Matthias Niemitz | Kuopio University (original) (raw)
Papers by Matthias Niemitz
The Journal of Organic Chemistry, 2016
The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bi... more The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling NMR data, X-ray crystallography, and the recent confirmation via full synthesis exemplify that the achievement of "structural correctness" depends on the completeness of the experimental evidence. Archived FIDs and newly acquired aquatolide spectra demonstrate that archiving and rigorous interpretation of 1D (1)H NMR data may enhance the reproducibility of (bio)chemical research and curb the growing trend of structural misassignments. Despite being the most accessible NMR experiment, 1D (1)H spectra encode a wealth of information about bonds and molecular geometry that may be fully mined by (1)H iterative full spin analysis (HiFSA). Fully characterized 1D (1)H spectra are unideterminant for a given structure. The corresponding FIDs may be readily submitted with publications and collected in databases. Proton NMR spectra are indispensable for structural characterization even in conjunction with 2D data. Quantum interaction and linkage tables (QuILTs) are introduced for a more intuitive visualization of 1D J-coupling relationships, NOESY correlations, and heteronuclear experiments. Overall, this study represents a significant contribution to best practices in NMR-based structural analysis and dereplication.
Chemie in unserer Zeit, 1990
CITATIONS 0 READS 353 5 authors, including:
Encyclopedia of Magnetic Resonance, 2007
The Journal of Organic Chemistry, 2003
6-Deoxy-l-mannose diphenyldithioacetal (1) unexpectedly gave the rearranged products phenyl 3,4-d... more 6-Deoxy-l-mannose diphenyldithioacetal (1) unexpectedly gave the rearranged products phenyl 3,4-di-O-acetyl-2-S-phenyl-1,2-dithio-6-deoxy-beta-l-glucopyranoside (9) and 3,4-di-O-acetyl-2,5-anhydro-6-deoxy-l-glucose diphenyldithioacetal (10) upon treatment with acetyl chloride, while 6-deoxy-l-mannose ethylenedithioacetal (3) yielded (4aR,6S,7S,8R,8aS)-7,8-diacetyloxy-6-methylhexahydro-4aH-[1,4]dithiino[2,3b]pyran (11), whose structure was further confirmed by X-ray diffraction, and 3,4-di-O-acetyl-2,5-anhydro-l-rhamnose ethylenedithioacetal (12). The geometry of the four rearranged products as well as that of 1-thio-6-deoxy-l-mannopyranosides 5 and 7 and their acetyl derivatives 6 and 8 was studied by density functional theory (B3LYP/6-31G) molecular models, in combination with a Karplus-type analysis of the NMR vicinal coupling constants, revealing that the six-membered ring of pyranosides 5-9 and 11 exists in a slightly distorted chair conformation (6-13% distortion) and that the conformational behavior of the 2,5-anhydro-6-deoxy-l-glucose dithioacetals 10 and 12 is strongly influenced by the presence of stabilizing intramolecular nonbonded sulfur-oxygen 1,4- and 1,5-interactions. Compounds 9-12 were formed by a molecular rearrangement via sulfonium ion intermediates followed by stereoselective intramolecular cyclizations as formulated by the quantum chemical calculations performed in the present study.
Journal of Chemical Information and Modeling, 2014
A fast 3D/4D structure-sensitive procedure was developed and assessed for the chemical shift pred... more A fast 3D/4D structure-sensitive procedure was developed and assessed for the chemical shift prediction of protons bonded to sp3carbons, which poses the maybe greatest challenge in the NMR spectral parameter prediction. The LPNC (Linear Prediction with Nonlinear Corrections) approach combines three well-established multivariate methods viz. the principal component regression (PCR), the random forest (RF) algorithm, and the k nearest neighbors (kNN) method. The role of RF is to find nonlinear corrections for the PCR predicted shifts, while kNN is used to take full advantage of similar chemical environments. Two basic molecular models were also compared and discussed: in the MC model the descriptors are computed from an ensemble of the conformers found by conformational search based on Metropolis Monte Carlo (MMC) simulation; in the 4D model the conformational space was further expanded to the fourth dimension (time) by adding molecular dynamics to the MC conformers. An illustrative case study about the application and interpretation of the 4D prediction for a conformationally flexible structure, scopolamine, is described in detail.
