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Mass Spectrometry Innovation with Integrity Selected Publications MALDI Imaging in the Scientific Literature
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Selected Publications - Bruker · PDF fileSelected Publications MALDI Imaging in the ... of MALDI imaging with histology can solve ... It features an extensive discussion and explana

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Page 1: Selected Publications - Bruker · PDF fileSelected Publications MALDI Imaging in the ... of MALDI imaging with histology can solve ... It features an extensive discussion and explana

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Mass SpectrometryInnovation with Integrity

Selected Publications

MALDI Imaging in the Scientific Literature

Page 2: Selected Publications - Bruker · PDF fileSelected Publications MALDI Imaging in the ... of MALDI imaging with histology can solve ... It features an extensive discussion and explana

Reviews

Selected review articles on different MALDI Imaging application areas Castellino S, Groseclose MR, Wagner D (2011(MALDI imaging mass spectrometry: bridging biology and chemistry in drug development.Bioanalysis. 3(21):2427-41This review explains how the combination of MALDI imaging with histology can solve problems in drug development. The review is illustrated with real life example from ClaxoSmithKline‘s DMPK unit, the data are acquired on a Solarix instrument. Highlights of the presented data include a Lapatinib meta-bolite that is only found in inflamed lesions in the liver, and another metabolite that is highly enriched in small bile ducts.

Schwamborn K, Caprioli RM (2010)Molecular imaging by mass spectrometry - looking beyond classical histology.Nat Rev Cancer. 10(9):639-46 A comprehensive review on imaging mass spectrometry in clinical cancer research.

Walch A, Rauser S, Deininger SO, Hofler H (2008)MALDI Imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology.Histochem Cell Biol. 130(3):421-34 A general review on imaging mass spectrome-try with a detailed description on the impor-tance of the combining histological information with MALDI Imaging.

Rauser S, Deininger SO, Suckau D, Hofler H, Walch A (2010)Approaching MALDI molecular imaging for clinical proteomic research: current state and fields of application.Expert Rev Proteomics. 7(6):927-41This review focuses on the application of MALDI Imaging for clinical proteomic research. It features an extensive discussion and explana-tion of relevant clinical questions where MALDI Imaging can be applied.

Bonnel D, Legouffe R, Willand N, Baulard A, Hamm G, Deprez B, Stauber J (2011)MALDI Imaging techniques dedicated to drug-distribution studies.Bioanalysis. 3(12):1399-406This review describes the use of MALDI Imaging for drug-distribution studies. It also features an extensive discussion of Brukers innovative FAST-SRM mode for drug imaging on MALDI-TOF instruments.

Grassl J, Taylor NL, Millar AH (2011)Matrix-assisted laser desorption/ionisation mass spectrometry imaging and its develop-ment for plant protein imaging.Plant Methods. 7(1):21 This review describes the use of MALDI Imaging for plant research.

Selected MALDI Imaging Publications

Figure 1: Drug Imaging / Histo-pharmacology: Correlation of histology and ion image in dog liver sections. The ion image (50 µm spatial resolution) shows the lapatinib metabolite M10, localized only in the regions associated with the inflammation. Adapted from: Castellino et al. (2011) Bioanalysis 3(21),2427-41 with kind permis-sion of the authors.

Serial tissue sectionsIon imagesH&E stain

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Clinical Research

MALDI Imaging is perfectly suited for clinical biomarker studies. This sections contains selected papers that have used MALDI Imaging to study human patient samples

Meding S, Nitsche U, Balluff B, Elsner M, Rauser S, Schone C, Nipp M, Maak M, Feith M, Ebert MP, Friess H, Langer R, Hofler H, Zitzels-berger H, Rosenberg R, Walch A (2012)Tumor Classification of Six Common Cancer Types Based on Proteomic Profiling by MALDI Imaging.J Proteome Res. 11(3):1996-2003The carcinoma of unknown primary (CUP) is a challenge in clinical oncology. MALDI imaging can classify tissue based on protein profiles. In this article, the authors describe how molecular classifiers allowed to differentiate different types of tumor. Interestingly, they were able to classify liver metastases from a known origin (colon) correctly. This shows that, in principle, a classification of metastases of unknown origin might be possible.

Balluff B, Rauser S, Meding S, Elsner M, Schone C, Feuchtinger A, Schuhmacher C, Novotny A, Jutting U, Maccarrone G, Sarioglu H, Ueffing M, Braselmann H, Zitzelsberger H, Schmid RM, Hofler H, Ebert MP, Walch A (2011)MALDI Imaging Identifies Prognostic Seven-Protein Signature of Novel Tissue Markers in Intestinal-Type Gastric Cancer.Am J Pathol. 179(6):2720-9 A comprehensive MALDI imaging study of gastric cancer: A seven protein signature was found to correlate with survival in a discovery cohort (n= 63). Three of the proteins were identified and the findings from the discovery cohort were subsequently validated on a larger independet cohort by immunohistochemistry.

