Volume 48 Issue 1
Jan.  2024
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Feasibility study of quantitative analysis in dual-isotope and dual-dynamic cardiac imaging using CZT SPECT

  • Objective To explore the feasibility of quantitative analysis in 99Tcm-methoxyisobutylisonitrile (MIBI)/123I-metaiodobenzylguanidine (MIBG) dual-isotope and dual-dynamic cardiac imaging using cadmium zinc telluride (CZT) SPECT. Methods Twenty-four patients (14 males and 10 females) aged (49.2±16.8) years with cardiac dysfunction were prospectively enrolled from October 2021 to June 2023 at Fuwai Hospital, Chinese Academy of Medical Sciences. All the patients underwent 99Tcm-MIBI single-isotope dynamic cardiac imaging (referred to as single-isotope imaging) on the first day and 99Tcm-MIBI/123I-MIBG dual-isotope dual-dynamic cardiac imaging (referred to as dual-isotope imaging) on the second day. And complete physical correction and incomplete-physical correction were performed. Myocardial blood flow (MBF) for left ventricle (LV), left anterior descending branch (LAD), left circumflex branch (LCX), and right coronary artery (RCA) dominant area was quantified. Differences, correlation, and agreement of these parameters from two imaging methods were analyzed using Wilcoxon rank sum test, Pearson correlation test, and Bland-Altman analysis. Results The MBF of LV and LAD, LCX, RCA dominant area of single-isotope imaging and dual-isotope imaging with complete physical correction were 0.74 (0.64, 0.79) ml·min−1·g−1 vs. 0.74 (0.64, 0.80) ml·min−1·g−1, 0.72 (0.68, 0.82) ml·min−1·g−1 vs. 0.74 (0.64, 0.84) ml·min−1·g−1, 0.73 (0.66, 0.80) ml·min−1·g−1 vs. 0.74 (0.61, 0.79) ml·min−1·g−1, and 0.77 (0.64, 0.82) ml·min−1·g−1 vs. 0.77 (0.66, 0.82) ml·min−1·g−1, respectively. The differences were not statistically significant (Z=−1.349, −0.396, −0.350, −1.126; all P>0.05). The MBF of LV and LAD, LCX, RCA dominant area between single-isotope imaging and dual-isotope imaging with complete physical correction showed good correlations (r=0.857, 0.832, 0.708, 0.815; all P<0.001). The MBF mean differences of LV and LAD, LCX, RCA dominant area between single-isotope imaging and dual-isotope imaging with complete physical correction were 0.023, 0.016, 0.008, 0.040 ml·min−1·g−1, and the 95% confidence intervals were −0.125 to 0.170, −0.196 to 0.228, −0.181 to 0.196, and −0.193 to 0.271, respectively. The agreement between the two acquisition methods was good. Conclusions CZT-SPECT can be used to obtain comparable MBF between single-isotope imaging and dual-isotope cardiac imaging on the basis of complete physical correction. It is feasible to conduct a quantitative analysis of MBF and cardiac sympathetic nervous system through a single examination.
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Feasibility study of quantitative analysis in dual-isotope and dual-dynamic cardiac imaging using CZT SPECT

    Corresponding author: Wei Fang, nuclearfw@126.com
  • 1. Peking Union Medical College, National Center for Cardiovascular Diseases, Department of Nuclear Medicine, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China

