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.     

肝脏占位性病变的磁共振成像研究：超顺磁性氧化铁与钆喷替酸葡甲胺的比较

通过与常用造影剂钆喷替酸葡甲胺（Gd-DTPA）的配对实验来评价新型造影剂超磁性氧化铁（SPIO）对有肝占位的检出率和定性诊断能力。材料和方法：53个病例132个肝占位首日行平扫及Gd-DTPA的动态增强扫描,次日行SPIO增强扫描,对照病理及临床随访证实结果,探讨各种占位SPIO增强扫描的强化特点,比较平扫联合Gd-DTPA动态增强扫描与平扫联合SPIO增强扫描的病灶检出率和定性诊断率。结果：SPIO增强扫描良性肝占位的信号随肝实质降低,而恶性肝占位的信号保持不变。平扫联合SPIO增强扫描的病灶检出率和定性诊断率较平扫联合Gd-DTPA增强扫描的略高,但统计学上相差不显著。结论：SPIO强化的原理、强化方式直至临床应用方法、特点与Gd-DTPA均完全不同,两者可相互补充和印证,当Gd-DTPA动态增强扫描定性诊断困难时应积极行SPIO增强扫描。     

急性心肌梗塞的SPIO磁共振增强实验

目的：研究超顺磁性氧化铁（ＳＰＩＯ）ＭＲ造影剂对犬急性心肌梗塞的诊断作用。材料和方法：用直接冠状动脉结扎法建立８只犬急性心肌梗塞模型；采用ＥＣＧ门控ＳＥ序列分别获增强前、后（静注ＳＰＩＯ剂量为１０ｍｇＦｅ／ｋｇ）犬心脏Ｔ２ＷＩ像，计算梗塞区的信号对比度／噪声比（ＣＮＲ）。结果：ＳＰＩＯ静注后３０ｍｉｎ，正常灌注心肌信号中等度下降，而梗塞区仍保持相对高信号，梗塞区ＣＮＲ由平扫的１．１３±０．１５提高至１．７３±０．２４。ＳＰＩＯ强化后显示的高信号心梗区，与ＴＴＣ离体心脏切片染色证实的梗塞区吻合。结论：ＳＰＩＯ是一种有价值的、潜在的心脏磁化率效应造影剂。     

Iron particle-enhanced visualization of inflammatory central nervous system lesions by high resolution: preliminary data in an animal model

BACKGROUND AND PURPOSE: The detection of cell infiltration is critical for the diagnosis and monitoring of inflammatory disorders, especially in the central nervous system (CNS). Superparamagnetic iron oxide (SPIO) particles have recently been introduced as a contrast agent to detect macrophage migration in vivo by MR imaging. We tested the hypothesis that focal hyperechogenicity due to SPIO-laden macrophages can also be visualized on high-resolution sonography. METHODS: Experimental autoimmune encephalomyelitis (EAE) was induced by myelin-oligodendrocyte glycoprotein (MOG) in congenic Lewis rats, an animal model mimicking many aspects of human multiple sclerosis. At the height of disease, rats underwent MR imaging with a 1.5T unit. Animals were injected with SPIO particles 24 hours before imaging. Control rats either received no contrast agent or were injected with SPIO particles without prior induction of EAE. Immediately after MR imaging, the rats were sacrificed, and the brains were removed and placed in saline. Sonography was performed directly after brain removal. Brains were embedded in paraffin, and sections were stained for iron with Perls stain and for macrophages with ED1 immunohistochemistry. RESULTS: SPIO-enhanced sonography of rat brains during a relapse of EAE specifically showed marked focal echogenicity in EAE-typical areas of the brain, including the periventricular region, the cerebellum, and the brain stem. The sonographic results corresponded to in vivo MR imaging findings of the respective animals as well to the clinical symptoms of EAE and to histology showing iron-laden macrophages in demyelinated lesions. CONCLUSION: SPIO particles allow the detection and demarcation of inflammatory CNS lesions on sonograms by specific macrophage imaging.     

