1、.555.中国临床医学影像杂志2 0 2 3年第34卷第8 期JChinClinMedImaging，2 0 2 3，V o l.34,No.8分层应变评价乳腺癌患者调强放射治疗后早期左心室收缩功能贾育昕，张旭，宋卫平，任卫东（中国医科大学附属盛京医院，辽宁沈阳110004)摘要目的：评估二维斑点追踪成像(2 D-STI)分层应变在乳腺癌患者接受调强放射治疗后早期左室收缩功能不全的临床意义。方法：纳入32 例接受胸部调强放射治疗的左侧乳腺癌患者，于放疗前、放疗结束时及放疗结束6 周后分别采集超声心动图图像。测量并比较乳腺癌患者放疗前、放疗结束时及放疗结束6 周后超声心动图常规参数及2 D-ST
2、I分层应变参数的差异，并分析其与放射剂量学参数（心脏受照射剂量平均值，MHD)、V5及V20（分别指受到5Gy、2 0 G y 以上剂量照射的心脏体积占全心脏总体积的百分比)的相关性。结果：在放疗前、放疗结束和放疗结束6 周后，左室射血分数及其它常规超声参数的差异无显著性(P0.05)。与放疗前比较,放疗结束时心内膜下心肌(GLS-endo）、中层心肌(GLS-mid)及心外膜下心肌(GLS-epi)的绝对值显著减低（均为P0.05),放疗结束6 周后GLS-endo、C LS-m i d 及GLS-epi的绝对值与放疗前、放疗结束时比较再次减低（均为P0.05），以CLS-endo减低最为明
3、显,GLS-mid及GLS-epi次之，三者间存在显著性差异（P0.05）。相关性分析显示ACLS-endo%与MHD和V20之间存在线性相关（r值为0.7 31和0.8 6 8,P0.05）。多元线性回归结果表明，V20与CLS-endo%之间存在着独立的相关性（为0.7 6 0,P0.05）。结论：左侧乳腺癌患者接受调强放射治疗后早期左心室三层心肌收缩功能均有不同程度受损，以心内膜下层心肌最为显著,其损伤程度与心脏受辐射剂量存在相关性，放射剂量学参数中V20与CLS-endo%呈独立相关。关键词乳腺肿瘤；心室功能，左；超声检查，多普勒，彩色中图分类号 R737.9;R322.11;R445
4、.1文献标识码 A文章编号 10 0 8-10 6 2(2 0 2 3)0 8-0 555-0 5D01:10.12117/jccmi.2023.08.006Evaluation of early left ventricular systolic function after intensity-modulated radiation therapy inbreast cancer patients by stratified strainJIA Yu-xin,ZHANG Xu,SONG Wei-ping,REN Wei-dong(Shengjing Hospital,China Medic
5、al University,Shenyang 110004,China)Abstract:Objective:To assess the clinical significance of two-dimensional speckle tracking imaging(2D-STI)stratifiedstrain in early left ventricular systolic insufficiency in breast cancer patients treated with intensity-modulated radiation therapy.Method:Thirty-t
6、wo patients with left-sided breast cancer treated with intensity-modulated radiation to the chest were includ-ed,and echocardiographic images were taken before,at the end of,and 6 weeks after radiotherapy.Echocardiographic param-eters and 2D-STI stratified strain parameters were measured and compare
7、d before,at the end of and 6 weeks after radiothera-py,and correlated with radiation dosimetric parameters(mean dose to the heart(MHD),the percentage of total heart volume ir-radiated with doses above 5 Gy and 20 Gy(V5,V20),respectively).Result:The differences in left ventricular ejection fractionan
8、d other conventional ultrasound parameters were not significant(P0.05)before,at the end of,and 6 weeks after radiothera-py.The absolute values of GLS-endo,GLS-mid and CLS-epi were significantly reduced at the end of radiotherapy comparedwith those before radiotherapy(P0.05 for all),and 6 weeks after
9、 radiotherapy,the absolute values of GLS-endo,GLS-mid andGLS-epi were again reduced compared with those before and at the end of radiotherapy(P0.05 for all),with the most signifi-cant reduction in GLS-endo,GLS-mid and GLS-epi.GLS-endo was the most significant,followed by GLS-mid and GLS-epi,and the
10、difference between the three was significant(P0.05).Correlation analysis showed that there was a linear correlationbetween AGLS-endo%and MHD and V20(r values of 0.731 and 0.868,P0.05).Multiple linear regression results showed that there was an independent correlation between V20 and G LS-e n-do%(of
11、0.760,P 0.0 5).C o n c l u s i o n:A l lthree layers of left ventricular myocardial systolic function were impaired to varying degrees in patients with left-sided breastcancer treated with intensity-modulated radiation therapy,with the most significant being the subendocardial layer.Key words:Breast
12、 Neoplasms;Ventricular Function,Left;Ultrasonography,Doppler,Color乳腺癌术后放射治疗是癌症辅助治疗的重要组成部分，乳腺癌术后放疗可显著降低肿瘤局部复发风险并提高患者生存率。然而,乳腺癌患者(尤其左乳癌患者）行胸部放疗期间正常的心脏组织将无收稿日期 2 0 2 3-0 6-0 4作者简介】贾育昕（19 9 6-），女，辽宁沈阳人，在读硕士研究生。E-mail：158 0 6 5312 9 q q.c o m通信作者】任卫东，中国医科大学附属盛京医院超声科，110 0 0 4。E-mail：r e n w d c m u 16 3.