Abstract:  Objective To explore the feasibility of quantitative analysis in 99Tcm-methoxyisobutylisonitrile (MIBI)/123I-metaiodobenzylguanidine (MIBG) dual-isotope and dual-dynamic cardiac imaging using cadmium zinc telluride (CZT) SPECT. Methods Twenty-four patients (14 males and 10 females) aged (49.2±16.8) years with cardiac dysfunction were prospectively enrolled from October 2021 to June 2023 at Fuwai Hospital, Chinese Academy of Medical Sciences. All the patients underwent 99Tcm-MIBI single-isotope dynamic cardiac imaging (referred to as single-isotope imaging) on the first day and 99Tcm-MIBI/123I-MIBG dual-isotope dual-dynamic cardiac imaging (referred to as dual-isotope imaging) on the second day. And complete physical correction and incomplete-physical correction were performed. Myocardial blood flow (MBF) for left ventricle (LV), left anterior descending branch (LAD), left circumflex branch (LCX), and right coronary artery (RCA) dominant area was quantified. Differences, correlation, and agreement of these parameters from two imaging methods were analyzed using Wilcoxon rank sum test, Pearson correlation test, and Bland-Altman analysis. Results The MBF of LV and LAD, LCX, RCA dominant area of single-isotope imaging and dual-isotope imaging with complete physical correction were 0.74 (0.64, 0.79) ml·min−1·g−1 vs. 0.74 (0.64, 0.80) ml·min−1·g−1, 0.72 (0.68, 0.82) ml·min−1·g−1 vs. 0.74 (0.64, 0.84) ml·min−1·g−1, 0.73 (0.66, 0.80) ml·min−1·g−1 vs. 0.74 (0.61, 0.79) ml·min−1·g−1, and 0.77 (0.64, 0.82) ml·min−1·g−1 vs. 0.77 (0.66, 0.82) ml·min−1·g−1, respectively. The differences were not statistically significant (Z=−1.349, −0.396, −0.350, −1.126; all P>0.05). The MBF of LV and LAD, LCX, RCA dominant area between single-isotope imaging and dual-isotope imaging with complete physical correction showed good correlations (r=0.857, 0.832, 0.708, 0.815; all P<0.001). The MBF mean differences of LV and LAD, LCX, RCA dominant area between single-isotope imaging and dual-isotope imaging with complete physical correction were 0.023, 0.016, 0.008, 0.040 ml·min−1·g−1, and the 95% confidence intervals were −0.125 to 0.170, −0.196 to 0.228, −0.181 to 0.196, and −0.193 to 0.271, respectively. The agreement between the two acquisition methods was good. Conclusions CZT-SPECT can be used to obtain comparable MBF between single-isotope imaging and dual-isotope cardiac imaging on the basis of complete physical correction. It is feasible to conduct a quantitative analysis of MBF and cardiac sympathetic nervous system through a single examination.

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  • 近年来,基于SPECT的心脏动态显像定量分析技术已逐步成熟并开始应用于临床。与传统的静态显像定性分析技术相比,定量分析技术更能满足临床精准诊断的迫切需求,在诊断准确率方面具有明显的优势。与传统的定性诊断技术相比,SPECT心肌灌注显像心肌血流定量分析技术诊断心肌缺血的灵敏度有了显著的提高[1-3];SPECT心脏神经显像也逐步建立了能够用于心脏疾病诊断和预后评估的定量指标[4-7]。传统的定性诊断技术与SPECT心肌灌注显像心肌血流定量分析技术联合应用能够进一步提高对心肌损伤的诊断效能,对因冠状动脉痉挛引起的一过性心肌缺血、急性心肌梗死后恶性心律失常等不良预后事件的预测等都有较好的诊断价值[8-9]

    另一方面,SPECT显像的性能也在不断提高。与传统SPECT相比,碲锌镉(cadmium zinc telluride,CZT)心脏专用SPECT(简称CZT SPECT)具有更优越的物理性能,其探测灵敏度、空间分辨率和能量分辨率均明显提高,能够对能峰较为接近的99Tcm123I信号进行有效地鉴别,从而实现双核素显像,明显提高了诊断效率[10]。已有研究人员对99Tcm-MIBI/123I-间碘苄胍(metaiodobenzylguanidine, MIBG)双核素心肌灌注/交感神经显像的可行性进行了探索,结果表明CZT SPECT能够较好地辨别99Tcm-MIBI和123I-MIBG信号,有效避免双核素间的干扰,一次检查可以同时得到较为清晰的99Tcm-MIBI心肌灌注显像和123I-MIBG心脏交感神经图像[11-13]。本研究在上述研究的基础上,进一步利用CZT SPECT进行99Tcm-MIBI/123I-MIBG双核素双动态心脏显像定量分析,探讨双核素采集对心脏定量分析指标是否会产生显著的影响,从而确定这一技术在临床中应用的可行性。

  • 1.   资料与方法

      1.1.   一般资料

    • 对2021年10月至2023年6月于中国医学科学院阜外医院治疗的24例心功能不全患者进行前瞻性研究,其中男性14例、女性10例,年龄(49.2±16.8)岁。纳入标准:心功能不全患者(射血分数<50%);年龄18~80岁。排除标准:妊娠和哺乳期女性。所有患者均于检查前签署了知情同意书。本研究获得了中国医学科学院阜外医院伦理委员会的批准(批准号:2021-1589)。

