Abstract
In the last few years, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has been successfully used to study the distribution of lipids within tissue sections. However, few efforts have been made to acquire reliable quantitative data regarding the localized concentrations of these molecules. Here we propose an approach based on brain homogenates for the quantification of phosphatidylcholines (PCs) in brain section by MALDI MSI. Homogenates were spiked with a range of PC(16:0 d31/18:1) concentrations. Sections from homogenates and intact brain were simultaneously prepared before being analyzed by MALDI MSI using a Fourier transform ion cyclotron resonance (FT-ICR) analyzer. Standard curves were generated from the signal intensity of the different PC(16:0 d31/18:1) ionic species ([M+H]+, [M+Na]+ and [M+K]+) detected from the homogenate sections. Localized quantitative data were finally extracted by correlating the standard curves with the signal intensities of endogenous PC (especially PC(16:0/18:1)) ionic species detected on different areas of the brain section. They were consistent with quantitative values found in the literature. This work introduces a new method to take directly into account biological matrix effects for the quantification of lipids as well as other endogenous compounds, in tissue sections by MALDI MSI.
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Abbreviations
- a.u.:
-
Arbitrary unit
- H&E:
-
Haematoxylin and eosin
- ITO:
-
Indium tin oxide
- MALDI:
-
Matrix-assisted laser desorption/ionization
- MSI:
-
Mass spectrometry imaging
- PC:
-
Phosphatidylcholine
- R 2 :
-
Coefficient of determination
- ROI:
-
Region of interest
References
Zemski Berry KA, Hankin JA, Barkley RM, Spraggins JM, Caprioli RM, Murphy RC (2011) MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chem Rev 111(10):6491–6512
Santos CR, Schulze A (2012) Lipid metabolism in cancer. FEBS J 279(15):2610–2623
Abrass CK (2004) Cellular lipid metabolism and the role of lipids in progressive renal disease. Am J Nephrol 24(1):46–53
Lee CH, Olson P, Evans RM (2003) Minireview: lipid metabolism, metabolic diseases, and peroxisome proliferator-activated receptors. Endocrinology 144(6):2201–2207
Frisardi V, Panza F, Seripa D, Farooqui T, Farooqui AA (2011) Glycerophospholipids and glycerophospholipid-derived lipid mediators: a complex meshwork in Alzheimer’s disease pathology. Prog Lipid Res 50(4):313–330
Paradisi G, Ianniello F, Tomei C, Bracaglia M, Carducci B, Gualano MR, La Torre G, Banci M, Caruso A (2010) Longitudinal changes of adiponectin, carbohydrate and lipid metabolism in pregnant women at high risk for gestational diabetes. Gynecol Endocrinol 26(7):539–545
Giannopoulos PF, Joshi YB, Praticò D (2014) Novel lipid signaling pathways in Alzheimer’s disease pathogenesis. Biochem Pharmacol 88(4):560–564
Gode D, Volmer DA (2013) Lipid imaging by mass spectrometry—a review. Analyst 138(5):1289–1315
Goto T, Terada N, Inoue T, Nakayama K, Okada Y, Yoshikawa T, Miyazaki Y, Uegaki M, Sumiyoshi S, Kobayashi T, Kamba T, Yoshimura K, Ogawa O (2014) The expression profile of phosphatidylinositol in high spatial resolution imaging mass spectrometry as a potential biomarker for prostate cancer. PLoS One 9(2):e90242
Veloso A, Fernández R, Astigarraga E, Barreda-Gómez G, Manuel I, Giralt MT, Ferrer I, Ochoa B, Rodríguez-Puertas R, Fernández JA (2011) Distribution of lipids in human brain. Anal Bioanal Chem 401(1):89–101
Thomas A, Charbonneau JL, Fournaise E, Chaurand P (2012) Sublimation of new matrix candidates for high spatial resolution imaging mass spectrometry of lipids: enhanced information in both positive and negative polarities after 1,5-diaminonapthalene deposition. Anal Chem 84(4):2048–2054
