Solid-state NMR adiabatic TOBSY sequences provide enhanced sensitivity for multidimensional high-resolution magic-angle-spinning 1H MR spectroscopy

Andronesi, Ovidiu C.; Mintzopoulos, Dionyssios; Struppe, Jochem; Black, Peter McLaren; Tzika, A. Aria

doi:10.1016/j.jmr.2008.05.017

Cited by 22 publications

(33 citation statements)

References 41 publications

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“…Metabolic profiling of intact tumor biopsies as small as 1 mg can be performed with high-resolution magic angle spinning (HRMAS) (51)(52)(53). HRMAS preserves the integrity of the samples that can be further analyzed with immunohistochemistry, genomics, or other metabolic profiling tools such as mass spectrometry.…”

Section: Ex Vivo Mrs Of D-2hg In Tumors With Idh Mutationsmentioning

confidence: 99%

Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate

Andronesi

Rapalino²,

Gerstner³

et al. 2013

J. Clin. Invest.

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154

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Section: Ex Vivo Mrs Of D-2hg In Tumors With Idh Mutationsmentioning

confidence: 99%

Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate

Andronesi

Rapalino²,

Gerstner³

et al. 2013

J. Clin. Invest.

Self Cite

154

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“…CPMG includes inter-pulse delay (τ=2π/ ωr=400 µs); 256 transients; spectral width of 7.2 kHz; 8k data points; TR=3 sec. Additional analysis of metabolites employed a novel approach combining two-dimensional (2D) solid-state, HRMAS proton ( 1 H) NMR, with total through-Bond Spectroscopy (TOBSY) (23), which maximizes the advantages of HRMAS and provides a robust classification strategy. Typical acquisition parameters included: 2k points direct dimension (13 ppm spectral width), 200k points indirect dimension (7.5 ppm spectral width), 8 scans with 2 dummy scans, 1 sec water pre-saturation, 2 sec total repetition time, 45 msec mixing time and total acquisition time 45 min.…”

Section: Methodsmentioning

confidence: 99%

Live-cell high resolution magic angle spinning magnetic resonance spectroscopy for in vivo analysis of Pseudomonas aeruginosa metabolomics

et al. 2013

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Abstract. Pseudomonas aeruginosa (PA) is a pathogenic gram-negative bacterium that is widespread in nature, inhabiting soil, water, plants and animals. PA is a prevalent cause of deleterious human infections, particularly in patients whose host defense mechanisms have been compromised. Metabolomics is an important tool used to study host-pathogen interactions and to identify novel therapeutic targets and corresponding compounds. The aim of the present study was to report the metabolic profile of live PA bacteria using in vivo high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance spectroscopy (NMR), in combination with 1-and 2-dimensional HRMAS NMR. This methodology provides a new and powerful technique to rapidly interrogate the metabolome of intact bacterial cells and has several advantages over traditional techniques that identify metabolome components from disrupted cells. Furthermore, application of multidimensional HRMAS NMR, in combination with the novel technique total through-Bond correlation Spectroscopy (TOBSY), is a promising approach that may be used to obtain in vivo metabolomics information from intact live bacterial cells and can mediate such analyses in a short period of time. Moreover, HRMAS 1 H NMR enables the investigation of the associations between metabolites and cell processes. In the present study, we detected and quantified several informative metabolic molecules in live PA cells, including N-acetyl, betaine, citrulline, alanine and glycine, which are important in peptidoglycan synthesis. The results provided a complete metabolic profile of PA for future studies of PA clinical isolates and mutants. In addition, this in vivo NMR biomedical approach might have clinical utility and should prove useful in gene function validation, the study of pathogenetic mechanisms, the classification of microbial strains into functional/clinical groups, the testing of anti-bacterial agents and the determination of metabolic profiles of bacterial mutants. IntroductionPseudomonas aeruginosa (PA) is a ubiquitous Gram-negative bacterium that inhabits a wide array of natural environments. This bacterium is of significant clinical interest as it is a multi-antibiotic-resistant human pathogen associated with hospital-acquired infections (1,2) and a major cause of morbidity and mortality in cystic fibrosis (CF) patients. It commonly colonizes the lower respiratory and gastrointestinal tracts and the mucosa and skin of hospital patients. The establishment of chronic PA respiratory infections requires a complex adaptive process that mediates essential physiological changes that allow bacterial cells to survive and persist in the host environment. Bacteria secrete small molecules that act as specific signals to positively regulate specialized processes (3), including the production of virulence factors that mediate pathogenic infection, host colonization and the promotion of interspecies microbial interactions (4).Bacterial cell walls are complex, consisting of integrated macromolecules including c...

