缺血性心脏病多层螺旋CT心肌灌注成像的实验和临床研究
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摘要
第一部分多层螺旋CT心肌灌注成像的实验研究
第一节急性心肌梗塞模型的建立
目的：采用经皮穿刺线段栓塞冠状动脉的方法，制备急性心肌梗塞动物模型。
材料和方法：健康杂种犬5只(编为1～5号)，均为雄性，体重10～15kg，平均12．5kg。1-5号犬均在麻醉下行股动脉穿刺左冠选择性插管，使用医用涤纶线线段栓塞左冠状动脉，并复查冠脉造影见冠脉局部闭塞、心博变慢为制模成功的标志。栓塞完成后3-4h处死动物制作大体标本和病理切片，以证实制模成功。
结果：1号犬在栓塞后超急性期(30min)内死亡，2～5号犬均存活至实验结束。冠脉造影发现1号犬左前降支高位闭塞，3号犬旋支局部闭塞，管腔内造影剂排空延迟。2、4、5号犬为前降支局部管腔闭塞。所有的犬心脏搏动在栓塞后变慢、收缩幅度减弱。大体标本证实相应冠脉走行区见线段栓塞；TTC染色后见梗塞区不染色，呈灰黄色或灰白色外观，TTC染色所见的心肌梗塞区均位于线段栓塞的冠脉的供血区内，1号犬为广泛左室游离壁梗塞，2～4号犬心肌梗塞位于室间隔部位，5号犬则位于前壁心尖。HE染色进一步证实所有的犬为早期心肌梗塞表现。
结论：经股动脉穿刺选择性冠状动脉线段栓塞的方法制作犬心肌梗死模型，操作较简便，成功率和动物成活率较高，可以片作心肌梗死的实验研究。
第二节急性心肌梗塞模型的MSCT心肌灌注成像的实验研究
目的：采用多层螺旋CT(Multi-slice CT，MSCT)回顾性心电门控多期全心增强扫描模式，探讨其评价心肌灌注的可行性，及对心肌梗塞评估的价值。
材料与方法：10只雄性健康杂种犬，体重10～15kg，平均12．5kg，随机分为正常组和实验组，各5只(各1-5号)，实验组模型制作见第一节，其中1号犬因死亡退出实验组。使用CaScroe序列对正常组和实验组动物进行全心、多期动态增强MSCT扫描，先行平扫，注射造影剂后约在第4s、20s、40s进行前三期扫描，在1、2、3、4、5分钟时各扫描一次。实验组2号犬延迟到7min，5号犬延迟到20min。使用DynEva软件绘制时间密度曲线并得到达峰时间和峰值等参数，并以左室强化为基准对相关指标进行标准化。实验组动物按第一节方法获得大体病理标本和病理切片证实。
结果：(1)正常犬的时间密度曲线特征呈快升快降型，峰值后有一个较长的平台期。标准化后的结果显示两相对节段的心肌强化峰值、达峰时间相同，心肌强化达峰时间与左室血池强化时间基本相同(分别为1．06±0．14，1．00)，心肌强化峰值约为左室血池强化峰值的50％±6％；(2)梗塞段心肌时间密度曲线基本呈一直线，缓慢上升缓慢下降，平台期与正常心肌接近。时间密度曲线的特征值提示实验组3～5号犬梗塞心肌达峰时间较正常心肌节段和正常对照组长：分别约1．56±0．52、1．00、1．00(P均＞0．05)；梗塞段心肌的峰值较对侧正常心肌明显减小：分别约0．26±0．04、0．45±0．08(P=0．02)。4只实验组犬MSCT发现心肌梗塞的部位均与TTC染色一致。
结论：(1)．在16层螺旋CT上，能够完成全心、多期动态增强扫描；不同于同层动态增强扫描，MSCT心电门控多期增强扫描可以从多层面、多方位观察心肌灌注缺损区，是一种较全面、较准确评价心肌血流灌注的方法；(2)．MSCT全心、多期动态增强扫描可以半定量评估心肌的灌注特征，有助于定性评价心肌梗塞。
第二部分双源CT首过心肌灌注成像的临床研究
第一节双源CT首过心肌灌注成像对正常人群的定性评估
目的：使用DSCT研究正常人群的不同时相和不同部位的心肌首过灌注强化表现，探讨其定性评估心肌血流灌注的价值，为进一步评价缺血性心脏病提供参考。
材料与方法：随机选取符合正常组入选标准的25例体检者DSCT冠脉成像资料，其中男15例，女10例，平均60±12．5岁。采用回顾性心电门控、非离子型对比剂行DSCT冠脉成像，观察以5％间隔重建的0～100％RR间期的图像，选择最佳收缩期和最佳舒张期作为评价时相，根据17节段法，测量左室基底、中部、心尖部三个层面共17个节段的收缩期和舒张期心肌首过强化值。17个节段的心肌首过灌注强化值的比较采用随机区组方差分析，以25例体检者为区组因素，即25个区组。每个节段收缩期和舒张期心肌首过灌注值的比较采用配对t检验。
结果：25例每个心肌节段收缩期的强化平均值均低于舒张期的强化平均值，除心底的少数节段和心尖外，绝大部分节段舒张期与收缩期强化平均值的差别有极显著的统计学意义(P≤0．001)。经随机区组方差分析和进一步的两两比较(LSD和SNK检验)表明前壁(1、7、13)、下壁(4、10)和心尖(17)各个节段两两比较均无显著性差异，可归为一组；室间隔壁(2、3、8、9、14)和左室侧壁(5、6、11、12、16)各个节段比较均无显著性差异，可归为另一组；两组间(前壁+下壁+心尖区与室间隔壁+左室侧壁)各个节段的差异则均有显著的统计学意义(P≤0．01)。
结论：DSCT冠脉成像作为心肌灌注的定性评估方法，在兼顾冠脉成像和心功能分析的基础上，能初步评价心肌首过灌注及其时相和节段的变化，为进一步评价缺血性心脏病提供参考。
第二节双源CT首过灌注成像定性评价心肌缺血的研究
目的：采用DSCT冠脉成像心肌首过灌注的方法，探讨心肌缺血和心肌梗塞患者的首过心肌灌注表现、不同时相变化的特点，及其鉴别诊断价值。
材料与方法：收集本院确诊的25例心肌缺血和心肌梗塞的DSCT检查资料，平其中男性21例，女性4例，平均年龄61．5±14．6岁。临床最终确诊急性心肌梗塞5例、陈旧性心肌梗塞9例，不稳定心型绞痛11例。采用回顾性心电门控、非离子型对比剂行DSCT冠脉成像，观察以5％为间隔重建0～100％RR间期图像，选择最佳收缩期、最佳舒张期图像作为评价时相。根据合并后的7分段法(本部分第一节研究结果)对早期灌注缺损(Early perfusion Defect，ED)及其对侧的心肌节段测值。所有患者接受了DSA选择性冠脉造影，8例进行了Tc~(99)—MIBI SPECT显像。对心肌梗塞组(14例)和心肌缺血组(11例)的首过强化值进行比较，并行统计学分析。组内收缩期和舒张期强化值的比较采用配对t检验，心肌梗塞组和心肌缺血组的强化值比较使用两独立样本的t检验。
