320排螺旋CT心肌灌注扫描在冠心病缺血心肌的综合应用研究
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摘要
研究背景
随着社会经济的发展及全球人口老龄化趋势越渐加重,冠状动脉粥样硬化性心脏病及其导致的心肌梗死的发病率越来越高,已成为当前严重危害人类生命安全的健康杀手。据WHO发布的《2011年世界卫生统计》中指出在全球每年因心脏病、糖尿病和癌症等非传染性疾病而死亡人数约有3500万人,占全球人口死亡总数的三分之二；其中中国地区的冠心病死亡人数已位列世界第二位。因此,早期诊断,早期防治,才能有效减少冠心病的发病率及降低其死亡率。常规冠状动脉造影虽然是冠状动脉疾病诊断与治疗的主要检查技术,但其不能直接检测心肌微循环血管损伤和显示病变心肌微观灌注变化情况。因此,要提高冠心病的临床诊治水平,除了要准确判断冠状动脉狭窄程度、有否并发心肌梗死、继发心肌形态变化等情况以外,还需鉴别心肌活性、掌握心功能变化的状况。这样对于治疗方案的选择、疗效和预后的判断均十分重要。心肌灌注是目前临床评价心肌组织微循环功能状况,鉴别心肌活性的主要方法。正常功能的心肌细胞在负荷状态下,心肌灌注量、心肌代谢和心肌收缩功能之间能保持动态平衡；但缺血性心脏病则多表现为心肌灌注量减少,继发心肌代谢、功能、灌注的失衡；CT心肌灌注比较其它的影像学检查手段,具有极高的时间、空间分辨率,能在一次冠状动脉CTA成像的同时,既获得冠状动脉形态学数据,也获取了左心室功能评价的数据。尽管多层螺旋CT(multi-slice spiral CT,MSCT)心肌灌注应用于评价冠心病心肌微循环状态及存活心肌鉴别方面具有良好的发展前景,但目前仍处于临床研究阶段,缺乏公认的参考依据和标准,甚至还存在诸多的矛盾和争议。本文尝试利用320排螺旋CT心肌灌注结合心肌负荷扫描探讨MSCT心肌灌注技术及结合心肌负荷试验方法在一站式心脏检查,获得心脏综合信息的可行性；即一次心脏扫描,同时获得冠状动脉、心功能评价的数据,甚至还能依据相同的数据资料进行梗死心肌和存活心肌的鉴别,对心肌微循环的功能状态进行定量分析,评价心肌活性状态。并通过对冠心病缺血心肌的应用分析,了解MSCT心肌灌注技术在冠心病缺血心肌综合应用的价值。
1研究目的
1.1探讨利用320排螺旋CT心肌灌注技术结合心肌负荷试验在一次心脏检查获得全部心脏影像学资料的可行性；即不仅可获得冠状动脉解剖形态信息,也同时获得左心室功能评价指标的数据,并能对心肌微循环的功能状态进行量化分析。
1.2探讨320排螺旋CT心肌灌注技术在评价冠心病缺血心肌的综合应用价值。
2研究方法
2.1临床资料
搜集2011.4～2011.12期间使用本院320排螺旋CT进行心脏灌注扫描的冠心病患者24例,其中男性13人,女性11人；年龄从37～72岁,中位数年龄52.5±3.2岁,以及正常成人对照组13例,男性9人,女性4人；平均年龄43.7岁。24例冠心病人均行核素心肌灌注显像证实心肌节段性灌注缺损(均为左心室壁灌注缺损),提示存在可逆性心肌缺血；其中16例有典型心绞痛发作的症状,8例出现疑似胸闷不适。13例正常人对照组受检者入选标准是：①既往及当前均无冠心病的临床症状及体征；②既往无高血压临床症状及体征；③既往无其他先天性或后天性心脏器质性病变；④无其他心脏功能性及传导性阻滞相关的病变；⑤无药物过敏史及心肝肺肾等功能衰竭病变；⑥既往心电图检查示正常；⑦心脏体格检查指标均正常；⑧对负荷用药(多巴酚丁胺)无不良反应。实验组与正常人对照组所有受检者均无碘对比剂过敏史、无β受体阻断剂使用禁忌证、无心电传导障碍、无心功能不全或心肾功能障碍、无不可控制的高血压,静息状态下血压≤190/120mmHg；无呼吸运动障碍、意识清醒能配合检查实施。CT扫描前所有受检者均进行宣教,告知试验的目的、方法,和相关不良反应以及相应处理措施,并让所有受检者在知情同意书上签字确认,知情同意书内容及格式如表1-1所示。
2.2心脏冠状动脉CTA成像及心肌CT灌注扫描前准备
检查前受检者需禁食禁水4-6h,检查前12小时内禁止摄入含咖啡因、或可乐的食物,冠心病受检者还需在检查前24h停用p-受体阻滞剂。扫描前常规测量心率,对心率高于80次/min的受检者,使用倍他乐克25～50mg,控制心率在60～75次/min范围内。测量受检者的基础血压、体重、身高,并计算相应BMI数值(BMI=体重(kg)/身高(m)的平方),并根据BMI值设定对应的管电压、管电流数值。对所有受检者检查前均进行呼吸指导训练,尽量要求病人在整个试验过程中保持浅慢、平静的呼吸状态。受检者采用仰卧位、脚先进,双臂上举于头两侧,连接心电导联线,同时在受检者右臂肘静脉放置18G-20G的静脉内套管针连接注射用双筒高压注射器。左上臂放置血压监测装置,间隔30sec自动测量血压、心率及平均压,设定HR≥150次/min,或者血压>190/120mmHg为阈值,当监测值超出此标准,则显示报警。
2.3心脏冠状动脉成像及心肌灌注扫描方法
2.3.1心脏冠状动脉CTA成像及静息心肌CT灌注扫描方法。
全部检查采用Toshiba Aquilion one320排动态容积CT,采用前瞻性心电触发技术靶区间扫描模式(一般设定为心动周期75%),一切准备就绪后进行双定位像扫描,扫描范围为自气管分叉至心脏膈面下1.5cm左右,屏气扫描。首先进行冠状动脉钙化积分平扫,扫描参数：管电压100kV,管电流300～450mAs/rot(具体数值根据受检者相应BMI值及体型设定),层厚0.5mm,间隔0.5mm,视野(FOV)180～220mm。然后采用屏气ECG门控动态容积扫描模式下常规剂量连续采集扫描,应用双筒高压注射器经右侧肘前静脉以5ml/s流速注射优维显(370mgI/m1)50～60ml(注射量依据受检者体重指数BMI而定),注射完后再以相同的流率注射30ml生理盐水冲管,设定增强范围与平扫时一致,扫描参数：管电压120kV,管电流350～450mAs/rot。应用Sure Star软件智能触发扫描系统选取胸主动脉近端为CT值监测的感兴趣区,当兴趣区内密度达到预设值(一般设为180Hu)时自动启动冠状动脉及静息心肌灌注扫描,扫描过程中同步记录心电图。分别设定自心肌灌注扫描启动时间起间隔10sec、20sec及30sec行延迟静息扫描,采用前瞻性心电触发技术靶区间扫描心脏,扫描参数管电压100kV,管电流300～400mAs/rot。
2.3.2心肌多巴酚丁胺负荷试验
采用5%葡萄糖注射液20ml稀释的盐酸多巴酚丁胺注射液20ml用微泵连接受检者左前臂肘静脉内置管进行滴注,启动滴注速率为15μg/kg·min,每隔3min增加速率5μg/kg·min,最大限值设定为30μg/kg·min;同时每隔1min启动血压监测装置密切观察受检者的血压、心率等监测指标变化以及精神、症状表现；当到达试验监测心率目标值{即0.85x(220-年龄)}；或出现心率、血压变动幅度过大(例如心率≥130次/min、收缩压>200mmHg或平均血压变化幅度>20mmHg等)、或者试验过程中受检者出现不能继续耐受负荷的症状(例如：出现心绞痛、心律失常、胸闷、胸痛等不适或出现头晕眼花、口干、面色苍白或四肢乏力等症状)即可终止负荷试验,启动后续的负荷心肌CT灌注扫描。
2.3.3负荷心肌CT灌注扫描方法。
心肌多巴酚丁胺负荷试验结束后,启动负荷后心肌灌注扫描,扫描范围与静息心肌灌注扫描一致；采用屏气ECG门控动态容积扫描模式下常规剂量连续采集扫描,应用双筒高压注射器经右侧肘前静脉以5ml/s流速注射优维显(370mgI/ml)30ml,注射完后再以相同的流率注射30ml生理盐水冲管。应用Sure Star软件智能触发扫描系统选取胸主动脉近端为CT值监测的感兴趣区,当兴趣区内密度达到预设值(一般亦设为180Hu)时自动启动负荷心肌灌注扫描,扫描过程中同步记录心电图。然后设定自心肌灌注扫描启动时间起间隔10sec、20sec及30sec行延迟负荷扫描,采用前瞻性心电触发技术靶区间扫描全心脏,扫描参数管电压100kV,管电流300-350mAs/rot,其余扫描参数同前。
2.4心肌灌注扫描心肌强化CT值的测量采集与评价方法以及心肌时间-密度强化曲线的绘制方法。
在副机工作站图像浏览窗浏览工作站自动计算机自动重建10个心动周期图像,选择心动周期中心脏运动伪影最少的时相,使用多平面重建软件(MPR)三维显示心脏及心形态；其中冠心病缺血心肌组受检者对应其心肌核素灌注显像提示心肌异常灌注的影像,选定心肌CT值测量的层面及放置感兴趣区(ROI),分别测量并记录心肌在静息状态下灌注期、延迟10sec、20sec、30sec以及负荷状态后灌注期、延迟10sec、20sec、30sec图像的心肌CT密度值,同时调节图像的色阶,叠加根据CT值高低的伪彩色阶图于三维平面展示的心脏图像上,以便直观清楚辨认心肌灌注异常区域的分布及相对严重度。另外,分别根据正常对照组、冠心病缺血心肌组各组内静息、负荷后灌注期、延迟10sec、20sec、30sec各期测量的心肌密度CT值绘制心肌时间密度曲线,以扫描时间为横坐标,心肌CT密度测量值为纵坐标；再对比正常对照组、冠心病缺血心肌组对应的静息、负荷的心肌时间密度曲线,观察正常心肌、缺血心肌在不同状态下的强化差别。
2.5MSCT心功能分析及测量方法
将采集的静息、负荷CT心肌灌注原始资料以层厚1.0mm,重叠0.5mm,间隔10%重建出10组心动周期数据,分别将两组重建数据导入Toshiba Vitreal2工作站,应用心功能分析(Cardial Functional CT)软件包,采用MPR技术获取左心室长、短轴切面图像,选择左心室腔最宽的长轴切面调整心尖方向,使心尖与左心室长轴处于同一直线上,由计算机自动勾画心内膜、外膜轮廓线,然后采用人工手动方法分别调整10个时相左心室壁内、外膜轮廓线(室间隔、肉柱及乳头肌不纳入计算范围)。逐期观察各时相取左心室腔面积最小的设定为收缩末期,面积最大的时相设定为舒张末期,然后输入受检者身高、体重、心率等资料,由计算机根据Simpson公式自动计算出各测量标值,包括左心室舒张末期容积(end-diastolic volume, EDV)、收缩末容积(end-systolic volume, ESV)、每搏输出量(stroke volume, SV)(SV=EDV-ESV)和射血分数(ejection fraction, EF)(EF=(EDV-ESV)/EDV)等数值；记录以上数值并进行统计学分析。
2.6MSCT静息、多巴酚丁胺负荷心肌灌注透壁灌注比率(TPR)的测量及其对应冠状动脉病变评价方法
在副机工作站图像浏览窗浏览工作站自动计算机自动重建10个心动周期图像,选择心动周期中心脏运动伪影最少的时相,同时排除有否存在运动和射线硬化伪影,在副机工作站Clincal Tools界面启动心肌灌注后处理软件‘"Myocardial Analysis application",分别在静息、负荷数据分析选项导入所选择的心动周期时相数据,分别在静息、负荷图像设定窗中设置左心室感兴趣区范围(Set LV ROI)(如图3-1所示),调整图像使左心室最大切面能恰好对应心脏短轴、垂直长轴和水平长轴方向,确保感兴趣区内能包括静息、负荷的左心室整体；然后由计算机自动勾画出左心室内壁和外壁轮廓,(其中心内壁轮廓线呈绿色,心外壁轮廓线呈红色),人工手动法逐层对左心室心内、外壁轮廓线进行修正,确保需灌注分析的左心室心肌壁位于取样范围内,其中心内膜下乳头肌不算入心内壁,以及不包括左心室流出道；确定需纳入计算分析的左心室心肌壁范围(即确定数据分析从心室壁什么地方开始,到哪里结束),最后把选定的心肌范围输入计算机自动分析出左心室壁各节段的透壁灌注比值(transmural perfusion ratio, TPR)图及其自动色阶调整灌注图,在图像颜色管理窗选择黑白灰阶显示,并在Basic Value(HU)的设定上手动输入基础阈值,即心肌在强化前的本底密度值。
