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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

    Steinhauser, Matthew L; Lechene, Claude P

    2013-01-01

    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.

  2. Multi-isotope SPECT imaging of the 225Ac decay chain: feasibility studies.

    PubMed

    Robertson, Andrew K H; Ramogida, Caterina; Rodriguez-Rodriguez, Cristina; Blinder, Stephan; Kunz, Peter; Sossi, Vesna; Schaffer, Paul

    2017-03-31

    Purpose: Effective use of the 225Ac decay chain in targeted internal radioimmunotherapy requires the retention of both 225Ac and progeny isotopes at the target site. Imaging-based pharmacokinetic tests of these pharmaceuticals must therefore separately yet simultaneously image multiple isotopes that may not be colocalized despite being part of the same decay chain. This work presents feasibility studies demonstrating the ability of a microSPECT/CT scanner equipped with a high energy collimator to simultaneously image two components of the 225Ac decay chain: 221Fr (218 keV) and 213Bi (440 keV). Methods: Image quality phantoms were used to assess the performance of two collimators for simultaneous 221Fr and 213Bi imaging in terms of contrast and noise. A hotrod resolution phantom containing clusters of thin rods with diameters ranging between 0.85 and 1.70 mm was used to assess resolution. To demonstrate ability to image dynamic 221Fr and 213Bi activity distributions, a phantom containing a 213Bi generator from 225Ac was imaged. These tests were performed with two collimators, a high-energy ultra-high resolution (HEUHR) collimator and an ultra-high sensitivity (UHS) collimator. Results: Values consistent with activity concentrations determined independently via gamma spectroscopy observed in high activity regions of the images. In hotrod phantom images, the HEUHR collimator resolved all rods for both 221Fr and 213Bi images. With the UHS collimator, no rods were resolvable in 213Bi images and only rods ≥1.3 mm were resolved in 221Fr images. After eluting the 213Bi generator, images accurately visualized the reestablishment of transient equilibrium of the 225Ac decay chain. Conclusion: A novel imaging method with potential to evaluate the pharmacokinetics of the 225

  3. 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

  4. Imaging Mass Cytometry.

    PubMed

    Chang, Qing; Ornatsky, Olga I; Siddiqui, Iram; Loboda, Alexander; Baranov, Vladimir I; Hedley, David W

    2017-02-01

    Imaging Mass Cytometry (IMC) is an expansion of mass cytometry, but rather than analyzing single cells in suspension, it uses laser ablation to generate plumes of particles that are carried to the mass cytometer by a stream of inert gas. Images reconstructed from tissue sections scanned by IMC have a resolution comparable to light microscopy, with the high content of mass cytometry enabled through the use of isotopically labeled probes and ICP-MS detection. Importantly, IMC can be performed on paraffin-embedded tissue sections, so can be applied to the retrospective analysis of patient cohorts whose outcome is known, and eventually to personalized medicine. Since the original description in 2014, IMC has evolved rapidly into a commercial instrument of unprecedented power for the analysis of histological sections. In this Review, we discuss the underlying principles of this new technology, and outline emerging applications of IMC in the analysis of normal and pathological tissues. © 2017 International Society for Advancement of Cytometry.

  5. 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.

  6. Imaging of pediatric neck masses.

    PubMed

    Friedman, Elliott R; John, Susan D

    2011-07-01

    Palpable neck masses are a common indication for pediatric imaging. Such lesions may be caused by infectious, inflammatory, tumoral, traumatic, lymphovascular, immunologic, or congenital etiologies. Radiological assessment of neck masses in young children should be tailored based on patient presentation and physical examination, as well as clinical suspicion. The goal of imaging should be to help arrive at a diagnosis or limited differential in an efficient manner while minimizing radiation exposure.

  7. The Solar Mass Ejection Imager

    NASA Technical Reports Server (NTRS)

    Jackson, B. V.; Buffington, A.; Hick, P. L.; Kahler, S. W.; Altrock, R. C.; Gold, R. E.; Webb, D. F.

    1995-01-01

    We are designing a Solar Mass Ejection Imager (SMEI) capable of observing the Thomson-scattered signal from transient density features in the heliosphere from a spacecraft situated near AU. The imager is designed to trace these features, which include coronal mass ejections. corotating structures and shock waves, to elongations greater than 90 deg from the Sun. The instrument may be regarded as a progeny of the heliospheric imaging capability shown possible by the zodiacal-light photometers of the HELIOS spacecraft. The instrument we are designing would make more effective use of in-situ solar wind data from spacecraft in the vicinity of the imager by extending these observations to the surrounding environment. The observations from the instrument should allow deconvolution of these structures from the perspective views obtained as they pass the spacecraft. An imager at Earth could allow up to three days warning of the arrival of a mass ejection from the Sun .

  8. Imaging of Solid Renal Masses.

    PubMed

    Kay, Fernando U; Pedrosa, Ivan

    2017-03-01

    Detection of solid renal masses has increased, although it has not resulted in significant mortality reduction from renal cell carcinoma. Efforts for improved lesion characterization have been pursued and incorporated in management algorithms, in order to distinguish clinically significant tumors from favorable or benign conditions. Concurrently, imaging methods have produced evidence supporting their role as useful tools not only in lesion detection but also characterization. In addition, newer modalities, such as contrast-enhanced ultrasonography, and advanced applications of MR imaging, are being investigated. This article reviews the current role of different imaging methods in the characterization of solid renal masses.

  9. Imaging mass spectrometry in microbiology

    PubMed Central

    Watrous, Jeramie D.; Dorrestein, Pieter C.

    2013-01-01

    Mass spectrometry tools which allow for the 2-D visualization of the distribution of trace metals, metabolites, surface lipids, peptides and proteins directly from biological samples without the need for chemical tagging or antibodies are becoming increasingly useful for microbiology applications. These tools, comprised of different imaging mass spectrometry techniques, are ushering in an exciting new era of discovery by allowing for the generation of chemical hypotheses based on of the spatial mapping of atoms and molecules that can correlate to or transcend observed phenotypes. In this review, we explore the wide range of imaging mass spectrometry techniques available to microbiologists and describe their unique applications to microbiology with respect to the types of microbiology samples to be investigated. PMID:21822293

  10. 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

  11. Imaging mass spectrometry demonstrates age-related decline in human adipose plasticity

    PubMed Central

    Fazeli, Pouneh K.; Kim, Soomin; Lun, Mingyue; Zuflacht, Jonah P.; Milian, Jessica; Lee, Hang; Francois-Saint-Cyr, Hugues; Horreard, Francois; Larson, David; Rosen, Evan D.; Lee, Richard T.; Lechene, Claude P.; Steinhauser, Matthew L.

    2017-01-01

    Quantification of stable isotope tracers has revealed the dynamic state of living tissues. A new form of imaging mass spectrometry quantifies isotope ratios in domains much smaller than a cubic micron, enabling measurement of cell turnover and metabolism with stable isotope tracers at the single-cell level with a methodology we refer to as multi-isotope imaging mass spectrometry. In a first-in-human study, we utilize stable isotope tracers of DNA synthesis and de novo lipogenesis to prospectively measure cell birth and adipocyte lipid turnover. In a study of healthy adults, we elucidate an age-dependent decline in new adipocyte generation and adipocyte lipid turnover. A linear regression model suggests that the aging effect could be mediated by a decline in insulin-like growth factor-1 (IGF-1). This study therefore establishes a method for measurement of cell turnover and metabolism in humans with subcellular resolution while implicating the growth hormone/IGF-1 axis in adipose tissue aging. PMID:28289709

  12. 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.

  13. 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.

  14. Experimental Validation of the Multi-Isotope Process Monitor Concept

    SciTech Connect

    Orton, Christopher R.; Schwantes, Jon M.; Fraga, Carlos G.; Douglas, Matthew; Christensen, Richard

    2010-05-13

    Researchers from Pacific Northwest National Laboratory, in conjunction with personnel from The Ohio State University, are working to develop a system for monitoring spent nuclear fuel reprocessing facilities on-line, non-destructively, 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 particular process streams. Distribution patterns, monitored on-line by gamma spectrometry, are then 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 the 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 validation is currently under way and significant results are available. The latest experimental results, along with an overview of the method will be presented.

  15. Absorption mode FTICR mass spectrometry imaging.

    PubMed

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

    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.

  16. 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

  17. Imaging of pediatric head and neck masses.

    PubMed

    Stern, Jessica S; Ginat, Daniel T; Nicholas, Jennifer L; Ryan, Maura E

    2015-02-01

    Medical imaging is an important tool in the evaluation and classification of pediatric head and neck masses. Such lesions may include congenital, inflammatory, infectious, vascular, or neoplastic processes. Ultrasound is often the first line modality in the workup of a neck mass in a child, followed by MRI or CT depending on the scenario. This information must be interpreted in the context of the patient's clinical history, physical examination, and demographics. The medical imaging workup of a neck mass in a child must be focused to yield the maximum information possible while minimizing the risks of radiation and sedation.

  18. Imaging of granulomatous neck masses in children.

    PubMed

    Nadel, D M; Bilaniuk, L; Handler, S D

    1996-10-01

    Non-tuberculous mycobacterial (NTM) infection is the most common cause of granulomatous inflammation in pediatric neck masses. Diagnosis relies upon culture, acid-fast bacilli (AFB) staining, chest radiograph, purified protein derivative (PPD) test, and clinical features. Computed tomography (CT) and magnetic resonance (MR) imaging may provide valuable information in the work-up of children with cervical masses. We reviewed 11 CT and 5 MR studies of children with a clinical diagnosis of NTM infection. Specific findings included stranding of the subcutaneous fat, thickening and enhancement of the overlying skin, obliteration of the tissue palnes, and multichambered masses. One patient had calcifications within the mass. MR with contrast better demonstrated the soft tissues and is our recommended imaging modality, although CT is more likely to detect calcifications within the neck mass.

  19. Gynecologic masses: value of magnetic resonance imaging.

    PubMed

    Hricak, H; Lacey, C; Schriock, E; Fisher, M R; Amparo, E; Dooms, G; Jaffe, R

    1985-09-01

    Forty-two women with gynecologic abnormalities were studied with the use of magnetic resonance imaging. Magnetic resonance imaging correctly assessed the origin of the pelvic mass in all patients. In the evaluation of leiomyoma, magnetic resonance imaging accurately depicted the number, size, and location of the lesion. In the evaluation of endometrial carcinoma, magnetic resonance imaging depicted the location of the lesion, the presence of cervical extension, and the depth of myometrial penetration in the majority of the cases. In the analysis of adnexal cysts, magnetic resonance imaging was sensitive in localizing the lesion and was able to distinguish serous from hemorrhagic fluid. This preliminary report indicates that magnetic resonance imaging may become a valuable imaging modality in the diagnosis of gynecologic abnormalities.

  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. 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

  2. Imaging thermal ion mass and velocity analyzer

    NASA Astrophysics Data System (ADS)

    Yau, A. W.; King, E. P.; Amerl, P.; Berg, K.; Enno, G.; Howarth, A.; Wevers, I.; White, A.

    2013-11-01

    The aim of an imaging thermal ion mass and velocity analyzer is to apply imaging techniques to measure in-situ the mass composition and detailed velocity phase space distributions of a thermal plasma population in a planetary ionosphere or magnetosphere and use the measured distributions to derive the bulk plasma parameters and to detect the possible presence of non-thermal distributions. A hemispherical electrostatic analyzer (HEA) with a planar entrance aperture can sample simultaneously incident ions or electrons over an extended energy range and the full 360° range of incident azimuth, and disperse them by their energy-per-charge while retaining their incident azimuth, thus providing a means to image the 2-dimensional (2D) ion or electron energy-per-charge and angular (azimuth) distribution. Therefore an ion mass and velocity analyzer consisting of a HEA embedded with an ion-mass spectrometer is capable of imaging the 2-D detailed ion velocity distribution—and measuring the 3D distribution on a spinning spacecraft if the planar entrance aperture is aligned along the spacecraft spin axis. For 3D velocity distribution measurements on a 3-axis stabilized spacecraft, an analyzer with electrostatic deflection capability will be required to deflect ions at arbitrary incident elevation angles into the planar entrance aperture for sampling. An imaging thermal ion mass and velocity analyzer is presented that combines a HEA, a time-of-flight ion mass spectrometer, and a pair of electrostatic deflectors, and is capable of sampling low-energy ions (˜1 to 100 eV/e) of all mass species (1 to > 40 AMU/e) from all incident directions on a non-spinning platform, at up to (10% energy resolution (ΔE/E) and ˜5° angular resolution. Using the HEA to measure the energy-percharge of each detected ion and the time-of-flight gate to measure the transit time of the ion inside the analyzer, this instrument can resolve all major ion species in the ionosphere including H+, He+ and O

  3. Integrated imaging of neonatal renal masses.

    PubMed

    Kirks, D R; Rosenberg, E R; Johnson, D G; King, L R

    1985-01-01

    Thirty-three neonatal renal masses were evaluated during a 2-year interval. The final diagnoses in these 33 patients were hydronephrosis [14], multicystic dysplastic kidney [10], renal vein thrombosis [3], obstructed upper pole duplication [2], polycystic kidney disease [2], nephroblastomatosis [1], and mesoblastic nephroma [1]. We recommend an integrated imaging approach that utilizes sonography to clarify anatomy and renal scintigraphy or excretory urography to determine renal function.

  4. 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

  5. Pb-Zn-Cd-Hg multi isotopic characterization of the Loire River Basin, France

    NASA Astrophysics Data System (ADS)

    Millot, R.; Widory, D.; Innocent, C.; Guerrot, C.; Bourrain, X.; Johnson, T. M.

    2012-12-01

    metal pollutants. The main objective of this study is to characterize the sources and the behavior of these heavy metals in the aquatic environment, and their spatial distribution using a multi-isotope approach. Each of these isotope systematics on their own reveals important information about their geogenic or anthropogenic origin but, considered together, provide a more integrated understanding of the budgets of these pollutants within the Loire River Basin.

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

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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 because of 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.

  7. 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

  8. 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

  9. 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

  10. 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.

  11. Lipid imaging by mass spectrometry - a review.

    PubMed

    Gode, David; Volmer, Dietrich A

    2013-03-07

    Mass spectrometry imaging (MSI) has proven to be extremely useful for applications such as the spatial analysis of peptides and proteins in biological tissue, the performance assessment of drugs in vivo or the measurement of protein or metabolite expression as tissue classifiers or biomarkers from disease versus control tissue comparisons. The most popular MSI technique is MALDI mass spectrometry. First invented by Richard Caprioli in the mid-1990s, it is the highest performing MSI technique in terms of spatial resolution, sensitivity for intact biomolecules and application range today. The unique ability to identify and spatially resolve numerous compounds simultaneously, based on m/z values has inter alia been applied to untargeted and targeted chemical mapping of biological compartments, revealing changes of physiological states, disease pathologies and metabolic faith and distribution of xenobiotics. Many MSI applications focus on lipid species because of the lipids' diverse roles as structural components of cell membranes, their function in the surfactant cycle, and their involvement as second messengers in signalling cascades of tissues and cells. This article gives a comprehensive overview of lipid imaging techniques and applications using established MALDI and SIMS methods but also other promising MSI techniques such as DESI.

  12. 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 .

  13. 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.

  14. 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

  15. Imaging thermal plasma mass and velocity analyzer

    NASA Astrophysics Data System (ADS)

    Yau, Andrew W.; Howarth, Andrew

    2016-07-01

    We present the design and principle of operation of the imaging ion mass and velocity analyzer on the Enhanced Polar Outflow Probe (e-POP), which measures low-energy (1-90 eV/e) ion mass composition (1-40 AMU/e) and velocity distributions using a hemispherical electrostatic analyzer (HEA), a time-of-flight (TOF) gate, and a pair of toroidal electrostatic deflectors (TED). The HEA and TOF gate measure the energy-per-charge and azimuth of each detected ion and the ion transit time inside the analyzer, respectively, providing the 2-D velocity distribution of each major ionospheric ion species and resolving the minor ion species under favorable conditions. The TED are in front of the TOF gate and optionally sample ions at different elevation angles up to ±60°, for measurement of 3-D velocity distribution. We present examples of observation data to illustrate the measurement capability of the analyzer, and show the occurrence of enhanced densities of heavy "minor" O++, N+, and molecular ions and intermittent, high-velocity (a few km/s) upward and downward flowing H+ ions in localized regions of the quiet time topside high-latitude ionosphere.

  16. Tracking Coronal Mass Ejections with a Heliospheric Imager: Case Studies from the Solar Mass Ejection Imager

    NASA Astrophysics Data System (ADS)

    Johnston, J. C.; Mizuno, D. R.; Webb, D. F.; Kuchar, T. A.; Howard, T. A.

    2005-05-01

    The Solar Mass Ejection Imager (SMEI) was launched on board the DoD Space Test Program's Coriolis satellite in January 2003. Two-thirds through its planned 3-year lifetime, SMEI has observed Coronal Mass Ejections (CMEs), comets and asteroids as they move through the heliosphere. More than 140 CMEs have been detected with the SMEI instrument, including well-documented "halo" events that led to geomagnetic storm conditions on Earth. These observations demonstrate the potential of a heliospheric imager for space weather specification and prediction purposes. We present several case studies of CMEs as they propagate through the SOHO LASCO and SMEI fields of view, and examine SMEI's "hit" rate for detection of geoeffective CMEs.

  17. 3D Imaging by Mass Spectrometry: A New Frontier

    PubMed Central

    Seeley, Erin H.; Caprioli, Richard M.

    2012-01-01

    Summary Imaging mass spectrometry can generate three-dimensional volumes showing molecular distributions in an entire organ or animal through registration and stacking of serial tissue sections. Here we review the current state of 3D imaging mass spectrometry as well as provide insights and perspectives on the process of generating 3D mass spectral data along with a discussion of the process necessary to generate a 3D image volume. PMID:22276611

  18. 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.

  19. Mass Spectrometry Imaging of Complex Microbial Communities

    PubMed Central

    2016-01-01

    Conspectus In the two decades since mass spectrometry imaging (MSI) was first applied to visualize the distribution of peptides across biological tissues and cells, the technique has become increasingly effective and reliable. MSI excels at providing complementary information to existing methods for molecular analysis—such as genomics, transcriptomics, and metabolomics—and stands apart from other chemical imaging modalities through its capability to generate information that is simultaneously multiplexed and chemically specific. Today a diverse family of MSI approaches are applied throughout the scientific community to study the distribution of proteins, peptides, and small-molecule metabolites across many biological models. The inherent strengths of MSI make the technique valuable for studying microbial systems. Many microbes reside in surface-attached multicellular and multispecies communities, such as biofilms and motile colonies, where they work together to harness surrounding nutrients, fend off hostile organisms, and shield one another from adverse environmental conditions. These processes, as well as many others essential for microbial survival, are mediated through the production and utilization of a diverse assortment of chemicals. Although bacterial cells are generally only a few microns in diameter, the ecologies they influence can encompass entire ecosystems, and the chemical changes that they bring about can occur over time scales ranging from milliseconds to decades. Because of their incredible complexity, our understanding of and influence over microbial systems requires detailed scientific evaluations that yield both chemical and spatial information. MSI is well-positioned to fulfill these requirements. With small adaptations to existing methods, the technique can be applied to study a wide variety of chemical interactions, including those that occur inside single-species microbial communities, between cohabitating microbes, and between microbes

  20. Example-based segmentation for breast mass images

    NASA Astrophysics Data System (ADS)

    Huang, Qingying; Xu, Songhua; Luo, Xiaonan

    2013-03-01

    A new example-based mass segmentation algorithm is proposed for breast mass images. The training examples used in the new algorithm are prepared by three medical imaging professionals who manually outlined mass contours of 45 sample breast mass images. These manually segmented mass images are then partitioned into small regular grid cells, which are used as reference samples by the algorithm. Each time when the algorithm is applied to segment a previously unseen breast mass image, it first detects grid cell regions in the image that likely overlap with the underlying mass region. Upon identifying such candidate regions, the algorithm then locates the exact mass contour through an example based segmentation procedure where the algorithm retrieves, transfers, and re-applies the human expert knowledge regarding mass segmentation as encoded in the reference samples. The key advantage of our approach lies in its adaptability in tailoring to the skills and preferences of multiple experts through simply switching to a different corpus of human segmentation samples. To explore the effectiveness of the new approach, we comparatively evaluated the accuracy of the algorithm for mass segmentation against segmentation results both manually produced by several medical imaging professionals and automatically by a state-of-the-art level set based method. The comparison results demonstrate that the new algorithm achieves a higher accuracy than the level set based peer method with statistical significance.2

  1. V are Interplanetary Coronal Mass Ejections Observed with the SOlar Mass Ejection Imager

    DTIC Science & Technology

    2007-01-01

    SUBTITLE V arc interplanetary coronal mass ejections observed with the Solar Mass Ejection Imager 5a. CONTRACT NUMBER 5b. GRANT NUMBER a. 5c...doi: 10.1029/2007JA012358 14. ABSTRACT Since February 2003, The Solar Mass Ejection Imager (SMEI) has been observing interplanetary- coronal mass...ejections (ICMEs) at solar elongation angles ^ > 20 degrees. The ICMEs generally appear as loops or arcs in the sky, but five show distinct outward

  2. 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.

  3. Mass Spectrometry Imaging: facts and perspectives from a non-mass spectrometrist point of view.

    PubMed

    Cameron, L C

    2012-08-01

    Mass Spectrometry Imaging (MSI, also called Imaging Mass Spectrometry) can be used to map molecules according to their chemical abundance and spatial distribution. This technique is not widely used in mass spectrometry circles and is barely known by other scientists. In this review, a brief overview of the mass spectrometer hardware used in MSI and some of the possible applications of this powerful technique are discussed. I intend to call attention to MSI uses from cell biology to histopathology for biological scientists who have little background in mass spectrometry. MSI facts and perspectives are presented from a non-mass spectrometrist point of view.

  4. A Multi-isotope Tracer Approach Linking Land Use With Carbon and Nitrogen Cycling in the San Joaquin River System

    NASA Astrophysics Data System (ADS)

    Young, M. B.; Kendall, C.; Silva, S. R.; Dahlgren, R. A.; Stringfellow, W. T.

    2008-12-01

    The San Joaquin River (SJR) is a large hypereutrophic river located in the Central Valley, California, a major agricultural region. Nutrient subsidies, algae, and other organic material from the San Joaquin River contribute to periods of low dissolved oxygen in the Stockton Deep Water Ship Channel, inhibiting salmon migration. We used a multi-isotope approach to link nitrate and particulate organic matter (POM) to different sources and related land uses. The isotope data was also used to better understand the physical and biological processes controlling the distribution of nitrate and POM throughout the river system. Samples collected from the mainstem SJR and tributaries twice-monthly to monthly between March 2005 and December 2007 were analyzed for nitrate, POM, and water isotopes. There are many land uses surrounding the SJR and its tributaries, including multiple types of agriculture, dairies, wetlands, and urban areas. Samples from SJR tributaries containing both major and minor contributions of wetland discharge generally had distinct nitrate and POM isotope signatures compared to other tributaries. Unique nitrate and POM isotope signatures associated with wetland discharges may reflect anaerobic biological processes occurring in flooded soils. For the mainstem SJR, we applied an isotope mass balance approach using nitrate and water isotopes to calculate the expected downstream isotope values based upon measured inputs from known water sources such as drains and tributaries. Differences between the calculated downstream isotope values and the measured values indicate locations and time periods when either biological processes such as algal uptake, or physical process such as the input of unidentified water sources, significantly altered the isotope signatures of water, POM, or nitrate within the SJR. This research will provide a better understanding of how different land uses affect the delivery of carbon and nitrogen to the SJR, and will provide a better

  5. 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.

  6. Multimodality imaging of placental masses: a pictorial review.

    PubMed

    Jha, Priyanka; Paroder, Viktoriya; Mar, Winnie; Horowtiz, Jeanne M; Poder, Liina

    2016-12-01

    Placental masses are uncommonly identified at the time of obstetric ultrasound evaluation. Understanding the pathologies presenting as placental masses is key for providing a differential diagnosis and guiding subsequent management, which may include additional imaging with magnetic resonance (MR) imaging. Potential benign entities include chorioangiomas and teratomas. Larger chorioangiomas can cause fetal cardiovascular issues from volume overload. Placental mesenchymal dysplasia has an association with fetal anomalies and detailed fetal evaluation should be performed when it is suspected. Identifying other cystic masses such as partial and complete moles is crucial to prevent erroneous pregnancy termination. This review addresses normal imaging appearance of the placenta on ultrasound and MR imaging and describes various trophoblastic and nontrophoblastic placental masses. Potential placental mass mimics including uterine contractions and thrombo-hematomas are also presented.

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

    DOE PAGES

    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

  8. 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.

  9. 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.

  10. 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

  11. Mesenteric lymphangioma mimicking a cystic ovarian mass on imaging.

    PubMed

    Hitzerd, Emilie; van Hamont, Dennis; Pijnenborg, Johanna M A

    2016-02-01

    Pelvic cystic masses are frequently observed in women. Most lesions are benign and of ovarian origin. However, non-ovarian lesions can be easily confused with cystic ovarian masses on imaging, which hampers diagnostic and therapeutic management. In this report, a rare case of mesenteric lymphangioma mimicking an ovarian cystic mass, discovered as an incidental finding on orthopaedic MRI in an adult female, is presented. The report highlights the sometimes difficult diagnostic process of pelvic cystic masses, due to an extensive differential diagnosis and the fact that imaging is often inconclusive. Even though most cystic masses are of ovarian origin, non-ovarian causes can mimic ovarian masses and should be considered as differential diagnoses. Surgical exploration may be necessary to exclude malignant causes.

  12. 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…

  13. Creating images by adding masses to gravitational point lenses

    NASA Astrophysics Data System (ADS)

    Sète, Olivier; Luce, Robert; Liesen, Jörg

    2015-04-01

    A well-studied maximal gravitational point lens construction of S. H. Rhie produces images of a light source using deflector masses. The construction arises from a circular, symmetric deflector configuration on masses (producing only images) by adding a tiny mass in the center of the other mass positions (and reducing all the other masses a little bit). In a recent paper we studied this "image creating effect" from a purely mathematical point of view (Sète, Luce & Liesen, Comput. Methods Funct. Theory 15(1), 2014). Here we discuss a few consequences of our findings for gravitational microlensing models. We present a complete characterization of the effect of adding small masses to these point lens models, with respect to the number of images. In particular, we give several examples of maximal lensing models that are different from Rhie's construction and that do not share its highly symmetric appearance. We give generally applicable conditions that allow the construction of maximal point lenses on masses from maximal lenses on masses.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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).

  1. Multi-Isotope Process (MIP) Monitor: A Near-Real-Time Monitor For Reprocessing Facilities

    SciTech Connect

    Schwantes, Jon M.; Douglas, Matthew; Orton, Christopher R.; Fraga, Carlos G.; Christensen, Richard

    2008-06-01

    INTRODUCTION The threat of protracted diversion of Pu from commercial reprocessing operations is perhaps the greatest concern to national and international agencies tasked with safeguarding these facilities. While it is generally understood that a method for direct monitoring of process on-line and in near-real time (NRT) would be the best defense against protracted diversion scenarios, an effective method with these qualities has yet to be developed. Here, we attempt to bridge this gap by proposing an on-line NRT process monitoring method that should be sensitive to minor alterations in process conditions and compatible with small, easily deployable, detection systems. This Approach is known as the Multi-Isotope Process (MIP) Monitor and involves the determination and recognition of the contaminant pattern within a process stream for a suite of indicator (radioactive) elements present in the spent fuel as a function of process variables. Utilization of a suite of radio-elements, including ones with multiple oxidation states, decreases the likelihood that attempts to divert Pu by altering the ReDox environment within the process would go undetected. In addition, by identifying gamma-emitting indicator isotopes, this Approach might eliminate the need for bulky neutron detection systems, relying instead on small, portable, high-resolution gamma detectors easily deployable throughout the facility.

  2. 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.

  3. Identification of the geographical place of origin of an unidentified individual by multi-isotope analysis.

    PubMed

    Font, Laura; van der Peijl, Gerard; van Leuwen, Carina; van Wetten, Isis; Davies, Gareth R

    2015-01-01

    A multi-isotope investigation (Sr and Pb isotopes and δ18O, δ13C and δ15N) was applied to bone and teeth from an unidentified male found drowned in the"IJ" Ruyterkade in Amsterdam, The Netherlands in March of 1999. The individual remained unidentified until mid 2013, after the isotope study was completed. Coupled δ13C and δ15N values in bone collagen recovered from rib and femur are consistent with an omnivore living in a region where C3-type diet dominates (i.e. Europe). Integrated Sr and Pb isotopes and δ18O values in canine and third molar teeth and femur and rib bone data exclude extended residence in north-west Europe and particularly The Netherlands. Characteristic Pb isotope ratios coupled with inferred δ18O values of drinking water argue for a most probable place of origin for the unidentified individual in west and south Poland, south-east Slovakia and the region of Ukraine-Romania-Bulgaria, specifically the region associated with the Carpathian Mountains. Independent of the isotope study, the Cold Case Team made a positive identification with an individual from south-west Poland, validating the results of the multiple-isotopic approach.

  4. 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.

  5. The Automatic Detection of Coronal Mass Ejections Using the Solar Mass Ejection Imager

    DTIC Science & Technology

    2009-10-30

    Res., 112, A09103, doi: 10.1029/2007JA012358, 2007. Low, B.C., Solar activity and the corona , Solar Phys. 167, p217, 1996. Robbrecht, E., and D...AFRL-RV-HA-TR-2009-1104 Q- o o o p o The Automatic Detection of Coronal Mass Ejections Using the Solar Mass Ejection Imager Timothy A. Howard... Solar Mass Ejection Imager 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6340IF 6. AUTHORS Timothy A. Howard S. James Tappin

  6. Image resolution influence on determination of resin injection rock mass

    NASA Astrophysics Data System (ADS)

    Wang, Weixing; Hakami, Eva

    2006-01-01

    In the context of nuclear waste repositories, an important approach to understanding brittle rock mass behavior to integrate new and powerful observational and numerical methods with multi-functional 3-D imaging and visualization techniques. Since 1994, Swedish Nuclear Fuel and Waste Management Company (SKB) have identified the need for a better understanding of radionuclide transport and retention processes in fractured rock. As a cooperation project between Sweden and China, we sampled a number of rock specimens for analyze rock fracture network by optical image technique. The samples are resin injected, in which way; opened fractures can be seen clearly by means of UV (Ultraviolet) light illumination. In the study period, we used different optical focuses to obtain the images from the same samples; we found that Image resolution influences on porosity determination of resin injected rock mass. This paper presents and discusses the six issues based on our research results: (1) Fracture porosity increases as camera focus distance decreases; (2) Porosity increases as illumination increases in resin injected fracture images; (3) To roughly estimate the porosity, the low resolution image can be used; (4) To collect more details of fracture information, the high resolution image is needed; (5) The resolution of image should be determined based on the aim of fracture analysis; (6) To acquire high resolution image, constructing a special illumination (standard) box maybe helpful to avoid light reflection and diffusion.

  7. 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.

  8. Advanced Mass Calibration and Visualization for FT-ICR Mass Spectrometry Imaging

    SciTech Connect

    Smith, Donald F.; Kharchenko, Andriy; Konijnenburg, Marco; Klinkert, Ivo; Pasa-Tolic, Ljiljana; Heeren, Ronald M.

    2012-11-01

    Mass spectrometry imaging by Fourier transform ion cyclotron resonance (FT-ICR) yields hundreds of unique peaks, many of which cannot be resolved by lower performance mass spectrometers. The high mass accuracy and high mass resolving power allow confident identification of small molecules and lipids directly from biological tissue sections. Here, calibration strategies for FT-ICR MS imaging were investigated. Sub-parts-per-million mass accuracy is demonstrated over an entire tissue section. Ion abundance fluctuations are corrected by addition of total and relative ion abundances for a root-mean-square error of 0.158 ppm on 16,764 peaks. A new approach for visualization of FT-ICR MS imaging data at high resolution is presented. The "Mosaic Datacube" provides a flexible means to visualize the entire mass range at a mass spectral bin width of 0.001 Da. The high resolution Mosaic Datacube resolves spectral features not visible at lower bin widths, while retaining the high mass accuracy from the calibration methods discussed.

  9. 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

  10. 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.

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

    ScienceCinema

    Bowen, Ben

    2016-07-12

    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.

  12. 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.

  13. 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

  14. Exoplanet mass determination using precision imaging astrometry and coronagraphy

    NASA Astrophysics Data System (ADS)

    Bendek, Eduardo; Belikov, Ruslan; Finan, Emily R.; Guyon, Olivier; Pluzhnik, Eugene; Ammons, Stephen

    2017-01-01

    Performing simultaneous high-contrast imaging and astrometry observations of a star increases the detection efficiency and characterization accuracy of single- and multiple- planetary systems around nearby stars. Combining the data generated with both techniques allows solving the Semi-Major Axis, period, and planetary mass in the system faster and more precisely than using imaging or astrometry data separately. In addition, it allows the planetary mass to be measured independently from its brightness, resolving the mass/albedo degeneracy when only direct imaging observations are available. Independent albedo determination allows calibrated planet photometry to be obtained, enabling better atmosphere characterization. To perform both direct imaging and astrometry observations, the telescope requires two instruments: a high-performance coronagraph to perform direct imaging, and a wide field camera astrometry accuracy able to deliver sub-micro arc second astrometry accuracy if earth-like planetary science is pursued. Such accuracy is only possible after calibrating relative distortions between astrometry observations, which at the sub-micro arc second regime dominates the error budget. We propose to utilize a diffractive pupil, in which an array of dots on the primary mirror generates polychromatic diffraction spikes in the focal plane, to calibrate the dynamic distortions of the optical system. In this talk, we present the results of the NASA TDEM effort to demonstrate the diffractive pupil concept on wide-field images while simultaneously performing high-contrast imaging. We also discuss the opportunity that this mission architecture could offer to future probe missions and flagships such as HabEX and LUVOIR.

  15. 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.

