肝脏特异性对比剂超顺磁性氧化铁的研究背景、现状及展望

绝大多数肝脏的影像都致力于分析肝脏占位性病变 ,肝脏磁共振对比剂也同样将重心放在分析肝脏占位性病变上 ,对占位性病变的检出和定性诊断是肝脏影像的两个截然不同又互相补充的重要组成部分 ,因此 ,评价肝脏对比剂的效果要从检出率和定性诊断率两个方面进行。研究背景肝脏特异性磁共振对比剂的研究开始于 80年代中期。当时快速序列 (如梯度回波等 )在商业ＭＲ扫描机上还不具备 ,腹部的扫描序列均需耗时数分钟以上。钆的螯合物 (如Ｇｄ ＤＴＰＡ)作为磁共振对比剂最初应用于神经系统 ,但很快也推及腹部。同ＣＴ的碘对比剂一样 ,这些钆的螯…     

超顺磁性氧化铁（SPIO）对比剂肝脾MR成像的比较研究

目的 比较两种超顺磁性氧化铁（superparamagnetic iron oxide,SPIO)对比剂,Ferumoxides及SHU－555A在肝脾MR成像中的效应。材料与方法 36例已知为肝转移癌患者于SPIO造影前后进行T2WI快速自旋回波成像（T2WI TSE）及T1WI梯度回波快去速相位成像（T1WI FLASH）。扫描伪为1．0T MR机。18例患者行Ferumoxides增强后90分钟进行MR成像;另18例行SHU－55A快速团柱增强,注药后即刻、30秒及480秒行T1WI FLASH成像,10分钟行T2WI TSE成像。测量肝脾、肝转移癌SPIO增强前后的信号强度（signal intensity,SI),计算两种SPIO对比剂在肝脾、肝转移癌增强前后SI变化的百分比（percentage signal intensity change,PSIC)及病灶肝脏对比噪声比（lesion-to-liver contrast-to-noise ratio,CNR)及其变化（ΔCNR）。结果 在T2WI TSE图像上,两种SPIO对比剂造成的肝实质SI下降无显著性差异（P＞0．05）。Ferumoxides引的脾信号下降显著大于SHU－555A（P＜0．05）。两种SPIO对比剂均导致肝实转移癌SNR显著增高。T1WI FLASH图像上,两种对比剂均可导致延迟像上肝脏SI的轻度下降及肝转移癌CNR下降,两者肝脏SIC之间无显著性差异。T1WI上两种对比剂均可导致脾脏SI显著升高,两者脾脏PSIC之间无显著性差异（P＞0．05）。结论 两种SPIO在肝脏的TI及T2增强效应相似,而脾脏的T2增强效应,Ferumoxides强于SHU－555A。     

超顺磁性氧化铁类对比剂及其在肝病变的应用

超顺磁性氧化铁粒子（ＳＰＩＯ）是一种网状内皮系统阴性对比剂，主要用于肝、脾、骨髓、淋巴结等的增强显像。本文主要讨论了ＳＰＩＯ的生物学特性、增强机制及其在肝脏病变的应用。     

超顺磁性氧化铁胶体用作网状内皮系统磁共振对比剂的实验研究

了解自制超顺磁性氧化铁胶体用于磁共振肝脾造影的一些特性。（１）ＳＤ大鼠静注ＳＰＩＰ胶体８９．３μｍｏｌＦｅ／ｋｇ，分别于４ｈ，２４ｈ，４ｄ，７ｄ，１０ｄ，１５ｄ时取肝，脾作组织学检查，观察铁微粒的动态分布；（２）带ｗａｌｋｅｒ－２５６肝癌肉瘤模型的ＳＤ大鼠和Ｇｄ－ＤＴＰＡ双重增强，定量分析双重增强和ＳＰＩＯ单独增强对肿瘤显示的差异；３．Ｃ 四氯化碳诱发ＳＤ大鼠肝弥漫性中毒改变，比较肝中毒大鼠与正常     

超顺磁性氧化铁纳米粒子在细胞标记及细胞成像中的应用

近10年来,细胞成像技术是一个快速发展的领域,其目的在于可视化活体内靶细胞,获得细胞在活体内的生物学分布及迁徙情况。细胞成像作为一种活体内细胞监测的技术具有非侵人性及可重复性的特点。MRI由于其高分辨率的优点,可以达到细胞水平,所以成为细胞成像中的研究热点。靶细胞必须经MR对比剂标记后才能区别于背景组织而被MR监测到,目前常用的MR对比剂为钆类及氧化铁类。钆类对比剂具有低弛豫率、细胞清除快、非生物相容性等缺点,且去螯合化后对细胞的毒性作用目前知道的很少。氧化铁类中的超顺磁性氧化铁纳米（SPIO）材料是继钆之后一种新的用于MR对比剂的材料。     

