Metabolomics denotes the comprehensive and simultaneous systematic profiling of metabolite levels through the study of biofluids and tissues. As such metabolomics is now considered an integral part of systems biology . Besides Mass Spectrometry, NMR Spectroscopy is the main analytical technique for simultaneous assessment of metabolites in biological fluids and tissues.
Besides the potential of biofluid NMR, our main interest currently aims at investigations of biopsies and cells. High resolution "Magic angle spinning" (HR-MAS) NMR makes NMR spectroscopy applicable also to semi-solid materials including biological tissues or cell cultures, which under static conditions yield only poorly resolved NMR spectra with very broad lines providing only little information. Fast spinning around an axis inclined at an angle of 54.7° (“magic angle”) with respect to the axis of the external magnetic field (B0) can average orientation dependent effects close to or equal to zero, thereby significantly reducing the linewidth and increasing both the spectral resolution and sensitivity. The non-destructive investigation of tissue probes has been one of the main and most promising applications for HR-MAS in recent years. It has been shown that HR-MAS allows to metabolically characterize tissue types like brain, prostate, breast, liver, or kidney. For recent excellent reviews on HR-MAS in tissue probes see (3-5). Advanced NMR methods in combination with recently developed “metabolomical” analysis tools, provide means for a detailed investigation of numerous metabolites in tissue samples, simultaneously. These methods obtain comprehensive metabolic fingerprints that have great potential to determine biomarkers, which are potentially indicative for pathological dysfunction. In an additional step, metabolites that gave rise to specific biomarkers may be identified also with advanced NMR methods for pathophysiological interpretation. The duration of NMR measurements varies between 5min and several hours, depending on the question. Sophisticated 2D-measurements used to identify new or unknown metabolites or advanced NMR methods used to investigate diffusion, structural or kinetic properties may last several hours, while routine 1D-measurements for metabolomical analysis can be performed within minutes.The biopsies remain intact during the investigation. The HR-MAS spectra can therefore be correlated with the histological characteristics of the same biopsy sample. In addition, the complementary use of NMR and mass spectrometry (MS) has been emphasized by several authors. Of special interest is the correlation of HR-MAS spectra with in vivo MR-spectra in living systems. However, the clinical usefulness of metabolomical HR-MAS has not yet been fully addressed, and most studies have been exploratory (4, 5).
Although “these (NMR) approaches are currently being implemented in hospital environments and in regional phenotyping centres worldwide” (6), the possibility to perform HR-MAS NMR of tissue probes is still quite rare at hospitals and universities. The combination of HR-MAS and MS may be very valuable. A review concluded (7) that "an exciting recent development is the combination of NMR and MS data, which allows improved identification of unknown analytes and creates an opportunity to expand the scope of metabolomics research." And further on: " ... because of the complementary analytical features of NMR and MS, opportunities for leveraging both methods are being considered which will create more comprehensive metabolic profiling."
1. Cottingham K. Systems biology: a boon for analytical chemists? Anal Chem 2005; 77:197A-200A.
2. Nicholson JK, Lindon JC. Systems biology: Metabonomics. Nature 2008; 455:1054-1056.
3. Lindon JC, Beckonert OP, Holmes E, Nicholson JK. High-resolution magic angle spinning NMR spectroscopy: Application to biomedical studies. Progress in Nuclear Magnetic Resonance Spectroscopy 2009; 55:79-100.
4. Sitter B, Bathen TF, Tessem MB, Gribbestad IS. High-resolution magic angle spinning (HR MAS) MR spectroscopy in metabolic characterization of human cancer. Progress in Nuclear Magnetic Resonance Spectroscopy 2009; 54:239-254.
5. Beckonert O, Coen M, Keun HC, et al. High-resolution magic-angle-spinning NMR spectroscopy for metabolic profiling of intact tissues. Nat Protoc 2010; 5:1019-1032.
6. Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JC. Metabolic phenotyping in clinical and surgical environments. Nature 2012; 491:384-392.
7. Pan Z, Raftery D. Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics. Anal Bioanal Chem 2007; 387:525-527.