Hardesty WM, Kelley MC, Mi D, Low RL, Caprioli RM (2011)Protein signatures for survival and recurrence in metastatic melanoma.J Proteomics. 74(7):1002-14 A study that utilised MALDI Imaging for sur-vival and reccurence in metastatic melanoma. Twelve proteins could be associated with survival and three proteins were found to be associated with reccurence.

Le Faouder J, Laouirem S, Chapelle M, Albuquerque M, Belghiti J, Degos F, Paradis V, Camadro JM, Bedossa P (2011)Imaging mass spectrometry provides finger-prints for distinguishing hepatocellular carci-noma from cirrhosis.J Proteome Res. 10(8):3755-65The differentiation of liver carcinoma and its predecessor, liver cirrhosis, was analyzed by MALDI Imaging. Among other mass signals, Ubiquitin was found to be up-regulated in the tumors, as was confirmed by immunohistoche-mistry. This paper also uses a supervisedclassification to differentiate cancerous from cirrhotic regions and shows how molecular images can be constructed from classification results („Classimaging“).

Han EC, Lee YS, Liao WS, Liu YC, Liao HY, Jeng LB (2011)Direct tissue analysis by MALDI-TOF mass spectrometry in human hepatocellulat carci-noma.Clin Chim Acta. 412(3-4):230-9At present, prognosis of hepatocellular carci-noma (HCC) relies primarily on histopathologi-cal imaging applications after surgical removal. In this study, MALDI Imaging was utilised for classification of various tumour to supplement current histophatological analysis in tumour margins. A progressive change of fourteen peaks was observed in a distance-dependent manner from non-tumour to tumour regions of the junction section of HCC.

Zaima N, Sasaki T, Tanaka H, Cheng XW, Onoue K, Hayasaka T, Goto-Inoue N, Enomoto H, Unno N, Kuzuya M, Setou M (2011)Imaging mass spectrometry-based histopatho-logic examination of atherosclerotic lesions.Atherosclerosis. 217(2):427-32This article describes the investigation of artherosclerotic lesions of ApoE deficient mice and humans with peripheral artery occlusive disease using IMS-based histopathologic examination (IbHE). Several lipids such as cholesterol linoleate (CE 18:2) and cholesterol oleate (CE 18:1) were specifically found in the lipid rich regions of both human and mouse, whilst triacylglycerol was localised in the lipid-rich regions of human samples. Other molecules were found to be localised in the calcified regions.

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Schwamborn K, Krieg RC, Jirak P, Ott G, Knuchel R, Rosenwald A, Wellmann A (2010)Application of MALDI Imaging for the diagno-sis of classical Hodgkin lymphoma.J Cancer Res Clin Oncol. 136(11):1651-5In this study, Hodgkin lymphoma was inve-stigated by MALDI Imaging. the differentially expressed protein profiles allowed the differen-tiation between classical Hodgkin lymphoma and lymphadenitis with a sensitivity and speci-ficity of 83.92 and 89.37%, respectively.

Tanaka H, Zaima N, Yamamoto N, Sagara D, Suzuki M, Nishiyama M, Mano Y, Sano M, Hayasaka T, Goto-Inoue N, Sasaki T, Konno H, Unno N, Setou M (2010)Imaging mass spectrometry reveals unique lipid distribution in primary varicose veins.Eur J Vasc Endovasc Surg. 40(5):657-63Various lipid molecules have been measured in varicose and normal human veins. The accumulation of various specific lipids (iden-tified using a combination of imaging mass spectrometry and MS/MS) in varicose veins suggested that inflammation with abnormal lipid metabolism is involved in the devlopment of varicose veins.

Oppenheimer SR, Mi D, Sanders ME, Caprioli RM (2010)Molecular analysis of tumor margins by MALDI mass spectrometry in renal carcinoma.J Proteome Res. 9(5):2182-90In surgery it is important to evaluate that the tumor margin has been completely resected. The tumor margin is usually evauated by histo-logy. The MALDI Imaging analysis of tumor margins in renal carcinoma in this study reve-laed that proteins that characteristically up-regulated in the tumour were also up-regulated in an area adjacent to the tumor, indicating a molecular tumor margin that is different from the histological tumor margin.

