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冠状动脉血流储备(coronary flow reserve,CFR)是反映冠状动脉(以下简称冠脉)潜在最大供血能力的指标,它是最大充血与静息状态下心肌血流量(myocardial blood flow,MBF)的比值。PET为国际公认的无创性定量MBF及CFR的“金标准”[1],对冠心病(coronary artery diseases,CAD)的早期诊断和准确评估均具有重要意义。但由于PET检查价格昂贵、医院配置率低[2]和需要配备加速器或正电子核素发生器等原因,其广泛应用于临床受到一定制约。相比较而言,SPECT安装普遍,所应用的显像剂价格相对便宜且易随时获得,应用SPECT测定MBF和CFR更具现实意义、高性价比和推广价值。本文旨在对SPECT测定MBF和CFR的不同方法、初步应用结果及临床意义作一综述。
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心肌对SPECT心肌血流灌注显像剂的摄取量与局部MBF呈正相关,显像剂进入体内后遵循一定的血流动力学原理,在细胞、生理腔室、器官或整个机体层面上逐步被运输、交换、代谢及排泄,通过体外SPECT设备连续记录其在体内随时间的变化的总过程,之后选择合适的动力学模型(腔室模型或微球模型),依据获得的动力学参数(动脉输入函数等)计算获得MBF,进而得出CFR。查阅以往文献,笔者总结主要有以下两种定量方法。
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多项研究使用此方法对SPECT定量MBF及CFR进行了分析[3-8]。此法基于“微球”模型,在负荷或静息状态下经静脉“弹丸”式注射显像剂后即刻行动态平面显像,并对动脉血流进行首过分析(first-pass analysis),通过勾画ROI(心脏大血管结构、左心室和主肺动脉等)分析获得区域时间放射性曲线(time activity curve,TAC)作为动脉输入函数,局部心肌放射性计数由静态SPECT心肌灌注显像(myocardial perfusion imaging,MPI)结果获得,根据测得的局部心肌计数及动脉输入函数代入相应数学公式获得MBF及CFR[3]。此法的假设条件是心肌对显像剂的摄取量取决于首次通过,且显像剂被摄取后滞留于心肌组织无再循环[9]。虽然99Tcm标记的显像剂[99Tcm-MIBI、99Tcm-替曲磷(99Tcm -tetrofosmin)等]的示踪动力学与微球模型并不完全相符,而且由于所用显像剂的首过心肌摄取分数较低,尤其在负荷状态冠脉血流量较高的情况下首过心肌摄取分数并非呈线性增加,因此,SPECT-CFR会显著低于PET及介入多普勒导丝测量结果,部分相关研究结果[3-7, 9-10]见表1。
研究者 显像剂 结 果 Sugihara等[3] 99Tcm-替曲磷 健康人CFR为1.47,梗死及缺血区为1.08、1.11,均较PET测量结果低 Taki等[4] 99Tcm-MIBI 以多普勒导丝测量CFR结果为参照,CFR<2.5时,心肌内显像剂滞留量与血流量呈正相关;CFR>2.5时,滞留量并不随血流量的增加而增加达到“平台期”。证明此法在高血流量时会低估CFR Ito等[5] 99Tcm-MIBI 健康人、CAD患者的CFR分别为2.13、1.48,而PET-CFR分别为3.76、1.97;两组数据呈显著相关性 Storto等[6] 99Tcm-MIBI CAD患者的CFR均数为1.36,多普勒导丝测量结果为1.39,呈显著相关性;较健康人CFR(2.19)显著降低 Pellegrino等[7] 99Tcm-MIBI 患者CFR较健康人显著降低,并且发现CFR降低与内皮功能障碍程度相关 Apostolopoulos等[9] 99Tcm-替曲磷 通过CT设备对采集数据进行散射及衰减校正,及对显像剂的“脱洗”(washout)量进行校正,测得的健康人及CAD患者CFR与负荷状态下MBF分别为1.68、1.72及1.39、1.42,该研究并未与PET结果直接对比 Nose等[10] 99Tcm-MIBI 所测CFR虽与PET-CFR显著相关,但该法在高血流量时低估CFR 注:表中,CFR:冠状动脉血流储备;CAD:冠心病;PET:正电子发射断层显像术;MBF:心肌血流量;SPECT:单光子发射体层摄影术;MIBI:甲氧基异丁基异腈。 表 1 使用动态平面采集与静态SPECT采集结合法测定CFR的部分研究结果