13、c o m【基金项目】国家自然科学基金项目（编号：8 157 16 8 6）。.556.中国临床医学影像杂志2 0 2 3年第34卷第8 期JChinClinMedImaging，2 0 2 3，V o l.34,No.8法避免地受到照射，导致放射性心脏损伤（Radia-tion-induced heart disease,RIHD),由此产生的疾患可能会抵消部分放疗对肿瘤控制的益处，并严重降低患者生活质量。研究发现，与单独接受手术的乳腺癌患者相比，接受手术加放疗的患者心脏病死亡率增加了2 7%3，其中主要原因为冠状动脉疾病(CHD)。另有研究在接受长期放疗的患者中发现，心脏受辐射剂量与心脏并
14、发症的发病率间存在剂量-反应关系4。调强放射治疗(Intensity-modulated ra-diationtherapy,IMRT）是当今最先进的放射治疗技术之一,其与传统的三维适形放射治疗(3D-CRT)相比具有可提高靶区辐射剂量并使靶区内剂量均匀一致的显著优势。然而IMRT与传统3D-CRT相比在心脏保护上的优势并不确切，甚至有研究表明使用IMRT患者的V5（即受照射 5Gy的心脏体积百分比,此参数与心脏病风险增加相关)通常大于使用3D-CRT的患者5。正因如此,乳腺癌病人进行IMRT时，及早发现其心脏的改变并进行适当的干预非常必要。在临床上，心肌损伤标志物（如肌钙蛋白）、心电图和超声
15、心动图常被用来对心脏结构及功能进行评估，但是亚临床心功能的早期损伤很难被发现。基于二维斑点追踪成像技术(2 D-STI)的应变成像技术可敏感地定量评估心肌活动，被认为是监测心脏早期亚临床功能改变的具有高度特异性的方法0本文采用2 D-STI最新的分层应变技术对乳腺癌患者IMRT后左心室心内膜下心肌(CLS-endo）、中层心肌(GLS-mid)及心外膜下心肌(GLS-epi)进行了应变测量，能够精准、定量地评价左心室的收缩功能。1资资料与方法1.1研究对象选取2 0 2 0 年1一12 月32 例我院接受左侧乳腺癌手术（保乳手术或乳房切除术伴或不伴腋下淋巴结清扫术)后放射治疗的患者。纳人标准：
16、患者首次接受放射治疗，放射治疗方案累计左心室且未行同步化疗、靶向治疗或内分泌治疗；放疗前血常规、肝肾功能及心肌酶谱正常，左室射血分数(LVEF)54%。排除标准：患心脏疾病，如冠心病、心肌病、心律失常或心力衰竭等；存在高血压、高脂血症、糖尿病等心血管疾病的高危因素或正在应用相关药物。检查前所有患者均签署知情同意书。本研究已通过中国医科大学附属盛京医院科研伦理委员会伦理审查（伦理编号：2 0 2 0 PS490K）1.2实验仪器与方法1.2.1超声心动图数据采集及处理应用PhilipsEPIQCVx(美国Philips)彩色多普勒超声诊断装置，S5-1型相控阵头，在患者放疗前、放疗结束、放疗结束
17、6 周进行图像采集，频率为1.05.0MHz,模式为高穿透模式。病人左侧卧位,安静呼吸，同时记录心电图。两位5年以上临床经验的超声医生，分别在心尖四、三腔和两腔心切面留取34个心动周期的动态影像，测得室间隔舒张末期厚度（IVSd）、左心室后壁舒张末期厚度（LVPWd）、左心室舒张末期内径(LVDd)及左心室收缩末期内径(LVDs)。Si mp s o n 双平面法测得左心室舒张末期容积（LVEDV）、左心室收缩末期容积（LVESV）及LVEF。脉冲多普勒测定二尖瓣口舒张早、晚期峰值流速（E、A 峰）,计算出二者的比率（E/A）。将DICOM格式影像导人QlabTOMTECH工作站进行离线分析，
18、选择aCMQ模式，依次选取心尖四腔心、三腔心、两腔心切面，于心内膜上选取三点，软件自动生成心肌轮廓并得出追踪结果。记录GLS-endo、G LS-m i d及GLS-epi纵向应变。每组数据测量3次，计算均值，保存牛眼图。1.2.2放射治疗计划设计及剂量学数据获取C T 模拟定位：采用热塑体膜仰卧位固定方式，患者在平静呼吸下行CT扫描，范围从下颚至隔肌水平，包括全肺，扫描层厚0.5cm。图像经网络系统传输至Monaco(ELEKTA,Sweden)治疗计划系统。靶区及危及器官勾画：临床靶体积(CTV)及危及器官（OARs)由同一位放疗科副主任医师完成勾画由CTV外扩0.7 cm（皮肤方向外扩至
