兔动脉粥样硬化斑块的USPIO增强MR研究
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摘要
第一部分三维对比增强MRA: USPIO与Gd-DTPA对比实验研究
目的:将自行研发的USPIO用于动物行三维对比增强MRA,并与Gd- DTPA增强MRA比较,评估USPIO增强MRA成像质量,为其临床应用提供实验证据。材料和方法:14只健康雄性新西兰大白兔随机分为两组,分别给予USPIO和Gd-DTPA行三维对比增强MRA扫描,1周后,待造影剂完全排泄,两组交换行相应对比剂增强扫描。所有扫描在1.5T磁共振扫描仪上完成,采用Cardiac心脏专用4通道相位-阵列线圈,行3D SPGR序列冠位扫描。使用高压注射器由耳缘静脉注入对比剂。给药前扫描1次观察扫描范围(蒙片),打药同时开始行扫描,共连续扫描9个时相,再分别于5、10、15、20、25、30min重复扫描1次。USPIO使用剂量为0.1mmol/kg体重,Gd-DTPA为0.5mmol/kg体重。结果:所有动物均能顺利完成扫描,图像质量显示清楚,通常在第2个时相可得到较好动脉期时相。USPIO和Gd-DTPA均可得到明显的血管增强效果。主动脉的SI(t)曲线显示USPIO在血管内信号强度达峰时间与Gd-DTPA相似,但持续时间比后者长,峰值信号强度弱于后者(P<0.05)。SNR(t)和CNR(t)曲线显示,USPIO与Gd-DTPA有交叉,但峰值相近,在后期(10min后)USPIO明显高于Gd-DTPA(P<0.05)。两种对比剂对主动脉及其一级分支显示率并无统计学差异(P>0.05)。在USPIO增强较晚时期,实验动物的静脉及门脉显示较Gd-DTPA增强同时期更加清楚。结论: USPIO在安全性、采集时间窗以及可同时动静脉、门脉显影上优于Gd-DTPA,更适于用作CE-MRA对比剂。自制USPIO作为血管对比增强剂具有良好的显像效果。
第二部分:兔动脉粥样硬化斑块:USPIO增强MR与Gd-DTPA增强MR对比实验研究
目的:在MR连续动态观察下,采用自制USPIO,对动脉粥样硬化兔模型行USPIO增强MR检查,并用Gd-DTPA增强作为对比,旨在探讨USPIO增强MR判断斑块易损性及其成分的价值。材料与方法:35只雄性新西兰大白兔随机分为两组,25只给予高脂饮食诱导动脉粥样硬化,10只给予正常饮食作为对照组。所有扫描均在1.5T磁共振扫描仪上进行,采用Cardiac心脏专用4通道相位-阵列线圈。扫描序列包括:T1WI SE,T1WI SE脂肪抑制,T2WI FSE, T2*WI GRE。所有动物于喂养10W时抽静脉血测量血清总胆固醇量,并开始进行扫描,在完成平扫、USPIO增强0h、24h扫描后,一周后行Gd-DTPA增强扫描,完成Gd-DTPA增强扫描当天处死不同喂养阶段模型兔及同期对照组动物,整个过程每两周重复一次。除5只模型兔喂养中途死亡,其余动物均完成全程扫描。USPIO使用剂量为0.05mmolFe/kg体重,Gd-DTPA使用剂量为0.25mmol/kg体重。磁共振所见与病理相对照。结果:喂养10W时模型兔血清总胆固醇值明显高于正常组(P<0.05),且所有模型兔大体标本均发生肉眼可见动脉粥样硬化样改变。MR对10W模型兔病灶检出率可达40.0%,随着喂养时间延长而检出率升高,并能动态监测斑块变化并与光镜结果对照,而光镜及电镜检查亦证实斑块内巨噬细胞吞噬USPIO。同时USPIO增强MR较Gd-DTPA增强能更好识别斑块内各种成分。结论:MR能动态监测AS病变并检出早期病灶。USPIO增强MR对识别斑块成分具有独特价值,并能反应斑块内炎性浸润,因此对判断斑块易损性优于Gd-DTPA增强MR。
PartⅠ:Three-dimensional contrast-enhanced MRA :comparison of an ultrasmall superparamagnetic iron oxide blood-pool contrast medium and gadopentetate dimeglumine in rabbits
Objective : To compare the intravascular enhancement of an ultrasmall superparamagnetic iron oxide (USPIO) blood-pool contrast medium to gadopentetate dimeglumine(Gd-DTPA ) for contrast-enhanced MR angiography (CE-MRA) in rabbits. Methods: Fourteen male New Zealand white rabbits were assigned to 2 groups randomly. One of the groups were perform CE-MRA with USPIO or Gd-DTPA,and a week delay ,to ensure the excretion of contrast agent,perform the MRA with the other contrast medium.MRA were performed in all the animals with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence on a high-resolution GE 1.5T MR scanner with the cardiac coil. The contrast agent was administrated through the ear venous with high-pressure syringe . All the animals were imaged prior to and 9 times after administration of contrast medium ,then the perform was repeated at time 5,10,15,20,25,30 minutes. USPIO was injected intravenously at a dose of 0.1mmol/kg body weight,and Gd-DTPA was injected intravenously at a dose of 0.5mmol/kg . Results: All the animals fininshed the MRA , and satisfactory arterial enhancement were obtained with injection of contrast