顺磁性对比剂Gd-DTPA-DG 的制备及其在肺癌裸鼠模型活体MR实验研究

目的 合成一种顺磁性脱氧葡萄糖类MR对比剂二乙三胺五乙酸-脱氧葡萄糖钆盐(Gd-DTPA-DG)并探讨其在荷瘤裸鼠体内肿瘤信号改变的规律.方法 首先合成DTPA-DG ,再与Gd2O3螯合,制得Gd-DTPA-DG.采用荷瘤裸鼠体内实验模型,将裸鼠随机分成实验组与对照组(n=10),前者尾静脉注射Gd-DTPA-DG,后者尾静脉注射含相同Gd3+浓度(0.1 mmol/kg)的Gd-DTPA, 测量SE T1WI平扫及引入对比剂30 s、2 min、5 min、 10 min、20 min、30 min、45 min、1 h、2 h后瘤体信号强度,并计算对比度噪声比(CNR).将右侧前肢肌肉组织信号变化作为参照物,并进行统计分析.结果 Gd-DTPA-DG比Gd-DTPA在肿瘤组织内表现为更强且更持久的强化.注射对比剂30 s后,实验组裸鼠瘤体信号增加与扫描前差异没有统计意义(P=0.171),在30 min左右差异性最大(P<0.001).对照组5 min时前后差异最大(P<0.001),但2 h时即与注射前没有显著差异性(P=0.057).结论 Gd-DTPA-DG 可在肺癌模型活体内起到肿瘤强化作用,是一种新型顺磁性Gd(III)类糖代谢MR对比剂.     

乙二胺四乙酸铁钠作为MRI口服胃肠道对比剂的实验研究

目的:研究乙二胺四乙酸铁钠溶液作为MRI口服胃肠道对比剂的可行性.方法:以乙二胺四乙酸铁钠溶液作为对比剂进行体外试验,根据浓度不同分10个等级进行T1 WI、T2 WI、PDWI和单次激发厚层水成像扫描,所得图像与水为对比剂时得到的图像作对比研究.结果:乙二胺四乙酸铁钠溶液浓度在7.5～10 mmol/l时各个序列增强效果均较佳,在T1 WI、PDWI表现为高信号,在T2 WI表现为低信号.结论:乙二胺四乙酸铁钠溶液可以作为MRI口服胃肠道对比剂.     

联合钆和超顺磁性氧化铁对比剂MR增强成像评估多发性硬化的活动性

摘要目的应用钆和超微超顺磁性氧化铁(USPIO)颗粒作为对比剂,比较多发性硬化病变随时间变化的MR成像特征。方法该研究获得当地伦理委员会批准,所有受试者签署知情同意书。对24例多发性硬化病人(10例复发型、14例进展型)给予钆和USPIO增强MRI检查并随访6个月。采用Pearsonχ2或Fisher确切检验比较单独使用钆增强强化的病变、USPIO增强强化的病变及两者都强化的病变数量,用U检验比较病变大小。     

Iron oxide nanoparticles as magnetic resonance contrast agent for tumor imaging via folate receptor-targeted delivery

RATIONALE AND OBJECTIVE: Targeted delivery is a highly desirable strategy for diagnostic imaging because of enhanced efficacy and reduced dosage/toxicity. Receptor-targeting was used to deliver contrast-producing superparamagnetic iron oxide (IO) nanoparticle to receptor-expressing tumors for in vivo magnetic resonance (MR) imaging. MATERIALS AND METHODS: Nanometer-sized, dextran-coated (maghemite) IO particles were prepared by a precipitation method. They were tethered with N-hydroxysuccinimide-folate and fluorescence isothiocyanate (FITC). For in vitro study of delivery specificity and efficiency, KB cells, a human nasopharyngeal epidermal carcinoma cell line expressing surface receptors for folic acid, were used as positive targets, and A549 cells, a human lung carcinoma cell line which lacks folate receptors, were used as negative control targets. In vivo MR images were obtained using mouse models with subcutaneous tumor xenografts grown from implanted KB cells. RESULTS: Internalization of nanoparticles into targeted cells only occurred when IO was conjugated to folate and when the folate receptors are available and accessible on the cells. The endocytosis was efficient and rapid, as 97.5% KB cells cultured with folate-FITC-IO showed FITC uptake after 1 hour of incubation. In in vivo MR imaging, an average intensity decrease of 38% was observed from precontrast to postcontrast images of the tumor, which was about three times the intensity decrease observed at a non-tumor-bearing muscle. CONCLUSION: Successful in vivo MR imaging of folate receptor-expressing tumors targeted by IO nanoparticles was demonstrated for the first time.     

