【作者】 王明慧；

【导师】 葛均波； 钱菊英； 王克强；

【作者基本信息】 复旦大学 ， 内科学， 2009， 博士

【摘要】 第一部分64层螺旋CT对冠状动脉病变的诊断价值目的:以冠状动脉造影检查(CAG)为标准,探讨64层螺旋CT(64-MDCT)冠状动脉成像技术对冠状动脉狭窄病变、先天性冠状动脉畸形和变异病变的诊断价值。方法:2006年12月至2008年10月,收集140例拟诊为冠心病入院的患者行64-MDCT检查,64-MDCT检查后1月内再行CAG检查。排除禁忌症后,所有患者检查前一小时给予口服美托洛尔(metoprolol)25mg,尽量控制心率在65次/分左右。配合回顾性ECG门控技术进行多角度观察(LAO,RAO,LAO Cranial/Caudal,RAO Cranial/Caudal)和横断面(cross—section)观察,并采用薄层最大密度投影(MIP)、多平面重建(MPR)和三维容积重建(VR)等后处理方法评价管腔≧1.5mm的冠脉,以管腔直径减少≧50%定义为有意义的狭窄病变,并根据狭窄率的不同分为Ⅰ级狭窄:50%≦DS＜70%;Ⅱ级狭窄:70%≦DS＜90%;Ⅲ级狭窄:90%≦DS≦99%;Ⅳ级:完全闭塞。64-MDCT结果以QCA结果为参照。心肌桥的诊断根据冠脉的横断面图像和MPR重建图像显示冠脉节段贴紧于心肌或明显可见被不同厚度的心肌或纤维脂肪组织覆盖,且该处的管腔于收缩期显示细小或模糊,但于舒张期可完全或部分恢复。以CAG结果为标准,分析64-MDCT对先天性冠状动脉畸形和变异病变诊断的准确性。结果:与QCA相比,64-MDCT可评价冠脉节段1863段(92.6%),64-MDCT对有意义冠状动脉狭窄病例的敏感性为95.6%(65/68),特异性为93%(67/72),阳性预测值为92.9%(65/70),阴性预测值为95.7%(67/70)。64-MDCT诊断Ⅰ、Ⅱ、Ⅲ、Ⅳ级冠脉狭窄病变的敏感度分别为97.2%、93.1%、96.3%和100%(P=0.69),特异性分别为99.0%、99.5%、99.8%和99.9%(P=0.87),各组间差异无统计学意义。64-MDCT对不同冠脉节段有意义狭窄的诊断敏感性各不相同,LMA可达100%,其次是LAD 98.7%、RCA 94.5%和LCX 92.3%。其中LCX和RCA的远段敏感性较低,分别为(75%和85.7%),对不同节段冠脉有意义狭窄的敏感性、特异性、阳性预测值、阴性预测值的差异无统计学意义。以CAG为金标准,64-MDCT准确诊断心肌桥23例,21段单处心肌桥,位于LAD中段,2段为非单处(双段)心肌桥,分别位于LAD中段及远段。其中3例心肌桥伴有近段的冠脉狭窄病变,冠脉狭窄达Ⅰ级。64-MDCT检出心肌桥的敏感性为92%,特异性为98.2%,阳性预测值为92%,阴性预测值为98.2%。全部12例先天性冠状动脉畸形和变异病变均被64-MDCT准确诊断。结论:64-MDCT可较好地显示冠状动脉及其分支,可作为冠心病常规筛查的无创性检查方法。但对于严重钙化斑块所致的冠脉狭窄,往往高估了狭窄病变的程度而直接影响其对冠脉狭窄判断的准确性,这仍是多层螺旋CT冠脉显像技术的难点。在诊断先天性冠状动脉畸形和变异方面,64-MDCT提供了可靠的无创伤性检查方法。在以后的研究中可进一步增加病例数,以更准确地评价64-MDCT的诊断价值。随着多层螺旋CT的不断发展,时间和空间分辨率的进一步提高,无创性多层螺旋CT在冠状动脉病变的诊断方面,将有更好的临床应用价值。第二部分急性冠状动脉综合征不稳定斑块病变的64-MDCT特征和相关的血清学研究目的:以血管内超声(IVUS)检查作为金标准,探讨64层螺旋CT(64-MDCT)冠状动脉成像技术对冠状动脉斑块性质定性和定量分析的准确性、比较急性冠状动脉综合征(ACS)和稳定性心绞痛(SAP)相关斑块病变的CT特征,探讨64-MDCT对诊断ACS的价值。从血清学角度探讨基质金属蛋白酶-9(MMP-9)、金属蛋白酶组织抑制剂-1(TIMP-1)、白介素6(IL-6)、白介素18(IL-18)及C-反应蛋白(CRP)与急性冠状动脉综合征(ACS)的关系。方法:2007年12月至2008年11月,收集70例冠心病患者,分为ACS组(35例)和稳定性心绞痛组(35例),64-MDCT检查后1月内接受CAG和IVUS检查。另外收集35例非冠心病患者作为血清学检查的对照组。在IVUS检查中,根据冠脉斑块的回声不同,把斑块分为软斑块、纤维性斑块、钙化性斑块和混合性斑块。在64-MDCT检查中,根据冠脉斑块的不同CT值(HU),将斑块分为软斑块:CT值为≤50HU:纤维斑块:CT值为50～119HU;钙化斑块:CT值≥120HU,检查的结果与IVUS对比。同时测量近端参照血管面积、远端参照血管面积、参照血管平均面积、斑块面积、斑块负荷和血管重构指数(remodeling index,RI),RI＞1.05为正性重构;RI＜0.95为负性重构。以IVUS作为金标准,分析64-MDCT对斑块定性和定量的可靠性。采用双抗体夹心(ABC-ELISA)法对35例ACS组,35例SAP组,35例非冠心病患者(对照组)外周血清MMP-9、TIMP-1、IL-6、IL-18、CRP水平进行测定。结果:103段64-MDCT和QCA均诊断为有意义的冠脉狭窄病变(DS≥50%)中,有15段因冠脉完全闭塞无法行IVUS检查而被排除。在IVUS检出的88段病变冠脉中,64-MDCT发现81段(92%)并纳入对照研究,其中ACS组占39段,不稳定性心绞痛组占42段,分别位于左前降支56段,左回转支5段,右冠状动脉18段,左主干2段。IVUS发现软斑块31个(斑块破裂2个)、纤维斑块18个、钙化斑块19个、混合性斑块13个;64-MDCT发现软斑块30个、CT值19±42HU(—22～45HU),纤维斑块19个、CT值81±23HU(61～112HU),钙化斑块20个、CT值302±91HU(175～567HU),混合斑块12个、CT值118±48HU(138～392),四种斑块的CT值差异有统计学意义(P＜0.01)。64-MDCT对不同斑块的诊断敏感性分别为软斑块(90.3%),纤维斑块(88.9%),钙化斑块(100%)和混合性斑块(92.3%),P=0.03,四者差异有统计学意义;以IVUS为金标准,ACS组患者斑块病变以软斑块为主(61.5%vs 14.3%(SAP组),P＜0.001)。其中2段(2/24)可见斑块破裂。