Balluff B, Elsner M, Kowarsch A, Rauser S, Meding S, Schuhmacher C, Feith M, Herrmann K, Rocken C, Schmid RM, Hofler H, Walch A, Ebert MP (2010)Classification of HER2/neu status in gastric cancer using a breast-cancer derived proteome classifier.J Proteome Res. 9(12):6317-22A paper that follows on an earlier breast cancer study (Rauser et al. J. Proteome Res. , 2010). It showed that a protein profile based classifier, trained to classify Her2 status in breast cancer, was also able to classify Her 2 status in an

independent gastric cancer cohort, providing strong evidence of the robustness of MALDI Imaging based tissue classifications.

Willems SM, van Remoortere A, van Zeijl R, Deelder AM, McDonnell LA, Hogendoorn PC (2010)Imaging mass spectrometry of myxoid sarco-mas identifies proteins and lipids specific to tumour type and grade, and reveals biochemi-cal intratumour heterogeneity.J Pathol. 222(4):400-9An article that investigates the expression of proteins and lipids in myxoid sarcomas. Peptide, protein and lipid profiles have been correlated with tumor grades and intra-tumor heterogeneity has been investigated by hiear-chical clustering of imaging data. In particular, lipid changes observed in myxoid liposarcomas could be related to pathways known to be affected during tumor development.

Rauser S, Marquardt C, Balluff B, Deininger SO, Albers C, Belau E, Hartmer R, Suckau D, Specht K, Ebert MP, Schmitt M, Aubele M, Hofler H, Walch A (2010)Classification of HER2 receptor status in breast cancer tissues by MALDI Imaging mass spec-trometry.J Proteome Res. 9(4):1854-63 In this article, MALDI Imaging has been used to classify HER2 receptor status in human breast cancer specimens. Protein profiles correlated strongly with HER2 expression. A protein signal with a particularly high correlation with HER2 expression has been identified as cysteine rich intestinal protein 1, a protein that was previously not known to be associated with HER2 expression.

Cazares LH, Troyer D, Mendrinos S, Lance RA, Nyalwidhe JO, Beydoun HA, Clements MA, Drake RR, Semmes OJ (2009)Imaging mass spectrometry of a specific fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2 discriminates cancer from uninvolved prostate tissue.Clin Cancer Res. 15(17):5541-51Prostate cancer is a cancer type in which the differentiation of begning tissue and cancrous tissue may be difficult. In this study prostate cancer and normal tissue was differentiated by MALDI Imaging. The original findings in a small discovery set were verified by the analysis of a validation set with 54 tissue sections. One marker that correlated with the tumor was

Page 5: Selected Publications - Bruker · PDF fileSelected Publications MALDI Imaging in the ... of MALDI imaging with histology can solve ... It features an extensive discussion and explana

identified as a fragment of mitogen-activated protein kinase/extracellular signal regulated kinase kinase kinase 2 (MEKK2).

Groseclose MR, Massion PP, Chaurand P, Caprioli RM (2008)High-throughput proteomic analysis of formalin-fixed paraffin-embedded tissue microarrays using MALDI Imaging mass spectrometry.Proteomics. 8(18):3715-24The analysis of tissue microarrays is of great interest, since it allows the analysis of a large number of samples in a relatively short time. This article describes how MALDI Imaging can be used to analyze FFPE tissue by tryptic digestion and how tumor types can be classi-fied based on their peptide patterns. The result of the classification of the individual pixels is visualized as image („Class imaging“).

Lemaire R, Menguellet SA, Stauber J, Marchaudon V, Lucot JP, Collinet P, Farine MO, Vinatier D, Day R, Ducoroy P, Salzet M, Fournier I (2007)Specific MALDI Imaging and profiling for biomarker hunting and validation: fragment of the 11S proteasome activator complex, Reg alpha fragment, is a new potential ovary cancer biomarker.J Proteome Res. 6(11):4127-34Early paper that shows the power of MALDI Imaging in clincial proteomic research for the analysis of ovary cancer. A specific 84 amino acid fragment from the protein Reg-alpha was identified as tumor marker and validated with other techniques, including immunohistochem-sitry.