MRI肝胆特异性对比剂Gd-EOB-DTPA对小肝细胞癌的诊断研究进展

肝细胞癌(HCC)是常见的原发性肝脏恶性肿瘤,全球的发病率逐年增长。HCC的早期发现与及时治疗是提高病人预后及生存率的关键。钆塞酸二钠(Gd-EOB-DTPA)是一种新型的MRI肝胆特异性对比剂,不仅具有普通细胞外间隙对比剂的功能,还可被肝细胞特异性摄取,进而提供肝胆期信息。Gd-EOB-DTPA增强MRI对HCC的诊断价值优于常规细胞外间隙对比剂增强MRI。就Gd-EOB-DTPA增强MRI在小HCC诊断及鉴别诊断中的应用现状进行综述。     

The effect of a gadolinium-based contrast agent on diffusion tensor imaging

Objective

The aim of this study was to investigate in detail the effect of gadolinium contrast on diffusion tensor imaging scans. As the present literature offers conflicting results, we have included a large selection of indices in the analysis.

Materials and methods

Sixteen patients harboring an intra-axial contrast enhancing brain tumor were included in this study. Two diffusion tensor imaging scans were performed—one natively, and the second following a gadolinium contrast agent application. Maps of the invariant indices fractional anisotropy (FA), linear, planar, and spherical indices, trace, eigenvalues λ₁, λ₂, λ₃ as well as of the components of the diffusion tensor matrix Dxx, Dyy, Dzz, Dxy, Dxz and Dyz were co-registered and compared statistically with matching ROI pairs in the contrast enhancing areas, peritumoral edema and the normal appearing white matter.

Results

We have observed a significant increase in the FA and disproportional decrease of the eigenvalues in the post-contrast scans. In accordance with these findings, the spherical index was decreased and the linear and planar indices were increased. There was a significant decrease of all diagonal components of the diffusion tensor matrix. These changes have been strongest in the contrast enhancing areas, but there were also significant changes in the peritumoral edema and the normal appearing white matter.

Conclusion

Diffusion tensor imaging scans performed after gadolinium contrast agent administration may display artificially increased FA values due to disproportional changes of the measured eigenvalues. The distortion of the diffusion measurement is strongest in, but not limited to the contrasting areas.     

体外磁共振成像对神经干细胞标记后弛豫活性的实验研究

目的:研究超顺磁性氧化铁颗粒(SPIO)标记细胞后在细胞成像领域的应用价值。方法:SPIO与多聚赖氨酸(PLL)联合标记神经干细胞,使用4.7T磁共振对标记细胞进行T1WI、T2WI及T2*WI扫描,并测量标记细胞及未标记细胞的弛豫率R2和R2*。结果:①与未标记细胞相比,标记细胞于T1WI时信号强度平均上升24.06%,T2WI时信号强度平均下降50.66%,T2*WI时信号强度平均下降53.70%。②未标记细胞和标记细胞的T2分别为516 ms和77 ms,弛豫率R2分别为1.94/s及12.98/s;T2*分别为109 ms和22.9 ms,其弛豫率R2*分别为9.17/s及43.67/s。标记细胞的R2及R2*分别约增强了5倍及4倍。结论:SPIO能够有效的标记神经干细胞,明显提高标记细胞的R2及R2*,T2WI和T2*WI序列对显示标记细胞与未标记细胞间的信号差异较敏感。     

MRI in acute cerebral ischaemia: perfusion imaging with superparamagnetic iron oxide in a rat model

An imaging technique capable of detecting ischaemic cerebral injury at an early stage could improve diagnosis in acute or transient cerebral ischaemia. We compared the ability of superparamagnetically contrastenhanced MRI and conventional T2-weighted MRI to detect ischaemic injury early after unilateral occlusion of the middle cerebral artery in 12 male Wistar rats. Permanent vessel occlusion was achieved by a transvascular approach, which has the advantage of not requiring a craniectomy. At 45–60 min after the procedure, the animals had conventional T2-weighted MRI before and after administration of a superparamagnetic contrast agent (iron oxide particles). Unenhanced images were normal in all animals. After administration of iron oxide particles, the presumed ischaemic area was clearly visible, as relatively increased signal, in all animals; this high signal area corresponded to the area of ischaemic brain infarction seen on histological studies. Magnetic susceptibility effects of iron particles cause low signal in normally perfused cerebral tissue, whereas tissue with reduced or absent blood flow continues to give relatively high signal. Our results suggest that superparamagnetic iron particles may significantly reduce the interval between an ischaemic insult and the appearance of parenchymal changes on MRI.     

