Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

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.

Quantitative images of metals in plant tissues measured by laser ablation inductively coupled plasma mass spectrometry

International Nuclear Information System (INIS)

Becker, J.S.; Dietrich, R.C.; Matusch, A.; Pozebon, D.; Dressler, V.L.

2008-01-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) was used for quantitative imaging of toxic and essential elements in thin sections (thickness of 30 or 40 μm) of tobacco plant tissues. Two-dimensional images of Mg, Fe, Mn, Zn, Cu, Cd, Rh, Pt and Pb in leaves, shoots and roots of tobacco were produced. Sections of the plant tissues (fixed onto glass slides) were scanned by a focused beam of a Nd:YAG laser in a laser ablation chamber. The ablated material was transported with argon as carrier gas to the ICP ion source at a quadrupole ICP-MS instrument. Ion intensities of the investigated elements were measured together with 13 C + , 33 S + and 34 S + within the entire plant tissue section. Matrix matching standards (prepared using powder of dried tobacco leaves) were used to constitute calibration curves, whereas the regression coefficient of the attained calibration curves was typically 0.99. The variability of LA-ICP-MS process, sample heterogeneity and water content in the sample were corrected by using 13 C + as internal standard. Quantitative imaging of the selected elements revealed their inhomogeneous distribution in leaves, shoots and roots

Imaging and mapping of mouse bone using MALDI-imaging mass spectrometry

Directory of Open Access Journals (Sweden)

Yoko Fujino

2016-12-01

Full Text Available Matrix-assisted laser desorption/ionization-imaging mass spectrometry (MALDI-IMS is an advanced method used globally to analyze the distribution of biomolecules on tissue cryosections without any probes. In bones, however, hydroxyapatite crystals make it difficult to determine the distribution of biomolecules using MALDI-IMS. Additionally, there is limited information regarding the use of this method to analyze bone tissues. To determine whether MALDI-IMS analysis of bone tissues can facilitate comprehensive mapping of biomolecules in mouse bone, we first dissected femurs and tibiae from 8-week-old male mice and characterized the quality of multiple fixation and decalcification methods for preparation of the samples. Cryosections were mounted on indium tin oxide-coated glass slides, dried, and then a matrix solution was sprayed on the tissue surface. Images were acquired using an iMScope at a mass-to-charge range of 100–1000. Hematoxylin-eosin, Alcian blue, Azan, and periodic acid-Schiff staining of adjacent sections was used to evaluate histological and histochemical features. Among the various fixation and decalcification conditions, sections from trichloroacetic acid-treated samples were most suitable to examine both histology and comprehensive MS images. However, histotypic MS signals were detected in all sections. In addition to the MS images, phosphocholine was identified as a candidate metabolite. These results indicate successful detection of biomolecules in bone using MALDI-IMS. Although analytical procedures and compositional adjustment regarding the performance of the device still require further development, IMS appears to be a powerful tool to determine the distribution of biomolecules in bone tissues. Keywords: Matrix-assisted laser desorption/ionization-imaging mass spectrometry, Tissue cryosection, Bone, Fixation, Decalcification

Automated, parallel mass spectrometry imaging and structural identification of lipids

DEFF Research Database (Denmark)

Ellis, Shane R.; Paine, Martin R.L.; Eijkel, Gert B.

2018-01-01

We report a method that enables automated data-dependent acquisition of lipid tandem mass spectrometry data in parallel with a high-resolution mass spectrometry imaging experiment. The method does not increase the total image acquisition time and is combined with automatic structural assignments....... This lipidome-per-pixel approach automatically identified and validated 104 unique molecular lipids and their spatial locations from rat cerebellar tissue....

[Imaging Mass Spectrometry in Histopathologic Analysis].

Science.gov (United States)

Yamazaki, Fumiyoshi; Seto, Mitsutoshi

2015-04-01

Matrix-assisted laser desorption/ionization (MALDI)-imaging mass spectrometry (IMS) enables visualization of the distribution of a range of biomolecules by integrating biochemical information from mass spectrometry with positional information from microscopy. IMS identifies a target molecule. In addition, IMS enables global analysis of biomolecules containing unknown molecules by detecting the ratio of the molecular weight to electric charge without any target, which makes it possible to identify novel molecules. IMS generates data on the distribution of lipids and small molecules in tissues, which is difficult to visualize with either conventional counter-staining or immunohistochemistry. In this review, we firstly introduce the principle of imaging mass spectrometry and recent advances in the sample preparation method. Secondly, we present findings regarding biological samples, especially pathological ones. Finally, we discuss the limitations and problems of the IMS technique and clinical application, such as in drug development.

Lipid imaging by mass spectrometry - a review.

Science.gov (United States)

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.

Protein biomarkers on tissue as imaged via MALDI mass spectrometry: A systematic approach to study the limits of detection.

Science.gov (United States)

van de Ven, Stephanie M W Y; Bemis, Kyle D; Lau, Kenneth; Adusumilli, Ravali; Kota, Uma; Stolowitz, Mark; Vitek, Olga; Mallick, Parag; Gambhir, Sanjiv S

2016-06-01

MALDI mass spectrometry imaging (MSI) is emerging as a tool for protein and peptide imaging across tissue sections. Despite extensive study, there does not yet exist a baseline study evaluating the potential capabilities for this technique to detect diverse proteins in tissue sections. In this study, we developed a systematic approach for characterizing MALDI-MSI workflows in terms of limits of detection, coefficients of variation, spatial resolution, and the identification of endogenous tissue proteins. Our goal was to quantify these figures of merit for a number of different proteins and peptides, in order to gain more insight in the feasibility of protein biomarker discovery efforts using this technique. Control proteins and peptides were deposited in serial dilutions on thinly sectioned mouse xenograft tissue. Using our experimental setup, coefficients of variation were biomarkers and a new benchmarking strategy that can be used for comparing diverse MALDI-MSI workflows. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three-Dimensional Imaging of Lipids and Metabolites in Tissues by Nanospray Desorption Electrospray Ionization Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Lanekoff, Ingela T.; Burnum-Johnson, Kristin E.; Thomas, Mathew; Cha, Jeeyeon; Dey, Sudhansu K.; yang, Pengxiang; Prieto, Mari; Laskin, Julia

2015-03-01

Abstract Three-dimensional (3D) imaging of tissue sections is a new frontier in mass spectrometry imaging (MSI). Here we report on fast 3D imaging of lipids and metabolites associated with mouse uterine decidual cells and embryo at the implantation site on day 6 of pregnancy. 2D imaging of 16-20 serial tissue sections deposited on the same glass slide was performed using nanospray desorption electrospray ionization (nano-DESI) – an ambient ionization technique that enables sensitive localized analysis of analytes on surfaces without special sample pre-treatment. In this proof-of-principle study, nano-DESI was coupled to a high-resolution Q-Exactive instrument operated at high repetition rate of >5 Hz with moderate mass resolution of 35,000 (m/Δm at m/z 200), which enabled acquisition of the entire 3D image with a spatial resolution of ~150 μm in less than 4.5 hours. The results demonstrate localization of acetylcholine in the primary decidual zone (PDZ) of the implantation site throughout the depth of the tissue examined, indicating an important role of this signaling molecule in decidualization. Choline and phosphocholine – metabolites associated with cell growth – are enhanced in the PDZ and abundant in other cellular regions of the implantation site. Very different 3D distributions were obtained for fatty acids (FA), oleic acid and linoleic acid (FA 18:1 and FA 18:2), differing only by one double bond. Localization of FA 18:2 in the PDZ indicates its important role in decidualization while FA 18:1 is distributed more evenly throughout the tissue. In contrast, several lysophosphatidylcholines (LPC) observed in this study show donut-like distributions with localization around the PDZ. Complementary distributions with minimal overlap were observed for LPC 18:0 and FA 18:2 while the 3D image of the potential precursor phosphatidylcholine (PC 36:2) showed a significant overlap with both LPC 18:0 and FA 18:2.

Imaging mass spectrometry statistical analysis.

Science.gov (United States)

Jones, Emrys A; Deininger, Sören-Oliver; Hogendoorn, Pancras C W; Deelder, André M; McDonnell, Liam A

2012-08-30

Imaging mass spectrometry is increasingly used to identify new candidate biomarkers. This clinical application of imaging mass spectrometry is highly multidisciplinary: expertise in mass spectrometry is necessary to acquire high quality data, histology is required to accurately label the origin of each pixel's mass spectrum, disease biology is necessary to understand the potential meaning of the imaging mass spectrometry results, and statistics to assess the confidence of any findings. Imaging mass spectrometry data analysis is further complicated because of the unique nature of the data (within the mass spectrometry field); several of the assumptions implicit in the analysis of LC-MS/profiling datasets are not applicable to imaging. The very large size of imaging datasets and the reporting of many data analysis routines, combined with inadequate training and accessible reviews, have exacerbated this problem. In this paper we provide an accessible review of the nature of imaging data and the different strategies by which the data may be analyzed. Particular attention is paid to the assumptions of the data analysis routines to ensure that the reader is apprised of their correct usage in imaging mass spectrometry research. Copyright © 2012 Elsevier B.V. All rights reserved.

