within regions of interest, and the temporal variation was analyzed by using the signed rank test. RESULTS: Visualization of USPIO-loaded macrophages was most sensitive with a T2*-weighted sequence. USPIO distribution pattern and quantitative analysis of T2 and T2* effects 3 hours after USPIO application were significantly different (P <.05) from those at 24 and 48 hours, reflecting the dynamic transit of the particle accumulation from the intravascular to the intracellular compartment by means of macrophage phagocytosis. Local signal intensity alterations could be correlated with iron-loaded macrophages at histopathologic examination. CONCLUSION: Activated macrophages in acute soft-tissue infection can be labeled with USPIOs and detected with MR imaging because of susceptibility effects.     

In Vivo MR Imaging of Magnetically Labeled Mesenchymal Stem Cells in a Rat Model of Renal Ischemia

Objective

This study was designed to evaluate in vivo MR imaging for the depiction of intraarterially injected superparamagnetic iron oxide (SPIO)-labeled mesenchymal stem cells (MSCs) in an experimental rat model of renal ischemia.

Materials and Methods

Left renal ischemia was induced in 12 male Sprague-Dawley rats by use of the catheter lodging method. In vivo MR signal intensity variations depicted on T2*-weighted sequences were evaluated in both the left and right kidneys prior to injection (n = 2), two hours (n = 4), 15 hours (n = 2), 30 hours (n = 2) and 72 hours (n = 2) after injection of SPIO-labeled MSCs in both kidneys. Signal intensity variations were correlated with the number of Prussian blue stain-positive cells as visualized in histological specimens.

Results

In an in vivo study, it was determined that there was a significant difference in signal intensity variation for both the left and right cortex (40.8 ± 4.12 and 26.4 ± 7.92, respectively) and for both the left and right medulla (23.2 ± 3.32 and 15.2 ± 3.31, respectively) until two hours after injection (p < 0.05). In addition, signal intensity variation in the left renal cortex was well correlated with the number of Prussian blue stain-positive cells per high power field (r = 0.98, p < 0.05).

Conclusion

Intraarterial injected SPIO-labeled MSCs in an experimental rat model of renal ischemia can be detected with the use of in vivo MR imaging immediately after injection.     

Differentiation of hepatocellular carcinomas from hyperplastic nodules induced in rat liver with ferrite-enhanced MR imaging.

The potential of superparamagnetic ferrite particles in magnetic resonance (MR) imaging to help differentiate between hyperplastic nodular lesions in the liver and hepatocellular carcinomas was evaluated with chemically induced liver tumors in cirrhotic rats. Ferrite particles decreased the signal intensity of hyperplastic nodules but not that of hepatocellular carcinomas, and stainable iron was found in the former but not in the latter with Prussian blue iron stain. T1-weighted spin-echo images made little contribution to the differentiation between these two lesions, while T2-weighted spin-echo images were effective for this purpose, since ferrite particles cause T2 shortening. Ferrite-enhanced MR imaging may be useful in differentiating these two lesion types according to their signal intensity changes on images, because Kupffer cells are present in hyperplastic nodular lesions but rarely in hepatocellular carcinomas.     

Hepatocellular carcinoma in cirrhotic livers: double-contrast thin-section MR imaging with pathologic correlation of explanted tissue