结果：(1)18例DSA冠脉造影证实LAD显著性狭窄的患者DSCT检出相应供血区早期灌注缺损(Early perfusion defect，ED)15例(83．3％)，CX则为5例中的3例(60％)，RCA则为6例中的4例(67．8％)分别被DSCT检出相应供血区的ED；以DSA冠脉造影为对照，DSCT有5例“假阳性”，但其中有2例临床确诊为陈旧性心肌梗塞和1例不稳定型心绞痛(微血管病变)。DSCT与SPECT二者对心肌灌注缺损的检出较一致。(2)收缩期心肌梗塞和心肌缺血首过灌注强化值分别为44．82±15．63HU、72．73±18．47HU(P＜0．001)；舒张期两组的首过灌注强化值分别约45．46±16．12HU、83．10±23．92HU(P＜0．001)。舒张期和收缩期相比，心肌梗塞首过强化值的变化没有显著性差异，而心肌缺血首过强化值的变化有极显著差异(P=0．003)；收缩期心肌梗塞与对侧心肌首过灌注的差值为-54．20±17．28HU，舒张期则为-48．86±17．04HU(P＜0．05)；收缩期和舒张期心肌缺血与对侧心肌首过灌注的差值则分别为-28．37±8．95HU和-24．09±9．92HU(P＜0．05)。
心肌缺血和对侧正常心肌节段首过强化值的95％置信区间在收缩期、舒张期均有一定程度的重叠，收缩期重叠较小；心肌梗塞和对侧正常心肌节段首过强化值的95％置信区间在收缩期、舒张期则没有重叠。
结论：(1)缺血心肌和梗塞心肌的首过强化程度和时相变化均有显著的差异，收缩期可能较舒张期更容易发现心肌缺血，因此DSCT首过灌注结合多时相分析能够为鉴别可逆性缺血和心肌坏死提供参考信息。(2)无论是对心肌缺血还是心肌梗塞，DSCT定位诊断都较准确，不同于DSA冠脉造影和SPECT。DSCT冠脉成像有望成为一站式综合评价冠脉、心功能和心肌灌注的一种新方法。
第三部分双源CT对冠心病患者左室功能和室壁运动的评价
目的：评价双源CT(Dual source CT，DSCT)在评估冠心病患者整体心功能和室壁运动与临床常规超声心动图(Echocardiogram，ECG)的一致性。
材料与方法：收集因胸痛疑为冠心病在我院行DSCT检查的25例患者的临床资料，平均年龄61．5±14．6岁，其中男性21例，女性4例。临床最终确诊急性心肌梗塞5例、陈旧性心肌梗塞9例，不稳定心型绞痛11例。以5％为间隔重建0～100％RR间期多时相数据，使用左室功能评价软件评估射血分数EF、左室短轴缩短率FS和节段性室壁运动，并和ECG对比。
结果：25例患者DSCT测得的FS和EF分别为35．16％±10．16％、63．08％±11．10％；ECG则分别为34．76％±7．37％、61．80％±9．50％，配对t检验两者的差异无显著统计学意义，且相关性良好(r分别约0．86和0．87，p均＜0．001)；按病例数和节段数计算两法对室壁运动的诊断一致性很好(Kappa值分别约0．85、0．86，P均＜0．001)；DSCT诊断的室壁运动异常节段的室壁增厚率较对侧显著减低，分别约20．55％±24．10％和78．63％±30．98％(P＜0．01)。
结论：DSCT时间分辨率高，对复杂心率情况也可完成对整体和节段性左室收缩功能的评估，与ECG一致性良好，能为冠脉形态和首过心肌灌注之外为冠心病的诊断提供更多的信息。
PartⅠAnimal Study of Myocardial Perfusion Imaging by MSCT
Section 1 Establishment of Acute Myocardial Infartction Model
Objective:Coronary artery angiography was performed with permanent medical threadocclusion,which aims for the establishment of acute myocardial infarction animal model.
Materials and Methods:Five domestic dogs weighting 10 to 15 kg (mean:12.5 kg) withnumerical order from 1 to 5,were included in this study.Following intramuscularpre-medication with anaesthesia,Under fluoroscopy guidance,a guiding catheter wasplaced at the origin of the left coronary artery,and a coronary angiogram was obtained.Afterwards permanent suture segments occlusion of the left anterior descending (LAD)coronary artery was performed at mid-section.Coronary artery occlusion was controlledwith coronary angiograms before and after to assure the successful establishement of acuteinfarction.Pathological verification was done afterwards.
