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Sample records for multi-isotope imaging mass

  1. Quantitative imaging of subcellular metabolism with stable isotopes and multi-isotope imaging mass spectrometry

    PubMed Central

    Steinhauser, Matthew L.; Lechene, Claude P.

    2014-01-01

    Multi-isotope imaging mass spectrometry (MIMS) is the quantitative imaging of stable isotope labels in cells with a new type of secondary ion mass spectrometer (NanoSIMS). The power of the methodology is attributable to (i) the immense advantage of using non-toxic stable isotope labels, (ii) high resolution imaging that approaches the resolution of usual transmission electron microscopy and (iii) the precise quantification of label down to 1 part-per-million and spanning several orders of magnitude. Here we review the basic elements of MIMS and describe new applications of MIMS to the quantitative study of metabolic processes including protein and nucleic acid synthesis in model organisms ranging from microbes to humans. PMID:23660233

  2. The new frontiers of multimodality and multi-isotope imaging

    NASA Astrophysics Data System (ADS)

    Behnam Azad, Babak; Nimmagadda, Sridhar

    2014-06-01

    Technological advances in imaging systems and the development of target specific imaging tracers has been rapidly growing over the past two decades. Recent progress in "all-in-one" imaging systems that allow for automated image coregistration has significantly added to the growth of this field. These developments include ultra high resolution PET and SPECT scanners that can be integrated with CT or MR resulting in PET/CT, SPECT/CT, SPECT/PET and PET/MRI scanners for simultaneous high resolution high sensitivity anatomical and functional imaging. These technological developments have also resulted in drastic enhancements in image quality and acquisition time while eliminating cross compatibility issues between modalities. Furthermore, the most cutting edge technology, though mostly preclinical, also allows for simultaneous multimodality multi-isotope image acquisition and image reconstruction based on radioisotope decay characteristics. These scientific advances, in conjunction with the explosion in the development of highly specific multimodality molecular imaging agents, may aid in realizing simultaneous imaging of multiple biological processes and pave the way towards more efficient diagnosis and improved patient care.

  3. Tracing of water masses using a multi isotope approach in the southern Indian Ocean

    NASA Astrophysics Data System (ADS)

    Povinec, P. P.; Breier, R.; Coppola, L.; Groening, M.; Jeandel, C.; Jull, A. J. T.; Kieser, W. E.; Lee, S.-H.; Liong Wee Kwong, L.; Morgenstern, U.; Park, Y.-H.; Top, Z.

    2011-02-01

    Anthropogenic radionuclides (3 H, 14 C, and 129I) stemmed from nuclear weapons tests were found in 1999 to be very abundant in the surface of the southern Indian Ocean, comparable to those in the subtropical Northwest Pacific Ocean. The observed radionuclide variations with latitude/longitude in the southern Indian Ocean are not due to deposition patterns of global fallout, but due to transport of water masses from the western Pacific through the Indonesian seas, and different water fronts present in the Crozet Basin of the Indian Ocean. High radionuclide concentrations observed in the latitudinal belt of 20-40°S are associated with the Indian Ocean Subtropical Gyre which acts as a reservoir of radionuclides, maintaining their high concentrations on a time scale of several decades. 14 C data documents that the southern Indian Ocean is an important for sink of anthropogenic carbon. The isotopic tracers reveal the evidence of the most intense surface gradients and presence of several water masses in the southern Indian Ocean, which makes the region one of the most dynamic places of the World Ocean.

  4. LaBr3:Ce small FOV gamma camera with excellent energy resolution for multi-isotope imaging

    NASA Astrophysics Data System (ADS)

    Pani, R.; Fabbri, A.; Cinti, M. N.; Orlandi, C.; Pellegrini, R.; Scafè, R.; Artibani, M.

    2015-06-01

    The simultaneous administration of radiopharmaceuticals labeled with more than one radioisotope is becoming of increasing interest in clinical practice. Because the photon energies of the utilized radioisotopes could be very close (less than 15% difference), a gamma camera with adequate energy resolution is required. The availability of scintillation crystals with high light yield, as lanthanum tri-bromide (LaBr3:Ce), is particularly appealing for these applications. In this work, a new small field of view gamma camera prototype is presented, based on a planar LaBr3:Ce scintillation crystal with surfaces treatment typical of spectrometric devices, in order to enhance energy resolution performances. The crystal has round shape and has been optically coupled with a position sensitive photomultiplier tube with high quantum efficiency. The presented gamma camera shows outstanding energy resolution results in the investigated energy range (32-662 keV). These relevant performances have been obtained through the application of uniformity correction on the raw data, necessary due to the presence of position sensitive phototube, characterized by a spread of anodic gain values. In spite of position linearity degradation at crystal edges, due to reflective treatment of surfaces, intrinsic spatial resolution values are satisfactory on the useful field of view.The characterization of the presented gamma camera, based on a continuous LaBr3:Ce scintillation crystal with reflective surfaces, indicates good performances in multi-isotope imaging due to the excellent energy resolution results, also in comparison with similar detectors.

  5. Brain stem cell division and maintenance studied using multi-isotope imaging mass spectrometry (MIMS)

    PubMed Central

    Enikolopov, G.; Guillermier, C.; Wang, M.; Trakimas, L.; Steinhauser, M.; Lechene, C.

    2015-01-01

    New neurons are continuously produced from neural stem cells in specific regions of the adult brain of animals and humans. In the hippocampus, a region crucial for cognitive function, neurogenesis responds to a multitude of extrinsic stimuli; emerging evidence indicates that it may be important for behavior, pathophysiology, brain repair, and response to drugs. We have developed an approach to identify and quantify the cellular targets of pro- and anti-neurogenic stimuli, based on reporter transgenic mouse lines in which neural stem and progenitor cells or their progeny are marked by fluorescent proteins. Here, we demonstrate the feasibility of using MIMS for studying adult neurogenesis. PMID:26379335

  6. Multi-Isotope Secondary Ion Mass Spectrometry Combining Heavy Water 2H with 15N Labeling As Complementary Tracers for Metabolic Heterogeneity at the Single-Cell Level

    NASA Astrophysics Data System (ADS)

    Kopf, S.; McGlynn, S.; Cowley, E.; Green, A.; Newman, D. K.; Orphan, V. J.

    2014-12-01

    Metabolic rates of microbial communities constitute a key physiological parameter for understanding the in situ growth constraints for life in any environment. Isotope labeling techniques provide a powerful approach for measuring such biological activity, due to the use of isotopically enriched substrate tracers whose incorporation into biological materials can be detected with high sensitivity by isotope-ratio mass spectrometry. Nano-meter scale secondary ion mass spectrometry (NanoSIMS) combined with stable isotope labeling provides a unique tool for studying the spatiometabolic activity of microbial populations at the single cell level in order to assess both community structure and population diversity. However, assessing the distribution and range of microbial activity in complex environmental systems with slow-growing organisms, diverse carbon and nitrogen sources, or heterotrophic subpopulations poses a tremendous technical challenge because the introduction of isotopically labeled substrates frequently changes the nutrient availability and can inflate or bias measures of activity. Here, we present the use of hydrogen isotope labeling with deuterated water as an important new addition to the isotopic toolkit and apply it for the determination of single cell microbial activities by NanoSIMS imaging. This tool provides a labeling technique that minimally alters any aquatic chemical environment, can be administered with strong labels even in minimal addition (natural background is very low), is an equally universal substrate for all forms of life even in complex, carbon and nitrogen saturated systems, and can be combined with other isotopic tracers. The combination of heavy water labeling with the most commonly used NanoSIMS tracer, 15N, is technically challenging but opens up a powerful new set of multi-tracer experiments for the study of microbial activity in complex communities. We present the first truly simultaneous single cell triple isotope system

  7. Digital Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Bamberger, Casimir; Renz, Uwe; Bamberger, Andreas

    2011-06-01

    Methods to visualize the two-dimensional (2D) distribution of molecules by mass spectrometric imaging evolve rapidly and yield novel applications in biology, medicine, and material surface sciences. Most mass spectrometric imagers acquire high mass resolution spectra spot-by-spot and thereby scan the object's surface. Thus, imaging is slow and image reconstruction remains cumbersome. Here we describe an imaging mass spectrometer that exploits the true imaging capabilities by ion optical means for the time of flight mass separation. The mass spectrometer is equipped with the ASIC Timepix chip as an array detector to acquire the position, mass, and intensity of ions that are imaged by matrix-assisted laser desorption/ionization (MALDI) directly from the target sample onto the detector. This imaging mass spectrometer has a spatial resolving power at the specimen of (84 ± 35) μm with a mass resolution of 45 and locates atoms or organic compounds on a surface area up to ~2 cm2. Extended laser spots of ~5 mm2 on structured specimens allows parallel imaging of selected masses. The digital imaging mass spectrometer proves high hit-multiplicity, straightforward image reconstruction, and potential for high-speed readout at 4 kHz or more. This device demonstrates a simple way of true image acquisition like a digital photographic camera. The technology may enable a fast analysis of biomolecular samples in near future.

  8. FY09 PROGRESS: MULTI-ISOTOPE PROCESS (MIP) MONITOR

    SciTech Connect

    Schwantes, Jon M.; Orton, Christopher R.; Fraga, Carlos G.; Christensen, Richard; Laspe, Amy R.; Ward, Rebecca M.

    2009-10-18

    Model and experimental estimates of the Multi-Isotope Process Monitor performance for determining burnup after dissolution and acid concentration during solvent extraction steps during reprocessing of spent nuclear fuel are presented.

  9. Imaging Mass Spectrometry in Neuroscience

    PubMed Central

    2013-01-01

    Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for studying neurobiological systems is evident, the relevance of the technique for application in neuroscience is still in its infancy. In the present Review, a principal overview of the different approaches, including matrix assisted laser desorption ionization and secondary ion mass spectrometry, is provided with particular focus on their strengths and limitations for studying different neurochemical species in situ and in vitro. The potential of the various approaches is discussed based on both fundamental and biomedical neuroscience research. This Review aims to serve as a general guide to familiarize the neuroscience community and other biomedical researchers with the technique, highlighting its great potential and suitability for comprehensive and specific chemical imaging. PMID:23530951

  10. Imaging mass spectrometer with mass tags

    DOEpatents

    Felton, James S.; Wu, Kuang Jen J.; Knize, Mark G.; Kulp, Kristen S.; Gray, Joe W.

    2013-01-29

    A method of analyzing biological material by exposing the biological material to a recognition element, that is coupled to a mass tag element, directing an ion beam of a mass spectrometer to the biological material, interrogating at least one region of interest area from the biological material and producing data, and distributing the data in plots.

  11. Imaging mass spectrometer with mass tags

    DOEpatents

    Felton, James S.; Wu, Kuang Jen; Knize, Mark G.; Kulp, Kristen S.; Gray, Joe W.

    2010-06-01

    A method of analyzing biological material by exposing the biological material to a recognition element, that is coupled to a mass tag element, directing an ion beam of a mass spectrometer to the biological material, interrogating at least one region of interest area from the biological material and producing data, and distributing the data in plots.

  12. Mass spectrometry imaging for biomedical applications

    PubMed Central

    Liu, Jiangjiang; Ouyang, Zheng

    2013-01-01

    The development of mass spectrometry imaging technologies is of significant current research interest. Mass spectrometry potentially is capable of providing highly specific information about the distribution of chemical compounds on tissues at highly sensitive levels. The required in-situ analysis for the tissue imaging forced MS analysis being performed off the traditional conditions optimized in pharmaceutical applications with intense sample preparation. This critical review seeks to present an overview of the current status of the MS imaging with different sampling ionization methods and to discuss the 3D imaging and quantitative imaging capabilities needed to be further developed, the importance of the multi-modal imaging, and a balance between the pursuit of the high imaging resolution and the practical application of MS imaging in biomedicine. PMID:23539099

  13. High-resolution quantitative imaging of mammalian and bacterial cells using stable isotope mass spectrometry

    PubMed Central

    Lechene, Claude; Hillion, Francois; McMahon, Greg; Benson, Douglas; Kleinfeld, Alan M; Kampf, J Patrick; Distel, Daniel; Luyten, Yvette; Bonventre, Joseph; Hentschel, Dirk; Park, Kwon Moo; Ito, Susumu; Schwartz, Martin; Benichou, Gilles; Slodzian, Georges

    2006-01-01

    Background Secondary-ion mass spectrometry (SIMS) is an important tool for investigating isotopic composition in the chemical and materials sciences, but its use in biology has been limited by technical considerations. Multi-isotope imaging mass spectrometry (MIMS), which combines a new generation of SIMS instrument with sophisticated ion optics, labeling with stable isotopes, and quantitative image-analysis software, was developed to study biological materials. Results The new instrument allows the production of mass images of high lateral resolution (down to 33 nm), as well as the counting or imaging of several isotopes simultaneously. As MIMS can distinguish between ions of very similar mass, such as 12C15N- and 13C14N-, it enables the precise and reproducible measurement of isotope ratios, and thus of the levels of enrichment in specific isotopic labels, within volumes of less than a cubic micrometer. The sensitivity of MIMS is at least 1,000 times that of 14C autoradiography. The depth resolution can be smaller than 1 nm because only a few atomic layers are needed to create an atomic mass image. We illustrate the use of MIMS to image unlabeled mammalian cultured cells and tissue sections; to analyze fatty-acid transport in adipocyte lipid droplets using 13C-oleic acid; to examine nitrogen fixation in bacteria using 15N gaseous nitrogen; to measure levels of protein renewal in the cochlea and in post-ischemic kidney cells using 15N-leucine; to study DNA and RNA co-distribution and uridine incorporation in the nucleolus using 15N-uridine and 81Br of bromodeoxyuridine or 14C-thymidine; to reveal domains in cultured endothelial cells using the native isotopes 12C, 16O, 14N and 31P; and to track a few 15N-labeled donor spleen cells in the lymph nodes of the host mouse. Conclusion MIMS makes it possible for the first time to both image and quantify molecules labeled with stable or radioactive isotopes within subcellular compartments. PMID:17010211

  14. Multi-isotopic transuranic waste interrogation using delayed neutron nondestructive assay and iterative quadratic programming techniques

    NASA Astrophysics Data System (ADS)

    Wu, Cheng-Wei

    1997-11-01

    Nuclear safeguards for Special Nuclear Materials is to protect the nuclear materials against malevolent use and to insure their peaceful usage. The nondestructive assay technique (NDA) offers an efficient and proliferation resistance method for nuclear safeguards technology. NDA techniques were investigated for multi-isotopic transuranic waste interrogation. This work was originally intended for the Integral Fast Reactor (IFR) under development at Argonne National Laboratory. One major feature of the IFR is its integral fuel cycle based on a pyrometallurgical process. More than 99% of transuranics produced in the fuel are returned to the makeup fuel and burned in the reactor. With the long-lived actinides removed from the waste stream, the waste produced will decay sufficiently in 300 years dropping below the cancer risk level of natural uranium ore and easing the perceived waste management problem. The feasibility of using nondestructive assay techniques for the IFR fuel cycle waste interrogation were studied. A special DNNDA experimental device was designed and analysis techniques were developed. The DNNDA technique uses the delayed neutrons emitted after the activation of a 14 MeV neutron source as the characteristic signature for each fissionable isotope. A tantalum/polyethylene filter was employed to enhance the discrimination between the fissile and the fissionable isotopes. Spontaneous fissions from 240Pu were also measured to assist the mass assay. A nonlinear overdetermined system was established based on the DNNDA measurements. An Iterative Quadratic Programming (IQP) method was applied to perform the estimates. The IQP method has several advantages over the linear least squares and Kalman filter methods, it has the flexibility of adding additional constraints, it has superlinear global convergence and it can be utilized for nonlinear problems. The results show that using the IQP method with the DNNDA technique is quite promising for multi-isotopic assay

  15. Atmospheric pressure femtosecond laser imaging mass spectrometry

    NASA Astrophysics Data System (ADS)

    Coello, Yves; Gunaratne, Tissa C.; Dantus, Marcos

    2009-02-01

    We present a novel imaging mass spectrometry technique that uses femtosecond laser pulses to directly ionize the sample. The method offers significant advantages over current techniques by eliminating the need of a laser-absorbing sample matrix, being suitable for atmospheric pressure sampling, and by providing 10μm resolution, as demonstrated here with a chemical image of vegetable cell walls.

  16. Spatial neuroproteomics using imaging mass spectrometry.

    PubMed

    Hanrieder, Jörg; Malmberg, Per; Ewing, Andrew G

    2015-07-01

    The nervous system constitutes arguably the most complicated and least understood cellular network in the human body. This consequently manifests itself in the fact that the molecular bases of neurodegenerative diseases remain unknown. The limited understanding of neurobiological mechanisms relates directly to the lack of appropriate bioanalytical technologies that allow highly resolved, sensitive, specific and comprehensive molecular imaging in complex biological matrices. Imaging mass spectrometry (IMS) is an emerging technique for molecular imaging. The technique is characterized by its high chemical specificity allowing comprehensive, spatial protein and peptide profiling in situ. Imaging MS represents therefore a powerful approach for investigation of spatio-temporal protein and peptide regulations in CNS derived tissue and cells. This review aims to provide a concise overview of major developments and applications concerning imaging mass spectrometry based protein and peptide profiling in neurobiological and biomedical research. This article is part of a Special Issue entitled: Neuroproteomics: Applications in Neuroscience and Neurology. PMID:25582083

  17. A mass spectrometry primer for mass spectrometry imaging

    PubMed Central

    Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2011-01-01

    Mass spectrometry imaging (MSI), a rapidly growing subfield of chemical imaging, employs mass spectrometry (MS) technologies to create single- and multi-dimensional localization maps for a variety of atoms and molecules. Complimentary to other imaging approaches, MSI provides high chemical specificity and broad analyte coverage. This powerful analytical toolset is capable of measuring the distribution of many classes of inorganics, metabolites, proteins and pharmaceuticals in chemically and structurally complex biological specimens in vivo, in vitro, and in situ. The MSI approaches highlighted in this Methods in Molecular Biology volume provide flexibility of detection, characterization, and identification of multiple known and unknown analytes. The goal of this chapter is to introduce investigators who may be unfamiliar with MS to the basic principles of the mass spectrometric approaches as used in MSI. In addition to guidelines for choosing the most suitable MSI method for specific investigations, cross-references are provided to the chapters in this volume that describe the appropriate experimental protocols. PMID:20680583

  18. Membrane composition analysis by imaging mass spectrometry

    SciTech Connect

    Boxer, S G; Kraft, M L; Longo, M; Hutcheon, I D; Weber, P K

    2006-03-29

    Membranes on solid supports offer an ideal format for imaging. Secondary ion mass spectrometry (SIMS) can be used to obtain composition information on membrane-associated components. Using the NanoSIMS50, images of composition variations in membrane domains can be obtained with a lateral resolution better than 100 nm. By suitable calibration, these variations in composition can be translated into a quantitative analysis of the membrane composition. Progress towards imaging small phase-separated lipid domains, membrane-associated proteins and natural biological membranes will be described.

  19. Compressed sensing in imaging mass spectrometry

    NASA Astrophysics Data System (ADS)

    Bartels, Andreas; Dülk, Patrick; Trede, Dennis; Alexandrov, Theodore; Maaß, Peter

    2013-12-01

    Imaging mass spectrometry (IMS) is a technique of analytical chemistry for spatially resolved, label-free and multipurpose analysis of biological samples that is able to detect the spatial distribution of hundreds of molecules in one experiment. The hyperspectral IMS data is typically generated by a mass spectrometer analyzing the surface of the sample. In this paper, we propose a compressed sensing approach to IMS which potentially allows for faster data acquisition by collecting only a part of the pixels in the hyperspectral image and reconstructing the full image from this data. We present an integrative approach to perform both peak-picking spectra and denoising m/z-images simultaneously, whereas the state of the art data analysis methods solve these problems separately. We provide a proof of the robustness of the recovery of both the spectra and individual channels of the hyperspectral image and propose an algorithm to solve our optimization problem which is based on proximal mappings. The paper concludes with the numerical reconstruction results for an IMS dataset of a rat brain coronal section.

  20. Cu-Zn-Pb multi isotopic characterization of a small watershed (Loire river basin, France)

    NASA Astrophysics Data System (ADS)

    Desaulty, A. M.; Millot, R.; Perret, S.; Bourrain, X.

    2015-12-01

    Combating metal pollution in surface water is a major environmental, public health and economic issue. Knowledge of the behavior of metals, such as copper (Cu), zinc (Zn) and lead (Pb) in sediments and dissolved load, is a key factor to improve the management of rivers. Recent advances in mass spectrometry related to the development of MC-ICPMS allow to analyze the isotopic composition of these elements, and previous studies show the effectiveness of isotopic analyses to determine the anthropogenic sources of pollution in environment. The goal of this study is to use the Cu-Zn-Pb multi-isotopic signature to track the pollutions in surface water, and to understand the complex processes causing the metals mobilization and transport in environment. More particularly we investigate the mechanisms of distribution between the dissolved load and particulate load, known to play an important role in the transport of metals through river systems. As case study, we chose a small watershed, poorly urbanized in the Loire river basin. Its spring is in a pristine area, while it is only impacted some kilometers further by the releases rich in metals coming from a hospital water treatment plant. First a sampling of these liquid effluents as well as dissolved load and sediment from upstream to downstream was realized and their concentrations and isotopic data were determined. Then to simulate a lot of potential natural and anthropogenic modifications of environmental conditions, we made sequential extraction protocol using various reagents on the sediments. Isotopic analyzes were performed also on the various extracting solutions. Isotopic ratios were measured using a Neptune MC-ICPMS at the BRGM, after a protocol of purification for Zn and Cu. The results showed that, these isotopic systematics reveal important informations about the mechanists of mobilization and transport of metals through river systems. However experiments performed under laboratory conditions will be necessary

  1. Spatial Autocorrelation in Mass Spectrometry Imaging.

    PubMed

    Cassese, Alberto; Ellis, Shane R; Ogrinc Potočnik, Nina; Burgermeister, Elke; Ebert, Matthias; Walch, Axel; van den Maagdenberg, Arn M J M; McDonnell, Liam A; Heeren, Ron M A; Balluff, Benjamin

    2016-06-01

    Mass spectrometry imaging (MSI) is a powerful molecular imaging technique. In microprobe MSI, images are created through a grid-wise interrogation of individual spots by mass spectrometry across a surface. Classical statistical tests for within-sample comparisons fail as close-by measurement spots violate the assumption of independence of these tests, which can lead to an increased false-discovery rate. For spatial data, this effect is referred to as spatial autocorrelation. In this study, we investigated spatial autocorrelation in three different matrix-assisted laser desorption/ionization MSI data sets. These data sets cover different molecular classes (metabolites/drugs, lipids, and proteins) and different spatial resolutions ranging from 20 to 100 μm. Significant spatial autocorrelation was detected in all three data sets and found to increase with decreasing pixel size. To enable statistical testing for differences in mass signal intensities between regions of interest within MSI data sets, we propose the use of Conditional Autoregressive (CAR) models. We show that, by accounting for spatial autocorrelation, discovery rates (i.e., the ratio between the features identified and the total number of features) could be reduced between 21% and 69%. The reliability of this approach was validated by control mass signals based on prior knowledge. In light of the advent of larger MSI data sets based on either an increased spatial resolution or 3D data sets, accounting for effects due to spatial autocorrelation becomes even more indispensable. Here, we propose a generic and easily applicable workflow to enable within-sample statistical comparisons. PMID:27180608

  2. Mass spectrometry imaging: Towards a lipid microscope?

    PubMed

    Touboul, David; Brunelle, Alain; Laprévote, Olivier

    2011-01-01

    Biological imaging techniques are the most efficient way to locally measure the variation of different parameters on tissue sections. These analyses are gaining increasing interest since 20 years and allow observing extremely complex biological phenomena at lower and lower time and resolution scale. Nevertheless, most of them only target very few compounds of interest, which are chosen a priori, due to their low resolution power and sensitivity. New chemical imaging technique has to be introduced in order to overcome these limitations, leading to more informative and sensitive analyses for biologists and physicians. Two major mass spectrometry methods can be efficiently used to generate the distribution of biological compounds over a tissue section. Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry (MALDI-MS) needs the co-crystallization of the sample with a matrix before to be irradiated by a laser, whereas the analyte is directly desorbed by a primary ion bombardment for Secondary Ion Mass Spectrometry (SIMS) experiments. In both cases, energy used for desorption/ionization is locally deposited -some tens of microns for the laser and some hundreds of nanometers for the ion beam- meaning that small areas over the surface sample can be separately analyzed. Step by step analysis allows spectrum acquisitions over the tissue sections and the data are treated by modern informatics software in order to create ion density maps, i.e., the intensity plot of one specific ion versus the (x,y) position. Main advantages of SIMS and MALDI compared to other chemical imaging techniques lie in the simultaneous acquisition of a large number of biological compounds in mixture with an excellent sensitivity obtained by Time-of-Flight (ToF) mass analyzer. Moreover, data treatment is done a posteriori, due to the fact that no compound is selectively marked, and let us access to the localization of different lipid classes in only one complete acquisition. PMID:20570708

  3. Mass Spectrometry Imaging under Ambient Conditions

    PubMed Central

    Wu, Chunping; Dill, Allison L.; Eberlin, Livia S.; Cooks, R. Graham; Ifa, Demian R.

    2012-01-01

    Mass spectrometry imaging (MSI) has emerged as an important tool in the last decade and it is beginning to show potential to provide new information in many fields owing to its unique ability to acquire molecularly specific images and to provide multiplexed information, without the need for labeling or staining. In MSI, the chemical identity of molecules present on a surface is investigated as a function of spatial distribution. In addition to now standard methods involving MSI in vacuum, recently developed ambient ionization techniques allow MSI to be performed under atmospheric pressure on untreated samples outside the mass spectrometer. Here we review recent developments and applications of MSI emphasizing the ambient ionization techniques of desorption electrospray ionization (DESI), laser ablation electrospray ionization (LAESI), probe electrospray ionization (PESI), desorption atmospheric pressure photoionization (DAPPI), femtosecond laser desorption ionization (fs-LDI), laser electrospray mass spectrometry (LEMS), infrared laser ablation metastable-induced chemical ionization (IR-LAMICI), liquid microjunction surface sampling probe mass spectrometry (LMJ-SSP MS), nanospray desorption electrospray ionization (nano-DESI), and plasma sources such as the low temperature plasma (LTP) probe and laser ablation coupled to flowing atmospheric-pressure afterglow (LA-FAPA). Included are discussions of some of the features of ambient MSI including the ability to implement chemical reactions with the goal of providing high abundance ions characteristic of specific compounds of interest and the use of tandem mass spectrometry to either map the distribution of targeted molecules with high specificity or to provide additional MS information in the structural identification of compounds. We also describe the role of bioinformatics in acquiring and interpreting the chemical and spatial information obtained through MSI, especially in biological applications for tissue

  4. Visualizing nanoparticle dissolution by imaging mass spectrometry.

    PubMed

    Szakal, Christopher; Ugelow, Melissa S; Gorham, Justin M; Konicek, Andrew R; Holbrook, R David

    2014-04-01

    We demonstrate the ability to visualize nanoparticle dissolution while simultaneously providing chemical signatures that differentiate between citrate-capped silver nanoparticles (AgNPs), AgNPs forced into dissolution via exposure to UV radiation, silver nitrate (AgNO3), and AgNO3/citrate deposited from aqueous solutions and suspensions. We utilize recently developed inkjet printing (IJP) protocols to deposit the different solutions/suspensions as NP aggregates and soluble species, which separate onto surfaces in situ, and collect mass spectral imaging data via time-of-flight secondary ion mass spectrometry (TOF-SIMS). Resulting 2D Ag(+) chemical images provide the ability to distinguish between the different Ag-containing starting materials and, when coupled with mass spectral peak ratios, provide information-rich data sets for quick and reproducible visualization of NP-based aqueous constituents. When compared to other measurements aimed at studying NP dissolution, the IJP-TOF-SIMS approach offers valuable information that can potentially help in understanding the complex equilibria in NP-containing solutions and suspensions, including NP dissolution kinetics and extent of overall dissolution. PMID:24611464

  5. Solar Mass Ejection Imager (SMEI) space experiment

    NASA Astrophysics Data System (ADS)

    Radick, Richard R.

    2001-12-01

    The Solar Mass Ejection Imager (SMEI) is a proof-of-concept space experiment designed to observe solar coronal mass ejections (CMEs) and forecast their arrival at Earth. SMEI will image CMEs by sensing sunlight scattered from the free electrons in these ejecta (i.e., Thomson scattering). SMEI will be launched by a Titan II rocket into a circular, 830-km, sun-synchronous orbit in mid-2002 as part of the Space Test Program's CORIOLIS mission. SMEI will image nearly the entire sky once per spacecraft orbit over a mission lifetime of three years. Successful operation of SMEI will represent a major step in improving space weather forecasts by providing one- to three-day predictions of geomagnetic storms at the Earth. The SMEI experiment is being designed and constructed by a team of scientists and engineers from the Air Force Research Laboratory, the University of Birmingham (UB) in the United Kingdom, the University of California at San Diego (UCSD), and Boston University. The Air Force, NASA, and UB are providing financial support.

  6. Improving Secondary Ion Mass Spectrometry Image Quality with Image Fusion

    PubMed Central

    Tarolli, Jay G.; Jackson, Lauren M.; Winograd, Nicholas

    2014-01-01

    The spatial resolution of chemical images acquired with cluster secondary ion mass spectrometry (SIMS) is limited not only by the size of the probe utilized to create the images, but also by detection sensitivity. As the probe size is reduced to below 1 µm, for example, a low signal in each pixel limits lateral resolution due to counting statistics considerations. Although it can be useful to implement numerical methods to mitigate this problem, here we investigate the use of image fusion to combine information from scanning electron microscope (SEM) data with chemically resolved SIMS images. The advantage of this approach is that the higher intensity and, hence, spatial resolution of the electron images can help to improve the quality of the SIMS images without sacrificing chemical specificity. Using a pan-sharpening algorithm, the method is illustrated using synthetic data, experimental data acquired from a metallic grid sample, and experimental data acquired from a lawn of algae cells. The results show that up to an order of magnitude increase in spatial resolution is possible to achieve. A cross-correlation metric is utilized for evaluating the reliability of the procedure. PMID:24912432

  7. MASS SPECTROMETRY IMAGING FOR DRUGS AND METABOLITES

    PubMed Central

    Greer, Tyler; Sturm, Robert; Li, Lingjun

    2011-01-01

    Mass spectrometric imaging (MSI) is a powerful analytical technique that provides two- and three-dimensional spatial maps of multiple compounds in a single experiment. This technique has been routinely applied to protein, peptide, and lipid molecules with much less research reporting small molecule distributions, especially pharmaceutical drugs. This review’s main focus is to provide readers with an up-to-date description of the substrates and compounds that have been analyzed for drug and metabolite composition using MSI technology. Additionally, ionization techniques, sample preparation, and instrumentation developments are discussed. PMID:21515430

  8. Mass Determination Of Directly Imaged Planet Candidates

    NASA Astrophysics Data System (ADS)

    Schmidt, Tobias; Neuhauser, R.; Seifahrt, A.

    2011-09-01

    About 20 sub-stellar companions with large separations (> 50 AU) to their young primary stars and brown dwarfs are confirmed by both common proper motion and late-M / early-L type spectra. The origin and early evolution of these objects is still under debate. While often these sub-stellar companions are regarded as brown dwarfs, they could possibly also be massive planets, the mass estimates are very uncertain so far. They are companions to primary stars or brown dwarfs in young associations and star forming regions like Taurus, Upper Scorpius, the TW Hya association, Beta Pic moving group, TucHor association, Lupus, Ophiuchus, and Chamaeleon, hence their ages and distances are well known, in contrast to free-floating brown dwarfs. Here we present how mass estimates of such young directly imaged companions can be derived, using e.g. evolutionary models, which are however currently almost uncalibrated by direct mass measurements of young objects. An empirical classification by medium-resolution spectroscopy is currently not possible, because a spectral sequence that is taking the lower gravity into account, is not existing. This problem leads to an apparent mismatch between spectra of old field type objects and young low-mass companions at the same effective temperature, hampering a determination of temperature and surface gravity independent from models. We show that from spectra of the objects, using the advantages of light concentration by an AO-assisted integral field spectrograph, temperature, extinction, metallicity and surface gravity can be derived using non-equilibrium radiative transfer atmosphere models as comparison and that this procedure as well allows a mass determination in combination with the luminosities found by the direct observations, as has recently been done by us for several young sub-stellar companions, as e.g. GQ Lup, CT Cha or UScoCTIO 108.

  9. imzML: Imaging Mass Spectrometry Markup Language: A common data format for mass spectrometry imaging.

    PubMed

    Römpp, Andreas; Schramm, Thorsten; Hester, Alfons; Klinkert, Ivo; Both, Jean-Pierre; Heeren, Ron M A; Stöckli, Markus; Spengler, Bernhard

    2011-01-01

    Imaging mass spectrometry is the method of scanning a sample of interest and generating an "image" of the intensity distribution of a specific analyte. The data sets consist of a large number of mass spectra which are usually acquired with identical settings. Existing data formats are not sufficient to describe an MS imaging experiment completely. The data format imzML was developed to allow the flexible and efficient exchange of MS imaging data between different instruments and data analysis software.For this purpose, the MS imaging data is divided in two separate files. The mass spectral data is stored in a binary file to ensure efficient storage. All metadata (e.g., instrumental parameters, sample details) are stored in an XML file which is based on the standard data format mzML developed by HUPO-PSI. The original mzML controlled vocabulary was extended to include specific parameters of imaging mass spectrometry (such as x/y position and spatial resolution). The two files (XML and binary) are connected by offset values in the XML file and are unambiguously linked by a universally unique identifier. The resulting datasets are comparable in size to the raw data and the separate metadata file allows flexible handling of large datasets.Several imaging MS software tools already support imzML. This allows choosing from a (growing) number of processing tools. One is no longer limited to proprietary software, but is able to use the processing software which is best suited for a specific question or application. On the other hand, measurements from different instruments can be compared within one software application using identical settings for data processing. All necessary information for evaluating and implementing imzML can be found at http://www.imzML.org . PMID:21063949

  10. Status of the Solar Mass Ejection Imager

    NASA Astrophysics Data System (ADS)

    Johnston, J. C.; Radick, R. R.; Webb, D. F.

    2001-05-01

    The Solar Mass Ejection Imager (SMEI) is a proof-of-concept experiment designed to detect and track coronal mass ejections (CMEs) as they propagate from the Sun through interplanetary space to the Earth and beyond. SMEI will Image CMEs by sensing sunlight scattered from the free electrons in these structures (Thomson scattering). SMEI will be launched by a Titan II rocket into a circular, sun-synchronous (830 km) orbit in 2002 as part of the Space Test Program's CORIOLIS mission. SMEI will image the entire sky once per spacecraft orbit over a mission lifetime of three years. The major subsystems of SMEI are three electronic camera assemblies and a data-handling unit. Each camera consists of a baffle, a radiator, a bright object sensor, an electronics box, and a strongbox containing a shutter, optics and a CCD. Each camera images a 3x60 degree field. Together, they view a 180-degree slice of sky, and sweep over the entire sky once per orbit. SMEI's basic data product will be a 100-minute cadence of all-sky maps of heliospheric brightness, with stars removed, having an angular resolution of about one degree and a photometric precision of about 0.1%. Successful operation of SMEI will represent a major step in improving space weather forecasts. When combined with in-situ solar wind measurements from upstream monitors such as WIND and ACE, SMEI will provide one- to three-day predictions of impending geomagnetic storms at the Earth. SMEI will complement missions such as SoHO, GOES SXI, Solar-B, and STEREO by providing data relating solar drivers to terrestrial effects. Other benefits of SMEI will include observations of variable stars, extra-Solar planetary transits, novae and supernovae, comets and asteroids. The SMEI experiment is being designed and constructed by a team of scientists and engineers from the Air Force Research Laboratory, the University of Birmingham (UB) in the United Kingdom, the University of California at San Diego (UCSD), and Boston University. The

  11. Diffusion of multi-isotopic chemical species in molten silicates

    NASA Astrophysics Data System (ADS)

    Watkins, James M.; Liang, Yan; Richter, Frank; Ryerson, Frederick J.; DePaolo, Donald J.

    2014-08-01

    Diffusion experiments in a simplified Na2O-CaO-SiO2 liquid system are used to develop a general formulation for the fractionation of Ca isotopes during liquid-phase diffusion. Although chemical diffusion is a well-studied process, the mathematical description of the effects of diffusion on the separate isotopes of a chemical element is surprisingly underdeveloped and uncertain. Kinetic theory predicts a mass dependence on isotopic mobility, but it is unknown how this translates into a mass dependence on effective binary diffusion coefficients, or more generally, the chemical diffusion coefficients that are housed in a multicomponent diffusion matrix. Our experiments are designed to measure Ca mobility, effective binary diffusion coefficients, the multicomponent diffusion matrix, and the effects of chemical diffusion on Ca isotopes in a liquid of single composition. We carried out two chemical diffusion experiments and one self-diffusion experiment, all at 1250 °C and 0.7 GPa and using a bulk composition for which other information is available from the literature. The self-diffusion experiment is used to determine the mobility of Ca in the absence of diffusive fluxes of other liquid components. The chemical diffusion experiments are designed to determine the effect on Ca isotope fractionation of changing the counter-diffusing component from fast-diffusing Na2O to slow-diffusing SiO2. When Na2O is the main counter-diffusing species, CaO diffusion is fast and larger Ca isotopic effects are generated. When SiO2 is the main counter-diffusing species, CaO diffusion is slow and smaller Ca isotopic effects are observed. In both experiments, the liquid is initially isotopically homogeneous, and during the experiment Ca isotopes become fractionated by diffusion. The results are used as a test of a new general expression for the diffusion of isotopes in a multicomponent liquid system that accounts for both self diffusion and the effects of counter-diffusing species. Our

  12. Ambient mass spectrometry imaging: plasma assisted laser desorption ionization mass spectrometry imaging and its applications.

    PubMed

    Feng, Baosheng; Zhang, Jialing; Chang, Cuilan; Li, Liping; Li, Min; Xiong, Xingchuang; Guo, Chengan; Tang, Fei; Bai, Yu; Liu, Huwei

    2014-05-01

    Mass spectrometry imaging (MSI) has been widely used in many research areas for the advantages of providing informative molecular distribution with high specificity. Among the recent progress, ambient MSI has attracted increasing interests owing to its characteristics of ambient, in situ, and nonpretreatment analysis. Here, we are presenting the ambient MSI for traditional Chinese medicines (TCMs) and authentication of work of art and documents using plasma assisted laser desorption ionization mass spectrometry (PALDI-MS). Compared with current ambient MSI methods, an excellent average resolution of 60 μm × 60 μm pixel size was achieved using this system. The feasibility of PALDI-based MSI was confirmed by seal imaging, and its authentication applications were demonstrated by imaging of printed Chinese characters. Imaging of the Radix Scutellariae slice showed that the two active components, baicalein and wogonin, mainly were distributed in the epidermis of the root, which proposed an approach for distinguishing TCMs' origins and the distribution of active components of TCMs and exploring the environmental effects of plant growth. PALDI-MS imaging provides a strong complement for the MSI strategy with the enhanced spatial resolution, which is promising in many research fields, such as artwork identification, TCMs' and botanic research, pharmaceutical applications, etc. PMID:24670045

  13. Imaging and differential diagnosis of suprarenal masses in the fetus.

    PubMed

    Maki, Erik; Oh, Karen; Rogers, Sarah; Sohaey, Roya

    2014-05-01

    Prenatal sonography and magnetic resonance imaging of suprarenal fetal masses is presented, along with clinical information and follow-up. Imaging pearls and differential considerations for each diagnosis will be discussed. Fetal suprarenal mass diagnoses include neuroblastoma, extralobar pulmonary sequestration, congenital adrenal hyperplasia, partial multicystic dysplastic kidney, renal duplication, urinoma, gastric duplication cyst, and splenic cyst. Recognizing the range of malignant and benign suprarenal fetal masses that can present on prenatal imaging can help guide patient counseling and management. PMID:24764345

  14. Structurally selective imaging mass spectrometry by imaging ion mobility-mass spectrometry.

    PubMed

    McLean, John A; Fenn, Larissa S; Enders, Jeffrey R

    2010-01-01

    This chapter describes the utility of structurally based separations combined with imaging mass spectrometry (MS) by ion mobility-MS (IM-MS) approaches. The unique capabilities of combining rapid (mus-ms) IM separations with imaging MS are detailed for an audience ranging from new to potential practitioners in IM-MS technology. Importantly, imaging IM-MS provides the ability to rapidly separate and elucidate various types of endogenous and exogenous biomolecules (e.g., nucleotides, carbohydrates, peptides, and lipids), including isobaric species. Drift tube and traveling wave IM-MS instrumentation are described and specific protocols are presented for calculating ion-neutral collision cross sections (i.e., apparent ion surface area or structure) from experimentally obtained IM-MS data. Special emphasis is placed on the use of imaging IM-MS for the analysis of samples in life sciences research (e.g., thin tissue sections), including selective imaging for peptide/protein and lipid distributions. Future directions for rapid and multiplexed imaging IM-MS/MS are detailed. PMID:20680602

  15. Preparation of a multi-isotope plutonium AMS standard and preliminary results of a first inter-lab comparison

    NASA Astrophysics Data System (ADS)

    Dittmann, B.-A.; Dunai, T. J.; Dewald, A.; Heinze, S.; Feuerstein, C.; Strub, E.; Fifield, L. K.; Froehlich, M. B.; Tims, S. G.; Wallner, A.; Christl, M.

    2015-10-01

    The motivation of this work is to establish a new multi-isotope plutonium standard for isotopic ratio measurements with accelerator mass spectrometry (AMS), since stocks of existing solutions are declining. To this end, certified reference materials (CRMs) of each of the individual isotopes 239Pu, 240Pu, 242Pu and 244Pu were obtained from JRC IRMM (Joint Research Center Institute for Reference Materials and Measurements). These certified reference materials (IRMM-081a, IRMM-083, IRMM-043 and IRMM-042a) were diluted with nitric acid and mixed to obtain a stock standard solution with an isotopic ratio of approximately 1.0:1.0:1.0:0.1 (239Pu:240Pu:242Pu:244Pu). From this stock solution, samples were prepared for measurement of the plutonium isotopic composition by AMS. These samples have been measured in a round-robin exercise between the AMS facilities at CologneAMS, at the ANU Canberra and ETH Zurich to verify the isotopic ratio and to demonstrate the reproducibility of the measurements. The results show good agreement both between the different AMS measurements and with the gravimetrically determined nominal ratios.

  16. Absorption Mode FT-ICR Mass Spectrometry Imaging

    SciTech Connect

    Smith, Donald F.; Kilgour, David P.; Konijnenburg, Marco; O'Connor, Peter B.; Heeren, Ronald M.

    2013-12-03

    Fourier transform ion cyclotron resonance mass spectrometry offers the highest mass resolving power for molecular imaging experiments. This high mass resolving power ensures that closely spaced peaks at the same nominal mass are resolved for proper image generation. Typically higher magnetic fields are used to increase mass resolving power. However, a gain in mass resolving power can also be realized by phase correction of the data for absorption mode display. In addition to mass resolving power, absorption mode offers higher mass accuracy and signal-to-noise ratio over the conventional magnitude mode. Here we present the first use of absorption mode for Fourier transform ion cyclotron resonance mass spectrometry imaging. The Autophaser algorithm is used to phase correct each spectrum (pixel) in the image and then these parameters are used by the Chameleon work-flow based data processing software to generate absorption mode ?Datacubes? for image and spectral viewing. Absorption mode reveals new mass and spatial features that are not resolved in magnitude mode and results in improved selected ion image contrast.

  17. Image reconstruction techniques applied to nuclear mass models

    NASA Astrophysics Data System (ADS)

    Morales, Irving O.; Isacker, P. Van; Velazquez, V.; Barea, J.; Mendoza-Temis, J.; Vieyra, J. C. López; Hirsch, J. G.; Frank, A.

    2010-02-01

    A new procedure is presented that combines well-known nuclear models with image reconstruction techniques. A color-coded image is built by taking the differences between measured masses and the predictions given by the different theoretical models. This image is viewed as part of a larger array in the (N,Z) plane, where unknown nuclear masses are hidden, covered by a “mask.” We apply a suitably adapted deconvolution algorithm, used in astronomical observations, to “open the window” and see the rest of the pattern. We show that it is possible to improve significantly mass predictions in regions not too far from measured nuclear masses.

  18. Suprasellar masses in children: Characteristic MR imaging features.

    PubMed

    Yildiz, Adalet Elcin; Oguz, Kader Karli; Fitoz, Suat

    2016-07-01

    Pediatric suprasellar masses are unique in their clinical presentation and imaging features. The differential diagnosis, incidence, surgical approach and adjuvant treatment options differ from adult tumors. Magnetic resonance (MR) imaging is fundamental in preoperative evaluation and provides detailed information about the suprasellar region. In this article, we review the characteristic MR imaging findings of common suprasellar masses in children. We also briefly discuss useful MR imaging sequences and planes used in the initial evaluation of a pediatric suprasellar mass and clinical findings at presentation. PMID:27131616

  19. Mass spectrometry-based imaging of metabolites and proteins.

    PubMed

    Peukert, Manuela; Becker, Michael; Matros, Andrea; Mock, Hans-Peter

    2014-01-01

    Imaging techniques based on mass spectrometry (MS) have become powerful approaches to decipher the spatial distribution of metabolites and proteins. MS imaging (MSI) mostly relies on matrix-assisted laser desorption/ionization coupled to MS detection, but desorption electrospray ionization is also frequently used. Here we describe our current protocols for MALDI-MSI of seed sections and for root tissue. Detailed procedures for cryo-sectioning, matrix application, image capture, mass spectrometry measurement and data analysis are given. PMID:24136526

  20. Secondary Ion Mass Spectrometry Imaging of Dictyostelium discoideum Aggregation Streams

    SciTech Connect

    Debord, J. Daniel; Smith, Donald F.; Anderton, Christopher R.; Heeren, Ronald M.; Pasa-Tolic, Ljiljana; Gomer, Richard H.; Fernandez-Lima, Francisco A.

    2014-06-09

    High resolution imaging mass spectrometry could become a valuable tool for cell and developmental biology, but both, high spatial and mass spectral resolution are needed to enable this. In this report, we employed Bi3 bombardment time-of-flight (Bi3 ToF-SIMS) and C60 bombardment Fourier transform ion cyclotron resonance secondary ion mass spectrometry (C60 FTICR-SIMS) to image Dictyostelium discoideum aggregation streams. Nearly 300 lipid species were identified from the aggregation streams. High resolution mass spectrometry imaging (FTICR-SIMS) enabled the generation of multiple molecular ion maps at the nominal mass level and provided good coverage for fatty acyls, prenol lipids, and sterol lipids. The comparison of Bi3 ToF-SIMS and C60 FTICR-SIMS suggested that while the first provides fast, high spatial resolution molecular ion images, the chemical complexity of biological samples warrants the use of high resolution analyzers for accurate ion identification.

  1. Imaging of presacral masses--a multidisciplinary approach.

    PubMed

    Patel, Nishant; Maturen, Katherine E; Kaza, Ravi K; Gandikota, Girish; Al-Hawary, Mahmoud M; Wasnik, Ashish P

    2016-01-01

    Our objective is to describe an approach for retrorectal/presacral mass evaluation on imaging with attention to imaging features, allowing for refinement of the differential diagnosis of these masses. Elaborate on clinically relevant features that may affect biopsy or surgical approach, of which the radiologist should be aware. A review of current literature regarding the diagnosis and treatment of retrorectal/presacral masses was performed with attention to specific findings, which may lend refinement to the differential diagnosis of these masses. Cases were obtained by searching through a radiology database at a single institution after Institutional Review Board approval. Recent advances in imaging and treatment methods have led to the increased role of radiology in both imaging and tissue diagnosis of retrorectal masses. Surgical philosophies surrounding the treatment of these masses have not significantly changed in recent years, but there are a few key factors of which the radiologist must be aware. The radiologist can offer refinement of the differential diagnosis of retrorectal masses and can elaborate on salient findings which could alter the need for neoadjuvant chemoradiation therapy, pre-surgical tissue diagnosis and surgical approach. This article presents an imaging approach to retrorectal/presacral masses with emphasis on findings which can dictate the ultimate need for neoadjuvant therapy and pre-surgical tissue diagnosis and alter the preferred surgical approach. This article consolidates key findings, so radiologists can become more clinically relevant in the evaluation of these masses. PMID:26828969

  2. Advances in imaging secondary ion mass spectrometry for biological samples

    SciTech Connect

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this has been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.

  3. Advances in imaging secondary ion mass spectrometry for biological samples

    DOE PAGESBeta

    Boxer, Steven G.; Kraft, Mary L.; Weber, Peter K.

    2008-12-16

    Imaging mass spectrometry combines the power of mass spectrometry to identify complex molecules based on mass with sample imaging. Recent advances in secondary ion mass spectrometry have improved sensitivity and spatial resolution, so that these methods have the potential to bridge between high-resolution structures obtained by X-ray crystallography and cyro-electron microscopy and ultrastructure visualized by conventional light microscopy. Following background information on the method and instrumentation, we address the key issue of sample preparation. Because mass spectrometry is performed in high vacuum, it is essential to preserve the lateral organization of the sample while removing bulk water, and this hasmore » been a major barrier for applications to biological systems. Furthermore, recent applications of imaging mass spectrometry to cell biology, microbial communities, and biosynthetic pathways are summarized briefly, and studies of biological membrane organization are described in greater depth.« less

  4. High mass accuracy and high mass resolving power FT-ICR secondary ion mass spectrometry for biological tissue imaging.

    PubMed

    Smith, Donald F; Kiss, Andras; Leach, Franklin E; Robinson, Errol W; Paša-Tolić, Ljiljana; Heeren, Ron M A

    2013-07-01

    Biological tissue imaging by secondary ion mass spectrometry has seen rapid development with the commercial availability of polyatomic primary ion sources. Endogenous lipids and other small bio-molecules can now be routinely mapped on the sub-micrometer scale. Such experiments are typically performed on time-of-flight mass spectrometers for high sensitivity and high repetition rate imaging. However, such mass analyzers lack the mass resolving power to ensure separation of isobaric ions and the mass accuracy for elemental formula assignment based on exact mass measurement. We have recently reported a secondary ion mass spectrometer with the combination of a C60 primary ion gun with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for high mass resolving power, high mass measurement accuracy, and tandem mass spectrometry capabilities. In this work, high specificity and high sensitivity secondary ion FT-ICR MS was applied to chemical imaging of biological tissue. An entire rat brain tissue was measured with 150 μm spatial resolution (75 μm primary ion spot size) with mass resolving power (m/Δm(50%)) of 67,500 (at m/z 750) and root-mean-square measurement accuracy less than two parts-per-million for intact phospholipids, small molecules and fragments. For the first time, ultra-high mass resolving power SIMS has been demonstrated, with m/Δm(50%) > 3,000,000. Higher spatial resolution capabilities of the platform were tested at a spatial resolution of 20 μm. The results represent order of magnitude improvements in mass resolving power and mass measurement accuracy for SIMS imaging and the promise of the platform for ultra-high mass resolving power and high spatial resolution imaging. PMID:23685962

  5. High Mass Accuracy and High Mass Resolving Power FT-ICR Secondary Ion Mass Spectrometry for Biological Tissue Imaging

    SciTech Connect

    Smith, Donald F.; Kiss, Andras; Leach, Franklin E.; Robinson, Errol W.; Pasa-Tolic, Ljiljana; Heeren, Ronald M.

    2013-07-01

    Biological tissue imaging by secondary ion mass spectrometry has seen rapid development with the commercial availability of polyatomic primary ion sources. Endogenous lipids and other small bio-molecules can now be routinely mapped on the micrometer scale. Such experiments are typically performed on time-of-flight mass spectrometers for high sensitivity and high repetition rate imaging. However, such mass analyzers lack the mass resolving power to ensure separation of isobaric ions and the mass accuracy for exact mass elemental formula assignment. We have recently reported a secondary ion mass spectrometer with the combination of a C60 primary ion gun with a Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS) for high mass resolving power, high mass measurement accuracy and tandem mass spectrometry capabilities. In this work, high specificity and high sensitivity secondary ion FT-ICR MS was applied to chemical imaging of biological tissue. An entire rat brain tissue was measured with 150 μm spatial resolution (75 μm primary ion spot size) with mass resolving power (m/Δm50%) of 67,500 (at m/z 750) and root-mean-square measurement accuracy less than two parts-per-million for intact phospholipids, small molecules and fragments. For the first time, ultra-high mass resolving power SIMS has been demonstrated, with m/Δm50% > 3,000,000. Higher spatial resolution capabilities of the platform were tested at a spatial resolution of 20 μm. The results represent order of magnitude improvements in mass resolving power and mass measurement accuracy for SIMS imaging and the promise of the platform for ultra-high mass resolving power and high spatial resolution imaging.

  6. Mass Spectrometry Imaging, an Emerging Technology in Neuropsychopharmacology

    PubMed Central

    Shariatgorji, Mohammadreza; Svenningsson, Per; Andrén, Per E

    2014-01-01

    Mass spectrometry imaging is a powerful tool for directly determining the distribution of proteins, peptides, lipids, neurotransmitters, metabolites and drugs in neural tissue sections in situ. Molecule-specific imaging can be achieved using various ionization techniques that are suited to different applications but which all yield data with high mass accuracies and spatial resolutions. The ability to simultaneously obtain images showing the distributions of chemical species ranging from metal ions to macromolecules makes it possible to explore the chemical organization of a sample and to correlate the results obtained with specific anatomical features. The imaging of biomolecules has provided new insights into multiple neurological diseases, including Parkinson's and Alzheimer's disease. Mass spectrometry imaging can also be used in conjunction with other imaging techniques in order to identify correlations between changes in the distribution of important chemical species and other changes in the properties of the tissue. Here we review the applications of mass spectrometry imaging in neuroscience research and discuss its potential. The results presented demonstrate that mass spectrometry imaging is a useful experimental method with diverse applications in neuroscience. PMID:23966069

  7. Imaging the mass structure of distant lens galaxies

    NASA Astrophysics Data System (ADS)

    Koopmans, Leon

    2005-07-01

    The surface brightness distribution of extended gravitationally lensed arcs and Einstein rings contains super-resolved information about the lensed object, and, more excitingly, about the smooth and clumpy mass distribution of the lens galaxies. The source and lens information can non-parametrically be separated, resulting in a direct "gravitational-mass image" of the inner mass-distribution of cosmologically-distant galaxies {Koopmans 2005}.With this goal in mind, we propose deep HST ACS-F555W/F814W and NICMOS-F160W imaging of 15 gravitational-lens systems with spatially resolved lensed sources, selected from the 17 new lens systems discovered by the Sloan Lens ACS Survey {Bolton et al. 2004}. Each system has been selected from the SDSS and confirmed in a time-efficient HST-ACS snapshot program {cycle-13}; they show highly-magnified arcs or Einstein rings, lensed by a massive early-type lens galaxy. High-fidelity multi-color HST images are required {not delivered by the 420-sec snapshot images} to isolate these lensed images {properly cleaned, dithered and extinction-corrected} from the lens galaxy surface brightness distribution, and apply our "gravitational-mass imaging" technique.The sample of galaxy mass distributions - determined through this method from the arcs and Einstein ring HST images - will be studied to: {i} measure the smooth mass distribution of the lens galaxies {Dark and luminous mass are separated using the HST images and the stellar M/L values derived from a joint stellar-dynamical analysis of each system}; {ii} quantify statistically and individually the incidence of mass-substructure {with or without obvious luminous counter-parts such as dwarf galaxies}. Since dark-matter substructure should be considerably more prevalent at higher redshift, both results provide a direct test of this prediction of the CDM hierarchical structure-formation model.

  8. Imaging Teachers: In Fact and in the Mass Media.

    ERIC Educational Resources Information Center

    Reyes, Xae Alicia; Rios, Diana I.

    2003-01-01

    The impact of mass media on public images of teachers and students is considered in a dialogue between two educational and mass media researchers. Stereotypes in films, such as teacher-savior and student-failure, and abundant reports about Latino dropout rates and low academic achievement impact teachers and the public, who accept negative images…

  9. Method for detecting a mass density image of an object

    DOEpatents

    Wernick, Miles N.; Yang, Yongyi

    2008-12-23

    A method for detecting a mass density image of an object. An x-ray beam is transmitted through the object and a transmitted beam is emitted from the object. The transmitted beam is directed at an angle of incidence upon a crystal analyzer. A diffracted beam is emitted from the crystal analyzer onto a detector and digitized. A first image of the object is detected from the diffracted beam emitted from the crystal analyzer when positioned at a first angular position. A second image of the object is detected from the diffracted beam emitted from the crystal analyzer when positioned at a second angular position. A refraction image is obtained and a regularized mathematical inversion algorithm is applied to the refraction image to obtain a mass density image.

  10. Determination of left ventricular mass through SPECT imaging

    NASA Astrophysics Data System (ADS)

    Zárate-Morales, A.; Rodríguez-Villafuerte, M.; Martínez-Rodríguez, F.; Arévila-Ceballos, N.

    1998-08-01

    An edge detection algorithm has been applied to estimate left ventricular (LV) mass from single photon emission computed tomography (SPECT) thallium-201 images. The algorithm was validated using SPECT images of a phantom. The algorithm was applied to 20 patient studies from the Hospital de Cardiologia, Centro Médico Nacional Siglo XXI. Left ventricular masses derived from the stress and redistribution studies were highly correlated (r=0.96). The average LV masses obtained were 162±37 g and 169±34 g in the redistribution and stress studies, respectively.

  11. Determination of left ventricular mass through SPECT imaging

    SciTech Connect

    Zarate-Morales, A.; Rodriguez-Villafuerte, M.; Martinez-Rodriguez, F.; Arevila-Ceballos, N.

    1998-08-28

    An edge detection algorithm has been applied to estimate left ventricular (LV) mass from single photon emission computed tomography (SPECT) thallium-201 images. The algorithm was validated using SPECT images of a phantom. The algorithm was applied to 20 patient studies from the Hospital de Cardiologia, Centro Medico Nacional Siglo XXI. Left ventricular masses derived from the stress and redistribution studies were highly correlated (r=0.96). The average LV masses obtained were 162{+-}37 g and 169{+-}34 g in the redistribution and stress studies, respectively.

  12. Renal masses in children. An integrated imaging approach to diagnosis

    SciTech Connect

    Wolfson, B.J.; Gainey, M.A.; Faerber, E.N.; Capitanio, M.A.

    1985-11-01

    In view of the continuing technologic advancements in the development and availability of diagnostic imaging modalities, it is appropriate to assess periodically the currently accepted approaches to the evaluation of renal masses in children. The roles, advantages, and disadvantages of plain film, intravenous urography, ultrasonography, radionuclide scintigraphy, computed tomography, angiography, and magnetic resonance imaging in the approach to the evaluation of renal masses in children are discussed. An integrated imaging approach that provides the most accurate and necessary information for diagnosis and treatment is recommended. 70 references.

  13. Mass Spectrometry-Based Tissue Imaging of Small Molecules

    PubMed Central

    Ferguson, Carly N.; Fowler, Joseph W.M.; Waxer, Jonathan F.; Gatti, Richard A.; Loo, Joseph A.

    2014-01-01

    Mass spectrometry imaging (MSI) of tissue samples is a promising analytical tool that has quickly become associated with biomedical and pharmacokinetic studies. It eliminates several labor-intensive protocols associated with more classical imaging techniques, and provides accurate, histological data at a rapid pace. Because mass spectrometry is used as the readout, MSI can be applied to almost any molecule, especially those that are biologically relevant. Many examples of its utility in the study of peptides and proteins have been reported; here we discuss its value in the mass range of small molecules. We explore its success and potential in the analysis of lipids, medicinals, and metal-based compounds by featuring representative studies from mass spectrometry imaging laboratories around the globe. PMID:24952187

  14. Mass spectrometry imaging and profiling of single cells

    PubMed Central

    Lanni, Eric J.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2012-01-01

    Mass spectrometry imaging and profiling of individual cells and subcellular structures provide unique analytical capabilities for biological and biomedical research, including determination of the biochemical heterogeneity of cellular populations and intracellular localization of pharmaceuticals. Two mass spectrometry technologies—secondary ion mass spectrometry (SIMS) and matrix assisted laser desorption ionization mass spectrometry (MALDI MS)—are most often used in micro-bioanalytical investigations. Recent advances in ion probe technologies have increased the dynamic range and sensitivity of analyte detection by SIMS, allowing two- and three-dimensional localization of analytes in a variety of cells. SIMS operating in the mass spectrometry imaging (MSI) mode can routinely reach spatial resolutions at the submicron level; therefore, it is frequently used in studies of the chemical composition of subcellular structures. MALDI MS offers a large mass range and high sensitivity of analyte detection. It has been successfully applied in a variety of single-cell and organelle profiling studies. Innovative instrumentation such as scanning microprobe MALDI and mass microscope spectrometers enable new subcellular MSI measurements. Other approaches for MS-based chemical imaging and profiling include those based on near-field laser ablation and inductively-coupled plasma MS analysis, which offer complementary capabilities for subcellular chemical imaging and profiling. PMID:22498881

  15. Deblurring molecular images using desorption electrospray ionization mass spectrometry

    PubMed Central

    Parry, R. Mitchell; Galhena, Asiri S.; Fernandez, Facundo M.; Wang, May D.

    2016-01-01

    Traditional imaging techniques for studying the spatial distribution of biological molecules such as proteins, metabolites, and lipids, require the a priori selection of a handful of target molecules. Imaging mass spectrometry provides a means to analyze thousands of molecules at a time within a tissue sample, adding spatial detail to proteomic, metabolomic, and lipidomic studies. Compared to traditional microscopic images, mass spectrometric images have reduced spatial resolution and require a destructive acquisition process. In order to increase spatial detail, we propose a constrained acquisition path and signal degradation model enabling the use of a general image deblurring algorithm. Our analysis shows the potential of this approach and supports prior observations that the effect of the sprayer focuses on a central region much smaller than the extent of the spray. PMID:19963935

  16. Analysis and interpretation of imaging mass spectrometry data by clustering mass-to-charge images according to their spatial similarity.

    PubMed

    Alexandrov, Theodore; Chernyavsky, Ilya; Becker, Michael; von Eggeling, Ferdinand; Nikolenko, Sergey

    2013-12-01

    Imaging mass spectrometry (imaging MS) has emerged in the past decade as a label-free, spatially resolved, and multipurpose bioanalytical technique for direct analysis of biological samples from animal tissue, plant tissue, biofilms, and polymer films. Imaging MS has been successfully incorporated into many biomedical pipelines where it is usually applied in the so-called untargeted mode-capturing spatial localization of a multitude of ions from a wide mass range.3 An imaging MS data set usually comprises thousands of spectra and tens to hundreds of thousands of mass-to-charge (m/z) images and can be as large as several gigabytes. Unsupervised analysis of an imaging MS data set aims at finding hidden structures in the data with no a priori information used and is often exploited as the first step of imaging MS data analysis. We propose a novel, easy-to-use and easy-to-implement approach to answer one of the key questions of unsupervised analysis of imaging MS data: what do all m/z images look like? The key idea of the approach is to cluster all m/z images according to their spatial similarity so that each cluster contains spatially similar m/z images. We propose a visualization of both spatial and spectral information obtained using clustering that provides an easy way to understand what all m/z images look like. We evaluated the proposed approach on matrix-assisted laser desorption ionization imaging MS data sets of a rat brain coronal section and human larynx carcinoma and discussed several scenarios of data analysis. PMID:24180335

  17. Silver Coating for High-Mass-Accuracy Imaging Mass Spectrometry of Fingerprints on Nanostructured Silicon.

    PubMed

    Guinan, Taryn M; Gustafsson, Ove J R; McPhee, Gordon; Kobus, Hilton; Voelcker, Nicolas H

    2015-11-17

    Nanostructure imaging mass spectrometry (NIMS) using porous silicon (pSi) is a key technique for molecular imaging of exogenous and endogenous low molecular weight compounds from fingerprints. However, high-mass-accuracy NIMS can be difficult to achieve as time-of-flight (ToF) mass analyzers, which dominate the field, cannot sufficiently compensate for shifts in measured m/z values. Here, we show internal recalibration using a thin layer of silver (Ag) sputter-coated onto functionalized pSi substrates. NIMS peaks for several previously reported fingerprint components were selected and mass accuracy was compared to theoretical values. Mass accuracy was improved by more than an order of magnitude in several cases. This straightforward method should form part of the standard guidelines for NIMS studies for spatial characterization of small molecules. PMID:26460234

  18. Tissue MALDI Mass Spectrometry Imaging (MALDI MSI) of Peptides.

    PubMed

    Beine, Birte; Diehl, Hanna C; Meyer, Helmut E; Henkel, Corinna

    2016-01-01

    Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a technique to visualize molecular features of tissues based on mass detection. This chapter focuses on MALDI MSI of peptides and provides detailed operational instructions for sample preparation of cryoconserved and formalin-fixed paraffin-embedded (FFPE) tissue. Besides sample preparation we provide protocols for the MALDI measurement, tissue staining, and data analysis. On-tissue digestion and matrix application are described for two different commercially available and commonly used spraying devices: the SunCollect (SunChrom) and the ImagePrep (Bruker Daltonik GmbH). PMID:26700046

  19. Interlabial masses in little girls: review and imaging recommendations

    SciTech Connect

    Nussbaum, A.R.; Lebowitz, R.L.

    1983-07-01

    When an interlabial mass is seen on physical examination in a little girl, there is often confusion about its etiology, its implications, and what should be done next. Five common interlabial masses, which superficially are strikingly similar, include a prolapsed ectopic ureterocele, a prolapsed urethra, a paraurethral cyst, hydro(metro)colpos, and rhabdomyosarcoma of the vagina (botryoid sarcoma). A prolapsed ectopic ureterocele occurs in white girls as a smooth mass which protrudes from the urethral meatus so that urine exits circumferentially. A prolapsed urethra occurs in black girls and resembles a donut with the urethral meatus in the center. A paraurethral cyst is smaller and displaces the meatus, so that the urinary stream is eccentric. Hydro(metro)colpos from hymenal imperforation presents as a smooth mass that fills the vaginal introitus, as opposed to the introital grapelike cluster of masses of botryoid sarcoma. Recommendations for efficient imaging are presented.

  20. Semitransparent nanostructured films for imaging mass spectrometry and optical microscopy.

    PubMed

    Forsythe, Jay G; Broussard, Joshua A; Lawrie, Jenifer L; Kliman, Michal; Jiao, Yang; Weiss, Sharon M; Webb, Donna J; McLean, John A

    2012-12-18

    Semitransparent porous silicon substrates have been developed for pairing nanostructure-initiator mass spectrometry (NIMS) imaging with traditional optical-based microscopy techniques. Substrates were optimized to generate the largest NIMS signal while maintaining sufficient transparency to allow visible light to pass through for optical microscopy. Using these substrates, both phase-contrast and NIMS images of phospholipids from a scratch-wounded cell monolayer were obtained. NIMS images were generated using a spatial resolution of 14 μm. Coupled with further improvements in spatial resolution, this approach may allow for the localization of intact biological molecules within cells without the need for labeling. PMID:23146026

  1. Atomic Force Microscope Controlled Topographical Imaging and Proximal Probe Thermal Desorption/Ionization Mass Spectrometry Imaging

    SciTech Connect

    Ovchinnikova, Olga S; Kjoller, Kevin; Hurst, Gregory {Greg} B; Pelletier, Dale A; Van Berkel, Gary J

    2014-01-01

    This paper reports on the development of a hybrid atmospheric pressure atomic force microscopy/mass spectrometry imaging system utilizing nano-thermal analysis probes for thermal desorption surface sampling with subsequent atmospheric pressure chemical ionization and mass analysis. The basic instrumental setup and the general operation of the system were discussed and optimized performance metrics were presented. The ability to correlate topographic images of a surface with atomic force microscopy and a mass spectral chemical image of the same surface, utilizing the same probe without moving the sample from the system, was demonstrated. Co-registered mass spectral chemical images and atomic force microscopy topographical images were obtained from inked patterns on paper as well as from a living bacterial colony on an agar gel. Spatial resolution of the topography images based on pixel size (0.2 m x 0.8 m) was better than the resolution of the mass spectral images (2.5 m x 2.0 m), which were limited by current mass spectral data acquisition rate and system detection levels.

  2. Multi-isotope composition of precipitation in Northern Germany during winter time

    NASA Astrophysics Data System (ADS)

    Böttcher, Michael E.; Schmiedinger, Iris; Lipka, Marko; Böttcher, Ernst O.; Böttcher, Tillman M. C.

    2014-05-01

    We investigated the multi-isotope (H-1, H-2, O-16, O-17, O-18) composition of precipitation (rain, snow) at locations in Northern Germany (Warnemünde, Oldenburg, Lüneburg) and the Netherlands (Texel Island) to derive local meteoric water lines. A particular focus was set on the impact of recent events Xaver and Dirk on stable isotope variations in high time-resolution. Sampling was carried out using a Hellmann-type rain gauge or, in the case of high-resolution sampling open sampling devices. At the Lüneburg site, the amount of fallen rain (volume per area of soil surface) was additionally quantified on a regular daily base. Isotope measurements were conducted by means of a new Picarro CRDS system (L2140-i) giving results in the usual delta-notation versus V-SMOW, and informations about H-2 and O-17 excess. Results are compared to continuous measurements at the GNIP station in Cuxhaven (NW-Germany) and the GMWL. As an example, during storm Xaver, respective variations in delta-18O and delta-2H values in snow and rain samples of up to 5 and 42 per mil were observed. Results for the German stations in the time period around storm Xaver are positioned close to the local meteoric water line proposed for Cuxhaven. Deviations from the GMWL are discussed.

  3. The Multi-Isotope Process (MIP) Monitor Project: FY13 Final Report

    SciTech Connect

    Meier, David E.; Coble, Jamie B.; Jordan, David V.; Mcdonald, Luther W.; Forrester, Joel B.; Schwantes, Jon M.; Unlu, Kenan; Landsberger, Sheldon; Bender, Sarah; Dayman, Kenneth J.; Reilly, Dallas D.

    2013-09-01

    The Multi-Isotope Process (MIP) Monitor provides an efficient approach to monitoring the process conditions in reprocessing facilities in support of the goal of “… (minimization of) the risks of nuclear proliferation and terrorism.” The MIP Monitor measures the distribution of the radioactive isotopes in product and waste streams of a nuclear reprocessing facility. These isotopes are monitored online by gamma spectrometry and compared, in near-real-time, to spectral patterns representing “normal” process conditions using multivariate analysis and pattern recognition algorithms. The combination of multivariate analysis and gamma spectroscopy allows us to detect small changes in the gamma spectrum, which may indicate changes in process conditions. By targeting multiple gamma-emitting indicator isotopes, the MIP Monitor approach is compatible with the use of small, portable, relatively high-resolution gamma detectors that may be easily deployed throughout an existing facility. The automated multivariate analysis can provide a level of data obscurity, giving a built-in information barrier to protect sensitive or proprietary operational data. Proof-of-concept simulations and experiments have been performed in previous years to demonstrate the validity of this tool in a laboratory setting for systems representing aqueous reprocessing facilities. However, pyroprocessing is emerging as an alternative to aqueous reprocessing techniques.

  4. The Multi-Isotope Process Monitor Project: FY11 Progress and Accomplishments

    SciTech Connect

    Orton, Christopher R.; Fraga, Carlos G.; Hayes, John W.; Schwantes, Jon M.; Bender, Sarah E.; Unlu, Kenan; Dayman, Kenneth J.; Schreiber, S. S.; Landsberger, Sheldon

    2012-08-01

    Summary The Multi-Isotope Process (MIP) Monitor represents a potentially new and efficient approach to monitoring process conditions in reprocessing facilities with the high-level goal of aiding in the “...(minimization of) the risks of nuclear proliferation and terrorism” (Office of Technology Assessment 1995). This approach relies on multivariate analysis and gamma spectroscopy of spent fuel product and waste streams to automatically and simultaneously monitor a variety of process conditions (e.g., acid concentrations, burnup, cooling time, etc.) in near real-time (NRT). While the conceptual basis for the MIP Monitor has been shown to be effective in an aqueous reprocessing system, the fundamental approach should also be viable in a pyro-processing recycle system. The MIP Monitor may be calibrated to provide online quantitative information about process variables for process control or domestic safeguards applications; or it can simply monitor, with a built-in information barrier, for off-normal conditions in process streams, making the approach well-suited for applications were it is necessary to respect proprietary information or for international safeguards applications. Proof-of-concept simulations and experiments were performed in previous years demonstrating the validity of this tool in a laboratory setting. This report details follow-on research and development efforts sponsored by the U.S. Department of Energy Fuel Cycle Research and Development (FCR&D) related to the MIP Monitor for fiscal year 2011 (FY11).

  5. The Multi-Isotope Process Monitor: Multivariate Analysis of Gamma Spectra

    SciTech Connect

    Orton, Christopher R.; Rutherford, Crystal E.; Fraga, Carlos G.; Schwantes, Jon M.

    2011-10-30

    The International Atomic Energy Agency (IAEA) has established international safeguards standards for fissionable material at spent fuel reprocessing plants to ensure that significant quantities of nuclear material are not diverted from these facilities. Currently, methods to verify material control and accountancy (MC&A) at these facilities require time-consuming and resource-intensive destructive assay (DA). The time delay between sampling and subsequent DA provides a potential opportunity to divert the material out of the appropriate chemical stream. Leveraging new on-line nondestructive assay (NDA) techniques in conjunction with the traditional and highly precise DA methods may provide a more timely, cost-effective and resource efficient means for MC&A verification at such facilities. Pacific Northwest National Laboratory (PNNL) is developing on-line NDA process monitoring technologies, including the Multi-Isotope Process (MIP) Monitor. The MIP Monitor uses gamma spectroscopy and pattern recognition software to identify off-normal conditions in process streams. Recent efforts have been made to explore the basic limits of using multivariate analysis techniques on gamma-ray spectra. This paper will provide an overview of the methods and report our on-going efforts to develop and demonstrate the technology.

  6. Coming to a hospital near you: mass spectrometry imaging

    ScienceCinema

    Bowen, Ben

    2014-06-24

    Berkeley Lab's Ben Bowen discusses "Coming to a hospital near you: mass spectrometry imaging" in this Oct. 28, 2013 talk, which is part of a Science at the Theater event entitled Eight Big Ideas. Go here to watch the entire event with all 8 speakers.

  7. Preparation of single cells for imaging mass spectrometry.

    PubMed

    Berman, Elena S F; Fortson, Susan L; Kulp, Kristen S

    2010-01-01

    Characterizing the molecular contents of individual cells is critical for understanding fundamental mechanisms of biological processes. Imaging mass spectrometry (IMS) of biological systems has been steadily gaining popularity for its ability to create precise chemical images of biological samples, thereby revealing new biological insights and improving understanding of disease. In order to acquire mass spectral images from single cells that contain relevant molecular information, samples must be prepared such that cell-culture components, especially salts, are eliminated from the cell surface and that the cell contents are accessible to the mass spectrometer. We have demonstrated a cellular preparation technique for IMS that preserves the basic morphology of cultured cells, allows mass spectrometric chemical profiling of cytosol, and removes the majority of the interfering species derived from the cellular growth medium. Using this protocol, we achieve high-quality, reproducible IMS images from three diverse cell types: MCF7 human breast cancer cells, Madin-Darby canine kidney (MDCK) cells, and NIH/3T3 mouse fibroblasts. This preparation method allows rapid and routine IMS analysis of cultured cells, making possible a wide variety of experiments to further scientific understanding of molecular processes within individual cells. PMID:20680596

  8. Coming to a hospital near you: mass spectrometry imaging

    SciTech Connect

    Bowen, Ben

    2013-10-31

    Berkeley Lab's Ben Bowen discusses "Coming to a hospital near you: mass spectrometry imaging" in this Oct. 28, 2013 talk, which is part of a Science at the Theater event entitled Eight Big Ideas. Go here to watch the entire event with all 8 speakers.