超小超顺磁性氧化铁粒子标记免疫细胞在多发性硬化症动物模型MRI中的应用

超小超顺磁性氧化铁粒子(USPIO)是一种外周包裹右旋糖酐的氧化铁纳米颗粒,可以被多种细胞吞噬,主要为单核巨噬细胞。由于其含铁,在T2和T2*加权磁共振(MR)图像上产生低信号。多发性硬化症(MS)是一种发生在中枢神经系统的自身免疫性脱髓鞘性疾病,实验性变态反应性脑脊髓炎(EAE)为其常用的动物模型,T细胞、单核巨噬细胞在疾病的发生、发展中起着重要作用,参与病程的各个阶段。USPIO标记免疫细胞MRI可以在体监测MS、EAE病灶的炎性细胞浸润情况,对疾病的复发、发展、早期诊断以及疗效监测均具有重要意义。     

超顺磁性氧化铁诊断肝脏小病灶的临床应用价值初探

目的：探讨超顺磁性氧化铁（商品名为菲立磁,Feridex)对肝脏小病灶的临床应用价值,以及滴注后的最佳扫描时间。方法：17例经B超或CT检查发现肝脏内小病灶患者,经常规MR平扫和增强扫描1－3d后,经静脉滴注菲立 （0.05ml/kg),并于0.5,3.6h后进行扫描。主观目测菲立磁增强后肝脏小病灶的显示情况,定量分析菲立磁增强后肝脏信号下降情况。结果;菲立磁增强后扫描可显著肝脏内直径小于1cm的病灶21个,明显多于常规MR检查（8个）。菲立磁应用后小肝癌和容易与肝癌混淆的局灶性结节增生和再生结节信号变化明显不同。菲立磁增强后扫描,肝脏T2WI,T1WI信号均较增强前下降（P＜0．01）,滴注菲立磁后0.5,3,6h扫描,T2WI各时间点的脏脏信号下降统计学上差异无显著性意义（P＞0．05）。结论：菲立磁能显著提高肝脏小病灶的检出率,而且对肝脏小病灶的鉴别诊断可提供有利的依据。     

家兔超急性期放射性肝损伤MRI表现与病理对照研究

目的　探讨超急性期放射性肝损伤MRI表现及其病理基础 ,评估MRI平扫及菲立磁增强扫描检出放射性肝损伤的时间效能。材料与方法　 18只家兔随机分成 3组后均给予 4 0Gy单次X线半肝照射 ,第 1组于照射后第1d、第 2、3组分别于照射后第 2、3d行肝区MRITSE T2 WI及TSE T1WI两个序列的平扫及菲立磁增强扫描 ,同时取材做组织学检查。对MRI表现与病理组织学检查结果进行对照分析。结果　所有家兔T2 WI及T1WI平扫、T1WI菲立磁增强扫描肝组织信号强度均未发现变化。T2 WI菲立磁增强扫描对放射性肝损伤的检出时间为照射后第 3d(P <0 .0 1) ,表现为肝组织信号强度受照区与非受照区均较T2 WI平扫时降低 ,但受照区肝组织信号强度较非受照区高 ,两者间可见分界线。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细胞数在照射后第 3d明显低于非受照区 (P <0 .0 1)。电镜下 ,照射后第 3d的受照区肝细胞及Kupffer细胞内见线粒体明显肿胀伴局部空泡样变。结论　T2 WI菲立磁增强扫描在照射后短时间内 (照射后第 3d)即可检出超急性期放射性肝损伤 ,并能提供直观、精细的影像学依据     