左心室壁各节段划分参考美国心脏协会ACC/AHA标准,将左心室划分为垂直于心室长轴的基底部、中部及心尖部三等份共16个节段显示(心尖部节段可划分为第17段,但一般不纳入数据分析),其中基底部是从二尖瓣延伸至舒张末期乳头肌尖,呈牛眼圈的外环,包括6个肌段：S1(前基底段)、S2(前隔基底段)、S3(下隔基底段)、S4(下基底段)、S5(下侧基底段)、S6(前侧基底段)；中部为中环包括乳头肌全长,其包括6个肌段：S7(前中段)、S8(前隔中段)、S9(下隔中段)、S10(下中段)、S11(下侧中段)及S12(前侧中段)；心尖部为内环,是乳头肌远端至心腔的末端,其包括4个肌段：S13(前尖段)、S14(隔尖段)、S15(下尖段)及S16(侧尖段)。各肌段与对应冠状动脉各支供血关系如下：①左侧冠状动脉前降支：S1、S2、S7、S8、S13、S14和不纳入分析的S17；②左侧冠状动脉回旋支：S5、S6、S11、S12、S16；③右侧冠状动脉：S3、S4、S9、S10、S15。最后,对照核素心肌灌注提示可逆性灌注异常的区域,并记录相应左心室壁节段透壁灌注比率(TPR)。
2统计学方法所有资料均使用SPSS17.0版本的统计软件包进行统计学分析,数据均以x±s表示,当P<0.05时,认为统计学有差异或相关性具有统计学意义。
2.1对正常对照组、冠心病缺血心肌各组内的静息、负荷对应的灌注期、延迟10sec、20sec、30sec各期的心肌密度CT测量值进行配对t检验。同时,对正常对照组、冠心病缺血心肌组两组间相对应的静息、负荷下灌注期、延迟10sec、20sec、30sec各期心肌密度CT测量值使用独立样本t检验分析。
2.2对正常对照组、冠心病缺血心肌组内的静息、多巴酚丁胺负荷灌注前后对应ESV、EDV、SV、EF等测量值进行配对t检验。对正常对照组、冠心病缺血心肌组间的静息灌注、多巴酚丁胺负荷灌注对应ESV、EDV、SV、EF等测量值进行独立样本t检验分析。
2.3对正常对照组、冠心病缺血心肌组组内静息、多巴酚丁胺负荷后透壁灌注比率分别进行配对t检验,对正常对照组、冠心病缺血心肌组组间对应静息、多巴酚丁胺负荷后透壁灌注比率进行独立样本t检验。
3研究结果
3.1正常人在静息和负荷下各对应点心肌密度CT测量值之间差异均未有显著统计学意义。冠心病缺血心肌组在静息和负荷状态下各对应点的心肌密度CT测量值差异均有显著统计学意义,其中以延迟10sec、20sec和30sec期统计学差异性最为显著。发现冠心病缺血心肌组和正常对照组之间除了在静息下延迟30sec这两期扫描的心肌密度CT测量值差异无显著统计学意义,其余两组间静息、负荷下各期的心肌密度CT测量值之间差异均有显著统计学意义。
3.2正常组在静息、多巴酚丁胺负荷后心功能指标除EF外,其余(ESV、EDV、SV)值差异均有显著统计学意义,冠心病缺血心肌组除EF值有差异性外,其余心功能指标在静息、负荷下差异无显著统计学意义。正常组和冠心缺血心肌组在静息、负荷下各对应心功能指标测量差异均有显著统计学意义。
3.3发现正常人透壁灌注比率TPR值在静息、负荷后对比差异无显著统计学意义；而冠心病缺血心肌组静息、多巴酚丁胺负荷后透壁灌注比率TPR值对比差异有显著统计学意义。并且正常对照组与冠心病缺血心肌组组间对应静息、多巴酚丁胺负荷后透壁灌注比率TPR值对比差异均具有显著统计学意义。
结论
1、多巴酚丁胺负荷的多排螺旋CT心肌灌注能应用于正常心肌和缺血心肌的鉴别,结合心肌时间强化密度曲线更能直观反映冠心病缺血心肌病变范围与程度。
2、利用多巴酚丁胺负荷CT心肌灌注扫描不仅可了解冠心病冠状动脉病变形态学变化及其影响的心肌范围,还能结合射血分数(EF)及其它心功能指标数据综合判断冠心病缺血心肌冠脉及相应心功能受损程度,为下一步的选择治疗方案或动态观察治疗效果提供全面可靠的依据。
3、应用320排螺旋CT ECG门控动态容积扫描心肌负荷灌注技术,结合心肌透壁灌注比率TPR值不但能通过TPR彩色色阶灌注图直观检测、判断心室壁肌层异常灌注的存在与范围,更可以根据TPR值精确到病变心肌段定量评价异常灌注的心肌病变程度及性质。
Background
With the development of society economy and the global trend of population aging is gradually serious, the incidence of coronary heart disease and myocardial infarction increases rapidly; and then has become a serious hazard to human life safety health killer. According to the WHO published the "2011World Health Statistics", it pointed out each year because of heart disease, diabetes and cancer and other non-communicable diseases lead to deaths of about35000000people in the world, accounted for2/3of the total global death population; the deaths of coronary heart disease which occur in China has ranked second in the world. Therefore, early diagnosis, early treatment, can effectively reduce the incidence of coronary heart disease and reduce the mortality rate. Conventional coronary angiography is the main examination technique in the diagnosis and treatment of coronary artery disease, but it cannot directly detect myocardial microcirculation vascular injury and myocardial perfusion changes of microscopic lesions. Therefore, to improve the level of diagnosis and treatment of coronary heart disease, in addition to accurately judge the degree of coronary artery stenosis, whether there have concurrent myocardial infarction, and secondary myocardial morphological changes, still need to identify myocardial activity, grasp the change of cardiac function condition. Such for the choice of treatment, curative effect and prognosis are very important. Myocardial perfusion is currently the clinical evaluation of myocardial microcirculation function, the main method for identification the myocardial viability. When the normal function with the myocardial cells under a stressing, between myocardial perfusion, myocardial metabolism and myocardial contractile function can be keep the dynamic balance. But the ischemic heart disease would show the reduction of myocardial perfusion, and secondary imbalance among myocardial metabolism, function and perfusion. The CT myocardial perfusion compared to other imaging methods, it has an extremely high temporal resolution, and spatial resolution.It can be in a coronary artery CTA imaging simultaneously to gain the data about the evaluation of left ventricular function. Although MSCT myocardial perfusion has a good prospects for develop in evaluation of microcirculation in coronary heart disease and the myocardial activity identification, but it stills in the stage of clinical research, the lack of reference and standard, even many of the contradictions and disputes. This research attempts to use the320-row spiral CT myocardial perfusion imaging combined with the dobutamine stress test to study the feasibility about the integration of imaging methods of myocardial examination in one-stop and obtain the comprehensive information of heart. That is mean we can gain the coronary and heart function evaluation data within once heart scan, even on can make an identification between infarcted myocardium and myocardial viability, or make a quantitative analysis about the functional status of myocardial microcirculation to evaluated the state of myocardial activity base on the same data. And through the application of coronary heart disease myocardial ischemia, understanding the comprehensive application value of MSCT myocardial perfusion in ischemic myocardium of coronary heart disease.