    • 1.2.   显像方法

    • 所有患者均采用美国通用电气公司Discovery NM 530 c型CZT心脏专用SPECT进行双核素双动态心脏显像。显像前24 h患者口服碘剂(中国医学科学院阜外医院院内制剂)封闭甲状腺。第1日行99Tcm-MIBI单核素动态SPECT心脏显像。动态显像前患者平躺于检查床,预注射3.7×107 Bq 99Tcm-MIBI(北京原子高科股份有限公司)用于心脏定位,并测量静息心率与血压。动态显像采用列表模式,共采集10 min,采集开始10 s后,立即通过静脉“弹丸”式注射99Tcm-MIBI 7.4×108 Bq。动态采集完成后,患者移至美国通用电气公司Optima 640型SPECT/CT进行低剂量CT扫描,用于组织衰减校正。第2日行99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像。显像前患者同样预注射3.7×107 Bq 99Tcm-MIBI用于心脏定位,并测量静息心率与血压。动态显像采用列表模式,共采集20 min,采集开始10 s后,通过静脉“弹丸”式注射123I-MIBG(北京原子高科股份有限公司)3.7×108 Bq,10 min后再“弹丸”式注射99Tcm-MIBI 7.4×108 Bq。

    • 1.3.   图像处理

      1.3.1.   列表模式数据重分
    • 99Tcm-MIBI单核素动态SPECT心脏显像的列表模式数据按照10帧×10 s+5帧×20 s+6帧×60 s的方式重分,重分能窗包括主峰能窗(131.6~148.4 keV)和下散射窗(118.5~138.5 keV)。99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像的列表模式数据也按照10帧×10 s+5帧×20 s+6帧×60 s的方式重分,123I-MIBG显像重分能窗包括主峰能窗(149.5~168.5 keV)、下散射窗(131.6~148.4 keV)及准直器穿透能窗(169.0~188.0 keV);99Tcm-MIBI显像重分能窗包括主峰能窗(131.6~148.4 keV)和下散射窗(118.5~138.5 keV)。

    • 1.3.2.   99Tcm-MIBI动态SPECT的图像重建和物理校正
    • 图像重建采用有序子集最大期望值法,共35次迭代,2个子集。第1日99Tcm-MIBI 单核素动态SPECT心脏显像采用的物理校正包括核素衰变校正、组织衰减校正、散射校正、空间分辨率校正及图像噪声校正,并将像素值转换为物理单位(Bq/ml)。99Tcm-MIBI自身的散射校正采用99Tcm-MIBI主峰能窗图像减去下散射窗图像的散射分量。第2日99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像的图像重建方法与第1日相似,其中核素衰变校正、组织衰减校正、空间分辨率校正及图像噪声校正与第1日方法相同,但散射校正不同。99Tcm-MIBI的散射校正包括两部分,其中99Tcm-MIBI自身的散射校正与第1日相同,除此之外,还需要在心肌同时存在123I-MIBG和99Tcm-MIBI摄取时校正123I-MIBG对99Tcm-MIBI的下散射干扰和准直器穿透干扰。校正方法为采用123I-MIBG下散射窗预估123I-MIBG对99Tcm-MIBI的下散射干扰和准直器穿透干扰程度,由此对99Tcm-MIBI主峰能窗图像进行校正。为验证123I-MIBG对99Tcm-MIBI的下散射干扰和准直器穿透干扰的影响,按物理校正方法不同分别对所有患者的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像的原始图像进行完整物理校正和非完整物理校正。完整物理校正包括核素衰变校正、组织衰减校正、散射校正、空间分辨率校正、图像噪声校正、下散射干扰和准直器穿透干扰校正;非完整物理校正不进行下散射干扰和准直器穿透干扰校正。

    • 1.3.3.   SPECT心肌血流定量
    • 第1日和第2日的99Tcm-MIBI动态SPECT心脏显像图像通过三维采样生成心血池与心肌的时间-放射性活度曲线,将时间-放射性活度曲线用单组织双腔室动力学模型进行拟合,计算心肌摄取速率参数K1,将99Tcm-MIBI心肌放射性计数转换为心肌血流量(myocardial blood flow,MBF),并以静息心率和血压的乘积进行校正。MBF包括:整体左心室(left ventride,LV)和冠状动脉左前降支(left anterior descending branch,LAD)、左回旋支(left circumflex branch,LCX)、右冠状动脉(right coronary artery,RCA)支配区域MBF。所有动态SPECT心脏显像图像的重建、物理校正和心肌血流的定量分析均应用MyoFlowQ软件(北京百灵云生物医学科技有限公司)完成。