  9. Current Status and Future Perspectives of Mass Spectrometry Imaging

    PubMed Central

    Nimesh, Surendra; Mohottalage, Susantha; Vincent, Renaud; Kumarathasan, Prem

    2013-01-01

    Mass spectrometry imaging is employed for mapping proteins, lipids and metabolites in biological tissues in a morphological context. Although initially developed as a tool for biomarker discovery by imaging the distribution of protein/peptide in tissue sections, the high sensitivity and molecular specificity of this technique have enabled its application to biomolecules, other than proteins, even in cells, latent finger prints and whole organisms. Relatively simple, with no requirement for labelling, homogenization, extraction or reconstitution, the technique has found a variety of applications in molecular biology, pathology, pharmacology and toxicology. By discriminating the spatial distribution of biomolecules in serial sections of tissues, biomarkers of lesions and the biological responses to stressors or diseases can be better understood in the context of structure and function. In this review, we have discussed the advances in the different aspects of mass spectrometry imaging processes, application towards different disciplines and relevance to the field of toxicology. PMID:23759983

  10. Use of mass spectrometry for imaging metabolites in plants

    SciTech Connect

    Lee, Young-Jin; Perdian, David; Song, Zhihong; Yeung, Edward; Nikolau, Basil

    2012-03-27

    We discuss and illustrate recent advances that have been made to image the distribution of metabolites among cells and tissues of plants using different mass spectrometry technologies. These technologies include matrix-assisted laser desorption ionization, desorption electrospray ionization, and secondary ion mass spectrometry. These are relatively new technological applications of mass spectrometry and they are providing highly spatially resolved data concerning the cellular distribution of metabolites. We discuss the advantages and limitations of each of these mass spectrometric methods, and provide a description of the technical barriers that are currently limiting the technology to the level of single-cell resolution. However, we anticipate that advances in the next few years will increase the resolving power of the technology to provide unprecedented data on the distribution of metabolites at the subcellular level, which will increase our ability to decipher new knowledge concerning the spatial organization of metabolic processes in plants.

  11. Use of Mass spectrometry for imaging metabolites in plants

    SciTech Connect

    Lee, Young Jin; Perdian, David C.; Song, Zhihong; Yeung, Edward S.; Nikolau, Basil

    2012-03-27

    We discuss and illustrate recent advances that have been made to image the distribution of metabolites among cells and tissues of plants using different mass spectrometry technologies. These technologies include matrix-assisted laser desorption ionization, desorption electrospray ionization, and secondary ion mass spectrometry. These are relatively new technological applications of mass spectrometry and they are providing highly spatially resolved data concerning the cellular distribution of metabolites. We discuss the advantages and limitations of each of these mass spectrometric methods, and provide a description of the technical barriers that are currently limiting the technology to the level of single-cell resolution. However, we anticipate that advances in the next few years will increase the resolving power of the technology to provide unprecedented data on the distribution of metabolites at the subcellular level, which will increase our ability to decipher new knowledge concerning the spatial organization of metabolic processes in plants.

  12. High-speed tandem mass spectrometric in situ imaging by nanospray desorption electrospray ionization mass spectrometry.

    PubMed

    Lanekoff, Ingela; Burnum-Johnson, Kristin; Thomas, Mathew; Short, Joshua; Carson, James P; Cha, Jeeyeon; Dey, Sudhansu K; Yang, Pengxiang; Prieto Conaway, Maria C; Laskin, Julia

    2013-10-15

    Nanospray desorption electrospray ionization (nano-DESI) combined with tandem mass spectrometry (MS/MS), high-resolution mass analysis of the fragment ions (m/Δm = 17 500 at m/z 200), and rapid spectral acquisition enabled simultaneous imaging and identification of a large number of metabolites and lipids from 92 selected m/z windows (±1 Da) with a spatial resolution of better than 150 μm. Mouse uterine sections of implantation sites on day 6 of pregnancy were analyzed in the ambient environment without any sample pretreatment. MS/MS imaging was performed by scanning the sample under the nano-DESI probe at 10 μm/s, while higher-energy collision-induced dissociation (HCD) spectra were acquired for a targeted inclusion list of 92 m/z values at a rate of ∼6.3 spectra/s. Molecular ions and their corresponding fragments, separated by high-resolution mass analysis, were assigned on the basis of accurate mass measurement. Using this approach, we were able to identify and image both abundant and low-abundance isobaric and isomeric species within each m/z window. MS/MS analysis enabled efficient separation and identification of isomeric and isobaric phospholipids that are difficult to separate in full-scan mode. Furthermore, we identified several metabolites associated with early pregnancy and obtained the first 2D images of these molecules. PMID:24040919

  13. High-Speed Tandem Mass Spectrometric in Situ Imaging by Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Lanekoff, Ingela T.; Burnum-Johnson, Kristin E.; Thomas, Mathew; Short, Joshua TL; Carson, James P.; Cha, Jeeyeon; Dey, Sudhansu K.; Yang, Pengxiang; Prieto Conaway, Maria C.; Laskin, Julia

    2013-10-15

    Nanospray desorption electrospray ionization (nano-DESI) combined with tandem mass spectrometry (MS/MS), high-resolution mass analysis (m/m=17,500 at m/z 200), and rapid spectral acquisition enabled simultaneous imaging and identification of more than 300 molecules from 92 selected m/z windows (± 1 Da) with a spatial resolution of better than 150 um. Uterine sections of implantation sites on day 6 of pregnancy were analyzed in the ambient environment without any sample pre-treatment. MS/MS imaging was performed by scanning the sample under the nano-DESI probe at 10 um/s while acquiring higher-energy collision-induced dissociation (HCD) spectra for a targeted inclusion list of 92 m/z values at a rate of ~6.3 spectra/s. Molecular ions and their corresponding fragments, separated using high-resolution mass analysis, were assigned based on accurate mass measurement. Using this approach, we were able to identify and image both abundant and low-abundance isobaric species within each m/z window. MS/MS analysis enabled efficient separation and identification of isobaric sodium and potassium adducts of phospholipids. Furthermore, we identified several metabolites associated with early pregnancy and obtained the first 2D images of these molecules.

  14. Estimating mass of crushed limestone particles from 2D images

    NASA Astrophysics Data System (ADS)

    Banta, Larry E.; Cheng, Ken; Zaniewski, John P.

    2002-02-01

    In the construction of asphalt pavements, the stability of the asphalt is determined in large part by the gradation, or size distribution of the mineral aggregates that make up the matrix. Gradation is specified on the basis of sieve sizes and percent passing, where the latter is a cumulative measure of the mass of the aggregate passing the sieve as fraction of the total mass in the batch. In this paper, an approach for predicting particle mass based on 2D electronic images is explored. Images of crushed limestone aggregates were acquired using backlighting to create silhouettes. A morphological erosion process was used to separate touching and overlapping particles. Useful features of the particle silhouettes, such as area, centroid and shape descriptors were collected. Several dimensionless parameters were defined and were used as regressor variables in a multiple linear regression model to predict particle mass. Regressor coefficients were found by fitting to a sample of 501 particles ranging in size from 4.75 mm < particle sieve size < 25 mm. When tested against a different aggregate sample, the model predicted the mass of the batch to within +/- 2%.

  15. Pineal region masses--imaging findings and surgical approaches.

    PubMed

    Lensing, Forrester D; Abele, Travis A; Sivakumar, Walavan; Taussky, Philipp; Shah, Lubdha M; Salzman, Karen L

    2015-01-01

    The anatomy of the pineal region is complex. Despite advances in surgical techniques since the first reported successful pineal region surgery in the early 20th century, pineal region surgery remains challenging owing to the proximity of deep cerebral veins and dorsal midbrain structures critical for vision. In this article, we review the relevant surgical anatomy of the pineal region and discuss historically important and current surgical approaches. We describe specific imaging features of pineal region masses that may affect surgical planning and review neoplastic and nonneoplastic masses that occur in the pineal region. PMID:25027864

  16. Ionization sources and mass analyzers in MS imaging.

    PubMed

    Tsai, Yu-Hsuan; Menger, Robert F; Drexler, Dieter M; Yost, Richard A; Garrett, Timothy J

    2015-01-01

    Drug absorption, distribution, metabolism, excretion and toxicology study is one important step in drug discovery and development. MS imaging has become one of the popular methods in this field. Here, selected ionization methods such as matrix-assisted laser desorption/ionization, secondary ion MS and desorption electrospray ionization have been briefly discussed. To differentiate drug and drug metabolites from endogenous compounds present in the biological system, exact mass and/or tandem MS is necessary. As a result, mass analyzers such as time-of-flight, Fourier transform ion cyclotron resonance or Orbitrap are often the method of choice and are briefly introduced. PMID:26511148

  17. Challenges and recent advances in mass spectrometric imaging of neurotransmitters

    PubMed Central

    Gemperline, Erin; Chen, Bingming; Li, Lingjun

    2014-01-01

    Mass spectrometric imaging (MSI) is a powerful tool that grants the ability to investigate a broad mass range of molecules, from small molecules to large proteins, by creating detailed distribution maps of selected compounds. To date, MSI has demonstrated its versatility in the study of neurotransmitters and neuropeptides of different classes toward investigation of neurobiological functions and diseases. These studies have provided significant insight in neurobiology over the years and current technical advances are facilitating further improvements in this field. neurotransmitters, focusing specifically on the challenges and recent Herein, we advances of MSI of neurotransmitters. PMID:24568355

  18. Imaging of Cells and Tissues with Mass Spectrometry: Adding Chemical Information to Imaging

    PubMed Central

    Zimmerman, Tyler A.; Monroe, Eric B.; Tucker, Kevin R.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2009-01-01

    Techniques that map the distribution of compounds in biological tissues can be invaluable in addressing a number of critical questions in biology and medicine. One of the newest methods, mass spectrometric imaging, has enabled investigation of spatial localization for a variety of compounds ranging from atomics to proteins. The ability of mass spectrometry to detect and differentiate a large number of unlabeled compounds makes the approach amenable to the study of complex biological tissues. This chapter focuses on recent advances in the instrumentation and sample preparation protocols that make mass spectrometric imaging of biological samples possible, including strategies for both tissue and single cell imaging using the following mass spectrometric ionization methods: matrix-assisted laser desorption/ionization, secondary ion, electrospray and desorption electrospray. PMID:19118682

  19. Preparation of Single Cells for Imaging Mass Spectrometry

    SciTech Connect

    Berman, E S; Fortson, S L; Kulp, K S; Checchi, K D; Wu, L; Felton, J S; Wu, K J

    2007-10-24

    Characterizing chemical changes within single cells is important for determining fundamental mechanisms of biological processes that will lead to new biological insights and improved disease understanding. Imaging biological systems with mass spectrometry (MS) has gained popularity in recent years as a method for creating precise chemical maps of biological samples. In order to obtain high-quality mass spectral images that provide relevant molecular information about individual cells, samples must be prepared so that salts and other cell-culture components are removed from the cell surface and the cell contents are rendered accessible to the desorption beam. We have designed a cellular preparation protocol for imaging MS that preserves the cellular contents for investigation and removes the majority of the interfering species from the extracellular matrix. Using this method, we obtain excellent imaging results and reproducibility in three diverse cell types: MCF7 human breast cancer cells, Madin-Darby canine kidney (MDCK) cells, and NIH/3T3 mouse fibroblasts. This preparation technique allows routine imaging MS analysis of cultured cells, allowing for any number of experiments aimed at furthering scientific understanding of molecular processes within individual cells.

  20. Laser desorption postionization mass spectrometry imaging of biological targets.

    PubMed

    Akhmetov, Artem; Bhardwaj, Chhavi; Hanley, Luke

    2015-01-01

    Laser desorption photoionization mass spectrometry (LDPI-MS) utilizes two separate light sources for desorption and photoionization of species from a solid surface. This technique has been applied to study a wide variety of molecular analytes in biological systems, but is not yet available in commercial instruments. For this reason, a generalized protocol is presented here for the use of LDPI-MS imaging to detect small molecules within intact biological samples. Examples are provided here for LDPI-MS imaging of an antibiotic within a tooth root canal and a metabolite within a coculture bacterial biofilm. PMID:25361678

  1. Mass Spectrometry Imaging Using the Stretched Sample Approach

    PubMed Central

    Zimmerman, Tyler A.; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2011-01-01

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) can determine tissue localization for a variety of analytes with high sensitivity, chemical specificity, and spatial resolution. MS image quality typically depends on the MALDI matrix application method used, particularly when the matrix solution or powder is applied directly to the tissue surface. Improper matrix application results in spatial redistribution of analytes and reduced MS signal quality. Here we present a stretched sample imaging protocol that removes the dependence of MS image quality on the matrix application process and improves analyte extraction and sample desalting. First, the tissue sample is placed on a monolayer of solid support beads that are embedded in a hydrophobic membrane. Stretching the membrane fragments the tissue into thousands of nearly single-cell sized islands, with the pieces physically isolated from each other by the membrane. This spatial isolation prevents analyte transfer between beads, allowing for longer exposure of the tissue fragments to the MALDI matrix, thereby improving detectability of small analyte quantities without sacrificing spatial resolution. When using this method to reconstruct chemical images, complications result from non-uniform stretching of the supporting membrane. Addressing this concern, several computational tools enable automated data acquisition at individual bead locations and allow reconstruction of ion images corresponding to the original spatial conformation of the tissue section. Using mouse pituitary, we demonstrate the utility of this stretched imaging technique for characterizing peptide distributions in heterogeneous tissues at nearly single-cell resolution. PMID:20680608

  2. The Multi-Isotope Process (MIP) Monitor Project: FY12 Progress and Accomplishments

    SciTech Connect

    Coble, Jamie B.; Orton, Christopher R.; Jordan, David V.; Schwantes, Jon M.; Bender, Sarah; Dayman, Kenneth J.; Unlu, Kenan; Landsberger, Sheldon

    2012-09-27

    The Multi-Isotope Process (MIP) Monitor, being developed at Pacific Northwest National Laboratory (PNNL), provides an efficient approach to monitoring the process conditions in reprocessing facilities in support of the goal of "...(minimization of) the risks of nuclear proliferation and terrorism." The MIP Monitor measures distributions of a suite of indicator (radioactive) isotopes present within product and waste streams of a nuclear reprocessing facility. These indicator isotopes are monitored on-line by gamma spectrometry and compared, in near-real-time, to spectral patterns representing "normal" process conditions using multivariate pattern recognition software. The monitor utilizes this multivariate analysis and gamma spectroscopy of reprocessing streams to detect small changes in the gamma spectrum, which may indicate changes in process conditions. Multivariate analysis methods common in chemometrics, such as principal component analysis (PCA) and partial least squares regression (PLS), act as pattern recognition techniques, which can detect small deviations from the expected, nominal condition. By targeting multiple gamma-emitting indicator isotopes, the MIP Monitor approach is compatible with the use of small, portable, relatively high-resolution gamma detectors that may be easily deployed throughout an existing facility. The automated multivariate analysis can provide a level of data obscurity, giving a built-in information barrier to protect sensitive or proprietary operational data. Proof-of-concept simulations and experiments have been performed in previous years to demonstrate the validity of this tool in a laboratory setting. Development of the MIP Monitor approach continues to evaluate the efficacy of the monitor for automated, real-time or near-real-time application. This report details follow-on research and development efforts sponsored by the U.S. Department of Energy Fuel Cycle Research and Development related to the MIP Monitor for fiscal year

  3. Computation of Mass Density Images from X-ray Refraction-Angle Images

    SciTech Connect

    Wernick,M.; Yang, Y.; Mondal, I.; Chapman, D.; Hasnah, M.; Parham, C.; Pisano, E.; Zhong, Z.

    2006-01-01

    In this paper, we investigate the possibility of computing quantitatively accurate images of mass density variations in soft tissue. This is a challenging task, because density variations in soft tissue, such as the breast, can be very subtle. Beginning from an image of refraction angle created by either diffraction-enhanced imaging (DEI) or multiple-image radiography (MIR), we estimate the mass-density image using a constrained least squares (CLS) method. The CLS algorithm yields accurate density estimates while effectively suppressing noise. Our method improves on an analytical method proposed by Hasnah et al (2005 Med. Phys. 32 549-52), which can produce significant artifacts when even a modest level of noise is present. We present a quantitative evaluation study to determine the accuracy with which mass density can be determined in the presence of noise. Based on computer simulations, we find that the mass-density estimation error can be as low as a few per cent for typical density variations found in the breast. Example images computed from less-noisy real data are also shown to illustrate the feasibility of the technique. We anticipate that density imaging may have application in assessment of water content of cartilage resulting from osteoarthritis, in evaluation of bone density, and in mammographic interpretation.

  4. Einstein imaging observations of clusters with a bimodal mass distribution

    NASA Technical Reports Server (NTRS)

    Forman, W.; Bechtold, J.; Blair, W.; Giacconi, R.; Van Speybroeck, L.; Jones, C.

    1981-01-01

    Einstein imaging observations of four X-ray clusters of galaxies characterized by a double X-ray surface brightness and thus mass distribution are presented. The clusters A98, A115, A1750 and SC 0627-54 were found to exhibit two enhancements in their X-ray surface brightness distributions in observations made with the Einstein Imaging Proportional Counter. Calculations of the probability that the clusters represent chance superpositions indicate that the double clusters are physically associated. The radial distributions of the components are inconsistent with those of single point sources, and have been used to derive cluster luminosities which are typical of rich clusters. Masses of the subclusters are also found to be typical of bound and virialized clusters with gas contributing 10%. Within the framework of the hierarchical theory of galactic clustering, the double clusters are suggested to represent an intermediate evolutionary stage before the merger of subclusters into a relaxed Coma-type cluster.

  5. Current cardiac imaging techniques for detection of left ventricular mass

    PubMed Central

    2010-01-01

    Estimation of left ventricular (LV) mass has both prognostic and therapeutic value independent of traditional risk factors. Unfortunately, LV mass evaluation has been underestimated in clinical practice. Assessment of LV mass can be performed by a number of imaging modalities. Despite inherent limitations, conventional echocardiography has fundamentally been established as most widely used diagnostic tool. 3-dimensional echocardiography (3DE) is now feasible, fast and accurate for LV mass evaluation. 3DE is also superior to conventional echocardiography in terms of LV mass assessment, especially in patients with abnormal LV geometry. Cardiovascular magnetic resonance (CMR) and cardiovascular computed tomography (CCT) are currently performed for LV mass assessment and also do not depend on cardiac geometry and display 3-dimensional data, as well. Therefore, CMR is being increasingly employed and is at the present standard of reference in the clinical setting. Although each method demonstrates advantages over another, there are also disadvantages to receive attention. Diagnostic accuracy of methods will also be increased with the introduction of more advanced systems. It is also likely that in the coming years new and more accurate diagnostic tests will become available. In particular, CMR and CCT have been intersecting hot topic between cardiology and radiology clinics. Thus, good communication and collaboration between two specialties is required for selection of an appropriate test. PMID:20515461

  6. Multigrid optimal mass transport for image registration and morphing

    NASA Astrophysics Data System (ADS)

    Rehman, Tauseef ur; Tannenbaum, Allen

    2007-02-01

    In this paper we present a computationally efficient Optimal Mass Transport algorithm. This method is based on the Monge-Kantorovich theory and is used for computing elastic registration and warping maps in image registration and morphing applications. This is a parameter free method which utilizes all of the grayscale data in an image pair in a symmetric fashion. No landmarks need to be specified for correspondence. In our work, we demonstrate significant improvement in computation time when our algorithm is applied as compared to the originally proposed method by Haker et al [1]. The original algorithm was based on a gradient descent method for removing the curl from an initial mass preserving map regarded as 2D vector field. This involves inverting the Laplacian in each iteration which is now computed using full multigrid technique resulting in an improvement in computational time by a factor of two. Greater improvement is achieved by decimating the curl in a multi-resolutional framework. The algorithm was applied to 2D short axis cardiac MRI images and brain MRI images for testing and comparison.

  7. Imaging of Biological Tissues by Desorption Electrospray Ionization Mass Spectrometry

    PubMed Central

    Fernández, Facundo M.

    2013-01-01

    Mass spectrometry imaging (MSI) provides untargeted molecular information with the highest specificity and spatial resolution for investigating biological tissues at the hundreds to tens of microns scale. When performed under ambient conditions, sample pre-treatment becomes unnecessary, thus simplifying the protocol while maintaining the high quality of information obtained. Desorption electrospray ionization (DESI) is a spray-based ambient MSI technique that allows for the direct sampling of surfaces in the open air, even in vivo. When used with a software-controlled sample stage, the sample is rastered underneath the DESI ionization probe, and through the time domain, m/z information is correlated with the chemical species' spatial distribution. The fidelity of the DESI-MSI output depends on the source orientation and positioning with respect to the sample surface and mass spectrometer inlet. Herein, we review how to prepare tissue sections for DESI imaging and additional experimental conditions that directly affect image quality. Specifically, we describe the protocol for the imaging of rat brain tissue sections by DESI-MSI. PMID:23892773

  8. Computer-Aided Diagnostic System For Mass Survey Chest Images

    NASA Astrophysics Data System (ADS)

    Yasuda, Yoshizumi; Kinoshita, Yasuhiro; Emori, Yasufumi; Yoshimura, Hitoshi

    1988-06-01

    In order to support screening of chest radiographs on mass survey, a computer-aided diagnostic system that automatically detects abnormality of candidate images using a digital image analysis technique has been developed. Extracting boundary lines of lung fields and examining their shapes allowed various kind of abnormalities to be detected. Correction and expansion were facilitated by describing the system control, image analysis control and judgement of abnormality in the rule type programing language. In the experiments using typical samples of student's radiograms, good results were obtained for the detection of abnormal shape of lung field, cardiac hypertrophy and scoliosis. As for the detection of diaphragmatic abnormality, relatively good results were obtained but further improvements will be necessary.

  9. Improved Imaging Resolution in Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Kertesz, Vilmos; Van Berkel, Gary J

    2008-01-01

    Imaging resolution of desorption electrospray ionization mass spectrometry (DESI-MS) was investigated using printed patterns on paper and thin-layer chromatography (TLC) plate surfaces. Resolution approaching 40 m was achieved with a typical DESI-MS setup, which is approximately 5 times better than the best resolution reported previously. This improvement was accomplished with careful control of operational parameters (particularly spray tip-to-surface distance, solvent flow rate, and spacing of lane scans). Also, an appropriately strong analyte/surface interaction and uniform surface texture on the size scale no larger that the desired imaging resolution were required to achieve this resolution. Overall, conditions providing the smallest possible effective desorption/ionization area in the DESI impact plume region and minimizing the analyte redistribution on the surface during analysis led to the improved DESI-MS imaging resolution.

  10. Determining the mass of Didymos' secondary by visual imaging

    NASA Astrophysics Data System (ADS)

    Grieger, Björn; Küppers, Michael

    2016-04-01

    A critical requirement for the Asteroid Impact Mission (AIM) is the ability to determine the mass of Didymos' secondary with an accuracy of about 10 %. On one hand, this is necessary in order to plan the delivery of the lander MASCOT-2 with sufficient precision, on the other hand, it is needed to estimate the momentum transfer by the impact of the DART spacecraft and hence to verify the concept of asteroid deflection. The conventional approach to estimate the mass of a solar system body through its gravitational effect by tracking the spacecraft trajectory is not viable for Didymos' secondary. With a diameter of only 163 m, its mass is too small to yield a significant impact on the spacecraft trajectory at reasonable fly-by distances. Instead, the idea to determine the mass of the secondary by measuring the "wobble" of the primary around the common centre of gravity has been put forward. The mass of the primary is about 100 times the mass of the secondary, thus the expected wobble radius is about one percent of the distance of 1180 m between the two, that is about 10 m. Such a wobble may be possible to measure either by means of using the optical communication device OPTEL-D as an altimeter or by direct observation with the visual imaging system VIS. Here, we investigate the latter approach. The idea is to identify landmarks in VIS images and to simultaneously solve for the positions of the landmarks and the spacecraft in the body fixed frame of the primary. The temporary evolution of the spacecraft position comprises three components: the drift of the spacecraft due to gravitational disturbance and solar radiation pressure (and errors in the knowledge of the initial state), the apparent motion of the spacecraft around the primary (in the body fixed frame) due to its rotation, an apparent oscillation of the spacecraft position due to the wobble of the primary with a known period. While the wobble component is quite small (about 10ṁ), its period is known and it is

  11. Optimization of Whole-Body Zebrafish Sectioning Methods for Mass Spectrometry Imaging

    EPA Science Inventory

    Mass spectrometry imaging methods and protocols have become widely adapted to a variety of tissues and species. However, the mass spectrometry imaging literature contains minimal information on whole-body cryosection preparation for the zebrafish (Danio rerio), a model organism ...

  12. Imaging mass spectrometry in biological tissues by laser ablation inductively coupled plasma mass spectrometry.

    PubMed

    Becker, J S; Becker, J Su; Zoriy, M V; Dobrowolska, J; Matucsh, A

    2007-01-01

    Of all the inorganic mass spectrometric techniques, laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) plays a key role as a powerful and sensitive microanalytical technique enabling multi- element trace analysis and isotope ratio measurements at trace and ultratrace level. LA-ICP-MS was used to produce images of detailed regionally-specific element distribution in 20 microm thin sections of different parts of the human brain. The quantitative determination of copper, zinc, lead and uranium distribution in thin slices of human brain samples was performed using matrix-matched laboratory standards via external calibration procedures. Imaging mass spectrometry provides new information on the spatially inhomogeneous element distribution in thin sections of human tissues, for example, of different brain regions (the insular region) or brain tumor tissues. The detection limits obtained for Cu, Zn, Pb and U were in the ng g(-1) range. Possible strategies of LA-ICP-MS in brain research and life sciences include the elemental imaging of thin slices of brain tissue or applications in proteome analysis by combination with matrix-assisted laser desorption/ionization MS to study phospho- and metal- containing proteins will be discussed. PMID:17885277

  13. Panoramic imaging mass-spectrometer for planetary studies

    NASA Astrophysics Data System (ADS)

    Vaisberg, O.; Berthelier, J.; Torkar, K.; Leblanc, F.; Escoubet, P.; Woch, J.; Baumjohann, W.; Avanov, L.; Burch, J.; McComas, D.; Delcourt, D.; Wurz, P.; Grishin, V.; Smirnov, V.; Babkin, V.; Szego, K.

    2004-12-01

    Plasma diagnostics can provide extremely useful information for solar system studies. Neutral and ion sputtering from the surface leads to the formation of neutral and ion exospheres with compositions that reflect the surface composition modified by ionization and transport processes around the body. Measurements of ion composition and velocity distributions provide important information about surface composition and its recycling. Plasma measurements from low altitude spacecraft and landers on planetary bodies without atmospheres can be used to map the surface composition, while spectrometers onboard spacecraft orbiting planets with atmosphere are used for study of planetary losses, mass-exchange with the solar wind, and the long-term evolution of their environment. To perform reliable measurements of planetary plasmas a complete 3-dimensional velocity distributions of various ion species is necessary. In addition, if fast measurements of the major ion species are the main goal of plasma physics studies, precise measurements of the minor ion composition are often essential to unveil important properties of the atmosphere or the surface. Therefore ion mass spectrometers for solar system missions require both the capability of making fast measurements of the 3D-velocity distribution of ions and high mass resolution for detailed composition studies. We describe a novel type of miniature panoramic ion mass-spectrometer suitable for making such 3-dimensional measurements of ion components with high mass resolution. The feeding electron optics of our plasma analyzer (CAMERA) allows for fast measurements within an instantaneous 2p field of view, which has no gaps and can be accomplished on either stabilized or rotating spacecraft, or landers. It is followed by a time-of-flight mass-spectrometer that retains imaging capabilities of the feeding optics and provides mass-resolution M/ΔM in excess of 100. Our spectrometer also provides flexible control of the energy

  14. Multigrid MALDI mass spectrometry imaging (mMALDI MSI).

    PubMed

    Urbanek, Annett; Hölzer, Stefan; Knop, Katrin; Schubert, Ulrich S; von Eggeling, Ferdinand

    2016-05-01

    Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is an important technique for the spatially resolved molecular analysis of tissue sections. The selection of matrices influences the resulting mass spectra to a high degree. For extensive and simultaneous analysis, the application of different matrices to one tissue sample is desirable. To date, only a single matrix could be applied to a tissue section per experiment. However, repetitive removal of the matrix makes this approach time-consuming and damaging to tissue samples. To overcome these drawbacks, we developed a multigrid MALDI MSI technique (mMALDI MSI) that relies on automated inkjet printing to place differing matrices onto predefined dot grids. We used a cooled printhead to prevent cavitation of low viscosity solvents in the printhead nozzle. Improved spatial resolution of the dot grids was achieved by using a triple-pulse procedure that reduced droplet volume. The matrices can either be applied directly to the thaw-mounted tissue sample or by precoating the slide followed by mounting of the tissue sample. During the MALDI imaging process, we were able to precisely target different matrix point grids with the laser to simultaneously produce distinct mass spectra. Unlike the standard method, the prespotting approach optimizes the spectra quality, avoids analyte delocalization, and enables subsequent hematoxylin and eosin (H&E) staining. Graphical Abstract Scheme of the pre-spotted multigrid MALDI MSI workflow. PMID:27039200

  15. Mass spectrograph for imaging low-energy neutral atoms

    SciTech Connect

    Ghielmetti, A.G.; Shelley, E.G.; Fuselier, S.A. ); Wurz, P.; Bochsler, P. . Physikalisches Inst.); Herrero, F.A.; Smith, M.F. . NASA Goddard Space Flight Center); Stephen, T.S. . Physics Dept.)

    1994-02-01

    The authors describe an instrument concept for measuring low-energy neutral H and O atoms with kinetic energies ranging from about 10 eV to several hundred. The instrument makes use of a low work function surface to convert neutral atoms to negative ions. These ions are then accelerated away from the surface and brought to an intermediate focus by a large aperture lens. After deflection in a spherical electrostatic analyzer, the ions are postaccelerated to [approximately]25-keV final energy into a carbon-foil time-of-flight mass analyzer. Mass resolution is adequate to resolve H, D, He, and O. Energy and azimuth angle information is obtained by means of position imaging the secondary electrons produced at the carbon foil. A large geometric factor combined with simultaneous angle-energy-mass imaging that eliminates the need for duty cycles provide the necessary high sensitivity. From a spinning spacecraft this instrument is capable of producing a 2-D map of low-energy neutral atom fluxes.

  16. Automatic analysis of double coronal mass ejections from coronagraph images

    NASA Astrophysics Data System (ADS)

    Jacobs, Matthew; Chang, Lin-Ching; Pulkkinen, Antti; Romano, Michelangelo

    2015-11-01

    Coronal mass ejections (CMEs) can have major impacts on man-made technology and humans, both in space and on Earth. These impacts have created a high interest in the study of CMEs in an effort to detect and track events and forecast the CME arrival time to provide time for proper mitigation. A robust automatic real-time CME processing pipeline is greatly desired to avoid laborious and subjective manual processing. Automatic methods have been proposed to segment CMEs from coronagraph images and estimate CME parameters such as their heliocentric location and velocity. However, existing methods suffered from several shortcomings such as the use of hard thresholding and an inability to handle two or more CMEs occurring within the same coronagraph image. Double-CME analysis is a necessity for forecasting the many CME events that occur within short time frames. Robust forecasts for all CME events are required to fully understand space weather impacts. This paper presents a new method to segment CME masses and pattern recognition approaches to differentiate two CMEs in a single coronagraph image. The proposed method is validated on a data set of 30 halo CMEs, with results showing comparable ability in transient arrival time prediction accuracy and the new ability to automatically predict the arrival time of a double-CME event. The proposed method is the first automatic method to successfully calculate CME parameters from double-CME events, making this automatic method applicable to a wider range of CME events.

  17. Interactive visualization of solar mass ejection imager (SMEI) volumetric data

    NASA Astrophysics Data System (ADS)

    Yu, Yang; Hick, P. P.; Jackson, Bernard V.

    2005-08-01

    We present a volume rendering system developed for the real time visualization and manipulation of 3D heliospheric volumetric solar wind density and velocity data obtained from the Solar Mass Ejection Imager (SMEI) and interplanetary scintillation (IPS) velocities over the same time period. Our system exploits the capabilities of the VolumePro 1000 board from TeraRecon, Inc., a low-cost 64-bit PCI board capable of rendering up to a 512-cubed array of volume data in real time at up to 30 frames per second on a standard PC. Many volume-rendering operations have been implemented with this system such as stereo/perspective views, animations of time-sequences, and determination of coronal mass ejection (CME) volumes and masses. In these visualizations we highlight one time period where a halo CMEs was observed by SMEI to engulf Earth on October 29, 2003. We demonstrate how this system is used to measure the distribution of structure and provide 3D mass for individual CME features, including the ejecta associated with the large prominence viewed moving to the south of Earth following the late October CME. Comparisons with the IPS velocity volumetric data give pixel by pixel and total kinetic energies for these events.

  18. New image of psychiatry, mass media impact and public relations.

    PubMed

    Jakovljević, Miro; Tomić, Zoran; Maslov, Boris; Skoko, Iko

    2010-06-01

    The mass media has a powerful impact on public attitudes about mental health and psychiatry. The question of identity of psychiatry as a medical profession as well as of the future of psychiatry has been the subject of much controversial discussion. Psychiatry today has the historical opportunity to shape the future of mental health care, medicine and society. It has gained in scientific and professional status by the tremendous increase of knowledge and treatment skills. Psychiatry should build up new transdisciplinary and integrative image of a specialized profession, promote it and make it public. Good public relations are very important for the future of psychiatry. PMID:20562738

  19. MALDI imaging mass spectrometry and analysis of endogenous peptides.

    PubMed

    Chatterji, Bijon; Pich, Andreas

    2013-08-01

    In recent years, MALDI imaging mass spectrometry (MALDI-IMS) has developed as a promising tool to investigate the spatial distribution of biomolecules in intact tissue specimens. Ion densities of various molecules can be displayed as heat maps while preserving anatomical structures. In this short review, an overview of different biomolecules that can be analyzed by MALDI-IMS is given. Many reviews have covered imaging of lipids, small metabolites, whole proteins and enzymatically digested proteins in the past. However, little is known about imaging of endogenous peptides, for example, in the rat brain, and this will therefore be highlighted in this review. Furthermore, sample preparation of frozen or formalin-fixed, paraffin-embedded (FFPE) tissue is crucial for imaging experiments. Therefore, some aspects of sample preparation will be addressed, including washing and desalting, the choice of MALDI matrix and its deposition. Apart from mapping endogenous peptides, their reliable identification in situ still remains challenging and will be discussed as well. PMID:23992420

  20. Panoramic imaging mass-spectrometer for planetary studies

    NASA Astrophysics Data System (ADS)

    Vaisberg, O.; Berthelier, J.-J.; Torkar, K.; Leblanc, F.; Woch, J.; Avanov, L.; Skalski, A.; Delcourt, D.; Smirnov, V.; Koinash, G.

    Plasma diagnostics can provide extremely useful information for solar system studies. Neutral and ion sputtering from the surface leads to the formation of neutral and ion exospheres with compositions that reflect the surface composition modified by ionization and transport processes around the body. Measurements of ion composition and velocity distributions provide important information about surface composition and its recycling. Plasma measurements from low altitude spacecraft and landers on planetary bodies without atmospheres can be used to map the surface composition, while spectrometers onboard spacecraft orbiting planets with atmosphere are used for study of planetary losses, mass-exchange with the solar wind, and the long-term evolution of their environment. To perform reliable measurements of planetary plasmas a complete 3-dimensional velocity distributions of various ion species is necessary. In addition, if fast measurements of the major ion species are the main goal of plasma physics studies, precise measurements of the minor ion composition are often essential to unveil important properties of the atmosphere or the surface. Therefore ion mass spectrometers for solar system missions require both the capability of making fast measurements of the 3D-velocity distribution of ions and high mass resolution for detailed composition studies. We describe a novel type of miniature panoramic ion mass-spectrometer suitable for making such 3-dimensional measurements of ion components with high mass resolution. The feeding electron optics of our plasma analyzer (CAMERA) allows for fast measurements within an instantaneous 2π field of view, which has no gaps and can be accomplished on either stabilized or rotating spacecraft, or landers. It is followed by a time-of-flight mass-spectrometer that retains imaging capabilities of the feeding optics and provides mass-resolution M/?M in excess of 100. Our spectrometer also provides flexible control of the energy

  1. Mass Spectrometry Imaging for Dissecting Steroid Intracrinology within Target Tissues

    PubMed Central

    Cobice, Diego F.; Mackay, C. Logan; Goodwin, Richard J. A.; McBride, Andrew; Langridge-Smith, Patrick R.; Webster, Scott P.; Walker, Brian R.; Andrew, Ruth

    2015-01-01

    Steroid concentrations within tissues are modulated by intracellular enzymes. Such ‘steroid intracrinology’ influences hormone-dependent cancers and obesity, and provides targets for pharmacological inhibition. However, no high resolution methods exist to quantify steroids within target tissues. We developed mass spectrometry imaging (MSI), combining matrix assisted laser desorption ionization with on-tissue derivatization with Girard T and Fourier Transform Ion Cyclotron Resonance Mass Spectrometry, to quantify substrate and product (11-dehydrocorticosterone and corticosterone) of the glucocorticoid-amplifying enzyme 11β-HSD1. Regional steroid distribution was imaged at 150-200μm resolution in rat adrenal gland and mouse brain sections, and confirmed with collision induced dissociation/liquid extraction surface analysis. In brains of mice with 11β-HSD1 deficiency or inhibition, MSI quantified changes in sub-regional corticosterone/11-dehydrocorticosterone ratio, distribution of inhibitor, and accumulation of the alternative 11β-HSD1 substrate, 7-ketocholesterol. MSI data correlated well with LC-MS/MS in whole brain homogenates. MSI with derivatization is a powerful new tool to investigate steroid biology within tissues. PMID:24134553

  2. Mass movement slope streaks imaged by the Mars Orbiter Camera

    NASA Astrophysics Data System (ADS)

    Sullivan, Robert; Thomas, Peter; Veverka, Joseph; Malin, Michael; Edgett, Kenneth S.

    2001-10-01

    Narrow, fan-shaped dark streaks on steep Martian slopes were originally observed in Viking Orbiter images, but a definitive explanation was not possible because of resolution limitations. Pictures acquired by the Mars Orbiter Camera (MOC) aboard the Mars Global Surveyor (MGS) spacecraft show innumerable examples of dark slope streaks distributed widely, but not uniformly, across the brighter equatorial regions, as well as individual details of these features that were not visible in Viking Orbiter data. Dark slope streaks (as well as much rarer bright slope streaks) represent one of the most widespread and easily recognized styles of mass movement currently affecting the Martian surface. New dark streaks have formed since Viking and even during the MGS mission, confirming earlier suppositions that higher contrast dark streaks are younger, and fade (brighten) with time. The darkest slope streaks represent ~10% contrast with surrounding slope materials. No small outcrops supplying dark material (or bright material, for bright streaks) have been found at streak apexes. Digitate downslope ends indicate slope streak formation involves a ground-hugging flow subject to deflection by minor topographic obstacles. The model we favor explains most dark slope streaks as scars from dust avalanches following oversteepening of air fall deposits. This process is analogous to terrestrial avalanches of oversteepened dry, loose snow which produce shallow avalanche scars with similar morphologies. Low angles of internal friction typically 10-30¡ for terrestrial loess and clay materials suggest that mass movement of (low-cohesion) Martian dusty air fall is possible on a wide range of gradients. Martian gravity, presumed low density of the air fall deposits, and thin (unresolved by MOC) failed layer depths imply extremely low cohesive strength at time of failure, consistent with expectations for an air fall deposit of dust particles. As speed increases during a dust avalanche, a

  3. Imaging mass spectrometry of a coral microbe interaction with fungi.

    PubMed

    Moree, Wilna J; Yang, Jane Y; Zhao, Xiling; Liu, Wei-Ting; Aparicio, Marystella; Atencio, Librada; Ballesteros, Javier; Sánchez, Joel; Gavilán, Ronnie G; Gutiérrez, Marcelino; Dorrestein, Pieter C

    2013-07-01

    Fungal infections are increasing worldwide, including in the aquatic environment. Microbiota that coexist with marine life can provide protection against fungal infections by secretion of metabolites with antifungal properties. Our laboratory has developed mass spectrometric methodologies with the goal of improving our functional understanding of microbial metabolites and guiding the discovery process of anti-infective agents from natural sources. GA40, a Bacillus amyloliquefaciens strain isolated from an octocoral in Panama, displayed antifungal activity against various terrestrial and marine fungal strains. Using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), the molecular species produced by this microbe were visualized in a side-by-side interaction with two representative fungal strains, Aspergillus fumigatus and Aspergillus niger. The visualization was performed directly on the agar without the need for extraction. By evaluating the spatial distributions, relative intensities and m/z values of GA40 secreted metabolites in the fungal interactions and singly grown control colonies, we obtained insight into the antifungal activity of secreted metabolites. Annotation of GA40 metabolites observed in MALDI-IMS was facilitated by MS/MS networking analysis, a mass spectrometric technique that clusters metabolites with similar MS/MS fragmentation patterns. This analysis established that the predominant GA40 metabolites belong to the iturin family. In a fungal inhibition assay of A. fumigatus, the GA40 iturin metabolites were found to be responsible for the antifungal properties of this Bacillus strain. PMID:23881443

  4. Atmospheric pressure infrared MALDI imaging mass spectrometry for plant metabolomics.

    PubMed

    Li, Yue; Shrestha, Bindesh; Vertes, Akos

    2008-01-15

    The utility of atmospheric pressure infrared MALDI mass spectrometry (AP IR-MALDI) was assessed for plant metabolomics studies. Tissue sections from plant organs, including flowers, ovaries, aggregate fruits, fruits, leaves, tubers, bulbs, and seeds were studied in both positive and negative ion modes. For leaves, single laser pulses sampled the cuticle and upper epidermal cells, whereas multiple pulses were demonstrated to ablate some mesophyll layers. Tandem mass spectra were obtained with collision-activated dissociation to aid with the identification of some observed ions. In the positive mode, most ions were produced as potassium, proton, or sometimes sodium ion adducts, whereas proton loss was dominant in the negative ion mode. Over 50 small metabolites and various lipids were detected in the spectra including, for example, 7 of the 10 intermediates in the citric acid cycle. Key components of the glycolysis pathway occurring in the plant cytosol were found along with intermediates of phospholipid biosynthesis and reactants or products of amino acid, nucleotide, oligosaccharide, and flavonoid biosynthesis. AP IR-MALDI mass spectrometry was used to follow the fluid transport driven by transpiration and image the spatial distributions of several metabolites in a white lily (Lilium candidum) flower petal. PMID:18088102

  5. Interactive Visualization of Solar Mass Ejection Imager (SMEI) Volumetric Data

    NASA Astrophysics Data System (ADS)

    Wang, X.; Hick, P. P.; Jackson, B. V.

    2004-12-01

    We present a volume rendering system developed for the real time visualization and manipulation of 3D heliospheric volumetric solar wind density and velocity data obtained from the Solar Mass Ejection Imager (SMEI) and interplanetary scintillation (IPS) velocities over the same time period. Our system exploits the capabilities of the VolumePro 1000 board from TeraRecon, Inc., a low-cost 64-bit PCI board capable of rendering up to a 512-cubed array of volume data in real time at up to 30 frames per second on a standard PC. Many volume-rendering operations have been implemented with this system such as stereo/perspective views, animations of time-sequences, and determination of CME volumes and masses. In these visualizations we highlight two time periods where halo CMEs were observed by SMEI to engulf Earth, on May 30, 2003 and on October 29, 2003. We demonstrate how this system is used to measure the distribution of structure and provide 3D mass for individual CME features, including the ejecta associated with the large prominence viewed moving to the south of Earth following the late October CME.

  6. IMAGING MASS SPECTROMETRY OF A CORAL MICROBE INTERACTION WITH FUNGI

    PubMed Central

    ZHAO, XILING; LIU, WEI-TING; APARICIO, MARYSTELLA; ATENCIO, LIBRADA; BALLESTEROS, JAVIER; SÁNCHEZ, JOEL; GAVILÁN, RONNIE G.; GUTIÉRREZ, MARCELINO; DORRESTEIN, PIETER C.

    2013-01-01

    Fungal infections are increasing worldwide, including in the aquatic environment. Microbiota that coexist with marine life can provide protection against fungal infections by secretion of metabolites with antifungal properties. Our laboratory has developed mass spectrometric methodologies with the goal of improving our functional understanding of microbial metabolites and guiding the discovery process of anti-infective agents from natural sources. GA40, a Bacillus amyloliquefaciens strain isolated from an octocoral in Panama, displayed antifungal activity against various terrestrial and marine fungal strains. Using matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS), the molecular species produced by this microbe were visualized in a side-by-side interaction with two representative fungal strains, Aspergillus fumigatus and Aspergillus niger. The visualization was performed directly on the agar without the need for extraction. By comparison of spatial distributions, relative intensities and m/z values of GA40 secreted metabolites in the fungal interactions versus singly grown control colonies, we obtained insight into the antifungal activity of secreted metabolites. Annotation of GA40 metabolites observed in MALDI-IMS was facilitated by MS/MS networking analysis, a mass spectrometric technique that clusters metabolites with similar MS/MS fragmentation patterns. This analysis established that the predominant GA40 metabolites belong to the iturin family. In a fungal inhibition assay of A. fumigatus, the GA40 iturin metabolites were found to be responsible for the antifungal properties of this Bacillus strain. PMID:23881443

  7. Significant advancement of mass spectrometry imaging for food chemistry.

    PubMed

    Yoshimura, Yukihiro; Goto-Inoue, Naoko; Moriyama, Tatsuya; Zaima, Nobuhiro

    2016-11-01

    Food contains various compounds that have an impact on our daily lives. Many technologies have been established to analyze these molecules of interest in foods. However, the analysis of the spatial distribution of these compounds in foods using conventional technology, such as high-performance liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry is difficult. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is considered an ideal complementary approach. MALDI-MSI is a two-dimensional MALDI-MS technology that can detect compounds in a tissue section without extraction, purification, separation, or labeling. MALDI-MSI can be used to visualize the spatial distribution of chemical compounds or biomolecules in foods. Although the methodology of MALDI-MSI in food science is not yet fully established, the versatility of MALDI-MSI is expected to open a new frontier in food science. Herein, we describe the principles and applications of MALDI-MSI in food science and related fields. PMID:27211639

  8. Ambient Mass Spectrometry Imaging Using Direct Liquid Extraction Techniques

    SciTech Connect

    Laskin, Julia; Lanekoff, Ingela

    2015-11-13

    Mass spectrometry imaging (MSI) is a powerful analytical technique that enables label-free spatial localization and identification of molecules in complex samples.1-4 MSI applications range from forensics5 to clinical research6 and from understanding microbial communication7-8 to imaging biomolecules in tissues.1, 9-10 Recently, MSI protocols have been reviewed.11 Ambient ionization techniques enable direct analysis of complex samples under atmospheric pressure without special sample pretreatment.3, 12-16 In fact, in ambient ionization mass spectrometry, sample processing (e.g., extraction, dilution, preconcentration, or desorption) occurs during the analysis.17 This substantially speeds up analysis and eliminates any possible effects of sample preparation on the localization of molecules in the sample.3, 8, 12-14, 18-20 Venter and co-workers have classified ambient ionization techniques into three major categories based on the sample processing steps involved: 1) liquid extraction techniques, in which analyte molecules are removed from the sample and extracted into a solvent prior to ionization; 2) desorption techniques capable of generating free ions directly from substrates; and 3) desorption techniques that produce larger particles subsequently captured by an electrospray plume and ionized.17 This review focuses on localized analysis and ambient imaging of complex samples using a subset of ambient ionization methods broadly defined as “liquid extraction techniques” based on the classification introduced by Venter and co-workers.17 Specifically, we include techniques where analyte molecules are desorbed from solid or liquid samples using charged droplet bombardment, liquid extraction, physisorption, chemisorption, mechanical force, laser ablation, or laser capture microdissection. Analyte extraction is followed by soft ionization that generates ions corresponding to intact species. Some of the key advantages of liquid extraction techniques include the ease

  9. Imaging Mass Spectrometric Analysis of Neurotransmitters: A Review

    PubMed Central

    Romero-Perez, Gustavo A.; Takei, Shiro; Yao, Ikuko

    2014-01-01

    Imaging mass spectrometry (IMS) is a toolbox of versatile techniques that enable us to investigate analytes in samples at molecular level. In recent years, IMS, and especially matrix-assisted laser desorption/ionisation (MALDI), has been used to visualise a wide range of metabolites in biological samples. Simultaneous visualisation of the spatial distribution of metabolites in a single sample with little tissue disruption can be considered as one important advantage of MALDI over other techniques. However, several technical hurdles including low concentrations and rapid degradation rates of small molecule metabolites, matrix interference of signals and poor ionisation, need to be addressed before MALDI can be considered as a reliable tool for the analysis of metabolites such as neurotransmitters in brain tissues from different sources including humans. In the present review we will briefly describe current MALDI IMS techniques used to study neurotransmitters and discuss their current status, challenges, as well as future prospects. PMID:26819893

  10. Research and design of high speed mass image storage system

    NASA Astrophysics Data System (ADS)

    Li, Yu-feng; Xue, Rong-kun; Liang, Fei

    2009-07-01

    The design of the high mass image storage system is introduced using DSP, FPGA and Flash structure. Texas Instruments Corporation DSP chip (TMS320VC5509APEG) is used as the main controller, Samsung's Flash chips (K9F2G08U0M) used as the main storage medium, and the Xilinx Corporation FPGA chip (XCV600E) used as logic control modules. In this system, Storage module consists of 32 Flash memory chips, which are divided into 8 groups that correspond to 8-level pipeline. The 4-Flash memory chip forms a basic 32-bit memory module. The entire system storage space is 64 G bit. Through simulation and verification, the storage speed is up to 352Mbps and readout speed is up to 290Mbps, it can meet the demand to the high-speed access, and which has strong environmental adaptability.

  11. High Resolution MALDI Imaging Mass Spectrometry of Retinal Tissue Lipids

    NASA Astrophysics Data System (ADS)

    Anderson, David M. G.; Ablonczy, Zsolt; Koutalos, Yiannis; Spraggins, Jeffrey; Crouch, Rosalie K.; Caprioli, Richard M.; Schey, Kevin L.

    2014-08-01

    Matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) has the ability to provide an enormous amount of information on the abundances and spatial distributions of molecules within biological tissues. The rapid progress in the development of this technology significantly improves our ability to analyze smaller and smaller areas and features within tissues. The mammalian eye has evolved over millions of years to become an essential asset for survival, providing important sensory input of an organism's surroundings. The highly complex sensory retina of the eye is comprised of numerous cell types organized into specific layers with varying dimensions, the thinnest of which is the 10 μm retinal pigment epithelium (RPE). This single cell layer and the photoreceptor layer contain the complex biochemical machinery required to convert photons of light into electrical signals that are transported to the brain by axons of retinal ganglion cells. Diseases of the retina, including age-related macular degeneration (AMD), retinitis pigmentosa, and diabetic retinopathy, occur when the functions of these cells are interrupted by molecular processes that are not fully understood. In this report, we demonstrate the use of high spatial resolution MALDI IMS and FT-ICR tandem mass spectrometry in the Abca4 -/- knockout mouse model of Stargardt disease, a juvenile onset form of macular degeneration. The spatial distributions and identity of lipid and retinoid metabolites are shown to be unique to specific retinal cell layers.

  12. Forecasting coronal mass ejections at 1 AU using Heliospheric Imagers

    NASA Astrophysics Data System (ADS)

    Möstl, Christian; Amla, Keshav; Hall, Jeffrey R.; Liewer, Paulett C.; De Jong, Eric; Temmer, Manuela; Davies, Jackie A.; Lugaz, Noé; Rollett, Tanja; Veronig, Astrid M.; Farrugia, Charles J.; Liu, Ying; Luhmann, Janet G.; Galvin, Antoinette B.; Zhang, Tielong

    2013-04-01

    We study the feasibility of using a Heliospheric Imager (HI) instrument, such as STEREO/HI, for operational space weather forecasting of interplanetary coronal mass ejections (ICMEs) at 1 AU. We compare the predictions for speed and arrival time for about 20 ICME events, each observed remotely by one STEREO spacecraft, to the speed and arrival time observed at various in situ observatories. We use geometrical modeling, which means we approximate the ICME fronts with various shapes (Fixed-Phi, Harmonic Mean, Self-Similar Expansion). These models are applied to the time-elongation functions extracted from STEREO/SECCHI images with the SolarSoft SATPLOT package. We use these techniques for a single-spacecraft HI observer, and consequently assume constant ICME speed and direction. Partly, the configuration mimics the situation of a single HI observatory parked at the L4 or L5 point in the Sun-Earth system. For assessing the accuracy of these predictions we look at plasma and magnetic field in situ data by Wind (MFI, SWE instruments) and STEREO-A/B (IMPACT, PLASTIC) around 1 AU. Wherever possible we include ICME arrivals in the inner heliosphere (< 1 AU), from the magnetic field data by Venus Express and MESSENGER. We also look at the ratio of prediction lead time to its accuracy, and see if there is a preferred value for the ICME width.

  13. Improved mass resolution and mass accuracy in TOF-SIMS spectra and images using argon gas cluster ion beams.

    PubMed

    Shon, Hyun Kyong; Yoon, Sohee; Moon, Jeong Hee; Lee, Tae Geol

    2016-06-01

    The popularity of argon gas cluster ion beams (Ar-GCIB) as primary ion beams in time-of-flight secondary ion mass spectrometry (TOF-SIMS) has increased because the molecular ions of large organic- and biomolecules can be detected with less damage to the sample surfaces. However, Ar-GCIB is limited by poor mass resolution as well as poor mass accuracy. The inferior quality of the mass resolution in a TOF-SIMS spectrum obtained by using Ar-GCIB compared to the one obtained by a bismuth liquid metal cluster ion beam and others makes it difficult to identify unknown peaks because of the mass interference from the neighboring peaks. However, in this study, the authors demonstrate improved mass resolution in TOF-SIMS using Ar-GCIB through the delayed extraction of secondary ions, a method typically used in TOF mass spectrometry to increase mass resolution. As for poor mass accuracy, although mass calibration using internal peaks with low mass such as hydrogen and carbon is a common approach in TOF-SIMS, it is unsuited to the present study because of the disappearance of the low-mass peaks in the delayed extraction mode. To resolve this issue, external mass calibration, another regularly used method in TOF-MS, was adapted to enhance mass accuracy in the spectrum and image generated by TOF-SIMS using Ar-GCIB in the delayed extraction mode. By producing spectra analyses of a peptide mixture and bovine serum albumin protein digested with trypsin, along with image analyses of rat brain samples, the authors demonstrate for the first time the enhancement of mass resolution and mass accuracy for the purpose of analyzing large biomolecules in TOF-SIMS using Ar-GCIB through the use of delayed extraction and external mass calibration. PMID:26861497

  14. Single hair cocaine consumption monitoring by mass spectrometric imaging.

    PubMed

    Porta, Tiffany; Grivet, Chantal; Kraemer, Thomas; Varesio, Emmanuel; Hopfgartner, Gérard

    2011-06-01

    Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was used to image the distribution of cocaine and its metabolites in intact single hair samples from chronic users down to a concentration of 5 ng/mg. Acquisitions were performed in rastering mode, at a speed of 1 mm/s and in the selected reaction monitoring (SRM) mode on a MALDI triple quadrupole linear ion trap fitted with a high repetition rate laser (1 kHz). Compared to traditional methods based on LC-MS/MS or GC-MS(/MS) which require to segment the hair to obtain spatial resolution, MALDI-MSI, with a straightforward sample preparation beforehand, allowed obtaining a spatial resolution of 1 mm and thus the chronological information about cocaine consumption contained in a single intact hair over several months could be monitored. The analysis time of an intact single hair sample of 6 cm is approximately of 6 min. Cocaine and its metabolites benzoylecgonine, ethylcocaine, and norcocaine were investigated in nine sets of hair samples for forensic purposes. The analyses were accomplished by spraying α-cyano-4-hydroxycinnamic acid (CHCA), 4-chloro-α-cyano-cinnamic acid (Cl-CCA), or (E)-2-cyano-3-(naphthalen-2-yl)acrylic acid (NpCCA) as MALDI matrices. We also propose a rapid strategy for sensitive confirmatory analyses with both MS/MS and MS(3) experiments performed directly on intact hair samples. Since only part of the hair strand is analyzed, additional analyses are possible at any time on the remaining hair from the strand. PMID:21510611

  15. Mass spectrometric imaging - Quantification strategies for created bio-images measured by LA-ICP-MS

    NASA Astrophysics Data System (ADS)

    Draxler, Johannes; Zitek, Andreas; Tschegg, Stefanie; Mingler, Bernhard; Weinberg, Annelie; Prohaska, Thomas

    2014-05-01

    Mass spectrometric imaging (MSI) using laser ablation - inductively coupled plasma - mass spectrometry (LA-ICP-MS) has been an emerging methodology in the analysis of biological matrices. A challenging step is the quantification and data processing to generate quantitative displays (bio-images) by avoiding analytical artefacts derived from image processing. Moreover, the procedure gets more challenging when features to be monitored are in the range or even smaller as compared to the size of the laser spot as the spatial resolution of the laser ablation system typically lies in the µm range (2 - 300 µm spot size). Here, we present the application of LA-ICP-MSI to biological tissues (bones) for the investigation of the distribution of alloying elements in bone material after the implantation of a Mg-based pin into the femur of rats. For the quantification of the elemental content, in-house standards were prepared by co-precipitation of the alloying elements (Mg, Ca, P, Mn, Zn, Zr, and Yb) in a hydroxyapatite matrix. The capability of this quantification approach was validated by comparative measurements of certified reference materials (SRM 1486, pressed into pellets for direct LA-ICP-MS analysis). ArcGIS® was used for the first time as standard tool for the spatially distinct statistical analysis of chemical data in so called "zones of interest".

  16. Forecasting coronal mass ejections at 1 AU using Heliospheric Imagers

    NASA Astrophysics Data System (ADS)

    Moestl, C.; Amla, K.; Temmer, M.; Hall, J. R.; Liewer, P. C.; De Jong, E. M.; Davies, J.; Lugaz, N.; Rollett, T.; Veronig, A.; Liu, Y.; Farrugia, C. J.; Luhmann, J. G.; Galvin, A. B.; Zhang, T.

    2012-12-01

    We study the feasibility of using a Heliospheric Imager (HI) instrument, such as STEREO/HI, for space weather forecasting of interplanetary coronal mass ejections (ICMEs) at 1 AU. We compare the predictions for speed and arrival time for ~15 ICME events, each observed remotely by one STEREO spacecraft, to the speed and arrival time observed at in situ observatories. We use three different models with varying ICME geometry, from point-like (Fixed-Phi) to a circle with a given width (Self-Similar-Expansion) to a very wide circle (Harmonic Mean). The models are fitted to density tracks on HI Jmaps with the SolarSoft SATPLOT tool. All these techniques assume constant ICME speed and direction. Partly, the configuration mimics the situation of a single HI observatory parked at the L4 or L5 point in the Sun-Earth system. We discuss problems associated with this study, such as CME-CME interactions leading to complicated Jmaps. For assessing the accuracy of these predictions we look at in situ data by Wind/ACE, STEREO-A/B, and Venus Express and MESSENGER. We also look at the ratio of prediction lead time to its accuracy, and see if there is a preferred value for the ICME width.

  17. Matrix Effects in Biological Mass Spectrometry Imaging: Identification and Compensation

    SciTech Connect

    Lanekoff, Ingela T.; Stevens, Susan; Stenzel-Poore, Mary; Laskin, Julia

    2014-07-21

    Matrix effects in mass spectrometry imaging (MSI) may affect the observed molecular distribution in chemical and biological systems. In this study, we introduce an experimental approach that efficiently compensates for matrix effects in nanospray desorption electrospray ionization (nano-DESI) MSI without introducing any complexity into the experimental protocol. We demonstrate compensation for matrix effects in nano-DESI MSI of phosphatidylcholine (PC) in normal and ischemic mouse brain tissue by doping the nano-DESI solvent with PC standards. Specifically, we use mouse brain tissue of a middle cerebral artery occlusion (MCAO) stroke model with an ischemic region localized to one hemisphere of the brain. Due to similar suppression in ionization of endogenous PC molecules extracted from the tissue and PC standards added to the solvent, matrix effects are eliminated by normalizing the intensity of the sodium and potassium adducts of endogenous PC to the intensity of the corresponding adduct of the PC standard. This approach efficiently compensates for signal variations resulting from differences in the local concentrations of sodium and potassium in tissue sections and from the complexity of the extracted analyte mixture derived from local variations in molecular composition.

  18. A fast microchannel plate-scintillator detector for velocity map imaging and imaging mass spectrometry

    SciTech Connect

    Winter, B.; King, S. J.; Vallance, C.; Brouard, M.

    2014-02-15

    The time resolution achievable using standard position-sensitive ion detectors, consisting of a chevron pair of microchannel plates coupled to a phosphor screen, is primarily limited by the emission lifetime of the phosphor, around 70 ns for the most commonly used P47 phosphor. We demonstrate that poly-para-phenylene laser dyes may be employed extremely effectively as scintillators, exhibiting higher brightness and much shorter decay lifetimes than P47. We provide an extensive characterisation of the properties of such scintillators, with a particular emphasis on applications in velocity-map imaging and microscope-mode imaging mass spectrometry. The most promising of the new scintillators exhibits an electron-to-photon conversion efficiency double that of P47, with an emission lifetime an order of magnitude shorter. The new scintillator screens are vacuum stable and show no signs of signal degradation even over longer periods of operation.

  19. Highly multiplexed imaging of tumor tissues with subcellular resolution by mass cytometry.

    PubMed

    Giesen, Charlotte; Wang, Hao A O; Schapiro, Denis; Zivanovic, Nevena; Jacobs, Andrea; Hattendorf, Bodo; Schüffler, Peter J; Grolimund, Daniel; Buhmann, Joachim M; Brandt, Simone; Varga, Zsuzsanna; Wild, Peter J; Günther, Detlef; Bodenmiller, Bernd

    2014-04-01

    Mass cytometry enables high-dimensional, single-cell analysis of cell type and state. In mass cytometry, rare earth metals are used as reporters on antibodies. Analysis of metal abundances using the mass cytometer allows determination of marker expression in individual cells. Mass cytometry has previously been applied only to cell suspensions. To gain spatial information, we have coupled immunohistochemical and immunocytochemical methods with high-resolution laser ablation to CyTOF mass cytometry. This approach enables the simultaneous imaging of 32 proteins and protein modifications at subcellular resolution; with the availability of additional isotopes, measurement of over 100 markers will be possible. We applied imaging mass cytometry to human breast cancer samples, allowing delineation of cell subpopulations and cell-cell interactions and highlighting tumor heterogeneity. Imaging mass cytometry complements existing imaging approaches. It will enable basic studies of tissue heterogeneity and function and support the transition of medicine toward individualized molecularly targeted diagnosis and therapies. PMID:24584193

  20. Automatic generic registration of mass spectrometry imaging data to histology using nonlinear stochastic embedding.

    PubMed

    Abdelmoula, Walid M; Škrášková, Karolina; Balluff, Benjamin; Carreira, Ricardo J; Tolner, Else A; Lelieveldt, Boudewijn P F; van der Maaten, Laurens; Morreau, Hans; van den Maagdenberg, Arn M J M; Heeren, Ron M A; McDonnell, Liam A; Dijkstra, Jouke

    2014-09-16

    The combination of mass spectrometry imaging and histology has proven a powerful approach for obtaining molecular signatures from specific cells/tissues of interest, whether to identify biomolecular changes associated with specific histopathological entities or to determine the amount of a drug in specific organs/compartments. Currently there is no software that is able to explicitly register mass spectrometry imaging data spanning different ionization techniques or mass analyzers. Accordingly, the full capabilities of mass spectrometry imaging are at present underexploited. Here we present a fully automated generic approach for registering mass spectrometry imaging data to histology and demonstrate its capabilities for multiple mass analyzers, multiple ionization sources, and multiple tissue types. PMID:25133861

  1. Multi-isotope approach: a tool to better constrain both sources and processes affecting NO3 pollution in watersheds

    NASA Astrophysics Data System (ADS)

    Widory, D.

    2006-12-01

    Nitrate is one of the major pollutants of drinking water resources worldwide. Recent European directives reduced inputs from intensive agriculture, but in most places NO3 levels are approaching the potable limit of 50 mg.l-1 in groundwater. Determining the source(s) of contamination in groundwater is an important first step for improving its quality by emission control. It is with this aim that we review here the benefit of using a multi- isotope approach (d15N, d180, d11B and 87Sr/86Sr), in addition to conventional hydrogeological analysis, to both constrain the watersheds hydrology and trace the origin of their NO3 pollution. Watersheds presented here include both fractured bedrock and alluvial (subsurface and deep) hydrogeological contexts. The strontium budget in watersheds is mainly controlled by the water-rock interactions (human inputs usually represents negligible fluxes). With the example of the Allier river (Central France), we show that, even on a very small watershed, the main water flows can usually be determined by the use of the 87Sr/86Sr ratios, thus helping understanding the hydrology controlling pollution processes. The characterisation of the different usual nitrate sources of pollution in groundwater (mineral fertilisers, wastewater and animals manure) shows that they can clearly be discriminated using isotopes. The isotopic composition of the dissolved nitrogen species has been used extensively to better constrain the sources and fate of nitrate in groundwater. The possibility of quantifying both origin and secondary processes affecting N concentrations by means of a single tracer appears more limited however. Nitrogen cannot be considered conservative because it is biologically modified through nitrification and denitrification reactions, both during infiltration of the water and in the groundwater body, causing isotopic fractionation that modifies the d15N-n signatures of the dissolved N species. Discriminating multiple NO3 sources by their N

  2. The Relationships among Body Image, Body Mass Index, Exercise, and Sexual Functioning in Heterosexual Women

    ERIC Educational Resources Information Center

    Weaver, Angela D.; Byers, E. Sandra

    2006-01-01

    Problems related to negative body image are very common among young women. In this study, we examined the relationship between women's body image and their sexual functioning over and above the effects of physical exercise and body mass index (BMI) in a sample of 214 university women. Low situational body image dysphoria and low body…

  3. Lung mass, right upper lung - chest x-ray (image)

    MedlinePlus

    This picture is a chest x-ray of a person with a lung mass. This is a front view, where the lungs are the two dark areas and ... visible in the middle of the chest. The x-ray shows a mass in the right upper lung, ...

  4. Lung mass, right upper lung - chest x-ray (image)

    MedlinePlus

    ... chest x-ray of a person with a lung mass. This is a front view, where the lungs are the two dark areas and the heart ... ray shows a mass in the right upper lung, indicated with the arrow (seen on the left ...

  5. Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance

    PubMed Central

    Wang, Shaopeng; Shan, Xiaonan; Patel, Urmez; Huang, Xinping; Lu, Jin; Li, Jinghong; Tao, Nongjian

    2010-01-01

    We report on label-free imaging, detection, and mass/size measurement of single viral particles in solution by high-resolution surface plasmon resonance microscopy. Diffraction of propagating plasmon waves along a metal surface by the viral particles creates images of the individual particles, which allow us to detect the binding of the viral particles to surfaces functionalized with and without antibodies. We show that the intensity of the particle image is related to the mass of the particle, from which we determine the mass and mass distribution of influenza viral particles with a mass detection limit of approximately 1 ag (or 0.2 fg/mm2). This work demonstrates a multiplexed method to measure the masses of individual viral particles and to study the binding activity of the viral particles. PMID:20798340

  6. Statistical fractal border features for MRI breast mass images

    NASA Astrophysics Data System (ADS)

    Penn, Alan I.; Bolinger, Lizann; Loew, Murray H.

    1998-06-01

    MRI has been proposed as an alternative method to mammography for detecting and staging breast cancer. Recent studies have shown that architectural features of breast masses may be useful in improving specificity. Since fractal dimension (fd) has been correlated with roughness, and border roughness is an indicator of malignancy, the fd of the mass border is a promising architectural feature for achieving improved specificity. Previous methods of estimating the fd of the mass border have been unreliable because of limited data or overlay restrictive assumptions of the fractal model. We present preliminary results of a statistical approach in which a sample space of fd estimates is generated from a family of self-affine fractal models. The fd of the mass border is then estimated from the statistics of the sample space.

  7. Foodomics imaging by mass spectrometry and magnetic resonance.

    PubMed

    Canela, Núria; Rodríguez, Miguel Ángel; Baiges, Isabel; Nadal, Pedro; Arola, Lluís

    2016-07-01

    This work explores the use of advanced imaging MS (IMS) and magnetic resonance imaging (MRI) techniques in food science and nutrition to evaluate food sensory characteristics, nutritional value and health benefits. Determining the chemical content and applying imaging tools to food metabolomics offer detailed information about food quality, safety, processing, storage and authenticity assessment. IMS and MRI are powerful analytical systems with an excellent capability for mapping the distribution of many molecules, and recent advances in these platforms are reviewed and discussed, showing the great potential of these techniques for small molecule-based food metabolomics research. PMID:26799681

  8. Determination of geographic provenance of cotton fibres using multi-isotope profiles and multivariate statistical analysis

    NASA Astrophysics Data System (ADS)

    Daeid, N. Nic; Meier-Augenstein, W.; Kemp, H. F.

    2012-04-01

    The analysis of cotton fibres can be particularly challenging within a forensic science context where discrimination of one fibre from another is of importance. Normally cotton fibre analysis examines the morphological structure of the recovered material and compares this with that of a known fibre from a particular source of interest. However, the conventional microscopic and chemical analysis of fibres and any associated dyes is generally unsuccessful because of the similar morphology of the fibres. Analysis of the dyes which may have been applied to the cotton fibre can also be undertaken though this can be difficult and unproductive in terms of discriminating one fibre from another. In the study presented here we have explored the potential for Isotope Ratio Mass Spectrometry (IRMS) to be utilised as an additional tool for cotton fibre analysis in an attempt to reveal further discriminatory information. This work has concentrated on un-dyed cotton fibres of known origin in order to expose the potential of the analytical technique. We report the results of a pilot study aimed at testing the hypothesis that multi-element stable isotope analysis of cotton fibres in conjunction with multivariate statistical analysis of the resulting isotopic abundance data using well established chemometric techniques permits sample provenancing based on the determination of where the cotton was grown and as such will facilitate sample discrimination. To date there is no recorded literature of this type of application of IRMS to cotton samples, which may be of forensic science relevance.

  9. Fractal morphology, imaging and mass spectrometry of single aerosol particles in flight (CXIDB ID 16)

    DOE Data Explorer

    Loh, N. Duane

    2012-06-20

    This deposition includes the aerosol diffraction images used for phasing, fractal morphology, and time-of-flight mass spectrometry. Files in this deposition are ordered in subdirectories that reflect the specifics.

  10. Origins and processes of groundwater salinization in the urban coastal aquifers of Recife (Pernambuco, Brazil): A multi-isotope approach.

    PubMed

    Cary, Lise; Petelet-Giraud, Emmanuelle; Bertrand, Guillaume; Kloppmann, Wolfram; Aquilina, Luc; Martins, Veridiana; Hirata, Ricardo; Montenegro, Suzana; Pauwels, Hélène; Chatton, Eliot; Franzen, Melissa; Aurouet, Axel

    2015-10-15

    In the coastal multilayer aquifer system of a highly urbanized southern city (Recife, Brazil), where groundwaters are affected by salinization, a multi-isotope approach (Sr, B, O, H) was used to investigate the sources and processes of salinization. The high diversity of the geological bodies, built since the Atlantic opening during the Cretaceous, highly constrains the heterogeneity of the groundwater chemistry, e.g. Sr isotope ratios, and needs to be integrated to explain the salinization processes and groundwater pathways. A paleoseawater intrusion, most probably the 120 kyB.P. Pleistocene marine transgression, and cationic exchange are clearly evidenced in the most salinized parts of the Cabo and Beberibe aquifers. All (87)Sr/(86)Sr values are above the past and present-day seawater signatures, meaning that the Sr isotopic signature is altered due to additional Sr inputs from dilution with different freshwaters, and water-rock interactions. Only the Cabo aquifer presents a well-delimitated area of Na-HCO3 water typical of a freshening process. The two deep aquifers also display a broad range of B concentrations and B isotope ratios with values among the highest known to date (63-68.5‰). This suggests multiple sources and processes affecting B behavior, among which mixing with saline water, B sorption on clays and mixing with wastewater. The highly fractionated B isotopic values were explained by infiltration of relatively salty water with B interacting with clays, pointing out the major role played by (palaeo)-channels for the deep Beberibe aquifer recharge. Based on an increase of salinity at the end of the dry season, a present-day seawater intrusion is identified in the surficial Boa Viagem aquifer. Our conceptual model presents a comprehensive understanding of the major groundwater salinization pathways and processes, and should be of benefit for other southern Atlantic coastal aquifers to better address groundwater management issues. PMID:26063126

  11. Imaging Mass Spectrometry Reveals a Decrease of Cardiolipin in the Kidney of NASH Model Mice.

    PubMed

    Hayasaka, Takahiro; Fuda, Hirotoshi; Hui, Shu-Ping; Chiba, Hitoshi

    2016-01-01

    Non-alcoholic steatohepatitis (NASH) can be complicated with chronic kidney disease (CKD). In this study, changes in the distribution of biomolecules in the kidney were studied in NASH model mice with the use of imaging mass spectrometry (IMS). The mass spectra and ion images of IMS showed that the signals of cardiolipin (CL) species were decreased in the kidney cortex of the NASH mice. The decrease of CL might therefore suggest the kidney involvement of NASH. PMID:27063723

  12. The Image of Public Relations in Mass Comm Texts.

    ERIC Educational Resources Information Center

    Cline, Carolyn

    1982-01-01

    Compared public relations sections in 12 introductory mass communication texts and found a confusion about the relationship of advertising and public relations, a lack of historical background, and an antipublic relations stance. Journal available from Communication Research Associates, 7100 Baltimore Blvd., Suite 500, College Park, MD 20740; sc…

  13. Optimizing Magnetite Nanoparticles for Mass Sensitivity in Magnetic Particle Imaging

    SciTech Connect

    Ferguson, R Matthew; Minard, Kevin R; Khandhar, Amit P; Krishnan, Kannan M

    2011-03-01

    Purpose: Magnetic particle imaging (MPI), using magnetite nanoparticles (MNPs) as tracer material, shows great promise as a platform for fast tomographic imaging. To date, the magnetic properties of MNPs used in imaging have not been optimized. As nanoparticle magnetism shows strong size dependence, we explore how varying MNP size impacts imaging performance in order to determine optimal MNP characteristics for MPI at any driving field frequency f0. Methods: Monodisperse MNPs of varying size were synthesized and their magnetic properties characterized. Their MPI response was measured experimentally, at an arbitrarily chosen f0 = 250 kHz, using a custom-built MPI transceiver designed to detect the third harmonic of MNP magnetization. Results were interpreted using a model of dynamic MNP magnetization that is based on the Langevin theory of superparamagnetism and accounts for sample size distribution, and size-dependent magnetic relaxation. Results: Our experimental results show clear variation in the MPI signal intensity as a function of MNP size that is in good agreement with modeled results. A maxima in the plot of MPI signal vs. MNP size indicates there is a particular size that is optimal for the chosen frequency of 250 kHz. Conclusions: For MPI at any chosen frequency, there will exist a characteristic particle size that generates maximum signal amplitude. We illustrate this at 250 kHz with particles of 15 nm core diameter.

  14. Optimizing magnetite nanoparticles for mass sensitivity in magnetic particle imaging

    PubMed Central

    Ferguson, R. Matthew; Minard, Kevin R.; Khandhar, Amit P.; Krishnan, Kannan M.