Table 1. Partial results of the coronary flow reserve determination using dynamic planar acquisition combined with static SPECT acquisition
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负荷及静息状态下经静脉“弹丸”式注射显像剂后即刻行动态断层数据(dynamic SPECT)采集,获得心室腔及局部心肌节段的TAC,并根据合适的房室模型计算出MBF及CFR [11-12] 。
使用传统SPECT进行动态断层采集,理论上需要探头的快速旋转以获取示踪剂在体内的快速变化信息,但从设备固有的构造、旋转速度及患者安全的角度考虑,具体实现有一定难度,并且降低了采集图像的空间、时间分辨率,使得使用传统SPECT这种方式难以获得足够的计数量以精准定量血流量[13]。
近年来上市的配备新型的碲锌镉(cadmium zinc telluride,CZT)固态半导体探测器的心脏专用SPECT(CZT SPECT)能量分辨率为传统SPECT的1.65倍,光子灵敏度是传统SPECT 的3~5倍,空间分辨率为传统SPECT的1.7~2.5倍[14],极大地缩短了成像时间及降低了显像剂的使用剂量[15-16],以及明显提高了成像的时间分辨率,使得快速动态断层采集成为现实。目前市面上该类设备有两个生产厂家:美国GE公司(Discovery NM530c/570c)及以色列Spectrum Dynamics Medical公司(D-SPECT),这两种设备的几何构型均采取半环形结构,且成像时所有探测器全部聚焦于心脏且在成像过程中均保持探头静止,使用该型设备可精确定量CFR及MBF。CZT SPECT可使用列表模式(list mode)[17]对心肌进行动态断层数据采集,精确记录显像剂进入血液及被血液输送,被器官和组织吸收,然后被细胞或细胞表面吸收,或者释放回血液的动态过程,该模式下的重建图像具有更高的对比度[18]。多项研究对该类型设备绝对定量MBF及CFR的可行性进行分析,并将定量结果直接与使用13N-氨水和15O-水的PET定量结果进行了对比[19-22],相关研究结果见表2。
研究者 显像剂 结果 Nkoulou等[19] 99Tcm-替曲磷 CFR中位数为1.32,PET为2.36,以PET为参照,截断值为1.26时,其探测异常的灵敏度为75% Agostini等[20] 99Tcm- MIBI 与PET所测CFR并无明显差异,但是整体及左前降支、左旋支支配区静息及负荷MBF均较PET测量值高 Miyagawa等[21] 99Tcm- MIBI 冠脉1、2、3支病变组的整体CFR中位数分别为1.46、1.33、1.18,并且与多普勒导丝血流储备分数呈显著相关性 Daquarti等[22] 99Tcm- MIBI 该研究负荷由运动诱导,无冠心病危险因素患者的CFR中位数为2.38 注:表中,CZT:碲锌镉;CFR;冠状动脉血流储备;PET:正电子发射断层显像术;MBF:心肌血流量;SPECT:单光子发射体层摄影术;MIBI:甲氧基异丁基异腈。 表 2 CZT SPECT使用动态SPECT采集法测定CFR的部分研究结果
Table 2. Partial results of the coronary flow reserve determination using dynamic SPECT acquisition with cadmium zinc telluride SPECT
