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核素肺通气/灌注(ventilation/perfusion,V/Q)显像是较早应用于慢性血栓栓塞性肺动脉高压(chronic thromboembolic pulmonary hypertension,CTEPH)的无创影像学技术,其主要根据血栓栓塞导致的肺血流灌注受损,肺V/Q不匹配进行诊断。但这种V/Q肺段性不匹配并不能反映肺动脉高压引起的V/Q分布紊乱情况,从而低估了CTEPH患者肺血管受损的程度和范围。目前临床尚缺乏有效的定量评价方法来全面评估肺V/Q分布的紊乱程度。已有研究结果证实,核素肺V/Q分布异质性可评估肺栓塞[1]和慢性阻塞性肺疾病[2]等疾病的肺V/Q分布失衡,从而提高了诊断的准确率。同时,基于SPECT软件计算的全肺的SUV也可定量评估肺血流灌注分布的异质性,与PET相比,更加经济、便捷,具有较高的稳定性和可重复性。本研究通过定量比较CTEPH组和健康对照组肺V/Q分布的异质性,探讨肺V/Q分布异质性指标与肺动脉压力之间的相关性,从而验证肺V/Q分布异质性的定量分析方法应用于CTEPH的可行性。
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根据2015年欧洲心脏病学会肺动脉高压诊断和治疗指南中的标准[3],收集中国医学科学院北京协和医学院阜外医院2018年2月至12月经右心导管及肺动脉造影确诊的CTEPH患者20例,其中男性12例、女性8例,年龄(48.75±14.07)岁,排除其他类型的肺动脉高压、急性肺栓塞和肺实质性病变等患者,同时入组以排除为目的行肺V/Q显像的患者。将肺V/Q显像诊断为正常的13名健康者作为对照组,其中男性7名、女性6名,年龄(54.46±8.56)岁。所有CTEPH患者同时接受超声心动图检查,估测肺动脉收缩压(pulmonary arterial systolic pressure,PASP),该检查与肺V/Q显像的时间间隔在一周内。本研究经中国医学科学院阜外医院伦理委员会批准(NO.402),受试者均符合核素肺V/Q显像安全标准且均签署了知情同意书。
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图像采集均采用德国SIEMENS公司的 Symbia T16 SPECT/CT仪,配低能高分辨率准直器。能峰:140 keV,窗宽20%。通气设备采用一次性肺通气导入器:99Tcm-锝气通气装置(澳大利亚VITA医疗有限公司)。肺V/Q显像采用两日法。
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嘱患者吸氧,氧气流量为2~4 L/min,吸入时间为 5~10 min。患者仰卧于检查床上,双臂抱头,使探头尽量贴近胸部。静脉注射74~185 MBq 99Tcm标记的大颗粒聚合人血清白蛋白(购自中国原子能科学研究院原子高科股份有限公司),行肺灌注断层显像。在注射前后分别测量并记录99Tcm-人血清白蛋白的放射性剂量和对应时间。两探头各旋转180°,每个探头采集32个投影,每个投影采集20 s,共采集64个投影,采集矩阵128
$\times $ 128,放大1倍。采集过程中嘱患者平稳呼吸,以减少呼吸运动对肺显像的干扰。 -
灌注SPECT采集之后同一床位进行低剂量CT扫描。采集参数[4]:管电压110 kV、管电流25 mAs、层厚5 mm,于吸气末屏气采集。
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灌注SPECT显像后第2天行通气采集。将高放射性浓度(>370 MBq/0.1 mL)的99TcmO4−注入锝气发生器的石墨钳锅内,在充满氩气的密闭装置内通电加温,99TcmO4−蒸发形成锝气,嘱患者通过连接管及面罩吸入锝气,吸入时间为1 min。嘱患者仰卧于检查床上,双臂抱头,使探头尽量贴近胸部行肺通气断层显像,采集参数同灌注SPECT显像。
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将全部采集图像导入HERMES工作站(HERMES Medical Solutions AB,瑞典)。选取灌注SPECT图像、通气SPECT图像及用于衰减校正的CT图像进行重建。重建后的数据根据通气、灌注放射性计数的10%作为阈值设定肺的边界。通气、灌注放射性计数经归一化校正后,可获得每个体素的通气、灌注的放射性计数及二者的比值,并计算三者的标准差(standard deviation,SD)。三者的SD经对数转换后获得V/Q放射性分布异质性的定量指标,分别记为LogSDV、LogSDQ和LogSDVQR。同时,校正后的每个体素的通气、灌注的放射性计数以及V/Q放射性计数比值经对数转换,范围从−3(log100.001)~2(log10100),放射性计数>100的所有体素被赋值为100,<0.001的体素被赋值为0.001,间隔为0.05,绘制V、Q及V/Q比值的分布-肺内占比曲线[1],上述LogSDV、LogSDQ 及LogSDVQR分别表示各曲线分布的宽度,即描述V/Q异质性情况。此外,将重建后的灌注SPECT及诊断CT图像导入仪器自带Hybrid 3D软件,在CT图像上,采用肺CT值作为阈值自动勾画左肺、右肺和全肺边界轮廓获得感兴趣体积(volume of interest,VOI),并将其复制于肺灌注图像上,将每一体素的放射性计数转换为每单位体积放射性活度[5],经体表面积(body surface area,BSA)校正后获得左肺、右肺和全肺的SUV(见下述公式),包括峰值(SUVpeak)、最大值(SUVmax)、最小值(SUVmin)、平均值(SUVmean)和SD(SUVSD),其中,SUVpeak为VOI内每立方厘米体素内SUV平均值的最大值,SUVSD则代表灌注分布的异质性。
