Skip to main content

Spatial Metabolite Profiling by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging

  • Chapter
  • First Online:
Metabolomics: From Fundamentals to Clinical Applications

Part of the book series: Advances in Experimental Medicine and Biology ((PMISB,volume 965))

Abstract

Mass spectrometry imaging (MSI) is rapidly maturing as an advanced method for spatial metabolite profiling. Herein, we provide an introduction to MSI including types of instrumentation, detailed sample preparation, data collection, overview of data analysis steps, software, common standards, and new developments. Further, we provide an overview of MSI in the clinical space over the past 3 years where MSI has been deployed in diverse research areas including cancer, neurobiology, lipidomics, and metabolite profiling and mapping to name only a few. We provide several examples demonstrating the applicability of MSI to spatially profile metabolites in unique systems requiring special considerations outside of the norm.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 139.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 179.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

3D-MSI:

Three-dimensional mass spectrometry imaging

9-AA:

9-Aminoacridine

AP-MALDI:

Atmospheric pressure matrix-assisted laser desorption ionization

CHCA (or HCCA):

α-Cyano-4-hydroxycinnamic acid

Cer:

Ceramide

DAN:

1,5-Diaminonapthalene

DESI:

Desorption electrospray ionization

DHAP:

2,5-Dihydroxyacetophenone

DHB:

2,5-Dihydroxybenzoic acid

DMAN:

1,8-Bis(dimethylamino)naphthalene

FA:

Fatty acid

FFPE:

Formalin-fixed paraffin embedded

fNPs:

Functional iron nanoparticles

FT:

Fourier transform

FTICR:

Fourier transform ion cyclotron resonance

FT-IR:

Fourier transform infrared spectroscopy

HCA:

Hierarchical cluster analysis

Hex:

Hexose

IR:

Infrared

IR-MALDI:

Infrared matrix-assisted laser desorption ionization

ITO:

Indium tin oxide

kMSI:

Kinetic mass spectrometry imaging

LDI:

Laser desorption ionization

MALDI:

Matrix-assisted laser desorption ionization

MIPC:

Ceramide phosphoinositol

MRI:

Magnetic resonance imaging

MS:

Mass spectrometry

MSn :

Multistage tandem mass spectrometry

MSI:

Mass spectrometry imaging

MS/MS:

Tandem mass spectrometry

m/z :

Mass-to-charge ratio

NIMS:

Nanostructure-initiator mass spectrometry

OCT:

Optimal cutting temperature

PA:

Phosphatidic acid

PCA:

Principal component analysis

PC:

Phosphatidylcholine

PE:

Phosphatidylethanolamine

PG:

Phosphatidylglycerol

PI:

Phosphatidylinositol

PS:

Phosphatidylserine

ROI:

Region of interest

RP:

Resolving power

SIMS:

Secondary ion mass spectrometry

TIC:

Total ion chromatogram

TOF:

Time of flight

References

  1. Spengler B. Mass spectrometry imaging of biomolecular information. Anal Chem. 2015;87(1):64–82.

    Article  CAS  PubMed  Google Scholar 

  2. Chaurand P. Imaging mass spectrometry of thin tissue sections: a decade of collective efforts. J Proteomics. 2012;75(16):4883–92.

    Article  CAS  PubMed  Google Scholar 

  3. Jungmann JH, Heeren RM. Emerging technologies in mass spectrometry imaging. J Proteomics. 2012;75(16):5077–92.

    Article  CAS  PubMed  Google Scholar 

  4. Miura D, Fujimura Y, Wariishi H. In situ metabolomic mass spectrometry imaging: recent advances and difficulties. J Proteomics. 2012;75(16):5052–60.

    Article  CAS  PubMed  Google Scholar 

  5. Seeley EH, Caprioli RM. 3D imaging by mass spectrometry: a new frontier. Anal Chem. 2012;84(5):2105–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Gode D, Volmer DA. Lipid imaging by mass spectrometry – a review. Analyst. 2013;138(5):1289–315.

    Article  CAS  PubMed  Google Scholar 

  7. Norris JL, Caprioli RM. Analysis of tissue specimens by matrix-assisted laser desorption/ionization imaging mass spectrometry in biological and clinical research. Chem Rev. 2013;113(4):2309–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Rompp A, Spengler B. Mass spectrometry imaging with high resolution in mass and space. Histochem Cell Biol. 2013;139(6):759–83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Wu C, Dill AL, Eberlin LS, Cooks RG, Ifa DR. Mass spectrometry imaging under ambient conditions. Mass Spectrom Rev. 2013;32(3):218–43.

    Article  CAS  PubMed  Google Scholar 

  10. Shariatgorji M, Svenningsson P, Andren PE. Mass spectrometry imaging, an emerging technology in neuropsychopharmacology. Neuropsychopharmacology. 2014;39(1):34–49.

    Article  CAS  PubMed  Google Scholar 

  11. Addie RD, Balluff B, Bovee JV, Morreau H, McDonnell LA. Current state and future challenges of mass spectrometry imaging for clinical research. Anal Chem. 2015;87(13):6426–33.

    Article  CAS  PubMed  Google Scholar 

  12. Aichler M, Walch A. MALDI imaging mass spectrometry: current frontiers and perspectives in pathology research and practice. Lab Invest. 2015;95(4):422–31.

    Article  CAS  PubMed  Google Scholar 

  13. Chughtai K, Heeren RM. Mass spectrometric imaging for biomedical tissue analysis. Chem Rev. 2010;110(5):3237–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Boughton BA, Thinagaran D, Sarabia D, Bacic A, Roessner U. Mass spectrometry imaging for plant biology: a review. Phytochem Rev. 2016;15(3):445–88.