大剂量对比剂团注在MRI检查中应用

目的：探讨大剂量对比剂注射器团注在脑转移瘤及其血管成像中的临床意义。方法：对35例脑转移瘤患者行MR平扫和增强扫描作为对照，其中26例脑转移瘤患者增强扫描分别采用单剂量手推方式注射(10ml和大剂量注射器团注，并对图像做对比分析。对22例体部血管病变患者和15例肝、肾移植患者及供体行常规扫描后的增强血管成像(enhancedMRA)。快速大剂量团注(20～40ml扫描以1．5～3ml／s流率经上肢大静脉注射造影，造影前根据病灶和血管大小，首先预设置流率、流量及注射时间，再对所选择的病变区域或血管行快速动态扫描和延迟扫描。结果：35例均已确诊有原发病灶的脑转移瘤忠者中23例经手术病理证实，12例经活检病理证实。19例体部血管病变经DSA证实。所有检查均获成功，且大剂量注射器团注组对病变显示优于小剂量手推组。结论：大剂量的注射冕团注能更清晰显示病灶数目和病灶大小、数目和病灶内钙化、坏死以及供给血管情况，为临床提供精确的诊断。     

The role of SPIO-enhanced MRI in the detection of malignant liver lesions

The aim of this study was to evaluate the efficacy of superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance imaging (MRI) in the detection of malignant liver tumors. MRI, using fast spin-echo T₂-weighted and gradient-echo T₁-weighted imagings before and after SPIO infusion, was performed in 32 patients with known or suspected hepatic lesions. Statistical analysis was performed using lesion-by-lesion analysis. SPIO-enhanced T₂-weighted MRI showed results comparable to those of unenhanced T₂-weighted MRI in the detection of focal liver lesions.     

功能MRI在评价对比剂诱导急性肾损伤中的研究进展

对比剂诱导急性肾损伤（CI-AKI）是注射碘对比剂后严重的并发症之一,早期诊断和治疗可以改善或延缓肾损伤。目前多种功能MRI（fMRI）技术可用于肾损伤后肾脏微循环和病理生理学的评估,包括扩散加权成像（DWI）、体素内不相干运动（IVIM）成像、扩散张量成像（DTI）、扩散峰度成像（DKI）、血氧水平依赖（BOLD）成像、动脉自旋标记（ASL）成像等。这些技术不但可以对肾功能损害进行定量分析,还可以在肾损伤的早期诊断和监测方面提供更多信息。就CI-AKI的发病机制及fMRI评价CI-AKI的研究现状做一综述。     

磁粒子成像的临床前应用研究进展

磁粒子成像（magnetic particle imaging,MPI）是由核磁共振成像（magnetic resonance imaging,MRI）衍生而来的新一代分子影像技术。其采用复合组合方式的旋转可变梯度磁场,直接检测体内超顺磁性氧化铁纳米粒子（superparamagnetic iron oxide,SPIO）,可以获得纳摩尔级的超高灵敏度成像。MPI具有高时空间分辨率、高灵敏度、无扫描深度限制且无电离辐射等特点,目前已应用于细胞示踪、血管成像以及肿瘤成像及治疗等临床前领域。自2005年出现以来,MPI在软件算法、硬件开发、示踪剂设计和临床前应用领域得到了快速的发展。文章在简述MPI历史及基本原理的基础上,对近年来MPI在细胞示踪、血管、肿瘤等临床前领域的研究进展进行了归纳与总结,并对MPI的临床转化前景进行了展望。     

MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients

This study was an initial phase II trial in humans of molecular magnetic resonance (MR) imaging for improved visualization of thrombi in vessel territories potentially responsible for stroke using a new fibrin-specific contrast agent (EP-2104R). Eleven patients with thrombus in the left ventricle (n = 2), left or right atrium (n = 4), thoracic aorta (n = 4) or carotid artery (n = 1) as verified by an index examination (ultrasound, computed tomograpy, or conventional MR) were enrolled. All MR imaging was performed on 1.5 T whole-body MR-system using an inversion-recovery black-blood gradient-echo sequence. The same sequence was performed before and 2-6 h after low-dose intravenous administration of 4 mumol/kg EP-2104R. Two investigators assessed image quality and signal amplification. Furthermore, contrast-to-noise ratios (CNR) between the clot and the blood pool/surrounding soft tissue before and after administration of the contrast agent were compared using Student's t-test. MR imaging and data analysis were successfully completed in 10 patients. No major adverse effects occurred. On enhanced images, thrombi demonstrated high signal amplification, typically at the clot surface, with a significantly increased contrast in comparison to the surrounding blood pool and soft tissue (CNR for clot vs. blood pool, unenhanced and enhanced: 6 +/- 8 and 29 +/- 14; CNR for clot vs. soft tissue, unenhanced and enhanced: 0 +/- 4 and 21 +/- 13; P < 0.01 for both comparisons). EP-2104R allows for molecular MR imaging of thrombi potentially responsible for stroke. High contrast between thrombus and surrounding blood and soft tissues can be achieved with enhanced imaging.