1H‐ and 31P‐MR spectroscopy of primary and recurrent human brain tumors in vitro: malignancy‐characteristic profiles of water soluble and lipophilic spectral components

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Abstract

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.

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