    • 1.4.   统计学方法

    • 应用IBM SPSS 21.0软件对数据进行统计学分析。不符合正态分布的计量资料以MQ1, Q3)表示,采用Wilcoxon秩和检验比较99Tcm-MIBI单核素动态SPECT心脏显像与99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像获得的LV和LAD、LCX、RCA支配区域MBF的差异。采用Pearson 相关性分析及 Bland-Altman 法分析两种显像方法得到的MBF的相关性和一致性。P<0.05为差异有统计学意义。

    2.   结果

      2.1.   99Tcm-MIBI单核素动态SPECT心脏显像与进行完整物理校正、非完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像MBF的比较

    • 表1可知,99Tcm-MIBI单核素动态SPECT心脏显像与进行完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像获得的LV和LAD、LCX、RCA支配区域的MBF的差异均无统计学意义(均P>0.05)。99Tcm-MIBI单核素动态SPECT心脏显像与进行非完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像获得的LV和LAD、LCX、RCA支配区域的MBF的差异均有统计学意义(均P<0.05)。

      显像方法 整体左心室 左前降支支配区域 左回旋支支配区域 右冠状动脉支配区域
      99Tcm-MIBI单核素动态SPECT心脏显像(n=24) 0.74 (0.64,0.79) 0.72 (0.68,0.82) 0.73 (0.66,0.80) 0.77 (0.64,0.82)
      完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像(n=24) 0.74 (0.64,0.80)a 0.74 (0.64,0.84)a 0.74 (0.61,0.79)a 0.77 (0.66,0.82)a
      非完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像(n=24) 0.88 (0.76,0.94)b 0.91 (0.82,1.10)b 0.92 (0.87,1.10)b 0.86 (0.65,0.98)b
      注:a表示与99Tcm-MIBI单核素动态SPECT心脏显像比较,差异均无统计学意义(Z=−1.349、−0.396、−0.350、−1.126,均P>0.05);b表示与99Tcm-MIBI单核素动态SPECT心脏显像比较,差异均有统计学意义(Z=−3.455、−3.849、−3.661、−2.273,均P<0.05)。MIBI为甲氧基异丁基异腈;SPECT为单光子发射计算机体层摄影术;MIBG为间碘苄胍

      Table 1.  Comparison of myocardial blood flow between 99Tcm-methoxyisobutylisonitrile (MIBI) single-isotope dynamic cardiac imaging and 99Tcm-MIBI/123I-metaiodobenzylguanidine (MIBG) dual-isotope dual-dynamic cardiac imaging with or without complete physical correction (ml·min−1·g−1, M(Q1, Q3))

    • 2.2.   99Tcm-MIBI单核素动态SPECT心脏显像与进行完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像获得的MBF的相关性和一致性分析

    • 图1所示,99Tcm-MIBI单核素动态SPECT心脏显像与进行完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像获得的LV和LAD、LCX、RCA支配区域的MBF均有较好的相关性(均P<0.001)。如图2所示,2种方法获得的LV和LAD、LCX、RCA支配区域的MBF的平均差值为0.023、0.016、0.008、0.040 ml·min−1·g−1,95%CI分别为−0.125~0.170、−0.196~0.228、−0.181~0.196、−0.193~0.271。99Tcm-MIBI单核素动态SPECT心脏显像与进行完整物理校正的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像获得的LV和LAD、LCX、RCA支配区域的MBF均有较好的相关性和一致性。

      Figure 1.  Correlation analysis of myocardial blood flow between 99Tcm-methoxyisobutylisonitrile (MIBI) single-isotope dynamic cardiac imaging and 99Tcm-MIBI/123I-metaiodobenzylguanidine (MIBG) dual-isotope dual-dynamic cardiac imaging with complete physical correction

      Figure 2.  Bland-Altman agreement analysis of myocardial blood flow between 99Tcm-methoxyisobutylisonitrile (MIBI) single-isotope dynamic cardiac imaging and 99Tcm-MIBI/123I-metaiodobenzylguanidine (MIBG) dual-isotope dual-dynamic cardiac imaging with complete physical correction

    3.   讨论
    • 在本研究中,我们发现,使用CZT SPECT进行的99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像经过散射校正后,较高能量的123I-MIBG信号不会对99Tcm-MIBI心肌血流定量产生明显的影响。

