【作者】 李涛；

【导师】 蔡祖龙；

【作者基本信息】 中国人民解放军军医进修学院 ， 影像医学与核医学， 2008， 博士

【摘要】 第一部分体外冠状动脉管壁高分辨MR成像的实验研究目的:使用1.5T MR扫描仪摸索出一套简单易行的体外冠状动脉管壁成像的程序,为进一步研究冠状动脉粥样硬化斑块的成分奠定基础。材料和方法:选入10个新鲜猪心行冠状动脉MR检查。3D快速稳态成像（FastImaging Employing Steady State Acquisition,FIESTA）序列用于前降支成像,分别选择八通道头表面线圈、膝关节线圈、颞下颌关节表面线圈进行SE T1WI成像,成像参数相同。然后使用颞下颌关节表面线圈,采用384X256和512X512的矩阵行SE T1WI像。之后在前降支内注入Resovist,使用不同的NEX,分别行脂肪抑制的SE T1WI,PDW和frFSE T2WI像。分别测量前降支近段管壁、管腔、前降支周围心外膜下的脂肪结缔组织、前降支邻近的室间隔心肌的信号强度,并测量周围空气的信号强度作为背景噪声,计算图像的信噪比（SNR）和冠状动脉管壁对管腔的对比噪声比（CNR1）及冠状动脉管壁对周围心外膜下脂肪结缔组织的对比噪声比（CNR2）。结果:颞下颌关节线圈成像前降支管壁SE T1WI的SNR（72.89）和CNR1（18.18）、CNR2（53.32）明显高于八通道头线圈（SNR:12.06;CNR1:4.70;CNR2:6.49）和膝关节线圈（SNR:14.42;CNR1:5.30;CNR2:9.06）。384X256的矩阵所得的SE T1WI的SNR（72.89）和CNR1（18.18）、CNR2（53.32）明显高于512X512的矩阵所得的SNR（34.18）和CNR1（11.72）和CNR2（24.85）。NEX为3时图像的SNR（SE T1WI:39.57;frFSE T2WI:27）和CNR1（SE T1WI:34.38;frFSE T2WI:27.60）、CNR2（SE T1WI:33.63;frFSET2WI:22.08）最高。结论:选择颞下颌关节线圈、384X256的矩阵、3个NEX可以得到良好的信噪比和对比噪声比。第二部分离体冠状动脉粥样硬化斑块64层螺旋CT、MRI及病理对照研究目的:使用64层螺旋CT和1.5T MR扫描仪显示离体冠状动脉粥样硬化斑块的成分,并与组织学相对照,评价CT和MRI在显示动脉粥样硬化斑块成分的作用。材料和方法:连续选入13个尸检患者（男性12例,平均年龄86岁）的心脏,于左冠状窦口插管后行冠状动脉左前降支近段CT及MR检查,并与病理学相对照。使用SIEMENS Sensation Cardiac-64螺旋CT扫描仪行冠脉检查,造影剂配置:100ml生理盐水加入4ml欧乃派克（350mgI/ml）。扫描参数:kV 120:200eff.mAs,螺距1.0,64x0.6准直,球管转速500ms/周,扫描时间3秒。回顾性的重建层厚0.6mm,重建间隔0.4mm。MR检查使用GE SIGNA 1.5T HD扫描仪,3D快速稳态成像序列用于左冠状动脉前降支成像,然后垂直于前降支行横轴位的T1WI,PDW和frFSE T2WI像扫描。扫描参数:SE T1WI:TR:440ms,TE:21ms,FOV 12cmx9cm,层厚2mm,间隔0.2mm,矩阵512x512,NEX为2。SE PDW:TR:2000ms,TE:21ms,FOV 12cmx9cm,层厚2mm,间隔0.2mm,矩阵512x512,NEX为2。frFSE:TR:4500ms,TE:105ms.FOV12cmx9cm,层厚2mm,间隔0.2mm,矩阵512x512,NEX为2。行PDW和T2WI像前于前降支注入MRI造影剂Resovist（0.5mmol Fe/ml）,配置:100ml生理盐水滴入4滴Resovist（约0.2ml）。组织学经固定、脱钙、包埋、切片后,行HE染色。CT、MRI影像和组织学切片独立分类和比较。采用诊断试验分析CT、MRI诊断各期斑块的敏感性和特异性,评价CT、MRI对斑块分类的准确性。结果:94个CT、MRI层面可以与相应的组织学层面相对应。CT对于各期斑块分类的敏感性和特异性分别为:Ⅰ-Ⅱ型,0%和100%;Ⅲ型,0%和100%;Ⅳ-Ⅴ型,92.3%和86.8%;Ⅵ型,0%和100%;Ⅶ型,100%和100%;Ⅷ,100%和97.8%。脂质成分为主的斑块（Ⅳ-Ⅴ期）CT值平均为53.7HU,钙化（Ⅶ期）成分为主的斑块CT值平均为1065HU,纤维（Ⅷ期）成分为主的斑块CT值平均为89.3。MRI对于各期斑块分类的敏感性和特异性分别为:Ⅰ-Ⅱ型,60%和100%;Ⅲ型,80%和100%;Ⅳ-Ⅴ型,96.2%和86.8%;Ⅵ型,100%和98.9%;Ⅶ型,93%和100%;Ⅷ,100%和98.9%。MRI示48.8%的钙化层面内有稍高信号,组织切片示脂质成分。45.7%的层面有新生血管。其中Ⅰ-Ⅱ型及Ⅲ型未见新生血管和炎细胞浸润,Ⅳ-Ⅴ型有13个层面,占Ⅳ-Ⅴ型斑块的50%,Ⅵ型有2个层面,占Ⅵ斑块的100%,Ⅶ型有25个层面,占Ⅶ型斑块的58%,Ⅷ型有3个层面,占100%。结论:CT、MRI都可以显示冠状动脉粥样硬化斑块的特点,对斑块进行分期MRI优于CT。MRI可以显示钙化斑块内的脂质成分,表现为低信号内的稍高信号。斑块内的炎细胞和新生血管有促使斑块不稳定的作用,进展期的斑块内炎细胞和新生血管明显增多。第三部分冠状动脉粥样硬化斑块对比增强磁共振血管成像:与CTA对照研究目的:通过非对比增强及对比增强呼吸导航3D-SSFP序列评价冠状动脉CTA显示的粥样硬化斑块的强化,研究斑块的强化与CT值之间的关系,识别不稳定斑块。材料与方法:选取19例经MDCT显示的位于冠状动脉近、中段的非钙化斑块或非钙化为主的混合性斑块作为MRA的研究对象。应用GE SIGNA 1.5THD磁共振扫描仪,采用呼吸导航3D-SSFP序列对斑块所在的血管进行成像。注射造影剂后对靶血管再进行2-3次扫描。用高压注射器自静脉注射磁共振造影剂马根维显30ml。先以1.5ml/s的速率注射10ml,然后以0.05ml/s的速率注射余下的20ml。用MPR的方法重建出冠状动脉粥样硬化斑块的横轴位影像用来评价斑块。斑块在MRA上的位置与CTA上的位置一致（距离分叉处或分支处相同的距离）。通过增强前后斑块与周围结缔组织的对比噪声比（CNR）评价斑块的强化。斑块的强化定义为增强后斑块与周围结缔组织的CNR增加50%以上。增强后斑块CNR的增加与CT值做相关分析。同时测量主动脉根部的信号强度、胸壁的信号强度,计算增强前后图像的信噪比（SNR）和CNR（（主动脉根部的信号强度-胸壁的信号强度）/背景噪声）,并做t检验分析增强前后图像的质量变化。结果:14例患者MRA上斑块显示清晰,共24个斑块,其中强化斑块11个。11个强化斑块中有5个斑块于增强后5分钟发生强化,佘6个斑块于增强后10-15分钟发生强化。13个未强化斑块中有4个于平扫呈高信号,9个呈低信号,平扫与管腔分界不清,增强后分界清晰。