1Objective
1.1To explore the feasibility about to obtained all cardiac imaging data in an examination of heart scan using the320-row spiral CT myocardial perfusion imaging combine with the myocardial stress test; that means not only can obtain the information of coronary anatomy, also can get the evaluative data of left ventricular function index, and can make a quantitative analysis the function of myocardial microcirculation.
1.2To evaluate the value of320-row spiral CT myocardial perfusion imaging in myocardial ischemia of coronary heart disease.
2Methods
2.1clinical data
24patients with coronary heart disease were collected in this research during Apr,2011to Dec,2011by using the320-row spiral CT myocardial perfusion scan, including13males,11females; aged from37to72years, median age of52.5±3.2years old. There were13cases of the normal group, including9males,4females; mean age43.7years. In24cases of coronary heart disease underwent radionuclide myocardial perfusion imaging confirmed myocardial segmental perfusion defect (both left ventricular wall perfusion defects), suggested the presence of reversible myocardial ischemia; of which16cases have typical angina symptoms,8cases of suspected chest discomfort. The criteria of the normal group was as follows:(1)no clinical symptoms with coronary heart disease and signs in past and at present;(2), no clinical symptoms and signs of hypertension;(3), no other congenital or acquired cardiac disorders;(4), no other lesions of cardiac function and conduction block related;(5), no history of drug allergy and heart lung and kidney function failure disease;(6),no abnormality of previous ECG examination;(7), indexes of cardiac physical examination are normal;(8),has no adverse reaction about drug (dobutamine) stressing.Among the myocardial ischemia of coronary heart disease group and the normal group, all subjects were without iodine contrast medium allergy history, without a beta blocker use of hypertension contraindication, no electric conduction disturbance, no dysfunction of cardiac or renal, the hypertension could be control, and the blood pressure<190/120mmHg in rest, no respiratory dyskinesia, consciousness sober could cooperate with the inspection carried out. All the subjects accepted education before the scan, made them to understand purpose and method of the test, and understand the adverse reaction and its corresponding treatment measures, and let all subjects signed the informed consent to confirm, informed consent content and format as shown in Tab1.1.
2.2Preparation for the heart coronary artery CTA angiography and myocardial perfusion CT scan before.
Before the examination subjects to fasting for4-6h,12hours before the examination no take caffeine or cola food, coronary heart disease subjects needed discontinuation of beta blockers before checking24h. To measured the heart rate before the scan, if the heart rate of subjects was higher than80/min, he must use the betaloc25-50mg, let the heart rate control within60～75/min range. To measure the basic blood pressure, weight, height of subject, and calculated the corresponding values of BMI (BMI is calculated by dividing weight in kilograms by height in meters squared), and set the values of tube voltage and tube current according to the corresponding value of BMI. All subjects were accepted the breath training before examination, try to ask the patient to keep breath with shallow slow and quiet during the whole test process, the subjects take the supine position, foot first, both arms held upward on the sides of head, connecting with the wire of electrocardiograph, at the same time in the subjects right arm elbow vein intravenous placed18G-20G trocar connection with high pressure twin injector.The left upper arm placed a blood pressure monitoring device, automatic measure the blood pressure, heart rate and mean pressure every interval30sec, set the heart rate≥150/min, or pressure≥190/120rnmHg as threshold, when the monitored value exceeds the standard, then display alarm.
2.3The heart coronary artery imaging and myocardial perfusion scanning method.
2.3.1The coronary artery CTA imaging and the method of myocardial perfusion CT rest scan.
All examination were performed by using Toshiba Aquilion one320row dynamic volume CT, with prospective ECG triggering technology target interval scan mode (the general setting for heartbeat cycle75%), everything is ready for the double orientation image scanning, scan range from the tracheal bifurcation to heart under the diaphragm about1.5cm, breath-hold scan. Firstly, make a coronary artery calcification score scan, scan parameters:100kV tube voltage, tube current of300-450mAs/rot (specific values were setted according to the corresponding values of BMI and the sizes of subjects), thickness0.5mm, interval0.5mm, vision (FOV)180to220mm. Then the routine dose of breath-hold ECG gated dynamic volume scan mode continuous acquisition scanning, application of double tube injector through the right antecubital vein with5ml/s flow inject Ultravist (370mgI/ml)50～60ml (volume of injection according to the body mass index (BMI) of subjects), after injection use30ml saline with same rate to wash pipe, set the enhanced range consistent with the plain scan. The scan parameters:120kV tube voltage, tube current of350～450mAs/rot. Apply the Sure Star software of intelligent trigger scan system and select the thoracic aortic proximal as the region of interest detected the value of CT, when the density within the interest area reaches a preset value (in general set to180Hu), the coronary artery CTA imaging and rest myocardial perfusion scan will automatic start, synchronous electrocardiogram recording the scanning process. Set separately from myocardial perfusion scan startup time interval of10sec,20sec and30sec to make a delayed scan, with prospective ECG triggering technology target interval scanning heart, scanning parameters of100kV tube voltage, tube current of300-400mAs/rot.
2.3.2The method of myocardial dobutamine stress test.
Using20ml5%glucose inject diluted dobutamine hydrochloride injection20ml, micro pump was connected with the subjects left forearm venous catheter for infusion, starting the infusion rate was15μg/kg·min, for every3min increase rate5μg/kg·min, the maximum limit value setting30μg/kg·min; at the same time every1min blood start the pressure monitoring device, Closely observed the index changes of blood pressure and heart rate and the changes in the spirit and the symptoms of subject; when monitoring heart rate reaching target value of the test {0.85x(220-age)}; or the change of heart rate or blood pressure were too dramatically (such as heart rate≥130/min, systolic pressure≥200mmHg or the average variation amplitude of blood pressure≥20mmHg), if during the test subjects could not continue to load tolerance symptoms (such as:angina pectoris, arrhythmia, chest tightness, chest pain and discomfort or symptoms of dizziness, dry mouth, pale or weakness in the limbs) to terminate the stress test, the starting load of myocardial perfusion CT scan subsequent.
2.3.3The method of myocardial perfusion CT scan with dobutamine stress.
After the myocardial dobutamine stress test, start the myocardial perfusion scan was performed. Then the routine dose of breath-hold ECG gated dynamic volume scan mode continuous acquisition scanning, application of double tube inject or through the right antecubital vein with5ml/s flow inject Ultravist (370mgl/ml)30ml, after injection use30ml saline with same rate to wash pipe. Set the enhanced range consistent with rest scan. Apply the Sure Star software of intelligent trigger scan system and select the thoracic aortic proximal as the region of interest detected the value of CT, when the density within the interest area reached a preset value (in general set to180Hu),the dobutamine stressing scan will automatic start, synchronous electrocardiogram recording the scanning process. Set separately from myocardial perfusion scan startup time interval of lOsec,20sec and30sec to make a delayed scan, with prospective ECG triggering technology target interval scanning heart, scanning parameters of100kV tube voltage, tube current of300～350mAs/rot, the rest of the scanning parameters same as before.
2.4The method of measured CT enhancement density using myocardial perfusion and the drawing method of myocardial time density curve.