  16. 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.

  17. Laser ablation sample transfer for mass spectrometry imaging.

    PubMed

    Park, Sung-Gun; Murray, Kermit K

    2015-01-01

    Infrared laser ablation sample transfer (IR-LAST) is a novel ambient sampling technique for mass spectrometry. In this technique, a pulsed mid-IR laser is used to ablate materials that are collected for mass spectrometry analysis; the material can be a solid sample or deposited on a sample target. After collection, the sample can be further separated or analyzed directly by mass spectrometry. For IR-LAST sample transfer tissue imaging using MALDI mass spectrometry, a tissue section is placed on a sample slide and material transferred to a target slide by scanning the tissue sample under a focused laser beam using transmission-mode (back side) IR laser ablation. After transfer, the target slide is analyzed using MALDI imaging. The spatial resolution is approximately 400 μm and limited by the spread of the laser desorption plume. IR-LAST for MALDI imaging provides several new capabilities including ambient sampling, area to spot concentration of ablated material, multiple ablation and analysis from a single section, and direct deposition on matrix-free nanostructured targets.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Atmospheric pressure molecular imaging by infrared MALDI mass spectrometry.

    PubMed

    Li, Yue; Shrestha, Bindesh; Vertes, Akos

    2007-01-15

    An atmospheric pressure (AP) MALDI imaging interface was developed for an orthogonal acceleration time-of-flight mass spectrometer and utilized to analyze peptides, carbohydrates, and other small biomolecules using infrared laser excitation. In molecular imaging experiments, the spatial distribution of mock peptide patterns was recovered with a detection limit of approximately 1 fmol/pixel from a variety of MALDI matrixes. With the use of oversampling for the image acquisition, a spatial resolution of 40 microm, 5 times smaller than the laser spot size, was achieved. This approach, however, required that the analyte was largely removed at the point of analysis before the next point was interrogated. Native water in plant tissue was demonstrated to be an efficient natural matrix for AP infrared laser desorption ionization. In soft fruit tissues from bananas, grapes, and strawberries, potassiated ions of the most abundant metabolites, small carbohydrates, and their clusters produced the strongest peaks in the spectra. Molecular imaging of a strawberry skin sample revealed the distribution of the sucrose, glucose/fructose, and citric acid species around the embedded seeds. Infrared AP MALDI mass spectrometric imaging without the addition of an artificial matrix enables the in vivo investigation of small biomolecules and biological processes (e.g., metabolomics) in their natural environment.

  4. 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.

  5. 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

  6. 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.

  7. The Solar Mass Ejection Imager (SMEI) Space Experiment

    DTIC Science & Technology

    2015-01-30

    SoloHI for Solar Orbiter [84] and WISPR for Solar Probe Plus [85]) that are scheduled for launch near the end of the decade. In addition, other more...Halain, J- P., and Lamy, P. L., “The Solar and Heliospheric Imager (SoloHI) Instrument for the Solar Orbiter Mission,” Proc. SPIE, 8862, Sep 2013...AFRL-RV-PS- AFRL-RV-PS- TR-2014-0197 TR-2014-0197 THE SOLAR MASS EJECTION IMAGER (SMEI) SPACE EXPERIMENT Richard R. Radick 30 January 2015

  8. Tissue Imaging Using Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Laskin, Julia; Heath, Brandi S.; Roach, Patrick J.; Cazares, Lisa H.; Semmes, O. John

    2012-01-03

    We present the first results showing the ambient imaging of biological samples in their native environment using nanospray desorption ionization (nanoDESI) mass spectrometry. NanoDESI is an ambient pressure ionization technique that enables precise control of ionization of molecules from substrates. We demonstrate highly sensitive and robust analysis of tissue samples with high spatial resolution (<12 {mu}m) without sample preparation, which will be essential for applications in clinical diagnostics, drug discovery, molecular biology, and biochemistry.

  9. 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

  10. Diffusion-weighted magnetic resonance imaging in cystic renal masses

    PubMed Central

    Balyemez, Fikret; Aslan, Ahmet; Inan, Ibrahim; Ayaz, Ercan; Karagöz, Vildan; Özkanli, Sıdıka Şeyma; Acar, Murat

    2017-01-01

    Introduction: We aimed to introduce the diagnostic value of diffusion-weighted (DWI) magnetic resonance imaging (MRI) for distinguishing benign and malignant renal cystic masses. Methods: Abdominal DWI-MRIs of patients with Bosniak categories 2F, 3, and 4 cystic renal masses were evaluated retrospectively. Cystic masses were assigned as benign or malignant according to histopathological or followup MRI findings and compared with apparent diffusion coefficient (ADC) values. Results: There were 30 patients (18 males and 12 females, mean age was 59.23 ± 12.08 years [range 38–83 years]) with cystic renal masses (eight Bosniak category 2F, 12 Bosniak category 3, 10 Bosniak category 4). Among them, 14 cysts were diagnosed as benign and 16 as malignant by followup imaging or histopathological findings. For the malignant lesions, the mean ADC values were lower than for benign lesions (p=0.001). An ADC value of ≤2.28 ×10−6 mm2/s or less had a sensitivity of 75% and a specificity of 92.86% for detecting malignancy. Conclusions: ADC can improve the diagnostic performance of MRI in the evaluation of complex renal cysts when used together with conventional MRI sequences. PMID:28163806

  11. 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.

  12. 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 ...

  13. Toward Digital Staining using Imaging Mass Spectrometry and Random Forests

    PubMed Central

    Hanselmann, Michael; Köthe, Ullrich; Kirchner, Marc; Renard, Bernhard Y.; Amstalden, Erika R.; Glunde, Kristine; Heeren, Ron M. A.; Hamprecht, Fred A.

    2009-01-01

    We show on Imaging Mass Spectrometry (IMS) data that the Random Forest classifier can be used for automated tissue classification and that it results in predictions with high sensitivities and positive predictive values, even when inter-sample variability is present in the data. We further demonstrate how Markov Random Fields and vector-valued median filtering can be applied to reduce noise effects to further improve the classification results in a post-hoc smoothing step. Our study gives clear evidence that digital staining by means of IMS constitutes a promising complement to chemical staining techniques. PMID:19469555

  14. 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.

  15. Is it really organic?--multi-isotopic analysis as a tool to discriminate between organic and conventional plants.

    PubMed

    Laursen, K H; Mihailova, A; Kelly, S D; Epov, V N; Bérail, S; Schjoerring, J K; Donard, O F X; Larsen, E H; Pedentchouk, N; Marca-Bell, A D; Halekoh, U; Olesen, J E; Husted, S

    2013-12-01

    Novel procedures for analytical authentication of organic plant products are urgently needed. Here we present the first study encompassing stable isotopes of hydrogen, carbon, nitrogen, oxygen, magnesium and sulphur as well as compound-specific nitrogen and oxygen isotope analysis of nitrate for discrimination of organically and conventionally grown plants. The study was based on wheat, barley, faba bean and potato produced in rigorously controlled long-term field trials comprising 144 experimental plots. Nitrogen isotope analysis revealed the use of animal manure, but was unable to discriminate between plants that were fertilised with synthetic nitrogen fertilisers or green manures from atmospheric nitrogen fixing legumes. This limitation was bypassed using oxygen isotope analysis of nitrate in potato tubers, while hydrogen isotope analysis allowed complete discrimination of organic and conventional wheat and barley grains. It is concluded, that multi-isotopic analysis has the potential to disclose fraudulent substitutions of organic with conventionally cultivated plants.

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

    NASA Astrophysics Data System (ADS)

    Grieger, Bjoern; Kueppers, Michael

    2016-10-01

    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 %. The conventional approach to estimate the mass of a solar system body through its gravitational effect by tracking the spacecraft trajectory is only marginally viable for Didymos' secondary. Instead, the idea to measure the "wobble" of the primary around the common centre of gravity has been put forward. This wobble with an expected radius of about 10 m can possible be measured either by means of optical or radar ranging devices or by direct observation with the Visual Imaging System (VIS). Here, we investigate the latter approach.We approach the problem of estimating the wobble in two steps: In the first step, the spacecraft trajectory relative to the primary asteroid is reconstructed from the locations of landmarks in images. This relative trajectory comprises the wobble. In the second step, the magnitude of the wobble is extracted from the reconstructed trajectory.In this preliminary investigation, we do not deal with the problem of landmark identification and determination of their location in images. We just randomly generate landmark positions in the body fixed frame employing a shape model based on radar observations and simulate observations as inertial viewing directions from the spacecraft (with some error). Then we solve simultaneously for the landmark positions in the body fixed frame, the orientation of the asteroid at each image acquisition time, and the spacecraft trajectory relative to the asteroid. This reconstruction is done without any a priori knowledge or modelling of spacecraft trajectory or asteroid rotation. In order to extract the wobble from the reconstructed trajectory in the second step, we only assume that we know the period and the direction of the wobble from the orbit of the secondary.We conduct Monte Carlo simulations for various scenarios and assess the accuracy of the determination

  17. Using Multi-Isotopic Analysis To Track The Origin Of NO3 In Groundwater And To Trace Natural Attenuation Processes

    NASA Astrophysics Data System (ADS)

    Otero, N.; Soler, A.

    2008-12-01

    Nitrate pollution has become a major threat to groundwater quality as the maximum nitrate concentration allowed by the European Directive 98/83/CE in waters for human consumption, 50 mg/L, is reached in most of the regional aquifers in Europe. In Catalonia, according to the nitrate directive, nine areas have been declared as vulnerable to nitrate pollution from agricultural sources. Five of these areas have been studied coupling hydro chemical data with a multi-isotopic approach, in an ongoing research project looking for an integrated application of classical hydrochemistry data, with a comprehensive isotopic characterisation (δ15N and δ18O of dissolved nitrate, δ34S and δ18O of dissolved sulphate, δ13C of dissolved inorganic carbon, and δ D and δ18O of water) in order to assess groundwater management in this area. The nitrogen isotopes have allowed to determine the origin of nitrate pollution for the different areas: fertilisers in the Maresme area, animal manure in the Osona and Empordà areas, and a mixed origin in Selva and Garrotxa areas. The coupled use of δ15N and δ18O permitted to determine the existence of denitrification processes (natural attenuation of pollution), and showed that this process is effective in the Osona, Selva and the Empordà areas, but not significant in the Maresme and Garrotxa areas. The multi-isotopic approach, coupling δ15N and δ18O of nitrate, with the isotopic composition of the ions involved in denitrification reactions (δ34S, δ18O, and δ13C ), showed the relationship between sulphide oxidation and nitrate attenuation in the Osona area. In the Empordà and Selva areas, the denitrification is not linked to sulphide oxidation, and organic matter must be the electron donor for denitrification, though further research is needed to confirm the role of organic matter. The observed denitrification processes reveal optional strategies for nitrogen attenuation.

  18. 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

  19. 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

  20. 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.

  1. 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

  2. Protocols for three-dimensional molecular imaging using mass spectrometry.

    PubMed

    Wucher, Andreas; Cheng, Juan; Winograd, Nicholas

    2007-08-01

    A protocol for three-dimensional molecular thin-film analysis is described that utilizes imaging time-of-flight secondary ion mass spectrometry and large-area atomic force microscopy. As a test study, a 300-nm trehalose film deposited on a Si substrate was structured by bombardment with a focused 15-keV Ga+ ion beam and analyzed using a 40-keV C60+ cluster ion beam. A three-dimensional sputter depth profile was acquired as a series of high-resolution lateral SIMS images with intermittent erosion cycles. As the most important result of this study, we find that the structured film exhibits a highly nonuniform erosion rate, thus preventing a simple conversion of primary ion fluence into eroded depth. Instead, the depth scale calibration must be performed individually on each pixel of the imaged area. The resulting laterally resolved depth profiles are discussed in terms of the chemical damage induced by the Ga+ bombardment along with the physics of the C60+ induced erosion process.

  3. MALDI Mass Spectrometry Imaging of Neuronal Cell Cultures

    NASA Astrophysics Data System (ADS)

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

    2011-05-01

    Mass spectrometry imaging (MSI) provides the ability to detect and identify a broad range of analytes and their spatial distributions from a variety of sample types, including tissue sections. Here we describe an approach for probing neuropeptides from sparse cell cultures using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MSI—at single cell spatial resolution—in both MS and tandem MS modes. Cultures of Aplysia californica neurons are grown on an array of glass beads embedded in a stretchable layer of Parafilm M. As the membrane is stretched, the beads/neurons are separated physically and the separated beads/neurons analyzed via MALDI TOF MS. Compared with direct MS imaging of samples, the stretching procedure enhances analyte extraction and incorporation into the MALDI matrix, with negligible analyte spread between separated beads. MALDI tandem MSI using the stretched imaging approach yields localization maps of both parent and fragment ions from Aplysia pedal peptide, thereby confirming peptide identification. This methodology represents a flexible platform for MSI investigation of a variety of cell cultures, including functioning neuronal networks.

  4. 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

  5. Matrix Factorization Techniques for Analysis of Imaging Mass Spectrometry Data

    PubMed Central

    Siy, Peter W.; Moffitt, Richard A.; Parry, R. Mitchell; Chen, Yanfeng; Liu, Ying; Sullards, M. Cameron; Merrill, Alfred H.; Wang, May D.

    2016-01-01

    Imaging mass spectrometry is a method for understanding the molecular distribution in a two-dimensional sample. This method is effective for a wide range of molecules, but generates a large amount of data. It is difficult to extract important information from these large datasets manually and automated methods for discovering important spatial and spectral features are needed. Independent component analysis and non-negative matrix factorization are explained and explored as tools for identifying underlying factors in the data. These techniques are compared and contrasted with principle component analysis, the more standard analysis tool. Independent component analysis and non-negative matrix factorization are found to be more effective analysis methods. A mouse cerebellum dataset is used for testing.

  6. 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.

  7. MALDI imaging mass spectrometry of neuropeptides in Parkinson's disease.

    PubMed

    Hanrieder, Jörg; Ljungdahl, Anna; Andersson, Malin

    2012-02-14

    MALDI imaging mass spectrometry (IMS) is a powerful approach that facilitates the spatial analysis of molecular species in biological tissue samples(2) (Fig.1). A 12 μm thin tissue section is covered with a MALDI matrix, which facilitates desorption and ionization of intact peptides and proteins that can be detected with a mass analyzer, typically using a MALDI TOF/TOF mass spectrometer. Generally hundreds of peaks can be assessed in a single rat brain tissue section. In contrast to commonly used imaging techniques, this approach does not require prior knowledge of the molecules of interest and allows for unsupervised and comprehensive analysis of multiple molecular species while maintaining high molecular specificity and sensitivity(2). Here we describe a MALDI IMS based approach for elucidating region-specific distribution profiles of neuropeptides in the rat brain of an animal model Parkinson's disease (PD). PD is a common neurodegenerative disease with a prevalence of 1% for people over 65 of age(3,4). The most common symptomatic treatment is based on dopamine replacement using L-DOPA(5). However this is accompanied by severe side effects including involuntary abnormal movements, termed L-DOPA-induced dyskinesias (LID)(1,3,6). One of the most prominent molecular change in LID is an upregulation of the opioid precursor prodynorphin mRNA(7). The dynorphin peptides modulate neurotransmission in brain areas that are essentially involved in movement control(7,8). However, to date the exact opioid peptides that originate from processing of the neuropeptide precursor have not been characterized. Therefore, we utilized MALDI IMS in an animal model of experimental Parkinson's disease and L-DOPA induced dyskinesia. MALDI imaging mass spectrometry proved to be particularly advantageous with respect to neuropeptide characterization, since commonly used antibody based approaches targets known peptide sequences and previously observed post-translational modifications. By

  8. MALDI Imaging Mass Spectrometry of Neuropeptides in Parkinson's Disease

    PubMed Central

    Hanrieder, Jörg; Ljungdahl, Anna; Andersson, Malin

    2012-01-01

    MALDI imaging mass spectrometry (IMS) is a powerful approach that facilitates the spatial analysis of molecular species in biological tissue samples2 (Fig.1). A 12 μm thin tissue section is covered with a MALDI matrix, which facilitates desorption and ionization of intact peptides and proteins that can be detected with a mass analyzer, typically using a MALDI TOF/TOF mass spectrometer. Generally hundreds of peaks can be assessed in a single rat brain tissue section. In contrast to commonly used imaging techniques, this approach does not require prior knowledge of the molecules of interest and allows for unsupervised and comprehensive analysis of multiple molecular species while maintaining high molecular specificity and sensitivity2. Here we describe a MALDI IMS based approach for elucidating region-specific distribution profiles of neuropeptides in the rat brain of an animal model Parkinson's disease (PD). PD is a common neurodegenerative disease with a prevalence of 1% for people over 65 of age3,4. The most common symptomatic treatment is based on dopamine replacement using L-DOPA5. However this is accompanied by severe side effects including involuntary abnormal movements, termed L-DOPA-induced dyskinesias (LID)1,3,6. One of the most prominent molecular change in LID is an upregulation of the opioid precursor prodynorphin mRNA7. The dynorphin peptides modulate neurotransmission in brain areas that are essentially involved in movement control7,8. However, to date the exact opioid peptides that originate from processing of the neuropeptide precursor have not been characterized. Therefore, we utilized MALDI IMS in an animal model of experimental Parkinson's disease and L-DOPA induced dyskinesia. MALDI imaging mass spectrometry proved to be particularly advantageous with respect to neuropeptide characterization, since commonly used antibody based approaches targets known peptide sequences and previously observed post-translational modifications. By contrast MALDI

  9. High resolution MALDI imaging mass spectrometry of retinal tissue lipids.

    PubMed

    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.

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

    PubMed Central

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

    2014-01-01

    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. PMID:24819461

  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. 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

    2016-06-09

    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.

  13. 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

  14. 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.

  15. Interkingdom metabolic transformations captured by microbial imaging mass spectrometry

    PubMed Central

    Moree, Wilna J.; Phelan, Vanessa V.; Wu, Cheng-Hsuan; Bandeira, Nuno; Cornett, Dale S.; Duggan, Brendan M.; Dorrestein, Pieter C.

    2012-01-01

    In polymicrobial infections, microbes can interact with both the host immune system and one another through direct contact or the secretion of metabolites, affecting disease progression and treatment options. The thick mucus in the lungs of patients with cystic fibrosis is highly susceptible to polymicrobial infections by opportunistic pathogens, including the bacterium Pseudomonas aeruginosa and the fungus Aspergillus fumigatus. Unravelling the hidden molecular interactions within such polymicrobial communities and their metabolic exchange processes will require effective enabling technologies applied to model systems. In the present study, MALDI-TOF and MALDI-FT-ICR imaging mass spectrometry (MALDI-IMS) combined with MS/MS networking were used to provide insight into the interkingdom interaction between P. aeruginosa and A. fumigatus at the molecular level. The combination of these technologies enabled the visualization and identification of metabolites secreted by these microorganisms grown on agar. A complex molecular interplay was revealed involving suppression, increased production, and biotransformation of a range of metabolites. Of particular interest is the observation that P. aeruginosa phenazine metabolites were converted by A. fumigatus into other chemical entities with alternative properties, including enhanced toxicities and the ability to induce fungal siderophores. This work highlights the capabilities of MALDI-IMS and MS/MS network analysis to study interkingdom interactions and provides insight into the complex nature of polymicrobial metabolic exchange and biotransformations. PMID:22869730

  16. 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.

  17. Magnetic resonance imaging of mass transport and structure inside a phototrophic biofilm.

    PubMed

    Ramanan, Baheerathan; Holmes, William M; Sloan, William T; Phoenix, Vernon R

    2013-05-01

    The aim of this study was to utilize magnetic resonance imaging (MRI) to image structural heterogeneity and mass transport inside a biofilm which was too thick for photon based imaging. MRI was used to map water diffusion and image the transport of the paramagnetically tagged macromolecule, Gd-DTPA, inside a 2.5 mm thick cyanobacterial biofilm. The structural heterogeneity of the biofilm was imaged at resolutions down to 22 × 22 μm, enabling the impact of biofilm architecture on the mass transport of both water and Gd-DTPA to be investigated. Higher density areas of the biofilm correlated with areas exhibiting lower relative water diffusion coefficients and slower transport of Gd-DTPA, highlighting the impact of biofilm structure on mass transport phenomena. This approach has potential for shedding light on heterogeneous mass transport of a range of molecular mass molecules in biofilms.

  18. Tools and strategies for visualization of large image data sets in high-resolution imaging mass spectrometry

    NASA Astrophysics Data System (ADS)

    Klinkert, Ivo; McDonnell, Liam A.; Luxembourg, Stefan L.; Maarten Altelaar, A. F.; Amstalden, Erika R.; Piersma, Sander R.; Heeren, Ron M. A.

    2007-05-01

    Mass spectrometry based proteomics is one of the scientific domains in which experiments produce a large amount of data that need special environments to interpret the results. Without the use of suitable tools and strategies, the transformation of the large data sets into information is not easily achievable. Therefore, in the context of the virtual laboratory of enhanced science, software tools are developed to handle mass spectrometry data sets. Using different data processing strategies for visualization, it enables fast mass spectrometric imaging of large surfaces at high-spatial resolution and thus aids in the understanding of various diseases and disorders. This article describes how to optimize the handling and processing of the data sets, including the selection of the most optimal data formats and the use of parallel processing. It also describes the tools and solutions and their application in mass spectrometric imaging strategies, including new measurement principles, image enhancement, and image artifact suppression.

  19. 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.

  20. 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…

  1. The multi-isotope process monitor: Non-destructive, near-real-time nuclear safeguards monitoring at a reprocessing facility

    NASA Astrophysics Data System (ADS)

    Orton, Christopher Robert

    The IAEA will require advanced technologies to effectively safeguard nuclear material at envisioned large scale nuclear reprocessing plants. This dissertation describes results from simulations and experiments designed to test the Multi-Isotope Process (MIP) Monitor, a novel safeguards approach for process monitoring in reprocessing plants. 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 near-real time (NRT). Three different models were used to predict spent nuclear fuel composition, estimate chemical distribution during separation, and simulate spectra from a variety of gamma detectors in product and raffinate streams for processed fuel. This was done for fuel with various irradiation histories and under a variety of plant operating conditions. Experiments were performed to validate the results from the model. Three segments of commercial spent nuclear fuel with variations in burnup and cooling time were dissolved and subjected to a batch PUREX method to separate the uranium and plutonium from fission and activation products. Gamma spectra were recorded by high purity germanium (HPGe) and cadmium zinc telluride (CZT) detectors. Hierarchal Cluster Analysis (HCA) and Principal Component Analysis (PCA) were applied to spectra from both model and experiment to investigate spectral variations as a function of acid concentration, burnup level and cooling time. Partial Least Squares was utilized to extract quantitative information about process variables, such as acid concentration or burnup. The MIP Monitor was found to be sensitive to the induced variations of the process and was capable of extracting quantitative process information from the analyzed spectra.

  2. 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.

  3. 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 ...

  4. 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

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

    SciTech Connect

    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.

  6. 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

  7. 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

  8. Disentangling the complexity of nitrous oxide cycling in coastal sediments: Results from a novel multi-isotope approach

    NASA Astrophysics Data System (ADS)

    Wankel, S. D.; Buchwald, C.; Charoenpong, C.; Ziebis, W.

    2014-12-01

    with water in influencing the O isotope composition of N2O from the sediment-water interface. A steady-state multi-isotope flux model will help to constraining rates and isotope effects of these processes and improve our understanding of the dynamics and pathways of N2O production and emission under varying scenarios of environmental change.

  9. An Image Morphing Technique Based on Optimal Mass Preserving Mapping

    DTIC Science & Technology

    2007-06-01

    Yan Yang, Steven Haker , and Allen Tannenbaum Abstract—Image morphing, or image interpolation in the time domain, deals with the metamorphosis of one...of Technology, Atlanta, GA 30332 USA (e-mail: zlzl@ece.gatech.edu; zhulei1976@hotmail.com; yan.yang@gatech.edu; tannenba@ece.gatech.edu). S. Haker is...with the Surgical Planning Laboratory, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115 USA (e-mail: haker @bwh.harvard.edu

  10. 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…

  11. Diagnostic value of magnetic resonance imaging and computed tomography for oral masses in dogs.

    PubMed

    Kafka, U C M; Carstens, A; Steenkamp, G; Symington, H

    2004-12-01

    The purpose of this study was to determine the diagnostic value of magnetic resonance imaging (MRI) and computed tomography (CT) in oral masses of dogs. Nineteen dogs underwent clinical, MR and CT examinations. Eleven malignant and ten non-malignant masses were evaluated. Osteosarcoma was the most commonly found malignant oral mass and gingival hyperplasia was the most commonly found benign mass. The results showed that MRI provided more accurate information regarding the size of the masses and invasion of adjacent structures although MRI and CT show similar accuracy in assessment of bone invasion. Calcification and cortical bone erosion was better seen on CT images. Whereas contrast-MRI provided useful additional information, contrast-CT had no added benefit. In general, oral masses located in the caudal mandible, oropharynx and maxilla are better evaluated using MRI, once the histological type has been verified.

  12. 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…

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

    DOE PAGES

    Ovchinnikova, Olga S.; Tai, Tamin; Bocharova, Vera; ...

    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

  14. 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.

  15. Secondary Ion Mass Spectrometry Imaging of Tissues, Cells, and Microbial Systems

    PubMed Central

    Gamble, Lara J.; Anderton, Christopher R.

    2016-01-01

    Secondary ion mass spectrometry (SIMS) is a technique capable of imaging tissues, single cells, and microbes revealing chemical species with sub-micrometer spatial resolution. The recently developed Fourier transform ion cyclotron resonance (FTICR) SIMS instrument provides high mass resolving power and mass accuracy, ToF-SIMS can generate chemical maps with an order of magnitude better lateral resolution than the FTICR-SIMS, and the NanoSIMS instrument offers sub-100 nm spatial resolution in chemical imaging. Many commercial ToF-SIMS instruments are also capable of depth profiling that allows three-dimensional reconstructions of cell and tissue structure. PMID:27660591

  16. Adrenal masses of varied etiology: anatomical and molecular imaging features on PET-CT.

    PubMed

    Sharma, Punit; Singh, Harmandeep; Dhull, Varun Singh; Suman KC, Sudhir; Kumar, Abhishek; Bal, Chandrasekhar; Kumar, Rakesh

    2014-03-01

    A wide spectrum of benign and malignant diseases can present as an adrenal mass. Combined PET-CT is useful for evaluation of adrenocortical and adrenomedullary masses. F-FDG has been extensively used as PET radiotracer for this purpose. F-FDOPA PET, Ga-DOTA peptide (Ga-DOTANOC/TATE) PET, and C-HED PET have also been used for imaging of adrenal medullary lesions, whereas C-MTO PET has been used for adrenocortical imaging. We provide a review of imaging characteristics of adrenal gland pathologies on PET-CT using different tracers.

  17. Quantifying Stellar Mass Loss with High Angular Resolution Imaging

    DTIC Science & Technology

    2009-02-19

    material – via massive winds, planetary nebulae and supernova explosions – seeding the interstellar medium with heavier elements. Subsequent...of Planetary Nebulae (Harpaz, ApJ, 498,293, (1998)), impacts the pre-explosion characteristic of SNII (Taylor, “The Stars”, Cambridge (1994)), and...A 464, 119) or may have an important role, such as Be Stars, W-R stars, and planetary nebulae . The Future of Interferometric O/IR Imaging. The

  18. Characterizing sources and natural attenuation of nitrate contamination in the Baix Ter aquifer system (NE Spain) using a multi-isotope approach.

    PubMed

    Puig, Roger; Soler, Albert; Widory, David; Mas-Pla, Josep; Domènech, Cristina; Otero, Neus

    2017-02-15

    Nitrate pollution is a widespread issue affecting global water resources with significant economic and health effects. Knowledge of both the corresponding pollution sources and of processes naturally attenuating them is thus of crucial importance in assessing water management policies and the impact of anthropogenic activities. In this study, an approach combining hydrodynamic, hydrochemical and multi-isotope systematics (8 isotopes) is used to characterize the sources of nitrate pollution and potential natural attenuation processes in a polluted basin of NE Spain. δ(2)H and δ(18)O isotopes were used to further characterize the sources of recharge of the aquifers. Results show that NO3(-) is not homogeneously distributed and presents a large range of concentrations, from no NO3(-) to up to 480mgL(-1). δ(15)N and δ(18)O of dissolved NO3(-) identified manure as the main source of nitrate, although sewage and mineral fertilizers can also be isotopically detected using boron isotopes (δ(11)B) and δ(34)S and δ(18)O of dissolved sulphate, respectively. The multi-isotope approach proved that natural denitrification is occurring, especially in near-river environments or in areas hydrologically related to fault zones. δ(34)S and δ(18)O indicated that denitrification is not driven by pyrite oxidation but rather by the oxidation of organic matter. This could not be confirmed by the study of δ(13)CHCO3 that was buffered by the entanglement of other processes and sources.

  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. Retrospective sputter depth profiling using 3D mass spectral imaging.

    PubMed

    Zheng, Leiliang; Wucher, Andreas; Winograd, Nicholas

    2011-02-01

    A molecular multilayer stack composed of alternating Langmuir-Blodgett films was analyzed by ToF-SIMS imaging in combination with intermediate sputter erosion using a focused C60(+) cluster ion beam. From the resulting dataset, depth profiles of any desired lateral portion of the analyzed field-of-view can be extracted in retrospect, allowing the influence of the gating area on the apparent depth resolution to be assessed. In a similar way, the observed degradation of depth resolution with increasing depth of the analyzed interface can be analyzed in order to determine the 'intrinsic' depth resolution of the method.

  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. 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

  4. Large-scale inhomogeneity in sapphire test masses revealed by Rayleigh scattering imaging

    NASA Astrophysics Data System (ADS)

    Yan, Zewu; Ju, Li; Eon, François; Gras, Slawomir; Zhao, Chunnong; Jacob, John; Blair, David G.

    2004-03-01

    Rayleigh scattering in test masses can introduce noise and reduce the sensitivity of laser interferometric gravitational wave detectors. In this paper, we present laser Rayleigh scattering imaging as a technique to investigate sapphire test masses. The system provides three-dimensional Rayleigh scattering mapping of entire test masses and quantitative evaluation of the Rayleigh scattering coefficient. Rayleigh scattering mapping of two sapphire samples reveals point defects as well as inhomogeneous structures in the samples. We present results showing significant non-uniform scattering within two 4.5 kg sapphire test masses manufactured by the heat exchanger method.

  5. Analysis of shear strain imaging for classifying breast masses: Finite element and phantom results

    PubMed Central

    Xu, Haiyan; Varghese, Tomy; Madsen, Ernest L.

    2011-01-01

    Purpose: Features extracted from axial-shear strain images of breast masses have been previously utilized to differentiate and classify benign from malignant breast masses. In this paper, we compare shear strain patterns exhibited by both the full-shear (axial and lateral component) versus only the axial-shear strain component for differentiating between bound masses (malignant) when compared to unbound masses (benign). Methods: We examine different breast mass characteristics such as mass shape, asymmetric location of masses, stiffness variations, and mass bonding characteristics to background tissue to assess their impact on shear strain patterns generated due to a uniaxial applied deformation. Two-dimensional finite element simulations of both circular and elliptical inclusions embedded within a uniform background were utilized. Different degrees of bonding were characterized using friction coefficient values ranging from 0.01 to 100 denoting loosely bound to firmly bound masses. Single-inclusion tissue-mimicking phantoms mimicking firmly bound and loosely bound ellipsoidal masses oriented at four different angles to the applied deformation were studied to corroborate the mass differentiation performance. Results: Our results indicate that the normalized axial-shear strain and full-shear strain area features are larger for bound when compared to unbound masses. A higher stiffness ratio or contrast between the inclusion and background also improves differentiation. Larger applied deformations reduce the discrimination performance for masses with friction coefficients lower than 0.4, due to increased mass slippage with applied deformations. Potential errors with the use of these features would occur for unbound inclusions at larger applied deformations and for asymmetric mass positions within the background normal tissue. Conclusions: Finite element and tissue-mimicking phantom results demonstrate the feasibility of utilizing both the normalized axial-shear and

  6. 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

  7. Diagnostic imaging of benign and malignant neck masses in children—a pictorial review

    PubMed Central

    Harave, Srikrishna

    2016-01-01

    Neck masses are frequently encountered in pediatric medicine, and can present a diagnostic dilemma for the clinicians involved. There are several means by which neck masses in children can be subdivided, for example by age at presentation, anatomical location including compartments and fascia of the neck, their classical appearance when imaged, or by etiology. When imaging children the clinicians must be mindful of radiation exposure and as such ultrasound (US) is often attempted first. Cross sectional imaging can be helpful for problem solving with CT being particularly useful for assessing the patient in more acute scenarios, for example when there is airway compromise. Nuclear medicine scintigraphy has a role in specific circumstances and can aid in staging in the presence of malignancy. If required, additional acquisition by means of magnetic resonance imaging (MRI) and computed tomography (CT) can be considered. This pictorial review describe the diagnostic imaging of (I) congenital and Developmental Pathologies, including thyroglossal duct cyst, branchial cleft cyst, cystic hygroma, dermoid cyst, thymic cyst and ectopic thymus; (II) neoplastic lesions, including hemangiomas and vascular malformations, pilomatrixoma, neurofibroma, neuroblastoma, rhabdomyosarcoma, papillary thyroid cancer, lymphoma & leukemia; (III) neck masses of Infective causes, including lymphadenitis, retropharyngeal and peritonsilar abscess, salivary gland inflammation; and (IV) other miscellaneous lesions, including ranula, sternocleidomastoid fibromatosis coli, and goiter. Neck masses are common in the pediatric population with a broad and varied differential; malignant etiologies are less frequently encountered when compared with adults but an awareness of its potential is important when reviewing imaging. PMID:27942480

  8. MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

    PubMed

    Hinsch, Andrea; Buchholz, Malte; Odinga, Sinje; Borkowski, Carina; Koop, Christina; Izbicki, Jacob R; Wurlitzer, Marcus; Krech, Till; Wilczak, Waldemar; Steurer, Stefan; Jacobsen, Frank; Burandt, Eike-Christian; Stahl, Phillip; Simon, Ronald; Sauter, Guido; Schlüter, Hartmut

    2017-01-24

    For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer we applied MALDI imaging mass spectrometry (IMS) to a tissue micro array (TMA) containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. 15 out of 27 IMS signals revealed a significant association with survival. For 7 signals (m/z 654, 776, 788, 904, 944, 975, and 1013) the absence, and for 8 signals (m/z 643, 678, 836, 886, 898, 1095, 1459, and 1477) the presence was associated with decreased life expectancy, including 5 masses (m/z 788, 836, 904, 944, and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these 5 masses resulted in a 3-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis, and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale TMAs to simultaneously identify and validate clinically useful molecular marker.