Results:One animal died within 30min after the occlusion.Coronary artery occlusion wascontrolled with coronary angiograms adapted to vessel size and location,ranging fromproximal to distal focal occlusions.Intraluminal wash-out of the contrast agent and weakenwall motion were indicated in all animals.TTC staining confirmed extents and location ofMI,which included extensive infarct the left ventricular myocardium in No.1 animal,septalsegment infarct of the left ventricular myocardium in No.2-4 animal,and the apex segmentinfarct in No.5 animal.Further confirmation of early acute myocardium infarction wasachieved with HE staining.
Conclusion:Establishment of acute myocardial infarction animal model by the occlusionof coronary artery is easily accessible,which can be used as the pre-clinical research formyocardial infarction.
Section 2 Experimental Study of Myocardial Perfusion by MSCT:Characterization of Ischemic Myocardium
Obejective:To assess the hemodynamic changes in ischemic cardiac segments usingretrospective ECG-gating contrastenhanced MSCT and its clinical value in the diagnosis ofmyocardial intarction.
Materials and Methods:10 dogs were randomly grouped into study and control groupwith 5 each,and the animal preparation was the same in section 1.MSCT examinationswere performed with a 16-MSCT scanner (SOMATOM Sensation 16,Siemens,Germany)in the supine position.Serial CT scanning of whole cardiac was performed at 4,20 and 40seconds after bolus injection of 1.5ml/kg of non-ionic contrast material (Ultravist 370,Schering) followed by a 30-ml saline chaser bolus,at a flow rate of 3.5～4.5 ml/s,whichwere acquired applying a retrospectively ECG-gated examination protocol with12×1.5-mm collimation and a rotation time of 420 ms.Tube voltage was 120 kV with80mAs.Delayed enhancement scans were performed at 1,2,3,4 and 5 minute afterwards,7and 20 minutes were done to the No.2 and 5 dog in the study group.Pathologicalverification was obtained as stated in section 1.
Results:Ⅰ) Time-density curves for MSCT in control froup demonstrated the maximumslope of consecutive measurements during the wash-in and wash-out period of the contrastmaterial calculated,and a flat-pattern phase after the peak enhancement.Signalintensity/attenuation was expressed as the percentage of increase over baseline ratio ofattenuation of myocardium and left ventricle blood pool,based on which the peakenhancement of the myocardium was 50%±6% with comparison to left ventricle cavum.The adjacent segments were almost the same as left ventricle cavum,in terms of peakenhancement,time to peak,etc.
Ⅱ) Time-density curves for MSCT in infarct group demonstrated the minmum slope ofconsecutive measurements during the wash-in and wash-out period of the contrast materialcalculated,and a flat-pattern phase after the peak enhancement almost the same as normalones.
Results of the semiquantitative analysis of the timedensity curves showed significantdifferences between infarcted and healthy myocardium for SImax,Tmax and slope,whichwere 1.56±0.52、1.00、1.00 (P＞0.05) for time to peak,0.26±0.04、0.45±0.08 (P=0.02)for peak enhancement.TTC staining confirmed extents and location of MI as indicated byMSCT.
Conclusion:16-slice CT imaging allows for the differentiation of hypoperfused andnormal myocardium using retrospective ECG-gating method,which has the potential for visual and semiquantitative assessment of firstpass myocardial perfusion.
PartⅡFirst-pass Myocardial Perfusion By Dual-source CT
Section 1 First-pass Normal Myocardial Perfusion by Dual-source CT
Objective:To investigate first-pass myocardial perfusion in normal segments during thecardiac cycle using contrast-enhanced dual-source CT,this can be future basis for theevaluation of ischemic heart disease.
Materials and methods:25 health check-up patients(15 male,10 female,mean age60±12.5) without suspected coronary artery disease were enrolled as normal casesrandomly doe dual-source CT coronary angiography(Siemens SomatomDefinition,Germany).Reconstructed cardiac images in diastolic and systolic phases wasevaluated using raw data from coronary CT angiography.The attenuation value (inHounsfield units) in the myocardium was used as an estimate of myocardial perfusion.Wemeasured the subendocardial intensity of 17 segments according to the American HeartAssociation classi-fication.Systolic perfusion or diastolic perfusion was calculated bydividing the subendocardial intensity at systole or diastole,respectively,for each segmentby the mean value across all segments for each patient.T-test was used for the statistics.
Results:Systolic perfusion was significantly lower than diastolic one for each segment.The difference between systolic perfusion and diastolic perfusion in ischemic segments wassignificantly lower than that in nonischemic segments (P(?)0.001).There was no significantdifference in diastolic perfusion betweenc segment 1,7,13;segment 4,10;and segment 17,which can be grouped together,as well as segment 2、3、5、6、8、9、11、12、14 and 16.The differencebetween systolic and diastolic perfusion varied among the regions.Systolicperfusion was lower than diastolic perfusion in the septal wall,whereas systolic perfusionwas higher than diastolic perfusion in few segments of the anterior and lateral walls.Systolic perfusion and diastolic perfusion in the inferior wall were similar (P(?)0.01).
Conclusion:DSCT can be utilized as qualitativer evaluation for a pattern of subendocardialhypoperfusion at systole and normal perfusion at diastole characterizes ischemic myocardium.
Section 2 First-pass Ischemic Myocardial Perfusion byDual-source CT
Objective:To Assess the hemodynamic changes in ischemic cardiac segments during thecardiac circle using dual source CT,and the clinical value for differential diagnosis.
Material and Methods:25 patients(21 male,4 female,mean age 61.5±l4.6) withconfirmed ischemic or infarct myocardial diaseas were enrolled for dual-source CTcoronary angiography(Siemens Somatom Definition,Germany).Reconstructed cardiacimages in diastolic and systolic phases was evaluated.We measured the subendocardialintensity of 17 segments according to the American Heart Association classi-fication.Systolic perfusion or diastolic perfusion was calculated by dividing the subendocardialintensity at systole or diastole,respectively,for each segment by the mean value across allsegments for each patient.Early perfusion Defect and its opposite segment was measured.The first-pass enhancement between the infarct patients(n=14) and ischemic ones(n=11)was compared using independent T-test for the statistics.