    2011-01-01

    Purpose: Magnetic particle imaging (MPI), using magnetite nanoparticles (MNPs) as tracer material, shows great promise as a platform for fast tomographic imaging. To date, the magnetic properties of MNPs used in imaging have not been optimized. As nanoparticle magnetism shows strong size dependence, the authors explore how varying MNP size impacts imaging performance in order to determine optimal MNP characteristics for MPI at any driving field frequency f0. Methods: Monodisperse MNPs of varying size were synthesized and their magnetic properties characterized. Their MPI response was measured experimentally using a custom-built MPI transceiver designed to detect the third harmonic of MNP magnetization. The driving field amplitude H0=6 mT μ0−1 and frequency f0=250 kHz were chosen to be suitable for imaging small animals. Experimental results were interpreted using a model of dynamic MNP magnetization that is based on the Langevin theory of superparamagnetism and accounts for sample size distribution and size-dependent magnetic relaxation. Results: The experimental results show a clear variation in the MPI signal intensity as a function of MNP diameter that is in agreement with simulated results. A maximum in the plot of MPI signal vs MNP size indicates there is a particular size that is optimal for the chosen f0. Conclusions: The authors observed that MNPs 15 nm in diameter generate maximum signal amplitude in MPI experiments at 250 kHz. The authors expect the physical basis for this result, the change in magnetic relaxation with MNP size, will impact MPI under other experimental conditions. PMID:21520874

  15. Co-registered Topographical, Band Excitation Nanomechanical, and Mass Spectral Imaging Using a Combined Atomic Force Microscopy/Mass Spectrometry Platform

    DOE PAGESBeta

    Ovchinnikova, Olga S.; Tai, Tamin; Bocharova, Vera; Okatan, Mahmut Baris; Belianinov, Alex; Kertesz, Vilmos; Jesse, Stephen; Van Berkel, Gary J.

    2015-03-18

    The advancement of a hybrid atomic force microscopy/mass spectrometry imaging platform demonstrating for the first time co-registered topographical, band excitation nanomechanical, and mass spectral imaging of a surface using a single instrument is reported. The mass spectrometry-based chemical imaging component of the system utilized nanothermal analysis probes for pyrolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. We discuss the basic instrumental setup and operation and the multimodal imaging capability and utility are demonstrated using a phase separated polystyrene/poly(2-vinylpyridine) polymer blend thin film. The topography and band excitation images showedmore » that the valley and plateau regions of the thin film surface were comprised primarily of one of the two polymers in the blend with the mass spectral chemical image used to definitively identify the polymers at the different locations. Data point pixel size for the topography (390 nm x 390 nm), band excitation (781 nm x 781 nm), mass spectrometry (690 nm x 500 nm) images was comparable and submicrometer in all three cases, but the data voxel size for each of the three images was dramatically different. The topography image was uniquely a surface measurement, whereas the band excitation image included information from an estimated 10 nm deep into the sample and the mass spectral image from 110-140 nm in depth. Moreover, because of this dramatic sampling depth variance, some differences in the band excitation and mass spectrometry chemical images were observed and were interpreted to indicate the presence of a buried interface in the sample. The spatial resolution of the mass spectral image was estimated to be between 1.5 m 2.6 m, based on the ability to distinguish surface features in that image that were also observed in the other images.« less

  16. Co-registered Topographical, Band Excitation Nanomechanical, and Mass Spectral Imaging Using a Combined Atomic Force Microscopy/Mass Spectrometry Platform

    SciTech Connect

    Ovchinnikova, Olga S.; Tai, Tamin; Bocharova, Vera; Okatan, Mahmut Baris; Belianinov, Alex; Kertesz, Vilmos; Jesse, Stephen; Van Berkel, Gary J.

    2015-03-18

    The advancement of a hybrid atomic force microscopy/mass spectrometry imaging platform demonstrating for the first time co-registered topographical, band excitation nanomechanical, and mass spectral imaging of a surface using a single instrument is reported. The mass spectrometry-based chemical imaging component of the system utilized nanothermal analysis probes for pyrolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. We discuss the basic instrumental setup and operation and the multimodal imaging capability and utility are demonstrated using a phase separated polystyrene/poly(2-vinylpyridine) polymer blend thin film. The topography and band excitation images showed that the valley and plateau regions of the thin film surface were comprised primarily of one of the two polymers in the blend with the mass spectral chemical image used to definitively identify the polymers at the different locations. Data point pixel size for the topography (390 nm x 390 nm), band excitation (781 nm x 781 nm), mass spectrometry (690 nm x 500 nm) images was comparable and submicrometer in all three cases, but the data voxel size for each of the three images was dramatically different. The topography image was uniquely a surface measurement, whereas the band excitation image included information from an estimated 10 nm deep into the sample and the mass spectral image from 110-140 nm in depth. Moreover, because of this dramatic sampling depth variance, some differences in the band excitation and mass spectrometry chemical images were observed and were interpreted to indicate the presence of a buried interface in the sample. The spatial resolution of the mass spectral image was estimated to be between 1.5 m 2.6 m, based on the ability to distinguish surface features in that image that were also observed in the other images.

  17. Local binary pattern texture-based classification of solid masses in ultrasound breast images

    NASA Astrophysics Data System (ADS)

    Matsumoto, Monica M. S.; Sehgal, Chandra M.; Udupa, Jayaram K.

    2012-03-01

    Breast cancer is one of the leading causes of cancer mortality among women. Ultrasound examination can be used to assess breast masses, complementarily to mammography. Ultrasound images reveal tissue information in its echoic patterns. Therefore, pattern recognition techniques can facilitate classification of lesions and thereby reduce the number of unnecessary biopsies. Our hypothesis was that image texture features on the boundary of a lesion and its vicinity can be used to classify masses. We have used intensity-independent and rotation-invariant texture features, known as Local Binary Patterns (LBP). The classifier selected was K-nearest neighbors. Our breast ultrasound image database consisted of 100 patient images (50 benign and 50 malignant cases). The determination of whether the mass was benign or malignant was done through biopsy and pathology assessment. The training set consisted of sixty images, randomly chosen from the database of 100 patients. The testing set consisted of forty images to be classified. The results with a multi-fold cross validation of 100 iterations produced a robust evaluation. The highest performance was observed for feature LBP with 24 symmetrically distributed neighbors over a circle of radius 3 (LBP24,3) with an accuracy rate of 81.0%. We also investigated an approach with a score of malignancy assigned to the images in the test set. This approach provided an ROC curve with Az of 0.803. The analysis of texture features over the boundary of solid masses showed promise for malignancy classification in ultrasound breast images.

  18. How to Determine the Centre of Mass of Bodies from Image Modelling

    ERIC Educational Resources Information Center

    Dias, Marco Adriano; Carvalho, Paulo Simeão; Rodrigues, Marcelo

    2016-01-01

    Image modelling is a recent technique in physics education that includes digital tools for image treatment and analysis, such as digital stroboscopic photography (DSP) and video analysis software. It is commonly used to analyse the motion of objects. In this work we show how to determine the position of the centre of mass (CM) of objects with…

  19. Imaging of Lipids and Metabolites Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Lanekoff, Ingela; Laskin, Julia

    2015-01-17

    In recent years, mass spectroscopy imaging (MSI) has emerged as a foundational technique in metabolomics and drug screening providing deeper understanding of complex mechanistic pathways within biochemical systems and biological organisms. We have been invited to contribute a chapter to a new Springer series volume, entitled “Mass Spectrometry Imaging of Small Molecules”. The volume is planned for the highly successful lab protocol series Methods in Molecular Biology, published by Humana Press, USA. The volume is aimed to equip readers with step-by-step mass spectrometric imaging protocols and bring rapidly maturing methods of MS imaging to life science researchers. The chapter will provide a detailed protocol of ambient MSI by use of nanospray desorption electrospray ionization.

  20. Three-dimensional nanoscale molecular imaging by extreme ultraviolet laser ablation mass spectrometry

    PubMed Central

    Kuznetsov, Ilya; Filevich, Jorge; Dong, Feng; Woolston, Mark; Chao, Weilun; Anderson, Erik H.; Bernstein, Elliot R.; Crick, Dean C.; Rocca, Jorge J.; Menoni, Carmen S.

    2015-01-01

    Analytical probes capable of mapping molecular composition at the nanoscale are of critical importance to materials research, biology and medicine. Mass spectral imaging makes it possible to visualize the spatial organization of multiple molecular components at a sample's surface. However, it is challenging for mass spectral imaging to map molecular composition in three dimensions (3D) with submicron resolution. Here we describe a mass spectral imaging method that exploits the high 3D localization of absorbed extreme ultraviolet laser light and its fundamentally distinct interaction with matter to determine molecular composition from a volume as small as 50 zl in a single laser shot. Molecular imaging with a lateral resolution of 75 nm and a depth resolution of 20 nm is demonstrated. These results open opportunities to visualize chemical composition and chemical changes in 3D at the nanoscale. PMID:25903827

  1. Solar Mass Ejection Imager 3-D reconstruction of the 27-28 May 2003 coronal mass ejection sequence

    NASA Astrophysics Data System (ADS)

    Jackson, B. V.; Bisi, M. M.; Hick, P. P.; Buffington, A.; Clover, J. M.; Sun, W.

    2008-03-01

    The Solar Mass Ejection Imager (SMEI) has recorded the inner-heliospheric response in white-light Thomson scattering for many hundreds of interplanetary coronal mass ejections (ICMEs). Some of these have been observed by the Solar and Heliospheric Observatory (SOHO) Large-Angle Spectroscopic Coronagraph (LASCO) instruments and also in situ by near-Earth spacecraft. This article presents a low-resolution three-dimensional (3-D) reconstruction of the 27-28 May 2003 halo CME event sequence observed by LASCO and later using SMEI observations; this sequence was also observed by all in situ monitors near Earth. The reconstruction derives its perspective views from outward flowing solar wind. Analysis results reveal the shape, extent, and mass of this ICME sequence as it reaches the vicinity of Earth. The extended shape has considerable detail that is compared with LASCO images and masses for this event. The 3-D reconstructed density, derived from the remote-sensed Thomson scattered brightness, is also compared with the Advanced Composition Explorer (ACE) and Wind spacecraft in situ plasma measurements. These agree well in peak and integrated total value for this ICME event sequence when an appropriately enhanced (˜20%) electron number density is assumed to account for elements heavier than hydrogen in the ionized plasma.

  2. Image guided versus palpation guided core needle biopsy of palpable breast masses: a prospective study

    PubMed Central

    Hari, Smriti; Kumari, Swati; Srivastava, Anurag; Thulkar, Sanjay; Mathur, Sandeep; Veedu, Prasad Thotton

    2016-01-01

    Background & objectives: Biopsy of palpable breast masses can be performed manually by palpation guidance or under imaging guidance. Based on retrospective studies, image guided biopsy is considered more accurate than palpation guided breast biopsy; however, these techniques have not been compared prospectively. We conducted this prospective study to verify the superiority and determine the size of beneficial effect of image guided biopsy over palpation guided biopsy. Methods: Over a period of 18 months, 36 patients each with palpable breast masses were randomized into palpation guided and image guided breast biopsy arms. Ultrasound was used for image guidance in 33 patients and mammographic (stereotactic) guidance in three patients. All biopsies were performed using 14 gauge automated core biopsy needles. Inconclusive, suspicious or imaging-histologic discordant biopsies were repeated. Results: Malignancy was found in 30 of 36 women in palpation guided biopsy arm and 27 of 36 women in image guided biopsy arm. Palpation guided biopsy had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 46.7, 100, 100, 27.3 per cent, respectively, for diagnosing breast cancer. Nineteen of 36 women (52.8%) required repeat biopsy because of inadequate samples (7 of 19), suspicious findings (2 of 19) or imaging-histologic discordance (10 of 19). On repeat biopsy, malignancy was found in all cases of imaging-histologic discordance. Image guided biopsy had 96.3 per cent sensitivity and 100 per cent specificity. There was no case of inadequate sample or imaging-histologic discordance with image guided biopsy. Interpretation & conclusions: Our results showed that in palpable breast masses, image guided biopsy was superior to palpation guided biopsy in terms of sensitivity, false negative rate and repeat biopsy rates. PMID:27488003

  3. Evaluation of risks of groundwater quality alteration in Recife urban area (Pernambuco, Brazil) using a multi-isotopic approach.

    NASA Astrophysics Data System (ADS)

    Bertrand, Guillaume; Hirata, Ricardo; Martins, Veridiana; Batista, Jonathan; Bertolo, Reginaldo; Santos, Jeane-Glaucia; Montenegro, Suzanna; Cary, Lise; Petelet-Giraud, Emmanuelle; Pauwels, Hélène; Picot, Géraldine; Braibant, Gilles; Chatton, Eliot; Aquilina, Luc; Labasque, Thierry; Hochreutener, Rebecca; Aurouet, Axel; Franzen, Melissa

    2015-04-01

    The Recife Metropolitan Region (RMR) is a heavily urbanized area located in a estuary zone and over a multi-layered sedimentary system on the Brazilian Atlantic coast. In a context of increasing land use pressures, involving aquifer overexploitation and surface water contamination, and repeated droughts, the identification of groundwater quality risks in RMR is a necessary management requirement. In this perspective, this work focused on the two shallow aquifer systems, named Boa Viagem and Barreiras aquifers, located at the interface between the city (the consumers) and the deeper semi-confined Cretaceous Cabo and Beberibe aquifers. The Holocenic Boa Viagem and Tertiary Barreiras formations conform unconfined sedimentary aquifers, with no more than 80 m of thickness. Cabo is the most important groundwater body for Recife private complementary water supply and it has experienced an intense exploitation in the last three decades. In contrast, Boa Viagem and Barreiras aquifers are more restrictively used, but it is important to understand their water quality degradation,because of hydraulic connections with deeper aquifers, mainly in the littoral part of Recife, where hydraulic potentiometric head of the Cabo aquifer is 60 m below sea water level in some places, with conditions for recharge from shallower aquifers. Through a multi-isotopic characterization (87Sr/86Sr, δ11B, δ18O-SO4, δ34S-SO4) of sampling of 19 wells and 3 surface waters, carried out during two field campaigns with additional geochemical parameters (major ions, noble and major gases, CFC' s and SF6), the spatio-temporal variability of groundwater quality was investigated. The detection of CFC' s, implying a modern recharge component, highlighted the vulnerability of Boa Viagem and Barreiras to surface contaminations. The increasing mineralization and decreasing 87Sr/86Sr from the inland sector wells to the wells located close to the coast or estuary, with higher well and population densities, were

  4. A spatially explicit multi-isotope approach to map influence regions of plant-plant interactions after exotic plant invasion

    NASA Astrophysics Data System (ADS)

    Hellmann, Christine; Oldeland, Jens; Werner, Christiane

    2015-04-01

    Exotic plant invasions impose profound alterations to native ecosystems, including changes of water, carbon and nutrient cycles. However, explicitly quantifying these impacts remains a challenge. Stable isotopes, by providing natural tracers of biogeochemical processes, can help to identify and measure such alterations in space and time. Recently, δ15N isoscapes, i.e. spatially continuous representations of isotopic values, derived from native plant foliage, enabled to accurately trace nitrogen introduced by the N2-fixing invasive Acacia longifolia into a native Portuguese dune system. It could be shown that the area of the system which was altered by the invasive species exceeded the area which was covered by the invader by far. But still, definition of clear regions of influence is to some extent ambiguous. Here, we present an approach using multiple isoscapes derived from measured foliar δ13C and δ15N values of a native, non-fixing species, Corema album. By clustering isotopic information, we obtained an objective classification of the study area. Properties and spatial position of clusters could be interpreted to distinguish areas that were or were not influenced by A. longifolia. Spatial clusters at locations where A. longifolia was present had δ15N values that were enriched, i.e. close to the atmospheric signal of 0 o compared to the depleted values of the uninvaded system (ca. -11 o). Furthermore, C. album individuals in these clusters were characterized by higher foliar N content and enriched δ13C. These results indicate that the N2-fixing A. longifolia added nitrogen to the system which originated from the atmosphere and was used by the native C. album, inducing functional changes, i.e. an increase in WUE. Additionally, clusters were identified that were presumably determined by inherent properties of the native system. Thus, combining isotope ecology with geostatistical methods is a promising approach for mapping regions of influence in multi-isotope

  5. Desorption Electrospray Ionization Mass Spectrometry for Lipid Characterization and Biological Tissue Imaging

    PubMed Central

    Eberlin, Livia S.; Ferreira, Christina R.; Dill, Allison L.; Ifa, Demian R.; Cooks, R. Graham

    2011-01-01

    Desorption electrospray ionization mass spectrometry (DESI-MS) imaging of biological samples allows untargeted analysis and structural characterization of lipids ionized from the near-surface region of a sample under ambient conditions. DESI is a powerful and sensitive MS ionization method for 2D and 3D imaging of lipids from direct and unmodified complex biological samples. This review describes the strengths and limitations of DESI-MS for lipid characterization and imaging together with the technical workflow and a survey of applications. Included are discussions of lipid mapping and biomarker discovery as well as a perspective on the future of DESI imaging. PMID:21645635

  6. Mass Detection in Mammographic Images Using Wavelet Processing and Adaptive Threshold Technique.

    PubMed

    Vikhe, P S; Thool, V R

    2016-04-01

    Detection of mass in mammogram for early diagnosis of breast cancer is a significant assignment in the reduction of the mortality rate. However, in some cases, screening of mass is difficult task for radiologist, due to variation in contrast, fuzzy edges and noisy mammograms. Masses and micro-calcifications are the distinctive signs for diagnosis of breast cancer. This paper presents, a method for mass enhancement using piecewise linear operator in combination with wavelet processing from mammographic images. The method includes, artifact suppression and pectoral muscle removal based on morphological operations. Finally, mass segmentation for detection using adaptive threshold technique is carried out to separate the mass from background. The proposed method has been tested on 130 (45 + 85) images with 90.9 and 91 % True Positive Fraction (TPF) at 2.35 and 2.1 average False Positive Per Image(FP/I) from two different databases, namely Mammographic Image Analysis Society (MIAS) and Digital Database for Screening Mammography (DDSM). The obtained results show that, the proposed technique gives improved diagnosis in the early breast cancer detection. PMID:26811073

  7. Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

    SciTech Connect

    Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain; Heeren, Ronald M.; Laprevote, Olivier; Prideaux, Brendan; Seyer, Alexandre; Spengler, Bernhard; Stoeckli, Markus; Smith, Donald F.

    2015-03-01

    Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common

  8. Computerized mass detection for digital breast tomosynthesis directly from the projection images

    SciTech Connect

    Reiser, I.; Nishikawa, R.M.; Giger, M.L.; Wu, T.; Rafferty, E.A.; Moore, R.; Kopans, D.B.

    2006-02-15

    Digital breast tomosynthesis (DBT) has recently emerged as a new and promising three-dimensional modality in breast imaging. In DBT, the breast volume is reconstructed from 11 projection images, taken at source angles equally spaced over an arc of 50 degrees. Reconstruction algorithms for this modality are not fully optimized yet. Because computerized lesion detection in the reconstructed breast volume will be affected by the reconstruction technique, we are developing a novel mass detection algorithm that operates instead on the set of raw projection images. Mass detection is done in three stages. First, lesion candidates are obtained for each projection image separately, using a mass detection algorithm that was initially developed for screen-film mammography. Second, the locations of a lesion candidate are backprojected into the breast volume. In this feature volume, voxel intensities are a combined measure of detection frequency (e.g., the number of projections in which a given lesion candidate was detected), and a measure of the angular range over which a given lesion was detected. Third, features are extracted after reprojecting the three-dimensional (3-D) locations of lesion candidates into projection images. Features are combined using linear discriminant analysis. The database used to test the algorithm consisted of 21 mass cases (13 malignant, 8 benign) and 15 cases without mass lesions. Based on this database, the algorithm yielded a sensitivity of 90% at 1.5 false positives per breast volume. Algorithm performance is positively biased because this dataset was used for development, training, and testing, and because the number of algorithm parameters was approximately the same as the number of patient cases. Our results indicate that computerized mass detection in the sequence of projection images for DBT may be effective despite the higher noise level in those images.

  9. LensPerfect: Gravitational Lens Mass Map Reconstructions Yielding Exact Reproduction of All Multiple Images

    NASA Astrophysics Data System (ADS)

    Coe, D.; Fuselier, E.; Benítez, N.; Broadhurst, T.; Frye, B.; Ford, H.

    2008-07-01

    We present a new approach to gravitational lens mass map reconstruction. Our mass map solutions perfectly reproduce the positions, fluxes, and shears of all multiple images, and each mass map accurately recovers the underlying mass distribution to a resolution limited by the number of multiple images detected. We demonstrate our technique given a mock galaxy cluster similar to Abell 1689, which gravitationally lenses 19 mock background galaxies to produce 93 multiple images. We also explore cases in which as few as four multiple images are observed. Mass map solutions are never unique, and our method makes it possible to explore an extremely flexible range of physical (and unphysical) solutions, all of which perfectly reproduce the data given. Each reconfiguration of the source galaxies produces a new mass map solution. An optimization routine is provided to find those source positions (and redshifts, within uncertainties) that produce the "most physical" mass map solution, according to a new figure of merit developed here. Our method imposes no assumptions about the slope of the radial profile or mass following light. However, unlike "nonparametric" grid-based methods, the number of free parameters that we solve for is only as many as the number of observable constraints (or slightly greater if fluxes are constrained). For each set of source positions and redshifts, mass map solutions are obtained "instantly" via direct matrix inversion by smoothly interpolating the deflection field using a recently developed mathematical technique. Our LensPerfect software is straightforward and easy to use, and is publicly available on our Web site.

  10. An Automated Platform for High-Resolution Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Lanekoff, Ingela T.; Heath, Brandi S.; Liyu, Andrey V.; Thomas, Mathew; Carson, James P.; Laskin, Julia

    2012-10-02

    An automated platform has been developed for acquisition and visualization of mass spectrometry imaging (MSI) data using nanospray desorption electrospray ionization (nano-DESI). The new system enables robust operation of the nano-DESI imaging source over many hours. This is achieved by controlling the distance between the sample and the probe by mounting the sample holder onto an automated XYZ stage and defining the tilt of the sample plane. This approach is useful for imaging of relatively flat samples such as thin tissue sections. Custom software called MSI QuickView was developed for visualization of large data sets generated in imaging experiments. MSI QuickView enables fast visualization of the imaging data during data acquisition and detailed processing after the entire image is acquired. The performance of the system is demonstrated by imaging rat brain tissue sections. High resolution mass analysis combined with MS/MS experiments enabled identification of lipids and metabolites in the tissue section. In addition, high dynamic range and sensitivity of the technique allowed us to generate ion images of low-abundance isobaric lipids. High-spatial resolution image acquired over a small region of the tissue section revealed the spatial distribution of an abundant brain metabolite, creatine, in the white and gray matter that is consistent with the literature data obtained using magnetic resonance spectroscopy.

  11. High Resolution Tissue Imaging Using the Single-probe Mass Spectrometry under Ambient Conditions

    NASA Astrophysics Data System (ADS)

    Rao, Wei; Pan, Ning; Yang, Zhibo

    2015-06-01

    Ambient mass spectrometry imaging (MSI) is an emerging field with great potential for the detailed spatial analysis of biological samples with minimal pretreatment. We have developed a miniaturized sampling and ionization device, the Single-probe, which uses in-situ surface micro-extraction to achieve high detection sensitivity and spatial resolution during MSI experiments. The Single-probe was coupled to a Thermo LTQ Orbitrap XL mass spectrometer and was able to create high spatial and high mass resolution MS images at 8 ± 2 and 8.5 μm on flat polycarbonate microscope slides and mouse kidney sections, respectively, which are among the highest resolutions available for ambient MSI techniques. Our proof-of-principle experiments indicate that the Single-probe MSI technique has the potential to obtain ambient MS images with very high spatial resolutions with minimal sample preparation, which opens the possibility for subcellular ambient tissue MSI to be performed in the future.

  12. Imaging mass-spectrometer of ions for studying near-planetary plasma

    NASA Astrophysics Data System (ADS)

    Vaisberg, O. L.; Leibov, A. V.; Smirnov, V. N.; Avanov, L. A.; Bertelier, J.-J.; Torcar, K.; Leblan, F.; Babkin, V. F.; Grishin, V. A.; Baumjohann, V.; Escoubet, F.

    2006-05-01

    A numerical model of an ion mass-spectrometer is developed based on the new type of charged-particle analyzer CAMERA suggested previously [1 3]. The spectrometer provides for complete instantaneous imaging of the flux distribution of various ions in a hemisphere. Such a type of the mass-spectrometer is chosen, which allows one to analyze a conelike beam of ions at the exit of the CAMERA. The mathematical model of the CAMERA with this time-of-flight mass-analyzer ensures sufficiently high mass resolution (M/ΔM > 100) at conserved imaging capabilities of the CAMERA. Such an instrument can find a wide application both in magnetospheric studies and in studying various objects of the solar system.

  13. Direct imaging of elemental distributions in tissue sections by laser ablation mass spectrometry.

    PubMed

    Shariatgorji, Mohammadreza; Nilsson, Anna; Bonta, Maximilian; Gan, Jinrui; Marklund, Niklas; Clausen, Fredrik; Källback, Patrik; Loden, Henrik; Limbeck, Andreas; Andrén, Per E

    2016-07-15

    We present a strategy for imaging of elements in biological tissues using laser ablation (LA) mass spectrometry (MS), which was compared to laser ablation inductively coupled plasma (LA-ICP) MS. Both methods were adopted for quantitative imaging of elements in mouse kidney, as well as traumatic brain injury model tissue sections. MS imaging (MSI) employing LA provides quantitative data by comparing signal abundances of sodium from tissues to those obtained by imaging quantitation calibration standards of the target element applied to adjacent control tissue sections. LA-ICP MSI provided quantitative data for several essential elements in both brain and kidney tissue sections using a dried-droplet approach. Both methods were used to image a rat model of traumatic brain injury, revealing accumulations of sodium and calcium in the impact area and its peripheral regions. LA MSI is shown to be a viable option for quantitative imaging of specific elements in biological tissue sections. PMID:27263025

  14. Early detection of tumor masses by in vivo hematoporphyrin-mediated fluorescence imaging

    NASA Astrophysics Data System (ADS)

    Autiero, Maddalena; Celentano, Luigi; Cozzolino, Rosanna; Laccetti, Paolo; Marotta, Marcello; Mettivier, Giovanni; Cristina Montesi, Maria; Quarto, Maria; Riccio, Patrizia; Roberti, Giuseppe; Russo, Paolo

    2007-02-01

    We investigated the capability of fluorescence reflectance imaging (FRI) for the early detection of surface tumors in mice. We used a hematoporphyrin (HP) compound (HP dichlorohydrate) as a red fluorescent marker and a low noise, high sensitivity, digital CCD camera for fluorescence imaging. In this preliminary study, highly malignant anaplastic human thyroid carcinoma cells were implanted subcutaneously in one mouse and their growth was monitored daily for 5 days by FRI. The selective HP uptake by the tumor tissues was successfully observed: we observed the fluorescence of tumor only 3 days after cancer cells injection, i.e. when the tumor mass was neither visible (to the naked eye) or palpable. These measurements indicate that FRI is a suitable technique to detect minute subcutaneous tumor masses. This FRI system will be coupled to a radionuclide imaging system based on a CdTe detector for in vivo multimodal imaging in mice.

  15. Sample Preparation for Mass Spectrometry Imaging of Plant Tissues: A Review

    PubMed Central

    Dong, Yonghui; Li, Bin; Malitsky, Sergey; Rogachev, Ilana; Aharoni, Asaph; Kaftan, Filip; Svatoš, Aleš; Franceschi, Pietro

    2016-01-01

    Mass spectrometry imaging (MSI) is a mass spectrometry based molecular ion imaging technique. It provides the means for ascertaining the spatial distribution of a large variety of analytes directly on tissue sample surfaces without any labeling or staining agents. These advantages make it an attractive molecular histology tool in medical, pharmaceutical, and biological research. Likewise, MSI has started gaining popularity in plant sciences; yet, information regarding sample preparation methods for plant tissues is still limited. Sample preparation is a crucial step that is directly associated with the quality and authenticity of the imaging results, it therefore demands in-depth studies based on the characteristics of plant samples. In this review, a sample preparation pipeline is discussed in detail and illustrated through selected practical examples. In particular, special concerns regarding sample preparation for plant imaging are critically evaluated. Finally, the applications of MSI techniques in plants are reviewed according to different classes of plant metabolites. PMID:26904042

  16. The Use of Random Projections for the Analysis of Mass Spectrometry Imaging Data

    NASA Astrophysics Data System (ADS)

    Palmer, Andrew D.; Bunch, Josephine; Styles, Iain B.

    2015-02-01

    The `curse of dimensionality' imposes fundamental limits on the analysis of the large, information rich datasets that are produced by mass spectrometry imaging. Additionally, such datasets are often too large to be analyzed as a whole and so dimensionality reduction is required before further analysis can be performed. We investigate the use of simple random projections for the dimensionality reduction of mass spectrometry imaging data and examine how they enable efficient and fast segmentation using k-means clustering. The method is computationally efficient and can be implemented such that only one spectrum is needed in memory at any time. We use this technique to reveal histologically significant regions within MALDI images of diseased human liver. Segmentation results achieved following a reduction in the dimensionality of the data by more than 99% (without peak picking) showed that histologic changes due to disease can be automatically visualized from molecular images.

  17. Classification of benign and malignant breast masses based on shape and texture features in sonography images.

    PubMed

    Zakeri, Fahimeh Sadat; Behnam, Hamid; Ahmadinejad, Nasrin

    2012-06-01

    The purpose of this research was evaluating novel shape and texture feature' efficiency in classification of benign and malignant breast masses in sonography images. First, mass regions were extracted from the region of interest (ROI) sub-image by implementing a new hybrid segmentation approach based on level set algorithms. Then two left and right side areas of the masses are elicited. After that, six features (Eccentricity_feature, Solidity_feature, DeferenceArea_Hull_Rectangular, DeferenceArea_Mass_Rectangular, Cross-correlation-left and Cross-correlation-right) based on shape, texture and region characteristics of the masses were extracted for further classification. Finally a support vector machine (SVM) classifier was utilized to classify breast masses. The leave-one-case-out protocol was utilized on a database of eighty pathologically-proven breast sonographic images of patients (forty-seven benign cases and thirty-three malignant cases) to evaluate our method. The classification results showed an overall accuracy of 95.00%, sensitivity of 90.91%, specificity of 97.87%, positive predictive value of 96.77%, negative predictive value of 93.88%, and Matthew's correlation coefficient of 89.71%. The experimental results declare that our proposed method is actually a beneficial tool for the diagnosis of the breast cancer and can provide a second opinion for a physician's decision or can be used for the medicine training especially when coupled with other modalities. PMID:21082222

  18. High-Speed MALDI-TOF Imaging Mass Spectrometry: Rapid Ion Image Acquisition and Considerations for Next Generation Instrumentation

    PubMed Central

    Spraggins, Jeffrey M.; Caprioli, Richard M.

    2012-01-01

    A prototype matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometer has been used for high-speed ion image acquisition. The instrument incorporates a Nd:YLF solid state laser capable of pulse repetition rates up to 5 kHz and continuous laser raster sampling for high-throughput data collection. Lipid ion images of a sagittal rat brain tissue section were collected in 10 min with an effective acquisition rate of roughly 30 pixels/s. These results represent more than a 10-fold increase in throughput compared with current commercially available instrumentation. Experiments aimed at improving conditions for continuous laser raster sampling for imaging are reported, highlighting proper laser repetition rates and stage velocities to avoid signal degradation from significant oversampling. As new high spatial resolution and large sample area applications present themselves, the development of high-speed microprobe MALDI imaging mass spectrometry is essential to meet the needs of those seeking new technologies for rapid molecular imaging. PMID:21953043

  19. MISSING LENSED IMAGES AND THE GALAXY DISK MASS IN CXOCY J220132.8-320144

    SciTech Connect

    Chen, Jacqueline; Lee, Samuel K.; Schechter, Paul L.; Castander, Francisco-Javier; Maza, Jose

    2013-05-20

    The CXOCY J220132.8-320144 system consists of an edge-on spiral galaxy lensing a background quasar into two bright images. Previous efforts to constrain the mass distribution in the galaxy have suggested that at least one additional image must be present. These extra images may be hidden behind the disk which features a prominent dust lane. We present and analyze Hubble Space Telescope observations of the system. We do not detect any extra images, but the observations further narrow the observable parameters of the lens system. We explore a range of models to describe the mass distribution in the system and find that a variety of acceptable model fits exist. All plausible models require 2 mag of dust extinction in order to obscure extra images from detection, and some models may require an offset between the center of the galaxy and the center of the dark matter halo of 1 kpc. Currently unobserved images will be detectable by future James Webb Space Telescope observations and will provide strict constraints on the fraction of mass in the disk.

  20. Controlled-Resonant Surface Tapping-Mode Scanning Probe Electrospray Ionization Mass Spectrometry Imaging

    SciTech Connect

    Lorenz, Matthias; Ovchinnikova, Olga S; Kertesz, Vilmos; Van Berkel, Gary J

    2014-01-01

    This paper reports on the advancement of a controlled-resonance surface tapping-mode single capillary liquid junction extraction/ESI emitter for mass spectrometry imaging. The basic instrumental setup and the general operation of the system were discussed and optimized performance metrics were presented. The ability to spot sample, lane scan and chemically image in an automated and controlled fashion were demonstrated. Rapid, automated spot sampling was demonstrated for a variety of compound types including the cationic dye basic blue 7, the oligosaccharide cellopentaose, and the protein equine heart cytochrome c. The system was used for lane scanning and chemical imaging of the cationic dye crystal violet in inked lines on glass and for lipid distributions in mouse brain thin tissue sections. Imaging of the lipids in mouse brain tissue under optimized conditions provided a spatial resolution of approximately 35 m based on the ability to distinguish between features observed both in the optical and mass spectral chemical images. The sampling spatial resolution of this system was comparable to the best resolution that has been reported for other types of atmospheric pressure liquid extraction-based surface sampling/ionization techniques used for mass spectrometry imaging.

  1. Constraints of costal aquifer functioning in a deeply antropized area through a multi-isotope fingerprinting (Recife, Brazil)

    NASA Astrophysics Data System (ADS)

    Petelet-Giraud, Emmanuelle; Cary, Lise; Bertrand, Guillaume; Hirata, Ricardo; Martins, Veridiana; Montenegro, Suzana; Pauwels, Hélène; Kloppmann, Wolfram; Aquilina, Luc

    2014-05-01

    The Metropolitan Region of Recife (RMR) went through large changes of water and land uses over the last decades due to an increasing demographic pressure (1.5 M of inhabitants). These evolutions gave rise to numerous environmental consequences, such as a dramatic decline of the water levels, groundwater salinization and contamination. This degradation of natural resources is linked to the increase of water demand that is also punctually amplified by drought periods, inducing the construction of thousands of private wells. Recife city was built on an estuarine area, at the geological limits of the two sedimentary basins of Pernambuco (north of the city) and Paraíba (south of the city) separated by a famous shear zone (the Pernambuco lineament). Tectonic and sedimentary events involved in the genesis and evolution of these basins were mainly controlled by the opening of the Atlantic Ocean leading to the deposition of cretaceous sediments which now constitute the two main exploited aquifers, the Beberibe and Cabo aquifers. These two deep aquiferous formations are topped by the unconfined Boa Viagem aquifer of quaternary sediments. It is the most directly exposed to contamination, since it is connected to mangroves, rivers, estuaries and highly urbanized areas. Both the Beberibe and Cabo aquifers contain large clay levels and are separated by a rather continuous clayed formation which seems to play a consistent role of screen and to interfere in the hydraulic connections between the three aquifers. Previous isotopic studies have shown that recharge processes are similar in the aquifers, suggesting that exchanges may occur and may be modified or amplified by overexploitation. This very complex aquifer system is studied through more than 60 water samples, including some surface water samples from the main rivers. A methodology based on multi-isotopes fingerprinting is applied, including stable isotopes of the water molecule, strontium isotopes, boron isotopes, sulfur

  2. Multi-Isotope Analysis as a Natural Reaction Probe of Biodegradation Mechanisms of 1,2- Dichloroethane

    NASA Astrophysics Data System (ADS)

    Hirschorn, S. K.; Dinglasan-Panlilio, M.; Edwards, E. A.; Lacrampe-Couloume, G.; Sherwood Lollar, B.

    2006-12-01

    1,2-Dichloroethane (1,2-DCA), a chlorinated aliphatic hydrocarbon, is an EPA priority pollutant and a widespread groundwater contaminant. Stable isotope fractionation during biodegradation of 1,2-DCA occurs due to differences in the reaction rates of heavy versus light atoms present at a reacting bond in the 1,2-DCA molecule. In general, light isotopic bonds react more quickly, producing a relative enrichment in the heavy isotope in the remaining contaminant pool. Compound specific isotope analysis has the potential to demonstrate the occurrence and extent of biodegradation at chlorinated solvent contaminated groundwater sites. In this study, stable carbon isotope fractionation was used as a novel reaction probe to provide information about the mechanism of 1,2-DCA biodegradation. Isotopic fractionation was measured during 1,2-DCA degradation by a microbial culture capable of degrading 1,2-DCA under O2-reducing and NO3-reducing conditions. The microbial culture produced isotopic enrichment values that are not only large and reproducible, but are the same whether O2 or NO3 was used as an electron acceptor. The mean isotopic enrichment value of -25.8 permil measured for the microbial culture during 1,2-DCA degradation under both O2 and NO3- reducing conditions can be converted into a kinetic isotope effect (KIE) value to relate the observed isotopic fractionation to the mechanism of degradation. This KIE value (1.05) is consistent with degradation via a hydrolysis (SN2) reaction under both electron-accepting conditions. Isotope analysis was able to provide a first line of evidence for the reaction mechanism of 1,2-DCA biodegradation by the microbial culture. Using a multi-isotope approach incorporating both carbon and hydrogen isotopic data, compound specific isotope analysis also has the potential to determine degradation mechanisms for 1,2-DCA under aerobic conditions where 1,2-DCA is known to be degraded by two distinct enzymatic pathways. Biodegradation of 1

  3. Note: A novel dual-channel time-of-flight mass spectrometer for photoelectron imaging spectroscopy

    SciTech Connect

    Qin Zhengbo; Wu Xia; Tang Zichao

    2013-06-15

    A novel dual-channel time-of-flight mass spectrometer (D-TOFMS) has been designed to select anions in the photoelectron imaging measurements. In this instrument, the radiation laser can be triggered precisely to overlap with the selected ion cloud at the first-order space focusing plane. Compared with that of the conventional single channel TOFMS, the in situ mass selection performance of D-TOFMS is significantly improved. Preliminary experiment results are presented for the mass-selected photodetachment spectrum of F{sup -} to demonstrate the capability of the instrument.

  4. Characterisation of a micro-plasma for ambient mass spectrometry imaging.

    PubMed

    Bowfield, Andrew; Bunch, Josephine; Salter, Tara L; Steven, Rory T; Gilmore, Ian S; Barrett, Dave A; Alexander, Morgan R; McKay, Kirsty; Bradley, James W

    2014-11-01

    Results are presented on the characterisation and optimisation of a non-thermal atmospheric pressure micro-plasma ion source used for ambient mass spectrometry imaging. The geometry of the experiment is optimised to produce the most intense and stable ion signals. Signal stabilities (relative standard deviation) of 2.3-6.5% are achieved for total ion current measurements from chromatograms. Parameters are utilised to achieve MS imaging by raster scanning of PTFE/glass samples with a spatial resolution of 147 ± 31 μm. A systematic study of resolution as a function of acquisition parameters was also undertaken to underpin future technique development. Mass spectra are obtained from PTFE/glass sample edges in negative ion mode and used to construct images to calculate the spatial resolution. Images are constructed using the intensity variation of the dominant ion observed in the PTFE spectrum. Mass spectra originating from the polymer are dominated by three series of ions in a m/z spectral window from 200-500 Da. These ions are each separated by 50 Da and have the chemical formula [C2F + [CF2]n](-), [CF + [CF2]n + O](-) and [CF + [CF2]n + O3](-). The mechanism for the generation of these ions appears to be a polymer chain scission followed by ionisation by atmospheric ion adduction. Positive and negative ion mode mass spectra of personal care products, amino acids and pharmaceuticals, dominated by the proton abstracted/protonated molecular ion, highlight the potential areas of application for such a device. Further to this end a mass spectral image of cardamom seeds, constructed using the variation in intensity of possible fragments of the 1,8-cineole molecule, is included to reveal the potential application to the imaging of foods and other biological materials. PMID:25142127

  5. Quantitative Mass Density Image Reconstructed from the Complex X-Ray Refractive Index.

    PubMed

    Mukaide, Taihei; Iida, Atsuo; Watanabe, Masatoshi; Takada, Kazuhiro; Noma, Takashi

    2015-01-01

    We demonstrate a new analytical X-ray computed tomography technique for visualizing and quantifying the mass density of materials comprised of low atomic number elements with unknown atomic ratios. The mass density was obtained from the experimentally observed ratio of the imaginary and real parts of the complex X-ray refractive index. An empirical linear relationship between the X-ray mass attenuation coefficient of the materials and X-ray energy was found for X-ray energies between 8 keV and 30 keV. The mass density image of two polymer fibers was quantified using the proposed technique using a scanning-type X-ray microbeam computed tomography system equipped with a wedge absorber. The reconstructed mass density agrees well with the calculated one. PMID:26114770

  6. Quantitative Mass Density Image Reconstructed from the Complex X-Ray Refractive Index

    PubMed Central

    Mukaide, Taihei; Iida, Atsuo; Watanabe, Masatoshi; Takada, Kazuhiro; Noma, Takashi

    2015-01-01

    We demonstrate a new analytical X-ray computed tomography technique for visualizing and quantifying the mass density of materials comprised of low atomic number elements with unknown atomic ratios. The mass density was obtained from the experimentally observed ratio of the imaginary and real parts of the complex X-ray refractive index. An empirical linear relationship between the X-ray mass attenuation coefficient of the materials and X-ray energy was found for X-ray energies between 8 keV and 30 keV. The mass density image of two polymer fibers was quantified using the proposed technique using a scanning-type X-ray microbeam computed tomography system equipped with a wedge absorber. The reconstructed mass density agrees well with the calculated one. PMID:26114770

  7. Axial Shear Strain Imaging for Differentiating Benign and Malignant Breast Masses

    PubMed Central

    Xu, Haiyan; Rao, Min; Varghese, Tomy; Sommer, Amy; Baker, Sara; Hall, Timothy J; Sisney, Gale A; Burnside, Elizabeth S

    2010-01-01

    Axial strain imaging has been utilized for the characterization of breast masses for over a decade; however, another important feature namely the shear strain distribution around breast masses has only recently been used. In this paper, we examine the feasibility of utilizing in-vivo axial-shear strain imaging for differentiating benign from malignant breast masses. Radiofrequency data was acquired using a VFX 13-5 linear array transducer on 41 patients using a Siemens SONOLINE Antares real-time clinical scanner at the University of Wisconsin Breast Cancer Center. Free-hand palpation using deformations of up to 10% was utilized to generate axial strain and axial-shear strain images using a two-dimensional cross-correlation algorithm from the radiofrequency data loops. Axial-shear strain areas normalized to the lesion size, applied strain and lesion strain contrast was utilized as a feature for differentiating benign from malignant masses. The normalized axial-shear strain area feature estimated on 8 patients with malignant tumors and 33 patients with fibroadenomas was utilized to demonstrate its potential for lesion differentiation. Biopsy results were considered the diagnostic standard for comparison. Our results indicate that the normalized axial-shear strain area is significantly larger for malignant tumors when compared to benign masses such as fibroadenomas. Axial-shear strain pixel values greater than a specified threshold, including only those with correlation coefficient values greater than 0.75, were overlaid on the corresponding B-mode image to aid in diagnosis. A scatter plot of the normalized area feature demonstrates the feasibility of developing a linear classifier to differentiate benign from malignant masses. The area under the receiver operator characteristic curve utilizing the normalized axial-shear strain area feature was 0.996, demonstrating the potential of this feature to noninvasively differentiate between benign and malignant breast masses

  8. An alternative paper based tissue washing method for mass spectrometry imaging: localized washing and fragile tissue analysis.

    PubMed

    van Hove, Erika R Amstalden; Smith, Donald F; Fornai, Lara; Glunde, Kristine; Heeren, Ron M A

    2011-10-01

    Surface treatment of biological tissue sections improves detection of peptides and proteins for mass spectrometry imaging. However, liquid surface treatments can result in diffusion of surface analytes and fragile tissue sections can be easily damaged by typical washing solvents. Here, we present a new surface washing procedure for mass spectrometry imaging. This procedure uses solvent wetted fiber-free paper to enable local washing of tissue sections for mass spectrometry imaging and tissue profiling experiments. In addition, the method allows fragile tissues that cannot be treated by conventional washing techniques to be analyzed by mass spectrometry imaging. PMID:21952901

  9. Optimization of Whole-body Zebrafish Sectioning Methods for Mass Spectrometry Imaging

    EPA Science Inventory

    Mass spectrometry imaging (MSI) methods and protocols have become widely adapted to a variety of tissues and species. However, the MSI literature lacks information on whole-body cryosection preparation for the zebrafish (ZF; Danio rerio), a model organism routinely used in devel...

  10. Imaging mass spectrometry and genome mining reveal highly antifungal virulence factor of mushroom soft rot pathogen.

    PubMed

    Graupner, Katharina; Scherlach, Kirstin; Bretschneider, Tom; Lackner, Gerald; Roth, Martin; Gross, Harald; Hertweck, Christian

    2012-12-21

    Caught in the act: imaging mass spectrometry of a button mushroom infected with the soft rot pathogen Janthinobacterium agaricidamnosum in conjunction with genome mining revealed jagaricin as a highly antifungal virulence factor that is not produced under standard cultivation conditions. The structure of jagaricin was rigorously elucidated by a combination of physicochemical analyses, chemical derivatization, and bioinformatics. PMID:23161559

  11. Relationship between Body Image and Body Mass Index in College Men

    ERIC Educational Resources Information Center

    Watkins, Julia A.; Christie, Catherine; Chally, Pamela

    2008-01-01

    Objective and Participants: The authors examined cognitive and affective dimensions of body image of a randomized sample of 188 college men on the basis of body mass index (BMI). Methods: They conducted chi-square tests and ANOVAs to determine differences between 4 BMI groups (underweight, normal weight, overweight, and obese) on demographics and…

  12. Anatomical Distribution of Lipids in Human Brain Cortex by Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Veloso, Antonio; Astigarraga, Egoitz; Barreda-Gómez, Gabriel; Manuel, Iván; Ferrer, Isidro; Teresa Giralt, María; Ochoa, Begoña; Fresnedo, Olatz; Rodríguez-Puertas, Rafael; Fernández, José A.

    2011-02-01

    Molecular mass images of tissues will be biased if differences in the physicochemical properties of the microenvironment affect the intensity of the spectra. To address this issue, we have performed—by means of MALDI-TOF mass spectrometry—imaging on slices and lipidomic analysis in extracts of frontal cortex, both from the same postmortem tissue samples of human brain. An external calibration was used to achieve a mass accuracy of 10 ppm (1 σ) in the spectra of the extracts, although the final assignment was based on a comparison with previously reported species. The spectra recorded directly from tissue slices (imaging) show excellent s/n ratios, almost comparable to those obtained from the extracts. In addition, they retain the information about the anatomical distribution of the molecular species present in autopsied frozen tissue. Further comparison between the spectra from lipid extracts devoid of proteins and those recorded directly from the tissue unambiguously show that the differences in lipid composition between gray and white matter observed in the mass images are not an artifact due to microenvironmental influences of each anatomical area on the signal intensity, but real variations in the lipid composition.

  13. Matrix-assisted laser desorption/ionisation mass spectrometry imaging and its development for plant protein imaging

    PubMed Central

    2011-01-01

    Matrix-Assisted Laser Desorption/Ionisation (MALDI) mass spectrometry imaging (MSI) uses the power of high mass resolution time of flight (ToF) mass spectrometry coupled to the raster of lasers shots across the cut surface of tissues to provide new insights into the spatial distribution of biomolecules within biological tissues. The history of this technique in animals and plants is considered and the potential for analysis of proteins by this technique in plants is discussed. Protein biomarker identification from MALDI-MSI is a challenge and a number of different approaches to address this bottleneck are discussed. The technical considerations needed for MALDI-MSI are reviewed and these are presented alongside examples from our own work and a protocol for MALDI-MSI of proteins in plant samples. PMID:21726462

  14. [Breast imaging of mass, architectural distortion and asymmetry: Clinical practice guidelines].

    PubMed

    Chopier, J; Roedlich, M N; Mathelin, C

    2015-12-01

    The development of the mammary imaging (mammography, ultrasound, MRI) enables the discovery of more and more lesions. The BI-RADS lexicon is the reference book for their descriptive analysis. Four elementary images must be individualized: masses and architectural distortion described in 3 imaging techniques, asymmetries and microcalcifications described in mammography. The aim of this work was to review three of these images: mass, architectural distortion and asymmetry, allowing the various actors involved in senology to propose an up-to-date diagnostic and interventional strategy, based on their positive predictive values (PPV) or negative predictive values of cancer and allowing the classification BI-RADS of the lesion. The masses are the most often encountered lesions as well in screening as in diagnosis. Their PPV is superior in diagnosis than in screening and it increases with the age. Their irregular forms, their spiculated outlines and their evolutionary character are the most relevant elements of suspicion. The architectural distortion is the rarest image and always classified suspect BI-RADS 4, except in case of a known scar. The asymmetry is less common; its PPV is low and rises only in case of evolutionary asymmetry. PMID:26541564

  15. High resolution mass spectrometry imaging of plant tissues: towards a plant metabolite atlas.

    PubMed

    Bhandari, Dhaka Ram; Wang, Qing; Friedt, Wolfgang; Spengler, Bernhard; Gottwald, Sven; Römpp, Andreas

    2015-11-21

    Mass spectrometry (MS) imaging provides spatial and molecular information for a wide range of compounds. This tool can be used to investigate metabolic changes in plant physiology and environmental interactions. A major challenge in our study was to prepare tissue sections that were compatible with high spatial resolution analysis and therefore dedicated sample preparation protocols were established and optimized for the physicochemical properties of all major plant organs. We combined high spatial resolution (5 μm), in order to detect cellular features, and high mass accuracy (<2 ppm root mean square error), for molecular specificity. Mass spectrometry imaging experiments were performed in positive and negative ion mode. Changes in metabolite patterns during plant development were investigated for germination of oilseed rape. The detailed localization of more than 90 compounds allowed assignment to metabolic processes and indicated possible functions in plant tissues. The 'untargeted' nature of MS imaging allows the detection of marker compounds for the physiological status, as demonstrated for plant-pathogen interactions. Our images show excellent correlation with optical/histological examination. In contrast to previous MS imaging studies of plants, we present a complete workflow that covers multiple species, such as oilseed rape, wheat seed and rice. In addition, different major plant organs and a wide variety of compound classes were analyzed. Thus, our method could be used to develop a plant metabolite atlas as a reference to investigate systemic and local effects of pathogen infection or environmental stress. PMID:26462298

  16. Mass

    SciTech Connect

    Chris Quigg

    2007-12-05

    In the classical physics we inherited from Isaac Newton, mass does not arise, it simply is. The mass of a classical object is the sum of the masses of its parts. Albert Einstein showed that the mass of a body is a measure of its energy content, inviting us to consider the origins of mass. The protons we accelerate at Fermilab are prime examples of Einsteinian matter: nearly all of their mass arises from stored energy. Missing mass led to the discovery of the noble gases, and a new form of missing mass leads us to the notion of dark matter. Starting with a brief guided tour of the meanings of mass, the colloquium will explore the multiple origins of mass. We will see how far we have come toward understanding mass, and survey the issues that guide our research today.

  17. High-mass-resolution MALDI mass spectrometry imaging of metabolites from formalin-fixed paraffin-embedded tissue.

    PubMed

    Ly, Alice; Buck, Achim; Balluff, Benjamin; Sun, Na; Gorzolka, Karin; Feuchtinger, Annette; Janssen, Klaus-Peter; Kuppen, Peter J K; van de Velde, Cornelis J H; Weirich, Gregor; Erlmeier, Franziska; Langer, Rupert; Aubele, Michaela; Zitzelsberger, Horst; McDonnell, Liam; Aichler, Michaela; Walch, Axel

    2016-08-01

    Formalin-fixed and paraffin-embedded (FFPE) tissue specimens are the gold standard for histological examination, and they provide valuable molecular information in tissue-based research. Metabolite assessment from archived tissue samples has not been extensively conducted because of a lack of appropriate protocols and concerns about changes in metabolite content or chemical state due to tissue processing. We present a protocol for the in situ analysis of metabolite content from FFPE samples using a high-mass-resolution matrix-assisted laser desorption/ionization fourier-transform ion cyclotron resonance mass spectrometry imaging (MALDI-FT-ICR-MSI) platform. The method involves FFPE tissue sections that undergo deparaffinization and matrix coating by 9-aminoacridine before MALDI-MSI. Using this platform, we previously detected ∼1,500 m/z species in the mass range m/z 50-1,000 in FFPE samples; the overlap compared with fresh frozen samples is 72% of m/z species, indicating that metabolites are largely conserved in FFPE tissue samples. This protocol can be reproducibly performed on FFPE tissues, including small samples such as tissue microarrays and biopsies. The procedure can be completed in a day, depending on the size of the sample measured and raster size used. Advantages of this approach include easy sample handling, reproducibility, high throughput and the ability to demonstrate molecular spatial distributions in situ. The data acquired with this protocol can be used in research and clinical practice. PMID:27414759

  18. Metabolomic Imaging of Prostate Cancer with Magnetic Resonance Spectroscopy and Mass Spectrometry

    PubMed Central

    Spur, Eva-Margarete; Decelle, Emily A.; Cheng, Leo L.

    2013-01-01

    Metabolomic imaging of prostate cancer (PCa) aims to improve in vivo imaging capability so that PCa tumors can be localized non-invasively to guide biopsy and evaluated for aggressiveness prior to prostatectomy, as well as to assess and monitor PCa growth for newly biopsy-diagnosed, asymptomatic PCa patients. Metabolomics studies global variations of metabolites with which malignancy conditions can be evaluated by profiling the entire measurable metabolome, instead of focusing only on certain metabolites or isolated metabolic pathways. At present, the study of PCa metabolomics is mainly accomplished utilizing magnetic resonance spectroscopy (MRS) and mass spectrometry (MS). With MRS imaging, the anatomic image, obtained from magnetic resonance imaging, is mapped with values of disease condition-specific metabolomic profiles calculated from MRS of each location. For example, imaging of removed whole prostates demonstrated the ability of metabolomic profiles to differentiate cancerous foci from histologically benign regions. Additionally, MS metabolomic imaging of prostate biopsies uncovered metabolomic expression patterns that could discriminate between PCa and benign tissue. Metabolomic imaging offers the potential to identify cancer lesions to guide prostate biopsy and evaluate PCa aggressiveness non-invasively in vivo, or ex vivo to increase the power of pathology analysis. Potentially, this imaging ability could be possible not only with PCa, but applied to different tissues and organs to evaluate other human malignancies or metabolic diseases. PMID:23549758

  19. Imaging Findings of an Unusually Located Hydatid Cyst Presented as a Sacrococcygeal Mass

    PubMed Central

    Yilmaz, Guliz; Halil Akpinar, Suha

    2015-01-01

    Hydatid disease (HD) is a parasitic infection that is most commonly caused by the larval stage of Echinococcus granulosus. Unusual location for this disease can cause diagnostic and therapeutic problems. We herein report a case of sacrococcygeal HD at an unusual location in a 30-year-old woman. She was evaluated using computed tomography (CT) imaging and magnetic resonance imaging (MRI) after the demonstration of the lucent bone lesion on plain pelvic radiography. There was an expansile lytic mass without contrast enhancement suggesting a cystic mass in the sacrococcygeal region. Medical history revealed that she had undergone surgery for liver HD and the serological test results were diagnostic for HD. In light of this, no surgery was carried out for this cystic mass and she was followed with the diagnosis of sacrococcygeal HD. PMID:25901257

  20. The evolving field of imaging mass spectrometry and its impact on future biological research

    PubMed Central

    Watrous, Jeramie D.; Alexandrov, Theodore; Dorrestein, Pieter C.

    2012-01-01

    Within the past decade, imaging mass spectrometry has been increasingly recognized as an indispensable technique for studying biological systems. Its rapid evolution has resulted in an impressive array of instrument variations and sample applications, yet the tools and data are largely confined to specialists. It is therefore important that at this junction the IMS community begin to establish IMS as a permanent fixture in life sciences research thereby making the technology and/or the data approachable by non-mass spectrometrists, leading to further integration into biological and clinical research. In this perspective article, we provide insight into the evolution and current state of imaging mass spectrometry and propose some of the directions that IMS could develop in order to stay on course to become one of the most promising new tools in life science research. PMID:21322093

  1. Targeted Multiplex Imaging Mass Spectrometry with Single Chain Fragment Variable (scfv) Recombinant Antibodies

    NASA Astrophysics Data System (ADS)

    Thiery, Gwendoline; Mernaugh, Ray L.; Yan, Heping; Spraggins, Jeffrey M.; Yang, Junhai; Parl, Fritz F.; Caprioli, Richard M.

    2012-10-01

    Recombinant scfv antibodies specific for CYP1A1 and CYP1B1 P450 enzymes were combined with targeted imaging mass spectrometry to simultaneously detect the P450 enzymes present in archived, paraffin-embedded, human breast cancer tissue sections. By using CYP1A1 and CYP1B1 specific scfv, each coupled to a unique reporter molecule (i.e., a mass tag) it was possible to simultaneously detect multiple antigens within a single tissue sample with high sensitivity and specificity using mass spectrometry. The capability of imaging multiple antigens at the same time is a significant advance that overcomes technical barriers encountered when using present day approaches to develop assays that can simultaneously detect more than a single antigen in the same tissue sample.

  2. Homogeneous Matrix Deposition on Dried Agar for MALDI Imaging Mass Spectrometry of Microbial Cultures

    NASA Astrophysics Data System (ADS)

    Hoffmann, Thomas; Dorrestein, Pieter C.

    2015-11-01

    Matrix deposition on agar-based microbial colonies for MALDI imaging mass spectrometry is often complicated by the complex media on which microbes are grown. This Application Note demonstrates how consecutive short spray pulses of a matrix solution can form an evenly closed matrix layer on dried agar. Compared with sieving dry matrix onto wet agar, this method supports analyte cocrystallization, which results in significantly more signals, higher signal-to-noise ratios, and improved ionization efficiency. The even matrix layer improves spot-to-spot precision of measured m/z values when using TOF mass spectrometers. With this technique, we established reproducible imaging mass spectrometry of myxobacterial cultures on nutrient-rich cultivation media, which was not possible with the sieving technique.

  3. Submicrometer Imaging by Laser Ablation-Inductively Coupled Plasma Mass Spectrometry via Signal and Image Deconvolution Approaches.

    PubMed

    Van Malderen, Stijn J M; van Elteren, Johannes T; Vanhaecke, Frank

    2015-06-16

    In this work, pre- and postacquisition procedures for enhancing the lateral resolution of laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS) in two- and three-dimensional (2D, 3D) nuclide distribution mapping beyond the laser beam waist are described. 2D images were constructed by projecting a rectangular grid of discrete LA positions, arranged at interspacings smaller than the dimensions of the laser beam waist, onto the sample surface, thus oversampling the region of interest and producing a 2D image convolved in the spatial domain. The pulse response peaks of a low-dispersion LA cell were isolated via signal deconvolution of the transient mass analyzer response. A 3D stack of 2D images was deconvolved by an iterative Richardson-Lucy algorithm with Total Variance regularization, enabling submicrometer image fidelity, demonstrated in the analysis of trace level features in corroded glass. A point spread function (PSF) could be derived from topography maps of single pulse craters from atomic force microscopy. This experimental PSF allows the approach to take into account the laser beam shape, beam aberrations, and the laser-solid interaction, which in turn enhances the spatial resolution of the reconstructed volume. PMID:25975805

  4. Polychromatic sparse image reconstruction and mass attenuation spectrum estimation via B-spline basis function expansion

    NASA Astrophysics Data System (ADS)

    Gu, Renliang; Dogandžić, Aleksandar

    2015-03-01

    We develop a sparse image reconstruction method for polychromatic computed tomography (CT) measurements under the blind scenario where the material of the inspected object and the incident energy spectrum are unknown. To obtain a parsimonious measurement model parameterization, we first rewrite the measurement equation using our mass-attenuation parameterization, which has the Laplace integral form. The unknown mass-attenuation spectrum is expanded into basis functions using a B-spline basis of order one. We develop a block coordinate-descent algorithm for constrained minimization of a penalized negative log-likelihood function, where constraints and penalty terms ensure nonnegativity of the spline coefficients and sparsity of the density map image in the wavelet domain. This algorithm alternates between a Nesterov's proximal-gradient step for estimating the density map image and an active-set step for estimating the incident spectrum parameters. Numerical simulations demonstrate the performance of the proposed scheme.

  5. Polychromatic sparse image reconstruction and mass attenuation spectrum estimation via B-spline basis function expansion

    SciTech Connect

    Gu, Renliang E-mail: ald@iastate.edu; Dogandžić, Aleksandar E-mail: ald@iastate.edu

    2015-03-31

    We develop a sparse image reconstruction method for polychromatic computed tomography (CT) measurements under the blind scenario where the material of the inspected object and the incident energy spectrum are unknown. To obtain a parsimonious measurement model parameterization, we first rewrite the measurement equation using our mass-attenuation parameterization, which has the Laplace integral form. The unknown mass-attenuation spectrum is expanded into basis functions using a B-spline basis of order one. We develop a block coordinate-descent algorithm for constrained minimization of a penalized negative log-likelihood function, where constraints and penalty terms ensure nonnegativity of the spline coefficients and sparsity of the density map image in the wavelet domain. This algorithm alternates between a Nesterov’s proximal-gradient step for estimating the density map image and an active-set step for estimating the incident spectrum parameters. Numerical simulations demonstrate the performance of the proposed scheme.

  6. How to determine the centre of mass of bodies from image modelling

    NASA Astrophysics Data System (ADS)

    Adriano Dias, Marco; Simeão Carvalho, Paulo; Rodrigues, Marcelo

    2016-03-01

    Image modelling is a recent technique in physics education that includes digital tools for image treatment and analysis, such as digital stroboscopic photography (DSP) and video analysis software. It is commonly used to analyse the motion of objects. In this work we show how to determine the position of the centre of mass (CM) of objects with either isotropic or anisotropic mass density, by video analyses as a video based experimental activity (VBEA). Strobe imaging is also presented in an educational view, helping students to visualize the complex motion of a rigid body with heterogeneous structure. As an example, we present a hammer tossed with translation and rotation. The technique shown here is valid for almost any kind of objects and it is very useful to work with the concept of CM.

  7. Development of an Organic Lateral Resolution Test Device for Imaging Mass Spectrometry

    PubMed Central

    2015-01-01

    An organic lateral resolution test device has been developed to measure the performance of imaging mass spectrometry (IMS) systems. The device contains periodic gratings of polyethylene glycol (PEG) and lipid bars covering a wide range of spatial frequencies. Microfabrication technologies were employed to produce well-defined chemical interfaces, which allow lateral resolution to be assessed using the edge-spread function (ESF). In addition, the design of the device allows for the direct measurement of the modulation transfer function (MTF) to assess image quality. Scanning electron microscopy (SEM) and time-of-flight secondary ion mass spectrometry (TOF-SIMS) were used to characterize the device. TOF-SIMS imaging was used to measure the chemical displacement of biomolecules in matrix-assisted laser desorption/ionization (MALDI) matrix crystals. In a proof-of-concept experiment, the platform was also used to evaluate MALDI matrix application methods, specifically aerosol spray and sublimation methods. PMID:25137365

  8. Mass spectrometry imaging reveals the sub-organ distribution of carbon nanomaterials

    NASA Astrophysics Data System (ADS)

    Chen, Suming; Xiong, Caiqiao; Liu, Huihui; Wan, Qiongqiong; Hou, Jian; He, Qing; Badu-Tawiah, Abraham; Nie, Zongxiu

    2015-02-01

    Label and label-free methods to image carbon-based nanomaterials exist. However, label-based approaches are limited by the risk of tag detachment over time, and label-free spectroscopic methods have slow imaging speeds, weak photoluminescence signals and strong backgrounds. Here, we present a label-free mass spectrometry imaging method to detect carbon nanotubes, graphene oxide and carbon nanodots in mice. The large molecular weights of nanoparticles are difficult to detect using conventional mass spectrometers, but our method overcomes this problem by using the intrinsic carbon cluster fingerprint signal of the nanomaterials. We mapped and quantified the sub-organ distribution of the nanomaterials in mice. Our results showed that most carbon nanotubes and nanodots were found in the outer parenchyma of the kidney, and all three materials were seen in the red pulp of the spleen. The highest concentrations of nanotubes in the spleen were found within the marginal zone.

  9. Ultrasound Image Discrimination between Benign and Malignant Adnexal Masses Based on a Neural Network Approach.

    PubMed

    Aramendía-Vidaurreta, Verónica; Cabeza, Rafael; Villanueva, Arantxa; Navallas, Javier; Alcázar, Juan Luis

    2016-03-01

    The discrimination between benign and malignant adnexal masses in ultrasound images represents one of the most challenging problems in gynecologic practice. In the study described here, a new method for automatic discrimination of adnexal masses based on a neural networks approach was tested. The proposed method first calculates seven different types of characteristics (local binary pattern, fractal dimension, entropy, invariant moments, gray level co-occurrence matrix, law texture energy and Gabor wavelet) from ultrasound images of the ovary, from which several features are extracted and collected together with the clinical patient age. The proposed technique was validated using 106 benign and 39 malignant images obtained from 145 patients, corresponding to its probability of appearance in general population. On evaluation of the classifier, an accuracy of 98.78%, sensitivity of 98.50%, specificity of 98.90% and area under the curve of 0.997 were calculated. PMID:26715189

  10. MALDI mass spectrometry imaging: A cutting-edge tool for fundamental and clinical histopathology.

    PubMed

    Longuespée, Rémi; Casadonte, Rita; Kriegsmann, Mark; Pottier, Charles; Picard de Muller, Gaël; Delvenne, Philippe; Kriegsmann, Jörg; De Pauw, Edwin

    2016-07-01

    Histopathological diagnoses have been done in the last century based on hematoxylin and eosin staining. These methods were complemented by histochemistry, electron microscopy, immunohistochemistry (IHC), and molecular techniques. Mass spectrometry (MS) methods allow the thorough examination of various biocompounds in extracts and tissue sections. Today, mass spectrometry imaging (MSI), and especially matrix-assisted laser desorption ionization (MALDI) imaging links classical histology and molecular analyses. Direct mapping is a major advantage of the combination of molecular profiling and imaging. MSI can be considered as a cutting edge approach for molecular detection of proteins, peptides, carbohydrates, lipids, and small molecules in tissues. This review covers the detection of various biomolecules in histopathological sections by MSI. Proteomic methods will be introduced into clinical histopathology within the next few years. PMID:27188927

  11. Matrix-Assisted Laser Desorption Ionization Imaging Mass Spectrometry: In Situ Molecular Mapping

    PubMed Central

    Angel, Peggi M.; Caprioli, Richard M.

    2013-01-01

    Matrix-assisted laser desorption ionization imaging mass spectrometry (IMS) is a relatively new imaging modality that allows mapping of a wide range of biomolecules within a thin tissue section. The technology uses a laser beam to directly desorb and ionize molecules from discrete locations on the tissue that are subsequently recorded in a mass spectrometer. IMS is distinguished by the ability to directly measure molecules in situ ranging from small metabolites to proteins, reporting hundreds to thousands of expression patterns from a single imaging experiment. This article reviews recent advances in IMS technology, applications, and experimental strategies that allow it to significantly aid in the discovery and understanding of molecular processes in biological and clinical samples. PMID:23259809

  12. Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution

    NASA Astrophysics Data System (ADS)

    Thiery-Lavenant, Gwendoline; Zavalin, Andre I.; Caprioli, Richard M.

    2013-04-01

    Targeted multiplex imaging mass spectrometry utilizes several different antigen-specific primary antibodies, each directly labeled with a unique photocleavable mass tag, to detect multiple antigens in a single tissue section. Each photocleavable mass tag bound to an antibody has a unique molecular weight and can be readily ionized by laser desorption ionization mass spectrometry. This article describes a mass spectrometry method that allows imaging of targeted single cells within tissue using transmission geometry laser desorption ionization mass spectrometry. Transmission geometry focuses the laser beam on the back side of the tissue placed on a glass slide, providing a 2 μm diameter laser spot irradiating the biological specimen. This matrix-free method enables simultaneous localization at the sub-cellular level of multiple antigens using specific tagged antibodies. We have used this technology to visualize the co-expression of synaptophysin and two major hormones peptides, insulin and somatostatin, in duplex assays in beta and delta cells contained in a human pancreatic islet.

  13. Laser Desorption Ionization Mass Spectrometry Imaging of Drosophila Brain Using Matrix Sublimation versus Modification with Nanoparticles.

    PubMed

    Phan, Nhu T N; Mohammadi, Amir Saeid; Dowlatshahi Pour, Masoumeh; Ewing, Andrew G

    2016-02-01

    Laser desorption ionization mass spectrometry (LDI-MS) is used to image brain lipids in the fruit fly, Drosophila, a common invertebrate model organism in biological and neurological studies. Three different sample preparation methods, including sublimation with two common organic matrixes for matrix-assisted laser desorption ionization (MALDI) and surface-assisted laser desorption ionization (SALDI) using gold nanoparticles, are examined for sample profiling and imaging the fly brain. Recrystallization with trifluoroacetic acid following matrix deposition in MALDI is shown to increase the incorporation of biomolecules with one matrix, resulting in more efficient ionization, but not for the other matrix. The key finding here is that the mass fragments observed for the fly brain slices with different surface modifications are significantly different. Thus, these approaches can be combined to provide complementary analysis of chemical composition, particularly for the small metabolites, diacylglycerides, phosphatidylcholines, and triacylglycerides, in the fly brain. Furthermore, imaging appears to be beneficial using modification with gold nanoparticles in place of matrix in this application showing its potential for cellular and subcellular imaging. The imaging protocol developed here with both MALDI and SALDI provides the best and most diverse lipid chemical images of the fly brain to date with LDI. PMID:26705612

  14. A ranklet-based image representation for mass classification in digital mammograms

    SciTech Connect

    Masotti, Matteo

    2006-10-15

    Regions of interest (ROIs) found on breast radiographic images are classified as either tumoral mass or normal tissue by means of a support vector machine classifier. Classification features are the coefficients resulting from the specific image representation used to encode each ROI. Pixel and wavelet image representations have already been discussed in one of our previous works. To investigate the possibility of improving classification performances, a novel nonparametric, orientation-selective, and multiresolution image representation is developed and evaluated, namely a ranklet image representation. A dataset consisting of 1000 ROIs representing biopsy-proven tumoral masses (either benign or malignant) and 5000 ROIs representing normal breast tissue is used. ROIs are extracted from the digital database for screening mammography collected by the University of South Florida. Classification performances are evaluated using the area A{sub z} under the receiver operating characteristic curve. By achieving A{sub z} values of 0.978{+-}0.003 and 90% sensitivity with a false positive fraction value of 4.5%, experiments demonstrate classification results higher than those reached by the previous image representations. In particular, the improvement on the A{sub z} value over that achieved by the wavelet image representation is statistically relevant with the two-tailed p value <0.0001. Besides, owing to the tolerance that the ranklet image representation reveals to variations in the ROIs' gray-level intensity histogram, this approach discloses to be robust also when tested on radiographic images having gray-level intensity histogram remarkably different from that used for training.

  15. Comparison of Echo and MRI in the Imaging Evaluation of Intracardiac Masses

    SciTech Connect

    Gulati, G. Sharma, S.; Kothari, S.S.; Juneja, R.; Saxena, A.; Talwar, K.K.

    2004-09-15

    We compared the efficacy of echocardiography (ECHO) and magnetic resonance imaging (MRI) for evaluating intracardiac masses. Over an 8-yr period, 28 patients, 21 males, 7 females, 16 days-60 years of age (mean 25 years) with a suspected intracardiac mass on ECHO (transthoracic in all; transesophageal in 9) underwent an MRI examination. Five patients had a contrast-enhanced MRI. ECHO and MRI were compared with respect to their technical adequacy, ability to detect and suggest the likely etiology of the mass, and provide additional information (masses not seen with the other technique, inflow or outflow obstruction, and intramural component of an intracavitary mass). With MRI, the image morphology (including signal intensity changes on the various sequences) and extracardiac manifestations were also evaluated. The diagnosis was confirmed by histopathology in 18, surgical inspection in 4, by follow- up imaging on conservative management in 5, and by typical extracardiac manifestations of the disease in 1 patient.Fifteen (54%) patients had tumors (benign 12, malignant 3), 5 had a thrombus or hematoma, and 4 each had infective or vascular lesions. Thirty-four masses (13 in ventricle, 11 septal, 7 atrial, 2 on valve and 1 in pulmonary artery) were seen on MRI, 28 of which were detected by ECHO. Transthoracic ECHO (TTE) and MRI were technically optimal in 82% and 100% of cases, respectively. Nine patients needed an additional transesophageal ECHO (TEE). Overall, MRI showed a mass in all patients, whereas ECHO missed it in 2 cases. In cases with a mass on both modalities, MRI detected 4 additional masses not seen on ECHO. MRI suggested the etiology in 21 (75%) cases, while the same was possible with ECHO (TTE and TEE) in 8 (29%) cases. Intramural component, extension into the inflow or outflow, outflow tract obstruction, and associated pericardial or extracardiac masses were better depicted on MRI. We conclude that MRI is advantageous over a combination of TTE and TEE for

  16. Laser Microdissection and Atmospheric Pressure Chemical Ionization Mass Spectrometry Coupled for Multimodal Imaging

    SciTech Connect

    Lorenz, Matthias; Ovchinnikova, Olga S; Kertesz, Vilmos; Van Berkel, Gary J

    2013-01-01

    This paper describes the coupling of ambient laser ablation surface sampling, accomplished using a laser capture microdissection system, with atmospheric pressure chemical ionization mass spectrometry for high spatial resolution multimodal imaging. A commercial laser capture microdissection system was placed in close proximity to a modified ion source of a mass spectrometer designed to allow for sampling of laser ablated material via a transfer tube directly into the ionization region. Rhodamine 6G dye of red sharpie ink in a laser etched pattern as well as cholesterol and phosphatidylcholine in a cerebellum mouse brain thin tissue section were identified and imaged from full scan mass spectra. A minimal spot diameter of 8 m was achieved using the 10X microscope cutting objective with a lateral oversampling pixel resolution of about 3.7 m. Distinguishing between features approximately 13 m apart in a cerebellum mouse brain thin tissue section was demonstrated in a multimodal fashion including co-registered optical and mass spectral chemical images.

  17. Fluorescence imaging for visualization of the ion cloud in a quadrupole ion trap mass spectrometer.

    PubMed

    Talbot, Francis O; Sciuto, Stephen V; Jockusch, Rebecca A

    2013-12-01

    Laser-induced fluorescence is used to visualize populations of gaseous ions stored in a quadrupole ion trap (QIT) mass spectrometer. Presented images include the first fluorescence image of molecular ions collected under conditions typically used in mass spectrometry experiments. Under these "normal" mass spectrometry conditions, the radial (r) and axial (z) full-width at half maxima (FWHM) of the detected ion cloud are 615 and 214 μm, respectively, corresponding to ~6% of r0 and ~3% of z0 for the QIT used. The effects on the shape and size of the ion cloud caused by varying the pressure of helium bath gas, the number of trapped ions, and the Mathieu parameter q z are visualized and discussed. When a "tickle voltage" is applied to the exit end-cap electrode, as is done in collisionally activated dissociation, a significant elongation in the axial, but not the radial, dimension of the ion cloud is apparent. Finally, using spectroscopically distinguishable fluorophores of two different m/z values, images are presented that illustrate stratification of the ion cloud; ions of lower m/z (higher qz) are located in the center of the trapping region, effectively excluding higher m/z (lower qz) ions, which form a surrounding layer. Fluorescence images such as those presented here provide a useful reference for better understanding the collective behavior of ions in radio frequency (rf) trapping devices and how phenomena such as collisions and space-charge affect ion distribution. PMID:24092629

  18. Fluorescence Imaging for Visualization of the Ion Cloud in a Quadrupole Ion Trap Mass Spectrometer

    NASA Astrophysics Data System (ADS)

    Talbot, Francis O.; Sciuto, Stephen V.; Jockusch, Rebecca A.

