MR对比剂超顺磁性氧化铁脂质体的研究现状:标记特点及其安全性和局限性

背景:近年来超顺磁性氧化铁(superparamagnetic iron oxide,SPIO)对比剂的研发受到了广泛关注,主要体现在干细胞移植后追踪成像、包裹有阿拉伯半乳聚糖的细胞膜受体靶向成像以及SPIO脂质体等剂型的研究方面.目的:对MR对比剂SPIO脂质体的研究现状做一综述.方法:应用计算机检索CNKI和Science Direct数据库中1998-01/2009-09关于超顺磁性氧化铁脂质体的文章,在标题和摘要中以"SPIO,超顺磁性氧化铁,脂质体,MR对比剂"或"SPIO,superparamagnetic iron oxide,Liposome,MR contrastagent"为检索词进行检索.选择文章内容与MR对比剂有关者,同一领域文献则选择近期发表或发表在权威杂志文章.初检得到48篇文献,根据纳入标准选择关于超顺磁性氧化铁脂质体的24篇文献及1部著作进行综述.结果与结论:MR对比剂的不断创新改良对MRI诊断技术的提高起到了不可磨灭的作用.超顺磁性对比剂的代表SPIO在多种疾病的诊断价值上超越了以往的MR对比剂.SPIO脂质体具有更低的毒副作用以及对特异组织良好的靶向性,在实验研究及临床应用上受到广泛关注并被逐步推广.随着功能影像和分子影像的迅速发展,SPIO脂质体在今后应用领域必将更为宽广.     

SPIO联合Gd-DTPA增强对大鼠肝癌结节诊断价值研究

目的探讨超顺磁性氧化铁(SPIO)联合钆剂(Gd-DTPA)增强对诱发大鼠肝硬化肝癌结节的诊断价值。方法Wistar大鼠50只(实验组n=40,对照组n=10),前者饮水中加入二乙基亚硝胺到第12周,第13~19周随机抽取大鼠进行SPIO联合Gd-DTPA增强扫描,取大于3mm结节送病理,区分肝硬化(RNs)和肝癌(HCC)结节;比较两种对比剂增强的肿瘤检出率,结果进行χ2检验。结果106个结节中RNs24个,HCC82个,SPIO、Gd-DTPA增强肿瘤检出率分别为95.12%、89.02%,SPIO肿瘤检出率高于Gad-DTPA(P>0.05)。结论SPIO较Gd-DTPA增强更易检出肝癌结节,SPIO联合Gad-DTPA增强对肝硬化、肝癌结节定性诊断有互补作用。     

超顺磁性(SPIO)氧化铁纳米粒子在肿瘤诊断方面的研究进展

正近年来,随着纳米医学的飞速的发展,分子影像学的不断深化,Fe_3O_4、γ-Fe_2O_3、CO-Fe_2O_4等为主的超顺磁性氧化铁纳米粒在肿瘤诊断方向的研究和应用日益广泛,本文从超顺磁性氧化铁纳米粒子的MRI成像原理出发,以合成方法为基础,阐述近年来超顺磁性氧化铁纳米粒子在肿瘤诊断方面的研究进展,展望超顺磁性纳米粒子未来在肿瘤诊断中     

中等粒径葡聚糖超顺磁性氧化铁纳米颗粒的制备

目的制备中等粒径葡聚糖超顺磁性氧化铁纳米颗粒，评估其作为一种新型的磁共振对比剂可行性。方法采用化学共沉淀法制作葡聚糖超顺磁性氧化铁纳米颗粒，通过凝胶色谱分离葡聚糖超顺磁性氧化铁纳米颗粒，用透射电子显微镜、粒度分析仪、X射线衍射和磁力计对葡聚糖超顺磁性氧化铁纳米颗粒进行表征分析。结果粒度分析仪与电子显微镜检测结果表明，目的粒子均匀一致，葡聚糖超顺磁性氧化铁纳米颗粒核心直径在35—41nm之间，平均粒径40nm。磁力仪检测结果显示，磁化曲线无磁滞现象，表现为超顺磁性，矫顽力为零，饱和磁化强度为23KA／m。结论实验结果表明，所制备的中等粒径聚糖超顺磁性氧化铁纳米可作为一种新型的磁共振造影对比剂，广泛应用于多种疾病的临床诊断和治疗。     

