Abstract
BackgroundHigh-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are "NMR visible" will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies.Results1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour (astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas). Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis.ConclusionsA number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours.
Highlights
High-resolution magic angle spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification
The main potential of Magnetic Resonance Spectroscopy (MRS) in radiological diagnosis lies in aiding binary decisions between tumour types that can be challenging for a radiological diagnosis using conventional MRI [3]; for example, between lymphoma and glioblastoma (GBM) or metastasis and GBM
Metabolite concentrations and artefacts Assignment of NMR visible small molecule metabolites Analysis of a subset of 15 samples of five different histopathological types of brain tumour allowed for the assignment of 29 small molecule metabolites
Summary
High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. In-vivo Magnetic Resonance Spectroscopy (MRS, reviewed in [1]) allows for the assignment and quantification of small molecule metabolites in intracranial tumours. Due to higher field strength MRI systems becoming more readily available (e.g. 3 T for routine clinical use and up to 9.4 T for clinical research), in-vivo MRS will be able to detect increasing numbers of metabolites. The quantification of these metabolites may provide useful biomarkers for diagnosis and prognosis of brain tumours.
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