    2013-12-01

    Laser-induced fluorescence is used to visualize populations of gaseous ions stored in a quadrupole ion trap (QIT) mass spectrometer. Presented images include the first fluorescence image of molecular ions collected under conditions typically used in mass spectrometry experiments. Under these "normal" mass spectrometry conditions, the radial ( r) and axial ( z) full-width at half maxima (FWHM) of the detected ion cloud are 615 and 214 μm, respectively, corresponding to ~6 % of r 0 and ~3 % of z 0 for the QIT used. The effects on the shape and size of the ion cloud caused by varying the pressure of helium bath gas, the number of trapped ions, and the Mathieu parameter q z are visualized and discussed. When a "tickle voltage" is applied to the exit end-cap electrode, as is done in collisionally activated dissociation, a significant elongation in the axial, but not the radial, dimension of the ion cloud is apparent. Finally, using spectroscopically distinguishable fluorophores of two different m/ z values, images are presented that illustrate stratification of the ion cloud; ions of lower m/ z (higher q z ) are located in the center of the trapping region, effectively excluding higher m/ z (lower q z ) ions, which form a surrounding layer. Fluorescence images such as those presented here provide a useful reference for better understanding the collective behavior of ions in radio frequency (rf) trapping devices and how phenomena such as collisions and space-charge affect ion distribution.

  19. The Sheath Transport Observer for the Redistribution of Mass (STORM) Imager

    NASA Technical Reports Server (NTRS)

    Collier, Michael R.; Sibeck, David G.; Porter, F. Scott; Burch, J.; Carter, J. A.; Cravens, Thomas; Kuntz, Kip; Omidi, N.; Read, A.; Robertson, Ina; Sembay, S.; Snowden, Steven L.

    2010-01-01

    All of the solar wind energy that powers magnetospheric processes passes through the magnetosheath and magnetopause. Global images of the magnetosheath and magnetopause boundary layers will resolve longstanding controversies surrounding fundamental phenomena that occur at the magnetopause and provide information needed to improve operational space weather models. Recent developments showing that soft X-rays (0.15-1 keV) result from high charge state solar wind ions undergoing charge exchange recombination through collisions with exospheric neutral atoms has led to the realization that soft X-ray imaging can provide global maps of the high-density shocked solar wind within the magnetosheath and cusps, regions lying between the lower density solar wind and magnetosphere. We discuss an instrument concept called the Sheath Transport Observer for the Redistribution of Mass (STORM), an X-ray imager suitable for simultaneously imaging the dayside magnetosheath, the magnetopause boundary layers, and the cusps.

  20. The Sheath Transport Observer for the Redistribution of Mass (STORM) Image

    NASA Technical Reports Server (NTRS)

    Kuntz, Kip; Collier, Michael; Sibeck, David G.; Porter, F. Scott; Carter, J. A.; Cravens, Thomas; Omidi, N.; Robertson, Ina; Sembay, S.; Snowden, Steven L.

    2008-01-01

    All of the solar wind energy that powers magnetospheric processes passes through the magnetosheath and magnetopause. Global images of the magnetosheath and magnetopause boundary layers will resolve longstanding controversy surrounding fundamental phenomena that occur at the magnetopause and provide information needed to improve operational space weather models. Recent developments showing that soft X-rays (0.15-1 keV) result from high charge state solar wind ions undergoing charge exchange recombination through collisions with exospheric neutral atoms has led to the realization that soft X-ray imaging can provide global maps of the high-density shocked solar wind within the magnetosheath and cusps, regions lying between the lower density solar wind and magnetosphere. We discuss an instrument concept called the Sheath Transport Observer for the Redistribution of Mass (STORM), an X-ray imager suitable for simultaneously imaging the dayside magnetosheath, the magnetopause boundary layers, and the cusps.

  1. Surface analysis of lipids by mass spectrometry: more than just imaging.

    PubMed

    Ellis, Shane R; Brown, Simon H; In Het Panhuis, Marc; Blanksby, Stephen J; Mitchell, Todd W

    2013-10-01

    Mass spectrometry is now an indispensable tool for lipid analysis and is arguably the driving force in the renaissance of lipid research. In its various forms, mass spectrometry is uniquely capable of resolving the extensive compositional and structural diversity of lipids in biological systems. Furthermore, it provides the ability to accurately quantify molecular-level changes in lipid populations associated with changes in metabolism and environment; bringing lipid science to the "omics" age. The recent explosion of mass spectrometry-based surface analysis techniques is fuelling further expansion of the lipidomics field. This is evidenced by the numerous papers published on the subject of mass spectrometric imaging of lipids in recent years. While imaging mass spectrometry provides new and exciting possibilities, it is but one of the many opportunities direct surface analysis offers the lipid researcher. In this review we describe the current state-of-the-art in the direct surface analysis of lipids with a focus on tissue sections, intact cells and thin-layer chromatography substrates. The suitability of these different approaches towards analysis of the major lipid classes along with their current and potential applications in the field of lipid analysis are evaluated. PMID:23623802

  2. High-resolution atmospheric pressure infrared laser desorption/ionization mass spectrometry imaging of biological tissue.

    PubMed

    Römpp, Andreas; Schäfer, Karl Christian; Guenther, Sabine; Wang, Zheng; Köstler, Martin; Leisner, Arne; Paschke, Carmen; Schramm, Thorsten; Spengler, Bernhard

    2013-09-01

    An atmospheric pressure laser desorption/ionization mass spectrometry imaging ion source has been developed that combines high spatial resolution and high mass resolution for the in situ analysis of biological tissue. The system is based on an infrared laser system working at 2.94 to 3.10 μm wavelength, employing a Nd:YAG laser-pumped optical parametrical oscillator. A Raman-shifted Nd:YAG laser system was also tested as an alternative irradiation source. A dedicated optical setup was used to focus the laser beam, coaxially with the ion optical axis and normal to the sample surface, to a spot size of 30 μm in diameter. No additional matrix was needed for laser desorption/ionization. A cooling stage was developed to reduce evaporation of physiological cell water. Ions were formed under atmospheric pressure and transferred by an extended heated capillary into the atmospheric pressure inlet of an orbital trapping mass spectrometer. Various phospholipid compounds were detected, identified, and imaged at a pixel resolution of up to 25 μm from mouse brain tissue sections. Mass accuracies of better than 2 ppm and a mass resolution of 30,000 at m/z = 400 were achieved for these measurements. PMID:23877173

  3. Multi-isotope (carbon and chlorine) analysis for fingerprinting and site characterization at a fractured bedrock aquifer contaminated by chlorinated ethenes.

    PubMed

    Palau, Jordi; Marchesi, Massimo; Chambon, Julie C C; Aravena, Ramon; Canals, Àngels; Binning, Philip J; Bjerg, Poul L; Otero, Neus; Soler, Albert

    2014-03-15

    The use of compound specific multi-isotope approach (C and Cl) in the characterization of a chlorinated ethenes contaminated fractured aquifer allows the identification of several sources and contaminant plumes, as well as the occurrence of biodegradation and mixing processes. The study site is located in Spain with contamination resulting in groundwater concentrations of up to 50mg/L of trichloroethene (TCE), the most abundant chlorinated ethene, and 7 mg/L of tetrachloroethene (PCE). The potential sources of contamination including abandoned barrels, an underground tank, and a disposal lagoon, showed a wide range in δ(13)C values from -15.6 to -40.5‰ for TCE and from -18.5 to -32.4‰ for PCE, allowing the use of isotope fingerprinting for tracing of the origin and migration of these contaminants in the aquifer. In contrast, there is no difference between the δ(37)Cl values for TCE in the contaminant sources, ranging from +0.53 to +0.66‰. Variations of δ(37)Cl and δ(13)C in the different contaminant plumes were used to investigate the role of biodegradation in groundwater. Moreover, the isotopic data were incorporated into a reactive transport model for determination of whether the isotope pattern observed downstream from the tank's source could be explained by the simultaneous effect of mixing and biodegradation. The results demonstrate that a multi-isotope approach is a valuable tool for characterization of complex sites such as fractured bedrock aquifer contaminated by multiple sources, providing important information which can be used by consultants and site managers to prioritize and design more successful remediation strategies. PMID:24419287

  4. Identifying source and formation altitudes of nitrates in drinking water from Réunion Island, France, using a multi-isotopic approach

    NASA Astrophysics Data System (ADS)

    Rogers, Karyne M.; Nicolini, Eric; Gauthier, Virginie

    2012-09-01

    Nitrate concentrations, water isotopes (δ2H and δ18Owater) and associated nitrate isotopes (δ15Nnitrate and δ18Onitrate) from 10 drinking water wells, 5 fresh water springs and the discharge from 3 wastewater treatment stations in Réunion Island, located in the Indian Ocean, were analysed. We used a multi isotopic approach to investigate the extent of nitrate contamination, nitrate formation altitude and source of nitrates in Réunion Island's principal aquifer. Water from these study sites contained between 0.1 and 85.3 mg/L nitrate. δ15Nnitrate values between + 6 and + 14‰ suggested the main sources of contamination were animal and/or human waste, rather than inorganic (synthetic) fertilisers, infiltrating through the subsurface into the saturated zone, due to rainfall leaching of the unsaturated zone at various altitudes of precipitation. Based on δ15Nnitrate values alone, it was not possible to distinguish between animal and human activities responsible for the contamination of each specific catchment. However, using a multi isotope approach (δ18Owater and δ15Nnitrate), it was possible to relate the average altitude of rainfall infiltration (δ18Owater) associated with the nitrate contamination (δ18Onitrate). This relationship between land use, rainfall recharge altitude and isotopic composition (δ15Nnitrate and δ18Owater) discriminated between the influences of human waste at lower (below 600 m elevation) or animal derived contamination (at elevations between 600 and 1300 m). By further comparing the theoretical altitude of nitrate formation calculated by the δ18Onitrate, it was possible to determine that only 5 out of 15 fresh water wells and springs followed the conservative nitrate formation mechanism of 2/3δ18Owater + 1/3δ18Oair, to give nitrate formation altitudes which corresponded to land use activities.

  5. Multi-matrix, dual polarity, tandem mass spectrometry imaging strategy applied to a germinated maize seed: toward mass spectrometry imaging of an untargeted metabolome

    SciTech Connect

    Feenstra, Adam D.; Hansen, Rebecca L.; Lee, Young Jin

    2015-08-27

    Mass spectrometry imaging (MSI) provides high spatial resolution information that is unprecedented in traditional metabolomics analyses; however, the molecular coverage is often limited to a handful of compounds and is insufficient to understand overall metabolomic changes of a biological system. Here, we propose an MSI methodology to increase the diversity of chemical compounds that can be imaged and identified, in order to eventually perform untargeted metabolomic analysis using MSI. We use the desorption/ionization bias of various matrixes for different metabolite classes along with dual polarities and a tandem MSI strategy. The use of multiple matrixes and dual polarities allows us to visualize various classes of compounds, while data-dependent MS/MS spectra acquired in the same MSI scans allow us to identify the compounds directly on the tissue. In a proof of concept application to a germinated corn seed, a total of 166 unique ions were determined to have high-quality MS/MS spectra, without counting structural isomers, of which 52 were identified as unique compounds. According to an estimation based on precursor MSI datasets, we expect over five hundred metabolites could be potentially identified and visualized once all experimental conditions are optimized and an MS/MS library is available. Finally, metabolites involved in the glycolysis pathway and tricarboxylic acid cycle were imaged to demonstrate the potential of this technology to better understand metabolic biology.

  6. Multi-matrix, dual polarity, tandem mass spectrometry imaging strategy applied to a germinated maize seed: toward mass spectrometry imaging of an untargeted metabolome.

    PubMed

    Feenstra, Adam D; Hansen, Rebecca L; Lee, Young Jin

    2015-11-01

    Mass spectrometry imaging (MSI) provides high spatial resolution information that is unprecedented in traditional metabolomics analyses; however, the molecular coverage is often limited to a handful of compounds and is insufficient to understand overall metabolomic changes of a biological system. Here, we propose an MSI methodology to increase the diversity of chemical compounds that can be imaged and identified, in order to eventually perform untargeted metabolomic analysis using MSI. In this approach, we use the desorption/ionization bias of various matrixes for different metabolite classes along with dual polarities and a tandem MSI strategy. The use of multiple matrixes and dual polarities allows us to visualize various classes of compounds, while data-dependent MS/MS spectra acquired in the same MSI scans allow us to identify the compounds directly on the tissue. In a proof of concept application to a germinated corn seed, a total of 166 unique ions were determined to have high-quality MS/MS spectra, without counting structural isomers, of which 52 were identified as unique compounds. According to an estimation based on precursor MSI datasets, we expect over five hundred metabolites could be potentially identified and visualized once all experimental conditions are optimized and an MS/MS library is available. Lastly, metabolites involved in the glycolysis pathway and tricarboxylic acid cycle were imaged to demonstrate the potential of this technology to better understand metabolic biology. PMID:26339687

  7. Multi-matrix, dual polarity, tandem mass spectrometry imaging strategy applied to a germinated maize seed: toward mass spectrometry imaging of an untargeted metabolome

    DOE PAGESBeta

    Feenstra, Adam D.; Hansen, Rebecca L.; Lee, Young Jin

    2015-08-27

    Mass spectrometry imaging (MSI) provides high spatial resolution information that is unprecedented in traditional metabolomics analyses; however, the molecular coverage is often limited to a handful of compounds and is insufficient to understand overall metabolomic changes of a biological system. Here, we propose an MSI methodology to increase the diversity of chemical compounds that can be imaged and identified, in order to eventually perform untargeted metabolomic analysis using MSI. We use the desorption/ionization bias of various matrixes for different metabolite classes along with dual polarities and a tandem MSI strategy. The use of multiple matrixes and dual polarities allows usmore » to visualize various classes of compounds, while data-dependent MS/MS spectra acquired in the same MSI scans allow us to identify the compounds directly on the tissue. In a proof of concept application to a germinated corn seed, a total of 166 unique ions were determined to have high-quality MS/MS spectra, without counting structural isomers, of which 52 were identified as unique compounds. According to an estimation based on precursor MSI datasets, we expect over five hundred metabolites could be potentially identified and visualized once all experimental conditions are optimized and an MS/MS library is available. Finally, metabolites involved in the glycolysis pathway and tricarboxylic acid cycle were imaged to demonstrate the potential of this technology to better understand metabolic biology.« less

  8. The Need for Speed in Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry

    PubMed Central

    Prentice, Boone M.; Caprioli, Richard M.

    2016-01-01

    Imaging mass spectrometry (IMS) has emerged as a powerful analytical tool enabling the direct molecular mapping of many types of tissue. Specifically, matrix-assisted laser desorption/ ionization (MALDI) represents one of the most broadly applicable IMS technologies. In recent years, advances in solid state laser technology, mass spectrometry instrumentation, computer technology, and experimental methodology have produced IMS systems capable of unprecedented data acquisition speeds (>50 pixels/second). In applications of this technology, throughput is an important consideration when designing an IMS experiment. As IMS becomes more widely adopted, continual improvements in experimental setups will be important to address biologically and clinically relevant time scales.

  9. MALDI Imaging Mass Spectrometry: Spatial Molecular Analysis to Enable a New Age of Discovery

    PubMed Central

    Gessel, Megan M.; Norris, Jeremy L.; Caprioli, Richard M.

    2014-01-01

    Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) combines the sensitivity and selectivity of mass spectrometry with spatial analysis to provide a new dimension for histological analyses to provide unbiased visualization of the arrangement of biomolecules in tissue. As such, MALDI IMS has the capability to become a powerful new molecular technology for the biological and clinical sciences. In this review, we briefly describe several applications of MALDI IMS covering a range of molecular weights, from drugs to proteins. Current limitations and challenges are discussed along with recent developments to address these issues. PMID:24686089

  10. Image-based mass-spring model of mitral valve closure for surgical planning

    NASA Astrophysics Data System (ADS)

    Hammer, Peter E.; Perrin, Douglas P.; del Nido, Pedro J.; Howe, Robert D.

    2008-03-01

    Surgical repair of the mitral valve is preferred in most cases over valve replacement, but replacement is often performed instead due to the technical difficulty of repair. A surgical planning system based on patient-specific medical images that allows surgeons to simulate and compare potential repair strategies could greatly improve surgical outcomes. In such a surgical simulator, the mathematical model of mechanics used to close the valve must be able to compute the closed state quickly and to handle the complex boundary conditions imposed by the chords that tether the valve leaflets. We have developed a system for generating a triangulated mesh of the valve surface from volumetric image data of the opened valve. We then compute the closed position of the mesh using a mass-spring model of dynamics. The triangulated mesh is produced by fitting an isosurface to the volumetric image data, and boundary conditions, including the valve annulus and chord endpoints, are identified in the image data using a graphical user interface. In the mass-spring model, triangle sides are treated as linear springs, and sides shared by two triangles are treated as bending springs. Chords are treated as nonlinear springs, and self-collisions are detected and resolved. Equations of motion are solved using implicit numerical integration. Accuracy was assessed by comparison of model results with an image of the same valve taken in the closed state. The model exhibited rapid valve closure and was able to reproduce important features of the closed valve.

  11. Chemical Imaging of Lipid Domains by High-Resolution Secondary Ion Mass Spectrometry

    SciTech Connect

    Kraft, M L; Weber, P K; Longo, M L; Hutcheon, I D; Boxer, S G

    2005-09-30

    Lipid microdomains within supported lipid bilayers composed of binary phosphocholine mixtures were chemically imaged by high-resolution secondary ion mass spectrometry performed with the NanoSIMS 50 (Cameca Instruments). This instrument images the sample components based on the elemental or isotopic composition of their atomic and small molecular secondary ions. Up to five different secondary ions can be simultaneously detected, and a lateral resolution of 50 nm can be achieved with high sensitivity at high mass resolution. In our experiments, the NanoSIMS 50 extensively fragmented the supported membrane, therefore an isotopic labeling strategy was used to encode the identities of the lipid components. Supported lipid membranes that contained distinct lipid microdomains were freeze-dried to preserve their lateral organization and analyzed with the NanoSIMS 50. Lipid microdomains as small as 100 nm in diameter were successfully imaged, and this was validated by comparison to AFM images taken at the same region prior to chemical imaging. Quantitative information on the lipid distribution within the domain was also determined by calibrating against supported membranes of known composition. We believe this will be a valuable approach for analyzing the composition of complex membrane domains with high spatial resolution.

  12. Image-guided fine-needle aspiration of retroperitoneal masses: The role of the cytopathologist

    PubMed Central

    Mehdi, Ghazala; Maheshwari, Veena; Afzal, Sheerin; Ansari, Hena A; Ahmad, Ibne

    2013-01-01

    Background: Retroperitoneal tumors constitute a difficult diagnostic category as they are not easily accessible. The advent of image-guided fine-needle aspiration (FNA) has resolved this problem significantly. Aims: We present a short study based on guided aspiration of retroperitoneal tumors, in which we have tried to assess the role of image-guided fine-needle aspiration cytology as a tool for pre-operative diagnosis. Materials and Methods: The study was conducted on patients diagnosed with retroperitoneal masses. FNA was performed under image guidance with the help of ultrasonography and/or computed tomography; smears were prepared and meticulously screened according to a fixed protocol. The results were analyzed to determine sensitivity, specificity, and diagnostic efficacy of cytopathological diagnosis using image-guided FNA techniques. Results: We assessed 38 patients with retroperitoneal masses. In all cases, adequate cellular material was obtained. No major complications were encountered. Statistical analysis was carried out in 35 cases; sensitivity, specificity, and diagnostic accuracy were 100% in these cases. Conclusion: FNA under image guidance should be considered a first-line diagnostic approach for retroperitoneal and other abdominal tumors, although caution should be exercised in case selection. In areas where advanced tests are not available, the cytotechnologist and cytopathologist have a very important role to play in ensuring accurate diagnoses. PMID:23661939

  13. Imaging MALDI mass spectrometry of sphingolipids using an oscillating capillary nebulizer matrix application system.

    PubMed

    Chen, Yanfeng; Liu, Ying; Allegood, Jeremy; Wang, Elaine; Cachón-González, Begoña; Cox, Timothy M; Merrill, Alfred H; Sullards, M Cameron

    2010-01-01

    Matrix deposition is a critical step in tissue imaging by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). It greatly affects the quality of MALDI imaging, especially for the analytes (such as lipids) that may easily dissolve in the solvent used for the matrix application. This chapter describes the use of an oscillating capillary nebulizer (OCN) to spray small droplets of matrix aerosol onto the sample surface for improved matrix homogeneity, reduced crystal size, and controlled solvent effects. This protocol allows visualization of many different lipid species and, of particular interest, sphingolipids in tissue slices of Tay-Sachs/Sandhoff disease by imaging MALDI-MS. The structures of these lipids were identified by analysis of tissue extracts using electrospray ionization in conjunction with tandem mass spectrometry (MS/MS and MS(3)). These results illustrate the usefulness of tissue imaging MALDI-MS with matrix deposition by OCN for the molecular analysis in normal physiology and pathology. In addition, the observation of numerous lipid subclasses with distinct localizations in the brain slices demonstrates that imaging MALDI-MS could be effectively used for "lipidomic" studies. PMID:20680588

  14. Matrix-free mass spectrometric imaging using laser desorption ionisation Fourier transform ion cyclotron resonance mass spectrometry.

    PubMed

    Goodwin, Richard J A; Pitt, Andrew R; Harrison, David; Weidt, Stefan K; Langridge-Smith, Pat R R; Barrett, Michael P; Logan Mackay, C

    2011-04-15

    Mass spectrometry imaging (MSI) is a powerful tool in metabolomics and proteomics for the spatial localization and identification of pharmaceuticals, metabolites, lipids, peptides and proteins in biological tissues. However, sample preparation remains a crucial variable in obtaining the most accurate distributions. Common washing steps used to remove salts, and solvent-based matrix application, allow analyte spreading to occur. Solvent-free matrix applications can reduce this risk, but increase the possibility of ionisation bias due to matrix adhesion to tissue sections. We report here the use of matrix-free MSI using laser desorption ionisation performed on a 12 T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. We used unprocessed tissue with no post-processing following thaw-mounting on matrix-assisted laser desorption ionisation (MALDI) indium-tin oxide (ITO) target plates. The identification and distribution of a range of phospholipids in mouse brain and kidney sections are presented and compared with previously published MALDI time-of-flight (TOF) MSI distributions. PMID:21416534

  15. Advancements in Imaging Technology for Detection and Diagnosis of Palpable Breast Masses.

    PubMed

    Jaeger, Barbara M; Hong, Andrea S; Letter, Haley; Odell, Matthew C

    2016-06-01

    Breast cancer is the most commonly diagnosed cancer among women worldwide and the most common cause of cancer death in women. The most common presentation of breast cancer is the presence of a palpable mass, whether noted by the patient during breast self-examination or noted during clinical breast examination. There are a variety of imaging modalities now available for the evaluation of a palpable abnormality. A thorough understanding of the indications, risks, and benefits can help the clinician guide the patient through an appropriate, comprehensive imaging work up. PMID:27101239

  16. Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models.

    PubMed

    Chughtai, Kamila; Jiang, Lu; Greenwood, Tiffany R; Glunde, Kristine; Heeren, Ron M A

    2013-02-01

    The lipid compositions of different breast tumor microenvironments are largely unknown due to limitations in lipid imaging techniques. Imaging lipid distributions would enhance our understanding of processes occurring inside growing tumors, such as cancer cell proliferation, invasion, and metastasis. Recent developments in MALDI mass spectrometry imaging (MSI) enable rapid and specific detection of lipids directly from thin tissue sections. In this study, we performed multimodal imaging of acylcarnitines, phosphatidylcholines (PC), a lysophosphatidylcholine (LPC), and a sphingomyelin (SM) from different microenvironments of breast tumor xenograft models, which carried tdTomato red fluorescent protein as a hypoxia-response element-driven reporter gene. The MSI molecular lipid images revealed spatially heterogeneous lipid distributions within tumor tissue. Four of the most-abundant lipid species, namely PC(16:0/16:0), PC(16:0/18:1), PC(18:1/18:1), and PC(18:0/18:1), were localized in viable tumor regions, whereas LPC(16:0/0:0) was detected in necrotic tumor regions. We identified a heterogeneous distribution of palmitoylcarnitine, stearoylcarnitine, PC(16:0/22:1), and SM(d18:1/16:0) sodium adduct, which colocalized primarily with hypoxic tumor regions. For the first time, we have applied a multimodal imaging approach that has combined optical imaging and MALDI-MSI with ion mobility separation to spatially localize and structurally identify acylcarnitines and a variety of lipid species present in breast tumor xenograft models. PMID:22930811

  17. Imaging ion and molecular transport at subcellular resolution by secondary ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Chandra, Subhash; Morrison, George H.

    1995-05-01

    The transport of K+, Na+, and Ca2+ were imaged in individual cells with a Cameca IMS-3f ion microscope. Strict cryogenic frozen freeze-dry sample preparations were employed. Ion redistribution artifacts in conventional chemical preparations are discussed. Cryogenically prepared freeze-fractured freeze-dried cultured cells allowed the three-dimensional ion microscopic imaging of elements. As smaller structures in calcium images can be resolved with the 0.5 [mu]m spatial resolution, correlative techniques are needed to confirm their identity. The potentials of reflected light microscopy, scanning electron microscopy and laser scanning confocal microscopy are discussed for microfeature recognition in freeze-fractured freeze-dried cells. The feasibility of using frozen freeze-dried cells for imaging molecular transport at subcellular resolution was tested. Ion microscopy successfully imaged the transport of the isotopically tagged (13C, 15N) amino acid, -arginine. The labeled amino acid was imaged at mass 28 with a Cs+ primary ion beam as the 28(13C15N)- species. After a 4 h exposure of LLC-PK1 kidney cells to 4 mM labeled arginine, the amino acid was localized throughout the cell with a preferential incorporation into the nucleus and nucleolus. An example is also shown of the ion microscopic imaging of sodium borocaptate, an experimental therapeutic drug for brain tumors, in cryogenically prepared frozen freeze-dried Swiss 3T3 cells.

  18. SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for β-cell mass assessments

    PubMed Central

    Eter, Wael A.; Parween, Saba; Joosten, Lieke; Frielink, Cathelijne; Eriksson, Maria; Brom, Maarten; Ahlgren, Ulf; Gotthardt, Martin

    2016-01-01

    Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, 111In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of 111In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers. PMID:27080529

  19. SPECT-OPT multimodal imaging enables accurate evaluation of radiotracers for β-cell mass assessments.

    PubMed

    Eter, Wael A; Parween, Saba; Joosten, Lieke; Frielink, Cathelijne; Eriksson, Maria; Brom, Maarten; Ahlgren, Ulf; Gotthardt, Martin

    2016-01-01

    Single Photon Emission Computed Tomography (SPECT) has become a promising experimental approach to monitor changes in β-cell mass (BCM) during diabetes progression. SPECT imaging of pancreatic islets is most commonly cross-validated by stereological analysis of histological pancreatic sections after insulin staining. Typically, stereological methods do not accurately determine the total β-cell volume, which is inconvenient when correlating total pancreatic tracer uptake with BCM. Alternative methods are therefore warranted to cross-validate β-cell imaging using radiotracers. In this study, we introduce multimodal SPECT - optical projection tomography (OPT) imaging as an accurate approach to cross-validate radionuclide-based imaging of β-cells. Uptake of a promising radiotracer for β-cell imaging by SPECT, (111)In-exendin-3, was measured by ex vivo-SPECT and cross evaluated by 3D quantitative OPT imaging as well as with histology within healthy and alloxan-treated Brown Norway rat pancreata. SPECT signal was in excellent linear correlation with OPT data as compared to histology. While histological determination of islet spatial distribution was challenging, SPECT and OPT revealed similar distribution patterns of (111)In-exendin-3 and insulin positive β-cell volumes between different pancreatic lobes, both visually and quantitatively. We propose ex vivo SPECT-OPT multimodal imaging as a highly accurate strategy for validating the performance of β-cell radiotracers. PMID:27080529

  20. MALDI imaging mass spectrometry as a novel tool for detecting histone modifications in clinical tissue samples.

    PubMed

    Lahiri, Shibojyoti; Sun, Na; Buck, Achim; Imhof, Axel; Walch, Axel

    2016-03-01

    Histone post-translational modifications (PTMs), histone variants and enzymes responsible for the incorporation or the removal of the PTMs are being increasingly associated with human disease. Combinations of histone PTMs and the specific incorporation of variants contribute to the establishment of cellular identity and hence are potential markers that could be exploited in disease diagnostics and prognostics and therapy response prediction. Due to the scarcity of suitable antibodies and the pre-requirement of tissue homogenization for more advanced analytical techniques, comprehensive information regarding the spatial distribution of these factors at the tissue level has been lacking. MALDI imaging mass spectrometry provides an ideal platform to measure histone PTMs and variants from tissues while maintaining the information about their spatial distribution. Discussed in this review are the relevance of histones in the context of human disease and the contribution of MALDI imaging mass spectrometry in measuring histones in situ. PMID:26808584

  1. Mass MOVEMENTS' Detection in Hirise Images of the North Pole of Mars

    NASA Astrophysics Data System (ADS)

    Fanara, L.; Gwinner, K.; Hauber, E.; Oberst, J.

    2016-06-01

    We are investigating change detection techniques to automatically detect mass movements at the steep north polar scarps of Mars, in order to improve our understanding of these dynamic processes. Here we focus on movements of blocks specifically. The precise detection of such small changes requires an accurate co-registration of the images, which is achieved by ortho-rectifying them using High Resolution Imaging Science Experiment (HiRISE) Digital Terrain Models (DTMs). Moreover, we deal with the challenge of deriving the true shape of the moved blocks. In a next step, these results are combined with findings based on HiRISE DTMs from different points in time in order to estimate the volume of mass movements.

  2. Mass Spectrometry Imaging and GC-MS Profiling of the Mammalian Peripheral Sensory-Motor Circuit

    NASA Astrophysics Data System (ADS)

    Rubakhin, Stanislav S.; Ulanov, Alexander; Sweedler, Jonathan V.

    2015-06-01

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) has evolved to become an effective discovery tool in science and clinical diagnostics. Here, chemical imaging approaches are applied to well-defined regions of the mammalian peripheral sensory-motor system, including the dorsal root ganglia (DRG) and adjacent nerves. By combining several MSI approaches, analyte coverage is increased and 195 distinct molecular features are observed. Principal component analysis suggests three chemically different regions within the sensory-motor system, with the DRG and adjacent nerve regions being the most distinct. Investigation of these regions using gas chromatography-mass spectrometry corroborate these findings and reveal important metabolic markers related to the observed differences. The heterogeneity of the structurally, physiologically, and functionally connected regions demonstrates the intricate chemical and spatial regulation of their chemical composition.

  3. MALDI mass spectrometry imaging for the simultaneous location of resveratrol, pterostilbene and viniferins on grapevine leaves.

    PubMed

    Becker, Loïc; Carré, Vincent; Poutaraud, Anne; Merdinoglu, Didier; Chaimbault, Patrick

    2014-01-01

    To investigate the in-situ response to a stress, grapevine leaves have been subjected to mass spectrometry imaging (MSI) experiments. The Matrix Assisted Laser Desorption/Ionisation (MALDI) approach using different matrices has been evaluated. Among all the tested matrices, the 2,5-dihydroxybenzoic acid (DHB) was found to be the most efficient matrix allowing a broader range of detected stilbene phytoalexins. Resveratrol, but also more toxic compounds against fungi such as pterostilbene and viniferins, were identified and mapped. Their spatial distributions on grapevine leaves irradiated by UV show their specific colocation around the veins. Moreover, MALDI MSI reveals that resveratrol (and piceids) and viniferins are not specifically located on the same area when leaves are infected by Plasmopara viticola. Results obtained by MALDI mass spectrometry imaging demonstrate that this technique would be essential to improve the level of knowledge concerning the role of the stilbene phytoalexins involved in a stress event. PMID:25050857

  4. Mass Spectrometry Imaging and GC-MS Profiling of the Mammalian Peripheral Sensory-Motor Circuit

    PubMed Central

    Rubakhin, Stanislav S.; Ulanov, Alexander; Sweedler, Jonathan V.

    2015-01-01

    Matrix-assisted laser desorption / ionization-mass spectrometry imaging (MSI) has evolved to become an effective discovery tool in science and clinical diagnostics. Here, chemical imaging approaches are applied to well-defined regions of the mammalian peripheral sensory-motor system, including the dorsal root ganglia (DRG) and adjacent nerves. By combining several MSI approaches, analyte coverage is increased and 195 distinct molecular features are observed. Principal component analysis suggests three chemically different regions within the sensory-motor system, with the DRG and adjacent nerve regions being the most distinct. Investigation of these regions using gas chromatography-mass spectrometry corroborate these findings and reveal important metabolic markers related to the observed differences. The heterogeneity of the structurally, physiologically, and functionally connected regions demonstrates the intricate chemical and spatial regulation of their chemical composition. PMID:25822927

  5. MALDI imaging mass spectrometry for direct tissue analysis: a new frontier for molecular histology

    PubMed Central

    Rauser, Sandra; Deininger, Sören-Oliver; Höfler, Heinz

    2008-01-01

    Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating the distribution of proteins and small molecules within biological systems through the in situ analysis of tissue sections. MALDI-IMS can determine the distribution of hundreds of unknown compounds in a single measurement and enables the acquisition of cellular expression profiles while maintaining the cellular and molecular integrity. In recent years, a great many advances in the practice of imaging mass spectrometry have taken place, making the technique more sensitive, robust, and ultimately useful. In this review, we focus on the current state of the art of MALDI-IMS, describe basic technological developments for MALDI-IMS of animal and human tissues, and discuss some recent applications in basic research and in clinical settings. PMID:18618129

  6. Ambient Mass Spectrometry Imaging with Picosecond Infrared Laser Ablation Electrospray Ionization (PIR-LAESI).

    PubMed

    Zou, Jing; Talbot, Francis; Tata, Alessandra; Ermini, Leonardo; Franjic, Kresimir; Ventura, Manuela; Zheng, Jinzi; Ginsberg, Howard; Post, Martin; Ifa, Demian R; Jaffray, David; Miller, R J Dwayne; Zarrine-Afsar, Arash

    2015-12-15

    A picosecond infrared laser (PIRL) is capable of cutting through biological tissues in the absence of significant thermal damage. As such, PIRL is a standalone surgical scalpel with the added bonus of minimal postoperative scar tissue formation. In this work, a tandem of PIRL ablation with electrospray ionization (PIR-LAESI) mass spectrometry is demonstrated and characterized for tissue molecular imaging, with a limit of detection in the range of 100 nM for reserpine or better than 5 nM for verapamil in aqueous solution. We characterized PIRL crater size using agar films containing Rhodamine. PIR-LAESI offers a 20-30 μm vertical resolution (∼3 μm removal per pulse) and a lateral resolution of ∼100 μm. We were able to detect 25 fmol of Rhodamine in agar ablation experiments. PIR-LAESI was used to map the distribution of endogenous methoxykaempferol glucoronide in zebra plant (Aphelandra squarrosa) leaves producing a localization map that is corroborated by the literature. PIR-LAESI was further used to image the distribution inside mouse kidneys of gadoteridol, an exogenous magnetic resonance contrast agent intravenously injected. Parallel mass spectrometry imaging (MSI) using desorption electrospray ionization (DESI) and matrix assisted laser desorption ionization (MALDI) were performed to corroborate PIR-LAESI images of the exogenous agent. We further show that PIR-LAESI is capable of desorption ionization of proteins as well as phospholipids. This comparative study illustrates that PIR-LAESI is an ion source for ambient mass spectrometry applications. As such, a future PIRL scalpel combined with secondary ionization such as ESI and mass spectrometry has the potential to provide molecular feedback to guide PIRL surgery. PMID:26561279

  7. [Imaging mass spectrometry: a new tool for the analysis of skin biopsy. Application in Fabry's disease].

    PubMed

    Roy, S; Touboul, D; Brunelle, A; Germain, D-P; Prognon, P; Laprévote, O; Chaminade, P

    2006-09-01

    The advent of innovative techniques in mass spectrometry, especially in the area of imaging, prompted us to evaluate two promising techniques: secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. For this purpose, sections of cutaneous biopsies from patients affected by Fabry's disease and control patients were analyzed. In the course of this disease, two physiological glycosphingolipids [globotriasylceramide (Gb3) and the galabiosylceramide (Ga2)] accumulate in certain tissues owing to a catabolism failure. The ability of these techniques to localize sites of accumulation in body tissues and their capacity to identify the accumulated lipid structures by mass spectra were evaluated. Results demonstrated that these two techniques provide complementary information:-secondary ion mass spectrometry enabled precise localization of areas of accumulation with lateral resolution in the micrometer range;-the signal obtained with matrix-assisted laser desorption/ionization mass spectrometry was high enough to identify these structures according to their molecular weight. PMID:17095952

  8. Mapping drug distribution in brain tissue using liquid extraction surface analysis mass spectrometry imaging.

    PubMed

    Swales, John G; Tucker, James W; Spreadborough, Michael J; Iverson, Suzanne L; Clench, Malcolm R; Webborn, Peter J H; Goodwin, Richard J A

    2015-10-01

    Liquid extraction surface analysis mass spectrometry (LESA-MS) is a surface sampling technique that incorporates liquid extraction from the surface of tissue sections with nanoelectrospray mass spectrometry. Traditional tissue analysis techniques usually require homogenization of the sample prior to analysis via high-performance liquid chromatography mass spectrometry (HPLC-MS), but an intrinsic weakness of this is a loss of all spatial information and the inability of the technique to distinguish between actual tissue penetration and response caused by residual blood contamination. LESA-MS, in contrast, has the ability to spatially resolve drug distributions and has historically been used to profile discrete spots on the surface of tissue sections. Here, we use the technique as a mass spectrometry imaging (MSI) tool, extracting points at 1 mm spatial resolution across tissue sections to build an image of xenobiotic and endogenous compound distribution to assess drug blood-brain barrier penetration into brain tissue. A selection of penetrant and "nonpenetrant" drugs were dosed to rats via oral and intravenous administration. Whole brains were snap-frozen at necropsy and were subsequently sectioned prior to analysis by matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) and LESA-MSI. MALDI-MSI, as expected, was shown to effectively map the distribution of brain penetrative compounds but lacked sufficient sensitivity when compounds were marginally penetrative. LESA-MSI was used to effectively map the distribution of these poorly penetrative compounds, highlighting its value as a complementary technique to MALDI-MSI. The technique also showed benefits when compared to traditional homogenization, particularly for drugs that were considered nonpenetrant by homogenization but were shown to have a measurable penetration using LESA-MSI. PMID:26350423

  9. Imaging of Proteins in Tissue Samples Using Nanospray Desorption Electrospray Ionization Mass Spectrometry.

    PubMed

    Hsu, Cheng-Chih; Chou, Pi-Tai; Zare, Richard N

    2015-11-17

    Chemical maps of tissue samples provide important information on biological processes therein. Recently, advances in tissue imaging have been achieved using ambient ionization techniques, such as desorption electrospray ionization mass spectrometry (DESI-MS), but such techniques have been almost exclusively confined to the mapping of lipids and metabolites. We report here the use of nanospray desorption electrospray ionization (nanoDESI) that allows us to image proteins in tissue samples in a label-free manner at atmospheric pressure with only minimum sample preparation. Multiply charged proteins with masses up to 15 kDa were successfully detected by nanoDESI using an LTQ Orbitrap mass spectrometer. In an adult mice brain section, expression of proteins including ubiquitin, β-thymosin, myelin basic protein, and hemoglobin were spatially mapped and characterized. We also determined the location of methylation on myelin basic protein. This imaging modality was further implemented to MYC-induced lymphomas. We observed an array of truncated proteins in the region where normal thymus cells were infiltrated by tumor cells, in contrast to healthy tissue. PMID:26509582

  10. Identification of Biomarkers of Necrosis in Xenografts Using Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Fernández, Roberto; Garate, Jone; Lage, Sergio; Terés, Silvia; Higuera, Mónica; Bestard-Escalas, Joan; López, Daniel H.; Guardiola-Serrano, Francisca; Escribá, Pablo V.; Barceló-Coblijn, Gwendolyn; Fernández, José A.

    2016-02-01

    Xenografts are commonly used to test the effect of new drugs on human cancer. However, because of their heterogeneity, analysis of the results is often controversial. Part of the problem originates in the existence of tumor cells at different metabolic stages: from metastatic to necrotic cells, as it happens in real tumors. Imaging mass spectrometry is an excellent solution for the analysis of the results as it yields detailed information not only on the composition of the tissue but also on the distribution of the biomolecules within the tissue. Here, we use imaging mass spectrometry to determine the distribution of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and their plasmanyl- and plasmenylether derivatives (PC-P/O and PE-P/O) in xenografts of five different tumor cell lines: A-549, NCI-H1975, BX-PC3, HT29, and U-87 MG. The results demonstrate that the necrotic areas showed a higher abundance of Na+ adducts and of PC-P/O species, whereas a large abundance of PE-P/O species was found in all the xenografts. Thus, the PC/PC-ether and Na+/K+ ratios may highlight the necrotic areas while an increase on the number of PE-ether species may be pointing to the existence of viable tumor tissues. Furthermore, the existence of important changes in the concentration of Na+ and K+ adducts between different tissues has to be taken into account while interpreting the imaging mass spectrometry results.

  11. Imaging Discovery of a Low-Mass Companion Around HR 3549

    NASA Astrophysics Data System (ADS)

    Stapelfeldt, Karl; Mawet, Dimitri; David, Trevor; Bottom, Michael; Hinkley, Sasha; Padgett, Deborah; Mennesson, Bertrand; Serabyn, Eugene; Morales, Farisa Y.; Kuhn, Jonas

    2015-12-01

    We report the discovery of a low-mass companion to HR 3549 , an A0V star surrounded by a debris disk with a warm excess detected by WISE. We imaged the companion at the Very Large Telescope with NAOS-CONICA in the L-band in January 2013 and January 2015. The companion is at a projected separation of 80 AU and position angle of 157° . Our age estimate for this object corresponds to a mass in the range 15-80 M J , spanning the brown dwarf regime, and so HR 3549 b is another recent addition to the growing list of brown dwarf desert objects with extreme mass ratios.

  12. From pixel to voxel: a deeper view of biological tissue by 3D mass spectral imaging

    PubMed Central

    Ye, Hui; Greer, Tyler; Li, Lingjun

    2011-01-01

    Three dimensional mass spectral imaging (3D MSI) is an exciting field that grants the ability to study a broad mass range of molecular species ranging from small molecules to large proteins by creating lateral and vertical distribution maps of select compounds. Although the general premise behind 3D MSI is simple, factors such as choice of ionization method, sample handling, software considerations and many others must be taken into account for the successful design of a 3D MSI experiment. This review provides a brief overview of ionization methods, sample preparation, software types and technological advancements driving 3D MSI research of a wide range of low- to high-mass analytes. Future perspectives in this field are also provided to conclude that the positive and promises ever-growing applications in the biomedical field with continuous developments of this powerful analytical tool. PMID:21320052

  13. Probing Neuropeptide Signaling at the Organ and Cellular Domains via Imaging Mass Spectrometry

    PubMed Central

    Ye, Hui; Greer, Tyler; Li, Lingjun

    2012-01-01

    Imaging mass spectrometry (IMS) has evolved to be a promising technology due to its ability to detect a broad mass range of molecular species and create density maps for selected compounds. It is currently one of the most useful techniques to determine the spatial distribution of neuropeptides in cells and tissues. Although IMS is conceptually simple, sample preparation steps, mass analyzers, and software suites are just a few of the factors that contribute to the successful design of a neuropeptide IMS experiment. This review provides a brief overview of IMS sampling protocols, instrumentation, data analysis tools, technological advancements and applications to neuropeptide localization in neurons and endocrine tissues. Future perspectives in this field are also provided, concluding that neuropeptide IMS could revolutionize neuronal network and biomarker discovery studies. PMID:22465716

  14. Mass-spectrometry based oxidative lipidomics and lipid imaging: applications in traumatic brain injury.

    PubMed

    Sparvero, Louis J; Amoscato, Andrew A; Kochanek, Patrick M; Pitt, Bruce R; Kagan, Valerian E; Bayir, Hülya

    2010-12-01

    Lipids, particularly phospholipids, are fundamental to CNS tissue architecture and function. Endogenous polyunsaturated fatty acid chains of phospholipids possess cis-double bonds each separated by one methylene group. These phospholipids are very susceptible to free-radical attack and oxidative modifications. A combination of analytical methods including different versions of chromatography and mass spectrometry allows detailed information to be obtained on the content and distribution of lipids and their oxidation products thus constituting the newly emerging field of oxidative lipidomics. It is becoming evident that specific oxidative modifications of lipids are critical to a number of cellular functions, disease states and responses to oxidative stresses. Oxidative lipidomics is beginning to provide new mechanistic insights into traumatic brain injury which may have significant translational potential for development of therapies in acute CNS insults. In particular, selective oxidation of a mitochondria-specific phospholipid, cardiolipin, has been associated with the initiation and progression of apoptosis in injured neurons thus indicating new drug discovery targets. Furthermore, imaging mass-spectrometry represents an exciting new opportunity for correlating maps of lipid profiles and their oxidation products with structure and neuropathology. This review is focused on these most recent advancements in the field of lipidomics and oxidative lipidomics based on the applications of mass spectrometry and imaging mass spectrometry as they relate to studies of phospholipids in traumatic brain injury. PMID:20950335

  15. Mass-Spectrometry Based Oxidative Lipidomics and Lipid Imaging: Applications in Traumatic Brain Injury

    PubMed Central

    Sparvero, LJ; Amoscato, AA; Kochanek, PM; Pitt, BR; Kagan, VE; Bayır, H

    2012-01-01

    Lipids, particularly phospholipids, are fundamental to central nervous system (CNS) tissue architecture and function. Endogenous polyunsaturated fatty acid chains of phospholipids possess cis-double bonds each separated by one methylene group. These phospholipids are very susceptible to free-radical attack and oxidative modifications. A combination of analytical methods including different versions of chromatography and mass spectrometry allows obtaining detailed information on the content and distribution of lipids and their oxidation products thus constituting the newly emerging field of oxidative lipidomics. It is becoming evident that specific oxidative modifications of lipids are critical to a number of cellular functions, disease states and responses to oxidative stresses. Oxidative lipidomics is beginning to provide new mechanistic insights into traumatic brain injury (TBI) which may have significant translational potential for development of therapies in acute CNS insults. In particular, selective oxidation of a mitochondria-specific phospholipid, cardiolipin, has been associated with the initiation and progression of apoptosis in injured neurons thus indicating new drug discovery targets. Further, imaging mass-spectrometry represents an exciting new opportunity for correlating maps of lipid profiles and their oxidation products with structure and neuropathology. This review is focused on these most recent advancements in the field of lipidomics and oxidative lipidomics based on the applications of mass-spectrometry and imaging mass-spectrometry as they relate to studies of phospholipids in TBI. PMID:20950335

  16. Surface-transfer mass spectrometry imaging on a monoisotopic silver nanoparticle enhanced target.

    PubMed

    Nizioł, Joanna; Ruman, Tomasz

    2013-12-17

    A new method for both high-resolution laser desorption/ionization mass spectrometry and mass spectrometry imaging is described. The method could be considered as matrix-less because no additional matrix is needed for MS measurements and also because of surface-assisted laser desorption/ionization due to the nanoparticle-rich surface. The standard matrix-assisted laser desorption/ionization target containing unique monoisotopic cationic (109)Ag nanoparticles ((109)AgNPs) was used for high-resolution mass spectrometry imaging of fingermarks and also plant flower and plant stem cross sections with high mass accuracy. The methodology presented in this work allowed visualization of two drugs--anti-inflammatory ibuprofen and anticancer 5-fluorouracil--along with many other compounds found on the finger. Moreover, visualization of herbicide localization inside of the plant stem is also shown. The simple inorganic ions ionized by silver nanoparticles were also found and may be used for their localization in biological material. In addition, the methodology presented here does not require freezing of species or slice-making equipment. PMID:24251730

  17. Magnetic resonance imaging and ultrasound evaluation of penile and testicular masses.

    PubMed

    Andipa, E; Liberopoulos, K; Asvestis, C

    2004-11-01

    The purpose of this study is to present the role of ultrasonography and MRI in the investigation of testicular and penile masses, as well as to review the literature. This article is based on our experience with 230 patients who presented with acute or subacute scrotal pain or painless enlargement of the scrotum or penis. Gray scale and color Doppler ultrasonography (CDU) were applied in all cases. In 73 cases, the final diagnosis was established by surgery and in 157 cases by follow-up. MRI was performed in 48 cases. Ultrasonography was the initial imaging modality in all cases. It provided detailed anatomic information with high sensitivity and accuracy in cases of torsion, inflammation, varicocele and trauma. In cases of tumor, US showed the presence of the mass in all cases, while it additionally revealed certain characteristic features of tissue constitution and blood supply. In most cases, differentiation between various types of tumors or differentiation between malignant and benign lesions was impossible. MRI, besides the detailed anatomic imaging, also provided a certain degree of tissue specificity. MRI could help in the detection and staging of penile cancer and in the evaluation of testicular and scrotal masses, especially when a diagnostic dilemma occurred on ultrasonographic examination. Ultrasonography, combining gray scale and color techniques, is irreplaceable in the diagnostic work-up of scrotal and penile masses, while MRI can serve as a problem solving diagnostic modality. PMID:15300391

  18. MALDI imaging mass spectrometry of Pacific White Shrimp L. vannamei and identification of abdominal muscle proteins.

    PubMed

    Schey, Kevin L; Hachey, Amanda J; Rose, Kristie L; Grey, Angus C

    2016-06-01

    MALDI imaging mass spectrometry (IMS) has been applied to whole animal tissue sections of Pacific White Shrimp, Litopenaeus vannamei, in an effort to identify and spatially localize proteins in specific organ systems. Frozen shrimp were sectioned along the ventral-dorsal axis and methods were optimized for matrix application. In addition, tissue microextraction and homogenization was conducted followed by top-down LC-MS/MS analysis of intact proteins and searches of shrimp EST databases to identify imaged proteins. IMS images revealed organ system specific protein signals that highlighted the hepatopancreas, heart, nervous system, musculature, and cuticle. Top-down proteomics identification of abdominal muscle proteins revealed the sequence of the most abundant muscle protein that has no sequence homology to known proteins. Additional identifications of abdominal muscle proteins included titin, troponin-I, ubiquitin, as well as intact and multiple truncated forms of flightin; a protein known to function in high frequency contraction of insect wing muscles. The combined use of imaging mass spectrometry and top-down proteomics allowed for identification of novel proteins from the sparsely populated shrimp protein databases. PMID:26990122

  19. On the autonomous detection of coronal mass ejections in heliospheric imager data

    NASA Astrophysics Data System (ADS)

    Tappin, S. J.; Howard, T. A.; Hampson, M. M.; Thompson, R. N.; Burns, C. E.

    2012-05-01

    We report on the development of an Automatic Coronal Mass Ejection (CME) Detection tool (AICMED) for the Solar Mass Ejection Imager (SMEI). CMEs observed with heliospheric imagers are much more difficult to detect than those observed by coronagraphs as they have a lower contrast compared with the background light, have a larger range of intensity variation and are easily confused with other transient activity. CMEs appear in SMEI images as very faint often-fragmented arcs amongst a much brighter and often variable background. AICMED operates along the same lines as Computer Aided CME Tracking (CACTus), using the Hough Transform on elongation-time J-maps to extract straight lines from the data set. We compare AICMED results with manually measured CMEs on almost three years of data from early in SMEI operations. AICMED identified 83 verifiable events. Of these 46 could be matched with manually identified events, the majority of the non-detections can be explained. The remaining 37 AICMED events were newly discovered CMEs. The proportion of false identification was high, at 71% of the autonomously detected events. We find that AICMED is very effective as a region of interest highlighter, and is a promising first step in autonomous heliospheric imager CME detection, but the SMEI data are too noisy for the tool to be completely automated.

  20. Interpolation of longitudinal shape and image data via optimal mass transport

    NASA Astrophysics Data System (ADS)

    Gao, Yi; Zhu, Liang-Jia; Bouix, Sylvain; Tannenbaum, Allen

    2014-03-01

    Longitudinal analysis of medical imaging data has become central to the study of many disorders. Unfortunately, various constraints (study design, patient availability, technological limitations) restrict the acquisition of data to only a few time points, limiting the study of continuous disease/treatment progression. Having the ability to produce a sensible time interpolation of the data can lead to improved analysis, such as intuitive visualizations of anatomical changes, or the creation of more samples to improve statistical analysis. In this work, we model interpolation of medical image data, in particular shape data, using the theory of optimal mass transport (OMT), which can construct a continuous transition from two time points while preserving "mass" (e.g., image intensity, shape volume) during the transition. The theory even allows a short extrapolation in time and may help predict short-term treatment impact or disease progression on anatomical structure. We apply the proposed method to the hippocampus-amygdala complex in schizophrenia, the heart in atrial fibrillation, and full head MR images in traumatic brain injury.

  1. Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea.

    PubMed

    Ong, Ta-Hsuan; Romanova, Elena V; Roberts-Galbraith, Rachel H; Yang, Ning; Zimmerman, Tyler A; Collins, James J; Lee, Ji Eun; Kelleher, Neil L; Newmark, Phillip A; Sweedler, Jonathan V

    2016-04-01

    Tissue regeneration is a complex process that involves a mosaic of molecules that vary spatially and temporally. Insights into the chemical signaling underlying this process can be achieved with a multiplex and untargeted chemical imaging method such as mass spectrometry imaging (MSI), which can enablede novostudies of nervous system regeneration. A combination of MSI and multivariate statistics was used to differentiate peptide dynamics in the freshwater planarian flatwormSchmidtea mediterraneaat different time points during cephalic ganglia regeneration. A protocol was developed to makeS. mediterraneatissues amenable for MSI. MS ion images of planarian tissue sections allow changes in peptides and unknown compounds to be followed as a function of cephalic ganglia regeneration. In conjunction with fluorescence imaging, our results suggest that even though the cephalic ganglia structure is visible after 6 days of regeneration, the original chemical composition of these regenerated structures is regained only after 12 days. Differences were observed in many peptides, such as those derived from secreted peptide 4 and EYE53-1. Peptidomic analysis further identified multiple peptides from various known prohormones, histone proteins, and DNA- and RNA-binding proteins as being associated with the regeneration process. Mass spectrometry data also facilitated the identification of a new prohormone, which we have named secreted peptide prohormone 20 (SPP-20), and is up-regulated during regeneration in planarians. PMID:26884331

  2. Mass imaging and identification of biomolecules with MALDI-QIT-TOF-based system.

    PubMed

    Shimma, Shuichi; Sugiura, Yuki; Hayasaka, Takahiro; Zaima, Nobuhiro; Matsumoto, Mineo; Setou, Mitsutoshi

    2008-02-01

    Imaging mass spectrometry is becoming a popular visualization technique in the medical and biological sciences. For its continued development, the ability to both visualize and identify molecules directly on the tissue surface using tandem mass spectrometry (MSn) is essential. We established an imaging system based on a matrix-assisted laser/desorption ionization quadrupole ion trap time-of-flight type instrument (AXIMA-QIT, Shimadzu, Kyoto, Japan), which was compatible with both imaging and highly sensitive MSn. In this paper, we present the operating conditions of the AXIMA-QIT as an imaging instrument and introduce the data converter we developed that is available free of charge. The converted data can be applied to Biomap, the commonly used visualization software. For the feasibility experiments, we demonstrated the visualization of phospholipids, glycolipid, and tryptic-digested proteins in the mouse cerebellum. The visualized lipids were successfully identified by MSn directly on the tissue surface, with a strong ability to isolate precursor ions. In the analysis of tryptic-digested proteins, we compared the product ion spectra between AXIMA-QIT and a tandem TOF-type instrument. The results confirmed that AXIMA-QIT can provide a high quality of product ion spectra even on the tissue surface. PMID:18166020

  3. Mass Spectrometry Imaging and Identification of Peptides Associated with Cephalic Ganglia Regeneration in Schmidtea mediterranea*

    PubMed Central

    Ong, Ta-Hsuan; Romanova, Elena V.; Roberts-Galbraith, Rachel H.; Yang, Ning; Zimmerman, Tyler A.; Collins, James J.; Lee, Ji Eun; Kelleher, Neil L.; Newmark, Phillip A.; Sweedler, Jonathan V.

    2016-01-01

    Tissue regeneration is a complex process that involves a mosaic of molecules that vary spatially and temporally. Insights into the chemical signaling underlying this process can be achieved with a multiplex and untargeted chemical imaging method such as mass spectrometry imaging (MSI), which can enable de novo studies of nervous system regeneration. A combination of MSI and multivariate statistics was used to differentiate peptide dynamics in the freshwater planarian flatworm Schmidtea mediterranea at different time points during cephalic ganglia regeneration. A protocol was developed to make S. mediterranea tissues amenable for MSI. MS ion images of planarian tissue sections allow changes in peptides and unknown compounds to be followed as a function of cephalic ganglia regeneration. In conjunction with fluorescence imaging, our results suggest that even though the cephalic ganglia structure is visible after 6 days of regeneration, the original chemical composition of these regenerated structures is regained only after 12 days. Differences were observed in many peptides, such as those derived from secreted peptide 4 and EYE53-1. Peptidomic analysis further identified multiple peptides from various known prohormones, histone proteins, and DNA- and RNA-binding proteins as being associated with the regeneration process. Mass spectrometry data also facilitated the identification of a new prohormone, which we have named secreted peptide prohormone 20 (SPP-20), and is up-regulated during regeneration in planarians. PMID:26884331

  4. MALDI mass spectrometry imaging of formalin-fixed paraffin-embedded tissues in clinical research.

    PubMed

    Gorzolka, Karin; Walch, Axel

    2014-11-01

    The molecular investigation of archived formalin-fixed, paraffin-embedded (FFPE) tissue samples provides the chance to obtain molecular patterns as indicatives for treatment and clinical end points. MALDI mass spectrometry imaging is capable of localizing molecules like proteins and peptides in tissue sections and became a favorite platform for the targeted and non-targeted approaches, especially in clinical investigations for biomarker research. In FFPE tissues the recovery of proteomic information is constrained by fixation-induced cross-links of proteins. The promising new insights obtained from FFPE in combination with the comprehensive patients' data caused much progress in the optimization of MS imaging protocols to investigate FFPE samples. This review presents the past and current research in MALDI MS imaging of FFPE tissues, demonstrating the improvement of analyses, their actual limitations, but also the promising future perspectives for histopathological and tissue-based research. PMID:24838644

  5. The adult body: how age, gender, and body mass index are related to body image.

    PubMed

    Algars, Monica; Santtila, Pekka; Varjonen, Markus; Witting, Katarina; Johansson, Ada; Jern, Patrick; Sandnabba, N Kenneth

    2009-12-01

    OBJECTIVE. Body image and perceived attractiveness were examined, and the impact of age, gender, and body mass index (BMI) was analyzed and discussed from an evolutionary and a sociocultural perspective. METHOD. The population-based sample consisted of 11,468 Finnish men and women aged 18 to 49 years. RESULTS. Both age-related decrease and increase in body satisfaction was detected as well as interactions between age and gender. Some effects were nonlinear. Women were generally less satisfied with their bodies than men. BMI had a stronger influence on women's body image than men's. DISCUSSION. It was proposed that it is insufficient to merely study how age affects general body image because adults might become more satisfied with some aspects of their bodies as a function of age and less satisfied with other aspects. Body satisfaction might also fluctuate during different phases of the adult life, and the patterns possibly differ between men and women. PMID:19897779

  6. Quantification of Absolute Fat Mass by Magnetic Resonance Imaging: a Validation Study against Chemical Analysis

    PubMed Central

    Hu, Houchun H.; Li, Yan; Nagy, Tim R.; Goran, Michael I.; Nayak, Krishna S.

    2011-01-01

    Objective To develop a magnetic resonance imaging (MRI)-based approach for quantifying absolute fat mass in organs, muscles, and adipose tissues, and to validate its accuracy against reference chemical analysis (CA). Methods Chemical-shift imaging can accurately decompose water and fat signals from the acquired MRI data. A proton density fat fraction (PDFF) can be computed from the separated images, and reflects the relative fat content on a voxel-by-voxel basis. The PDFF is mathematically closely related to the fat mass fraction and can be converted to absolute fat mass in grams by multiplying by the voxel volume and the mass density of fat. In this validation study, 97 freshly excised and unique samples from four pigs, comprising of organs, muscles, and adipose and lean tissues were imaged by MRI and then analyzed independently by CA. Linear regression was used to assess correlation, agreement, and measurement differences between MRI and CA. Results Considering all 97 samples, a strong correlation and agreement was obtained between MRI and CA-derived fat mass (slope = 1.01, intercept = 1.99g, r2 = 0.98, p < 0.01). The mean difference d between MRI and CA was 2.17±3.40g. MRI did not exhibit any tendency to under or overestimate CA (p > 0.05). When considering samples from each pig separately, the results were (slope = 1.05, intercept = 1.11g, r2 = 0.98, d = 2.66±4.36g), (slope = 0.99, intercept = 2.33g, r2 = 0.99, d = 1.88±2.68g), (slope = 1.07, intercept = 1.52g, r2 = 0.96, d = 2.73±2.50g), and (slope=0.92, intercept=2.84g, r2 = 0.97, d = 1.18±3.90g), respectively. Conclusion Chemical-shift MRI and PDFF provides an accurate means of determining absolute fat mass in organs, muscles, and adipose and lean tissues. PMID:23204926

  7. Development and Application of a High-Resolution Imaging Mass Spectrometer for the Study of Plant Tissues.

    PubMed

    Takahashi, Katsutoshi; Kozuka, Toshiaki; Anegawa, Aya; Nagatani, Akira; Mimura, Tetsuro

    2015-07-01

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) or imaging mass spectrometry (imaging MS) has been a powerful tool to map the spatial distribution of molecules on the surface of biological materials. This technique has frequently been applied to animal tissue slices for the purpose of mapping proteins, peptides, lipids, sugars or small metabolites to find disease-specific biomarkers or to study drug metabolism. Recently, it has also been applied to intact plant tissues or thin slices thereof using commercial mass spectrometers. The present work is concerned with the refinement of MALDI/laser desorption/ionization (LDI)-Fourier transform ion cyclotron resonance (FTICR)-MS incorporating certain specific features namely, ultra-high mass resolution (>100,000), ultra-high molecular mass accuracy (<1 p.p.m.) and high spatial resolution (<10 µm) for imaging MS of plant tissues. Employing an in-house built mass spectrometer, the imaging MS analysis of intact Arabidopsis thaliana tissues, namely etiolated seedlings and roots of seedlings, glued to a small transparent ITO (indium tin oxide)-coated conductive glass was performed. A matrix substance was applied to the vacuum-dried intact tissues by sublimation prior to the imaging MS analysis. The images of various small metabolites representing their two-dimensional distribution on the dried intact tissues were obtained with or without different matrix substances. The effects of MALDI matrices on the ionization of small metabolites during imaging MS acquisition are discussed. PMID:26063395

  8. Analysis of Mammalian Sphingolipids by Liquid Chromatography Tandem Mass Spectrometry (LC-MS/MS) and Tissue Imaging Mass Spectrometry (TIMS)

    PubMed Central

    Sullards, M. Cameron; Liu, Ying; Chen, Yanfeng; Merrill, Alfred H.

    2011-01-01

    Sphingolipids are a highly diverse category of molecules that serve not only as components of biological structures but also as regulators of numerous cell functions. Because so many of the structural features of sphingolipids give rise to their biological activity, there is a need for comprehensive or “sphingolipidomic” methods for identification and quantitation of as many individual subspecies as possible. This review defines sphingolipids as a class, briefly discusses classical methods for their analysis, and focuses primarily on liquid chromatography tandem mass spectrometry (LC-MS/MS) and tissue imaging mass spectrometry (TIMS). Recently, a set of evolving and expanding methods have been developed and rigorously validated for the extraction, identification, separation, and quantitation of sphingolipids by LC-MS/MS. Quantitation of these biomolecules is made possible via the use of an internal standard cocktail. The compounds that can be readily analyzed are free long-chain (sphingoid) bases, sphingoid base 1-phosphates, and more complex species such as ceramides, ceramide 1-phosphates, sphingomyelins, mono- and di-hexosylceramides sulfatides, and novel compounds such as the 1-deoxy- and 1-(deoxymethyl)-sphingoid bases and their N-acyl-derivatives. These methods can be altered slightly to separate and quantitate isomeric species such as glucosyl/galactosylceramide. Because these techniques require the extraction of sphingolipids from their native environment, any information regarding their localization in histological slices is lost. Therefore, this review also describes methods for TIMS. This technique has been shown to be a powerful tool to determine the localization of individual molecular species of sphingolipids directly from tissue slices. PMID:21749933

  9. High-Spatial and High-Mass Resolution Imaging of Surface Metabolites of Arabidopsis thaliana by Laser Desorption-Ionization Mass Spectrometry Using Colloidal Silver

    SciTech Connect

    Jun, Ji Hyun; Song, Zhihong; Liu, Zhenjiu; Nikolau, Basil J.; Yeung, Edward S.; and Lee, Young Jin

    2010-03-17

    High-spatial resolution and high-mass resolution techniques are developed and adopted for the mass spectrometric imaging of epicuticular lipids on the surface of Arabidopsis thaliana. Single cell level spatial resolution of {approx}12 {micro}m was achieved by reducing the laser beam size by using an optical fiber with 25 {micro}m core diameter in a vacuum matrix-assisted laser desorption ionization-linear ion trap (vMALDI-LTQ) mass spectrometer and improved matrix application using an oscillating capillary nebulizer. Fine chemical images of a whole flower were visualized in this high spatial resolution showing substructure of an anther and single pollen grains at the stigma and anthers. The LTQ-Orbitrap with a MALDI ion source was adopted to achieve MS imaging in high mass resolution. Specifically, isobaric silver ion adducts of C29 alkane (m/z 515.3741) and C28 aldehyde (m/z 515.3377), indistinguishable in low-resolution LTQ, can now be clearly distinguished and their chemical images could be separately constructed. In the application to roots, the high spatial resolution allowed molecular MS imaging of secondary roots and the high mass resolution allowed direct identification of lipid metabolites on root surfaces.

  10. Detection systems for mass spectrometry imaging: a perspective on novel developments with a focus on active pixel detectors.

    PubMed

    Jungmann, Julia H; Heeren, Ron M A

    2013-01-15

    Instrumental developments for imaging and individual particle detection for biomolecular mass spectrometry (imaging) and fundamental atomic and molecular physics studies are reviewed. Ion-counting detectors, array detection systems and high mass detectors for mass spectrometry (imaging) are treated. State-of-the-art detection systems for multi-dimensional ion, electron and photon detection are highlighted. Their application and performance in three different imaging modes--integrated, selected and spectral image detection--are described. Electro-optical and microchannel-plate-based systems are contrasted. The analytical capabilities of solid-state pixel detectors--both charge coupled device (CCD) and complementary metal oxide semiconductor (CMOS) chips--are introduced. The Medipix/Timepix detector family is described as an example of a CMOS hybrid active pixel sensor. Alternative imaging methods for particle detection and their potential for future applications are investigated. PMID:23239313

  11. Mapping of neuropeptides in the crustacean stomatogastric nervous system by imaging mass spectrometry.

    PubMed

    Ye, Hui; Hui, Limei; Kellersberger, Katherine; Li, Lingjun

    2013-01-01

    Considerable effort has been devoted to characterizing the crustacean stomatogastric nervous system (STNS) with great emphasis on comprehensive analysis and mapping distribution of its diverse neuropeptide complement. Previously, immunohistochemistry (IHC) has been applied to this endeavor, yet with identification accuracy and throughput compromised. Therefore, molecular imaging methods are pursued to unequivocally determine the identity and location of the neuropeptides at a high spatial resolution. In this work, we developed a novel, multi-faceted mass spectrometric strategy combining profiling and imaging techniques to characterize and map neuropeptides from the blue crab Callinectes sapidus STNS at the network level. In total, 55 neuropeptides from 10 families were identified from the major ganglia in the C. sapidus STNS for the first time, including the stomatogastric ganglion (STG), the paired commissural ganglia (CoG), the esophageal ganglion (OG), and the connecting nerve stomatogastric nerve (stn) using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) and the MS/MS capability of this technique. In addition, the locations of multiple neuropeptides were documented at a spatial resolution of 25 μm in the STG and upstream nerve using MALDI-TOF/TOF and high-mass-resolution and high-mass-accuracy MALDI-Fourier transform ion cyclotron resonance (FT-ICR) instrument. Furthermore, distributions of neuropeptides in the whole C. sapidus STNS were examined by imaging mass spectrometry (IMS). Different isoforms from the same family were simultaneously and unambiguously mapped, facilitating the functional exploration of neuropeptides present in the crustacean STNS and exemplifying the revolutionary role of this novel platform in neuronal network studies. PMID:23192703

  12. Mapping of Neuropeptides in the Crustacean Stomatogastric Nervous System by Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Ye, Hui; Hui, Limei; Kellersberger, Katherine; Li, Lingjun

    2013-01-01

    Considerable effort has been devoted to characterizing the crustacean stomatogastric nervous system (STNS) with great emphasis on comprehensive analysis and mapping distribution of its diverse neuropeptide complement. Previously, immunohistochemistry (IHC) has been applied to this endeavor, yet with identification accuracy and throughput compromised. Therefore, molecular imaging methods are pursued to unequivocally determine the identity and location of the neuropeptides at a high spatial resolution. In this work, we developed a novel, multi-faceted mass spectrometric strategy combining profiling and imaging techniques to characterize and map neuropeptides from the blue crab Callinectes sapidus STNS at the network level. In total, 55 neuropeptides from 10 families were identified from the major ganglia in the C. sapidus STNS for the first time, including the stomatogastric ganglion (STG), the paired commissural ganglia (CoG), the esophageal ganglion (OG), and the connecting nerve stomatogastric nerve ( stn) using matrix-assisted laser desorption/ionization tandem time-of-flight (MALDI-TOF/TOF) and the MS/MS capability of this technique. In addition, the locations of multiple neuropeptides were documented at a spatial resolution of 25 μm in the STG and upstream nerve using MALDI-TOF/TOF and high-mass-resolution and high-mass-accuracy MALDI-Fourier transform ion cyclotron resonance (FT-ICR) instrument. Furthermore, distributions of neuropeptides in the whole C. sapidus STNS were examined by imaging mass spectrometry (IMS). Different isoforms from the same family were simultaneously and unambiguously mapped, facilitating the functional exploration of neuropeptides present in the crustacean STNS and exemplifying the revolutionary role of this novel platform in neuronal network studies.

  13. Proteome-wide drug screening using mass spectrometric imaging of bead-arrays

    PubMed Central

    Zhou, Ying; Liu, Ziying; Rothschild, Kenneth J.; Lim, Mark J.

    2016-01-01

    A fundamental challenge in the drug discovery process is to develop compounds with high efficacy and minimal side-effects. We describe a new approach to proteome-wide drug screening for detection of on- and off-target binding which combines the advantages of mass spectrometry with microarray technology. The method involves matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) of agarose micro-beads randomly arrayed at high-density in custom micro-well plates. Each bead carries a unique protein target and a corresponding photocleavable mass-tag for coding (PC-Mass-Tag). Compounds bound to specific protein beads and a photo-released coding PC-Mass-Tag are detected simultaneously using MALDI-MSI. As an initial demonstration of this approach, two kinase-targeted drugs, Dasatinib and Brigatinib (AP26113), were simultaneously screened against a model 50-member kinase-bead library. A MALDI-MSI scan performed at the equivalent density of 495,000 beads in the footprint of a microscope slide yielded 100% sensitivity for detecting known strong interactions with no false positives. PMID:27194112

  14. Proteome-wide drug screening using mass spectrometric imaging of bead-arrays.

    PubMed

    Zhou, Ying; Liu, Ziying; Rothschild, Kenneth J; Lim, Mark J

    2016-01-01

    A fundamental challenge in the drug discovery process is to develop compounds with high efficacy and minimal side-effects. We describe a new approach to proteome-wide drug screening for detection of on- and off-target binding which combines the advantages of mass spectrometry with microarray technology. The method involves matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) of agarose micro-beads randomly arrayed at high-density in custom micro-well plates. Each bead carries a unique protein target and a corresponding photocleavable mass-tag for coding (PC-Mass-Tag). Compounds bound to specific protein beads and a photo-released coding PC-Mass-Tag are detected simultaneously using MALDI-MSI. As an initial demonstration of this approach, two kinase-targeted drugs, Dasatinib and Brigatinib (AP26113), were simultaneously screened against a model 50-member kinase-bead library. A MALDI-MSI scan performed at the equivalent density of 495,000 beads in the footprint of a microscope slide yielded 100% sensitivity for detecting known strong interactions with no false positives. PMID:27194112

  15. A new and fast image feature selection method for developing an optimal mammographic mass detection scheme

    PubMed Central

    Tan, Maxine; Pu, Jiantao; Zheng, Bin

    2014-01-01

    Purpose: Selecting optimal features from a large image feature pool remains a major challenge in developing computer-aided detection (CAD) schemes of medical images. The objective of this study is to investigate a new approach to significantly improve efficacy of image feature selection and classifier optimization in developing a CAD scheme of mammographic masses. Methods: An image dataset including 1600 regions of interest (ROIs) in which 800 are positive (depicting malignant masses) and 800 are negative (depicting CAD-generated false positive regions) was used in this study. After segmentation of each suspicious lesion by a multilayer topographic region growth algorithm, 271 features were computed in different feature categories including shape, texture, contrast, isodensity, spiculation, local topological features, as well as the features related to the presence and location of fat and calcifications. Besides computing features from the original images, the authors also computed new texture features from the dilated lesion segments. In order to select optimal features from this initial feature pool and build a highly performing classifier, the authors examined and compared four feature selection methods to optimize an artificial neural network (ANN) based classifier, namely: (1) Phased Searching with NEAT in a Time-Scaled Framework, (2) A sequential floating forward selection (SFFS) method, (3) A genetic algorithm (GA), and (4) A sequential forward selection (SFS) method. Performances of the four approaches were assessed using a tenfold cross validation method. Results: Among these four methods, SFFS has highest efficacy, which takes 3%–5% of computational time as compared to GA approach, and yields the highest performance level with the area under a receiver operating characteristic curve (AUC) = 0.864 ± 0.034. The results also demonstrated that except using GA, including the new texture features computed from the dilated mass segments improved the AUC

  16. MALDI FTICR IMS of intact proteins: Using mass accuracy to link protein images with proteomics data

    PubMed Central

    Spraggins, Jeffrey M.; Rizzo, David G.; Moore, Jessica L.; Rose, Kristie L.; Hammer, Neal D.; Skaar, Eric P.; Caprioli, Richard M.

    2015-01-01

    MALDI imaging mass spectrometry is a highly sensitive and selective tool used to visualize biomolecules in tissue. However, identification of detected proteins remains a difficult task. Indirect identifications strategies have been limited by insufficient mass accuracy to confidently link ion images to proteomics data. Here we demonstrate the capabilities of MALDI FTICR MS for imaging intact proteins. MALDI FTICR IMS provides an unprecedented combination of mass resolving power (∼75,000 at m/z 5,000) and accuracy (<5 ppm) for proteins up to ∼12 kDa enabling identification based on correlation with LC-MS/MS proteomics data. Analysis of rat brain tissue was performed as a proof-of-concept highlighting the capabilities of this approach by imaging and identifying a number of proteins including N-terminally acetylated Thymosin β4 (m/z 4,963.502, 0.6 ppm) and ATP Synthase subunit ε (m/z 5,636.074, −2.3 ppm). MALDI FTICR IMS was also used to differentiate a series of oxidation products of S100A8 (m/z 10,164.03, −2.1 ppm), a subunit of the heterodimer calprotectin, in kidney tissue from mice infected with Staphylococcus aureus. S100A8 – M37O/C42O3 (m/z 10228.00, −2.6 ppm) was found to co-localize with bactierial microcolonies at the center of infectious foci. The ability of MALDI FTICR IMS to distinguish S100A8 modifications is critical to understanding calprotectin’s roll in nutritional immunity. PMID:25904064

  17. MALDI FTICR IMS of Intact Proteins: Using Mass Accuracy to Link Protein Images with Proteomics Data

    NASA Astrophysics Data System (ADS)

    Spraggins, Jeffrey M.; Rizzo, David G.; Moore, Jessica L.; Rose, Kristie L.; Hammer, Neal D.; Skaar, Eric P.; Caprioli, Richard M.