OBJECTIVE: The aim of our study was to determine the sensitivity of double-contrast MR imaging in the detection of hepatocellular carcinomas in patients with a cirrhotic liver. SUBJECTS AND METHODS: Thirty-one patients underwent double-contrast MR imaging and subsequent liver transplantation. Breath-hold T1- and T2-weighted MR images were obtained before and after administration of superparamagnetic iron oxide, and three-dimensional T1-weighted gradient-recalled echo MR images were obtained 10, 40, and 120 sec after a bolus injection of gadolinium. Hypervascular lesions that failed to take up superparamagnetic iron oxide were regarded as showing typical characteristics of hepatocellular carcinoma; lesions that had only one of these two characteristics (either hypervascularity or failure to take up superparamagnetic iron oxide) were regarded as highly suspicious for hepatocellular carcinoma. Radiology reports were correlated with pathology reports for the explanted livers. RESULTS: Thirty-two hepatocellular carcinomas were found in 14 of the 31 patients. Combining the number of MR imaging reports citing lesions that were "typical of hepatocellular carcinoma" with the number of those citing lesions that were "highly suspicious," we found that for 25 of 32 lesions, an accurate MR imaging diagnosis of hepatocellular carcinoma was made (overall sensitivity, 78%). These lesions included 10 of the 11 lesions that were larger than 20 mm (sensitivity, 91%), 12 of the 13 lesions that were 11-20 mm (sensitivity, 92%), and three of the eight lesions that were 10 mm or less (sensitivity, 38%). Nineteen (76%) of 25 lesions had characteristics considered typical of hepatocellular carcinoma; the remaining six lesions either failed to take up superparamagnetic iron oxide and were hypovascular or were hypervascular but showed some uptake of superparamagnetic iron oxide. CONCLUSION: In patients with a cirrhotic liver, double-contrast MR imaging is highly sensitive in the diagnosis of hepatocellular carcinomas of 10 mm or larger, but success in the identification of tumors smaller than 10 mm is still limited.     

USPIO (Ferumoxtran-10)-enhanced MRI to visualize reticuloendothelial system cells in neonatal rats: feasibility and biodistribution study

Purpose

To investigate whether USPIO‐enhanced magnetic resonance imaging (MRI) detected reticuloendothelial system (RES) cells in newborn normal rats.

Materials and Methods

Newborn normal rats were imaged in vivo on a 1.5 T MR system, 2–96 hours after intraperitoneal Ferumoxtran‐10 (n = 38) or saline injection (control group, n = 5). Signals from liver, spleen, and vertebral bone marrow were measured (T2‐weighted Turbo Spin Echo) to describe the kinetics of enhancement. The pups were sacrificed and iron concentrations in plasma and peritoneal fluid were measured using atomic absorption spectrometry. Prussian blue‐labeled cells density in liver, spleen, and vertebral bone marrow was assessed.

Results

Significant (P < 0.05) negative enhancement of the liver, spleen, and vertebral bone marrow was noted after Ferumoxtran‐10 injection (2–96 hours for liver and spleen, 4–96 hours for bone marrow). Ferumoxtran‐10 was absorbed from the peritoneum in the first 8 hours postinjection, entering the circulation with a plasma peak (8 hours); then Ferumoxtran‐10 returned over the baseline in plasma (96 hours). Important intracellular iron deposition in liver and spleen was measured postinjection (3–96 hours, P < 0.05). Limited but significant intracellular iron deposition was noted in vertebral bone marrow postinjection (96 hours, P < 0.05), suggesting that Ferumoxtran‐10 selectively labeled RES cells after 96 hours and produced nonspecific labeling at earlier timepoints.

Conclusion

Ferumoxtran‐10‐enhanced MRI visualizes RES cells in vivo in newborn rats. J. Magn. Reson. Imaging 2008;28:1046–1052. © 2008 Wiley‐Liss, Inc.     

Iron-oxide labeling of hematogenous macrophages in a model of experimental autoimmune encephalomyelitis and the contribution to signal loss in fast imaging employing steady state acquisition (FIESTA) images

PURPOSE: To determine the contribution of blood-derived macrophages to the signal loss observed in MR images of inflammatory lesions in experimental autoimmune encephalomyelitis (EAE). MATERIALS AND METHODS: A relapsing-remitting form of EAE was induced in transgenic mice that express enhanced green fluorescent protein (EGFP) specifically in hematopoietic cells of the myelomonocytic lineage. Animals were injected with Feridex, a superparamagnetic iron oxide (SPIO) nanoparticle, 24 hours prior to in vivo MRI. MRI was performed using a 1.5T whole-body scanner; a high-performance, custom-built gradient coil insert; and a 3D steady-state free precession (SSFP) imaging pulse sequence. Comparisons were made between MR images and corresponding anti-GFP and Perl's Prussian blue (PPB)-stained brain sections. RESULTS: MR images revealed the presence of discrete regions of signal loss throughout the brains of EAE animals that were administered Feridex. Histological staining showed that regions of signal loss on MR images corresponded anatomically with regions of PPB- and GFP-positive cells. CONCLUSION: This experiment provides the first direct evidence that macrophages of hematogenous origin are labeled with SPIO after intravenous administration of Feridex, and contribute to the regions of signal loss detected in MR images of EAE brain.     