Drug imaging / Xenobiotics / Pharmaceutical research

MALDI Imaging can be used to directly measure drugs, metabolites and xenobiotics in tissue

Seppala U, Francese S, Turillazzi S, Moneti G, Clench M, Barber D (2011)In situ imaging of honeybee (Apis mellifera) venom components from aqueous and alumi-num hydroxide-adsorbed venom immunothe-rapy preparations.J Allergy Clin Immunol. 129(5):1314-1320.e3An article that utilised MALDI Imaging to assess purified aqueous and aluminum hydro-xide (Al[OH]3)adsorbed purified honeybee (Apis mellifera) venom (HBV) immunotherapy preparations in situ, which can reduce the inci-dence of side effects associated with venom immunotherapy. The study assessed the distribution of HBV components and showed that the majority of low-molecular-weight HBV components are rapidly removed from the site of venom immunotherapy administration. Fur-thermore, Al(OH)3-adsorbed HBV preparation demonstrated a depot effect, prolonging the availability of bee venom allergens at the site of administration.

Goodwin RJ, Mackay CL, Nilsson A, Harrison D, Farde L, Andren PE, Iverson SL (2011)Qualitative and quantitative MALDI Imaging of the positron emission tomography ligands raclopride (a D2 dopamine antagonist) and SCH 23390 (a D1 dopamine antagonist) in rat brain tissue sections using a solvent-free dry matrix application method.Anal Chem. 83(24):9694-701An article that describes a dry matrix prepara-tion for the detection of two dopamine receptor antagonists. Rats were dosed at 5 mg/kg and the distribution of the drug in the brain could be detected.

Enthaler B, Pruns JK, Wessel S, Rapp C, Fischer M, Wittern KP (2011)Improved sample preparation for MALDI-MSI of endogenous compounds in skin tissue sec-tions and mapping of exogenous active com-pounds subsequent to ex-vivo skin penetration.Anal Bioanal Chem. 402(3):1159-67In this article, MALDI Imaging was utilised for the determination of the pathway and depth of penetration of an exogenous model com-pound, Nile Red, after ex-vivo penetration into porcine skin. Additionally, the localisation of

Figure 2: Class Imaging: Visual representation of the statistical classification of four biopsies compared to the assignment based on histology. From: Groseclose et. al (2008),Proteomics 8(18) 3715© 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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endogenous compounds, including cholesterol sulphate, was measured directly on tissue at a resolution of approximately 30 m.

Miki A, Katagi M, Kamata T, Zaitsu K, Tatsuno M, Nakanishi T, Tsuchihashi H, Takubo T, Suzuki K (2011)MALDI-TOF and MALDI-FTICR Imaging mass spectrometry of methamphetamine incorpora-ted into hair.J Mass Spectrom. 46(4):411-6This paper describes the potential use of MALDI Imaging in forensics. Cocaine was measured directly in human hair and the spatial profile of cocaine in the hair could be translated to a temporary consumption profile.

Marshall P, Toteu-Djomte V, Bareille P, Perry H, Brown G, Baumert M, Biggadike K (2010)Correlation of skin blanching and percutaneous absorption for glucocorticoid receptor agonists by matrix-assisted laser desorption ionization mass spectrometry imaging and liquid extrac-tion surface analysis with nanoelectrospray ionization mass spectrometry.Anal Chem. 82(18):7787-94In this study, the percutaneous absorption of three novel nonsteroid glucocorticoid receptor agonists has been investigated.

Nilsson A, Fehniger TE, Gustavsson L, Andersson M, Kenne K, Marko-Varga G, Andren PE (2010)Fine mapping the spatial distribution and concentration of unlabeled drugs within tissue micro-compartments using imaging mass spectrometry.PLoS One. 5(7):e11411This article describes the use of MALDI Imaging for monitoring in vivo transport of unlabelled drugs within specific organ tissue compartments. A reference compound (tiotro-pium) would be tracked and quantified within the lungs of dosed rats, using systematic point-by-point MS and MS/MS sampling across the tissue.

Francese S, Lambardi D, Mastrobuoni G, la Marca G, Moneti G, Turillazzi S (2009)Detection of honeybee venom in envenomed tissues by direct MALDI MSI.J Am Soc Mass Spectrom. 20(1):112-23In this study, MALDI Imaging has been used to map the diffusion and distribution of venom allergen and toxins in skin.

Acquadro E, Cabella C, Ghiani S, Miragoli L, Bucci EM, Corpillo D (2009)Matrix-assisted laser desorption ionization imaging mass spectrometry detection of a magnetic resonance imaging contrast agent in mouse liver.Anal Chem. 81(7):2779-84This article describes the use of MALDI Imaging to detect a magnetic resonance imaging (MRI) contrast agent in both frozen and paraformaldehyde-fixed mouse livers after its in vivo administration.

Dekker LJ, van Kampen JJ, Reedijk ML, Burgers PC, Gruters RA, Osterhaus AD, Luider TM (2009)A mass spectrometry based imaging method developed for the intracellular detection of HIV protease inhibitors.Rapid Commun Mass Spectrom. 23(8):1183-8HIV protease inhibitors have been measured in cultured cells using MALDI-TOF and MALDI-FTMS.