  9. 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.

  10. 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.

  11. WFC3-IR Imaging of Dense, Embedded Outflows from Intermediate-Mass Protostars in Carina

    NASA Astrophysics Data System (ADS)

    Smith, Nathan

    2013-10-01

    Based on H-alpha imaging of the Carina Nebula with ACS, we discovered 40 new Herbig-Haro {HH} jets marking outflows from young stars. This is valuable because {1} it is a large sample of jets at one distance, {2} the driving sources are intermediate-mass {IM} stars {1-8 Msun}, allowing us to investigate the bridge between low- and high-mass star formation, and {3} the jets are exposed to the same feedback source and trace various stages of being uncovered by the advancing ionization front. This sample is all the more valuable because it can be placed in the context of a well-understood environment that has been studied extensively with HST, Spitzer, Chandra, and from the ground. We propose to image 13 of these jets in the [Fe II] 1.26-micron and 1.64-micron lines. These lines suffer less extincton than optical lines, trace embedded jets, and are essential to measure the total mass in these dense outflows. Four jets have already been imaged in the F126N and F164N filters to make public release images; these images demonstrate that [FeII] emission traces a large mass of neutral gas not seen in H-alpha emission and traces the jet back into the cloud to the Spitzer-identified driving source. This study will permit a detailed comparison of the jet properties {e.g. mass-loss rate, momentum injection, mass-loss history} to IM protostar properties {e.g. accretion rate, luminosity, envelope mass and structure} during the most active accretion. These relationships are poorly determined for IM protostars. Additionally, the flux ratio of [Fe II] lines will trace the spatially dependent extinction through the cloud, providing a map of the density structure in the extended envelope.

  12. Application of imaging mass spectrometry approaches to facilitate metal-based anticancer drug research.

    PubMed

    Lee, Ronald F S; Theiner, Sarah; Meibom, Anders; Koellensperger, Gunda; Keppler, Bernhard K; Dyson, Paul J

    2017-02-03

    Mass spectrometry imaging is being increasingly used in metal-based anticancer drug development to study elemental and/or molecular drug distributions in different biological systems. The main analytical tools employed are SIMS (especially nanoSIMS), LA-ICP-MSI and MALDI-MSI as well as a combination of complementary imaging techniques. Main challenges are appropriate sample preparation methods, reliable and validated quantification strategies and a trade-off between sensitivity and spatial resolution. So far, research has mostly focused on the development of analytical methods for imaging with the long term goal to study drug uptake into tumor tissue and toxicity affected organs and to identify cellular targets of metal-based drugs. In this review we cover the technological features of the mass spectrometry imaging methods used and give an overview of the applications in metal-based anticancer drug research as well as some future perspectives.

  13. 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.

  14. 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

  15. Development of capabilities for imaging mass spectrometry under ambient conditions with desorption electrospray ionization (DESI)

    NASA Astrophysics Data System (ADS)

    Ifa, Demian R.; Wiseman, Justin M.; Song, Qingyu; Cooks, R. Graham

    2007-01-01

    Aspects of the development of mass spectrometry over the past three decades are briefly reviewed and growth points in the subject are identified. Molecular imaging by mass spectrometry is one such growth area. The development of a capability for 2D chemical imaging of surfaces is described, based on the combination of a desorption electrospray ionization (DESI) ion source with an automated surface stage capable of x, y translational motion. The lateral resolution of this new system is found to be less than 200 microns, using a test ink pattern. Chemical imaging of surfaces is demonstrated using model examples of organic and biological systems: (i) imaging of a 2D pattern written in different colored inks on photographic paper and (ii) imaging of thin coronal sections of rat brain tissue fixed onto a glass microscope slide. In both cases, full mass spectra are recorded as a function of x,y-position on the surface. In the chemical imaging example, the distributions of the two different inks on the paper surface were mapped by tracking the abundance of the intact organic cation which characterizes each particular ink dye. In the tissue imaging example, distributions of specific lipids in coronal sections of rat brain tissue were followed from the abundance distributions in 2D space of the deprotonated lipid molecules recorded in the negative ion mass spectra. These latter distributions reveal distinct anatomical features of the rat brain. The results of these studies demonstrate the feasibility of performing surface imaging studies using DESI and show that at this stage of its development it has a lateral spatial resolution of a few hundred microns.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. Mass spectrometry imaging of cassette-dosed drugs for higher throughput pharmacokinetic and biodistribution analysis.

    PubMed

    Swales, John G; Tucker, James W; Strittmatter, Nicole; Nilsson, Anna; Cobice, Diego; Clench, Malcolm R; Mackay, C Logan; Andren, Per E; Takáts, Zoltán; Webborn, Peter J H; Goodwin, Richard J A

    2014-08-19

    Cassette dosing of compounds for preclinical drug plasma pharmacokinetic analysis has been shown to be a powerful strategy within the pharmaceutical industry for increasing throughput while decreasing the number of animals used. Presented here for the first time is data on the application of a cassette dosing strategy for label-free tissue distribution studies. The aim of the study was to image the spatial distribution of eight nonproprietary drugs (haloperidol, bufuralol, midazolam, clozapine, terfenadine, erlotinib, olanzapine, and moxifloxacin) in multiple tissues after oral and intravenous cassette dosing (four compounds per dose route). An array of mass spectrometry imaging technologies, including matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI), liquid extraction surface analysis tandem mass spectrometry (LESA-MS/MS), and desorption electrospray ionization mass spectrometry (DESI-MS) was used. Tissue analysis following intravenous and oral administration of discretely and cassette-dosed compounds demonstrated similar relative abundances across a range of tissues indicating that a cassette dosing approach was applicable. MALDI MSI was unsuccessful in detecting all of the target compounds; therefore, DESI MSI, a complementary mass spectrometry imaging technique, was used to detect additional target compounds. In addition, by adapting technology used for tissue profiling (LESA-MS/MS) low spatial resolution mass spectrometry imaging (∼1 mm) was possible for all targets across all tissues. This study exemplifies the power of multiplatform MSI analysis within a pharmaceutical research and development (R&D) environment. Furthermore, we have illustrated that the cassette dosing approach can be readily applied to provide combined, label-free pharmacokinetic and drug distribution data at an early stage of the drug discovery/development process while minimizing animal usage.

  1. 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.

  2. Combined X-ray CT and mass spectrometry for biomedical imaging applications

    NASA Astrophysics Data System (ADS)

    Schioppa, E., Jr.; Ellis, S.; Bruinen, A. L.; Visser, J.; Heeren, R. M. A.; Uher, J.; Koffeman, E.

    2014-04-01

    Imaging technologies play a key role in many branches of science, especially in biology and medicine. They provide an invaluable insight into both internal structure and processes within a broad range of samples. There are many techniques that allow one to obtain images of an object. Different techniques are based on the analysis of a particular sample property by means of a dedicated imaging system, and as such, each imaging modality provides the researcher with different information. The use of multimodal imaging (imaging with several different techniques) can provide additional and complementary information that is not possible when employing a single imaging technique alone. In this study, we present for the first time a multi-modal imaging technique where X-ray computerized tomography (CT) is combined with mass spectrometry imaging (MSI). While X-ray CT provides 3-dimensional information regarding the internal structure of the sample based on X-ray absorption coefficients, MSI of thin sections acquired from the same sample allows the spatial distribution of many elements/molecules, each distinguished by its unique mass-to-charge ratio (m/z), to be determined within a single measurement and with a spatial resolution as low as 1 μm or even less. The aim of the work is to demonstrate how molecular information from MSI can be spatially correlated with 3D structural information acquired from X-ray CT. In these experiments, frozen samples are imaged in an X-ray CT setup using Medipix based detectors equipped with a CO2 cooled sample holder. Single projections are pre-processed before tomographic reconstruction using a signal-to-thickness calibration. In the second step, the object is sliced into thin sections (circa 20 μm) that are then imaged using both matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and secondary ion (SIMS) mass spectrometry, where the spatial distribution of specific molecules within the sample is determined. The

  3. IMAGE-PLANE ANALYSIS OF n-POINT-MASS LENS CRITICAL CURVES AND CAUSTICS

    SciTech Connect

    Danek, Kamil; Heyrovský, David E-mail: heyrovsky@utf.mff.cuni.cz

    2015-06-10

    The interpretation of gravitational microlensing events caused by planetary systems or multiple stars is based on the n-point-mass lens model. The first planets detected by microlensing were well described by the two-point-mass model of a star with one planet. By the end of 2014, four events involving three-point-mass lenses had been announced. Two of the lenses were stars with two planetary companions each; two were binary stars with a planet orbiting one component. While the two-point-mass model is well understood, the same cannot be said for lenses with three or more components. Even the range of possible critical-curve topologies and caustic geometries of the three-point-mass lens remains unknown. In this paper we provide new tools for mapping the critical-curve topology and caustic cusp number in the parameter space of n-point-mass lenses. We perform our analysis in the image plane of the lens. We show that all contours of the Jacobian are critical curves of re-scaled versions of the lens configuration. Utilizing this property further, we introduce the cusp curve to identify cusp-image positions on all contours simultaneously. In order to track cusp-number changes in caustic metamorphoses, we define the morph curve, which pinpoints the positions of metamorphosis-point images along the cusp curve. We demonstrate the usage of both curves on simple two- and three-point-mass lens examples. For the three simplest caustic metamorphoses we illustrate the local structure of the image and source planes.

  4. MALDI-TOF imaging mass spectrometry of artifacts in "dried droplet" polymer samples.

    PubMed

    Weidner, Steffen; Knappe, Patrick; Panne, Ulrich

    2011-07-01

    Matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) imaging of polystyrenes with various molecular masses was applied to study spatial molecular mass distribution of polymers in sample spots prepared by the "dried droplet" method. When different solvents and target surfaces were examined, a segregation of single homologous polymers was observed depending upon the evaporation rate of the solvent. For the observed patterns left by the evaporating droplet, a hypothesis is offered taking into account different hydrodynamic interactions and diffusion. The results illustrate that spot preparation using the conventionally "dried droplet" method is prone to artifacts and should be avoided for reliable and reproducible MALDI mass spectrometry experiments with regards to the determination of molecular masses and mass distributions.

  5. 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

  6. Complementarity of MALDI and LA ICP mass spectrometry for platinum anticancer imaging in human tumor.

    PubMed

    Bianga, Juliusz; Bouslimani, Amina; Bec, Nicole; Quenet, François; Mounicou, Sandra; Szpunar, Joanna; Bouyssiere, Brice; Lobinski, Ryszard; Larroque, Christian

    2014-08-01

    The follow-up of the Heated Intraoperative Chemotherapy (HIPEC) of peritoneal carcinomatosis would benefit from the monitoring of the penetration, distribution and metabolism of the drug within the tumor. As tumor nodules can be resected during the therapy, mass spectrometry imaging is a suitable tool for the evaluation of treatment efficacy, and, as a result, the therapy can be re-optimized. In this work we demonstrate the complementarity of laser ablation (LA) ICP mass spectrometry and MALDI imaging to study the penetration and distribution of two Pt-based metallodrugs (cisplatin and oxaliplatin) in human tumor samples removed from patients diagnosed with colorectal or ovarian peritoneal carcinomatosis. LA ICP MS offered sensitive (LOD for (195)Pt 4.8 pg s(-1)) imaging of platinum quasi-independently of the original species and the sample matrix and thus an ultimate way of verifying the penetration of the Pt-containing drug or its moieties into the tumor. MALDI imaging was found to suffer in some cases from signal suppression by the matrix leading to false negatives. In the case of the oxaliplatin metallodrug, the results obtained from ICP and MALDI MS imaging were coherent whereas in the case of cisplatin, species detected by ICP MS imaging could not be validated by MALDI MS. The study is the first application of the dual ICP and MALDI MS imaging to the follow-up of metallodrugs in human tumors.

  7. Quantification of left ventricular mass using cardiac magnetic resonance imaging compared with echocardiography in domestic cats.

    PubMed

    MacDonald, Kristin A; Kittleson, Mark D; Reed, Tracy; Larson, Richard; Kass, Philip; Wisner, Erik R

    2005-01-01

    The hypotheses were that cardiac magnetic resonance imaging (cMRI) would accurately determine LV mass in domestic cats and would do so more accurately than echocardiography (ECHO). ECHO was performed on seven sedated cats. LV mass was calculated using the truncated ellipse formula from a right parasternal long-axis view. T1 weighted gradient echo cMRI was acquired from anesthetized cats during multiple phases of the cardiac cycle. Short-axis images were obtained by acquiring 3 mm thick contiguous slices perpendicular to the cardiac long axis. LV mass was determined using Simpson's rule. Endocardial and epicardial borders were traced on each slice at end-systole, end-diastole, and mid-cycle and the difference in areas was myocardial area. Myocardial area was multiplied by slice thickness to calculate myocardial volume. Total (summated) myocardial volume was multiplied by myocardial density (1.05) to obtain LV mass at three measured phases of the cardiac cycle. Cats were euthanized and the LV was dissected and weighed to determine true mass. CMRI at end-systole most accurately quantified LV mass and was more accurate than echocardiography (P = 0.0078). Actual LV mass ranged from 6.5 to 10.5 g (mean = 8.5 g, SD = 1.6 g) compared with MRI LV mass at end-systole, which ranged from 6.7 to 11.1 g (mean = 8.7 g, SD = 1.7 g) and echocardiographic LV mass at enddiastole, which ranged from 5.2 to 9.1 g (mean= 7.1 g, SD = 1.8 g). Inter- and intraobserver variability for cMRI was 2%. CMRI obtained at end-systole accurately and reliably quantifies LV mass in domestic cats. It is more accurate than the echocardiographic method used in this study.

  8. Matrix Sublimation/Recrystallization for Imaging Proteins by Mass Spectrometry at High Spatial Resolution

    PubMed Central

    Yang, Junhai; Caprioli, Richard M.

    2011-01-01

    We have employed matrix deposition by sublimation for protein image analysis on tissue sections using a hydration/recrystallization process that produces high quality MALDI mass spectra and high spatial resolution ion images. We systematically investigated different washing protocols, the effect of tissue section thickness, the amount of sublimated matrix per unit area and different recrystallization conditions. The results show that an organic solvent rinse followed by ethanol/water rinses substantially increased sensitivity for the detection of proteins. Both the thickness of tissue section and amount of sinapinic acid sublimated per unit area have optimal ranges for maximal protein signal intensity. Ion images of mouse and rat brain sections at 50, 20 and 10 µm spatial resolution are presented and are correlated with H&E stained optical images. For targeted analysis, histology directed imaging can be performed using this protocol where MS analysis and H&E staining are performed on the same section. PMID:21639088

  9. Abdominal masses in children: multiorgan imaging with /sup 99m/Tc methylene diphosphonate

    SciTech Connect

    Siddiqui, A.R.; Cohen, M.; Moran, D.P.

    1982-07-01

    /sup 99m/Tc methylene diphosphonate (/sup 99m/Tc MDP) imaging was performed in 29 consecutive children with abdominal masses. Dynamic images of the inferior vena cava were obtained by injecting the radiotracer in the feet. Serial renal images were obtained for the next 30 min. Routine bone imaging was performed at about 3 hr. The radionuclide studies of the inferior vena cava accurately diagnosed total obstruction and displacement to the left but not partial obstruction and displacement to the right. The abnormalities on early renal imaging included displacement (14), distortion (seven), obstruction (eight), and nonvisualization (one). All patients with Wilms tumor (eight) had either nonvisualized or distorted renal parenchyma. Patients with neuroblastoma (17) and other tumors (four) had displacement and obstruction. Soft-tissue accumulation of /sup 99m/Tc MDP was noted in two Wilms tumors and 12 neuroblastomas.

  10. 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.

  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. 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...

  13. Air flow-assisted ionization imaging mass spectrometry method for easy whole-body molecular imaging under ambient conditions.

    PubMed

    Luo, Zhigang; He, Jiuming; Chen, Yi; He, Jingjing; Gong, Tao; Tang, Fei; Wang, Xiaohao; Zhang, Ruiping; Huang, Lan; Zhang, Lianfeng; Lv, Haining; Ma, Shuanggang; Fu, Zhaodi; Chen, Xiaoguang; Yu, Shishan; Abliz, Zeper

    2013-03-05

    Whole-body molecular imaging is able to directly map spatial distribution of molecules and monitor its biotransformation in intact biological tissue sections. Imaging mass spectrometry (IMS), a label-free molecular imaging method, can be used to image multiple molecules in a single measurement with high specificity. Herein, a novel easy-to-implement, whole-body IMS method was developed with air flow-assisted ionization in a desorption electrospray ionization mode. The developed IMS method can effectively image molecules in a large whole-body section in open air without sample pretreatment, such as chemical labeling, section division, or matrix deposition. Moreover, the signal levels were improved, and the spatial assignment errors were eliminated; thus, high-quality whole-body images were obtained. With this novel IMS method, in situ mapping analysis of molecules was performed in adult rat sections with picomolar sensitivity under ambient conditions, and the dynamic information of molecule distribution and its biotransformation was provided to uncover molecular events at the whole-animal level. A global view of the differential distribution of an anticancer agent and its metabolites was simultaneously acquired in whole-body rat and model mouse bearing neuroglioma along the administration time. The obtained drug distribution provided rich information for identifying the targeted organs and predicting possible tumor spectrum, pharmacological activity, and potential toxicity of drug candidates.

  14. Classification of breast masses by ultrasonic Nakagami imaging: a feasibility study.

    PubMed

    Tsui, Po-Hsiang; Yeh, Chih-Kuang; Chang, Chien-Cheng; Liao, Yin-Yin

    2008-11-07

    Ultrasound is an important clinical tool in noninvasive diagnoses of breast cancer. The Nakagami statistical parameter estimated from the ultrasonic backscattered envelope has been demonstrated to be useful in complementing conventional B-mode scans when classifying breast masses. However, the shadowing effect caused by certain high-attenuation tumors in the B-mode image makes the tumor contour unclear, and thus it is more difficult to choose an appropriate region of interest from which to collect tumor data for estimating the Nakagami parameter. This study explored the feasibility of using the Nakagami parametric image to overcome the shadowing effect for visualizing the properties of breast masses. Experiments were performed on a breast-mimicking phantom and on some typical clinical cases for cysts, fat and tumors (fibroadenoma) (n = 18) in order to explore the performance of the Nakagami image under ideal and practical conditions. The experimental results showed that the Nakagami image pixels (i.e. the local Nakagami parameter) in the cyst, tumor and fat are 0.21 +/- 0.01, 0.65 +/- 0.05 and 0.98 +/- 0.07, respectively, for six independent phantom measurements, and 0.14 +/- 0.03, 0.67 +/- 0.11 and 0.89 +/- 0.08, respectively, for clinical experiments. This suggests that the Nakagami image is able to classify various breast masses (p < 0.005) although the clinical results from tumors of different cases have a larger variance that may be caused by the complexity of real breast tissues. In particular, unlike the B-mode image, the Nakagami image is not subject to significant shadowing effects, making it useful to complement the B-mode image to describe the tumor contour for identifying the tumor-related region when the shadowing effect is stronger or a low system gain is used.

  15. Classification of breast masses by ultrasonic Nakagami imaging: a feasibility study

    NASA Astrophysics Data System (ADS)

    Tsui, Po-Hsiang; Yeh, Chih-Kuang; Chang, Chien-Cheng; Liao, Yin-Yin

    2008-11-01

    Ultrasound is an important clinical tool in noninvasive diagnoses of breast cancer. The Nakagami statistical parameter estimated from the ultrasonic backscattered envelope has been demonstrated to be useful in complementing conventional B-mode scans when classifying breast masses. However, the shadowing effect caused by certain high-attenuation tumors in the B-mode image makes the tumor contour unclear, and thus it is more difficult to choose an appropriate region of interest from which to collect tumor data for estimating the Nakagami parameter. This study explored the feasibility of using the Nakagami parametric image to overcome the shadowing effect for visualizing the properties of breast masses. Experiments were performed on a breast-mimicking phantom and on some typical clinical cases for cysts, fat and tumors (fibroadenoma) (n = 18) in order to explore the performance of the Nakagami image under ideal and practical conditions. The experimental results showed that the Nakagami image pixels (i.e. the local Nakagami parameter) in the cyst, tumor and fat are 0.21 ± 0.01, 0.65 ± 0.05 and 0.98 ± 0.07, respectively, for six independent phantom measurements, and 0.14 ± 0.03, 0.67 ± 0.11 and 0.89 ± 0.08, respectively, for clinical experiments. This suggests that the Nakagami image is able to classify various breast masses (p < 0.005) although the clinical results from tumors of different cases have a larger variance that may be caused by the complexity of real breast tissues. In particular, unlike the B-mode image, the Nakagami image is not subject to significant shadowing effects, making it useful to complement the B-mode image to describe the tumor contour for identifying the tumor-related region when the shadowing effect is stronger or a low system gain is used.

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. Bilateral ectopic cervical thymus presenting as a neck mass: Ultrasound and magnetic resonance imaging.

    PubMed

    Tanrivermis Sayit, Asli; Elmali, Muzaffer; Hashimov, Jalal; Ceyhan Bilgici, Meltem; Dağdemir, Ayhan

    2016-09-01

    Ectopic cervical thymus (ECT) is a rare cause of neck mass in the pediatric age group. It is extremely uncommon in infants. Overall more than 100 cases have been reported in the literature, though fewer than 10% involved infants. Furthermore, ECT is usually unilateral and more frequently seen in men than in women. Ultrasound (US) is the preferred initial imaging modality, especially in pediatric neck masses given its wide availability, low cost and lack of radiation exposure. US can show the location, extension, and echotexture of the ECT. Magnetic resonance imaging (MRI) can be performed to verify the diagnosis and confirm communication between the ECT and the mediastinal thymus. Diffusion restriction can aid diagnosis when seen in a neck mass similar to that in the mediastinal thymus. Herein is described a case of bilateral ECT in a 2-month-old boy with associated US and MRI findings.

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

    PubMed Central

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

    2012-01-01

    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. PMID:22869296

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Uncertainties and biases of source masses derived from fits of integrated fluxes or image intensities

    NASA Astrophysics Data System (ADS)

    Men'shchikov, A.

    2016-09-01

    Fitting spectral distributions of total fluxes or image intensities are two standard methods for estimating the masses of starless cores and protostellar envelopes. These mass estimates, which are the main source and basis of our knowledge of the origin and evolution of self-gravitating cores and protostars, are uncertain. It is important to clearly understand sources of statistical and systematic errors stemming from the methods and minimize the errors. In this model-based study, a grid of radiative transfer models of starless cores and protostellar envelopes was computed and their total fluxes and image intensities were fitted to derive the model masses. To investigate intrinsic effects related to the physical objects, all observational complications were explicitly ignored. Known true values of the numerical models allow assessment of the qualities of the methods and fitting models, as well as the effects of nonuniform temperatures, far-infrared opacity slope, selected subsets of wavelengths, background subtraction, and angular resolutions. The method of fitting intensities gives more accurate masses for more resolved objects than the method of fitting fluxes. With the latter, a fitting model that assumes optically thin emission gives much better results than the one allowing substantial optical depths. Temperature excesses within the objects above the mass-averaged values skew their spectral shapes towards shorter wavelengths, leading to masses underestimated typically by factors 2-5. With a fixed opacity slope deviating from the true value by a factor of 1.2, masses are inaccurate within a factor of 2. The most accurate masses are estimated by fitting just two or three of the longest wavelength measurements. Conventional algorithm of background subtraction is a likely source of large systematic errors. The absolute values of masses of the unresolved or poorly resolved objects in star-forming regions are uncertain to within at least a factor of 2-3.

  8. Software tools of the Computis European project to process mass spectrometry images.

    PubMed

    Robbe, Marie-France; Both, Jean-Pierre; Prideaux, Brendan; Klinkert, Ivo; Picaud, Vincent; Schramm, Thorsten; Hester, Atfons; Guevara, Victor; Stoeckli, Markus; Roempp, Andreas; Heeren, Ron M A; Spengler, Bernhard; Gala, Olivier; Haan, Serge

    2014-01-01

    Among the needs usually expressed by teams using mass spectrometry imaging, one that often arises is that for user-friendly software able to manage huge data volumes quickly and to provide efficient assistance for the interpretation of data. To answer this need, the Computis European project developed several complementary software tools to process mass spectrometry imaging data. Data Cube Explorer provides a simple spatial and spectral exploration for matrix-assisted laser desorption/ionisation-time of flight (MALDI-ToF) and time of flight-secondary-ion mass spectrometry (ToF-SIMS) data. SpectViewer offers visualisation functions, assistance to the interpretation of data, classification functionalities, peak list extraction to interrogate biological database and image overlay, and it can process data issued from MALDI-ToF, ToF-SIMS and desorption electrospray ionisation (DESI) equipment. EasyReg2D is able to register two images, in American Standard Code for Information Interchange (ASCII) format, issued from different technologies. The collaboration between the teams was hampered by the multiplicity of equipment and data formats, so the project also developed a common data format (imzML) to facilitate the exchange of experimental data and their interpretation by the different software tools. The BioMap platform for visualisation and exploration of MALDI-ToF and DESI images was adapted to parse imzML files, enabling its access to all project partners and, more globally, to a larger community of users. Considering the huge advantages brought by the imzML standard format, a specific editor (vBrowser) for imzML files and converters from proprietary formats to imzML were developed to enable the use of the imzML format by a broad scientific community. This initiative paves the way toward the development of a large panel of software tools able to process mass spectrometry imaging datasets in the future.

  9. Atmospheric-pressure Molecular Imaging of Biological Tissues and Biofilms by LAESI Mass Spectrometry

    PubMed Central

    Nemes, Peter; Vertes, Akos

    2010-01-01

    Ambient ionization methods in mass spectrometry allow analytical investigations to be performed directly on a tissue or biofilm under native-like experimental conditions. Laser ablation electrospray ionization (LAESI) is one such development and is particularly well-suited for the investigation of water-containing specimens. LAESI utilizes a mid-infrared laser beam (2.94 μm wavelength) to excite the water molecules of the sample. When the ablation fluence threshold is exceeded, the sample material is expelled in the form of particulate matter and these projectiles travel to tens of millimeters above the sample surface. In LAESI, this ablation plume is intercepted by highly charged droplets to capture a fraction of the ejected sample material and convert its chemical constituents into gas-phase ions. A mass spectrometer equipped with an atmospheric-pressure ion source interface is employed to analyze and record the composition of the released ions originating from the probed area (pixel) of the sample. A systematic interrogation over an array of pixels opens a way for molecular imaging in the microprobe analysis mode. A unique aspect of LAESI mass spectrometric imaging is depth profiling that, in combination with lateral imaging, enables three-dimensional (3D) molecular imaging. With current lateral and depth resolutions of ~100 μm and ~40 μm, respectively, LAESI mass spectrometric imaging helps to explore the molecular structure of biological tissues. Herein, we review the major elements of a LAESI system and provide guidelines for a successful imaging experiment. PMID:20834223

  10. 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.

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

    PubMed Central

    Lavenant, Gwendoline Thiery; Zavalin, Andrey I.; Caprioli, Richard M.

    2013-01-01

    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 manuscript 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. PMID:23397138

  12. Automatic registration of imaging mass spectrometry data to the Allen Brain Atlas transcriptome

    NASA Astrophysics Data System (ADS)

    Abdelmoula, Walid M.; Carreira, Ricardo J.; Shyti, Reinald; Balluff, Benjamin; Tolner, Else; van den Maagdenberg, Arn M. J. M.; Lelieveldt, B. P. F.; McDonnell, Liam; Dijkstra, Jouke

    2014-03-01

    Imaging Mass Spectrometry (IMS) is an emerging molecular imaging technology that provides spatially resolved information on biomolecular structures; each image pixel effectively represents a molecular mass spectrum. By combining the histological images and IMS-images, neuroanatomical structures can be distinguished based on their biomolecular features as opposed to morphological features. The combination of IMS data with spatially resolved gene expression maps of the mouse brain, as provided by the Allen Mouse Brain atlas, would enable comparative studies of spatial metabolic and gene expression patterns in life-sciences research and biomarker discovery. As such, it would be highly desirable to spatially register IMS slices to the Allen Brain Atlas (ABA). In this paper, we propose a multi-step automatic registration pipeline to register ABA histology to IMS- images. Key novelty of the method is the selection of the best reference section from the ABA, based on pre-processed histology sections. First, we extracted a hippocampus-specific geometrical feature from the given experimental histological section to initially localize it among the ABA sections. Then, feature-based linear registration is applied to the initially localized section and its two neighbors in the ABA to select the most similar reference section. A non-rigid registration yields a one-to-one mapping of the experimental IMS slice to the ABA. The pipeline was applied on 6 coronal sections from two mouse brains, showing high anatomical correspondence, demonstrating the feasibility of complementing biomolecule distributions from individual mice with the genome-wide ABA transcriptome.

  13. 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.

  14. Mass

    SciTech Connect

    Quigg, Chris

    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.

  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. Mass spectrometric monitoring of interfacial photoelectron transfer and imaging of active crystalline facets of semiconductors

    NASA Astrophysics Data System (ADS)

    Zhong, Hongying; Zhang, Juan; Tang, Xuemei; Zhang, Wenyang; Jiang, Ruowei; Li, Rui; Chen, Disong; Wang, Peng; Yuan, Zhiwei

    2017-02-01

    Monitoring of interfacial electron transfer (ET) in situ is important to understand the ET mechanism and designing efficient photocatalysts. We describe herein a mass spectrometric approach to investigate the ultrafast transfer of photoelectrons that are generated by ultraviolet irradiation on surfaces of semiconductor nanoparticles or crystalline facets. The mass spectrometric approach can not only untargetedly detect various intermediates but also monitor their reactivity through associative or dissociative photoelectron capture dissociation, as well as electron detachment dissociation of adsorbed molecules. Proton-coupled electron transfer and proton-uncoupled electron transfer with radical initiated polymerization or hydroxyl radical abstraction have been unambiguously demonstrated with the mass spectrometric approach. Active crystalline facets of titanium dioxide for photocatalytic degradation of juglone and organochlorine dichlorodiphenyltrichloroethane are visualized with mass spectrometry imaging based on ion scanning and spectral reconstruction. This work provides a new technique for studying photo-electric properties of various materials.

  17. Mass spectrometric monitoring of interfacial photoelectron transfer and imaging of active crystalline facets of semiconductors

    PubMed Central

    Zhong, Hongying; Zhang, Juan; Tang, Xuemei; Zhang, Wenyang; Jiang, Ruowei; Li, Rui; Chen, Disong; Wang, Peng; Yuan, Zhiwei

    2017-01-01

    Monitoring of interfacial electron transfer (ET) in situ is important to understand the ET mechanism and designing efficient photocatalysts. We describe herein a mass spectrometric approach to investigate the ultrafast transfer of photoelectrons that are generated by ultraviolet irradiation on surfaces of semiconductor nanoparticles or crystalline facets. The mass spectrometric approach can not only untargetedly detect various intermediates but also monitor their reactivity through associative or dissociative photoelectron capture dissociation, as well as electron detachment dissociation of adsorbed molecules. Proton-coupled electron transfer and proton-uncoupled electron transfer with radical initiated polymerization or hydroxyl radical abstraction have been unambiguously demonstrated with the mass spectrometric approach. Active crystalline facets of titanium dioxide for photocatalytic degradation of juglone and organochlorine dichlorodiphenyltrichloroethane are visualized with mass spectrometry imaging based on ion scanning and spectral reconstruction. This work provides a new technique for studying photo-electric properties of various materials. PMID:28224986

  18. 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.

  19. Molecular Imaging of Tissue Sections by Mass Spectrometry: Looking Beyond the Microscope

    PubMed Central

    Caprioli, Richard

    2012-01-01

    Imaging MALDI MS (matrix-assisted laser desorption ionization mass spectrometry) produces molecular images of peptides, proteins, lipids and metabolites present in intact tissue sections. It employs desorption of molecules by direct laser irradiation to map the location of specific molecules from fresh frozen and formalin fixed tissue sections without the need of target specific reagents such as antibodies. Molecular maps can be directly correlated to known histological regions within the tissue. A high density of spots (pixels) ablated by the laser over the entire tissue produces many hundreds of molecular images or density maps with spatial resolutions from 5–200 microns. Images are produced in specific m/z (mass-to-charge) values, or ranges of values, typically covering the MW range 1000-100,000. Individual m/z values derived from each pixel can then be assembled to produce selected molecular images. Similarly, the approach has also been applied to a protocol termed histology-directed molecular analysis whereby only selected areas of cells in the tissue are of interest are ablated and analyzed based on studies performed by microscopy and other histology protocols. Both fresh frozen and formalin fixed tissues can be analyzed. The technology is extraordinarily high throughput with high molecular specificity, easily lending itself to the analysis of tissue microarrays. Sections obtained from any tissue type can be imaged, including sections through whole organs or animals. We have employed Imaging MS in studies of a variety of diseases, including several types of cancers, neurodegenerative diseases and kidney diseases, comparing proteins differentially expressed in diseased tissue with those in the corresponding normal tissue. From such comparisons, molecular signatures are developed that differentiate these tissues, typically consisting of 10-20 or more different proteins. Imaging MS has been applied to drug targeting and metabolic studies following drug

  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. Body Image, Food Addiction, Depression, and Body Mass Index in University Students.