Results:1)15 out of 18 with proven stenosis in LAD (83.3%) were indicated by DSCT forEarly perfusion defect,3 out of 5(60%) with proven CX stenosis were indicated by DSCT,and 4 out of 6(67.8%0 were for RCA.Good agreement was reached between DSCT andSPECT in this regard.
2)systolic phase,the peak enhancement for infarction and i schemia were 44.82±15.63HU、72.73±18.47HU (P＜0.001) repectively;45.46±16.12HU、83.10±23.92HU (P＜0.001)respectively in the diastolic phase.No significant diference was indicated between thefirst-pass peak enhancement in the infarction group,while significant difference in theischemia group(P=0.003).The difference between the infarct myocardium and the oppositeone was-54.20±17.28HU in systolic phase,while-48.86±17.04HU in diastolic phase (P＜0.05).Those were-28.37±8.95HU和-24.09±9.92HU in dsystolic and iastolic phase forischemia (P＜0.05)
Conclusion:Quantification of first-pass perfusion CT images with dual source CT allowscharacterization of intramural myocardial perfusion in patients with myocardial ischemia,and myocardial ischemia could be found in systolic phase much easy than diastole phase,which brings up DSCT as a potential for the comprehensive evaluation for the coronary,cardiac function and myocardium perfusion.
PartⅢAssessment of The Global and Regional Left VentricleFunction by Dual Source CT
Objective:To evaluate the agreement between DSCT and ECG to assess the global andregional left ventricle function in patients with coronary artery disease.
Materials and Methods:25 cases with coronary disease underwent DSCT coronaryangiography (SOMATOM Definition,Siemens,Germany),and the same data were used toassess the ejection fraction (EF),fractional shortening (FS) and regional wall motion(Siemens MMWP,Germany).ECG served as reference.
Results:There was no significant difference between DSCT and ECG to evaluate the EFand FS (p＞0.05),with good correlation (r=0.86 and 0.87,p＜0.001,respectively).Theagreement between DSCT and ECG in diagnosing regional wall motion abnormality wasgood.no matter counted as cases(Kappa=0.85,p＜0.001) or segments(Kappa=0.87,p＜0.001).The wall thickening fraction of the segments with abnormal motion diagnosed byDSCT were significant lower than its opposite segments(20.55%±24.10% vs 78.63%±30.98%,P＜0.01).
Conclusion:With the breakthrough of the temporal resolution,DSCT permits accurateassessing left ventricle function even in patients with heart rate variability,and agreementwith routine ECG is good.DSCT is expected to provide more information for CADdiagnosis and prognosis.
第一节急性心肌梗塞模型的建立
目的：采用经皮穿刺线段栓塞冠状动脉的方法，制备急性心肌梗塞动物模型。
材料和方法：健康杂种犬5只(编为1～5号)，均为雄性，体重10～15kg，平均12．5kg。1-5号犬均在麻醉下行股动脉穿刺左冠选择性插管，使用医用涤纶线线段栓塞左冠状动脉，并复查冠脉造影见冠脉局部闭塞、心博变慢为制模成功的标志。栓塞完成后3-4h处死动物制作大体标本和病理切片，以证实制模成功。
结果：1号犬在栓塞后超急性期(30min)内死亡，2～5号犬均存活至实验结束。冠脉造影发现1号犬左前降支高位闭塞，3号犬旋支局部闭塞，管腔内造影剂排空延迟。2、4、5号犬为前降支局部管腔闭塞。所有的犬心脏搏动在栓塞后变慢、收缩幅度减弱。大体标本证实相应冠脉走行区见线段栓塞；TTC染色后见梗塞区不染色，呈灰黄色或灰白色外观，TTC染色所见的心肌梗塞区均位于线段栓塞的冠脉的供血区内，1号犬为广泛左室游离壁梗塞，2～4号犬心肌梗塞位于室间隔部位，5号犬则位于前壁心尖。HE染色进一步证实所有的犬为早期心肌梗塞表现。
结论：经股动脉穿刺选择性冠状动脉线段栓塞的方法制作犬心肌梗死模型，操作较简便，成功率和动物成活率较高，可以片作心肌梗死的实验研究。
第二节急性心肌梗塞模型的MSCT心肌灌注成像的实验研究
目的：采用多层螺旋CT(Multi-slice CT，MSCT)回顾性心电门控多期全心增强扫描模式，探讨其评价心肌灌注的可行性，及对心肌梗塞评估的价值。
材料与方法：10只雄性健康杂种犬，体重10～15kg，平均12．5kg，随机分为正常组和实验组，各5只(各1-5号)，实验组模型制作见第一节，其中1号犬因死亡退出实验组。使用CaScroe序列对正常组和实验组动物进行全心、多期动态增强MSCT扫描，先行平扫，注射造影剂后约在第4s、20s、40s进行前三期扫描，在1、2、3、4、5分钟时各扫描一次。实验组2号犬延迟到7min，5号犬延迟到20min。使用DynEva软件绘制时间密度曲线并得到达峰时间和峰值等参数，并以左室强化为基准对相关指标进行标准化。实验组动物按第一节方法获得大体病理标本和病理切片证实。
结果：(1)正常犬的时间密度曲线特征呈快升快降型，峰值后有一个较长的平台期。标准化后的结果显示两相对节段的心肌强化峰值、达峰时间相同，心肌强化达峰时间与左室血池强化时间基本相同(分别为1．06±0．14，1．00)，心肌强化峰值约为左室血池强化峰值的50％±6％；(2)梗塞段心肌时间密度曲线基本呈一直线，缓慢上升缓慢下降，平台期与正常心肌接近。时间密度曲线的特征值提示实验组3～5号犬梗塞心肌达峰时间较正常心肌节段和正常对照组长：分别约1．56±0．52、1．00、1．00(P均＞0．05)；梗塞段心肌的峰值较对侧正常心肌明显减小：分别约0．26±0．04、0．45±0．08(P=0．02)。4只实验组犬MSCT发现心肌梗塞的部位均与TTC染色一致。
