采用自制超小超顺磁性氧化铁行兔VX2肿瘤MR成像

目的 观察自制USPIO在兔VX2肿瘤MR成像中的价值.方法 以一步法实现葡聚糖对Fe_3O_4纳米粒子的表面包裹,制备USPIO.7只新西兰大白兔双侧大腿肌肉内接种VX2肿瘤;6只于接种后2周分别行Gd-DTPA和USPIO T2~*WI增强扫描.1只未注射对比剂的实验兔留电镜和元素分析作对照研究.计算不同对比剂的病灶对比度噪声比(CNR)和增强对比度.MR成像结束后,行普鲁士蓝染色、电镜及元素分析.结果 经傅立叶变换红外光谱仪证实,葡聚糖成功包裹到Fe_3O_4磁性纳米粒子的表面;且合成USPIO大小在10～20 nm,分散性较好.增强扫描中两种对比剂的CNR差异有统计学意义(P<0.005).病理、电镜及元素分析共同证实肿瘤组织与正常肌肉USPIO的含量有显著差异.结论 VX2肿瘤血管基底膜对USPIO具有高通透性.USPIO T2~*WI增强扫描可以提高肿瘤组织的增强效果.自制USPIO可被肿瘤细胞吞噬,是用于肿瘤成像的理想对比剂.     

超顺磁性氧化铁纳米粒子在脑磁共振成像中的应用

超顺磁性氧化铁纳米粒子的磁性及生物相容性,使其在生物医学多个领域的应用研究都逐渐发展起来。本文介绍磁共振成像（MRI）及脑功能磁共振成像（fMRI）基本原理。列举不同性能的磁性氧化铁粒子作为磁共振成像对比剂在脑科学应用中的研究进展。表面结合单克隆抗体、蛋白质、多肽、核苷酸分子或其它特殊聚合物的磁性氧化铁粒子具有吸收特异性（靶向性）,结合MRI可实现对脑部病变前期改变、药物输运及治疗的监测,对细胞、生物分子包括mRNA的成像及探测。经葡聚糖或聚乙二醇修饰的超顺磁性氧化铁纳米粒子血液半衰期较长,可作为对比剂用于脑fMRI成像。控制氧化铁纳米粒子的粒度及表面修饰物的物理化学性质、提高饱和磁化强度、借以接枝以各种靶向性的物质、开发具有荧光-磁性等多种性能的复合纳米粒子及掌握纳米粒子与生物分子、细胞、及生物组织之间的相互作用,则需要更深入的研究。     

超顺磁性氧化铁粒子增强MR成像在脾脏荷VX2肿瘤动物模型的影像学与病理学对照研究

目的：建立大鼠脾脏VX2肿瘤模型，分析大鼠脾VX2肿瘤超顺磁性氧化铁（SPIO）增强MR图像上信号强度变化与病理学改变之间的关系。探讨SPIO增强MR在大鼠脾脏转移瘤的应用价值。材料和方法：制作8只脾脏荷VX2肿瘤模型鼠，注射SPIO后行MR扫描，扫描序列采用T1WI（450/12ms)和T2WI（4000/128ms）。分析SPIO增强扫描前后MR图像上不同组织的信号特点。结果：SPIO增强T2WI MR图像上正常脾实质信号强度下降百分比（PSIL）为55.04％；脾脏VX2肿瘤PSIL为0.87％，与正常脾实质的信号强度下降程度有显著性差异（P<0.001）。脾VX2肿瘤的CNR较增强前显著提高（P<0.001）。结论：SPIO增强T2WI MR图像上脾脏－肿瘤的对比显著，提高了病灶的检出率，改善了病灶的影像学特征的描述。     

