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The optimal program of 99Tcmlabeled radionuclide imaging in diagnosing coronary disease

  • Department of Nuclear Medicine, The 88th Hospital of Chinese People's Liberation Army, Tai'an 271000, China

  • Corresponding author: Zhao-sheng LUAN, luanzs@sina.com ; 
  • Received Date: 2009-12-31
  • Objective To investigate the optimal program of 99Tcmlabeled radionuclide imaging in diagnosing coronary disease. Methods Four-thousand-two-hundred and thirty-six patients who were suspected or diagnosed with coronary disease were chosen.Eight-thousand-eight-hundred and seventy-three times 99Tcmlabeled radionuclide imaging were taken and analyzed.The optimal program of 99Tcmlabeled radionuclide imaging were drawn, compared and verified with their clinical information. Results The optimal program had high accuracy in diagnosing the patients of coronary disease, myocardial ischemia, myocardial infarction.It also was exact in special clinical needs of detecting myocardial viability, culprit vessel, ischemic cardiomyopathy and therapy effect. Conclusions The optimal program could satisfy many requirements of diagnosing coronary disease and overcome some defects of radionuclide imaging.So it was one highperforming, convenient and economical program and had significant clinical value.
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    [3] Turgut B, Unlu M, Temiz NH, et al. Dobutamine Tc-99m furifosmin SPECT in detection of coronary artery disease: evaluation of same day, rest-stress protocol. Ann Nucl Med, 2003, 17(7): 531-539. doi: 10.1007/BF03006665
    [4] Korosoglou G, Dubart AE, DaSilva KG Jr, et al. Real-time myocardial perfusion imaging for pharmacologic stress testing: added value to single photon emission computed tomography. Am Heart J, 2006, 151(1): 131-138. doi: 10.1016/j.ahj.2005.02.046
    [5] Bestetti A, Triulzi A, Di Leo C, et al. Enhanced prognostic stratification of CAD patients with low ejection fraction by stress-rest Tc-99m tetrofosmin gated-SPECT. Acta Cardiol, 2004, 59(1): 17-23. doi: 10.2143/AC.59.1.2005154
    [6] Canbaz F, Basoglu T, Semirgin SU, et al. Cold infarction areas of varying size in the presence of left ventricular dysfunction: the impact on left ventricular ejection fraction determination by gated SPECT compared to radionuclide ventriculography. Hell J Nucl Med, 2005, 8(3): 149-153.
    [7] Ohtaki Y, Chikamori T, Igarashi Y, et al. Differential effects comparing exercise and pharmacologic stress on left ventricular function using gated Tc-99m sestamibi SPECT. Ann Nucl Med, 2008, 22(3): 185-190. doi: 10.1007/s12149-007-0106-z
    [8] Hayat SA, Dwivedi G, Jacobsen A, et al. Effects of left bundlebranch block on cardiac structure, function, perfusion, and perfusion reserve: implications for myocardial contrast echocardiography versus radionuclide perfusion imaging for the detection of coronary artery disease. Circulation, 2008, 117(14): 1832-1841. doi: 10.1161/CIRCULATIONAHA.107.726711
    [9] Khalil MM, Elgazzar A, Khalil W, et al. Assessment of left ventricular ejection fraction by four different methods using 99mTc tetrofosmin gated SPECT in patients with small hearts: correlation with gated blood pool. Nucl Med Commun, 2005, 26(10): 885-893. doi: 10.1097/00006231-200510000-00007
    [10] Cain PA, Ugander M, Palmer J, et al. Quantitative polar representation of left ventricular myocardial perfusion, function and viability using SPECT and cardiac magnetic resonance: initial results. Clin Physiol Funct Imaging, 2005, 25(4): 215-222. doi: 10.1111/j.1475-097X.2005.00618.x