结论：(1)．在16层螺旋CT上，能够完成全心、多期动态增强扫描；不同于同层动态增强扫描，MSCT心电门控多期增强扫描可以从多层面、多方位观察心肌灌注缺损区，是一种较全面、较准确评价心肌血流灌注的方法；(2)．MSCT全心、多期动态增强扫描可以半定量评估心肌的灌注特征，有助于定性评价心肌梗塞。
第二部分双源CT首过心肌灌注成像的临床研究
第一节双源CT首过心肌灌注成像对正常人群的定性评估
目的：使用DSCT研究正常人群的不同时相和不同部位的心肌首过灌注强化表现，探讨其定性评估心肌血流灌注的价值，为进一步评价缺血性心脏病提供参考。
材料与方法：随机选取符合正常组入选标准的25例体检者DSCT冠脉成像资料，其中男15例，女10例，平均60±12．5岁。采用回顾性心电门控、非离子型对比剂行DSCT冠脉成像，观察以5％间隔重建的0～100％RR间期的图像，选择最佳收缩期和最佳舒张期作为评价时相，根据17节段法，测量左室基底、中部、心尖部三个层面共17个节段的收缩期和舒张期心肌首过强化值。17个节段的心肌首过灌注强化值的比较采用随机区组方差分析，以25例体检者为区组因素，即25个区组。每个节段收缩期和舒张期心肌首过灌注值的比较采用配对t检验。
结果：25例每个心肌节段收缩期的强化平均值均低于舒张期的强化平均值，除心底的少数节段和心尖外，绝大部分节段舒张期与收缩期强化平均值的差别有极显著的统计学意义(P≤0．001)。经随机区组方差分析和进一步的两两比较(LSD和SNK检验)表明前壁(1、7、13)、下壁(4、10)和心尖(17)各个节段两两比较均无显著性差异，可归为一组；室间隔壁(2、3、8、9、14)和左室侧壁(5、6、11、12、16)各个节段比较均无显著性差异，可归为另一组；两组间(前壁+下壁+心尖区与室间隔壁+左室侧壁)各个节段的差异则均有显著的统计学意义(P≤0．01)。
结论：DSCT冠脉成像作为心肌灌注的定性评估方法，在兼顾冠脉成像和心功能分析的基础上，能初步评价心肌首过灌注及其时相和节段的变化，为进一步评价缺血性心脏病提供参考。
第二节双源CT首过灌注成像定性评价心肌缺血的研究
目的：采用DSCT冠脉成像心肌首过灌注的方法，探讨心肌缺血和心肌梗塞患者的首过心肌灌注表现、不同时相变化的特点，及其鉴别诊断价值。
材料与方法：收集本院确诊的25例心肌缺血和心肌梗塞的DSCT检查资料，平其中男性21例，女性4例，平均年龄61．5±14．6岁。临床最终确诊急性心肌梗塞5例、陈旧性心肌梗塞9例，不稳定心型绞痛11例。采用回顾性心电门控、非离子型对比剂行DSCT冠脉成像，观察以5％为间隔重建0～100％RR间期图像，选择最佳收缩期、最佳舒张期图像作为评价时相。根据合并后的7分段法(本部分第一节研究结果)对早期灌注缺损(Early perfusion Defect，ED)及其对侧的心肌节段测值。所有患者接受了DSA选择性冠脉造影，8例进行了Tc~(99)—MIBI SPECT显像。对心肌梗塞组(14例)和心肌缺血组(11例)的首过强化值进行比较，并行统计学分析。组内收缩期和舒张期强化值的比较采用配对t检验，心肌梗塞组和心肌缺血组的强化值比较使用两独立样本的t检验。
结果：(1)18例DSA冠脉造影证实LAD显著性狭窄的患者DSCT检出相应供血区早期灌注缺损(Early perfusion defect，ED)15例(83．3％)，CX则为5例中的3例(60％)，RCA则为6例中的4例(67．8％)分别被DSCT检出相应供血区的ED；以DSA冠脉造影为对照，DSCT有5例“假阳性”，但其中有2例临床确诊为陈旧性心肌梗塞和1例不稳定型心绞痛(微血管病变)。DSCT与SPECT二者对心肌灌注缺损的检出较一致。(2)收缩期心肌梗塞和心肌缺血首过灌注强化值分别为44．82±15．63HU、72．73±18．47HU(P＜0．001)；舒张期两组的首过灌注强化值分别约45．46±16．12HU、83．10±23．92HU(P＜0．001)。舒张期和收缩期相比，心肌梗塞首过强化值的变化没有显著性差异，而心肌缺血首过强化值的变化有极显著差异(P=0．003)；收缩期心肌梗塞与对侧心肌首过灌注的差值为-54．20±17．28HU，舒张期则为-48．86±17．04HU(P＜0．05)；收缩期和舒张期心肌缺血与对侧心肌首过灌注的差值则分别为-28．37±8．95HU和-24．09±9．92HU(P＜0．05)。
心肌缺血和对侧正常心肌节段首过强化值的95％置信区间在收缩期、舒张期均有一定程度的重叠，收缩期重叠较小；心肌梗塞和对侧正常心肌节段首过强化值的95％置信区间在收缩期、舒张期则没有重叠。
结论：(1)缺血心肌和梗塞心肌的首过强化程度和时相变化均有显著的差异，收缩期可能较舒张期更容易发现心肌缺血，因此DSCT首过灌注结合多时相分析能够为鉴别可逆性缺血和心肌坏死提供参考信息。(2)无论是对心肌缺血还是心肌梗塞，DSCT定位诊断都较准确，不同于DSA冠脉造影和SPECT。DSCT冠脉成像有望成为一站式综合评价冠脉、心功能和心肌灌注的一种新方法。
第三部分双源CT对冠心病患者左室功能和室壁运动的评价
目的：评价双源CT(Dual source CT，DSCT)在评估冠心病患者整体心功能和室壁运动与临床常规超声心动图(Echocardiogram，ECG)的一致性。
材料与方法：收集因胸痛疑为冠心病在我院行DSCT检查的25例患者的临床资料，平均年龄61．5±14．6岁，其中男性21例，女性4例。临床最终确诊急性心肌梗塞5例、陈旧性心肌梗塞9例，不稳定心型绞痛11例。以5％为间隔重建0～100％RR间期多时相数据，使用左室功能评价软件评估射血分数EF、左室短轴缩短率FS和节段性室壁运动，并和ECG对比。
结果：25例患者DSCT测得的FS和EF分别为35．16％±10．16％、63．08％±11．10％；ECG则分别为34．76％±7．37％、61．80％±9．50％，配对t检验两者的差异无显著统计学意义，且相关性良好(r分别约0．86和0．87，p均＜0．001)；按病例数和节段数计算两法对室壁运动的诊断一致性很好(Kappa值分别约0．85、0．86，P均＜0．001)；DSCT诊断的室壁运动异常节段的室壁增厚率较对侧显著减低，分别约20．55％±24．10％和78．63％±30．98％(P＜0．01)。
结论：DSCT时间分辨率高，对复杂心率情况也可完成对整体和节段性左室收缩功能的评估，与ECG一致性良好，能为冠脉形态和首过心肌灌注之外为冠心病的诊断提供更多的信息。
PartⅠAnimal Study of Myocardial Perfusion Imaging by MSCT
Section 1 Establishment of Acute Myocardial Infartction Model
Objective:Coronary artery angiography was performed with permanent medical threadocclusion,which aims for the establishment of acute myocardial infarction animal model.
Materials and Methods:Five domestic dogs weighting 10 to 15 kg (mean:12.5 kg) withnumerical order from 1 to 5,were included in this study.Following intramuscularpre-medication with anaesthesia,Under fluoroscopy guidance,a guiding catheter wasplaced at the origin of the left coronary artery,and a coronary angiogram was obtained.Afterwards permanent suture segments occlusion of the left anterior descending (LAD)coronary artery was performed at mid-section.Coronary artery occlusion was controlledwith coronary angiograms before and after to assure the successful establishement of acuteinfarction.Pathological verification was done afterwards.