    Article  CAS  PubMed  Google Scholar 

  15. Sumner LW, Lei Z, Nikolau BJ, Saito K. Modern plant metabolomics: advanced natural product gene discoveries, improved technologies, and future prospects. Nat Prod Rep. 2015;32(2):212–29.

    Article  CAS  PubMed  Google Scholar 

  16. Van de Plas R, Yang J, Spraggins J, Caprioli RM. Image fusion of mass spectrometry and microscopy: a multimodality paradigm for molecular tissue mapping. Nat Methods. 2015;12(4):366–72.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Spengler B, Kaufmann R. “Development of a new scanning UV-laser microprobe for Ion imaging and confocal microscopy”, proceedings of the 42nd ASMS conference on mass spectrometry and allied topics: May 29-june 3, 1994. Chicago: ASMS; 1994.

    Google Scholar 

  18. Caprioli RM, Farmer TB, Gile J. Molecular imaging of biological samples: localization of peptides and proteins using MALDI-TOF MS. Anal Chem. 1997;69(23):4751–60.

    Article  CAS  PubMed  Google Scholar 

  19. Thiery-Lavenant G, Zavalin AI, Caprioli RM. Targeted multiplex imaging mass spectrometry in transmission geometry for subcellular spatial resolution. J Am Soc Mass Spectrom. 2013;24(4):609–14.

    Article  CAS  PubMed  Google Scholar 

  20. Korte AR, Yandeau-Nelson MD, Nikolau BJ, Lee YJ. Subcellular-level resolution MALDI-MS imaging of maize leaf metabolites by MALDI-linear ion trap-Orbitrap mass spectrometer. Anal Bioanal Chem. 2015;407(8):2301–9.

    Article  CAS  PubMed  Google Scholar 

  21. Krasny L, Hoffmann F, Ernst G, Trede D, Alexandrov T, Havlicek V, et al. Spatial segmentation of MALDI FT-ICR MSI data: a powerful tool to explore the head and neck tumor in situ lipidome. J Am Soc Mass Spectrom. 2015;26(1):36–43.

    Article  CAS  PubMed  Google Scholar 

  22. Steurer S, Borkowski C, Odinga S, Buchholz M, Koop C, Huland H, et al. MALDI mass spectrometric imaging based identification of clinically relevant signals in prostate cancer using large-scale tissue microarrays. Int J Cancer. 2013;133(4):920–8.

    Article  CAS  PubMed  Google Scholar 

  23. Nemes P, Barton AA, Vertes A. Three-dimensional imaging of metabolites in tissues under ambient conditions by laser ablation electrospray ionization mass spectrometry. Anal Chem. 2009;81(16):6668–75.

    Article  CAS  PubMed  Google Scholar 

  24. Ye H, Greer T, Li L. From pixel to voxel: a deeper view of biological tissue by 3D mass spectral imaging. Bioanalysis. 2011;3(3):313–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Lanekoff I, Burnum-Johnson K, Thomas M, Cha J, Dey SK, Yang P, et al. Three-dimensional imaging of lipids and metabolites in tissues by nanospray desorption electrospray ionization mass spectrometry. Anal Bioanal Chem. 2015;407(8):2063–71.

    Article  CAS  PubMed  Google Scholar 

  26. Monge ME, Harris GA, Dwivedi P, Fernandez FM. Mass spectrometry: recent advances in direct open air surface sampling/ionization. Chem Rev. 2013;113(4):2269–308.

    Article  CAS  PubMed  Google Scholar 

  27. Stauber J, MacAleese L, Franck J, Claude E, Snel M, Kaletas BK, et al. On-tissue protein identification and imaging by MALDI-ion mobility mass spectrometry. J Am Soc Mass Spectrom. 2010;21(3):338–47.

    Article  CAS  PubMed  Google Scholar 

  28. Jackson SN, Barbacci D, Egan T, Lewis EK, Schultz JA, Woods AS. MALDI-ion mobility mass spectrometry of lipids in negative ion mode. Anal Methods. 2014;6(14):5001–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Uetrecht C, Rose RJ, van Duijn E, Lorenzen K, Heck AJR. Ion mobility mass spectrometry of proteins and protein assemblies. Chem Soc Rev. 2010;39(5):1633–55.

    Article  CAS  PubMed  Google Scholar 

  30. Liu FC, Kirk SR, Bleiholder C. On the structural denaturation of biological analytes in trapped ion mobility spectrometry ─ mass spectrometry. Analyst. 2016;141(12):3722–30.

    Article  CAS  PubMed  Google Scholar 

  31. Kyle JE, Zhang X, Weitz KK, Monroe ME, Ibrahim YM, Moore RJ, et al. Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry. Analyst. 2016;141(5):1649–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Groessl M, Graf S, Knochenmuss R. High resolution ion mobility-mass spectrometry for separation and identification of isomeric lipids. Analyst. 2015;140(20):6904–11.

    Article  CAS  PubMed  Google Scholar 

  33. Goodwin RJ, Dungworth JC, Cobb SR, Pitt AR. Time-dependent evolution of tissue markers by MALDI-MS imaging. Proteomics. 2008;8(18):3801–8.

    Article  CAS  PubMed  Google Scholar 

  34. Goodwin RJ, Lang AM, Allingham H, Boren M, Pitt AR. Stopping the clock on proteomic degradation by heat treatment at the point of tissue excision. Proteomics. 2010;10(9):1751–61.