增强前后24个斑块与周围结缔组织的CNR分别为10.29±4.28和14.08±5.8,两者之间有显著的统计学差异（P＜0.05）。11个强化斑块与周围结缔组织的CNR增强前后分别为8.43±3.59和17.55±6.18,两者之间有显著差异（P＜0.05）。13个未强化斑块与周围结缔组织的CNR增强前后分别为11.86±4.3和11.15±3.48,两者之间无差异（P＞0.05）。强化斑块（68.44±24.72）和未强化斑块（57.82±24.13）的CT值之间没有统计学差异。冠状动脉粥样硬化斑块CEMRA示CNR增加的百分比与斑块的CT值之间无相关关系（P=0.19）。增强后5分钟图像的SNR和CNR分别是35.37±6.84和21.57±6.08,明显高于增强前图像的SNR和CNR（27.38±6.24和13.19±6.50）（p＜0.05）。增强后15分钟图像的SNR（33.81±9.43）高于增强前图像的SNR,但未达到统计学意义（p=0.074）,增强后15分钟图像的CNR（21.20±7.65）高于增强前（p＜0.05）。增强后5分钟和15分钟图像的SNR和CNR无明显差异。结论:对比增强MRA可以显示冠状动脉粥样硬化斑块的强化,强化与斑块的CT值无关。短时期内快速注射结合缓慢注射对比剂可以较长时间的维持血池内的短T1效应。第四部分64层MDCT评价冠状动脉粥样硬化斑块的准确性:与IVUS对照研究目的:评价64层螺旋CT在判断冠状动脉粥样硬化斑块性质及测量血管大小、斑块负担的应用价值。材料和方法:14例患者（男9例,女5例,平均年龄58岁）经MDCT显示的位于冠状动脉近、中段的粥样硬化斑块作为研究对象。患者行MDCT检查后一周内行IVUS检查。采用Siemens Sensation Cardiac 64螺旋CT扫描仪行冠脉扫描,采用最大密度投影（MIP）、多平面重建（MPR）进行重建并获得冠状动脉横断面影像。在斑块的最大层面测量每一个斑块的CT值,根据CT值将斑块分为软斑块、纤维斑块和钙化斑块三种类型。并测量、计算最小管腔面积（MLA）、血管外膜面积（EEM CSA）,斑块面积（plaque area）斑块负荷（plaque burden）。采用Galaxy^TM2（Boston Scientific Scimed Inc,USA）操作系统,行冠脉IVUS检查,根据斑块的回声判断斑块的性质并测量MLA、EEM CSA,斑块面积、斑块负荷。以IVUS为金标准,分别计算MDCT判断斑块性质的敏感性、特异性,及各类斑块的平均CT值,并对血管测量进行统计学检验。结果:14例患者共分析粥样硬化斑块25个,软斑块11个,平均CT值为49±32HU,纤维斑块7个,平均CT值为93±23HU,钙化斑块7个,平均CT值为1138±350HU。MDCT对脂质斑块诊断的敏感性为90.9%,特异性为92.9%;对纤维斑块诊断的敏感性为85.7%,特异性为94.4%,对钙化斑块诊断的敏感性为100%,特异性为100%。MDCT测量的血管面积、管腔面积、斑块面积、斑块负荷（16.2±5.1mm²,6.58±4.1mm²,9.61±3.8mm²,60±18%）高于IVUS测量的结果（14.5±4.8mm²,6.28±4.3mm²,8.22±3.6mm²,58.5±20.1%）,但两者之间没有统计学差异。结论:64层MDCT是一种准确的无创的诊断和测量冠状动脉粥样硬化斑块的工具。更多还原

【Abstract】 Part oneHigh Resolution MR Imaging of Coronary Arterial Wall in Vitro:an Experimental Study on PorcineObjective:To get a MR imaging protocol for coronary arterial wall in vitro and assessment of atherosclerotic plaque composition.Materials and methods:MRI examinations were performed in ten fresh porcine hearts.Fast imaging employing steady state acquisition(FIESTA)were used to delineate anterior descending artery(LAD).2D spin-echo T1WI imaging was performed using temporomandibular surface coil,eight-channel head surface coil and knee coil with the same parameters.Then,T1WI was performed with 384x256 or 512x512 in matrix using temporomandibular surface coil.And then 2D T1WI,PDW and T2WI with fat saturation were performed with different NEX using temporomandibular surface coil after injecting Resovist in LAD.Signal of the LAD wall,lumen,fat tissue adjacent to LAD,myocardium of anterior part of interventricular septum and noise were respectively measured.SNR of image, CNR1 between the wall and lumen,CNR2 between the wall and surrounding fatty tissue were calculated.Results:The SNR(72.89)and CNR1(18.18),CNR2(53.32)of SE T1WI with temporomandibular coil were higher than that with eight-channel head surface coil(SNR:12.06;CNR1:4.70;CNR2:6.49)and knee coil(SNR:14.42; CNR1:5.30;CNR2.9.06).The SNR(72.89)and CNR1(18.18),CNR2 (53.32)of SE T1WI with 384X256 matrix were higher than that(SNR:34.18; CNR1:11.72;CNR2:24.85)with 512X512.The SNR(SE T1WI:39.57;frFSE T2WI.27)and CNR1(SE T1WI:34.38;frFSE T2WI:27.60),CNR2(SE T1WI:33.63;frFSE T2WI:22.08)using 