超小型超顺磁性氧化铁颗粒小鼠胰腺增强磁共振成像

目的 探讨超小型超顺磁性氧化铁颗粒(USPIO)小鼠胰腺增强磁共振成像方法.方法 BALb/c小鼠23只,分A、B、C、D四组,每组5只,另外1只小鼠用来研究小鼠胰腺的解剖位置;2只用来注射USPIO前后自身对比.A、B两组确定麻醉剂量后,C、D两组分别为注射USPIO和正常对照组,均采用GE Signa Horizon LX 1.5T双梯度磁共振仪行双回波序列扫描并建立图像定量分析方法,并使用USPIO增强MRI扫描,计算T2值并观察注射USPIO前后胰腺区域影像学改变.结果 使用1.5T磁共振仪及小鼠实验专用线圈在T2序列获得小鼠横断面、矢状位、冠状位图像,图像清晰,能分辨各组织器官.增强磁共振可确定小鼠胰腺所在横断面图像中的层面及具体位置.注射USPIO后和未注射USPIO的胰腺的区域,T2值比较差异有统计学意义(P<0.05).结论 超小型USPIO小鼠胰腺增强MR扫描为检测小鼠胰腺胰岛炎奠定方法学基础.     

超顺磁性氧化铁标记骨髓间充质干细胞的磁共振成像研究

目的明确顺磁性氧化铁纳米粒子(SPIO)体外标记兔骨髓间充质干细胞(MSCs)的适当浓度和不同标记浓度对细胞的生物学活性影响,以及经MR成像的特征和可成像的最低标记细胞量等。方法分离、纯化、培养兔MSCs,体外不同浓度SPIO标记,荧光显微镜观察铁颗粒在细胞内的位置、不同标记浓度下的最佳孵育时间、不同标记浓度细胞形态的改变、细胞内铁颗粒的分布及标记率;测量并绘制未标记细胞和标记细胞的MTT生长曲线;选取适当浓度标记量,对不同细胞量组进行标记后MR成像,测量不同扫描序列标记细胞管的信号强度改变,并进行统计学分析。结果标记后的铁颗粒均位于细胞质内;20～50μgFe/ml培养液是SPIO标记干细胞的适当浓度阈值,超过50μgFe/ml培养液浓度可使细胞的变形增殖能力受到不同程度的抑制;在此浓度阈值标记后孵育18～24h即可有效标记细胞97%～100%;细胞对铁颗粒的吸收与细胞的数量、标记浓度和孵育时间呈正相关;SPIO标记的MSCs在T2WI尤其是FFE(T2WI)序列信号明显降低;在35μgFe/ml培养液标记浓度下,MR可成像的最低细胞量为5×104;35μgFe/ml培养液浓度时,标记细胞1×105和5×104MR成像可使T2WI、FFE图像信号均降低,而且没有使靶灶扩大的磁敏感伪影。结论SPIO可以简便标记MSCs并且在适当浓度下对MSCs的生物学活性没有影响,MRT2WI和T2WI序列可敏感显像磁性标记的干细胞。     

超顺磁性氧化铁对肝脏MR成像效果的影响

目的 观察超顺磁性氧化铁(SPIO)对肝脏MR成像效果的影响.方法 用化学共沉淀法制备具有肝脏特异性的MR对比剂SPIO,分别将生理盐水、SPIO样品及目前临床广泛使用的Gd-DTPA注入30只大白兔体内,5 min、30 min、60 min后进行MR成像,分别测量肝脏和背部肌肉的信号强度并计算相对信号强度比(相对信号强度比＝肝脏信号强度/肌肉信号强度).结果 Gd-DTPA使肝脏T1WI相对信号强度比(ENH)显著升高,但30 min即开始恢复,持续时间短,SPIO使肝脏T2WI相对信号强度比显著降低,60 min仍能维持高ENH,持续时间长.结论 SPIO具有良好的晶体结构和均匀的纳米尺寸,能显著降低肝脏MR T2WI相对信号强度比,可作为MRI阴性对比剂.     