medium. SI (t) of aorta showed that the tendency of USPIO was as same as Gd-DTPA,but the SI peak of USPIO was lower than Gd-DTPA(P<0.05). SNR(t) and CNR(t) showed that there was a cross of USPIO and Gd-DTPA at the earily time,but USPIO was much higher than Gd-DTPA from 10 minutes(P<0.05). To view the aorta and the branches, there was no difference between USPIO and Gd-DTPA.Both arterial , venous and portal vein enhancement on delayed acquisitions ,and USPIO was much better than Gd-DTPA . Conclusion: USPIO is safer,longer acquisition time than Gd-DTPA ,which makes it more suitable for CE-MRA.
PartⅡ: Control study of USPIO-enhanced MR Imaging and Gd-DTPA-enhanced MR Imaging in atherosclerotic plaques of rabbits
Purpose: To explore the value of USPIO-enhanced MR imaging of atherosclerotic plaques in rabbits ,and compared with Gd-DTPA-enhacned MR imaging. Materials and methods: 35 male New Zealand white rabbits were randomly assigned to two groups. 25 rabbits were induced by atherogenic diet to set up the model. 10 rabbits with the normal diet were served as the control group. All MR imagings were performed on a high-resolution 1.5T MR scanner with the cardiac coil. Routine sequences included T1-weighted spin-echo, T1-weighted spin-echo with fat saturation, T2-weighted fast spin-echo, T2*-weighted gradient-echo. Up to 10 weeks,the blood of all the rabbits were gathered to test the content of total cholesterol. Then ,they were imaged prior to ,0 hour and 24 hours after administration of USPIO.A week delay ,to ensure the excretion of contrast agent,all the animals performed Gd-DTPA-enhanced MR imaging,then the rabbits were killed in different raising periods.And this was repeated every 2 weeks. All the rabbits were finished the whole study except for 5 model rabbits ,which were died a natural death. USPIO was injected intravenously at a dose of 0.05mmolFe/kg body weight. Gd-DTPA was injected intravenously at a dose of 0.25mmol/kg body weight. MR findings were correlated with histopathologic findings.Results:The total cholesterol in model group was obviously higher then the normal group(p<0.05). Rabbits induced by atherogenic diet were all developed atherosclerotic lesion on gross. The detection rate of 10 week model rabbit on MR was 40.0%,and rate was raising in the progress of lesions.And the lesions monitored by MR were well correlated with histopathologic findings. The analysis of electron microscopical and light microscope proved that the USPIO particles were in the macrophages of the plaque. USPIO-enhanced MR imaging characterize the composition of atherosclerotic plaques better then Gd-DTPA-enhanced MR imaging . Conclusions: MR imaging can dynamic monitor the progress of AS,and the early lesions can be detected.USPIO-enhanced MR imaging can help to depicting the vulnerable of atherosclerotic plaque ,and characterizing the composition of atherosclerotic plaques.