    PubMed

    Şanlier, Nevin; Türközü, Duygu; Toka, Onur

    2016-01-01

    The relationship between body image, depression, food addiction and body mass index (BMI) and differences in these variables due to gender and field of education have not been studied extensively. This study was conducted on a total of 793 university students (20.19 ± 1.90 years). The Beck Depression Inventory, Yale Food Addiction, and Body Image Scale were used. It was determined that body image scores of females and individuals enrolled in health sciences programs were lower compared to those of males and those enrolled in the social sciences. There was a negative relationship between body image and depression and food addiction scores. There was a positive relationship between food addiction and depression scores, in addition to a positive relationship between food addiction and BMI.

  2. 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.

  3. MALDI-LTQ-Orbitrap mass spectrometry imaging for lipidomic analysis in kidney under cisplatin chemotherapy.

    PubMed

    Moreno-Gordaliza, Estefanía; Esteban-Fernández, Diego; Lázaro, Alberto; Humanes, Blanca; Aboulmagd, Sarah; Tejedor, Alberto; Linscheid, Michael W; Gómez-Gómez, M Milagros

    2017-03-01

    Imaging techniques for mapping molecular distributions in tissue sections can reveal valuable information on biomolecules involved in relevant biochemical processes. A method has been developed for comprehensive, reproducible and sensitive lipid imaging by matrix-assisted laser/desorption ionization-LTQ-Orbitrap mass spectrometry in kidney sections, showing the benefits of exact mass determination. Matrix deposition parameters for positive and negative lipid ion imaging using different matrices such as 2,5-dihydroxybenzoic acid (DHB), 9-aminoacridine (9-AA) or α-cyano-4-hydroxycinnamic acid (CHCA) have been optimized for the broadest detection and identification of renal lipids. The combination of 9-AA and DHB was found as the most suitable for negative and positive ion mode lipid imaging, respectively. Lipid mapping and related identification strategies and limitations have also been discussed. Production of 100-µm resolution images was proved to be enough for discerning lipid distribution in kidney substructures. Imaging reproducibility was assessed on parallel kidney slices with time. This method has been applied to the lipidomics analysis on kidney sections from rats treated with the antitumor drug cisplatin and compared to healthy control rats. Up to 66 different renal lipids out of 450 extracted ion images (mainly phospholipid species, in addition to sulfatides and cholesterol sulfate) have been found and identified showing a modified distribution pattern due to cisplatin-induced nephrotoxicity. These lipid species reflect either topographic, signaling or structural processes in damaged kidney and could potentially be used for nephrotoxicity assessment or as therapeutic targets. This is, to our knowledge, the first imaging lipidomics study for nephrotoxicity assessment of cisplatin chemotherapy.

  4. Testing for Multivariate Normality in Mass Spectrometry Imaging Data: A Robust Statistical Approach for Clustering Evaluation and the Generation of Synthetic Mass Spectrometry Imaging Data Sets.

    PubMed

    Dexter, Alex; Race, Alan M; Styles, Iain B; Bunch, Josephine

    2016-11-15

    Spatial clustering is a powerful tool in mass spectrometry imaging (MSI) and has been demonstrated to be capable of differentiating tumor types, visualizing intratumor heterogeneity, and segmenting anatomical structures. Several clustering methods have been applied to mass spectrometry imaging data, but a principled comparison and evaluation of different clustering techniques presents a significant challenge. We propose that testing whether the data has a multivariate normal distribution within clusters can be used to evaluate the performance when using algorithms that assume normality in the data, such as k-means clustering. In cases where clustering has been performed using the cosine distance, conversion of the data to polar coordinates prior to normality testing should be performed to ensure normality is tested in the correct coordinate system. In addition to these evaluations of internal consistency, we demonstrate that the multivariate normal distribution can then be used as a basis for statistical modeling of MSI data. This allows the generation of synthetic MSI data sets with known ground truth, providing a means of external clustering evaluation. To demonstrate this, reference data from seven anatomical regions of an MSI image of a coronal section of mouse brain were modeled. From this, a set of synthetic data based on this model was generated. Results of r(2) fitting of the chi-squared quantile-quantile plots on the seven anatomical regions confirmed that the data acquired from each spatial region was found to be closer to normally distributed in polar space than in Euclidean. Finally, principal component analysis was applied to a single data set that included synthetic and real data. No significant differences were found between the two data types, indicating the suitability of these methods for generating realistic synthetic data.

  5. 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.

  6. Mass Spectrometric Imaging Using Laser Ablation and Solvent Capture by Aspiration (LASCA)

    NASA Astrophysics Data System (ADS)

    Brauer, Jonathan I.; Beech, Iwona B.; Sunner, Jan

    2015-09-01

    A novel interface for ambient, laser ablation-based mass spectrometric imaging (MSI) referred to as laser ablation and solvent capture by aspiration (LASCA) is presented and its performance demonstrated using selected, unaltered biological materials. LASCA employs a pulsed 2.94 μm laser beam for specimen ablation. Ablated materials in the laser plumes are collected on a hanging solvent droplet with electric field-enhanced trapping, followed by aspiration of droplets and remaining plume material in the form of a coarse aerosol into a collection capillary. The gas and liquid phases are subsequently separated in a 10 μL-volume separatory funnel, and the solution is analyzed with electrospray ionization in a high mass resolution Q-ToF mass spectrometer. The LASCA system separates the sampling and ionization steps in MSI and combines high efficiencies of laser plume sampling and of electrospray ionization (ESI) with high mass resolution MS. Up to 2000 different compounds are detected from a single ablation spot (pixel). Using the LASCA platform, rapid (6 s per pixel), high sensitivity, high mass-resolution ambient imaging of "as-received" biological material is achieved routinely and reproducibly.

  7. Natural products in Glycyrrhiza glabra (licorice) rhizome imaged at the cellular level by atmospheric pressure matrix-assisted laser desorption/ionization tandem mass spectrometry imaging.

    PubMed

    Li, Bin; Bhandari, Dhaka Ram; Janfelt, Christian; Römpp, Andreas; Spengler, Bernhard

    2014-10-01

    The rhizome of Glycyrrhiza glabra (licorice) was analyzed by high-resolution mass spectrometry imaging and tandem mass spectrometry imaging. An atmospheric pressure matrix-assisted laser desorption/ionization imaging ion source was combined with an orbital trapping mass spectrometer in order to obtain high-resolution imaging in mass and space. Sections of the rhizome were imaged with a spatial resolution of 10 μm in the positive ion mode, and a large number of secondary metabolites were localized and identified based on their accurate mass and MS/MS fragmentation patterns. Major tissue-specific metabolites, including free flavonoids, flavonoid glycosides and saponins, were successfully detected and visualized in images, showing their distributions at the cellular level. The analytical power of the technique was tested in the imaging of two isobaric licorice saponins with a mass difference of only 0.02 Da. With a mass resolving power of 140 000 and a bin width of 5 ppm in the image processing, the two compounds were well resolved in full-scan mode, and appeared with different distributions in the tissue sections. The identities of the compounds and their distributions were validated in a subsequent MS/MS imaging experiment, thereby confirming their identities and excluding possible analyte interference. The use of high spatial resolution, high mass resolution and tandem mass spectrometry in imaging experiments provides significant information about the biosynthetic pathway of flavonoids and saponins in legume species, combing the spatially resolved chemical information with morphological details at the microscopic level. Furthermore, the technique offers a scheme capable of high-throughput profiling of metabolites in plant tissues.

  8. 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.

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

    DOE PAGES

    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

  10. Activity-Based Probes linked with Laser-Cleavable Mass Tags for Signal Amplification in Imaging Mass Spectrometry: Analysis of Serine Hydrolase Enzymes in Mammalian Tissue

    PubMed Central

    Yang, Junhai; Chaurand, Pierre; Norris, Jeremy L.; Porter, Ned A.; Caprioli, Richard M.

    2012-01-01

    A novel functional Imaging Mass Spectrometry technology is described that utilizes activity-based probes for imaging enzyme active sites in tissue sections. We demonstrate this technology using an activity-based probe (fluorophosphate) that is specific for serine hydrolases. A dendrimer containing multiple mass tags that is attached to the activity-based probe is used to analyze the binding sites of the probe through release and measurement of the mass tags on laser irradiation. A generation 8 Poly(amido amine) dendrimer with 1024 amino groups was labeled with an azide group and then more than 900 mass tags were attached in order to achieve signal amplification of nearly three orders of magnitude. The experimental protocol first involves binding of the activity-based probe containing an alkyne group to serine hydrolases in the tissue section followed by attachment of the dendrimer labeled with mass tags to the bound probe by Click chemistry. On irradiation of the labeled tissue by the laser beam in a raster pattern, the mass tags are liberated and recorded by the mass analyzer, consequently, the ion image of the mass tag reveals the distribution of serine hydrolases in the tissue. This process was shown using rat brain and mouse embryo sections. Targeted imaging has the advantage of providing high spatial resolution and high sensitivity through the use of signal amplification chemistry with high target specificity through the use of an enzyme activity probe. PMID:22424244

  11. 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.

  12. 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.

  13. Enhanced Sensitivity for High Spatial Resolution Lipid Analysis by Negative Ion Mode MALDI Imaging Mass Spectrometry

    PubMed Central

    Angel, Peggi M.; Spraggins, Jeffrey M.; Baldwin, H. Scott; Caprioli, Richard

    2012-01-01

    We have achieved enhanced lipid imaging to a ~10 μm spatial resolution using negative ion mode matrix assisted laser desorption ionization (MALDI) imaging mass spectrometry, sublimation of 2,5-dihydroxybenzoic acid as the MALDI matrix and a sample preparation protocol that uses aqueous washes. We report on the effect of treating tissue sections by washing with volatile buffers at different pHs prior to negative ion mode lipid imaging. The results show that washing with ammonium formate, pH 6.4, or ammonium acetate, pH 6.7, significantly increases signal intensity and number of analytes recorded from adult mouse brain tissue sections. Major lipid species measured were glycerophosphoinositols, glycerophosphates, glycerolphosphoglycerols, glycerophosphoethanolamines, glycerophospho-serines, sulfatides, and gangliosides. Ion images from adult mouse brain sections that compare washed and unwashed sections are presented and show up to fivefold increases in ion intensity for washed tissue. The sample preparation protocol has been found to be applicable across numerous organ types and significantly expands the number of lipid species detectable by imaging mass spectrometry at high spatial resolution. PMID:22243218

  14. 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.

  15. Imaging of β-cell mass and insulitis in insulin-dependent (Type 1) diabetes mellitus.

    PubMed

    Di Gialleonardo, Valentina; de Vries, Erik F J; Di Girolamo, Marco; Quintero, Ana M; Dierckx, Rudi A J O; Signore, Alberto

    2012-12-01

    Insulin-dependent (type 1) diabetes mellitus is a metabolic disease with a complex multifactorial etiology and a poorly understood pathogenesis. Genetic and environmental factors cause an autoimmune reaction against pancreatic β-cells, called insulitis, confirmed in pancreatic samples obtained at autopsy. The possibility to noninvasively quantify β-cell mass in vivo would provide important biological insights and facilitate aspects of diagnosis and therapy, including follow-up of islet cell transplantation. Moreover, the availability of a noninvasive tool to quantify the extent and severity of pancreatic insulitis could be useful for understanding the natural history of human insulin-dependent (type 1) diabetes mellitus, to early diagnose children at risk to develop overt diabetes, and to select patients to be treated with immunotherapies aimed at blocking the insulitis and monitoring the efficacy of these therapies. In this review, we outline the imaging techniques currently available for in vivo, noninvasive detection of β-cell mass and insulitis. These imaging techniques include magnetic resonance imaging, ultrasound, computed tomography, bioluminescence and fluorescence imaging, and the nuclear medicine techniques positron emission tomography and single-photon emission computed tomography. Several approaches and radiopharmaceuticals for imaging β-cells and lymphocytic insulitis are reviewed in detail.

  16. 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. PMID:27570788

  17. 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

  18. MALDI imaging mass spectrometry: statistical data analysis and current computational challenges.

    PubMed

    Alexandrov, Theodore

    2012-01-01

    Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) imaging mass spectrometry, also called MALDI-imaging, is a label-free bioanalytical technique used for spatially-resolved chemical analysis of a sample. Usually, MALDI-imaging is exploited for analysis of a specially prepared tissue section thaw mounted onto glass slide. A tremendous development of the MALDI-imaging technique has been observed during the last decade. Currently, it is one of the most promising innovative measurement techniques in biochemistry and a powerful and versatile tool for spatially-resolved chemical analysis of diverse sample types ranging from biological and plant tissues to bio and polymer thin films. In this paper, we outline computational methods for analyzing MALDI-imaging data with the emphasis on multivariate statistical methods, discuss their pros and cons, and give recommendations on their application. The methods of unsupervised data mining as well as supervised classification methods for biomarker discovery are elucidated. We also present a high-throughput computational pipeline for interpretation of MALDI-imaging data using spatial segmentation. Finally, we discuss current challenges associated with the statistical analysis of MALDI-imaging data.

  19. 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

  20. 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

    2016-04-15

    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.

  1. High mass and spatial resolution mass spectrometry imaging of Nicolas Poussin painting cross section by cluster TOF-SIMS.

    PubMed

    Noun, M; Van Elslande, E; Touboul, D; Glanville, H; Bucklow, S; Walter, P; Brunelle, A

    2016-12-01

    The painting Rebecca and Eliezer at the Well, which hangs in the Fitzwilliam Museum, Cambridge, UK, is possibly one of the last figure painting executed by Nicolas Poussin at the very end of his life and is usually dated to the early 1660s. In this perspective special feature, Philippe Walter, Alain Brunelle and colleagues give new insights on the artist's working methods by a careful stateof-the-art imaging ToF-SIMS study of one sample taken on the edge of the painting. This approach allowed for the identification of the pigments used in the painting, their nature and components and those of the ground and preparatory layers, with the identification of the binder(s) and possible other additions of organic materials such as glue. This study paves the way to a wider use of ToF-SIMS for the analysis of ancient cultural heritage artefacts. Dr. Walter is the Director of the Molecular and Structural Archeology Laboratory (Université Pierre et Marie Curie, Paris, France). Dr. Brunelle is Head of the Mass Spectrometry Laboratory at the Institut de Chimie des Substances Naturelles (CNRS, Gif-sur-Yvette, France). Their long standing collaboration has led to several seminal publications on the analysis of ancient artefacts by mass spectrometry.

  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. 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.

  4. Experimental study on acoustic subwavelength imaging based on zero-mass metamaterials

    NASA Astrophysics Data System (ADS)

    Xu, Xianchen; Li, Pei; Zhou, Xiaoming; Hu, Gengkai

    2015-01-01

    Anisotropic zero-mass acoustic metamaterials are able to transmit evanescent waves without decaying to a far distance, and have been used for near-field acoustic subwavelength imaging. In this work, we design and fabricate such metamaterial lens based on clamped paper membrane units. The zero-mass frequency is determined by normal-incidence acoustic transmission measurement. At this frequency, we verify in experiment that the fabricated metamaterial lens is able to distinguish clearly two sound sources separated with a distance 0.16λ0 (λ0 is the wavelength in air) below the diffraction limit. We also demonstrate that the imaging frequency is invariant to the change of the lens thickness.

  5. Detection of high molecular weight proteins by MALDI imaging mass spectrometry.

    PubMed

    Mainini, Veronica; Bovo, Giorgio; Chinello, Clizia; Gianazza, Erica; Grasso, Marco; Cattoretti, Giorgio; Magni, Fulvio

    2013-06-01

    MALDI imaging mass spectrometry (IMS) is a unique technology to explore the spatial distribution of biomolecules directly on tissues. It allows the in situ investigation of a large number of small proteins and peptides. Detection of high molecular weight proteins through MALDI IMS still represents an important challenge, as it would allow the direct investigation of the distribution of more proteins involved in biological processes, such as cytokines, enzymes, neuropeptide precursors and receptors. In this work we compare the traditional method performed with sinapinic acid with a comparable protocol using ferulic acid as the matrix. Data show a remarkable increase of signal acquisition in the mass range of 20k to 150k Th. Moreover, we report molecular images of biomolecules above 70k Th, demonstrating the possibility of expanding the application of this technology both in clinical investigations and basic science.

  6. 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

    2014-07-21

    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.

  7. 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.

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

    PubMed

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

    2012-09-01

    Nitrate concentrations, water isotopes (δ(2)H and δ(18)O(water)) and associated nitrate isotopes (δ(15)N(nitrate) and δ(18)O(nitrate)) 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. δ(15)N(nitrate) 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 δ(15)N(nitrate) 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 (δ(18)O(water) and δ(15)N(nitrate)), it was possible to relate the average altitude of rainfall infiltration (δ(18)O(water)) associated with the nitrate contamination (δ(18)O(nitrate)). This relationship between land use, rainfall recharge altitude and isotopic composition (δ(15)N(nitrate) and δ(18)O(water)) 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 δ(18)O(nitrate), it was possible to determine that only 5 out of 15 fresh water wells and springs followed the conservative nitrate formation mechanism of 2/3δ(18)O(water)+1/3δ(18)O(air), to give nitrate formation altitudes which corresponded to land use activities.

  9. 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

    2015-10-06

    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.

  10. Secondary Ion Mass Spectrometry Imaging of Tissues, Cells, and Microbial Systems

    SciTech Connect

    Gamble, Lara J.; Anderton, Christopher R.

    2016-03-18

    Mass spectrometry imaging (MSI) techniques are increasingly being utilized within many biological fields, including medicine, pathology, microbial ecology, and more. Of the MSI methods available, secondary ion mass spectrometry (SIMS) offers the highest lateral resolution of any technique. Moreover, SIMS versatility in the number of different operating modes and types of mass spectrometers available has made it an increasing popular method for bio-related measurements. Here, we discuss SIMS ability to image tissues, single cells, and microbes with a particular emphasis on the types chemical and spatial information that can be ascertained by the different types of SIMS instruments and methods. The recently developed Fourier transform ion cyclotron resonance (FTICR) SIMS located at PNNL is capable of generating molecular maps of tissues with an unprecedented mass resolving power and mass accuracy, with respect to SIMS measurements. ToF-SIMS can generate chemical maps, where detection of small molecules and fragments can be acquired with an order of magnitude better lateral resolution than the FTICR-SIMS. Furthermore, many of commercially available ToF-SIMS instruments are capable of depth profiling measurements, offering the ability to attain three-dimensional information of one’s sample. The NanoSIMS instrument offers the highest lateral resolution of any MSI method available. In practice, NanoSIMS regularly achieves sub-100 nm resolution of atomic and diatomic secondary ions within biological samples. The strengths of the different SIMS methods are more and more being leveraged in both multimodal-imaging endeavors that use complementary MSI techniques as well with optical, fluorescence, and force microscopy methods.

  11. 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.

  12. Hybrid Imaging Labels: Providing the Link Between Mass Spectrometry-Based Molecular Pathology and Theranostics

    PubMed Central

    Buckle, Tessa; van der Wal, Steffen; van Malderen, Stijn J.M.; Müller, Larissa; Kuil, Joeri; van Unen, Vincent; Peters, Ruud J.B.; van Bemmel, Margaretha E.M.; McDonnell, Liam A.; Velders, Aldrik H.; Koning, Frits; Vanhaeke, Frank; van Leeuwen, Fijs W. B.

    2017-01-01

    Background: Development of theranostic concepts that include inductively coupled plasma mass spectrometry (ICP-MS) and laser ablation ICP-MS (LA-ICP-MS) imaging can be hindered by the lack of a direct comparison to more standardly used methods for in vitro and in vivo evaluation; e.g. fluorescence or nuclear medicine. In this study a bimodal (or rather, hybrid) tracer that contains both a fluorescent dye and a chelate was used to evaluate the existence of a direct link between mass spectrometry (MS) and in vitro and in vivo molecular imaging findings using fluorescence and radioisotopes. At the same time, the hybrid label was used to determine whether the use of a single isotope label would allow for MS-based diagnostics. Methods: A hybrid label that contained both a DTPA chelate (that was coordinated with either 165Ho or 111In) and a Cy5 fluorescent dye was coupled to the chemokine receptor 4 (CXCR4) targeting peptide Ac-TZ14011 (hybrid-Cy5-Ac-TZ4011). This receptor targeting tracer was used to 1) validate the efficacy of (165Ho-based) mass-cytometry in determining the receptor affinity via comparison with fluorescence-based flow cytometry (Cy5), 2) evaluate the microscopic binding pattern of the tracer in tumor cells using both fluorescence confocal imaging (Cy5) and LA-ICP-MS-imaging (165Ho), 3) compare in vivo biodistribution patterns obtained with ICP-MS (165Ho) and radiodetection (111In) after intravenous administration of hybrid-Cy5-Ac-TZ4011 in tumor-bearing mice. Finally, LA-ICP-MS-imaging (165Ho) was linked to fluorescence-based analysis of excised tissue samples (Cy5). Results: Analysis with both mass-cytometry and flow cytometry revealed a similar receptor affinity, respectively 352 ± 141 nM and 245 ± 65 nM (p = 0.08), but with a much lower detection sensitivity for the first modality. In vitro LA-ICP-MS imaging (165Ho) enabled clear discrimination between CXCR4 positive and negative cells, but fluorescence microscopy was required to determine the

  13. 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

  14. Higher sensitivity secondary ion mass spectrometry of biological molecules for high resolution, chemically specific imaging.

    PubMed

    McDonnell, Liam A; Heeren, Ron M A; de Lange, Robert P J; Fletcher, Ian W

    2006-09-01

    To expand the role of high spatial resolution secondary ion mass spectrometry (SIMS) in biological studies, numerous developments have been reported in recent years for enhancing the molecular ion yield of high mass molecules. These include both surface modification, including matrix-enhanced SIMS and metal-assisted SIMS, and polyatomic primary ions. Using rat brain tissue sections and a bismuth primary ion gun able to produce atomic and polyatomic primary ions, we report here how the sensitivity enhancements provided by these developments are additive. Combined surface modification and polyatomic primary ions provided approximately 15.8 times more signal than using atomic primary ions on the raw sample, whereas surface modification and polyatomic primary ions yield approximately 3.8 and approximately 8.4 times more signal. This higher sensitivity is used to generate chemically specific images of higher mass biomolecules using a single molecular ion peak.

  15. DENSITY DIAGNOSTICS OF CORONAL MASS EJECTION CORES WITH THE SOLAR DYNAMICS OBSERVATORY/ATMOSPHERIC IMAGING ASSEMBLY

    SciTech Connect

    Landi, E.; Miralles, M. P.

    2014-01-01

    In this Letter, we investigate the application of the intensity ratio from pairs of narrow-band images from the Atmospheric Imaging Assembly (AIA) on the Solar Dynamics Observatory, the Extreme Ultraviolet (EUV) Imager (EUVI) on board the Sun Earth Connection Coronal and Heliospheric Investigation, and the EUV Imaging Telescope (EIT) on board the Solar and Heliospheric Observatory, to density diagnostics of optically thin plasmas. By inspecting the filtered spectra allowed by each instrument's effective area, we find that ratios between AIA images in the 171 Å and 193 Å channels can be used to determine the plasma electron density at transition region temperatures. This diagnostic potential is due to a pair of O V transitions which dominate the effective spectra of these two channels at temperatures around ≈2.5-3.0 × 10{sup 5} K. The temperature and electron density ranges where the 171/193 ratio is density sensitive are relevant for the cores of accelerating coronal mass ejections (CMEs) in the inner solar corona. We discuss how AIA series of images can be used for simultaneous temperature and density diagnostics of CME cores.

  16. Relationship between perceived body image and recorded body mass index among Kuwaiti female university students.

    PubMed

    Kabir, Yearul; Zafar, Tasleem A; Waslien, Carol

    2013-01-01

    The associations between body image and attitudes toward obesity and thinness and their associations with measured body mass index (BMI) among female students of Kuwait University (n = 137) was examined in 2008. The body image perceptions were assessed using nine female silhouettes figures. The difference between current perceived body image (PBI) and ideal body image (IBI) was used as a measure of body image dissatisfaction (BID). Students tended to have a bigger PBI and smaller IBI than would be expected from their BMI category, leading to high levels of BID in each BMI category. PBI, IBI, BID, RBI were highly correlated with each other, and BMI was significantly correlated with each of them. The coefficients of these associations were not significantly altered in multiple regression analysis by the addition of potential confounding variables, such as age, marital status, physical activity, dieting behavior, parental education, and family size. These results suggest that PBI and a desire to be thinner were strongly related to BID and that thinness is becoming more desired in Kuwaiti society than the plump body image of the past.

  17. Imaging features of periosteal chondroma manifesting as a subcutaneous mass in the index finger.

    PubMed

    Kosaka, Hidetomo; Nishio, Jun; Matsunaga, Taiki; Aoki, Mikiko; Iwasaki, Hiroshi; Naito, Masatoshi

    2014-01-01

    Periosteal chondroma is a rare benign hyaline cartilage neoplasm that occurs most commonly in the metaphases of long tubular bones. We present a unique case of periosteal chondroma arising in the proximal phalanx of the left index finger in a 12-year-old boy. Physical examination revealed a slightly protuberant, subcutaneous mass. Plain radiographs and computed tomography scans showed a periosteal lesion producing saucerization of the cortex and subjacent cortical sclerosis, without internal matrix calcification. On magnetic resonance imaging, the lesion exhibited intermediate signal intensity on T1-weighted images and high signal intensity on T2-weighted images. Contrast-enhanced fat-suppressed T1-weighted images demonstrated peripheral and septal enhancement. The patient underwent a marginal excision with curettage of the underlying bone cortex. Histological examination confirmed the diagnosis of periosteal chondroma. There has been no evidence of local recurrence eight months after surgery. Periosteal chondroma can protrude into the subcutaneous soft tissue causing a palpable mass. Recognition of the typical radiological features can lead to an accurate diagnosis of this rare condition.

  18. Active learning for convenient annotation and classification of secondary ion mass spectrometry images.

    PubMed

    Hanselmann, Michael; Röder, Jens; Köthe, Ullrich; Renard, Bernhard Y; Heeren, Ron M A; Hamprecht, Fred A

    2013-01-02

    Digital staining for the automated annotation of mass spectrometry imaging (MSI) data has previously been achieved using state-of-the-art classifiers such as random forests or support vector machines (SVMs). However, the training of such classifiers requires an expert to label exemplary data in advance. This process is time-consuming and hence costly, especially if the tissue is heterogeneous. In theory, it may be sufficient to only label a few highly representative pixels of an MS image, but it is not known a priori which pixels to select. This motivates active learning strategies in which the algorithm itself queries the expert by automatically suggesting promising candidate pixels of an MS image for labeling. Given a suitable querying strategy, the number of required training labels can be significantly reduced while maintaining classification accuracy. In this work, we propose active learning for convenient annotation of MSI data. We generalize a recently proposed active learning method to the multiclass case and combine it with the random forest classifier. Its superior performance over random sampling is demonstrated on secondary ion mass spectrometry data, making it an interesting approach for the classification of MS images.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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

    2016-04-08

    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.

  4. Modeling of errors in Nakagami imaging: illustration on breast mass characterization.

    PubMed

    Larrue, Aymeric; Noble, J Alison

    2014-05-01

    Nakagami imaging is an attractive tissue characterization method, as the parameter estimated at each location is related to properties of the tissues. The application to clinical ultrasound images is problematic, as the estimation of the parameters is disturbed by the presence of complex structures. We propose to consider separately the different aspects potentially affecting the value of the Nakagami parameters and quantify their effects on the estimation. This framework is applied to the classification of breast masses. Quantitative parameters are computed on two groups of ultrasound images of benign and malignant tumors. A statistical analysis of the result indicated that the previously observed difference between average values of the Nakagami parameters is explained mostly by estimation errors. In the future, new methods for reliable computation of Nakagami parameters need to be developed, and factors of error should be considered in studies using Nakagami parameters.

  5. Laser beam filtration for high spatial resolution MALDI imaging mass spectrometry.

    PubMed

    Zavalin, Andre; Yang, Junhai; Caprioli, Richard

    2013-07-01

    We describe an easy and inexpensive way to provide a highly defined Gaussian shaped laser spot on target of 5 μm diameter for imaging mass spectrometry using a commercial MALDI TOF instrument that is designed to produce a 20 μm diameter laser beam on target at its lowest setting. A 25 μm pinhole filter on a swivel arm was installed in the laser beam optics outside the vacuum ion source chamber so it is easily flipped into or out of the beam as desired by the operator. The resulting ion images at 5 μm spatial resolution are sharp since the satellite secondary laser beam maxima have been removed by the filter. Ion images are shown to demonstrate the performance and are compared with the method of oversampling to achieve higher spatial resolution when only a larger laser beam spot on target is available.

  6. Imaging in Rare and Atypical Sinonasal Masses: An Interesting Case Series.

    PubMed

    Sanyal, Shantiranjan; Prasad, Akhila; Baruah, Deb Kumar; Garga, Umesh Chandra

    2015-12-01

    Sinonasal tumours present a myriad of radiographic findings. While many of these tumours have been well described with regard to their typical sites of origin, age group and radiological appearance we have come across lesions in our daily practice which are exceedingly rare with regard to site of origin in sinonasal cavity. The radiological appearances of 4 such rare and unusual tumours arising in sinonasal region evaluated by cross sectional imaging (CT/MRI) have been illustrated in this article with a purpose to review the radio-pathological correlation of these tumours and to explain the utility of cross-sectional imaging CT and MRI in exploring diagnostic clues. Morphological features and radiological patterns of each tumour have been graded into mild, moderate and severe based on the extent of tumoural involvement. This review is intended to acquaint radiologists with the appearance of atypical sinonasal masses and their radiological appearance on cross sectional imaging to make an early diagnosis.

  7. Laser Beam Filtration for High Spatial Resolution MALDI Imaging Mass Spectrometry

    PubMed Central

    Zavalin, Andre; Yang, Junhai; Caprioli, Richard

    2013-01-01

    We describe an easy and inexpensive way to provide a highly defined Gaussian shaped laser spot on target of 5 μm diameter for Imaging Mass Spectrometry using a commercial MALDI TOF instrument that is designed to produce a 20 μm diameter laser beam on target at its lowest setting. A 25 μm pinhole filter on a swivel arm was installed in the laser beam optics outside the vacuum ion source chamber so it is easily flipped into or out of the beam as desired by the operator. The resulting ion images at 5 μm spatial resolution are sharp since the satellite secondary laser beam maxima have been removed by the filter. Ion images are shown to demonstrate the performance and are compared to the method of oversampling to achieve higher spatial resolution when only a larger laser beam spot on target is available. PMID:23661425

  8. Concordance of computer-extracted image features with BI-RADS descriptors for mammographic mass margin

    NASA Astrophysics Data System (ADS)

    Sahiner, Berkman; Hadjiiski, Lubomir M.; Chan, Heang-Ping; Paramagul, Chintana; Nees, Alexis; Helvie, Mark; Shi, Jiazheng

    2008-03-01

    The purpose of this study was to develop and evaluate computer-extracted features for characterizing mammographic mass margins according to BI-RADS spiculated and circumscribed categories. The mass was automatically segmented using an active contour model. A spiculation measure for a pixel on the mass boundary was defined by using the angular difference between the image gradient vector and the normal to the mass, averaged over pixels in a spiculation search region. For the circumscribed margin feature, the angular difference between the principal eigenvector of the Hessian matrix and the normal to the mass was estimated in a band of pixels centered at each point on the boundary, and the feature was extracted from the resulting profile along the boundary. Three MQSA radiologists provided BI-RADS margin ratings for a data set of 198 regions of interest containing breast masses. The features were evaluated with respect to the individual radiologists' characterization using receiver operating characteristic (ROC) analysis, as well as with respect to that from the majority rule, in which a mass was labeled as spiculated (circumscribed) if it was characterized as such by 2 or 3 radiologists, and non-spiculated (non-circumscribed) otherwise. We also investigated the performance of the features for consensus masses, defined as those labeled as spiculated (circumscribed) or nonspiculated (non-circumscribed) by all three radiologists. When masses were labeled according to radiologists R1, R2, and R3 individually, the spiculation feature had an area A z under the ROC curve of 0.90+/-0.04, 0.90+/-0.03, 0.88+/-0.03, respectively, while the circumscribed margin feature had an A z value of 0.77+/-0.04, 0.74+/-0.04, and 0.80+/-0.03, respectively. When masses were labeled according to the majority rule, the A z values for the spiculation and the circumscribed margin features were 0.92+/-0.03 and 0.80+/-+/-0.03, respectively. When only the consensus masses were considered, the A z

  9. 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

  10. THE MULTI-ISOTOPE PROCESS (MIP) MONITOR: A NEAR-REAL-TIME, NON-DESTRUCTIVE, INDICATOR OF SPENT NUCLEAR FUEL REPROCESSING CONDITIONS

    SciTech Connect

    Schwantes, Jon M.; Orton, Christopher R.; Fraga, Carlos G.; Douglas, Matthew; Christensen, Richard

    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, non-destructively, 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 validation is currently under way and significant results are available. The latest experimental results, along with an overview of the method will be presented.

  11. 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.

  12. Proof of concept simulations of the Multi-Isotope Process monitor: An online, nondestructive, near-real-time safeguards monitor for nuclear fuel reprocessing facilities

    NASA Astrophysics Data System (ADS)

    Orton, Christopher R.; Fraga, Carlos G.; Christensen, Richard N.; Schwantes, Jon M.

    2011-02-01

    The International Atomic Energy Agency will require the development of advanced technologies to effectively safeguard nuclear material at increasingly large-scale nuclear recycling facilities. Ideally, the envisioned technologies would be capable of nondestructive, near-real-time, autonomous process monitoring. This paper describes recent results from model simulations designed to test the Multi-Isotope Process (MIP) monitor, a novel addition to a safeguards system for 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 near-real-time. Three computer models including ORIGEN-ARP, AMUSE, and SYNTH were used in series to predict spent nuclear fuel composition, estimate element partitioning during separation, and simulate spectra from product and raffinate streams using a variety of gamma detectors, respectively. Simulations were generated for fuel with various irradiation histories and under a variety of plant operating conditions. Principal component analysis was applied to the simulated gamma spectra to investigate pattern variations as a function of acid concentration, burnup, and cooling time. Hierarchical cluster analysis and partial least squares (PLS) were also used in the analysis. The MIP monitor was found to be sensitive to induced variations of several operating parameters including distinguishing ±2.5% variation from normal process acid concentrations. The ability of PLS to predict burnup levels from simulated spectra was also demonstrated to be within 3.5% of measured values.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. MALDI imaging mass spectrometry of integral membrane proteins from ocular lens and retinal tissue.