    2015-06-01

    MALDI imaging mass spectrometry is a highly sensitive and selective tool used to visualize biomolecules in tissue. However, identification of detected proteins remains a difficult task. Indirect identification strategies have been limited by insufficient mass accuracy to confidently link ion images to proteomics data. Here, we demonstrate the capabilities of MALDI FTICR MS for imaging intact proteins. MALDI FTICR IMS provides an unprecedented combination of mass resolving power (~75,000 at m/z 5000) and accuracy (<5ppm) for proteins up to ~12kDa, enabling identification based on correlation with LC-MS/MS proteomics data. Analysis of rat brain tissue was performed as a proof-of-concept highlighting the capabilities of this approach by imaging and identifying a number of proteins including N-terminally acetylated thymosin β4 ( m/z 4,963.502, 0.6ppm) and ATP synthase subunit ɛ ( m/z 5,636.074, -2.3ppm). MALDI FTICR IMS was also used to differentiate a series of oxidation products of S100A8 ( m/z 10,164.03, -2.1ppm), a subunit of the heterodimer calprotectin, in kidney tissue from mice infected with Staphylococcus aureus. S100A8 - M37O/C42O3 ( m/z 10228.00, -2.6ppm) was found to co-localize with bacterial microcolonies at the center of infectious foci. The ability of MALDI FTICR IMS to distinguish S100A8 modifications is critical to understanding calprotectin's roll in nutritional immunity.

  18. NICMOS Imaging Survey of Dusty Debris Around Nearby Stars Across the Stellar Mass Spectrum

    NASA Astrophysics Data System (ADS)

    Rhee, Joseph

    2007-07-01

    Association of planetary systems with dusty debris disks is now quite secure, and advances in our understanding of planet formation and evolution can be achieved by the identification and characterization of an ensemble of debris disks orbiting a range of central stars with different masses and ages. Imaging debris disks in starlight scattered by dust grains remains technically challenging so that only about a dozen systems have thus far been imaged. A further advance in this field needs an increased number of imaged debris disks. However, the technical challege of such observations, even with the superb combination of HST and NICMOS, requires the best targets. Recent HST imaging investigations of debris disks were sample-limited not limited by the technology used. We performed a search for debris disks from a IRAS/Hipparcos cross correlation which involved an exhaustive background contamination check to weed out false excess stars. Out of ~140 identified debris disks, we selected 22 best targets in terms of dust optical depth and disk angular size. Our target sample represents the best currently available target set in terms of both disk brightness and resolvability. For example, our targets have higher dust optical depth, in general, than newly identified Spitzer disks. Also, our targets cover a wider range of central star ages and masses than previous debris disk surveys. This will help us to investigate planetary system formation and evolution across the stellar mass spectrum.The technical feasibility of this program in two-gyro mode guiding has been proven with on-orbit calibration and science observations during HST cycles 13, 14, and 15.

  19. Validation of fuzzy logic method for automated mass spectral classification for mineral imaging

    NASA Astrophysics Data System (ADS)

    Yan, B.; McJunkin, T. R.; Stoner, D. L.; Scott, J. R.

    2006-12-01

    Imaging mass spectrometry requires the acquisition and interpretation of hundreds to thousands of individual spectra in order to map the mineral phases within heterogeneous geomatrices. A fuzzy logic inference engine (FLIE) was developed to automate data interpretation. To evaluate the strengths and limitations of FLIE, the chemical images obtained using FLIE were compared with those developed using two chemometric methods: principle component analysis (PCA) and cluster analysis (K-Means). Two heterogeneous geomatrices, a low-grade chalcopyrite ore and basalt, were imaged using a laser-desorption Fourier transform mass spectrometer. Similar mineral distribution patterns in the chalcopyrite ore sample were obtained by the three data analysis methods with most of the differences occurring at the interfaces between mineral phases. PCA missed one minor mineral phase in the chalcopyrite ore sample and did not clearly differentiate among the mineral classes of the basalt. K-Means cluster analysis differentiated among the various mineral phases in both samples, but improperly grouped some spectra in the chalcopyrite sample that only contained unanticipated high mass peaks. Unlike the chemometric methods, FLIE was able to classify spectra as unknowns for those spectra that fell below the confidence level threshold. A nearest neighbor approach, included in FLIE, was used to classify the unknowns to form a visually complete image; however, the unknowns identified by FLIE can be informative because they highlight potential problems or overlooked results. In conclusion, this study validated the fuzzy logic-based approach used in our laboratory and reveald some limitations in the three techniques that were evaluated.

  20. Validation of Fuzzy Logic Method for Automated Mass Spectral Classification for Mineral Imaging

    SciTech Connect

    B. Yan; B. Yan; T. R. McJunkiin; D. L. Stoner

    2006-12-01

    Imaging mass spectrometry requires the acquisition and interpretation of hundreds to thousands of individual spectra in order to map the mineral phases within heterogeneous geomatrices. A fuzzy logic inference engine (FLIE) was developed to automate data interpretation. To evaluate the strengths and limitations of FLIE, the chemical images obtained using FLIE were compared with those developed using two chemometric methods: principle component analysis (PCA) and cluster analysis (K-Means). Two heterogeneous geomatrices, a low-grade chalcopyrite ore and basalt, were imaged using a laser-desorption Fourier transform mass spectrometer. Similar mineral distribution patterns in the chalcopyrite ore sample were obtained by the three data analysis methods with most of the differences occurring at the interfaces between mineral phases. PCA missed one minor mineral phase in the chalcopyrite ore sample and did not clearly differentiate among the mineral classes of the basalt. K-Means cluster analysis differentiated among the various mineral phases in both samples, but improperly grouped some spectra in the chalcopyrite sample that only contained unanticipated high mass peaks. Unlike the chemometric methods, FLIE was able to classify spectra as unknowns for those spectra that fell below the confidence level threshold. A nearest neighbor approach, included in FLIE, was used to classify the unknowns to form a visually complete image; however, the unknowns identified by FLIE can be informative because they highlight potential problems or overlooked results. In conclusion, this study validated the fuzzy logic-based approach used in our laboratory and reveald some limitations in the three techniques that were evaluated.

  1. Mass spectrometry imaging: an expeditious and powerful technique for fast in situ lignin assessment in Eucalyptus.

    PubMed

    Araújo, Pedro; Ferreira, Mônica Siqueira; de Oliveira, Diogo Noin; Pereira, Luciano; Sawaya, Alexandra Christine Helena Frankland; Catharino, Rodrigo Ramos; Mazzafera, Paulo

    2014-04-01

    Plant biomass has been suggested as an alternative to produce bioethanol. The recalcitrance of plant biomass to convert cellulose into simpler carbohydrates used in the fermentation process is partially due to lignin, but the standard methods used to analyze lignin composition frequently use toxic solvents and are laborious and time-consuming. MS imaging was used to study lignin in Eucalyptus, since this genus is the main source of cellulose in the world. Hand-cut sections of stems of two Eucalyptus species were covered with silica and directly analyzed by matrix-assisted laser sesorption ionization (MALDI)-imaging mass spectrometry (MS). Information available in the literature about soluble lignin subunits and structures were used to trace their distribution in the sections and using a software image a relative quantification could be made. Matrixes routinely used in MALDI-imaging analysis are not satisfactory to analyze plant material and were efficiently substituted by thin layer chromatography (TLC) grade silica. A total of 22 compounds were detected and relatively quantified. It was also possible to establish a proportion between syringyl and guaiacyl monolignols, characteristic for each species. Because of the simple way that samples are prepared, the MALDI-imaging approach presented here can replace, in routine analysis, complex and laborious MS methods in the study of lignin composition. PMID:24451041

  2. High-Speed MALDI MS/MS Imaging Mass Spectrometry Using Continuous Raster Sampling

    PubMed Central

    Prentice, Boone M.; Chumbley, Chad W.; Caprioli, Richard M.

    2015-01-01

    A matrix-assisted laser desorption/ionization time of flight/time of flight tandem mass spectrometer (MALDI TOF/TOF) has been used for high-speed precursor/fragment ion transition image acquisition. High throughput analysis is facilitated by a Nd:YLF solid state laser capable of pulse repetition rates up to 5 kHz, a high digitizer acquisition rate (up to 50 pixels/second), and continuous laser raster sampling. MS/MS experiments are enabled through the use of a precision timed ion selector, second source acceleration, and a dedicated collision cell. Continuous raster sampling is shown here to facilitate rapid MS/MS ion image acquisition from thin tissue sections for the drug rifampicin and of a common kidney lipid, SM4s(d18:1/24:1). The ability to confirm the structural identity of an analyte as part of the MS/MS imaging experiment is an essential part of the analysis. Additionally, the increase in sensitivity and specificity afforded by an MS/MS approach is highly advantageous, especially when interrogating complex chemical environments such as those in biological tissues. Herein, we report continuous laser raster sampling TOF/TOF imaging methodologies which demonstrate 8-14 fold increases in throughput compared to existing MS/MS instrumentation, an important advantage when imaging large areas on tissues. PMID:26149115

  3. Distribution of terfenadine and its metabolites in locusts studied by desorption electrospray ionization mass spectrometry imaging.

    PubMed

    Olsen, Line Rørbæk; Hansen, Steen Honoré; Janfelt, Christian

    2015-03-01

    Desorption electrospray ionization (DESI) mass spectrometry (MS) imaging was used to image locusts dosed with the antihistamine drug terfenadine. The study was conducted in order to elucidate a relatively high elimination rate of terfenadine from the locust hemolymph. In this one of the few MS imaging studies on insects, a method for cryosectioning of whole locusts was developed, and the distributions of a number of endogenous compounds are reported, including betaine and a number of amino acids and phospholipids. Terfenadine was detected in the stomach region and the intestine walls, whereas three different metabolites-terfenadine acid (fexofenadine), terfenadine glucoside, and terfenadine phosphate-were detected in significantly smaller amounts and only in the unexcreted feces in the lower part of the intestine. The use of MS/MS imaging was necessary in order to detect the metabolites. With use of DESI-MS imaging, no colocalization of the drug and the metabolites was observed, suggesting a very rapid excretion of metabolites into the feces. Additional liquid chromatography-MS investigations were performed on hemolymph and feces and showed some abundance of terfenadine and the three metabolites, although at low levels, in both the hemolymph and the feces. PMID:25404166

  4. Application of Paramagnetically Tagged Molecules for Magnetic Resonance Imaging of Biofilm Mass Transport Processes▿

    PubMed Central

    Ramanan, B.; Holmes, W. M.; Sloan, W. T.; Phoenix, V. R.

    2010-01-01

    Molecules become readily visible by magnetic resonance imaging (MRI) when labeled with a paramagnetic tag. Consequently, MRI can be used to image their transport through porous media. In this study, we demonstrated that this method could be applied to image mass transport processes in biofilms. The transport of a complex of gadolinium and diethylenetriamine pentaacetic acid (Gd-DTPA), a commercially available paramagnetic molecule, was imaged both in agar (as a homogeneous test system) and in a phototrophic biofilm. The images collected were T1 weighted, where T1 is an MRI property of the biofilm and is dependent on Gd-DTPA concentration. A calibration protocol was applied to convert T1 parameter maps into concentration maps, thus revealing the spatially resolved concentrations of this tracer at different time intervals. Comparing the data obtained from the agar experiment with data from a one-dimensional diffusion model revealed that transport of Gd-DTPA in agar was purely via diffusion, with a diffusion coefficient of 7.2 × 10−10 m2 s−1. In contrast, comparison of data from the phototrophic biofilm experiment with data from a two-dimensional diffusion model revealed that transport of Gd-DTPA inside the biofilm was by both diffusion and advection, equivalent to a diffusion coefficient of 1.04 × 10−9 m2 s−1. This technology can be used to further explore mass transport processes in biofilms, either by using the wide range of commercially available paramagnetically tagged molecules and nanoparticles or by using bespoke tagged molecules. PMID:20435773

  5. Next-generation technologies for spatial proteomics: Integrating ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR imaging mass spectrometry for protein analysis.

    PubMed

    Spraggins, Jeffrey M; Rizzo, David G; Moore, Jessica L; Noto, Michael J; Skaar, Eric P; Caprioli, Richard M

    2016-06-01

    MALDI imaging mass spectrometry is a powerful analytical tool enabling the visualization of biomolecules in tissue. However, there are unique challenges associated with protein imaging experiments including the need for higher spatial resolution capabilities, improved image acquisition rates, and better molecular specificity. Here we demonstrate the capabilities of ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR IMS platforms as they relate to these challenges. High spatial resolution MALDI-TOF protein images of rat brain tissue and cystic fibrosis lung tissue were acquired at image acquisition rates >25 pixels/s. Structures as small as 50 μm were spatially resolved and proteins associated with host immune response were observed in cystic fibrosis lung tissue. Ultra-high speed MALDI-TOF enables unique applications including megapixel molecular imaging as demonstrated for lipid analysis of cystic fibrosis lung tissue. Additionally, imaging experiments using MALDI FTICR IMS were shown to produce data with high mass accuracy (<5 ppm) and resolving power (∼75 000 at m/z 5000) for proteins up to ∼20 kDa. Analysis of clear cell renal cell carcinoma using MALDI FTICR IMS identified specific proteins localized to healthy tissue regions, within the tumor, and also in areas of increased vascularization around the tumor. PMID:27060368

  6. Mass imaging of ketamine in a single scalp hair by MALDI-FTMS.

    PubMed

    Shen, Min; Xiang, Ping; Shi, Yan; Pu, Hai; Yan, Hui; Shen, Baohua

    2014-07-01

    Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) coupled with mass spectrometry imaging (MSI) is a rapidly emerging technology that produces distribution maps of small pharmaceutical molecules in situ in tissue sections. Segmental hair analysis provides useful information regarding the state and history of drug use. A preliminary MALDI-Fourier transform ion cyclotron resonance (FTICR)-MSI method was developed for direct identification and imaging of ketamine in hair samples. After decontamination, the scalp hair samples from ketamine users were scraped gently and were fixed onto a stainless steel MALDI plate using double-sided adhesive tape. A Bruker 9.4 T solariX FTICR mass spectrometer with continuous accumulation of selected ions function was used in the positive ion mode. Four single hairs from the same drug abuser were analyzed. Three of four single hairs demonstrated ketamine spatial distribution, while only traces of ketamine were identified in the other one. The platform could provide detection power of ketamine down to the 7.7 ng/mg level in hair. MALDI-FTICR-MSI demonstrated the drug distribution over the whole hair length with higher spatial resolution compared with the traditional LC-MS/MS method after scissor cutting. Greater caution is needed in the interpretation of a single hair result because of the considerable variations in the growth rate and sample collection. PMID:24906693

  7. Imaging of Endogenous Metabolites of Plant Leaves by Mass Spectrometry Based on Laser Activated Electron Tunneling

    PubMed Central

    Huang, Lulu; Tang, Xuemei; Zhang, Wenyang; Jiang, Ruowei; Chen, Disong; Zhang, Juan; Zhong, Hongying

    2016-01-01

    A new mass spectrometric imaging approach based on laser activated electron tunneling (LAET) was described and applied to analysis of endogenous metabolites of plant leaves. LAET is an electron-directed soft ionization technique. Compressed thin films of semiconductor nanoparticles of bismuth cobalt zinc oxide were placed on the sample plate for proof-of-principle demonstration because they can not only absorb ultraviolet laser but also have high electron mobility. Upon laser irradiation, electrons are excited from valence bands to conduction bands. With appropriate kinetic energies, photoexcited electrons can tunnel away from the barrier and eventually be captured by charge deficient atoms present in neutral molecules. Resultant unpaired electron subsequently initiates specific chemical bond cleavage and generates ions that can be detected in negative ion mode of the mass spectrometer. LAET avoids the co-crystallization process of routinely used organic matrix materials with analyzes in MALDI (matrix assisted-laser desorption ionization) analysis. Thus uneven distribution of crystals with different sizes and shapes as well as background peaks in the low mass range resulting from matrix molecules is eliminated. Advantages of LAET imaging technique include not only improved spatial resolution but also photoelectron capture dissociation which produces predictable fragment ions. PMID:27053227

  8. Imaging of Endogenous Metabolites of Plant Leaves by Mass Spectrometry Based on Laser Activated Electron Tunneling

    NASA Astrophysics Data System (ADS)

    Huang, Lulu; Tang, Xuemei; Zhang, Wenyang; Jiang, Ruowei; Chen, Disong; Zhang, Juan; Zhong, Hongying

    2016-04-01

    A new mass spectrometric imaging approach based on laser activated electron tunneling (LAET) was described and applied to analysis of endogenous metabolites of plant leaves. LAET is an electron-directed soft ionization technique. Compressed thin films of semiconductor nanoparticles of bismuth cobalt zinc oxide were placed on the sample plate for proof-of-principle demonstration because they can not only absorb ultraviolet laser but also have high electron mobility. Upon laser irradiation, electrons are excited from valence bands to conduction bands. With appropriate kinetic energies, photoexcited electrons can tunnel away from the barrier and eventually be captured by charge deficient atoms present in neutral molecules. Resultant unpaired electron subsequently initiates specific chemical bond cleavage and generates ions that can be detected in negative ion mode of the mass spectrometer. LAET avoids the co-crystallization process of routinely used organic matrix materials with analyzes in MALDI (matrix assisted-laser desorption ionization) analysis. Thus uneven distribution of crystals with different sizes and shapes as well as background peaks in the low mass range resulting from matrix molecules is eliminated. Advantages of LAET imaging technique include not only improved spatial resolution but also photoelectron capture dissociation which produces predictable fragment ions.

  9. Imaging of Endogenous Metabolites of Plant Leaves by Mass Spectrometry Based on Laser Activated Electron Tunneling.

    PubMed

    Huang, Lulu; Tang, Xuemei; Zhang, Wenyang; Jiang, Ruowei; Chen, Disong; Zhang, Juan; Zhong, Hongying

    2016-01-01

    A new mass spectrometric imaging approach based on laser activated electron tunneling (LAET) was described and applied to analysis of endogenous metabolites of plant leaves. LAET is an electron-directed soft ionization technique. Compressed thin films of semiconductor nanoparticles of bismuth cobalt zinc oxide were placed on the sample plate for proof-of-principle demonstration because they can not only absorb ultraviolet laser but also have high electron mobility. Upon laser irradiation, electrons are excited from valence bands to conduction bands. With appropriate kinetic energies, photoexcited electrons can tunnel away from the barrier and eventually be captured by charge deficient atoms present in neutral molecules. Resultant unpaired electron subsequently initiates specific chemical bond cleavage and generates ions that can be detected in negative ion mode of the mass spectrometer. LAET avoids the co-crystallization process of routinely used organic matrix materials with analyzes in MALDI (matrix assisted-laser desorption ionization) analysis. Thus uneven distribution of crystals with different sizes and shapes as well as background peaks in the low mass range resulting from matrix molecules is eliminated. Advantages of LAET imaging technique include not only improved spatial resolution but also photoelectron capture dissociation which produces predictable fragment ions. PMID:27053227

  10. Polarization of Directly Imaged Young Giant Planets as a Probe of Mass, Rotation, and Clouds

    NASA Technical Reports Server (NTRS)

    Marley, Mark Scott; Sengupta, Sujan

    2012-01-01

    Young, hot gas giant planets at large separations from their primaries have been directly imaged around several nearby stars. More such planets will likely be detected by ongoing and new imaging surveys with instruments such as the Gemini Planet Imager (GPI). Efforts continue to model the spectra of these planets in order to constrain their masses, effective temperatures, composition, and cloud structure. One potential tool for analyzing these objects, which has received relatively less attention, is polarization. Linear polarization of gas giant exoplanets can arise from the combined influences of light scattering by atmospheric dust and a rotationally distorted shape. The oblateness of gas giant planet increases of course with rotation rate and for fixed rotation also rises with decreasing gravity. Thus young, lower mass gas giant planets with youthful inflated radii could easily have oblateness greater than that of Saturn s 10%. We find that polarizations of over 1% may easily be produced in the near-infrared in such cases. This magnitude of polarization may be measurable by GPI and other instruments. Thus if detected, polarization of a young Jupiter places constraints on the combination of its gravity, rotation rate, and degree of cloudiness. We will present results of our multiple scattering analysis coupled with a self-consistent dusty atmospheric models to demonstrate the range of polarizations that might be expected from resolved exoplanets and the range of parameter space that such observations may inform.

  11. Three-dimensional segmentation of the tumor mass in computed tomographic images of neuroblastoma

    NASA Astrophysics Data System (ADS)

    Deglint, Hanford J.; Rangayyan, Rangaraj M.; Boag, Graham S.

    2004-05-01

    Tumor definition and diagnosis require the analysis of the spatial distribution and Hounsfield unit (HU) values of voxels in computed tomography (CT) images, coupled with a knowledge of normal anatomy. Segmentation of the tumor in neuroblastoma is complicated by the fact that the mass is almost always heterogeneous in nature; furthermore, viable tumor, necrosis, fibrosis, and normal tissue are often intermixed. Rather than attempt to separate these tissue types into distinct regions, we propose to explore methods to delineate the normal structures expected in abdominal CT images, remove them from further consideration, and examine the remaining parts of the images for the tumor mass. We explore the use of fuzzy connectivity for this purpose. Expert knowledge provided by the radiologist in the form of the expected structures and their shapes, HU values, and radiological characteristics are also incorporated in the segmentation algorithm. Segmentation and analysis of the tissue composition of the tumor can assist in quantitative assessment of the response to chemotherapy and in the planning of delayed surgery for resection of the tumor. The performance of the algorithm is evaluated using cases acquired from the Alberta Children's Hospital.

  12. Molecular Surface Sampling and Chemical Imaging using Proximal Probe Thermal Desorption/Secondary Ionization Mass Spectrometry

    SciTech Connect

    Ovchinnikova, Olga S; Kertesz, Vilmos; Van Berkel, Gary J

    2011-01-01

    Proximal probe thermal desorption/secondary ionization mass spectrometry was studied and applied to molecular surface sampling and chemical imaging using printed patterns on photopaper as test substrates. With the use of a circular cross section proximal probe with a tip diameter of 50 m and fixed temperature (350 C), the influence of probe-to-surface distance, lane scan spacing, and surface scan speed on signal quality and spatial resolution were studied and optimized. As a compromise between signal amplitude, signal reproducibility, and data acquisition time, a surface scan speed of 100 m/s, probe-to-paper surface distance of 5 m, and lane spacing of 10 m were used for imaging. Under those conditions the proximal probe thermal desorption/secondary ionization mass spectrometry method was able to achieve a spatial resolution of about 50 m as determined by the ability to distinguish surface patterns of known dimensions that were printed on the paper substrate. It is expected that spatial resolution and chemical image quality could be further improved by using probes of smaller cross section size and by incorporating a means to maintain a fixed optimal probe-to-surface distance real time, continuously adapting to the changing topography of the surface during a lane scan.

  13. Small molecule ambient mass spectrometry imaging by infrared laser ablation metastable-induced chemical ionization.

    PubMed

    Galhena, Asiri S; Harris, Glenn A; Nyadong, Leonard; Murray, Kermit K; Fernández, Facundo M

    2010-03-15

    Presented here is a novel ambient ion source termed infrared laser ablation metastable-induced chemical ionization (IR-LAMICI). IR-LAMICI integrates IR laser ablation and direct analysis in real time (DART)-type metastable-induced chemical ionization for open air mass spectrometry (MS) ionization. The ion generation in the IR-LAMICI source is a two step process. First, IR laser pulses impinge the sample surface ablating surface material. Second, a portion of ablated material reacts with the metastable reactive plume facilitating gas-phase chemical ionization of analyte molecules generating protonated or deprotonated species in positive and negative ion modes, respectively. The successful coupling of IR-laser ablation with metastable-induced chemical ionization resulted in an ambient plasma-based spatially resolved small molecule imaging platform for mass spectrometry (MS). The analytical capabilities of IR-LAMICI are explored by imaging pharmaceutical tablets, screening counterfeit drugs, and probing algal tissue surfaces for natural products. The resolution of a chemical image is determined by the crater size produced with each laser pulse but not by the size of the metastable gas jet. The detection limits for an active pharmaceutical ingredient (acetaminophen) using the IR-LAMICI source is calculated to be low picograms. Furthermore, three-dimensional computational fluid dynamic simulations showed improvements in the IR-LAMICI ion source are possible. PMID:20155978

  14. Imaging and Rapid-Scanning Ion Mass Spectrometer (IRM) for the CASSIOPE e-POP Mission

    NASA Astrophysics Data System (ADS)

    Yau, Andrew W.; Howarth, Andrew; White, Andrew; Enno, Greg; Amerl, Peter

    2015-06-01

    The imaging and rapid-scanning ion mass spectrometer (IRM) is part of the Enhanced Polar Outflow Probe (e-POP) instrument suite on the Canadian CASSIOPE small satellite. Designed to measure the composition and detailed velocity distributions of ions in the ˜1-100 eV/q range on a non-spinning spacecraft, the IRM sensor consists of a planar entrance aperture, a pair of electrostatic deflectors, a time-of-flight (TOF) gate, a hemispherical electrostatic analyzer, and a micro-channel plate (MCP) detector. The TOF gate measures the transit time of each detected ion inside the sensor. The hemispherical analyzer disperses incident ions by their energy-per-charge and azimuth in the aperture plane onto the detector. The two electrostatic deflectors may be optionally programmed to step through a sequence of deflector voltages, to deflect ions of different incident elevation out of the aperture plane and energy-per-charge into the sensor aperture for sampling. The position and time of arrival of each detected ion at the detector are measured, to produce an image of 2-dimensional (2D), mass-resolved ion velocity distribution up to 100 times per second, or to construct a composite 3D velocity distribution by combining successive images in a deflector voltage sequence. The measured distributions are then used to investigate ion composition, density, drift velocity and temperature in polar ion outflows and related acceleration and transport processes in the topside ionosphere.

  15. Anti-theft device staining on banknotes detected by mass spectrometry imaging.

    PubMed

    Correa, Deleon Nascimento; Zacca, Jorge Jardim; Rocha, Werickson Fortunato de Carvalho; Borges, Rodrigo; de Souza, Wanderley; Augusti, Rodinei; Eberlin, Marcos Nogueira; Vendramini, Pedro Henrique

    2016-03-01

    We describe the identification and limits of detection of ink staining by mass spectrometry imaging (MSI), as used in anti-theft devices (ATDs). Such ink staining is applied to banknotes during automated teller machine (ATM) explosions. Desorption electrospray ionization (DESI) coupled with high-resolution and high-accuracy orbitrap mass spectrometry (MS) and a moving stage device were applied to obtain 2D molecular images of the major dyes used for staining, that is, 1-methylaminoanthraquinone (MAAQ), rhodamine B (RB) and rhodamine 6G (R6G). MAAQ could not be detected because of its inefficient desorption by DESI from the banknote cellulose surface. By contrast, ATD staining on banknotes is perceptible by the human naked eye only at concentrations higher than 0.2 μg cm(-2), whereas both RB and R6G at concentrations 200 times lower (as low as 0.001 μg cm(-2)) could be easily detected and imaged by DESI-MSI, with selective and specific identification of each analyte and their spatial distribution on samples from suspects. This technique is non-destructive, and no sample preparation is required, which ensures sample preservation for further forensic investigations. PMID:26784008

  16. Mass Estimates of Rapidly Moving Prominence Material from High-cadence EUV Images

    NASA Astrophysics Data System (ADS)

    Williams, David R.; Baker, Deborah; van Driel-Gesztelyi, Lidia

    2013-02-01

    We present a new method for determining the column density of erupting filament material using state-of-the-art multi-wavelength imaging data. Much of the prior work on filament/prominence structure can be divided between studies that use a polychromatic approach with targeted campaign observations and those that use synoptic observations, frequently in only one or two wavelengths. The superior time resolution, sensitivity, and near-synchronicity of data from the Solar Dynamics Observatory's Advanced Imaging Assembly allow us to combine these two techniques using photoionization continuum opacity to determine the spatial distribution of hydrogen in filament material. We apply the combined techniques to SDO/AIA observations of a filament that erupted during the spectacular coronal mass ejection on 2011 June 7. The resulting "polychromatic opacity imaging" method offers a powerful way to track partially ionized gas as it erupts through the solar atmosphere on a regular basis, without the need for coordinated observations, thereby readily offering regular, realistic mass-distribution estimates for models of these erupting structures.

  17. Standard Reticle Slide To Objectively Evaluate Spatial Resolution and Instrument Performance in Imaging Mass Spectrometry.

    PubMed

    Zubair, Faizan; Prentice, Boone M; Norris, Jeremy L; Laibinis, Paul E; Caprioli, Richard M

    2016-07-19

    Spatial resolution is a key parameter in imaging mass spectrometry (IMS). Aside from being a primary determinant in overall image quality, spatial resolution has important consequences on the acquisition time of the IMS experiment and the resulting file size. Hardware and software modifications during instrumentation development can dramatically affect the spatial resolution achievable using a given imaging mass spectrometer. As such, an accurate and objective method to determine the working spatial resolution is needed to guide instrument development and ensure quality IMS results. We have used lithographic and self-assembly techniques to fabricate a pattern of crystal violet as a standard reticle slide for assessing spatial resolution in matrix-assisted laser desorption/ionization (MALDI) IMS experiments. The reticle is used to evaluate spatial resolution under user-defined instrumental conditions. Edgespread analysis measures the beam diameter for a Gaussian profile and line scans measure an "effective" spatial resolution that is a convolution of beam optics and sampling frequency. The patterned crystal violet reticle was also used to diagnose issues with IMS instrumentation such as intermittent losses of pixel data. PMID:27299987

  18. High-contrast Imaging of Intermediate-mass Giants with Long-term Radial Velocity Trends

    NASA Astrophysics Data System (ADS)

    Ryu, Tsuguru; Sato, Bun’ei; Kuzuhara, Masayuki; Narita, Norio; Takahashi, Yasuhiro H.; Uyama, Taichi; Kudo, Tomoyuki; Kusakabe, Nobuhiko; Hashimoto, Jun; Omiya, Masashi; Harakawa, Hiroki; Abe, Lyu; Ando, Hiroyasu; Brandner, Wolfgang; Brandt, Timothy D.; Carson, Joseph C.; Currie, Thayne; Egner, Sebastian; Feldt, Markus; Goto, Miwa; Grady, Carol A.; Guyon, Olivier; Hayano, Yutaka; Hayashi, Masahiko; Hayashi, Saeko S.; Hełminiak, Krzysztof G.; Henning, Thomas; Hodapp, Klaus W.; Ida, Shigeru; Ishii, Miki; Itoh, Yoichi; Iye, Masanori; Izumiura, Hideyuki; Janson, Markus; Kambe, Eiji; Kandori, Ryo; Knapp, Gillian R.; Kokubo, Eiichiro; Kwon, Jungmi; Matsuo, Taro; Mayama, Satoshi; McElwain, Michael W.; Mede, Kyle; Miyama, Shoken; Morino, Jun-Ichi; Moro-Martin, Amaya; Nishimura, Tetsuo; Pyo, Tae-Soo; Serabyn, Eugene; Suenaga, Takuya; Suto, Hiroshi; Suzuki, Ryuji; Takami, Michihiro; Takato, Naruhisa; Takeda, Yoichi; Terada, Hiroshi; Thalmann, Christian; Turner, Edwin L.; Watanabe, Makoto; Wisniewski, John; Yamada, Toru; Yoshida, Michitoshi; Takami, Hideki; Usuda, Tomonori; Tamura, Motohide

    2016-07-01

    A radial velocity (RV) survey for intermediate-mass giants has been in operation for over a decade at Okayama Astrophysical Observatory (OAO). The OAO survey has revealed that some giants show long-term linear RV accelerations (RV trends), indicating the presence of outer companions. Direct-imaging observations can help clarify what objects generate these RV trends. We present the results of high-contrast imaging observations of six intermediate-mass giants with long-term RV trends using the Subaru Telescope and HiCIAO camera. We detected co-moving companions to γ Hya B ({0.61}-0.14+0.12{M}ȯ ), HD 5608 B (0.10+/- 0.01{M}ȯ ), and HD 109272 B (0.28+/- 0.06{M}ȯ ). For the remaining targets (ι Dra, 18 Del, and HD 14067), we exclude companions more massive than 30–60 M Jup at projected separations of 1″–7″. We examine whether these directly imaged companions or unidentified long-period companions can account for the RV trends observed around the six giants. We find that the Kozai mechanism can explain the high eccentricity of the inner planets ι Dra b, HD 5608 b, and HD 14067 b.

  19. Mass spectrometry imaging of surface lipids on intact Drosophila melanogaster flies.

    PubMed

    Kaftan, Filip; Vrkoslav, Vladimír; Kynast, Philipp; Kulkarni, Purva; Böcker, Sebastian; Cvačka, Josef; Knaden, Markus; Svatoš, Aleš

    2014-03-01

    The spatial distribution of neutral lipids and semiochemicals on the surface of six-day-old separately reared naive Drosophila melanogaster flies has been visualized and studied using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry and laser-assisted desorption/ionization (LDI)-TOF imaging (MSI). Metal targets were designed for two-dimensional MSI of the surface of 3-D biological objects. Targets with either simple grooves or profiled holes designed to accurately accommodate the male and female bodies were fabricated. These grooves and especially holes ensured correct height fixation and spatial orientation of the flies on the targets after matrix application and sample drying. For LDI-TOF to be used, the flies were arranged into holes and fixed to a plane of the target using fast-setting glue. In MALDI-TOF mode, the flies were fixed as above and sprayed with a lithium 2,5-dihydroxybenzoate matrix using up to 100 airbrush spray cycles. The scanning electron microscopy images revealed that the deposits of matrix were homogenous and the matrix formed mostly into the clusters of crystals (40-80 µm) that were separated from each other by an uncovered cuticle surface (30-40 µm). The MSI using target with profiled holes provided superior results to the targets with simple grooves, eliminating the ion suppression/mass deviation due to the 3-D shape of the flies. Attention was paid to neutral lipids and other compounds including the male anti-attractant 11-cis-vaccenyl acetate for which the expected distribution with high concentration on the tip of the male abdomen was confirmed. The red and blue mass shift (PlusMinus1 colour scale) was observed associated with mass deviation predominantly between ±0.2 and 0.3 Da. We use in-house developed software for mass recalibration, to eliminate the mass deviation effects and help with the detection of low-intensity mass signals. PMID:24619548

  20. Application of Tapping-Mode Scanning Probe Electrospray Ionization to Mass Spectrometry Imaging of Additives in Polymer Films

    PubMed Central

    Shimazu, Ryo; Yamoto, Yoshinari; Kosaka, Tomoya; Kawasaki, Hideya; Arakawa, Ryuichi

    2014-01-01

    We report the application of tapping-mode scanning probe electrospray ionization (t-SPESI) to mass spectrometry imaging of industrial materials. The t-SPESI parameters including tapping solvent composition, solvent flow rate, number of tapping at each spot, and step-size were optimized using a quadrupole mass spectrometer to improve mass spectrometry (MS) imaging of thin-layer chromatography (TLC) and additives in polymer films. Spatial resolution of approximately 100 μm was achieved by t-SPESI imaging mass spectrometry using a fused-silica capillary (50 μm i.d., 150 μm o.d.) with the flow rate set at 0.2 μL/min. This allowed us to obtain discriminable MS imaging profiles of three dyes separated by TLC and the additive stripe pattern of a PMMA model film depleted by UV irradiation. PMID:26819894

  1. Skeletal muscle fiber analysis by atmospheric pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometric imaging at high mass and high spatial resolution.

    PubMed

    Tsai, Yu-Hsuan; Bhandari, Dhaka Ram; Garrett, Timothy J; Carter, Christy S; Spengler, Bernhard; Yost, Richard A

    2016-06-01

    Skeletal muscles are composed of heterogeneous muscle fibers with various fiber types. These fibers can be classified into different classes based on their different characteristics. MALDI mass spectrometric imaging (MSI) has been applied to study and visualize different metabolomics profiles of different fiber types. Here, skeletal muscles were analyzed by atmospheric pressure scanning microprobe MALDI-MSI at high spatial and high mass resolution. PMID:27198224

  2. Left ventricular dimensions and mass using magnetic resonance imaging in female endurance athletes

    NASA Technical Reports Server (NTRS)

    Riley-Hagan, M.; Peshock, R. M.; Stray-Gundersen, J.; Katz, J.; Ryschon, T. W.; Mitchell, J. H.

    1992-01-01

    Few published studies of left ventricular (LV) mass in female endurance athletes have been performed with M-mode echocardiography, which involves assumptions of LV geometry. Therefore, magnetic resonance imaging, a 3-dimensional technique, was used to examine LV mass, LV end-diastolic volume and mean wall thickness in female long distance runners (n = 13; mean age 29 years), cyclists (n = 12; mean age 26 years) and cross-country skiers (n = 11; mean age 24 years), and the findings were compared with sedentary control subjects (n = 10; mean age 27 years) matched for height and body weight. The physical characteristics for all subjects included height (mean 166 cm, and body weight (mean 56 kg). The percent body fat (mean 11.7) and maximal oxygen uptake (VO2max, mean 63 ml.kg-1.min-1) were similar (p greater than 0.05) among all athletic groups, but significantly different from the control group (body fat, mean 22.5%; VO2max, mean 35 ml.kg-1.min-1). LV mass (mean 159 kg), LV end-diastolic volume (mean 122 ml), and mean wall thickness (mean 11.5 mm) were also similar among the athletic groups and significantly larger than the following control values: LV mass (mean 115 g), LV end-diastolic volume (mean 93 ml) and mean wall thickness (mean 9.8 mm). Ratios of LV mass to lean body weight were similar among all athletic groups, although athletic groups had larger ratios (p less than 0.05) than the sedentary control subjects. LV mass/LV end-diastolic volume ratio was similar (p greater than 0.05) among all groups.(ABSTRACT TRUNCATED AT 250 WORDS).

  3. Proteomic analysis of formalin-fixed paraffin embedded tissue by MALDI imaging mass spectrometry

    PubMed Central

    Casadonte, Rita; Caprioli, Richard M

    2012-01-01

    Archived formalin-fixed paraffin-embedded (FFPE) tissue collections represent a valuable informational resource for proteomic studies. Multiple FFPE core biopsies can be assembled in a single block to form tissue microarrays (TMAs). We describe a protocol for analyzing protein in FFPE -TMAs using matrix-assisted laser desorption/ionization (MAL DI) imaging mass spectrometry (IMS). The workflow incorporates an antigen retrieval step following deparaffinization, in situ trypsin digestion, matrix application and then mass spectrometry signal acquisition. The direct analysis of FFPE -TMA tissue using IMS allows direct analysis of multiple tissue samples in a single experiment without extraction and purification of proteins. The advantages of high speed and throughput, easy sample handling and excellent reproducibility make this technology a favorable approach for the proteomic analysis of clinical research cohorts with large sample numbers. For example, TMA analysis of 300 FFPE cores would typically require 6 h of total time through data acquisition, not including data analysis. PMID:22011652

  4. Depth profiling and imaging capabilities of an ultrashort pulse laser ablation time of flight mass spectrometer

    PubMed Central

    Cui, Yang; Moore, Jerry F.; Milasinovic, Slobodan; Liu, Yaoming; Gordon, Robert J.; Hanley, Luke

    2012-01-01

    An ultrafast laser ablation time-of-flight mass spectrometer (AToF-MS) and associated data acquisition software that permits imaging at micron-scale resolution and sub-micron-scale depth profiling are described. The ion funnel-based source of this instrument can be operated at pressures ranging from 10−8 to ∼0.3 mbar. Mass spectra may be collected and stored at a rate of 1 kHz by the data acquisition system, allowing the instrument to be coupled with standard commercial Ti:sapphire lasers. The capabilities of the AToF-MS instrument are demonstrated on metal foils and semiconductor wafers using a Ti:sapphire laser emitting 800 nm, ∼75 fs pulses at 1 kHz. Results show that elemental quantification and depth profiling are feasible with this instrument. PMID:23020378

  5. Multimodal Mass Spectrometry Imaging of N-Glycans and Proteins from the Same Tissue Section.

    PubMed

    Heijs, Bram; Holst, Stephanie; Briaire-de Bruijn, Inge H; van Pelt, Gabi W; de Ru, Arnoud H; van Veelen, Peter A; Drake, Richard R; Mehta, Anand S; Mesker, Wilma E; Tollenaar, Rob A; Bovée, Judith V M G; Wuhrer, Manfred; McDonnell, Liam A

    2016-08-01

    On-tissue digestion matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) can be used to record spatially correlated molecular information from formalin-fixed, paraffin-embedded (FFPE) tissue sections. In this work, we present the in situ multimodal analysis of N-linked glycans and proteins from the same FFPE tissue section. The robustness and applicability of the method are demonstrated for several tumors, including epithelial and mesenchymal tumor types. Major analytical aspects, such as lateral diffusion of the analyte molecules and differences in measurement sensitivity due to the additional sample preparation methods, have been investigated for both N-glycans and proteolytic peptides. By combining the MSI approach with extract analysis, we were also able to assess which mass spectral peaks generated by MALDI-MSI could be assigned to unique N-glycan and peptide identities. PMID:27373711

  6. STABILITY OF THE DIRECTLY IMAGED MULTIPLANET SYSTEM HR 8799: RESONANCE AND MASSES

    SciTech Connect

    Fabrycky, Daniel C.; Murray-Clay, Ruth A.

    2010-02-20

    A new era of directly imaged extrasolar planets has produced a three-planet system, where the masses of the planets have been estimated by untested cooling models. We point out that the nominal circular, face-on orbits of the planets lead to a dynamical instability in {approx}10{sup 5} yr, a factor of at least 100 shorter than the estimated age of the star. Reduced planetary masses produce stability only for unreasonably small planets ({approx}<2 M{sub Jup}). Relaxing the face-on assumption, but still requiring circular orbits while fitting the observed positions, makes the instability time even shorter. A promising solution is that the inner two planets have a 2:1 commensurability between their periods, and they avoid close encounters with each other through this resonance. The fact that the inner resonance has lasted until now, in spite of the perturbations of the outer planet, leads to a limit {approx}<10 M{sub Jup} on the masses unless the outer two planets are also engaged in a 2:1 mean-motion resonance. In a double resonance, which is consistent with the current data, the system could survive until now even if the planets have masses of {approx}20 M{sub Jup}. Apsidal alignment can further enhance the stability of a mean-motion resonant system. A completely different dynamical configuration, with large eccentricities and large mutual inclinations among the planets, is possible but finely tuned.

  7. Direct gravitational imaging of intermediate mass black holes in extragalactic haloes

    NASA Astrophysics Data System (ADS)

    Inoue, Kaiki Taro; Rashkov, Valery; Silk, Joseph; Madau, Piero

    2013-11-01

    A galaxy halo may contain a large number of intermediate mass black holes (IMBHs) with masses in the range of 102 M⊙ ≲ MBH ≲ 106 M⊙. We propose to directly detect these IMBHs by observing multiply imaged QSO-galaxy or galaxy-galaxy strong lens systems in the submillimetre bands with high angular resolution. The silhouette of an IMBH in the lensing galaxy halo would appear as either a monopole-like or a dipole-like variation at the scale of the Einstein radius against the Einstein ring of the dust-emitting region surrounding the QSO. We use a particle tagging technique to dynamically populate a Milky Way-sized dark matter halo with black holes (BHs), and show that the surface mass density and number density of IMBHs have power-law dependences on the distance from the centre of the host halo if smoothed on a scale of ˜ 1 kpc. Most of the BHs orbiting close to the centre are freely roaming as they have lost their dark matter hosts during infall due to tidal stripping. Next generation submillimetre telescopes with high angular resolution (≲0.3 mas) will be capable of directly mapping such off-nuclear freely roaming BHs with a mass of ≲106 M⊙ in a lensing galaxy that harbours an O(109) M⊙ supermassive black hole in its nucleus.

  8. Test Sample for the Spatially Resolved Quantification of Illicit Drugs on Fingerprints Using Imaging Mass Spectrometry.

    PubMed

    Muramoto, Shin; Forbes, Thomas P; van Asten, Arian C; Gillen, Greg

    2015-01-01

    A novel test sample for the spatially resolved quantification of illicit drugs on the surface of a fingerprint using time-of-flight secondary ion mass spectrometry (ToF-SIMS) and desorption electrospray ionization mass spectrometry (DESI-MS) was demonstrated. Calibration curves relating the signal intensity to the amount of drug deposited on the surface were generated from inkjet-printed arrays of cocaine, methamphetamine, and heroin with a deposited-mass ranging nominally from 10 pg to 50 ng per spot. These curves were used to construct concentration maps that visualized the spatial distribution of the drugs on top of a fingerprint, as well as being able to quantify the amount of drugs in a given area within the map. For the drugs on the fingerprint on silicon, ToF-SIMS showed great success, as it was able to generate concentration maps of all three drugs. On the fingerprint on paper, only the concentration map of cocaine could be constructed using ToF-SIMS and DESI-MS, as the signals of methamphetamine and heroin were completely suppressed by matrix and substrate effects. Spatially resolved quantification of illicit drugs using imaging mass spectrometry is possible, but the choice of substrates could significantly affect the results. PMID:25915085

  9. Precision Mass Measurements at the Canadian Penning Trap using a Phase-Imaging Technique

    NASA Astrophysics Data System (ADS)

    Nystrom, Andrew; Aprahamian, A.; Marley, S. T.; Mumpower, M.; Paul, N.; Siegl, K.; Strauss, S.; Surman, R.; Kuta, T.; Savard, G.; Clark, J. A.; Levand, A. F.; Perez Galvan, A.; Hirsh, T.; Rohrer, J.; Caldwell, S.; van Schelt, J.; Orford, R.; Buchinger, F.; Morgan, G.; Sharma, K.

    2015-10-01

    Precision mass measurements at Penning Trap facilities have traditionally used a time-of-flight (TOF) technique to measure the cyclotron frequency of ions and therefore determine their masses. At the Canadian Penning Trap (CPT), this technique is able to provide mass measurements to a precision of about δm/m = 10-8 with measurement times as low as 200ms. However, a new phase-imaging technique, which instead determines the cyclotron frequency by projecting the radial ion motion on a position-sensitive detector, is being implemented at the CPT. It provides at least a tenfold gain in resolving power while allowing for measurement times of less than 100 ms, allowing measurements of more exotic neutron-rich nuclei from CARIBU with respect to the TOF technique. Details of its commissioning at the CPT will be discussed alongside new neutron-rich mass measurements. This work is supported by the following: NSERC, Canada, appl. # 239591, the U.S. DOE, Office of Nuclear Physics, under Contract DE-AC02-06CH11357, and NSF Grants PHY-1419765 and PHY-1430152.

  10. Considerations for quantification of lipids in nerve tissue using MALDI mass spectrometric imaging

    PubMed Central

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

    2013-01-01

    MALDI mass spectrometric imaging is a technique that provides the ability to identify and characterize endogenous and exogenous compounds spatially within tissue with relatively little sample preparation. While it is a proven methodology for qualitative analysis, little has been reported for its utility in quantitative measurements. In the current work, inherent challenges in MALDI quantification are addressed. Signal response is monitored over successive analyses of a single tissue section to minimize error due to variability in the laser, matrix application, and sample inhomogeneity. Methods for the application of an internal standard to tissue sections are evaluated and used to quantify endogenous lipids in nerve tissue. A precision of 5% or less standard error was achieved, illustrating that MALDI imaging offers a reliable means of in situ quantification for microgram-sized samples and requires minimal sample preparation. PMID:21953974

  11. Shotgun Approach for Quantitative Imaging of Phospholipids Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Lanekoff, Ingela T.; Thomas, Mathew; Laskin, Julia

    2014-02-04

    Mass spectrometry imaging (MSI) has been extensively used for determining spatial distributions of molecules in biological samples, and there is increasing interest in using MSI for quantification. Nanospray desorption electrospray ionization, or nano-DESI, is an ambient MSI technique where a solvent is used for localized extraction of molecules followed by nanoelectrospray ionization. Doping the nano-DESI solvent with carefully selected standards enables online quantification during MSI experiments. In this proof-of-principle study, we demonstrate this quantification approach can be extended to provide shotgun-like quantification of phospholipids in thin brain tissue sections. Specifically, two phosphatidylcholine (PC) standards were added to the nano-DESI solvent for simultaneous imaging and quantification of 22 PC species observed in nano-DESI MSI. Furthermore, by combining the quantitative data obtained in the individual pixels, we demonstrate quantification of these PC species in seven different regions of a rat brain tissue section.

  12. Label free biochemical 2D and 3D imaging using secondary ion mass spectrometry

    PubMed Central

    Fletcher, John S.; Vickerman, John C.; Winograd, Nicholas

    2011-01-01

    Time-of-flight Secondary ion mass spectrometry (ToF-SIMS) provides a method for the detection of native and exogenous compounds in biological samples on a cellular scale. Through the development of novel ion beams the amount of molecular signal available from the sample surface has been increased. Through the introduction of polyatomic ion beams, particularly C60, ToF-SIMS can now be used to monitor molecular signals as a function of depth as the sample is eroded thus proving the ability to generate 3D molecular images. Here we describe how this new capability has led to the development of novel instrumentation for 3D molecular imaging while also highlighting the importance of sample preparation and discuss the challenges that still need to be overcome to maximise the impact of the technique. PMID:21664172

  13. Fuzzy Logic Classification of Imaging Laser Desorption Fourier Transform Mass Spectrometry Data

    SciTech Connect

    Timothy R. McJunkin; Jill R. Scott

    2008-06-01

    The fuzzy logic method is applied to classification of mass spectra obtained with an imaging internal source Fourier transform mass spectrometer (I2LD-FTMS). Traditionally, an operator uses the relative abundance of ions with specific mass-to-charge (m/z) ratios to categorize spectra. An operator does this by comparing the spectrum of m/z versus abundance of an unknown sample against a library of spectra from known samples. Automated positioning and acquisition allow the I2LD-FTMS to acquire data from very large grids, which would require classification of up to 3600 spectra per hour to keep pace with the acquisition. The tedious job of classifying numerous spectra generated in an I2LD-FTMS imaging application can be replaced by a fuzzy rule base if the cues an operator uses can be encapsulated. Appropriate methods for assigning fuzzy membership values for inputs (e.g., mass spectrum abundances) and choice of fuzzy inference operators to translate linguistic antecedent into confidence values for the consequence (or in this case the classification) is followed by using the maximum confidence and a necessary minimum threshold for making a crisp decision. This paper also describes a method for gathering statistics on ions, which are not currently used in the rule base, but which may be candidates for making the rule base more accurate and complete or to form new rule bases based on data obtained from known samples. A spatial method for classifying spectra with low membership values, based on neighboring sample classifications, is also presented.

  14. Applications of the Single-probe: Mass Spectrometry Imaging and Single Cell Analysis under Ambient Conditions

    PubMed Central

    Rao, Wei; Pan, Ning; Yang, Zhibo

    2016-01-01

    Mass spectrometry imaging (MSI) and in-situ single cell mass spectrometry (SCMS) analysis under ambient conditions are two emerging fields with great potential for the detailed mass spectrometry (MS) analysis of biomolecules from biological samples. The single-probe, a miniaturized device with integrated sampling and ionization capabilities, is capable of performing both ambient MSI and in-situ SCMS analysis. For ambient MSI, the single-probe uses surface micro-extraction to continually conduct MS analysis of the sample, and this technique allows the creation of MS images with high spatial resolution (8.5 µm) from biological samples such as mouse brain and kidney sections. Ambient MSI has the advantage that little to no sample preparation is needed before the analysis, which reduces the amount of potential artifacts present in data acquisition and allows a more representative analysis of the sample to be acquired. For in-situ SCMS, the single-probe tip can be directly inserted into live eukaryotic cells such as HeLa cells, due to the small sampling tip size (< 10 µm), and this technique is capable of detecting a wide range of metabolites inside individual cells at near real-time. SCMS enables a greater sensitivity and accuracy of chemical information to be acquired at the single cell level, which could improve our understanding of biological processes at a more fundamental level than previously possible. The single-probe device can be potentially coupled with a variety of mass spectrometers for broad ranges of MSI and SCMS studies. PMID:27341402

  15. Visualizing fungal metabolites during mycoparasitic interaction by MALDI mass spectrometry imaging.

    PubMed

    Holzlechner, Matthias; Reitschmidt, Sonja; Gruber, Sabine; Zeilinger, Susanne; Marchetti-Deschmann, Martina

    2016-06-01

    Studying microbial interactions by MALDI mass spectrometry imaging (MSI) directly from growing media is a difficult task if high sensitivity is demanded. We present a quick and robust sample preparation strategy for growing fungi (Trichoderma atroviride, Rhizoctonia solani) on glass slides to establish a miniaturized confrontation assay. By this we were able to visualize metabolite distributions by MALDI MSI after matrix deposition with a home-built sublimation device and thorough recrystallization. We present for the first time MALDI MSI data for secondary metabolite release during active mycoparasitism. PMID:26959280

  16. Analysis of colorectal adenocarcinoma tissue by desorption electrospray ionization mass spectrometric imaging.

    PubMed

    Gerbig, Stefanie; Golf, Ottmar; Balog, Julia; Denes, Julia; Baranyai, Zsolt; Zarand, Attila; Raso, Erzsebet; Timar, Jozsef; Takats, Zoltan

    2012-06-01

    Negative ion desorption electrospray ionization (DESI) was used for the analysis of an ex vivo tissue sample set comprising primary colorectal adenocarcinoma samples and colorectal adenocarcinoma liver metastasis samples. Frozen sections (12 μm thick) were analyzed by means of DESI imaging mass spectrometry (IMS) with spatial resolution of 100 μm using a computer-controlled DESI imaging stage mounted on a high resolution Orbitrap mass spectrometer. DESI-IMS data were found to predominantly feature complex lipids, including phosphatidyl-inositols, phophatidyl-ethanolamines, phosphatidyl-serines, phosphatidyl-ethanolamine plasmalogens, phosphatidic acids, phosphatidyl-glycerols, ceramides, sphingolipids, and sulfatides among others. Molecular constituents were identified based on their exact mass and MS/MS fragmentation spectra. An identified set of molecules was found to be in good agreement with previously reported DESI imaging data. Different histological tissue types were found to yield characteristic mass spectrometric data in each individual section. Histological features were identified by comparison to hematoxylin-eosin stained neighboring sections. Ions specific to certain histological tissue types (connective tissue, smooth muscle, healthy mucosa, healthy liver parenchyma, and adenocarcinoma) were identified by semi-automated screening of data. While each section featured a number of tissue-specific species, no potential global biomarker was found in the full sample set for any of the tissue types. As an alternative approach, data were analyzed by principal component analysis (PCA) and linear discriminant analysis (LDA) which resulted in efficient separation of data points based on their histological types. A pixel-by-pixel tissue identification method was developed, featuring the PCA/LDA analysis of authentic data set, and localization of unknowns in the resulting 60D, histologically assigned LDA space. Novel approach was found to yield results which are

  17. Mass Spectrometry Imaging of Therapeutics from Animal Models to Three-Dimensional Cell Cultures

    PubMed Central

    Liu, Xin; Hummon, Amanda B.

    2016-01-01

    Mass spectrometry imaging (MSI) is a powerful label-free technique for the investigation of the spatial distribution of molecules at complex surfaces and has been widely used in the pharmaceutical sciences to understand the distribution of different drugs and their metabolites in various biological samples, ranging from cell-based models to tissues. Here, we review the current applications of MSI for drug studies in animal models, followed by a discussion of the novel advances of MSI in three-dimensional (3D) cell cultures for accurate, efficient and high-throughput analyses to evaluate therapeutics. PMID:26084404

  18. Visualizing fungal metabolites during mycoparasitic interaction by MALDI mass spectrometry imaging

    PubMed Central

    Holzlechner, Matthias; Reitschmidt, Sonja; Gruber, Sabine; Zeilinger, Susanne

    2016-01-01

    Studying microbial interactions by MALDI mass spectrometry imaging (MSI) directly from growing media is a difficult task if high sensitivity is demanded. We present a quick and robust sample preparation strategy for growing fungi (Trichoderma atroviride, Rhizoctonia solani) on glass slides to establish a miniaturized confrontation assay. By this we were able to visualize metabolite distributions by MALDI MSI after matrix deposition with a home‐built sublimation device and thorough recrystallization. We present for the first time MALDI MSI data for secondary metabolite release during active mycoparasitism. PMID:26959280

  19. Compound and metabolite distribution measured by MALDI mass spectrometric imaging in whole-body tissue sections

    NASA Astrophysics Data System (ADS)

    Stoeckli, Markus; Staab, Dieter; Schweitzer, Alain

    2007-02-01

    The determination of the compound distribution in laboratory animal tissue in early development is a standard process in pharmaceutical research. While this information is traditionally obtained by means of whole-body autoradiography using radiolabeled compounds, this technology does not distinguish between metabolites and parent compound. The technique described in this article, termed matrix-assisted laser desorption/ionization (MALDI) mass spectrometric imaging, can fill this gap by simultaneously measuring compound and multiple metabolites distributed in whole-body tissue sections, using non-labeled compounds.

  20. Imaging Mass Spectrometry: Enabling a New Age of Discovery in Biology and Medicine Through Molecular Microscopy

    NASA Astrophysics Data System (ADS)

    Caprioli, Richard M.

    2015-06-01

    Imaging mass spectrometry (IMS) has become a valuable tool for the production of molecular maps in samples ranging from solid inorganic materials to biologicals such as cells and tissues. The unique features of IMS are its ability to map a wide variety of different types of molecules, its superb molecular specificity, and its potential for discovery since no target-specific reagents are needed. IMS has made significant contributions in biology and medicine and promises to be a next generation tool in anatomic pathology.

  1. Improved MALDI-TOF Microbial Mass Spectrometry Imaging by Application of a Dispersed Solid Matrix

    NASA Astrophysics Data System (ADS)

    Vergeiner, Stefan; Schafferer, Lukas; Haas, Hubertus; Müller, Thomas

    2014-08-01

    The key step in high quality microbial matrix-assisted laser desorption/ionization mass spectrometry imaging (microbial MALDI MSI) is the fabrication of a homogeneous matrix coating showing a fine-grained morphology. This application note addresses a novel method to apply solid MALDI matrices onto microbial cultures grown on thin agar media. A suspension of a mixture of 2,5-DHB and α-CHCA is sprayed onto the agar sample surface to form highly homogeneous matrix coatings. As a result, the signal intensities of metabolites secreted by the fungus Aspergillus fumigatus were found to be clearly enhanced.

  2. Imaging Mass Spectrometry: Enabling a New Age of Discovery in Biology and Medicine Through Molecular Microscopy

    PubMed Central

    Caprioli, Richard M.

    2015-01-01

    Imaging mass spectrometry (IMS) has become a valuable tool for the production of molecular maps in samples ranging from solid inorganic materials to biologicals such as cells and tissues. The unique features of IMS are its ability to map a wide variety of different types of molecules, its superb molecular specificity, and its potential for discovery since no target specific reagents are needed. IMS has made significant contributions in biology and medicine and promises to be a next generation tool in anatomic pathology. PMID:25801587

  3. Direct imaging search for planets around low-mass stars and spectroscopic characterization of young exoplanets

    NASA Astrophysics Data System (ADS)

    Bowler, Brendan Peter

    Low--mass stars between 0.1--0.6 M⊙ are the most abundant members our galaxy and may be the most common sites of planet formation, but little is known about the outer architecture of their planetary systems. We have carried out a high-contrast adaptive imaging search for gas giant planets between 1--13 MJup around 122 newly identified young M dwarfs in the solar neighborhood ( ≲ 35 pc). Half of our targets are younger than 145 Myr, and 90% are younger than 580 Myr. After removing 39 resolved stellar binaries, our homogeneous sample of 83 single young M dwarfs makes it the largest imaging search for planets around low--mass stars to date. Our H- and K- band coronagraphic observations with Subaru/HiCIAO and Keck/NIRC2 achieve typical contrasts of 9--13 mag and 12--14 mag at 100, respectively, which corresponds to limiting masses of ˜1--10 M Jup at 10--30 AU for most of our sample. We discovered four brown dwarfs with masses between 25--60 MJup at projected separations of 4--190 AU. Over 100 candidate planets were discovered, nearly all of which were found to be background stars from follow-up second epoch imaging. Our null detection of planets nevertheless provides strong statistical constraints on the occurrence rate of giant planets around M dwarfs. Assuming circular orbits and a logarithmically-flat power law distribution in planet mass and semi--major axis of the form d 2N=(dloga dlogm) infinity m0 a0, we measure an upper limit (at the 95% confidence level) of 8.8% and 12.6% for 1--13 MJup companions between 10--100 AU for hot start and cold start evolutionary models, respectively. For massive gas giant planets in the 5--13 M Jup range like those orbiting HR 8799, GJ 504, and beta Pictoris, we find that fewer than 5.3% (7.8%) of M dwarfs harbor these planets between 10--100 AU for a hot start (cold start) formation scenario. Our best constraints are for brown dwarf companions; the frequency of 13--75 MJup companions between (de--projected) physical

  4. DetectTLC: Automated Reaction Mixture Screening Utilizing Quantitative Mass Spectrometry Image Feature

    PubMed Central

    Kaddi, Chanchala D.; Bennett, Rachel V.; Paine, Martin R. L.; Banks, Mitchel D.; Weber, Arthur L.; Fernández, Facundo M.; Wang, May D.

    2016-01-01

    Full characterization of complex reaction mixtures is necessary to understand mechanisms, optimize yields, and elucidate secondary reaction pathways. Molecular-level information for species in such mixtures can be readily obtained by coupling mass spectrometry imaging (MSI) with thin layer chromatography (TLC) separations. User-guided investigation of imaging data for mixture components with known m/z values is generally straightforward; however, spot detection for unknowns is highly tedious, and limits the applicability of MSI in conjunction with TLC. To accelerate imaging data mining, we developed DetectTLC, an approach that automatically identifies m/z values exhibiting TLC spot-like regions in MS molecular images. Furthermore, DetectTLC can also spatially match m/z values for spots acquired during alternating high and low collision-energy scans, pairing product ions with precursors to enhance structural identification. As an example, DetectTLC is applied to the identification and structural confirmation of unknown, yet significant, products of abiotic pyrazinone and aminopyrazine nucleoside analog synthesis. PMID:26508443

  5. AUTOMATIC DETECTION AND TRACKING OF CORONAL MASS EJECTIONS. II. MULTISCALE FILTERING OF CORONAGRAPH IMAGES

    SciTech Connect

    Byrne, Jason P.; Morgan, Huw; Habbal, Shadia R.; Gallagher, Peter T.

    2012-06-20

    Studying coronal mass ejections (CMEs) in coronagraph data can be challenging due to their diffuse structure and transient nature, and user-specific biases may be introduced through visual inspection of the images. The large amount of data available from the Solar and Heliospheric Observatory (SOHO), Solar TErrestrial RElations Observatory (STEREO), and future coronagraph missions also makes manual cataloging of CMEs tedious, and so a robust method of detection and analysis is required. This has led to the development of automated CME detection and cataloging packages such as CACTus, SEEDS, and ARTEMIS. Here, we present the development of a new CORIMP (coronal image processing) CME detection and tracking technique that overcomes many of the drawbacks of current catalogs. It works by first employing the dynamic CME separation technique outlined in a companion paper, and then characterizing CME structure via a multiscale edge-detection algorithm. The detections are chained through time to determine the CME kinematics and morphological changes as it propagates across the plane of sky. The effectiveness of the method is demonstrated by its application to a selection of SOHO/LASCO and STEREO/SECCHI images, as well as to synthetic coronagraph images created from a model corona with a variety of CMEs. The algorithms described in this article are being applied to the whole LASCO and SECCHI data sets, and a catalog of results will soon be available to the public.

  6. Automatic Detection and Tracking of Coronal Mass Ejections. II. Multiscale Filtering of Coronagraph Images

    NASA Astrophysics Data System (ADS)

    Byrne, Jason P.; Morgan, Huw; Habbal, Shadia R.; Gallagher, Peter T.

    2012-06-01

    Studying coronal mass ejections (CMEs) in coronagraph data can be challenging due to their diffuse structure and transient nature, and user-specific biases may be introduced through visual inspection of the images. The large amount of data available from the Solar and Heliospheric Observatory (SOHO), Solar TErrestrial RElations Observatory (STEREO), and future coronagraph missions also makes manual cataloging of CMEs tedious, and so a robust method of detection and analysis is required. This has led to the development of automated CME detection and cataloging packages such as CACTus, SEEDS, and ARTEMIS. Here, we present the development of a new CORIMP (coronal image processing) CME detection and tracking technique that overcomes many of the drawbacks of current catalogs. It works by first employing the dynamic CME separation technique outlined in a companion paper, and then characterizing CME structure via a multiscale edge-detection algorithm. The detections are chained through time to determine the CME kinematics and morphological changes as it propagates across the plane of sky. The effectiveness of the method is demonstrated by its application to a selection of SOHO/LASCO and STEREO/SECCHI images, as well as to synthetic coronagraph images created from a model corona with a variety of CMEs. The algorithms described in this article are being applied to the whole LASCO and SECCHI data sets, and a catalog of results will soon be available to the public.

  7. DetectTLC: Automated Reaction Mixture Screening Utilizing Quantitative Mass Spectrometry Image Features

    NASA Astrophysics Data System (ADS)

    Kaddi, Chanchala D.; Bennett, Rachel V.; Paine, Martin R. L.; Banks, Mitchel D.; Weber, Arthur L.; Fernández, Facundo M.; Wang, May D.

    2016-02-01

    Full characterization of complex reaction mixtures is necessary to understand mechanisms, optimize yields, and elucidate secondary reaction pathways. Molecular-level information for species in such mixtures can be readily obtained by coupling mass spectrometry imaging (MSI) with thin layer chromatography (TLC) separations. User-guided investigation of imaging data for mixture components with known m/z values is generally straightforward; however, spot detection for unknowns is highly tedious, and limits the applicability of MSI in conjunction with TLC. To accelerate imaging data mining, we developed DetectTLC, an approach that automatically identifies m/z values exhibiting TLC spot-like regions in MS molecular images. Furthermore, DetectTLC can also spatially match m/z values for spots acquired during alternating high and low collision-energy scans, pairing product ions with precursors to enhance structural identification. As an example, DetectTLC is applied to the identification and structural confirmation of unknown, yet significant, products of abiotic pyrazinone and aminopyrazine nucleoside analog synthesis.

  8. Ultrafast High-Resolution Mass Spectrometric Finger Pore Imaging in Latent Finger Prints

    NASA Astrophysics Data System (ADS)

    Elsner, Christian; Abel, Bernd

    2014-11-01

    Latent finger prints (LFPs) are deposits of sweat components in ridge and groove patterns, left after human fingers contact with a surface. Being important targets in biometry and forensic investigations they contain more information than topological patterns. With laser desorption mass spectrometry imaging (LD-MSI) we record `three-dimensional' finger prints with additional chemical information as the third dimension. Here we show the potential of fast finger pore imaging (FPI) in latent finger prints employing LD-MSI without a classical matrix in a high- spatial resolution mode. Thin films of gold rapidly sputtered on top of the sample are used for desorption. FPI employing an optical image for rapid spatial orientation and guiding of the desorption laser enables the rapid analysis of individual finger pores, and the chemical composition of their excretions. With this approach we rapidly detect metabolites, drugs, and characteristic excretions from the inside of the human organism by a minimally-invasive strategy, and distinguish them from chemicals in contact with fingers without any labeling. The fast finger pore imaging, analysis, and screening approach opens the door for a vast number of novel applications in such different fields as forensics, doping and medication control, therapy, as well as rapid profiling of individuals.

  9. Ultrafast High-Resolution Mass Spectrometric Finger Pore Imaging in Latent Finger Prints

    PubMed Central

    Elsner, Christian; Abel, Bernd

    2014-01-01

    Latent finger prints (LFPs) are deposits of sweat components in ridge and groove patterns, left after human fingers contact with a surface. Being important targets in biometry and forensic investigations they contain more information than topological patterns. With laser desorption mass spectrometry imaging (LD-MSI) we record ‘three-dimensional' finger prints with additional chemical information as the third dimension. Here we show the potential of fast finger pore imaging (FPI) in latent finger prints employing LD-MSI without a classical matrix in a high- spatial resolution mode. Thin films of gold rapidly sputtered on top of the sample are used for desorption. FPI employing an optical image for rapid spatial orientation and guiding of the desorption laser enables the rapid analysis of individual finger pores, and the chemical composition of their excretions. With this approach we rapidly detect metabolites, drugs, and characteristic excretions from the inside of the human organism by a minimally-invasive strategy, and distinguish them from chemicals in contact with fingers without any labeling. The fast finger pore imaging, analysis, and screening approach opens the door for a vast number of novel applications in such different fields as forensics, doping and medication control, therapy, as well as rapid profiling of individuals. PMID:25366032

  10. Ultrafast high-resolution mass spectrometric finger pore imaging in latent finger prints.

    PubMed

    Elsner, Christian; Abel, Bernd

    2014-01-01

    Latent finger prints (LFPs) are deposits of sweat components in ridge and groove patterns, left after human fingers contact with a surface. Being important targets in biometry and forensic investigations they contain more information than topological patterns. With laser desorption mass spectrometry imaging (LD-MSI) we record 'three-dimensional' finger prints with additional chemical information as the third dimension. Here we show the potential of fast finger pore imaging (FPI) in latent finger prints employing LD-MSI without a classical matrix in a high- spatial resolution mode. Thin films of gold rapidly sputtered on top of the sample are used for desorption. FPI employing an optical image for rapid spatial orientation and guiding of the desorption laser enables the rapid analysis of individual finger pores, and the chemical composition of their excretions. With this approach we rapidly detect metabolites, drugs, and characteristic excretions from the inside of the human organism by a minimally-invasive strategy, and distinguish them from chemicals in contact with fingers without any labeling. The fast finger pore imaging, analysis, and screening approach opens the door for a vast number of novel applications in such different fields as forensics, doping and medication control, therapy, as well as rapid profiling of individuals. PMID:25366032

  11. Characterization of Bacillus subtilis Colony Biofilms via Mass Spectrometry and Fluorescence Imaging.

    PubMed

    Si, Tong; Li, Bin; Zhang, Ke; Xu, Yiran; Zhao, Huimin; Sweedler, Jonathan V

    2016-06-01

    Colony biofilms of Bacillus subtilis are a widely used model for studying cellular differentiation. Here, we applied matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to examine cellular and molecular heterogeneity in B. subtilis colony biofilms. From B. subtilis cells cultivated on a biofilm-promoting medium, we detected two cannibalistic factors not found in previous MALDI MSI studies of the same strain under different culturing conditions. Given the importance of cannibalism in matrix formation of B. subtilis biofilms, we employed a transcriptional reporter to monitor matrix-producing cell subpopulations using fluorescence imaging. These two complementary imaging approaches were used to characterize three B. subtilis strains, the wild type isolate NCIB3610, and two mutants, Δspo0A and ΔabrB, with defective and enhanced biofilm phenotypes, respectively. Upon deletion of key transcriptional factors, correlated changes were observed in biofilm morphology, signaling, cannibalistic factor distribution, and matrix-related gene expression, providing new insights on cannibalism in biofilm development. This work underscores the advantages of using multimodal imaging to compare spatial patterns of selected molecules with the associated protein expression patterns, obtaining information on cellular heterogeneity and function not obtainable when using a single method to characterize biofilm formation. PMID:27136705

  12. Characterization of Bacillus subtilis Colony Biofilms via Mass Spectrometry and Fluorescence Imaging

    PubMed Central

    2016-01-01

    Colony biofilms of Bacillus subtilis are a widely used model for studying cellular differentiation. Here, we applied matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to examine cellular and molecular heterogeneity in B. subtilis colony biofilms. From B. subtilis cells cultivated on a biofilm-promoting medium, we detected two cannibalistic factors not found in previous MALDI MSI studies of the same strain under different culturing conditions. Given the importance of cannibalism in matrix formation of B. subtilis biofilms, we employed a transcriptional reporter to monitor matrix-producing cell subpopulations using fluorescence imaging. These two complementary imaging approaches were used to characterize three B. subtilis strains, the wild type isolate NCIB3610, and two mutants, Δspo0A and ΔabrB, with defective and enhanced biofilm phenotypes, respectively. Upon deletion of key transcriptional factors, correlated changes were observed in biofilm morphology, signaling, cannibalistic factor distribution, and matrix-related gene expression, providing new insights on cannibalism in biofilm development. This work underscores the advantages of using multimodal imaging to compare spatial patterns of selected molecules with the associated protein expression patterns, obtaining information on cellular heterogeneity and function not obtainable when using a single method to characterize biofilm formation. PMID:27136705

  13. Interpolation of Longitudinal Shape and Image Data via Optimal Mass Transport

    PubMed Central

    Gao, Yi; Zhu, Liang-Jia; Bouix, Sylvain; Tannenbaum, Allen

    2014-01-01

    Longitudinal analysis of medical imaging data has become central to the study of many disorders. Unfortunately, various constraints (study design, patient availability, technological limitations) restrict the acquisition of data to only a few time points, limiting the study of continuous disease/treatment progression. Having the ability to produce a sensible time interpolation of the data can lead to improved analysis, such as intuitive visualizations of anatomical changes, or the creation of more samples to improve statistical analysis. In this work, we model interpolation of medical image data, in particular shape data, using the theory of optimal mass transport (OMT), which can construct a continuous transition from two time points while preserving “mass” (e.g., image intensity, shape volume) during the transition. The theory even allows a short extrapolation in time and may help predict short-term treatment impact or disease progression on anatomical structure. We apply the proposed method to the hippocampus-amygdala complex in schizophrenia, the heart in atrial fibrillation, and full head MR images in traumatic brain injury. PMID:25302008

  14. Imaging mass spectrometry of the visual system: Advancing the molecular understanding of retina degenerations.

    PubMed

    Bowrey, Hannah E; Anderson, David M; Pallitto, Patrick; Gutierrez, Danielle B; Fan, Jie; Crouch, Rosalie K; Schey, Kevin L; Ablonczy, Zsolt

    2016-04-01

    Visual sensation is fundamental for quality of life, and loss of vision to retinal degeneration is a debilitating condition. The eye is the only part of the central nervous system that can be noninvasively observed with optical imaging. In the clinics, various spectroscopic methods provide high spatial resolution images of the fundus and the developing degenerative lesions. However, the currently utilized tools are not specific enough to establish the molecular underpinnings of retinal diseases. In contrast, mass spectrometric imaging (MSI) is a powerful tool to identify molecularly specific disease indicators and classification markers. This technique is particularly well suited to the eye, where molecular information can be correlated with clinical data collected via noninvasive diagnostic imaging modalities. Recent studies during the last few recent years have uncovered a plethora of new spatially defined molecular information on several vision-threatening diseases, including age-related macular degeneration, Stargardt disease, glaucoma, cataract, as well as lipid disorders. Even though MS inside the eye cannot be performed noninvasively, by linking diagnostic and molecular information, these studies are the first step toward the development of smart ophthalmic diagnostic and surgical tools. Here, we provide an overview of current approaches applying MSI technology to ocular pathology. PMID:26586164

  15. DetectTLC: Automated Reaction Mixture Screening Utilizing Quantitative Mass Spectrometry Image Features.

    PubMed

    Kaddi, Chanchala D; Bennett, Rachel V; Paine, Martin R L; Banks, Mitchel D; Weber, Arthur L; Fernández, Facundo M; Wang, May D

    2016-02-01

    Full characterization of complex reaction mixtures is necessary to understand mechanisms, optimize yields, and elucidate secondary reaction pathways. Molecular-level information for species in such mixtures can be readily obtained by coupling mass spectrometry imaging (MSI) with thin layer chromatography (TLC) separations. User-guided investigation of imaging data for mixture components with known m/z values is generally straightforward; however, spot detection for unknowns is highly tedious, and limits the applicability of MSI in conjunction with TLC. To accelerate imaging data mining, we developed DetectTLC, an approach that automatically identifies m/z values exhibiting TLC spot-like regions in MS molecular images. Furthermore, DetectTLC can also spatially match m/z values for spots acquired during alternating high and low collision-energy scans, pairing product ions with precursors to enhance structural identification. As an example, DetectTLC is applied to the identification and structural confirmation of unknown, yet significant, products of abiotic pyrazinone and aminopyrazine nucleoside analog synthesis. Graphical Abstract ᅟ. PMID:26508443

  16. 2 MASS Near-Infared Imaging of the Supernova Remnant IC443

    NASA Astrophysics Data System (ADS)

    Rho, Jeonghee; van Dyk, Schuyler; Jarrett, T.; Roc, C.; Reach, W. T.