目的:将自行研发的USPIO用于动物行三维对比增强MRA,并与Gd- DTPA增强MRA比较,评估USPIO增强MRA成像质量,为其临床应用提供实验证据。材料和方法:14只健康雄性新西兰大白兔随机分为两组,分别给予USPIO和Gd-DTPA行三维对比增强MRA扫描,1周后,待造影剂完全排泄,两组交换行相应对比剂增强扫描。所有扫描在1.5T磁共振扫描仪上完成,采用Cardiac心脏专用4通道相位-阵列线圈,行3D SPGR序列冠位扫描。使用高压注射器由耳缘静脉注入对比剂。给药前扫描1次观察扫描范围(蒙片),打药同时开始行扫描,共连续扫描9个时相,再分别于5、10、15、20、25、30min重复扫描1次。USPIO使用剂量为0.1mmol/kg体重,Gd-DTPA为0.5mmol/kg体重。结果:所有动物均能顺利完成扫描,图像质量显示清楚,通常在第2个时相可得到较好动脉期时相。USPIO和Gd-DTPA均可得到明显的血管增强效果。主动脉的SI(t)曲线显示USPIO在血管内信号强度达峰时间与Gd-DTPA相似,但持续时间比后者长,峰值信号强度弱于后者(P<0.05)。SNR(t)和CNR(t)曲线显示,USPIO与Gd-DTPA有交叉,但峰值相近,在后期(10min后)USPIO明显高于Gd-DTPA(P<0.05)。两种对比剂对主动脉及其一级分支显示率并无统计学差异(P>0.05)。在USPIO增强较晚时期,实验动物的静脉及门脉显示较Gd-DTPA增强同时期更加清楚。结论: USPIO在安全性、采集时间窗以及可同时动静脉、门脉显影上优于Gd-DTPA,更适于用作CE-MRA对比剂。自制USPIO作为血管对比增强剂具有良好的显像效果。
第二部分:兔动脉粥样硬化斑块:USPIO增强MR与Gd-DTPA增强MR对比实验研究
目的:在MR连续动态观察下,采用自制USPIO,对动脉粥样硬化兔模型行USPIO增强MR检查,并用Gd-DTPA增强作为对比,旨在探讨USPIO增强MR判断斑块易损性及其成分的价值。材料与方法:35只雄性新西兰大白兔随机分为两组,25只给予高脂饮食诱导动脉粥样硬化,10只给予正常饮食作为对照组。所有扫描均在1.5T磁共振扫描仪上进行,采用Cardiac心脏专用4通道相位-阵列线圈。扫描序列包括:T1WI SE,T1WI SE脂肪抑制,T2WI FSE, T2*WI GRE。所有动物于喂养10W时抽静脉血测量血清总胆固醇量,并开始进行扫描,在完成平扫、USPIO增强0h、24h扫描后,一周后行Gd-DTPA增强扫描,完成Gd-DTPA增强扫描当天处死不同喂养阶段模型兔及同期对照组动物,整个过程每两周重复一次。除5只模型兔喂养中途死亡,其余动物均完成全程扫描。USPIO使用剂量为0.05mmolFe/kg体重,Gd-DTPA使用剂量为0.25mmol/kg体重。磁共振所见与病理相对照。结果:喂养10W时模型兔血清总胆固醇值明显高于正常组(P<0.05),且所有模型兔大体标本均发生肉眼可见动脉粥样硬化样改变。MR对10W模型兔病灶检出率可达40.0%,随着喂养时间延长而检出率升高,并能动态监测斑块变化并与光镜结果对照,而光镜及电镜检查亦证实斑块内巨噬细胞吞噬USPIO。同时USPIO增强MR较Gd-DTPA增强能更好识别斑块内各种成分。结论:MR能动态监测AS病变并检出早期病灶。USPIO增强MR对识别斑块成分具有独特价值,并能反应斑块内炎性浸润,因此对判断斑块易损性优于Gd-DTPA增强MR。
PartⅠ:Three-dimensional contrast-enhanced MRA :comparison of an ultrasmall superparamagnetic iron oxide blood-pool contrast medium and gadopentetate dimeglumine in rabbits
Objective : To compare the intravascular enhancement of an ultrasmall superparamagnetic iron oxide (USPIO) blood-pool contrast medium to gadopentetate dimeglumine(Gd-DTPA ) for contrast-enhanced MR angiography (CE-MRA) in rabbits. Methods: Fourteen male New Zealand white rabbits were assigned to 2 groups randomly. One of the groups were perform CE-MRA with USPIO or Gd-DTPA,and a week delay ,to ensure the excretion of contrast agent,perform the MRA with the other contrast medium.MRA were performed in all the animals with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence on a high-resolution GE 1.5T MR scanner with the cardiac coil. The contrast agent was administrated through the ear venous with high-pressure syringe . All the animals were imaged prior to and 9 times after administration of contrast medium ,then the perform was repeated at time 5,10,15,20,25,30 minutes. USPIO was injected intravenously at a dose of 0.1mmol/kg body weight,and Gd-DTPA was injected intravenously at a dose of 0.5mmol/kg . Results: All the animals fininshed the MRA , and satisfactory arterial enhancement were obtained with injection of contrast medium. SI (t) of aorta showed that the tendency of USPIO