$ {\rm{SU}}{{\rm{V}}_{{\rm{BSA}}}} = {\rm{A}} \times \frac{{{\rm{BSA}}}}{{\rm{D}}} \times 10\;000 $ 公式中,A为单位体积的放射性活度(Bq/cm3)、D为注射剂量(Bq)、BSA(m2)=(体重0.425
$\times $'/> 身高0.725)$\times $'/> 0.007 184、10 000的单位为cm2。 -
使用 SPSS 19.0 软件进行统计学分析。符合正态分布的计量资料以均数±标准差表示。在方差齐的条件下,CTEPH组与对照组、左肺与右肺的测量指标组间比较采用两独立样本t检验。CTEPH组患者的肺V/Q分布异质性指标与PASP的相关性采用Pearson相关性分析。P<0.05 为差异有统计学意义。
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由表1可见,CTEPH组和健康对照组在年龄、性别、身高和体重等方面的比较,差异均无统计学意义(均P>0.05)。
组别 年龄(岁) 女性/男性(例) 身高(cm) 体重(kg) CTEPH组
(n=20)48.75±14.07 8/12 166.45±7.83 65.25±11.00 健康对照组
(n=13)54.46±8.56 6/7 168.46±9.68 71.69±18.01 检验值 t=−1.31 χ2=0.122 t=−0.66 t=−1.28 P值 0.200 >0.99 0.516 0.210 注:表中,CTEPH:慢性血栓栓塞性肺动脉高压;PASP:肺动脉收缩压 表 1 2组临床资料的比较
Table 1. Comparison of clinical data between two groups
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对照组的肺V/Q放射性分布曲线呈对称性单峰状分布(图1中C、D),而CTEPH组患者的肺V/Q放射性分布曲线呈非对称性的多峰分布(图2中C、D),2组图像有明显差别。典型病例的肺V/Q平面显像图分别见图1和2中的C、D。
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由表2可见,CTEPH组的LogSDVQR、SUVSD分别为0.61±0.15、3.54±1.44;对照组的LogSDVQR、SUVSD分别为0.40±0.14、2.42±0.91,2组间的差异有统计学意义(均P<0.05);与健康对照组相比,CTEPH组的LogSDV、LogSDVQR、全肺灌注的SUVpeak、SUVmax、SUVSD均明显升高,差异有统计学意义(均P<0.05);2组的LogSDQ、SUVmean和SUVmin之间的差异均无统计学意义。CTEPH组的左肺SUVmean、SUVSD较右肺明显增高(均P<0.05);左、右肺的SUVpeak、SUVmax、SUVmin比较,差异均无统计学意义,对照组的左、右肺各项SUV比较,差异均无统计学意义(表3)。
组别 全肺 SUV参数 V/Q 放射性计数 峰值 平均值 最小值 最大值 标准差 LogSDV LogSDQ LogSDVQR CTEPH组(n=20) 19.12±7.94 2.78±1.15 0.002±0.003 20.19±8.30 3.54±1.44 0.56±0.16 0.44±0.09 0.61±0.15 健康对照组(n=13) 10.81±4.05 3.36±2.21 0.011±0.024 11.44±4.33 2.42±0.91 0.31±0.11 0.35±0.16 0.40±0.14 t值 3.48 −0.98 −1.37 3.49 2.50 4.91 1.72 3.89 P值 0.002 0.334 0.197 0.001 0.018 0.000 0.103 0.001 注:表中,SUV:标准化摄取值;V:通气;Q:灌注;CTEPH:慢性血栓栓塞性肺动脉高压;SD:标准差;VQR:V、Q的放射性计数的比值 表 2 2组肺的SUV参数和V/Q 放射性计数的比较(
±s)$\bar {{x}}$ Table 2. Comparison of standardized uptake value parameters and ventilation/perfusion radioactive counts in two groups (