    PubMed

    Grey, Angus C; Chaurand, Pierre; Caprioli, Richard M; Schey, Kevin L

    2009-07-01

    A tissue preparation protocol for MALDI (matrix-assisted laser desorption/ionization) imaging mass spectrometry of integral membrane proteins was developed using ocular lens and retinal tissues as model samples. Frozen bovine and human lenses were cryosectioned equatorially or axially at -20 degrees C into 20 mum-thick tissue sections. Lens sections were mounted onto gold-coated MALDI targets by methanol soft-landing to maintain tissue integrity. Tissue sections underwent extensive water washing to deplete the samples of highly abundant water-soluble proteins. Automated matrix deposition was achieved using an acoustic reagent multispotter, with sinapinic acid as matrix and high percentage acetonitrile as solvent, with a center-to-center spot spacing of 200-300 mum. Molecular images of full-length Aquaporin-0 (AQP0) and its most abundant truncation products were obtained from mass spectral data acquired across whole bovine and human lens sections. In equatorial and axial sections of bovine lenses, full-length AQP0 was detected throughout the lens. A truncation product corresponding to AQP0 (1-260) was detected in the bovine lens core at low abundance. In axial lens sections, no antero-posterior variation was detected. In 11 year-old human lens sections, full-length AQP0 was most abundant in the lens periphery, but was detected throughout the lens. The major truncation product, consisting of AQP0 residues 1-246, was absent from the lens periphery and increased in abundance in the lens core. This tissue preparation protocol was then applied to image the distribution of the G-protein coupled receptor, opsin, in the rabbit retina. This protocol has expanded the variety of target analytes which can be detected by MALDI imaging mass spectrometry to include intact integral membrane proteins.

  18. 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.

  19. 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.

  20. 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

  1. Predicting muscle mass from anthropometry using magnetic resonance imaging as reference: a systematic review.

    PubMed

    Al-Gindan, Yasmin Y; Hankey, Catherine R; Leslie, Wilma; Govan, Lindsay; Lean, Michael E J

    2014-02-01

    Identification and management of sarcopenia are limited by lack of reliable simple approaches to assess muscle mass. The aim of this review is to identify and evaluate simple methods to quantify muscle mass/volume of adults. Using Cochrane Review methodology, Medline (1946-2012), Embase (1974-2012), Web of Science (1898-2012), PubMed, and the Cochrane Library (to 08/2012) were searched for publications that included prediction equations (from anthropometric measurements) to estimate muscle mass by magnetic resonance imaging (MRI) in adults. Of 257 papers identified from primary search terms, 12 studies met the inclusion criteria. Most studies (n = 10) assessed only regional/limb muscle mass/volume. Many studies (n = 9) assessed limb circumference adjusted for skinfold thickness, which limits their practical applications. Only two included validation in separate subject-samples, and two reported relationships between whole-body MRI-measured muscle mass and anthropometry beyond linear correlations. In conclusion, one simple prediction equation shows promise, but it has not been validated in a separate population with different investigators. Furthermore, it did not incorporate widely available trunk/limb girths, which have offered valuable prediction of body composition in other studies.

  2. The utilization of fluorescence to identify the components of lipofuscin by imaging mass spectrometry

    PubMed Central

    Ablonczy, Zsolt; Smith, Noah; Anderson, David M; Grey, Angus C.; Spraggins, Jeffrey; Koutalos, Yiannis; Schey, Kevin L.; Crouch, Rosalie K.

    2014-01-01

    Lipofuscin, an aging marker in the retinal pigment epithelium (RPE) associated with the development of age-related macular degeneration, is primarily characterized by its fluorescence. The most abundant component of RPE lipofuscin is N-retinylidene-N-retinylethanolamine (A2E) but its exact composition is not known due to the complexity of the RPE extract. In this study, we utilized MALDI imaging to find potential molecules responsible for lipofuscin fluorescence in RPE tissue from Abca4−/−, Sv129, and C57Bl6/J mice ages 2 and 6 month. To assert relationships, the individual images in the MALDI imaging datasets were correlated with lipofuscin fluorescence recorded from the same tissues following proper registration. Spatial correlation information, which is usually is lost in bioanalytics, pinpointed a relatively small number of potential lipofuscin components. The comparison of four samples in each condition further limited the possibility of false positives and provided various new, age- and strain-specific targets. Validating the usefulness of the fluorescence-enhanced imaging strategy, many known adducts of A2E were identified in the short list of lipofuscin components. These results provided evidence that mass spectrometric imaging can be utilized as a tool to begin to identify the molecular substructure of clinically-relevant diagnostic information. PMID:24453194

  3. Agreement and association between different indicators of body image and body mass index in adolescents.

    PubMed

    Santos, Carla Fernandez Dos; Castro, Inês Rugani Ribeiro de; Cardoso, Letícia de Oliveira; Tavares, Letícia Ferreira

    2014-01-01

    The aim of the study was to examine the correlation among different indicators of body image; between each one of these and nutritional status; and the association of these indicators with the Body Mass Index (BMI) of adolescents. A random sample of 152 students from public and private schools in the city of Rio de Janeiro, Brazil, was studied. On four occasions, two silhouette scales and two questions regarding the opinion of the student about his/her body and weight were applied and weight and height were measured. The BMI was examined both as a continuous and as a categorical variable. The agreement between the variables was analyzed using the quadratic weighted Kappa statistics. The association between body image variables and BMI was examined by the comparison among median, mean, standard deviation and 95% confidence interval of BMI for each category of the body image variables. In general, the correlation among the body image variables ranged from reasonable to good; between these and the variable nutritional status, correlation ranged from regular to reasonable. Best results were observed among boys and students from private schools. All body image variables showed good discriminatory power for BMI, when it was analyzed as a continuous variable, even when controlling for potential confounders. The question about body seems to be better than that about weight to compose the questionnaire of a surveillance system for risk and protective factors for adolescent health.

  4. Document authentication at molecular levels using desorption atmospheric pressure chemical ionization mass spectrometry imaging.

    PubMed

    Li, Ming; Jia, Bin; Ding, Liying; Hong, Feng; Ouyang, Yongzhong; Chen, Rui; Zhou, Shumin; Chen, Huanwen; Fang, Xiang

    2013-09-01

    Molecular images of documents were obtained by sequentially scanning the surface of the document using desorption atmospheric pressure chemical ionization mass spectrometry (DAPCI-MS), which was operated in either a gasless, solvent-free or methanol vapor-assisted mode. The decay process of the ink used for handwriting was monitored by following the signal intensities recorded by DAPCI-MS. Handwritings made using four types of inks on four kinds of paper surfaces were tested. By studying the dynamic decay of the inks, DAPCI-MS imaging differentiated a 10-min old from two 4 h old samples. Non-destructive forensic analysis of forged signatures either handwritten or computer-assisted was achieved according to the difference of the contour in DAPCI images, which was attributed to the strength personalized by different writers. Distinction of the order of writing/stamping on documents and detection of illegal printings were accomplished with a spatial resolution of about 140 µm. A Matlab® written program was developed to facilitate the visualization of the similarity between signature images obtained by DAPCI-MS. The experimental results show that DAPCI-MS imaging provides rich information at the molecular level and thus can be used for the reliable document analysis in forensic applications.

  5. 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

  6. Molecular typing of Meningiomas by Desorption Electrospray Ionization Mass Spectrometry Imaging for Surgical Decision-Making

    PubMed Central

    Calligaris, David; Feldman, Daniel R.; Norton, Isaiah; Brastianos, Priscilla K.; Dunn, Ian F.; Santagata, Sandro; Agar, Nathalie Y. R.

    2014-01-01

    Meningiomas are the most frequent intracranial tumors. The majority is benign slow-growing tumors but they can be difficult to treat depending on their location and size. While meningiomas are well delineated on magnetic resonance imaging by their uptake of contrast, surgical limitations still present themselves from not knowing the extent of invasion of the dura matter by meningioma cells. The development of tools to characterize tumor tissue in real or near real time could prevent recurrence after tumor resection by allowing for more precise surgery, i.e. removal of tumor with preservation of healthy tissue. The development of ambient ionization mass spectrometry for molecular characterization of tissue and its implementation in the surgical decision-making workflow carry the potential to fulfill this need. Here, we present the characterization of meningioma and dura mater by desorption electrospray ionization mass spectrometry to validate the technique for the molecular assessment of surgical margins and diagnosis of meningioma from surgical tissue in real-time. Nine stereotactically resected surgical samples and three autopsy samples were analyzed by standard histopathology and mass spectrometry imaging. All samples indicated a strong correlation between results from both techniques. We then highlight the value of desorption electrospray ionization mass spectrometry for the molecular subtyping/subgrouping of meningiomas from a series of forty genetically characterized specimens. The minimal sample preparation required for desorption electrospray ionization mass spectrometry offers a distinct advantage for applications relying on real-time information such as surgical decision-making. The technology here was tested to distinguish meningioma from dura mater as an approach to precisely define surgical margins. In addition we classify meningiomas into fibroblastic and meningothelial subtypes and more notably recognize meningiomas with NF2 genetic aberrations. PMID

  7. A multi-isotope (radium, boron,strontium, sulfur, carbon, oxygen, hydrogen) investigation of fossil groundwater from the Disi Aquifer in southern Jordan: tracing water sources, water-rock interactions, and residence time (Invited)

    NASA Astrophysics Data System (ADS)

    Vengosh, A.; Rimawi, O.; Al-Zoubi, A.; Marie, A.; Ganor, J.

    2010-12-01

    The rise in population, consecutive droughts induced from climate change, and associated increased water demands in the Middle East have placed an increasing pressure on available water resources, which in turn has accelerated the rates of their depletion and contamination. In addition to desalination and recycling waste water, exploitation of non-renewable (“fossil”) groundwater has become an alternative water source. Most of the fossil groundwater in the Middle East and Northern Africa occupies confined sandstone aquifers and is typically characterized by high water quality. Recent findings have shown, however, that fossil groundwater from the Nubian Sandstone aquifers in southern Jordan and Israel has high levels of naturally occurring and carcinogenic radium isotopes that largely exceed the international drinking water standards, and poses a health risk upon long-term utilization. Here we present the results of a multi-isotope study of low-saline (TDS=250-450 mg/L) groundwater from the Cambro-Ordovician Disi-Mudawarra sandstone aquifer systems in southern Jordan. The δ18O, δ2H, and 14C variations show at least three recharge phases into the confined and unconfined zones of the aquifer. High δ11B values (34-47‰) and B/Cl ratios (>>seawater ratio) suggests that the recharge water originated from rainwater of an early stage of air mass evolution, with negligible water-rock interaction in the aquifer. This meteoric composition is consistent with 87Sr/86Sr (70804 to 0.70860) and δ34S (9-16‰) values, and infers minimum dissolution of diagenetic carbonates that could have contributed depleted 11B, high 87Sr/86Sr, and dead carbon. The uncorrected 14C ages point to three major recharge episodes to the northwestern Arabian Peninsula: (1) >30 ka (Khrein aquifer); (2) 15-29 ka (confined Disi aquifer); and (3) 8-12 ka (unconfined Disi aquifer), in which the latter coincide with the “pluvial maximum” of Early Holocene. The stable isotope composition of the

  8. Characterization of mammographic masses based on level set segmentation with new image features and patient information

    SciTech Connect

    Shi Jiazheng; Sahiner, Berkman; Chan Heangping; Ge Jun; Hadjiiski, Lubomir; Helvie, Mark A.; Nees, Alexis; Wu Yita; Wei Jun; Zhou Chuan; Zhang Yiheng; Cui Jing

    2008-01-15

    Computer-aided diagnosis (CAD) for characterization of mammographic masses as malignant or benign has the potential to assist radiologists in reducing the biopsy rate without increasing false negatives. The purpose of this study was to develop an automated method for mammographic mass segmentation and explore new image based features in combination with patient information in order to improve the performance of mass characterization. The authors' previous CAD system, which used the active contour segmentation, and morphological, textural, and spiculation features, has achieved promising results in mass characterization. The new CAD system is based on the level set method and includes two new types of image features related to the presence of microcalcifications with the mass and abruptness of the mass margin, and patient age. A linear discriminant analysis (LDA) classifier with stepwise feature selection was used to merge the extracted features into a classification score. The classification accuracy was evaluated using the area under the receiver operating characteristic curve. The authors' primary data set consisted of 427 biopsy-proven masses (200 malignant and 227 benign) in 909 regions of interest (ROIs) (451 malignant and 458 benign) from multiple mammographic views. Leave-one-case-out resampling was used for training and testing. The new CAD system based on the level set segmentation and the new mammographic feature space achieved a view-based A{sub z} value of 0.83{+-}0.01. The improvement compared to the previous CAD system was statistically significant (p=0.02). When patient age was included in the new CAD system, view-based and case-based A{sub z} values were 0.85{+-}0.01 and 0.87{+-}0.02, respectively. The study also demonstrated the consistency of the newly developed CAD system by evaluating the statistics of the weights of the LDA classifiers in leave-one-case-out classification. Finally, an independent test on the publicly available digital database

  9. Molecular morphology of the chick heart visualized by MALDI imaging mass spectrometry.

    PubMed

    Grey, Angus C; Gelasco, Andrew K; Section, Jarren; Moreno-Rodriguez, Ricardo A; Krug, Edward L; Schey, Kevin L

    2010-05-01

    Utilization of MALDI-MS (matrix-assisted laser desorption/ionization mass spectrometry) for tissue imaging is a relatively new proteomic technique that simultaneously maps the spatial distribution of multiple proteins directly within a single frozen tissue section. Here, we report the development of a methodology to apply MALDI tissue imaging to chick heart tissue sections acquired from fixed and paraffin-embedded samples. This protocol produces molecular images that can be related to the high-quality histological tissue sections. Perfused term chick hearts were fixed in acidic ethanol and embedded in paraffin wax. Tissue sections (15 microm) were collected onto conductive slides, deparaffinized with xylene, and transitioned into water with graded ethanol washes and allowed to air dry. In separate experiments, three different MALDI matrices were applied to chick heart tissue sections through repeated cycles from a glass nebulizer. Tissue sections were then analyzed by MALDI mass spectrometry using a raster step-size of 75-100 microm, and molecular images for specific m/z ratios reconstituted. MALDI tissue imaging revealed spatially resolved protein signals within single heart sections that are specific to structures or regions of the heart, for example, vessels, valves, endocardium, myocardium, or septa. Moreover, no prior knowledge of protein expression is required as is the case for immunohistochemistry and in situ hybridization methodologies. The ability to simultaneously localize a large number of unique protein signals within a single tissue section, with good preservation of histological features, provides cardiovascular researchers a new tool to give insight into the molecular mechanisms underlying normal and pathological conditions.

  10. 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 Central

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

    2016-01-01

    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

  11. Connecting Imaging Mass Spectrometry and Magnetic Resonance Imaging-based Anatomical Atlases for Automated Anatomical Interpretation and Differential Analysis.

    PubMed

    Verbeeck, Nico; Spraggins, Jeffrey M; Murphy, Monika J M; Wang, Hui-Dong; Deutch, Ariel Y; Caprioli, Richard M; de Plas, Raf Van

    2017-02-27

    Imaging mass spectrometry (IMS) is a molecular imaging technology that can measure thousands of biomolecules concurrently without prior tagging, making it particularly suitable for exploratory research. However, the data size often makes thorough extraction of relevant information impractical. To help guide and accelerate IMS data analysis, we recently developed a framework that integrates IMS measurements with anatomical atlases, opening up opportunities for anatomy-driven exploration of IMS data. One example is the automated anatomical interpretation of ion images, where empirically measured ion distributions are automatically decomposed into their underlying anatomical structures. While offering significant potential, IMS-atlas integration has thus far been restricted to the Allen Mouse Brain Atlas (AMBA) and mouse brain samples. Here, we expand the applicability of this framework by extending towards new animal species and a new set of anatomical atlases retrieved from the Scalable Brain Atlas (SBA). Furthermore, as many SBA atlases are based on magnetic resonance imaging (MRI) data, a new registration pipeline was developed that enables direct non-rigid IMS-to-MRI registration. These developments are demonstrated on protein-focused FTICR IMS measurements from coronal brain sections of a Parkinson's disease (PD) rat model, which are integrated with an MRI-based rat brain atlas from the SBA. The new rat-focused IMS-atlas integration is used to perform automated anatomical interpretation and to find differential ions between healthy and diseased tissue. IMS-atlas integration can serve as an important accelerator in IMS data exploration, and with these new developments it can now be applied to a wider variety of animal species and modalities.

  12. 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

    2016-04-07

    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.

  13. 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

  14. Mass spectrometry imaging of small molecules in biological tissues using graphene oxide as a matrix.

    PubMed

    Zhou, Dan; Guo, Shuai; Zhang, Mo; Liu, Yujie; Chen, Tianjing; Li, Zhili

    2017-04-15

    With the development of matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI), molecular interrogation of tissue sections over a wide mass range has become feasible, but small molecule analysis is still far from being fully reached due to the limited sensitivity and matrix interference. Herein, graphene oxide (GO) is used as a MALDI matrix to image small molecules in tissues in negative ion mode. Finally, 212 of molecules including 190 of lipids and 22 of low molecular weight metabolites were detected and spatially visualized in mouse brain tissue sections without the interference of matrix ions/clusters, and the structures of 69 of the lipids were confirmed by using in situ tandem mass spectrometry. A further application of GO matrix could reveal distinct spatio-molecular signatures in viable and necrotic tumor regions derived from a mouse breast cancer tissue. In addition, GO as a MALDI matrix has exhibited a better performance in MSI of lipids relative to N-(1-naphthyl) ethylenediamine dihydrochloride and 9-aminoacridine.

  15. 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.

  16. 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.

  17. 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.

  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}⊙ ), HD 5608 B (0.10+/- 0.01{M}⊙ ), and HD 109272 B (0.28+/- 0.06{M}⊙ ). 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. 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.

  20. On-tissue chemical derivatization of 3-methoxysalicylamine for MALDI-imaging mass spectrometry

    PubMed Central

    Chacon, Almary; Zagol-Ikapitte, Irene; Amarnath, Venkataraman; Reyzer, Michelle L.; Oates, John A.; Caprioli, Richard M.; Boutaud, Olivier

    2011-01-01

    MALDI-imaging mass spectrometry (IMS) has been shown to be a powerful tool to study drug distributions in organ tissue as well as whole animal bodies. Nevertheless, not all drugs are amenable to MALDI while others may be limited by poor sensitivity poor sensitivity. The use of chemical derivatization to improve detection of small molecules by mass spectrometry techniques is well documented. To our knowledge, however, this approach has not been applied to direct tissue analysis of small organic molecules. In this manuscript, we demonstrate the use of on-tissue chemical derivatization of a small organic molecule, 3-methoxysalicylamine (3-MoSA) a scavenger of γ -ketoaldehydes. Derivatization of 3-MoSA with 1,1′-thiocarbonyldiimidazole (TCDI) results in an oxothiazolidine derivative which is detected with much greater sensitivity by MALDI than 3-MoSA itself. TCDI treatment of tissue from mice dosed with 3-MoSA allowed images to be obtained showing its spatial distribution as well as its pharmacokinetic profile in different organs. These images correlated well with results obtained from HPLC-MS/MS analyses of the same tissues. These results provide proof-of-concept that on-tissue chemical derivatization can be used to improve detection of a small organic molecule by MALDI-IMS. PMID:21834023

  1. A Simple Method for Improving the Spatial Resolution in Infrared Laser Ablation Mass Spectrometry Imaging

    NASA Astrophysics Data System (ADS)

    Hieta, Juha-Pekka; Vaikkinen, Anu; Auno, Samuli; Räikkönen, Heikki; Haapala, Markus; Scotti, Gianmario; Kopra, Jaakko; Piepponen, Petteri; Kauppila, Tiina J.

    2017-01-01

    In mass spectrometry imaging of tissues, the size of structures that can be distinguished is determined by the spatial resolution of the imaging technique. Here, the spatial resolution of IR laser ablation is markedly improved by increasing the distance between the laser and the focusing lens. As the distance between the laser and the lens is increased from 1 to 18 m, the ablation spot size decreases from 440 to 44 μm. This way, only the collimated center of the divergent laser beam is directed on the focusing lens, which results in better focusing of the beam. Part of the laser energy is lost at longer distance, but this is compensated by focusing of the radiation to a smaller area on the sample surface. The long distance can also be achieved by a set of mirrors, between which the radiation travels before it is directed to the focusing lens and the sample. This method for improving the spatial resolution can be utilized in mass spectrometry imaging of tissues by techniques that utilize IR laser ablation, such as laser ablation electrospray ionization, laser ablation atmospheric pressure photoionization, and matrix-assisted laser desorption electrospray ionization.

  2. Identifying important ions and positions in mass spectrometry imaging data using CUR matrix decompositions.

    PubMed

    Yang, Jiyan; Rübel, Oliver; Prabhat; Mahoney, Michael W; Bowen, Benjamin P

    2015-01-01

    Mass spectrometry imaging enables label-free, high-resolution spatial mapping of the chemical composition of complex, biological samples. Typical experiments require selecting ions and/or positions from the images: ions for fragmentation studies to identify keystone compounds and positions for follow up validation measurements using microdissection or other orthogonal techniques. Unfortunately, with modern imaging machines, these must be selected from an overwhelming amount of raw data. Existing techniques to reduce the volume of data, the most popular of which are principle component analysis and non-negative matrix factorization, have the disadvantage that they return difficult-to-interpret linear combinations of actual data elements. In this work, we show that CX and CUR matrix decompositions can be used directly to address this selection need. CX and CUR matrix decompositions use empirical statistical leverage scores of the input data to provide provably good low-rank approximations of the measured data that are expressed in terms of actual ions and actual positions, as opposed to difficult-to-interpret eigenions and eigenpositions. We show that this leads to effective prioritization of information for both ions and positions. In particular, important ions can be found either by using the leverage scores as a ranking function and using a deterministic greedy selection algorithm or by using the leverage scores as an importance sampling distribution and using a random sampling algorithm; however, selection of important positions from the original matrix performed significantly better when they were chosen with the random sampling algorithm. Also, we show that 20 ions or 40 locations can be used to reconstruct the original matrix to a tolerance of 17% error for a widely studied image of brain lipids; and we provide a scalable implementation of this method that is applicable for analysis of the raw data where there are often more than a million rows and/or columns

  3. 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.

  4. 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).

  5. 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

  6. 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

  7. Quantitative, nondestructive assessment of beech scale (Hemiptera: Cryptococcidae) density using digital image analysis of wax masses.

    PubMed

    Teale, Stephen A; Letkowski, Steven; Matusick, George; Stehman, Stephen V; Castello, John D

    2009-08-01

    Beech scale, Cryptococcus fagisuga Lindinger, is a non-native invasive insect associated with beech bark disease. A quantitative method of measuring viable scale density at the levels of the individual tree and localized bark patches was developed. Bark patches (10 cm(2)) were removed at 0, 1, and 2 m above the ground and at the four cardinal directions from 13 trees in northern New York and 12 trees in northern Michigan. Digital photographs of each patch were made, and the wax mass area was measured from two random 1-cm(2) subsamples on each bark patch using image analysis software. Viable scale insects were counted after removing the wax under a dissecting microscope. Separate regression analyses at the whole tree level for the New York and Michigan sites each showed a strong positive relationship of wax mass area with the number of underlying viable scale insects. The relationships for the New York and Michigan data were not significantly different from each other, and when pooling data from the two sites, there was still a significant positive relationship between wax mass area and the number of scale insects. The relationships between viable scale insects and wax mass area were different at the 0-, 1-, and 2-m sampling heights but do not seem to affect the relationship. This method does not disrupt the insect or its interactions with the host tree.

  8. Diffusion weighted magnetic resonance imaging in the diagnosis of parotid masses. Preliminary results

    PubMed Central

    Yologlu, Zeynel; Aydin, Hasan; Alp, Nalan A.; Aribas, Bilgin K.; Kizilgoz, Volkan; Arda, Kemal

    2016-01-01

    Objective To demonstrate the diagnostic potentials of MRI, diffusion weighted imaging (DWI), and apparent diffusion coefficient (ADC) mapping in the detection of parotid masses correlated to the histopathological results. Methods Study design was retrospective. Fifteen patients with parotid gland masses were included as the study group and contralateral normal parotis glands of same patients were taken as the control group. Patients with bilateral parotid gland tumors were excluded, 7 right-sided and 8 left-sided parotid masses were included in the research. The study took place at the Department of Radiology, Ankara, Turkey, between May 2012 and September 2014. Results Apparent diffusion coefficient measurements of 15 parotis tumors in 1000 and 750 sec/mm2 b-values with comparison to the contralateral normal gland parenchyma were demonstrated. Neurofibromas was predicted as the highest, and lipomas as the lowest ADC values. Pleomorphic adenomas, Warthin’s tumor, and normal parotid parenchyma indicate significant statistical differences from each other on the basis of mean ADC values (p<0.05). Conclusion The DWI and ADC mapping of parotis gland could aid in the differential diagnosis of benign and malignant masses. PMID:27874161

  9. 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.

  10. 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.

  11. Enzymatic resistance to the lipopeptide surfactin as identified through imaging mass spectrometry of bacterial competition

    PubMed Central

    Hoefler, B. Christopher; Gorzelnik, Karl V.; Yang, Jane Y.; Hendricks, Nathan; Dorrestein, Pieter C.; Straight, Paul D.

    2012-01-01

    Many species of bacteria secrete natural products that inhibit the growth or development of competing species. In turn, competitors may develop or acquire resistance to antagonistic molecules. Few studies have investigated the interplay of these countervailing forces in direct competition between two species. We have used an imaging mass spectrometry (IMS) approach to track metabolites exchanged between Bacillus subtilis and Streptomyces sp. Mg1 cultured together. Surfactin is a cyclic lipopeptide produced by B. subtilis that inhibits the formation of aerial hyphae by streptomycetes. IMS analysis exposed an addition of 18 mass units to surfactin in the agar proximal to Streptomyces sp. Mg1 but not other streptomycetes tested. The spatially resolved change in the mass of surfactin indicated hydrolysis of the molecule. We observed that the aerial growth of Streptomyces sp. Mg1 was resistant to inhibition by surfactin, which suggests that hydrolysis was a mechanism of resistance. To identify possible enzymes from Streptomyces sp. Mg1 with surfactin hydrolase activity, we isolated secreted proteins and identified candidates by mass spectrometry. We purified one candidate enzyme that hydrolyzed surfactin in vitro. We tested the role of this enzyme in surfactin resistance by deleting the corresponding gene from the S. Mg1 genome. We observed that aerial growth by the ΔsfhA mutant strain was now sensitive to surfactin. Our results identify an enzyme that hydrolyzes surfactin and confers resistance to aerial growth inhibition, which demonstrates the effective use of an IMS approach to track natural product modifications during interspecies competition. PMID:22826229

  12. 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.

  13. Tracking Nonradial Motions and Azimuthal Expansions of Interplanetary CMEs with the Solar Mass Ejection Imager

    SciTech Connect

    Kahler, Stephen

    2010-03-25

    The trajectories of interplanetary CMEs (ICMEs) are modified by their interactions with solar wind streams. These interactions can result in non-radial deflections of ICME trajectories and changes to their rates of azimuthal expansion. The Solar Mass Ejection Imager (SMEI), launched earlier in 2003 January, has provided heliospheric images of several hundred ICMEs during the declining portion of solar cycle 23. We selected three SMEI ICMEs, each traversing a range of solar elongation angles epsilon>20 deg. , and measured the time changes of their leading-edge profiles plotted against position angle, PA. The parabolic fits to those profiles yielded the propagation directions of the ICMEs as well as their leading-edge curvatures and time profiles. The selected ICMEs were associated with LASCO CMEs, so we tracked the PA variations in their propagation over 1 to 3-day periods. We found good fits for two of the ICMEs, but one yielded generally poor fits.

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

    PubMed

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

    2011-10-01

    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 C(60), 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.

  15. Imaging mass spectrometry of elements in forensic cases by LA-ICP-MS.

    PubMed

    Lauer, Estelle; Villa, Max; Jotterand, Morgane; Vilarino, Raquel; Bollmann, Marc; Michaud, Katarzyna; Grabherr, Silke; Augsburger, Marc; Thomas, Aurélien

    2017-03-01

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was performed to map elements in thin formalin-fixed paraffin-embedded tissue sections of two forensic cases with firearm and electrocution injuries, respectively. In both cases, histological examination of the wounded tissue regions revealed the presence of exogenous aggregates that may be interpreted as metallic depositions. The use of imaging LA-ICP-MS allowed us to unambiguously determine the elemental composition of the observed aggregates assisting the pathologist in case assessments. To the best of our knowledge, we demonstrate for the first time the use of imaging LA-ICP-MS as a complementary tool for forensic pathologists and toxicologists in order to map the presence of metals and other elements in thin tissue sections of post-mortem cases.

  16. Magnetic resonance imaging of Whipple's disease confined to the CNS presenting with multiple intracerebral mass lesions.

    PubMed

    Poureisa, Masoud; Daghighi, Mohammad Hossein; Esmaili, Haidar; Mazaheri-Khameneh, Ramin

    2015-01-01

    We report a patient diagnosed with Whipple's disease (WD) who presented only with neurological symptoms. Neuroimaging (MRI) showed lesions with marked mass effect similar to infiltrative tumors, which were hypersignal on long TR and hyposignal on short TR images, located in several areas of the brain. In serial controls, lesions resolved with gliosis and atrophic changes as well as migration of active infiltrative-like lesions to new areas. MR findings of the brain WD are discussed, which confirmed by stereotactic brain biopsy. Familiarity with the range of possible MR imaging appearances of WD enables the radiologist to place WD more effectively on the differential diagnosis which motivates the clinician to consider both the diagnosis and early initiation of treatment; so, this may significantly impact outcome. Moreover, repeated MR investigations may serve as a valuable method to evaluate efficacy of treatment and long term follow-up of WD involving the CNS.

  17. Evaluation of C60 secondary ion mass spectrometry for the chemical analysis and imaging of fingerprints.

    PubMed

    Sisco, Edward; Demoranville, Leonard T; Gillen, Greg

    2013-09-10

    The feasibility of using C60(+) cluster primary ion bombardment secondary ion mass spectrometry (C60(+) SIMS) for the analysis of the chemical composition of fingerprints is evaluated. It was found that C60(+) SIMS could be used to detect and image the spatial localization of a number of sebaceous and eccrine components in fingerprints. These analyses were also found to not be hindered by the use of common latent print powder development techniques. Finally, the ability to monitor the depth distribution of fingerprint constituents was found to be possible - a capability which has not been shown using other chemical imaging techniques. This paper illustrates a number of strengths and potential weaknesses of C60(+) SIMS as an additional or complimentary technique for the chemical analysis of fingerprints.

  18. Results from the AFRL Solar Mass Ejection Imager Mission - Four Years of Operation

    NASA Astrophysics Data System (ADS)

    Johnston, J. C.; Radick, R. R.

    2006-12-01

    This January marks the fourth anniversary of the launch of the Coriolis spacecraft that carries SMEI. Since 2003, SMEI has been recording nearly-full sky images every orbit (103 minutes) to at least 9th magnitude with 1o resolution and transmitting them to Earth. SMEI's main mission was to demonstrate that coronal mass ejections (CMEs) could be detected and tracked through the inner heliosphere en route to Earth to improve space weather forecasts. Besides mission applications, this unique dataset has provided insight into CME morphology and driving forces, interactions between comet tails and the heliosphere, zodiacal light, stellar variability and high altitude auroral phenomena. SMEI also observes asteroids and debris. This talk will briefly highlight accomplishments of the SMEI team and discuss future directions for the SMEI research program, such as tracking CMEs to other planets, searching for streamers and co-rotating interactive regions, and what might be the next step in operational heliospheric imaging of CMEs.

  19. Mass spectrometry imaging of therapeutics from animal models to three-dimensional cell cultures.

    PubMed

    Liu, Xin; Hummon, Amanda B

    2015-10-06

    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.

  20. Imaging time-of-flight secondary ion mass spectrometry of solid-phase peptide syntheses.

    PubMed

    Aubagnac, J L; Enjalbal, C; Drouot, C; Combarieu, R; Martinez, J

    1999-07-01

    Imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) of solid-phase peptide syntheses carried out by the Merrifield and Sheppard strategies is described. Mixtures of resin beads mixed at random from batch syntheses or obtained in combinatorial chemistry by the mix and split technique, where each bead is functionalized by a unique peptide, were analyzed directly without any chemical cleavage of the growing chains to assess the nature of the growing structure on any bead of the mixture without its isolation.

  1. 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

  2. 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

  3. Microbial competition between Bacillus subtilis and Staphylococcus aureus monitored by imaging mass spectrometry.

    PubMed

    Gonzalez, David J; Haste, Nina M; Hollands, Andrew; Fleming, Tinya C; Hamby, Matthew; Pogliano, Kit; Nizet, Victor; Dorrestein, Pieter C

    2011-09-01

    Microbial competition exists in the general environment, such as soil or aquatic habitats, upon or within unicellular or multicellular eukaryotic life forms. The molecular actions that govern microbial competition, leading to niche establishment and microbial monopolization, remain undetermined. The emerging technology of imaging mass spectrometry (IMS) enabled the observation that there is directionality in the metabolic output of the organism Bacillus subtilis when co-cultured with Staphylococcus aureus. The directionally released antibiotic alters S. aureus virulence factor production and colonization. Therefore, IMS provides insight into the largely hidden nature of competitive microbial encounters and niche establishment, and provides a paradigm for future antibiotic discovery.