ACS组以偏心斑块为主(71.4%vs 52.5%(SAP组),P＞0.05),但两组差别无统计学意义,对两组患者64-MDCT的测量数据进行比较,ACS组患者的近端参照血管EEM CSA(15.9±1.8 vs 14.8±2.0mm~2,P=0.039)、远段参照血管EEM CSA(13.1±2.3 vs 12.6±2.0mm~2,P=0.026)、参照血管平均EEM CSA(14.1±1.7 vs 13.7±1.6mm~2,P=0.018),病变处EEM CSA(14.8±2.2 vs 13.9±2.1mm~2,P=0.029),斑块面积(11.1±2.0 vs 9.8±1.8mm~2,P=0.012)和斑块负荷(72.8±8.2%vs67.4±8.1%,P=0.001)明显大于SAP组;而管腔CSA(3.7±1.4 vs 4.3±1.3,P=0.035)较SAP组小。ACS组患者的病变重构指数大于SAP组(1.05±0.09 vs 0.99±0.06,P=0.032),差别有统计学意义。ACS组斑块病变多表现为正性重构(61.6%vs 33.3%,P＜0.05),差别有统计学意义。两种技术测量近端参照血管EEM CSA、远段参照血管EEM CSA和参照血管平均EEM CSA有较好的相关性,r分别为0.785、0.732和、0.745,P＜0.001;病变处EEM CSA、管腔CSA、斑块面积、斑块负荷和重构指数的相关性相对较弱,r分别为0.521、0.667、0.711、0.701和0.672,P＜0.05。ACS组血清MMP-9、TIMP-1、IL-6、IL-18、CRP水平明显高于SAP组,差异具有统计学意义(P＜0.01或P＜0.05),SAP组血清MMP—9、IL-18和IL-6的水平高于对照组差异具有统计学意义(P＜0.01或P＜0.05);TIMP-1和CRP水平与对照组无差异(P＞0.05)。ACS组血清MMP-9水平与TIMP-1无相关性(r=-0.169,P=0.33),与IL—18呈正相关(r=0.398,P＜0.05)。在SAP组血清MMP-9与TIMP-1呈正相关(r=0.381,P＜0.05)。结论:64-MDCT对于冠脉斑块的检出率高(92%),ACS的斑块病变以软斑块为主,64-MDCT图像上显示为低密度斑块影(CT值≤50HU)。64-MDCT可作为预测不稳定性斑块的无创检查方法。在斑块定量分析方面,64-MDCT与IVUS有较好的相关性,ACS组斑块病变多表现为正性重构,但对于钙化严重的节段,可直接影响CT测量的准确性。血清MMP—9、TIMP-1、IL-6、IL-18和CRP可作为检测ACS的血清学指标,其中MMP—9、IL-18的高水平以及MMP-9和TIMP-1的动态失衡在ACS的发生和病情演变中起着关键的因素,同时配合64-MDCT冠脉检查的结果,可为临床提供更可靠的诊断依据。血清学检查具有简单、经济、方便、无创性和重复性高的优点,适合临床开展,但还需要更大量的样本作前瞻性研究,以证实相关指标的临床价值。第三部分64-MDCT对冠脉支架术后随访的应用价值目的:以定量冠状动脉造影检查(QCA)检查作为标准,探讨64-MDCT在评价支架置入术后患者支架内再狭窄(in-stent restonsis,ISR)的诊断价值。方法:2008年4月至2008年11月共收集35例拟行冠脉造影复查的支架置入术后患者。所有患者均为窦性心律,无肾功能不全(Cr＜120mmol/L),心功能不全＜3级,无碘造影剂过敏史,无冠状动脉搭桥术史。全部患者先行64-MDCT冠脉成像检查,1月内再行CAG检查。64-MDCT根据MPR、MIP、VR的重建图像,结合重组后的横断面图像,根据支架内管腔造影剂显示的增强(Contrastenhancement)或衰减(Contrast attenuation),进一步评价是否存在ISR,通过自动冠状动脉血管分析软件(Cardiac Automatic Vessel analysis,CVA)对冠状动脉血管行定性定量分析,利用线径测量通过电子测径器对支架的管腔进行测量,若直径狭窄率≧50%,则诊断为ISR。64-MDCT诊断的结果与QCA的诊断结果进行比较分析。结果:32例患者共43根支架纳入研究,QCA共诊断14根支架存在支架内再狭窄,64-MDCT准确评价13根,准确排除25根。64-MDCT漏诊1根,误诊4根支架内再狭窄。64-MDCT诊断支架内再狭窄的敏感性和特异性分别为92.8%(13/14)和86.2%(25/29),阳性预测值为76.4%(13/17),阴性预测值为96.1%(25/26)。结论:64-MDCT可作为诊断支架内再狭窄首选的无创性检查方法,特别是对临床上考虑支架内再狭窄可能性较低的患者。但对于支架内径较小(＜2.5mm),冠脉远段及严重钙化斑块病变处的支架,64-MDCT仍未能提供理想的评价。在观察支架图像时,必需同时结合和比较支架的MIP及横断面图像,以更好的判断支架内管腔的情况,提高诊断的准确性。更多还原

【Abstract】 PartⅠThe value of 64-multidetector Computed Tomography in the diagnosis of coronary artery diseaseObjectives:To evaluate 64-multidetector computed tomography(64-MDCT) in the diagnosis of coronary artery stenosis and congenital anomalies.Methods:From 2006/12 to 2008/10,140 patients suspected of coronary artery disease were undergoing 64-MDCT imaging and within one month, coronary angiography(CAG) was performed.All patients were took a dose of 25 mg metoprolol orally one hour before 64-MDCT imaging.Together with the retrospectively ECG-gated reconstruction,some observation methods (including LAO,RAO,LAO Cranial/Caudal,RAO