    Article  CAS  PubMed  Google Scholar 

  35. Goodwin RJ, Iverson SL, Andren PE. The significance of ambient-temperature on pharmaceutical and endogenous compound abundance and distribution in tissues sections when analyzed by matrix-assisted laser desorption/ionization mass spectrometry imaging. Rapid Commun Mass Spectrom. 2012;26(5):494–8.

    Article  CAS  PubMed  Google Scholar 

  36. Marques JV, Dalisay DS, Yang H, Lee C, Davin LB, Lewis NG. A multi-omics strategy resolves the elusive nature of alkaloids in Podophyllum species. Mol Biosyst. 2014;10(11):2838–49.

    Article  CAS  PubMed  Google Scholar 

  37. Horn PJ, Silva JE, Anderson D, Fuchs J, Borisjuk L, Nazarenus TJ, et al. Imaging heterogeneity of membrane and storage lipids in transgenic Camelina sativa seeds with altered fatty acid profiles. Plant J. 2013;76(1):138–50.

    CAS  PubMed  Google Scholar 

  38. Ye H, Gemperline E, Venkateshwaran M, Chen R, Delaux PM, Howes-Podoll M, et al. MALDI mass spectrometry-assisted molecular imaging of metabolites during nitrogen fixation in the Medicago truncatula-Sinorhizobium meliloti symbiosis. Plant J. 2013;75(1):130–45.

    Article  CAS  PubMed  Google Scholar 

  39. Gemperline E, Li L. MALDI-mass spectrometric imaging for the investigation of metabolites in Medicago truncatula root nodules. J Vis Exp. 2014(85). doi:10.3791/51434.

  40. Horn PJ, Sturtevant D, Chapman KD. Modified oleic cottonseeds show altered content, composition and tissue-specific distribution of triacylglycerol molecular species. Biochimie. 2014;96:28–36.

    Article  CAS  PubMed  Google Scholar 

  41. Korte AR, Lee YJ. MALDI-MS analysis and imaging of small molecule metabolites with 1,5-diaminonaphthalene (DAN). J Mass Spectrom. 2014;49(8):737–41.

    Article  CAS  PubMed  Google Scholar 

  42. Bencivenni M, Faccini A, Zecchi R, Boscaro F, Moneti G, Dossena A, et al. Electrospray MS and MALDI imaging show that non-specific lipid-transfer proteins (LTPs) in tomato are present as several isoforms and are concentrated in seeds. J Mass Spectrom. 2014;49(12):1264–71.

    Article  CAS  PubMed  Google Scholar 

  43. Yoshimura Y, Zaima N, Moriyama T, Kawamura Y. Different localization patterns of anthocyanin species in the pericarp of black rice revealed by imaging mass spectrometry. PLoS One. 2012;7(2):e31285.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schwartz SA, Reyzer ML, Caprioli RM. Direct tissue analysis using matrix-assisted laser desorption/ionization mass spectrometry: practical aspects of sample preparation. J Mass Spectrom. 2003;38(7):699–708.

    Article  CAS  PubMed  Google Scholar 

  45. Gorzolka K, Kölling J, Nattkemper TW, Niehaus K. Spatio-temporal metabolite profiling of the barley germination process by MALDI MS imaging. PLoS One. 2016;11(3):e0150208.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Kawamoto T, Kawamoto K. Preparation of thin frozen sections from nonfixed and undecalcified hard tissues using Kawamot’s film method (2012). In: Hilton JM, editor. Skeletal development and repair: methods and protocols. Totowa: Humana Press; 2014. p. 149–64.

    Chapter  Google Scholar 

  47. Kawamoto T. Use of a new adhesive film for the preparation of multi-purpose fresh-frozen sections from hard tissues, whole-animals, insects and plants. Arch Histol Cytol. 2003;66(2):123–43.

    Article  PubMed  Google Scholar 

  48. Powers TW, Neely BA, Shao Y, Tang H, Troyer DA, Mehta AS, et al. MALDI imaging mass spectrometry profiling of N-glycans in formalin-fixed paraffin embedded clinical tissue blocks and tissue microarrays. PLoS One. 2014;9(9), e106255.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Ly A, Buck A, Balluff B, Sun N, Gorzolka K, Feuchtinger A, et al. High-mass-resolution MALDI mass spectrometry imaging of metabolites from formalin-fixed paraffin-embedded tissue. Nat Protoc. 2016;11(8):1428–43.

    Article  PubMed  Google Scholar 

  50. Buck A, Balluff B, Voss A, Langer R, Zitzelsberger H, Aichler M, et al. How suitable is matrix-assisted laser desorption/ionization-time-of-flight for metabolite imaging from clinical formalin-fixed and paraffin-embedded tissue samples in comparison to matrix-assisted laser desorption/ionization-Fourier transform ion cyclotron resonance mass spectrometry? Anal Chem. 2016;88(10):5281–9.

    Article  CAS  PubMed  Google Scholar 

  51. Buck A, Ly A, Balluff B, Sun N, Gorzolka K, Feuchtinger A, et al. High-resolution MALDI-FT-ICR MS imaging for the analysis of metabolites from formalin-fixed, paraffin-embedded clinical tissue samples. J Pathol. 2015;237(1):123–32.

    Article  CAS  PubMed  Google Scholar 

  52. Undheim EAB, Sunagar K, Hamilton BR, Jones A, Venter DJ, Fry BG, et al. Multifunctional warheads: diversification of the toxin arsenal of centipedes via novel multidomain transcripts. J Proteomics. 2014;102:1–10.

    Article  CAS  PubMed  Google Scholar 

  53. Burrell M, Earnshaw C, Clench M. Imaging matrix assisted laser desorption ionization mass spectrometry: a technique to map plant metabolites within tissues at high spatial resolution. J Exp Bot. 2007;58(4):757–63.