Analytical Chemistry, 2013
Identification of natural compounds, especially secondary metabolites, has been hampered by the l... more Identification of natural compounds, especially secondary metabolites, has been hampered by the lack of easy to use and accessible reference databases. Nuclear magnetic resonance (NMR) spectroscopy is the most selective technique for identification of unknown metabolites. High quality (1)H NMR (proton nuclear magnetic resonance) spectra combined with elemental composition obtained from mass spectrometry (MS) are essential for the identification process. Here, we present MetIDB, a reference database of experimental and predicted (1)H NMR spectra of 6000 flavonoids. By incorporating the stereochemistry, intramolecular interactions, and solvent effects into the prediction model, chemical shifts and couplings were predicted with great accuracy. A user-friendly web-based interface for MetIDB has been established providing various interfaces to the data and data-mining possibilities. For each compound, additional information is available comprising compound annotation, a (1)H NMR spectrum, 2D and 3D structure with correct stereochemistry, and monoisotopic mass as well as links to other web resources. The combination of chemical formula and (1)H NMR chemical shifts proved to be very efficient in metabolite identification, especially for isobaric compounds. Using this database, the process of flavonoid identification can then be significantly shortened by avoiding repetitive elucidation of already described compounds.
The Journal of Organic Chemistry, 2015
The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properti... more The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3-4.5 nm wide space via protein-polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, ent-epicatechin-(4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (3), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case from two congeneric PAC dimers, a detailed structural analysis decoded the stereochemistry, spatial arrangement, and chemical properties of three dentin biomodifiers. Quantum-mechanics-driven (1)H iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously unrecognized details such as higher order J coupling and provided valuable information about 3D structure. Detection and quantification of H/D-exchange effects by QM-HiFSA identified C-8 and C-6 as (re)active sites, explain preferences in biosynthetic linkage, and suggest their involvement in dentin cross-linking activity. Mapping of these molecular properties underscored the significance of high δ precision in both (1)H and (13)C NMR spectroscopy. Occurring at low- to subppb levels, these newly characterized chemical shift differences in ppb are small but diagnostic measures of dynamic processes inherent to the OPAC pharmacophores and can help augment our understanding of nanometer-scale intermolecular interactions in biomodified dentin macromolecules.
![Research paper thumbnail of Metabolism of the dimethyl ester of [2,3-(13)C]succinic acid in rat hepatocytes](https://attachments.academia-assets.com/50512704/thumbnails/1.jpg)
](Molecular and cellular biochemistry, 1998
Hepatocytes prepared from overnight fasted rats were incubated for 120 min in the presence of the... more Hepatocytes prepared from overnight fasted rats were incubated for 120 min in the presence of the dimethyl ester of [2,3-(13)C]succinic acid (10 mM). The identification and quantification of 13C-enriched metabolites in the incubation medium were performed by a novel computational strategy for the deconvolution of NMR spectra with multiplet structures and constraints. The generation of 13C-labelled metabolites, including succinate, fumarate, malate, lactate, alanine, aspartate and glucose accounted for about half of the initial amount of the ester present in the incubation medium. A fair correlation was observed between the experimental abundance of each 13C-labelled glucose isotopomer and the corresponding values derived from a model for the metabolism of [2,3-(13)C]succinate. Newly formed glucose was more efficiently labelled in the carbon C5 than C2, as well as the carbon C6 than C1, supporting the concept that D-glyceraldehyde-3-phosphate may undergo enzyme-to-enzyme channelling ...
European journal of pharmacology, Jan 3, 1994
Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and... more Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and tissue esterases. Microsomal oxidative metabolism is of importance in cocaine N-demethylation, this being a principal pathway of cocaine bioactivation and hepatotoxicity. The contribution of different cytochrome P450 (CYP) enzymes to cocaine N-demethylase activity was studied in vitro with DBA/2 mouse and human liver microsomes, and cocaine hepatotoxicity was examined in vivo in DBA/2 male mice. Species dependent enzyme kinetics was observed. Cocaine N-demethylase displayed two Km values in murine liver (40-60 microM and 2-3 mM), whereas only one Km value was observed in human liver microsomes (2.3-2.7 mM). We suggest that CYP3A plays a prominent role in the N-demethylation of cocaine for the following reasons: (i) pregnenolone-16 alpha-carbonitrile, an inducer of CYP3As increases cocaine N-demethylase in parallel with testosterone 6 beta-hydroxylase activity and immunoreactive 3A prote...