was as same as Gd-DTPA,but the SI peak of USPIO was lower than Gd-DTPA(P<0.05). SNR(t) and CNR(t) showed that there was a cross of USPIO and Gd-DTPA at the earily time,but USPIO was much higher than Gd-DTPA from 10 minutes(P<0.05). To view the aorta and the branches, there was no difference between USPIO and Gd-DTPA.Both arterial , venous and portal vein enhancement on delayed acquisitions ,and USPIO was much better than Gd-DTPA . Conclusion: USPIO is safer,longer acquisition time than Gd-DTPA ,which makes it more suitable for CE-MRA.
PartⅡ: Control study of USPIO-enhanced MR Imaging and Gd-DTPA-enhanced MR Imaging in atherosclerotic plaques of rabbits
Purpose: To explore the value of USPIO-enhanced MR imaging of atherosclerotic plaques in rabbits ,and compared with Gd-DTPA-enhacned MR imaging. Materials and methods: 35 male New Zealand white rabbits were randomly assigned to two groups. 25 rabbits were induced by atherogenic diet to set up the model. 10 rabbits with the normal diet were served as the control group. All MR imagings were performed on a high-resolution 1.5T MR scanner with the cardiac coil. Routine sequences included T1-weighted spin-echo, T1-weighted spin-echo with fat saturation, T2-weighted fast spin-echo, T2*-weighted gradient-echo. Up to 10 weeks,the blood of all the rabbits were gathered to test the content of total cholesterol. Then ,they were imaged prior to ,0 hour and 24 hours after administration of USPIO.A week delay ,to ensure the excretion of contrast agent,all the animals performed Gd-DTPA-enhanced MR imaging,then the rabbits were killed in different raising periods.And this was repeated every 2 weeks. All the rabbits were finished the whole study except for 5 model rabbits ,which were died a natural death. USPIO was injected intravenously at a dose of 0.05mmolFe/kg body weight. Gd-DTPA was injected intravenously at a dose of 0.25mmol/kg body weight. MR findings were correlated with histopathologic findings.Results:The total cholesterol in model group was obviously higher then the normal group(p<0.05). Rabbits induced by atherogenic diet were all developed atherosclerotic lesion on gross. The detection rate of 10 week model rabbit on MR was 40.0%,and rate was raising in the progress of lesions.And the lesions monitored by MR were well correlated with histopathologic findings. The analysis of electron microscopical and light microscope proved that the USPIO particles were in the macrophages of the plaque. USPIO-enhanced MR imaging characterize the composition of atherosclerotic plaques better then Gd-DTPA-enhanced MR imaging . Conclusions: MR imaging can dynamic monitor the progress of AS,and the early lesions can be detected.USPIO-enhanced MR imaging can help to depicting the vulnerable of atherosclerotic plaque ,and characterizing the composition of atherosclerotic plaques.