Browse the images showed in browse window of auxiliary machine workstation, the images were reconstructed in10heartbeat cycle by computer; selected the cardiac cycle least cardiac motion artifacts, used the multiple planar reconstruction software (MPR)to display the heart morphology in three-dimensional. For patients with coronary heart disease should be contrasted the abnormal area of myocardial perfusion showed by nuclide myocardial perfusion imaging. Selected the measured images of myocardial CT density values and placed a region of interest (ROI) in it. Respectively, measured and recorded the values of myocardial CT density at the scan time point of perfusion, delay10sec, delay20sec, delay30sec corresponding in rest state and after dobutamine stress-state. At the same time to adjust the image color, superposition pseudo color graph setting according to the CT values range in the heart image by3D plane display; in order to clearly identify the distribution of abnormal myocardial perfusion areas and its relative severity degree.In addition, according the measured values of myocardial CT density were respective gain from the scan time point at perfusion period, delay10sec, delay20sec,delay30sec corresponding in the rest and after dobutamine stress to outlining a time-density curves of myocardial. In the map the abscissa is scan time, the values of myocardial CT density as the ordinate. And then, make a comparsion myocardial time density curve corresponding in the rest and the dobutamine stress between normal group and myocardial ischemia of coronary heart disease group. To observed the differential change between normal myocardium and myocardial ischemia myocardium in different pathological state.
2.5MSCT cardiac functional analysis and measuring method
To collect the CT myocardial perfusion raw data of the rest and the stress, reconstructed to10groups of the cardiac cycle data by1.0mm thickness,0.5mm overlap, interval of10%.Input the two groups of reconstruct data into the Toshiba Vitreal2workstation, respectively. Apply the Cardial Functional CT package to get the image of left ventricular long axis and short axis in MPR, and choose the widest long axis of left ventricular cavity to adjust the apex direction. So that the apical of left ventricular and its long axis are on the same line, the computer outlining contours line of endocardium and epicardium automatically. And then, through the manual method, we can adjusted each phases contours of endocardium and epicardium in the left ventricular (interventricular septum and papillary muscles are not included within the calculation). By observing each periods, we take the minimum left ventricular cavity area as the end-systolic phase, and the largest area as the end-diastolic phase.Then through input height, weight, heart rate of the subjects, the values would be automatically calculated by computer according to the Simpson formula, including the end-diastolic volume of left ventricular(end-diastolic volume,EDV), the end-systolic volume(end-systolic volume, ESV), the stroke volume (stroke volume SV)(SV=EDV-ESV) and the values of ejection fraction [(ejection fraction, EF) EF=(EDV-ESV)/EDV] and so on, and then recording and analyzing the above datas statistically.
2.6The transmural perfusion ratio(TPR) measurement in rest and after dobutamine stress by MSCT myocardial perfusion and the corresponding evaluation methods in coronary artery lesions.
In the image browser windows of vice workstations browse the images, which were reconstruct into10phases of cardiac cycle images automatically by the computer workstation; selected the phase of cardiac cycle which had the least motion artifacts. Also exclude the presence of motion and beam hardening artifact. In the Clincal Tools interface of vice workstation start the myocardial perfusion reprocessing software--"Myocardial Analysis application", and import the selected the cardiac cycle phase data into rest and stress data analysis option,respectively; in the rest and the stress image management window setting the region of interest about left ventricular, respectively(Set LV ROI)(as shown Fig3-1). Then adjust the image so that the left ventricular maximum section can correspond exactly with cardiac short axis, vertical long axis and the horizontal axis direction, Ensure that the sense of left ventricular region of interest can include the whole of rest and stress; and then by computer automatic outlining the left ventricular inner wall and outer wall contour line (the inner wall contour line is green,the outer wall contour line is red). Through the manual mode, we adjust the contour line of inner wall and outer wall of left ventricular, ensuring the region of left ventricular myocardium wall which required to be analysed within the sampling range. And the subendocardial papillary muscle is not within the inner wall, and does not include the left ventricular outflow tract; confirming the range of left ventricular myocardial wall have been incorporated into the calculation and analysis (determine the data analysis where to start, where to end). Finally, import the selected cardiac cycle data of myocardial perfusion into the computer and make a analysis automatically, then it will calculate the TPR(transmural perfusion ratio, TPR) values of each myocardial segments in the left ventricular wall, and adjust the pseudo color graph of the myocardial perfusion, choose the black and white gray scale to display, and then setting the basic threshold in the Basic Value (HU) by manual, which is basic density value of the myocardium before strengthen.
Left ventricular wall segments divided is refer to the standards of the American Heart Association ACC/AHA, the left ventricle is divided into vertical ventricular long axis of the basal, middle and apical three portions of16segment display (apical segments can be divided into seventeenth sections, but generally not included in the data analysis), the base is from mitral extending to the end-diastolic papillary muscle tip, display the bull's-eye outer ring, include6muscle segments:S1(anterior basal segment),S2(anterior-septal basal segment),S3(down-septal basal segment), S4(down basal segment),S5(down-side basal segment),S6(anterior-side basal segment); middle ring including overall length of papillary muscle, which comprises of6muscle segments:S7(anterior-middle middle segment)S8(anterior-septal middle segment), S9(down-septal middle segment),S10(down-middle segement),S11(down-side middle segment) and S12(anterior-side middle segment); the interior ring is apical segment, from the distal papillary muscle extending to end of heart cavity, which comprises4muscle segments:S13(anterior-apical segment),S14(apical-septal segment),S15(the apical segment) and S16(apical-side segement). The each muscle segment and its corresponding coronary artery branches supplying relationship as follow:the left anterior descending coronary artery:S1, S2, S7, S8, S13, S14and S17(the not included in the analysis); the circumflex branch of left coronary artery:S5, S6, S11, S12, S16; the right coronary artery:S3, S4, S9, S10, S15. Finally, contrast to the reversible perfusion abnormality area was displayed by the radionuclide myocardial perfusion, and record the corresponding values of transmural perfusion ratio (TPR) at left ventricular segmental wall.
3Statistical methods The statistical software SPSS17version of the package was be used for all data statistical analysis, all data were displayed with x±s, when P<0.05, think the statistics have difference or correlation statistical significance.
3.1The corresponding myocardial density CT values of perfusion period, delay10sec,20sec,30sec in resting and in dobutamine stress within the normal control group or the ischemic myocardium with coronary heart disease group were analyzed by paired t test, respectively. The corresponding myocardial density CT values of perfusion period, delay10sec,20sec,30sec in resting or in dobutamine stress between the normal control group and the ischemic myocardium with coronary heart disease group were analyzed by independent samples t test.
3.2The corresponding values of ESV, EDV, SV, EF in resting and after dobutamine stress within the normal control group or the ischemic myocardium with coronary heart disease group were analyzed by paired t test, respectively. The corresponding values of ESV, EDV, SV, EF in resting or after dobutamine stress between the normal control group and the ischemic myocardium with coronary heart disease group were analyzed by independent samples t test.
3.3The values of transmural perfusion ratio in resting and after dobutamine stress within the normal control group or the ischemic myocardium with coronary heart disease group were analyzed by paired t test, respectively. The values of transmural perfusion ratio in resting or after dobutamine stress between the normal control group and the ischemic myocardium with coronary heart disease group were analyzed by independent samples t test.
4Results
4.1The measured values of myocardial CT enhance density at corresponding time points had no statistically significant difference between in the rest and after the dobutamine stress in normal group. The measured values of myocardial CT enhance density at corresponding time points had statistically significant difference between in the rest and after the dobutamine stress in myocardial ischemia of coronary heart disease group, the delay10sec, delay20sec and delay30sec were the most significant statistical difference. The measured values of myocardial CT density had significant difference between the myocardial ischemia of coronary heart disease group and the normal group at corresponding time points in the rest and after the dobutamine stress, in addition to the scan and delay30sec in rest.
4.2The values of left ventricular function index had significant statistical difference between in the rest and after the dobutamine stress in normal group except the ejection fraction(EF). The values of left ventricular function index had no significant statistical difference between in the rest and after the dobutamine stress in myocardial ischemia of coronary heart disease group except the ejection fraction (EF). And the values of left ventricular function index had significant statistical difference between the myocardial ischemia of coronary heart disease group and the normal group corresponding in the rest and after the dobutamine stress.
4.3The value of transmural perfusion ratio(TPR) had no significant statistical difference between in the rest and after the dobutamine stress in normal group. The value of transmural perfusion ratio(TPR) had significant statistical difference between in the rest and after the dobutamine stress in myocardial ischemia of coronary heart disease group. And the values of transmural perfusion ratio(TPR) had significant statistical difference between the myocardial ischemia of coronary heart disease group and the normal group corresponding in the rest and after the dobutamine stress.
Conclusion
1. The multi-slice spiral CT perfusion imaging combine with dobutamine stress test can be used to differentiate the normal myocardium and the ischemic myocardium, combined with the TAC curve of myocardial perfusion can reflect the scope and degree of myocardial ischemia in coronary heart disease.
2. The multi-slice spiral CT perfusion imaging combine with dobutamine stress test can not only be used to show the morphological changes of coronary artery disease and its influence range of the myocardium, but also can be combined with the ejection fraction(EF) and other left ventricular function indexes to make a comprehensive judging about the myocardial ischemia of coronary heart disease and its influence degrees of cardiac function; it can provide reliable basis for the next step to the treatment choice or observe the effect of treatment in dynamic.
3. The320-row spiral CT myocardial perfusion ECG Dynamic Volume Scan technique combine with myocardial stress test can not only combined with the value of myocardial transmural perfusion ratio(TPR) and its color perfusion map to visual detected with or without the abnormal perfusion in the ventricular wall and its scope;but also can more accurately to quantitative evaluation the degree of myocardial segment lesions existed the abnormal perfusion and its characteristic according to the TPR value.
