【作者】 鞠蓉晖；

【导师】 徐克；

【作者基本信息】 中国医科大学 ， 影像医学与核医学， 2009， 博士

【摘要】 目的本课题研究目的是对脑转移瘤患者在放射治疗前后不同时间进行MRS及DTI扫描,测量放疗前后肿瘤内各代谢物值及扩散成像各指标值,分析各值及其与对侧正常脑组织比值的分布情况、随时间的变化趋势,并分析各数值与肿瘤体积变化的相关性,筛选出可以用做预测治疗效果的早期评价指标,评价MRS和DTI对脑转移瘤放射治疗疗效判断的应用价值,为临床医生选择恰当的治疗方法提供帮助。材料与方法收集2007年9月至2009年3月在中国医科大学附属第一临床学院放疗科接受头部颅脑X-刀联合全脑照射治疗的肺癌脑转移患者33例,均有病理学证实,其中男20例,女13例,年龄46～78岁,平均62.7岁。因中途患者死亡及不配合的患者有12例,纳入本组患者共21例,其中鳞癌6例,腺癌10例,小细胞癌5例,单发11例,多发10例,共计42个病灶。各病例分别于治疗前3天内、治疗后第1天、1周、1个月、3个月、6个月进行常规MR检查及MRS、DTI及3D SPGR序列检查。另外于治疗前、治疗后第3个月、6个月同时行MR增强扫描。头刀治疗使用西门子公司PRIMUS直线加速器,Brain LAB公司立体定向治疗系统及SCAN4.0版本三维计划系统进行靶点定位和剂量计算,所有病灶均采用分次治疗,4～6次完成,间隔1天。颅脑X-刀治疗前或治疗后间隔1周时问给予全脑照射(WBRT),3～4周完成。肿瘤治疗后的疗效评价:放射治疗结束6个月行增强MRI检查,与治疗前的增强MRI检查做对比,确定肿瘤退缩情况。采用WHO制定的实体肿瘤评价标准(1)完全缓解(CR):病灶完全消失;(2)部分缓解(PR):病灶缩小50%以上或出现失增强效应及瘤体囊性变;(3)病灶稳定(NC):病灶缩小不及50%,或增大未及25%;(4)病变进展(PD):病灶增大25%以上或靶区周边复发。将1、2、3级病灶纳入治疗有效组,4级病灶纳入治疗无效组。采用SPSS13.0软件进行统计分析,脑肿瘤在MRS及DTI中各数值采用均数±标准差表示。通过重复测量的方差分析来检验不同时间点数值有无统计学差异,组间两两比较采用L-S-D检验,并分析各数值随时间变化的趋势。采用多元逐步线性回归分析方法分析各值与肿瘤体积变化的相关性。结果一、磁共振波谱成像对脑转移瘤放射治疗疗效评价的应用研究1、不同时间点MRS各指标测量值与病理类型间均无交互作用。2、有效组与无效组间有统计学差异的指标有Cho/Cr、Cho/nCho、Cr/nCr(P<0.05)。3、不同组间Cho/Cr比值随时间变化的趋势不同。Cho/Cr比值在放疗后一周到一个月期问曲线走行相反,且放疗后一个月时无效组变化程度较大,为41.73%,有效组变化程度为-19.84%。4、有效组与无效组Cho/nCho比值在放疗后一周时差异最大,无效组在放疗后一周Cho/nCho比值出现明显增高,且与有效组间差异最大。而有效组Cho/nCho比值持续呈下降趋势。无效组变化程度为96.92%,有效组变化程度为-7.14%。5、有效组与无效组Cr/nCr比值在放疗后一周时差异最大,无效组在放疗后一周Cr/nCr比值出现明显增高,且与有效组间差异最大。而有效组Cr/nCr比值相对较平稳。无效组变化程度为158.91%,有效组变化程度为5.53%。6、指标Cho、Cho/Cr、Cho/nCho与体积之间存在显著的正相关关系,即随着体积的增大而逐渐增加,以Cho与体积变化的相关性最显著。二、磁共振扩散张量成像对脑转移瘤放射治疗疗效评价的应用研究1、不同时间点各指标测量值与病理类型间有无交互作用。2、有效组与无效组间有统计学差异的指标有FA,rFA值。3、有效组和无效组间FA值差别有统计学意义(P=0.015),不同时间点间FA值差别有统计学意义(P=0.000),不同组别间FA值随时间变化的趋势不同。有效组与无效组FA值的变化趋势均呈上升趋势,其中有效组放疗后一周至一个月时FA值变化程度较大,为24.66%,而无效组FA值均较有效组减低,且随时间延长整体略有升高,但变化不明显。4、有效组和无效组间差别有统计学意义(P=0.023),不同时间点间rFA峰值差别有统计学意义(P=0.017),rFA峰的时间与组别间存在交互作用(P=0.002),即不同组别间rFA峰值随时间变化的趋势不同。有效组rFA值的变化趋势均呈上升趋势,其中有效组放疗后一周开始上升,一周至一个月时FA值变化程度较大为17.38%,而无效组rFA值均较有效组减低,且随时间延长整体升高不明显。5、FA与体积之间存在显著的负相关关系(r=-0.847,P=0.033),即FA值随着体积的增大而逐渐减小。结论1、肺癌脑转移瘤放疗前后MRS各代谢物值及DTI各指标的变化与病理类型无关。2、放疗后肿瘤的Cho、Cho/Cr、Cho/nCho值随着体积的增大而逐渐增大,以Cho与体积变化的相关性最明显。FA值随着体积的增大而逐渐减小。3、放疗后一个月时Cho/Cr比值和FA值的变化方向及变化程度要早于肿瘤体积的变化,可作为早期预测治疗效果指标,Cho/Cr比值增加41.73%,表明肿瘤对放疗不敏感,治疗无效,Cho/Cr比值降低19.84%,表明放射治疗有效。而FA值增加24.66%,表明放射治疗有效,FA值变化不明显,表明肿瘤对放疗不敏感,治疗无效。更多还原