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。     

以SPIO为增强对比剂的脑功能MRI原理和应用

近年,以SPIO(超顺磁性氧化铁)为增强对比剂的功能MRI在生物医学神经成像研究领域被广泛应用,该技术主要探测脑功能活动引起的CBV(脑血体积)的改变,并且在成像技术上具有提高CNR(比噪比)和屏蔽血管伪影的显著优势。本文从原理、研究特点、实验方法和应用等方面介绍了该技术的发展近况。     

磁性纳米材料的研究现状及其在神经干细胞移植中的应用

目前 ,常用的磁性纳米材料如三氧化二铁(Fe2 O3)、四氧化三铁 (Fe3O4)、铁钴合金等 ,这些磁性纳米材料具有较好的磁响应性 ,采用适当的方式可以方便地得到纳米磁性材料 ,最小的平均粒度只有纳米 ,粒度一般呈正态分布。磁性纳米材料经过包衣等处理后可作为超顺磁性氧化铁纳米材料用于磁共振成像 ,在疾病诊断上有重要用途。超顺磁性氧化铁粒子 (SPIOs)是具有组织特异性高、更安全的新型的磁共振阴性对比剂 ,目前主要用于富含网状内皮系统的肝、肺、淋巴结、骨髓等增强成像 ,具有其独特的临床诊断价值[2 ] ,但对于网状内皮系统以外的其他组…     

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。     

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.     

超顺磁性氧化铁标记的骨髓间充质干细胞

背景：目前,超顺磁性氧化铁纳米颗粒标记的骨髓间充质干细胞在治疗心、肝、肾及中枢神经系统疾病方面已经得到了快速的应用。目的：对国内外应用超顺磁性氧化铁标记骨髓间充质干细胞的现状及新进展作一综述。方法：应用计算机检索CNKI和Pubmed数据库中2001-12/2009-12关于超顺磁性氧化铁标记骨髓间充质干细胞的文章,在标题和摘要中以＂超顺磁性氧化铁,干细胞,标记,磁共振成像＂或＂superparamagnetic iron oxide,stem cells,label,magnetic resonance imaging＂为检索词进行检索。选择近5年内文章内容与超顺磁性氧化铁标记骨髓间充质干细胞有关者,同一领域文献则选择近期发表或发表在权威杂志文章。初检得到243篇文献,根据纳入标准选择关于超顺磁性氧化铁标记骨髓间充质干细胞的40篇文献进行综述。结果与结论：以往通过光镜识别干细胞标记物的研究中,必须用传统的组织病理学检查,从体内取得组织才能进行细胞探测,这显然不适合进行动态观察,更不适用于临床研究。超顺磁性氧化铁可以有效地进行活细胞标记,而这种标记方法不会影响细胞的活力、生长、分裂、迁移、分化等生物学功能,对细胞没有毒性,具有良好的安全性,可以用MRI进行活体示踪研究。     

超顺磁性氧化铁(SPIO)增强MRI对原发性肝癌的诊断价值

目的：检验SPIO增强MRI对原发性肝癌的定位，定量，定性诊断价值。方法：选取经螺旋CT增强，MR平扫，SPIO增强扫描检查且有手术或穿刺活检病理或DSA血管造影资料并经随访，实验室生化检查及临床资料证实为原性肝癌者20例。结果：SPIO增强T2MRI检出79个病灶，其中经手术，穿刺活检病理证实或DSA血管造影显示有肿瘤血管团和/或肿瘤染色的原发性肝癌病灶69个；另有10个为异常信号灶，SPIO增强MRI较CT增强及MR平扫病灶检出率分别增加66%和59%，病灶-肝脏对比噪声比增加52%（P=0.004)。结论：（1）SPIO增强T2WI病灶-肝脏对比噪声比显著增加；（2）病灶检出率明显高于MR平扫及螺旋CT增强影像；（3）结合MR平扫影像，SPIO增强MR影像对肝癌病灶的定位。定量及定性诊断有重要意义；（4）SPIO增强MR影像对肝脏良恶性肿瘤的鉴别诊断有重要意义。     