超顺磁性纳米氧化铁颗粒标记胰腺癌细胞的MR分子成像

目的 探讨超顺磁性纳米氧化铁颗粒（SPION）靶向标记胰腺癌细胞（BxPC-3）行MR分子成像的可行性。方法 制备黏蛋白1（MUC1）靶向修饰的探针MUC1-SPION（靶向组）,并以牛血清蛋白（BSA）制备非靶向探针BSA-SPION（非靶向组）。采过噻唑蓝（MTT）法测试不同MUC1-SPION浓度下（铁浓度为0、6.25、12.50、25、50、100、200 μg/ml）的细胞毒性。并分别于铁浓度为50、100、200 μg/ml条件下,对靶向组及对照组与BxPC-3细胞共同孵育2 h后的细胞悬液进行MR成像,测定横向弛豫时间（T2）,计算T2强化率。以普鲁士蓝染色观察靶向探针与细胞结合情况。结果 MTT法细胞毒性实验显示,不同MUC1-SPION浓度下BXPC-3细胞增殖率差异无统计学意义（F=1.74,P=0.183）。铁浓度50、100、200 μg/ml条件下,2组间T2值和T2强化率的差异均有统计学意义（P均<0.05）。普鲁士蓝染色显示靶向组的蓝染颗粒更多。结论 MUC1-SPION对BxPC-3细胞具有良好的靶向性,以SPION靶向标记BxPC-3细胞进行MRI安全、可行。     

超顺磁性氧化铁纳米粒子在肝癌诊断与治疗中的研究进展

超顺磁性氧化铁纳米粒子（SPION）作为MR负性对比剂被广泛认知,通过对其进行表面修饰,可明显提高其生物相容性与作用效果。利用外加磁场及交变电流,SPION还可具有靶向传递和磁热疗的作用。本文旨在对SPION在肝癌诊断和治疗方面的研究进展进行综述。     

LyP-1标记超顺磁性氧化铁的制备及体外成像

目的 探讨LyP-1标记超顺磁性氧化铁(SPIO)与乳腺癌细胞结合进行体外成像的可行性。方法 以共沉淀法制备SPIO,用LyP-1与3-氨丙基三甲氧基硅烷(APTMS)包被的SPIO耦联,以乳腺癌MDA-MB-231细胞株为研究对象,设立LyP-1-SPIO组、竞争组、SPIO组和对照组,普鲁士蓝染色,评价不同组中铁颗粒在细胞中的分布情况,四甲基偶氮唑盐(MTT)比色法检测细胞活性并观察其体外MR成像效果。结果 成功制备SPIO。 LyP-1-SPIO组有较多铁颗粒进入细胞内,竞争组和SPIO组仅有少量铁颗粒进入细胞中,对照组细胞中无铁颗粒。MTT比色法检测结果显示不同作用时间LyP-1-SPIO和SPIO对细胞的生长均无显著影响;体外MR成像提示LyP-1-SPIO能够显著增强阴性对比效果。结论 LyP-1-SPIO对MDA-MB-231细胞具有较好的靶向作用,可用于对肿瘤细胞的影像学诊断。     

超小超顺磁性氧化铁体外标记SD大鼠脂肪来源干细胞

  目的  评估超小超顺磁性氧化铁(ultrasmall superparamagnetic iron oxide, USPIO)标记SD大鼠脂肪来源干细胞(adipose derived stem cells, ADSCs)的有效性及安全性, 探讨标记细胞体外磁共振成像(magnetic resonance imaging, MRI)特点。  方法  将USPIO 40 μg/ml及多聚赖氨酸(poly-L-lysine, PLL)1.5 μg/ml的培养基与ADSCs共孵育培养24 h, 检测USPIO标记的有效性及安全性, 并用MRI对标记细胞进行体外成像。  结果  普鲁士蓝染色显示USPIO标记ADSCs的阳性率为99%, 透射电镜提示USPIO颗粒主要位于胞质内溶酶体中; 台盼蓝染色实验显示活细胞数大于95%, MTS[3-(4, 5-dimethylthiazol-2-yl)-5(3-carboxymethoxyphenyl)-2-(4-sulfopheny)-2H-tetrazolium, 溴化噻唑蓝四氮唑]实验提示USPIO浓度为10、20、40、80和160 μg/ml时不影响ADSCs增殖。ELISA结果表明标记细胞与未标记细胞组间培养液中血管内皮生长因子(vascular endothelial growth factor, VEGF)水平无显著差异; 体外条件下, MRI图像信号强度与标记细胞数量呈正相关。  结论  USPIO标记ADSCs安全有效, MRI图像信号强度与标记细胞数量存在一定相关性, 提示USPIO可用于在体条件下MRI成像示踪标记细胞。     

Superparamagnetic iron oxide nanoparticles for in vivo molecular and cellular imaging

In the last decade, the biomedical applications of nanoparticles (NPs) (e.g. cell tracking, biosensing, magnetic resonance imaging (MRI), targeted drug delivery, and tissue engineering) have been increasingly developed. Among the various NP types, superparamagnetic iron oxide NPs (SPIONs) have attracted considerable attention for early detection of diseases due to their specific physicochemical properties and their molecular imaging capabilities. A comprehensive review is presented on the recent advances in the development of in vitro and in vivo SPION applications for molecular imaging, along with opportunities and challenges. Copyright © 2015 John Wiley & Sons, Ltd.     