Cornett DS, Frappier SL, Caprioli RM (2008)MALDI-FTICR Imaging mass spectrometry of drugs and metabolites in tissue.Anal Chem. 80(14):5648-53In this work, the authors show how the high precision of FTMS mass measurements increase the confidence in the results of drug imaging experiments.

Meistermann H, Norris JL, Aerni HR, Cornett DS, Friedlein A, Erskine AR, Augustin A, De Vera Mudry MC, Ruepp S, Suter L, Langen H, Caprioli RM, Ducret A (2006)Biomarker discovery by imaging mass spectro-metry: transthyretin is a biomarker for gentami-cin-induced nephrotoxicity in rat.Mol Cell Proteomics. 5(10):1876-86In this article, MALDI Imaging has been used to find a surrogate biomarker in kidney that indi-cates the nephrotoxic effect of an administered drug, gentamicin.

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Model Organisms

A selection of studies that have used MALDI Imaging for general biological or biomedical research on model organisms

Qureshi A, Subathra M, Grey A, Schey K, Del Poeta M, Luberto C (2010)Role of sphingomyelin synthase in controlling the antimicrobial activity of neutrophils against Cryptococcus neoformans.PLoS One. 5(12):e15587 This study performed MALDI Imaging on lungs infected with Cryptococcus neoformans to provide new insights into the key host cellular pathway(s) necessary to control infection caused from inhalation of Cryptococcus neofor-mans. MALDI Imaging revealed specific lipid (SM - sphingomyelin) species are associated with neutrophil infiltration at the site of the infection.

Magalhaes BS, Melo JA, Leite JR, Silva LP, Prates MV, Vinecky F, Barbosa EA, Verly RM, Mehta A, Nicoli JR, Bemquerer MP, Andrade AC, Bloch C Jr (2008)Post-secretory events alter the peptide content of the skin secretion of Hypsiboas raniceps.Biochem Biophys Res Commun. 377(4):1057-61In this article, MALDI Imaging demonstrated that mature raniseptin peptides (a novel family of antimicrobial peptides characterised from skin secretion of the anuran Hypsibas raniceps) are in fact secreted as intact molecules within a defined glandular domain of the dorsal skin,

challenging the physiological role of the obser-ved raniseptin fragments, identified only as part of the crude secretion.

Brand GD, Krause FC, Silva LP, Leite JR, Melo JA, Prates MV, Pesquero JB, Santos EL, Nakaie CR, Costa-Neto CM, Bloch C Jr (2006)Bradykinin-related peptides from Phyllomedusa hypochondrialis.Peptides. 27(9):2137-46 link Frog mucus contains biologically active pepti-des that are e.g. protective of fungal infections or predators. MALDI Imaging has been used to map such peptides directly in frog skin.

Neuroscience

Selected MALDI Imaging papers in neurosci-ence

Hanrieder J, Karlsson A, Falth M, Eriksson-Mammo S, Bergquist J, Andersson M (2011)L-DOPA-induced dyskinesia is associated with regional increase of striatal dynorphin peptides as elucidated by imaging mass spectrometry.Mol Cell Proteomics. 10(10):M111.009308MALDI Imaging was used for characterization, localization, and relative quantification of striatal neuropeptides in a rat model of l-DOPA-indu-ced dyskinesia (LID) in Parkinson‘s disease.

Yuki D, Sugiura Y, Zaima N, Akatsu H, Hashizume Y, Yamamoto T, Fujiwara M, Sugiyama K, Setou M (2011)Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex.Neuroscience. 193:44-53This article studies the distribution of sulfatide lipids in human cerebral cortex. It was found that hydroxylated and non-hydroxylated sul-fatides are differently distributed in white and grey matter. An alzheimer brain has also been investigated and showed a similar distribution of sulfatides compared to normal tissue.

Yang H, Sugiura Y, Ikegami K, Konishi Y, Setou M (2011)Axonal gradient of arachidonic acid-containing phosphatidylcholine and its dependence on actin dynamics.J Biol Chem. 287(8):5290-300This article used MALDI Imaging to characte-rise the distribution of phosphatidylcholine (PC) species in cultured neurons of superior cervical ganglia.