  4. 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.

  5. 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.

  6. 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

  7. 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

  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. 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.

  10. 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.

  11. Heterogeneity of paclitaxel distribution in different tumor models assessed by MALDI mass spectrometry imaging

    PubMed Central

    Giordano, Silvia; Zucchetti, Massimo; Decio, Alessandra; Cesca, Marta; Fuso Nerini, Ilaria; Maiezza, Marika; Ferrari, Mariella; Licandro, Simonetta Andrea; Frapolli, Roberta; Giavazzi, Raffaella; Maurizio, D’Incalci; Davoli, Enrico; Morosi, Lavinia

    2016-01-01

    The penetration of anticancer drugs in solid tumors is important to ensure the therapeutic effect, so methods are needed to understand drug distribution in different parts of the tumor. Mass spectrometry imaging (MSI) has great potential in this field to visualize drug distribution in organs and tumor tissues with good spatial resolution and superior specificity. We present an accurate and reproducible imaging method to investigate the variation of drug distribution in different parts of solid tumors. The method was applied to study the distribution of paclitaxel in three ovarian cancer models with different histopathological characteristics and in colon cancer (HCT116), breast cancer (MDA-MB-231) and malignant pleural mesothelioma (MPM487). The heterogeneous drug penetration in the tumors is evident from the MALDI imaging results and from the images analysis. The differences between the various models do not always relate to significant changes in drug content in tumor homogenate examined by classical HPLC analysis. The specificity of the method clarifies the heterogeneity of the drug distribution that is analyzed from a quantitative point of view too, highlighting how marked are the variations of paclitaxel amounts in different part of solid tumors. PMID:28000726

  12. A Nanostructured Matrices Assessment to Study Drug Distribution in Solid Tumor Tissues by Mass Spectrometry Imaging

    PubMed Central

    Giordano, Silvia; Pifferi, Valentina; Morosi, Lavinia; Morelli, Melinda; Falciola, Luigi; Cappelletti, Giuseppe; Visentin, Sonja; Licandro, Simonetta A.; Frapolli, Roberta; Zucchetti, Massimo; Pastorelli, Roberta; Brunelli, Laura; D’Incalci, Maurizio; Davoli, Enrico

    2017-01-01

    The imaging of drugs inside tissues is pivotal in oncology to assess whether a drug reaches all cells in an adequate enough concentration to eradicate the tumor. Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging (MALDI-MSI) is one of the most promising imaging techniques that enables the simultaneous visualization of multiple compounds inside tissues. The choice of a suitable matrix constitutes a critical aspect during the development of a MALDI-MSI protocol since the matrix ionization efficiency changes depending on the analyte structure and its physico-chemical properties. The objective of this study is the improvement of the MALDI-MSI technique in the field of pharmacology; developing specifically designed nanostructured surfaces that allow the imaging of different drugs with high sensitivity and reproducibility. Among several nanomaterials, we tested the behavior of gold and titanium nanoparticles, and halloysites and carbon nanotubes as possible matrices. All nanomaterials were firstly screened by co-spotting them with drugs on a MALDI plate, evaluating the drug signal intensity and the signal-to-noise ratio. The best performing matrices were tested on control tumor slices, and were spotted with drugs to check the ion suppression effect of the biological matrix. Finally; the best nanomaterials were employed in a preliminary drug distribution study inside tumors from treated mice. PMID:28336905

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Ambient mass spectrometry imaging metabolomics method provides novel insights into the action mechanism of drug candidates.

    PubMed

    He, Jingjing; Luo, Zhigang; Huang, Lan; He, Jiuming; Chen, Yi; Rong, Xianfang; Jia, Shaobo; Tang, Fei; Wang, Xiaohao; Zhang, Ruiping; Zhang, Jianjun; Shi, Jiangong; Abliz, Zeper

    2015-01-01

    Elucidation of the mechanism of action for drug candidates is fundamental to drug development, and it is strongly facilitated by metabolomics. Herein, we developed an imaging metabolomics method based on air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) under ambient conditions. This method was subsequently applied to simultaneously profile a novel anti-insomnia drug candidate, N(6)-(4-hydroxybenzyl)-adenosine (NHBA), and various endogenous metabolites in rat whole-body tissue sections after the administration of NHBA. The principal component analysis (PCA) represented by an intuitive color-coding scheme based on hyperspectral imaging revealed in situ molecular profiling alterations in response to stimulation of NHBA, which are in a very low intensity and hidden in massive interferential peaks. We found that the abundance of six endogenous metabolites changed after drug administration. The spatiotemporal distribution indicated that five altered molecules—including neurotransmitter γ-aminobutyric acid, neurotransmitter precursors choline and glycerophosphocholine, energy metabolism-related molecules adenosine (an endogenous sleep factor), and creatine—are closely associated with insomnia or other neurological disorders. These findings not only provide insights into a deep understanding on the mechanism of action of NHBA, but also demonstrate that the AFADESI-MSI-based imaging metabolomics is a powerful technique to investigate the molecular mechanism of drug action, especially for drug candidates with multitarget or undefined target in the preclinical study stage.

  18. 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

  19. 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

  20. Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry for the Investigation of Proteins and Peptides

    NASA Astrophysics Data System (ADS)

    Burnum, Kristin E.; Frappier, Sara L.; Caprioli, Richard M.

    2008-07-01

    Mass spectrometry (MS) is an excellent technology for molecular imaging because of its high data dimensionality. MS can monitor thousands of individual molecular data channels measured as mass-to-charge (m/z). We describe the use of matrix-assisted laser desorption/ionization (MALDI) MS for the image analysis of proteins, peptides, lipids, drugs, and metabolites in tissues. We discuss the basic instrumentation and sample preparation methods needed to produce high-resolution images and high image reproducibility. Matrix-addition protocols are briefly discussed along with normal operating procedures, and selected biological and medical applications of MALDI imaging MS are described. We give examples of both two- and three-dimensional imaging, including normal mouse embryo implantation, sperm maturation in mouse epididymis, protein distributions in brain sections, protein alterations as a result of drug administration, and protein changes in brain due to neurodegeneration and tumor formation. Advantages of this technology and future challenges for its improvement are discussed.

  1. Nonlinear simultaneous reconstruction of inhomogeneous compressibility and mass density distributions in unidirectional pulse-echo ultrasound imaging

    NASA Astrophysics Data System (ADS)

    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.

  2. Building materials as intrinsic sources of sulphate: a hidden face of salt weathering of historical monuments investigated through multi-isotope tracing (B, O, S).

    PubMed

    Kloppmann, W; Bromblet, P; Vallet, J M; Vergès-Belmin, V; Rolland, O; Guerrot, C; Gosselin, C

    2011-04-01

    Sulphate neoformation is a major factor of degradation of stone monuments. Boron, sulphur and oxygen isotope signatures were investigated for five French historical monuments (Bourges, Chartres and Marseille cathedrals, Chenonceau castle, and Versailles garden statues) to investigate the role of intrinsic sulphate sources (gypsum plasters and mortars) in stone degradation, compared to the influence of extrinsic sources such as atmospheric pollution. Gypsum plasters and gypsum-containing mortars fall systematically in the δ(34)S and δ(18)O range of Paris Basin Eocene evaporites indicating the origin of the raw materials (so-called "Paris plaster"). Black crusts show the typical S and O isotope signatures observed elsewhere in Europe that can be attributed to atmospheric pollution, together with a marine component for Marseille. Boron isotopes for black crusts indicate coal combustion as principal boron source. Mortar isotope compositions discriminate three types, one similar to gypsum plasters, one strongly depleted in (34)S, attributed to pyrite oxidation, and a third one close to atmospheric sulphates. The isotopic composition of sulphates and boron of most degraded building stones of the different monuments is well explained by the identified sulphate sources. In several cases (in particular for Chenonceau and Bourges, to some extent for Chartres), the impact of gypsum plaster as building and restoration material on the degradation of the stones in its vicinity was clearly demonstrated. The study illustrates the usefulness of multi-isotope studies to investigate stone degradation factors, as the combination of several isotope systematics increases the discriminatory power of isotope studies with respect to contaminant sources.

  3. Proof of concept experiments of the multi-isotope process monitor: An online, nondestructive, near real-time monitor for spent nuclear fuel reprocessing facilities

    NASA Astrophysics Data System (ADS)

    Orton, Christopher R.; Fraga, Carlos G.; Christensen, Richard N.; Schwantes, Jon M.

    2012-04-01

    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 monitoring and 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.

  4. Optimization of whole-body zebrafish sectioning methods for mass spectrometry imaging.

    PubMed

    Nelson, Kimberly A; Daniels, Gabrielle J; Fournie, John W; Hemmer, Michael J

    2013-09-01

    Mass spectrometry imaging (MSI) methods and protocols have become widely adapted to a variety of tissues and species. However, the MSI literature contains minimal information on whole-body cryosection preparation for the zebrafish (ZF; Danio rerio), a model organism routinely used in developmental, toxicity, and carcinogenicity studies. The optimal medium for embedding and cryosectioning a whole organism or soft-tissue specimen for histological examination is a synthetic polymer mixture that is incompatible with MSI as a result of ion suppression. We describe the optimal methods and results for embedding and cryosectioning whole-body ZF for MALDI-MSI. We evaluated 13 distinct embedding media formulations and found a supportive hydrogel with the consistency of cartilage to be the optimal embedding medium. The hydrogel medium does not interfere with MSI data collection, aids in tissue stability, is readily available for purchase, and is easy to prepare and handle during cryosectioning. Additionally, we decreased the matrix cluster interference commonly caused by α-cyano-4-hydroxycinnamic acid by adding ammonium phosphate to the solvent spray solution. The optimized methods developed in our laboratory produced high-quality cryosections, as well as high-quality mass spectral images of sectioned ZF.

  5. Mass spectrometry imaging of biomarker lipids for phagocytosis and signalling during focal cerebral ischaemia

    PubMed Central

    Nielsen, Mette M. B.; Lambertsen, Kate L.; Clausen, Bettina H.; Meyer, Morten; Bhandari, Dhaka R.; Larsen, Søren T.; Poulsen, Steen S.; Spengler, Bernhard; Janfelt, Christian; Hansen, Harald S.

    2016-01-01

    Focal cerebral ischaemia has an initial phase of inflammation and tissue injury followed by a later phase of resolution and repair. Mass spectrometry imaging (desorption electrospray ionization and matrix assisted laser desorption ionization) was applied on brain sections from mice 2 h, 24 h, 5d, 7d, and 20d after permanent focal cerebral ischaemia. Within 24 h, N-acyl-phosphatidylethanolamines, lysophosphatidylcholine, and ceramide accumulated, while sphingomyelin disappeared. At the later resolution stages, bis(monoacylglycero)phosphate (BMP(22:6/22:6)), 2-arachidonoyl-glycerol, ceramide-phosphate, sphingosine-1-phosphate, lysophosphatidylserine, and cholesteryl ester appeared. At day 5 to 7, dihydroxy derivates of docosahexaenoic and docosapentaenoic acid, some of which may be pro-resolving mediators, e.g. resolvins, were found in the injured area, and BMP(22:6/22:6) co-localized with the macrophage biomarker CD11b, and probably with cholesteryl ester. Mass spectrometry imaging can visualize spatiotemporal changes in the lipidome during the progression and resolution of focal cerebral inflammation and suggests that BMP(22:6/22:6) and N-acyl-phosphatidylethanolamines can be used as biomarkers for phagocytizing macrophages/microglia cells and dead neurones, respectively. PMID:28004822

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

    PubMed Central

    Nelson, Kimberly A.; Daniels, Gabrielle J.; Fournie, John W.; Hemmer, Michael J.

    2013-01-01

    Mass spectrometry imaging (MSI) methods and protocols have become widely adapted to a variety of tissues and species. However, the MSI literature contains minimal information on whole-body cryosection preparation for the zebrafish (ZF; Danio rerio), a model organism routinely used in developmental, toxicity, and carcinogenicity studies. The optimal medium for embedding and cryosectioning a whole organism or soft-tissue specimen for histological examination is a synthetic polymer mixture that is incompatible with MSI as a result of ion suppression. We describe the optimal methods and results for embedding and cryosectioning whole-body ZF for MALDI-MSI. We evaluated 13 distinct embedding media formulations and found a supportive hydrogel with the consistency of cartilage to be the optimal embedding medium. The hydrogel medium does not interfere with MSI data collection, aids in tissue stability, is readily available for purchase, and is easy to prepare and handle during cryosectioning. Additionally, we decreased the matrix cluster interference commonly caused by α-cyano-4-hydroxycinnamic acid by adding ammonium phosphate to the solvent spray solution. The optimized methods developed in our laboratory produced high-quality cryosections, as well as high-quality mass spectral images of sectioned ZF. PMID:23997659

  7. 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.

  8. Epithelial ovarian carcinoma diagnosis by desorption electrospray ionization mass spectrometry imaging

    PubMed Central

    Dória, Maria Luisa; McKenzie, James S.; Mroz, Anna; Phelps, David L.; Speller, Abigail; Rosini, Francesca; Strittmatter, Nicole; Golf, Ottmar; Veselkov, Kirill; Brown, Robert; Ghaem-Maghami, Sadaf; Takats, Zoltan

    2016-01-01

    Ovarian cancer is highly prevalent among European women, and is the leading cause of gynaecological cancer death. Current histopathological diagnoses of tumour severity are based on interpretation of, for example, immunohistochemical staining. Desorption electrospray mass spectrometry imaging (DESI-MSI) generates spatially resolved metabolic profiles of tissues and supports an objective investigation of tumour biology. In this study, various ovarian tissue types were analysed by DESI-MSI and co-registered with their corresponding haematoxylin and eosin (H&E) stained images. The mass spectral data reveal tissue type-dependent lipid profiles which are consistent across the n = 110 samples (n = 107 patients) used in this study. Multivariate statistical methods were used to classify samples and identify molecular features discriminating between tissue types. Three main groups of samples (epithelial ovarian carcinoma, borderline ovarian tumours, normal ovarian stroma) were compared as were the carcinoma histotypes (serous, endometrioid, clear cell). Classification rates >84% were achieved for all analyses, and variables differing statistically between groups were determined and putatively identified. The changes noted in various lipid types help to provide a context in terms of tumour biochemistry. The classification of unseen samples demonstrates the capability of DESI-MSI to characterise ovarian samples and to overcome existing limitations in classical histopathology. PMID:27976698

  9. Salamander retina phospholipids and their localization by MALDI imaging mass spectrometry at cellular size resolution.

    PubMed

    Roy, Michael C; Nakanishi, Hiroki; Takahashi, Kazuteru; Nakanishi, Setsuko; Kajihara, Shigeki; Hayasaka, Takahiro; Setou, Mitsutoshi; Ogawa, Kiyoshi; Taguchi, Ryo; Naito, Takayuki

    2011-03-01

    Salamander large cells facilitated identification and localization of lipids by MALDI imaging mass spectrometry. Salamander retina lipid extract showed similarity with rodent retina lipid extract in phospholipid content and composition. Like rodent retina section, distinct layer distributions of phospholipids were observed in the salamander retina section. Phosphatidylcholines (PCs) composing saturated and monounsaturated fatty acids (PC 32:0, PC 32:1, and PC 34:1) were detected mainly in the outer and inner plexiform layers (OPL and IPL), whereas PCs containing polyunsaturated fatty acids (PC 36:4, PC 38:6, and PC 40:6) composed the inner segment (IS) and outer segment (OS). The presence of PCs containing polyunsaturated fatty acids in the OS layer implied that these phospholipids form flexible lipid bilayers, which facilitate phototransduction process occurring in the rhodopsin rich OS layer. Distinct distributions and relative signal intensities of phospholipids also indicated their relative abundance in a particular cell or a cell part. Using salamander large cells, a single cell level localization and identification of biomolecules could be achieved by MALDI imaging mass spectrometry.

  10. Observing the Invisible through Imaging Mass Spectrometry, a Window into the Metabolic Exchange Patterns of Microbes

    PubMed Central

    Gonzalez, David J.; Xu, Yuquan; Yang, Yu-Liang; Esquenazi, Eduardo; Liu, Wei-Ting; Edlund, Anna; Duong, Tram; Du, Liangcheng; Molnár, István; Gerwick, William H.; Jensen, Paul R.; Fischbach, Michael; Liaw, Chih-Chuang; Straight, Paul; Nizet, Victor; Dorrestein, Pieter C.

    2012-01-01

    Many microbes can be cultured as single-species communities. Often, these colonies are controlled and maintained via the secretion of metabolites. Such metabolites have been an invaluable resource for the discovery of therapeutics (e.g. penicillin, taxol, rapamycin, epothilone). In this article, written for a special issue on imaging mass spectrometry, we show that MALDI-imaging mass spectrometry can be adapted to observe, in a spatial manner, the metabolic exchange patterns of a diverse array of microbes, including thermophilic and mesophilic fungi, cyanobacteria, marine and terrestrial actinobacteria, and pathogenic bacteria. Dependent on media conditions, on average and based on manual analysis, we observed 11.3 molecules associated with each microbial IMS experiment, which was split nearly 50:50 between secreted and colony-associated molecules. The spatial distributions of these metabolic exchange factors are related to the biological and ecological functions of the organisms. This work establishes that MALDI-based IMS can be used as a general tool to study a diverse array of microbes. Furthermore the article forwards the notion of the IMS platform as a window to discover previously unreported molecules by monitoring the metabolic exchange patterns of organisms when grown on agar substrates. PMID:22641157

  11. Pancreatic Cancer Surgical Resection Margins: Molecular Assessment by Mass Spectrometry Imaging

    PubMed Central

    Eberlin, Livia S.; Zare, Richard N.; Tibshirani, Robert; Longacre, Teri A.; Jalali, Moe; Norton, Jeffrey A.; Poultsides, George A.

    2016-01-01

    Background Surgical resection with microscopically negative margins remains the main curative option for pancreatic cancer; however, in practice intraoperative delineation of resection margins is challenging. Ambient mass spectrometry imaging has emerged as a powerful technique for chemical imaging and real-time diagnosis of tissue samples. We applied an approach combining desorption electrospray ionization mass spectrometry imaging (DESI-MSI) with the least absolute shrinkage and selection operator (Lasso) statistical method to diagnose pancreatic tissue sections and prospectively evaluate surgical resection margins from pancreatic cancer surgery. Methods and Findings Our methodology was developed and tested using 63 banked pancreatic cancer samples and 65 samples (tumor and specimen margins) collected prospectively during 32 pancreatectomies from February 27, 2013, to January 16, 2015. In total, mass spectra for 254,235 individual pixels were evaluated. When cross-validation was employed in the training set of samples, 98.1% agreement with histopathology was obtained. Using an independent set of samples, 98.6% agreement was achieved. We used a statistical approach to evaluate 177,727 mass spectra from samples with complex, mixed histology, achieving an agreement of 81%. The developed method showed agreement with frozen section evaluation of specimen margins in 24 of 32 surgical cases prospectively evaluated. In the remaining eight patients, margins were found to be positive by DESI-MSI/Lasso, but negative by frozen section analysis. The median overall survival after resection was only 10 mo for these eight patients as opposed to 26 mo for patients with negative margins by both techniques. This observation suggests that our method (as opposed to the standard method to date) was able to detect tumor involvement at the margin in patients who developed early recurrence. Nonetheless, a larger cohort of samples is needed to validate the findings described in this study

  12. 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.

  13. On-Chip Peptide Mass Spectrometry Imaging for Protein Kinase Inhibitor Screening.

    PubMed

    Cho, Young-Lai; Kim, Young-Pil; Son, Jin Gyeong; Son, Miyoung; Lee, Tae Geol

    2017-01-03

    Protein kinases are enzymes that are important targets for drug discovery because of their involvement in regulating the essential cellular processes. For this reason, the changes in protein kinase activity induced by each drug candidate (the inhibitor in this case) need to be accurately determined. Here, an on-chip secondary ion mass spectrometry (SIMS) imaging technique of the peptides was developed for determining protein kinase activity and inhibitor screening without a matrix. In our method, cysteine-tethered peptides adsorbed onto a gold surface produced changes in the relative peak intensities of the phosphorylated and unphosphorylated substrate peptides, which were quantitatively dependent on protein kinase activity. Using mass spectrometry imaging of multiple compartments on the gold surface in the presence of a peptide substrate, we screened 13,727 inhibitors, of which seven were initially found to have inhibitor efficiencies that surpassed 50%. Of these, we were able to identify a new breakpoint cluster region-abelson (BCR-ABL)(T315I) kinase inhibitor, henceforth referred to as KR135861. KR135861 showed no cytotoxicity and was subsequently confirmed to be superior to imatinib, a commercial drug marketed as Gleevec. Moreover, KR135861 exhibited a greater inhibitory effect on the BCR-ABL(T315I) tyrosine kinase, with an IC50 value as low as 1.3 μM. In in vitro experiments, KR135861 reduced the viability of both Ba/F3 cells expressing wild-type BCR-ABL and BCR-ABL(T315I), in contrast to imatinib's inhibitory effects only on Ba/F3 cells expressing wild-type BCR-ABL. Due to the surface sensitivity and selectivity of SIMS imaging, it is anticipated that our approach will make it easier to validate the small modifications of a substrate in relation to enzyme activity as well as for drug discovery. This mass spectrometry imaging analysis enables efficient screening for protein kinase inhibitors, thus permitting high-throughput drug screening with high accuracy

  14. Full Adaptive Optics Images of ADS 9731 and MU Cassiopeiae: Orbits and Masses

    NASA Astrophysics Data System (ADS)

    Drummond, Jack D.; Christou, Julian C.; Fugate, Robert Q.

    1995-09-01

    The double double ADS 9731 and the nearby Population II astrometric binary μ Cas have been imaged with full adaptive optics employed at the 1.5 m telescope belonging to the USAF Phillips Laboratory's Starfire Optical Range near Albuquerque, New Mexico. On 1994 May 4 at a wavelength of 0.85 μm, the Δmag values and separations for ADS 9731 components AB were observed to be 2.19 and 1".27, 0.90 and 1".55 for CD, and 0.40 and 14".8 between A and C. Combining these observations with earlier ones, we have obtained circular, highly inclined, long-period (834 and 1230 yr) preliminary orbits for both pairs and derived their masses along with other astrophysical quantities. However, consideration of stellar evolutionary models leads to a disagreement in the derived distance to the system (108.1 pc) and/or masses, which will perhaps be resolved by subsequent orbital refinement. The first ever real-time images at short wavelengths (<1 μm) of the faint companion to the astrometric binary μ Cas A component were easily made at 0.85 microns on 1994 August 28 and October 22, with movement noted between the two dates. The Δmag value was determined to be 4.9±0.1, and the separation on the two dates was 0".73 and 0".66. Combining our measurements with astrometric data from both Sproul and Allegheny Observatories, we make a simultaneous fit for a new master orbit and find masses of 0.742±0.059 and 0.173±0.011 Msun for A and B, respectively. From further analysis we derive a presumably primordial helium abundance f6r μ Cas of Y = 0.24±0.07 for an assumed age of 1010 yr and the latest measured metallicity of Z = 0.0021.

  15. Imaging Mass Spectrometry: A New Tool for Pathology in a Molecular Age

    PubMed Central

    Norris, Jeremy L.; Caprioli, Richard M.

    2014-01-01

    Mass spectrometry provides unique advantages for the analysis of clinical specimens, and these capabilities have been critical to the advancement of diagnostic medicine. To date, liquid chromatography mass spectrometry (LC-MS) is the platform most commonly used for diagnostics; however, LC-MS based proteomics is very labor intensive and costly to implement for high volume assays. Furthermore, when analyzing tissue samples, additional laborious sample preparation steps must be employed (e.g., extraction methods or laser microdissection). The direct analysis of cells and tissues by matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) has developed significant momentum for applications that have diagnostic potential. MALDI IMS provides molecular information from specific cell types within tissue sections; however, this laser-based approach significantly reduces the analysis time for each location sampled. This Viewpoint discusses the technologies for direct analysis of tissues, the potential for diagnostic applications using MALDI IMS, and the challenges faced in the transfer of the technology to the clinical laboratory. PMID:24178781

  16. Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging.

    PubMed

    Lou, Sha; Balluff, Benjamin; Cleven, Arjen H G; Bovée, Judith V M G; McDonnell, Liam A

    2017-02-01

    Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival (m/z 180.9436 and 241.0118) and metastasis-free survival (m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine. Graphical Abstract ᅟ.

  17. Prognostic Metabolite Biomarkers for Soft Tissue Sarcomas Discovered by Mass Spectrometry Imaging

    NASA Astrophysics Data System (ADS)

    Lou, Sha; Balluff, Benjamin; Cleven, Arjen H. G.; Bovée, Judith V. M. G.; McDonnell, Liam A.

    2017-02-01

    Metabolites can be an important read-out of disease. The identification and validation of biomarkers in the cancer metabolome that can stratify high-risk patients is one of the main current research aspects. Mass spectrometry has become the technique of choice for metabolomics studies, and mass spectrometry imaging (MSI) enables their visualization in patient tissues. In this study, we used MSI to identify prognostic metabolite biomarkers in high grade sarcomas; 33 high grade sarcoma patients, comprising osteosarcoma, leiomyosarcoma, myxofibrosarcoma, and undifferentiated pleomorphic sarcoma were analyzed. Metabolite MSI data were obtained from sections of fresh frozen tissue specimens with matrix-assisted laser/desorption ionization (MALDI) MSI in negative polarity using 9-aminoarcridine as matrix. Subsequent annotation of tumor regions by expert pathologists resulted in tumor-specific metabolite signatures, which were then tested for association with patient survival. Metabolite signals with significant clinical value were further validated and identified by high mass resolution Fourier transform ion cyclotron resonance (FTICR) MSI. Three metabolite signals were found to correlate with overall survival ( m/z 180.9436 and 241.0118) and metastasis-free survival ( m/z 160.8417). FTICR-MSI identified m/z 241.0118 as inositol cyclic phosphate and m/z 160.8417 as carnitine.

  18. Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging.

    PubMed

    Swales, John G; Strittmatter, Nicole; Tucker, James W; Clench, Malcolm R; Webborn, Peter J H; Goodwin, Richard J A

    2016-11-24

    Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.

  19. Essential tactics of tissue preparation and matrix nano-spotting for successful compound imaging mass spectrometry.

    PubMed

    Végvári, Akos; Fehniger, Thomas E; Gustavsson, Lena; Nilsson, Anna; Andrén, Per E; Kenne, Kerstin; Nilsson, Johan; Laurell, Thomas; Marko-Varga, György

    2010-04-18

    The ultimate goal of MALDI-Imaging Mass Spectrometry (MALDI-IMS) is to achieve spatial localization of analytes in tissue sections down to individual tissue compartments or even at the level of a few cells. With compound tissue imaging, it is possible to track the transportation of an unlabelled, inhaled reference compound within lung tissue, through the application of MALDI-IMS. The procedure for isolation and preparation of lung tissues is found to be crucial in order to preserve the anatomy and structure of the pulmonary compartments. To avoid delocalization of analytes within lung tissue compartments we have applied an in-house designed nano-spotter, based on a microdispenser mounted on an XY table, of which movement and spotting functionality were fully computer controlled. We demonstrate the usefulness of this platform in lung tissue sections isolated from rodent in vivo model, applied to compound tissue imaging as exemplified with the determination of the spatial distribution of (1alpha,2beta,4beta,7beta)-7-[(hydroxidi-2-thienylacetyl)oxy]-9,9-dimethyl-3-oxa-9-azoniatricyclo[3.3.1.0(2,4)]nonane, also known as tiotropium. We provide details on tissue preparation protocols and sample spotting technology for successful identification of drug in mouse lung tissue by using MALDI-Orbitrap instrumentation.

  20. 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.

  1. Five Micron High Resolution MALDI Mass Spectrometry Imaging with Simple, Interchangeable, Multi-Resolution Optical System

    DOE PAGES

    Feenstra, Adam D.; Dueñas, Maria Emilia; Lee, Young Jin

    2017-01-03

    High-spatial resolution mass spectrometry imaging (MSI) is crucial for the mapping of chemical distributions at the cellular and subcellular level. Here in this work, we improved our previous laser optical system for matrix-assisted laser desorption ionization (MALDI)-MSI, from ~9 μm practical laser spot size to a practical laser spot size of ~4 μm, thereby allowing for 5 μm resolution imaging without oversampling. This is accomplished through a combination of spatial filtering, beam expansion, and reduction of the final focal length. Most importantly, the new laser optics system allows for simple modification of the spot size solely through the interchanging ofmore » the beam expander component. Using 10×, 5×, and no beam expander, we could routinely change between ~4, ~7, and ~45 μm laser spot size, in less than 5 min. We applied this multi-resolution MALDI-MSI system to a single maize root tissue section with three different spatial resolutions of 5, 10, and 50 μm and compared the differences in imaging quality and signal sensitivity. Lastly, we also demonstrated the difference in depth of focus between the optical systems with 10× and 5× beam expanders.« less

  2. 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.

  3. 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.

  4. 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.

  5. Chemical imaging of latent fingerprints by mass spectrometry based on laser activated electron tunneling.

    PubMed

    Tang, Xuemei; Huang, Lulu; Zhang, Wenyang; Zhong, Hongying

    2015-03-03

    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.

  6. Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging

    PubMed Central

    Swales, John G.; Strittmatter, Nicole; Tucker, James W.; Clench, Malcolm R.; Webborn, Peter J. H.; Goodwin, Richard J. A.

    2016-01-01

    Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported. PMID:27883030

  7. Five Micron High Resolution MALDI Mass Spectrometry Imaging with Simple, Interchangeable, Multi-Resolution Optical System

    NASA Astrophysics Data System (ADS)

    Feenstra, Adam D.; Dueñas, Maria Emilia; Lee, Young Jin

    2017-01-01

    High-spatial resolution mass spectrometry imaging (MSI) is crucial for the mapping of chemical distributions at the cellular and subcellular level. In this work, we improved our previous laser optical system for matrix-assisted laser desorption ionization (MALDI)-MSI, from 9 μm practical laser spot size to a practical laser spot size of 4 μm, thereby allowing for 5 μm resolution imaging without oversampling. This is accomplished through a combination of spatial filtering, beam expansion, and reduction of the final focal length. Most importantly, the new laser optics system allows for simple modification of the spot size solely through the interchanging of the beam expander component. Using 10×, 5×, and no beam expander, we could routinely change between 4, 7, and 45 μm laser spot size, in less than 5 min. We applied this multi-resolution MALDI-MSI system to a single maize root tissue section with three different spatial resolutions of 5, 10, and 50 μm and compared the differences in imaging quality and signal sensitivity. We also demonstrated the difference in depth of focus between the optical systems with 10× and 5× beam expanders.

  8. Spatial Quantitation of Drugs in tissues using Liquid Extraction Surface Analysis Mass Spectrometry Imaging

    NASA Astrophysics Data System (ADS)

    Swales, John G.; Strittmatter, Nicole; Tucker, James W.; Clench, Malcolm R.; Webborn, Peter J. H.; Goodwin, Richard J. A.

    2016-11-01

    Liquid extraction surface analysis mass spectrometry imaging (LESA-MSI) has been shown to be an effective tissue profiling and imaging technique, producing robust and reliable qualitative distribution images of an analyte or analytes in tissue sections. Here, we expand the use of LESA-MSI beyond qualitative analysis to a quantitative analytical technique by employing a mimetic tissue model previously shown to be applicable for MALDI-MSI quantitation. Liver homogenate was used to generate a viable and molecularly relevant control matrix for spiked drug standards which can be frozen, sectioned and subsequently analyzed for the generation of calibration curves to quantify unknown tissue section samples. The effects of extraction solvent composition, tissue thickness and solvent/tissue contact time were explored prior to any quantitative studies in order to optimize the LESA-MSI method across several different chemical entities. The use of a internal standard to normalize regional differences in ionization response across tissue sections was also investigated. Data are presented comparing quantitative results generated by LESA-MSI to LC-MS/MS. Subsequent analysis of adjacent tissue sections using DESI-MSI is also reported.

  9. Spatially resolved chemical imaging of individual atmospheric particles using nanoscale imaging mass spectrometry: insight into particle origin and chemistry

    SciTech Connect

    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 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. 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.

  10. Spatially resolved chemical imaging of individual atmospheric particles using nanoscale imaging mass spectrometry: insight into particle origin and chemistry

    DOE PAGES

    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

  11. 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.

  12. 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.

  13. Application of digital image processing to a beta-gauge for determining mass concentration of suspending particulate matter in atmosphere.

    PubMed

    Gotoh, T

    1992-05-01

    A two-dimensional image of the mass concentration of suspending particulate matter (SPM) collected on Millipore filter paper was photographed with Ultrofilm-3H. The printed paper image was transformed into a digital image (256 x 256 pixels) with 256 gray levels. Two results were obtained. The averaged values of gray level over all pixels of the digital image was found to correlate with the mass value measured by a beta-gauge. The characteristical range of the digital image which was transformed to frequency by two-dimensional fast fourier transformation was found in the low frequency. It was presumed to relate to SPM from anthropogenic sources because the SPMs usually show higher density and smaller particle size than SPMs from natural sources.

  14. 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

  15. Quantification-based mass spectrometry imaging of proteins by parafilm assisted microdissection.

    PubMed

    Franck, Julien; Quanico, Jusal; Wisztorski, Maxence; Day, Robert; Salzet, Michel; Fournier, Isabelle

    2013-09-03

    MALDI mass spectrometry imaging (MALDI-MSI) was presented as a good strategy to highlight regions presenting specific phenotypes based on molecular content. The proteins present in the different areas can be identified by MALDI MSI; however, the number of protein identifications remains low in comparison with classical MS-based proteomics approaches. To overcome this, a new strategy, involving the microdissection of tissue sections mounted on parafilm M-covered glass slides, is presented. Extraction and fractionation of proteins from a specific region of interest were investigated, leading to the identification of more than 1000 proteins from each microdissected piece. The strength of this cheap technique lies in the facile excision of millimeter-sized portions from the tissue allowing for the identification of proteins from cells of a specific phenotype obtained from the MALDI MS imaging-based molecular classification using hierarchical clustering. This approach can be extended to whole tissue sections in order to generate images of the section based on label-free quantification obtained from identification data. As a proof of concept, we have studied a tissue mounted on a parafilm M-covered glass slide, cut it into regular pieces, and submitted each piece to identification and quantification according to the developed parafilm-assisted microdissection (PAM) method. Images were then reconstructed by relative quantification of identified proteins based on spectral counting of the peptides analyzed by nanoLC-MS and MS/MS. This strategy of quantification-based MSI offers new possibilities for mapping a large number of high and low abundance proteins.

