小粒径磁共振成像超敏感纳米对比剂的研制及初步动物实验

目的 制备一种小粒径磁共振成像(MRI)超敏感的纳米对比剂并进行初步动物实验,探讨其用于分子影像学研究的可行性.方法 利用聚乙二醇(PEG)引发ε-己内酯(CL)开环聚合与自组装技术制备嵌段聚合物PEG-b-PCL,在其疏水性内核负载单颗粒超顺磁性氧化铁(SPIO)制成纳米对比剂.应用透射电子显微镜测量该纳米对比剂的粒径,原子吸收法测量其SPIO负载率,多平面回波SE序列测量T2值并计算横向弛豫率R2,同时对其进行磁学性质测量.将纳米对比剂由鼠尾静脉注射入Balb/c裸鼠体内,利用MRI于注射前、注射后1、3、6、12、24 h共6个时间点进行扫描,观察其在裸鼠体内的分布特点及循环时间.结果 制备的纳米对比剂粒径为(38±3)am,Fe3O4含量为37.0％,横向弛豫率R2为110 Fe(mmol/L)-1·s-1;磁学性质测定结果表明其具有超顺磁性.经外周静脉注射后,主要分布于肝脏,且循环时间长,与注射前相比,1 h信号强度明显降低(498±60比120±32,P＜0.05),至24 h降低至88+28(P＜0.05).结论 负载单颗粒SPIO的聚合物纳米对比剂粒径小、MRI超敏感,具有成为MRI对比剂并用于分子靶向成像的潜能.     

超微超顺磁性纳米氧化铁标记犬口腔黏膜上皮细胞与磁共振成像实验

BACKGROUND: Epithelial cells are commonly used as the seed cell in tissue engineering; however, there is still a lack of an effective in vivo noninvasive trace technology. OBJECTIVE: To investigate the feasibility of labeling canine oral epithelial cells with ultrasmall superparamagnetie iron oxide (USPIO) and magnetic resonance imaging (MRI) in vitro.  METHODS: Oral epithelial cells from beagles were primary cultured, and then labeled by 0.75 mg/L poly-L-lysine combined with USPIO (0, 5, 10, 25, 50 and 100 mg/L), respectively. To determine the optimal dosage, the intracellular iron expression was identified by Prussian blue staining, and the cell viability in different groups was detected by cell counting kit-8. Finally, 2×105 labeled cells were suspended with 1 mL PBS buffer, and were screened using 3.0 T MR on T2*WI sequences in vitro.  RESULTS AND CONCLUSION: USPIO prepared with 0.75 mg/L poly-L-lysine could successfully label dog oral epithelial cells. Prussian blue staining showed intracellular blue spots, and the intracellular blue spots became more with the concentration increasing and saturated at the concentration of 25 mg/L. Cell counting kit-8 indicated that the cell viability did not change when the concentration < 25 mg/L. Among the T2*WI sequences, the MRI signal intensity decreased with the concentration increasing. In conclusion, canine oral epithelial cells can be effectively labeled with USPIO making no impact on cell viability when the concentration < 25 mg/L, and MRI can be used to track these labeled cells in vitro．     

超顺磁性氧化铁增强的磁共振成像在肝占位病变诊断中的价值

肝脏占位病变的检出与定性一直是影像学研究的重点与难点之一。CT、磁共振(MRI)的问世,使这一领域有了突飞猛进的发展。但某些占位病变,在常规CT、MRI平扫和增强扫描中与正常肝组织之间密度／信号差较小而易漏诊及误诊或定性困难。为弥补这一不足,各种用于肝脏的特异性对比剂应运而生,超顺磁性氧化铁(SPIO)就是其中之一。自     

磁共振对超顺磁性氧化铁标记的大鼠间充质干细胞成像的研究

目的:探讨磁共振对超顺磁性氧化铁(SPIO)纳米颗粒体外标记大鼠间充质干细胞进行成像的可行性.方法:多聚赖氨酸修饰的Fe3O4纳米颗粒.分别培养大鼠间充质干细胞至对数生长期,更换为分散多聚赖氨酸修饰的Fe3O4纳米颗粒的培养液,取所培养的细胞进行电镜超微结构观察.磁共振T1WI、FSE T2WI、FIESTA T2*WI三个序列对培养6 h的细胞群成像.结果:同一条件下培养6 h.见有多聚赖氨酸修饰的Fe3O4纳米颗粒进入大鼠间充质干细胞的细胞质内.对培养6h的细胞群磁共振成像中.标记后的大鼠间充质干细胞在FSE T1WI、FSET2WI、FIESTA T2WT三个序列中均可显示SPIO信号.其中在FSE T2WI上各标记细胞的EP管信号均较T1WI信号改变明显.结论:超顺磁性氧化铁纳米颗粒可以标记大鼠间充质干细胞,应用磁共振可以对其进行监测.     