引文
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1王毅,沈天真,陈星荣等.Spio胶体用作网状内皮系统磁共振造影剂的研究[J].中国医学影像学杂志.1994,2(3):181-185
2 Harisinghani MG,Dixon WT,Saksena MA,et al. Hahn. MR Lymphangiography: Imaging Strategies to Optimize the Imaging of Lymph Nodes with Ferumoxtran-101[J] . RadioGraphics 2004,24(3):867-878
3 Weissleder R,Stark DD,Englestad BI,et al.Superparamagnetic iron oxide: pharmaco kinetics and toxicity[J].AJR,1989,152(1):167
4 Powliquen D , Le Jeune JJ , Perdrison R , et al. Iron oxide nanoparticles for us as an MRI contrast agent :pharmacokinetics and metabolism[J]. Magn Reson Imaging .1991;9(3):275-83
5范我,杨凯,钱建华等。59Fe示踪法测定纳米级磁性氧化铁在小鼠体内的分布[J].同位素.2001,14(1):31-35
6徐亮,郭启勇.超顺磁性氧化铁的研究现状及其在肝增强磁共振成像的临床应用及前景[J].国外医学临床放射学分册,2000,(1):31.
7 Fahlvik AK,Klaveness J,Stark DD.Iron oxide as MR imaging contrast agents[J].J Magn Reson Imaging,1993,3(2):187.
8 Tanimoto A,Pouliquen D,Kreft BP,et al.Effects of spatial distribution on proton relaxation enhancement by particulate iron oxide[J].J Magn Reson Imaging,1994, 4(4):653.
9 Naghavi M,Libby P,Falk E,et al.From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:part I[J]. Circulation,2003, 108(14): 1664-1672.
10 Naghavi M,Libby P,Falk E,et al.From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:part II[J]. Circulation,2003,108 (15):1772-1778
11 Becker CR, Knez A, Leber A,et al. Detection of coronary artery stenoses with multislice helical CT angiography.J Comput Assist Tomogr. 2002 ,26(5):750-5.
12 Wolf RL, Wehrli SL, Popescu AM,et al. Mineral Volume and Morphology in Carotid Plaque Specimens Using High-Resolution MRI and CT[J]. Arteriosclerosis,Thrombosis, and Vascular Biology. 2005;25(8):1729.
13 Zarrabi A, Gul K, Willerson JT, Casscells W, Naghavi M. Intravascular thermography: a novel approach for detection of vulnerable plaque.Curr Opin Cardiol. 2002 ,17(6):656-62.
14 MacNeill BD,Lowe HC,Takano M,et al.Intravascular modalities for detection of vulnerable plaque:current status[J].Arterioscler Thromb Vasc Biol,2003,23 (8):1333- 1342.
15 Cappendijk VC,Cleutjens K, Kessels A,et al. Assessment of Human Atherosclerotic Carotid Plaque Components with Multisequence MR Imaging: Initial Experience[J]. Radiology 2005;234(2):487-492
16 Yuan C,Zhang SX,Polissar NL,et al.Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke[J].Circulation,2002,105:181-185.
17 Yuan C , Mitsumori LM, Ferguson MS ,et al . In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques[J].Circulation , 2001 , 104(17) :2051-6
18 Hatsukami TS , Ross R , Polissar NL ,et al . Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging[J]. Circulation , 2000 , 102(9) :959-64
19 Moody AR.Magnetic resonance direct thrombus imaging[J].J Thromb Haemost,2003, 1(7):1403-9.
20 Clarke SE,Beletsky V,Hammond RR, et al.Validation of Automatically Classified Magnetic Resonance Images for Carotid Plaque Compositional Analysis[J]. Stroke. 2006;37(1):93-7
21 Zimmerman-Paul GG,Quick HH,Vogt P,et al.High resolution intravascular magnetic resonance imaging:monitoring of plaque formation in heritable hyperlipidemic rabbits[J].Circulation,1999,99(8):1054-61.
22 Schmitz SA , Coupland SE , Gust R ,et al . Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyper-lipidemic rabbits[J]. Invest Radiol , 2000 , 35(8) :460-71
23 Schmitz SA , TaupitzM, Wagner S , et al . Iron-oxide-enhanced magnetic resonance imaging of atherosclerotic plaques : postmortem analysis of accuracy , inter-observeragreement , and pitfalls[J]. Invest Radiol , 2002 ,37(7) :405-11
24 Ruehm SG, Corot C , Vogt P , et al . Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits[J]. Circulation , 2001 , 103(3) :415-22.
