TY - JOUR A1 - Becker, Johanna Sabine A1 - Matusch, Andreas A1 - Becker, Julia Susanne A1 - Wu, Bei A1 - Palm, Christoph A1 - Becker, Albert Johann A1 - Salber, Dagmar T1 - Mass spectrometric imaging (MSI) of metals using advanced BrainMet techniques for biomedical research JF - International Journal of Mass Spectrometry N2 - Mass spectrometric imaging (MSI) is a young innovative analytical technique and combines different fields of advanced mass spectrometry and biomedical research with the aim to provide maps of elements and molecules, complexes or fragments. Especially essential metals such as zinc, copper, iron and manganese play a functional role in signaling, metabolism and homeostasis of the cell. Due to the high degree of spatial organization of metals in biological systems their distribution analysis is of key interest in life sciences. We have developed analytical techniques termed BrainMet using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging to measure the distribution of trace metals in biological tissues for biomedical research and feasibility studies—including bioaccumulation and bioavailability studies, ecological risk assessment and toxicity studies in humans and other organisms. The analytical BrainMet techniques provide quantitative images of metal distributions in brain tissue slices which can be combined with other imaging modalities such as photomicrography of native or processed tissue (histochemistry, immunostaining) and autoradiography or with in vivo techniques such as positron emission tomography or magnetic resonance tomography. Prospective and instrumental developments will be discussed concerning the development of the metalloprotein microscopy using a laser microdissection (LMD) apparatus for specific sample introduction into an inductively coupled plasma mass spectrometer (LMD-ICP-MS) or an application of the near field effect in LA-ICP-MS (NF-LA-ICP-MS). These nano-scale mass spectrometric techniques provide improved spatial resolution down to the single cell level. KW - Bioimaging KW - Brain tissue KW - Laser ablation inductively coupled plasma mass spectrometry KW - Laser microdissection inductively coupled plasma mass spectrometry KW - Metals KW - Metallomics KW - Nano-LA-ICP-MS KW - Tumour KW - Massenspektrometrie KW - Bildgebendes Verfahren KW - Metalle KW - Metallproteide KW - Gehirn Y1 - 2011 U6 - https://doi.org/10.1016/j.ijms.2011.01.015 VL - 307 IS - 1-3 SP - 3 EP - 15 PB - eLSEVIER CY - Elsevier ER - TY - JOUR A1 - Becker, Johanna Sabine A1 - Zoriy, Miroslav A1 - Matusch, Andreas A1 - Wu, Bei A1 - Salber, Dagmar A1 - Palm, Christoph A1 - Becker, Julia Susanne T1 - Bioimaging of Metals by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) JF - Mass Spectrometry Reviews N2 - The distribution analysis of (essential, beneficial, or toxic) metals (e.g., Cu, Fe, Zn, Pb, and others), metalloids, and non‐metals in biological tissues is of key interest in life science. Over the past few years, the development and application of several imaging mass spectrometric techniques has been rapidly growing in biology and medicine. Especially, in brain research metalloproteins are in the focus of targeted therapy approaches of neurodegenerative diseases such as Alzheimer's and Parkinson's disease, or stroke, or tumor growth. Laser ablation inductively coupled plasma mass spectrometry (LA‐ICP‐MS) using double‐focusing sector field (LA‐ICP‐SFMS) or quadrupole‐based mass spectrometers (LA‐ICP‐QMS) has been successfully applied as a powerful imaging (mapping) technique to produce quantitative images of detailed regionally specific element distributions in thin tissue sections of human or rodent brain. Imaging LA‐ICP‐QMS was also applied to investigate metal distributions in plant and animal sections to study, for example, the uptake and transport of nutrient and toxic elements or environmental contamination. The combination of imaging LA‐ICP‐MS of metals with proteomic studies using biomolecular mass spectrometry identifies metal‐containing proteins and also phosphoproteins. Metal‐containing proteins were imaged in a two‐dimensional gel after electrophoretic separation of proteins (SDS or Blue Native PAGE). Recent progress in LA‐ICP‐MS imaging as a stand‐alone technique and in combination with MALDI/ESI‐MS for selected life science applications is summarized. KW - Bildgebendes Verfahren KW - ICP-Massenspektrometrie KW - Metalle KW - Metallproteide KW - Elektrophorese KW - Gehirnkarte KW - Bioimaging of metals KW - Laser ablation inductively coupled plasma mass spectrometry KW - metal distribution KW - metallomics KW - neurodegenerative diseases Y1 - 2010 U6 - https://doi.org/10.1002/mas.20239 VL - 29 SP - 156 EP - 175 ER - TY - JOUR A1 - Becker, Johanna Sabine A1 - Matusch, Andreas A1 - Palm, Christoph A1 - Salber, Dagmar A1 - Morton, Kathryn A. A1 - Becker, Julia Susanne T1 - Bioimaging of metals in brain tissue by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and metallomics JF - Metallomics N2 - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed and established as an emerging technique in the generation of quantitative images of metal distributions in thin tissue sections of brain samples (such as human, rat and mouse brain), with applications in research related to neurodegenerative disorders. A new analytical protocol is described which includes sample preparation by cryo-cutting of thin tissue sections and matrix-matched laboratory standards, mass spectrometric measurements, data