急性实验性变态反应性脑脊髓炎模型的MRI表现及其病理基础

目的 探讨急性实验性变态反应性脑脊髓炎(EAE)模型的MRI表现及其病理基础.方法 用豚鼠全脑脊髓匀浆诱导EAE大鼠模型(6只),观察其体重变化和临床表现,同时设对照组(6只).在EAE大鼠发病后进行MR常规扫描、钆剂增强扫描,并静脉使用超小超顺磁性氧化铁(USPIO),24 h后行USPIO增强扫描,扫描完毕立即处死大鼠取脑,行脑组织切片的HE染色、髓鞘染色和普鲁士蓝染色.观察MRI和病理检查的异常所见,并进行对照.结果EAE大鼠组在诱导后第8～9天开始体重下降,在第10～11天出现临床症状.MR常规扫描未见明确异常,钆剂增强后仅见脑膜弥漫增厚及增强,USPIO增强扫描可见T2WI上延髓实质内大片低信号区,T1WI可见对应部位的高信号.梯度回波T2*WI比T2WI显示在脑干病灶以外的小脑白质内低信号.临床评分高的大鼠其低信号范围也较大.对照组大鼠未见异常.病理检查发现发病大鼠脑白质内散在血管套袖,部分伴相邻区域的脱髓鞘改变.普鲁士蓝染色发现病灶内巨噬细胞胞质内有蓝染颗粒,沉积部位与T2WI上低信号对应.结论USPIO增强MRI可以揭示常规MRI和钆剂增强成像未能显示的急性EAE病变,活体显示EAE病灶内巨噬细胞的分布,具有重要的研究价值和应用前景.     

大鼠肝硬化肝癌SPIO增强MRI表现与Kupffer细胞的关系

目的：建立二乙基亚硝胺（DENA）诱导的大鼠肝硬化肝细胞癌（HCC）模型,探讨超顺磁性氧化铁（SPIO）增强MRI上肝硬化肝癌信号改变与肝Kupffer细胞（KCs）之间的关系。方法：22只大鼠肝硬化肝癌模型,其中6只为单纯性肝硬化,16只为肝硬化肝癌,对照组为10只清洁级Wistar雄性大白鼠,均行SPIO增强前后T1WI和T2WI扫描,并行病理检查（HE染色及普鲁士蓝染色）,分析肝脏Kupffer细胞数量与SPIO增强后信号之间的关系。结果：普鲁士兰染色切片上肝硬化组织内蓝染Kupffer细胞数量略减少,蓝色颗粒不均匀;高分化肝癌中Kupffer细胞减少,低分化肝癌Kupffer细胞显著减少甚至消失。肝癌与正常肝实质、硬化肝组织相比,Kupffer细胞数量减少,差异有显著性意义（P〈0．001）;正常肝实质与肝硬化组织内Kupffer细胞数量的差异无显著性意义（P＝0．088）。SPIO增强T2WI上,正常肝实质、肝硬化组织信号强度（SI）较增强前明显下降,信号强度下降百分比（PSIL）分别为42％和38％,两组间差异无统计学意义（P＝0．409）;肝癌信号强度较增强前无明显下降,PSIL为12％,明显低于正常肝实质和肝硬化组织（P〈0．001）;SPIO增强后肝癌对比噪声比（CNR）较增强前显著提高（P＝0．002）。SPIO增强T1WI上。正常肝实质及硬化肝组织PSIL分别为15％和6％,而肝癌的信号强度较增强前升高9％,部分小病灶呈不均匀轻度强化,肝癌CNR较增强前明显降低（P〈0．001）。SPIO增强T2WI上,肝组织PSIL与Kupffer细胞数量呈曲线趋势,随着组织内Kupffer细胞数量的增多病灶信号强度下降程度越明显,曲线估计3次模型决定系数R^2为0．920,有显著性意义（P〈0．001）。结论：SPIO增强T2WI上肝脏信号强度改变与Kupffer细胞数量及其吞噬功能有相关性,随着Kupffer细胞增多PSIL呈升高趋势。SPIO增强MRI不?     

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.     

Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyperlipidemic rabbits

RATIONALE AND OBJECTIVES: Inflammatory atherosclerotic plaques are characterized by increased endothelial permeability and multiple macrophages. Blood-pool MRI contrast agents like superparamagnetic iron oxide (SPIO) have an affinity for the monocyte-macrophage system and thus, may label inflammatory plaques. The objective was to demonstrate SPIO uptake in plaques of atherosclerotic rabbits by MRI and histology. METHODS: Aortas of anesthetized Watanabe hereditable hyperlipidemic rabbits were studied with a moderately T2*-weighted gradient-echo sequence at 1.5 T. Four groups of five animals each were studied: (1) without ultrasmall SPIO (carboxydextran coating; particle size, 25 nm; estimated plasma half-life, 6 hours) or with imaging after intravenous injection of SPIO at a dose (micromol Fe/kg) and postcontrast time delay (hours) of 50/8 (2), 50/24 (3), or 200/48 (4). In vivo MRI was compared with corresponding ex vivo histological iron stains. RESULTS: Animals receiving 200 micromol Fe/kg demonstrated areas of focal signal loss clearly confined to the aortic wall on a mean of 24 +/- 9 (31% +/- 11%) of 76 +/- 5 images compared with 0 +/- 0 of 76 +/- 5 images in controls (P = 0.009). The number of images with this finding in groups 2 and 3 was not significantly different compared with controls. By microscopy, SPIO-iron was seen in the endothelial cells and subendothelial intimal macrophages of atherosclerosis-prone aortic wall segments. Atherosclerotic lesions demonstrating iron uptake also showed a high macrophage content. CONCLUSIONS: SPIO accumulates in aortic plaques of atherosclerotic rabbits, producing a characteristic MRI finding. As SPIO accumulates in plaques with increased endothelial permeability and a high macrophage content, two established features of plaque inflammation, it may have a potential for noninvasive assessment of inflammatory atherosclerotic plaques.     

菲立磁增强MRI检测肝脏占位病变与三期动态增强CT扫描的比较研究

目的　比较菲立磁增强MRI和增强CT扫描在肝脏实性占位病变检测中的应用价值。方法　对 18例肝内局灶性占位患者行MR平扫及菲立磁增强扫描。观察肝脏与病灶信号强度变化 ,形态及数目 ,比较增强前后T2 WI病灶及肝脏的信噪比 (SNR)及对比噪声比 (CNR) ,做出MRI定性诊断 ,并与增强CT扫描诊断进行比较。其中肝细胞肝癌 4例 ,复发性肝癌 4例 ,转移瘤 4例 ,肝血管瘤 6例。结果　菲立磁增强明显降低正常肝组织信号强度 ,而恶性肿瘤的信号强度无强化 ,病灶—肝脏信噪比增加可清晰显示病变 ,并发现新病灶。肝血管瘤的血池效应与增强CT扫描比较有鉴别诊断意义。结论　做为增强CT扫描和Gd -DTPAMR增强的补充方法 ,SPIO增强MRI对肝脏占位病变的显示 ,小病灶发现和定性诊断中有重要的临床意义     

Fractionated Feridex and positive contrast: in vivo MR imaging of atherosclerosis.

Macrophages have been identified as a critical factor in the pathogenesis of atherosclerosis. Ultrasmall iron oxide particles (USPIOs) have been used to passively target intraplaque macrophages. For dextran-based USPIOs, uptake into macrophages may be modulated by particle size. The aim of the current study was to test the efficacy of fractionated Feridex with respect to macrophage uptake in atherosclerotic rabbits. Fractionation of Feridex resulted in a 15-nm USPIO that exhibited a blood half-life of 15.9 h and liver retention of 6.4%. Blood clearance and liver retention of Feridex was 0.46 h and 60%, following administration of 4.8 mg Fe/kg Feridex. Atherosclerotic rabbits were administered 0.5 or 4.8 mg Fe/kg dosages of either fractionated Feridex or Feridex. MRI was performed at 1.5T over a 24-h time period postinjection. Perls and RAM-11 staining was performed to identify iron deposition. MRI showed a dose-dependent signal loss using conventional gradient echo (GRE) sequences following administration of fractionated Feridex. Even at low dose, significant signal loss was observed that correlated with histology. No signal attenuation or iron deposition was observed in the vessel wall of rabbits administered Feridex. Results of this study suggest that it may be possible to optimize USPIOs for intraplaque macrophage detection.     