    [11] 栾兆生, 田嘉禾, 盖鲁粤, 等. 静脉滴注硝酸甘油介入99mTc-MIBI心肌显像评价存活心肌. 中华核医学杂志, 1998, 18(4): 201-208.
    [12] Matsunari I, Kanayama S, Yoneyama T, et al. Myocardial distribution of 18F-FDG and 99mTc-sestamibi on dual-isotope simultaneous acquisition SPET compared with PET. Eur J Nucl Med Mol Imaging, 2002, 29(10): 1357-1364. doi: 10.1007/s00259-002-0889-z
    [13] He ZX, Shi RF, Wu YJ, et al. Direct imaging of exercise-induced myocardial ischemia with fluorine-18-labeled deoxyglucose and Tc-99m-sestamibi in coronary artery disease. Circulation, 2003, 108(10): 1208-1213. doi: 10.1161/01.CIR.0000088784.25089.D9
    [14] Kamínek M, Meluzín J, Janousek S, et al. The role of quantitative Tc-99m-MIBI gated SPECT/F-18-FDG PET imaging in the monitoring of intracoronary bone marrow cell transplantation. Nucl Med Rev Cent East Eur, 2006, 9(1): 60-64.
    [15] Marini C, Giorgetti A, Gimelli A, et al. Extension of myocardial necrosis differently affects MIBG retention in heart failure caused by ischaemic heart disease or by dilated cardiomyopathy. Eur J Nucl Med Mol Imaging, 2005, 32(6): 682-688. doi: 10.1007/s00259-004-1735-2
    [16] Patel GM, Hauser TH, Parker JA, et al. Quantitative relationship of stress Tc-99m sestamibi lung uptake with resting Tl-201 lung uptake and with indices of left ventricular dysfunction and coronary arterydisease. J Nucl Cardiol, 2004, 11(4): 408-413. doi: 10.1016/j.nuclcard.2004.03.032
    [17] Prior JO, Monbaron D, Koehli M, et al. Prevalence of symptomatic and silent stress-induced perfusion defects in diabetic patients with suspected coronary artery disease referred for myocardial perfusion scintigraphy. Eur J Nucl Med Mol Imaging, 2005, 32(1): 60-69. doi: 10.1007/s00259-004-1591-0
    [18] Fleet R, Lespérance F, Arsenault A, et al. Myocardial perfusion study of panic attacks in patients with coronary artery disease. Am J Cardiol, 2005, 96(8): 1064-1068. doi: 10.1016/j.amjcard.2005.06.035
    [19] Soman P, Lahiri A, Mieres JH, et al. Etiology and pathophysiology of new-onset heart failure: evaluation by myocardial perfusion imaging. J Nucl Cardiol, 2009, 16(1): 82-91. doi: 10.1007/s12350-008-9010-8
    [20] Shishehbor MH, Lauer MS, Singh IM, et al. In unstable angina or non-ST-segment acute coronary syndrome, should patients with multivessel coronary artery disease undergo multivessel or culpritonly stenting?. J Am Coll Cardiol, 2007, 49(8): 849-854. doi: 10.1016/j.jacc.2006.10.054
    [21] Brener SJ, Milford-Beland S, Roe MT, et al. Culprit-only or multivessel revascularization in patients with acute coronary syndromes: an American College of Cardiology National Cardiovascular Database Registry report. Am Heart J, 2008, 155(1): 140-146. doi: 10.1016/j.ahj.2007.09.007
    [22] Senior R, Monaghan M, Main ML, et al. Detection of coronary artery disease with perfusion stress echocardiography using a novel ultrasound imaging agent: two Phase 3 international trials in comparison with radionuclide perfusion imaging. Eur J Echocardiogr, 2009, 10(1): 26-35. doi: 10.1093/ejechocard/jen321
    [23] Elhendy A, Schinkel AF, van Domburg RT, et al. Incidence and predictors of heart failure during long-term follow-up after stress Tc-99m sestamibi tomography in patients with suspected coronary artery disease. J Nucl Cardiol, 2004, 11(5): 527-533. doi: 10.1016/j.nuclcard.2004.04.011
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The optimal program of 99Tcmlabeled radionuclide imaging in diagnosing coronary disease