Detection of liver metastases: comparison of gadobenate dimeglumine-enhanced and ferumoxides-enhanced MR imaging examinations

PURPOSE: To compare gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance (MR) imaging with ferumoxides-enhanced MR imaging for detection of liver metastases. MATERIALS AND METHODS: Twenty consecutive patients known to have malignancy and suspected of having focal liver lesions at ultrasonography (US) underwent 1.0-T MR imaging with gradient-recalled-echo T1-weighted breath-hold sequences before, immediately after, and 60 minutes after Gd-BOPTA injection. Subsequently, MR imaging was performed with turbo spin-echo short inversion time inversion-recovery T2-weighted sequences before and 60 minutes after ferumoxides administration. All patients subsequently underwent intraoperative US within 15 days, and histopathologic analysis of their resected lesion-containing specimens was performed. Separate qualitative analyses were performed to assess lesion detection with each contrast agent. Quantitative analyses were performed by measuring signal-to-noise and contrast-to-noise ratios (CNRs) on pre- and postcontrast Gd-BOPTA and ferumoxides MR images. Statistical analyses were performed with Wilcoxon signed rank and Monte Carlo tests. RESULTS: Sensitivity of ferumoxides-enhanced MR imaging was superior to that of Gd-BOPTA-enhanced MR imaging for liver metastasis detection (P <.05). Ferumoxides MR images depicted 36 (97%) of 37 metastases detected at intraoperative US, whereas Gd-BOPTA MR images depicted 30 (81%) metastases during delayed phase and 20 (54%) during dynamic phase. All six metastases identified only at ferumoxides-enhanced MR imaging were 5-10 mm in diameter. There was a significant increase in CNR between the lesion and liver before and after ferumoxides administration (from 3.8 to 6.8, P <.001) but not before or after Gd-BOPTA injection (from -4.8 to -5.5, P >.05). CONCLUSION: Ferumoxides-enhanced MR imaging seems to be superior to Gd-BOPTA-enhanced MR imaging for liver metastasis detection. Copyright RSNA, 2002     

High field magnetic resonance imaging evaluation of superparamagnetic iron oxide nanoparticles in a permanent rat myocardial infarction

RATIONALE AND OBJECTIVES: The purpose of this study was to evaluate superparamagnetic iron oxide (SPIO) nanoparticles to discriminate infarcted from normal tissue after myocardial infarction using high field MR imaging (7 tesla).MATERIALS AND METHODS: Permanent myocardial infarction was induced in rats. SPIO nanoparticles (1 mg Fe/kg) were assessed with T1-weighted gradient echo sequence to visualize the myocardial infarction 48 hours after ligature (n = 6). Furthermore, MR Imaging was performed using a T2-weighted RARE sequence and nanoparticles were injected (5 or 10 mg Fe/kg) on 36 rats 5, 24 or 48 hours after infarction. RESULTS: No changes in contrast between normal and infarcted myocardium was observed after nanoparticle injection on T1-weighted images. However, nanoparticles induced a significant contrast increase between normal and infarcted myocardium on T2-weighted images whatever the delay between infarction and imaging (2.99 +/- 1.66 preinjection vs. 7.82 +/- 1.96 after SPIO injection at a dose of 5 mg Fe/kg 5 hours postinfarction, P = 0.0001). CONCLUSIONS: Nanoparticle injection made it possible to discriminate normal from infarcted myocardium on T2-weighted images. However, the high magnetic field prevented the visualization of the T1 effect of SPIO nanoparticles.     