In vivo MR imaging of bone marrow cells trafficking to atherosclerotic plaques

PURPOSE: To develop a magnetic resonance imaging (MRI)-based method to monitor in vivo trafficking of bone marrow (BM) cells to atherosclerotic lesions. MATERIALS AND METHODS: BM cells from LacZ-transgenic mice were labeled with a superparamagnetic iron oxide (Feridex) and then transplanted into ApoE(-/-) recipient mice that were fed an atherogenic diet. Twenty-four ApoE(-/-) mice were divided into three study groups: 1) group I with Feridex-labeled BM transplantation (BMT) cells (N = 9), 2) group II with unlabeled BMT cells (N = 10), and 3) group III with no BMT cells (N = 5). Migrated Feridex/LacZ-BM cells to atherosclerotic aortic walls were monitored in vivo using a 4.7T MR scanner and correlated with histopathological findings. RESULTS: In group I with Feridex-BMT cells, histology examination displayed plaques in five of nine animals. In four of these five animals, in vivo MRI showed large MR signal voids of the aorta walls (due to the "blooming" effect of migrated Feridex-BM cells in plaques), which were correlated with Feridex- and/or LacZ-positive cells detected in the atherosclerotic lesions. No signal voids could be visualized in the two control animal groups (groups II and III). CONCLUSION: This study demonstrates the potential use of in vivo MRI to monitor the trafficking of magnetically labeled BM cells to atherosclerotic lesions.     

Magnetic resonance imaging of atherosclerotic plaques using superparamagnetic iron oxide particles

Experimental data show accumulation of superparamagnetic iron oxide (SPIO) particles in atherosclerotic plaques. SPIO uptake occurred in plaques, suggesting an increased endothelial permeability and macrophage infiltrates as signs of inflammatory plaque activity. We incidentally observed SPIO uptake in aortic and arterial wall segments in patients who had originally received the magnetic resonance (MR) contrast agent for staging lymph node metastases. Twenty patients (19 male, 1 female; mean age, 64; range, 41-78 years) with bladder or prostate cancer underwent MR imaging (MRI) using a T2*-weighted high-resolution gradient-echo sequence prior to and 24-36 hours after intravenous injection of 2.6 mg of Fe/kg of SPIO (Sinerem). The aorta, both common external and internal iliac, as well as both superficial femoral arteries, were retrospectively analyzed for atherosclerotic wall changes. One patient was excluded. A positive finding was defined as an area of pronounced signal loss on postcontrast images clearly confined to the arterial wall, which was absent in the precontrast examination or increased in size. Such a finding was observed in one to three arteries in 7 of the 19 patients. The pronounced signal loss in the wall of the aorta and pelvic arteries seen in part of an elderly patient population after intravenous SPIO administration strongly suggests that this contrast agent accumulates in human atherosclerotic plaques.     

Iron particles enhance visualization of experimental gliomas with high-resolution sonography

BACKGROUND AND PURPOSE: Intraoperative MR imaging and sonography are used for navigation during neurosurgical procedures. The purpose of this experimental study was to evaluate the potential of high-resolution sonography using superparamagnetic iron oxide (SPIO) particles as a contrast medium to delineate brain tumors and to relate these findings with those of MR imaging. METHODS: C6 gliomas were implanted in 36 rats. Eleven days after tumor implantation, the animals underwent MR imaging with a 1.5-T MR imaging unit. Twelve animals received gadopentetate dimeglumine immediately before the MR examination, 12 animals were injected with SPIO particles 24 hours before MR imaging, and 12 animals received no contrast agent. Immediately after MR imaging, the animals were sacrificed and their brains were removed and placed in saline. Sonography was performed instantly after brain removal. Brains were embedded in paraffin, and sections were stained for iron with Perl's stain and for macrophages with ED-1 immunohistochemistry. RESULTS: At MR imaging, the tumors appeared hyperintense on T2-weighted and gadolinium-enhanced T1-weighted images. After application of SPIO particles, they became markedly hypointense on T2-weighted images and hypo- to hyperintense on T1-weighted images. On sonograms, gliomas were iso- to slightly hyperechoic to normal brain parenchyma on nonenhanced and on gadolinium-enhanced images. After application of SPIO particles, tumors became markedly hyperechoic and were distinctly demarcated from the surrounding brain tissue. CONCLUSION: SPIO particles improved the detection and demarcation of the experimental gliomas on sonograms, which may improve intraoperative neuronavigation with sonography.     

Applicability and limitations of MR tracking of neural stem cells with asymmetric cell division and rapid turnover: the case of the shiverer dysmyelinated mouse brain.