Tetrahedron, 1999
... Anu J. Airaksinen * , Kari A. Tuppurainen, Simo E. Lötjönen, Matthias Niemitz, Meixiang Yu, J... more ... Anu J. Airaksinen * , Kari A. Tuppurainen, Simo E. Lötjönen, Matthias Niemitz, Meixiang Yu, Jouko J. Vepsäläinen and Reino Laatikainen. ... Robb, MA; Cheeseman, JR; Keith, T.; Petersson, GA; Montgomery, JA; Raghavachari, K.; AILaham, MA; Zakrzewski, VG; Ortiz, JV; Foresman ...
Magnetic Resonance in Medicine, 1996
A computational strategy for the deconvolution of complex spectra involving scalar multiplet patt... more A computational strategy for the deconvolution of complex spectra involving scalar multiplet patterns is presented. This approach fits spectra that can be composed of single resonances as well as scalar coupling multiplets for which resonance frequencies, intensities, and lineshape parameters can be optimized. For multiplets, the coupling constant also is optimized. Any external information about the optimizable parameters can be taken into account as external constraints. A lineshape described by absorptive and dispersive Lorentzian and Gaussian contributions and the baseline with up to 40 Fourier and polynomial terms can likewise be optimized. The effectiveness of the procedure is assessed on the basis of computer simulated deconvolutions of a composite of 'J(13C-*H) multiplets arising from a mixture of all possible 13C-*H isotopomers of deuterated L-[3-'3C]lactate generated from cell preparations incubated with D-[1 -'3C]glucose in D,O, which was analyzed previously with a manual deconvolution procedure (R. Willem, M. Biesemans, F. Kayser, W. J. Malaisse, Magn. Reson. Med. 31, ). The use of constraints is shown to lead to an improvement in the results. The fitting strategies and the importance of the baseline as an origin of bias are discussed.
Magnetic Resonance in Chemistry, 1997
ABSTRACT
Magnetic Resonance in Chemistry, 2008
The natural abundance 1H-coupled 13C NMR spectra of all proteogenic amino acids were measured in ... more The natural abundance 1H-coupled 13C NMR spectra of all proteogenic amino acids were measured in D2O at pH* 1. The accurate 1H,13C spin-spin coupling constants were analyzed using total-line-shape fitting. The obtained spectral parameters can be used to establish a spectral library of amino acid 13C isotopomers. The adaptive spectral library principle is introduced and discussed in this article. The simulated spectra can be applied to quantification of 13C isotopomer mixtures of amino acids and, thus, for exploring metabolic pathways. Also a protocol for amino acid 13C isotopomer metabolomic profiling in 13C labeled glucose feeding experiments is outlined. The approach is suggested to give invaluable information about positional fractional 13C enrichments, which are not easily available by any other method.
Journal of Cancer Research and Clinical Oncology, 1999
Experiments were carried out to assess the potential of artificial neural network (ANN) analysis ... more Experiments were carried out to assess the potential of artificial neural network (ANN) analysis in the differential diagnosis of brain tumours (low- and high-grade gliomas) from non-neoplastic focal brain lesions (tuberculomas and abscesses), using proton magnetic resonance spectroscopy (1H MRS) as input data. Single-voxel stimulated echo acquisition mode (STEAM) (echo time of 20 ms) spectra were acquired from 138 subjects including 15 with low-grade gliomas, 47 with high-grade gliomas, 18 with tuberculomas, 18 with abscesses and 40 healthy controls. Two neural networks were constructed using the spectral points from 0.6 to 3.4 parts per million. In the first network construction, the ANN had to differentiate between tumours from infections, while the second network had to differentiate between all five histological classes. ANN analysis gave a histologically correct diagnosis for low- and high-grade gliomas with an accuracy of 73% and 98% respectively. None of the 62 tumours was diagnosed as an infectious lesion. Among the non-neoplastic lesions, ANN classification was correct in 89% of tuberculomas and in 83% of brain abscesses. The specificity of ANN diagnosis was 98%, 92%, 99%, and 100% for low-grade gliomas, high-grade gliomas, tuberculomas and abscesses respectively. The present data show the clinical utility of non-invasive 1H MRS by automated ANN analysis in the diagnosis of tumour and non-tumour cerebral disorders.
