Increased choline levels coincide with enhanced proliferative activity of human neuroepithelial brain tumors
Increased choline levels coincide with enhanced proliferative activity of human neuroepithelial brain tumors
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DOI：
10.1002/nbm.793
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发表时间：
2002-10-01
影响因子：
2.9
通讯作者：
Zanella, FE
中科院分区：
文献类型：
--
作者：
Herminghaus, S;Pilatus, U;Zanella, FE
质子磁共振波谱（H-1 MRS）-可见总胆碱化合物（tCho-化合物）是膜磷脂的衍生物，在某种程度上可能充当细胞增殖的长期第二信使系统。实验证据表明细胞增殖过程中 tCho 化合物的浓度不断增加。进行本研究的目的是检验以下假设：使用 H-1 MRS 体内测量 tCho 浓度可以在术前评估神经上皮脑肿瘤的增殖活性。对 101 名神经上皮性脑肿瘤患者和 19 名健康志愿者在术前进行了单体素 H-1 MRS（PRESS、TR 1500 ms、TE 135 ms）。根据世界卫生组织分类，术后确认组织学诊断。测量的 tCho 化合物信号强度针对线圈负载、采集次数和体素大小以及作为机构任意单位计算的 tCho 浓度进行校正。根据 Spearman 的相关分析，将它们与细胞增殖的平均免疫组织化学标记 Ki-67 (MIB.1) 标记指数相匹配。与低级别肿瘤（即 WHO I/II 级）和正常脑白质相比，高级别肿瘤（即 WHO III/IV 级）显示标记指数显着升高（p < 0.05），同时 tCho 浓度也逐渐升高。相反，低级别肿瘤中的 tCho 浓度与生理值没有显着差异。 tCho 浓度和标记指数之间存在高度显着的正相关性（p < 0.0001，r(2) = 0.81）。结论是，使用体内 H-1 MRS 测定 tCho 浓度可以为神经上皮脑肿瘤的增殖活性提供一种新颖且无创的评估，表明 H-1 MRS 作为区分增殖组织和非增殖组织的有用方法。因此，H-1 MRS 临床应用的潜在适应症是术前对肿瘤进行分级、早期检测间变性转化以及监测治疗。版权所有 (C) 2002 John Wiley Sons, Ltd.
Proton MR spectroscopy (H-1 MRS)-visible total choline-containing compounds (tCho-compounds) are derivatives of membrane phospholipids and, in part, may act as a long-term second-messenger system for cellular proliferation. Experimental evidence suggests increasing concentrations of tCho-compounds during cellular proliferation. The present study was conducted in order to test the hypothesis that in vivo measurements of tCho-concentrations using H-1 MRS allow assessment of the proliferative activity of neuroepithelial brain tumors presurgically. Single-voxel H-1 MRS (PRESS, TR 1500 ms, TE 135 ms) was performed in 101 patients with neuroepithelial brain tumors prior to surgery and 19 healthy volunteers. Histological diagnoses were confirmed postsurgically according to the WHO classification. Measured tCho-compound signal intensities were corrected for coil loading, numbers of acquisitions and voxel size, and tCho concentrations calculated as institutional arbitrary units. They were matched with the mean immunohistochemical marker of cell proliferation, the Ki-67 (MIB.1) labeling index, using correlation analysis according to Spearman. Compared with low-grade tumors (i.e. WHO grade I/II) and normal white brain matter, high-grade tumors (i.e. WHO grade III/IV) revealed significantly (p < 0.05) elevated labeling indices paralleled by increasingly elevated tCho-concentrations. In contrast tCho-concentrations in low-grade tumor did not differ significantly from physiological values. A highly significant positive correlation (p < 0.0001, r(2) = 0.81) was found between the tCho-concentration and the labeling index. It was concluded that the determination of tCho-concentrations using in vivo H-1 MRS could provide a novel and noninvasive assessment of the proliferative activity of neuroepithelial brain tumors, pointing at H-1 MRS as a useful method for differentiating proliferating from non-proliferating tissues. Hence, potential indications for the clinical application of H-1 MRS are grading tumors presurgically, early detection of anaplastic transformation, and monitoring treatment. Copyright (C) 2002 John Wiley Sons, Ltd.