术前氢质子磁共振波谱主要代谢物水平与术中胶质母细胞瘤荧光强度的比较

Major Metabolite Levels of Preoperative Proton Magnetic Resonance Sectroscopy and Intraoperative Fluorescence Intensity in Glioblastoma

目的对比分析术前氢质子磁共振波谱成像(~1H-MRS)主要代谢物水平和术中荧光素钠(FLs)标记胶质母细胞瘤(GBM)的荧光强度,探讨不同荧光强度GBM组织代谢水平的变化,为GBM荧光手术治疗提供客观依据。方法对2014年4月1日至2015年12月31日磁共振扫描成像平扫+增强序列新诊断的GBM,完成~1H-MRS检查和FLs标记下手术治疗,术后病理确诊为GBM的病例行肿瘤边界Ki67免疫组织化学检测。对~1H-MRS主要代谢物水平与肿瘤荧光强度进行对比分析。结果 33例纳入研究,术前~1H-MRS诊断结果:25例提示为高级别胶质瘤,N-乙酰门冬氨酸(NAA)峰明显降低,胆碱(Cho)峰明显增高;Cho/NAA、NAA/肌酸(Cr)和Cho/Cr在不同肿瘤区域差异有统计学意义(P=0.02,P=0.01,P=0.00)。FLs标记手术结果:术中清晰看见组织荧光;29例全切、4例次全切;术后无急性脑膨出,癫痫发生2例。术后常规病理结果:28例确诊为GBM(22例与~1H-MRS诊断一致)。GBM肿瘤荧光显影结果:肿瘤实质区域荧光强度高于肿瘤边界和瘤周水肿(P=0.01)。~1H-MRS代谢物分析结果:不同荧光强度的GBM实质,NAA和Cho峰高度不同(P=0.01,P=0.02),Cho/NAA不同(P=0.01);不同荧光强度的GBM边界,NAA峰高度差异无统计学意义,Cho峰高度不同,Cho/NAA不同(P=0.02,P=0.00);不同荧光强度GBM瘤周水肿中,NAA和Cho峰高度、Cho/NAA差异无统计学意义(P=0.23,P=0.09,P=0.14)。GBM肿瘤边界免疫组织化学结果:不同荧光显影边界,Ki67表达程度不同(P=0.03)。结论 GBM肿瘤实质荧光强度高于其他区域,不同荧光强度的GBM,代谢水平不同;FLs标记下实施GBM手术治疗,需重视术前~1H-MRS提供的代谢信息,并就两者的相关性做进一步探讨。

Objective To compare the intraoperative major metabolite level of preoperative proton mag-netic resonance spectroscopy（^1H-MRS） and fluorescence intensity marked with fluorescein sodium（FLs） in glioblastoma（GBM） and thus provide an objective basis for fluorescence surgical treatment of GBM.Methods All newly diagnosed patients by plain and enhanced magnetic resonance imaging from the April 1,2014 to December 31,2015 were enrolled in this study.All of them received ^1H-MRS and marked with FLs.The expression of Ki67 in tumor boundary were confirmed by postoperative pathology and determined by immunostaining assay.The relationship between ^1H-MRS metabolite levels and tumor fluorescence intensity was analyzed.Results Totally 33 patients were included in the study.Preoperative ^1H-MRS revealed high-grade gliomas in 25 cases.The N-acetylaspartate（NAA） decreased significantly and choline（Cho） increased significantly in high-grade gliomas.The ratios of Cho/NAA,NAA/creatine（Cr）,and Cho/Cr significantly differed in different tumor regions（P=0.02,P=0.01,and P=0.00,respectively）.Surgical results were marked with FLs intraoperatively.Tissue fluorescence were clearly seen.There were 29 patients undergoing total resection and 4 cases undergoing subtotal resection.No acute encephalocele occured after operation,while 2 patients suffered from epilepsy.Postoperative pathology results included：28 cases were diagnosed as GBM（22 cases consistent with ^1H-MRS diagnosis）.The results of GBM fluorescence imaging included：the level of fluorescence intensity in tumor parenchyma was significantly higher than that in tumor boundary and peritumoral edema（P=0.01）.The result of ^1H-MRS metabolite analysis included：The kurtosis of NAA and of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor parenchyma（P=0.01,P=0.02,and P=0.01）.While there was no difference in the kurtosis of NAA,the kurtosis of Cho and the ratio of Cho/NAA were significantly different according the fluorescence intensity in tumor boundary（P=0.02,P=0.00）.In peritumoral edema,there was no significant different in kurtosis of NAA and of Cho and in the ratio of Cho/NAA（P=0.23,P=0.09,P=0.14）.Immunohistochemistry in GBM tumor boundary showed different Ki67 expressions according to different fluorescence imaging（P=0.03）.Conclusions The fluorescence intensity in GBM parenchyma is higher than that in other tumor regions,and there are different metabolic levels in different fluorescence intensity.The metabolic information marked by FLs and provided by ^1H-MRS before operationis are important,and the correlation between them should be further investigated.