The Journal of Organic Chemistry, 2016
The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bi... more The revision of the structure of the sesquiterpene aquatolide from a bicyclo[2.2.0]hexane to a bicyclo[2.1.1]hexane structure using compelling NMR data, X-ray crystallography, and the recent confirmation via full synthesis exemplify that the achievement of "structural correctness" depends on the completeness of the experimental evidence. Archived FIDs and newly acquired aquatolide spectra demonstrate that archiving and rigorous interpretation of 1D (1)H NMR data may enhance the reproducibility of (bio)chemical research and curb the growing trend of structural misassignments. Despite being the most accessible NMR experiment, 1D (1)H spectra encode a wealth of information about bonds and molecular geometry that may be fully mined by (1)H iterative full spin analysis (HiFSA). Fully characterized 1D (1)H spectra are unideterminant for a given structure. The corresponding FIDs may be readily submitted with publications and collected in databases. Proton NMR spectra are indispensable for structural characterization even in conjunction with 2D data. Quantum interaction and linkage tables (QuILTs) are introduced for a more intuitive visualization of 1D J-coupling relationships, NOESY correlations, and heteronuclear experiments. Overall, this study represents a significant contribution to best practices in NMR-based structural analysis and dereplication.
Chemie in unserer Zeit, 1990
CITATIONS 0 READS 353 5 authors, including:
Encyclopedia of Magnetic Resonance, 2007
The Journal of Organic Chemistry, 2003
6-Deoxy-l-mannose diphenyldithioacetal (1) unexpectedly gave the rearranged products phenyl 3,4-d... more 6-Deoxy-l-mannose diphenyldithioacetal (1) unexpectedly gave the rearranged products phenyl 3,4-di-O-acetyl-2-S-phenyl-1,2-dithio-6-deoxy-beta-l-glucopyranoside (9) and 3,4-di-O-acetyl-2,5-anhydro-6-deoxy-l-glucose diphenyldithioacetal (10) upon treatment with acetyl chloride, while 6-deoxy-l-mannose ethylenedithioacetal (3) yielded (4aR,6S,7S,8R,8aS)-7,8-diacetyloxy-6-methylhexahydro-4aH-[1,4]dithiino[2,3b]pyran (11), whose structure was further confirmed by X-ray diffraction, and 3,4-di-O-acetyl-2,5-anhydro-l-rhamnose ethylenedithioacetal (12). The geometry of the four rearranged products as well as that of 1-thio-6-deoxy-l-mannopyranosides 5 and 7 and their acetyl derivatives 6 and 8 was studied by density functional theory (B3LYP/6-31G) molecular models, in combination with a Karplus-type analysis of the NMR vicinal coupling constants, revealing that the six-membered ring of pyranosides 5-9 and 11 exists in a slightly distorted chair conformation (6-13% distortion) and that the conformational behavior of the 2,5-anhydro-6-deoxy-l-glucose dithioacetals 10 and 12 is strongly influenced by the presence of stabilizing intramolecular nonbonded sulfur-oxygen 1,4- and 1,5-interactions. Compounds 9-12 were formed by a molecular rearrangement via sulfonium ion intermediates followed by stereoselective intramolecular cyclizations as formulated by the quantum chemical calculations performed in the present study.
Journal of Chemical Information and Modeling, 2014
A fast 3D/4D structure-sensitive procedure was developed and assessed for the chemical shift pred... more A fast 3D/4D structure-sensitive procedure was developed and assessed for the chemical shift prediction of protons bonded to sp3carbons, which poses the maybe greatest challenge in the NMR spectral parameter prediction. The LPNC (Linear Prediction with Nonlinear Corrections) approach combines three well-established multivariate methods viz. the principal component regression (PCR), the random forest (RF) algorithm, and the k nearest neighbors (kNN) method. The role of RF is to find nonlinear corrections for the PCR predicted shifts, while kNN is used to take full advantage of similar chemical environments. Two basic molecular models were also compared and discussed: in the MC model the descriptors are computed from an ensemble of the conformers found by conformational search based on Metropolis Monte Carlo (MMC) simulation; in the 4D model the conformational space was further expanded to the fourth dimension (time) by adding molecular dynamics to the MC conformers. An illustrative case study about the application and interpretation of the 4D prediction for a conformationally flexible structure, scopolamine, is described in detail.