Figure 3: Statistical Analysis: Spatial segmentation map based on hierarchical clustering of a rat whole body section and principal com-ponent analysis of selected organs. From: Speir. et al. Proceedings of the 60th ASMS Conference on MassSpectrometry and Allied Topics, May 20-24,2012

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Sugiura Y, Taguchi R, Setou M (2011)Visualization of spatiotemporal energy dynamics of hippocampal neurons by mass spectrometry during a kainate-induced seizure.PLoS One. 6(3):e17952In this paper, MALDI Imaging combined with capillary electrophoresis (CE) mass spectrome-try were utilised to visualise energy metabo-lism by imaging energy-related metabolites in mouse brains to reveal the spatiotemporal energy metabolism of the mouse hippocampus.

Sugiura Y, Shimma S, Konishi Y, Yamada MK, Setou M (2008)Imaging mass spectrometry technology and application on ganglioside study; visualization of age-dependent accumulation of C20-ganglio-side molecular species in the mouse hippocam-pus.PLoS One. 3(9):e3232The distrubtion of ganglioside molecular species in the brain was revealed by MALDI Imaging, enabling discrimination of species raised from both oligosaccharide and ceramide structure by the difference in mass-to-charge ratio and structural elucidation by MSMS.

Plants

MALDI Imaging in the investigation of plants

Poth AG, Mylne JS, Grassl J, Lyons RE, Millar AH, Colgrave ML, Craik DJ (2012)Cyclotides associate with leaf vasculature and are the products of a novel precursor in Petunia (Solanaceae).J Biol Chem. doi:10.1074/jbc.M112.370841Cyclotides are defense related cylic peptides. In this study the spatial distribution of cyclotides was assessed by MALDI Imaging. The major cyclotide component showed a non-uniform distribution in petunia leaves.

Holscher D, Shroff R, Knop K, Gottschaldt M, Crecelius A, Schneider B, Heckel DG, Schubert US, Svatos A (2009)Matrix-free UV-laser desorption/ionization (LDI) mass spectrometric imaging at the single-cell level: distribution of secondary metabolites of Arabidopsis thaliana and Hypericum species.Plant J. 60(5):907-18 A paper that describes the direct analysis of secondary metabolites in Hypericum and Arabodopsis. The distribution of Naphtodian-thrones were measured in Hypericum leavesm placenta, stamens and styli. The highest achie-ved spatial resolution was 10 micrometers.

MALDI Imaging methodology

MALDI Imaging is a field that is under research itself. This section shows interesting ongoing development in this field

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-diaminonaptha-lene deposition.Anal Chem. 84(4):2048-54 As matrix sublimation has demonstrated to be a powerful approach for high-resolution MALDI Imaging of lipids, this study aimed to evaluate current and novel matrix candidates for high spatial resolution MALDI Imaging mass spectrometry of lipids from tissue section after deposition by sublimation.

Angel PM, Spraggins JM, Baldwin HS, Caprioli R (2012)Enhanced sensitivity for high spatial resolution lipid analysis by negative ion mode matrix assi-sted laser desorption ionization imaging mass spectrometry.Anal Chem. 84(3):1557-64A paper that shows high spatial resolution of 10 micrometer with an Ultraflextreme on tissue.

Yang J, Caprioli RM (2011)Matrix sublimation/recrystallization for imaging proteins by mass spectrometry at high spatial resolution.Anal Chem. 83(14):5728-34A paper that investigates improved sample preparation methods based on matrix subli-mation. It shows the technical possibilities of resolution obtainable with Brukers advanced instrumentation.

Khatib-Shahidi S, Andersson M, Herman JL, Gillespie TA, Caprioli RM (2006)Direct molecular analysis of whole-body animal tissue sections by imaging MALDI mass spec-trometry.Anal Chem. 78(18):6448-56 A paper that shows how different substance classes can be measured in whole body sec-tions of rats.

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Method - Computational

Computational methods are an important part of MALDI Imaging analysis. This section lists interesting papers in this field

Trede D, Schiffler S, Becker M, Wirtz S, Steinhorst K, Strehlow J, Aichler M, Kobarg JH, Oetjen J, Dyatlov A, Heldmann S, Walch A, Thiele H, Maass P, Alexandrov T (2012)Exploring Three-Dimensional Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry Data: Three-Dimensional Spatial Segmentation of Mouse Kidney.Anal Chem. doi:10.1021/ac300673y This paper describes an efficient computational pipeline which allows analysis and interpre-tation of three dimensional MALDI Imaging datasets.

Andersson M, Groseclose MR, Deutch AY, Caprioli RM (2008)Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction.Nat Methods. 5(1):101-8 The article presents an optimised step-by-step procedure describing how to make 3D volume reconstructions of MALDI Imaging data, as applied to the rat brain.