    We present near-infrared imaging of IC443, covering the entire supernova remnant (50' diameter) from The Two Micron All Sky Survey (2MASS). 2MASS imaging is taken simultaneously in the J (1.25 microns), H (1.65 microns) and K_s (2.17 microns) bands using a 1.3 m telescope with a three-channel camera. The images have 3.5'' spatial resolution with a pixel size of 1''. The bands include lines of Pβ, [Ni~II] and [Fe~II] for J band, Br10 and [Fe~II] for H band, and Brγ and H_2 for K_s band. Emission from IC443 was detected in all 3 bands from most of the optically bright parts of the remnant, revealing a shell-like morphology. This is the first near-infrared image of the northeastern and eastern parts. The color and structure are very different between the northeastern and southern parts. The northeastern shell shows sheet-like filamentary structure, similar to that of optical emission, with J and H band emission equivalently bright, and weak K_s emission. The H flux is higher than the K flux in the northeast; its ratio is similar order of magnitude to that of previously measured infrared spectroscopy from 2 positions. The ratio implies that the H band emission from the northeastern shell is mostly [Fe II] (1.64 microns), and the [Fe II] emission is much stronger than Brγ. This contrasts to the ratio of 0.06 observed in H~II regions. The strong [Fe II] line is produced not only by efficient excitation of Fe but also by grain destruction. Most of bright J band emission can be explained by hydrogen line of Pβ (1.28 microns) when we estimate the expected intensity relative to Brγ and Hα. In contrast, the south ridge is dominated by K_s band light with knotty structure, and has weak J and H band emission. The shocked H_2 line emission is well known from the sinus ridge produced by an interaction with dense molecular clouds. The large field of view of the 2MASS image shows that the H_2 emission extends to the east and inner shell of northeastern optical emission, which

  17. 2 MASS Near-Infrared Imaging of the Supernova Remnant IC443

    NASA Astrophysics Data System (ADS)

    Rho, J.; van Dyk, S.; Jarrett, T.; Cutri, R.; Reach, W.

    1999-05-01

    We present near-infrared imaging of IC443, covering the entire supernova remnant (50' diameter) from The Two Micron All Sky Survey (2MASS). 2MASS imaging is taken simultaneously in the J (1.25mu m), H (1.65mu m) and K_s (2.17mu m) bands using a 1.3 m telescope with a three-channel camera. The images have 3.5'' spatial resolution with a pixel size of 1''. The bands include lines of Pbeta , [Ni II] and [Fe II] for J band, Br10 and [Fe II] for H band, and Brgamma and H_2 for K_s band. Emission from IC443 was detected in all 3 bands from most of the optically bright parts of the remnant, revealing a shell-like morphology. This is the first near-infrared image of the northeastern and eastern parts. The color and structure are very different between the northeastern and southern parts. The northeastern shell shows sheet-like filamentary structure, similar to that of optical emission, with J and H band emission equivalently bright, and weak K_s emission. The H flux is higher than the K flux in the northeast; its ratio is similar order of magnitude to that of previously measured infrared spectroscopy from 2 positions. The ratio implies that the H band emission from the northeastern shell is mostly [Fe II] (1.64mu m), and the [Fe II] emission is much stronger than Brgamma . This contrasts to the ratio of 0.06 observed in H II regions. The strong [Fe II] line is produced not only by efficient excitation of Fe but also by grain destruction. Most of bright J band emission can be explained by hydrogen line of Pbeta (1.28mu m) when we estimate the expected intensity relative to Brgamma and Hα . In contrast, the south ridge is dominated by K_s band light with knotty structure, and has weak J and H band emission. The shocked H_2 line emission is well known from the sinus ridge produced by an interaction with dense molecular clouds. The large field of view of the 2MASS image shows that the H_2 emission extends to the east and inner shell of northeastern optical emission, which is

  18. Estimating Mass Properties of Dinosaurs Using Laser Imaging and 3D Computer Modelling

    PubMed Central

    Bates, Karl T.; Manning, Phillip L.; Hodgetts, David; Sellers, William I.

    2009-01-01

    Body mass reconstructions of extinct vertebrates are most robust when complete to near-complete skeletons allow the reconstruction of either physical or digital models. Digital models are most efficient in terms of time and cost, and provide the facility to infinitely modify model properties non-destructively, such that sensitivity analyses can be conducted to quantify the effect of the many unknown parameters involved in reconstructions of extinct animals. In this study we use laser scanning (LiDAR) and computer modelling methods to create a range of 3D mass models of five specimens of non-avian dinosaur; two near-complete specimens of Tyrannosaurus rex, the most complete specimens of Acrocanthosaurus atokensis and Strutiomimum sedens, and a near-complete skeleton of a sub-adult Edmontosaurus annectens. LiDAR scanning allows a full mounted skeleton to be imaged resulting in a detailed 3D model in which each bone retains its spatial position and articulation. This provides a high resolution skeletal framework around which the body cavity and internal organs such as lungs and air sacs can be reconstructed. This has allowed calculation of body segment masses, centres of mass and moments or inertia for each animal. However, any soft tissue reconstruction of an extinct taxon inevitably represents a best estimate model with an unknown level of accuracy. We have therefore conducted an extensive sensitivity analysis in which the volumes of body segments and respiratory organs were varied in an attempt to constrain the likely maximum plausible range of mass parameters for each animal. Our results provide wide ranges in actual mass and inertial values, emphasizing the high level of uncertainty inevitable in such reconstructions. However, our sensitivity analysis consistently places the centre of mass well below and in front of hip joint in each animal, regardless of the chosen combination of body and respiratory structure volumes. These results emphasize that future

  19. Estimating mass properties of dinosaurs using laser imaging and 3D computer modelling.

    PubMed

    Bates, Karl T; Manning, Phillip L; Hodgetts, David; Sellers, William I

    2009-01-01

    Body mass reconstructions of extinct vertebrates are most robust when complete to near-complete skeletons allow the reconstruction of either physical or digital models. Digital models are most efficient in terms of time and cost, and provide the facility to infinitely modify model properties non-destructively, such that sensitivity analyses can be conducted to quantify the effect of the many unknown parameters involved in reconstructions of extinct animals. In this study we use laser scanning (LiDAR) and computer modelling methods to create a range of 3D mass models of five specimens of non-avian dinosaur; two near-complete specimens of Tyrannosaurus rex, the most complete specimens of Acrocanthosaurus atokensis and Strutiomimum sedens, and a near-complete skeleton of a sub-adult Edmontosaurus annectens. LiDAR scanning allows a full mounted skeleton to be imaged resulting in a detailed 3D model in which each bone retains its spatial position and articulation. This provides a high resolution skeletal framework around which the body cavity and internal organs such as lungs and air sacs can be reconstructed. This has allowed calculation of body segment masses, centres of mass and moments or inertia for each animal. However, any soft tissue reconstruction of an extinct taxon inevitably represents a best estimate model with an unknown level of accuracy. We have therefore conducted an extensive sensitivity analysis in which the volumes of body segments and respiratory organs were varied in an attempt to constrain the likely maximum plausible range of mass parameters for each animal. Our results provide wide ranges in actual mass and inertial values, emphasizing the high level of uncertainty inevitable in such reconstructions. However, our sensitivity analysis consistently places the centre of mass well below and in front of hip joint in each animal, regardless of the chosen combination of body and respiratory structure volumes. These results emphasize that future

  20. Automated ambient desorption-ionization platform for surface imaging integrated with a commercial Fourier transform ion cyclotron resonance mass spectrometer.

    PubMed

    Pól, Jaroslav; Vidová, Veronika; Kruppa, Gary; Kobliha, Václav; Novák, Petr; Lemr, Karel; Kotiaho, Tapio; Kostiainen, Risto; Havlícek, Vladimír; Volný, Michael

    2009-10-15

    A fully automated atmospheric pressure ionization platform has been built and coupled with a commercial high-resolution Fourier transform ion cyclotron resonance mass spectrometer (FTICR-MS) instrument. The outstanding performance of this instrument allowed screening on the basis of exact masses in imaging mode. The main novel aspect was in the integration of the atmospheric pressure ionization imaging into the current software for matrix-assisted laser desorption ionization (MALDI) imaging, which allows the user of this commercial dual-source mass spectrometer to perform MALDI-MS and different ambient MS imaging from the same user interface and to utilize the same software tools. Desorption electrospray ionization (DESI) and desorption atmospheric pressure photoionization (DAPPI) were chosen to test the ambient surface imaging capabilities of this new ionization platform. Results of DESI imaging experiments performed on brain tissue sections are in agreement with previous MS imaging reports obtained by DESI imaging, but due to the high resolution and mass accuracy of the FTICR instrument it was possible to resolve several ions at the same nominal mass in the DESI-MS spectra of brain tissue. These isobaric interferences at low resolution are due to the overlap of ions from different lipid classes with different biological relevance. It was demonstrated that with the use of high-resolution MS fast imaging screening of lipids can be achieved without any preseparation steps. DAPPI, which is a relatively new and less developed ambient ionization technique compared to DESI, was used in imaging mode for the first time ever. It showed promise in imaging of phytocompounds from plant leaves, and selective ionization of a sterol lipid was achieved by DAPPI from a brain tissue sample. PMID:19761221

  1. MONITORING SPENT NUCLEAR FUEL REPROCESSING CONDITIONS NON-DESTRUCTIVELY AND IN NEAR-REAL-TIME USING THE MULTI-ISOTOPE PROCESS (MIP) MONITOR

    SciTech Connect

    Orton, Christopher R.; Fraga, Carlos G.; Douglas, Matthew; Christensen, Richard; Schwantes, Jon M.

    2010-05-07

    Researchers from Pacific Northwest National Laboratory and The Ohio State University are working to develop a system for monitoring spent nuclear fuel reprocessing facilities on-line, nondestructively, and in near-real-time. This method, known as the Multi-Isotope Process (MIP) Monitor, is based upon the measurement of distribution patterns of a suite of indicator (radioactive) isotopes present within product and waste streams of a nuclear reprocessing facility. Signatures from these indicator isotopes are monitored on-line by gamma spectrometry and compared, in near-real-time, to patterns representing "normal" process conditions using multivariate pattern recognition software. By targeting gamma-emitting indicator isotopes, the MIP Monitor approach is compatible with the use of small, portable, high-resolution gamma detectors that may be easily deployed throughout an existing facility. In addition, utilization of a suite of radio-elements, including ones with multiple oxidation states, increases the likelihood that attempts to divert material via process manipulation would be detected. Proof-of-principle modeling exercises simulating changes in acid strength have been completed and the results are promising. Laboratory testing is currently under way and significant results are available. Recent experimental results, along with an overview of the method are presented.

  2. Nonlinear simultaneous reconstruction of inhomogeneous compressibility and mass density distributions in unidirectional pulse-echo ultrasound imaging.

    PubMed

    Hesse, Markus C; Salehi, Leili; Schmitz, Georg

    2013-09-01

    In diagnostic ultrasound imaging, the image reconstruction quality is crucial for reliable diagnosis. Applying reconstruction algorithms based on the acoustic wave equation, the obtained image quality depends significantly on the physical material parameters accounted for in the equation. In this contribution, we extend a proposed iterative nonlinear one-parameter compressibility reconstruction algorithm by the additional reconstruction of the object's inhomogeneous mass density distribution. The improved iterative algorithm is able to reconstruct inhomogeneous maps of the object's compressibility and mass density simultaneously using only one conventional linear transducer array at a fixed location for wave transmission and detection. The derived approach is based on an acoustic wave equation including spatial compressibility and mass density variations, and utilizes the Kaczmarz method for iterative material parameter reconstruction. We validate our algorithm numerically for an unidirectional pulse-echo breast imaging application, and thus generate simulated measurements acquired from a numerical breast phantom with realistic compressibility and mass density values. Applying these measurements, we demonstrate with two reconstruction experiments the necessity to calculate the mass density in case of tissues with significant mass density inhomogeneities. When reconstructing spatial mass density variations, artefacts in the breast's compressibility image are reduced resulting in improved spatial resolution. Furthermore, the compressibility relative error magnitude within a diagnostically significant region of interest (ROI) decreases from 3.04% to 2.62%. Moreover, a second image showing the breast's inhomogeneous mass density distribution is given to provide additional diagnostic information. In the compressibility image, a spatial resolution moderately higher than the classical half-wavelength limit is observed. PMID:23948675

  3. Imaging Mass Spectrometry of Intact Proteins from Alcohol-Preserved Tissue Specimens: Bypassing Formalin Fixation

    PubMed Central

    Chaurand, Pierre; Latham, Joey C.; Lane, Kirk B.; Mobley, James A.; Polosukhin, Vasiliy V.; Wirth, Pamela S.; Nanney, Lillian B.; Caprioli, Richard M.

    2010-01-01

    Imaging mass spectrometry is becoming a key technology for the investigation of the molecular content of biological tissue sections in direct correlation with the underlying histology. Much of our work has been done with fresh-frozen tissue sections that has undergone minimal protein degradation between the time a tissue biopsy is sampled and the time it is snap-frozen so that no preserving or fixing agents need to be added to the frozen biopsy. However, in many sampling environments, immediate flash freezing may not be possible and so we have explored the use of ethanol-preserved, paraffin-embedded tissue specimens for proteomic analyses. Solvent-only preserved tissue specimens provide long-term preservation at room temperature, generation of high quality histological sections and little if any chemical alteration of the proteins. Using mouse organs, several key steps involved in the tissue dehydration process have been investigated to assess the potential of such preserved specimens for profiling and imaging mass spectrometry investigations. PMID:18613713

  4. Time-course mass spectrometry imaging for depicting drug incorporation into hair.

    PubMed

    Kamata, Tooru; Shima, Noriaki; Sasaki, Keiko; Matsuta, Shuntaro; Takei, Shiori; Katagi, Munehiro; Miki, Akihiro; Zaitsu, Kei; Nakanishi, Toyofumi; Sato, Takako; Suzuki, Koichi; Tsuchihashi, Hitoshi

    2015-06-01

    In order to investigate the incorporation of drugs into hair, matrix-assisted laser desorption/ionization-time-of-flight tandem mass spectrometry (MS/MS) imaging was performed on the longitudinal sections of single scalp hair shafts sampled from volunteers after a single oral administration of methoxyphenamine (MOP), a noncontrolled analogue of methamphetamine. Hair specimens were collected by plucking out with the roots intact, and these specimens were prepped by an optimized procedure based on freeze-sectioning to detect the drug inside the hair shaft and hair root. Time-course changes in the imaging results, with confirmatory quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis for each 1-mm segment of single hair strands, revealed a substantial concentration of the drug first onto the hair bulbs after ingestion, while only a small portion appeared to be incorporated into the hair matrix, forming a 2-3 mm distinctive drug band with tailing. Comparable amount of the drug also appeared to be incorporated into the keratinized hair shaft in the upper dermis zone, forming another distinct drug band of about 2 mm, which both moved toward the distal side, following the strand's growth rate. These findings provide forensically crucial information: there are two major drug incorporation sites, at least for MOP, which cause overlap of the recordings and deteriorates its chronological resolution down to about 11 days or perhaps longer. PMID:25919888

  5. An accessible, scalable ecosystem for enabling and sharing diverse mass spectrometry imaging analyses.

    PubMed

    Fischer, Curt R; Ruebel, Oliver; Bowen, Benjamin P

    2016-01-01

    Mass spectrometry imaging (MSI) is used in an increasing number of biological applications. Typical MSI datasets contain unique, high-resolution mass spectra from tens of thousands of spatial locations, resulting in raw data sizes of tens of gigabytes per sample. In this paper, we review technical progress that is enabling new biological applications and that is driving an increase in the complexity and size of MSI data. Handling such data often requires specialized computational infrastructure, software, and expertise. OpenMSI, our recently described platform, makes it easy to explore and share MSI datasets via the web - even when larger than 50 GB. Here we describe the integration of OpenMSI with IPython notebooks for transparent, sharable, and replicable MSI research. An advantage of this approach is that users do not have to share raw data along with analyses; instead, data is retrieved via OpenMSI's web API. The IPython notebook interface provides a low-barrier entry point for data manipulation that is accessible for scientists without extensive computational training. Via these notebooks, analyses can be easily shared without requiring any data movement. We provide example notebooks for several common MSI analysis types including data normalization, plotting, clustering, and classification, and image registration. PMID:26365033

  6. Direct profiling of myelinated and demyelinated regions in mouse brain by imaging mass spectrometry

    NASA Astrophysics Data System (ADS)

    Ceuppens, Ruben; Dumont, Debora; van Brussel, Leen; van de Plas, Babs; Daniels, Ruth; Noben, Jean-Paul; Verhaert, Peter; van der Gucht, Estel; Robben, Johan; Clerens, Stefan; Arckens, Lutgarde

    2007-02-01

    One of the newly developed imaging mass spectrometry (IMS) technologies utilizes matrix-assisted laser desorption/ionization (MALDI) mass spectrometry to map proteins in thin tissue sections. In this study, we evaluated the power of MALDI IMS as we developed it in our (Bruker) MALDI TOF (Reflex IV) and TOF-TOF (Ultraflex II) systems to study myelin patterns in the mouse central nervous system under normal and pathological conditions. MALDI IMS was applied to assess myelin basic protein (MBP) isoform-specific profiles in different regions throughout the mouse brain. The distribution of ions of m/z 14,144 and 18,447 displayed a striking resemblance with white matter histology and were identified as MBP isoform 8 and 5, respectively. In addition, we demonstrated a significant reduction of the MBP-8 peak intensity upon MALDI IMS analysis of focal ethidium bromide-induced demyelinated brain areas. Our MS images were validated by immunohistochemistry using MBP antibodies. This study underscores the potential of MALDI IMS to study the contribution of MBP to demyelinating diseases.

  7. Photodissociation dynamics of ethanethiol in clusters: complementary information from velocity map imaging, mass spectrometry and calculations.

    PubMed

    Svrčková, Pavla; Pysanenko, Andriy; Lengyel, Jozef; Rubovič, Peter; Kočišek, Jaroslav; Poterya, Viktoriya; Slavíček, Petr; Fárník, Michal

    2015-10-21

    We investigate the solvent effects on photodissociation dynamics of the S-H bond in ethanethiol CH3CH2SH (EtSH). The H fragment images are recorded by velocity map imaging (VMI) at 243 nm in various expansion regimes ranging from isolated molecules to clusters of different sizes and compositions. The VMI experiment is accompanied by electron ionization mass spectrometry using a reflectron time-of-flight mass spectrometer (RTOFMS). The experimental data are interpreted using ab initio calculations. The direct S-H bond fission results in a peak of fast fragments at Ekin(H) ≈ 1.25 eV with a partly resolved structure corresponding to vibrational levels of the CH3CH2S cofragment. Clusters of different nature ranging from dimers to large (EtSH)N, N ≥ 10, clusters and to ethanethiol clusters embedded in larger argon "snowballs" are investigated. In the clusters a sharp peak of near-zero kinetic energy fragments occurs due to the caging. The dynamics of the fragment caging is pictured theoretically, using multi-reference ab initio theory for the ethanethiol dimer. The larger cluster character is revealed by the simultaneous analysis of the VMI and RTOFMS experiments; none of these tools alone can provide the complete picture. PMID:25743944

  8. Review of hepatic imaging and a problem-oriented approach to liver masses.

    PubMed

    Bennett, W F; Bova, J G

    1990-10-01

    We believe that imaging of the liver is complicated. The sporadic appearance of incidental benign lesions and variability in scanning techniques, equipment and artifacts add difficulties to the evaluation of liver masses. Therefore we emphasize the need to define the problem for which the patient is being imaged. This information helps in choosing the procedure of choice and the technique needed to give the most expedient, accurate answer. This will also help apply the lowest risk and most cost-efficient care. Imaging algorithms vary depending on the suspected pathological conditions. Dynamic bolus-enhanced CT is the modality of choice in most situations. Tc99m sulfur-colloid liver-spleen scans are helpful in patients with suspected FNH, and Tc99m-tagged-RBC-SPECT scans are recommended to confirm cavernous hemangiomas. Cysts are easily confirmed by US. Although MRI is competitive with CT, it has not become a primary modality because of cost, availability, patient selection and variability of scanner capabilities among the many manufacturers and models. It is hard to predict what future development of imaging techniques will bring. Many feel that significant advances have plateaued. Time and money will more likely be concentrated on improving image resolution, speed of scanning and ability to transfer this information to sites outside of the radiology department. In addition to faster scanning, we expect to soon have available safe intravenous and enteric contrast agents for MRI. Certainly this will lead to a new round of investigations to compare MRI with CT scanning. PMID:2210679

  9. Mass balance of Mars' residual south polar cap from CTX images and other data

    NASA Astrophysics Data System (ADS)

    Thomas, P. C.; Calvin, W.; Cantor, B.; Haberle, R.; James, P. B.; Lee, S. W.

    2016-04-01

    Erosion of pits in the residual south polar cap (RSPC) of Mars concurrent with deposition and fluctuating cap boundaries raises questions about the mass balance and long term stability of the cap. Determining a mass balance by measurement of a net gain or loss of atmospheric CO2 by direct pressure measurements (Haberle, R.M. et al. [2014]. Secular climate change on Mars: An update using one Mars year of MSL pressure data. American Geophysical Union (Fall). Abstract 3947), although perhaps the most direct method, has so far given ambiguous results. Estimating volume changes from imaging data faces challenges, and has previously been attempted only in isolated areas of the cap. In this study we use 6 m/pixel Context Imager (CTX) data from Mars year 31 to map all the morphologic units of the RSPC, expand the measurement record of pit erosion rates, and use high resolution images to place limits on vertical changes in the surface of the residual cap. We find the mass balance in Mars years 9-31 to be -6 to +4 km3/♂y, or roughly -0.039% to +0.026% of the mean atmospheric CO2 mass/♂y. The indeterminate sign results chiefly from uncertainty in the amounts of deposition or erosion on the upper surfaces of deposits (as opposed to scarp retreat). Erosion and net deposition in this period appear to be controlled by summertime planetary scale dust events, the largest occurring in MY 9, another, smaller one in MY 28. The rates of erosion and the deposition observed since MY 9 appear to be consistent with the types of deposits and erosional behavior found in most of the residual cap. However, small areas (<10%) of the cap are distinguished by their greater thickness, polygonal troughs, and embayed contacts with thinner units. These deposits may require extended periods (>100 ♂y) of depositional and/or erosional conditions different from those occurring in the period since MY 9, although these environmental differences could be subtle.

  10. Efficient spatial segmentation of large imaging mass spectrometry datasets with spatially aware clustering

    PubMed Central

    Alexandrov, Theodore; Kobarg, Jan Hendrik

    2011-01-01

    Motivation: Imaging mass spectrometry (IMS) is one of the few measurement technology s of biochemistry which, given a thin sample, is able to reveal its spatial chemical composition in the full molecular range. IMS produces a hyperspectral image, where for each pixel a high-dimensional mass spectrum is measured. Currently, the technology is mature enough and one of the major problems preventing its spreading is the under-development of computational methods for mining huge IMS datasets. This article proposes a novel approach for spatial segmentation of an IMS dataset, which is constructed considering the important issue of pixel-to-pixel variability. Methods: We segment pixels by clustering their mass spectra. Importantly, we incorporate spatial relations between pixels into clustering, so that pixels are clustered together with their neighbors. We propose two methods. One is non-adaptive, where pixel neighborhoods are selected in the same manner for all pixels. The second one respects the structure observable in the data. For a pixel, its neighborhood is defined taking into account similarity of its spectrum to the spectra of adjacent pixels. Both methods have the linear complexity and require linear memory space (in the number of spectra). Results: The proposed segmentation methods are evaluated on two IMS datasets: a rat brain section and a section of a neuroendocrine tumor. They discover anatomical structure, discriminate the tumor region and highlight functionally similar regions. Moreover, our methods provide segmentation maps of similar or better quality if compared to the other state-of-the-art methods, but outperform them in runtime and/or required memory. Contact: theodore@math.uni-bremen.de PMID:21685075

  11. Computer-aided diagnosis of mammographic masses using scalable image retrieval.

    PubMed

    Jiang, Menglin; Zhang, Shaoting; Li, Hongsheng; Metaxas, Dimitris N

    2015-02-01

    Computer-aided diagnosis of masses in mammograms is important to the prevention of breast cancer. Many approaches tackle this problem through content-based image retrieval techniques. However, most of them fall short of scalability in the retrieval stage, and their diagnostic accuracy is, therefore, restricted. To overcome this drawback, we propose a scalable method for retrieval and diagnosis of mammographic masses. Specifically, for a query mammographic region of interest (ROI), scale-invariant feature transform (SIFT) features are extracted and searched in a vocabulary tree, which stores all the quantized features of previously diagnosed mammographic ROIs. In addition, to fully exert the discriminative power of SIFT features, contextual information in the vocabulary tree is employed to refine the weights of tree nodes. The retrieved ROIs are then used to determine whether the query ROI contains a mass. The presented method has excellent scalability due to the low spatial-temporal cost of vocabulary tree. Extensive experiments are conducted on a large dataset of 11 553 ROIs extracted from the digital database for screening mammography, which demonstrate the accuracy and scalability of our approach. PMID:25361497

  12. Mapping Lipid Alterations in Traumatically Injured Rat Spinal Cord by Desorption Electrospray Ionization Imaging Mass Spectrometry

    PubMed Central

    Girod, Marion; Shi, Yunzhou; Cheng, Ji-Xin; Cooks, R. Graham

    2010-01-01

    Desorption electrospray ionization (DESI) mass spectrometry is used in an imaging mode to interrogate the lipid profiles of 15 µm thin tissues cross sections of injured rat spinal cord and normal healthy tissue. Increased relative intensities of fatty acids, diacylglycerols and lysolipids (between +120% and +240%) as well as a small decrease in intensities of lipids (−30%) were visualized in the lesion epi-center and adjacent areas after spinal cord injury. This indicates the hydrolysis of lipids during the demyelination process due to activation of phospholipase A2 enzyme. In addition, signals corresponding to oxidative degradation products, such as prostaglandin and hydroxyeicosatetraenoic acid, exhibited increased signal intensity by a factor of two in the negative ion mode in lesions relative to the normal healthy tissue. Analysis of malondialdehyde, a product of lipid peroxidation and marker of oxidative stress, was accomplished in the ambient environment using reactive DESI mass spectrometry imaging. This was achieved by electrospraying reagent solution containing dinitrophenylhydrazine as high velocity charged droplets onto the tissue section. The hydrazine reacts selectively and rapidly with the carbonyl groups of malondialdehyde and signal intensity of twice the intensity was detected in the lesions compared to healthy spinal cord. With a small amount of tissue sample, DESI-MS imaging provides information on the composition and distribution of specific compounds (limited by the occurrence of isomeric lipids with very similar fragmentation patterns) in lesions after spinal cord injury in comparison with normal healthy tissue allowing identification of the extent of the lesion and its repair. PMID:21142140

  13. MALDI-imaging mass spectrometry - An emerging technique in plant biology.

    PubMed

    Kaspar, Stephanie; Peukert, Manuela; Svatos, Ales; Matros, Andrea; Mock, Hans-Peter

    2011-05-01

    Recent advances in instrumentation and sample preparation have facilitated the mass spectrometric (MS) imaging of a large variety of biological molecules from small metabolites to large proteins. The technique can be applied at both the tissue and the single-cell level, and provides information regarding the spatial distribution of specific molecules. Nevertheless, the use of MS imaging in plant science remains far from routine, and there is still a need to adapt protocols to suit specific tissues. We present an overview of MALDI-imaging MS (MSI) technology and its use for the analysis of plant tissue. Recent methodological developments have been summarized, and the major challenges involved in using MALDI-MSI, including sample preparation, the analysis of metabolites and peptides, and strategies for data evaluation are all discussed. Some attention is given to the identification of differentially distributed compounds. To date, the use of MALDI-MSI in plant research has been limited. Examples include leaf surface metabolite maps, the characterization of soluble metabolite translocation in planta, and the profiling of protein/metabolite patterns in cereal grain cross-sections. Improvements to both sample preparation strategies and analytical platforms (aimed at both spectrum acquisition and post-acquisition analysis) will enhance the relevance of MALDI-MSI technology in plant research. PMID:21462348

  14. Interactions between Coronal Mass Ejections Viewed in Coordinated Imaging and In Situ Observations

    NASA Technical Reports Server (NTRS)

    Liu, Ying D.; Luhmann, Janet G.; Moestl, Christian; Martinez-Oliveros, Juan C.; Bale, Stewart D.; Lin, Robert P.; Harrison, Richard A.; Temmer, Manuela; Webb, David F.; Odstrcil, Dusan

    2013-01-01

    The successive coronal mass ejections (CMEs) from 2010 July 30 - August 1 present us the first opportunity to study CME-CME interactions with unprecedented heliospheric imaging and in situ observations from multiple vantage points. We describe two cases of CME interactions: merging of two CMEs launched close in time and overtaking of a preceding CME by a shock wave. The first two CMEs on August 1 interact close to the Sun and form a merged front, which then overtakes the July 30 CME near 1 AU, as revealed by wide-angle imaging observations. Connections between imaging observations and in situ signatures at 1 AU suggest that the merged front is a shock wave, followed by two ejecta observed at Wind which seem to have already merged. In situ measurements show that the CME from July 30 is being overtaken by the shock at 1 AU and is significantly compressed, accelerated and heated. The interaction between the preceding ejecta and shock also results in variations in the shock strength and structure on a global scale, as shown by widely separated in situ measurements from Wind and STEREO B. These results indicate important implications of CME-CME interactions for shock propagation, particle acceleration and space weather forecasting.

  15. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  16. Quantitative images of metals in plant tissues measured by laser ablation inductively coupled plasma mass spectrometry

    NASA Astrophysics Data System (ADS)

    Becker, J. S.; Dietrich, R. C.; Matusch, A.; Pozebon, D.; Dressler, V. L.

    2008-11-01

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used for quantitative imaging of toxic and essential elements in thin sections (thickness of 30 or 40 μm) of tobacco plant tissues. Two-dimensional images of Mg, Fe, Mn, Zn, Cu, Cd, Rh, Pt and Pb in leaves, shoots and roots of tobacco were produced. Sections of the plant tissues (fixed onto glass slides) were scanned by a focused beam of a Nd:YAG laser in a laser ablation chamber. The ablated material was transported with argon as carrier gas to the ICP ion source at a quadrupole ICP-MS instrument. Ion intensities of the investigated elements were measured together with 13C +, 33S + and 34S + within the entire plant tissue section. Matrix matching standards (prepared using powder of dried tobacco leaves) were used to constitute calibration curves, whereas the regression coefficient of the attained calibration curves was typically 0.99. The variability of LA-ICP-MS process, sample heterogeneity and water content in the sample were corrected by using 13C + as internal standard. Quantitative imaging of the selected elements revealed their inhomogeneous distribution in leaves, shoots and roots.

  17. Interaction between Coronal Mass Ejections Viewed in Coordinated Imaging and In Situ Observations

    NASA Astrophysics Data System (ADS)

    Liu, Y.; Luhmann, J. G.; Moestl, C.; Martinez Oliveros, J. C.; Harrison, R.; Temmer, M.; Bale, S.; Lin, R. P.

    2011-12-01

    Interaction between coronal mass ejections (CMEs), which is expected to be a frequent phenomenon, has important implications for both space weather and basic plasma physics. First, the interaction alters the global heliospheric configuration, which may lead to favorable conditions for geomagnetic storm generation. Second, the interaction implies significant energy and momentum transfer between the interacting CMEs where magnetic reconnection may take place. Third, in case a shock is driven by the trailing CME, interesting physical processes may occur when the shock is propagating through the preceding one, such as modifications in the shock strength, particle intensity and transport. There are successive CMEs on July 30 - August 1, 2011, which presents us the first opportunity to study CME-CME interaction with unprecedented heliospheric imaging and in situ observations from a fleet of spacecraft. The first two CMEs on August 1 interact close to the Sun and form a merged front, which then overtakes the July 30 CME near 1 AU, as revealed by wide-angle imaging observations. In situ measurements indicate that the first two CMEs on August 1 seem to have already merged at 0.7 and 1 AU, and at 1 AU their shock is propagating into the CME from July 30. We will report and discuss the CME-CME interaction signatures from the coordinated imaging and in situ observations in this presentation.

  18. Nanostructure imaging mass spectrometry: the role of fluorocarbons in metabolite analysis and yoctomole level sensitivity.

    PubMed

    Kurczy, Michael E; Northen, Trent R; Trauger, Sunia A; Siuzdak, Gary

    2015-01-01

    Nanostructure imaging mass spectrometry (NIMS) has become an effective technology for generating ions in the gas phase, providing high sensitivity and imaging capabilities for small molecules, metabolites, drugs, and drug metabolites. Specifically, laser desorption from the nanostructure surfaces results in efficient energy transfer, low background chemical noise, and the nondestructive release of analyte ions into the gas phase. The modification of nanostructured surfaces with fluorous compounds, either covalent or non-covalent, has played an important role in gaining high efficiency/sensitivity by facilitating analyte desorption from the nonadhesive surfaces, and minimizing the amount of laser energy required. In addition, the hydrophobic fluorinated nanostructure surfaces have aided in concentrating deposited samples into fine micrometer-sized spots, a feature that further facilitates efficient desorption/ionization. These fluorous nanostructured surfaces have opened up NIMS to very broad applications including enzyme activity assays and imaging, providing low background, efficient energy transfer, nondestructive analyte ion generation, super-hydrophobic surfaces, and ultra-high detection sensitivity. PMID:25361674

  19. Chemical imaging of latent fingerprints by mass spectrometry based on laser activated electron tunneling.

    PubMed

    Tang, Xuemei; Huang, Lulu; Zhang, Wenyang; Zhong, Hongying

    2015-03-01

    Identification of endogenous and exogenous chemicals contained in latent fingerprints is important for forensic science in order to acquire evidence of criminal identities and contacts with specific chemicals. Mass spectrometry has emerged as a powerful technique for such applications without any derivatization or fluorescent tags. Among these techniques, MALDI (Matrix Assisted Laser Desorption Ionization) provides small beam size but has interferences with MALDI matrix materials, which cause ion suppressions as well as limited spatial resolution resulting from uneven distribution of MALDI matrix crystals with different sizes. LAET (Laser Activated Electron Tunneling) described in this work offers capabilities for chemical imaging through electron-directed soft ionization. A special film of semiconductors has been designed for collection of fingerprints. Nanoparticles of bismuth cobalt zinc oxide were compressed on a conductive metal substrate (Al or Cu sticky tape) under 10 MPa pressure. Resultant uniform thin films provide tight and shining surfaces on which fingers are impressed. Irradiation of ultraviolet laser pulses (355 nm) on the thin film instantly generates photoelectrons that can be captured by adsorbed organic molecules and subsequently cause electron-directed ionization and fragmentation. Imaging of latent fingerprints is achieved by visualization of the spatial distribution of these molecular ions and structural information-rich fragment ions. Atomic electron emission together with finely tuned laser beam size improve spatial resolution. With the LAET technique, imaging analysis not only can identify physical shapes but also reveal endogenous metabolites present in females and males, detect contacts with prohibited substances, and resolve overlapped latent fingerprints. PMID:25647159

  20. GEOMETRIC TRIANGULATION OF IMAGING OBSERVATIONS TO TRACK CORONAL MASS EJECTIONS CONTINUOUSLY OUT TO 1 AU

    SciTech Connect

    Liu Ying; Luhmann, Janet G.; Bale, Stuart D.; Lin, Robert P.; Davies, Jackie A.; Vourlidas, Angelos

    2010-02-10

    We describe a geometric triangulation technique, based on time-elongation maps constructed from imaging observations, to track coronal mass ejections (CMEs) continuously in the heliosphere and predict their impact on the Earth. Taking advantage of stereoscopic imaging observations from the Solar Terrestrial Relations Observatory, this technique can determine the propagation direction and radial distance of CMEs from their birth in the corona all the way to 1 AU. The efficacy of the method is demonstrated by its application to the 2008 December 12 CME, which manifests as a magnetic cloud (MC) from in situ measurements at the Earth. The predicted arrival time and radial velocity at the Earth are well confirmed by the in situ observations around the MC. Our method reveals non-radial motions and velocity changes of the CME over large distances in the heliosphere. It also associates the flux-rope structure measured in situ with the dark cavity of the CME in imaging observations. Implementation of the technique, which is expected to be a routine possibility in the future, may indicate a substantial advance in CME studies as well as space weather forecasting.

  1. MALDI-Mass Spectrometric Imaging for the Investigation of Metabolites in Medicago truncatula Root Nodules

    PubMed Central

    Gemperline, Erin; Li, Lingjun

    2014-01-01

    Most techniques used to study small molecules, such as pharmaceutical drugs or endogenous metabolites, employ tissue extracts which require the homogenization of the tissue of interest that could potentially cause changes in the metabolic pathways being studied1. Mass spectrometric imaging (MSI) is a powerful analytical tool that can provide spatial information of analytes within intact slices of biological tissue samples1-5. This technique has been used extensively to study various types of compounds including proteins, peptides, lipids, and small molecules such as endogenous metabolites. With matrix-assisted laser desorption/ionization (MALDI)-MSI, spatial distributions of multiple metabolites can be simultaneously detected. Herein, a method developed specifically for conducting untargeted metabolomics MSI experiments on legume roots and root nodules is presented which could reveal insights into the biological processes taking place. The method presented here shows a typical MSI workflow, from sample preparation to image acquisition, and focuses on the matrix application step, demonstrating several matrix application techniques that are useful for detecting small molecules. Once the MS images are generated, the analysis and identification of metabolites of interest is discussed and demonstrated. The standard workflow presented here can be easily modified for different tissue types, molecular species, and instrumentation. PMID:24637669

  2. STEREO DIRECT IMAGING OF A CORONAL MASS EJECTION-DRIVEN SHOCK TO 0.5 AU

    SciTech Connect

    Maloney, Shane A.; Gallagher, Peter T.

    2011-07-20

    Fast coronal mass ejections (CMEs) generate standing or bow shocks as they propagate through the corona and solar wind. Although CME shocks have previously been detected indirectly via their emission at radio frequencies, direct imaging has remained elusive due to their low contrast at optical wavelengths. Here we report the first images of a CME-driven shock as it propagates through interplanetary space from 8 R{sub sun} to 120 R{sub sun} (0.5 AU), using observations from the STEREO Heliospheric Imager. The CME was measured to have a velocity of {approx}1000 km s{sup -1} and a Mach number of 4.1 {+-} 1.2, while the shock front standoff distance ({Delta}) was found to increase linearly to {approx}20 R{sub sun} at 0.5 AU. The normalized standoff distance ({Delta}/D{sub O} ) showed reasonable agreement with semi-empirical relations, where D{sub O} is the CME radius. However, when normalized using the radius of curvature, {Delta}/R{sub O} did not agree well with theory, implying that R{sub O} was underestimated by a factor of {approx}3-8. This is most likely due to the difficulty in estimating the larger radius of curvature along the CME axis from the observations, which provide only a cross-sectional view of the CME.

  3. Lipid imaging in the zebra finch brain with secondary ion mass spectrometry

    NASA Astrophysics Data System (ADS)

    Amaya, Kensey R.; Monroe, Eric B.; Sweedler, Jonathan V.; Clayton, David F.

    2007-02-01

    Lipids have diverse functions in the nervous system, but the study of their anatomical distributions in the intact brain is rather difficult using conventional methodologies. Here we demonstrate the application of high resolution time-of-flight (ToF) secondary ion mass spectrometry (SIMS) to image various lipid components and cholesterol across an entire brain section prepared from an adult zebra finch (Taeniopygia guttata), with a spatial resolution of 2.3 [mu]m, resulting in the formation of 11.5 megapixel chemical images. The zebra finch is a songbird in which specific neural and developmental functions have been ascribed to discrete "song control nuclei" of the forebrain. We have observed a relative increase of palmitic acid C16:0 and oleic acid C18:1 in song control nuclei versus the surrounding tissue, while phosphate (PO3-), representative of phospholipids, was lower in these regions. Cholesterol was present at a high level only in the white matter of the optic tectum. More diffuse distributions were observed for stearic, arachidonic, linolenic, and palmitoleic acids. The presented results illustrate that SIMS imaging is a useful approach for assessing changes in lipid content during song circuit development and song learning.

  4. Geometric Triangulation of Imaging Observations to Track Coronal Mass Ejections Continuously Out to 1 AU

    NASA Astrophysics Data System (ADS)

    Liu, Ying; Davies, Jackie A.; Luhmann, Janet G.; Vourlidas, Angelos; Bale, Stuart D.; Lin, Robert P.

    2010-02-01

    We describe a geometric triangulation technique, based on time-elongation maps constructed from imaging observations, to track coronal mass ejections (CMEs) continuously in the heliosphere and predict their impact on the Earth. Taking advantage of stereoscopic imaging observations from the Solar Terrestrial Relations Observatory, this technique can determine the propagation direction and radial distance of CMEs from their birth in the corona all the way to 1 AU. The efficacy of the method is demonstrated by its application to the 2008 December 12 CME, which manifests as a magnetic cloud (MC) from in situ measurements at the Earth. The predicted arrival time and radial velocity at the Earth are well confirmed by the in situ observations around the MC. Our method reveals non-radial motions and velocity changes of the CME over large distances in the heliosphere. It also associates the flux-rope structure measured in situ with the dark cavity of the CME in imaging observations. Implementation of the technique, which is expected to be a routine possibility in the future, may indicate a substantial advance in CME studies as well as space weather forecasting.

  5. Living cell dry mass measurement using quantitative phase imaging with quadriwave lateral shearing interferometry: an accuracy and sensitivity discussion

    NASA Astrophysics Data System (ADS)

    Aknoun, Sherazade; Savatier, Julien; Bon, Pierre; Galland, Frédéric; Abdeladim, Lamiae; Wattellier, Benoit; Monneret, Serge

    2015-12-01

    Single-cell dry mass measurement is used in biology to follow cell cycle, to address effects of drugs, or to investigate cell metabolism. Quantitative phase imaging technique with quadriwave lateral shearing interferometry (QWLSI) allows measuring cell dry mass. The technique is very simple to set up, as it is integrated in a camera-like instrument. It simply plugs onto a standard microscope and uses a white light illumination source. Its working principle is first explained, from image acquisition to automated segmentation algorithm and dry mass quantification. Metrology of the whole process, including its sensitivity, repeatability, reliability, sources of error, over different kinds of samples and under different experimental conditions, is developed. We show that there is no influence of magnification or spatial light coherence on dry mass measurement; effect of defocus is more critical but can be calibrated. As a consequence, QWLSI is a well-suited technique for fast, simple, and reliable cell dry mass study, especially for live cells.

  6. Spatially resolved chemical imaging of individual atmospheric particles using nanoscale imaging mass spectrometry: insight into particle origin and chemistry

    DOE PAGESBeta

    Ghosal, Sutapa; Weber, Peter K.; Laskin, Alexander

    2014-01-14

    Knowledge of the spatially resolved composition of atmospheric particles is essential for differentiating between their surface versus bulk chemistry and understanding particle reactivity and the potential environmental impact. Here, we demonstrate the application of nanometer-scale secondary ion mass spectrometry (CAMECA NanoSIMS 50 ion probe) for 3D chemical imaging of individual atmospheric particles without any sample pre-treatment, such as sectioning of particles. Use of NanoSIMS depth profile analysis enables elemental mapping of particles with nanometer spatial resolution over a broad range of particle sizes. We have used this technique to probe the spatially resolved composition of ambient particles collected during amore » field campaign in Mexico City. Particles collected during this campaign have been extensively characterized in the past using other particle analysis techniques and hence offer a unique opportunity for exploring the utility of depth-resolved chemical imaging in ambient particle research. The particles that we examined in our study include those collected during a pollution episode related to urban waste incineration as well as background particles from the same location before the episode. Particles from the pollution episode show substantial intra-particle compositional variability typical of particles resulting from multiple emission sources. In contrast, the background particles have relatively homogeneous compositions with enhanced presence of nitrogen, oxygen, and chlorine at the particle surface. We also observed the surface enhancement of nitrogen and oxygen species is consistent with the presence of surface nitrates resulting from gas–particle heterogeneous interactions and is indicative of atmospheric ageing of the particles. The results presented here illustrate 3D characterization of ambient particles for insight into their chemical history.« less

  7. Spatially resolved chemical imaging of individual atmospheric particles using nanoscale imaging mass spectrometry: Insighs into particle origin and chemistry

    SciTech Connect

    Ghosal, Sutapa; Weber, Peter K.; Laskin, Alexander

    2014-04-21

    Knowledge of the spatially-resolved composition of atmospheric particles is essential for differentiating between their surface versus bulk chemistry, understanding particle reactivity and the potential environmental impact. We demonstrate the application of nanometer-scale secondary ion mass spectrometry (Cameca NanoSIMS 50 ion probe) for 3D chemical imaging of individual atmospheric particles without any sample pre-treatment, such as the sectioning of particles. Use of NanoSIMS depth profile analysis enables elemental mapping of particles with nanometer spatial resolution over a broad of range of particle sizes. We have used this technique to probe spatially resolved composition of ambient particles collected during a field campaign in Mexico City. Particles collected during this campaign have been extensively characterized in the past using other particle analysis techniques and hence offer a unique opportunity for exploring the utility of depth resolved chemical imaging in ambient particle research. 1 Particles examined in this study include those collected during a pollution episode related to urban waste incineration as well as background particles from the same location prior to the episode. Particles from the pollution episode show substantial intra-particle compositional variability typical of particles resulting from multiple emission sources. In contrast, the background particles have relatively homogeneous compositions with enhanced presence of nitrogen, oxygen and chlorine at the particle surface. The observed surface enhancement of nitrogen and oxygen species is consistent with the presence of surface nitrates resulting from gas-particle heterogeneous interactions and is indicative of atmospheric ageing of the particles. The results presented here illustrate 3D characterization of ambient particles for insights into their chemical history.

  8. Spatially resolved chemical imaging of individual atmospheric particles using nanoscale imaging mass spectrometry: Insights into particle origin and chemistry

    NASA Astrophysics Data System (ADS)

    Ghosal, S.; Weber, P. K.; Laskin, A.

    2014-12-01

    Knowledge of the spatially-resolved composition of atmospheric particles is essential for differentiating between their surface versus bulk chemistry, understanding particle reactivity and the potential environmental impact. We demonstrate the application of nanometer-scale secondary ion mass spectrometry (Cameca NanoSIMS 50 ion probe) for 3D chemical imaging of individual atmospheric particles without any sample pre-treatment, such as the sectioning of particles. Use of NanoSIMS depth profile analysis enables elemental mapping of particles with nanometer spatial resolution over a broad of range of particle sizes. We have used this technique to probe spatially resolved composition of ambient particles collected during a field campaign in Mexico City. Particles collected during this campaign have been extensively characterized in the past using other particle analysis techniques and hence offer a unique opportunity for exploring the utility of depth resolved chemical imaging in ambient particle research. Particles examined in this study include those collected during a pollution episode related to urban waste incineration as well as background particles from the same location prior to the episode. Particles from the pollution episode show substantial intra-particle compositional variability typical of particles resulting from multiple emission sources. In contrast, the background particles have relatively homogeneous compositions with enhanced presence of nitrogen, oxygen and chlorine at the particle surface. The observed surface enhancement of nitrogen and oxygen species is consistent with the presence of surface nitrates resulting from gas-particle heterogeneous interactions and is indicative of atmospheric ageing of the particles. The results presented here illustrate 3D characterization of ambient particles for insights into their chemical history.

  9. From Whole-body Sections Down to Cellular Level, Multiscale Imaging of Phospholipids by MALDI Mass Spectrometry*

    PubMed Central

    Chaurand, Pierre; Cornett, Dale S.; Angel, Peggi M.; Caprioli, Richard M.

    2011-01-01

    Significant progress in instrumentation and sample preparation approaches have recently expanded the potential of MALDI imaging mass spectrometry to the analysis of phospholipids and other endogenous metabolites naturally occurring in tissue specimens. Here we explore some of the requirements necessary for the successful analysis and imaging of phospholipids from thin tissue sections of various dimensions by MALDI time-of-flight mass spectrometry. We address methodology issues relative to the imaging of whole-body sections such as those cut from model laboratory animals, sections of intermediate dimensions typically prepared from individual organs, as well as the requirements for imaging areas of interests from these sections at a cellular scale spatial resolution. We also review existing limitations of MALDI imaging MS technology relative to compound identification. Finally, we conclude with a perspective on important issues relative to data exploitation and management that need to be solved to maximize biological understanding of the tissue specimen investigated. PMID:20736411

  10. Mass Spectrometry Imaging as a Tool for Surgical Decision-Making

    PubMed Central

    Calligaris, David; Norton, Isaiah; Feldman, Daniel R.; Ide, Jennifer L.; Dunn, Ian F.; Eberlin, Livia S.; Cooks, R. Graham; Jolesz, Ferenc A.; Golby, Alexandra J.; Santagata, Sandro; Agar, Nathalie Y.

    2014-01-01

    Despite significant advances in image-guided therapy, surgeons are still too often left with uncertainty when deciding to remove tissue. This binary decision between removing and leaving tissue during surgery implies that the surgeon should be able to distinguish tumor from healthy tissue. In neurosurgery, current image-guidance approaches such as magnetic resonance imaging (MRI) combined with neuro-navigation offer a map as to where the tumor should be, but the only definitive method to characterize the tissue at stake is histopathology. While extremely valuable information is derived from this gold standard approach, it is limited to very few samples during surgery and is not practically used for the delineation of tumor margins. The development and implementation of faster, comprehensive and complementary approaches for tissue characterization are required to support surgical decision-making – an incremental and iterative process with tumor removed in multiple and often minute biopsies. The development of atmospheric pressure ionization sources makes it possible to analyze tissue specimens with little to no sample preparation. Here, we highlight the value of desorption electrospray ionization (DESI) as one of many available approaches for the analysis of surgical tissue. Twelve surgical samples resected from a patient during surgery were analyzed and diagnosed as glioblastoma (GBM) tumor or necrotic tissue by standard histopathology, and mass spectrometry results were further correlated to histopathology for critical validation of the approach. The use of a robust statistical approach reiterated results from the qualitative detection of potential biomarkers of these tissue types. The correlation of the MS and histopathology results to magnetic resonance images brings significant insight into tumor presentation that could not only serve to guide tumor resection, but that is worthy of more detailed studies on our understanding of tumor presentation on MRI. PMID

  11. ACCELERATION OF CORONAL MASS EJECTIONS FROM THREE-DIMENSIONAL RECONSTRUCTION OF STEREO IMAGES

    SciTech Connect

    Joshi, Anand D.; Srivastava, Nandita

    2011-09-20

    We employ a three-dimensional (3D) reconstruction technique for the first time to study the kinematics of six coronal mass ejections (CMEs), using images obtained from the COR1 and COR2 coronagraphs on board the twin STEREO spacecraft, and also the eruptive prominences (EPs) associated with three of them using images from the Extreme UltraViolet Imager. A feature in the EPs and leading edges (LEs) of all the CMEs was identified and tracked in images from the two spacecraft, and a stereoscopic reconstruction technique was used to determine the 3D coordinates of these features. True velocity and acceleration were determined from the temporal evolution of the true height of the CME features. Our study of the kinematics of the CMEs in 3D reveals that the CME LE undergoes maximum acceleration typically below 2 R{sub sun}. The acceleration profiles of CMEs associated with flares and prominences exhibit different behaviors. While the CMEs not associated with prominences show a bimodal acceleration profile, those associated with prominences do not. Two of the three associated prominences in the study show a high and increasing value of acceleration up to a distance of almost 4 R{sub sun}, but acceleration of the corresponding CME LE does not show the same behavior, suggesting that the two may not be always driven by the same mechanism. One of the CMEs, although associated with a C-class flare, showed unusually high acceleration of over 1500 m s{sup -2}. Our results therefore suggest that only the flare-associated CMEs undergo residual acceleration, which indicates that the flux injection theoretical model holds well for the flare-associated CMEs, but a different mechanism should be considered for EP-associated CMEs.

  12. Development of high-spatial and high-mass resolution mass spectrometric imaging (MSI) and its application to the study of small metabolites and endogenous molecules of plants

    SciTech Connect

    Jun, Ji Hyun

    2012-01-01

    High-spatial and high-mass resolution laser desorption ionization (LDI) mass spectrometric (MS) imaging technology was developed for the attainment of MS images of higher quality containing more information on the relevant cellular and molecular biology in unprecedented depth. The distribution of plant metabolites is asymmetric throughout the cells and tissues, and therefore the increase in the spatial resolution was pursued to reveal the localization of plant metabolites at the cellular level by MS imaging. For achieving high-spatial resolution, the laser beam size was reduced by utilizing an optical fiber with small core diameter (25 μm) in a vacuum matrix-assisted laser desorption ionization-linear ion trap (vMALDI-LTQ) mass spectrometer. Matrix application was greatly improved using oscillating capillary nebulizer. As a result, single cell level spatial resolution of ~ 12 μm was achieved. MS imaging at this high spatial resolution was directly applied to a whole Arabidopsis flower and the substructures of an anther and single pollen grains at the stigma and anther were successfully visualized. MS imaging of high spatial resolution was also demonstrated to the secondary roots of Arabidopsis thaliana and a high degree of localization of detected metabolites was successfully unveiled. This was the first MS imaging on the root for molecular species. MS imaging with high mass resolution was also achieved by utilizing the LTQ-Orbitrap mass spectrometer for the direct identification of the surface metabolites on the Arabidopsis stem and root and differentiation of isobaric ions having the same nominal mass with no need of tandem mass spectrometry (MS/MS). MS imaging at high-spatial and high-mass resolution was also applied to cer1 mutant of the model system Arabidopsis thaliana to demonstrate its usefulness in biological studies and reveal associated metabolite changes in terms of spatial distribution and/or abundances compared to those of wild-type. The spatial

  13. Using collective expert judgements to evaluate quality measures of mass spectrometry images

    PubMed Central

    Palmer, Andrew; Ovchinnikova, Ekaterina; Thuné, Mikael; Lavigne, Régis; Guével, Blandine; Dyatlov, Andrey; Vitek, Olga; Pineau, Charles; Borén, Mats; Alexandrov, Theodore

    2015-01-01

    Motivation: Imaging mass spectrometry (IMS) is a maturating technique of molecular imaging. Confidence in the reproducible quality of IMS data is essential for its integration into routine use. However, the predominant method for assessing quality is visual examination, a time consuming, unstandardized and non-scalable approach. So far, the problem of assessing the quality has only been marginally addressed and existing measures do not account for the spatial information of IMS data. Importantly, no approach exists for unbiased evaluation of potential quality measures. Results: We propose a novel approach for evaluating potential measures by creating a gold-standard set using collective expert judgements upon which we evaluated image-based measures. To produce a gold standard, we engaged 80 IMS experts, each to rate the relative quality between 52 pairs of ion images from MALDI-TOF IMS datasets of rat brain coronal sections. Experts’ optional feedback on their expertise, the task and the survey showed that (i) they had diverse backgrounds and sufficient expertise, (ii) the task was properly understood, and (iii) the survey was comprehensible. A moderate inter-rater agreement was achieved with Krippendorff’s alpha of 0.5. A gold-standard set of 634 pairs of images with accompanying ratings was constructed and showed a high agreement of 0.85. Eight families of potential measures with a range of parameters and statistical descriptors, giving 143 in total, were evaluated. Both signal-to-noise and spatial chaos-based measures performed highly with a correlation of 0.7 to 0.9 with the gold standard ratings. Moreover, we showed that a composite measure with the linear coefficients (trained on the gold standard with regularized least squares optimization and lasso) showed a strong linear correlation of 0.94 and an accuracy of 0.98 in predicting which image in a pair was of higher quality. Availability and implementation: The anonymized data collected from the survey

  14. Two methods for firn-area and mass-balance monitoring of Svalbard glaciers with SAR satellite images

    NASA Astrophysics Data System (ADS)

    König, Max; Winther, Jan-Gunnar; Kohler, Jack; König, Florian

    This paper presents two methods for glacier monitoring on Svalbard using synthetic aperture radar (SAR) satellite images. Both methods were developed on glaciers in the Kongsfjorden area. The first method monitors the firn area extent and the firn line over time by thresholding and filtering the SAR image. Manual detection of the threshold is preferable, but using a constant threshold for all images also gives adequate results. A retreat of the firn-line position is visible, especially on Kongsvegen, corresponding to consecutive years of negative mass balance. The second method applies a k-means classification to three clusters on the glacier surface. The areal extent of the resulting class on the upper part of the glacier correlates remarkably well with the independently measured mass balance of Kongsvegen, having a correlation coefficient of around 0.89 for the various glaciers. This is because the snow from the accumulation area influences the k-means classification. Thus, on glaciers where mass-balance values are available, new mass-balance values can be predicted solely from SAR images. For glaciers where no mass balance is available, the area change cannot be calibrated to absolute mass-balance values, but relative changes can be predicted.

  15. Nova Light Curves From The Solar Mass Ejection Imager (SMEI) - II. The extended catalog

    NASA Astrophysics Data System (ADS)

    Hounsell, R.; Darnley, M. J.; Bode, M. F.; Harman, D. J.; Surina, F.; Starrfield, S.; Holdsworth, D. L.; Bewsher, D.; Hick, P. P.; Jackson, B. V.; Buffington, A.; Clover, J. M.; Shafter, A. W.

    2016-04-01

    We present the results from observing nine Galactic novae in eruption with the Solar Mass Ejection Imager (SMEI) between 2004 and 2009. While many of these novae reached peak magnitudes that were either at or approaching the detection limits of SMEI, we were still able to produce light curves that in many cases contained more data at and around the initial rise, peak, and decline than those found in other variable star catalogs. For each nova, we obtained a peak time, maximum magnitude, and for several an estimate of the decline time ({t}{{2}}). Interestingly, although of lower quality than those found in Hounsell et al., two of the light curves may indicate the presence of a pre-maximum halt. In addition, the high cadence of the SMEI instrument has allowed the detection of low-amplitude variations in at least one of the nova light curves.

  16. Mass spectrometric imaging of flavonoid glycosides and biflavonoids in Ginkgo biloba L.

    PubMed

    Beck, Sebastian; Stengel, Julia

    2016-10-01

    Ginkgo biloba L. is known to be rich in flavonoids and flavonoid glycosides. However, the distribution within specific plant organs (e.g. within leaves) is not known. By using HPLC-MS and MS/MS we have identified a number of previously known G. biloba flavonoid glycosides and biflavonoids from leaves. Namely, kaempferol, quercetin, isorhamnetin, myricetin, laricitrin/mearnsetin and apigenin glycosides were identified. Furthermore, biflavonoids like ginkgetin/isoginkgetin were also detected. The application of MALDI mass spectrometric imaging, enabled the compilation of concentration profiles of flavonoid glycosides and biflavonoids in G. biloba L. leaves. Both, flavonoid glycosides and biflavonoids show a distinct distribution in leaf thin sections of G. biloba L. PMID:27233155

  17. Exploring Atmospheric Aerosol Chemistry with Advanced High-Resolution Mass Spectrometry and Particle Imaging Methods

    NASA Astrophysics Data System (ADS)

    Nizkorodov, S.

    2014-12-01

    Physical and chemical complexity of atmospheric aerosols presents significant challenges both to experimentalists working on aerosol characterization and to modelers trying to parameterize critical aerosol properties. Multi-modal approaches that combine state-of-the-art experimental, theoretical, and modeling methods are becoming increasingly important in aerosol research. This presentation will discuss recent applications of unique high-resolution mass spectrometry and particle imaging tools developed at two Department of Energy's user facilities, the Environmental Molecular Science Laboratory (EMSL) and Advanced Light Source (ALS), to studies of molecular composition, photochemical aging, and properties of laboratory-generated and field aerosols. Specifically, this presentation will attempt to address the following questions: (a) how do NO2, SO2, and NH3 affect molecular level composition of anthropogenic aerosols?; (b) what factors determine viscosity/surface tension of organic aerosol particles?; (c) how does photolysis affect molecular composition and optical properties of organic aerosols?

  18. Development of Laser Desorption Imaging Mass Spectrometry Methods to Investigate the Molecular Composition of Latent Fingermarks

    NASA Astrophysics Data System (ADS)

    Lauzon, Nidia; Dufresne, Martin; Chauhan, Vinita; Chaurand, Pierre

    2015-06-01

    For a century, fingermark analysis has been one of the most important and common methods in forensic investigations. Modern chemical analysis technologies have added the potential to determine the molecular composition of fingermarks and possibly identify chemicals a suspect may have come into contact with. Improvements in analytical detection of the molecular composition of fingermarks is therefore of great importance. In this regard, matrix-assisted laser desorption ionization (MALDI) and laser desorption ionization (LDI) imaging mass spectrometry (IMS) have proven to be useful technologies for fingermark analysis. In these analyses, the choice of ionizing agent and its mode of deposition are critical steps for the identification of molecular markers. Here we propose two novel and complementary IMS approaches for endogenous and exogenous substance detection in fingermarks: sublimation of 2-mercaptobenzothiazol (2-MBT) matrix and silver sputtering.

  19. Development of laser desorption imaging mass spectrometry methods to investigate the molecular composition of latent fingermarks.

    PubMed

    Lauzon, Nidia; Dufresne, Martin; Chauhan, Vinita; Chaurand, Pierre

    2015-06-01

    For a century, fingermark analysis has been one of the most important and common methods in forensic investigations. Modern chemical analysis technologies have added the potential to determine the molecular composition of fingermarks and possibly identify chemicals a suspect may have come into contact with. Improvements in analytical detection of the molecular composition of fingermarks is therefore of great importance. In this regard, matrix-assisted laser desorption ionization (MALDI) and laser desorption ionization (LDI) imaging mass spectrometry (IMS) have proven to be useful technologies for fingermark analysis. In these analyses, the choice of ionizing agent and its mode of deposition are critical steps for the identification of molecular markers. Here we propose two novel and complementary IMS approaches for endogenous and exogenous substance detection in fingermarks: sublimation of 2-mercaptobenzothiazol (2-MBT) matrix and silver sputtering. PMID:25846823

  20. Infrared matrix-assisted laser desorption electrospray ionization mass spectrometry imaging analysis of biospecimens.

    PubMed

    Bokhart, M T; Muddiman, D C

    2016-09-21

    Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) is a technique well suited for analysis of biological specimens. This tutorial review focuses on recent advancements and applications of IR-MALDESI MSI to better understand key biological questions. Through optimization of user-defined source parameters, comprehensive and quantitative MSI data can be obtained for a variety of analytes. The effect of an ice matrix layer is well defined in the context of desorption dynamics and resulting ion abundance. Optimized parameters and careful control of conditions affords quantitative MSI data which provides valuable information for targeted, label-free drug distribution studies and untargeted metabolomic datasets. Challenges and limitations of MSI using IR-MALDESI are addressed in the context of the bioimaging field. PMID:27484166

  1. Calculating the propagation direction of coronal mass ejections by connecting in situ observations with heliospheric images

    NASA Astrophysics Data System (ADS)

    Rollett, Tanja; Möstl, Christian; Temmer, Manuela; Veronig, Astrid; Biernat, Helfried K.

    2010-05-01

    We determined the propagation direction of two coronal mass ejections by using data provided by the Heliospheric Imagers (HI) and the PLASTIC and IMPACT instruments onboard the two STEREO satellites. To facilitate the tracking of the CME's leading edge we made time-elongation plots (J-plots) for the investigated events and tracked the apparent leading edge therein several times in order to estimate the measurement error. For converting elongation to distance we compared several methods (Point-P, Fixed-Phi and their harmonic mean). To determine the direction of the CME's propagation in the ecliptic we connected the CME-track derived from HI J-plots with the measured in situ arrival time by modifying the propagation direction within the used model equations. The resulting directions and their errors are discussed with respect to the different assumptions used for each technique.

  2. Nonresonant, femtosecond laser vaporization and electrospray post-ionization mass spectrometry as a tool for biological tissue imaging.

    PubMed

    Shi, Fengjian; Archer, Jieutonne J; Levis, Robert J

    2016-07-15

    An ambient mass spectrometry imaging (MSI) source is demonstrated with both high spatial and mass resolution that enables measurement of the compositional heterogeneity within a biological tissue sample. The source is based on nonresonant, femtosecond laser electrospray mass spectrometry (LEMS) coupled to a quadrupole time-of-flight (QTOF) mass analyzer. No matrix deposition and minimal sample preparation is necessary for the source. The laser, translation stage, and mass spectrometer are synchronized and controlled using a customized user interface. Single or multiple laser shots may be applied to each pixel. A scanning rate of 2.0s per pixel is achieved. Measurement of a patterned ink film indicates the potential of LEMS for ambient imaging with a lateral resolution of ∼60μm. Metabolites including sugar, anthocyanins and other small metabolites were successfully mapped from plant samples without oversampling using a spot size of 60×70μm(2). Molecular identification of the detected analytes from the tissue was enabled by accurate mass measurement in conjunction with tandem mass spectrometry. Statistical analysis, non-negative matrix factorization and principle component analysis, were applied to the imaging data to extract regions with distinct and/or correlated spectral profiles. PMID:26931651

  3. Multi-Isotopic (o, H, Sr, Li) Tracing of the Fluxes Involved in the Water Status of a Peatland (la Sauvetat, Massif Central, France)

    NASA Astrophysics Data System (ADS)

    Agnès, B.; Negrel, P. J.; Millot, R.; Clotilde, B.

    2010-12-01

    The bio-diversity (vegetation and fauna) of peatlands, like all wetlands ecosystems, are strongly fragile as they are requiring very specific wet conditions. In the past 20 years, increasing efforts were engaged to restore degraded wetlands, to create new wetlands where they have been totally lost and to manage wetlands sustainably in order to assess their multiple benefits. However, engaging specific actions to restore and preserve wetlands require an important knowledge on the water cycle in such systems. In this study, we propose to use chemical and multi-isotopic approaches combined with hydrological measurements (piezometric level and stream flow measurements) to trace the fluxes of water and dissolved element involved in the “Narces de la Sauvetat” peatland (France) and for the stream draining the area. Aims are to evaluate the water status of this ecosystem as well as the origin of dissolved elements and possible anthropogenic impacts. These approaches clearly demonstrated their effectiveness to improve the knowledge on the hydrological functioning of wetlands ecosystems. Main results are (1) at least three fluxes with distinct chemical and isotopic signatures are providing water supplies to peatland (Sr and stable isotopes), (2) water flow that comes out of the peatland through the stream is certainly negligible (Li isotopes) and 3) water within the peat land exhibits Sr and Li -isotopes values consistent with carbonate amendments inputs used in local agriculture. The outcomes of this study are that peatland ecosystem water balance is poorly affected by its outlet but are strongly controlled by groundwater replenishment. This could lead to a better adjustment of decision maker choices to maintain the water balance of the peatland, which is essential for the preservation of this fragile ecosystem. This study also opens a new field for Li isotope investigations in hydro-systems and highlights the possibility of using Li isotopes as environmental tracers.

  4. Proof of Concept Experiments of the Multi-Isotope Process Monitor: An Online, Nondestructive, Near Real-Time Monitor for Spent Nuclear Fuel Reprocessing Facilities

    SciTech Connect

    Orton, Christopher R.; Fraga, Carlos G.; Christensen, Richard; Schwantes, Jon M.

    2012-04-21

    Operators, national regulatory agencies and the IAEA will require the development of advanced technologies to efficiently control and safeguard nuclear material at increasingly large-scale nuclear recycling facilities. Ideally, the envisioned technologies would be capable of non-destructive, near-real-time (NRT), autonomous process monitoring. This paper describes results from proof-of-principle experiments designed to test the Multi-Isotope Process (MIP) Monitor, a novel approach to safeguarding reprocessing facilities. The MIP Monitor combines the detection of intrinsic gamma ray signatures emitted from process solutions with multivariate analysis to detect off-normal conditions in process streams nondestructively and in NRT. Commercial spent nuclear fuel of various irradiation histories was dissolved and separated using a PUREX-based batch solvent extraction. Extractions were performed at various nitric acid concentrations to mimic both normal and off-normal industrial plant operating conditions. Principal Component Analysis (PCA) was applied to the simulated gamma spectra to investigate pattern variations as a function of acid concentration, burnup and cooling time. Partial Least Squares (PLS) regression was applied to attempt to quantify both the acid concentration and burnup of the dissolved spent fuel during the initial separation stage of recycle. The MIP Monitor demonstrated sensitivity to induced variations of acid concentration, including the distinction of {+-} 1.3 M variation from normal process conditions by way of PCA. Acid concentration was predicted using measurements from the organic extract and PLS resulting in predictions with <0.7 M relative error. Quantification of burnup levels from dissolved fuel spectra using PLS was demonstrated to be within 2.5% of previously measured values.

  5. Molecular assessment of surgical-resection margins of gastric cancer by mass-spectrometric imaging.

    PubMed

    Eberlin, Livia S; Tibshirani, Robert J; Zhang, Jialing; Longacre, Teri A; Berry, Gerald J; Bingham, David B; Norton, Jeffrey A; Zare, Richard N; Poultsides, George A

    2014-02-18

    Surgical resection is the main curative option for gastrointestinal cancers. The extent of cancer resection is commonly assessed during surgery by pathologic evaluation of (frozen sections of) the tissue at the resected specimen margin(s) to verify whether cancer is present. We compare this method to an alternative procedure, desorption electrospray ionization mass spectrometric imaging (DESI-MSI), for 62 banked human cancerous and normal gastric-tissue samples. In DESI-MSI, microdroplets strike the tissue sample, the resulting splash enters a mass spectrometer, and a statistical analysis, here, the Lasso method (which stands for least absolute shrinkage and selection operator and which is a multiclass logistic regression with L1 penalty), is applied to classify tissues based on the molecular information obtained directly from DESI-MSI. The methodology developed with 28 frozen training samples of clear histopathologic diagnosis showed an overall accuracy value of 98% for the 12,480 pixels evaluated in cross-validation (CV), and 97% when a completely independent set of samples was tested. By applying an additional spatial smoothing technique, the accuracy for both CV and the independent set of samples was 99% compared with histological diagnoses. To test our method for clinical use, we applied it to a total of 21 tissue-margin samples prospectively obtained from nine gastric-cancer patients. The results obtained suggest that DESI-MSI/Lasso may be valuable for routine intraoperative assessment of the specimen margins during gastric-cancer surgery. PMID:24550265

  6. MALDI mass spectrometric imaging meets "omics": recent advances in the fruitful marriage.

    PubMed

    Crecelius, A C; Schubert, U S; von Eggeling, F

    2015-09-01

    Matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI MSI) is a method that allows the investigation of the molecular content of surfaces, in particular, tissues, within its morphological context. The applications of MALDI MSI in the field of large-scale mass spectrometric studies, which are typically denoted by the suffix "omics", are steadily increasing. This is because, on the one hand, technical advances regarding sample collection and preparation, matrix application, instrumentation, and data processing have enhanced the molecular specificity and sensitivity of MALDI MSI; on the other hand, the focus of the "omics" community has moved from establishing an inventory of certain compound classes to exploring their spatial distribution to gain novel insights. Thus, the aim of this mini-review is twofold, to display the state-of-the-art in terms of technical aspects in MALDI MSI and to highlight selected applications in the last two years, which either have significantly advanced a certain "omics" field or have introduced a new one through pioneering efforts. PMID:26161715

  7. Mass Spectrometry Based Imaging Techniques for Spatially Resolved Analysis of Molecules

    PubMed Central

    Matros, Andrea; Mock, Hans-Peter

    2013-01-01

    Higher plants are composed of a multitude of tissues with specific functions, reflected by distinct profiles for transcripts, proteins, and metabolites. Comprehensive analysis of metabolites and proteins has advanced tremendously within recent years, and this progress has been driven by the rapid development of sophisticated mass spectrometric techniques. In most of the current “omics”-studies, analysis is performed on whole organ or whole plant extracts, rendering to the loss of spatial information. Mass spectrometry imaging (MSI) techniques have opened a new avenue to obtain information on the spatial distribution of metabolites and of proteins. Pioneered in the field of medicine, the approaches are now applied to study the spatial profiles of molecules in plant systems. A range of different plant organs and tissues have been successfully analyzed by MSI, and patterns of various classes of metabolites from primary and secondary metabolism could be obtained. It can be envisaged that MSI approaches will substantially contribute to build spatially resolved biochemical networks. PMID:23626593

  8. MALDI-in source decay applied to mass spectrometry imaging: a new tool for protein identification.

    PubMed

    Debois, Delphine; Bertrand, Virginie; Quinton, Loïc; De Pauw-Gillet, Marie-Claire; De Pauw, Edwin

    2010-05-15

    Matrix-assisted laser desorption ionization-mass spectrometry (MALDI-MS) imaging is a powerful technique giving access to the distribution of a large range of biomolecules directly from a tissue section, allowing, for example, the discovery of new pathological biomarkers. Nevertheless, one main difficulty lies in the identification of the detected species, especially proteins. MALDI-in source decay (ISD) is used to fragment ions directly in the mass spectrometer ion source. This technique does not require any special sample treatment but only the use of a specific MALDI matrix such as 2,5-dihydroxybenzoic acid or 1,5-diaminonaphthalene. MALDI-ISD is generally employed on classical, purified samples, but here we demonstrate that ISD can also be performed directly on mixtures and on a tissue slice leading to fragment ions, allowing the identification of major proteins without any further treatment. On a porcine eye lens slice, de novo sequencing was even performed. Crystallins not yet referenced in databases were identified by sequence homology with other mammalian species. On a mouse brain slice, we demonstrate that results obtained with ISD are comparable and even better than those obtained with a classical in situ digestion. PMID:20397712

  9. Liposome-based chemical barcodes for single molecule DNA detection using imaging mass spectrometry.

    PubMed

    Gunnarsson, Anders; Sjövall, Peter; Höök, Fredrik

    2010-02-10

    We report on a mass-spectrometry (time-of-flight secondary ion mass spectrometry, TOF-SIMS) based method for multiplexed DNA detection utilizing a random array, where the lipid composition of small unilamellar liposomes act as chemical barcodes to identify unique DNA target sequences down to the single molecule level. In a sandwich format, suspended target-DNA to be detected mediates the binding of capture-DNA modified liposomes to surface-immobilized probe-DNA. With the lipid composition of each liposome encoding a unique target-DNA sequence, TOF-SIMS analysis was used to determine the chemical fingerprint of the bound liposomes. Using high-resolution TOF-SIMS imaging, providing sub-200 nm spatial resolution, single DNA targets could be detected and identified via the chemical fingerprint of individual liposomes. The results also demonstrate the capability of TOF-SIMS to provide multiplexed detection of DNA targets on substrate areas in the micrometer range. Together with a high multiplexing capacity, this makes the concept an interesting alternative to existing barcode concepts based on fluorescence, Raman, or graphical codes for small-scale bioanalysis. PMID:20085369

  10. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging.

    PubMed

    Aikawa, Hiroaki; Hayashi, Mitsuhiro; Ryu, Shoraku; Yamashita, Makiko; Ohtsuka, Naoto; Nishidate, Masanobu; Fujiwara, Yasuhiro; Hamada, Akinobu

    2016-01-01

    In the development of anticancer drugs, drug concentration measurements in the target tissue have been thought to be crucial for predicting drug efficacy and safety. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is commonly used for determination of average drug concentrations; however, complete loss of spatial information in the target tissue occurs. Mass spectrometry imaging (MSI) has been recently applied as an innovative tool for detection of molecular distribution of pharmacological agents in heterogeneous targets. This study examined the intra-brain transitivity of alectinib, a novel anaplastic lymphoma kinase inhibitor, using a combination of matrix-assisted laser desorption ionization-MSI and LC-MS/MS techniques. We first analyzed the pharmacokinetic profiles in FVB mice and then examined the effect of the multidrug resistance protein-1 (MDR1) using Mdr1a/b knockout mice including quantitative distribution of alectinib in the brain. While no differences were observed between the mice for the plasma alectinib concentrations, diffuse alectinib distributions were found in the brain of the Mdr1a/b knockout versus FVB mice. These results indicate the potential for using quantitative MSI for clarifying drug distribution in the brain on a microscopic level, in addition to suggesting a possible use in designing studies for anticancer drug development and translational research. PMID:27026287

  11. Identification of hypoxia-regulated proteins using MALDI-mass spectrometry imaging combined with quantitative proteomics.