负载超顺磁性氧化铁颗粒聚合物纳米囊泡的制备及MR成像

目的 制备负载油性、水性超顺磁性氧化铁(SPIO)颗粒聚合物纳米囊泡,并观察其表征和MRI成像特点.方法 经多步化学反应得到共聚物聚乙二醇-聚(D,L-丙交酯)(PEG-PDLLA),通过多次乳化及溶剂挥散法使共聚物在水溶液中自组装成囊泡,并分别负载油性和水性SPIO.使用扫描电镜和透视电镜观察负载油性、水性SPIO聚合物纳米囊泡的直径、形态、分布,并用MRT2 mapping软件测量单纯SPIO水溶液、负载油性、水性SPIO聚合物纳米囊泡的T2弛豫率(1/T2).溶液浓度分别取原液、原液的1/2、1/4、1/8、1/16、1/32.结果 负载油性SPIO和水性SPIO聚合物纳米囊泡的的平均直径分别为( 182.2 ±23.9) nm、(191.7 ±28.7) nm.电镜显示油性SPIO均匀地分散于囊泡的中心膜上;水性SPIO以团簇的形式被包裹在囊泡的内腔中.负载SPIO的聚合物囊泡比单纯SPIO水溶液表现更高MRI敏感性.在相同铁离子浓度下,负载水性SPIO聚合物囊泡的T2弛豫率(1/8浓度时为4.60)高于负载油性SPIO聚合物纳米囊泡(1/8浓度时为2.85).结论 负载SPIO聚合物纳米囊泡比单纯SPIO水溶液表现出更高的MRI敏感性,负载水性SPIO聚合物囊泡的T2弛豫率高于负载油性SPIO聚合物纳米囊泡.     

SPIO结构,功能及应用浓度研究新进展

超顺磁性氧化铁（SPIO）具有典型的晶体结构,有效成分是Fe3O4晶体核心,其作为纳米粒子,常包被葡聚糖右旋糖酐或其他物质而具有一定的水溶性或生物活性。Fe3O4具有极强铁磁性和超顺磁性,能缩短周围氢质子的弛豫时间,降低正常组织的信号强度,使T2加权图像信号明显下降,SPIO因能被网状内皮系统所摄取而已被用作临床磁共振成像（MRI）T2加权造影剂;同时,SPIO也可被组织中不同类型细胞所摄取的浓度的不同而显示出不同的影像学差异,因此SPIO的应用浓度对细胞的活性及MRI效应有着重要的影响。本文就相关进展做一综述。     

超顺磁性氧化铁纳米颗粒体外标记兔骨髓间充质干细胞的安全性以及MRI成像特征*☆

背景：传统的干细胞标记方法常需要病理组织学等侵袭性手段检测,无法动态观察整个实验过程,也不适合临床研究。 目的：观察超顺磁性氧化铁纳米颗粒体外标记对兔骨髓间充质干细胞生物学特性的影响以及标记兔骨髓间充质干细胞的体外MRI成像特征。 方法：采用红细胞裂解贴壁法培养扩增兔骨髓间充质干细胞。采用不同浓度超顺磁性氧化铁纳米颗粒(100,50,25,12.5 mg/L)联合多聚赖氨酸(0.75 mg/L)标记兔骨髓间充质干细胞。对标记兔骨髓间充质干细胞进行MRI检测,观察其成像特征。 结果与结论：25 mg/L的超顺磁性氧化铁纳米颗粒联合0.75 mg/L多聚赖氨酸标记兔骨髓间充质干细胞具有较好的安全性和有效性。此浓度对细胞的生长活性没有影响,不影响骨髓间充质干细胞的成骨成脂分化能力。MRI扫描在T2*WI序列上能明显有效地显像超顺磁性氧化铁纳米颗粒标记的兔骨髓间充质干细胞。 关键词：超顺磁性氧化铁纳米颗粒;骨髓间充质干细胞;标记;磁共振;安全性 doi:10.3969/j.issn.1673-8225.2012.06.001     