Hepatocellular carcinoma in the cirrhotic liver: double-contrast MR imaging for diagnosis

PURPOSE: To measure the sensitivity and accuracy of double-contrast magnetic resonance (MR) imaging for the diagnosis of hepatocellular carcinoma (HCC) in the cirrhotic liver. MATERIALS AND METHODS: Twenty-seven patients with MR features of dysplastic nodules and/or HCC were examined. T2-weighted spin-echo and T1-weighted gradient-echo imaging was performed before and after superparamagnetic iron oxide (SPIO) administration and immediately followed by T1-weighted gradient-echo imaging at 10, 40, and 120 seconds after bolus injection of a gadolinium-based contrast material. Nonenhanced, nonenhanced plus SPIO-enhanced, and nonenhanced plus SPIO-enhanced plus gadolinium-enhanced images were reviewed. Alternative-free response receiver operating characteristic (ROC) methodology was used to analyze the results, which were correlated with histopathologic findings after transplantation in 15 patients and at biopsy in 12. Lesions visualized with all three techniques were characterized as a dysplastic nodule or HCC, and ROC analysis was performed. RESULTS: For all observers, SPIO-enhanced MR imaging (mean accuracy, 0.76) was more accurate than nonenhanced MR imaging (mean accuracy, 0.64) (P <.04), and double-contrast MR imaging (mean accuracy, 0.86) was more accurate than SPIO-enhanced imaging (P <.05). Both types of lesions were correctly characterized with all three techniques, although observer confidence for lesion characterization was greatest with double-contrast MR imaging. CONCLUSION: Double-contrast MR imaging significantly improves the diagnosis of HCC compared with SPIO-enhanced and nonenhanced imaging (P <.01).     

磁性标记的小胶质细胞在大鼠脑内的MR示踪

目的 探讨超顺磁性氧化铁颗粒(SPIO)标记的小胶质细胞在正常大鼠及阿尔茨海默病(AD)大鼠体内移植后,MR活体示踪的可行性.方法 以日本血液凝集病毒包膜(HVJ-E)为标记载体,将SPIO标记的小胶质细胞经颈内动脉注入正常大鼠(5只)及AD大鼠动物模型(5只)体内,3 d后应用7.0 T MR行T2*序列扫描,并与脑组织切片组织化学染色结果对照.结果 在正常大鼠脑内,MRI可见数个点状的信号改变区,这些信号改变区散在地分布在脑内各处,脑组织切片显示铁颗粒标记细胞位置与信号改变部位一致.MRI能够检测到由数个标记细胞引起的信号强度的改变.在AD大鼠模型脑内,MRI可见β-淀粉样蛋白42(Aβ42)注射区信号强度明显下降,信号改变区面积较大.与之相比,生理盐水注射区信号改变的强度及面积均不如Aβ42注射区改变明显.Aβ42注射区的标记细胞数为(454±47)个/mm2,明显高于生理盐水注射区的标记细胞数(83±13)个/mm2(P<0.05).结论 MRI可作为一种非侵入性检测手段在活的动物体内追踪标记细胞,在AD细胞水平的治疗中具有一定临床应用前景.     

超急性期放射性肝损伤MRI菲立磁增强与照射剂量相关性研究

目的　探讨MRITSE -T2 WI菲立磁增强扫描对超急性期放射性肝损伤的诊断与评估价值。方法　 2 5只家兔随机分成 5组。除对照组外 ,其余 4组分别给予 10、2 0、3 0、40Gy单次X线半肝照射。照射后第 3天对肝区行MRITSE -T2 WI平扫及菲立磁增强扫描。分析辐照后肝组织损伤的强化特征 ,并进行组织学检查对照分析。结果　T2 WI菲立磁增强扫描在照射后第 3天能确切检出的放射性肝损伤的最小照射剂量为 3 0Gy(Ρ <0 .0 5 ) ,表现为受照区肝组织信号强度较非受照区高 ,两者间可见分界线。受照区肝组织菲立磁增强程度 (ER)的绝对值与照射剂量成正相关 (Ρ <0 .0 5 )。所有家兔受照区肝组织在光镜下未见明确组织水肿、纤维化及炎症细胞浸润等病理征象 ,但其单位视野面积内含有SPIO颗粒的Kupffer细胞数在≥ 2 0Gy组明显低于非受照区 (Ρ <0 .0 5 ) ,且与照射剂量成负相关 (Ρ <0 .0 5 )。结论　T2 WI菲立磁增强扫描不仅能早期发现 (照射后第 3天 )、明确诊断超急性期放射性肝损伤 ,还可通过测量肝组织ER对损伤程度进行估测。