Advancements in mass spectrometry for biological samples: Protein chemical cross-linking and metabolite analysis of plant tissues

Energy Technology Data Exchange (ETDEWEB)

Klein, Adam [Iowa State Univ., Ames, IA (United States)

2015-01-01

This thesis presents work on advancements and applications of methodology for the analysis of biological samples using mass spectrometry. Included in this work are improvements to chemical cross-linking mass spectrometry (CXMS) for the study of protein structures and mass spectrometry imaging and quantitative analysis to study plant metabolites. Applications include using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) to further explore metabolic heterogeneity in plant tissues and chemical interactions at the interface between plants and pests. Additional work was focused on developing liquid chromatography-mass spectrometry (LC-MS) methods to investigate metabolites associated with plant-pest interactions.

Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry

Science.gov (United States)

Manier, M. Lisa; Reyzer, Michelle L.; Goh, Anne; Dartois, Veronique; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.

2011-08-01

Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.

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

Science.gov (United States)

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. Graphical Abstract ᅟ.

Quantitating subcellular metabolism with multi-isotope imaging mass spectrometry

OpenAIRE

Steinhauser, Matthew L.; Bailey, Andrew; Senyo, Samuel E.; Guillermier, Christelle; Perlstein, Todd S.; Gould, Alex P.; Lee, Richard T.; Lechene, Claude P.

2012-01-01

Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter 1,2 but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with sub-micron resolution 3,4 . Here we apply MIMS to diverse organisms, including Drosophila, mice, and humans. We test the “immortal strand hypothesis,” which predicts that during asymmetric stem cell division ch...

Mass spectrometry imaging: Towards a lipid microscope?

Science.gov (United States)

Touboul, David; Brunelle, Alain; Laprévote, Olivier

2011-01-01

Biological imaging techniques are the most efficient way to locally measure the variation of different parameters on tissue sections. These analyses are gaining increasing interest since 20 years and allow observing extremely complex biological phenomena at lower and lower time and resolution scale. Nevertheless, most of them only target very few compounds of interest, which are chosen a priori, due to their low resolution power and sensitivity. New chemical imaging technique has to be introduced in order to overcome these limitations, leading to more informative and sensitive analyses for biologists and physicians. Two major mass spectrometry methods can be efficiently used to generate the distribution of biological compounds over a tissue section. Matrix-Assisted Laser Desorption/Ionisation-Mass Spectrometry (MALDI-MS) needs the co-crystallization of the sample with a matrix before to be irradiated by a laser, whereas the analyte is directly desorbed by a primary ion bombardment for Secondary Ion Mass Spectrometry (SIMS) experiments. In both cases, energy used for desorption/ionization is locally deposited -some tens of microns for the laser and some hundreds of nanometers for the ion beam- meaning that small areas over the surface sample can be separately analyzed. Step by step analysis allows spectrum acquisitions over the tissue sections and the data are treated by modern informatics software in order to create ion density maps, i.e., the intensity plot of one specific ion versus the (x,y) position. Main advantages of SIMS and MALDI compared to other chemical imaging techniques lie in the simultaneous acquisition of a large number of biological compounds in mixture with an excellent sensitivity obtained by Time-of-Flight (ToF) mass analyzer. Moreover, data treatment is done a posteriori, due to the fact that no compound is selectively marked, and let us access to the localization of different lipid classes in only one complete acquisition. Copyright © 2010

Final LDRD report : development of sample preparation methods for ChIPMA-based imaging mass spectrometry of tissue samples.

Energy Technology Data Exchange (ETDEWEB)

Maharrey, Sean P.; Highley, Aaron M.; Behrens, Richard, Jr.; Wiese-Smith, Deneille

2007-12-01

The objective of this short-term LDRD project was to acquire the tools needed to use our chemical imaging precision mass analyzer (ChIPMA) instrument to analyze tissue samples. This effort was an outgrowth of discussions with oncologists on the need to find the cellular origin of signals in mass spectra of serum samples, which provide biomarkers for ovarian cancer. The ultimate goal would be to collect chemical images of biopsy samples allowing the chemical images of diseased and nondiseased sections of a sample to be compared. The equipment needed to prepare tissue samples have been acquired and built. This equipment includes an cyro-ultramicrotome for preparing thin sections of samples and a coating unit. The coating unit uses an electrospray system to deposit small droplets of a UV-photo absorbing compound on the surface of the tissue samples. Both units are operational. The tissue sample must be coated with the organic compound to enable matrix assisted laser desorption/ionization (MALDI) and matrix enhanced secondary ion mass spectrometry (ME-SIMS) measurements with the ChIPMA instrument Initial plans to test the sample preparation using human tissue samples required development of administrative procedures beyond the scope of this LDRD. Hence, it was decided to make two types of measurements: (1) Testing the spatial resolution of ME-SIMS by preparing a substrate coated with a mixture of an organic matrix and a bio standard and etching a defined pattern in the coating using a liquid metal ion beam, and (2) preparing and imaging C. elegans worms. Difficulties arose in sectioning the C. elegans for analysis and funds and time to overcome these difficulties were not available in this project. The facilities are now available for preparing biological samples for analysis with the ChIPMA instrument. Some further investment of time and resources in sample preparation should make this a useful tool for chemical imaging applications.

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

Science.gov (United States)

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.

Automated Morphological and Morphometric Analysis of Mass Spectrometry Imaging Data: Application to Biomarker Discovery

Science.gov (United States)

Picard de Muller, Gaël; Ait-Belkacem, Rima; Bonnel, David; Longuespée, Rémi; Stauber, Jonathan

2017-12-01

Mass spectrometry imaging datasets are mostly analyzed in terms of average intensity in regions of interest. However, biological tissues have different morphologies with several sizes, shapes, and structures. The important biological information, contained in this highly heterogeneous cellular organization, could be hidden by analyzing the average intensities. Finding an analytical process of morphology would help to find such information, describe tissue model, and support identification of biomarkers. This study describes an informatics approach for the extraction and identification of mass spectrometry image features and its application to sample analysis and modeling. For the proof of concept, two different tissue types (healthy kidney and CT-26 xenograft tumor tissues) were imaged and analyzed. A mouse kidney model and tumor model were generated using morphometric - number of objects and total surface - information. The morphometric information was used to identify m/z that have a heterogeneous distribution. It seems to be a worthwhile pursuit as clonal heterogeneity in a tumor is of clinical relevance. This study provides a new approach to find biomarker or support tissue classification with more information. [Figure not available: see fulltext.

Comparison of drug distribution images from whole-body thin tissue sections obtained using desorption electrospray ionization tandem mass spectrometry and autoradiography.

Science.gov (United States)

Kertesz, Vilmos; Van Berkel, Gary J; Vavrek, Marissa; Koeplinger, Kenneth A; Schneider, Bradley B; Covey, Thomas R

2008-07-01

Desorption electrospray ionization tandem mass spectrometry (DESI-MS/MS) and whole-body autoradiography (WBA) were used for chemical imaging of whole-body thin tissue sections of mice intravenously dosed with propranolol (7.5 mg/kg). DESI-MS/MS imaging utilized selected reaction monitoring detection performed on an AB/MDS SCIEX 4000 QTRAP mass spectrometer equipped with a prototype extended length particle discriminator interface. Propranolol images of the tissue sections using DESI-MS/MS were obtained at surface scan rates of 0.1, 0.5, 2, and 7 mm/s. Although signal decreased with increasing scan rate, useful whole-body images for propranolol were obtained from the tissues even at 7 mm/s, which required just 79 min of analysis time. Attempts to detect and image the distribution of the known propranolol metabolites were unsuccessful. Regions of the tissue sections showing the most radioactivity from WBA sections were excised and analyzed by high-performance liquid chromatography (HPLC) with radiochemical detection to determine relative levels of propranolol and metabolites present. Comparison of the DESI-MS/MS signal for propranolol and the radioactivity attributed to propranolol from WBA sections indicated nominal agreement between the two techniques for the amount of propranolol in the brain, lung, and liver. Data from the kidney showed an unexplained disparity between the two techniques. The results of this study show the feasibility of using DESI-MS/MS to obtain useful chemical images of a drug in whole-body thin tissue sections following drug administration at a pharmacologically relevant level. Further optimization to improve sensitivity and enable detection of the drug metabolites will be among the requirements necessary to move DESI-MS/MS chemical imaging forward as a practical tool in drug discovery.

From whole-body sections down to cellular level, multiscale imaging of phospholipids by MALDI mass spectrometry.

Science.gov (United States)

Chaurand, Pierre; Cornett, Dale S; Angel, Peggi M; Caprioli, Richard M

2011-02-01

Significant progress in instrumentation and sample preparation approaches have recently expanded the potential of MALDI imaging mass spectrometry to the analysis of phospholipids and other endogenous metabolites naturally occurring in tissue specimens. Here we explore some of the requirements necessary for the successful analysis and imaging of phospholipids from thin tissue sections of various dimensions by MALDI time-of-flight mass spectrometry. We address methodology issues relative to the imaging of whole-body sections such as those cut from model laboratory animals, sections of intermediate dimensions typically prepared from individual organs, as well as the requirements for imaging areas of interests from these sections at a cellular scale spatial resolution. We also review existing limitations of MALDI imaging MS technology relative to compound identification. Finally, we conclude with a perspective on important issues relative to data exploitation and management that need to be solved to maximize biological understanding of the tissue specimen investigated.