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“…We used a previously designed 2D ex vivo HRMAS 1 H MRS procedure for brain tumors, based on novel concepts rooted in solid-state NMR spectroscopy (49). All HRMAS 1 H MRS using TOBSY experiments were performed on a Bruker BioSpin Avance NMR spectrometer (600.13 MHz) using a 4-mm triple resonance ( 1 H, 13 C, 2 H) HRMAS probe (Bruker).…”

Section: Hrmasmentioning

confidence: 99%

“…Prior data have provided the following information and advances: a) measurements using one-dimensional (1D) ex vivo HighResolution Magic Angle Spinning (HRMAS) proton ( 1 H) MRS at 9.4 T correlated directly with the neuropathology of intact brain tumor biopsies. The intracellular metabolite phosphocholine (PCho), a constituent of the choline (Cho) peak, was associated with cellularity and proliferative activity (17); b) MRS-detectable lipid changes were implicated in brain tumor apoptosis and necrosis (17); c) in vivo MRS spectra correlated with ex vivo MRS measurements (17); d) Gene expression analyses of embryonal CNS tumors distinguished between tumor types that could not be clearly distinguished by histopathology (18,19); e) HRMAS 1 H MRS and genomic analyses of microscale tissue biopsies (~2 mg) yielded quality data, enabling MRS-derived metabolites and gene expression differences to be related and cross validated (15); f) an optimized adiabatic solid-state NMR method, Total ThroughBond Spectroscopy (TOBSY), maximized the advantages of HRMAS applied to intact biopsies when compared to more conventional liquid-state NMR approaches (20,21); g) a structured network knowledge-based approach was demonstrated to be capable of analyzing genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules, and phenotypes (13); and h) the design and initial testing of our classification algorithms was successful (22).…”

Section: Introductionmentioning

confidence: 99%

Combining magnetic resonance spectroscopy and molecular genomics offers better accuracy in brain tumor typing and prediction of survival than either methodology alone

Astrakas

Blekas²,

Constantinou³

et al. 2011

Int J Oncol

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Abstract. Recent advents in magnetic resonance spectroscopy (MRS) techniques permit subsequent microarray analysis over the entire human transcriptome in the same tissue biopsies. However, extracting information from such immense quantities of data is limited by difficulties in recognizing and evaluating the relevant patterns of apparent gene expression in the context of the existing knowledge of phenotypes by histopathology. Using a quantitative approach derived from a knowledge base of pathology findings, we present a novel methodology used to process genome-wide transcription and MRS data. This methodology was tested to examine metabolite and genomewide profiles in MRS and RNA in 55 biopsies from human subjects with brain tumors with ~100% certainty. With the guidance of histopathology and clinical outcome, 15 genes with the assistance of 15 MRS metabolites were able to be distinguished by tumor categories and the prediction of survival was better than when either method was used alone.This new method, combining MRS, genomics, statistics and biological content, improves the typing and understanding of the complexity of human brain tumors, and assists in the search for novel tumor biomarkers. It is an important step for novel drug development, it generates testable hypotheses regarding neoplasia and promises to guide human brain tumor therapy provided improved in vivo methods for monitoring response to therapy are developed.

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Solid-state NMR adiabatic TOBSY sequences provide enhanced sensitivity for multidimensional high-resolution magic-angle-spinning 1H MR spectroscopy

Cited by 22 publications

References 41 publications

Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate

Detection of oncogenic IDH1 mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate

Live-cell high resolution magic angle spinning magnetic resonance spectroscopy for in vivo analysis of Pseudomonas aeruginosa metabolomics

Combining magnetic resonance spectroscopy and molecular genomics offers better accuracy in brain tumor typing and prediction of survival than either methodology alone

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