25 Kooi ME , Cappendijk VC , Cleutjens KB ,et al . Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging[J]. Circulation , 2003 , 107(19) : 2453-8
26 Trivedi RA,Mallawarachi C, U-King-Im J,et al. Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque[J] . Macrophages. Arterioscler Thromb vasc Biol ,2006,Jul,26(7):1601-1606
27 Tang T, Howarth SP, Miller SR,et al. Assessment of Inflammatory Burden Contralateral to the Symptomatic Carotid Stenosis Using High-Resolution Ultrasmall, Superparamagnetic Iron Oxide–Enhanced MRI[J].stroke,2006,37(9):2266-2270
28 Schmitz SA, Winterhalter S, Schiffler S,et al. USPIO-enhanced Direct MR Imaging of Thrombus: Preclinical Evaluation in Rabbits[J]. Radiology. 2001;221(1):237-243
29 Klein C , Schalla S , Schnackenburg B , et al . Improvement of image quality of non-invasive coronary artery imaging with magnetic resonance by the use of the intravascular contrast agent Clariscan (NC100150 injection) in patients with coronary artery disease[J]. J Magn Reson Imaging ,2003 , 17(6) :656-62
30 Stillman AE , Wilke N , Li D ,et al . Ultrasmall superparamagnetic iron oxide to enhance MRA of the renal and coronary arteries : studies in human patients[J]. J Comput Assist Tomogr , 1996 , 20(1) :51-5
31 Trivedi RA , U King Im JM. Graves MJ , et al . In Vivo Detection of Macrophages in Human Carotid Atheroma Temporal Dependence of Ultrasmall Superparamagnetic Particles of Iron Oxide-Enhanced MRI[J]. Stroke ,2004 , 35(7) :1631-5
32 Herborn CU, Vogt FM, Lauenstein TC,et al. Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide. J Magn Reson Imaging[J]. 2006 Aug;24(2):388-93.
33刘祖黎,杜玉卿,胡道予,等.超小型超顺磁性氧化铁磁共振对比剂的制备及性能研究[J].功能材料,2005,36(3),350-352,356
2 Willinek WA ,von Falkenhausen M, Born M, et al.Noninvasive Detection of Steno-Occlusive Disease of the Supra-Aortic Arteries With Three-Dimensional Contrast-Enhanced Magnetic Resonance Angiography[J]. Stroke. 2005;36(1):38
3刘祖黎,杜玉卿,胡道予,等.超小型超顺磁性氧化铁磁共振对比剂的制备及性能研究[J].功能材料,2005,36(3),350-352,356
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5 Tombach B, Reimer P, Bremer C, et al.First-pass and equilibrium-MRA of the aortoiliac region with a superparamagnetic iron oxide blood pool MR contrast agent (SHU-555 C): results of a human pilot study[J]. NMR Biomed. 2004 Nov;17(7):500-6
6 Allkemper T,Bremer C, Matuszewski L, et al.Contrast-enhanced Blood-Pool MR Angiography with Optimized Iron Oxides: Effect of Size and Dose on Vascular Contrast Enhancement in Rabbits[J].Radiology 2002;223(2):432-438
7罗健君,李晓兵,许建铭,等.磁共振对比增强血管三维成像技术的方法探讨[J].中国医学影像技术,2004,20(6):891-893.
8 Klein C , Schalla S , Schnackenburg B , et al . Improvement of image quality of non-invasive coronary artery imaging with magnetic resonance by the use of theintravascular contrast agent Clariscan (NC100150 injection) in patients with coronary artery disease[J]. J Magn Reson Imaging ,2003 , 17(6) :656-62
9 Stillman AE , Wilke N , Li D ,et al . Ultrasmall superparamagnetic iron oxide to enhance MRA of the renal and coronary arteries : studies in human patients[J]. J Comput Assist Tomogr , 1996 , 20(1) :51-5
10 Ruehm SG, Corot C, Vogt P,et al. Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits[J]. Circulation 2001; 103(3):415-422
11 Allkemper T, Walter H , Hendrik K et al.Effect of Field Strengths on Magnetic Resonance Angiography: Comparison of an Ultrasmall Superparamagnetic Iron Oxide Blood-Pool Contrast Agent and Gadopentetate Dimeglumine in Rabbits at 1.5 and 3.0 Tesla[J].Investigative Radiology. Volume 41(2), February 2006, 97-104
12徐亮,郭启勇.超顺磁性氧化铁的研究现状及其在肝增强磁共振成像的临床应用及前景[J].国外医学临床放射学分册,2000,(1):31.