【Abstract】 The purpose of this research was to measure the metabolite value and the index value in patients with brain metastases before and after radiotherapy by using MRS and DTI,analyze the value and the ratio of the tumor tissue to the contralateral normal brain tissue and the relationship between the values,screen the value that could be used for early prediction of efficacy.Methods and materialsThirty-three patients(20 male,13 female,age range from 46 to 78 years old, average 62.7 years old) with brain metastasis from pathologic confirmed lung cancer were treated by LINAC radiosurgery in combination with WBRT.21 cases were included in this group,but 12 cases were excluded because they died or didn’t cooperate.There were 6 cases of squamous cell carcinoma,10 cases of adenocarcinoma, and 5 cases of small cell carcinoma.11 cases were with single lesion,10 cases were with multiple lesions,and with 42 lesions in all.All cases were underwent examination of MRS and DTI before treatment,1 day after treatment,1 week after treatment,1 month after treatment,3 months after treatment and 6 months after treatment. Contrast-enhanced MRI was undertaken before treatment,3 months after treatment and 6 months after treatment to get the precise change of metastatic volume.LINAC radiosurgery was undertaken by 6 MV X-ray,6-8Gy/F,1 day for interval,4-6 fractions in all,and in combination with WBRT.The therapeutic efficacy was evaluated 6 months after LINAC radiosurgery.Therapeutic efficacy was classified to complete response(CR),partial response(PR),stable disease(SD) and progressive disease(PD), and the metastases of PR,CR and SD belonged to efficacy significant group,as well as those of PD belonged to efficacy insignificant group.SPSS13.0 software was used for statistical analysis.The comparison of the examined values of MRS and DTI between the two groups was undertaken.The multiple stepwise linear regression was used to analysis the relevance between the tumor volume and the values.Results1,Application of MRS in evaluating the efficacy of patients with brain metastasis treated by radiotherapyThere was no interaction between the pathologic type and MRS values at different time points.Cho/Cr,Cho/nCho,Cr/nCr had significant difference between the effective group and the ineffective group(P<0.05).Cho/Cr ratio was over time in different trends between the two groups.The curves were opposite at 1 week to 1 month.The changing degree was 41.73%in the ineffective group and -19.84%in the effective group.The curves of Cho/nCho,Cr/nCr were different at 1 week.The changing degree was 96.92%,158.91%in the ineffective group and -7.14%,5.53%in the effective group respectively.There was a significant positive correlation between Cho,Cho/Cr,Cho/nCho and metastatic volume.That was to say the ratios would increase with the volume increase. Cho had the most significant relevance.2,Application of DTI in evaluating the efficacy of patients with brain metastasis treated by radiotherapyThere was no interaction between the pathologic type and DTI values at different time points.FA and rFA had significant difference between the effective group and the ineffective group.FA and rFA was over time in different trends between the two groups.The curves were opposite at 1 week to 1 month.The changing degree was 24.66%in the effective group,but did not change significantly in the ineffective group.There was a significant negative correlation between FA and the metastatic volume(r=-0.847,P=0.033).That was to say FA would decrease with the volume increase. Conclusion1,There was no interaction between the pathologic type and MRS and DTI values at different time points in brain metastasis from lung cancer.2,The value of Cho,Cho/Cr,and Cho/nCho would increase with the volume increase,but of FA would decrease with the volume increase.3,The change of the direction and degree of Cho/Cr and of FA 1 month after treatment was earlier than the change of volume,and could be used as the early indicators of the efficacy of radiotherapy.更多还原