A new classification method for MALDI imaging mass spectrometry data acquired on formalin-fixed paraffin-embedded tissue samples.

Science.gov (United States)

Boskamp, Tobias; Lachmund, Delf; Oetjen, Janina; Cordero Hernandez, Yovany; Trede, Dennis; Maass, Peter; Casadonte, Rita; Kriegsmann, Jörg; Warth, Arne; Dienemann, Hendrik; Weichert, Wilko; Kriegsmann, Mark

2017-07-01

Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) shows a high potential for applications in histopathological diagnosis, and in particular for supporting tumor typing and subtyping. The development of such applications requires the extraction of spectral fingerprints that are relevant for the given tissue and the identification of biomarkers associated with these spectral patterns. We propose a novel data analysis method based on the extraction of characteristic spectral patterns (CSPs) that allow automated generation of classification models for spectral data. Formalin-fixed paraffin embedded (FFPE) tissue samples from N=445 patients assembled on 12 tissue microarrays were analyzed. The method was applied to discriminate primary lung and pancreatic cancer, as well as adenocarcinoma and squamous cell carcinoma of the lung. A classification accuracy of 100% and 82.8%, resp., could be achieved on core level, assessed by cross-validation. The method outperformed the more conventional classification method based on the extraction of individual m/z values in the first application, while achieving a comparable accuracy in the second. LC-MS/MS peptide identification demonstrated that the spectral features present in selected CSPs correspond to peptides relevant for the respective classification. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

Imaging mass spectrometry in papillary thyroid carcinoma for the identification and validation of biomarker proteins.

Science.gov (United States)

Min, Kyueng-Whan; Bang, Joo-Young; Kim, Kwang Pyo; Kim, Wan-Seop; Lee, Sang Hwa; Shanta, Selina Rahman; Lee, Jeong Hwa; Hong, Ji Hye; Lim, So Dug; Yoo, Young-Bum; Na, Chan-Hyun

2014-07-01

Direct tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization and time-of-flight (MALDI-TOF) mass spectrometry has become increasingly important in biology and medicine, because this technology can detect the relative abundance and spatial distribution of interesting proteins in tissues. Five thyroid cancer samples, along with normal tissue, were sliced and transferred onto conductive glass slides. After laser scanning by MALDI-TOF equipped with a smart beam laser, images were created for individual masses and proteins were classified at 200-µm spatial resolution. Based on the spatial distribution, region-specific proteins on a tumor lesion could be identified by protein extraction from tumor tissue and analysis using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Using all the spectral data at each spot, various intensities of a specific peak were detected in the tumor and normal regions of the thyroid. Differences in the molecular weights of expressed proteins between tumor and normal regions were analyzed using unsupervised and supervised clustering. To verify the presence of discovered proteins through IMS, we identified ribosomal protein P2, which is specific for cancer. We have demonstrated the feasibility of IMS as a useful tool for the analysis of tissue sections, and identified the tumor-specific protein ribosomal protein P2.

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

Directory of Open Access Journals (Sweden)

Millar A Harvey

2011-07-01

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

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

DEFF Research Database (Denmark)

Li, Bin; Bhandari, Dhaka Ram; Janfelt, Christian

2014-01-01

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 o...... 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....

On the Importance of Mathematical Methods for Analysis of MALDI-Imaging Mass Spectrometry Data

Directory of Open Access Journals (Sweden)

Trede Dennis

2012-03-01

Full Text Available In the last decade, matrix-assisted laser desorption/ionization (MALDI imaging mass spectrometry (IMS, also called as MALDI-imaging, has proven its potential in proteomics and was successfully applied to various types of biomedical problems, in particular to histopathological label-free analysis of tissue sections. In histopathology, MALDI-imaging is used as a general analytic tool revealing the functional proteomic structure of tissue sections, and as a discovery tool for detecting new biomarkers discriminating a region annotated by an experienced histologist, in particular, for cancer studies.

Mass Spectrometry Imaging under Ambient Conditions

Science.gov (United States)

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

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

DEFF Research Database (Denmark)

Nielsen, Mette M B; Lambertsen, Kate L; Clausen, Bettina H

2016-01-01

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......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, 7...

Histology-directed and imaging mass spectrometry: an emerging technology in ectopic calcification

OpenAIRE

Taverna, Domenico; Boraldi, Federica; 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...

Mass spectrometry imaging: a novel technology in rheumatology.

Science.gov (United States)

Rocha, Beatriz; Ruiz-Romero, Cristina; Blanco, Francisco J

2017-01-01

Mass spectrometry imaging (MSI) is used to determine the relative abundance and spatial distribution of biomolecules such as peptides, proteins, lipids and other organic compounds in tissue sections by their molecular masses. This technique provides a sensitive and label-free approach for high-resolution imaging, and is currently used in an increasing number of biomedical applications such as biomarker discovery, tissue classification and drug monitoring. Owing to technological advances in the past 5 years in diverse MSI strategies, this technology is expected to become a standard tool in clinical practice and provides information complementary to that obtained using existing methods. Given that MSI is able to extract mass-spectral signatures from pathological tissue samples, this technique provides a novel platform to study joint-related tissues affected by rheumatic diseases. In rheumatology, MSI has been performed on articular cartilage, synovium and bone to increase the understanding of articular destruction and to characterize diagnostic and prognostic biomarkers for osteoarthritis, rheumatoid arthritis and osteoporosis. In this Review, we provide an overview of MSI technology and of the studies in which joint tissues have been analysed by use of this methodology. This approach might increase knowledge of rheumatic pathologies and ultimately prompt the development of targeted strategies for their management.

Characterization of a novel miniaturized burst-mode infrared laser system for IR-MALDESI mass spectrometry imaging.

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Ekelöf, Måns; Manni, Jeffrey; Nazari, Milad; Bokhart, Mark; Muddiman, David C

2018-03-01

Laser systems are widely used in mass spectrometry as sample probes and ionization sources. Mid-infrared lasers are particularly suitable for analysis of high water content samples such as animal and plant tissues, using water as a resonantly excited sacrificial matrix. Commercially available mid-IR lasers have historically been bulky and expensive due to cooling requirements. This work presents a novel air-cooled miniature mid-IR laser with adjustable burst-mode output and details an evaluation of its performance for mass spectrometry imaging. The miniature laser was found capable of generating sufficient energy for complete ablation of animal tissue in the context of an IR-MALDESI experiment with exogenously added ice matrix, yielding several hundred confident metabolite identifications. Graphical abstract The use of a novel miniature 2.94 μm burst-mode laser in IR-MALDESI allows for rapid and sensitive mass spectrometry imaging of a whole mouse.

Aspects of Quantitation in Mass Spectrometry Imaging Investigated on Cryo-Sections of Spiked Tissue Homogenates

DEFF Research Database (Denmark)

Hansen, Heidi Toft; Janfelt, Christian

2016-01-01

for differences in tissue types in, for example, whole-body imaging, a set of tissue homogenates of different tissue types (lung, liver, kidney, heart, and brain) from rabbit was spiked to the same concentration with the drug amitriptyline and imaged in the same experiment using isotope labeled amitriptyline...... for these results range approximately within a factor of 3 (but for other compounds in other tissues could be higher), underscore the importance of preparing the standard curve in the same matrix as the unknown sample whenever possible. In, for example, whole-body imaging where a diversity of tissue types...... are present, this variation across tissue types will therefore add to the overall uncertainty in quantitation. The tissue homogenates were also used in a characterization of various phenomena in quantitative MSI, such as to study how the signal depends of the thickness of the cryo-section, and to assess...

Molecular imaging of myocardial infarction with Gadofluorine P – A combined magnetic resonance and mass spectrometry imaging approach

Directory of Open Access Journals (Sweden)

Fabian Lohöfer

2018-04-01

Full Text Available Background: Molecular MRI is becoming increasingly important for preclinical research. Validation of targeted gadolinium probes in tissue however has been cumbersome up to now. Novel methodology to assess gadolinium distribution in tissue after in vivo application is therefore needed. Purpose: To establish combined Magnetic Resonance Imaging (MRI and Mass Spectrometry Imaging (MSI for improved detection and quantification of Gadofluorine P deposition in scar formation and myocardial remodeling. Materials and methods: Animal studies were performed according to institutionally approved protocols. Myocardial infarction was induced by permanent ligation of the left ascending artery (LAD in C57BL/6J mice. MRI was performed at 7T at 1 week and 6 weeks after myocardial infarction. Gadofluorine P was used for dynamic T1 mapping of extracellular matrix synthesis during myocardial healing and compared to Gd-DTPA. After in vivo imaging contrast agent concentration as well as distribution in tissue were validated and quantified by spatially resolved Matrix-Assisted Laser Desorption Ionization (MALDI MSI and Laser Ablation – Inductively Coupled Plasma – Mass Spectrometry (LA-ICP-MS imaging. Results: Both Gadofluorine P enhancement as well as local tissue content in the myocardial scar were highest at 15 minutes post injection. R1 values increased from 1 to 6 weeks after MI (1.62 s−1 vs 2.68 s−1, p = 0.059 paralleled by an increase in Gadofluorine P concentration in the infarct from 0.019 mM at 1 week to 0.028 mM at 6 weeks (p = 0.048, whereas Gd-DTPA enhancement showed no differences (3.95 s−1 vs 3.47 s−1, p = 0.701. MALDI-MSI results were corroborated by elemental LA-ICP-MS of Gadolinium in healthy and infarcted myocardium. Histology confirmed increased extracellular matrix synthesis at 6 weeks compared to 1 week. Conclusion: Adding quantitative MSI to MR imaging enables a quantitative validation of Gadofluorine P distribution in the heart

Imaging of Selenium by Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS) in 2-D Electrophoresis Gels and Biological Tissues.