Results:One animal died within 30min after the occlusion.Coronary artery occlusion wascontrolled with coronary angiograms adapted to vessel size and location,ranging fromproximal to distal focal occlusions.Intraluminal wash-out of the contrast agent and weakenwall motion were indicated in all animals.TTC staining confirmed extents and location ofMI,which included extensive infarct the left ventricular myocardium in No.1 animal,septalsegment infarct of the left ventricular myocardium in No.2-4 animal,and the apex segmentinfarct in No.5 animal.Further confirmation of early acute myocardium infarction wasachieved with HE staining.
Conclusion:Establishment of acute myocardial infarction animal model by the occlusionof coronary artery is easily accessible,which can be used as the pre-clinical research formyocardial infarction.
Section 2 Experimental Study of Myocardial Perfusion by MSCT:Characterization of Ischemic Myocardium
Obejective:To assess the hemodynamic changes in ischemic cardiac segments usingretrospective ECG-gating contrastenhanced MSCT and its clinical value in the diagnosis ofmyocardial intarction.
Materials and Methods:10 dogs were randomly grouped into study and control groupwith 5 each,and the animal preparation was the same in section 1.MSCT examinationswere performed with a 16-MSCT scanner (SOMATOM Sensation 16,Siemens,Germany)in the supine position.Serial CT scanning of whole cardiac was performed at 4,20 and 40seconds after bolus injection of 1.5ml/kg of non-ionic contrast material (Ultravist 370,Schering) followed by a 30-ml saline chaser bolus,at a flow rate of 3.5～4.5 ml/s,whichwere acquired applying a retrospectively ECG-gated examination protocol with12×1.5-mm collimation and a rotation time of 420 ms.Tube voltage was 120 kV with80mAs.Delayed enhancement scans were performed at 1,2,3,4 and 5 minute afterwards,7and 20 minutes were done to the No.2 and 5 dog in the study group.Pathologicalverification was obtained as stated in section 1.
Results:Ⅰ) Time-density curves for MSCT in control froup demonstrated the maximumslope of consecutive measurements during the wash-in and wash-out period of the contrastmaterial calculated,and a flat-pattern phase after the peak enhancement.Signalintensity/attenuation was expressed as the percentage of increase over baseline ratio ofattenuation of myocardium and left ventricle blood pool,based on which the peakenhancement of the myocardium was 50%±6% with comparison to left ventricle cavum.The adjacent segments were almost the same as left ventricle cavum,in terms of peakenhancement,time to peak,etc.
Ⅱ) Time-density curves for MSCT in infarct group demonstrated the minmum slope ofconsecutive measurements during the wash-in and wash-out period of the contrast materialcalculated,and a flat-pattern phase after the peak enhancement almost the same as normalones.
Results of the semiquantitative analysis of the timedensity curves showed significantdifferences between infarcted and healthy myocardium for SImax,Tmax and slope,whichwere 1.56±0.52、1.00、1.00 (P＞0.05) for time to peak,0.26±0.04、0.45±0.08 (P=0.02)for peak enhancement.TTC staining confirmed extents and location of MI as indicated byMSCT.
Conclusion:16-slice CT imaging allows for the differentiation of hypoperfused andnormal myocardium using retrospective ECG-gating method,which has the potential for visual and semiquantitative assessment of firstpass myocardial perfusion.
PartⅡFirst-pass Myocardial Perfusion By Dual-source CT
Section 1 First-pass Normal Myocardial Perfusion by Dual-source CT
Objective:To investigate first-pass myocardial perfusion in normal segments during thecardiac cycle using contrast-enhanced dual-source CT,this can be future basis for theevaluation of ischemic heart disease.