±s)$\bar {{x}}$ SUV参数 CTEPH组(n=20) t值 P 值 健康对照组(n=13) t值 P 值 右肺 左肺 右肺 左肺 峰值 14.12±6.42 18.27±7.88 −1.83 0.075 10.39±4.06 10.23±3.93 0.10 0.919 平均值 2.04±1.23 3.61±2.00 −2.98 0.005 3.42±2.37 3.29±2.05 0.15 0.885 最小值 0.003±0.004 0.005±0.008 −0.95 0.346 0.031±0.066 0.012±0.024 0.98 0.338 最大值 15.25±6.84 19.28±8.29 −1.68 0.102 10.91±4.30 10.78±4.15 0.08 0.937 标准差 2.55±1.44 3.84±1.66 −2.63 0.012 2.42±0.92 2.39±0.91 0.10 0.921 注:表中,CTEPH:慢性血栓栓塞性肺动脉高压;SUV:标准化摄取值 表 3 CTEPH组和健康对照组的右肺、左肺SUV参数的比较(
±s)$\bar {{x}}$ Table 3. Comparison of standardized uptake value of right lung and left lung in chronic thromboembolic pulmonary hypertension group and healthy control group (
±s)$\bar {{x}}$ -
CTEPH组患者的PASP为(72.80±0.15) mmHg。LogSDVQR与PASP呈中等程度相关(R=0.544,P=0.013),SUV各项指标与PASP无显著相关性(均P>0.05,图3)。
慢性血栓栓塞性肺动脉高压患者核素肺通气/灌注分布异质性的初步定量研究
Preliminary quantitative analysis of the distribution heterogeneity of lung ventilation/perfusion in patients with chronic thromboembolic pulmonary hypertension
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摘要:
目的 研究核素肺通气/灌注(V/Q)SPECT显像在慢性血栓栓塞性肺动脉高压(CTEPH)分布异质性中的应用,探讨分布异质性定量指标与肺动脉压力之间的相关性。 方法 收集中国医学科学院阜外医院2018年2月至12月经右心导管及肺动脉造影确诊的CTEPH患者20例(CTEPH组),其中男性12例、女性8例,年龄(48.75±14.07)岁;13名正常健康者作为对照组,其中男性7名、女性6名,年龄(54.46±8.56)岁。CTEPH组患者和对照组健康者均行肺V/Q SPECT显像及同床位低剂量CT扫描,CTEPH患者在一周内行超声心动检查,估测肺动脉收缩压(PASP)。通过图像重建和分析,获得肺V/Q放射性分布异质性指标LogSDV、LogSDQ和LogSDVQR(SD为标准差;V、Q、VQR分别为通气、灌注的放射性计数及二者的比值)。在CT图像上采用肺CT阈值的方法自动勾画左肺、右肺和全肺的感兴趣区,并将之复制于肺灌注图像上,获得左肺、右肺和全肺的标准化摄取值(SUV),包括SUV的峰值(SUVpeak)、最大值(SUVmax)、最小值(SUVmin)、平均值(SUVmean)和标准差(SUVSD),其中SUVSD代表肺灌注放射性分布的异质性。2组之间的比较采用t检验,分布异质性指标与PASP的相关性采用Pearson相关性分析。 结果 健康对照组的肺V/Q放射性分布曲线呈对称性单峰状分布,而CTEPH组的肺V/Q放射性分布曲线呈非对称性的多峰分布。与健康对照组相比,CTEPH组的LogSDV、LogSDVRQ、全肺灌注的SUVpeak、SUVmax、SUVSD均明显升高,且差异均有统计学意义(LogSDV:0.56±0.16对0.31±0.11,t=4.91,P=0.000;LogSDVQR:0.61±0.15对0.40±0.14,t=3.89,P=0.001;SUVpeak:19.12±7.94对10.81±4.05,t=3.48,P=0.002;SUVmax:20.19±8.30对11.44±4.33,t=3.49,P=0.001;SUVSD:3.54±1.44 对2.42±0.91,t=2.50,P=0.018);而2组的LogSDQ、SUVmean和SUVmin 的差异均无统计学意义。CTEPH组的PASP为(72.80±0.15) mmHg,LogSDVQR与PASP呈中等程度相关(R=0.544,P=0.013)。 结论 核素肺V/Q显像可定量评估CTEPH患者肺V/Q放射性分布的异质性,同时可反映CTEPH患者肺动脉压力的状态。 -
关键词:
- 通气-灌注显像 /
- 高血压,肺性;肺栓塞 /
- 体层摄影术,发射型计算机,单光子 /
- 体层摄影术,X线计算机 /
- 异质性
