Considerations for quantification of lipids in nerve tissue using matrix‐assisted laser desorption/ionization mass spectrometric imaging

Landgraf, Rachelle R.; Garrett, Timothy J.; Conaway, Maria C. Prieto; Calcutt, Nigel A.; Stacpoole, Peter W.; Yost, Richard A.

doi:10.1002/rcm.5189

Cited by 40 publications

(42 citation statements)

References 21 publications

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“…Phospholipid standards applied to a sample holder prior to tissue overlay have been successfully analyzed by MALDI-MSI after migration through the tissue (Landgraf et al, 2011). This demonstrates that a degree of extraction can occur either during matrix application or immediately prior to it.…”

Section: Discussionmentioning

confidence: 99%

“…This image represents the spatial distribution and relative abundance of that particular lipid-ion, and can be correlated with histological features (Burnum et al, 2009) (Delvolve et al, 2011) (Carter et al, 2011). By adding internal standards, absolute abundances of several lipid classes can be measured with high precision using MALDI-MSI (Landgraf et al, 2011). MALDI-MSI does not require specific antibodies such as those used in immunohistochemical methods.…”

Section: Introductionmentioning

confidence: 99%

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Mapping of phospholipids by MALDI imaging (MALDI-MSI): realities and expectations

Sparvero¹,

Amoscato²,

Dixon

et al. 2012

Chemistry and Physics of Lipids

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Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has emerged as a novel powerful MS methodology that has the ability to generate both molecular and spatial information within a tissue section. Application of this technology as a new type of biochemical lipid microscopy may lead to new discoveries of the lipid metabolism and biomarkers associated with area-specific alterations or damage under stress/disease conditions such as traumatic brain injury or acute lung injury, among others. However there are limitations in the range of what it can detect as compared with liquid chromatography-MS (LC-MS) of a lipid extract from a tissue section. The goal of the current work was to critically consider remarkable new opportunities along with the limitations and approaches for further improvements of MALDI-MSI. Based on our experimental data and assessments, improvements of the spectral and spatial resolution, sensitivity and specificity towards low abundance species of lipids are proposed. This is followed by a review of the current literature, including methodologies that other laboratories have used to overcome these challenges.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mapping of phospholipids by MALDI imaging (MALDI-MSI): realities and expectations

Sparvero¹,

Amoscato²,

Dixon

et al. 2012

Chemistry and Physics of Lipids

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“…In addition, when complemented with high‐resolution mass spectrometry, the analyses of biological surfaces can take advantage of the high mass accuracy for direct lipid identification . Recent work has shown that lipid quantification is possible when using internal standards …”

Section: Introductionmentioning

confidence: 99%

Changes in lipid distribution inE. colistrains in response to norfloxacin

et al. 2015

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Bacterial resistance to antibiotics has become an increasing threat, requiring not only the development of new targets in drug discovery, but more importantly, a better understanding of cellular response. In the current study, three closely related Escherichia coli strains, a wild type (MG1655), and an isogenic pair derived from the wild type (DPB635 and DPB636) are studied following exposure to sub lethal concentrations of antibiotic (norfloxacin) over time. In particular, genotype similarities between the three strains were assessed based on the lipid regulation response (e.g., presence/absence and up/down regulation). Lipid identification was performed using direct surface probe analysis (Matrix-assisted laser desorption/ionization, MALDI), coupled to high-resolution mass spectrometry (Fourier transform ion cyclotron resonance mass spectrometry, FT-ICR MS) followed by statistical analysis of variability and reproducibility across batches using internal standards. Inspection of the lipid profile showed that for the MG1655, DPB635 and DPB636 E. coli strains, a similar distribution of the altered lipids were observed after exposure to norfloxacin antibiotic (e.g., fatty acids and glycerol phospholipids are up and down regulated, respectively). Additionally, variations in the lipid distribution resemble the extent to which each strain can combat the antibiotic exposure. That is, the topA66 topoisomerase I mutation of DPB636 translates into diminished response related to antibiotic sensitivity when compared to MG1655 and the DPB635 strains.

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“…In addition, the molecular diversity of lipids allows them to perform essential structural, modulating and signaling functions in cells and tissues making them highly desirable imaging targets . Recent MALDI‐MSI studies of lipids led to the development of protocols that afforded higher spatial resolution and addressed the possibility for introduction of quantitative criteria for data analysis …”

Section: Discussionmentioning

confidence: 99%

Improved spatial resolution of matrix-assisted laser desorption/ionization imaging of lipids in the brain by alkylated derivatives of 2,5-dihydroxybenzoic acid

Stoyanovsky

Sparvero

Amoscato

et al. 2014

Rapid Commun. Mass Spectrom.

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RATIONALE Matrix‐assisted laser desorption/ionization (MALDI) is one of the major techniques for mass spectrometry imaging (MSI) of biological systems along with secondary‐ion mass spectrometry (SIMS) and desorption electrospray mass spectrometry (DESI). The inherent variability of MALDI‐MSI signals within intact tissues is related to the heterogeneity of both the sample surface and the matrix crystallization. To circumvent some of these limitations of MALDI‐MSI, we have developed improved matrices for lipid analysis based on structural modification of the commonly used matrix 2,5‐dihydroxybenzoic acid (DHB). METHODS We have synthesized DHB containing ‐C6H13 and ‐C12H25 alkyl chains and applied these matrices to rat brain using a capillary sprayer. We utilized a Bruker Ultraflex II MALDI‐TOF/TOF mass spectrometer to analyze lipid extracts and tissue sections, and examined these sections with polarized light microscopy and differential interference contrast microscopy. RESULTS O‐alkylation of DHB yields matrices, which, when applied to brain sections, follow a trend of phase transition from crystals to an oily layer in the sequence DHB → DHB‐C6H13 → DHB‐C12H25. MALDI‐MSI images acquired with DHB‐C12H25 exhibited a considerably higher density of lipids than DHB. CONCLUSIONS Comparative experiments with DHB and DHB‐C12H25 are presented, which indicate that the latter matrix affords higher lateral resolution than the former. Copyright © 2014 John Wiley & Sons, Ltd.

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Considerations for quantification of lipids in nerve tissue using matrix‐assisted laser desorption/ionization mass spectrometric imaging

Cited by 40 publications

References 21 publications

Mapping of phospholipids by MALDI imaging (MALDI-MSI): realities and expectations

Mapping of phospholipids by MALDI imaging (MALDI-MSI): realities and expectations

Changes in lipid distribution inE. colistrains in response to norfloxacin

Improved spatial resolution of matrix-assisted laser desorption/ionization imaging of lipids in the brain by alkylated derivatives of 2,5-dihydroxybenzoic acid

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