acquisition, and quantitative analysis. Specific examples of the bioimaging of metal distributions in normal rodent brains are provided. Differences to the normal were assessed in a Parkinson’s disease and a stroke brain model. Furthermore, changes during normal aging were studied. Powerful analytical techniques are also required for the determination and characterization of metal-containing proteins within a large pool of proteins, e.g., after denaturing or non-denaturing electrophoretic separation of proteins in one-dimensional and two-dimensional gels. LA-ICP-MS can be employed to detect metalloproteins in protein bands or spots separated after gel electrophoresis. MALDI-MS can then be used to identify specific metal-containing proteins in these bands or spots. The combination of these techniques is described in the second section. KW - ICP-Massenspektrometrie KW - Metalle KW - Metallproteide KW - Elektrophorese KW - Gehirn Y1 - 2010 U6 - https://doi.org/10.1039/b916722f IS - 2 SP - 104 EP - 111 PB - Oxford Academic Press ER - TY - JOUR A1 - Matusch, Andreas A1 - Depboylu, Candan A1 - Palm, Christoph A1 - Wu, Bei A1 - Höglinger, Günter U. A1 - Schäfer, Martin K.-H. A1 - Becker, Johanna Sabine T1 - Cerebral bio-imaging of Cu, Fe, Zn and Mn in the MPTP mouse model of Parkinsons disease using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) JF - Journal of the American Society for Mass Spectrometry N2 - Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been established as a powerful technique for the determination of metal and nonmetal distributions within biological systems with high sensitivity. An imaging LA-ICP-MS technique for Fe, Cu, Zn, and Mn was developed to produce large series of quantitative element maps in native brain sections of mice subchronically intoxicated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin (MPTP) as a model of Parkinson’s disease. Images were calibrated using matrix-matched laboratory standards. A software solution allowing a precise delineation of anatomical structures was implemented. Coronal brain sections were analyzed crossing the striatum and the substantia nigra, respectively. Animals sacrificed 2 h, 7 d, or 28 d after the last MPTP injection and controls were investigated. We observed significant decreases of Cu concentrations in the periventricular zone and the fascia dentata at 2 h and 7d and a recovery or overcompensation at 28 d, most pronounced in the rostral periventricular zone (+40%). In the cortex Cu decreased slightly to −10%. Fe increased in the interpeduncular nucleus (+40%) but not in the substantia nigra. This pattern is in line with a differential regulation of periventricular and parenchymal Cu, and with the histochemical localization of Fe, and congruent to regions of preferential MPTP binding described in the rodent brain. The LA-ICP-MS technique yielded valid and statistically robust results in the present study on 39 slices from 19 animals. Our findings underline the value of routine micro-local analytical techniques in the life sciences and affirm a role of Cu availability in Parkinson’s disease. KW - Inductively Couple Plasma Mass Spectrometry KW - Substantia Nigra KW - MPTP KW - Laser Ablation Inductively Couple Plasma Mass Spectrometry KW - MPTP Treatment KW - ICP-Massenspektrometrie KW - Metalle KW - Gehirnkarte KW - MPTP Y1 - 2010 U6 - https://doi.org/10.1016/j.jasms.2009.09.022 VL - 21 IS - 1 SP - 161 EP - 171 ER - TY - JOUR A1 - Osterholt, Tobias A1 - Salber, Dagmar A1 - Matusch, Andreas A1 - Becker, Johanna Sabine A1 - Palm, Christoph T1 - IMAGENA: Image Generation and Analysis BT - An Interactive Software Tool handling LA-ICP-MS Data JF - International Journal of Mass Spectrometry N2 - Metals are involved in many processes of life. They are needed for enzymatic reactions, are involved in healthy processes but also yield diseases if the metal homeostasis is disordered. Therefore, the interest to assess the spatial distribution of metals is rising in biomedical science. Imaging metal (and non-metal) isotopes by laser ablation mass spectrometry with inductively coupled plasma (LA-ICP-MS) requires a special software solution to process raw data obtained by scanning a sample line-by-line. As no software ready to use was available we developed an interactive software tool for Image Generation and Analysis (IMAGENA). Unless optimised for LA-ICP-MS, IMAGENA can handle other raw data as well. The general purpose was to reconstruct images from a continuous list of raw data points, to visualise these images, and to convert them into a commonly readable image file format that can be further analysed by standard image analysis software. The generation of the image starts with loading a text file that holds a data column of every measured isotope. Specifying general spatial domain settings like the data offset and the image dimensions is done by the user getting a direct feedback by means of a preview image. IMAGENA provides tools for calibration and to correct for a signal drift in the y-direction. Images are visualised in greyscale as well a pseudo-colours with possibilities for contrast enhancement. Image analysis is performed in terms of smoothed line plots in row and column direction. KW - LA-ICP-MS KW - ICP-Massenspektrometrie KW - Bilderzeugung KW - Graphische Benutzeroberfläche KW - Image generation KW - Image analysis KW - Graphical user interface Y1 - 2011 U6 - https://doi.org/10.1016/j.ijms.2011.03.010 VL - 307 IS - 1-3 SP - 232 EP - 239 ER -