    Article  CAS  PubMed  Google Scholar 

  54. Patterson NH, Thomas A, Chaurand P. Monitoring time-dependent degradation of phospholipids in sectioned tissues by MALDI imaging mass spectrometry. J Mass Spectrom. 2014;49(7):622–7.

    Article  CAS  PubMed  Google Scholar 

  55. Seeley EH, Oppenheimer SR, Mi D, Chaurand P, Caprioli RM. Enhancement of protein sensitivity for MALDI imaging mass spectrometry after chemical treatment of tissue sections. J Am Soc Mass Spectrom. 2008;19(8):1069–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. van Hove ER, Smith DF, Fornai L, Glunde K, Heeren RM. An alternative paper based tissue washing method for mass spectrometry imaging: localized washing and fragile tissue analysis. J Am Soc Mass Spectrom. 2011;22(10):1885–90.

    Article  PubMed  CAS  Google Scholar 

  57. Angel PM, Spraggins JM, Baldwin HS, Caprioli R. Enhanced sensitivity for high spatial resolution lipid analysis by negative ion mode matrix assisted laser desorption ionization imaging mass spectrometry. Anal Chem. 2012;84(3):1557–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Hankin JA, Barkley RM, Murphy RC. Sublimation as a method of matrix application for mass spectrometric imaging. J Am Soc Mass Spectrom. 2007;18(9):1646–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Baluya DL, Garrett TJ, Yost RA. Automated MALDI matrix deposition method with inkjet printing for imaging mass spectrometry. Anal Chem. 2007;79(17):6862–7.

    Article  CAS  PubMed  Google Scholar 

  60. Becker L, Carre V, Poutaraud A, Merdinoglu D, Chaimbault P. MALDI mass spectrometry imaging for the simultaneous location of resveratrol, pterostilbene and viniferins on grapevine leaves. Molecules. 2014;19(7):10587–600.

    Article  PubMed  CAS  Google Scholar 

  61. Meriaux C, Franck J, Wisztorski M, Salzet M, Fournier I. Liquid ionic matrixes for MALDI mass spectrometry imaging of lipids. J Proteomics. 2010;73(6):1204–18.

    Article  CAS  PubMed  Google Scholar 

  62. Anderson DM, Floyd KA, Barnes S, Clark JM, Clark JI, McHaourab H, et al. A method to prevent protein delocalization in imaging mass spectrometry of non-adherent tissues: application to small vertebrate lens imaging. Anal Bioanal Chem. 2015;407(8):2311–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Fraser PD, Enfissi EM, Goodfellow M, Eguchi T, Bramley PM. Metabolite profiling of plant carotenoids using the matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Plant J. 2007;49(3):552–64.

    Article  CAS  PubMed  Google Scholar 

  64. Debois D, Jourdan E, Smargiasso N, Thonart P, De Pauw E, Ongena M. Spatiotemporal monitoring of the antibiome secreted by bacillus biofilms on plant roots using MALDI mass spectrometry imaging. Anal Chem. 2014;86(9):4431–8.

    Article  CAS  PubMed  Google Scholar 

  65. Franceschi P, Dong Y, Strupat K, Vrhovsek U, Mattivi F. Combining intensity correlation analysis and MALDI imaging to study the distribution of flavonols and dihydrochalcones in golden delicious apples. J Exp Bot. 2012;63(3):1123–33.

    Article  CAS  PubMed  Google Scholar 

  66. Gemperline E, Li L. MALDI-Mass Spectrometric Imaging of Endogenous Metabolites in Biological Systems. eLS, Wiley; 2014. doi:10.1002/9780470015902.a0023207.

  67. Horka P, Vrkoslav V, Hanus R, Peckova K, Cvacka J. New MALDI matrices based on lithium salts for the analysis of hydrocarbons and wax esters. J Mass Spectrom. 2014;49(7):628–38.

    Article  CAS  PubMed  Google Scholar 

  68. Shroff R, Schramm K, Jeschke V, Nemes P, Vertes A, Gershenzon J, et al. Quantification of plant surface metabolites by matrix-assisted laser desorption-ionization mass spectrometry imaging: glucosinolates on Arabidopsis thaliana leaves. Plant J. 2015;81(6):961–72.

    Article  CAS  PubMed  Google Scholar 

  69. Horn PJ, Korte AR, Neogi PB, Love E, Fuchs J, Strupat K, et al. Spatial mapping of lipids at cellular resolution in embryos of cotton. Plant Cell. 2012;24(2):622–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Cha S, Zhang H, Ilarslan HI, Wurtele ES, Brachova L, Nikolau BJ, et al. Direct profiling and imaging of plant metabolites in intact tissues by using colloidal graphite-assisted laser desorption ionization mass spectrometry. Plant J. 2008;55(2):348–60.

    Article  CAS  PubMed  Google Scholar 

  71. Wang X, Han J, Chou A, Yang J, Pan J, Borchers CH. Hydroxyflavones as a new family of matrices for MALDI tissue imaging. Anal Chem. 2013;85(15):7566–73.

    Article  CAS  PubMed  Google Scholar 

  72. Yang H, Liu N, Qiu X, Liu S. A New method for analysis of disulfide-containing proteins by matrix-assisted laser desorption ionization (MALDI) mass spectrometry. J Am Soc Mass Spectrom. 2009;20(12):2284–93.

    Article  CAS  PubMed  Google Scholar 

  73. Molin L, Seraglia R, Dani FR, Moneti G, Traldi P. The double nature of 1,5-diaminonaphthalene as matrix-assisted laser desorption/ionization matrix: some experimental evidence of the protonation and reduction mechanisms. Rapid Commun Mass Spectrom. 2011;25(20):3091–6.