Science.gov (United States)

Cruz, Elisa Castañeda Santa; Susanne Becker, J; Sabine Becker, J; Sussulini, Alessandra

2018-01-01

Selenium and selenoproteins are important components of living organisms that play a role in different biological processes. Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is a powerful analytical technique that has been employed to obtain distribution maps of selenium in biological tissues in a direct manner, as well as in selenoproteins, previously separated by their molecular masses and isoelectric points using two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). In this chapter, we present the protocols to perform LA-ICP-MS imaging experiments, allowing the distribution visualization and determination of selenium and/or selenoproteins in biological systems.

microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling

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Comi, Troy J.; Neumann, Elizabeth K.; Do, Thanh D.; Sweedler, Jonathan V.

2017-09-01

Image-guided mass spectrometry (MS) profiling provides a facile framework for analyzing samples ranging from single cells to tissue sections. The fundamental workflow utilizes a whole-slide microscopy image to select targets of interest, determine their spatial locations, and subsequently perform MS analysis at those locations. Improving upon prior reported methodology, a software package was developed for working with microscopy images. microMS, for microscopy-guided mass spectrometry, allows the user to select and profile diverse samples using a variety of target patterns and mass analyzers. Written in Python, the program provides an intuitive graphical user interface to simplify image-guided MS for novice users. The class hierarchy of instrument interactions permits integration of new MS systems while retaining the feature-rich image analysis framework. microMS is a versatile platform for performing targeted profiling experiments using a series of mass spectrometers. The flexibility in mass analyzers greatly simplifies serial analyses of the same targets by different instruments. The current capabilities of microMS are presented, and its application for off-line analysis of single cells on three distinct instruments is demonstrated. The software has been made freely available for research purposes. [Figure not available: see fulltext.

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

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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. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mass spectrometry imaging enriches biomarker discovery approaches with candidate mapping.

Science.gov (United States)

Scott, Alison J; Jones, Jace W; Orschell, Christie M; MacVittie, Thomas J; Kane, Maureen A; Ernst, Robert K

2014-01-01

Integral to the characterization of radiation-induced tissue damage is the identification of unique biomarkers. Biomarker discovery is a challenging and complex endeavor requiring both sophisticated experimental design and accessible technology. The resources within the National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Consortium, Medical Countermeasures Against Radiological Threats (MCART), allow for leveraging robust animal models with novel molecular imaging techniques. One such imaging technique, MALDI (matrix-assisted laser desorption ionization) mass spectrometry imaging (MSI), allows for the direct spatial visualization of lipids, proteins, small molecules, and drugs/drug metabolites-or biomarkers-in an unbiased manner. MALDI-MSI acquires mass spectra directly from an intact tissue slice in discrete locations across an x, y grid that are then rendered into a spatial distribution map composed of ion mass and intensity. The unique mass signals can be plotted to generate a spatial map of biomarkers that reflects pathology and molecular events. The crucial unanswered questions that can be addressed with MALDI-MSI include identification of biomarkers for radiation damage that reflect the response to radiation dose over time and the efficacy of therapeutic interventions. Techniques in MALDI-MSI also enable integration of biomarker identification among diverse animal models. Analysis of early, sublethally irradiated tissue injury samples from diverse mouse tissues (lung and ileum) shows membrane phospholipid signatures correlated with histological features of these unique tissues. This paper will discuss the application of MALDI-MSI for use in a larger biomarker discovery pipeline.

MALDI Imaging Mass Spectrometry (MALDI-IMS―Application of Spatial Proteomics for Ovarian Cancer Classification and Diagnosis

Directory of Open Access Journals (Sweden)

Johan O. R. Gustafsson

2011-01-01

Full Text Available MALDI imaging mass spectrometry (MALDI-IMS allows acquisition of mass data for metabolites, lipids, peptides and proteins directly from tissue sections. IMS is typically performed either as a multiple spot profiling experiment to generate tissue specific mass profiles, or a high resolution imaging experiment where relative spatial abundance for potentially hundreds of analytes across virtually any tissue section can be measured. Crucially, imaging can be achieved without prior knowledge of tissue composition and without the use of antibodies. In effect MALDI-IMS allows generation of molecular data which complement and expand upon the information provided by histology including immuno-histochemistry, making its application valuable to both cancer biomarker research and diagnostics. The current state of MALDI-IMS, key biological applications to ovarian cancer research and practical considerations for analysis of peptides and proteins on ovarian tissue are presented in this review.

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

Science.gov (United States)

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

2017-06-01

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. [Figure not available: see fulltext.

Matrix-Assisted Laser Desorption Ionization Mass Spectrometry Imaging for Peptide and Protein Analyses: A Critical Review of On-Tissue Digestion

NARCIS (Netherlands)

Cillero-Pastor, B.; Heeren, R.M.A.

2013-01-01

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) has established itself among the plethora of mass spectrometry applications. In the biomedical field, MALDI-MSI is being more frequently recognized as a new method for the discovery of biomarkers and targets of

New Ionization and Detection Technologies for Mass Spectrometry Imaging. From Small Molecules to Intact Proteins

NARCIS (Netherlands)

Kiss, A.

2014-01-01

There is a constantly growing interest in biomedical research to visualize changes in the location of various biomolecules in tissue sections as a result of complex diseases. Mass spectrometry imaging is one of the techniques that enable the mapping of molecules on a 2D surface. However, the

A Comparison of Tissue Spray and Lipid Extract Direct Injection Electrospray Ionization Mass Spectrometry for the Differentiation of Eutopic and Ectopic Endometrial Tissues

Science.gov (United States)

Chagovets, Vitaliy; Wang, Zhihao; Kononikhin, Alexey; Starodubtseva, Natalia; Borisova, Anna; Salimova, Dinara; Popov, Igor; Kozachenko, Andrey; Chingin, Konstantin; Chen, Huanwen; Frankevich, Vladimir; Adamyan, Leila; Sukhikh, Gennady

2018-02-01

Recent research revealed that tissue spray mass spectrometry enables rapid molecular profiling of biological tissues, which is of great importance for the search of disease biomarkers as well as for online surgery control. However, the payback for the high speed of analysis in tissue spray analysis is the generally lower chemical sensitivity compared with the traditional approach based on the offline chemical extraction and electrospray ionization mass spectrometry detection. In this study, high resolution mass spectrometry analysis of endometrium tissues of different localizations obtained using direct tissue spray mass spectrometry in positive ion mode is compared with the results of electrospray ionization analysis of lipid extracts. Identified features in both cases belong to three lipid classes: phosphatidylcholines, phosphoethanolamines, and sphingomyelins. Lipids coverage is validated by hydrophilic interaction liquid chromatography with mass spectrometry of lipid extracts. Multivariate analysis of data from both methods reveals satisfactory differentiation of eutopic and ectopic endometrium tissues. Overall, our results indicate that the chemical information provided by tissue spray ionization is sufficient to allow differentiation of endometrial tissues by localization with similar reliability but higher speed than in the traditional approach relying on offline extraction.

Recent advances in matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) for in situ analysis of endogenous molecules in plants.

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Qin, Liang; Zhang, Yawen; Liu, Yaqin; He, Huixin; Han, Manman; Li, Yanyan; Zeng, Maomao; Wang, Xiaodong

2018-04-17

Mass spectrometry imaging (MSI) as a label-free and powerful imaging technique enables in situ evaluation of a tissue metabolome and/or proteome, becoming increasingly popular in the detection of plant endogenous molecules. The characterization of structure and spatial information of endogenous molecules in plants are both very important aspects to better understand the physiological mechanism of plant organism. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a commonly-used tissue imaging technique, which requires matrix to assist in situ detection of a variety of molecules on the surface of a tissue section. In previous studies, MALDI-MSI was mostly used for the detection of molecules from animal tissue sections, compared to plant samples due to cell structural limitations, such as plant cuticles, epicuticular waxes, and cell walls. Despite the enormous progress that has been made in tissue imaging, there is still a challenge for MALDI-MSI suitable for the imaging of endogenous compounds in plants. This review summarises the recent advances in MALDI-MSI, focusing on the application of in situ detection of endogenous molecules in different plant organs, i.e. root, stem, leaf, flower, fruit, and seed. Further improvements on instrumentation sensitivity, matrix selection, image processing and sample preparation will expand the application of MALDI-MSI in plant research. Copyright © 2018 John Wiley & Sons, Ltd.