超顺磁性氧化铁微粒磁标记骨髓间充质干细胞效率实验研究

目的探讨不同浓度超微超顺磁性氧化铁微粒（USPIO）与多聚左旋赖氨酸（PLL）标记大鼠骨髓问充质十细胞（BMSCs）的磁标记效率及对细胞生长活力的影响,寻找最佳配比浓度。方法实验采用6周龄Wister近交系大鼠,150g芹右．雄性。用贴壁法分离培养BMSCs。使用6nmUSPIO—PLL复合物标记BMSCs。实验分6组,对照组为未标记的BMSCs（A组）。按照PLL的有无及PLL质量浓度梯度（0、0．25、0．50、0．75、1．00μg／mL）分为5个实验组（B～F组）;其中每个实验组再根据不同浓度铁离子与PLL结合（USPIO的终质量浓度分别为25、50、100、150μg/mL）。使用电子显微镜及光学显微镜观察标记后的BMSCs及BMSCs内的USPIO微粒。BMSCs活力测定采用台盼蓝排除实验。BMSCs生长曲线绘制采用MTT法。MRI观察体外标记后BMSCs的显影。火焰法测量BMSCs内铁含量,验证铁含量与MRI信号的关系。统计学分析采用方差分析。,结果台盼蓝染色证实90％以上标记后BMSCs均拒染台盼蓝。根据BMSCs生长曲线判断单纯使用铁离子质量浓度达到200μg／mL时或PLL用量达1．00μg／mL会对BMSCs的生长产生一定的抑制作用。火焰法测得单独USPIO标记BMSCs与USPIO—PLL标记BMSCs铁含量差异有统计学意义（P〈0．05）。T2WI及SWI序列图像从B组至F组信号强度逐级下降,反映出铁离子的变化情况。结论使用USPIO（100μg／mL）结合PLL（0．75μg／mL）标记BMSCs即对细胞活性和生长无不利影响．且标记BMSCs的信号强度较强。     

超顺磁性氧化铁的合成及其对细胞标记相关研究进展

细胞移植在修复损伤组织等方面具有极大的前景.应用细胞治疗常规治疗效果不佳的疾病或建立更为优化的治疗方案,移植细胞的在体连续动态追踪显得尤为重要.超顺磁性氧化铁(SPIO)的应用,改善了以往只能依靠免疫组织化学、电镜等侵袭性方法的不便.研究者建立了多种制备该颗粒的方法,并摸索其标记细胞的最佳条件,通过动物实验,证实了SPIO活体示踪细胞的可行性及其优势,为细胞移植运用于临床治疗及疗效评价提供了可靠手段.     

钆螯合物磁共振成像对比剂的研究进展

在综合文献的基础上,对新型细胞外、肝特异性、网状内皮系统特异性、血池和其它组织特异性钆螯合物磁共振对比剂的研究进展作了较详细的介绍。提示新型组织特异性钆螯合物磁共振对比剂更安全更有效,也是当前钆螯合物磁共振对比剂研究的发展方向。     

Muscle cross-section measurement by magnetic resonance imaging

Summary Muscle cross-section areas were measured by magnetic resonance imaging (MRI) in the thigh of a human cadaver,. the results being compared with those obtained by photography of corresponding anatomic macroslices. A close correlation was found between MRI and photographic evaluation, differences between the methods ranging from nil to 9.5%, depending on the scan position and the muscle groups. In vivo MRI measurements were performed on 12 female and 16 male students, the objectivity, the test-retest reliability and the variability of the MRI measurements being studied by fixing the scan position either manually or by coronary scan. The latter method appeared to be more objective and reliable. The coefficients of variation for muscle cross-section areas measured by MRI were in the range of those for the planimetry of given cross-section areas. Allowing for differentiation between several small muscle bundles in a given area, MRI proved to be a suitable method to quantify muscle cross-sections for intra- and interindividual analysis of muscle size.     

Design of field-cycled magnetic resonance systems for small animal imaging

This paper presents a design study for a field-cycled magnetic resonance imaging (MRI) system directed at small animal imaging applications. A field-cycled MRI system is different from a conventional MRI system in that it uses two separate and dynamically controllable magnetic fields. A strong magnetic field is used to polarize the object, and a relatively weak magnetic field is used during signal acquisition. The potential benefits of field-cycled MRI are described. The theoretical dependences of field-cycled MRI performance on system design are introduced and investigated. Electromagnetic, mechanical and thermal performances of the system were considered in this design study. A system design for imaging 10 cm diameter objects is presented as an example, capable of producing high-duty-cycle polarizing magnetic fields of 0.5 T and readout magnetic fields corresponding to a proton Larmor frequency of 5 MHz. The specifications of the final design are presented along with its expected electromagnetic and thermal performance.     