3 NEX were highest.Conclusion:The good SNR and CNR of coronary wall can be achieved using temporomandibular surface coil,384X256 in matrix and 3 NEX.Part Two64-slice Spiral CT and MRI Study of Coronary Atherosclerotic Plaques in Vitro:Comparison with PathologyObjective:To assess the values of 64-slice CT and MRI in demonstrating the component of coronary atherosclerotic plaques in vitro.Materials and Methods:Thirteen consecutive autopsy hearts(12 males,mean age 86 years old)were examined after intubating into left main trunk successfully. CT was performed on Siemens sensation cardiac 64 spiral CT scanner with 120 kV,200 eff.mAs,pitch 1.0,slice collimation 64x0.6mm,0.5s/r,scan time 3s, thickness 0.6mm,increment 0.4mm.4 ml contrast agent(omnipaque 350mgI/ml)was infused into 100ml saline and then was injected into LAD.MRI was performed on GE SIGNA 1.5T HD with 3D FIESTA sequence which was used to locate left anterior descending artery(LAD)and the cross-sectional images of 2D T1WI,PDW,frFSE T2WI perpendicular to long axis of LAD were obtained.Scan parameters included:SE T1WI:TR 440ms,TE 21ms,FOV 12cmx9cm,thickness 2mm,slice space 0.2mm,matrix 512x512,NEX 2;SE PDW:TR 2000ms,TE 21ms,FOV 12cmx9cm,thickness 2mm,slice space 0.2mm,matrix 512x512,NEX 2;frFSE:TR 4500ms,TE 105ms,FOV 12cmx9cm, thickness 2mm,slice space 0.2mm,matrix 512x512,NEX 2.0.2ml Resovist (0.5mmol Fe/ml)was infused into 100ml saline and then injected into LAD before PDW and T2WI started.Standard pathologic sections were obtained corresponding to the MRI and CT images perpendicular to LAD.CT、MRI images and pathologic sections were independently reviewed,categorized and compared. The sensitivity,specificity of CT and MRI classification of plaques were analyzed respectively using diagnostic test.Results:Ninty-four histological sections were matched with CT and MRI images. The sensitivity and specificity,respectively,of CT for categorizing each lesion type were as follows:typeⅠ-Ⅱ,0%and 100%;typeⅢ,0%and 100%; typeⅣ-Ⅴ,92.3%and 86.8%;typeⅥ,0%and 100%;typeⅦ,100%and 100%;typeⅧ,100%and 97.8%.The mean CT values for each lesion type were as follows:typeⅣ-Ⅴ,53.7HU;typeⅦ,1065HU;typeⅧ,89.3HU.The sensitivity and specificity of MRI for categorizing each lesion type were as follows:typeⅠ-Ⅱ,60%and 100%;typeⅢ,80%and 100%;typeⅣ-Ⅴ,96.2%and 86.8%;typeⅥ,100%and 98.9%;typeⅦ,93%and 100%; typeⅧ,100%and 98.9%.Slightly high signal on MRI images representing lipid component pathologically could be detected in 48.8%calcified lesions. Neovascularization could be found in 45.7%histological sections.The neovascularization and inflammatory cells on histological sections were found in 50%of typeⅣ-Ⅴlesions,100%of typeⅥlesions,58%of typeⅦlesions and 100%of typeⅧlesions.Conclusions:MRI is superior to CT for demonstrating the characteristics of coronary atherosclerotic plaques and plaque classification.Inflammatory cells and neovascularization in the lesions can promote instability of plaques and be dramatically increased in the advanced