    PubMed

    Djidja, Marie-Claude; Chang, Joan; Hadjiprocopis, Andreas; Schmich, Fabian; Sinclair, John; Mršnik, Martina; Schoof, Erwin M; Barker, Holly E; Linding, Rune; Jørgensen, Claus; Erler, Janine T

    2014-05-01

    Hypoxia is present in most solid tumors and is clinically correlated with increased metastasis and poor patient survival. While studies have demonstrated the role of hypoxia and hypoxia-regulated proteins in cancer progression, no attempts have been made to identify hypoxia-regulated proteins using quantitative proteomics combined with MALDI-mass spectrometry imaging (MALDI-MSI). Here we present a comprehensive hypoxic proteome study and are the first to investigate changes in situ using tumor samples. In vitro quantitative mass spectrometry analysis of the hypoxic proteome was performed on breast cancer cells using stable isotope labeling with amino acids in cell culture (SILAC). MS analyses were performed on laser-capture microdissected samples isolated from normoxic and hypoxic regions from tumors derived from the same cells used in vitro. MALDI-MSI was used in combination to investigate hypoxia-regulated protein localization within tumor sections. Here we identified more than 100 proteins, both novel and previously reported, that were associated with hypoxia. Several proteins were localized in hypoxic regions, as identified by MALDI-MSI. Visualization and data extrapolation methods for the in vitro SILAC data were also developed, and computational mapping of MALDI-MSI data to IHC results was applied for data validation. The results and limitations of the methodologies described are discussed. PMID:24702160

  12. A Vision for Better Health: Mass Spectrometry Imaging for Clinical Diagnostics

    PubMed Central

    Ye, Hui; Gemperline, Erin; Li, Lingjun

    2012-01-01

    Background Mass spectrometry imaging (MSI) is a powerful tool that grants the ability to investigate a broad mass range of molecules from small molecules to large proteins by creating detailed distribution maps of selected compounds. Its usefulness in biomarker discovery towards clinical applications has obtained success by correlating the molecular expression of tissues acquired from MSI with well-established histology. Results To date, MSI has demonstrated its versatility in clinical applications, such as biomarker diagnostics of different diseases, prognostics of disease severities and metabolic response to drug treatment, etc. These studies have provided significant insight in clinical studies over the years and current technical advances are further facilitating the improvement of this field. Although the underlying concept is simple, factors such as choice of ionization method, sample preparation, instrumentation and data analysis must be taken into account for successful applications of MSI. Herein, we briefly reviewed these key elements yet focused on the clinical applications of MSI that cannot be addressed by other means. Conclusions Challenges and future perspectives in this field are also discussed to conclude that the ever-growing applications with continuous development of this powerful analytical tool will lead to a better understanding of the biology of diseases and improvements in clinical diagnostics. PMID:23078851

  13. Mass spectrometric imaging of red fluorescent protein in breast tumor xenografts.

    PubMed

    Chughtai, Kamila; Jiang, Lu; Post, Harm; Winnard, Paul T; Greenwood, Tiffany R; Raman, Venu; Bhujwalla, Zaver M; Heeren, Ron M A; Glunde, Kristine

    2013-05-01

    Mass spectrometric imaging (MSI) in combination with electrospray mass spectrometry (ESI-MS) is a powerful technique for visualization and identification of a variety of different biomolecules directly from thin tissue sections. As commonly used tools for molecular reporting, fluorescent proteins are molecular reporter tools that have enabled the elucidation of a multitude of biological pathways and processes. To combine these two approaches, we have performed targeted MS analysis and MALDI-MSI visualization of a tandem dimer (td)Tomato red fluorescent protein, which was expressed exclusively in the hypoxic regions of a breast tumor xenograft model. For the first time, a fluorescent protein has been visualized by both optical microscopy and MALDI-MSI. Visualization of tdTomato by MALDI-MSI directly from breast tumor tissue sections will allow us to simultaneously detect and subsequently identify novel molecules present in hypoxic regions of the tumor. MS and MALDI-MSI of fluorescent proteins, as exemplified in our study, is useful for studies in which the advantages of MS and MSI will benefit from the combination with molecular approaches that use fluorescent proteins as reporters. PMID:23184411

  14. Visualizing spatial distribution of alectinib in murine brain using quantitative mass spectrometry imaging

    PubMed Central

    Aikawa, Hiroaki; Hayashi, Mitsuhiro; Ryu, Shoraku; Yamashita, Makiko; Ohtsuka, Naoto; Nishidate, Masanobu; Fujiwara, Yasuhiro; Hamada, Akinobu

    2016-01-01

    In the development of anticancer drugs, drug concentration measurements in the target tissue have been thought to be crucial for predicting drug efficacy and safety. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is commonly used for determination of average drug concentrations; however, complete loss of spatial information in the target tissue occurs. Mass spectrometry imaging (MSI) has been recently applied as an innovative tool for detection of molecular distribution of pharmacological agents in heterogeneous targets. This study examined the intra-brain transitivity of alectinib, a novel anaplastic lymphoma kinase inhibitor, using a combination of matrix-assisted laser desorption ionization–MSI and LC-MS/MS techniques. We first analyzed the pharmacokinetic profiles in FVB mice and then examined the effect of the multidrug resistance protein-1 (MDR1) using Mdr1a/b knockout mice including quantitative distribution of alectinib in the brain. While no differences were observed between the mice for the plasma alectinib concentrations, diffuse alectinib distributions were found in the brain of the Mdr1a/b knockout versus FVB mice. These results indicate the potential for using quantitative MSI for clarifying drug distribution in the brain on a microscopic level, in addition to suggesting a possible use in designing studies for anticancer drug development and translational research. PMID:27026287

  15. IR-MALDESI MASS SPECTROMETRY IMAGING OF BIOLOGICAL TISSUE SECTIONS USING ICE AS A MATRIX

    PubMed Central

    Robichaud, Guillaume; Barry, Jeremy A.; Muddiman, David C.

    2014-01-01

    Infrared Matrix-Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) Mass Spectrometry imaging of biological tissue sections using a layer of deposited ice as an energy absorbing matrix was investigated. Dynamics of plume ablation were first explored using a nanosecond exposure shadowgraphy system designed to simultaneously collect pictures of the plume with a camera and collect the FT-ICR mass spectrum corresponding to that same ablation event. Ablation of fresh tissue analyzed with and without using ice as a matrix were both compared using this technique. Effect of spot-to-spot distance, number of laser shots per pixel and tissue condition (matrix) on ion abundance was also investigated for 50 µm thick tissue sections. Finally, the statistical method called design of experiments was used to compare source parameters and determine the optimal conditions for IR-MALDESI of tissue sections using deposited ice as a matrix. With a better understanding of the fundamentals of ablation dynamics and a systematic approach to explore the experimental space, it was possible to improve ion abundance by nearly one order of magnitude. PMID:24385399

  16. Identification of Protein Markers Specific for Papillary Renal Cell Carcinoma Using Imaging Mass Spectrometry

    PubMed Central

    Na, Chan Hyun; Hong, Ji Hye; Kim, Wan Sup; Shanta, Selina Rahman; Bang, Joo Yong; Park, Dongmin; Kim, Hark Kyun; Kim, Kwang Pyo

    2015-01-01

    Since the emergence of proteomics methods, many proteins specific for renal cell carcinoma (RCC) have been identified. Despite their usefulness for the specific diagnosis of RCC, such proteins do not provide spatial information on the diseased tissue. Therefore, the identification of cancer-specific proteins that include information on their specific location is needed. Recently, matrix-assisted laser desorption ionization (MALDI) mass spectrometry (MS) based imaging mass spectrometry (IMS) has emerged as a new tool for the analysis of spatial distribution as well as identification of either proteins or small molecules in tissues. In this report, surgical tissue sections of papillary RCC were analyzed using MALDI-IMS. Statistical analysis revealed several discriminative cancer-specific m/z-species between normal and diseased tissues. Among these m/z-species, two particular proteins, S100A11 and ferritin light chain, which are specific for papillary RCC cancer regions, were successfully identified using LC-MS/MS following protein extraction from independent RCC samples. The expressions of S100A11 and ferritin light chain were further validated by immunohistochemistry of human tissues and tissue microarrays (TMAs) of RCC. In conclusion, MALDI-IMS followed by LC-MS/MS analysis in human tissue identified that S100A11 and ferritin light chain are differentially expressed proteins in papillary RCC cancer regions. PMID:26062552

  17. Optimization of OSEM parameters in myocardial perfusion imaging reconstruction as a function of body mass index: a clinical approach*

    PubMed Central

    de Barros, Pietro Paolo; Metello, Luis F.; Camozzato, Tatiane Sabriela Cagol; Vieira, Domingos Manuel da Silva

    2015-01-01

    Objective The present study is aimed at contributing to identify the most appropriate OSEM parameters to generate myocardial perfusion imaging reconstructions with the best diagnostic quality, correlating them with patients’ body mass index. Materials and Methods The present study included 28 adult patients submitted to myocardial perfusion imaging in a public hospital. The OSEM method was utilized in the images reconstruction with six different combinations of iterations and subsets numbers. The images were analyzed by nuclear cardiology specialists taking their diagnostic value into consideration and indicating the most appropriate images in terms of diagnostic quality. Results An overall scoring analysis demonstrated that the combination of four iterations and four subsets has generated the most appropriate images in terms of diagnostic quality for all the classes of body mass index; however, the role played by the combination of six iterations and four subsets is highlighted in relation to the higher body mass index classes. Conclusion The use of optimized parameters seems to play a relevant role in the generation of images with better diagnostic quality, ensuring the diagnosis and consequential appropriate and effective treatment for the patient. PMID:26543282

  18. EXQUISITE NOVA LIGHT CURVES FROM THE SOLAR MASS EJECTION IMAGER (SMEI)

    SciTech Connect

    Hounsell, R.; Bode, M. F.; Darnley, M. J.; Mawson, N. R.; Steele, I. A.; Hick, P. P.; Buffington, A.; Jackson, B. V.; Clover, J. M.; Shafter, A. W.; Evans, A.; Eyres, S. P. S.; O'Brien, T. J.

    2010-11-20

    We present light curves of three classical novae (CNe; KT Eridani, V598 Puppis, V1280 Scorpii) and one recurrent nova (RS Ophiuchi) derived from data obtained by the Solar Mass Ejection Imager (SMEI) on board the Coriolis satellite. SMEI provides near complete skymap coverage with precision visible-light photometry at 102 minute cadence. The light curves derived from these skymaps offer unprecedented temporal resolution around, and especially before, maximum light, a phase of the eruption normally not covered by ground-based observations. They allow us to explore fundamental parameters of individual objects including the epoch of the initial explosion, the reality and duration of any pre-maximum halt (found in all three fast novae in our sample), the presence of secondary maxima, speed of decline of the initial light curve, plus precise timing of the onset of dust formation (in V1280 Sco) leading to estimation of the bolometric luminosity, white dwarf mass, and object distance. For KT Eri, Liverpool Telescope SkyCamT data confirm important features of the SMEI light curve and overall our results add weight to the proposed similarities of this object to recurrent rather than to CNe. In RS Oph, comparison with hard X-ray data from the 2006 outburst implies that the onset of the outburst coincides with extensive high-velocity mass loss. It is also noted that two of the four novae we have detected (V598 Pup and KT Eri) were only discovered by ground-based observers weeks or months after maximum light, yet these novae reached peak magnitudes of 3.46 and 5.42, respectively. This emphasizes the fact that many bright novae per year are still overlooked, particularly those of the very fast speed class. Coupled with its ability to observe novae in detail even when relatively close to the Sun in the sky, we estimate that as many as five novae per year may be detectable by SMEI.

  19. THE CHARA ARRAY ANGULAR DIAMETER OF HR 8799 FAVORS PLANETARY MASSES FOR ITS IMAGED COMPANIONS

    SciTech Connect

    Baines, Ellyn K.; White, Russel J.; Jones, Jeremy; Boyajian, Tabetha; McAlister, Harold A.; Ten Brummelaar, Theo A.; Turner, Nils H.; Sturmann, Judit; Sturmann, Laszlo; Goldfinger, P. J.; Farrington, Christopher D.; Riedel, Adric R.; Huber, Daniel; Ireland, Michael; Von Braun, Kaspar; Ridgway, Stephen T.

    2012-12-10

    HR 8799 is an hF0 mA5 {gamma} Doradus-, {lambda} Bootis-, Vega-type star best known for hosting four directly imaged candidate planetary companions. Using the CHARA Array interferometer, we measure HR 8799's limb-darkened angular diameter to be 0.342 {+-} 0.008 mas (an error of only 2%). By combining our measurement with the star's parallax and photometry from the literature, we greatly improve upon previous estimates of its fundamental parameters, including stellar radius (1.44 {+-} 0.06 R{sub Sun }), effective temperature (7193 {+-} 87 K, consistent with F0), luminosity (5.05 {+-} 0.29 L{sub Sun }), and the extent of the habitable zone (HZ; 1.62-3.32 AU). These improved stellar properties permit much more precise comparisons with stellar evolutionary models, from which a mass and age can be determined, once the metallicity of the star is known. Considering the observational properties of other {lambda} Bootis stars and the indirect evidence for youth of HR 8799, we argue that the internal abundance, and what we refer to as the effective abundance, is most likely near solar. Finally, using the Yonsei-Yale evolutionary models with uniformly scaled solar-like abundances, we estimate HR 8799's mass and age considering two possibilities: 1.516{sup +0.038}{sub -0.024} M{sub Sun} and 33{sup +7}{sub -13.2} Myr if the star is contracting toward the zero-age main sequence or 1.513{sup +0.023}{sub -0.024} M{sub Sun} and 90{sup +381}{sub -50} Myr if it is expanding from it. This improved estimate of HR 8799's age with realistic uncertainties provides the best constraints to date on the masses of its orbiting companions, and strongly suggests they are indeed planets. They nevertheless all appear to orbit well outside the HZ of this young star.

  20. The CHARA Array Angular Diameter of HR 8799 Favors Planetary Masses for its Imaged Companions

    NASA Astrophysics Data System (ADS)

    Baines, Ellyn K.; White, Russel J.; Huber, Daniel; Jones, Jeremy; Boyajian, Tabetha; McAlister, Harold A.; ten Brummelaar, Theo A.; Turner, Nils H.; Sturmann, Judit; Sturmann, Laszlo; Goldfinger, P. J.; Farrington, Christopher D.; Riedel, Adric R.; Ireland, Michael; von Braun, Kaspar; Ridgway, Stephen T.

    2012-12-01

    HR 8799 is an hF0 mA5 γ Doradus-, λ Bootis-, Vega-type star best known for hosting four directly imaged candidate planetary companions. Using the CHARA Array interferometer, we measure HR 8799's limb-darkened angular diameter to be 0.342 ± 0.008 mas (an error of only 2%). By combining our measurement with the star's parallax and photometry from the literature, we greatly improve upon previous estimates of its fundamental parameters, including stellar radius (1.44 ± 0.06 R ⊙), effective temperature (7193 ± 87 K, consistent with F0), luminosity (5.05 ± 0.29 L ⊙), and the extent of the habitable zone (HZ; 1.62-3.32 AU). These improved stellar properties permit much more precise comparisons with stellar evolutionary models, from which a mass and age can be determined, once the metallicity of the star is known. Considering the observational properties of other λ Bootis stars and the indirect evidence for youth of HR 8799, we argue that the internal abundance, and what we refer to as the effective abundance, is most likely near solar. Finally, using the Yonsei-Yale evolutionary models with uniformly scaled solar-like abundances, we estimate HR 8799's mass and age considering two possibilities: 1.516+0.038 -0.024 M ⊙ and 33+7 -13.2 Myr if the star is contracting toward the zero-age main sequence or 1.513+0.023 -0.024 M ⊙ and 90+381 -50 Myr if it is expanding from it. This improved estimate of HR 8799's age with realistic uncertainties provides the best constraints to date on the masses of its orbiting companions, and strongly suggests they are indeed planets. They nevertheless all appear to orbit well outside the HZ of this young star.

  1. Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry-based imaging.

    PubMed

    Subramanian, Nithya; Srimany, Amitava; Kanwar, Jagat R; Kanwar, Rupinder K; Akilandeswari, Balachandran; Rishi, Pukhraj; Khetan, Vikas; Vasudevan, Madavan; Pradeep, Thalappil; Krishnakumar, Subramanian

    2016-01-01

    Retinoblastoma (RB) is an intraocular childhood tumor which, if left untreated, leads to blindness and mortality. Nucleolin (NCL) protein which is differentially expressed on the tumor cell surface, binds ligands and regulates carcinogenesis and angiogenesis. We found that NCL is over expressed in RB tumor tissues and cell lines compared to normal retina. We studied the effect of nucleolin-aptamer (NCL-APT) to reduce proliferation in RB tumor cells. Aptamer treatment on the RB cell lines (Y79 and WERI-Rb1) led to significant inhibition of cell proliferation. Locked nucleic acid (LNA) modified NCL-APT administered subcutaneously (s.c.) near tumor or intraperitoneally (i.p.) in Y79 xenografted nude mice resulted in 26 and 65% of tumor growth inhibition, respectively. Downregulation of inhibitor of apoptosis proteins, tumor miRNA-18a, altered serum cytokines, and serum miRNA-18a levels were observed upon NCL-APT treatment. Desorption electrospray ionization mass spectrometry (DESI MS)-based imaging of cell lines and tumor tissues revealed changes in phosphatidylcholines levels upon treatment. Thus, our study provides proof of concept illustrating NCL-APT-based targeted therapeutic strategy and use of DESI MS-based lipid imaging in monitoring therapeutic responses in RB. PMID:27574784

  2. Mass image data storage system for high resolution aerial photographic survey

    NASA Astrophysics Data System (ADS)

    Zen, Luan; Tan, Jiubin; Zhao, Zhongwen

    2008-10-01

    In order to make it possible for an image data acquisition and storage system used for aerial photographic survey to have a continuous storage speed of 144 MB/s and data storage capacity of 260GB, three main problems have been solved in this paper. First, with multi-channel synchronous DMA transfer, parallel data storage of four SCSI hard disks is realized. It solved the problem of the data transfer rate too high for direct storage. Then, to increase the data transfer rate, a high speed BUS based on LVDS and a SCSI control circuit based on FAS368M were designed. It solved the problem of PCI BUS limiting the storage speed. Finally, the problem of the SCSI hard disk continuous storage speed declining led by much time interval between two DMA transfers is solved by optimizing DMA channel. The practical system test shows that the acquisition and storage system has a continuous storage speed of 150 MB/s and a data storage capacity of 280GB. Therefore, it is a new storage method for high speed and mass image data.

  3. In situ detection of histone variants and modifications in mouse brain using imaging mass spectrometry.

    PubMed

    Lahiri, Shibojyoti; Sun, Na; Solis-Mezarino, Victor; Fedisch, Andreas; Ninkovic, Jovica; Feuchtinger, Annette; Götz, Magdalena; Walch, Axel; Imhof, Axel

    2016-02-01

    Histone posttranslational modifications and histone variants control the epigenetic regulation of gene expression and affect a wide variety of biological processes. A complex pattern of such modifications and variants defines the identity of cells within complex organ systems and can therefore be used to characterize cells at a molecular level. However, their detection and identification in situ has been limited so far due to lack of specificity, selectivity, and availability of antihistone antibodies. Here, we describe a novel MALDI imaging MS based workflow, which enables us to detect and characterize histones by their intact mass and their correlation with cytological properties of the tissue using novel statistical and image analysis tools. The workflow allows us to characterize the in situ distribution of the major histone variants and their modification in the mouse brain. This new analysis tool is particularly useful for the investigation of expression patterns of the linker histone H1 variants for which suitable antibodies are so far not available. PMID:26593131

  4. MALDI Mass Spectrometry Imaging for Visualizing In Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals

    PubMed Central

    Fujimura, Yoshinori; Miura, Daisuke

    2014-01-01

    Understanding the spatial distribution of bioactive small molecules is indispensable for elucidating their biological or pharmaceutical roles. Mass spectrometry imaging (MSI) enables determination of the distribution of ionizable molecules present in tissue sections of whole-body or single heterogeneous organ samples by direct ionization and detection. This emerging technique is now widely used for in situ label-free molecular imaging of endogenous or exogenous small molecules. MSI allows the simultaneous visualization of many types of molecules including a parent molecule and its metabolites. Thus, MSI has received much attention as a potential tool for pathological analysis, understanding pharmaceutical mechanisms, and biomarker discovery. On the other hand, several issues regarding the technical limitations of MSI are as of yet still unresolved. In this review, we describe the capabilities of the latest matrix-assisted laser desorption/ionization (MALDI)-MSI technology for visualizing in situ metabolism of endogenous metabolites or dietary phytochemicals (food factors), and also discuss the technical problems and new challenges, including MALDI matrix selection and metabolite identification, that need to be addressed for effective and widespread application of MSI in the diverse fields of biological, biomedical, and nutraceutical (food functionality) research. PMID:24957029

  5. Application of desorption electrospray ionization mass spectrometry imaging in breast cancer margin analysis

    PubMed Central

    Calligaris, David; Caragacianu, Diana; Liu, Xiaohui; Norton, Isaiah; Thompson, Christopher J.; Richardson, Andrea L.; Golshan, Mehra; Easterling, Michael L.; Santagata, Sandro; Dillon, Deborah A.; Jolesz, Ferenc A.; Agar, Nathalie Y. R.

    2014-01-01

    Distinguishing tumor from normal glandular breast tissue is an important step in breast-conserving surgery. Because this distinction can be challenging in the operative setting, up to 40% of patients require an additional operation when traditional approaches are used. Here, we present a proof-of-concept study to determine the feasibility of using desorption electrospray ionization mass spectrometry imaging (DESI-MSI) for identifying and differentiating tumor from normal breast tissue. We show that tumor margins can be identified using the spatial distributions and varying intensities of different lipids. Several fatty acids, including oleic acid, were more abundant in the cancerous tissue than in normal tissues. The cancer margins delineated by the molecular images from DESI-MSI were consistent with those margins obtained from histological staining. Our findings prove the feasibility of classifying cancerous and normal breast tissues using ambient ionization MSI. The results suggest that an MS-based method could be developed for the rapid intraoperative detection of residual cancer tissue during breast-conserving surgery. PMID:25246570

  6. Langartech: A Custom-Made MALDI Matrix Sprayer for MALDI Imaging Mass Spectrometry.

    PubMed

    Iloro, Ibon; Bueno, Amaia; Calvo, Javier; Urreta, Harkaitz; Elortza, Felix

    2016-04-01

    Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a powerful tool for investigating the distribution of proteins and other molecules within biological systems through the in situ analysis of tissue sections, enabling molecular histology. MALDI IMS can determine the distribution of hundreds of unknown compounds in a single measurement while maintaining spatial and molecular integrity. The matrix spraying stage is a key factor in making this technique more sensitive and robust. In this article, we describe a custom-made matrix sprayer (Langartech), which is both inexpensive (estimated cost of about €3000, or $3500) and reliable compared with the alternatives present in the market today, with prices greater than €20,000 ($25,000). Several comparisons were made between our Langartech sprayer and one of the high-end matrix sprayers commercially available: ImagePrep (Bruker Daltonics). Focusing on lateral resolution and observed peak intensities, overall results show that our sprayer behaves in a very competitive fashion, especially when taking into account the huge difference in sophistication level and price. PMID:26391011

  7. Rapid and widespread distribution of doxycycline in rat brain: a mass spectrometric imaging study.

    PubMed

    Munyeza, Chiedza F; Shobo, Adeola; Baijnath, Sooraj; Bratkowska, Dominika; Naiker, Suhashni; Bester, Linda A; Singh, Sanil D; Maguire, Glenn E M; Kruger, Hendrik G; Naicker, Tricia; Govender, Thavendran

    2016-01-01

    1. The penetration of tetracyclines into the brain has been widely documented. The aim of this work was to develop a matrix assisted laser desorption ionization-mass spectrometry imaging (MALDI MSI) method for the molecular histology of doxycycline (DOX) in the healthy rat brain. 2. The time-dependent distribution was investigated after an i.p. dose of 25 mg/kg at 0, 5, 30, 120, 240, 360 and 480 min postdose. LCMS/MS was used to quantify the drug in plasma and brain homogenates and MALDI MSI was used to determine the distribution of the analyte. 3. Within the first-hour postdose, the drug showed slow accumulation into the plasma and brain tissues. DOX brain concentration gradually increased and reached a peak (Cmax) of 1034.9 ng/mL at 240 min postdose, resulting in a brain plasma ratio of 31%. The images acquired by MSI matched the quantification results and clearly showed drug distribution over the entire rat brain coronal section from 5 min and its slow elimination after 360-min postdose. 4. Our findings confirm that MALDI MSI provides an advanced, label-free and faster alternative technique for xenobiotic distribution such as DOX in tissues, making it an essential drug discovery tool for other possible neuroprotective agents. PMID:26327274

  8. Absolute Quantitative MALDI Imaging Mass Spectrometry: A Case of Rifampicin in Liver Tissues.

    PubMed

    Chumbley, Chad W; Reyzer, Michelle L; Allen, Jamie L; Marriner, Gwendolyn A; Via, Laura E; Barry, Clifton E; Caprioli, Richard M

    2016-02-16

    Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) elucidates molecular distributions in thin tissue sections. Absolute pixel-to-pixel quantitation has remained a challenge, primarily lacking validation of the appropriate analytical methods. In the present work, isotopically labeled internal standards are applied to tissue sections to maximize quantitative reproducibility and yield accurate quantitative results. We have developed a tissue model for rifampicin (RIF), an antibiotic used to treat tuberculosis, and have tested different methods of applying an isotopically labeled internal standard for MALDI IMS analysis. The application of the standard and subsequently the matrix onto tissue sections resulted in quantitation that was not statistically significantly different from results obtained using HPLC-MS/MS of tissue extracts. Quantitative IMS experiments were performed on liver tissue from an animal dosed in vivo. Each microspot in the quantitative images measures the local concentration of RIF in the thin tissue section. Lower concentrations were detected from the blood vessels and around the portal tracts. The quantitative values obtained from these measurements were comparable (>90% similarity) to HPLC-MS/MS results obtained from extracts of the same tissue. PMID:26814665

  9. Matrix assisted laser desorption ionization mass spectrometry imaging identifies markers of ageing and osteoarthritic cartilage

    PubMed Central

    2014-01-01

    Introduction Cartilage protein distribution and the changes that occur in cartilage ageing and disease are essential in understanding the process of cartilage ageing and age related diseases such as osteoarthritis. The aim of this study was to investigate the peptide profiles in ageing and osteoarthritic (OA) cartilage sections using matrix assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI). Methods The distribution of proteins in young, old and OA equine cartilage was compared following tryptic digestion of cartilage slices and MALDI-MSI undertaken with a MALDI SYNAPT™ HDMS system. Protein identification was undertaken using database searches following multivariate analysis. Peptide intensity differences between young, ageing and OA cartilage were imaged with Biomap software. Analysis of aggrecanase specific cleavage patterns of a crude cartilage proteoglycan extract were used to validate some of the differences in peptide intensity identified. Immunohistochemistry studies validated the differences in protein abundance. Results Young, old and OA equine cartilage was discriminated based on their peptide signature using discriminant analysis. Proteins including aggrecan core protein, fibromodulin, and cartilage oligomeric matrix protein were identified and localised. Fibronectin peptides displayed a stronger intensity in OA cartilage. Age-specific protein markers for collectin-43 and cartilage oligomeric matrix protein were identified. In addition potential fibromodulin and biglycan peptides targeted for degradation in OA were detected. Conclusions MALDI-MSI provided a novel platform to study cartilage ageing and disease enabling age and disease specific peptides in cartilage to be elucidated and spatially resolved. PMID:24886698

  10. Decellularization of intact tissue enables MALDI imaging mass spectrometry analysis of the extracellular matrix.

    PubMed

    Gessel, Megan; Spraggins, Jeffrey M; Voziyan, Paul; Hudson, Billy G; Caprioli, Richard M

    2015-11-01

    Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a powerful molecular mapping technology that offers unbiased visualization of the spatial arrangement of biomolecules in tissue. Although there has been a significant increase in the number of applications employing this technology, the extracellular matrix (ECM) has received little attention, likely because ECM proteins are mostly large, insoluble and heavily cross-linked. We have developed a new sample preparation approach to enable MALDI IMS analysis of ECM proteins in tissue. Prior to freezing and sectioning, intact tissues are decellularized by incubation in sodium dodecyl sulfate. Decellularization removes the highly abundant, soluble species that dominate a MALDI IMS spectrum while preserving the structural integrity of the ECM. In situ tryptic hydrolysis and imaging of tryptic peptides are then carried out to accommodate the large sizes of ECM proteins. This new approach allows the use of MALDI IMS for identification of spatially specific changes in ECM protein expression and modification in tissue. PMID:26505774

  11. Dynamical Masses of Young M Dwarfs: Masses and Orbital Parameters of GJ 3305 AB, the Wide Binary Companion to the Imaged Exoplanet Host 51 Eri

    NASA Astrophysics Data System (ADS)

    Montet, Benjamin T.; Bowler, Brendan P.; Shkolnik, Evgenya L.; Deck, Katherine M.; Wang, Ji; Horch, Elliott P.; Liu, Michael C.; Hillenbrand, Lynne A.; Kraus, Adam L.; Charbonneau, David

    2015-11-01

    We combine new high resolution imaging and spectroscopy from Keck/NIRC2, Discovery Channel Telescope/DSSI, and Keck/HIRES with published astrometry and radial velocities to measure individual masses and orbital elements of the GJ 3305 AB system, a young (˜20 Myr) M+M binary (unresolved spectral type M0) member of the β Pictoris moving group comoving with the imaged exoplanet host 51 Eri. We measure a total system mass of 1.11 ± 0.04 {M}⊙ , a period of 29.03 ± 0.50 year, a semimajor axis of 9.78 ± 0.14 AU, and an eccentricity of 0.19 ± 0.02. The primary component has a dynamical mass of 0.67 ± 0.05 {M}⊙ and the secondary has a mass of 0.44 ± 0.05 {M}⊙ . The recently updated BHAC15 models are consistent with the masses of both stars to within 1.5σ . Given the observed masses the models predict an age of the GJ 3305 AB system of 37 ± 9 Myr. Based on the observed system architecture and our dynamical mass measurement, it is unlikely that the orbit of 51 Eri b has been significantly altered by the Kozai-Lidov mechanism. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

  12. Dynamical Masses of Young M Dwarfs: Masses and Orbital Parameters of GJ 3305 AB, the Wide Binary Companion to the Imaged Exoplanet Host 51 Eri

    NASA Astrophysics Data System (ADS)

    Montet, Benjamin T.; Bowler, Brendan P.; Shkolnik, Evgenya L.; Deck, Katherine M.; Wang, Ji; Horch, Elliott P.; Liu, Michael C.; Hillenbrand, Lynne A.; Kraus, Adam L.; Charbonneau, David

    2015-11-01

    We combine new high resolution imaging and spectroscopy from Keck/NIRC2, Discovery Channel Telescope/DSSI, and Keck/HIRES with published astrometry and radial velocities to measure individual masses and orbital elements of the GJ 3305 AB system, a young (∼20 Myr) M+M binary (unresolved spectral type M0) member of the β Pictoris moving group comoving with the imaged exoplanet host 51 Eri. We measure a total system mass of 1.11 ± 0.04 {M}ȯ , a period of 29.03 ± 0.50 year, a semimajor axis of 9.78 ± 0.14 AU, and an eccentricity of 0.19 ± 0.02. The primary component has a dynamical mass of 0.67 ± 0.05 {M}ȯ and the secondary has a mass of 0.44 ± 0.05 {M}ȯ . The recently updated BHAC15 models are consistent with the masses of both stars to within 1.5σ . Given the observed masses the models predict an age of the GJ 3305 AB system of 37 ± 9 Myr. Based on the observed system architecture and our dynamical mass measurement, it is unlikely that the orbit of 51 Eri b has been significantly altered by the Kozai–Lidov mechanism. Some of the data presented herein were obtained at the W. M. Keck Observatory, which is operated as a scientific partnership among the California Institute of Technology, the University of California and the National Aeronautics and Space Administration. The Observatory was made possible by the generous financial support of the W. M. Keck Foundation.

  13. MALDI Imaging Mass Spectrometry (MALDI-IMS)—Application of Spatial Proteomics for Ovarian Cancer Classification and Diagnosis

    PubMed Central

    Gustafsson, Johan O. R.; Oehler, Martin K.; Ruszkiewicz, Andrew; McColl, Shaun R.; Hoffmann, Peter

    2011-01-01

    MALDI imaging mass spectrometry (MALDI-IMS) allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review. PMID:21340013

  14. OpenMSI: A High-Performance Web-Based Platform for Mass Spectrometry Imaging

    SciTech Connect

    Rubel, Oliver; Greiner, Annette; Cholia, Shreyas; Louie, Katherine; Bethel, E. Wes; Northen, Trent R.; Bowen, Benjamin P.

    2013-10-02

    Mass spectrometry imaging (MSI) enables researchers to directly probe endogenous molecules directly within the architecture of the biological matrix. Unfortunately, efficient access, management, and analysis of the data generated by MSI approaches remain major challenges to this rapidly developing field. Despite the availability of numerous dedicated file formats and software packages, it is a widely held viewpoint that the biggest challenge is simply opening, sharing, and analyzing a file without loss of information. Here we present OpenMSI, a software framework and platform that addresses these challenges via an advanced, high-performance, extensible file format and Web API for remote data access (http://openmsi.nersc.gov). The OpenMSI file format supports storage of raw MSI data, metadata, and derived analyses in a single, self-describing format based on HDF5 and is supported by a large range of analysis software (e.g., Matlab and R) and programming languages (e.g., C++, Fortran, and Python). Careful optimization of the storage layout of MSI data sets using chunking, compression, and data replication accelerates common, selective data access operations while minimizing data storage requirements and are critical enablers of rapid data I/O. The OpenMSI file format has shown to provide >2000-fold improvement for image access operations, enabling spectrum and image retrieval in less than 0.3 s across the Internet even for 50 GB MSI data sets. To make remote high-performance compute resources accessible for analysis and to facilitate data sharing and collaboration, we describe an easy-to-use yet powerful Web API, enabling fast and convenient access to MSI data, metadata, and derived analysis results stored remotely to facilitate high-performance data analysis and enable implementation of Web based data sharing, visualization, and analysis.

  15. OpenMSI: a high-performance web-based platform for mass spectrometry imaging.

    PubMed

    Rübel, Oliver; Greiner, Annette; Cholia, Shreyas; Louie, Katherine; Bethel, E Wes; Northen, Trent R; Bowen, Benjamin P

    2013-11-01

    Mass spectrometry imaging (MSI) enables researchers to directly probe endogenous molecules directly within the architecture of the biological matrix. Unfortunately, efficient access, management, and analysis of the data generated by MSI approaches remain major challenges to this rapidly developing field. Despite the availability of numerous dedicated file formats and software packages, it is a widely held viewpoint that the biggest challenge is simply opening, sharing, and analyzing a file without loss of information. Here we present OpenMSI, a software framework and platform that addresses these challenges via an advanced, high-performance, extensible file format and Web API for remote data access (http://openmsi.nersc.gov). The OpenMSI file format supports storage of raw MSI data, metadata, and derived analyses in a single, self-describing format based on HDF5 and is supported by a large range of analysis software (e.g., Matlab and R) and programming languages (e.g., C++, Fortran, and Python). Careful optimization of the storage layout of MSI data sets using chunking, compression, and data replication accelerates common, selective data access operations while minimizing data storage requirements and are critical enablers of rapid data I/O. The OpenMSI file format has shown to provide >2000-fold improvement for image access operations, enabling spectrum and image retrieval in less than 0.3 s across the Internet even for 50 GB MSI data sets. To make remote high-performance compute resources accessible for analysis and to facilitate data sharing and collaboration, we describe an easy-to-use yet powerful Web API, enabling fast and convenient access to MSI data, metadata, and derived analysis results stored remotely to facilitate high-performance data analysis and enable implementation of Web based data sharing, visualization, and analysis. PMID:24087878

  16. Automated anatomical interpretation of ion distributions in tissue: linking imaging mass spectrometry to curated atlases.

    PubMed

    Verbeeck, Nico; Yang, Junhai; De Moor, Bart; Caprioli, Richard M; Waelkens, Etienne; Van de Plas, Raf

    2014-09-16

    Imaging mass spectrometry (IMS) has become a prime tool for studying the distribution of biomolecules in tissue. Although IMS data sets can become very large, computational methods have made it practically feasible to search these experiments for relevant findings. However, these methods lack access to an important source of information that many human interpretations rely upon: anatomical insight. In this work, we address this need by (1) integrating a curated anatomical data source with an empirically acquired IMS data source, establishing an algorithm-accessible link between them and (2) demonstrating the potential of such an IMS-anatomical atlas link by applying it toward automated anatomical interpretation of ion distributions in tissue. The concept is demonstrated in mouse brain tissue, using the Allen Mouse Brain Atlas as the curated anatomical data source that is linked to MALDI-based IMS experiments. We first develop a method to spatially map the anatomical atlas to the IMS data sets using nonrigid registration techniques. Once a mapping is established, a second computational method, called correlation-based querying, gives an elementary demonstration of the link by delivering basic insight into relationships between ion images and anatomical structures. Finally, a third algorithm moves further beyond both registration and correlation by providing automated anatomical interpretation of ion images. This task is approached as an optimization problem that deconstructs ion distributions as combinations of known anatomical structures. We demonstrate that establishing a link between an IMS experiment and an anatomical atlas enables automated anatomical annotation, which can serve as an important accelerator both for human and machine-guided exploration of IMS experiments. PMID:25153352

  17. NICMOS Imaging of 2MASSWJ 1207334-393254 - A Planetary-Mass Companion Candidate

    NASA Astrophysics Data System (ADS)

    Schneider, G.; Song, I.; Zuckerman, B.; Becklin, E.; Lowrance, P.; Macintosh, B.; Bessell, M.; Dumas, C.; Chauvin, G.

    2004-12-01

    2MASSWJ 1207334-393254, a likely member of the nearby TW Hya association (age app 10 Myr and app 70 pc from Earth), is an app 30 Mjupiter brown dwarf (M8V spectrum due to its youth) for which a putative candidate planetary-mass companion was identified by Chauvin et al (Astron. and Astroph. 425, L29) with VLT/NACO observations in April 2004. Earlier, 2MASSWJ 1207334-393254 had been scheduled for observation in HST cycle 13 in a NICMOS H-band coronagraphic companion detection survey (GO 10176), but was re-programmed as an early "follow-up" observation given the ground-based derived implications for shorter wavelength space-based detection and efficacious diagnostic photometric measurements. Here, we present NICMOS camera 1 imaging photometry observations of 2MASSWJ 1207334-393254 and its point-like companion candidate in three bands: F090M (0.80 - 1.00 microns; similar to I-band), F110M (1.00 - 1.20 microns) and F160W (1.40 - 1.60 microns; similar to H-band) obtained on 28 Aug 2004. For the 773.7 +/- 2.2 mas (app 55 AU projected separation) distant companion we find in-band magnitudes for the companion candidate of F090M = 22.34 +/- 0.35 (delta-F090M = +7.14), F110M = 20.61 +/- 0.15 and (delta-F110M = +7.02) F160W = 18.24 +/- 0.02 (delta-F160W = +5.62). The NICMOS [0.90] - [1.6] micron color index of +4.1 +/- 0.4 is consistent with expectations for the spectral energy distribution of a mid to late L-dwarf (e.g., I - H of app +4.4 for spectral type L4). At the likely age of this candidate, the NICMOS and longer wavelength VLT/NACO derived photometric measures may implicate an object of several Jupiter masses. If the candidate companion is (as is yet to be) demonstrated to exhibit common proper motion with 2MASSWJ 1207334-393254 then the first image of a gravitationally bound companion of planetary mass may have already been secured. This work is supported through grants to the GO 10176 and 10177 teams from STScI, which is operated by AURA, Inc., under NASA contract

  18. Characterization of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging

    DOE PAGESBeta

    Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

    2015-10-22

    Herein, a commercial optical microscope, laser microdissection instrument was coupled with an electrospray ionization mass spectrometer via a low profile liquid vortex capture probe to yield a hybrid optical microscopy/mass spectrometry imaging system. The instrument has bright-field and fluorescence microscopy capabilities in addition to a highly focused UV laser beam that is utilized for laser ablation of samples. With this system, material laser ablated from a sample using the microscope was caught by a liquid vortex capture probe and transported in solution for analysis by electrospray ionization mass spectrometry. Both lane scanning and spot sampling mass spectral imaging modes weremore » used. The smallest area the system was able to ablate was ~0.544 μm × ~0.544 μm, achieved by oversampling of the smallest laser ablation spot size that could be obtained (~1.9 μm). With use of a model photoresist surface, known features as small as ~1.5 μm were resolved. The capabilities of the system with real world samples were demonstrated first with a blended polymer thin film containing poly(2-vinylpyridine) and poly(N-vinylcarbazole). Using spot sampling imaging, sub-micrometer sized features (0.62, 0.86, and 0.98 μm) visible by optical microscopy were clearly distinguished in the mass spectral images. A second real world example showed the imaging of trace amounts of cocaine in mouse brain thin tissue sections. Lastly, with use of a lane scanning mode with ~6 μm × ~6 μm data pixels, features in the tissue as small as 15 μm in size could be distinguished in both the mass spectral and optical images.« less

  19. Characterization of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging

    SciTech Connect

    Cahill, John F.; Kertesz, Vilmos; Van Berkel, Gary J.

    2015-10-22

    Herein, a commercial optical microscope, laser microdissection instrument was coupled with an electrospray ionization mass spectrometer via a low profile liquid vortex capture probe to yield a hybrid optical microscopy/mass spectrometry imaging system. The instrument has bright-field and fluorescence microscopy capabilities in addition to a highly focused UV laser beam that is utilized for laser ablation of samples. With this system, material laser ablated from a sample using the microscope was caught by a liquid vortex capture probe and transported in solution for analysis by electrospray ionization mass spectrometry. Both lane scanning and spot sampling mass spectral imaging modes were used. The smallest area the system was able to ablate was ~0.544 μm × ~0.544 μm, achieved by oversampling of the smallest laser ablation spot size that could be obtained (~1.9 μm). With use of a model photoresist surface, known features as small as ~1.5 μm were resolved. The capabilities of the system with real world samples were demonstrated first with a blended polymer thin film containing poly(2-vinylpyridine) and poly(N-vinylcarbazole). Using spot sampling imaging, sub-micrometer sized features (0.62, 0.86, and 0.98 μm) visible by optical microscopy were clearly distinguished in the mass spectral images. A second real world example showed the imaging of trace amounts of cocaine in mouse brain thin tissue sections. Lastly, with use of a lane scanning mode with ~6 μm × ~6 μm data pixels, features in the tissue as small as 15 μm in size could be distinguished in both the mass spectral and optical images.

  20. Desorption Electrospray Ionization (DESI) Mass Spectrometric Imaging of the Distribution of Rohitukine in the Seedling of Dysoxylum binectariferum Hook. F

    PubMed Central

    Mohana Kumara, Patel; Srimany, Amitava; Arunan, Suganya; Ravikanth, Gudasalamani; Uma Shaanker, Ramanan; Pradeep, Thalappil

    2016-01-01

    Ambient ionization mass spectrometric imaging of all parts of the seedling of Dysoxylum binectariferum Hook. f (Meliaceae) was performed to reconstruct the molecular distribution of rohitukine (Rh) and related compounds. The species accumulates Rh, a prominent chromone alkaloid, in its seeds, fruits, and stem bark. Rh possesses anti-inflammatory, anti-cancer, and immuno-modulatory properties. Desorption electrospray ionization mass spectrometry imaging (DESI MSI) and electrospray ionization (ESI) tandem mass spectrometry (MS/MS) analysis detected Rh as well as its glycosylated, acetylated, oxidized, and methoxylated analogues. Rh was predominantly distributed in the main roots, collar region of the stem, and young leaves. In the stem and roots, Rh was primarily restricted to the cortex region. The identities of the metabolites were assigned based on both the fragmentation patterns and exact mass analyses. We discuss these results, with specific reference to the possible pathways of Rh biosynthesis and translocation during seedling development in D. binectariferum. PMID:27362422

  1. Laser desorption/ionization mass spectrometry for direct profiling and imaging of small molecules from raw biological materials

    SciTech Connect

    Cha, Sangwon

    2008-01-01

    Matrix-assisted laser desorption/ionization(MALDI) mass spectrometry(MS) has been widely used for analysis of biological molecules, especially macromolecules such as proteins. However, MALDI MS has a problem in small molecule (less than 1 kDa) analysis because of the signal saturation by organic matrixes in the low mass region. In imaging MS (IMS), inhomogeneous surface formation due to the co-crystallization process by organic MALDI matrixes limits the spatial resolution of the mass spectral image. Therefore, to make laser desorption/ionization (LDI) MS more suitable for mass spectral profiling and imaging of small molecules directly from raw biological tissues, LDI MS protocols with various alternative assisting materials were developed and applied to many biological systems of interest. Colloidal graphite was used as a matrix for IMS of small molecules for the first time and methodologies for analyses of small metabolites in rat brain tissues, fruits, and plant tissues were developed. With rat brain tissues, the signal enhancement for cerebroside species by colloidal graphite was observed and images of cerebrosides were successfully generated by IMS. In addition, separation of isobaric lipid ions was performed by imaging tandem MS. Directly from Arabidopsis flowers, flavonoids were successfully profiled and heterogeneous distribution of flavonoids in petals was observed for the first time by graphite-assisted LDI(GALDI) IMS.

  2. Quantifying element incorporation in multispecies biofilms using nanoscale secondary ion mass spectrometry image analysis.

    PubMed

    Renslow, Ryan S; Lindemann, Stephen R; Cole, Jessica K; Zhu, Zihua; Anderton, Christopher R

    2016-06-01

    Elucidating nutrient exchange in microbial communities is an important step in understanding the relationships between microbial systems and global biogeochemical cycles, but these communities are complex and the interspecies interactions that occur within them are not well understood. Phototrophic consortia are useful and relevant experimental systems to investigate such interactions as they are not only prevalent in the environment, but some are cultivable in vitro and amenable to controlled scientific experimentation. Nanoscale secondary ion mass spectrometry (NanoSIMS) is a powerful, high spatial resolution tool capable of visualizing the metabolic activities of single cells within a biofilm, but quantitative analysis of the resulting data has typically been a manual process, resulting in a task that is both laborious and susceptible to human error. Here, the authors describe the creation and application of a semiautomated image-processing pipeline that can analyze NanoSIMS-generated data, applied to phototrophic biofilms as an example. The tool employs an image analysis process, which includes both elemental and morphological segmentation, producing a final segmented image that allows for discrimination between autotrophic and heterotrophic biomass, the detection of individual cyanobacterial filaments and heterotrophic cells, the quantification of isotopic incorporation of individual heterotrophic cells, and calculation of relevant population statistics. The authors demonstrate the functionality of the tool by using it to analyze the uptake of (15)N provided as either nitrate or ammonium through the unicyanobacterial consortium UCC-O and imaged via NanoSIMS. The authors found that the degree of (15)N incorporation by individual cells was highly variable when labeled with (15)NH4 (+), but much more even when biofilms were labeled with (15)NO3 (-). In the (15)NH4 (+)-amended biofilms, the heterotrophic distribution of (15)N incorporation was highly skewed, with

  3. 'Plug and Play' assembly of a low-temperature plasma ionization mass spectrometry imaging (LTP-MSI) system.

    PubMed

    Maldonado-Torres, Mauricio; López-Hernández, José Fabricio; Jiménez-Sandoval, Pedro; Winkler, Robert

    2014-05-01

    Mass spectrometry imaging (MSI) is of high and growing interest in life science research, but the investment for necessary equipment is often prohibitive for small research groups. Therefore, we developed a basic MSI system from low cost 'Plug and Play' components, which are connected to the Universal Serial Bus (USB) of a standard computer. Our open source software OpenMZxy (http://www.bioprocess.org/openmzxy) enables automatic and manual sampling, as well as the recording of position data. For ionization we used a low-temperature plasma probe (LTP), coupled to a quadrupole mass analyzer. The current set-up has a practical resolution of 1mm, and a sampling area of 100×100mm, resulting in up to 10,000 sampling points. Our prototype is easy and economical to adopt for different types of mass analyzers. We prove the usability of the LTP-MSI system for macroscopic samples by imaging the distribution of metabolites in the longitudinal cross-cut of a chili (Capsicum annuum, 'Jalapeño pepper') fruit. The localization of capsaicin in the placenta could be confirmed. But additionally, yet unknown low molecular weight compounds were detected in defined areas, which underline the potential of LTP-MSI for the imaging of volatile and semi-volatile metabolites and for the discovery of new natural products. Biological significance Knowledge about the spatial distribution of metabolites, proteins, or lipids in a given tissue often leads to novel findings in medicine and biology. Therefore, mass spectrometry based imaging (MSI) is becoming increasingly popular in life science research. However, the investment for necessary equipment is often prohibitive for small research groups. We built a prototype with an ambient ionization source, which is easy and economical to adopt for different types of mass analyzers. Therefore, we hope that our system contributes to a broader use of mass spectrometry imaging for answering biological questions. PMID:24642210

  4. MALDI Imaging Mass Spectrometry for In Situ Proteomic Analysis of Preneoplastic Lesions in Pancreatic Cancer

    PubMed Central

    Grüner, Barbara M.; Hahne, Hannes; Mazur, Pawel K.; Trajkovic-Arsic, Marija; Maier, Stefan; Esposito, Irene; Kalideris, Evdokia; Michalski, Christoph W.; Kleeff, Jörg; Rauser, Sandra; Schmid, Roland M.; Küster, Bernhard; Walch, Axel; Siveke, Jens T.

    2012-01-01

    The identification of new biomarkers for preneoplastic pancreatic lesions (PanINs, IPMNs) and early pancreatic ductal adenocarcinoma (PDAC) is crucial due to the diseasés high mortality rate upon late detection. To address this task we used the novel technique of matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) on genetically engineered mouse models (GEM) of pancreatic cancer. Various GEM were analyzed with MALDI IMS to investigate the peptide/protein-expression pattern of precursor lesions in comparison to normal pancreas and PDAC with cellular resolution. Statistical analysis revealed several discriminative m/z-species between normal and diseased tissue. Intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasm (IPMN) could be distinguished from normal pancreatic tissue and PDAC by 26 significant m/z-species. Among these m/z-species, we identified Albumin and Thymosin-beta 4 by liquid chromatography and tandem mass spectrometry (LC-MS/MS), which were further validated by immunohistochemistry, western blot, quantitative RT-PCR and ELISA in both murine and human tissue. Thymosin-beta 4 was found significantly increased in sera of mice with PanIN lesions. Upregulated PanIN expression of Albumin was accompanied by increased expression of liver-restricted genes suggesting a hepatic transdifferentiation program of preneoplastic cells. In conclusion we show that GEM of endogenous PDAC are a suitable model system for MALDI-IMS and subsequent LC-MS/MS analysis, allowing in situ analysis of small precursor lesions and identification of differentially expressed peptides and proteins. PMID:22761793

  5. Mass spectrometric imaging of in vivo protein and lipid adsorption on biodegradable vascular replacement systems.

    PubMed

    Fröhlich, Sophie M; Eilenberg, Magdalena; Svirkova, Anastasiya; Grasl, Christian; Liska, Robert; Bergmeister, Helga; Marchetti-Deschmann, Martina

    2015-09-01

    Cardiovascular diseases present amongst the highest mortality risks in Western civilization and are frequently caused by arteriosclerotic vessel failure. Coronary artery and peripheral vessel reconstruction necessitates the use of small diameter systems that are mechanically stress-resistant and biocompatible. Expanded polytetrafluorethylene (ePTFE) is amongst the materials used most frequently for non-degradable and bio-degradable vessel reconstruction procedures, with thermoplastic polyurethanes (TPU) representing a promising substitute. The present study describes and compares the biological adsorption and diffusion occurring with both materials following implantation in rat models. Gel electrophoresis and thin-layer chromatography, combined with mass spectrometry and mass spectrometry imaging, were utilized to identify the adsorbed lipids and proteins. The results were compared with the analytes present in native aorta tissue. It was revealed that both polymers were severely affected by biological adsorption after 10 min in vivo. Proteins associated with cell growth and migration were identified, especially on the luminal graft surface, while lipids were found to be located on both the luminal and abluminal surfaces. Lipid adsorption and cholesterol diffusion were found to be correlated with the polymer modifications identified on degradable thermoplastic urethane graft samples, with the latter revealing extensive cholesterol adsorption. The present study demonstrates an interaction between biological matter and both graft materials, and provides insights into polymer changes, in particular, those observed with thermoplastic urethanes already after 10 min in vivo exposure. ePTFE demonstrated minor polymer modifications, whereas several different polymer signals were observed for TPU, all were co-localized with biological signals. PMID:26198453

  6. Mass spectrometric imaging of metabolites in kidney tissues from rats treated with furosemide.

    PubMed

    Jung, Jin Woo; Lee, Mi Suk; Choi, Hyo-Jung; Jung, Sunhee; Lee, Yu-Jung; Hwang, Geum-Sook; Kwon, Tae-Hwan

    2016-06-01

    In the kidney, metabolic processes are different among the cortex (COR), outer medulla (OM), and inner medulla (IM). Using matrix-assisted laser desorption/ionization (MALDI) and imaging mass spectrometry (IMS), we examined the change of metabolites in the COR, OM, and IM of the rat kidney after furosemide treatment compared with vehicle-treated controls. Osmotic minipumps were implanted in male Sprague-Dawley rats to deliver 12 mg·day(-1)·rat(-1) of furosemide. Vehicle-treated (n = 14) and furosemide-treated (furosemide rats, n = 15) rats in metabolic cages received a fixed amount of rat chow (15 g·220 g body wt(-1)·day(-1) for each rat) with free access to water intake for 6 days. At day 6, higher urine output (32 ± 4 vs. 9 ± 1 ml/day) and lower urine osmolality (546 ± 44 vs. 1,677 ± 104 mosmol/kgH2O) were observed in furosemide rats. Extracts of COR, OM, and IM were analyzed by ultraperformance liquid chromatography coupled with quadrupole time-of-flight (TOF) mass spectrometry, where multivariate analysis revealed significant differences between the two groups. Several metabolites, including acetylcarnitine, betaine, carnitine, choline, and glycerophosphorylcholine (GPC), were significantly changed. The changes of metabolites were further identified by MALDI-TOF/TOF and IMS. Their spatial distribution and relative quantitation in the kidneys were analyzed by IMS. Carnitine compounds were increased in COR and IM, whereas carnitine and acetylcarnitine were decreased in OM. Choline compounds were increased in COR and OM but decreased in IM from furosemide rats. Betaine and GPC were decreased in OM and IM. Taken together, MALDI-TOF/TOF and IMS successfully provide the spatial distribution and relative quantitation of metabolites in the kidney. PMID:26962105

  7. Imaging Mass Spectrometry of Diversified Cardiolipin Molecular Species in the Brain

    PubMed Central

    2015-01-01

    MALDI imaging mass spectrometry (MALDI-IMS) has been used successfully in mapping different lipids in tissue sections, yet existing protocols fail to detect the diverse species of mitochondria-unique cardiolipins (CLs) in the brain which are essential for cellular and mitochondrial physiology. We have developed methods enabling the imaging of individual CLs in brain tissue. This was achieved by eliminating ion suppressive effects by (i) cross-linking carboxyl/amino containing molecules on tissue with 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride and (ii) removing highly abundant phosphatidylcholine head groups via phospholipase C treatment. These treatments allowed the detection of CL species at 100 μm resolution and did not affect the amount or molecular species distribution of brain tissue CLs. When combined with augmented matrix application, these modifications allowed the visualization and mapping of multiple CL species in various regions of the brain including the thalamus, hippocampus, and cortex. Areas such as the dentate and stratum radiatum exhibited higher CL signals than other areas within the hippocampal formation. The habenular nuclear (Hb)/dorsal third ventricle (D3 V) and lateral ventricle (LV) areas were identified as CL “hot spots”. Our method also allowed structural MS/MS fragmentation and mapping of CLs with identified fatty acid residues and demonstrated a nonrandom distribution of individual oxidizable (polyunsaturated fatty acid containing) and nonoxidizable (nonpolyunsaturated containing) CLs in different anatomical areas of the brain. To our knowledge, this method is the first label-free approach for molecular mapping of diversified CLs in brain tissue. PMID:24949523

  8. Imaging mass spectrometry of diversified cardiolipin molecular species in the brain.

    PubMed

    Amoscato, A A; Sparvero, L J; He, R R; Watkins, S; Bayir, H; Kagan, V E

    2014-07-01

    MALDI imaging mass spectrometry (MALDI-IMS) has been used successfully in mapping different lipids in tissue sections, yet existing protocols fail to detect the diverse species of mitochondria-unique cardiolipins (CLs) in the brain which are essential for cellular and mitochondrial physiology. We have developed methods enabling the imaging of individual CLs in brain tissue. This was achieved by eliminating ion suppressive effects by (i) cross-linking carboxyl/amino containing molecules on tissue with 1-ethyl-3-[3-(dimethylamino)propyl]-carbodiimide hydrochloride and (ii) removing highly abundant phosphatidylcholine head groups via phospholipase C treatment. These treatments allowed the detection of CL species at 100 μm resolution and did not affect the amount or molecular species distribution of brain tissue CLs. When combined with augmented matrix application, these modifications allowed the visualization and mapping of multiple CL species in various regions of the brain including the thalamus, hippocampus, and cortex. Areas such as the dentate and stratum radiatum exhibited higher CL signals than other areas within the hippocampal formation. The habenular nuclear (Hb)/dorsal third ventricle (D3 V) and lateral ventricle (LV) areas were identified as CL "hot spots". Our method also allowed structural MS/MS fragmentation and mapping of CLs with identified fatty acid residues and demonstrated a nonrandom distribution of individual oxidizable (polyunsaturated fatty acid containing) and nonoxidizable (nonpolyunsaturated containing) CLs in different anatomical areas of the brain. To our knowledge, this method is the first label-free approach for molecular mapping of diversified CLs in brain tissue. PMID:24949523

  9. Noninvasive quantification of left ventricular mass by cardiac magnetic resonance imaging: Development of the method and experimental validation

    SciTech Connect

    Maddahi, J.; Crues, J.; Berman, D.S.; Mericle, J.; Garcia, E.V.; Becerra, A.M.; Henderson, R.; Bradley, W.

    1985-05-01

    Determination of left ventricular myocardial (LV) mass may aid evaluation of hypertrophic cardiomyopathies as well as percent viable myocardium in ischemic heart disease. The validity of cardiac NMR for determination of LV mass was evaluated in 9 dogs using a superconducting magnet operating at 0.35 Tesla. In-vivo gated spin echo pulsing sequences were used obtaining 0.7 cm thick slices of the heart, spaced by 1 cm, in three orthogonal planes. After sacrifice, the nonbeating hearts were imaged in-situ without gating. On each NMR slice, the LV surface area was planimetered and multiplied by slice spacing (1) and myocardial specific gravity (1.05) to obtain slice mass. For total LV mass, slice masses were added on coronal (Method (Meth) 1), transaxial (Meth 2), and sagittal (Meth 3) planes. Mass of the LV portions subject to partial volume effect were derived from an orthogonal plane. Excised LV weight ranged from 27 to 134 grams. The intra- and inter-observer agreement for planimetry of the NMR slices was high (r=.99 and r=.97, respectively). For in-situ imaging, r values of all methods were high (r=.99, .99, and .98); however, the slope and intercept of the regression line were closes to the line of identity with Meth 1 (y=0.94x+0.52). For in-vivo beating heart images, Meth 1 also had the best results (r=.99, y= 0.99x+8.3). Failure to correct for partial volume effect resulted in underestimation of in-situ and in-vivo LV masses as indicated by slope of <1 (r=,.98, y=0.77x+3.9; r=.98, y= 0.88x+0.98, respectively, Meth 1). Thus, cardiac NMR is a reproducible and accurate method for noninvasive determination of LV myocardial mass.

  10. Cellular-level mass spectrometry imaging using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) by oversampling.

    PubMed

    Nazari, Milad; Muddiman, David C

    2015-03-01

    Mass spectrometry imaging (MSI) allows for the direct and simultaneous analysis of the spatial distribution of molecular species from sample surfaces such as tissue sections. One of the goals of MSI is monitoring the distribution of compounds at the cellular resolution in order to gain insights about the biology that occurs at this spatial level. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) imaging of cervical tissue sections was performed using a spot-to-spot distance of 10 μm by utilizing the method of oversampling, where the target plate is moved by a distance that is less than the desorption radius of the laser. In addition to high spatial resolution, high mass accuracy (±1 ppm) and high mass resolving power (140,000 at m/z = 200) were achieved by coupling the IR-MALDESI imaging source to a hybrid quadrupole Orbitrap mass spectrometer. Ion maps of cholesterol in tissues were generated from voxels containing <1 cell, on average. Additionally, the challenges of imaging at the cellular level in terms of loss of sensitivity and longer analysis time are discussed. PMID:25486925

  11. Development of matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) for plant metabolite analysis

    SciTech Connect

    Korte, Andrew R

    2014-12-01

    This thesis presents efforts to improve the methodology of matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) as a method for analysis of metabolites from plant tissue samples. The first chapter consists of a general introduction to the technique of MALDI-MSI, and the sixth and final chapter provides a brief summary and an outlook on future work.

  12. Cellular Level Mass Spectrometry Imaging using Infrared Matrix Assisted Laser Desorption Electrospray Ionization (IR-MALDESI) by Oversampling

    PubMed Central

    Nazari, Milad; Muddiman, David C.

    2014-01-01

    Mass spectrometry imaging (MSI) allows for the direct and simultaneous analysis of the spatial distribution of molecular species from sample surfaces such as tissue sections. One of the goals of MSI is monitoring the distribution of compounds at the cellular resolution in order to gain insights about the biology that occurs at this spatial level. Infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) imaging of cervical tissue sections was performed using a spot-to-spot distance of 10 μm by utilizing the method of oversampling; where the target plate is moved by a distance that is less than the desorption radius of the laser. In addition to high spatial resolution, high mass accuracy (± 1 ppm) and high mass resolving power (140,000 at m/z=200) was achieved by coupling the IR-MALDESI imaging source to a hybrid quadrupole Orbitrap mass spectrometer. Ion maps of cholesterol in tissues were generated from voxels containing <1 cell, on average. Additionally, the challenges of imaging at the cellular level in terms of loss of sensitivity and longer analysis time are discussed. PMID:25486925

  13. ASTER image based assessment of glacier mass balance of Nanga Parbat massif, Pakistan

    NASA Astrophysics Data System (ADS)

    Kargel, Jeffrey; Leonard, Gregory; Haritashya, Umesh

    2014-05-01

    Starting with the analytical approach given in detail by Nuth and Kääb (2011; henceforth NK2011), we have further developed an approach toward analysis of repeat stereo ASTER-derived DEMs to extract specific and net annual mass balance of glaciers of Nanga Parbat, Pakistan. We used the approach of NK2011 to coregister DEMs obtained from ASTER stereo images acquired in September 2004 and October 2010, and the glacier outlines produced by Haritashya et al. (2014 in prep) as a mask to isolate glacier from stable (nonglacier) areas. We then devised a protocol to remove DEM data deemed to be the pits, cones, and bulges that are common artifacts with ASTER DEM data. We developed an approach similar to that given by NK2011 to make corrections for cross- and along-track errors of elevation differences and to zero out the mean elevation difference bias for stable (non-glacier points). The largest sources of correctable error were cross-track and along-track slope-dependent artifacts, which we corrected using an approach modified from that of NK2011. Several small systematic errors, such as that related to elevation, became even smaller when cross- and along-track errors were corrected. We then proceeded to analyze the statistics for the cumulative ice area and for individual glaciers. Also using the DEM-change spread function for stable areas, we deconvolved the random error from the actual change signal present in the glacier areas. Ten glaciers of Nanga Parbat thinned by an average of 6 m, i.e., 1 m/year over the 6-year period. Ice in the highest elevations remained fairly stable or even thickened by a few meters, whereas that in lower elevations thinned. Bazhin Glacier apparently was undergoing a surge-like phenomenon of rapid mass transfer from higher elevations (where thinning occurred) to lower elevations (where it thickened), though the terminus advanced by only ~182 m (Haritashya et al. 2014). Hence, our results indicate fluctuations of glaciers in Nanga Parbat

  14. Use of a multi-isotope and multi-tracer approach including organic matter isotopes for quantifying nutrient contributions from agricultural vs wastewater sources

    NASA Astrophysics Data System (ADS)

    Kendall, C.; Silva, S. R.; Young, M. B.

    2013-12-01

    While nutrient isotopes are a well-established tool for quantifying nutrients inputs from agricultural vs wastewater treatment plant (WWTP) sources, we have found that combining nutrient isotopes with the C, N, and S isotopic compositions of dissolved and particulate organic matter, as part of a comprehensive multi-isotope and multi-tracer approach, is a much more diagnostic approach. The main reasons why organic matter C-N-S isotopes are a useful adjunct to studies of nutrient sources and biogeochemical processes are that the dissolved and particulate organic matter associated with (1) different kinds of animals (e.g., humans vs cows) often have distinctive isotopic compositions reflecting the different diets of the animals, and (2) the different processes associated with the different land uses (e.g., in the WWTP or associated with different crop types) often result in significant differences in the isotopic compositions of the organics. The analysis of the δ34S of particulate organic matter (POM) and dissolved organic matter (DOM) has been found to be especially useful for distinguishing and quantifying water, nutrient, and organic contributions from different land uses in aquatic systems where much of the organic matter is aquatic in origin. In such environments, the bacteria and algae incorporate S from sulfate and sulfide that is isotopically labeled by the different processes associated with different land uses. We have found that there is ~35 permil range in δ34S of POM along the river-estuary continuum in the San Joaquin/Sacramento River basin, with low values associated with sulfate reduction in the upstream wetlands and high values associated with tidal inputs of marine water into the estuary. Furthermore, rice agriculture results in relatively low δ34S values whereas WWTP effluent in the Sacramento River produces distinctly higher values than upstream of the WWTP, presumably because SO2 is used to treat chlorinated effluent. The fish living

  15. Using Multi-Isotope Tracer Methods to Understand the Sources of Nitrate in Aerosols, Fog and River Water in Podocarpus National Forest, Ecuador

    NASA Astrophysics Data System (ADS)

    Brothers, L. A.; Dominguez, G.; Fabian, P.; Thiemens, M. H.

    2008-12-01

    sulfate and nitrate concentrations in rain and fog water by standard methods to investigate water and nutrient pathways along with data from satellite and ground based remote sensing, observations and numerical models. We hope to pair this with a multi-isotope tracer method and NOAA Hysplit Back trajectories, and satellite imagery for information about the number of fires burning in the region to help identify sources of the high nitrate deposition.

  16. Transmission Geometry Laser Ablation into a Non-Contact Liquid Vortex Capture Probe for Mass Spectrometry Imaging

    SciTech Connect

    Ovchinnikova, Olga S; Bhandari, Deepak; Lorenz, Matthias; Van Berkel, Gary J

    2014-01-01

    RATIONALE: Capture of material from a laser ablation plume into a continuous flow stream of solvent provides the means for uninterrupted sampling, transport and ionization of collected material for coupling with mass spectral analysis. Reported here is the use of vertically aligned transmission geometry laser ablation in combination with a new non-contact liquid vortex capture probe coupled with electrospray ionization for spot sampling and chemical imaging with mass spectrometry. Methods: A vertically aligned continuous flow liquid vortex capture probe was positioned directly underneath a sample surface in a transmission geometry laser ablation (355 nm, 10 Hz, 7 ns pulse width) setup to capture into solution the ablated material. The outlet of the vortex probe was coupled to the Turbo V ion source of an AB SCIEX TripleTOF 5600+ mass spectrometer. System operation and performance metrics were tested using inked patterns and thin tissue sections. Glass slides and slides designed especially for laser capture microdissection, viz., DIRECTOR slides and PEN 1.0 (polyethylene naphthalate) membrane slides, were used as sample substrates. Results: The estimated capture efficiency of laser ablated material was 24%, which was enabled by the use of a probe with large liquid surface area (~ 2.8 mm2) and with gravity to help direct ablated material vertically down towards the probe. The swirling vortex action of the liquid surface potentially enhanced capture and dissolution of not only particulates, but also gaseous products of the laser ablation. The use of DIRECTOR slides and PEN 1.0 (polyethylene naphthalate) membrane slides as sample substrates enabled effective ablation of a wide range of sample types (basic blue 7, polypropylene glycol, insulin and cyctochrome c) without photodamage using a UV laser. Imaging resolution of about 6 m was demonstrated for stamped ink on DIRECTOR slides based on the ability to distinguish features present both in the optical and in the

  17. Chemiluminescence Imaging of Superoxide Anion Detects Beta-Cell Function and Mass

    PubMed Central

    Bronsart, Laura L.; Stokes, Christian; Contag, Christopher H.

    2016-01-01

    Superoxide anion is produced during normal cellular respiration and plays key roles in cellular physiology with its dysregulation being associated with a variety of diseases. Superoxide anion is a short-lived molecule and, therefore, its homeostatic regulation and role in biology and disease requires dynamic quantification with fine temporal resolution. Here we validated coelenterazine as a reporter of intracellular superoxide anion concentration and used it as a dynamic measure both in vitro and in vivo. Chemiluminescence was dependent upon superoxide anion levels, including those produced during cellular respiration, and concentrations varied both kinetically and temporally in response to physiologically relevant fluctuations in glucose levels. In vivo imaging with coelenterazine revealed that beta cells of the pancreas have increased levels of superoxide anion, which acted as a measure of beta-cell function and mass and could predict the susceptibility of mice to diabetes mellitus. Glucose response and regulation are key elements of cellular physiology and organismal biology, and superoxide anion appears to play a fundamental and dynamic role in both of these processes. PMID:26752052

  18. Deciphering the Lipid Architecture of the Rat Sciatic Nerve Using Imaging Mass Spectrometry.

    PubMed

    Fernández, Roberto; Carriel, Víctor; Lage, Sergio; Garate, Jone; Díez-García, Javier; Ochoa, Begoña; Castro, Begoña; Alaminos, Miguel; Fernández, José A

    2016-05-18

    Knowledge on the normal structure and molecular composition of the peripheral nerves is essential to understand their pathophysiology and to select the regeneration strategies after injury. However, the precise lipid composition of the normal peripheral nerve is still poorly known. Here, we present the first study of distribution of individual lipids in the mature sciatic nerve of rats by imaging mass spectrometry. Both positive and negative ion modes were used to detect, identify and in situ map 166 molecular species of mainly glycerophospholipids, sphingomyelins, sulfatides, and diacyl and triacylglycerols. In parallel, lipid extracts were analyzed by LC-MS/MS to verify and complement the identification of lipids directly from the whole tissue. Three anatomical regions were clearly identified by its differential lipid composition: the nerve fibers, the connective tissue and the adipose tissue that surrounds the nerve. Unexpectedly, very little variety of phosphatidylcholine (PC) species was found, being by far PC 34:1 the most abundant species. Also, a rich composition on sulfatides was detected in fibers, probably due to the important role they play in the myelin cover around axons, as well as an abundance of storage lipids in the adipose and connective tissues. The database of lipids here presented for each region and for the whole sciatic nerve is a first step toward understanding the variety of the peripheral nerves' lipidome and its changes associated with different diseases and mechanical injuries. PMID:27043994

  19. Imaging mass spectrometry for the precise design of antibody-drug conjugates

    PubMed Central

    Fujiwara, Yuki; Furuta, Masaru; Manabe, Shino; Koga, Yoshikatsu; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-01-01

    Antibody-drug conjugates (ADCs) are a class of immunotherapeutic agents that enable the delivery of cytotoxic drugs to target malignant cells. Because various cancers and tumour vascular endothelia strongly express anti-human tissue factor (TF), we prepared ADCs consisting of a TF-specific monoclonal antibody (mAb) linked to the anticancer agent (ACA) monomethyl auristatin E (MMAE) via a valine-citrulline (Val-Cit) linker (human TF ADC). Identifying the most efficient drug design in advance is difficult because ADCs have complicated structures. The best method of assessing ADCs is to examine their selectivity and efficiency in releasing and distributing the ACA within tumour tissue. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) can be used to directly detect the distributions of native molecules within tumour tissues. Here, MALDI-IMS enabled the identification of the intratumour distribution of MMAE released from the ADC. In conclusion, MALDI-IMS is a useful tool to assess ADCs and facilitate the optimization of ADC design. PMID:27098163

  20. Application of imaging mass spectrometry for the molecular diagnosis of human breast tumors

    PubMed Central

    Mao, Xinxin; He, Jiuming; Li, Tiegang; Lu, Zhaohui; Sun, Jian; Meng, Yunxiao; Abliz, Zeper; Chen, Jie

    2016-01-01

    Distinguishing breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS) is a key step in breast surgery, especially to determine whether DCIS is associated with tumor cell micro-invasion. However, there is currently no reliable method to obtain molecular information for breast tumor analysis during surgery. Here, we present a novel air flow-assisted ionization (AFAI) mass spectrometry imaging method that can be used in ambient environments to differentiate breast cancer by analyzing lipids. In this study, we demonstrate that various subtypes and histological grades of IDC and DCIS can be discriminated using AFAI-MSI: phospholipids were more abundant in IDC than in DCIS, whereas fatty acids were more abundant in DCIS than in IDC. The classification of specimens in the subtype and grade validation sets showed 100% and 78.6% agreement with the histopathological diagnosis, respectively. Our work shows the rapid classification of breast cancer utilizing AFAI-MSI. This work suggests that this method could be developed to provide surgeons with nearly real-time information to guide surgical resections. PMID:26868906

  1. MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation

    PubMed Central

    Calligaris, David; Feldman, Daniel R.; Norton, Isaiah; Olubiyi, Olutayo; Changelian, Armen N.; Machaidze, Revaz; Vestal, Matthew L.; Laws, Edward R.; Dunn, Ian F.; Santagata, Sandro; Agar, Nathalie Y. R.

    2015-01-01

    We present a proof of concept study designed to support the clinical development of mass spectrometry imaging (MSI) for the detection of pituitary tumors during surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI six nonpathological (NP) human pituitary glands and 45 hormone secreting and nonsecreting (NS) human pituitary adenomas. We show that the distribution of pituitary hormones such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach. The presence of most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS methods, and subtyping of pituitary adenomas was performed by using principal component analysis (PCA) and support vector machine (SVM). Our proof of concept study demonstrates that MALDI MSI could be used to directly detect excessive hormonal production from functional pituitary adenomas and generally classify pituitary adenomas by using statistical and machine learning analyses. The tissue characterization can be completed in fewer than 30 min and could therefore be applied for the near-real-time detection and delineation of pituitary tumors for intraoperative surgical decision-making. PMID:26216958

  2. Automated MALDI matrix coating system for multiple tissue samples for imaging mass spectrometry.

    PubMed

    Mounfield, William P; Garrett, Timothy J

    2012-03-01

    Uniform matrix deposition on tissue samples for matrix-assisted laser desorption/ionization (MALDI) is key for reproducible analyte ion signals. Current methods often result in nonhomogenous matrix deposition, and take time and effort to produce acceptable ion signals. Here we describe a fully-automated method for matrix deposition using an enclosed spray chamber and spray nozzle for matrix solution delivery. A commercial air-atomizing spray nozzle was modified and combined with solenoid controlled valves and a Programmable Logic Controller (PLC) to control and deliver the matrix solution. A spray chamber was employed to contain the nozzle, sample, and atomized matrix solution stream, and to prevent any interference from outside conditions as well as allow complete control of the sample environment. A gravity cup was filled with MALDI matrix solutions, including DHB in chloroform/methanol (50:50) at concentrations up to 60 mg/mL. Various samples (including rat brain tissue sections) were prepared using two deposition methods (spray chamber, inkjet). A linear ion trap equipped with an intermediate-pressure MALDI source was used for analyses. Optical microscopic examination showed a uniform coating of matrix crystals across the sample. Overall, the mass spectral images gathered from tissues coated using the spray chamber system were of better quality and more reproducible than from tissue specimens prepared by the inkjet deposition method. PMID:22234508

  3. Electron flood gun damage effects in 3D secondary ion mass spectrometry imaging of organics.

    PubMed

    Havelund, Rasmus; Seah, Martin P; Shard, Alexander G; Gilmore, Ian S

    2014-09-01

    Electron flood guns used for charge compensation in secondary ion mass spectrometry (SIMS) cause chemical degradation. In this study, the effect of electron flood gun damage on argon cluster depth profiling is evaluated for poly(vinylcarbazole), 1,4-bis((1-naphthylphenyl)amino)biphenyl and Irganox 3114. Thin films of these three materials are irradiated with a range of doses from a focused beam of 20 eV electrons used for charge neutralization. SIMS chemical images of the irradiated surfaces show an ellipsoidal damaged area, approximately 3 mm in length, created by the electron beam. In depth profiles obtained with 5 keV Ar(2000)(+) sputtering from the vicinity of the damaged area, the characteristic ion signal intensity rises from a low level to a steady state. For the damaged thin films, the ion dose required to sputter through the thin film to the substrate is higher than for undamaged areas. It is shown that a damaged layer is formed and this has a sputtering yield that is reduced by up to an order of magnitude and that the thickness of the damaged layer, which increases with the electron dose, can be as much as 20 nm for Irganox 3114. The study emphasizes the importance of minimizing the neutralizing electron dose prior to the analysis. PMID:24912434

  4. MALDI Mass Spectrometric Imaging of Lipids in Rat Brain Injury Models

    NASA Astrophysics Data System (ADS)

    Hankin, Joseph A.; Farias, Santiago E.; Barkley, Robert M.; Heidenreich, Kim; Frey, Lauren C.; Hamazaki, Kei; Kim, Hee-Yong; Murphy, Robert C.