随着社会经济的发展及全球人口老龄化趋势越渐加重,冠状动脉粥样硬化性心脏病及其导致的心肌梗死的发病率越来越高,已成为当前严重危害人类生命安全的健康杀手。据WHO发布的《2011年世界卫生统计》中指出在全球每年因心脏病、糖尿病和癌症等非传染性疾病而死亡人数约有3500万人,占全球人口死亡总数的三分之二；其中中国地区的冠心病死亡人数已位列世界第二位。因此,早期诊断,早期防治,才能有效减少冠心病的发病率及降低其死亡率。常规冠状动脉造影虽然是冠状动脉疾病诊断与治疗的主要检查技术,但其不能直接检测心肌微循环血管损伤和显示病变心肌微观灌注变化情况。因此,要提高冠心病的临床诊治水平,除了要准确判断冠状动脉狭窄程度、有否并发心肌梗死、继发心肌形态变化等情况以外,还需鉴别心肌活性、掌握心功能变化的状况。这样对于治疗方案的选择、疗效和预后的判断均十分重要。心肌灌注是目前临床评价心肌组织微循环功能状况,鉴别心肌活性的主要方法。正常功能的心肌细胞在负荷状态下,心肌灌注量、心肌代谢和心肌收缩功能之间能保持动态平衡；但缺血性心脏病则多表现为心肌灌注量减少,继发心肌代谢、功能、灌注的失衡；CT心肌灌注比较其它的影像学检查手段,具有极高的时间、空间分辨率,能在一次冠状动脉CTA成像的同时,既获得冠状动脉形态学数据,也获取了左心室功能评价的数据。尽管多层螺旋CT(multi-slice spiral CT,MSCT)心肌灌注应用于评价冠心病心肌微循环状态及存活心肌鉴别方面具有良好的发展前景,但目前仍处于临床研究阶段,缺乏公认的参考依据和标准,甚至还存在诸多的矛盾和争议。本文尝试利用320排螺旋CT心肌灌注结合心肌负荷扫描探讨MSCT心肌灌注技术及结合心肌负荷试验方法在一站式心脏检查,获得心脏综合信息的可行性；即一次心脏扫描,同时获得冠状动脉、心功能评价的数据,甚至还能依据相同的数据资料进行梗死心肌和存活心肌的鉴别,对心肌微循环的功能状态进行定量分析,评价心肌活性状态。并通过对冠心病缺血心肌的应用分析,了解MSCT心肌灌注技术在冠心病缺血心肌综合应用的价值。
1研究目的
1.1探讨利用320排螺旋CT心肌灌注技术结合心肌负荷试验在一次心脏检查获得全部心脏影像学资料的可行性；即不仅可获得冠状动脉解剖形态信息,也同时获得左心室功能评价指标的数据,并能对心肌微循环的功能状态进行量化分析。
1.2探讨320排螺旋CT心肌灌注技术在评价冠心病缺血心肌的综合应用价值。
2研究方法
2.1临床资料
搜集2011.4～2011.12期间使用本院320排螺旋CT进行心脏灌注扫描的冠心病患者24例,其中男性13人,女性11人；年龄从37～72岁,中位数年龄52.5±3.2岁,以及正常成人对照组13例,男性9人,女性4人；平均年龄43.7岁。24例冠心病人均行核素心肌灌注显像证实心肌节段性灌注缺损(均为左心室壁灌注缺损),提示存在可逆性心肌缺血；其中16例有典型心绞痛发作的症状,8例出现疑似胸闷不适。13例正常人对照组受检者入选标准是：①既往及当前均无冠心病的临床症状及体征；②既往无高血压临床症状及体征；③既往无其他先天性或后天性心脏器质性病变；④无其他心脏功能性及传导性阻滞相关的病变；⑤无药物过敏史及心肝肺肾等功能衰竭病变；⑥既往心电图检查示正常；⑦心脏体格检查指标均正常；⑧对负荷用药(多巴酚丁胺)无不良反应。实验组与正常人对照组所有受检者均无碘对比剂过敏史、无β受体阻断剂使用禁忌证、无心电传导障碍、无心功能不全或心肾功能障碍、无不可控制的高血压,静息状态下血压≤190/120mmHg；无呼吸运动障碍、意识清醒能配合检查实施。CT扫描前所有受检者均进行宣教,告知试验的目的、方法,和相关不良反应以及相应处理措施,并让所有受检者在知情同意书上签字确认,知情同意书内容及格式如表1-1所示。
2.2心脏冠状动脉CTA成像及心肌CT灌注扫描前准备
检查前受检者需禁食禁水4-6h,检查前12小时内禁止摄入含咖啡因、或可乐的食物,冠心病受检者还需在检查前24h停用p-受体阻滞剂。扫描前常规测量心率,对心率高于80次/min的受检者,使用倍他乐克25～50mg,控制心率在60～75次/min范围内。测量受检者的基础血压、体重、身高,并计算相应BMI数值(BMI=体重(kg)/身高(m)的平方),并根据BMI值设定对应的管电压、管电流数值。对所有受检者检查前均进行呼吸指导训练,尽量要求病人在整个试验过程中保持浅慢、平静的呼吸状态。受检者采用仰卧位、脚先进,双臂上举于头两侧,连接心电导联线,同时在受检者右臂肘静脉放置18G-20G的静脉内套管针连接注射用双筒高压注射器。左上臂放置血压监测装置,间隔30sec自动测量血压、心率及平均压,设定HR≥150次/min,或者血压>190/120mmHg为阈值,当监测值超出此标准,则显示报警。
2.3心脏冠状动脉成像及心肌灌注扫描方法
2.3.1心脏冠状动脉CTA成像及静息心肌CT灌注扫描方法。
全部检查采用Toshiba Aquilion one320排动态容积CT,采用前瞻性心电触发技术靶区间扫描模式(一般设定为心动周期75%),一切准备就绪后进行双定位像扫描,扫描范围为自气管分叉至心脏膈面下1.5cm左右,屏气扫描。首先进行冠状动脉钙化积分平扫,扫描参数：管电压100kV,管电流300～450mAs/rot(具体数值根据受检者相应BMI值及体型设定),层厚0.5mm,间隔0.5mm,视野(FOV)180～220mm。然后采用屏气ECG门控动态容积扫描模式下常规剂量连续采集扫描,应用双筒高压注射器经右侧肘前静脉以5ml/s流速注射优维显(370mgI/m1)50～60ml(注射量依据受检者体重指数BMI而定),注射完后再以相同的流率注射30ml生理盐水冲管,设定增强范围与平扫时一致,扫描参数：管电压120kV,管电流350～450mAs/rot。应用Sure Star软件智能触发扫描系统选取胸主动脉近端为CT值监测的感兴趣区,当兴趣区内密度达到预设值(一般设为180Hu)时自动启动冠状动脉及静息心肌灌注扫描,扫描过程中同步记录心电图。分别设定自心肌灌注扫描启动时间起间隔10sec、20sec及30sec行延迟静息扫描,采用前瞻性心电触发技术靶区间扫描心脏,扫描参数管电压100kV,管电流300～400mAs/rot。
2.3.2心肌多巴酚丁胺负荷试验
采用5%葡萄糖注射液20ml稀释的盐酸多巴酚丁胺注射液20ml用微泵连接受检者左前臂肘静脉内置管进行滴注,启动滴注速率为15μg/kg·min,每隔3min增加速率5μg/kg·min,最大限值设定为30μg/kg·min;同时每隔1min启动血压监测装置密切观察受检者的血压、心率等监测指标变化以及精神、症状表现；当到达试验监测心率目标值{即0.85x(220-年龄)}；或出现心率、血压变动幅度过大(例如心率≥130次/min、收缩压>200mmHg或平均血压变化幅度>20mmHg等)、或者试验过程中受检者出现不能继续耐受负荷的症状(例如：出现心绞痛、心律失常、胸闷、胸痛等不适或出现头晕眼花、口干、面色苍白或四肢乏力等症状)即可终止负荷试验,启动后续的负荷心肌CT灌注扫描。
2.3.3负荷心肌CT灌注扫描方法。
心肌多巴酚丁胺负荷试验结束后,启动负荷后心肌灌注扫描,扫描范围与静息心肌灌注扫描一致；采用屏气ECG门控动态容积扫描模式下常规剂量连续采集扫描,应用双筒高压注射器经右侧肘前静脉以5ml/s流速注射优维显(370mgI/ml)30ml,注射完后再以相同的流率注射30ml生理盐水冲管。应用Sure Star软件智能触发扫描系统选取胸主动脉近端为CT值监测的感兴趣区,当兴趣区内密度达到预设值(一般亦设为180Hu)时自动启动负荷心肌灌注扫描,扫描过程中同步记录心电图。然后设定自心肌灌注扫描启动时间起间隔10sec、20sec及30sec行延迟负荷扫描,采用前瞻性心电触发技术靶区间扫描全心脏,扫描参数管电压100kV,管电流300-350mAs/rot,其余扫描参数同前。
2.4心肌灌注扫描心肌强化CT值的测量采集与评价方法以及心肌时间-密度强化曲线的绘制方法。
在副机工作站图像浏览窗浏览工作站自动计算机自动重建10个心动周期图像,选择心动周期中心脏运动伪影最少的时相,使用多平面重建软件(MPR)三维显示心脏及心形态；其中冠心病缺血心肌组受检者对应其心肌核素灌注显像提示心肌异常灌注的影像,选定心肌CT值测量的层面及放置感兴趣区(ROI),分别测量并记录心肌在静息状态下灌注期、延迟10sec、20sec、30sec以及负荷状态后灌注期、延迟10sec、20sec、30sec图像的心肌CT密度值,同时调节图像的色阶,叠加根据CT值高低的伪彩色阶图于三维平面展示的心脏图像上,以便直观清楚辨认心肌灌注异常区域的分布及相对严重度。另外,分别根据正常对照组、冠心病缺血心肌组各组内静息、负荷后灌注期、延迟10sec、20sec、30sec各期测量的心肌密度CT值绘制心肌时间密度曲线,以扫描时间为横坐标,心肌CT密度测量值为纵坐标；再对比正常对照组、冠心病缺血心肌组对应的静息、负荷的心肌时间密度曲线,观察正常心肌、缺血心肌在不同状态下的强化差别。
2.5MSCT心功能分析及测量方法
将采集的静息、负荷CT心肌灌注原始资料以层厚1.0mm,重叠0.5mm,间隔10%重建出10组心动周期数据,分别将两组重建数据导入Toshiba Vitreal2工作站,应用心功能分析(Cardial Functional CT)软件包,采用MPR技术获取左心室长、短轴切面图像,选择左心室腔最宽的长轴切面调整心尖方向,使心尖与左心室长轴处于同一直线上,由计算机自动勾画心内膜、外膜轮廓线,然后采用人工手动方法分别调整10个时相左心室壁内、外膜轮廓线(室间隔、肉柱及乳头肌不纳入计算范围)。逐期观察各时相取左心室腔面积最小的设定为收缩末期,面积最大的时相设定为舒张末期,然后输入受检者身高、体重、心率等资料,由计算机根据Simpson公式自动计算出各测量标值,包括左心室舒张末期容积(end-diastolic volume, EDV)、收缩末容积(end-systolic volume, ESV)、每搏输出量(stroke volume, SV)(SV=EDV-ESV)和射血分数(ejection fraction, EF)(EF=(EDV-ESV)/EDV)等数值；记录以上数值并进行统计学分析。
2.6MSCT静息、多巴酚丁胺负荷心肌灌注透壁灌注比率(TPR)的测量及其对应冠状动脉病变评价方法
在副机工作站图像浏览窗浏览工作站自动计算机自动重建10个心动周期图像,选择心动周期中心脏运动伪影最少的时相,同时排除有否存在运动和射线硬化伪影,在副机工作站Clincal Tools界面启动心肌灌注后处理软件‘"Myocardial Analysis application",分别在静息、负荷数据分析选项导入所选择的心动周期时相数据,分别在静息、负荷图像设定窗中设置左心室感兴趣区范围(Set LV ROI)(如图3-1所示),调整图像使左心室最大切面能恰好对应心脏短轴、垂直长轴和水平长轴方向,确保感兴趣区内能包括静息、负荷的左心室整体；然后由计算机自动勾画出左心室内壁和外壁轮廓,(其中心内壁轮廓线呈绿色,心外壁轮廓线呈红色),人工手动法逐层对左心室心内、外壁轮廓线进行修正,确保需灌注分析的左心室心肌壁位于取样范围内,其中心内膜下乳头肌不算入心内壁,以及不包括左心室流出道；确定需纳入计算分析的左心室心肌壁范围(即确定数据分析从心室壁什么地方开始,到哪里结束),最后把选定的心肌范围输入计算机自动分析出左心室壁各节段的透壁灌注比值(transmural perfusion ratio, TPR)图及其自动色阶调整灌注图,在图像颜色管理窗选择黑白灰阶显示,并在Basic Value(HU)的设定上手动输入基础阈值,即心肌在强化前的本底密度值。