Spatial distribution of theobromine--a low MW drug--in tissues via matrix-free NALDI-MS imaging.

Science.gov (United States)

Tata, Alessandra; Montemurro, Chiara; Porcari, Andreia M; Silva, Kamila C; Lopes de Faria, José B; Eberlin, Marcos N

2014-09-01

The ability of nano-assisted laser desorption-ionization mass spectrometry imaging (NALDI-IMS) to provide selective chemical monitoring with appropriate spatial distribution of a low molecular drug in a biological tissue was investigated. NALDI-IMS is a matrix-free laser desorption ionization (LDI) protocol based on imprinting of tissue constituents on a nanostructured surface. Using the accumulation of theobromine in rat kidney as a model, NALDI-IMS was found to provide well-resolved images of the special distribution of this low molecular weight (MW) drug in tissue. Copyright © 2014 John Wiley & Sons, Ltd.

Utility of imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization (MALDI) on an ion trap mass spectrometer in the analysis of drugs and metabolites in biological tissues.

Science.gov (United States)

Drexler, Dieter M; Garrett, Timothy J; Cantone, Joseph L; Diters, Richard W; Mitroka, James G; Prieto Conaway, Maria C; Adams, Stephen P; Yost, Richard A; Sanders, Mark

2007-01-01

The properties and potential liabilities of drug candidate are investigated in detailed ADME assays and in toxicity studies, where findings are placed in context of exposure to dosed drug and metabolites. The complex nature of biological samples may necessitate work-up procedures prior to high performance liquid chromatography-mass spectrometric (HPLC-MS) analysis of endogenous or xenobiotic compounds. This concept can readily be applied to biological fluids such as blood or urine, but in localized samples such as organs and tissues potentially important spatial, thus anatomical, information is lost during sample preparation as the result of homogenization and extraction procedures. However, the localization of test article or spatial identification of metabolites may be critical to the understanding of the mechanism of target-organ toxicity and its relevance to clinical safety. Tissue imaging mass spectrometry (IMS) by matrix-assisted laser desorption ionization (MALDI) and ion trap mass spectrometry (MS) with higher order mass spectrometric scanning functions was utilized for localization of dosed drug or metabolite in tissue. Laser capture microscopy (LCM) was used to obtain related samples from tissue for analyses by standard MALDI-MS and HPLC-MS. In a toxicology study, rats were administered with a high dosage of a prodrug for 2 weeks. Birefringent microcrystalline material (10-25 microm) was observed in histopathologic formalin-fixed tissue samples. Direct analysis by IMS provided the identity of material in the microcrystals as circulating active drug while maintaining spatial orientation. Complementary data from visual cross-polarized light microscopy as well as standard MALDI-MS and HPLC-MS experiments on LCM samples validated the qualitative results obtained by IMS. Furthermore, the HPLC-MS analysis on the LCM samples afforded a semi-quantitative assessment of the crystalline material in the tissue samples. IMS by MALDI ion trap MS proved sensitive

Molecular imaging of lipids in cells and tissues

Science.gov (United States)

Borner, Katrin; Malmberg, Per; Mansson, Jan-Eric; Nygren, Hakan

2007-02-01

The distribution pattern of lipid species in biological tissues was analyzed with imaging mass spectrometry (TOF-SIMS; time-of-flight secondary ion mass spectrometry). The first application shows distribution of a glycosphingolipid, the galactosylceramide-sulfate (sulfatide) with different hydrocarbon chain lengths and the fatty acids palmitate and oleate in rat cerebellum. Sulfatides were seen localized in regions suggested as paranodal areas of rat cerebellar white matter as well as in the granular layer, with highest concentrations at the borders of the white matter. Different distribution patterns could be shown for the fatty acid C16:0 palmitate and C18:1 oleate in rat cerebellum, which seem to origin partly from the hydrocarbon chains of phosphatidylcholine. Results were shown for two different tissue preparation methods, which were plunge-freezing and cryostat sectioning as well as high-pressure freezing, freeze-fracturing and freeze-drying. The second application shows TOF-SIMS analysis on a biological trial of choleratoxin treatment in mouse intestine. The effect of cholera toxin on lipids in the intestinal epithelium was shown by comparing control and cholera toxin treated mouse intestine samples. A significant increase of the cholesterol concentration was seen after treatment. Cholesterol was mainly localized to the brush border of enterocytes of the intestinal villi, which could be explained by the presence of cholesterol-rich lipid rafts present on the microvilli or by relations to cholesterol uptake. After cholera toxin exposure, cholesterol was seen increased in the nuclei of enterocytes and apparently in the interstitium of the villi. We find that imaging TOF-SIMS is a powerful tool for studies of lipid distributions in cells and tissues, enabling the elucidation of their role in cell function and biology.

MALDI TOF imaging mass spectrometry in clinical pathology: a valuable tool for cancer diagnostics (review).

Science.gov (United States)

Kriegsmann, Jörg; Kriegsmann, Mark; Casadonte, Rita

2015-03-01

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) imaging mass spectrometry (IMS) is an evolving technique in cancer diagnostics and combines the advantages of mass spectrometry (proteomics), detection of numerous molecules, and spatial resolution in histological tissue sections and cytological preparations. This method allows the detection of proteins, peptides, lipids, carbohydrates or glycoconjugates and small molecules.Formalin-fixed paraffin-embedded tissue can also be investigated by IMS, thus, this method seems to be an ideal tool for cancer diagnostics and biomarker discovery. It may add information to the identification of tumor margins and tumor heterogeneity. The technique allows tumor typing, especially identification of the tumor of origin in metastatic tissue, as well as grading and may provide prognostic information. IMS is a valuable method for the identification of biomarkers and can complement histology, immunohistology and molecular pathology in various fields of histopathological diagnostics, especially with regard to identification and grading of tumors.

Imaging Mass Spectrometry in Neuroscience

Science.gov (United States)

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

Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and mass spectrometry

International Nuclear Information System (INIS)

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

2013-01-01

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

Metabolomic imaging of prostate cancer with magnetic resonance spectroscopy and mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Spur, Eva-Margarete [Massachusetts General Hospital, Harvard Medical School, Department of Pathology, Boston, MA (United States); Massachusetts General Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States); Charite Universitaetsmedizin, Berlin (Germany); Decelle, Emily A.; Cheng, Leo L. [Massachusetts General Hospital, Harvard Medical School, Department of Pathology, Boston, MA (United States); Massachusetts General Hospital, Harvard Medical School, Department of Radiology, Boston, MA (United States)

2013-07-15

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

ToF-SIMS Parallel Imaging MS/MS of Lipid Species in Thin Tissue Sections.

Science.gov (United States)

Bruinen, Anne Lisa; Fisher, Gregory L; Heeren, Ron M A

2017-01-01

Unambiguous identification of detected species is essential in complex biomedical samples. To date, there are not many mass spectrometry imaging techniques that can provide both high spatial resolution and identification capabilities. A new and patented imaging tandem mass spectrometer, exploiting the unique characteristics of the nanoTOF II (Physical Electronics, USA) TOF-SIMS TRIFT instrument, was developed to address this.Tandem mass spectrometry is based on the selection of precursor ions from the full secondary ion spectrum (MS 1 ), followed by energetic activation and fragmentation, and collection of the fragment ions to obtain a tandem MS spectrum (MS 2 ). The PHI NanoTOF II mass spectrometer is equipped with a high-energy collision induced dissociation (CID) fragmentation cell as well as a second time-of-flight analyzer developed for simultaneous ToF-SIMS and tandem MS imaging experiments.We describe here the results of a ToF-SIMS imaging experiment on a thin tissue section of an infected zebrafish as a model organism for tuberculosis. The focus is on the obtained ion distribution plot of a fatty acid as well as its identification by tandem mass spectrometry.

Proteomic Mass Spectrometry Imaging for Skin Cancer Diagnosis.

Science.gov (United States)

Lazova, Rossitza; Seeley, Erin H

2017-10-01

Mass spectrometry imaging can be successfully used for skin cancer diagnosis, particularly for the diagnosis of challenging melanocytic lesions. This method analyzes proteins within benign and malignant melanocytic tumor cells and, based on their differences, which constitute a unique molecular signature of 5 to 20 proteins, can render a diagnosis of benign nevus versus malignant melanoma. Mass spectrometry imaging may assist in the differentiation between metastases and nevi as well as between proliferative nodules in nevi and melanoma arising in a nevus. In the difficult area of atypical Spitzoid neoplasms, mass spectrometry diagnosis can predict clinical outcome better than histopathology. Copyright © 2017 Elsevier Inc. All rights reserved.