    2011-06-01

    Matrix-assisted laser desorption ionization/ionization imaging mass spectrometry (MALDI IMS) with a time-of-flight analyzer was used to characterize the distribution of lipid molecular species in the brain of rats in two injury models. Ischemia/reperfusion injury of the rat brain after bilateral occlusion of the carotid artery altered appearance of the phospholipids present in the hippocampal region, specifically the CA1 region. These brain regions also had a large increase in the ion abundance at m/z 548.5 and collisional activation supported identification of this ion as arising from ceramide (d18:1/18:0), a lipid known to be associated with cellular apoptosis. Traumatic brain injury model in the rat was examined by MALDI IMS and the area of damage also showed an increase in ceramide (d18:1/18:0) and a remarkable loss of signal for the potassium adduct of the most abundant phosphocholine molecular species 16:0/18:1 (PC) with a corresponding increase in the sodium adduct ion. This change in PC alkali attachment ion was suggested to be a result of edema and influx of extracellular fluid likely through a loss of Na/K-ATPase caused by the injury. These studies reveal the value of MALDI IMS to examine tissues for changes in lipid biochemistry and will provide data needed to eventually understand the biochemical mechanisms relevant to tissue injury.

  5. Metabolic Profiling Directly from the Petri Dish Using Nanospray Desorption Electrospray Ionization Imaging Mass Spectrometry

    SciTech Connect

    Watrous, Jeramie D.; Roach, Patrick J.; Heath, Brandi S.; Alexandrov, Theodore; Laskin, Julia; Dorrestein, Pieter C.

    2013-11-05

    Understanding molecular interaction pathways in complex biological systems constitutes a treasure trove of knowledge that might facilitate the specific, chemical manipulation of the countless microbiological systems that occur throughout our world. However, there is a lack of methodologies that allow the direct investigation of chemical gradients and interactions in living biological systems, in real time. Here, we report the use of nanospray desorption electrospray ionization (nanoDESI) imaging mass spectrometry for in vivo metabolic profiling of living bacterial colonies directly from the Petri dish with absolutely no sample preparation needed. Using this technique, we investigated single colonies of Shewanella oneidensis MR-1, Bacillus subtilis 3610, and Streptomyces coelicolor A3(2) as well as a mixed biofilm of S. oneidensis MR-1 and B. subtilis 3610. Data from B. subtilis 3610 and S. coelicolor A3(2) provided a means of validation for the method while data from S. oneidensis MR-1 and the mixed biofilm showed a wide range of compounds that this bacterium uses for the dissimilatory reduction of extracellular metal oxides, including riboflavin, iron-bound heme and heme biosynthetic intermediates, and the siderophore putrebactin.

  6. Imaging mass spectrometry for the precise design of antibody-drug conjugates.

    PubMed

    Fujiwara, Yuki; Furuta, Masaru; Manabe, Shino; Koga, Yoshikatsu; Yasunaga, Masahiro; Matsumura, Yasuhiro

    2016-01-01

    Antibody-drug conjugates (ADCs) are a class of immunotherapeutic agents that enable the delivery of cytotoxic drugs to target malignant cells. Because various cancers and tumour vascular endothelia strongly express anti-human tissue factor (TF), we prepared ADCs consisting of a TF-specific monoclonal antibody (mAb) linked to the anticancer agent (ACA) monomethyl auristatin E (MMAE) via a valine-citrulline (Val-Cit) linker (human TF ADC). Identifying the most efficient drug design in advance is difficult because ADCs have complicated structures. The best method of assessing ADCs is to examine their selectivity and efficiency in releasing and distributing the ACA within tumour tissue. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) can be used to directly detect the distributions of native molecules within tumour tissues. Here, MALDI-IMS enabled the identification of the intratumour distribution of MMAE released from the ADC. In conclusion, MALDI-IMS is a useful tool to assess ADCs and facilitate the optimization of ADC design. PMID:27098163

  7. Imaging Mass Spectrometry for Assessing Cutaneous Wound Healing: Analysis of Pressure Ulcers

    PubMed Central

    2015-01-01

    Imaging mass spectrometry (IMS) was employed for the analysis of frozen skin biopsies to investigate the differences between stage IV pressure ulcers that remain stalled, stagnant, and unhealed versus those exhibiting clinical and histological signs of improvement. Our data reveal a rich diversity of proteins that are dynamically modulated, and we selectively highlight a family of calcium binding proteins (S-100 molecules) including calcyclin (S100-A6), calgranulins A (S100-A8) and B (S100-A9), and calgizzarin (S100-A11). IMS allowed us to target three discrete regions of interest: the wound bed, adjacent dermis, and hypertrophic epidermis. Plots derived using unsupervised principal component analysis of the global protein signatures within these three spatial niches indicate that these data from wound signatures have potential as a prognostic tool since they appear to delineate wounds that are favorably responding to therapeutic interventions versus those that remain stagnant or intractable in their healing status. Our discovery-based approach with IMS augments current knowledge of the molecular signatures within pressure ulcers while providing a rationale for a focused examination of the role of calcium modulators within the context of impaired wound healing. PMID:25488653

  8. Application of imaging mass spectrometry for the molecular diagnosis of human breast tumors.

    PubMed

    Mao, Xinxin; He, Jiuming; Li, Tiegang; Lu, Zhaohui; Sun, Jian; Meng, Yunxiao; Abliz, Zeper; Chen, Jie

    2016-01-01

    Distinguishing breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS) is a key step in breast surgery, especially to determine whether DCIS is associated with tumor cell micro-invasion. However, there is currently no reliable method to obtain molecular information for breast tumor analysis during surgery. Here, we present a novel air flow-assisted ionization (AFAI) mass spectrometry imaging method that can be used in ambient environments to differentiate breast cancer by analyzing lipids. In this study, we demonstrate that various subtypes and histological grades of IDC and DCIS can be discriminated using AFAI-MSI: phospholipids were more abundant in IDC than in DCIS, whereas fatty acids were more abundant in DCIS than in IDC. The classification of specimens in the subtype and grade validation sets showed 100% and 78.6% agreement with the histopathological diagnosis, respectively. Our work shows the rapid classification of breast cancer utilizing AFAI-MSI. This work suggests that this method could be developed to provide surgeons with nearly real-time information to guide surgical resections. PMID:26868906

  9. Automated MALDI Matrix Coating System for Multiple Tissue Samples for Imaging Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Mounfield, William P.; Garrett, Timothy J.

    2012-03-01

    Uniform matrix deposition on tissue samples for matrix-assisted laser desorption/ionization (MALDI) is key for reproducible analyte ion signals. Current methods often result in nonhomogenous matrix deposition, and take time and effort to produce acceptable ion signals. Here we describe a fully-automated method for matrix deposition using an enclosed spray chamber and spray nozzle for matrix solution delivery. A commercial air-atomizing spray nozzle was modified and combined with solenoid controlled valves and a Programmable Logic Controller (PLC) to control and deliver the matrix solution. A spray chamber was employed to contain the nozzle, sample, and atomized matrix solution stream, and to prevent any interference from outside conditions as well as allow complete control of the sample environment. A gravity cup was filled with MALDI matrix solutions, including DHB in chloroform/methanol (50:50) at concentrations up to 60 mg/mL. Various samples (including rat brain tissue sections) were prepared using two deposition methods (spray chamber, inkjet). A linear ion trap equipped with an intermediate-pressure MALDI source was used for analyses. Optical microscopic examination showed a uniform coating of matrix crystals across the sample. Overall, the mass spectral images gathered from tissues coated using the spray chamber system were of better quality and more reproducible than from tissue specimens prepared by the inkjet deposition method.

  10. MALDI mass spectrometry imaging analysis of pituitary adenomas for near-real-time tumor delineation.

    PubMed

    Calligaris, David; Feldman, Daniel R; Norton, Isaiah; Olubiyi, Olutayo; Changelian, Armen N; Machaidze, Revaz; Vestal, Matthew L; Laws, Edward R; Dunn, Ian F; Santagata, Sandro; Agar, Nathalie Y R

    2015-08-11

    We present a proof of concept study designed to support the clinical development of mass spectrometry imaging (MSI) for the detection of pituitary tumors during surgery. We analyzed by matrix-assisted laser desorption/ionization (MALDI) MSI six nonpathological (NP) human pituitary glands and 45 hormone secreting and nonsecreting (NS) human pituitary adenomas. We show that the distribution of pituitary hormones such as prolactin (PRL), growth hormone (GH), adrenocorticotropic hormone (ACTH), and thyroid stimulating hormone (TSH) in both normal and tumor tissues can be assessed by using this approach. The presence of most of the pituitary hormones was confirmed by using MS/MS and pseudo-MS/MS methods, and subtyping of pituitary adenomas was performed by using principal component analysis (PCA) and support vector machine (SVM). Our proof of concept study demonstrates that MALDI MSI could be used to directly detect excessive hormonal production from functional pituitary adenomas and generally classify pituitary adenomas by using statistical and machine learning analyses. The tissue characterization can be completed in fewer than 30 min and could therefore be applied for the near-real-time detection and delineation of pituitary tumors for intraoperative surgical decision-making. PMID:26216958

  11. Histology-directed and imaging mass spectrometry: an emerging technology in ectopic calcification

    PubMed Central

    De Santis, Giorgio; Caprioli, Richard M; Quaglino, Daniela

    2015-01-01

    The present study was designed to demonstrate the potential of an optimized histology directed protein identification combined with imaging mass spectrometry technology to reveal and identify molecules associated to ectopic calcification in human tissue. As a proof of concept, mineralized and non-mineralized areas were compared within the same dermal tissue obtained from a patient affected by Pseudoxanthoma elasticum, a genetic disorder characterized by calcification only at specific sites of soft connective tissues. Data have been technically validated on a contralateral dermal tissue from the same subject and compared with those from control healthy skin. Results demonstrate that this approach 1) significantly reduces the effects generated by techniques that, disrupting tissue organization, blend data from affected and unaffected areas; 2) demonstrates that, abolishing differences due to inter-individual variability, mineralized and non-mineralized areas within the same sample have a specific protein profile and have a different distribution of molecules; 3) avoiding the bias of focusing on already known molecules, reveals a number of proteins that have been never related to the disease nor to the calcification process, thus paving the way for the selection of new molecules to be validated as pathogenic or as potential pharmacological targets. PMID:25595835

  12. Metabolic profiling directly from the Petri dish using nanospray desorption electrospray ionization imaging mass spectrometry.

    PubMed

    Watrous, Jeramie; Roach, Patrick; Heath, Brandi; Alexandrov, Theodore; Laskin, Julia; Dorrestein, Pieter C

    2013-11-01

    Understanding molecular interaction pathways in complex biological systems constitutes a treasure trove of knowledge that might facilitate the specific, chemical manipulation of the countless microbiological systems that occur throughout our world. However, there is a lack of methodologies that allow the direct investigation of chemical gradients and interactions in living biological systems, in real time. Here, we report the use of nanospray desorption electrospray ionization (nanoDESI) imaging mass spectrometry for in vivo metabolic profiling of living bacterial colonies directly from the Petri dish with absolutely no sample preparation needed. Using this technique, we investigated single colonies of Shewanella oneidensis MR-1, Bacillus subtilis 3610, and Streptomyces coelicolor A3(2) as well as a mixed biofilm of S. oneidensis MR-1 and B. subtilis 3610. Data from B. subtilis 3610 and S. coelicolor A3(2) provided a means of validation for the method while data from S. oneidensis MR-1 and the mixed biofilm showed a wide range of compounds that this bacterium uses for the dissimilatory reduction of extracellular metal oxides, including riboflavin, iron-bound heme and heme biosynthetic intermediates, and the siderophore putrebactin. PMID:24047514

  13. Dual-Modal Magnetic Resonance/Fluorescent Zinc Probes for Pancreatic β-Cell Mass Imaging

    PubMed Central

    Stasiuk, Graeme J; Minuzzi, Florencia; Sae-Heng, Myra; Rivas, Charlotte; Juretschke, Hans-Paul; Piemonti, Lorenzo; Allegrini, Peter R; Laurent, Didier; Duckworth, Andrew R; Beeby, Andrew; Rutter, Guy A; Long, Nicholas J

    2015-01-01

    Despite the contribution of changes in pancreatic β-cell mass to the development of all forms of diabetes mellitus, few robust approaches currently exist to monitor these changes prospectively in vivo. Although magnetic-resonance imaging (MRI) provides a potentially useful technique, targeting MRI-active probes to the β cell has proved challenging. Zinc ions are highly concentrated in the secretory granule, but they are relatively less abundant in the exocrine pancreas and in other tissues. We have therefore developed functional dual-modal probes based on transition-metal chelates capable of binding zinc. The first of these, Gd⋅1, binds ZnII directly by means of an amidoquinoline moiety (AQA), thus causing a large ratiometric Stokes shift in the fluorescence from λem=410 to 500 nm with an increase in relaxivity from r1=4.2 up to 4.9 mM−1 s−1. The probe is efficiently accumulated into secretory granules in β-cell-derived lines and isolated islets, but more poorly by non-endocrine cells, and leads to a reduction in T1 in human islets. In vivo murine studies of Gd⋅1 have shown accumulation of the probe in the pancreas with increased signal intensity over 140 minutes. PMID:25736590

  14. High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

    NASA Astrophysics Data System (ADS)

    Anderson, David M. G.; Spraggins, Jeffrey M.; Rose, Kristie L.; Schey, Kevin L.

    2015-06-01

    The human optic nerve carries signals from the retina to the visual cortex of the brain. Each optic nerve is comprised of approximately one million nerve fibers that are organized into bundles of 800-1200 fibers surrounded by connective tissue and supportive glial cells. Damage to the optic nerve contributes to a number of blinding diseases including: glaucoma, neuromyelitis optica, optic neuritis, and neurofibromatosis; however, the molecular mechanisms of optic nerve damage and death are incompletely understood. Herein we present high spatial resolution MALDI imaging mass spectrometry (IMS) analysis of lipids and proteins to define the molecular anatomy of the human optic nerve. The localization of a number of lipids was observed in discrete anatomical regions corresponding to myelinated and unmyelinated nerve regions as well as to supporting connective tissue, glial cells, and blood vessels. A protein fragment from vimentin, a known intermediate filament marker for astrocytes, was observed surrounding nerved fiber bundles in the lamina cribrosa region. S100B was also found in supporting glial cell regions in the prelaminar region, and the hemoglobin alpha subunit was observed in blood vessel areas. The molecular anatomy of the optic nerve defined by MALDI IMS provides a firm foundation to study biochemical changes in blinding human diseases.

  15. On-tissue localization of ceramides and other sphingolipids by MALDI mass spectrometry imaging.

    PubMed

    Jones, E Ellen; Dworski, Shaalee; Canals, Daniel; Casas, Josefina; Fabrias, Gemma; Schoenling, Drew; Levade, Thierry; Denlinger, Chadrick; Hannun, Yusuf A; Medin, Jeffrey A; Drake, Richard R

    2014-08-19

    A novel MALDI-FTICR imaging mass spectrometry (MALDI-IMS) workflow is described for on-tissue detection, spatial localization, and structural confirmation of low abundance bioactive ceramides and other sphingolipids. Increasingly, altered or elevated levels of sphingolipids, sphingolipid metabolites, and sphingolipid metabolizing enzymes have been associated with a variety of disorders such as diabetes, obesity, lysosomal storage disorders, and cancer. Ceramide, which serves as a metabolic hub in sphingolipid metabolism, has been linked to cancer signaling pathways and to metabolic regulation with involvement in autophagy, cell-cycle arrest, senescence, and apoptosis. Using kidney tissues from a new Farber disease mouse model in which ceramides of all acyl chain lengths and other sphingolipid metabolites accumulate in tissues, specific ceramides and sphingomyelins were identified by on-tissue isolation and fragmentation, coupled with an on-tissue digestion by ceramidase or sphingomyelinase. Multiple glycosphingolipid species were also detected. The newly generated library of sphingolipid ions was then applied to MALDI-IMS of human lung cancer tissues. Multiple tumor specific ceramide and sphingomyelin species were detected and confirmed by on-tissue enzyme digests and structural confirmation. High-resolution MALDI-IMS in combination with novel on-tissue ceramidase and sphingomyelinase enzyme digestions makes it now possible to rapidly visualize the distribution of bioactive ceramides and sphingomyelin in tissues. PMID:25072097

  16. On-Tissue Localization of Ceramides and Other Sphingolipids by MALDI Mass Spectrometry Imaging

    PubMed Central

    2015-01-01

    A novel MALDI-FTICR imaging mass spectrometry (MALDI-IMS) workflow is described for on-tissue detection, spatial localization, and structural confirmation of low abundance bioactive ceramides and other sphingolipids. Increasingly, altered or elevated levels of sphingolipids, sphingolipid metabolites, and sphingolipid metabolizing enzymes have been associated with a variety of disorders such as diabetes, obesity, lysosomal storage disorders, and cancer. Ceramide, which serves as a metabolic hub in sphingolipid metabolism, has been linked to cancer signaling pathways and to metabolic regulation with involvement in autophagy, cell-cycle arrest, senescence, and apoptosis. Using kidney tissues from a new Farber disease mouse model in which ceramides of all acyl chain lengths and other sphingolipid metabolites accumulate in tissues, specific ceramides and sphingomyelins were identified by on-tissue isolation and fragmentation, coupled with an on-tissue digestion by ceramidase or sphingomyelinase. Multiple glycosphingolipid species were also detected. The newly generated library of sphingolipid ions was then applied to MALDI-IMS of human lung cancer tissues. Multiple tumor specific ceramide and sphingomyelin species were detected and confirmed by on-tissue enzyme digests and structural confirmation. High-resolution MALDI-IMS in combination with novel on-tissue ceramidase and sphingomyelinase enzyme digestions makes it now possible to rapidly visualize the distribution of bioactive ceramides and sphingomyelin in tissues. PMID:25072097

  17. Laser ablation inductively coupled plasma mass spectrometry imaging of metals in experimental and clinical Wilson's disease

    PubMed Central

    Boaru, Sorina Georgiana; Merle, Uta; Uerlings, Ricarda; Zimmermann, Astrid; Flechtenmacher, Christa; Willheim, Claudia; Eder, Elisabeth; Ferenci, Peter; Stremmel, Wolfgang; Weiskirchen, Ralf

    2015-01-01

    Wilson's disease is an autosomal recessive disorder in which the liver does not properly release copper into bile, resulting in prominent copper accumulation in various tissues. Affected patients suffer from hepatic disorders and severe neurological defects. Experimental studies in mutant mice in which the copper-transporting ATPase gene (Atp7b) is disrupted revealed a drastic, time-dependent accumulation of hepatic copper that is accompanied by formation of regenerative nodes resembling cirrhosis. Therefore, these mice represent an excellent exploratory model for Wilson's disease. However, the precise time course in hepatic copper accumulation and its impact on other trace metals within the liver is yet poorly understood. We have recently established novel laser ablation inductively coupled plasma mass spectrometry protocols allowing quantitative metal imaging in human and murine liver tissue with high sensitivity, spatial resolution, specificity and quantification ability. By use of these techniques, we here aimed to comparatively analyse hepatic metal content in wild-type and Atp7b deficient mice during ageing. We demonstrate that the age-dependent accumulation of hepatic copper is strictly associated with a simultaneous increase in iron and zinc, while the intrahepatic concentration and distribution of other metals or metalloids is not affected. The same findings were obtained in well-defined human liver samples that were obtained from patients suffering from Wilson's disease. We conclude that in Wilson's disease the imbalances of hepatic copper during ageing are closely correlated with alterations in intrahepatic iron and zinc content. PMID:25704483

  18. High-grade sarcoma diagnosis and prognosis: Biomarker discovery by mass spectrometry imaging.

    PubMed

    Lou, Sha; Balluff, Benjamin; de Graaff, Marieke A; Cleven, Arjen H G; Briaire-de Bruijn, Inge; Bovée, Judith V M G; McDonnell, Liam A

    2016-06-01

    The combination of high heterogeneity, both intratumoral and intertumoral, with their rarity has made diagnosis, prognosis of high-grade sarcomas difficult. There is an urgent need for more objective molecular biomarkers, to differentiate between the many different subtypes, and to also provide new treatment targets. Mass spectrometry imaging (MSI) has amply demonstrated its ability to identify potential new markers for patient diagnosis, survival, metastasis and response to therapy in cancer research. In this study, we investigated the ability of MALDI-MSI of proteins to distinguish between high-grade osteosarcoma (OS), leiomyosarcoma (LMS), myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS) (Ntotal = 53). We also investigated if there are individual proteins or protein signatures that are statistically associated with patient survival. Twenty diagnostic protein signals were found characteristic for specific tumors (p ≤ 0.05), amongst them acyl-CoA-binding protein (m/z 11 162), macrophage migration inhibitory factor (m/z 12 350), thioredoxin (m/z 11 608) and galectin-1 (m/z 14 633) were assigned. Another nine protein signals were found to be associated with overall survival (p ≤ 0.05), including proteasome activator complex subunit 1 (m/z 9753), indicative for non-OS patients with poor survival; and two histone H4 variants (m/z 11 314 and 11 355), indicative of poor survival for LMS patients. PMID:27174013

  19. Toward Direct Imaging of Low-mass Gas-Giant Planets with the James Webb Space Telescope

    NASA Astrophysics Data System (ADS)

    Schlieder, J. E.; Beichman, C. A.; Meyer, M. R.; Greene, T.

    2016-01-01

    In preparation for observations with the James Webb Space Telescope (JWST), we have identified new members of the nearby, young M dwarf sample and compiled an up to date list of these stars. Here we summarize our efforts to identify young M dwarfs, describe the current sample, and detail its demographics in the context of direct planet imaging. We also describe our investigations of the unprecedented sensitivity of the JWST when imaging nearby, young M dwarfs. The JWST is the only near term facility capable of routinely pushing direct imaging capabilities around M dwarfs to sub-Jovian masses and will provide key insight into questions regarding low-mass gas-giant properties, frequency, formation, and architectures.

  20. Submicron mass spectrometry imaging of single cells by combined use of mega electron volt time-of-flight secondary ion mass spectrometry and scanning transmission ion microscopy

    SciTech Connect

    Siketić, Zdravko; Bogdanović Radović, Ivančica; Jakšić, Milko; Popović Hadžija, Marijana; Hadžija, Mirko

    2015-08-31

    In order to better understand biochemical processes inside an individual cell, it is important to measure the molecular composition at the submicron level. One of the promising mass spectrometry imaging techniques that may be used to accomplish this is Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS), using MeV energy heavy ions for excitation. MeV ions have the ability to desorb large intact molecules with a yield that is several orders of magnitude higher than conventional SIMS using keV ions. In order to increase the spatial resolution of the MeV TOF-SIMS system, we propose an independent TOF trigger using a STIM (scanning transmission ion microscopy) detector that is placed just behind the thin transmission target. This arrangement is suitable for biological samples in which the STIM detector simultaneously measures the mass distribution in scanned samples. The capability of the MeV TOF-SIMS setup was demonstrated by imaging the chemical composition of CaCo-2 cells.

  1. Scanning mass spectrometry probe: a scanning probe electrospray ion source for imaging mass spectrometry of submerged interfaces and transient events in solution.

    PubMed

    Kottke, Peter A; Degertekin, F Levent; Fedorov, Andrei G

    2010-01-01

    The scanning mass spectrometry (SMS) probe is a new electrospray ion source. Motivated by the need for untargeted chemical imaging of dynamic events in solution, we have exploited an approach to electrospray ionization (ESI) that allows continuous sampling from a highly localized volume (approximately picoliters) in a liquid environment, softly ionizes molecules in the sample to render them amenable for mass spectrometric analysis, and sends the ions to the mass spectrometer. The key underlying concepts for our approach are (1) treating the electrospray capillary inlet as a chemical scanning probe and (2) locating the electrospray point as close as possible to the sampling point, thus providing the shortest response time possible. This approach enables chemical monitoring or imaging of submerged interfaces, providing access to details of spatial heterogeneity and temporal changes within liquid samples. It also permits direct access to liquid/ liquid interfaces for ESI-MS analysis. In this letter we report the first demonstrations of these capabilities of the SMS probe and describe some of the probe's basic characteristics. PMID:19904914

  2. MALDI Imaging Mass Spectrometry Spatially Maps Age-Related Deamidation and Truncation of Human Lens Aquaporin-0

    PubMed Central

    Wenke, Jamie L.; Rose, Kristie L.; Spraggins, Jeffrey M.; Schey, Kevin L.

    2015-01-01

    Purpose To spatially map human lens Aquaporin-0 (AQP0) protein modifications, including lipidation, truncation, and deamidation, from birth through middle age using matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS). Methods Human lens sections were water-washed to facilitate detection of membrane protein AQP0. We acquired MALDI images from eight human lenses ranging in age from 2 months to 63 years. In situ tryptic digestion was used to generate peptides of AQP0 and peptide images were acquired on a 15T Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Peptide extracts were analyzed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) and database searched to identify peptides observed in MALDI imaging experiments. Results Unmodified, truncated, and fatty acid–acylated forms of AQP0 were detected in protein imaging experiments. Full-length AQP0 was fatty acid acylated in the core and cortex of young (2- and 4-month) lenses. Acylated and unmodified AQP0 were C-terminally truncated in older lens cores. Deamidated tryptic peptides (+0.9847 Da) were mass resolved from unmodified peptides by FTICR MS. Peptide images revealed differential localization of un-, singly-, and doubly-deamidated AQP0 C-terminal peptide (239–263). Deamidation was present at 4 months and increases with age. Liquid chromatography–MS/MS results indicated N246 undergoes deamidation more rapidly than N259. Conclusions Results indicated AQP0 fatty acid acylation and deamidation occur during early development. Progressive age-related AQP0 processing, including deamidation and truncation, was mapped in human lenses as a function of age. The localization of these modified AQP0 forms suggests where AQP0 functions may change throughout lens development and aging. PMID:26574799

  3. Improving the Accuracy of Computer-aided Diagnosis for Breast MR Imaging by Differentiating between Mass and Nonmass Lesions.

    PubMed

    Gallego-Ortiz, Cristina; Martel, Anne L

    2016-03-01

    Purpose To determine suitable features and optimal classifier design for a computer-aided diagnosis (CAD) system to differentiate among mass and nonmass enhancements during dynamic contrast material-enhanced magnetic resonance (MR) imaging of the breast. Materials and Methods Two hundred eighty histologically proved mass lesions and 129 histologically proved nonmass lesions from MR imaging studies were retrospectively collected. The institutional research ethics board approved this study and waived informed consent. Breast Imaging Reporting and Data System classification of mass and nonmass enhancement was obtained from radiologic reports. Image data from dynamic contrast-enhanced MR imaging were extracted and analyzed by using feature selection techniques and binary, multiclass, and cascade classifiers. Performance was assessed by measuring the area under the receiver operating characteristics curve (AUC), sensitivity, and specificity. Bootstrap cross validation was used to predict the best classifier for the classification task of mass and nonmass benign and malignant breast lesions. Results A total of 176 features were extracted. Feature relevance ranking indicated unequal importance of kinetic, texture, and morphologic features for mass and nonmass lesions. The best classifier performance was a two-stage cascade classifier (mass vs nonmass followed by malignant vs benign classification) (AUC, 0.91; 95% confidence interval (CI): 0.88, 0.94) compared with one-shot classifier (ie, all benign vs malignant classification) (AUC, 0.89; 95% CI: 0.85, 0.92). The AUC was 2% higher for cascade (median percent difference obtained by using paired bootstrapped samples) and was significant (P = .0027). Our proposed two-stage cascade classifier decreases the overall misclassification rate by 12%, with 72 of 409 missed diagnoses with cascade versus 82 of 409 missed diagnoses with one-shot classifier. Conclusion Separately optimizing feature selection and training classifiers

  4. The mass distribution of CL0939+4713 obtained from a `weak' lensing analysis of a WFPC2 image.

    NASA Astrophysics Data System (ADS)

    Seitz, C.; Kneib, J.-P.; Schneider, P.; Seitz, S.

    1996-10-01

    The image distortions of high-redshift galaxies caused by gravitational light deflection of foreground clusters of galaxies can be used to reconstruct the two-dimensional surface mass density of these clusters. We apply an unbiased parameter-free reconstruction technique to the cluster CL0939+4713 (Abell 851), observed with the WFPC2 on board of the HST. We demonstrate that a single deep WFPC2 observation can be used for cluster mass reconstruction despite its small field of view and the irregular shape of the data field (especially for distant clusters). For CL0939, we find a strong correlation between the reconstructed mass distribution and the bright cluster galaxies indicating that mass follows light on average. The detected anti-correlation between the faint galaxies and the reconstructed mass is most likely an effect of the magnification (anti) bias, which was detected previously in the cluster A1689. Because of the high redshift of CL0939 (z_d_=0.41), the redshift distribution of the lensed, faint galaxies has to be accounted for in the reconstruction technique. We derive an approximate global transformation for the surface mass density which leaves the mean image ellipticities invariant, resulting in an uncertainty in the normalization of the mass. From the non-negativity of the surface mass density, we derive lower limits on the mass inside the observed field of 0.75(h^-1^_50_Mpc)^2^ ranging from M>3.6x10^14^h^-1^_50_Msun_ to M>6.3x10^14^h^-1^_50_Msun_ for a mean redshift of to of the faint galaxy images with R{in}(23,25.5). However, we can break the invariance transformation for the mass using the magnification effect on the observed number density of the background galaxies. Assuming a mean redshift of and a fraction of x=15% (x=20%) of cluster galaxies in the observed galaxy sample with R{in}(23,25.5) we obtain for the mass inside the field M=~5x10^14^h^-1^_50_Msun_ (M=~7x10^14^h^-1^_50_Msun_) which corresponds to M/L=~100 h_50

  5. Determination of pharmaceutical compounds in skin by imaging matrix-assisted laser desorption/ionisation mass spectrometry.

    PubMed

    Bunch, Josephine; Clench, Malcolm R; Richards, Don S

    2004-01-01

    Matrix-assisted laser desorption/ionisation (MALDI) quadrupole time-of-flight mass spectrometry (Q-TOFMS) has been used to detect and image the distribution of a xenobiotic substance in skin. Porcine epidermal tissue was treated with 'Nizoral', a medicated shampoo containing ketoconazole (+/-)-1-acetyl-4-[p-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) as active ingredient. Following incubation for 1 h at 37 degrees C all excess formulation was washed from the surface. A cross-section of the drug-treated tissue was then blotted onto a cellulose membrane, precoated in matrix (alpha-cyano-4-hydroxycinnamic acid (CHCA)), by airspray deposition. In separate experiments the tissue surface was treated with Nizoral within a triangular former, and subsequently blotted onto a matrix-coated membrane. Sample membranes were then mounted into the recess of specialised MALDI targets with adhesive tape. All samples were analysed by MALDI-TOFMS using an Applied Biosystem 'Q-star Pulsar i' hybrid Q-TOF mass spectrometer fitted with an orthagonal MALDI ion source and imaging software. Detection of the protonated molecule was readily achievable by this technique. Treatment of the tissue within a template gave rise to images depicting the expected distribution of the drug, demonstrating that this technique is capable of producing spatially useful data. Ion images demonstrating the permeation of the applied compound into the skin were achieved by imaging a cross-sectional imprint of treated tissue. A calibration graph for the determination of ketoconazole was prepared using the sodium adduct of the matrix ion as an internal standard. This enabled construction of a quantitative profile of drug in skin. Conventional haematoxylin and eosin staining and microscopy methods were employed to obtain a histological image of the porcine epidermal tissue. Superimposing the mass spectrometric and histological images appeared to indicate drug

  6. Associations between Chinese/Asian versus Western mass media influences and body image disturbances of young Chinese women.

    PubMed

    Jackson, Todd; Jiang, Chengcheng; Chen, Hong

    2016-06-01

    In this study, we evaluated associations of experiences with mass media imported from Western nations such as the United States versus mass media from China and other Asian countries with eating and body image disturbances of young Chinese women. Participating women (N=456) completed self-report measures of disordered eating, specific sources of appearance dissatisfaction (fatness, facial features, stature), and Western versus Chinese/Asian mass media influences. The sample was significantly more likely to report perceived pressure from, comparisons with, and preferences for physical appearance depictions in Chinese/Asian mass media than Western media. Chinese/Asian media influences also combined for more unique variance in prediction models for all disturbances except stature concerns. While experiences with Western media were related to disturbances as well, the overall impact of Chinese/Asian media influences was more prominent. PMID:27110965

  7. In Situ Mass Spectrometry Imaging and Ex Vivo Characterization of Renal Crystalline Deposits Induced in Multiple Preclinical Drug Toxicology Studies

    PubMed Central

    Bjurström, Sivert; Goodwin, Richard J. A.; Basmaci, Elisa; Gustafsson, Ingela; Annas, Anita; Hellgren, Dennis; Svanhagen, Alexander; Andrén, Per E.; Lindberg, Johan

    2012-01-01

    Drug toxicity observed in animal studies during drug development accounts for the discontinuation of many drug candidates, with the kidney being a major site of tissue damage. Extensive investigations are often required to reveal the mechanisms underlying such toxicological events and in the case of crystalline deposits the chemical composition can be problematic to determine. In the present study, we have used mass spectrometry imaging combined with a set of advanced analytical techniques to characterize such crystalline deposits in situ. Two potential microsomal prostaglandin E synthase 1 inhibitors, with similar chemical structure, were administered to rats over a seven day period. This resulted in kidney damage with marked tubular degeneration/regeneration and crystal deposits within the tissue that was detected by histopathology. Results from direct tissue section analysis by matrix-assisted laser desorption ionization mass spectrometry imaging were combined with data obtained following manual crystal dissection analyzed by liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy. The chemical composition of the crystal deposits was successfully identified as a common metabolite, bisulphonamide, of the two drug candidates. In addition, an un-targeted analysis revealed molecular changes in the kidney that were specifically associated with the area of the tissue defined as pathologically damaged. In the presented study, we show the usefulness of combining mass spectrometry imaging with an array of powerful analytical tools to solve complex toxicological problems occurring during drug development. PMID:23110069

  8. Secondary Ion Mass Spectrometry Imaging of Molecular Distributions in Cultured Neurons and their Processes: Comparative Analysis of Sample Preparation

    PubMed Central

    Tucker, Kevin R.; Li, Zhen; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2012-01-01

    Neurons often exhibit a complex chemical distribution and topography; therefore, sample preparation protocols that preserve structures ranging from relatively large cell somata to small neurites and growth cones are an important factor in secondary ion mass spectrometry (SIMS) imaging studies. Here, SIMS was used to investigate the subcellular localization of lipids and lipophilic species in neurons from Aplysia californica. Using individual neurons cultured on silicon wafers, we compared and optimized several SIMS sampling approaches. After an initial step to remove the high salt culturing media, formaldehyde, paraformaldehyde and glycerol, and various combinations thereof, were tested for their ability to achieve cell stabilization during and after the removal of extracellular media. These treatments improved the preservation of cellular morphology as visualized with SIMS imaging. For analytes >250 Da, coating the cell surface with a 3.2 nm-thick gold layer increased the ion intensity; multiple analytes previously not observed or observed at low abundance were detected, including intact cholesterol and vitamin E molecular ions. However, once a sample was coated, many of the lower molecular mass (<200 Da) analyte signals were suppressed. The optimum approach depended on the analyte being studied, and these approaches included rinsing with water and cell stabilization with glycerol and 4% paraformaldehyde. The sample preparation methods described here enhance SIMS imaging of processes of individual cultured neurons over a broad mass range with enhanced image contrast. PMID:22930440

  9. Secondary ion mass spectrometry imaging of molecular distributions in cultured neurons and their processes: comparative analysis of sample preparation.

    PubMed

    Tucker, Kevin R; Li, Zhen; Rubakhin, Stanislav S; Sweedler, Jonathan V

    2012-11-01

    Neurons often exhibit a complex chemical distribution and topography; therefore, sample preparation protocols that preserve structures ranging from relatively large cell somata to small neurites and growth cones are important factors in secondary ion mass spectrometry (SIMS) imaging studies. Here, SIMS was used to investigate the subcellular localization of lipids and lipophilic species in neurons from Aplysia californica. Using individual neurons cultured on silicon wafers, we compared and optimized several SIMS sampling approaches. After an initial step to remove the high salt culturing media, formaldehyde, paraformaldehyde, and glycerol, and various combinations thereof, were tested for their ability to achieve cell stabilization during and after the removal of extracellular media. These treatments improved the preservation of cellular morphology as visualized with SIMS imaging. For analytes >250 Da, coating the cell surface with a 3.2 nm-thick gold layer increased the ion intensity; multiple analytes previously not observed or observed at low abundance were detected, including intact cholesterol and vitamin E molecular ions. However, once a sample was coated, many of the lower molecular mass (<200 Da) analyte signals were suppressed. The optimum approach depended on the analyte being studied; the approaches evaluated included rinsing with water and cell stabilization with glycerol and 4 % paraformaldehyde. The sample preparation methods described here enhance SIMS imaging of processes of individual cultured neurons over a broad mass range with enhanced image contrast. PMID:22930440

  10. Secondary Ion Mass Spectrometry Imaging of Molecular Distributions in Cultured Neurons and Their Processes: Comparative Analysis of Sample Preparation

    NASA Astrophysics Data System (ADS)

    Tucker, Kevin R.; Li, Zhen; Rubakhin, Stanislav S.; Sweedler, Jonathan V.

    2012-11-01

    Neurons often exhibit a complex chemical distribution and topography; therefore, sample preparation protocols that preserve structures ranging from relatively large cell somata to small neurites and growth cones are important factors in secondary ion mass spectrometry (SIMS) imaging studies. Here, SIMS was used to investigate the subcellular localization of lipids and lipophilic species in neurons from Aplysia californica. Using individual neurons cultured on silicon wafers, we compared and optimized several SIMS sampling approaches. After an initial step to remove the high salt culturing media, formaldehyde, paraformaldehyde, and glycerol, and various combinations thereof, were tested for their ability to achieve cell stabilization during and after the removal of extracellular media. These treatments improved the preservation of cellular morphology as visualized with SIMS imaging. For analytes >250 Da, coating the cell surface with a 3.2 nm-thick gold layer increased the ion intensity; multiple analytes previously not observed or observed at low abundance were detected, including intact cholesterol and vitamin E molecular ions. However, once a sample was coated, many of the lower molecular mass (<200 Da) analyte signals were suppressed. The optimum approach depended on the analyte being studied; the approaches evaluated included rinsing with water and cell stabilization with glycerol and 4 % paraformaldehyde. The sample preparation methods described here enhance SIMS imaging of processes of individual cultured neurons over a broad mass range with enhanced image contrast.

  11. Topographical and Chemical Imaging of a Phase Separated Polymer Using a Combined Atomic Force Microscopy/Infrared Spectroscopy/Mass Spectrometry Platform

    DOE PAGESBeta

    Tai, Tamin; Karácsony, Orsolya; Bocharova, Vera; Van Berkel, Gary J.; Kertesz, Vilmos

    2016-02-18

    This article describes how the use of a hybrid atomic force microscopy/infrared spectroscopy/mass spectrometry imaging platform was demonstrated for the acquisition and correlation of nanoscale sample surface topography and chemical images based on infrared spectroscopy and mass spectrometry.

  12. A solar type II radio burst from coronal mass ejection-coronal ray interaction: Simultaneous radio and extreme ultraviolet imaging

    SciTech Connect

    Chen, Yao; Du, Guohui; Feng, Shiwei; Kong, Xiangliang; Wang, Bing; Feng, Li; Guo, Fan; Li, Gang

    2014-05-20

    Simultaneous radio and extreme ultraviolet (EUV)/white-light imaging data are examined for a solar type II radio burst occurring on 2010 March 18 to deduce its source location. Using a bow-shock model, we reconstruct the three-dimensional EUV wave front (presumably the type-II-emitting shock) based on the imaging data of the two Solar TErrestrial RElations Observatory spacecraft. It is then combined with the Nançay radio imaging data to infer the three-dimensional position of the type II source. It is found that the type II source coincides with the interface between the coronal mass ejection (CME) EUV wave front and a nearby coronal ray structure, providing evidence that the type II emission is physically related to the CME-ray interaction. This result, consistent with those of previous studies, is based on simultaneous radio and EUV imaging data for the first time.

  13. The LEECH Exoplanet Imaging Survey: Orbit and Component Masses of the Intermediate-age, Late-type Binary NO UMa

    NASA Astrophysics Data System (ADS)

    Schlieder, Joshua E.; Skemer, Andrew J.; Maire, Anne-Lise; Desidera, Silvano; Hinz, Philip; Skrutskie, Michael F.; Leisenring, Jarron; Bailey, Vanessa; Defrère, Denis; Esposito, Simone; Strassmeier, Klaus G.; Weber, Michael; Biller, Beth A.; Bonnefoy, Mickaël; Buenzli, Esther; Close, Laird M.; Crepp, Justin R.; Eisner, Josh A.; Hofmann, Karl-Heinz; Henning, Thomas; Morzinski, Katie M.; Schertl, Dieter; Weigelt, Gerd; Woodward, Charles E.

    2016-02-01

    We present high-resolution Large Binocular Telescope LBTI/LMIRcam images of the spectroscopic and astrometric binary NO UMa obtained as part of the LBT Interferometer Exozodi Exoplanet Common Hunt exoplanet imaging survey. Our H-, Ks-, and L‧-band observations resolve the system at angular separations <0.″09. The components exhibit significant orbital motion over a span of ∼7 months. We combine our imaging data with archival images, published speckle interferometry measurements, and existing spectroscopic velocity data to solve the full orbital solution and estimate component masses. The masses of the K2.0 ± 0.5 primary and K6.5 ± 0.5 secondary are 0.83 ± 0.02 M⊙ and 0.64 ± 0.02 M⊙, respectively. We also derive a system distance of d = 25.87 ± 0.02 pc and revise the Galactic kinematics of NO UMa. Our revised Galactic kinematics confirm NO UMa as a nuclear member of the ∼500 Myr old Ursa Major moving group, and it is thus a mass and age benchmark. We compare the masses of the NO UMa binary components to those predicted by five sets of stellar evolution models at the age of the Ursa Major group. We find excellent agreement between our measured masses and model predictions with little systematic scatter between the models. NO UMa joins the short list of nearby, bright, late-type binaries having known ages and fully characterized orbits. Based on data obtained with the STELLA robotic telescope in Tenerife, an AIP facility jointly operated by AIP and IAC.

  14. Accuracy of radionuclide imaging in distinguishing renal masses from normal variants

    SciTech Connect

    Older, R.A.; Korobkin, M.; Workman, J.; Cleeve, D.M.; Cleeve, L.K.; Sullivan, D.; Webster, G.D.

    1980-08-01

    To determine the accuracy of scintigraphy in distinguishing true renal masses from normal variants, 40 patients with excretory urographic findings indicating a possible, but not definite, mass lesion were studied. Scintigraphy correctly identified 17 true masses and 17 normal variants. Four false positive and two false negative results were obtained.

  15. THE M87 BLACK HOLE MASS FROM GAS-DYNAMICAL MODELS OF SPACE TELESCOPE IMAGING SPECTROGRAPH OBSERVATIONS

    SciTech Connect

    Walsh, Jonelle L.; Barth, Aaron J.; Ho, Luis C.; Sarzi, Marc

    2013-06-20

    The supermassive black hole of M87 is one of the most massive black holes known and has been the subject of several stellar and gas-dynamical mass measurements; however, the most recent revision to the stellar-dynamical black hole mass measurement is a factor of about two larger than the previous gas-dynamical determinations. Here, we apply comprehensive gas-dynamical models that include the propagation of emission-line profiles through the telescope and spectrograph optics to new Space Telescope Imaging Spectrograph observations from the Hubble Space Telescope. Unlike the previous gas-dynamical studies of M87, we map out the complete kinematic structure of the emission-line disk within {approx}40 pc from the nucleus, and find that a small amount of velocity dispersion internal to the gas disk is required to match the observed line widths. We examine a scenario in which the intrinsic velocity dispersion provides dynamical support to the disk, and determine that the inferred black hole mass increases by only 6%. Incorporating this effect into the error budget, we ultimately measure a mass of M{sub BH}= (3.5{sup +0.9}{sub -0.7}) Multiplication-Sign 10{sup 9} M{sub sun} (68% confidence). Our gas-dynamical black hole mass continues to differ from the most recent stellar-dynamical mass by a factor of two, underscoring the need for carrying out more cross-checks between the two main black hole mass measurement methods.

  16. INNER HELIOSPHERIC FLUX ROPE EVOLUTION VIA IMAGING OF CORONAL MASS EJECTIONS

    SciTech Connect

    Howard, T. A.; DeForest, C. E.

    2012-02-10

    Understanding the evolution of flux ropes in coronal mass ejections (CMEs) is of importance both to the scientific and technological communities. Scientifically their presence is critical to models describing CME launch and they likely play a role in CME evolution. Technologically they are the major contributor to severe geomagnetic storms. Using a new processing technique on the STEREO/SECCHI heliospheric imaging data, we have tracked a magnetic flux rope observed by the Wind spacecraft in December 2008 to its origins observed by coronagraphs. We thereby establish that the cavity in the classic three-part coronagraph CME is the feature that becomes the magnetic cloud. This implies that the bright material ahead of the cavity is piled-up coronal or solar wind material. We track the evolution of the cavity en-route and find that its structure transforms from concave inward (curving away from the Sun) to concave outward (toward the Sun) around 0.065 AU from the Sun. The pileup was tracked and its leading edge remained concave inward throughout its journey. Two other CMEs in January 2009 are also inspected and a similar cavity is observed in each, suggesting that they too each contained a flux rope. The results presented here are the first direct observation, through continuous tracking, associating a particular flux rope observed in situ with the same flux rope before ejection from the corona. We speculate that detailed heliospheric imagery of CMEs may lead to a means by which flux ropes can be identified remotely in the heliosphere.

  17. Future technology insight: mass spectrometry imaging as a tool in drug research and development

    PubMed Central

    Cobice, D F; Goodwin, R J A; Andren, P E; Nilsson, A; Mackay, C L; Andrew, R

    2015-01-01

    In pharmaceutical research, understanding the biodistribution, accumulation and metabolism of drugs in tissue plays a key role during drug discovery and development. In particular, information regarding pharmacokinetics, pharmacodynamics and transport properties of compounds in tissues is crucial during early screening. Historically, the abundance and distribution of drugs have been assessed by well-established techniques such as quantitative whole-body autoradiography (WBA) or tissue homogenization with LC/MS analysis. However, WBA does not distinguish active drug from its metabolites and LC/MS, while highly sensitive, does not report spatial distribution. Mass spectrometry imaging (MSI) can discriminate drug and its metabolites and endogenous compounds, while simultaneously reporting their distribution. MSI data are influencing drug development and currently used in investigational studies in areas such as compound toxicity. In in vivo studies MSI results may soon be used to support new drug regulatory applications, although clinical trial MSI data will take longer to be validated for incorporation into submissions. We review the current and future applications of MSI, focussing on applications for drug discovery and development, with examples to highlight the impact of this promising technique in early drug screening. Recent sample preparation and analysis methods that enable effective MSI, including quantitative analysis of drugs from tissue sections will be summarized and key aspects of methodological protocols to increase the effectiveness of MSI analysis for previously undetectable targets addressed. These examples highlight how MSI has become a powerful tool in drug research and development and offers great potential in streamlining the drug discovery process. PMID:25766375

  18. Future technology insight: mass spectrometry imaging as a tool in drug research and development.

    PubMed

    Cobice, D F; Goodwin, R J A; Andren, P E; Nilsson, A; Mackay, C L; Andrew, R

    2015-07-01

    In pharmaceutical research, understanding the biodistribution, accumulation and metabolism of drugs in tissue plays a key role during drug discovery and development. In particular, information regarding pharmacokinetics, pharmacodynamics and transport properties of compounds in tissues is crucial during early screening. Historically, the abundance and distribution of drugs have been assessed by well-established techniques such as quantitative whole-body autoradiography (WBA) or tissue homogenization with LC/MS analysis. However, WBA does not distinguish active drug from its metabolites and LC/MS, while highly sensitive, does not report spatial distribution. Mass spectrometry imaging (MSI) can discriminate drug and its metabolites and endogenous compounds, while simultaneously reporting their distribution. MSI data are influencing drug development and currently used in investigational studies in areas such as compound toxicity. In in vivo studies MSI results may soon be used to support new drug regulatory applications, although clinical trial MSI data will take longer to be validated for incorporation into submissions. We review the current and future applications of MSI, focussing on applications for drug discovery and development, with examples to highlight the impact of this promising technique in early drug screening. Recent sample preparation and analysis methods that enable effective MSI, including quantitative analysis of drugs from tissue sections will be summarized and key aspects of methodological protocols to increase the effectiveness of MSI analysis for previously undetectable targets addressed. These examples highlight how MSI has become a powerful tool in drug research and development and offers great potential in streamlining the drug discovery process. PMID:25766375

  19. Dust and Pollution Aerosol Air Mass Mapping from Satellite Multi-angle Imaging

    NASA Astrophysics Data System (ADS)

    Kahn, R. A.; Nelson, D. L.; Yau, K. S.; Martonchik, J.; Diner, D. J.; Gaitley, B. J.; Russell, P.; Livingston, J.; Redemann, J.; Quinn, P. R.; Clarke, A. R.; Howell, S.; McNaughton, C.; Reid, J.; Holben, B.; Wendisch, M.; Petzold, A.

    2006-12-01

    One objective of the NASA Earth Observing System's Multi-angle Imaging SpectroRadiometer (MISR) is to map aerosol air mass types, based on retrieved column-average particle microphysical properties. Early results demonstrated the ability to distinguish three-to-five bins over the 0.1 to 2.5 micron aerosol size range, about two-to-four groupings of single-scattering albedo, and to separate spherical from randomly oriented non- spherical particles, under good but not ideal viewing conditions. These results relied heavily on the MISR Research Aerosol Retrieval algorithm, which allows flexibility in choosing retrieval patch size and location, component aerosol properties and mixtures, and mixture acceptance criteria, compared to early versions of the MISR Standard algorithm, designed to routinely process the entire global data set. Early mid-visible column aerosol optical depth results were validated against surface-based sun photometer measurements. The corresponding particle property results appeared qualitatively promising, but formal validation requires quantitative constraints on component particle properties and mixtures in a range of natural settings, available mainly from the combination of height-resolved and total column data collected by surface and airborne instruments during field campaigns. This presentation will highlight the latest detailed, multi-platform case studies, as well as MISR regional mapping, of smoke, Saharan dust, and mixtures of pollution aerosol and desert dust collected during the INTEX, SAMUM, and UAE-2 campaigns, respectively. The broader implications of these results for global, and especially regional, aerosol climate and air quality studies will also be discussed. This work is performed at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.

  20. Vacuum compatible sample positioning device for matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry imaging

    PubMed Central

    Aizikov, Konstantin; Smith, Donald F.; Chargin, David A.; Ivanov, Sergei; Lin, Tzu-Yung; Heeren, Ron M. A.; O’Connor, Peter B.

    2011-01-01

    The high mass accuracy and resolving power of Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS) make them ideal mass detectors for mass spectrometry imaging (MSI), promising to provide unmatched molecular resolution capabilities. The intrinsic low tolerance of FT-ICR MS to RF interference, however, along with typically vertical positioning of the sample, and MSI acquisition speed requirements present numerous engineering challenges in creating robotics capable of achieving the spatial resolution to match. This work discusses a two-dimensional positioning stage designed to address these issues. The stage is capable of operating in ∼1 × 10–8 mbar vacuum. The range of motion is set to 100 mm × 100 mm to accommodate large samples, while the positioning accuracy is demonstrated to be less than 0.4 micron in both directions under vertical load over the entire range. This device was integrated into three different matrix assisted laser desorption/ionization (MALDI) FT-ICR instruments and showed no detectable RF noise. The “oversampling” MALDI-MSI experiments, under which the sample is completely ablated at each position, followed by the target movement of the distance smaller than the laser beam, conducted on the custom-built 7T FT-ICR MS demonstrate the stability and positional accuracy of the stage robotics which delivers high spatial resolution mass spectral images at a fraction of the laser spot diameter. PMID:21639522

  1. Vacuum compatible sample positioning device for matrix assisted laser desorption/ionization Fourier transform ion cyclotron resonance mass spectrometry imaging

    SciTech Connect

    Aizikov, Konstantin; Lin, Tzu-Yung; Smith, Donald F.; Heeren, Ron M. A.; Chargin, David A.; Ivanov, Sergei; O'Connor, Peter B.

    2011-05-15

    The high mass accuracy and resolving power of Fourier transform ion cyclotron resonance mass spectrometers (FT-ICR MS) make them ideal mass detectors for mass spectrometry imaging (MSI), promising to provide unmatched molecular resolution capabilities. The intrinsic low tolerance of FT-ICR MS to RF interference, however, along with typically vertical positioning of the sample, and MSI acquisition speed requirements present numerous engineering challenges in creating robotics capable of achieving the spatial resolution to match. This work discusses a two-dimensional positioning stage designed to address these issues. The stage is capable of operating in {approx}1 x 10{sup -8} mbar vacuum. The range of motion is set to 100 mm x 100 mm to accommodate large samples, while the positioning accuracy is demonstrated to be less than 0.4 micron in both directions under vertical load over the entire range. This device was integrated into three different matrix assisted laser desorption/ionization (MALDI) FT-ICR instruments and showed no detectable RF noise. The ''oversampling'' MALDI-MSI experiments, under which the sample is completely ablated at each position, followed by the target movement of the distance smaller than the laser beam, conducted on the custom-built 7T FT-ICR MS demonstrate the stability and positional accuracy of the stage robotics which delivers high spatial resolution mass spectral images at a fraction of the laser spot diameter.

  2. Topographical and Chemical Imaging of a Phase Separated Polymer Using a Combined Atomic Force Microscopy/Infrared Spectroscopy/Mass Spectrometry Platform.

    PubMed

    Tai, Tamin; Karácsony, Orsolya; Bocharova, Vera; Van Berkel, Gary J; Kertesz, Vilmos

    2016-03-01

    In this paper, the use of a hybrid atomic force microscopy/infrared spectroscopy/mass spectrometry imaging platform was demonstrated for the acquisition and correlation of nanoscale sample surface topography and chemical images based on infrared spectroscopy and mass spectrometry. The infrared chemical imaging component of the system utilized photothermal expansion of the sample at the tip of the atomic force microscopy probe recorded at infrared wave numbers specific to the different surface constituents. The mass spectrometry-based chemical imaging component of the system utilized nanothermal analysis probes for thermolytic surface sampling followed by atmospheric pressure chemical ionization of the gas phase species produced with subsequent mass analysis. The basic instrumental setup, operation, and image correlation procedures are discussed, and the multimodal imaging capability and utility are demonstrated using a phase separated poly(2-vinylpyridine)/poly(methyl methacrylate) polymer thin film. The topography and both the infrared and mass spectral chemical images showed that the valley regions of the thin film surface were comprised primarily of poly(2-vinylpyridine) and hill or plateau regions were primarily poly(methyl methacrylate). The spatial resolution of the mass spectral chemical images was estimated to be 1.6 μm based on the ability to distinguish surface features in those images that were also observed in the topography and infrared images of the same surface. PMID:26890087

  3. Visibility of microcalcification clusters and masses in breast tomosynthesis image volumes and digital mammography: A 4AFC human observer study

    SciTech Connect

    Timberg, P.; Baath, M.; Andersson, I.; Mattsson, S.; Tingberg, A.; Ruschin, M.

    2012-05-15

    Purpose: To investigate the visibility of simulated lesions in digital breast tomosynthesis (BT) image volumes compared with 2D digital mammography (DM). Methods: Simulated lesions (masses and microcalcifications) were added to images of the same women acquired on a DM system (Mammomat Novation, Siemens) and a BT prototype. The same beam quality was used for the DM and BT acquisitions. The total absorbed dose resulting from a 25-projection BT acquisition and reconstruction (BT{sub 25}) was approximately twice that of a single DM view. By excluding every other projection image from the reconstruction (BT{sub 13}), approximately the same dose as in DM was effected. Simulated microcalcifications were digitally added with varying contrast to the DM and BT images. Simulated masses with 8 mm diameter were also added to BT images. A series of 4-alternative forced choice (4AFC) human observer experiments were conducted. Four medical physicists participated in all experiments, each consisting of 60 trials per experimental condition. The observers interpreted the BT image volumes in cine-mode at a fixed image sequence speed. The required threshold contrast (S{sub t}) to achieve a detectability index (d') of 2.5 (i.e., 92.5% correct decisions) was determined. Results: The S{sub t} for mass detection in DM was approximately a factor of 2 higher than required in BT indicating that the detection of masses was improved under BT conditions compared to DM. S{sub t} for microcalcification detection was higher for BT than for DM at both BT dose levels (BT{sub 25} and BT{sub 13}), with a statistically significant difference in S{sub t} between DM and BT{sub 13}. These results indicate a dose-dependent decrease in detection performance in BT for detection of microcalcifications. Conclusions: In agreement with previous investigations, masses of size 8 mm can be detected with less contrast in BT than in DM indicating improved detection performance for BT. However, for the investigated

  4. Optical Projection Tomography Technique for Image Texture and Mass Transport Studies in Hydrogels Based on Gellan Gum.

    PubMed

    Soto, Ana M; Koivisto, Janne T; Parraga, Jenny E; Silva-Correia, Joana; Oliveira, Joaquim M; Reis, Rui L; Kellomäki, Minna; Hyttinen, Jari; Figueiras, Edite

    2016-05-24

    The microstructure and permeability are crucial factors for the development of hydrogels for tissue engineering, since they influence cell nutrition, penetration, and proliferation. The currently available imaging methods able to characterize hydrogels have many limitations. They often require sample drying and other destructive processing, which can change hydrogel structure, or they have limited imaging penetration depth. In this work, we show for the first time an alternative nondestructive method, based on optical projection tomography (OPT) imaging, to characterize hydrated hydrogels without the need of sample processing. As proof of concept, we used gellan gum (GG) hydrogels obtained by several cross-linking methods. Transmission mode OPT was used to analyze image microtextures, and emission mode OPT to study mass transport. Differences in hydrogel structure related to different types of cross-linking and between modified and native GG were found through the acquired Haralick's image texture features followed by multiple discriminant analysis (MDA). In mass transport studies, the mobility of FITC-dextran (MW 20, 150, 2000 kDa) was analyzed through the macroscopic hydrogel. The FITC-dextran velocities were found to be inversely proportional to the size of the dextran as expected. Furthermore, the threshold size in which the transport is affected by the hydrogel mesh was found to be 150 kDa (Stokes' radii between 69 and 95 Å). On the other hand, the mass transport study allowed us to define an index of homogeneity to assess the cross-linking distribution, structure inside the hydrogel, and repeatability of hydrogel production. As a conclusion, we showed that the set of OPT imaging based material characterization methods presented here are useful for screening many characteristics of hydrogel compositions in relatively short time in an inexpensive manner, providing tools for improving the process of designing hydrogels for tissue engineering and drugs

  5. Probing amyloid-β pathology in transgenic Alzheimer's disease (tgArcSwe) mice using MALDI imaging mass spectrometry.

    PubMed

    Carlred, Louise; Michno, Wojciech; Kaya, Ibrahim; Sjövall, Peter; Syvänen, Stina; Hanrieder, Jörg

    2016-08-01

    The pathological mechanisms underlying Alzheimer's disease (AD) are still not understood. The disease pathology is characterized by the accumulation and aggregation of amyloid-β (Aβ) peptides into extracellular plaques, however the factors that promote neurotoxic Aβ aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides and proteins in biological tissues. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)-based imaging was used to study Aβ deposition in transgenic mouse brain tissue and to elucidate the plaque-associated chemical microenvironment. The imaging experiments were performed in brain sections of transgenic Alzheimer's disease mice carrying the Arctic and Swedish mutation of amyloid-beta precursor protein (tgArcSwe). Multivariate image analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their chemical identity. This include cortical and hippocampal Aβ deposits, whose amyloid peptide content was further verified using immunohistochemistry and laser microdissection followed by MALDI MS analysis. Subsequent statistical analysis on spectral data of regions of interest revealed brain region-specific differences in Aβ peptide aggregation. Moreover, other plaque-associated protein species were identified including macrophage migration inhibitory factor suggesting neuroinflammatory processes and glial cell reactivity to be involved in AD pathology. The presented data further highlight the potential of IMS as a powerful approach in neuropathology. Hanrieder et al. described an imaging mass spectrometry based study on comprehensive spatial profiling of C-terminally truncated Aβ species within individual plaques in tgArcSwe mice. Here, brain region-dependent differences in Aβ truncation and other plaque-associated proteins, such as

  6. Improvement of biological time-of-flight-secondary ion mass spectrometry imaging with a bismuth cluster ion source.

    PubMed

    Touboul, David; Kollmer, Felix; Niehuis, Ewald; Brunelle, Alain; Laprévote, Olivier

    2005-10-01

    A new liquid metal ion gun (LMIG) filled with bismuth has been fitted to a time-of-flight-secondary ion mass spectrometer (TOF-SIMS). This source provides beams of Bi(n)q+ clusters with n = 1-7 and q = 1 and 2. The appropriate clusters have much better intensities and efficiencies than the Au3+ gold clusters recently used in TOF-SIMS imaging, and allow better lateral and mass resolution. The different beams delivered by this ion source have been tested for biological imaging of rat brain sections. The results show a great improvement of the imaging capabilities in terms of accessible mass range and useful lateral resolution. Secondary ion yields Y, disappearance cross sections sigma, efficiencies E = Y/sigma , and useful lateral resolutions deltaL have been compared using the different bismuth clusters, directly onto the surface of rat brain sections and for several positive and negative secondary ions with m/z ranging from 23 up to more than 750. The efficiency and the imaging capabilities of the different primary ions are compared by taking into account the primary ion current for reasonable acquisition times. The two best primary ions are Bi3+ and Bi5(2+). The Bi3+ ion beam has a current at least five times larger than Au3+ and therefore is an excellent beam for large-area imaging. Bi5(2+) ions exhibit large secondary ions yields and a reasonable intensity making them suitable for small-area images with an excellent sensitivity and a possible useful lateral resolution <400 nm. PMID:16112869

  7. DISCOVERY OF A PROBABLE 4-5 JUPITER-MASS EXOPLANET TO HD 95086 BY DIRECT IMAGING

    SciTech Connect

    Rameau, J.; Chauvin, G.; Lagrange, A.-M.; Delorme, P.; Quanz, S. P.; Bonnefoy, M.; Klahr, H.; Mordasini, C.; Girard, J. H.; Dumas, C.; Desidera, S.; Bonavita, M.

    2013-08-01

    Direct imaging has only begun to inventory the population of gas giant planets on wide orbits around young stars in the solar neighborhood. Following this approach, we carried out a deep imaging survey in the near-infrared using VLT/NaCo to search for substellar companions. Here we report the discovery of a probable companion orbiting the young (10-17 Myr), dusty, early-type (A8) star HD 95086 at 56 AU in L' (3.8 {mu}m) images. This discovery is based on observations with more than a year time lapse. Our first epoch clearly revealed the source at {approx_equal} 10{sigma}, while our second epoch lacks good observing conditions, yielding a {approx_equal} 3{sigma} detection. Various tests were thus made to rule out possible artifacts. This recovery is consistent with the signal at the first epoch but requires cleaner confirmation. Nevertheless, our astrometric precision suggests that the companion is comoving with the star with a 3{sigma} confidence level. The planetary nature of the source is reinforced by a non-detection in the Ks-band (2.18 {mu}m) images according to its possible extremely red Ks-L' color. Conversely, background contamination is rejected with good confidence level. The luminosity yields a predicted mass of about 4-5 M{sub Jup} (at 10-17 Myr) using ''hot-start'' evolutionary models, making HD 95086 b the exoplanet with the lowest mass ever imaged around a star.

  8. Determination of agrochemical compounds in soya plants by imaging matrix-assisted laser desorption/ionisation mass spectrometry.

    PubMed

    Mullen, Alexander K; Clench, Malcolm R; Crosland, Susan; Sharples, Kate R

    2005-01-01

    Detection and imaging of the herbicide mesotrione (2-(4-mesyl-2-nitrobenzoyl)cyclohexane-1,3-dione) and the fungicide azoxystrobin (methyl (E)-2-{2-[6-(2-cyanophenoxy)pyrimidin-4-yloxy]phenyl}-3-methoxyacrylate), on the surface of the soya leaf, and the detection and imaging of azoxystrobin inside the stem of the soya plant, have been achieved using matrix-assisted laser desorption/ionisation quadrupole time-of-flight mass spectrometry. In leaf analysis experiments, the two pesticides were deposited onto the surface of individual soya leaves on growing plants. The soya leaves were removed and prepared for direct and indirect (following blotting onto matrix-coated cellulose membranes) imaging analysis at different periods after initial pesticide application. In stem analysis experiments, azoxystrobin was added to the nutrient solution of a soya plant growing in a hydroponics system. The plant was left for 48 h, and then horizontal and vertical stem sections were prepared for direct imaging analysis. The images obtained demonstrate the applicability of MALDI imaging to the detection and imaging of small organic compounds in plant tissue and further extend the analytical repertoire of the versatile MALDI technique. PMID:16106343

  9. Dead-time correction for time-of-flight secondary-ion mass spectral images: a critical issue in multivariate image analysis.

    PubMed

    Tyler, Bonnie J; Peterson, Richard E

    2013-01-01

    Dead-time effects result in a non-linear detector response in the common time-of-flight secondary-ion mass spectrometry instruments. This can result in image artifacts that can often be misinterpreted. Although the Poisson correction procedure has been shown to effectively eliminate this non-linearity in spectra, applying the correction to images presents difficulties because the low number of counts per pixel can create large statistical errors. The efficacy of three approaches to dead-time correction in images has been explored. These approaches include: pixel binning, image segmentation and a binomial statistical correction. When few pixels are fully saturated, all three approaches work satisfactorily. When a large number of pixels are fully saturated, the statistical approach fails to remove the dead-time artifacts revealed by multivariate analysis. Pixel binning is accurate at higher levels of saturation so long as the bin size is much smaller than the feature size. The segmentation approach works well independent of feature size or the number of fully saturated pixels but requires an accurate segmentation algorithm. It is recommended that images be collected under conditions that minimize the number of fully saturated pixels. When this is impractical and small features are present in the image, segmentation can provide an accurate way to correct for the detector saturation effect. PMID:24707067

  10. Combined Use of GIS, Hydrostratigraphic, Geochemical, and Multi-Isotope Analysis for Groundwater Preservation and Development in a Complex Karst Setting

    NASA Astrophysics Data System (ADS)

    Murgulet, D.; Cook, M. R.

    2011-12-01

    The complex stratigraphy and geologic structure characteristic to fractured karst aquifers underlying an urban part of the north-central Alabama Valley and Ridge Setting make the development and protection of groundwater sources difficult. In this area, population growth accompanied by increased impervious surfaces, storm water runoff, contaminants, subsidence, and pumping rates have rendered the groundwater resource. The potential for aquifer recharge and flow conditions were evaluated in order to determine the current and future alternative water sources available in this area. Geochemical and multi-isotope techniques were coupled with hydrostratigraphic and geomorphic spatial (GIS) analyses to determine the primary mechanisms controlling recharge and flow and evaluate seasonal impacts on groundwater resources and recharge environments. Groundwater samples, collected in summer and fall (2010) from wells developed in the Bangor Limestone and Tuscumbia Fort Payne aquifers (north-central Alabama), were analyzed for major ions, stable isotopes of oxygen (δ^18O), hydrogen (δD), and carbon (δ^13C), and anthropogenic isotopes such as chlorofluorocarbon (CFCs) and sulphur hexafluoride (SF_6). Stable isotope investigations suggest that recharge occurs under relatively closed conditions, with fast percolation rates in short periods (characteristic to karst aquifers) and low evaporation rates during the colder seasons. The average δ^13C value (-11.4±2% PDB, n=9) lies near the combined average δ^13C values of soil CO_2 and the carbonate. Therefore, groundwater δ^13C signature is mainly controlled by two factors: soil CO_2 and carbonate dissolution. Static water levels decrease over the summer causing drawdowns (2 to 5.2 meters) in all the production wells and a slight shift of the δ^18O and δD values towards a more positive member (summer range--δ^18O: -5.1±0.1 to -5.7±0.1% VSMOW, n=11; δD: -25.0±1 to -30.6±1% VSMOW, n=11 and fall range--δ^18O: -4.8±0.1 to

  11. Affinity imaging mass spectrometry (AIMS): high-throughput screening for specific small molecule interactions with frozen tissue sections.

    PubMed

    Yoshimi, T; Kawabata, S; Taira, S; Okuno, A; Mikawa, R; Murayama, S; Tanaka, K; Takikawa, O

    2015-11-01

    A novel screening system, using affinity imaging mass spectrometry (AIMS), has been developed to identify protein aggregates or organ structures in unfixed human tissue. Frozen tissue sections are positioned on small (millimetre-scale) stainless steel chips and incubated with an extensive library of small molecules. Candidate molecules showing specific affinity for the tissue section are identified by imaging mass spectrometry (IMS). As an example application, we screened over a thousand compounds against Alzheimer's disease (AD) brain tissue and identified several compounds with high affinity for AD brain sections containing tau deposits compared to age-matched controls. It should also be possible to use AIMS to isolate chemical compounds with affinity for tissue structures or components that have been extensively modified by events such as oxidation, phosphorylation, acetylation, aggregation, racemization or truncation, for example, due to aging. It may also be applicable to biomarker screening programs. PMID:26365298

  12. Molecule-Specific Imaging Analysis of Carcinogens in Breast Cancer Cells Using Time-of-Flight Secondary Ion Mass Spectrometry

    SciTech Connect

    Quong, J N; Knize, M G; Kulp, K S; Wu, K J

    2003-08-19

    Imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) is used to study the localization of heterocyclic amines in MCF7 line of human breast cancer cells. The detection sensitivities of a model rodent mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were determined. Following an established criteria for the determination of status of freeze-fracture cells, the distribution of PhIP in the MCF7 cells are reported.

  13. A Search for Early Optical Emission at Gamma-Ray Burst Locations by the Solar Mass Ejection Imager (SMEI)

    NASA Technical Reports Server (NTRS)

    Band, David L.; Buffington, Andrew; Jackson, Bernard V.; Hick, P. Paul; Smith, Aaron C.

    2005-01-01

    The Solar Mass Ejection Imager (SMEI) views nearly every point on the sky once every 102 minutes and can detect point sources as faint as R approx. 10th magnitude. Therefore, SMEI can detect or provide upper limits for the optical afterglow from gamma-ray bursts in the tens of minutes after the burst when different shocked regions may emit optically. Here we provide upper limits for 58 bursts between 2003 February and 2005 April.

  14. Observation of Accumulated Metal Cation Distribution in Fish by Novel Stigmatic Imaging Time-of-Flight Mass Spectrometer

    NASA Astrophysics Data System (ADS)

    Aoki, Jun; Ikeda, Shinichiro; Toyoda, Michisato

    2014-02-01

    The accumulation of radioactive substances in biological organisms is a matter of great concern since the incident at the nuclear power plant in Fukushima, Japan. We have developed a novel technique for observing the distribution of accumulated metal cations in fish that employs a new imaging mass spectrometer, MULTUM-IMG2. Distributions of 133Cs and 88Sr in a sliced section of medaka (Oryzias latipes) are obtained with spatial resolution of µm-scale.

  15. Sonographic findings of axillary masses: what can be imaged in this space?

    PubMed

    Park, Ji Eun; Sohn, Yu-Mee; Kim, Eun-Kyung

    2013-07-01

    The diagnosis of axillary masses can be challenging because various tumors can develop in parts of the axilla other than lymph nodes, even though we frequently encounter axillary masses in daily practice. These lesions include soft tissue masses associated with nontumorous conditions (accessory breast tissue and chronic granulomatous inflammation) and benign and malignant tumorous conditions (lipomas, epidermal inclusion cysts, lymphangiomas, fibroadenomas, schwannomas, malignant neuroendocrine tumors, and lymph node-associated diseases). In this pictorial essay, we display commonly encountered sonographic findings of various axillary lesions to assist in the differential diagnosis of axillary masses. PMID:23804349

  16. Final LDRD report : development of sample preparation methods for ChIPMA-based imaging mass spectrometry of tissue samples.

    SciTech Connect

    Maharrey, Sean P.; Highley, Aaron M.; Behrens, Richard, Jr.; Wiese-Smith, Deneille

    2007-12-01

    The objective of this short-term LDRD project was to acquire the tools needed to use our chemical imaging precision mass analyzer (ChIPMA) instrument to analyze tissue samples. This effort was an outgrowth of discussions with oncologists on the need to find the cellular origin of signals in mass spectra of serum samples, which provide biomarkers for ovarian cancer. The ultimate goal would be to collect chemical images of biopsy samples allowing the chemical images of diseased and nondiseased sections of a sample to be compared. The equipment needed to prepare tissue samples have been acquired and built. This equipment includes an cyro-ultramicrotome for preparing thin sections of samples and a coating unit. The coating unit uses an electrospray system to deposit small droplets of a UV-photo absorbing compound on the surface of the tissue samples. Both units are operational. The tissue sample must be coated with the organic compound to enable matrix assisted laser desorption/ionization (MALDI) and matrix enhanced secondary ion mass spectrometry (ME-SIMS) measurements with the ChIPMA instrument Initial plans to test the sample preparation using human tissue samples required development of administrative procedures beyond the scope of this LDRD. Hence, it was decided to make two types of measurements: (1) Testing the spatial resolution of ME-SIMS by preparing a substrate coated with a mixture of an organic matrix and a bio standard and etching a defined pattern in the coating using a liquid metal ion beam, and (2) preparing and imaging C. elegans worms. Difficulties arose in sectioning the C. elegans for analysis and funds and time to overcome these difficulties were not available in this project. The facilities are now available for preparing biological samples for analysis with the ChIPMA instrument. Some further investment of time and resources in sample preparation should make this a useful tool for chemical imaging applications.

  17. Live-cell imaging of actin dynamics reveals mechanisms of stereocilia length regulation in the inner ear.

    PubMed

    Drummond, Meghan C; Barzik, Melanie; Bird, Jonathan E; Zhang, Duan-Sun; Lechene, Claude P; Corey, David P; Cunningham, Lisa L; Friedman, Thomas B

    2015-01-01

    The maintenance of sensory hair cell stereocilia is critical for lifelong hearing; however, mechanisms of structural homeostasis remain poorly understood. Conflicting models propose that stereocilia F-actin cores are either continually renewed every 24-48 h via a treadmill or are stable, exceptionally long-lived structures. Here to distinguish between these models, we perform an unbiased survey of stereocilia actin dynamics in more than 500