左心室壁各节段划分参考美国心脏协会ACC/AHA标准,将左心室划分为垂直于心室长轴的基底部、中部及心尖部三等份共16个节段显示(心尖部节段可划分为第17段,但一般不纳入数据分析),其中基底部是从二尖瓣延伸至舒张末期乳头肌尖,呈牛眼圈的外环,包括6个肌段：S1(前基底段)、S2(前隔基底段)、S3(下隔基底段)、S4(下基底段)、S5(下侧基底段)、S6(前侧基底段)；中部为中环包括乳头肌全长,其包括6个肌段：S7(前中段)、S8(前隔中段)、S9(下隔中段)、S10(下中段)、S11(下侧中段)及S12(前侧中段)；心尖部为内环,是乳头肌远端至心腔的末端,其包括4个肌段：S13(前尖段)、S14(隔尖段)、S15(下尖段)及S16(侧尖段)。各肌段与对应冠状动脉各支供血关系如下：①左侧冠状动脉前降支：S1、S2、S7、S8、S13、S14和不纳入分析的S17；②左侧冠状动脉回旋支：S5、S6、S11、S12、S16；③右侧冠状动脉：S3、S4、S9、S10、S15。最后,对照核素心肌灌注提示可逆性灌注异常的区域,并记录相应左心室壁节段透壁灌注比率(TPR)。
2统计学方法所有资料均使用SPSS17.0版本的统计软件包进行统计学分析,数据均以x±s表示,当P<0.05时,认为统计学有差异或相关性具有统计学意义。
2.1对正常对照组、冠心病缺血心肌各组内的静息、负荷对应的灌注期、延迟10sec、20sec、30sec各期的心肌密度CT测量值进行配对t检验。同时,对正常对照组、冠心病缺血心肌组两组间相对应的静息、负荷下灌注期、延迟10sec、20sec、30sec各期心肌密度CT测量值使用独立样本t检验分析。
2.2对正常对照组、冠心病缺血心肌组内的静息、多巴酚丁胺负荷灌注前后对应ESV、EDV、SV、EF等测量值进行配对t检验。对正常对照组、冠心病缺血心肌组间的静息灌注、多巴酚丁胺负荷灌注对应ESV、EDV、SV、EF等测量值进行独立样本t检验分析。
2.3对正常对照组、冠心病缺血心肌组组内静息、多巴酚丁胺负荷后透壁灌注比率分别进行配对t检验,对正常对照组、冠心病缺血心肌组组间对应静息、多巴酚丁胺负荷后透壁灌注比率进行独立样本t检验。
3研究结果
3.1正常人在静息和负荷下各对应点心肌密度CT测量值之间差异均未有显著统计学意义。冠心病缺血心肌组在静息和负荷状态下各对应点的心肌密度CT测量值差异均有显著统计学意义,其中以延迟10sec、20sec和30sec期统计学差异性最为显著。发现冠心病缺血心肌组和正常对照组之间除了在静息下延迟30sec这两期扫描的心肌密度CT测量值差异无显著统计学意义,其余两组间静息、负荷下各期的心肌密度CT测量值之间差异均有显著统计学意义。
3.2正常组在静息、多巴酚丁胺负荷后心功能指标除EF外,其余(ESV、EDV、SV)值差异均有显著统计学意义,冠心病缺血心肌组除EF值有差异性外,其余心功能指标在静息、负荷下差异无显著统计学意义。正常组和冠心缺血心肌组在静息、负荷下各对应心功能指标测量差异均有显著统计学意义。
3.3发现正常人透壁灌注比率TPR值在静息、负荷后对比差异无显著统计学意义；而冠心病缺血心肌组静息、多巴酚丁胺负荷后透壁灌注比率TPR值对比差异有显著统计学意义。并且正常对照组与冠心病缺血心肌组组间对应静息、多巴酚丁胺负荷后透壁灌注比率TPR值对比差异均具有显著统计学意义。
结论
1、多巴酚丁胺负荷的多排螺旋CT心肌灌注能应用于正常心肌和缺血心肌的鉴别,结合心肌时间强化密度曲线更能直观反映冠心病缺血心肌病变范围与程度。
2、利用多巴酚丁胺负荷CT心肌灌注扫描不仅可了解冠心病冠状动脉病变形态学变化及其影响的心肌范围,还能结合射血分数(EF)及其它心功能指标数据综合判断冠心病缺血心肌冠脉及相应心功能受损程度,为下一步的选择治疗方案或动态观察治疗效果提供全面可靠的依据。
3、应用320排螺旋CT ECG门控动态容积扫描心肌负荷灌注技术,结合心肌透壁灌注比率TPR值不但能通过TPR彩色色阶灌注图直观检测、判断心室壁肌层异常灌注的存在与范围,更可以根据TPR值精确到病变心肌段定量评价异常灌注的心肌病变程度及性质。
Background
With the development of society economy and the global trend of population aging is gradually serious, the incidence of coronary heart disease and myocardial infarction increases rapidly; and then has become a serious hazard to human life safety health killer. According to the WHO published the "2011World Health Statistics", it pointed out each year because of heart disease, diabetes and cancer and other non-communicable diseases lead to deaths of about35000000people in the world, accounted for2/3of the total global death population; the deaths of coronary heart disease which occur in China has ranked second in the world. Therefore, early diagnosis, early treatment, can effectively reduce the incidence of coronary heart disease and reduce the mortality rate. Conventional coronary angiography is the main examination technique in the diagnosis and treatment of coronary artery disease, but it cannot directly detect myocardial microcirculation vascular injury and myocardial perfusion changes of microscopic lesions. Therefore, to improve the level of diagnosis and treatment of coronary heart disease, in addition to accurately judge the degree of coronary artery stenosis, whether there have concurrent myocardial infarction, and secondary myocardial morphological changes, still need to identify myocardial activity, grasp the change of cardiac function condition. Such for the choice of treatment, curative effect and prognosis are very important. Myocardial perfusion is currently the clinical evaluation of myocardial microcirculation function, the main method for identification the myocardial viability. When the normal function with the myocardial cells under a stressing, between myocardial perfusion, myocardial metabolism and myocardial contractile function can be keep the dynamic balance. But the ischemic heart disease would show the reduction of myocardial perfusion, and secondary imbalance among myocardial metabolism, function and perfusion. The CT myocardial perfusion compared to other imaging methods, it has an extremely high temporal resolution, and spatial resolution.It can be in a coronary artery CTA imaging simultaneously to gain the data about the evaluation of left ventricular function. Although MSCT myocardial perfusion has a good prospects for develop in evaluation of microcirculation in coronary heart disease and the myocardial activity identification, but it stills in the stage of clinical research, the lack of reference and standard, even many of the contradictions and disputes. This research attempts to use the320-row spiral CT myocardial perfusion imaging combined with the dobutamine stress test to study the feasibility about the integration of imaging methods of myocardial examination in one-stop and obtain the comprehensive information of heart. That is mean we can gain the coronary and heart function evaluation data within once heart scan, even on can make an identification between infarcted myocardium and myocardial viability, or make a quantitative analysis about the functional status of myocardial microcirculation to evaluated the state of myocardial activity base on the same data. And through the application of coronary heart disease myocardial ischemia, understanding the comprehensive application value of MSCT myocardial perfusion in ischemic myocardium of coronary heart disease.