Ben-Haim等[13]使用D-SPECT进行了定量整体及局部CFR的可行性研究,使用因子分析获得时间活性曲线并作为二室模型的血流动力学函数,分别计算负荷及静息时的K1(显像剂的摄取)值,并将K2(显像剂脱洗)值设置为0。CFR为负荷与静息时的K1值之比;对静态MPI图像进行半定量评价,总灌注缺损(total perfusion defect,TPD)大于5%定义为异常,结果发现灌注异常及经冠脉造影证实冠脉显著狭窄区域的CFR显著较正常区域低;同时作者认为由于MBF与心肌对显像剂的摄取直接呈非线性相关关系,该种方法在高血流量时有低估CFR的可能。Nkoulou等[19]使用NM 570c SPECT/CT(SPECT部分同NM530c)对MBF及CFR进行绝对定量研究并将结果与PET所测得的结果(显像剂为13N-氨水)进行对比,负荷/静息采用列表模式采集,对左右心腔及左室壁勾画ROI,获取相应区域时间活性曲线作为一室模型的输入函数,结果表明静息MBF与PET测量结果无明显差异,但是由于负荷的MBF显著低于PET测量值,导致所测CFR较PET所测显著低;将PET-CFR作为标准,SPECT-CFR截断值设定为1.26时,PET-CFR分别为2、>2及<2时,SPECT-CFR的灵敏度分别为78%、70%及75%。Agostini等[20]将CZT SPECT定量结果与PET(显像剂为15O-H2O)及多普勒导丝测得血流储备分数进行对比,其使用净滞留动力学模型评估整体心肌摄取值,并对显像剂摄取分数进行校正,得出MBF,结果静息及负荷时整体及左冠脉前降支、回旋支支配区MBF显著高于PET测量值(校正摄取分数所致),但是CFR差异并无统计学意义,探测血流储备分数<0.8的病变区域,CZT设备的灵敏度、特异度、准确率、阳性预测值及阴性预测值分别为58.3%、84.6%、81.1%、36.8%及93%。为了缩短检查时间、充分发挥CZT设备的性能优势,Fang等[23]设计了一个单次采集共计24 min定量负荷MBF的方案:静息状态下注射显像剂1 h后,采用列表模式连续动态采集,先采集5 min,后药物负荷高峰注射显像剂(注射总时间4 min),延迟5 min后行10 min动态采集,第二次采集数据获取负荷TAC及输入函数时均减去静息残余活性数据,结果测得的负荷MBF与磁共振MBF呈强相关,与磁共振CFR呈中等相关,以磁共振结果作为参照(CFR<1.3),该法探测冠脉狭窄的灵敏度、特异度和准确率为94%、90%和93%。考虑到运动负荷试验更具有生理学意义,可以评估心功能、运动诱发性心律失常和心率恢复等信息,Daquarti等[22]使用D-SPECT测定CFR,负荷由运动试验诱导,结果无CAD危险因素的受检者CFR中位数为2.38,静息及负荷MBF中位数分别为1.26、3.59,1例有糖尿病及抽烟史的患者CFR为1.37,不过该研究仅有10例患者。
SPECT定量心肌血流及冠状动脉血流储备的研究进展
Research progress of quantifying myocardial flow and coronary flow reserve with SPECT
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摘要: 应用SPECT、单光子显像剂及示踪动力学技术能方便地定量心肌血流量(MBF)及冠状动脉血流储备(CFR)。特别是碲锌镉心脏专用SPECT的使用,能更快速、准确地获得定量结果。MBF、CFR的获得对冠心病诊断准确性的提高、患者的再分层及进一步预后评估具有重要意义,并且为冠状动脉微血管疾病的诊断提供客观依据。但是使用SPECT定量MBF及CFR仍存在一些不足之处尚待解决。笔者旨在对SPECT定量MBF及CFR的不同方法、初步应用结果及临床意义作一综述。
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关键词:
- 单光子发射型计算机体层摄影术 /
- 冠心病 /
- 心肌血流量 /
- 心肌血流储备
Abstract: Quantitative measurement of myocardial blood flow (MBF) and coronary flow reserve (CFR) can be derived from myocardial perfusion imaging by using SPECT, single-photon tracers, and tracer kinetic techniques. The use of cadmium zinc telluride cadmium heart dedicated SPECT (CZT SPECT) enables faster and more accurate quantitative results. The determination of MBF and CFR is of great significance