  16. Body image flexibility as a protective factor against disordered eating behavior for women with lower body mass index.

    PubMed

    Hill, Mary L; Masuda, Akihiko; Latzman, Robert D

    2013-08-01

    The purpose of the current study was to examine whether body dissatisfaction and body image flexibility would be uniquely and significantly associated with disordered eating behavior. In addition, the study examined if body mass index (BMI) moderated the relationships between each of the body image related variables and disordered eating. Two-hundred-fifty-eight female participants completed the web-based survey. Body dissatisfaction and body image flexibility were significantly related to disordered eating behavior, after controlling for ethnicity and BMI, and BMI moderated the relation between body image flexibility and disordered eating. Specifically, for those with low BMI, greater body image flexibility was associated with reduced disordered eating behavior. Body image flexibility was not associated with disordered eating behavior among those with average or high BMI. These results suggest that greater body image flexibility may serve as a protective factor against disordered eating behaviors for those with low BMI.

  17. 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

  18. 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

  19. Reduced Sampling Size with Nanopipette for Tapping-Mode Scanning Probe Electrospray Ionization Mass Spectrometry Imaging

    PubMed Central

    Kohigashi, Tsuyoshi; Otsuka, Yoichi; Shimazu, Ryo; Matsumoto, Takuya; Iwata, Futoshi; Kawasaki, Hideya; Arakawa, Ryuichi

    2016-01-01

    Mass spectrometry imaging (MSI) with ambient sampling and ionization can rapidly and easily capture the distribution of chemical components in a solid sample. Because the spatial resolution of MSI is limited by the size of the sampling area, reducing sampling size is an important goal for high resolution MSI. Here, we report the first use of a nanopipette for sampling and ionization by tapping-mode scanning probe electrospray ionization (t-SPESI). The spot size of the sampling area of a dye molecular film on a glass substrate was decreased to 6 μm on average by using a nanopipette. On the other hand, ionization efficiency increased with decreasing solvent flow rate. Our results indicate the compatibility between a reduced sampling area and the ionization efficiency using a nanopipette. MSI of micropatterns of ink on a glass and a polymer substrate were also demonstrated. PMID:28101441

  20. 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.

  1. 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.

  2. Automated Detection of Coronal Mass Ejections in STEREO Heliospheric Imager Data

    NASA Astrophysics Data System (ADS)

    Pant, V.; Willems, S.; Rodriguez, L.; Mierla, M.; Banerjee, D.; Davies, J. A.

    2016-12-01

    We have performed, for the first time, the successful automated detection of coronal mass ejections (CMEs) in data from the inner heliospheric imager (HI-1) cameras on the STEREO-A spacecraft. Detection of CMEs is done in time-height maps based on the application of the Hough transform, using a modified version of the CACTus software package, conventionally applied to coronagraph data. In this paper, we describe the method of detection. We present the results of the application of the technique to a few CMEs, which are well detected in the HI-1 imagery, and compare these results with those based on manual-cataloging methodologies. We discuss, in detail, the advantages and disadvantages of this method.

  3. Imaging combinatorial libraries by mass spectrometry: from peptide to organic-supported syntheses.

    PubMed

    Enjalbal, Christine; Maux, Delphine; Combarieu, Robert; Martinez, Jean; Aubagnac, Jean-Louis

    2003-01-01

    Supported peptide and drug-like organic molecule libraries were profiled in single nondestructive imaging static secondary ion mass spectrometric experiments. The selective rupture of the bond linking the compound and the insoluble polymeric support (resin) produced ions that were characteristic of the anchored molecules, thus allowing unambiguous resin bead assignment. Very high sensitivity and specificity were obtained with such a direct analytical method, which avoids the chemical release of the molecules from the support. Libraries issued from either mix-and-split or parallel solid-phase organic syntheses were profiled, demonstrating the usefulness of such a technique for characterization and optimization during combinatorial library development. Moreover, the fact that the control was effected at the bead level whatever the structure and quantity of the anchored molecules allows the sole identification of active beads selected from on-bead screening. Under such circumstances, the time-consuming whole-library characterization could thus be suppressed, enhancing the throughput of the analytical process.

  4. Proteomic profiles of thyroid tumors by mass spectrometry-imaging on tissue microarrays.

    PubMed

    Galli, Manuel; Pagni, Fabio; De Sio, Gabriele; Smith, Andrew; Chinello, Clizia; Stella, Martina; L'Imperio, Vincenzo; Manzoni, Marco; Garancini, Mattia; Massimini, Diego; Mosele, Niccolò; Mauri, Giancarlo; Zoppis, Italo; Magni, Fulvio

    2016-12-09

    The current study proposes the successful use of a mass spectrometry-imaging technology that explores the composition of biomolecules and their spatial distribution directly on-tissue to differentially classify benign and malignant cases, as well as different histotypes. To identify new specific markers, we investigated with this technology a wide histological Tissue Microarray (TMA)-based thyroid lesion series. Results showed specific protein signatures for malignant and benign specimens and allowed to build clusters comprising several proteins with discriminant capabilities. Among them, FINC, ACTB1, LMNA, HSP7C and KAD1 were identified by LC-ESI-MS/MS and found up-expressed in malignant lesions. These findings represent the opening of further investigations for their translation into clinical practice, e.g. for setting up new immunohistochemical stainings, and for a better understanding of thyroid lesions.

  5. Assessment of pathological response to therapy using lipid mass spectrometry imaging

    PubMed Central

    Patterson, Nathan Heath; Alabdulkarim, Balqis; Lazaris, Anthoula; Thomas, Aurélien; Marcinkiewicz, Mieczyslaw M.; Gao, Zu-hua; Vermeulen, Peter B.; Chaurand, Pierre; Metrakos, Peter

    2016-01-01

    In many cancers, the establishment of a patient’s future treatment regime often relies on histopathological assessment of tumor tissue specimens in order to determine the extent of the ‘pathological response’ to a given therapy. However, histopathological assessment of pathological response remains subjective. Here we use MALDI mass spectrometry imaging to generate lipid signatures from colorectal cancer liver metastasis specimens resected from patients preoperatively treated with chemotherapy. Using these signatures we obtained a unique pathological response score that correlates with prognosis. In addition, we identify single lipid moieties that are overexpressed in different histopathological features of the tumor, which have potential as new biomarkers for assessing response to therapy. These data show that computational methods, focusing on the lipidome, can be used to determine prognostic markers for response to chemotherapy and may potentially improve risk assessment and patient care. PMID:27841360

  6. Mass spectrometry MALDI imaging of colon cancer biomarkers: a new diagnostic paradigm.

    PubMed

    Pevsner, Paul H; Melamed, Jonathan; Remsen, Tiffany; Kogos, Alexander; Francois, Fritz; Kessler, Paul; Stern, Arnold; Anand, Sury

    2009-02-01

    Colorectal cancer (CRC), is the second-leading cause of cancer-related deaths in the USA, affecting both men and women. Current projections show little or no change since the publication of a morbidity and mortality study in 2005. The projected number of new cases for 2008 is 154,000, and the projected number of CRC cancer deaths for 2008 is 53,000. The standard diagnostic paradigm is based on histopathology of either biopsy or surgical specimens. This article suggests a new paradigm for colon cancer diagnosis and staging using matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS or IMS). IMS may identify potential tumors in normal tissue of cancer patients and predict those cancer patients who are at risk for recurrent cancer.

  7. Simultaneous hydrogen and heavier element isotopic ratio images with a scanning submicron ion probe and mass resolved polyatomic ions.

    PubMed

    Slodzian, Georges; Wu, Ting-Di; Bardin, Noémie; Duprat, Jean; Engrand, Cécile; Guerquin-Kern, Jean-Luc

    2014-04-01

    In situ microanalysis of solid samples is often performed using secondary ion mass spectrometry (SIMS) with a submicron ion probe. The destructive nature of the method makes it mandatory to prevent information loss by using instruments combining efficient collection of secondary ions and a mass spectrometer with parallel detection capabilities. The NanoSIMS meets those requirements with a magnetic spectrometer but its mass selectivity has to be improved for accessing opportunities expected from polyatomic secondary ions. We show here that it is possible to perform D/H ratio measurement images using 12CD-/12CH-, 16OD-/16OH-, or 12C2D-/12C2H- ratios. These polyatomic species allow simultaneous recording of D/H ratios and isotopic compositions of heavier elements like 15N/14N (via 12C15N-/12C14N-) and they provide a powerful tool to select the phase of interest (e.g., mineral versus organics). We present high mass resolution spectra and an example of isotopic imaging where D/H ratios were obtained via the 12C2D-/12C2H- ratio with 12C2D- free from neighboring mass interferences. Using an advanced mass resolution protocol, a "conventional" mass resolving power of 25,000 can be achieved. Those results open many perspectives for isotopic imaging at a fine scale in biology, material science, geochemistry, and cosmochemistry.

  8. 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

  9. Studying Geoeffective Interplanetary Coronal Mass Ejections Between the Sun and Earth: Space Weather Implications of Solar Mass Ejection Imager Observations

    DTIC Science & Technology

    2009-05-14

    during the Mav 12th, 1997 ICME, /. Ahnos. Sol. Terr. Phys., 66, 1295-1309. Billings, D. E. (1966), A Guide to the Solar Corona , Academic, San Diego...SUBTITLE Studying geoeffective interplanetary coronal mass ejections Between the Sun and Earth: Space weather implications of Solar Mass Ejection...DISTRIBUTION . „ . ru^en.1 nomicmcni Approved for Public Release; Distribution Unlimited. *Boston College, Chestnut Hill, MA, **AFRL, National Solar Ob

  10. 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.

  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

    2014-05-02

    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.

  12. Sample preparation for mass spectrometry imaging: small mistakes can lead to big consequences.

    PubMed

    Goodwin, Richard J A

    2012-08-30

    Mass spectrometry imaging (MSI) enables the direct analysis of molecules from the surface of a wide variety of samples, allowing the multiplex measurement of both abundance and distribution of small molecules, lipids, peptides and proteins. As the technology has been refined an increasing number of ionization methods and mass analyzers has been used that enable increased spatial and spectral resolution measurements to be made at an increased speed. Alongside the instrumentation improvements there has been optimization of sample preparation procedures that allow the highest quality data to be obtained, reproducibly, from an ever increasing diversity of samples. This review will consider the development and standardization of sample preparation methods applicable to MSI, describing the stages and procedures undertaken from the instance of sample collection, through storage, preparation and on through final processing prior to analysis. Recent technical advancements will be highlighted and areas where further experimentation and optimization may well be required will be described. All aspects of the sample preparation pipeline will be considered in detail, with examples from the literature used to emphasize why rigorous sample preparation for MSI is vital to achieve the most accurate, reproducible and validated MSI data possible.

  13. Reweighted mass center based object-oriented sparse subspace clustering for hyperspectral images

    NASA Astrophysics Data System (ADS)

    Zhai, Han; Zhang, Hongyan; Zhang, Liangpei; Li, Pingxiang

    2016-10-01

    Considering the inevitable obstacles faced by the pixel-based clustering methods, such as salt-and-pepper noise, high computational complexity, and the lack of spatial information, a reweighted mass center based object-oriented sparse subspace clustering (RMC-OOSSC) algorithm for hyperspectral images (HSIs) is proposed. First, the mean-shift segmentation method is utilized to oversegment the HSI to obtain meaningful objects. Second, a distance reweighted mass center learning model is presented to extract the representative and discriminative features for each object. Third, assuming that all the objects are sampled from a union of subspaces, it is natural to apply the SSC algorithm to the HSI. Faced with the high correlation among the hyperspectral objects, a weighting scheme is adopted to ensure that the highly correlated objects are preferred in the procedure of sparse representation, to reduce the representation errors. Two widely used hyperspectral datasets were utilized to test the performance of the proposed RMC-OOSSC algorithm, obtaining high clustering accuracies (overall accuracy) of 71.98% and 89.57%, respectively. The experimental results show that the proposed method clearly improves the clustering performance with respect to the other state-of-the-art clustering methods, and it significantly reduces the computational time.

  14. MALDI mass spectrometric imaging meets "omics": recent advances in the fruitful marriage.

    PubMed

    Crecelius, A C; Schubert, U S; von Eggeling, F

    2015-09-07

    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.

  15. 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

  16. Deep JH Imaging of the LITTLE THINGS Galaxies: Stellar Mass Assembly in Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    Zhang, Hongxin; Hunter, Deidre; Herrmann, Kim; LITTLE THINGS Team

    2011-02-01

    We propose to obtain deep broadband JH images for 6 dwarf irregular galaxies (dIm) which are part of a larger sample assembled by the LITTLE THINGS project (a VLA Large Proposal). Using the NIR data requested here and other multi-band data we have collected, we will, for the first time, construct high-quality spectral energy distributions (SEDs) covering the whole spectral range of stellar emission for a representative sample of dIm galaxies. dIm galaxies numerically dominate the local Universe, yet our understanding of the star formation processes in dIm galaxies is very poor. For example, the star formation rate profile often correlates closely with the stellar surface brightness profile of the older stars, but not with the gas, and we do not know why. Also, abrupt changes in the slope of the stellar exponential profile imply a change in the star formation process at the surface brightness breaks according to some models, but this has not been shown observationally. With the SEDs constructed as a function of radius within each galaxy and our stellar population synthesis technique, we will answer the questions: 1) How is the stellar mass across the disks assembled throughout the lifetime of dwarf irregular galaxies? 2) Are there corresponding surface mass density breaks at the surface brightness breaks seen in many dIm galaxies? And is there any difference in the stellar populations before and beyond the surface brightness breaks?

  17. Deep JH Imaging of the LITTLE THINGS Galaxies: Stellar Mass Assembly in Dwarf Galaxies

    NASA Astrophysics Data System (ADS)

    Zhang, Hongxin; Hunter, Deidre; Herrmann, Kim; Little Things Team

    2011-08-01

    We propose to obtain deep broadband JH images for 2 dwarf irregular galaxies (dIm) which are part of a larger sample assembled by the LITTLE THINGS project (a VLA Large Proposal). Using the NIR data requested here and other multi-band data we have collected, we will, for the first time, construct high-quality spectral energy distributions (SEDs) covering the whole spectral range of stellar emission for a representative sample of dIm galaxies. dIm galaxies numerically dominate the local universe, yet our understanding of the star formation processes in dIm galaxies is very poor. For example, the star formation rate profile often correlates closely with the stellar surface brightness profile of the older stars, but not with the gas, and we do not know why. Also, abrupt changes in the slope of the stellar exponential profile imply a change in the star formation process at the surface brightness breaks according to some models, but this has not been shown observationally. With the SEDs constructed as a function of radius within each galaxy and our stellar population synthesis technique, we will answer the questions: 1) How is the stellar mass across the disks assembled throughout the lifetime of dwarf irregular galaxies? 2) Are there corresponding surface mass density breaks at the surface brightness breaks seen in many dIm galaxies? 3) Is there any difference in the stellar populations before and beyond the surface brightness breaks?

  18. Mass Spectrometric Imaging of Red Fluorescent Protein in Breast Tumor Xenografts

    NASA Astrophysics Data System (ADS)

    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.

  19. Investigating nephrotoxicity of polymyxin derivatives by mapping renal distribution using mass spectrometry imaging.

    PubMed

    Nilsson, Anna; Goodwin, Richard J A; Swales, John G; Gallagher, Richard; Shankaran, Harish; Sathe, Abhishek; Pradeepan, Selvi; Xue, Aixiang; Keirstead, Natalie; Sasaki, Jennifer C; Andren, Per E; Gupta, Anshul

    2015-09-21

    Colistin and polymyxin B are effective treatment options for Gram-negative resistant bacteria but are used as last-line therapy due to their dose-limiting nephrotoxicity. A critical factor in developing safer polymyxin analogues is understanding accumulation of the drugs and their metabolites, which is currently limited due to the lack of effective techniques for analysis of these challenging molecules. Mass spectrometry imaging (MSI) allows direct detection of targets (drugs, metabolites, and endogenous compounds) from tissue sections. The presented study exemplifies the utility of MSI by measuring the distribution of polymyxin B1, colistin, and polymyxin B nonapeptide (PMBN) within dosed rat kidney tissue sections. The label-free MSI analysis revealed that the nephrotoxic compounds (polymyxin B1 and colistin) preferentially accumulated in the renal cortical region. The less nephrotoxic analogue, polymyxin B nonapeptide, was more uniformly distributed throughout the kidney. In addition, metabolites of the dosed compounds were detected by MSI. Kidney homogenates were analyzed using LC/MS/MS to determine total drug exposure and for metabolite identification. To our knowledge, this is the first time such techniques have been utilized to measure the distribution of polymyxin drugs and their metabolites. By simultaneously detecting the distribution of drug and drug metabolites, MSI offers a powerful alternative to tissue homogenization analysis and label or antibody-based imaging.

  20. Nucleolin-aptamer therapy in retinoblastoma: molecular changes and mass spectrometry–based imaging

    PubMed Central

    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

  1. 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

  2. Decellularization of intact tissue enables MALDI imaging mass spectrometry analysis of the extracellular matrix

    PubMed Central

    Gessel, Megan; Spraggins, Jeffrey M.; Voziyan, Paul; Hudson, Billy G; Caprioli, Richard M

    2017-01-01

    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

  3. Direct Imaging and Interferometric Followup of Our Closest Low-Mass Stellar Neighbors

    NASA Astrophysics Data System (ADS)

    Girard, J.

    2014-04-01

    Luhman 16 AB is a L/T brown dwarf binary system at only 2 pc from us. Discovered a year ago thanks to WISE (Luhman 2013), it has already been extensively studied (spectral types, variability, cloud map, etc. a total of 8 refereed publications). In this contribution I tackle the possibility of following up such target with the state of the art high contrast imaging and interferometric techniques. Though the system isn't young, it is so close and its components have mild effective temperature that we can probe for planetary-mass companions down to solar system scales. I will present results from our deep NACO L'-band search and expose our strategy and attempt with VLTI/PIONIER H-band (four 8m telescopes) to reach the habitable zone (~0.005 AU) and provide direct upper limits on the diameter of both Luhman A and B. Finally I will discuss the possibility of tackling such objects with the coming generation of high contrast imagers.

  4. Analysis of Epsilon Aurigae light curve from the Solar Mass Ejection Imager

    NASA Astrophysics Data System (ADS)

    Clover, John; Jackson, B. V.; Buffington, A.; Hick, P. P.; Kloppenborg, B.; Stencel, R.

    2011-01-01

    The Solar Mass Ejection Imager (SMEI) was launched aboard the Coriolis spacecraft in 2003. It is equipped with 3 CCD cameras to measure the brightness of Thomson-scattered electrons in the heliosphere. Each CCD images a strip of the sky that is 3°x60°. The three cameras are mounted on the satellite with their fields of view aligned end-to-end so that SMEI sweeps nearly the entire sky each 102 minute orbit. SMEI has now accumulated stellar time series for about 5700 bright stars, including epsilon Aurigae, for each orbit where data is available. SMEI data provide nearly year-round coverage of epsilon Aurigae. The baffled SMEI optics provide more accurate photometric data than ground-based observations, particularly at mid-eclipse when epsilon Aurigae is close to the Sun. We present an analysis of the brightness variations of the epsilon Aurigae system, before and during the eclipse. The University of Denver participants are grateful for support under NSFgrant 10-16678 and the bequest of William Hershel Womble in support of astronomy at the University of Denver.

  5. Molecular imaging of brain localization of liposomes in mice using MALDI mass spectrometry

    PubMed Central

    Fülöp, Annabelle; Sammour, Denis A.; Erich, Katrin; von Gerichten, Johanna; van Hoogevest, Peter; Sandhoff, Roger; Hopf, Carsten

    2016-01-01

    Phospholipids have excellent biocompatibility and are therefore often used as main components of liposomal drug carriers. In traditional bioanalytics, the in-vivo distribution of liposomal drug carriers is assessed using radiolabeled liposomal constituents. This study presents matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as an alternative, label-free method for ex-vivo molecular imaging of liposomal drug carriers in mouse tissue. To this end, indocyanine green as cargo and two liposomal markers, 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine conjugated with monodisperse polyethylene glycol (PEG36-DSPE) were incorporated into liposomal carriers and administered to mice. We used MALDI MSI of the two lipid markers in both positive and negative ion mode for visualization of liposome integrity and distribution in mouse organs. Additional MSI of hemoglobin in the same tissue slice and pixel-by-pixel computational analysis of co-occurrence of lipid markers and hemoglobin served as indicator of liposome localization either in parenchyma or in blood vessels. Our proof-of-concept study suggests that liposomal components and indocyanine green distributed into all investigated organs. PMID:27650487

  6. 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.

  7. 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.

  8. Imaging mass spectrometry of proteins and peptides: 3D volume reconstruction.

    PubMed

    Andersson, Malin; Groseclose, M Reid; Deutch, Ariel Y; Caprioli, Richard M

    2008-01-01

    As large genomic and proteomic datasets are generated from homogenates of various tissues, the need for information on the spatial localization of their encoded products has become more pressing. Matrix-assisted laser desorption-ionization (MALDI) imaging mass spectrometry (IMS) offers investigators the means with which to unambiguously study peptides and proteins with molecular specificity, and to determine their distribution in two and three dimensions. In the past few years, several parameters have been optimized for IMS, including sample preparation, matrix application and instrumental acquisition parameters (Box 1). These developments have resulted in a high degree of reproducibility in mass accuracy and peak intensities (Supplementary Fig. 1 online). Recently, we have optimized our protocol to be able to increase the number of molecular species analyzed by collecting two sets of sections, covering one set of sections with sinapinic acid for optimal detection of proteins and adjacent sections with 2,5-dihydroxybenzoic acid (DHB) matrix for the optimal detection of low-mass species, including peptides. Approximately 1,000 peaks can be observed in each dataset (Fig. 1). Furthermore, the sections are collected at an equal distance, 200 mum instead of 400-500 mum used previously, thus enabling the use of virtual z-stacks and three-dimensional (3D) volume renderings to investigate differential localization patterns in much smaller brain structures such as the substantia nigra and the interpeduncular nucleus. Here we present our optimized step-by-step procedure based on previous work in our laboratory, describing how to make 3D volume reconstructions of MALDI IMS data, as applied to the rat brain.

  9. 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.

  10. 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.

  11. 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

    2013-11-05

    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.

  12. Mass spectrometry for the molecular imaging of angiotensin metabolism in kidney

    PubMed Central

    Grobe, Nadja; Elased, Khalid M.; Cool, David R.

    2012-01-01

    To better understand the tissue distribution and activity of enzymes involved in angiotensin II (Ang II) processing, we developed a novel molecular imaging method using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. Mouse kidney sections (12 μm) were incubated with 10–1,000 μmol/l Ang II for 5–15 min at 37°C. The formed peptides Ang III and Ang-(1–7) were identified by MALDI-TOF/TOF. A third metabolite, Ang-(1–4), was generated from further degradation of Ang-(1–7). Enzymatic processing of Ang II was dose and time dependent and absent in heat-treated kidney sections. Distinct spatial distribution patterns (pseudocolor images) were observed for the peptides. Ang III was localized in renal medulla, whereas Ang-(1–7)/Ang-(1–4) was present in cortex. Regional specific peptide formation was confirmed using microdissected cortical and medullary biopsies. In vitro studies with recombinant enzymes confirmed activity of peptidases known to generate Ang III or Ang-(1–7) from Ang II: aminopeptidase A (APA), Ang-converting enzyme 2 (ACE2), prolyl carboxypeptidase (PCP), and prolyl endopeptidase (PEP). Renal medullary Ang III generation was blocked by APA inhibitor glutamate phosphonate. The ACE2 inhibitor MLN-4760 and PCP/PEP inhibitor Z-pro-prolinal reduced cortical Ang-(1–7) formation. Our results establish the power of MALDI imaging as a highly specific and information-rich analytical technique that will further aid our understanding of the role and site of Ang II processing in cardiovascular and renal pathologies. PMID:22318946

  13. Automated Anatomical Interpretation of Ion Distributions in Tissue: Linking Imaging Mass Spectrometry to Curated Atlases

    PubMed Central

    2015-01-01

    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

  14. Hydrogen peroxide reactions on cocaine in hair using imaging mass spectrometry.

    PubMed

    Cuypers, Eva; Flinders, Bryn; Bosman, Ingrid J; Lusthof, Klaas J; Van Asten, Arian C; Tytgat, Jan; Heeren, Ron M A

    2014-09-01

    Today, forensic hair analysis is considered to be a standard method for identifying chronic drug users since information about drug use stored and located in hair can cover several months to even years. When interpreting these results, one should be aware of all kind of pitfalls. External factors such as bleaching might influence the analytical result. Although the effect of hydrogen peroxide on cocaine in a solution was described before, it was never investigated whether the described reaction products (ecgonine methylester, benzoylecgonine, hydroxynorcocaine and dihydroxycocaine) are indeed found on contaminated or user hair. Since it is of great importance in forensic hair analysis to know whether cocaine and/or reaction products are detectable in hair after bleaching, matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) was used to study the effect of hydrogen peroxide treatment on incorporated cocaine in hairs. Cocaine oxidation products were identified in a solution based on MS/MS spectra and spatial distribution of these products in hair was explored using MALDI TOF-MS. All images were accomplished by spraying α-Cyano-4-hydroxycinnamic acid (CHCA) as a MALDI-matrix. Images revealed a loss of detectability of cocaine and its reaction products in hairs already after a short bleaching period. Since all compounds of interest are found in the hydrogen peroxide and wash solution, these findings indicate that all evidence of cocaine use might be lost after a hair bleaching treatment. Therefore, forensic toxicologists should take into consideration whether hair samples were bleached before making any conclusions from hair analysis results.

  15. Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues

    PubMed Central

    Wiseman, Justin M.; Ifa, Demian R.; Zhu, Yongxin; Kissinger, Candice B.; Manicke, Nicholas E.; Kissinger, Peter T.; Cooks, R. Graham

    2008-01-01

    Ambient ionization methods for MS enable direct, high-throughput measurements of samples in the open air. Here, we report on one such method, desorption electrospray ionization (DESI), which is coupled to a linear ion trap mass spectrometer and used to record the spatial intensity distribution of a drug directly from histological sections of brain, lung, kidney, and testis without prior chemical treatment. DESI imaging provided identification and distribution of clozapine after an oral dose of 50 mg/kg by: i) measuring the abundance of the intact ion at m/z 327.1, and ii) monitoring the dissociation of the protonated drug compound at m/z 327.1 to its dominant product ion at m/z 270.1. In lung tissues, DESI imaging was performed in the full-scan mode over an m/z range of 200-1100, providing an opportunity for relative quantitation by using an endogenous lipid to normalize the signal response of clozapine. The presence of clozapine was detected in all tissue types, whereas the presence of the N-desmethyl metabolite was detected only in the lung sections. Quantitation of clozapine from the brain, lung, kidney, and testis, by using LC-MS/MS, revealed concentrations ranging from 0.05 μg/g (brain) to a high of 10.6 μg/g (lung). Comparisons of the results recorded by DESI with those by LC-MS/MS show good agreement and are favorable for the use of DESI imaging in drug and metabolite detection directly from biological tissues. PMID:18697929

  16. 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.

  17. High Spatial Resolution Laser Desorption/Ionization Mass Spectrometry Imaging of Organic Layers in an Organic Light-Emitting Diode

    PubMed Central

    Tachibana, Yuko; Nakajima, Yoji; Isemura, Tsuguhide; Yamamoto, Kiyoshi; Satoh, Takaya; Aoki, Jun; Toyoda, Michisato

    2016-01-01

    To improve the durability of organic materials in electronic devices, an analytical method that can obtain information about the molecular structure directly from specific areas on a device is desired. For this purpose, laser desorption/ionization mass spectrometry imaging (LDI-MSI) is one of the most promising methods. The high spatial resolution stigmatic LDI-MSI with MULTUM-IMG2 in the direct analysis of organic light-emitting diodes was shown to obtain a detailed mass image of organic material in the degraded area after air exposure. The mass image was observed to have a noticeably improved spatial resolution over typical X-ray photoelectron spectroscopy, generally used technique in analysis of electronic devices. A prospective m/z was successfully deduced from the high spatial resolution MSI data. Additionally, mass resolution and accuracy using a spiral-orbit TOF mass spectrometer, SpiralTOF, were also investigated. The monoisotopic mass for the main component, N,N′-di-1-naphthalenyl-N,N′-diphenyl-1,1′-biphenyl-4,4′-diamine (m/z 588), was measured with a mass resolution of approximately 80,000 and a mass error of about 5 mDa using an external calibrant. This high mass resolution and accuracy data successfully deduced a possible elemental composition of partially remained material in the degraded area, C36H24, which was determined as anthracene, 9-[1,1′-biphenyl]-4-yl-10-(2-naphthalenyl) by combining structural information with high-energy CID data. The high spatial resolution of 1 μm in LDI-MSI along with high mass resolution and accuracy could be useful in obtaining molecular structure information directly from specific areas on a device, and is expected to contribute to the evolution of electrical device durability. PMID:28101440

  18. Characterization of a Hybrid Optical Microscopy/Laser Ablation Liquid Vortex Capture/Electrospray Ionization System for Mass Spectrometry Imaging

    DOE PAGES

    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. The International Deep Planet Survey. II. The frequency of directly imaged giant exoplanets with stellar mass

    NASA Astrophysics Data System (ADS)

    Galicher, R.; Marois, C.; Macintosh, B.; Zuckerman, B.; Barman, T.; Konopacky, Q.; Song, I.; Patience, J.; Lafrenière, D.; Doyon, R.; Nielsen, E. L.

    2016-10-01

    Context. Radial velocity and transit methods are effective for the study of short orbital period exoplanets but they hardly probe objects at large separations for which direct imaging can be used. Aims: We carried out the international deep planet survey of 292 young nearby stars to search for giant exoplanets and determine their frequency. Methods: We developed a pipeline for a uniform processing of all the data that we have recorded with NIRC2/Keck II, NIRI/Gemini North, NICI/Gemini South, and NACO/VLT for 14 yr. The pipeline first applies cosmetic corrections and then reduces the speckle intensity to enhance the contrast in the images. Results: The main result of the international deep planet survey is the discovery of the HR 8799 exoplanets. We also detected 59 visual multiple systems including 16 new binary stars and 2 new triple stellar systems, as well as 2279 point-like sources. We used Monte Carlo simulations and the Bayesian theorem to determine that 1.05+2.80-0.70% of stars harbor at least one giant planet between 0.5 and 14 MJ and between 20 and 300 AU. This result is obtained assuming uniform distributions of planet masses and semi-major axes. If we consider power law distributions as measured for close-in planets instead, the derived frequency is 2.30+5.95-1.55%, recalling the strong impact of assumptions on Monte Carlo output distributions. We also find no evidence that the derived frequency depends on the mass of the hosting star, whereas it does for close-in planets. Conclusions: The international deep planet survey provides a database of confirmed background sources that may be useful for other exoplanet direct imaging surveys. It also puts new constraints on the number of stars with at least one giant planet reducing by a factor of two the frequencies derived by almost all previous works. Tables 11-15 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (http://130.79.128.5) or via http://cdsarc

  1. Comparison of sample pre-treatments for laser desorption ionization and secondary ion mass spectrometry imaging of Miscanthus x giganteus.

    PubMed

    Li, Zhen; Bohn, Paul W; Sweedler, Jonathan V

    2010-07-01

    Efforts to further the potential of the large perennial grass Miscanthusxgiganteus as a biofuel feedstock would be aided by the ability to image the chemical species present during the fuel production process. Toward this end, two mass spectrometry imaging (MSI) approaches have been investigated here-laser desorption/ionization mass spectrometry (LDI-MS) and secondary ion mass spectrometry (SIMS). As a first step, cross sections of Miscanthus were subjected to a variety of sample preparation methods to optimize conditions for MSI. For LDI-MS, a thin metal coating (2 nm thick Au) provided high quality signals of saccharide-related ions. The traditional matrix-assisted laser desorption/ionization matrix, 2,5-dihydroxybenzoic acid, also showed high efficiency for the desorption of saccharide-related ions. In contrast, with alpha-cyano-4-hydroxycinnamic acid matrix, these ions were nearly absent in the mass spectra. Direct laser ablation of untreated Miscanthus sections was also performed. High resolution images, where the fine structure of the vascular bundle could be clearly visualized, were obtained using SIMS. Although coating the sections with a nanometer thick Au layer can greatly enhance the quality of SIMS images, the coating had limited effect on secondary ion signal enhancement. Using the optimized mass spectrometry approaches described here, information on the spatial distribution of several saccharides was obtained.