lesions. Part ThreeEvaluating the Enhancement of Atherosclerotic Plaque on Contrast-enhanced MRA:Comparison with CTAObjective:To evaluate the enhancement of coronary atherosclerotic plaque revealed by CTA using pre- and post-contrast navigator-gated 3D-SSFP sequence and the relationship between plaque enhancement on contrast-enhanced MRA and CT value of the plaque.Materials and methods:Nineteen patients(mean age 56 years old,15 males) with non-calcified or mixed plaques with main non-calcified component on the proximal or middle segments of coronary artery detected by MDCT were recruited for MRA study with GE 1.5T HD MRI scanner.The coronary MRA was performed using a navigator-gated 3D-SSFP sequence before and after administration of Gd-DTPA.Coronary MRA was acquired 2～3 times after Gd-DTPA administration on the segments with plaques.30ml Gd-DTPA was injected with biphase:10ml at a flow rate of 1.5ml/s and 20ml at 0.05ml/s.The cross-sectional images perpendicular to the long axis of coronary artery were reformatted on MRA.The locations of plaques on MRA were corresponding to sites on CTA,at the same distance to the origin or bifurcation.Plaque enhancement was assessed using CNR(contrast-to-noise ratio:signal of plaque minus signal of adjacent fat tissue divided by noise).An 50%increasing of CNR was defined as enhancement.The relationship between CNR increment and CT value was analyzed.Signal of the aortic root and thoracic muscle were measured and SNR(signal-to-noise:signal of aortic root divided by noise)and CNR(signal of aortic root minus signal of thoracic muscle divided by noise)were calculated pre- and post-contrast MRA.Image quality were compared before and after contrast injection using t-test.Results:Twenty-four plaques of 14 patients were identified on both pre- and post-contrast MRA at the corresponding site of CTA.11 plaques showed enhancement and 13 plaques showed no enhancement.Of 11 enhanced plaques,5 plaques showed enhancement at 5 minutes after contrast injection,others at 10-15 minutes.Of 13 unenhanced plaques,4 plaques showed high signal on pre-contrast scan and others showed low signal.It is helpful to differentiate plaques and lumen after contrast injection.CNR between 24 plaques and surrounding fat tissue were respectively 10.29±4.28 and 14.08±5.8 in pre- and post-contrast MRA and there was a significant difference(P＜0.01).CNR were significantly increased from 8.43±3.59 to 17.55±6.18 after contrast administration in 11 enhanced plaques and no significant change(11.86±4.3 versus 11.15±3.48)in 13 non-enhanced plaques. There was no significant difference of CT value between the enhanced plaques (68.44±24.72)and non-enhanced plaques(57.82±24.13).There was no relationship between CNR increase of coronary atherosclerotic plaque on MRA and CT value.The SNR and CNR at 5 minutes after contrast injection (35.37±6.84 and 21.57±6.08)were significantly higher than that of pre-contrast MRA(27.38±6.24 and 13.19±6.50).The SNR at 15 minutes after contrast injection(33.81±9.43)was