1Objective
1.1To explore the feasibility about to obtained all cardiac imaging data in an examination of heart scan using the320-row spiral CT myocardial perfusion imaging combine with the myocardial stress test; that means not only can obtain the information of coronary anatomy, also can get the evaluative data of left ventricular function index, and can make a quantitative analysis the function of myocardial microcirculation.
1.2To evaluate the value of320-row spiral CT myocardial perfusion imaging in myocardial ischemia of coronary heart disease.
2Methods
2.1clinical data
24patients with coronary heart disease were collected in this research during Apr,2011to Dec,2011by using the320-row spiral CT myocardial perfusion scan, including13males,11females; aged from37to72years, median age of52.5±3.2years old. There were13cases of the normal group, including9males,4females; mean age43.7years. In24cases of coronary heart disease underwent radionuclide myocardial perfusion imaging confirmed myocardial segmental perfusion defect (both left ventricular wall perfusion defects), suggested the presence of reversible myocardial ischemia; of which16cases have typical angina symptoms,8cases of suspected chest discomfort. The criteria of the normal group was as follows:(1)no clinical symptoms with coronary heart disease and signs in past and at present;(2), no clinical symptoms and signs of hypertension;(3), no other congenital or acquired cardiac disorders;(4), no other lesions of cardiac function and conduction block related;(5), no history of drug allergy and heart lung and kidney function failure disease;(6),no abnormality of previous ECG examination;(7), indexes of cardiac physical examination are normal;(8),has no adverse reaction about drug (dobutamine) stressing.Among the myocardial ischemia of coronary heart disease group and the normal group, all subjects were without iodine contrast medium allergy history, without a beta blocker use of hypertension contraindication, no electric conduction disturbance, no dysfunction of cardiac or renal, the hypertension could be control, and the blood pressure<190/120mmHg in rest, no respiratory dyskinesia, consciousness sober could cooperate with the inspection carried out. All the subjects accepted education before the scan, made them to understand purpose and method of the test, and understand the adverse reaction and its corresponding treatment measures, and let all subjects signed the informed consent to confirm, informed consent content and format as shown in Tab1.1.
2.2Preparation for the heart coronary artery CTA angiography and myocardial perfusion CT scan before.
Before the examination subjects to fasting for4-6h,12hours before the examination no take caffeine or cola food, coronary heart disease subjects needed discontinuation of beta blockers before checking24h. To measured the heart rate before the scan, if the heart rate of subjects was higher than80/min, he must use the betaloc25-50mg, let the heart rate control within60～75/min range. To measure the basic blood pressure, weight, height of subject, and calculated the corresponding values of BMI (BMI is calculated by dividing weight in kilograms by height in meters squared), and set the values of tube voltage and tube current according to the corresponding value of BMI. All subjects were accepted the breath training before examination, try to ask the patient to keep breath with shallow slow and quiet during the whole test process, the subjects take the supine position, foot first, both arms held upward on the sides of head, connecting with the wire of electrocardiograph, at the same time in the subjects right arm elbow vein intravenous placed18G-20G trocar connection with high pressure twin injector.The left upper arm placed a blood pressure monitoring device, automatic measure the blood pressure, heart rate and mean pressure every interval30sec, set the heart rate≥150/min, or pressure≥190/120rnmHg as threshold, when the monitored value exceeds the standard, then display alarm.
2.3The heart coronary artery imaging and myocardial perfusion scanning method.
2.3.1The coronary artery CTA imaging and the method of myocardial perfusion CT rest scan.
All examination were performed by using Toshiba Aquilion one320row dynamic volume CT, with prospective ECG triggering technology target interval scan mode (the general setting for heartbeat cycle75%), everything is ready for the double orientation image scanning, scan range from the tracheal bifurcation to heart under the diaphragm about1.5cm, breath-hold scan. Firstly, make a coronary artery calcification score scan, scan parameters:100kV tube voltage, tube current of300-450mAs/rot (specific values were setted according to the corresponding values of BMI and the sizes of subjects), thickness0.5mm, interval0.5mm, vision (FOV)180to220mm. Then the routine dose of breath-hold ECG gated dynamic volume scan mode continuous acquisition scanning, application of double tube injector through the right antecubital vein with5ml/s flow inject Ultravist (370mgI/ml)50～60ml (volume of injection according to the body mass index (BMI) of subjects), after injection use30ml saline with same rate to wash pipe, set the enhanced range consistent with the plain scan. The scan parameters:120kV tube voltage, tube current of350～450mAs/rot. Apply the Sure Star software of intelligent trigger scan system and select the thoracic aortic proximal as the region of interest detected the value of CT, when the density within the interest area reaches a preset value (in general set to180Hu), the coronary artery CTA imaging and rest myocardial perfusion scan will automatic start, synchronous electrocardiogram recording the scanning process. Set separately from myocardial perfusion scan startup time interval of10sec,20sec and30sec to make a delayed scan, with prospective ECG triggering technology target interval scanning heart, scanning parameters of100kV tube voltage, tube current of300-400mAs/rot.
2.3.2The method of myocardial dobutamine stress test.
Using20ml5%glucose inject diluted dobutamine hydrochloride injection20ml, micro pump was connected with the subjects left forearm venous catheter for infusion, starting the infusion rate was15μg/kg·min, for every3min increase rate5μg/kg·min, the maximum limit value setting30μg/kg·min; at the same time every1min blood start the pressure monitoring device, Closely observed the index changes of blood pressure and heart rate and the changes in the spirit and the symptoms of subject; when monitoring heart rate reaching target value of the test {0.85x(220-age)}; or the change of heart rate or blood pressure were too dramatically (such as heart rate≥130/min, systolic pressure≥200mmHg or the average variation amplitude of blood pressure≥20mmHg), if during the test subjects could not continue to load tolerance symptoms (such as:angina pectoris, arrhythmia, chest tightness, chest pain and discomfort or symptoms of dizziness, dry mouth, pale or weakness in the limbs) to terminate the stress test, the starting load of myocardial perfusion CT scan subsequent.
2.3.3The method of myocardial perfusion CT scan with dobutamine stress.
After the myocardial dobutamine stress test, start the myocardial perfusion scan was performed. Then the routine dose of breath-hold ECG gated dynamic volume scan mode continuous acquisition scanning, application of double tube inject or through the right antecubital vein with5ml/s flow inject Ultravist (370mgl/ml)30ml, after injection use30ml saline with same rate to wash pipe. Set the enhanced range consistent with rest scan. Apply the Sure Star software of intelligent trigger scan system and select the thoracic aortic proximal as the region of interest detected the value of CT, when the density within the interest area reached a preset value (in general set to180Hu),the dobutamine stressing scan will automatic start, synchronous electrocardiogram recording the scanning process. Set separately from myocardial perfusion scan startup time interval of lOsec,20sec and30sec to make a delayed scan, with prospective ECG triggering technology target interval scanning heart, scanning parameters of100kV tube voltage, tube current of300～350mAs/rot, the rest of the scanning parameters same as before.
2.4The method of measured CT enhancement density using myocardial perfusion and the drawing method of myocardial time density curve.