Analytical Chemistry, 2013
Identification of natural compounds, especially secondary metabolites, has been hampered by the l... more Identification of natural compounds, especially secondary metabolites, has been hampered by the lack of easy to use and accessible reference databases. Nuclear magnetic resonance (NMR) spectroscopy is the most selective technique for identification of unknown metabolites. High quality (1)H NMR (proton nuclear magnetic resonance) spectra combined with elemental composition obtained from mass spectrometry (MS) are essential for the identification process. Here, we present MetIDB, a reference database of experimental and predicted (1)H NMR spectra of 6000 flavonoids. By incorporating the stereochemistry, intramolecular interactions, and solvent effects into the prediction model, chemical shifts and couplings were predicted with great accuracy. A user-friendly web-based interface for MetIDB has been established providing various interfaces to the data and data-mining possibilities. For each compound, additional information is available comprising compound annotation, a (1)H NMR spectrum, 2D and 3D structure with correct stereochemistry, and monoisotopic mass as well as links to other web resources. The combination of chemical formula and (1)H NMR chemical shifts proved to be very efficient in metabolite identification, especially for isobaric compounds. Using this database, the process of flavonoid identification can then be significantly shortened by avoiding repetitive elucidation of already described compounds.
The Journal of Organic Chemistry, 2015
The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properti... more The ability of certain oligomeric proanthocyanidins (OPACs) to enhance the biomechanical properties of dentin involves collagen cross-linking of the 1.3-4.5 nm wide space via protein-polyphenol interactions. A systematic interdisciplinary search for the bioactive principles of pine bark has yielded the trimeric PAC, ent-epicatechin-(4β→8)-epicatechin-(2β→O→7,4β→8)-catechin (3), representing the hitherto most potent single chemical entity capable of enhancing dentin stiffness. Building the case from two congeneric PAC dimers, a detailed structural analysis decoded the stereochemistry, spatial arrangement, and chemical properties of three dentin biomodifiers. Quantum-mechanics-driven (1)H iterative full spin analysis (QM-HiFSA) of NMR spectra distinguished previously unrecognized details such as higher order J coupling and provided valuable information about 3D structure. Detection and quantification of H/D-exchange effects by QM-HiFSA identified C-8 and C-6 as (re)active sites, explain preferences in biosynthetic linkage, and suggest their involvement in dentin cross-linking activity. Mapping of these molecular properties underscored the significance of high δ precision in both (1)H and (13)C NMR spectroscopy. Occurring at low- to subppb levels, these newly characterized chemical shift differences in ppb are small but diagnostic measures of dynamic processes inherent to the OPAC pharmacophores and can help augment our understanding of nanometer-scale intermolecular interactions in biomodified dentin macromolecules.
Molecular and cellular biochemistry, 1998
Hepatocytes prepared from overnight fasted rats were incubated for 120 min in the presence of the... more Hepatocytes prepared from overnight fasted rats were incubated for 120 min in the presence of the dimethyl ester of [2,3-(13)C]succinic acid (10 mM). The identification and quantification of 13C-enriched metabolites in the incubation medium were performed by a novel computational strategy for the deconvolution of NMR spectra with multiplet structures and constraints. The generation of 13C-labelled metabolites, including succinate, fumarate, malate, lactate, alanine, aspartate and glucose accounted for about half of the initial amount of the ester present in the incubation medium. A fair correlation was observed between the experimental abundance of each 13C-labelled glucose isotopomer and the corresponding values derived from a model for the metabolism of [2,3-(13)C]succinate. Newly formed glucose was more efficiently labelled in the carbon C5 than C2, as well as the carbon C6 than C1, supporting the concept that D-glyceraldehyde-3-phosphate may undergo enzyme-to-enzyme channelling ...
European journal of pharmacology, Jan 3, 1994
Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and... more Cocaine is eliminated and detoxified principally through the metabolism of nonspecific plasma and tissue esterases. Microsomal oxidative metabolism is of importance in cocaine N-demethylation, this being a principal pathway of cocaine bioactivation and hepatotoxicity. The contribution of different cytochrome P450 (CYP) enzymes to cocaine N-demethylase activity was studied in vitro with DBA/2 mouse and human liver microsomes, and cocaine hepatotoxicity was examined in vivo in DBA/2 male mice. Species dependent enzyme kinetics was observed. Cocaine N-demethylase displayed two Km values in murine liver (40-60 microM and 2-3 mM), whereas only one Km value was observed in human liver microsomes (2.3-2.7 mM). We suggest that CYP3A plays a prominent role in the N-demethylation of cocaine for the following reasons: (i) pregnenolone-16 alpha-carbonitrile, an inducer of CYP3As increases cocaine N-demethylase in parallel with testosterone 6 beta-hydroxylase activity and immunoreactive 3A prote...
