Metabolic differences between primary and recurrent human brain tumors: a ¹H NMR spectroscopic investigation

Abstract

High-resolution proton magnetic resonance spectroscopy was performed on tissue specimens from 33 patients with astrocytic tumors (22 astrocytomas, 11 glioblastomas) and 13 patients with meningiomas. For all patients, samples of primary tumors and their first recurrences were examined. Increased anaplasia, with respect to malignant transformation, resulting in a higher malignancy grade, was present in 11 recurrences of 22 astrocytoma patients. Spectroscopic features of tumor types, as determined on samples of the primary occurrences, were in good agreement with previous studies. Compared with the respective primary astrocytomas, characteristic features of glioblastomas were significantly increased concentrations of alanine (Ala) (p ¼ 0.005), increased metabolite ratios of glycine (Gly)/total creatine (tCr) (p ¼ 0.0001) and glutamate (Glu)/glutamine (Gln) (p ¼ 0.004). Meningiomas showed increased Ala (p ¼ 0.02) and metabolite ratios [Gly, total choline (tCho), Ala] over tCr (p ¼ 0.001) relative to astrocytomas, and N-acetylaspartate and myo-inositol were absent. Metabolic changes of an evolving tumor were observed in recurrent astrocytomas: owing to their consecutive assessments, more indicators of malignant degeneration were detected in astrocytoma recurrences (e.g. Gly, p ¼ 0.029; tCho, p ¼ 0.034; Glu, p ¼ 0.015; tCho/tCr, p ¼ 0.001) in contrast to the comparison of primary astrocytomas with primary glioblastomas. The present investigation demonstrated a correlation of the tCho-signal with tumor progression. Significantly elevated concentrations of Ala (p ¼ 0.037) and Glu (p ¼ 0.003) and metabolite ratio tCho/tCr (p ¼ 0.005) were even found in recurrent low-grade astrocytomas with unchanged histopathological grading (n ¼ 11). This may be related to an early stage of malignant transformation, not yet detectable morphologically, and emphasizes the high sensitivity of 1 H NMR spectroscopy in elucidating characteristics of brain tumor metabolism.

Manual and semi-automatic quantification of in vivo ¹H-MRS data for the classification of human primary brain tumors

“…This partially explains the fact that we have a pronounced overlap between the spectra of different tumor groups. Even with these limitations, using both manual and semi-automatic analyses, we found a metabolic pattern in tumors and controls that was consistent with recent studies (3,4,6,7,(23)(24)(25)(26)(27). Tumors showed a reduction in the levels of NAA and creatine and an increase in the levels of choline, compared to normal tissue.…”

“…Several studies have been conducted to assess the metabolic patterns of brain tumors in an attempt to correlate them with the histology of the tumor, aggressiveness, and clinical outcome (4)(5)(6)(7)(8)(9)(10)(11)(12). Some studies have compared different kinds of spectral fitting methods, either in the time (13) or frequency domain (14).…”

Diffusion-Weighted MR Imaging: Diagnosing Atypical or Malignant Meningiomas and Detecting Tumor Dedifferentiation

“…31 Several methods, including positron-emission tomography, perfusion MR imaging, and MR spectroscopy, have been proposed to study tumor grading and malignant progression in glial neoplasms. [32][33][34][35][36][37] Spectroscopic methods in particular may be useful in eliciting the metabolic correlates of genetic progression of gliomas or the malignant potential of meningiomas 38,39 during follow-up neuro-oncologic imaging. The role of decreasing ADC as a biomarker of worsening histologic grade has been less widely studied in intracranial neoplasms [40][41][42] (M.S.…”

In vivo measurement of glycine with short echo-time 1H MRS in human brain at 7 T

“…It has been shown that glycine administration to schizophrenia patients improves the NMDA receptor function [2]. Furthermore, elevated levels of glycine have been observed in brain tumors and glycine possibly represents a marker for tumor malignancy [3,4]. Thus, it is of great interest to explore non-invasive methods to measure brain glycine.…”