Kawashima M, Iwamoto N, Kawaguchi-Sakita N, Sugimoto M, Ueno T, Mikami Y, Terasawa K, Sato TA, Tanaka K, Shimizu K, Toi M (2013) High-resolution imaging mass spectrometry reveals detailed spatial distribution of phosphatidylinositols in human breast cancer. Cancer Sci 104(10):1372–1379
Berry KAZ, Gordon WC, Murphy RC, Bazan NG (2014) Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry. J Lipid Res 55(3):504–515
Dyer JM, Deb-Choudhury S, Cornellison CD, Krsinic G, Dobbie P, Rosenvold K, Clerens S (2014) Spatial and temporal mass spectrometric profiling and imaging of lipid degradation in bovine M. longissimus dorsi lumborum. J Food Compos Anal 33(2):203–209
Wang HYJ, Wu HW, Tsai PJ, Liu CB, Zheng ZF (2014) Matrix-assisted laser desorption/ionization mass spectrometry imaging of cardiolipins in rat organ sections. Anal Bioanal Chem 406(2):565–575
Matsumoto J, Sugiura Y, Yuki D, Hayasaka T, Goto-Inoue N, Zaima N, Kunii Y, Wada A, Yang Q, Nishiura K, Akatsu H, Hori A, Hashizume Y, Yamamoto T, Ikemoto K, Setou M, Niwa SI (2011) Abnormal phospholipids distribution in the prefrontal cortex from a patient with schizophrenia revealed by matrix-assisted laser desorption/ionization imaging mass spectrometry. Anal Bioanal Chem 400(7):1933–1943
Arafah K, Longuespee R, Desmons A, Kerdraon O, Fournier I, Salzet M (2014) Lipidomics for clinical diagnosis: dye-assisted laser desorption/ionization (DALDI) method for lipids detection in MALDI mass spectrometry imaging. Omics: J Integr Biol. doi:10.1089/omi.2013.0175
Sparvero LJ, Amoscato AA, Dixon CE, Long JB, Kochanek PM, Pitt BR, Bayir H, Kagan VE (2012) Mapping of phospholipids by MALDI imaging (MALDI-MSI): realities and expectations. Chem Phys Lipids 165(5):545–562
Cimino J, Calligaris D, Far J, Debois D, Blacher S, Sounni NE, Noel A, De Pauw E (2013) Towards lipidomics of low-abundant species for exploring tumor heterogeneity guided by high-resolution mass spectrometry imaging. Int J Mol Sci 14(12):24560–24580
Ellis SR, Bruinen AL, Heeren RMA (2014) A critical evaluation of the current state-of-the-art in quantitative imaging mass spectrometry. Anal Bioanal Chem 406(5):1275–1289
Pirman DA, Yost RA (2011) Quantitative tandem mass spectrometric imaging of endogenous acetyl-l-carnitine from piglet brain tissue using an internal standard. Anal Chem 83(22):8575–8581
Takai N, Tanaka Y, Inazawa K, Saji H (2012) Quantitative analysis of pharmaceutical drug distribution in multiple organs by imaging mass spectrometry. Rapid Commun Mass Spectrom 26(13):1549–1556
Hamm G, Bonnel D, Legouffe R, Pamelard F, Delbos JM, Bouzom F, Stauber J (2012) Quantitative mass spectrometry imaging of propranolol and olanzapine using tissue extinction calculation as normalization factor. J Proteomics 75(16):4952–4961
Pirman DA, Reich RF, Kiss A, Heeren RMA, Yost RA (2013) Quantitative MALDI tandem mass spectrometric imaging of cocaine from brain tissue with a deuterated internal standard. Anal Chem 85(2):1081–1089
Nilsson A, Fehniger TE, Gustavsson L, Andersson M, Kenne K, Marko-Varga G, Andrén PE (2010) Fine mapping the spatial distribution and concentration of unlabeled drugs within tissue micro-compartments using imaging mass spectrometry. PLoS One 5(7):e11411
Groseclose MR, Castellino S (2013) A mimetic tissue model for the quantification of drug distributions by MALDI imaging mass spectrometry. Anal Chem 85(21):10099–10106
Takai N, Tanaka Y, Saji H (2014) Quantification of small molecule drugs in biological tissue sections by imaging mass spectrometry using surrogate tissue-based calibration standards. Mass Spectrom 3(1):A0025