Browse the images showed in browse window of auxiliary machine workstation, the images were reconstructed in10heartbeat cycle by computer; selected the cardiac cycle least cardiac motion artifacts, used the multiple planar reconstruction software (MPR)to display the heart morphology in three-dimensional. For patients with coronary heart disease should be contrasted the abnormal area of myocardial perfusion showed by nuclide myocardial perfusion imaging. Selected the measured images of myocardial CT density values and placed a region of interest (ROI) in it. Respectively, measured and recorded the values of myocardial CT density at the scan time point of perfusion, delay10sec, delay20sec, delay30sec corresponding in rest state and after dobutamine stress-state. At the same time to adjust the image color, superposition pseudo color graph setting according to the CT values range in the heart image by3D plane display; in order to clearly identify the distribution of abnormal myocardial perfusion areas and its relative severity degree.In addition, according the measured values of myocardial CT density were respective gain from the scan time point at perfusion period, delay10sec, delay20sec,delay30sec corresponding in the rest and after dobutamine stress to outlining a time-density curves of myocardial. In the map the abscissa is scan time, the values of myocardial CT density as the ordinate. And then, make a comparsion myocardial time density curve corresponding in the rest and the dobutamine stress between normal group and myocardial ischemia of coronary heart disease group. To observed the differential change between normal myocardium and myocardial ischemia myocardium in different pathological state.
2.5MSCT cardiac functional analysis and measuring method
To collect the CT myocardial perfusion raw data of the rest and the stress, reconstructed to10groups of the cardiac cycle data by1.0mm thickness,0.5mm overlap, interval of10%.Input the two groups of reconstruct data into the Toshiba Vitreal2workstation, respectively. Apply the Cardial Functional CT package to get the image of left ventricular long axis and short axis in MPR, and choose the widest long axis of left ventricular cavity to adjust the apex direction. So that the apical of left ventricular and its long axis are on the same line, the computer outlining contours line of endocardium and epicardium automatically. And then, through the manual method, we can adjusted each phases contours of endocardium and epicardium in the left ventricular (interventricular septum and papillary muscles are not included within the calculation). By observing each periods, we take the minimum left ventricular cavity area as the end-systolic phase, and the largest area as the end-diastolic phase.Then through input height, weight, heart rate of the subjects, the values would be automatically calculated by computer according to the Simpson formula, including the end-diastolic volume of left ventricular(end-diastolic volume,EDV), the end-systolic volume(end-systolic volume, ESV), the stroke volume (stroke volume SV)(SV=EDV-ESV) and the values of ejection fraction [(ejection fraction, EF) EF=(EDV-ESV)/EDV] and so on, and then recording and analyzing the above datas statistically.
2.6The transmural perfusion ratio(TPR) measurement in rest and after dobutamine stress by MSCT myocardial perfusion and the corresponding evaluation methods in coronary artery lesions.
In the image browser windows of vice workstations browse the images, which were reconstruct into10phases of cardiac cycle images automatically by the computer workstation; selected the phase of cardiac cycle which had the least motion artifacts. Also exclude the presence of motion and beam hardening artifact. In the Clincal Tools interface of vice workstation start the myocardial perfusion reprocessing software--"Myocardial Analysis application", and import the selected the cardiac cycle phase data into rest and stress data analysis option,respectively; in the rest and the stress image management window setting the region of interest about left ventricular, respectively(Set LV ROI)(as shown Fig3-1). Then adjust the image so that the left ventricular maximum section can correspond exactly with cardiac short axis, vertical long axis and the horizontal axis direction, Ensure that the sense of left ventricular region of interest can include the whole of rest and stress; and then by computer automatic outlining the left ventricular inner wall and outer wall contour line (the inner wall contour line is green,the outer wall contour line is red). Through the manual mode, we adjust the contour line of inner wall and outer wall of left ventricular, ensuring the region of left ventricular myocardium wall which required to be analysed within the sampling range. And the subendocardial papillary muscle is not within the inner wall, and does not include the left ventricular outflow tract; confirming the range of left ventricular myocardial wall have been incorporated into the calculation and analysis (determine the data analysis where to start, where to end). Finally, import the selected cardiac cycle data of myocardial perfusion into the computer and make a analysis automatically, then it will calculate the TPR(transmural perfusion ratio, TPR) values of each myocardial segments in the left ventricular wall, and adjust the pseudo color graph of the myocardial perfusion, choose the black and white gray scale to display, and then setting the basic threshold in the Basic Value (HU) by manual, which is basic density value of the myocardium before strengthen.
Left ventricular wall segments divided is refer to the standards of the American Heart Association ACC/AHA, the left ventricle is divided into vertical ventricular long axis of the basal, middle and apical three portions of16segment display (apical segments can be divided into seventeenth sections, but generally not included in the data analysis), the base is from mitral extending to the end-diastolic papillary muscle tip, display the bull's-eye outer ring, include6muscle segments:S1(anterior basal segment),S2(anterior-septal basal segment),S3(down-septal basal segment), S4(down basal segment),S5(down-side basal segment),S6(anterior-side basal segment); middle ring including overall length of papillary muscle, which comprises of6muscle segments:S7(anterior-middle middle segment)S8(anterior-septal middle segment), S9(down-septal middle segment),S10(down-middle segement),S11(down-side middle segment) and S12(anterior-side middle segment); the interior ring is apical segment, from the distal papillary muscle extending to end of heart cavity, which comprises4muscle segments:S13(anterior-apical segment),S14(apical-septal segment),S15(the apical segment) and S16(apical-side segement). The each muscle segment and its corresponding coronary artery branches supplying relationship as follow:the left anterior descending coronary artery:S1, S2, S7, S8, S13, S14and S17(the not included in the analysis); the circumflex branch of left coronary artery:S5, S6, S11, S12, S16; the right coronary artery:S3, S4, S9, S10, S15. Finally, contrast to the reversible perfusion abnormality area was displayed by the radionuclide myocardial perfusion, and record the corresponding values of transmural perfusion ratio (TPR) at left ventricular segmental wall.
3Statistical methods The statistical software SPSS17version of the package was be used for all data statistical analysis, all data were displayed with x±s, when P<0.05, think the statistics have difference or correlation statistical significance.
3.1The corresponding myocardial density CT values of perfusion period, delay10sec,20sec,30sec in resting and in dobutamine stress within the normal control group or the ischemic myocardium with coronary heart disease group were analyzed by paired t test, respectively. The corresponding myocardial density CT values of perfusion period, delay10sec,20sec,30sec in resting or in dobutamine stress between the normal control group and the ischemic myocardium with coronary heart disease group were analyzed by independent samples t test.
3.2The corresponding values of ESV, EDV, SV, EF in resting and after dobutamine stress within the normal control group or the ischemic myocardium with coronary heart disease group were analyzed by paired t test, respectively. The corresponding values of ESV, EDV, SV, EF in resting or after dobutamine stress between the normal control group and the ischemic myocardium with coronary heart disease group were analyzed by independent samples t test.
3.3The values of transmural perfusion ratio in resting and after dobutamine stress within the normal control group or the ischemic myocardium with coronary heart disease group were analyzed by paired t test, respectively. The values of transmural perfusion ratio in resting or after dobutamine stress between the normal control group and the ischemic myocardium with coronary heart disease group were analyzed by independent samples t test.
4Results
4.1The measured values of myocardial CT enhance density at corresponding time points had no statistically significant difference between in the rest and after the dobutamine stress in normal group. The measured values of myocardial CT enhance density at corresponding time points had statistically significant difference between in the rest and after the dobutamine stress in myocardial ischemia of coronary heart disease group, the delay10sec, delay20sec and delay30sec were the most significant statistical difference. The measured values of myocardial CT density had significant difference between the myocardial ischemia of coronary heart disease group and the normal group at corresponding time points in the rest and after the dobutamine stress, in addition to the scan and delay30sec in rest.
4.2The values of left ventricular function index had significant statistical difference between in the rest and after the dobutamine stress in normal group except the ejection fraction(EF). The values of left ventricular function index had no significant statistical difference between in the rest and after the dobutamine stress in myocardial ischemia of coronary heart disease group except the ejection fraction (EF). And the values of left ventricular function index had significant statistical difference between the myocardial ischemia of coronary heart disease group and the normal group corresponding in the rest and after the dobutamine stress.
4.3The value of transmural perfusion ratio(TPR) had no significant statistical difference between in the rest and after the dobutamine stress in normal group. The value of transmural perfusion ratio(TPR) had significant statistical difference between in the rest and after the dobutamine stress in myocardial ischemia of coronary heart disease group. And the values of transmural perfusion ratio(TPR) had significant statistical difference between the myocardial ischemia of coronary heart disease group and the normal group corresponding in the rest and after the dobutamine stress.
Conclusion
1. The multi-slice spiral CT perfusion imaging combine with dobutamine stress test can be used to differentiate the normal myocardium and the ischemic myocardium, combined with the TAC curve of myocardial perfusion can reflect the scope and degree of myocardial ischemia in coronary heart disease.
2. The multi-slice spiral CT perfusion imaging combine with dobutamine stress test can not only be used to show the morphological changes of coronary artery disease and its influence range of the myocardium, but also can be combined with the ejection fraction(EF) and other left ventricular function indexes to make a comprehensive judging about the myocardial ischemia of coronary heart disease and its influence degrees of cardiac function; it can provide reliable basis for the next step to the treatment choice or observe the effect of treatment in dynamic.
3. The320-row spiral CT myocardial perfusion ECG Dynamic Volume Scan technique combine with myocardial stress test can not only combined with the value of myocardial transmural perfusion ratio(TPR) and its color perfusion map to visual detected with or without the abnormal perfusion in the ventricular wall and its scope;but also can more accurately to quantitative evaluation the degree of myocardial segment lesions existed the abnormal perfusion and its characteristic according to the TPR value.
引文
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