for improving the accuracy of coronary heart disease (CAD) diagnosis, re-stratification of CAD patients, and further prognosis evaluation. It can also provide an objective way for diagnosing coronary microvascular disease. However, some deficiencies need to be addressed. This article reviewed the different methods, preliminary results, and clinical significance of quantifying MBF and CFR with SPECT. -
表 1 使用动态平面采集与静态SPECT采集结合法测定CFR的部分研究结果
Table 1. Partial results of the coronary flow reserve determination using dynamic planar acquisition combined with static SPECT acquisition
研究者 显像剂 结 果 Sugihara等[3] 99Tcm-替曲磷 健康人CFR为1.47,梗死及缺血区为1.08、1.11,均较PET测量结果低 Taki等[4] 99Tcm-MIBI 以多普勒导丝测量CFR结果为参照,CFR<2.5时,心肌内显像剂滞留量与血流量呈正相关;CFR>2.5时,滞留量并不随血流量的增加而增加达到“平台期”。证明此法在高血流量时会低估CFR Ito等[5] 99Tcm-MIBI 健康人、CAD患者的CFR分别为2.13、1.48,而PET-CFR分别为3.76、1.97;两组数据呈显著相关性 Storto等[6] 99Tcm-MIBI CAD患者的CFR均数为1.36,多普勒导丝测量结果为1.39,呈显著相关性;较健康人CFR(2.19)显著降低 Pellegrino等[7] 99Tcm-MIBI 患者CFR较健康人显著降低,并且发现CFR降低与内皮功能障碍程度相关 Apostolopoulos等[9] 99Tcm-替曲磷 通过CT设备对采集数据进行散射及衰减校正,及对显像剂的“脱洗”(washout)量进行校正,测得的健康人及CAD患者CFR与负荷状态下MBF分别为1.68、1.72及1.39、1.42,该研究并未与PET结果直接对比 Nose等[10] 99Tcm-MIBI 所测CFR虽与PET-CFR显著相关,但该法在高血流量时低估CFR 注:表中,CFR:冠状动脉血流储备;CAD:冠心病;PET:正电子发射断层显像术;MBF:心肌血流量;SPECT:单光子发射体层摄影术;MIBI:甲氧基异丁基异腈。 表 2 CZT SPECT使用动态SPECT采集法测定CFR的部分研究结果
Table 2. Partial results of the coronary flow reserve determination using dynamic SPECT acquisition with cadmium zinc telluride SPECT
研究者 显像剂 结果 Nkoulou等[19] 99Tcm-替曲磷 CFR中位数为1.32,PET为2.36,以PET为参照,截断值为1.26时,其探测异常的灵敏度为75% Agostini等[20] 99Tcm- MIBI 与PET所测CFR并无明显差异,但是整体及左前降支、左旋支支配区静息及负荷MBF均较PET测量值高 Miyagawa等[21] 99Tcm- MIBI 冠脉1、2、3支病变组的整体CFR中位数分别为1.46、1.33、1.18,并且与多普勒导丝血流储备分数呈显著相关性 Daquarti等[22] 99Tcm- MIBI 该研究负荷由运动诱导,无冠心病危险因素患者的CFR中位数为2.38 注:表中,CZT:碲锌镉;CFR;冠状动脉血流储备;PET:正电子发射断层显像术;MBF:心肌血流量;SPECT:单光子发射体层摄影术;MIBI:甲氧基异丁基异腈。 -
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