    Article  CAS  PubMed  Google Scholar 

  74. Robichaud G, Barry J, Muddiman D. IR-MALDESI mass spectrometry imaging of biological tissue sections using ice as a matrix. J Am Soc Mass Spectrom. 2014;25(3):319–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dufresne M, Thomas A, Breault-Turcot J, Masson J-F, Chaurand P. Silver-assisted laser desorption ionization for high spatial resolution imaging mass spectrometry of olefins from thin tissue sections. Anal Chem. 2013;85(6):3318–24.

    Article  CAS  PubMed  Google Scholar 

  76. Jackson SN, Baldwin K, Muller L, Womack VM, Schultz JA, Balaban C, et al. Imaging of lipids in rat heart by MALDI-MS with silver nanoparticles. Anal Bioanal Chem. 2014;406(5):1377–86.

    Article  CAS  PubMed  Google Scholar 

  77. Muller L, Kailas A, Jackson SN, Roux A, Barbacci DC, Schultz JA, et al. Lipid imaging within the normal rat kidney using silver nanoparticles by matrix-assisted laser desorption/ionization mass spectrometry. Kidney Int. 2015;88(1):186–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wu HP, Yu CJ, Lin CY, Lin YH, Tseng WL. Gold nanoparticles as assisted matrices for the detection of biomolecules in a high-salt solution through laser desorption/ionization mass spectrometry. J Am Soc Mass Spectrom. 2009;20(5):875–82.

    Article  CAS  PubMed  Google Scholar 

  79. Jackson SN, Ugarov M, Egan T, Post JD, Langlais D, Albert Schultz J, et al. MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue. J Mass Spectrom. 2007;42(8):1093–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Taira S, Sugiura Y, Moritake S, Shimma S, Ichiyanagi Y, Setou M. Nanoparticle-assisted laser desorption/ionization based mass imaging with cellular resolution. Anal Chem. 2008;80(12):4761–6.

    Article  CAS  PubMed  Google Scholar 

  81. Schramm T, Hester A, Klinkert I, Both JP, Heeren RM, Brunelle A, et al. imzML-a common data format for the flexible exchange and processing of mass spectrometry imaging data. J Proteomics. 2012;75(16):5106–10.

    Article  CAS  PubMed  Google Scholar 

  82. Klinkert I, Chughtai K, Ellis SR, Heeren RMA. Methods for full resolution data exploration and visualization for large 2D and 3D mass spectrometry imaging datasets. Int J Mass Spectrom. 2014;362:40–7.

    Article  CAS  Google Scholar 

  83. Horn PJ, Chapman KD. Metabolite Imager: customized spatial analysis of metabolite distributions in mass spectrometry imaging. Metabolomics. 2013;10(2):337–48.

    Article  CAS  Google Scholar 

  84. Paschke C, Leisner A, Hester A, Maass K, Guenther S, Bouschen W, et al. Mirion--a software package for automatic processing of mass spectrometric images. J Am Soc Mass Spectrom. 2013;24(8):1296–306.

    Article  CAS  PubMed  Google Scholar 

  85. Robichaud G, Garrard KP, Barry JA, Muddiman DC. MSiReader: an open-source interface to view and analyze high resolving power MS imaging files on Matlab platform. J Am Soc Mass Spectrom. 2013;24(5):718–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Rübel O, Greiner A, Cholia S, Louie K, Bethel EW, Northen TR, et al. OpenMSI: a high-performance web-based platform for mass spectrometry imaging. Anal Chem. 2013;85(21):10354–61.

    Article  PubMed  CAS  Google Scholar 

  87. Bemis KD, Harry A, Eberlin LS, Ferreira C, van de Ven SM, Mallick P, et al. Cardinal: an R package for statistical analysis of mass spectrometry-based imaging experiments. Bioinformatics. 2015;31(14):2418–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Parry RM, Galhena AS, Gamage CM, Bennett RV, Wang MD, Fernández FM. OmniSpect: an open MATLAB-based tool for visualization and analysis of matrix-assisted laser desorption/ionization and desorption electrospray ionization mass spectrometry images. J Am Soc Mass Spectrom. 2013;24(4):646–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Källback P, Nilsson A, Shariatgorji M, Andrén PE. MsIQuant – quantitation software for mass spectrometry imaging enabling fast access, visualization, and analysis of large data sets. Anal Chem. 2016;88(8):4346–53.

    Article  PubMed  CAS  Google Scholar 

  90. Takahashi K, Kozuka T, Anegawa A, Nagatani A, Mimura T. Development and application of a high-resolution imaging mass spectrometer for the study of plant tissues. Plant Cell Physiol. 2015;56(7):1329–38.

    Article  CAS  PubMed  Google Scholar 

  91. Gamboa-Becerra R, Ramírez-Chávez E, Molina-Torres J, Winkler R. MSI.R scripts reveal volatile and semi-volatile features in low-temperature plasma mass spectrometry imaging (LTP-MSI) of chilli (Capsicum annuum). Anal Bioanal Chem. 2015;407(19):5673–84.

    Article  CAS  PubMed  Google Scholar 

  92. Gibb S, Strimmer K. MALDIquant: a versatile R package for the analysis of mass spectrometry data. Bioinformatics. 2012;28(17):2270–1.