    Corresponding author: Zhao-sheng LUAN, luanzs@sina.com; 
  • Department of Nuclear Medicine, The 88th Hospital of Chinese People's Liberation Army, Tai'an 271000, China
  • Received Date: 2009-12-31
  • Available Online: 2010-01-25

Abstract:  Objective To investigate the optimal program of 99Tcmlabeled radionuclide imaging in diagnosing coronary disease. Methods Four-thousand-two-hundred and thirty-six patients who were suspected or diagnosed with coronary disease were chosen.Eight-thousand-eight-hundred and seventy-three times 99Tcmlabeled radionuclide imaging were taken and analyzed.The optimal program of 99Tcmlabeled radionuclide imaging were drawn, compared and verified with their clinical information. Results The optimal program had high accuracy in diagnosing the patients of coronary disease, myocardial ischemia, myocardial infarction.It also was exact in special clinical needs of detecting myocardial viability, culprit vessel, ischemic cardiomyopathy and therapy effect. Conclusions The optimal program could satisfy many requirements of diagnosing coronary disease and overcome some defects of radionuclide imaging.So it was one highperforming, convenient and economical program and had significant clinical value.

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  • 冠心病治疗方法的进展对诊断提出了更高的要求, 核素显像是冠心病诊断的重要手段。核素显像方法种类很多, 各种方法检测的重点、意义均不相同[1]。在同一个患者中, 实施所有的核素检查项目是不可能的, 也是不必要的。如何将核素显像方案进行优化, 选择最具临床价值、最符合临床要求、最具有可行性的核素检测项目或组合项目, 需要进一步深入研究。自1991年10月至2009年6月, 我们选择临床可疑或确诊的冠心病患者4236例, 进行99Tcm标记化合物显像8873例次, 分析显像结果, 并与临床对照, 以期探讨99Tcm标记化合物显像检测冠心病的优化方案。

1.   资料与方法

    1.1.   病例资料

  • 选择临床可疑或确诊的冠心病患者4236例, 其中男性3205例、女性1031例, 年龄26~91岁, 平均年龄(56.5±18.9)岁。此组病例由冠状动脉造影或临床随访证实。

    • 1.2.   主要仪器和显像剂

  • 显像仪器为GE公司生产的带符合线路和定位CT的SPECT-CT, 机型为Hawkeye Millennium VG, 配低能平行孔、99Tcm/18F双核素和符合线路准直器, 具备心电图触发门控采集功能。显像剂包括放射性核素和标记化合物, 分别由北京原子高科股份有限公司、江苏省原子医学研究所江原制药厂和山东省肿瘤医院提供。99Tcm-甲氧基异丁基异腈(99Tcm-methoxyisobutylisonitrile, 99Tcm-MIBI)每次显像剂量为555~740 MBq(1 mCi=37 MBq); 99Tcm-红细胞(99Tcm-red blood cell, 99Tcm-RBC)、99Tcm-高锝酸盐(99Tcm-sodium pertechnetate, 99TcmO4-)、99Tcm-焦磷酸盐(99Tcm-pyrophosphate, 99Tcm-PYP)每次显像的剂量均为740 MBq; 18F-FDG每次显像剂量为185~296 MBq; 201Tl每次显像剂量为111 MBq。

    • 1.3.   核素显像常用项目

  • ① 99Tcm-MIBI静息心肌灌注断层显像[1-2]; ②99Tcm-MIBI负荷(运动或药物)心肌灌注断层显像[3-4]; ③99Tcm-MIBI门控心肌断层显像[5-7]; ④99Tcm-RBC门控心血池显像[8-9]; ⑤静脉滴注(或含服)硝酸甘油介入99Tcm-MIBI心肌显像[10-11]; ⑥99TcmO4-首次通过法心血管造影[1]; ⑦99Tcm-PYP梗死灶阳性显像[1]; ⑧18F-FDG心肌葡萄糖代谢显像[12]; ⑨18F-FDG与99Tcm-MIBI双核素心肌显像[13-14]; ⑩201Tl心肌显像[15-16]。

    • 1.4.   优化方案的表达格式

  • 按临床诊断要求, 将核素显像各项目分为8个方案。方案一: 可疑冠心病确诊或排除[1-4], 检测病例数1349例; 方案二: 心肌缺血检测[17], 检测病例数1796例; 方案三: 陈旧性心肌梗死检测[12-14], 检测病例数984例; 方案四: 急性心肌梗死诊断[18-19], 检测病例数107例; 方案五: 心肌存活评价[10-14], 选择的检测病例数210例; 方案六: “罪犯”血管检测[20-21], 选择的检测病例数146例; 方案七: 缺血性心肌病诊断[22], 选择的检测病例352例; 方案八: 疗效评价[23], 选择的检测病例74例。其中, 方案一至四为冠心病常用诊断要求; 方案五至八为冠心病临床特需诊断要求, 选择的病例在前四个方案的病例总数内。