动脉粥样硬化斑块OxLDL靶向的MR分子影像学实验研究

目的 研究氧化低密度脂蛋白(oxLDL)靶向的超微超顺磁性纳米氧化铁(USPIO)探针在载脂蛋白E基因敲除小鼠(ApoE-/-)颈动脉动脉粥样硬化MR成像中的作用.方法 将聚乙二醇(PEG)包被的USPIO与抗小鼠oxLDL抗体结合,构建anti-oxLDL-USPIO靶向探针.以非特异性IgG-USPIO及单纯USP...     

SPIO纳米颗粒在肝癌磁共振早期诊断的基础研究进展

原发性肝癌(primary hepatic carcinoma,PHC)的早期发现和诊断是肝癌诊疗领域中的重要课题之一。近些年来,对分子影像学(Molecular Imaging)研究的不断深入,为肝细胞癌的早期检测和早期诊断提供了一种全新的思维方法。相对于传统的磁共振对比剂钆剂,超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)具有很多优点,能够产生磁共振负性强化。在生物医学领域,超顺磁性氧化铁的应用很多,可以作为载体应用在多个方面,例如靶向探针的载体、携带药物的载体等,作为科研热点在分子影像学方面被充分关注。本文通过总结既往的研究,对SPIO纳米颗粒在肝癌磁共振早期诊断的基础研究进展进行综述。     

Superparamagnetic iron-oxide-enhanced diffusion-weighted magnetic resonance imaging for the diagnosis of intrapancreatic accessory spleen

Purpose

To evaluate the diagnostic performance of superparamagnetic iron-oxide (SPIO)-enhanced diffusion-weighted image (DWI) for distinguishing an intrapancreatic accessory spleen from pancreatic tumors.

Materials and methods

Twenty-six cases of intrapancreatic accessory spleen and nine cases of pancreatic tail tumors [neuroendocrine tumor (n = 8) and pancreatic adenocarcinoma (n = 1)] were analyzed. Two blind reviewers retrospectively reviewed the SPIO-enhanced magnetic resonance imaging (MRI) scans. The lesion visibility grades were compared and the diagnostic performance of SPIO-enhanced DWI was compared to those of SPIO-enhanced T2WI and T2*WI with the use of a receiver operating characteristic (ROC) analysis.

Results

The grade of lesion visibility was the highest on DWI [mean ± standard deviation (SD): 2.8 ± 0.3] followed by T2WI (2.3 ± 0.7, p < 0.001) and T2*WI (2.1 ± 0.7, p < 0.0001). Reviewers 1 and 2 correctly characterized the presence or absence of SPIO uptake in 34 of 35 cases (97.1%) on DWI, 24 (68.6%) and 25 (71.4%) cases on T2WI, respectively, and 16 (45.7%) and 17 (48.6%) cases on T2*WI. The area under the ROC curve (AUC) of DWI was 0.974 and 0.989 for reviewers 1 and 2, respectively. For Reviewer 1, the AUC of DWI was significantly higher than that of T2*WI (0.756, p < 0.01), although it was not significantly different from that of T2WI (0.868, p = 0.0857). For Reviewer 2, the AUC of DWI was significantly higher than those of T2WI (0.846, p < 0.05) and T2*WI (0.803, p < 0.01).

Conclusion

The diagnostic performance of SPIO-enhanced DWI was better than those of SPIO-enhanced T2*WI and T2WI for the diagnosis of intrapancreatic accessory spleen.

