Herminghaus Sebastian, Pilatus Ulrich, Möller-Hartmann Walter, Raab Peter, Lanfermann Heinrich, Schlote Wolfgang, Zanella Friedhelm E
Institute of Neuroradiology, Johann W. Goethe University, Schleusenweg 2-16, 60528 Frankfurt/Main, Germany.
NMR Biomed. 2002 Oct;15(6):385-92. doi: 10.1002/nbm.793.
Proton MR spectroscopy ((1)H 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 (1)H MRS allow assessment of the proliferative activity of neuroepithelial brain tumors presurgically. Single-voxel (1)H 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 (1)H MRS could provide a novel and noninvasive assessment of the proliferative activity of neuroepithelial brain tumors, pointing at (1)H MRS as a useful method for differentiating proliferating from non-proliferating tissues. Hence, potential indications for the clinical application of (1)H MRS are grading tumors presurgically, early detection of anaplastic transformation, and monitoring treatment.
质子磁共振波谱（（1）H MRS）可见的总含胆碱化合物（tCho化合物）是膜磷脂的衍生物，部分可能作为细胞增殖的长期第二信使系统。实验证据表明，在细胞增殖过程中tCho化合物的浓度会增加。本研究旨在检验以下假设：使用（1）H MRS在体内测量tCho浓度可在术前评估神经上皮性脑肿瘤的增殖活性。对101例神经上皮性脑肿瘤患者和19名健康志愿者在手术前进行了单体素（1）H MRS（PRESS序列，重复时间1500毫秒，回波时间135毫秒）检查。术后根据世界卫生组织分类标准确认组织学诊断。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进行了校正，并将tCho浓度计算为机构任意单位。使用Spearman相关分析将其与细胞增殖的平均免疫组化标志物Ki-67（MIB.1）标记指数进行匹配。与低级别肿瘤（即世界卫生组织I/II级）和正常脑白质相比，高级别肿瘤（即世界卫生组织III/IV级）显示出显著（p < 0.05）升高的标记指数，同时tCho浓度也逐渐升高。相比之下，低级别肿瘤中的tCho浓度与生理值无显著差异。在tCho浓度和标记指数之间发现了高度显著的正相关（p < 0.0001，r（2） = 0.81）。得出的结论是，使用体内（1）H MRS测定tCho浓度可为神经上皮性脑肿瘤的增殖活性提供一种新的无创评估方法，表明（1）H MRS是区分增殖组织和非增殖组织的有用方法。因此，（1）H MRS临床应用的潜在指征包括术前肿瘤分级、间变转化的早期检测以及治疗监测。