Koeniger SL, Talaty N, Luo Y, Ready D, Voorbach M, Seifert T, Cepa S, Fagerland JA, Bouska J, Buck W, Johnson RW, Spanton S (2011) A quantitation method for mass spectrometry imaging. Rapid Commun Mass Spectrom 25(4):503–510
Hankin JA, Murphy RC (2010) Relationship between MALDI IMS intensity and measured quantity of selected phospholipids in rat brain sections. Anal Chem 82(20):8476–8484
Landgraf RR, Garrett TJ, Prieto Conaway MC, Calcutt NA, Stacpoole PW, Yost RA (2011) Considerations for quantification of lipids in nerve tissue using matrix-assisted laser desorption/ionization mass spectrometric imaging. Rapid Commun Mass Spectrom 25(20):3178–3184
Hankin JA, Barkley RM, Murphy RC (2007) Sublimation as a method of matrix application for mass spectrometric imaging. J Am Soc Mass Spectrom 18(9):1646–1652
Carter CL, McLeod CW, Bunch J (2011) Imaging of phospholipids in formalin fixed rat brain sections by matrix assisted laser desorption/ionization mass spectrometry. J Am Soc Mass Spectrom 22(11):1991–1998
Jackson SN, Wang HYJ, Woods AS (2005) Direct profiling of lipid distribution in brain tissue using MALDI-TOFMS. Anal Chem 77(14):4523–4527
Jackson SN, Wang HYJ, Woods AS, Ugarov M, Egan T, Schultz JA (2005) Direct tissue analysis of phospholipids in rat brain using MALDI-TOFMS and MALDI-ion mobility-TOFMS. J Am Soc Mass Spectrom 16(2):133–138
Mikawa S, Suzuki M, Fujimoto C, Sato K (2009) Imaging of phosphatidylcholines in the adult rat brain using MALDI-TOF MS. Neurosci Lett 451(1):45–49
Deininger SO, Cornett DS, Paape R, Becker M, Pineau C, Rauser S, Walch A, Wolski E (2011) Normalization in MALDI-TOF imaging datasets of proteins: practical considerations. Anal Bioanal Chem 401(1):167–181
Barnard T (1987) Rapid freezing techniques and cryoprotection of biomedical specimens. Scanning Microsc 1(3):1217–1224
Krafft C, Sobottka SB, Schackert G, Salzer R (2005) Near infrared Raman spectroscopic mapping of native brain tissue and intracranial tumors. Analyst 130(7):1070–1077
Dreissig I, Machill S, Salzer R, Krafft C (2009) Quantification of brain lipids by FTIR spectroscopy and partial least squares regression. Spectrochim Acta Part A Mol Biomol Spectrosc 71(5):2069–2075
Herculano-Houzel S (2009) The human brain in numbers: a linearly scaled-up primate brain. Front Human Neurosci 3:1–11
Petković M, Schiller J, Müller M, Benard S, Reichl S, Arnold K, Arnhold J (2001) Detection of individual phospholipids in lipid mixtures by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: phosphatidylcholine prevents the detection of further species. Anal Biochem 289(2):202–216
Acknowledgments
L. J. thanks the REFRACT project for funding (“Action de Recherche Concertée,” ULg, Belgium). R. L. is a postdoc fellow of the ULg Research Council. The FTMS instrument was acquired with European Funds for Regional Development (FEDER) and the FNRS.
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The authors have declared no conflict of interest.
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Published in the topical collection Mass Spectrometry Imaging with guest editors Andreas Römpp and Uwe Karst.
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Jadoul, L., Longuespée, R., Noël, A. et al. A spiked tissue-based approach for quantification of phosphatidylcholines in brain section by MALDI mass spectrometry imaging. Anal Bioanal Chem 407, 2095–2106 (2015). https://doi.org/10.1007/s00216-014-8232-7
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DOI: https://doi.org/10.1007/s00216-014-8232-7