     

High-field magnetic resonance imaging of brain iron in Alzheimer disease

OBJECTIVES: Increased iron deposition in the brain may occur in several neurodegenerative diseases, including Alzheimer disease (AD). Iron deposits shorten T2 relaxation times on T2-weighted magnetic resonance (MR) images. Iron-dependent contrast increases with magnetic field strength. We hypothesized that T2 mapping using 3 T MR imaging (MRI) can disclose differences between normal controls and AD subjects. METHODS: High-resolution brain imaging protocols were developed and applied to 24 AD patients and 20 age-matched controls using 3 T MRI. Eight anatomical regions of interest were manually segmented, and T2 histograms were computed. A visual analysis technique, the heat map, was modified and applied to the large image data sets generated by these protocols. RESULTS: A large number (163) of features from these histograms were examined, and 38 of these were significantly different (P < 0.05) between the groups. In the hippocampus, evidence was found for AD-related increases in iron deposition (shortened T2) and in the concentration of free tissue water (lengthened T2). Imaging of a section of postmortem brain before and after chemically extracting the iron established the presence of MRI-detectable iron in the hippocampus, cortex, and white matter in addition to brain regions traditionally viewed as containing high iron concentrations.     

大鼠骨髓间充质干细胞的超顺磁氧化铁颗粒标记及MR成像

目的描述超顺磁氧化铁(SPIO)颗粒标记大鼠骨髓间充质干细胞(BMSCs)后对细胞的影响及MR成像特点,评价其标记效果。方法分离、纯化并培养大鼠BMSCs,使用多聚赖氨酸(PLL)对细胞进行SPIO(50μgFe/ml,48h)标记,采用普鲁士蓝染色、细胞内铁含量检测等评定SPIO标记BMSCs的效率;通过台盼蓝染色、二甲基亚砜比色法检测细胞活力和增殖情况,通过Hoechst染色观察细胞凋亡情况,评价SPIO是否影响BMSCs的生物学特性;并对标记的BMSCs进行MR成像(序列:T1SE、T2FSE及T2*GRE)。结果细胞标记率达100%,标记细胞铁含量明显高于未标记细胞;细胞活力、增殖、周期和凋亡检测显示标记细胞与未标记细胞间无统计学差异(P>0.05);MR成像显示标记细胞数目大于5×103个细胞时,3个序列图像均能够观察到信号变化,以T2*WI最为明显。结论大鼠BMSCs可以被SPIO(50μgFe/ml,48h)有效标记,且对细胞的生物学特性无明显影响;1.5TMR能够在体外观察到标记后的细胞。     

Gadolinium-labelled iron/iron oxide core/shell nanoparticles as T1–T2 contrast agent for magnetic resonance imaging

Magnetic resonance imaging (MRI) is indispensable and powerful in modern clinical diagnosis and has some advantages such as non-invasiveness and high penetration depth. Furthermore, dual T₁–T₂ MR imaging has attracted crucial interest as it can decrease the risk of pseudo-positive signals in diagnosing lesions. And it''s worth nothing that the dual-mode MR imaging displays a vital platform to provide relatively comprehensive diagnosis information and receive accurate results. Herein, we report a dual T₁–T₂ MR imaging contrast agent (CA) grounded on the iron/iron oxide core/shell nanomaterials conjugated with gadolinium chelate. The Gd-labeled Fe@Fe₃O₄ NPs reveal the feasibility to utilize them to serve as a dual T₁–T₂ MR imaging CA, and the relaxivity results in a 0.5 T MR system showed a longitudinal relaxivity value (r₁) and transverse relaxivity value (r₂) of 7.2 mM⁻¹ s⁻¹ and 109.4 mM⁻¹ s⁻¹, respectively. The MTT results demonstrate the Gd-labeled Fe@Fe₃O₄ NPs have no obvious cytotoxicity and a good compatibility. The in vitro and in vivo MRI generated a brighter effect and darkening in T₁-weighted MR imaging and T₂-weighted images, respectively. The results clearly indicate that Gd-labeled Fe@Fe₃O₄ NPs have potential as a magnetic resonance imaging contrast reagent.

Magnetic resonance imaging (MRI) is indispensable and powerful in modern clinical diagnosis and has some advantages such as non-invasiveness and high penetration depth.