19、皮下0.3cm）生成计划靶体积(PTV）。O A Rs 包括患侧肺、健侧肺、心脏、健侧乳腺等。治疗计划设计：利用Monaco（5.11.0 3版本）治疗计划系统为每位患者制作放疗计划。靶区处方剂量50 Gy/25次，选择医科达Syn-ergy加速器(Elekta,Crawley,UK),6MV光子线。采用动态多页准直器调强技术(DMLC)，布野方式为以患侧乳腺两个对穿切线野为基准，顺时针及逆时针每隔10 15度增加1个人射野，共6 个射野。危及器官限制剂量为患侧肺V2025%,V560%，平均剂量 15Gy。心脏平均剂量 8 Gy,V205%,V1030%。健侧乳腺V55%。剂量学数据获取：利
20、用治疗计划系统生成靶区及危及器官剂量体积直方图(DVH)及剂量参数表格,得到患者心脏平均剂量，V5及V20等剂量学信息1.3统计学方法采用SPSS26.0软件对测量数据进行统计分析，计量资料表示为x土s，计数资料以百分率表示。重复测量方差分析比较放疗前、放疗结束及放疗6周后的参数，Spearman相关分析对两变量间的相关性进行分析，多变量相关的独立性采用多元线性回.557.中国临床医学影像杂志2 0 2 3年第34卷第8 期JChinClinMedImaging，2 0 2 3，V o l.34，No.8归分析。P0.05）,如表1所示。2.3左室分层应变参数比较与放疗前相比,GLS-endo
21、、G LS-m i d 及 GLS-epi的绝对值于放疗结束时减低，差异有统计学意义(P0.05)；与放疗前及放疗结束相比,GLS-endo、GLS-mid及GLS-epi绝对值于放疗结束6 周后再次减低，差异有统计学意义(P0.05),如表2,图1,2所示。分别计算并比较左室3层心肌纵向应变变化率(GLS%，定义为放疗前与放疗结束6 周后左室心肌纵向应变差值与放疗前纵向应变的百分比），其中GLS-endo%(0.120.55）大于GLS-mid%(0.080.49)及AGLS-epi%(0.060.46)，差异有统计学意义(P0.05)。表1放疗前后常规二维超声心动图指标比较（n=32，x
22、s）参数放疗前放疗结束放疗结束6 周后PLVDd(mm)45.771.8945.951.7846.151.770.87LVDs(mm)26.761.3126.791.1526.911.110.94IVSd(mm)8.120.498.080.478.090.500.97LVPWd(mm)8.150.448.270.538.250.510.82LVEDV(mL)97.572.8197.692.7098.202.650.82LVESV(mL)36.151.3236.221.0536.061.180.94.LVEF(%)62.931.4962.891.4863.251.610.81E/A1.190.0
23、71.140.061.160.070.11表2放疗前后二维整体分层应变值比较（n=32,x士s）GLS-endoGLS-midCLS-epi放疗前23.680.9222.580.9721.421.16放疗结束21.861.13120.841.08119.911.081放疗结束6 周后21.031.401.220.081.221;219.051.181.2F42.8043.2834.18P0.050.050.05注：与放疗前比较，1:P0.05；与放疗结束比较，2:P0.05。GLS-endo=22.6GLS-endo=20.3GLS-endo=19.3ab图1女，37 岁，左侧乳腺癌术后，2
24、D-STI显示放疗前后心内膜下层心肌纵向应变曲线。图1a：放疗前；图1b：放疗结束；图1c：放疗结束6周后。Figure 1.Female,37 years old,after left-sided breast cancer,2D-STI shows longitudinal strain curve of myocardium in the subendo-cardial layer before and after radiotherapy.Figure la:Before radiotherapy.Figure lb:At the end of radiotherapy.Figure
25、lc:6 weeks aftertheendofradiotherapyAANT-SEPBANT-SEPANT-SEP2020920特-14.525123527.616822-721214265282246.329.9-15.11956.06-3-182139208-12.5-18.0-11.4-158A-169454134-11.9-10:02440.7297219-16.043.344.024.130.525-0INF-LATINF-LATINF-LATR.Peak SystolicR.PeakSystolic20R.PeakSystolicLVAPlEpiPoakLSrdn28LVAPa