Cryo-sectioning of mice for whole-body imaging of drugs and metabolites with desorption electrospray ionization mass spectrometry imaging - a simplified approach

DEFF Research Database (Denmark)

Okutan, Seda; Hansen, Harald S; Janfelt, Christian

2016-01-01

A method is presented for whole-body imaging of drugs and metabolites in mice with desorption electrospray ionization mass spectrometry imaging (DESI-MSI). Unlike most previous approaches to whole-body imaging which are based on cryo-sectioning using a cryo-macrotome, the presented approach...... to simple, sensitive and highly selective whole-body imaging in drug distribution and metabolism studies....... is based on use of the cryo-microtome which is found in any histology lab. The tissue sections are collected on tape which is analyzed directly by DESI-MSI. The method is demonstrated on mice which have been dosed intraperitoneally with the antidepressive drug amitriptyline. By combining full...

Imaging and differentiation of mouse embryo tissues by ToF-SIMS

Energy Technology Data Exchange (ETDEWEB)

Wu, L; Lu, X; Kulp, K; Knize, M; Berman, E; Nelson, E; Felton, J; Wu, K J

2006-06-16

Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) equipped with a gold ion gun was used to image mouse embryos and differentiate tissue types (brain, spinal cord, skull, rib, heart and liver). Embryos were paraffin-embedded and then de-paraffinized. The robustness and repeatability of the method was determined by analyzing nine tissue slices from three different embryos over a period of several weeks. Using Principal Component Analysis (PCA) to reduce the spectral data generated by ToF-SIMS, histopathologically identified tissue types of the mouse embryos can be differentiated based on the characteristic differences in their mass spectra. These results demonstrate the ability of ToF-SIMS to determine subtle chemical differences even in fixed histological specimens.

Scores for standardization of on-tissue digestion of formalin-fixed paraffin-embedded tissue in MALDI-MS imaging.

Science.gov (United States)

Erich, Katrin; Sammour, Denis A; Marx, Alexander; Hopf, Carsten

2017-07-01

On-slide digestion of formalin-fixed and paraffin-embedded human biopsy tissue followed by mass spectrometry imaging of resulting peptides may have the potential to become an additional analytical modality in future ePathology. Multiple workflows have been described for dewaxing, antigen retrieval, digestion and imaging in the past decade. However, little is known about suitable statistical scores for method comparison and systematic workflow standardization required for development of processes that would be robust enough to be compatible with clinical routine. To define scores for homogeneity of tissue processing and imaging as well as inter-day repeatability for five different processing methods, we used human liver and gastrointestinal stromal tumor tissue, both judged by an expert pathologist to be >98% histologically homogeneous. For mean spectra-based as well as pixel-wise data analysis, we propose the coefficient of determination R 2 , the natural fold-change (natFC) value and the digest efficiency DE% as readily accessible scores. Moreover, we introduce two scores derived from principal component analysis, the variance of the mean absolute deviation, MAD, and the interclass overlap, J overlap , as computational scores that may help to avoid user bias during future workflow development. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

Transmission Geometry Laser Ablation into a Non-Contact Liquid Vortex Capture Probe for Mass Spectrometry Imaging

Energy Technology Data Exchange (ETDEWEB)

Ovchinnikova, Olga S [ORNL; Bhandari, Deepak [ORNL; Lorenz, Matthias [ORNL; Van Berkel, Gary J [ORNL

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

Silver nanostructures in laser desorption/ionization mass spectrometry and mass spectrometry imaging.

Science.gov (United States)

Sekuła, Justyna; Nizioł, Joanna; Rode, Wojciech; Ruman, Tomasz

2015-09-21

Silver nanoparticles have been successfully applied as a matrix replacement for the laser desorption/ionization time-of-flight mass spectrometry (LDI-ToF-MS). Nanoparticles, producing spectra with highly reduced chemical background in the low m/z region, are perfectly suited for low-molecular weight compound analysis and imaging. Silver nanoparticles (AgNPs) can efficiently absorb ultraviolet laser radiation, transfer energy to the analyte and promote analyte desorption, but also constitute a source of silver ions suitable for analyte cationisation. This review provides an overview of the literature on silver nanomaterials as non-conventional desorption and ionization promoters in LDI-MS and mass spectrometry imaging.

Imaging mass spectrometry identifies prognostic ganglioside species in rodent intracranial transplants of glioma and medulloblastoma.

Directory of Open Access Journals (Sweden)

Leonardo Ermini

Full Text Available Matrix-assisted laser desorption ionization (MALDI imaging mass spectrometry (MALDI-MSI allows us to investigate the distribution of lipid molecules within tissues. We used MALDI-MSI to identify prognostic gangliosides in tissue sections of rat intracranial allografts of rat glioma and mouse intracranial xenografts of human medulloblastoma. In the healthy adult rodent brain, GM1 and GD1 were the main types of glycolipids. Both gangliosides were absent in both intracranial transplants. The ganglioside GM3 was not present in the healthy adult brain but was highly expressed in rat glioma allografts. In combination with tandem mass spectrometry GM3 (d18:1/C24:0 was identified as the most abundant ganglioside species in the glioma allotransplant. By contrast, mouse xenografts of human medulloblastoma were characterized by prominent expression of the ganglioside GM2 (d18:0/C18:0. Together, these data demonstrate that tissue-based MALDI-MSI of gangliosides is able to discriminate between different brain tumors and may be a useful clinical tool for their classification and grading.

Tissue Harmonic Synthetic Aperture Imaging

DEFF Research Database (Denmark)

Rasmussen, Joachim

The main purpose of this PhD project is to develop an ultrasonic method for tissue harmonic synthetic aperture imaging. The motivation is to advance the field of synthetic aperture imaging in ultrasound, which has shown great potentials in the clinic. Suggestions for synthetic aperture tissue...... system complexity compared to conventional synthetic aperture techniques. In this project, SASB is sought combined with a pulse inversion technique for 2nd harmonic tissue harmonic imaging. The advantages in tissue harmonic imaging (THI) are expected to further improve the image quality of SASB...

Monitoring Toxic Ionic Liquids in Zebrafish ( Danio rerio) with Desorption Electrospray Ionization Mass Spectrometry Imaging (DESI-MSI)

Science.gov (United States)

Perez, Consuelo J.; Tata, Alessandra; de Campos, Michel L.; Peng, Chun; Ifa, Demian R.

2017-06-01

Ambient mass spectrometry imaging has become an increasingly powerful technique for the direct analysis of biological tissues in the open environment with minimal sample preparation and fast analysis times. In this study, we introduce desorption electrospray ionization mass spectrometry imaging (DESI-MSI) as a novel, rapid, and sensitive approach to localize the accumulation of a mildly toxic ionic liquid (IL), AMMOENG 130 in zebrafish ( Danio rerio). The work demonstrates that DESI-MSI has the potential to rapidly monitor the accumulation of IL pollutants in aquatic organisms. AMMOENG 130 is a quaternary ammonium-based IL reported to be broadly used as a surfactant in commercialized detergents. It is known to exhibit acute toxicity to zebrafish causing extensive damage to gill secondary lamellae and increasing membrane permeability. Zebrafish were exposed to the IL in a static 96-h exposure study in concentrations near the LC50 of 1.25, 2.5, and 5.0 mg/L. DESI-MS analysis of zebrafish gills demonstrated the appearance of a dealkylated AMMOENG 130 metabolite in the lowest concentration of exposure identified by a high resolution hybrid LTQ-Orbitrap mass spectrometer as the trimethylstearylammonium ion, [C21H46N]+. With DESI-MSI, the accumulation of AMMOENG 130 and its dealkylated metabolite in zebrafish tissue was found in the nervous and respiratory systems. AMMOENG 130 and the metabolite were capable of penetrating the blood brain barrier of the fish with significant accumulation in the brain. Hence, we report for the first time the simultaneous characterization, distribution, and metabolism of a toxic IL in whole body zebrafish analyzed by DESI-MSI. This ambient mass spectrometry imaging technique shows great promise for the direct analysis of biological tissues to qualitatively monitor foreign, toxic, and persistent compounds in aquatic organisms from the environment. [Figure not available: see fulltext.

Absorption Mode FT-ICR Mass Spectrometry Imaging

Energy Technology Data Exchange (ETDEWEB)

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.

Development of matrix-assisted laser desorption ionization-mass spectrometry imaging (MALDI-MSI) for plant metabolite analysis

Energy Technology Data Exchange (ETDEWEB)

Korte, Andrew R [Iowa State Univ., Ames, IA (United States)

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.

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

Science.gov (United States)

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 .

Top-Down and Bottom-Up Identification of Proteins by Liquid Extraction Surface Analysis Mass Spectrometry of Healthy and Diseased Human Liver Tissue

Science.gov (United States)

Sarsby, Joscelyn; Martin, Nicholas J.; Lalor, Patricia F.; Bunch, Josephine; Cooper, Helen J.