      99Tcm123I的能峰分别为140 keV和159 keV,二者非常接近,传统的碘化钠(NaI)晶体SPECT的能量分辨率>10%,难以区分这两种核素的能峰,因此无法实现99Tcm/123I双核素显像。但CZT SPECT的能量分辨率显著提高,可达到5%~6%[14],能够对99Tcm123I的双核素信号进行有效地鉴别。以往的研究结果表明,即使不进行物理校正,CZT SPECT采集到的心脏模型99Tcm单核素显像和99Tcm/123I双核素显像放射性计数相对分布的差异无统计学意义,其对人体99Tcm-MIBI单核素显像和99Tcm-MIBI/123I-MIBG双核素显像心脏图像的半定量评分差异无统计学意义[11]。上述研究结果均是基于放射性计数的相对分布得出的,并未进行绝对定量分析,对于常规的心肌灌注显像和心脏神经显像的定性诊断是基本可行的。但本研究对于99Tcm-MIBI/123I-MIBG双核素显像MBF和心脏交感神经均进行绝对定量分析,因此与以往研究不同。

      进行心脏SPECT绝对定量分析的前提是基于对心肌放射性计数的准确测量,因此在行99Tcm-MIBI/123I-MIBG双核素显像时还需要对高能123I对低能99Tcm信号的影响进行校正;低能99Tcm对高能123I信号不会产生明显影响,因此不需要校正。行双核素SPECT心脏显像时,可以从能谱与原始投影图观察到心肌的123I-MIBG摄取对99Tcm-MIBI心肌图像产生的下散射干扰和准直器穿透干扰,这种干扰会增加99Tcm-MIBI主峰能窗的放射性计数,进而影响动态SPECT图像重建和定量分析的准确性[15-18]。因此,99Tcm-MIBI动态显像的散射校正应包括两个部分,除99Tcm-MIBI自身的散射校正外,还需要校正123I-MIBG对99Tcm-MIBI的下散射干扰和准直器穿透干扰。99Tcm-MIBI自身的散射校正采用99Tcm-MIBI主峰能窗图像减去下散射窗放射性计数估算的主峰能窗内的散射分量图像;采用未注射99Tcm-MIBI前的123I-MIBG下散射窗放射性计数和准直器穿透窗计数分别估算123I-MIBG对99Tcm-MIBI的下散射干扰和准直器穿透干扰,并在99Tcm-MIBI主峰能窗图像中去除。经过上述校正后,123I-MIBG对99Tcm-MIBI的散射影响基本可以消除,从而保证了图像重建和定量分析的准确性。

      99Tcm-MIBI心肌灌注显像和123I-MIBG心脏交感神经显像均是目前临床应用的重要的心脏功能评价技术,两者联合应用对心肌损伤性质和程度的判断、高危心肌的识别、预后评估等均具有重要的临床意义[9, 19-22]。近年来,基于动态显像的定量分析技术在99Tcm-MIBI心肌灌注显像和123I-MIBG心脏交感神经显像中的研究均已开展。通过99Tcm-MIBI心肌血流定量测定的负荷MBF和心肌血流储备可进一步提高对心肌缺血的诊断准确率,123I-MIBG心脏交感神经分布定量指标的优化也是目前重要的研究课题[23-25]。CZT SPECT为99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像提供了可能,极大地提高了诊断效率。本研究进一步证实了这一技术应用的可行性,且具有重要的临床意义。

      本研究具有一定的局限性:一是样本量相对较少,还需要更大样本量的研究进一步证实;二是受患者难以进行多次重复检查的限制,没有行99Tcm-MIBI/123I-MIBG双核素显像与123I-MIBG单核素显像获得的123I-MIBG定量指标的比较,虽然理论上99Tcm的能量较低,不会明显影响123I的放射性计数,但仍然需要进一步研究结果的证实,我们将在后续的研究中逐步完善。

      综上所述,我们认为,利用CZT SPECT同时行99Tcm-MIBI/123I-MIBG双核素双动态SPECT心脏显像,通过一次检查完成MBF和心脏交感神经的定量分析是完全可行的。

      利益冲突 所有作者声明无利益冲突

      作者贡献声明 任俊灵负责研究方法的设计、数据的采集、论文的撰写;张宗耀、汪蕾负责图像的分析、数据的统计与分析;王小迪负责研究方法的设计、文献的检索;方纬负责命题的设计、研究的指导、论文的审阅

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