磁共振成像中伪影的研究

磁共振成像中所产生的伪影会严重影响图像的质量及对病灶的精确识别。对磁共振成像中各种伪影形成的原因及抑制方法进行阐述。大量研究表明,怎样快速有效地抑制各种原因产生的伪影,仍然是研究人员所面临的一个非常棘手的问题。因此,还需不断寻求新的方法及思路来解决这一难题,为医学观察和临床诊断提供可靠的依据。     

Cell labeling for magnetic resonance imaging with the T1 agent manganese chloride

There is growing interest in using MRI to track cellular migration. To date, most work in this area has been performed using ultra-small particles of iron oxide. Immune cells are difficult to label with iron oxide particles. The ability of adoptively infused tumor specific T cells and N cells to traffic to the tumor microenvironment may be a critical determinant of their therapeutic efficacy. We tested the hypothesis that lymphocytes and B cells would label with MnCl2 to a level that would allow their detection by T1-weighted MRI. Significant signal enhancement was observed in human lymphocytes after a 1 h incubation with 0.05-1.0 mM MnCl2. A flow cytometry-based evaluation using propidium iodide and Annexin V staining showed that lymphocytes did not undergo apoptosis or necrosis immediately after and 24 h following a 1 h incubation with up to 1.0 mM MnCl2. Importantly, NK cells and cytotoxic T cells maintained their in vitro killing capacity after being incubated with up to 0.5 mM MnCl2. This is the first report to describe the use of MnCl2 to label lymphocytes. Our data suggests MnCl2 might be an alternative to iron oxide cell labeling for MRI-based cell migration studies.     

A theranostic agent to enhance osteogenic and magnetic resonance imaging properties of calcium phosphate cements

With biomimetic biomaterials, like calcium phosphate cements (CPCs), non-invasive assessment of tissue regeneration is challenging. This study describes a theranostic agent (TA) to simultaneously enhance both imaging and osteogenic properties of such a bone substitute material. For this purpose, mesoporous silica beads were produced containing an iron oxide core to enhance bone magnetic resonance (MR) contrast. The same beads were functionalized with silane linkers to immobilize the osteoinductive protein BMP-2, and finally received a calcium phosphate coating, before being embedded in the CPC. Both in vitro and in vivo tests were performed. In vitro testing showed that the TA beads did not interfere with essential material properties like cement setting. Furthermore, bioactive BMP-2 could be efficiently released from the carrier-beads. In vivo testing in a femoral condyle defect rat model showed long-term MR contrast enhancement, as well as improved osteogenic capacity. Moreover, the TA was released during CPC degradation and was not incorporated into the newly formed bone. In conclusion, the described TA was shown to be suitable for longitudinal material degradation and bone healing studies.     

超低场磁共振成像技术研究现状

超低场磁共振成像技术是磁共振成像研究领域中最新的发展方向.与常规磁共振成像相比,超低场磁共振成像技术所需的成像磁体可降至mT级甚至uT级,不仅大大降低了设备的成本和体积,还能够获得普通高场磁共振成像设备无法得到的特殊图像,具有非常广阔的应用前景.综述了近年来超低场磁共振成像技术的发展概况,重点介绍了其中的预极化磁共振成像、质子-电子双共振成像、激光磁共振成像和超导量子干涉仪(SQUID)磁共振成像.     

磁共振空间定位成像的实现与验证

目的:为了实现任意斜面的选择,本文提供了一种磁共振空间定位成像的实现方式。方法:通过定位线旋转绘制功能,实现任意斜面的选择。基于LaBVIEW实现了磁共振在三维空间任意方向的定位功能,在磁共振主计算机实现夹角余弦运算,在FPGA实现了矩阵运算。本文从仿真和成像实验两方面进行了定位成像功能验证。结果:首先验证了单个平面的成像结果,然后再对任意截面进行成像,从这两方面都证明了实验结果的正确性。结论:从仿真和成像实验两方面验证了本文设计的定位功能满足成像要求。