Main applications of hybrid PET‐MRI contrast agents: a review

In medical imaging, the continuous quest to improve diagnostic performance and optimize treatment strategies has led to the use of combined imaging modalities. Positron emission tomography (PET) and computed tomography (CT) is a hybrid imaging existing already for many years. The high spatial and contrast resolution of magnetic resonance imaging (MRI) and the high sensitivity and molecular information from PET imaging are leading to the development of this new hybrid imaging along with hybrid contrast agents. To create a hybrid contrast agent for PET‐MRI device, a PET radiotracer needs to be combined with an MRI contrast agent. The most common approach is to add a radioactive isotope to the surface of a small superparamagnetic iron oxide (SPIO) particle. The resulting agents offer a wide range of applications, such as pH variation monitoring, non‐invasive angiography and early imaging diagnosis of atherosclerosis. Oncology is the most promising field with the detection of sentinel lymph nodes and the targeting of tumor neoangiogenesis. Oncology and cardiovascular imaging are thus major areas of development for hybrid PET‐MRI imaging systems and hybrid contrast agents. The aim is to combine high spatial resolution, high sensitivity, morphological and functional information. Future prospects include the use of specific antibodies and hybrid multimodal PET‐MRI‐ultrasound‐fluorescence imaging with the potential to provide overall pre‐, intra‐ and postoperative patient care. Copyright © 2015 John Wiley & Sons, Ltd.     

Diagnostic accuracy of multi-/single-detector row CT and contrast-enhanced MRI in the detection of hepatocellular carcinomas meeting the milan criteria before liver transplantation

Liver transplantation has been considered to be the only causal treatment for liver cirrhosis patients with hepatocellular carcinoma (HCC) due to its theoretical advantage of eliminating both the tumor and liver disease. However, because of the shortage of donor organs, it is strongly recommended that liver transplantations should be performed on cirrhotic patients with HCCs only when the patients meet the predetermined criteria in terms of number and extent of HCCs. Imaging is thus decisive in the patient inclusion or exclusion from transplantation lists. The imaging techniques used are CT, MRI and ultrasonography. The latter has been proven to be ineffective for HCC surveillance in transplant recipients because of its heavy operator dependence and unreliable detection of small and intermediately sized HCCs. The purpose of this article, then, is to systematically review the diagnostic performances of single-/multidetector row CT, dynamic gadolinium-enhanced MRI, superparamagnetic iron oxide (SPIO)-enhanced MRI and double-contrast MRI using both gadolinium and SPIO for the detection of HCCs with special emphasis on liver transplantation.     

SWI与MRI增强扫描诊断小肝癌的对比性研究

目的对磁敏感加权成像(SWI)与MRI动态增强扫描诊断小肝癌进行对比性研究,探索SWI对小肝癌的临床应用价值。材料与方法采用双盲法,对60例临床诊断为小肝癌的患者同时进行SWI和MRI动态增强扫描并由3名高年资放射诊断医生进行独立诊断,并对诊断结果进行对比统计分析。结果 60例小肝癌中,应用SWI扫描48例阳性,12例阴性,MRI增强50例阳性,10例阴性。统计学分析结果显示,两种扫描方法诊断小肝癌差异并无统计学意义(P0.05)。结论本研究发现MRI增强扫描诊断小肝癌是临床上常规应用且可靠性较高的诊断方法,SWI扫描可作为MRI增强扫描的补充序列。应用SWI对肝硬化结节信号改变进行动态追踪,对小肝癌的诊断有重要的临床价值,但诊断小肝癌MRI增强扫描仍然不可替代。     

相位校正多回波GRE Dixon序列在原发性肝癌诊断价值的初步探讨

目的初步探讨相位校正多回波GRE Dixon序列在原发性肝癌诊断中的作用。材料与方法利用GRE Dixon序列扫描22例原发性肝癌患者,分析其在GRE Dixon序列生成的水像、脂像、水/脂相位图、R2*像的影像特点,并与传统T1、T2像及病理结果对照。结果胆管细胞癌与含脂肝细胞癌在水像上大多呈低信号,不含脂的肝细胞癌在水像上大多呈等信号。多数肿瘤中的出血、坏死在R2*像能够显示,优于T2像。胆管细胞癌的R2*值低于肝细胞癌(P=0.003)。R2*像中肿瘤与肝组织的对比噪声比低于T2像。结论分析相位校正多回波GRE Dixon的图像能够判断肝脏肿瘤组织内的出血、坏死、脂变、纤维成份,有利于胆管细胞癌与肝细胞癌的鉴别。     

Diagnostic value of imaging examinations in patients with primary hepatocellular carcinoma

Primary hepatocellular carcinoma (PHC) includes hepatocellular carcinoma, intrahepatic cholangiocarcinoma and other pathological types and is characterized by rapid progression. Most of the clinical diagnoses are made at late stage or when distant metastasis occurs, increasing the difficulty of treatment and resulting in a poor prognosis. Therefore, the early diagnosis of PHC plays an important role in timely treatment and the improvement of prognosis. The gold standard for the diagnosis of primary liver cancer is liver biopsy, but it has limitations as an invasive examination. Presently, imaging has become the first choice for the diagnosis of liver cancer. We here summarize the new methods and techniques of imaging in diagnosis and evaluation of primary liver cancer in recent years, including ultrasonography, computed tomography perfusion imaging, diffusion-weighted imaging technology-voxel incoherent motion, diffusion tensor imaging, iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantification, dynamic enhanced magnetic resonance imaging and hepatocyte-specific contrast medium imaging. Imaging diagnosis can not only evaluate the degree of differentiation, blood supply and perfusion, and invasiveness of the lesion, but also predict the prognosis, evaluate liver function, and provide references for clinical diagnosis and treatment.     