Cranial/Caudal and cross—section) and reconstruction methods(including Maximum Intensity Projection(MIP)、Multi-planar Reconstruction(MPR) and Volume Rendering (VR)) were used to image the coronary artery segments,of which the diameter was no little than 1.5mm.The presence of diameter reduction(DS)≥50%in 64-MDCT imaging was considered as significant coronary stenosis, the degree of which was classified as:GradeⅠ,50%≦DS＜70%;GradeⅡ, 70%≦DS＜90%;GradeⅢ,90%≦DS≦99%;GradeⅣ,complete obstruction. Myocardial bridging was diagnosed in 64-MDCT imaging when an intramuscular segment of a coronary artery was visualized on axial and MPR images,covered by myocardial muscle or fibrous-fatty tissue partial or entirely.They were compressed during systole phage and recovery on diasystole phage.All results were compared with CAG.Results:2009 segments can be evaluated by QCA,of which 1863 segments (92.6%) can be evaluable by 64-MDCT.The sensitivity and the specificity to diagnose significant coronary stenosis(DS≧50%) cases was 95.6%(65/68) and 93%(67/72) respectively,the positive and negative predictive value was 92.9%(65/70) and 95.7%(67/70) respectively.The sensitivity and the specificity to diagnose significant coronary stenosis(DS≧50%) segments was 96.6%(141/146) and 98.3%(1688/1717) respectively,the positive and negative predictive value was 82.9%(141/170) and 99.7%(1688/1693) respectively.In addition,the detection sensitivity of GradeⅠ,Ⅱ,ⅢandⅣstenosis were 97.2%,93.1%,96.3%and 100%respectively(P=0.69), the specificity were 99.0%,99.5%,99.8%and 99.9%respectively(P=0.87). The detection sensitivities of significant coronary stenosis differed in different coronary segments(P＞0.05):the highest was seen in LMA(100%), then in LAD(98.7%),RCA(94.5%) and LCX(92.3%).The lowest was in distal LCX(75%) and distal RCA(85.7%).There were 141 segments of GradeⅠ～Ⅲstenosis evaluated by 64-MDCT:77 segments in LAD,24 segments in LCX,35 segments in RCA and 5 segments in LMA.Compared with CAG,23 myocardial bridging cases were found through 64-MDCT,including 21 cases of single myocardial bridging in LAD and 2 cases of dual myocardial bridgings.The sensitivity,specificity,positive and negative predictive value to diagnose myocardial bridging were 92%,98.2%,92%and 98.2%respectively.64-MDCT detected all 12 cases of congenital coronary artery anomalies and malformations correctly.Conclusions:As a non-invasive technology,64-MDCT can image coronary arteries and branches excellently.It can evaluate stenosis,congenital anomalies and malformations correctly.But severe calcification can affect imaging and tend to overestimate the degree of stenosis.PartⅡThe 64-MDCT characteristics of unstable plaques in acute coronary syndrome patients and the related serum marks