2014-09-01

Liquid extraction surface analysis mass spectrometry (LESA MS) has the potential to become a useful tool in the spatially-resolved profiling of proteins in substrates. Here, the approach has been applied to the analysis of thin tissue sections from human liver. The aim was to determine whether LESA MS was a suitable approach for the detection of protein biomarkers of nonalcoholic liver disease (nonalcoholic steatohepatitis, NASH), with a view to the eventual development of LESA MS for imaging NASH pathology. Two approaches were considered. In the first, endogenous proteins were extracted from liver tissue sections by LESA, subjected to automated trypsin digestion, and the resulting peptide mixture was analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS) (bottom-up approach). In the second (top-down approach), endogenous proteins were extracted by LESA, and analyzed intact. Selected protein ions were subjected to collision-induced dissociation (CID) and/or electron transfer dissociation (ETD) mass spectrometry. The bottom-up approach resulted in the identification of over 500 proteins; however identification of key protein biomarkers, liver fatty acid binding protein (FABP1), and its variant (Thr→Ala, position 94), was unreliable and irreproducible. Top-down LESA MS analysis of healthy and diseased liver tissue revealed peaks corresponding to multiple (~15-25) proteins. MS/MS of four of these proteins identified them as FABP1, its variant, α-hemoglobin, and 10 kDa heat shock protein. The reliable identification of FABP1 and its variant by top-down LESA MS suggests that the approach may be suitable for imaging NASH pathology in sections from liver biopsies.

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

Science.gov (United States)

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.

Soft tissue tumors - imaging methods

International Nuclear Information System (INIS)

Arlart, I.P.

1985-01-01

Soft Tissue Tumors - Imaging Methods: Imaging methods play an important diagnostic role in soft tissue tumors concerning a preoperative evaluation of localization, size, topographic relationship, dignity, and metastatic disease. The present paper gives an overview about diagnostic methods available today such as ultrasound, thermography, roentgenographic plain films and xeroradiography, radionuclide methods, computed tomography, lymphography, angiography, and magnetic resonance imaging. Besides sonography particularly computed tomography has the most important diagnostic value in soft tissue tumors. The application of a recently developed method, the magnetic resonance imaging, cannot yet be assessed in its significance. (orig.) [de

Murine cutaneous leishmaniasis investigated by MALDI mass spectrometry imaging.

Science.gov (United States)

Negrão, Fernanda; de O Rocha, Daniele F; Jaeeger, Caroline F; Rocha, Francisca J S; Eberlin, Marcos N; Giorgio, Selma

2017-09-26

Imaging mass spectrometry (IMS) is recognized as a powerful tool to investigate the spatial distribution of untargeted or targeted molecules of a wide variety of samples including tissue sections. Leishmania is a protozoan parasite that causes different clinical manifestations in mammalian hosts. Leishmaniasis is a major public health risk in different continents and represents one of the most important neglected diseases. Cutaneous lesions from mice experimentally infected with Leishmania spp. were investigated by matrix-assisted laser desorption ionization MS using the SCiLS Lab software for statistical analysis. Being applied to cutaneous leishmaniasis (CL) for the first time, MALDI-IMS was used to search for peptides and low molecular weight proteins (2-10 kDa) as candidates for potential biomarkers. Footpad sections of Balb/c mice infected with (i) Leishmania amazonensis or (ii) Leishmania major were imaged. The comparison between healthy and infected skin highlighted a set of twelve possible biomarker proteins for L. amazonenis and four proteins for L. major. Further characterization of these proteins could reveal how these proteins act in pathology progression and confirm their values as biomarkers.

Development of stereotactic mass spectrometry for brain tumor surgery.

Science.gov (United States)

Agar, Nathalie Y R; Golby, Alexandra J; Ligon, Keith L; Norton, Isaiah; Mohan, Vandana; Wiseman, Justin M; Tannenbaum, Allen; Jolesz, Ferenc A

2011-02-01

Surgery remains the first and most important treatment modality for the majority of solid tumors. Across a range of brain tumor types and grades, postoperative residual tumor has a great impact on prognosis. The principal challenge and objective of neurosurgical intervention is therefore to maximize tumor resection while minimizing the potential for neurological deficit by preserving critical tissue. To introduce the integration of desorption electrospray ionization mass spectrometry into surgery for in vivo molecular tissue characterization and intraoperative definition of tumor boundaries without systemic injection of contrast agents. Using a frameless stereotactic sampling approach and by integrating a 3-dimensional navigation system with an ultrasonic surgical probe, we obtained image-registered surgical specimens. The samples were analyzed with ambient desorption/ionization mass spectrometry and validated against standard histopathology. This new approach will enable neurosurgeons to detect tumor infiltration of the normal brain intraoperatively with mass spectrometry and to obtain spatially resolved molecular tissue characterization without any exogenous agent and with high sensitivity and specificity. Proof of concept is presented in using mass spectrometry intraoperatively for real-time measurement of molecular structure and using that tissue characterization method to detect tumor boundaries. Multiple sampling sites within the tumor mass were defined for a patient with a recurrent left frontal oligodendroglioma, World Health Organization grade II with chromosome 1p/19q codeletion, and mass spectrometry data indicated a correlation between lipid constitution and tumor cell prevalence. The mass spectrometry measurements reflect a complex molecular structure and are integrated with frameless stereotaxy and imaging, providing 3-dimensional molecular imaging without systemic injection of any agents, which can be implemented for surgical margins delineation of

Laser desorption/ionization mass spectrometry for direct profiling and imaging of small molecules from raw biological materials

Energy Technology Data Exchange (ETDEWEB)

Cha, Sangwon [Iowa State Univ., Ames, IA (United States)

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.

Boron concentration measurements by alpha spectrometry and quantitative neutron autoradiography in cells and tissues treated with different boronated formulations and administration protocols

International Nuclear Information System (INIS)

Bortolussi, Silva; Ciani, Laura; Postuma, Ian; Protti, Nicoletta; Luca Reversi,; Bruschi, Piero; Ferrari, Cinzia; Cansolino, Laura; Panza, Luigi; Ristori, Sandra; Altieri, Saverio

2014-01-01

The possibility to measure boron concentration with high precision in tissues that will be irradiated represents a fundamental step for a safe and effective BNCT treatment. In Pavia, two techniques have been used for this purpose, a quantitative method based on charged particles spectrometry and a boron biodistribution imaging based on neutron autoradiography. A quantitative method to determine boron concentration by neutron autoradiography has been recently set-up and calibrated for the measurement of biological samples, both solid and liquid, in the frame of the feasibility study of BNCT. This technique was calibrated and the obtained results were cross checked with those of α spectrometry, in order to validate them. The comparisons were performed using tissues taken form animals treated with different boron administration protocols. Subsequently the quantitative neutron autoradiography was employed to measure osteosarcoma cell samples treated with BPA and with new boronated formulations. - Highlights: • A method for 10B measurements in samples based on neutron autoradiography was developed. • The results were compared with those of alpha spectrometry applied on tissue and cell samples. • Boronated liposomes were developed and administered to osteosarcoma cell cultures. • Neutron autoradiography was employed to measure boron concentration due to liposomes. • Liposomes were proved to be more effective in concentrating boron in cells than BPA

Tissue imaging with a stigmatic mass microscope using laser desorption/ionization

Science.gov (United States)

Awazu, Kunio; Hazama, Hisanao; Hamanaka, Tomonori; Aoki, Jun; Toyoda, Michisato; Naito, Yasuhide

2012-03-01

A novel stigmatic mass microscope using laser desorption/ionization and a multi-turn time-of-flight mass spectrometer, MULTUM-IMG, has been developed. Stigmatic ion images of crystal violet masked by a fine square mesh grid with a 12.7 μm pitch were clearly observed, and the estimated spatial resolution was about 3 μm in the linear mode with a 20-fold ion optical magnification. Tissue sections of a brain and eyes of a mouse stained with crystal violet and methylene blue were observed in the linear mode, and the stigmatic total ion images of crystal violet and methylene blue agreed well with the optical photomicrograph of the same sections. Especially, the fine structure in the cornea tissue was clearly observed with a spatial resolution in the range of micrometers. Although the total measurement time of the stigmatic ion image for the whole-eye section was about 59 minutes using a laser with a 10 Hz repetition rate, the measurement time could be reduced to about 35 s using a laser with a 1 kHz repetition rate and automation of measurements. The stigmatic mass microscope developed in this research should be suitable for high-spatial resolution and high-throughput imaging mass spectrometry for pathology, pharmacokinetics, and so on.

Imaging of musculoskeletal soft tissue infections

Energy Technology Data Exchange (ETDEWEB)

Turecki, Marcin B.; Taljanovic, Mihra S.; Holden, Dean A.; Hunter, Tim B.; Rogers, Lee F. [University of Arizona HSC, Department of Radiology, Tucson, AZ (United States); Stubbs, Alana Y. [Southern Arizona VA Health Care System, Department of Radiology, Tucson, AZ (United States); Graham, Anna R. [University of Arizona HSC, Department of Pathology, Tucson, AZ (United States)

2010-10-15

Prompt and appropriate imaging work-up of the various musculoskeletal soft tissue infections aids early diagnosis and treatment and decreases the risk of complications resulting from misdiagnosis or delayed diagnosis. The signs and symptoms of musculoskeletal soft tissue infections can be nonspecific, making it clinically difficult to distinguish between disease processes and the extent of disease. Magnetic resonance imaging (MRI) is the imaging modality of choice in the evaluation of soft tissue infections. Computed tomography (CT), ultrasound, radiography and nuclear medicine studies are considered ancillary. This manuscript illustrates representative images of superficial and deep soft tissue infections such as infectious cellulitis, superficial and deep fasciitis, including the necrotizing fasciitis, pyomyositis/soft tissue abscess, septic bursitis and tenosynovitis on different imaging modalities, with emphasis on MRI. Typical histopathologic findings of soft tissue infections are also presented. The imaging approach described in the manuscript is based on relevant literature and authors' personal experience and everyday practice. (orig.)