Imaging monocytes with iron oxide nanoparticles targeted towards the monocyte integrin MAC‐1 (CD11b/CD18) does not result in improved atherosclerotic plaque detection by in vivo MRI

Imaging of macrophages with superparamagnetic iron oxide particles (SPIO) has been performed to improve detection of atherosclerotic plaque inflammation in human and mouse studies by molecular magnetic resonance imaging (MRI). Since affinity of the monocyte/macrophage integrin MAC‐1 (CD11b/CD18) is upregulated in inflammation, we generated a contrast agent targeting CD11b (CD11b‐SPIOs) for improved macrophage detection in plaques. CD11b‐SPIOs and non‐targeted SPIOs (control‐SPIOs) were incubated in vitro with human monocytes/macrophages. As quantified by SPIO‐induced MRI signal extinction, intracellular iron‐content was significantly higher in monoytes/macrophages incubated with CD11b‐SPIO than with control‐SPIO in vitro (p < 0.05), suggesting an improved uptake of CD11b‐SPIOs into monocytes. Therefore, the aortic arch (AA) and vessel branches of ApoE^?/?‐knockout mice on a Western‐type diet were imaged before and 48 h after contrast agent injection of either CD11b‐SPIOs or control‐SPIOs, using a 9.4 T animal MRI system. The SPIO‐induced change in the MRI signal was quantified, as well as the macrophage‐content by anti‐CD68 immunhistochemistry and the iron‐content by Prussian‐blue staining. However, SPIO‐induced signal extinction in in vivo‐MRI was similar in CD11b‐SPIO and control‐SPIO‐injected animals, with a non‐significant trend towards an improved uptake of CD11b‐SPIOs in the subclavian artery and subsections of the AA. These data correlated well with the results obtained by histology. Although in vitro MRI‐data indicated an increased uptake of targeted CD11b‐SPIOs in monocytes/macrophages, in vivo mouse data do not allow improved atherosclerotic plaque detection compared WITH non‐targeted SPIOs. Therefore, CD11b‐targeted MRI contrast labelling of monocytes/macrophages does not seem to be a successful strategy in stable atherosclerotic plaques such as found in the ApoE^?/?‐knockout‐model. However, the impressive correlation between MRI and histology data encourages further development of inflammation‐ and plaque‐specific contrast agents for vulnerable plaque imaging. Copyright © 2010 John Wiley & Sons, Ltd.     

Hepatocellular nodules in liver cirrhosis: MR evaluation

Liver cirrhosis is a major public health problem worldwide. Common causes of cirrhosis include hepatitis C virus, hepatitis B virus, alcohol consumption, and nonalcoholic steatohepatitis. Cirrhotic livers are characterized by advanced hepatic fibrosis and the development of hepatocellular nodules such as regenerative nodules, dysplastic or neoplastic nodules. Cirrhosis is the strongest predisposing factor for hepatocellular carcinoma (HCC). For example, viral hepatitis is the main risk factor for cirrhosis and is associated with the increased incidence (1%–4% per year) of HCC after development of cirrhosis. Currently, a variety of imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET) are used in noninvasive evaluation of patients with chronic liver disease and suspected HCC. With technological development of MR scanners, MR imaging has emerged as an important imaging modality for assessing cirrhosis and its complications such as HCC. The recent advance in MR is the introduction of faster sequences which have allowed high-quality imaging of the entire liver with high intrinsic soft-tissue contrast, and also multiphasic dynamic MRI that is essential for the detection and characterization of HCC. In addition, functional MRI including diffusion-weighted MRI, MR elastography, and new MR contrast agent with dual function have been investigated for the clinical utility of detection and characterization of HCCs. In this article, we provide an overview of the state-of-the-art MR imaging techniques being used for noninvasive assessment of hepatocellular nodules including conventional dynamic imaging, liver-specific contrast-enhanced MR imaging, diffusion-weighted imaging, MR spectroscopy, and MR elastography.