    将每一方案的核素显像各项目分为四个层次: 第一层为首选项目, 是达到临床诊断要求的必做项目; 第二层为次选项目, 是能为临床提供更充分的诊断信息, 或诊断价值大但对仪器或放射性药物要求较高的项目; 第三层为可选项目, 是非临床诊断要求的优势项目, 但对临床有一定帮助; 第四层为特选项目, 是临床或科研特别需要的项目。

    显像方法中, 各项目的序号(①~⑩)规定为该项目的简明代号。在同一层次内, 多个项目相加时, 为一个组合项目, 此组合内的项目全做, 并按排列次序作为检查的时间次序; 无相加标志时为可选其中之一, 次序以临床常用者为先(表 1)。

    方案 诊断要求 首选项目 次选项目 可选项目 特选项目
    方案一 可疑冠心病的确诊或排除 ①99TC--MiBi静息心肌灌注断层显像+②99TCm-MIBI负荷（运动或药物)心肌灌注断层显像 ③门控99Tcm-MIBI心肌断层显像 ④99Tcm-RBC门控心血池显像；⑦99Tcm-PYP梗死灶阳性显像 其他项目
    方案二 心肌缺血检测 ①99Tcm-MIBI静息心肌灌注断层显像 ②99Tcm-MIBI负荷(运动或药物）心肌灌注断层显像 ③门控心肌99Tcm-MIBI心肌断层显像；④99Tcm-RBC门控心血池显像 其他项目
    方案三 陈旧性心肌梗死检测 ①99Tcm-MIBI静息心肌灌注断层显像 ④99Tcm-RBC门控心血池显像；③99Tcm-MIBI门控心肌断层显像 ②99Tcm-MIBI负荷(运动或药物)心肌灌注断层显像 其他项目
    方案四 急性心肌梗死诊断 ①99Tcm-MIBI提前静息心肌灌注断层显像 ⑦99Tcm-PYP梗死灶阳性显像④99Tcm-RBC门控心血池显像 ③99Tcm-MIBI门控心肌断层显像 其他项目
    方案五 心肌存活评价 ①99Tcm-MIBI静息心肌灌注断层显像+⑤静滴(或含服）硝酸甘油介入99Tcm-MIBI心肌显像 ②99Tcm-MIBI负荷（运动或药物)心肌灌注断层显像；⑨ 18F-FDG与99Tcm-MIBI双核素心肌显像；⑧18F-FDG心肌葡萄糖代谢显像 ⑩201Tl心肌显像。 其他项目
    方案六 “罪犯”血管检测 ①99Tcm-MIBI静息心肌灌注断层显像+②99Tcm-MIBI负荷(运动或药物）心肌灌注断层显像+⑤静滴(或含服）硝酸甘油介人99Tcm-MIBI心肌显像 - ⑨l8F-FDG与99Tcm-MIBI双核素心肌显像；⑧l8F-FDG心肌葡萄糖代谢显像 其他项目
    方案七 缺血性心肌病诊断 ①静息99Tcm-MIBI心肌灌注断层显像+④99Tcm-RBC门控心血池显像 - - 其他项目
    方案八 疗效评价 ①静息99Tcm-MIBI心肌灌注断层显像+④99Tcm-RBC门控心血池显像 ②99Tcm-MIBI负荷（运动或药物）心肌灌注断层显像；③门控99Tcm-MIBI心肌断层显像 ⑥99TcmO4-首次通过心血管造影 其他项目
    注：表中“-”表示该栏目中无可选项目；99Tcm-MIBI为99Tcm-甲氧基异丁基异腈；99Tcm-RBC为99Tcm-红细胞；99TcmO4-为99Tcm-高锝酸盐；99Tcm-PYP为99Tcm-焦磷酸盐；18F-FDG为l8F-氟脱氧葡萄糖。
2.   结果