  2. MALDI imaging mass spectrometry analysis-A new approach for protein mapping in multiple sclerosis brain lesions.

    PubMed

    Maccarrone, Giuseppina; Nischwitz, Sandra; Deininger, Sören-Oliver; Hornung, Joachim; König, Fatima Barbara; Stadelmann, Christine; Turck, Christoph W; Weber, Frank

    2017-03-15

    Multiple sclerosis is a disease of the central nervous system characterized by recurrent inflammatory demyelinating lesions in the early disease stage. Lesion formation and mechanisms leading to lesion remyelination are not fully understood. Matrix Assisted Laser Desorption Ionisation Mass Spectrometry imaging (MALDI-IMS) is a technology which analyses proteins and peptides in tissue, preserves their spatial localization, and generates molecular maps within the tissue section. In a pilot study we employed MALDI imaging mass spectrometry to profile and identify peptides and proteins expressed in normal-appearing white matter, grey matter and multiple sclerosis brain lesions with different extents of remyelination. The unsupervised clustering analysis of the mass spectra generated images which reflected the tissue section morphology in luxol fast blue stain and in myelin basic protein immunohistochemistry. Lesions with low remyelination extent were defined by compounds with molecular weight smaller than 5300Da, while more completely remyelinated lesions showed compounds with molecular weights greater than 15,200Da. An in-depth analysis of the mass spectra enabled the detection of cortical lesions which were not seen by routine luxol fast blue histology. An ion mass, mainly distributed at the rim of multiple sclerosis lesions, was identified by liquid chromatography and tandem mass spectrometry as thymosin beta-4, a protein known to be involved in cell migration and in restorative processes. The ion mass of thymosin beta-4 was profiled by MALDI imaging mass spectrometry in brain slides of 12 multiple sclerosis patients and validated by immunohistochemical analysis. In summary, our results demonstrate the ability of the MALDI-IMS technology to map proteins within the brain parenchyma and multiple sclerosis lesions and to identify potential markers involved in multiple sclerosis pathogenesis and/or remyelination.

  3. 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.

  4. Direct matrix-assisted laser desorption/ionization mass spectrometric imaging of cellulose and hemicellulose in Populus tissue.

    PubMed

    Lunsford, Kyle Ann; Peter, Gary F; Yost, Richard A

    2011-09-01

    Imaging applied toward lignocellulosic materials requires high molecular specificity to map specific compounds within intact tissue. Although secondary ionization mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) with a single stage of MS have been used to image lignocellulosic biomass, the complexity of the plant tissue requires tandem MS, which limits the interpretation of simple MS. MALDI linear ion trap (LIT) tandem MS offers the high molecular specificity needed for lignocellulosic analyses. MALDI-LIT MS analyses of cellulose and xylan (hemicellulose) standards were performed to determine mass-to-charge ratios and fragmentation pathways for identification of these compounds in intact tissue. The MALDI-LIT-MS images of young Populus wood stem showed even distribution of both cellulose and hemicellulose ions; in contrast, the tandem MS images of cellulose and hemicellulose generated by plotting characteristic fragment ions resulted in drastically different images. This demonstrates that isobaric ions are present during MALDI-LIT-MS analyses of wood tissue and tandem MS is necessary to distinguish between isobaric species for selective imaging of carbohydrates in biomass.

  5. Quantifying element incorporation in multispecies biofilms using nanoscale secondary ion mass spectrometry image analysis

    SciTech Connect

    Renslow, Ryan S.; Lindemann, Stephen R.; Cole, Jessica K.; Zhu, Zihua; Anderton, Christopher R.

    2016-02-12

    EElucidating 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 vivo and amenable to controlled scientific experimentation. High spatial resolution secondary ion mass spectrometry (NanoSIMS) is a powerful 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, we describe the creation and application of a semi-automated image-processing pipeline that can analyze NanoSIMS-generated data of phototrophic biofilms. 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. We demonstrate the functionality of the tool by using it to analyze the uptake of 15N provided as either nitrate or ammonium through the unicyanobacterial consortium UCC-O and imaged via NanoSIMS. We found that the degree of 15N incorporation by individual cells was highly variable when labeled with 15NH4 +, but much more even when biofilms were labeled with 15NO3-. In the 15NH4 +-amended biofilms, the heterotrophic distribution of 15N incorporation was highly skewed, with a large population showing moderate 15N incorporation and a small number of

  6. 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

    2016-06-12

    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

  7. Variation in spectral and mass dimension on 3D soil image processing

    NASA Astrophysics Data System (ADS)

    Sanchez, M. E.; Tarquis, A. M.; Fabregat, J.; Andina, D.; Jimenez, J.; Crawford, J. W.

    2009-04-01

    Knowledge on three dimensional soil pore architecture is important for understanding soil processes as it controls biological, chemical and physical processes on various scales. Recent advances in non-destructive imaging, such as X-ray Computed Tomography (CT), provide several ways to analyze pore space features mainly concentrating on the visualization of soil structure. Fractal formalism has revealed as useful tool in these cases where highly complex and heterogeneous medium are studied. One of these quantifications is mass dimension (Dm) and spectral dimension (d) applied for water and gas diffusion coefficient in soil. At the same time that these techniques give a unique opportunity to quantify and describe pore space, they presents steps in their procedures on which the results depend. In this work, intact soil samples were collected from four horizons of a Brazilian soil and 3D images, of 45.1 micro-m resolution (256x256x256 voxels), were obtained. Four different threshold criteria were used to transform CT grey-scale imagery in binary imagery (pore/solid), based on the frequency of CT units. Then the threshold effect on the estimation of Dm and d, as well as their ratio was studied. Each threshold criteria had a direct influence on Dm as it has been previously reported [1], through the increase on porosity obtained. Meanwhile Dm showed a clear logarithmic relation with the apparent porosity in the image obtained for each threshold, d showed an almost linear one. In any case the increase of each one of them respect to porosity was different for each horizon. The Dm/d ratio was practically constant through all the porosity achieved in this study when Dm was estimated using all the scale range available. On the other hand, when Dm was estimated based on smaller scales this ratio depended on the threshold criteria applied to the image. This fact has a direct implication in diffusion parameters for a pore network modeling based on both fractal dimensions. [1] A

  8. Time‐of‐flight secondary ion mass spectrometry imaging of biological samples with delayed extraction for high mass and high spatial resolutions

    PubMed Central

    Vanbellingen, Quentin P.; Elie, Nicolas; Eller, Michael J.; Della‐Negra, Serge; Touboul, David

    2015-01-01

    Rationale In Time‐of‐Flight Secondary Ion Mass Spectrometry (TOF‐SIMS), pulsed and focused primary ion beams enable mass spectrometry imaging, a method which is particularly useful to map various small molecules such as lipids at the surface of biological samples. When using TOF‐SIMS instruments, the focusing modes of the primary ion beam delivered by liquid metal ion guns can provide either a mass resolution of several thousand or a sub‐µm lateral resolution, but the combination of both is generally not possible. Methods With a TOF‐SIMS setup, a delayed extraction applied to secondary ions has been studied extensively on rat cerebellum sections in order to compensate for the effect of long primary ion bunches. Results The use of a delayed extraction has been proven to be an efficient solution leading to unique features, i.e. a mass resolution up to 10000 at m/z 385.4 combined with a lateral resolution of about 400 nm. Simulations of ion trajectories confirm the experimental determination of optimal delayed extraction and allow understanding of the behavior of ions as a function of their mass‐to‐charge ratio. Conclusions Although the use of a delayed extraction has been well known for many years and is very popular in MALDI, it is much less used in TOF‐SIMS. Its full characterization now enables secondary ion images to be recorded in a single run with a submicron spatial resolution and with a mass resolution of several thousand. This improvement is very useful when analyzing lipids on tissue sections, or rare, precious, or very small size samples. © 2015 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd. PMID:26395603

  9. Monitoring time-dependent degradation of phospholipids in sectioned tissues by MALDI imaging mass spectrometry.

    PubMed

    Patterson, Nathan Heath; Thomas, Aurélien; Chaurand, Pierre

    2014-07-01

    Imaging mass spectrometry (IMS) is useful for visualizing the localization of phospholipids on biological tissue surfaces creating great opportunities for IMS in lipidomic investigations. With advancements in IMS of lipids, there is a demand for large-scale tissue studies necessitating stable, efficient and well-defined sample handling procedures. Our work within this article shows the effects of different storage conditions on the phospholipid composition of sectioned tissues from mouse organs. We have taken serial sections from mouse brain, kidney and liver thaw mounted unto ITO-coated glass slides and stored them under various conditions later analyzing them at fixed time points. A global decrease in phospholipid signal intensity is shown to occur and to be a function of time and temperature. Contrary to the global decrease, oxidized phospholipid and lysophospholipid species are found to increase within 2 h and 24 h, respectively, when mounted sections are kept at ambient room conditions. Imaging experiments reveal that degradation products increase globally across the tissue. Degradation is shown to be inhibited by cold temperatures, with sample integrity maintained up to a week after storage in -80 °C freezer under N2 atmosphere. Overall, the results demonstrate a timeline of the effects of lipid degradation specific to sectioned tissues and provide several lipid species which can serve as markers of degradation. Importantly, the timeline demonstrates oxidative sample degradation begins appearing within the normal timescale of IMS sample preparation of lipids (i.e. 1-2 h) and that long-term degradation is global. Taken together, these results strengthen the notion that standardized procedures are required for phospholipid IMS of large sample sets, or in studies where many serial sections are prepared together but analyzed over time such as in 3-D IMS reconstruction experiments.

  10. VizieR Online Data Catalog: 2MASS J16042165-2130284 high-contrast images (Canovas+, 2017)

    NASA Astrophysics Data System (ADS)

    Canovas, H.; Hardy, A.; Zurlo, A.; Wahhaj, Z.; Schreiber, M. R.; Vigan, A.; Villaver, E.; Olofsson, J.; Meeus, G.; Menard, F.; Caceres, C.; Cieza, L. A.; Garufi, A.

    2016-10-01

    The article describes high-contrast images of the protoplanetary disk 2MASS J16042165-2130284, obtained with the Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE). * Fig1.fits: It corresponds to Fig. 1 of the article. The file contains the Angular Differential Imaging (ADI) + Principal Component Analysis (PCA) image of the disk in K1 band, showing no point sources inside of the disk cavity from ~22 au onwards. * Fig4_ifs.fits: It corresponds to Fig. 4 (IFS part) of the article. The datacube contains the 3 IFS broadband images, corresponding to the Y [*,*, 0], J [*,*,1], H [*,*,2] bands. * Fig4_ird.fits: It corresponds to Fig. 4 (IRDIS part) of the article. The datacube contains the 2 IRDIS images (220x220pix), corresponding to the K1 [*,*, 0], and K2 [*,*,1] bands. (2 data files).

  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

    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.

  13. Mass spectrometry imaging (MSI) of metals in mouse spinal cord by laser ablation ICP-MS.

    PubMed

    Becker, J Sabine; Kumtabtim, Usarat; Wu, Bei; Steinacker, Petra; Otto, Markus; Matusch, Andreas

    2012-03-01

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been developed as a powerful MS imaging (MSI) tool for the direct investigation of element distributions in biological tissues. Here, this technique was adapted for the analysis of native mouse spinal cord cryosections of 3.1 mm × 1.7 mm by implementing a new conventional ablation system (NWR-213) and improving the spatial resolution from 120 μm to 65 μm in routine mode. Element images of the spinal cord are provided for the first time and the metalloarchitecture was established using a multimodal atlas approach. Furthermore, the spatial distribution of Rb was mapped for the first time in biological tissue. Metal concentrations were quantified using matrix-matched laboratory standards and normalization of the respective ion intensities to the average (13)C ion intensity of standards and samples as a surrogate of slice thickness. The "butterfly" shape of the central spinal grey matter was visualized in positive contrast by the distributions of Fe, Mn, Cu and Zn and in negative contrast by C and P. Mg, Na, K, S and Rb showed a more homogenous distribution. The concentrations averaged throughout grey matter and white matter were 8 and 4 μg g(-1) of Fe, 3 and 2 μg g(-1) of Cu, 8 and 5 μg g(-1) of Zn, 0.4 and 0.2 μg g(-1) of Mn. The carbon concentration in white matter exceeded that of grey matter by a factor of 1.44. Zn and Cu at 9 and 4 μg g(-1), respectively, were particularly enriched in the laminae I and II, in line with the high synaptic and cellular density there. Surprisingly Zn but not Cu was enriched in the central channel. Rb occurred at 0.3 μg g(-1) with a distribution pattern congruent to that of K. The coefficients of variation were 6%, 5%, 8% and 10% for Fe, Cu, Zn and Mn, respectively, throughout three different animals measured on different days. These MSI analyses of healthy wild type spinal cords demonstrate the suitability of the established techniques for

  14. 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

  15. 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

  16. Automated Sampling and Imaging of Analytes Separated on Thin-Layer Chromatography Plates Using Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Van Berkel, Gary J; Kertesz, Vilmos

    2006-01-01

    Modest modifications to the atmospheric sampling capillary of a commercial electrospray mass spectrometer and upgrades to an in-house developed surface positioning control software package (HandsFree TLC/MS ) were used to enable the automated sampling and imaging of analytes on and/or within large area surface substrates using desorption electrospray ionization mass spectrometry. Sampling and imaging of rhodamine dyes separated on TLC plates were used to illustrate some of the practical applications of this system. Examples are shown for user-defined spot sampling from separated bands on a TLC plate (one or multiple spots), scanning of a complete development lane (one or multiple lanes), or imaging of analyte bands in a development lane (i.e. multiple lane scans with close spacing). The post data processing and data display aspects of the software system are also discussed.

  17. 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.

  18. 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.

  19. Laser ablation inductively coupled plasma mass spectrometry imaging of metals in experimental and clinical Wilson's disease.

    PubMed

    Boaru, Sorina Georgiana; Merle, Uta; Uerlings, Ricarda; Zimmermann, Astrid; Flechtenmacher, Christa; Willheim, Claudia; Eder, Elisabeth; Ferenci, Peter; Stremmel, Wolfgang; Weiskirchen, Ralf

    2015-04-01

    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.

  20. 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

  1. High spatial resolution imaging mass spectrometry of human optic nerve lipids and proteins.

    PubMed

    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.

  2. Spatial Localization and Quantitation of Androgens in Mouse Testis by Mass Spectrometry Imaging

    PubMed Central

    2016-01-01

    Androgens are essential for male development and reproductive function. They are transported to their site of action as blood-borne endocrine hormones but can also be produced within tissues to act in intracrine and paracrine fashions. Because of this, circulating concentrations may not accurately reflect the androgenic influence within specific tissue microenvironments. Mass spectrometry imaging permits regional analysis of small molecular species directly from tissue surfaces. However, due to poor ionization and localized ion suppression, steroid hormones are difficult to detect. Here, derivatization with Girard T reagent was used to charge-tag testosterone and 5α-dihydrotestosterone allowing direct detection of these steroids in mouse testes, in both basal and maximally stimulated states, and in rat prostate. Limits of detection were ∼0.1 pg for testosterone. Exemplary detection of endogenous steroids was achieved by matrix-assisted laser desorption ionization and either Fourier transform ion cyclotron resonance detection (at 150 μm spatial resolution) or quadrupole-time-of-flight detection (at 50 μm spatial resolution). Structural confirmation was achieved by collision induced fragmentation following liquid extraction surface analysis and electrospray ionization. This application broadens the scope for derivatization strategies on tissue surfaces to elucidate local endocrine signaling in health and disease. PMID:27676129

  3. 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

  4. 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

  5. 3D Mass Spectrometry Imaging Reveals a Very Heterogeneous Drug Distribution in Tumors

    PubMed Central

    Giordano, S.; Morosi, L.; Veglianese, P.; Licandro, S. A.; Frapolli, R.; Zucchetti, M.; Cappelletti, G.; Falciola, L.; Pifferi, V.; Visentin, S.; D’Incalci, M.; Davoli, E.

    2016-01-01

    Mass Spectrometry Imaging (MSI) is a widespread technique used to qualitatively describe in two dimensions the distribution of endogenous or exogenous compounds within tissue sections. Absolute quantification of drugs using MSI is a recent challenge that just in the last years has started to be addressed. Starting from a two dimensional MSI protocol, we developed a three-dimensional pipeline to study drug penetration in tumors and to develop a new drug quantification method by MALDI MSI. Paclitaxel distribution and concentration in different tumors were measured in a 3D model of Malignant Pleural Mesothelioma (MPM), which is known to be a very heterogeneous neoplasm, highly resistant to different drugs. The 3D computational reconstruction allows an accurate description of tumor PTX penetration, adding information about the heterogeneity of tumor drug distribution due to the complex microenvironment. The use of an internal standard, homogenously sprayed on tissue slices, ensures quantitative results that are similar to those obtained using HPLC. The 3D model gives important information about the drug concentration in different tumor sub-volumes and shows that the great part of each tumor is not reached by the drug, suggesting the concept of pseudo-resistance as a further explanation for ineffective therapies and tumors relapse. PMID:27841316

  6. Mass Spectrometry Imaging of Kidney Tissue Sections of Rat Subjected to Unilateral Ureteral Obstruction

    PubMed Central

    Liu, Huihui; Li, Wan; He, Qing; Xue, Jinjuan; Wang, Jiyun; Xiong, Caiqiao; Pu, Xiaoping; Nie, Zongxiu

    2017-01-01

    Chronic kidney disease (CKD) poses a serious threat to the quality of human life and health with an increasing incidence worldwide. Renal fibrosis is closely related to CKD and regarded as the final common pathophysiological pathway in most cases of end-stage renal diseases. Elucidating the mechanisms underlying renal fibrosis and developing novel therapeutic strategies are of great importance. Herein, matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) based on 1, 5-diaminonaphthalene hydrochloride was applied to the rat model of unilateral ureteral obstruction (UUO) to investigate metabolic changes during renal fibrosis. Among identified endogenous compounds, twenty-one metabolites involved in metabolic networks such as glycolysis, tricarboxylic acid (TCA) cycle, ATP metabolism, fatty acids metabolism, antioxidants, and metal ions underwent relatively obvious changes after 1 and 3 weeks of UUO. Unique distribution of the metabolites was obtained, and metabolic changes of kidneys during renal fibrosis were investigated simultaneously for the first time. These findings once again highlighted the promising potential of the organic salt matrix for application in small molecule in situ MSI and in the field of biomedical research. PMID:28157191

  7. Evaluation of Sparfloxacin Distribution by Mass Spectrometry Imaging in a Phototoxicity Model

    NASA Astrophysics Data System (ADS)

    Boudon, Stéphanie Marie; Morandi, Grégory; Prideaux, Brendan; Staab, Dieter; Junker, Ursula; Odermatt, Alex; Stoeckli, Markus; Bauer, Daniel

    2014-10-01

    Mass spectrometry imaging (MSI) was applied to samples from mouse skin and from a human in vitro 3D skin model in order to assess its suitability in the context of photosafety evaluation. MSI proved to be a suitable method for the detection of the model compound sparfloxacin in biological tissues following systemic administration (oral gavage, 100 mg/kg) and subsequent exposure to simulated sunlight. In the human in vitro 3D skin model, a concentration-dependent increase as well as an irradiation-dependent decrease of sparfloxacin was observed. The MSI data on samples from mouse skin showed high signals of sparfloxacin 8 h after dosing. In contrast, animals irradiated with simulated sunlight showed significantly lower signals for sparfloxacin starting already at 1 h postirradiation, with no measurable intensity at the later time points (3 h and 6 h), suggesting a time- and irradiation-dependent degradation of sparfloxacin. The acquisition resolution of 100 μm proved to be adequate for the visualization of the distribution of sparfloxacin in the gross ear tissue samples, but distinct skin compartments were unable to be resolved. The label-free detection of intact sparfloxacin was only the first step in an attempt to gain a deeper understanding of the phototoxic processes. Further work is needed to identify the degradation products of sparfloxacin implicated in the observed inflammatory processes in order to better understand the origin and the mechanism of the phototoxic reaction.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Mass spectrometry imaging: towards mapping the elemental and molecular composition of the rhizosphere

    DOE PAGES

    Veličković, Dušan; Anderton, Christopher R.

    2017-03-22

    In our short review provides perspective regarding the use of mass spectrometry imaging (MSI) to study the rhizosphere. It also serves to complement the multi-omic-focused review by White et al. in this journals’ issue. MSI is capable of elucidating chemical distributions within samples of interest in situ, and thus can provide spatial context to MS omics data in complementary experimental endeavors. Most MSI-based studies of plant-microbe interactions have focused on the phyllosphere and on the “associated rhizosphere” (our term for material that is not removed during harvesting). Sample preparation for these in situ analyses tends to be a limiting factor.more » Our studies, however, have provided valuable insights into the spatial arrangement of proteins, peptides, lipids, and other metabolites within these systems. We intend this short review to be a primer on the fundamentals of MSI and its role in plant-microbe analysis. Finally, we offer a perspective on the future of MSI and its use in understanding the molecular transformations beyond what we call the associated rhizosphere, one which extends to the rest of rhizosphere and into the bulk soil.« less

  13. 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

  14. Revealing praziquantel molecular targets using mass spectrometry imaging: an expeditious approach applied to Schistosoma mansoni.

    PubMed

    Ferreira, Mônica Siqueira; de Oliveira, Rosimeire Nunes; de Oliveira, Diogo Noin; Esteves, Cibele Zanardi; Allegretti, Silmara Marques; Catharino, Rodrigo Ramos

    2015-05-01

    Finding specific molecular targets and the mechanism of action of praziquantel in the treatment of schistosomiasis remains a challenging task. Our efforts were focused on obtaining further information on worm composition before and after exposure to praziquantel in the treatment of schistosomiasis to elucidate the potential sites of action of this drug. Evidence indicates that the lipid bilayer is changed by treatment with praziquantel. Following this rationale, we employed a mass spectrometry imaging-based approach that helped to characterise lipids in specific locations, which are directly involved in the biochemical pathways of the BH strain of Schistosoma mansoni, as well as differentiating the molecular response that each worm sex presents in vivo. Our findings demonstrated significant differences between the chemical markers found in adult worms before and after praziquantel exposure, especially in phospholipids, which were predominantly identified as chemical markers in all samples. Results also indicate that distinct molecular pathways in both male and female worms could be differentially affected by praziquantel treatment. These data shine new light on the mechanism of action of praziquantel, taking a further step towards its full understanding.

  15. Automated MALDI matrix deposition method with inkjet printing for imaging mass spectrometry.

    PubMed

    Baluya, Dodge L; Garrett, Timothy J; Yost, Richard A

    2007-09-01

    Careful matrix deposition on tissue samples for matrix-assisted laser desorption/ionization (MALDI) is critical for producing reproducible analyte ion signals. Traditional methods for matrix deposition are often considered an art rather than a science, with significant sample-to-sample variability. Here we report an automated method for matrix deposition, employing a desktop inkjet printer (<$200) with 5760 x 1440 dpi resolution and a six-channel piezoelectric head that delivers 3 pL/drop. The inkjet printer tray, designed to hold CDs and DVDs, was modified to hold microscope slides. Empty ink cartridges were filled with MALDI matrix solutions, including DHB in methanol/water (70:30) at concentrations up to 40 mg/mL. Various samples (including rat brain tissue sections and standards of small drug molecules) were prepared using three deposition methods (electrospray, airbrush, inkjet). A linear ion trap equipped with an intermediate-pressure MALDI source was used for analyses. Optical microscopic examination showed that matrix crystals were formed evenly across the sample. There was minimal background signal after storing the matrix in the cartridges over a 6-month period. Overall, the mass spectral images gathered from inkjet-printed tissue specimens were of better quality and more reproducible than from specimens prepared by the electrospray and airbrush methods.

  16. Chemiluminescence Imaging of Superoxide Anion Detects Beta-Cell Function and Mass.

    PubMed

    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.

  17. 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.

  18. 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

  19. 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

  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. The Scanning Mass Spectrometry Probe: A Scanning Probe Electrospray Ion Source for Imaging Mass Spectrometry of Submerged Interfaces and Transient Events in Solution

    PubMed Central

    Kottke, Peter A.; Degertekin, F. Levent; Fedorov, Andrei G.

    2009-01-01

    The scanning mass spectrometry (SMS) probe is 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 (~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 are1)Treating the electrospray capillary inlet as a chemical scanning probe, and2)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. Organic ion imaging of biological tissue with secondary ion mass spectrometry and matrix-assisted laser desorption/ionization.

    PubMed

    Todd, P J; Schaaff, T G; Chaurand, P; Caprioli, R M

    2001-04-01

    Organic secondary ion mass spectrometry (SIMS) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry can be used to produce molecular images of samples. This is achieved through ionization from a clearly identified point on a flat sample, and performing a raster of the sample by moving the point of ionization over the sample surface. The unique analytical capabilities of mass spectrometry for mapping a variety of biological samples at the tissue level are discussed. SIMS provides information on the spatial distribution of the elements and low molecular mass compounds as well as molecular structures on these compounds, while MALDI yields spatial information about higher molecular mass compounds, including their distributions in tissues at very low levels, as well as information on the molecular structures of these compounds. Application of these methods to analytical problems requires appropriate instrumentation, sample preparation methodology, and a data presentation usually in a three-coordinate plot where x and y are physical dimensions of the sample and z is the signal amplitude. The use of imaging mass spectrometry is illustrated with several biological systems.

  3. 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

    2015-04-21

    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 utricle hair cells. Live-imaging EGFP-β-actin or dendra2-β-actin reveal stable F-actin cores with turnover and elongation restricted to stereocilia tips. Fixed-cell microscopy of wild-type and mutant β-actin demonstrates that incorporation of actin monomers into filaments is required for localization to stereocilia tips. Multi-isotope imaging mass spectrometry and live imaging of single differentiating hair cells capture stereociliogenesis and explain uniform incorporation of (15)N-labelled protein and EGFP-β-actin into nascent stereocilia. Collectively, our analyses support a model in which stereocilia actin cores are stable structures that incorporate new F-actin only at the distal tips.

  4. 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

  5. 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.

  6. Detection of Metastatic Breast and Thyroid Cancer in Lymph Nodes by Desorption Electrospray Ionization Mass Spectrometry Imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Jialing; Feider, Clara L.; Nagi, Chandandeep; Yu, Wendong; Carter, Stacey A.; Suliburk, James; Cao, Hop S. Tran; Eberlin, Livia S.

    2017-02-01

    Ambient ionization mass spectrometry has been widely applied to image lipids and metabolites in primary cancer tissues with the purpose of detecting and understanding metabolic changes associated with cancer development and progression. Here, we report the use of desorption electrospray ionization mass spectrometry (DESI-MS) to image metastatic breast and thyroid cancer in human lymph node tissues. Our results show clear alterations in lipid and metabolite distributions detected in the mass spectra profiles from 42 samples of metastatic thyroid tumors, metastatic breast tumors, and normal lymph node tissues. 2D DESI-MS ion images of selected molecular species allowed discrimination and visualization of specific histologic features within tissue sections, including regions of metastatic cancer, adjacent normal lymph node, and fibrosis or adipose tissues, which strongly correlated with pathologic findings. In thyroid cancer metastasis, increased relative abundances of ceramides and glycerophosphoinisitols were observed. In breast cancer metastasis, increased relative abundances of various fatty acids and specific glycerophospholipids were seen. Trends in the alterations in fatty acyl chain composition of lipid species were also observed through detailed mass spectra evaluation and chemical identification of molecular species. The results obtained demonstrate DESI-MSI as a potential clinical tool for the detection of breast and thyroid cancer metastasis in lymph nodes, although further validation is needed.

  7. Topographical and Chemical Imaging of a Phase Separated Polymer Using a Combined Atomic Force Microscopy/Infrared Spectroscopy/Mass Spectrometry Platform

    SciTech Connect

    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.

  8. 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.

  9. Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI - MS)

    NASA Astrophysics Data System (ADS)

    Fernandes, Anna Maria A. P.; Vendramini, Pedro H.; Galaverna, Renan; Schwab, Nicolas V.; Alberici, Luciane C.; Augusti, Rodinei; Castilho, Roger F.; Eberlin, Marcos N.

    2016-12-01

    Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels.

  10. Direct Visualization of Neurotransmitters in Rat Brain Slices by Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI - MS).

    PubMed

    Fernandes, Anna Maria A P; Vendramini, Pedro H; Galaverna, Renan; Schwab, Nicolas V; Alberici, Luciane C; Augusti, Rodinei; Castilho, Roger F; Eberlin, Marcos N

    2016-12-01

    Mass spectrometry imaging (MSI) of neurotransmitters has so far been mainly performed by matrix-assisted laser desorption/ionization (MALDI) where derivatization reagents, deuterated matrix and/or high resolution, or tandem MS have been applied to circumvent problems with interfering ion peaks from matrix and from isobaric species. We herein describe the application of desorption electrospray ionization mass spectrometry imaging (DESI)-MSI in rat brain coronal and sagittal slices for direct spatial monitoring of neurotransmitters and choline with no need of derivatization reagents and/or deuterated materials. The amino acids γ-aminobutyric (GABA), glutamate, aspartate, serine, as well as acetylcholine, dopamine, and choline were successfully imaged using a commercial DESI source coupled to a hybrid quadrupole-Orbitrap mass spectrometer. The spatial distribution of the analyzed compounds in different brain regions was determined. We conclude that the ambient matrix-free DESI-MSI is suitable for neurotransmitter imaging and could be applied in studies that involve evaluation of imbalances in neurotransmitters levels. Graphical Abstract ᅟ.

  11. 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.

  12. High-resolution matrix-assisted laser desorption ionization–imaging mass spectrometry of lipids in rodent optic nerve tissue

    PubMed Central

    Anderson, David M. G.; Mills, Daniel; Spraggins, Jeffrey; Lambert, Wendi S.; Calkins, David J.

    2013-01-01

    Purpose To develop a method for generating high spatial resolution (10 µm) matrix-assisted laser desorption ionization (MALDI) images of lipids in rodent optic nerve tissue. Methods Ice-embedded optic nerve tissue from rats and mice were cryosectioned across the coronal and sagittal axes of the nerve fiber. Sections were thaw mounted on gold-coated MALDI plates and were washed with ammonium acetate to remove biologic salts before being coated in 2,5-dihydroxybenzoic acid by sublimation. MALDI images were generated in positive and negative ion modes at 10 µm spatial resolution. Lipid identification was performed with a high mass resolution Fourier transform ion cyclotron resonance mass spectrometer. Results Several lipid species were observed with high signal intensity in MALDI images of optic nerve tissue. Several lipids were localized to specific structures including in the meninges surrounding the optic nerve and in the central neuronal tissue. Specifically, phosphatidylcholine species were observed throughout the nerve tissue in positive ion mode while sulfatide species were observed in high abundance in the meninges surrounding the optic nerve in negative ion mode. Accurate mass measurements and fragmentation using sustained off-resonance irradiation with a high mass resolution Fourier transform ion cyclotron resonance mass spectrometer instrument allowed for identification of lipid species present in the small structure of the optic nerve directly from tissue sections. Conclusions An optimized sample preparation method provides excellent sensitivity for lipid species present within optic nerve tissue. This allowed the laser spot size and fluence to be reduced to obtain a high spatial resolution of 10 µm. This new imaging modality can now be applied to determine spatial and molecular changes in optic nerve tissue with disease. PMID:23559852

  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. THE LEECH EXOPLANET IMAGING SURVEY: ORBIT AND COMPONENT MASSES OF THE INTERMEDIATE-AGE, LATE-TYPE BINARY NO UMa

    SciTech Connect

    Schlieder, Joshua E.; Skemer, Andrew J.; Hinz, Philip; Leisenring, Jarron; Defrère, Denis; Close, Laird M.; Eisner, Josh A.; Maire, Anne-Lise; Desidera, Silvano; Skrutskie, Michael F.; Bailey, Vanessa; Esposito, Simone; Strassmeier, Klaus G.; Weber, Michael; Biller, Beth A.; Bonnefoy, Mickaël; Buenzli, Esther; Henning, Thomas; Crepp, Justin R.; Hofmann, Karl-Heinz; and others

    2016-02-10

    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-, K{sub s}-, 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{sub ⊙} and 0.64 ± 0.02 M{sub ⊙}, 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  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. OGLE-2012-BLG-0563Lb: A Saturn-mass Planet around an M Dwarf with the Mass Constrained by Subaru AO Imaging

    NASA Astrophysics Data System (ADS)

    Fukui, A.; Gould, A.; Sumi, T.; Bennett, D. P.; Bond, I. A.; Han, C.; Suzuki, D.; Beaulieu, J.-P.; Batista, V.; Udalski, A.; Street, R. A.; Tsapras, Y.; Hundertmark, M.; Abe, F.; Bhattacharya, A.; Freeman, M.; Itow, Y.; Ling, C. H.; Koshimoto, N.; Masuda, K.; Matsubara, Y.; Muraki, Y.; Ohnishi, K.; Philpott, L. C.; Rattenbury, N.; Saito, T.; Sullivan, D. J.; Tristram, P. J.; Yonehara, A.; MOA Collaboration; Choi, J.-Y.; Christie, G. W.; DePoy, D. L.; Dong, Subo; Drummond, J.; Gaudi, B. S.; Hwang, K.-H.; Kavka, A.; Lee, C.-U.; McCormick, J.; Natusch, T.; Ngan, H.; Park, H.; Pogge, R. W.; Shin, I.-G.; Tan, T.-G.; Yee, J. C.; μFUN Collaboration; Szymański, M. K.; Pietrzyński, G.; Soszyński, I.; Poleski, R.; Kozłowski, S.; Pietrukowicz, P.; Ulaczyk, K.; Wyrzykowski, Ł.; OGLE Collaboration; Bramich, D. M.; Browne, P.; Dominik, M.; Horne, K.; Ipatov, S.; Kains, N.; Snodgrass, C.; Steele, I. A.; RoboNet Collaboration

    2015-08-01

    We report the discovery of a microlensing exoplanet OGLE-2012-BLG-0563Lb with the planet-star mass ratio of ˜ 1× {10}-3. Intensive photometric observations of a high-magnification microlensing event allow us to detect a clear signal of the planet. Although no parallax signal is detected in the light curve, we instead succeed at detecting the flux from the host star in high-resolution JHK‧-band images obtained by the Subaru/AO188 and Infrared Camera and Spectrograph instruments, allowing us to constrain the absolute physical parameters of the planetary system. With the help of spectroscopic information about the source star obtained during the high-magnification state by Bensby et al., we find that the lens system is located at 1.3{}-0.8+0.6 kpc from us, and consists of an M dwarf (0.34 {}-0.20+0.12M{}⊙ ) orbited by a Saturn-mass planet (0.39 {}-0.23+0.14MJup) at the projected separation of 0.74{}-0.42+0.26 AU (close model) or 4.3{}-2.5+1.5 AU (wide model). The probability of contamination in the host star’s flux, which would reduce the masses by a factor of up to three, is