Lehnhardt F G, Röhn G, Ernestus R I, Grüne M, Hoehn M
Max-Planck-Institute for Neurological Research, Cologne, Germany.
NMR Biomed. 2001 Aug;14(5):307-17. doi: 10.1002/nbm.708.
In vitro NMR spectroscopy was performed on specimen of human brain tumors. From all patients, tissue samples of primary tumors and their first recurrences were examined. (31)P- and (1)H-spectra were recorded from samples of meningioma, astrocytoma and glioblastoma. A double extraction procedure of the tissue samples permitted acquisition of information from the membrane fraction and from the cytosolic fraction. (31)P-spectra were used to analyze the lipophilic fraction (phospholipids of the membrane) of the tissue extracts, while the (1)H-spectra reflected information on the metabolic alterations of the hydrophilic, cytosolic fraction of the tissue. The tumor types showed distinctive spectral patterns in both the (31)P- and the (1)H-spectra. Based on the total detectable (31)P signal, the level of phosphatidylcholine was about 34% lower in primary astrocytomas than in primary glioblastomas (p = 0.0003), whereas the level of sphingomyelin was about 45% lower in primary glioblastomas than in primary astrocytomas (p = 0.0061). A similar tendency of these phospholipids was observed when comparing primary and recurrent astrocytoma samples from the same individuals [+15% (p = 0.0103) and -23% (p = 0.0314) change, respectively]. (1)H-spectra of gliomas were characterized by an increase of the ratios of alanine, glycine and choline over creatine as a function of the degree of malignancy. In agreement with findings in the (31)P-spectra, the (1)H-spectra of recurrent astrocytomas showed metabolic profiles of increased malignancy in comparison to their primary occurrence. Since gliomas tend to increase in malignancy upon recurrence, this may reflect evolving tumor metabolism. (1)H-spectra of meningiomas showed the highest ratio of alanine over creatine accompanied by a near absence of myo-inositol. Phospholipid profiles of meningiomas showed higher fractional contents of phosphatidylcholine along with lower phosphatidylserine compared to astrocytomas, while higher phosphatidylethanolamine and sphingomyelin fractional contents distinguished meningiomas from glioblastomas. The extraction method being used in this study combined with high-resolution (1)H- and (31)P-MRS provides a wide range of biochemical information, which enables differentiation not only between tumor types but also between primary and recurrent gliomas, reflecting an evolving tumor metabolism.
对人脑肿瘤标本进行了体外核磁共振波谱分析。从所有患者中,检查了原发性肿瘤及其首次复发的组织样本。记录了脑膜瘤、星形细胞瘤和胶质母细胞瘤样本的(31)P谱和(1)H谱。组织样本的双重提取程序允许从膜部分和胞质部分获取信息。(31)P谱用于分析组织提取物的亲脂部分(膜的磷脂),而(1)H谱反映了组织亲水性胞质部分代谢改变的信息。肿瘤类型在(31)P谱和(1)H谱中均显示出独特的光谱模式。基于可检测到的总(31)P信号,原发性星形细胞瘤中磷脂酰胆碱的水平比原发性胶质母细胞瘤低约34%(p = 0.0003),而原发性胶质母细胞瘤中鞘磷脂的水平比原发性星形细胞瘤低约45%(p = 0.0061)。在比较来自同一患者的原发性和复发性星形细胞瘤样本时,观察到这些磷脂有类似的变化趋势[分别变化 +15%(p = 0.0103)和 -23%(p = 0.0314)]。胶质瘤的(1)H谱特征是随着恶性程度的增加,丙氨酸、甘氨酸和胆碱与肌酸的比率升高。与(31)P谱的结果一致,复发性星形细胞瘤的(1)H谱显示与其原发性肿瘤相比,恶性程度增加的代谢谱。由于胶质瘤复发时恶性程度往往会增加,这可能反映了肿瘤代谢的演变。脑膜瘤的(1)H谱显示丙氨酸与肌酸的比率最高,且几乎没有肌醇。与星形细胞瘤相比,脑膜瘤的磷脂谱显示磷脂酰胆碱的分数含量较高,同时磷脂丝氨酸含量较低,而磷脂酰乙醇胺和鞘磷脂的分数含量较高则将脑膜瘤与胶质母细胞瘤区分开来。本研究中使用的提取方法与高分辨率(1)H和(31)P磁共振波谱相结合,提供了广泛的生化信息,不仅能够区分肿瘤类型,还能区分原发性和复发性胶质瘤,反映了肿瘤代谢的演变。