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23. Wolf RL, Wehrli SL, Popescu AM,et al. Mineral Volume and Morphology in Carotid Plaque Specimens Using High-Resolution MRI and CT[J]. Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25(8):1729.
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1王毅,沈天真,陈星荣等.Spio胶体用作网状内皮系统磁共振造影剂的研究[J].中国医学影像学杂志.1994,2(3):181-185
2 Harisinghani MG,Dixon WT,Saksena MA,et al. Hahn. MR Lymphangiography: Imaging Strategies to Optimize the Imaging of Lymph Nodes with Ferumoxtran-101[J] . RadioGraphics 2004,24(3):867-878
3 Weissleder R,Stark DD,Englestad BI,et al.Superparamagnetic iron oxide: pharmaco kinetics and toxicity[J].AJR,1989,152(1):167
4 Powliquen D , Le Jeune JJ , Perdrison R , et al. Iron oxide nanoparticles for us as an MRI contrast agent :pharmacokinetics and metabolism[J]. Magn Reson Imaging .1991;9(3):275-83
5范我,杨凯,钱建华等。59Fe示踪法测定纳米级磁性氧化铁在小鼠体内的分布[J].同位素.2001,14(1):31-35
6徐亮,郭启勇.超顺磁性氧化铁的研究现状及其在肝增强磁共振成像的临床应用及前景[J].国外医学临床放射学分册,2000,(1):31.
7 Fahlvik AK,Klaveness J,Stark DD.Iron oxide as MR imaging contrast agents[J].J Magn Reson Imaging,1993,3(2):187.
8 Tanimoto A,Pouliquen D,Kreft BP,et al.Effects of spatial distribution on proton relaxation enhancement by particulate iron oxide[J].J Magn Reson Imaging,1994, 4(4):653.
9 Naghavi M,Libby P,Falk E,et al.From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:part I[J]. Circulation,2003, 108(14): 1664-1672.
10 Naghavi M,Libby P,Falk E,et al.From vulnerable plaque to vulnerable patient:a call for new definitions and risk assessment strategies:part II[J]. Circulation,2003,108 (15):1772-1778
11 Becker CR, Knez A, Leber A,et al. Detection of coronary artery stenoses with multislice helical CT angiography.J Comput Assist Tomogr. 2002 ,26(5):750-5.
12 Wolf RL, Wehrli SL, Popescu AM,et al. Mineral Volume and Morphology in Carotid Plaque Specimens Using High-Resolution MRI and CT[J]. Arteriosclerosis,Thrombosis, and Vascular Biology. 2005;25(8):1729.
13 Zarrabi A, Gul K, Willerson JT, Casscells W, Naghavi M. Intravascular thermography: a novel approach for detection of vulnerable plaque.Curr Opin Cardiol. 2002 ,17(6):656-62.
14 MacNeill BD,Lowe HC,Takano M,et al.Intravascular modalities for detection of vulnerable plaque:current status[J].Arterioscler Thromb Vasc Biol,2003,23 (8):1333- 1342.
15 Cappendijk VC,Cleutjens K, Kessels A,et al. Assessment of Human Atherosclerotic Carotid Plaque Components with Multisequence MR Imaging: Initial Experience[J]. Radiology 2005;234(2):487-492
16 Yuan C,Zhang SX,Polissar NL,et al.Identification of fibrous cap rupture with magnetic resonance imaging is highly associated with recent transient ischemic attack or stroke[J].Circulation,2002,105:181-185.