Sinha TK, Khatib-Shahidi S, Yankeelov TE, Mapara K, Ehtesham M, Cornett DS, Dawant BM, Caprioli RM, Gore JC (2008)Integrating spatially resolved three-dimensional MALDI IMS with in vivo magnetic resonance imaging.Nat Methods. 5(1):57-9 The article describes a method for integration of 3D volume reconstructions of proteomic MALDI Imaging datasets of whole mouse heads with in vivo high-resolution images from other imaging modalities (magnetic resonance imaging).

Hanselmann M, Kirchner M, Renard BY, Amstalden ER, Glunde K, Heeren RM, Hamprecht FA (2008)Concise representation of mass spectrometry images by probabilistic latent semantic analysis.Anal Chem. 80(24):9649-58 This paper describes a very interesting sta-tistical method, named probabibilistic latent sematics analysis (pLSA), for the concise repre-sentation of complex imaging mass spectrome-try data. Although the data was not recorded on Bruker instrumentation,In the meantime, pLSA has been implemented in Brukers MALDI imaging software package.

Figure 4: Drug Imaging / Histopharmacology: Sagittal rabbit brain section showing distribution of a cysteine conjugate metabolite. (A) Monochromatic ion image showing brain distribution of cysteine conjugate metabolite (170 µm spatial resolution). (B) Same ion image shown in rainbow intensity format. (C) Hematoxylin and eosin histology slide showing regions of the rabbit brain. From: Castellino et al. (2011) Bioanalysis 3(21),2427-41 with kind permission of the authors.

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Development

MALDI imaging papers in developmental biology

Lagarrigue M, Becker M, Lavigne R, Deininger SO, Walch A, Aubry F, Suckau D, Pineau C (2011)Revisiting rat spermatogenesis with MALDI Imaging at 20-microm resolution.Mol Cell Proteomics. 10(3):M110.005991This article investigates the protein expression in rat testis. It shows state-of-the-art protein images at a spatial resolution of 20 micrometer. The observed protein profiles were linked to the stages of spermatogenesis as determined by histology. The article therefore shows the importance of the correlation of molecular MALDI images and histology. Some of the observed proteins were identified and their expression further investigated by immunohi-stochemistry.

Goto-Inoue N, Hayasaka T, Zaima N, Setou M (2009)The specific localization of seminolipid mole-cular species on mouse testis during testicular maturation revealed by imaging mass spectro-metry.Glycobiology. 19(9):950-7MALDI Imaging was utilised to show cell-spe-cific localisation of each molecular species of seminolipid (a unique sulphated glyceroglycoli-pid, which constitutes more than 90% of the glycolipid in mammalian testis) during testicular maturation.

Burnum KE, Cornett DS, Puolitaival SM, Milne SB, Myers DS, Tranguch S, Brown HA, Dey SK, Caprioli RM (2009)Spatial and temporal alterations of phospholi-pids determined by mass spectrometry during mouse embryo implantation.J Lipid Res. 50(11):2290-8 MALDI Imaging was used to characterise the spatial patial and temporal distribution of phospholipid species associated with mouse embryo implantation. LC-ESI-MSMS validated the phospholipid distribution patterns observed using MALDI Imaging.

Burnum KE, Tranguch S, Mi D, Daikoku T, Dey SK, Caprioli RM (2008)Imaging mass spectrometry reveals unique protein profiles during embryo implantation.Endocrinology. 149(7):3274-8

Chaurand P, Rahman MA, Hunt T, Mobley JA, Gu G, Latham JC, Caprioli RM, Kasper S (2008)Monitoring mouse prostate development by profiling and imaging mass spectrometry.Mol Cell Proteomics. 7(2):411-23 This article describes the use of MALDI Imaging to evaluate protein expression profiles in the normal mouse prostate during develop-ment, at sexual maturation and in adult stages.

Microbiology

Interesting papers of the use of MALDI Ima-ging to study microbial interactions

Liu WT, Kersten RD, Yang YL, Moore BS, Dorrestein PC (2011)Imaging mass spectrometry and genome mining via short sequence tagging identified the anti-infective agent arylomycin in Strepto-myces roseosporus.J Am Chem Soc. 133(45):18010-3 A paper that utilised MALDI Imaging along with a peptidogenomic approach (expanded to short sequence tagging SST) for discovery of anti-infective agent arylomycin and its biosynthetic gene cluster in an industrial daptomycin produ-cing strain Streptomyces roseosporus.

