Correlations between in vivo <sup>1</sup>H MRS and ex vivo <sup>1</sup>H HRMAS metabolite measurements in adult human gliomas

Opstad, Kirstie S.; Wright, Alan J.; Bell, B. Anthony; Griffiths, John R.; Howe, Franklyn A.

doi:10.1002/jmri.22039

Cited by 59 publications

(65 citation statements)

References 38 publications

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“…With these resonances, discrimination between PCNSL and high-grade tumours has been successful in more than 82 % (short TE) and 72 % (long TE) of our test cases. Lipid resonances at 1.2 ppm have been related to tumour necrosis [18][19][20]. Although PCNSL is considered a highly malignant tumour, necrosis is not a prominent finding of this highly cellular tumour.…”

Section: Discussionmentioning

confidence: 95%

1H-MRS is useful to reinforce the suspicion of primary central nervous system lymphoma prior to surgery

et al. 2014

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Section: Discussionmentioning

confidence: 95%

1H-MRS is useful to reinforce the suspicion of primary central nervous system lymphoma prior to surgery

et al. 2014

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“…This effect, however, was not shared by all brain regions, as serotonin levels remained stable over an 18-h postmortem interval in the cingulate cortex (25). Furthermore, concentrations of many metabolites, such as myo-inositol, creatine, glutamine, glutamate, N-acetylaspartate, and taurine were shown to remain stable in the postmortem brain tissue over long time intervals (22,23,26,27). Similarly, experiments quantifying brain polyamines, such as spermine, spermidine, and putrescine, in postmortem human brain using GC-MS did not report any significant relationship between these metabolite concentrations and postmortem interval (28).…”

Section: Freely Available Online Through the Pnas Open Access Optionmentioning

confidence: 91%

“…Previous studies that have used proton magnetic resonance spectroscopy in human and rat brain biopsy samples have shown that concentrations of metabolites associated with anaerobic glycolysis, such as glucose, alanine, glutathione and lactate, change after death (21)(22)(23)(24). In rat brain, postmortem delay also leads to concentration changes of dopamine, norepinephrine, and serotonin in the occipital cortex.…”

Section: Freely Available Online Through the Pnas Open Access Optionmentioning

confidence: 99%

Rapid metabolic evolution in human prefrontal cortex

Giavalisco

Liu

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Human evolution is characterized by the rapid expansion of brain size and drastic increase in cognitive capabilities. It has long been suggested that these changes were accompanied by modifications of brain metabolism. Indeed, human-specific changes on gene expression or amino acid sequence were reported for a number of metabolic genes, but actual metabolite measurements in humans and apes have remained scarce. Here, we investigate concentrations of more than 100 metabolites in the prefrontal and cerebellar cortex in 49 humans, 11 chimpanzees, and 45 rhesus macaques of different ages using gas chromatography-mass spectrometry (GC-MS). We show that the brain metabolome undergoes substantial changes, both ontogenetically and evolutionarily: 88% of detected metabolites show significant concentration changes with age, whereas 77% of these metabolic changes differ significantly among species. Although overall metabolic divergence reflects phylogenetic relationships among species, we found a fourfold acceleration of metabolic changes in prefrontal cortex compared with cerebellum in the human lineage. These human-specific metabolic changes are paralleled by changes in expression patterns of the corresponding enzymes, and affect pathways involved in synaptic transmission, memory, and learning.H uman evolution is characterized by rapid expansion of brain size and increase in cognitive capabilities, leading to the emergence of unique and complex cognitive skills. These changes have long been associated with changes in brain metabolism, in particular with respect to increased energy demand (1). Large brains are metabolically costly. Thus, humans allocate approximately 20% of their total energy to the brain, compared with 11-13% for apes and 2-8% for other mammalian species (2). This increased metabolic demand has been associated with elevated expression of genes involved in neuronal functions and energy metabolism (3, 4). These changes may have been evolutionary advantageous, as indicated by signatures of positive selection reported for the amino acid changes, which occur in the mitochondrial electron-transport chain proteins, in anthropoid primates and humans, as well as elevated expression of the energy metabolism pathways in the human brain (5, 6). On the histological level, human brains show the largest density of glia cells relative to neurons in the prefrontal cortex, which provides an indirect indication of increased neuronal metabolic demand (7).Changes in brain metabolism are also implicated in neuropsychiatric disorders, such as schizophrenia, which affect some of the human-specific cognitive abilities (8, 9). Furthermore, direct measurements of 21 metabolites in the prefrontal cortex of adult human controls compared with human schizophrenia patients, chimpanzees, and rhesus macaques, carried out using proton NMR spectroscopy have shown significant overlap between human-specific evolutionary changes and metabolic differences between controls and schizophrenia patients (10). Notably, this study has identified not ...