26、EptPeakL-Strain-20.7%LVAP4EpiPeakLStrain-18.9%bLVAP3EpiPeakLStrainasLVAP3E0PeokLSIain-20.9%ELVAP3EpiPeakLStrain#-19.5%LVAP2EpPeakL.Strain255SaLVAP2EpiPeakL-Strain-28.55L.V.AP2EpiPeakL-Strain-19.4CkohaEniPeakStrain20.7VlohalniPeakLStrain9图2 女，43岁，左侧乳腺癌术后，放疗前、放疗结束及放疗结束6 周后心外膜下层心肌纵向应变牛眼图。图2 a：放疗前；图2 b：
27、放疗结束；图2 c：放疗结束6 周后。Figure 2.Female,43 years old,post-operative left-sided breast cancer,bulls eye view of longitudinal strainin the subepicardial layer before,at the end of and 6 weeks after radiotherapy.Figure 2a:Before radiotherapy.Fig-ure 2b:At the end of radiotherapy.Figure 2c:6 weeks after the
28、end of radiotherapy.558.中国临床医学影像杂志2 0 2 3年第34卷第8 期JChinClinMedImaging，2 0 2 3，V o l.34,No.82.4相关性分析左侧乳腺癌患者放疗前后GLS-endo%与MHD、V 5及V20的相关性分析如表3所示，其中MHD及V20与GLS-endo%呈明显正相关（r分别为0.7 31及0.8 6 8,P均0.05）。图3为GLS-endo%与MHD及V20相关性散点图。2.5多元线性回归分析在纳人BMI及年龄后，多元线性回归分析显示V20与GLS-endo%独立相关（为0.7 6 0,P0.05）,如表4所示。表3G L
29、S-e n d o%与MHD、V 5、V 2 0 相关性分析MHDV5V20值0.7310.3370.868P值0.010.06 30 Gy与RIHD风险增加相关2 1,但其后的研究观察到,即使暴露于 5Gy的剂量下，心脏引起的死亡率也会增加，且V5是最重要的剂量体积预测参数2 。在此次研究中,我们评估了接受IMRT的左侧乳腺癌患者的心脏辐射剂量与亚临床左心室功能障碍之间的关系。在单变量分析中，我们观察到V20和MHD与CLS-endo%相关性显著，这与Donnellan等2 3 的研究结果一致，然而V5与AGLS-endo%并无显著相关性，可能提示短时间内低剂量辐射对左心室功能影响并不十分显
30、著。考虑到年龄及BMI对RIHD的发生存在影响，其中放疗年龄50岁被认为会增加RIHD的发生风险，而BMI不仅单独与RIHD的发生率相关，还同时影响心脏受辐射体积及剂量2 4,我们将年龄及BMI因素纳入多因素回归分析中。此时MHD的相关性不再显著，而V20的相关性显著，这表明即使在目前允许的心脏剂量下,IMRT仍会对心脏功能造成损害。此外由于部分化疗药物、靶向药物及内分泌药物的使用（如葱环类或曲妥珠单抗等)已被证实存在心脏毒性，本研究将同步化疗、靶向治疗及内分泌治疗的患者排除，使得我们能够准确地评估与辐射暴露与心脏功能的关系2 5。由于纳入条件严格，本研究样本量少，仅作为初步研究，还需扩大样本
31、数来证实这一结论。此外，由于本研究旨在评估放疗后早期心脏功能变化，随访时间较短，不能评估放疗对乳腺癌患者远期心功能影响。最后，心脏存在结构异质性，本研究未对心脏各节段及重要亚结构（如冠状动脉等）的辐射剂量及应变进行精确分析。2D-STI分层应变技术可以准确、灵敏地检测到乳腺癌患者IMRT后的早期心肌损害，其中GLS-Endo最为敏感，其受损程度与心脏辐射剂量相关，且心脏辐射剂量参数中V20与GLS-endo%呈独立相关。2 D-STI分层应变技术有助于乳腺癌患者IMRT后亚临床心肌损伤的早期识别及动态监测，并提示临床及时干预。参考文献1jShah C,Bauer-Nilsen K,Mcnult
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