17 Yuan C , Mitsumori LM, Ferguson MS ,et al . In vivo accuracy of multispectral magnetic resonance imaging for identifying lipid-rich necrotic cores and intraplaque hemorrhage in advanced human carotid plaques[J].Circulation , 2001 , 104(17) :2051-6
18 Hatsukami TS , Ross R , Polissar NL ,et al . Visualization of fibrous cap thickness and rupture in human atherosclerotic carotid plaque in vivo with high-resolution magnetic resonance imaging[J]. Circulation , 2000 , 102(9) :959-64
19 Moody AR.Magnetic resonance direct thrombus imaging[J].J Thromb Haemost,2003, 1(7):1403-9.
20 Clarke SE,Beletsky V,Hammond RR, et al.Validation of Automatically Classified Magnetic Resonance Images for Carotid Plaque Compositional Analysis[J]. Stroke. 2006;37(1):93-7
21 Zimmerman-Paul GG,Quick HH,Vogt P,et al.High resolution intravascular magnetic resonance imaging:monitoring of plaque formation in heritable hyperlipidemic rabbits[J].Circulation,1999,99(8):1054-61.
22 Schmitz SA , Coupland SE , Gust R ,et al . Superparamagnetic iron oxide-enhanced MRI of atherosclerotic plaques in Watanabe hereditable hyper-lipidemic rabbits[J]. Invest Radiol , 2000 , 35(8) :460-71
23 Schmitz SA , TaupitzM, Wagner S , et al . Iron-oxide-enhanced magnetic resonance imaging of atherosclerotic plaques : postmortem analysis of accuracy , inter-observeragreement , and pitfalls[J]. Invest Radiol , 2002 ,37(7) :405-11
24 Ruehm SG, Corot C , Vogt P , et al . Magnetic resonance imaging of atherosclerotic plaque with ultrasmall superparamagnetic particles of iron oxide in hyperlipidemic rabbits[J]. Circulation , 2001 , 103(3) :415-22.
25 Kooi ME , Cappendijk VC , Cleutjens KB ,et al . Accumulation of ultrasmall superparamagnetic particles of iron oxide in human atherosclerotic plaques can be detected by in vivo magnetic resonance imaging[J]. Circulation , 2003 , 107(19) : 2453-8
26 Trivedi RA,Mallawarachi C, U-King-Im J,et al. Identifying Inflamed Carotid Plaques Using In Vivo USPIO-Enhanced MR Imaging to Label Plaque[J] . Macrophages. Arterioscler Thromb vasc Biol ,2006,Jul,26(7):1601-1606
27 Tang T, Howarth SP, Miller SR,et al. Assessment of Inflammatory Burden Contralateral to the Symptomatic Carotid Stenosis Using High-Resolution Ultrasmall, Superparamagnetic Iron Oxide–Enhanced MRI[J].stroke,2006,37(9):2266-2270
28 Schmitz SA, Winterhalter S, Schiffler S,et al. USPIO-enhanced Direct MR Imaging of Thrombus: Preclinical Evaluation in Rabbits[J]. Radiology. 2001;221(1):237-243
29 Klein C , Schalla S , Schnackenburg B , et al . Improvement of image quality of non-invasive coronary artery imaging with magnetic resonance by the use of the intravascular contrast agent Clariscan (NC100150 injection) in patients with coronary artery disease[J]. J Magn Reson Imaging ,2003 , 17(6) :656-62
30 Stillman AE , Wilke N , Li D ,et al . Ultrasmall superparamagnetic iron oxide to enhance MRA of the renal and coronary arteries : studies in human patients[J]. J Comput Assist Tomogr , 1996 , 20(1) :51-5
31 Trivedi RA , U King Im JM. Graves MJ , et al . In Vivo Detection of Macrophages in Human Carotid Atheroma Temporal Dependence of Ultrasmall Superparamagnetic Particles of Iron Oxide-Enhanced MRI[J]. Stroke ,2004 , 35(7) :1631-5
32 Herborn CU, Vogt FM, Lauenstein TC,et al. Magnetic resonance imaging of experimental atherosclerotic plaque: comparison of two ultrasmall superparamagnetic particles of iron oxide. J Magn Reson Imaging[J]. 2006 Aug;24(2):388-93.
33刘祖黎,杜玉卿,胡道予,等.超小型超顺磁性氧化铁磁共振对比剂的制备及性能研究[J].功能材料,2005,36(3),350-352,356