study.Objectives:To evaluate 64-MDCT in the diagnosis of different coronary plaque and plaque characteristics of acute coronary syndrome(ACS) patients.The value of serum MMP-9,TIMP-1,IL-6,IL-18 and CRP in the diagnosis of ACS also was evaluated. Methods:From 2007/12 to 2008/11,70 patients of coronary artery disease were enrolled.According to clinical symptoms,they were divided into ACS (n=35) group and SAP(n=35) group.These patients were undergoing 64-MDCT imaging and within one month,CAG and IVUS were performed.In 64-MDCT imaging,the density CT measurement(Hounsfield units,HU) was used to determine different types of plaques:soft plaque(≦50HU),fibrous plaque (50-119HU) and calcified plaque(≧12onu).The results were compared with IVUS.IVUS and 64-MDCT analysis included quantitative measurements of cross-sectional area of external elastic membrane(EEM CSA) of the lesion site and at the proximal and distal reference sites.The plaque burden and remodeling index(RI) were also analyzed.Positive remodeling was defined as RI＞1.05 and negative remodeling as RI＜0.95.Serum MMP-9, TIMP-1,IL-6,IL-18 and CRP were evaluated using ABC-ELISA,compared with 35 control subjects(without coronary heart disease).Results:88 segments were evaluated by IVUS,of which 81 segments(92%) can be evaluated by 64-MDCT:56 segments in LAD,5 segments in LCX,18 segments in RCA and 2 segments in LMA.We found 31 soft plaques、18 fibrous plaques、20 calcified plaques and 12 mixed plaque by IVUS.64-MDCT found 30 soft plaques(19±42HU(—22～45HU)),19 fibrous plaques(81±23HU (61～112HU)),20 calcified plaques 302±91HU(175～567HU) and 12 mixed plaques(118±48HU(138～392HU)),P＜0.01.The detection sensitivity of soft plaques、fibrous plaques、calcified plaques and mixed plaques were 90.3%,88.9%,100%and 92.3%respectively(P=0.03).Soft plaque was observed more frequently in ACS group than in SAP group(61.5%vs 14.3%, P＜0.001),including 2 plaque rupture;whereas calcified plaque was more common in SAP group(38.1%vs 7.7%)(P=0.001).Eccentric plaque was observed more frequently in ACS group than in SAP group(71.4%vs 52.5%, P＞0.05).Compared with SAP group,the EEM CSA at the proximal reference sites(15.9±1.8 mm~2 vs 14.8±2.0 mm~2,P=0.039) and distal reference sites (13.1±2.3 mm~2 vs 12.6±2.0 mm~2,P=0.026) were larger in ACS group in 64-MDCT imaging.The mean EEM CSA of reference sites((14.1±1.7 mm~2 vs 13.7±1.6 mm~2,P=0.018),lesion EEM CSA(14.8±2.2 mm~2 vs 13.9±2.1mm~2, P=0.029),the plaque EEM CSA(11.1±2.0 mm~2 vs 9.8±1.8mm~2,P=0.012) and the plaque burden(72.8±8.2 mm~2 vs 67.4±8.1mm~2,P=0.001) were significantly greater in ACS group rather than SAP group,while the lumen EEM CSA(3.7±1.4mm~2 vs 4.3±1.3mm~2,P=0.035) was smaller in ACS group. RI was significantly higher(1.05±0.09 vs 0.99±0.06,P=0.032) and