    Article  CAS  PubMed  Google Scholar 

  93. Alexandrov T. MALDI imaging mass spectrometry: statistical data analysis and current computational challenges. BMC Bioinformatics. 2012;13 Suppl 16:S11.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Alexandrov T, Chernyavsky I, Becker M, von Eggeling F, Nikolenko S. Analysis and interpretation of imaging mass spectrometry data by clustering mass-to-charge images according to their spatial similarity. Anal Chem. 2013;85(23):11189–95.

    Article  CAS  PubMed  Google Scholar 

  95. Norris JL, Cornett DS, Mobley JA, Andersson M, Seeley EH, Chaurand P, et al. Processing MALDI mass spectra to improve mass spectral direct tissue analysis. Int J Mass Spectrom. 2007;260(2–3):212–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Franceschi P, Wehrens R. Self-organizing maps: a versatile tool for the automatic analysis of untargeted imaging datasets. Proteomics. 2014;14(7–8):853–61.

    Article  CAS  PubMed  Google Scholar 

  97. Fonville JM, Carter CL, Pizarro L, Steven RT, Palmer AD, Griffiths RL, et al. Hyperspectral visualization of mass spectrometry imaging data. Anal Chem. 2013;85(3):1415–23.

    Article  CAS  PubMed  Google Scholar 

  98. Wijetunge CD, Saeed I, Halgamuge SK, Boughton B, Roessner U, editors. Unsupervised learning for exploring MALDI imaging mass spectrometry ‘omics’ data. Information and Automation for Sustainability (ICIAfS), 2014 7th International Conference on; 22–24 Dec. 2014.

    Google Scholar 

  99. Andersson M, Groseclose MR, Deutch AY, Caprioli RM. Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction. Nat Methods. 2008;5(1):101–8.

    Article  CAS  PubMed  Google Scholar 

  100. Oetjen J, Veselkov K, Watrous J, McKenzie JS, Becker M, Hauberg-Lotte L, et al. Benchmark datasets for 3D MALDI- and DESI-imaging mass spectrometry. Gigascience. 2015;4:20.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Weaver EM, Hummon AB, Keithley RB. Chemometric analysis of MALDI mass spectrometric images of three-dimensional cell culture systems. Anal Methods. 2015;7(17):7208–19.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Fletcher JS, Lockyer NP, Vickerman JC. Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions. Mass Spectrom Rev. 2011;30(1):142–74.

    Article  CAS  PubMed  Google Scholar 

  103. Fletcher JS, Vickerman JC, Winograd N. Label free biochemical 2D and 3D imaging using secondary ion mass spectrometry. Curr Opin Chem Biol. 2011;15(5):733–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. McDonnell LA, Rompp A, Balluff B, Heeren RM, Albar JP, Andren PE, et al. Discussion point: reporting guidelines for mass spectrometry imaging. Anal Bioanal Chem. 2015;407(8):2035–45.

    Article  CAS  PubMed  Google Scholar 

  105. Creek DJ, Dunn WB, Fiehn O, Griffin JL, Hall RD, Lei Z, et al. Metabolite identification: are you sure? And how do your peers gauge your confidence? Metabolomics. 2014;10(3):350–3.

    Article  CAS  Google Scholar 

  106. Rompp A, Wang R, Albar JP, Urbani A, Hermjakob H, Spengler B, et al. A public repository for mass spectrometry imaging data. Anal Bioanal Chem. 2015;407(8):2027–33.

    Article  PubMed  CAS  Google Scholar 

  107. Anderson DM, Ablonczy Z, Koutalos Y, Spraggins J, Crouch RK, Caprioli RM, et al. High resolution MALDI imaging mass spectrometry of retinal tissue lipids. J Am Soc Mass Spectrom. 2014;25(8):1394–403.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Fernandez R, Lage S, Abad-Garcia B, Barcelo-Coblijn G, Teres S, Lopez DH, et al. Analysis of the lipidome of xenografts using MALDI-IMS and UHPLC-ESI-QTOF. J Am Soc Mass Spectrom. 2014;25(7):1237–46.

    Article  CAS  PubMed  Google Scholar 

  109. Martin-Lorenzo M, Balluff B, Maroto AS, Carreira RJ, van Zeijl RJ, Gonzalez-Calero L, et al. Molecular anatomy of ascending aorta in atherosclerosis by MS imaging: specific lipid and protein patterns reflect pathology. J Proteomics. 2015;126:245–51.

    Article  CAS  PubMed  Google Scholar 

  110. Roux A, Muller L, Jackson SN, Post J, Baldwin K, Hoffer B, et al. Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury. J Neurosci Methods. 2016. doi:10.1016/j.jneumeth.2016.02.004.

    PubMed  Google Scholar 

  111. Ruh H, Salonikios T, Fuchser J, Schwartz M, Sticht C, Hochheim C, et al. MALDI imaging MS reveals candidate lipid markers of polycystic kidney disease. J Lipid Res. 2013;54(10):2785–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Uzbekova S, Elis S, Teixeira-Gomes AP, Desmarchais A, Maillard V, Labas V. MALDI mass spectrometry imaging of lipids and gene expression reveals differences in fatty acid metabolism between follicular compartments in porcine ovaries. Biology (Basel). 2015;4(1):216–36.

    Google Scholar 

  113. Chatterji B, Dickhut C, Mielke S, Kruger J, Just I, Glage S, et al. MALDI imaging mass spectrometry to investigate endogenous peptides in an animal model of Usher’s disease. Proteomics. 2014;14(13–14):1674–87.

    Article  CAS  PubMed  Google Scholar 

  114. Gustafsson OJ, Eddes JS, Meding S, McColl SR, Oehler MK, Hoffmann P. Matrix-assisted laser desorption/ionization imaging protocol for in situ characterization of tryptic peptide identity and distribution in formalin-fixed tissue. Rapid Commun Mass Spectrom. 2013;27(6):655–70.