LacZ-transfected C17.2 neural stem cells (NSCs) were labeled with the superparamagnetic iron oxide formulation Feridex prior to ICV injection in shi/shi neonates. Feridex labeling did not alter cell differentiation in vitro and in vivo. Initially, MR images obtained at 11.7T correlated closely to NSC distribution as assessed with anti-dextran and anti-beta-galactosidase double-fluorescent immunostaining. However, at 6 days postgrafting there was already a pronounced mismatch between the hypointense MR signal and the histologically determined cell distribution, with a surprisingly sharp cutoff rather than a gradual decrease of signal. Positive in vivo BrdU labeling of NSCs showed that significant cell replication occurred post-transplantation, causing rapid dilution of Feridex particles between mother and daughter cells toward undetectable levels. Neural differentiation experiments demonstrated asymmetric cell division, explaining the observed sharp cutoff. At later time points (2 weeks), the mismatch further increased by the presence of non-cell-associated Feridex particles resulting from active excretion or cell death. These results are a first demonstration of the inability of MRI to track rapidly dividing and self-renewing, asymmetrically dividing SCs. Therefore, MR cell tracking should only be applied for nonproliferating cells or short-term monitoring of highly-proliferative cells, with mitotic symmetry or asymmetry being important for determining its applicability.     

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.     

Macrophage infiltration into the rat knee detected by MRI in a model of antigen-induced arthritis.

Three-dimensional (3D) MR images were obtained from the knees of rats in a model of antigen-induced arthritis, elicited by the intraarticular administration of methylated bovine serum albumin (mBSA) to previously immunized rats. Superparamagnetic particles of iron oxide (SPIO) were administered i.v. 24 hr before each imaging session. Starting 4 days postantigen injection, images from arthritic knees exhibited distinctive signal attenuation in the synovium. This signal attenuation was significantly smaller in knees from animals treated with dexamethasone, a glucocorticosteroid, and completely absent in contralateral knees that had been challenged with vehicle. A significant negative correlation was found between the MRI signal intensity in the synovium and the histologically determined iron content in macrophages located in the same region. These results suggest the feasibility of detecting macrophage infiltration into the knee synovium in this model of antigen-induced arthritis by labeling the cells with SPIO. This readout could provide an early marker of disease progression, before more aggressive changes like cartilage and bone erosion take place. Monitoring early changes associated with arthritis can have an impact in preclinical studies by shortening the duration of the experimental period and by facilitating the investigation of novel immunomodulatory therapies acting on macrophages. Also, the approach can be potentially adapted to clinical studies.     

A physiological barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery

BACKGROUND AND PURPOSE: Osmotic disruption of the blood-brain barrier (BBB) provides a method for transvascular delivery of therapeutic agents to the brain. The apparent global delivery of viral-sized iron oxide particles to the rat brain after BBB opening as seen on MR images was compared with the cellular and subcellular location and distribution of the particles. METHODS: Two dextran-coated superparamagnetic monocrystalline iron oxide nanoparticle contrast agents, MION and Feridex, were administered intraarterially in rats at 10 mg Fe/kg immediately after osmotic opening of the BBB with hyperosmolar mannitol. After 2 to 24 hours, iron distribution in the brain was evaluated first with MR imaging then by histochemical analysis and electron microscopy to assess perivascular and intracellular distribution. RESULTS: After BBB opening, MR images showed enhancement throughout the disrupted hemisphere for both Feridex and MION. Feridex histochemical staining was found in capillaries of the disrupted hemisphere. Electron microscopy showed that the Feridex particles passed the capillary endothelial cells but did not cross beyond the basement membrane. In contrast, after MION delivery, iron histochemistry was detected within cell bodies in the disrupted hemisphere, and the electron-dense MION core was detected intracellularly and extracellularly in the neuropil. CONCLUSION: MR images showing homogeneous delivery to the brain at the macroscopic level did not indicate delivery at the microscopic level. These data support the presence of a physiological barrier at the basal lamina, analogous to the podocyte in the kidney, distal to the anatomic (tight junction) BBB, which may limit the distribution of some proteins and viral particles after transvascular delivery to the brain.