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“…This study demonstrates very low concentrations of lactate in benign biopsy tissue, which exclude the problem of depletion and ischemia during surgical removal. Several studies using HR MAS on surgically removed tissue discuss tissue oxygen depletion and ischemia investigating lactate as a biomarker [92,95].…”

Section: Lactate Productionmentioning

confidence: 99%

“…Overall, the amount of biochemical information in HR MAS spectra was on the same scale as spectra from tissue extracts. HR MAS has later been applied to human cancers in the brain [10,20,46,47,81,82,86,[89][90][91][92][93][94][95][96][97][98][99][100][101], breast [9,19,38,102], prostate [15,18,[103][104][105][106][107][108][109][110], cervix [40,50,[111][112][113][114], kidney [36,115,116], colorectal [42,43,45,51] and other neoplastic tissues [39,49,…”

Section: Studies Of Chocc In Cancer Using Hr Masmentioning

confidence: 99%

HR MAS MR Spectroscopy in Metabolic Characterization of Cancer

Moestue¹,

Sitter²,

Bathen³

et al. 2011

CTMC

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One of the central hallmarks of cancer is the rapid and infinite cellular proliferation. In order to cope with increased requirement for building blocks and energy, cancer cells develop abnormal metabolic properties. Detailed assessment of cancer cell metabolism can provide biological information for use in both drug discovery and development of personalized cancer therapy. Analysis of intact tissue using high resolution magic angle spinning (HR MAS) magnetic resonance spectroscopy (MRS) gives qualitative and quantitative metabolite measures with minimal sample preparation. Multivariate statistical methods are important tools for analysis of complex MR data and have in recent years been used for analysis of HR MAS data from intact tissue. HR MAS analysis of intact tissue allows combination of metabolomic data with genomic or proteomic data, and can therefore be used both for exploring the molecular biology of cancer and for clinical improvements in cancer diagnostics, prognostics and treatment planning. In this review, the basic concepts of HR MAS are presented, and its use in characterisation of cancer metabolism is discussed with specific focus on selected pathways such as choline metabolism and glycolysis. The use of HR MAS in analysis of amino acids and lipid metabolism in cancer is also reviewed. Finally, the expected role of HR-MAS in metabolic characterisation in the near future is discussed.

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Correlations between in vivo ¹H MRS and ex vivo ¹H HRMAS metabolite measurements in adult human gliomas

Abstract: Within defined limitations, ex vivo astrocytoma biopsy HRMAS (1)H spectra have similar metabolic profiles to that obtained in vivo and therefore detailed ex vivo characterization of glioma biopsies can directly relate to the original tumor.

Cited by 59 publications

References 38 publications

1H-MRS is useful to reinforce the suspicion of primary central nervous system lymphoma prior to surgery

1H-MRS is useful to reinforce the suspicion of primary central nervous system lymphoma prior to surgery

Rapid metabolic evolution in human prefrontal cortex

HR MAS MR Spectroscopy in Metabolic Characterization of Cancer

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Correlations between in vivo 1H MRS and ex vivo 1H HRMAS metabolite measurements in adult human gliomas

Abstract: Within defined limitations, ex vivo astrocytoma biopsy HRMAS (1)H spectra have similar metabolic profiles to that obtained in vivo and therefore detailed ex vivo characterization of glioma biopsies can directly relate to the original tumor.

Cited by 59 publications

References 38 publications

1H-MRS is useful to reinforce the suspicion of primary central nervous system lymphoma prior to surgery

1H-MRS is useful to reinforce the suspicion of primary central nervous system lymphoma prior to surgery

Rapid metabolic evolution in human prefrontal cortex

HR MAS MR Spectroscopy in Metabolic Characterization of Cancer

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Product

Resources

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Correlations between in vivo ¹H MRS and ex vivo ¹H HRMAS metabolite measurements in adult human gliomas