    Article  CAS  PubMed  Google Scholar 

  115. Hunt NJ, Phillips L, Waters KA, Machaalani R. Proteomic MALDI-TOF/TOF-IMS examination of peptide expression in the formalin fixed brainstem and changes in sudden infant death syndrome infants. J Proteomics. 2016;138:48–60.

    Article  CAS  PubMed  Google Scholar 

  116. Ljungdahl A, Hanrieder J, Bergquist J, Andersson M. Analysis of neuropeptides by MALDI imaging mass spectrometry. Methods Mol Biol. 2013;1023:121–36.

    Article  CAS  PubMed  Google Scholar 

  117. Meding S, Martin K, Gustafsson OJ, Eddes JS, Hack S, Oehler MK, et al. Tryptic peptide reference data sets for MALDI imaging mass spectrometry on formalin-fixed ovarian cancer tissues. J Proteome Res. 2013;12(1):308–15.

    Article  CAS  PubMed  Google Scholar 

  118. Park KM, Moon JH, Kim KP, Lee SH, Kim MS. Relative quantification in imaging of a peptide on a mouse brain tissue by matrix-assisted laser desorption ionization. Anal Chem. 2014;86(10):5131–5.

    Article  CAS  PubMed  Google Scholar 

  119. Sosnowski P, Zera T, Wilenska B, Szczepanska-Sadowska E, Misicka A. Imaging and identification of endogenous peptides from rat pituitary embedded in egg yolk. Rapid Commun Mass Spectrom. 2015;29(4):327–35.

    Article  CAS  PubMed  Google Scholar 

  120. Winderbaum LJ, Koch I, Gustafsson OJR, Meding S, Hoffmann P. Feature extraction for proteomics imaging mass spectrometry data. Ann Appl Statistics. 2015;9(4):1973–96.

    Article  Google Scholar 

  121. Anderson DM, Van de Plas R, Rose KL, Hill S, Schey KL, Solga AC, et al. 3-D imaging mass spectrometry of protein distributions in mouse Neurofibromatosis 1 (NF1)-associated optic glioma. J Proteomics. 2016. doi:10.1016/j.jprot.2016.02.004.

    PubMed  Google Scholar 

  122. Spraggins JM, Rizzo DG, Moore JL, Noto MJ, Skaar EP, Caprioli RM. Next-generation technologies for spatial proteomics: integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis. Proteomics. 2016;16(11–12):1678–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Undheim EA, Hamilton BR, Kurniawan ND, Bowlay G, Cribb BW, Merritt DJ, et al. Production and packaging of a biological arsenal: evolution of centipede venoms under morphological constraint. Proc Natl Acad Sci U S A. 2015;112(13):4026–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. He J, Luo Z, Huang L, He J, Chen Y, Rong X, et al. Ambient mass spectrometry imaging metabolomics method provides novel insights into the action mechanism of drug candidates. Anal Chem. 2015;87(10):5372–9.

    Article  CAS  PubMed  Google Scholar 

  125. Wijetunge CD, Saeed I, Boughton BA, Spraggins JM, Caprioli RM, Bacic A, et al. EXIMS: an improved data analysis pipeline based on a new peak picking method for EXploring Imaging Mass Spectrometry data. Bioinformatics. 2015;31(19):3198–206.

    Article  CAS  PubMed  Google Scholar 

  126. Zhao YY, Miao H, Cheng XL, Wei F. Lipidomics: Novel insight into the biochemical mechanism of lipid metabolism and dysregulation-associated disease. Chem Biol Interact. 2015;240:220–38.

    Article  CAS  PubMed  Google Scholar 

  127. Barry JA, Robichaud G, Bokhart MT, Thompson C, Sykes C, Kashuba AD, et al. Mapping antiretroviral drugs in tissue by IR-MALDESI MSI coupled to the Q Exactive and comparison with LC-MS/MS SRM assay. J Am Soc Mass Spectrom. 2014;25(12):2038–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Bianga J, Bouslimani A, Bec N, Quenet F, Mounicou S, Szpunar J, et al. Complementarity of MALDI and LA ICP mass spectrometry for platinum anticancer imaging in human tumor. Metallomics. 2014;6(8):1382–6.

    Article  CAS  PubMed  Google Scholar 

  129. Huber K, Aichler M, Sun N, Buck A, Li Z, Fernandez IE, et al. A rapid ex vivo tissue model for optimising drug detection and ionisation in MALDI imaging studies. Histochem Cell Biol. 2014;142(4):361–71.

    Article  CAS  PubMed  Google Scholar 

  130. Huber K, Feuchtinger A, Borgmann DM, Li Z, Aichler M, Hauck SM, et al. Novel approach of MALDI drug imaging, immunohistochemistry, and digital image analysis for drug distribution studies in tissues. Anal Chem. 2014;86(21):10568–75.

    Article  CAS  PubMed  Google Scholar 

  131. Salphati L, Shahidi-Latham S, Quiason C, Barck K, Nishimura M, Alicke B, et al. Distribution of the phosphatidylinositol 3-kinase inhibitors Pictilisib (GDC-0941) and GNE-317 in U87 and GS2 intracranial glioblastoma models-assessment by matrix-assisted laser desorption ionization imaging. Drug Metab Dispos. 2014;42(7):1110–6.

    Article  PubMed  CAS  Google Scholar 

  132. Shariatgorji M, Nilsson A, Goodwin RJ, Kallback P, Schintu N, Zhang X, et al. Direct targeted quantitative molecular imaging of neurotransmitters in brain tissue sections. Neuron. 2014;84(4):697–707.