higher than that of pre-contrast MRA,but there was no statistically difference.The CNR at 15 minutes after contrast injection(21.20±7.65)was significantly higher than that of pre-contrast MRA.The SNR and CNR at 15 minutes after contrast injection were no significant differences compared with that at 5 minutes after contrast injection.Conclusions:Enhancement of coronary atherosclerotic plaques can be demonstrated on CEMRA.Enhancement of plaques may be associated with inflammation,fibrosis and neovascularization pathologically,predicting the vulnerability of atherosclerotic plaques.The enhancement of plaques on MRA has no relationship with CT value on CTA.T1-shorting effect in the blood can be prolonged by quick injection combining with slow infusion of Gd-DTPA and the SNR and CNR can be improved during multiple scans of coronary MRA compared with pre-contrast MRA. Spiral computed tomography;Contrast mediaPart FourThe Accuracy of Assessing Coronary Atherosclerotic Plaque by 64-Slice Spiral CT:Comparison with IVUSObjective:To assess the value of 64-slice spiral CT in demonstrating coronary atherosclerotic plaque composition and quantification of plaque burden by comparison with intravascular ultrasound(IVUS).Materials and Methods:Fourteen patients(9 males,mean age 58 years)with atherosclerotic plaques on the proximal or middle segments of coronary artery demonstrated by MDCT were included.IVUS was performed after CT examination within a week.The coronary angiography(CTA)was performed using Siemens Sensation Cardiac-64 MDCT.Coronary arteries were reconstructed using MIP and MPR and the cross-sectional images perpendicular to the long axis of coronary artery were obtained.The CT values of the plaques were measured. The plaques were classified as soft,fibrotic and calcified plaques according to CT values.The minimum lumen area(MLA),external elastic membrane cross sectional area(EEM CSA)were measured and plaque area,plaque burden were calculated.The composition of plaques were confirmed by IVUS and the MLA, EEM CSA,plaque area,plaque burden measured or calculated by MDCT were compared with IVUS.The sensitivity and specificity of classifying plaques types by MDCT were assessed and average CT value of every type plaque was acquired.Results:Total 25 plaques were included in this study.The average CT value of 11 soft plaques was 49±32HU,7 fibrotic plaques was 93±23HU,7 calcified plaques was 1138±350HU.The sensitivity and specificity of MDCT for identifying soft plaques were 90.9%and 92.9%,85.7%and 94.4%for fibrotic plaques,100%and 100%for calcified plaques.Vessel area,lumen area,plaque area and plaque burden measured or calculated by MDCT(16.2±5.1mm~2, 6.58±4.1mm~2,9.61±3.8mm~2,60±18%)were higher than those by IVUS (14.5±4.8mm~2,6.28±4.3mm~2,8.22±3.6mm~2,58.5±20.1%),but there was no statistical difference.Conclusion:64-slices MDCT is an accurate and noninvasive tool for assessment of coronary atherosclerotic plaques composition and quantification of plaque burden.更多还原