Liu WT, Yang YL, Xu Y, Lamsa A, Haste NM, Yang JY, Ng J, Gonzalez D, Ellermeier CD, Straight PD, Pevzner PA, Pogliano J, Nizet V, Pogliano K, Dorrestein PC (2010)Imaging mass spectrometry of intraspecies metabolic exchange revealed the cannibalistic factors of Bacillus subtilis.Proc Natl Acad Sci U S A. 107(37):16286-90 This paper studies molecular interactions in bacterial cannibalism.

Yang YL, Xu Y, Straight P, Dorrestein PC (2009)Translating metabolic exchange with imaging mass spectrometry.Nat Chem Biol. 5(12):885-7 In this article the metabolic interaction of different bacterial strains on an agar plate are monitored by MALDI Imaging. This allowed a direct molecular characterization of a chemical fight between the bacterial strains and provided evidence that Bacillus subtilis silenced the defensive arsenal of Streptomyces coelicolor.

Page 11: Selected Publications - Bruker · PDF fileSelected Publications MALDI Imaging in the ... of MALDI imaging with histology can solve ... It features an extensive discussion and explana

Figure 5: Lipids in mouse cerebellum measured at 10 µm spatial resolution.Reprinted from: Thomas A, Charbonneau JL, Fournaise E, Chaurand P. 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. 2012;84(4):2048-54 Copyright (2012) American Chemical Society

Figure 6: Bruker offers the complete MALDI Imaging solution.

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Statistical Analysis

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Page 12: Selected Publications - Bruker · PDF fileSelected Publications MALDI Imaging in the ... of MALDI imaging with histology can solve ... It features an extensive discussion and explana

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Bruker does actively contribute to research in the MALDI Imaging field, having introduced key innovations in both hard- and software. This section lists papers with key conttributi-ons form Bruker authors

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):167-81 Normalization is an important step in the data preparation of MALDI Imaging data, mostly to account random real-world influences in the data. Commonly used normalization techni-ques such as the total ion count, can introduce artifacts in rare cases. This paper discusses the applicability of different normalization approa-ches and introduces robust methods, such as normalization to median intensity. These normalization options are included in Brukers MALDI Imaging software.

Alexandrov T, Becker M, Deininger SO, Ernst G, Wehder L, Grasmair M, von Eggeling F, Thiele H, Maass P (2010)Spatial segmentation of imaging mass spec-trometry data with edge-preserving image denoising and clustering.J Proteome Res. 9(12):6535-46 This paper describes how MALDI Imaging data can be improved by spatially aware de-noising. Compared to mere smoothing of the images, edge-preserving de-noising can improve MALDI images, while keeping highly resolved fine structures in the images.

Agar NY, Kowalski JM, Kowalski PJ, Wong JH, Agar JN (2010)Tissue preparation for the in situ MALDI MS Imaging of proteins, lipids, and small molecules at cellular resolution.Methods Mol Biol. 656:415-31

For research use only. Not for use in diagnostic procedures.

Bruker Daltonik GmbH

Bremen · GermanyPhone +49 (0)421-2205-0 Fax +49 (0)421-2205-103 [email protected]

Bruker Daltonics Inc.

Billerica, MA · USA Fremont, CA · USAPhone +1 (978) 663-3660 Phone +1 (510) 683-4300 Fax +1 (978) 667-5993 Fax +1 (510) 490-6586 [email protected] [email protected]

www.bruker.com/maldiimaging

This chapter presents three methods that minimise the delocalisation of analytes during matrix deposition, including a method where image resolution is not limited by the laser focal diameter.

Deininger SO, Ebert MP, Futterer A, Gerhard M, Rocken C (2008)MALDI Imaging combined with hierarchical clustering as a new tool for the interpretation of complex human cancers.J Proteome Res. 7(12):5230-6This paper describes how hierarchical cluste-ring can be used to do a highly interactive and consice detailed annotation of MALDI Imaging datasets. The user interface for the clustering and the software to perform the analysis is part of Brukers MALDI Imaging software.

Taban IM, Altelaar AF, van der Burgt YE, McDonnell LA, Heeren RM, Fuchser J, Baykut G (2007)Imaging of peptides in the rat brain using MALDI-FTICR mass spectrometry.J Am Soc Mass Spectrom. 18(1):145-51The first paper that shows MALDI Imaging with very high mass spectrometric resolution on FTMS instrumentation.

Holle A, Haase A, Kayser M, Hohndorf J (2006)Optimizing UV laser focus profiles for impro-ved MALDI performance.J Mass Spectrom. 41(6):705-16 The laser is an important part of the MALDI process; even being contained in the term „MALDI“. Brukers proprietary smartbeam laser is widely recognized for its superior performance, softness of ionization and spatial resolution. This paper describes the principle and performance advantages of the smart-beam laser.