Materials and methods:25 health check-up patients(15 male,10 female,mean age60±12.5) without suspected coronary artery disease were enrolled as normal casesrandomly doe dual-source CT coronary angiography(Siemens SomatomDefinition,Germany).Reconstructed cardiac images in diastolic and systolic phases wasevaluated using raw data from coronary CT angiography.The attenuation value (inHounsfield units) in the myocardium was used as an estimate of myocardial perfusion.Wemeasured the subendocardial intensity of 17 segments according to the American HeartAssociation classi-fication.Systolic perfusion or diastolic perfusion was calculated bydividing the subendocardial intensity at systole or diastole,respectively,for each segmentby the mean value across all segments for each patient.T-test was used for the statistics.
Results:Systolic perfusion was significantly lower than diastolic one for each segment.The difference between systolic perfusion and diastolic perfusion in ischemic segments wassignificantly lower than that in nonischemic segments (P(?)0.001).There was no significantdifference in diastolic perfusion betweenc segment 1,7,13;segment 4,10;and segment 17,which can be grouped together,as well as segment 2、3、5、6、8、9、11、12、14 and 16.The differencebetween systolic and diastolic perfusion varied among the regions.Systolicperfusion was lower than diastolic perfusion in the septal wall,whereas systolic perfusionwas higher than diastolic perfusion in few segments of the anterior and lateral walls.Systolic perfusion and diastolic perfusion in the inferior wall were similar (P(?)0.01).
Conclusion:DSCT can be utilized as qualitativer evaluation for a pattern of subendocardialhypoperfusion at systole and normal perfusion at diastole characterizes ischemic myocardium.
Section 2 First-pass Ischemic Myocardial Perfusion byDual-source CT
Objective:To Assess the hemodynamic changes in ischemic cardiac segments during thecardiac circle using dual source CT,and the clinical value for differential diagnosis.
Material and Methods:25 patients(21 male,4 female,mean age 61.5±l4.6) withconfirmed ischemic or infarct myocardial diaseas were enrolled for dual-source CTcoronary angiography(Siemens Somatom Definition,Germany).Reconstructed cardiacimages in diastolic and systolic phases was evaluated.We measured the subendocardialintensity of 17 segments according to the American Heart Association classi-fication.Systolic perfusion or diastolic perfusion was calculated by dividing the subendocardialintensity at systole or diastole,respectively,for each segment by the mean value across allsegments for each patient.Early perfusion Defect and its opposite segment was measured.The first-pass enhancement between the infarct patients(n=14) and ischemic ones(n=11)was compared using independent T-test for the statistics.
Results:1)15 out of 18 with proven stenosis in LAD (83.3%) were indicated by DSCT forEarly perfusion defect,3 out of 5(60%) with proven CX stenosis were indicated by DSCT,and 4 out of 6(67.8%0 were for RCA.Good agreement was reached between DSCT andSPECT in this regard.
2)systolic phase,the peak enhancement for infarction and i schemia were 44.82±15.63HU、72.73±18.47HU (P＜0.001) repectively;45.46±16.12HU、83.10±23.92HU (P＜0.001)respectively in the diastolic phase.No significant diference was indicated between thefirst-pass peak enhancement in the infarction group,while significant difference in theischemia group(P=0.003).The difference between the infarct myocardium and the oppositeone was-54.20±17.28HU in systolic phase,while-48.86±17.04HU in diastolic phase (P＜0.05).Those were-28.37±8.95HU和-24.09±9.92HU in dsystolic and iastolic phase forischemia (P＜0.05)
Conclusion:Quantification of first-pass perfusion CT images with dual source CT allowscharacterization of intramural myocardial perfusion in patients with myocardial ischemia,and myocardial ischemia could be found in systolic phase much easy than diastole phase,which brings up DSCT as a potential for the comprehensive evaluation for the coronary,cardiac function and myocardium perfusion.
PartⅢAssessment of The Global and Regional Left VentricleFunction by Dual Source CT
Objective:To evaluate the agreement between DSCT and ECG to assess the global andregional left ventricle function in patients with coronary artery disease.
Materials and Methods:25 cases with coronary disease underwent DSCT coronaryangiography (SOMATOM Definition,Siemens,Germany),and the same data were used toassess the ejection fraction (EF),fractional shortening (FS) and regional wall motion(Siemens MMWP,Germany).ECG served as reference.
Results:There was no significant difference between DSCT and ECG to evaluate the EFand FS (p＞0.05),with good correlation (r=0.86 and 0.87,p＜0.001,respectively).Theagreement between DSCT and ECG in diagnosing regional wall motion abnormality wasgood.no matter counted as cases(Kappa=0.85,p＜0.001) or segments(Kappa=0.87,p＜0.001).The wall thickening fraction of the segments with abnormal motion diagnosed byDSCT were significant lower than its opposite segments(20.55%±24.10% vs 78.63%±30.98%,P＜0.01).
Conclusion:With the breakthrough of the temporal resolution,DSCT permits accurateassessing left ventricle function even in patients with heart rate variability,and agreementwith routine ECG is good.DSCT is expected to provide more information for CADdiagnosis and prognosis.
引文
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[3] White FC , Carrol SM ,Magent A , et al . Coronary Collateral Development in Swine after Coronary Artery Occlusion[J ] . Circ Res ,1992 ,71 :1 490 - 1 500.
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[1].George RT,Silva C,Cordeiro MA,et al.Multidetector computed tomography myocardial perfusion imaging during adenosine stress.J Am Coll Cardiol.2006;48:153-60.
[2]:Nagao M,Matsuoka H,Kawakami H,et al.Quantification of myocardial perfusion by contrast-enhanced 64-MDCT:characterization of ischemic myocardium.Am J Roentgenol.2008;191:19-25.