Tetrahedron, 1999
... Anu J. Airaksinen * , Kari A. Tuppurainen, Simo E. Lötjönen, Matthias Niemitz, Meixiang Yu, J... more ... Anu J. Airaksinen * , Kari A. Tuppurainen, Simo E. Lötjönen, Matthias Niemitz, Meixiang Yu, Jouko J. Vepsäläinen and Reino Laatikainen. ... Robb, MA; Cheeseman, JR; Keith, T.; Petersson, GA; Montgomery, JA; Raghavachari, K.; AILaham, MA; Zakrzewski, VG; Ortiz, JV; Foresman ...
Magnetic Resonance in Medicine, 1996
A computational strategy for the deconvolution of complex spectra involving scalar multiplet patt... more A computational strategy for the deconvolution of complex spectra involving scalar multiplet patterns is presented. This approach fits spectra that can be composed of single resonances as well as scalar coupling multiplets for which resonance frequencies, intensities, and lineshape parameters can be optimized. For multiplets, the coupling constant also is optimized. Any external information about the optimizable parameters can be taken into account as external constraints. A lineshape described by absorptive and dispersive Lorentzian and Gaussian contributions and the baseline with up to 40 Fourier and polynomial terms can likewise be optimized. The effectiveness of the procedure is assessed on the basis of computer simulated deconvolutions of a composite of 'J(13C-*H) multiplets arising from a mixture of all possible 13C-*H isotopomers of deuterated L-[3-'3C]lactate generated from cell preparations incubated with D-[1 -'3C]glucose in D,O, which was analyzed previously with a manual deconvolution procedure (R. Willem, M. Biesemans, F. Kayser, W. J. Malaisse, Magn. Reson. Med. 31, ). The use of constraints is shown to lead to an improvement in the results. The fitting strategies and the importance of the baseline as an origin of bias are discussed.
Magnetic Resonance in Chemistry, 1997
ABSTRACT
Magnetic Resonance in Chemistry, 2008
The natural abundance 1H-coupled 13C NMR spectra of all proteogenic amino acids were measured in ... more The natural abundance 1H-coupled 13C NMR spectra of all proteogenic amino acids were measured in D2O at pH* 1. The accurate 1H,13C spin-spin coupling constants were analyzed using total-line-shape fitting. The obtained spectral parameters can be used to establish a spectral library of amino acid 13C isotopomers. The adaptive spectral library principle is introduced and discussed in this article. The simulated spectra can be applied to quantification of 13C isotopomer mixtures of amino acids and, thus, for exploring metabolic pathways. Also a protocol for amino acid 13C isotopomer metabolomic profiling in 13C labeled glucose feeding experiments is outlined. The approach is suggested to give invaluable information about positional fractional 13C enrichments, which are not easily available by any other method.
Journal of Cancer Research and Clinical Oncology, 1999
Experiments were carried out to assess the potential of artificial neural network (ANN) analysis ... more Experiments were carried out to assess the potential of artificial neural network (ANN) analysis in the differential diagnosis of brain tumours (low- and high-grade gliomas) from non-neoplastic focal brain lesions (tuberculomas and abscesses), using proton magnetic resonance spectroscopy (1H MRS) as input data. Single-voxel stimulated echo acquisition mode (STEAM) (echo time of 20 ms) spectra were acquired from 138 subjects including 15 with low-grade gliomas, 47 with high-grade gliomas, 18 with tuberculomas, 18 with abscesses and 40 healthy controls. Two neural networks were constructed using the spectral points from 0.6 to 3.4 parts per million. In the first network construction, the ANN had to differentiate between tumours from infections, while the second network had to differentiate between all five histological classes. ANN analysis gave a histologically correct diagnosis for low- and high-grade gliomas with an accuracy of 73% and 98% respectively. None of the 62 tumours was diagnosed as an infectious lesion. Among the non-neoplastic lesions, ANN classification was correct in 89% of tuberculomas and in 83% of brain abscesses. The specificity of ANN diagnosis was 98%, 92%, 99%, and 100% for low-grade gliomas, high-grade gliomas, tuberculomas and abscesses respectively. The present data show the clinical utility of non-invasive 1H MRS by automated ANN analysis in the diagnosis of tumour and non-tumour cerebral disorders.