positive remodeling was more frequent in ACS group(61.6%vs 33.3%, P＜0.05).Compared 64-MDCT and IVUS,the correlation coefficients for the EEM CSA at the proximal and distal reference sites,the mean EEM CSA of reference sites were 0.785,0.732 and 0.745 respectively,P＜0.001.The correlation coefficients for the lesion EEM CSA,the lumen CSA,the plaque CSA,the plaque burden and RI were 0.521,0.667,0.711,0.701 and 0.672 respectively,P＜0.05.The serum MMP-9,TIMP-1,IL-6,IL-8 and CRP were significant higher in ACS group than SAP group,P＜0.05.The serum MMP-9, IL-6 and IL-18 were significant higher in SAP group than control group, P＜0.05,but serum TIMP-1 and CRP were similar,P＞0.05.In ACS group,There was no correlation between serum MMP-9 and TIMP-1(r=-0.169,P=0.33),and there was positive correlation between serum MMP-9 and IL-18(r=0.389, P＜0.05).In SAP group,there was positive correlation between serum MMP-9 and TIMP-1(r=0.381,P＜0.05).Conclusions:64-MDCT can identify different coronary plaques based on CT measurement,but may he difficult to differ soft plaques from fibrous plaques.Soft plaque and positive remodeling were observed more frequently in ACS patients.The imbalance of serum MMP-9 and TIMP-1 may be the key point to involve the course of ACS.PartⅢThe value of 64-MDCT in the follow-up of percutaneous coronary intervention(PCI) stenting patientsObjectives:To evaluate the application of 64-MDCT in the follow-up of percutaneous coronary intervention(PCI) stenting patients with the attention to in- stent restenosis(ISR). Methods:From 2008/4 to 2008/11,35 patients with prior percutaneous coronary intervention and coronary stent implantation referred for repeated QCA underwent 64-MDCT imaging.And no more than one month later, they received QCA.All the patients didn’t have arrhythmia,renal failure (Cr＜120mmol/L) or heart failure(Grade＜3).Together with the retrospectively ECG-gated reconstruction,Maximum Intensity Projection (MIP)、Multi-planar Reconstruction(MPR) and Volume Rendering(VR) were used to reconstruct every segment of the coronary artery.Based on contrast enhancement and attenuation in the lumen of stented segments, the presence of diameter reduction≧50%was considered as ISR after PCI stenting.All the results were compared with that of QCA.Results:43 stents from 32 cases were included,14 ISR after PCI stenting were found by QCA,of which 64-MDCT could detect 13 ISR and rule out 25 non-ISR correctly.The sensitivity,specificity,the positive and negative predictive value of 64-MDCT were 92.8%(13/14),86.2%(25/29), 76.4%(13/17) and 96.1%(25/26) respectively.Conclusions:64-MDCT may be a non-invasive follow-up method to evaluate if there exists ISR after PCI stenting,especially in the patients no ISR existing clinically.更多还原