[3]．叶任高主编，陆再英副主编，内科学，第5版．北京：人民卫生出版社，2000；310-312．
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[12].Mahnken AH,Bruners P,Katoh M.Dynamic multi-section CT imaging in acute myocardial infarction:preliminary animal experience.Eur Radiol.2006,16(3):746-52.
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[14].Hoffmann U, Millea R, Enzweiler C, et al. Acute myocardial infarction:contrast-enhanced multi-detector row CT in a porcine model.Radiology. 2004;231:697-701.
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[1]. Mahnken AH, Koos R, Katoh M, et al. Assessment of myocardial viability in reperfused acute myocardial infarction using 16-slice computed tomography in comparison to magnetic resonance imaging. J Am Coll Cardiol. 2005; 45:2042-2047
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[7].Cerqueira MD, Weissman NJ, Dilsizian V, et al. Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart: a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association. Circulation. 2002;105:539-42.
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[1].Lessick J, Ghersin E, Dragu R, et al.Diagnostic accuracy of myocardial hypoenhancement on multidetector computed tomography in identifying myocardial infarction in patients admitted with acute chest pain syndrome. J Comput Assist Tomogr.2007;31:780-788.
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[6].Wintersperger BJ, Ruff J, Becker CR, et al.Assessment of regional myocardial perfusion using multirow-detector computed tomography(MSCT).Eur Radiol 2002;12:S294.
[7].Mahnken AH, Bruners P, Katoh M, et al.Dynamic multi-section CT imaging in acute myocardial infarction: preliminary animal experience. Eur Radiol. 2006,16:746-752.
[8].George RT, Jerosch-Herold M, Silva C, et al.Quantification of myocardial perfusion using dynamic 64-detector computed tomography. Invest Radiol. 2007;42:815-822.
[9]. David C Crossman .The pathophysiology of myocardial ischaemia. Heart.2004;90:576-580
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[12].Cury RC, Nieman K, Shapiro MD, Comprehensive assessment of myocardial
??perfusion defects, regional wall motion, and left ventricular function by using 64-section multidetector CT. Radiology. 2008;248:466-475.
[13].Henneman MM, Schuijf JD, Jukema JW, Comprehensive cardiac assessment with multislice computed tomography: evaluation of left ventricular function and perfusion in addition to coronary anatomy in patients with previous myocardial infarction. Heart. 2006;92:1779-1783.
[14].Baks T, Cademartiri F, Moelker AD, Multislice computed tomography and magnetic resonance imaging for the assessment of reperfused acute myocardial infarction. J Am Coll Cardiol. 2006; 48:144-152.
[15].Mohlenkamp S, Lerman LO, Lerman A, et al. Minimally invasive evaluation of coronary microvascular function by electron beam computed tomography. Circulation.2000;102:2411-2416.
[16].Mohlenkamp S, Behrenbeck TR, Lerman A, et al.Coronary microvascular functional reserve: quantification of long-term changes with electron-beam CT preliminary results in a porcine model. Radiology. 2001;221:229-236.
[17].陈在嘉,高润霖主编,冠心病,第1版,北京:人民卫生出版社.2002:67—68.
[18].Mahnken AH, Koos R, Katoh M, et al. Assessment of myocardial viability in reperfused acute myocardial infarction using 16-slice computed tomography in comparison to magnetic resonance imaging. J Am Coll Cardiol. 2005; 45:2042-2047
[19].Lessick J, Dragu R, Mutlak D, et al.Is functional improvement after myocardial infarction predicted with myocardial enhancement patterns at multidetector CT? Radiology.2007; 244:736-744.
[20].Lardo AC, Cordeiro MA, Silva C, et al.Contrast-enhanced multidetector computed tomography viability imaging after myocardial infarction: characterization of myocyte death, microvascular obstruction, and chronic scar. Circulation. 2006; 113:394-404
[21].Koyama Y, Matsuoka H, Mochizuki T, et al.Assessment of reperfused acute myocardial infarction with two-phase contrast-enhanced helical CT: prediction of left ventricular function and wall thickness.Radiology. 2005 ;235:804-811.
[22].Buecker A, Katoh M, Krombach GA ,et al.A feasibility study of contrast enhancement of acute myocardial infarction in multislice computed tomography: comparison with magnetic resonance imaging and gross morphology in pigs.Invest Radiol. 2005 ;40:700-704
[23].Paul JF, Wartski M, Caussin C, et al. Late defect on delayed contrast-enhanced multi-detector row CT scans in the prediction of SPECT infarct size after reperfused acute myocardial infarction: initial experience. Radiology. 2005;236:485-489.
[24].Koyama Y, Mochizuki T, Higaki J.Computed tomography assessment of myocardial perfusion, viability, and function. J Magn Reson Imaging. 2004; 19:800-815
[25].Blankstein R, Okada DR, Rocha-Filho JA, et al Cardiac myocardial perfusion imaging using dual source computed tomography. Int J Cardiovasc Imaging. 2009, Epub ahead of print
[1].George RT,Silva C,Cordeiro MA,et al.Multidetector computed tomography myocardial perfusion imaging during adenosine stress.J Am Coll Cardiol.2006;48:153-60.
[2]:Nagao M,Matsuoka H,Kawakami H,et al.Quantification of myocardial perfusion by contrast-enhanced 64-MDCT:characterization of ischemic myocardium.Am J Roentgenol.2008;191:19-25.
[3]．叶任高主编，陆再英副主编，内科学，第5版．北京：人民卫生出版社，2000；310-312．
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[5].Cerqueira MD,Weissman NJ,Dilsizian V,et al.Standardized myocardial segmentation and nomenclature for tomographic imaging of the heart:a statement for healthcare professionals from the Cardiac Imaging Committee of the Council on Clinical Cardiology of the American Heart Association.Circulation.2002;105:539-42.
[6].Knollmann FD,Muschick P,Krause W,et al.Detection of myocardialischemia by electron beam CT.Experimental studies.Acta Radiol,2001,42:386-392.
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