    2.1.   冠心病常用诊断要求完成情况

  • 4236例患者的检测结果见表 2。结果显示, 方案一至方案四的首选项目皆为99Tcm标记化合物显像项目, 能够很好的完成冠心病的临床常用诊断要求。

    病例分类 例数 检测方法 真阳性/阳性例数 真阴性/阴性例数 准确率(%) (真阳性+真阴性例数)/病例数
    可疑冠心病组 1349 方案一 562/649 675/700 91.7 1237/1349
    心肌缺血组 1796 方案二 1796/1674 0/122 93.2 674/1796
    陈旧性心肌梗死组 984 方案三 984/967 0/17 98.3 967/984
    急性心肌梗死组 107 方案四 107/107 0/0 100 107/107
    合计 4236 3449/3397 675/839 94.1 3985/4236

    • 2.2.   冠心病临床特需诊断要求完成情况

    2.2.1.   存活心肌检测

  • 210例冠脉造影确诊的冠心病患者用方案五组合显像, 与经皮冠状动脉介入治疗(percutaneous-coronary intervention, PCI)后的疗效比较, 证实该方案首选项目检测存活心肌的准确率为86.2%(181/210)。

    • 2.2.2.   “罪犯”血管检测

  • 146例冠脉造影确诊的冠心病多支血管病变患者用方案六组合显像, 与PCI后的疗效对比, 显示该方案首选项目检测“罪犯”血管的准确率为95.9%(140/146)。

    • 2.2.3.   缺血性心肌病诊断

  • 352例冠心病并缺血性心肌病患者用方案七组合显像, 结果显示, 该方案首选项目在本病中有明显的影像特点, 对比临床诊断结果, 该方案诊断缺血性心肌病的准确率为92.3%。

    • 2.2.4.   疗效评价

  • 74例接受血流重建治疗的患者用方案八组合显像进行疗效评价, 结果显示, 74例患者经临床评价: 治愈5例, 好转63例, 无效6例, 有效率为91.9%(68/74);方案八首选项目评价: 显效7例, 有效62例, 无效5例, 有效率为93.2%(69/74), 与临床评价接近。

3.   讨论

  • 本研究选择4236例临床确诊或可疑的冠心病患者进行了99Tcm标记化合物显像, 通过显像结果分析, 尝试提出了99Tcm标记化合物显像检测冠心病的优化方案。其应用结果显示, 在可疑冠心病的诊断中, 采用静息加运动99Tcm-MIBI心肌显像, 即可确诊或排除冠心病的存在, 准确率达91.7%。针对此类病例的诊断, 本方案强调运动试验的重要性, 运动显像可明显提高检出率和准确性。对于心肌缺血、陈旧性心肌梗死的检测和急性心肌梗死的诊断, 通过静息99Tcm-MIBI心肌显像单一项目, 既可了解心肌缺血的部位、范围和程度, 又可直观有无心脏扩大和心室重构, 其检测准确性高, 克服了核素显像检查步骤繁琐的缺陷。对临床特需的检测要求, 如存活心肌检测、“罪犯”血管检测、缺血性心肌病诊断、疗效监测等, 采用本方案所列的首选项目检测, 也有较高的准确性。本组病例检测方案的首选项目均为组合项目, 弥补了单一项目信息量不足的缺陷。

    本组病例结果表明，本优化方案在冠心病检测 中准确、可行，符合高效原则。采用本方案的首选 项目，简化了检测程序，减少了检测项目，缩短了 检测时间，方便了临床应用，提高了工作效率，符 合简便原则。本优化方案的首选项目均为99Tcm标记化合物显像项目，其显像剂供应充分、价格相对 低廉、检测费用便宜，降低了运行成本，减轻了患 者负担，符合节约原则，利于将核素显像这一优势 项目在临床冠心病诊断中推广应用。

    此优化方案立足于99Tcm标记化合物显像, 与201Tl相比, 核素更易得, 费用更低廉, 图像质量更好。在心肌存活的检测中, 虽然99Tcm标记化合物显像的准确率略低于18F-FDG代谢显像, 但却明显降低了检测条件和成本, 其性价比更高。应用的检测仪器也以普通SPECT或能够进行正电子成像的SPECT-CT为主, 较PET或PET-CT的检测成本与条件更低, 也利于临床的普及应用。未来随着核心脏病学的发展, 新的更优越的核素显像剂、显像仪器和显像方法不断应用, 本方案也会随之改进, 以进一步达到对冠心病全面诊断的要求。

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