Abstract:Objective To quantitatively assess the distribution heterogeneity of lung ventilation/perfusion (V/Q) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to evaluate the correlation between distribution heterogeneity parameters and pulmonary artery pressure. Methods Twenty CTEPH patients, comprising twelve males and eight females (age, 48.75±14.07 years old), who were hospitalized in Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from February 2018 to December 2018, were confirmed to have CTEPH by means of right heart catheterization and pulmonary angiography. Thirteen controls, comprising seven males and six females (age, 54.46±8.56 years old), were also enrolled. Patients and controls underwent V/Q san and low-dose CT, and echocardiography was performed within 1 week to estimate pulmonary artery systolic pressure (PASP). The heterogeneity indexes of lung V/Q distribution include LogSDV, LogSDQ, and LogSDVQR (V and Q and V/Q are the radioactivity count of ventilation and perfusionand, and its ratio). SD is the standard deviation. The abovementioned indexes were obtained by image reconstruction and analysis. Then, on CT images, the lung CT threshold was used to automatically delineate the boundary of the left lung, the right lung, and the whole lung as the volume of interest, and it was replicated on the pulmonary perfusion images to acquire the standardized uptake value (SUV), including peak of SUV (SUVpeak), maximum of SUV (SUVmax), minimum of SUV (SUVmin), mean of SUV (SUVmean), and standard deviation of SUV (SUVSD). SUVSD represents the heterogeneity of perfusion distribution. The comparation of two groups by utilising t-test. Using Pearson correlation to analyse distribution heterogeneity parameters and PASP correlation. Results The distribution of lung V/Q in the healthy control patients presented a symmetrical unimodal distribution, whereas the distribution curve of lung V/Q in patients with CTEPH presented an asymmetric multi-peak distribution. Compared with the control group, LogSDV, LogSDVQR, total pulmonary perfusion SUVpeak, SUVmax, and SUVSD significantly increased in the CTEPH group. The differences were statistically significant (LogSDV: 0.56±0.16 vs. 0.31±0.11, t=4.91, P=0.000; LogSDVQR: 