    Article  CAS  PubMed  Google Scholar 

  133. Connell JJ, Sugihara Y, Torok S, Dome B, Tovari J, Fehniger TE, et al. Localization of sunitinib in in vivo animal and in vitro experimental models by MALDI mass spectrometry imaging. Anal Bioanal Chem. 2015;407(8):2245–53.

    Article  CAS  PubMed  Google Scholar 

  134. Kamata T, Shima N, Sasaki K, Matsuta S, Takei S, Katagi M, et al. Time-course mass spectrometry imaging for depicting drug incorporation into hair. Anal Chem. 2015;87(11):5476–81.

    Article  CAS  PubMed  Google Scholar 

  135. Shobo A, Bratkowska D, Baijnath S, Naiker S, Bester LA, Singh SD, et al. Visualization of time-dependent distribution of rifampicin in rat brain using MALDI MSI and quantitative LCMS/MS. Assay Drug Dev Technol. 2015;13(5):277–84.

    Article  CAS  PubMed  Google Scholar 

  136. Fujiwara Y, Furuta M, Manabe S, Koga Y, Yasunaga M, Matsumura Y. Imaging mass spectrometry for the precise design of antibody-drug conjugates. Sci Rep. 2016;6:24954.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Goodwin RJ, Nilsson A, Mackay CL, Swales JG, Johansson MK, Billger M, et al. Exemplifying the screening power of mass spectrometry imaging over label-based technologies for simultaneous monitoring of drug and metabolite distributions in tissue sections. J Biomol Screen. 2016;21(2):187–93.

    Article  CAS  PubMed  Google Scholar 

  138. Hayasaka T. Application of imaging mass spectrometry for drug discovery. Yakugaku Zasshi: J Pharm Soc Japan. 2016;136(2):163–70.

    Article  CAS  Google Scholar 

  139. Sun N, Fernandez IE, Wei M, Wu Y, Aichler M, Eickelberg O, et al. Pharmacokinetic and pharmacometabolomic study of pirfenidone in normal mouse tissues using high mass resolution MALDI-FTICR-mass spectrometry imaging. Histochem Cell Biol. 2016;145(2):201–11.

    Article  CAS  PubMed  Google Scholar 

  140. Yarnold JE, Hamilton BR, Welsh DT, Pool GF, Venter DJ, Carroll AR. High resolution spatial mapping of brominated pyrrole-2-aminoimidazole alkaloids distributions in the marine sponge Stylissa flabellata via MALDI-mass spectrometry imaging. Mol Biosyst. 2012;8(9):2249–59.

    Article  CAS  PubMed  Google Scholar 

  141. Louie KB, Bowen BP, McAlhany S, Huang Y, Price JC, Mao JH, et al. Mass spectrometry imaging for in situ kinetic histochemistry. Sci Rep. 2013;3:1656.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Seaman C, Flinders B, Eijkel G, Heeren RM, Bricklebank N, Clench MR. “Afterlife experiment”: use of MALDI-MS and SIMS imaging for the study of the nitrogen cycle within plants. Anal Chem. 2014;86(20):10071–7.

    Article  CAS  PubMed  Google Scholar 

  143. Hanrieder J, Karlsson O, Brittebo EB, Malmberg P, Ewing AG. Probing the lipid chemistry of neurotoxin-induced hippocampal lesions using multimodal imaging mass spectrometry. Surf Interface Anal. 2014;46(S1):375–8.

    Article  CAS  Google Scholar 

  144. Chughtai S, Chughtai K, Cillero-Pastor B, Kiss A, Agrawal P, MacAleese L, et al. A multimodal mass spectrometry imaging approach for the study of musculoskeletal tissues. Int J Mass Spectrom. 2012;325–327:150–60.

    Article  CAS  Google Scholar 

  145. Ogrinc Potočnik N, Škrášková K, Flinders B, Pelicon P, Heeren RMA. Gold sputtered fiducial markers for combined secondary ion mass spectrometry and MALDI imaging of tissue samples. Anal Chem. 2014;86(14):6781–5.

    Article  PubMed  CAS  Google Scholar 

  146. Amstalden van Hove ER, Blackwell TR, Klinkert I, Eijkel GB, Heeren RMA, Glunde K. Multimodal mass spectrometric imaging of small molecules reveals distinct spatio-molecular signatures in differentially metastatic breast tumor models. Cancer Res. 2010;70(22):9012–21.

    Article  CAS  PubMed  Google Scholar 

  147. Soltwisch J, Kettling H, Vens-Cappell S, Wiegelmann M, Muthing J, Dreisewerd K. Mass spectrometry imaging with laser-induced postionization. Science. 2015;348(6231):211–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Mr Dinaiz Thinagaran, University of Melbourne, for literature search and collation of references. Ms Sydney Currier, University of Toronto, for sample preparation of kangaroo brain images. Mr Sean O’Callaghan, Metabolomics Australia, for bioinformatics support. Metabolomics Australia, a NCRIS initiative under Bioplatforms Australia Pty Ltd. Dr Eivind Undheim, University of Queensland for Thereuopoda longicornis venom gland sample. Dr Anthony Carroll, Griffith University, for the Stylissa flabellata sample.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Berin A. Boughton .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Boughton, B.A., Hamilton, B. (2017). Spatial Metabolite Profiling by Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging. In: Sussulini, A. (eds) Metabolomics: From Fundamentals to Clinical Applications. Advances in Experimental Medicine and Biology(), vol 965. Springer, Cham. https://doi.org/10.1007/978-3-319-47656-8_12

Download citation

Publish with us

Policies and ethics