0.61±0.15 vs. 0.40±0.14, t=3.89, P=0.001; SUVpeak: 19.12±7.94 vs. 10.81±4.05, t=3.48, P=0.002; SUVmax: 20.19±8.30 vs. 11.44±4.33, t=3.49, P=0.001; SUVSD: 3.54±1.44 vs. 2.42±0.91, t=2.50, P=0.018). The differences of LogSDQ, SUVmean, and SUVmin were not statistically significant between the two groups. PASP of CTEPH patients was (72.80±0.15) mmHg. The LogSDVQR was moderately correlated with PASP in patients with CTEPH (R=0.544, P=0.013). Conclusion The lung V/Q scan can quantitatively assess the distribution heterogeneity and reflect the pulmonary artery pressure status of the patients with CTEPH. -
表 1 2组临床资料的比较
Table 1. Comparison of clinical data between two groups
组别 年龄(岁) 女性/男性(例) 身高(cm) 体重(kg) CTEPH组
(n=20)48.75±14.07 8/12 166.45±7.83 65.25±11.00 健康对照组
(n=13)54.46±8.56 6/7 168.46±9.68 71.69±18.01 检验值 t=−1.31 χ2=0.122 t=−0.66 t=−1.28 P值 0.200 >0.99 0.516 0.210 注:表中,CTEPH:慢性血栓栓塞性肺动脉高压;PASP:肺动脉收缩压 表 2 2组肺的SUV参数和V/Q 放射性计数的比较(
±s)$\bar {{x}}$ Table 2. Comparison of standardized uptake value parameters and ventilation/perfusion radioactive counts in two groups (
±s)$\bar {{x}}$ 组别 全肺 SUV参数 V/Q 放射性计数 峰值 平均值 最小值 最大值 标准差 LogSDV LogSDQ LogSDVQR CTEPH组(n=20) 19.12±7.94 2.78±1.15 0.002±0.003 20.19±8.30 3.54±1.44 0.56±0.16 0.44±0.09 0.61±0.15 健康对照组(n=13) 10.81±4.05 3.36±2.21 0.011±0.024 11.44±4.33 2.42±0.91 0.31±0.11 0.35±0.16 0.40±0.14 t值 3.48 −0.98 −1.37 3.49 2.50 4.91 1.72 3.89 P值 0.002 0.334 0.197 0.001 0.018 0.000 0.103 0.001 注:表中,SUV:标准化摄取值;V:通气;Q:灌注;CTEPH:慢性血栓栓塞性肺动脉高压;SD:标准差;VQR:V、Q的放射性计数的比值 表 3 CTEPH组和健康对照组的右肺、左肺SUV参数的比较(
±s)$\bar {{x}}$ Table 3. Comparison of standardized uptake value of right lung and left lung in chronic thromboembolic pulmonary hypertension group and healthy control group (
±s)$\bar {{x}}$ SUV参数 CTEPH组(n=20) t值 P 值 健康对照组(n=13) t值 P 值 右肺 左肺 右肺 左肺 峰值 14.12±6.42 18.27±7.88 −1.83 0.075 10.39±4.06 10.23±3.93 0.10 0.919 平均值 2.04±1.23 3.61±2.00 −2.98 0.005 3.42±2.37 3.29±2.05 0.15 0.885 最小值 0.003±0.004 0.005±0.008 −0.95 0.346 0.031±0.066 0.012±0.024 0.98 0.338 最大值 15.25±6.84 19.28±8.29 −1.68 0.102 10.91±4.30 10.78±4.15 0.08 0.937 标准差 2.55±1.44 3.84±1.66 −2.63 0.012 2.42±0.92 2.39±0.91 0.10 0.921 注:表中,CTEPH:慢性血栓栓塞性肺动脉高压;SUV:标准化摄取值 -
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