Imaging of musculoskeletal soft tissue infections

International Nuclear Information System (INIS)

Turecki, Marcin B.; Taljanovic, Mihra S.; Holden, Dean A.; Hunter, Tim B.; Rogers, Lee F.; Stubbs, Alana Y.; Graham, Anna R.

2010-01-01

Prompt and appropriate imaging work-up of the various musculoskeletal soft tissue infections aids early diagnosis and treatment and decreases the risk of complications resulting from misdiagnosis or delayed diagnosis. The signs and symptoms of musculoskeletal soft tissue infections can be nonspecific, making it clinically difficult to distinguish between disease processes and the extent of disease. Magnetic resonance imaging (MRI) is the imaging modality of choice in the evaluation of soft tissue infections. Computed tomography (CT), ultrasound, radiography and nuclear medicine studies are considered ancillary. This manuscript illustrates representative images of superficial and deep soft tissue infections such as infectious cellulitis, superficial and deep fasciitis, including the necrotizing fasciitis, pyomyositis/soft tissue abscess, septic bursitis and tenosynovitis on different imaging modalities, with emphasis on MRI. Typical histopathologic findings of soft tissue infections are also presented. The imaging approach described in the manuscript is based on relevant literature and authors' personal experience and everyday practice. (orig.)

Automated MALDI Matrix Coating System for Multiple Tissue Samples for Imaging Mass Spectrometry

Science.gov (United States)

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.

Quantitating subcellular metabolism with multi-isotope imaging mass spectrometry

Science.gov (United States)

Steinhauser, Matthew L.; Bailey, Andrew; Senyo, Samuel E.; Guillermier, Christelle; Perlstein, Todd S.; Gould, Alex P.; Lee, Richard T.; Lechene, Claude P.

2011-01-01

Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter1,2 but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with sub-micron resolution3,4. Here we apply MIMS to diverse organisms, including Drosophila, mice, and humans. We test the “immortal strand hypothesis,” which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labeling mice with 15N-thymidine from gestation through post-natal week 8, we find no 15N label retention by dividing small intestinal crypt cells after 4wk chase. In adult mice administered 15N-thymidine pulse-chase, we find that proliferating crypt cells dilute label consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human hematopoietic system. These studies show that MIMS provides high-resolution quantitation of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research. PMID:22246326

Identification and localization of trauma-related biomarkers using matrix assisted laser desorption/ionization imaging mass spectrometry

Science.gov (United States)

Jones, Kirstin; Reilly, Matthew A.; Glickman, Randolph D.

2017-02-01

Current treatments for ocular and optic nerve trauma are largely ineffective and may have adverse side effects; therefore, new approaches are needed to understand trauma mechanisms. Identification of trauma-related biomarkers may yield insights into the molecular aspects of tissue trauma that can contribute to the development of better diagnostics and treatments. The conventional approach for protein biomarker measurement largely relies on immunoaffinity methods that typically can only be applied to analytes for which antibodies or other targeting means are available. Matrix assisted laser-assisted desorption/ionization imaging mass spectrometry (MALDI-IMS) is a specialized application of mass spectrometry that not only is well suited to the discovery of novel or unanticipated biomarkers, but also provides information about the spatial localization of biomarkers in tissue. We have been using MALDI-IMS to find traumarelated protein biomarkers in retina and optic nerve tissue from animal models subjected to ocular injury produced by either blast overpressure or mechanical torsion. Work to date by our group, using MALDI-IMS, found that the pattern of protein expression is modified in the injured ocular tissue as soon as 24 hr post-injury, compared to controls. Specific proteins may be up- or down-regulated by trauma, suggesting different tissue responses to a given injury. Ongoing work is directed at identifying the proteins affected and mapping their expression in the ocular tissue, anticipating that systematic analysis can be used to identify targets for prospective therapies for ocular trauma.

MALDI-Imaging Mass Spectrometry of Ochratoxin A and Fumonisins in Mold-Infected Food.

Science.gov (United States)

Hickert, Sebastian; Cramer, Benedikt; Letzel, Matthias C; Humpf, Hans-Ulrich

2016-09-06

Mycotoxins are toxic secondary metabolites produced by various fungi. Their distribution within contaminated material is of high interest to obtain insight into infection mechanisms and the possibility of reducing contamination during food processing. Various vegetable foodstuffs were infected with fungi of the genera Fusarium and Aspergillus. The localization of the produced mycotoxins was studied by matrix assisted laser desorption ionization time of flight imaging mass spectrometry (MALDI-MSI) of cryosections obtained from infected material. The results were confirmed by HPLC-electrospray ionization triple quadrupole mass spectrometry (HPLC/MS/MS). The mycotoxins ochratoxin A (OTA) and fumonisins of the B- and C-series (FB 1 , FB 2 , FB 3 , FB 4 , FC 2/3 , and FC 4 ) as well as partially hydrolyzed fumonisins (pHFB 1 , pHFB 2 , pHFB 3 , pHFC 1 , and pHFC 2/3 ) could successfully be detected by MALDI-IMS in mold-infested foodstuffs. The toxins are distributed differently in the material: OTA is co-localized with visible fungal spoilage while fumonisins could be detected throughout the whole sample. This work shows the applicability of MALDI-Imaging Mass Spectrometry (MALDI-MSI) to mycotoxin analysis. It has been demonstrated that the analyzed mycotoxins are differently distributed within moldy foodstuffs. These findings show the potential of MALDI-MSI for the localization of these hazardous compounds in various plant tissues. This article is protected by copyright. All rights reserved.

[Application of Imaging Mass Spectrometry for Drug Discovery].

Science.gov (United States)

Hayasaka, Takahiro

2016-01-01

Imaging mass spectrometry (IMS) can reveal the distribution of biomolecules on tissue sections. In this process, the biomolecules are directly ionized within tissue sections using matrix-assisted laser desorption/ionization, and then their distribution is visualized by pseudo-color based on the relative signal intensity. The biomolecules, such as fatty acids, phospholipids, glycolipids, peptides, proteins, and neurotransmitters, have been analyzed at a spatial resolution of 5 μm. A special instrument for IMS analysis was developed by Shimadzu. The IMS analysis does not require the labeling of biomolecules and is capable of analyzing all the ionized biomolecules. Interest in this method has expanded to many research fields, including biology, agriculture, medicine, and pharmacology. The technique is especially relevant to the drug discovery process. As practiced currently, drug discovery is expensive and time consuming, requiring the preparation of probes for each drug and its metabolites, followed by systematic probe tracking in animal models. The IMS technique is expected to overcome these drawbacks by revealing the distribution of drugs and their metabolites using only a single analysis. In this symposium, I introduced the methodology and applications of IMS and discussed the feasibility of its application to drug discovery in the near future.

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

Science.gov (United States)

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.

Tissue spray ionization mass spectrometry for rapid recognition of human lung squamous cell carcinoma

Science.gov (United States)

Wei, Yiping; Chen, Liru; Zhou, Wei; Chingin, Konstantin; Ouyang, Yongzhong; Zhu, Tenggao; Wen, Hua; Ding, Jianhua; Xu, Jianjun; Chen, Huanwen

2015-05-01

Tissue spray ionization mass spectrometry (TSI-MS) directly on small tissue samples has been shown to provide highly specific molecular information. In this study, we apply this method to the analysis of 38 pairs of human lung squamous cell carcinoma tissue (cancer) and adjacent normal lung tissue (normal). The main components of pulmonary surfactants, dipalmitoyl phosphatidylcholine (DPPC, m/z 757.47), phosphatidylcholine (POPC, m/z 782.52), oleoyl phosphatidylcholine (DOPC, m/z 808.49), and arachidonic acid stearoyl phosphatidylcholine (SAPC, m/z 832.43), were identified using high-resolution tandem mass spectrometry. Monte Carlo sampling partial least squares linear discriminant analysis (PLS-LDA) was used to distinguish full-mass-range mass spectra of cancer samples from the mass spectra of normal tissues. With 5 principal components and 30 - 40 Monte Carlo samplings, the accuracy of cancer identification in matched tissue samples reached 94.42%. Classification of a tissue sample required less than 1 min, which is much faster than the analysis of frozen sections. The rapid, in situ diagnosis with minimal sample consumption provided by TSI-MS is advantageous for surgeons. TSI-MS allows them to make more informed decisions during surgery.

Identification and High-Resolution Imaging of α-Tocopherol from Human Cells to Whole Animals by TOF-SIMS Tandem Mass Spectrometry

Science.gov (United States)

Bruinen, Anne L.; Fisher, Gregory L.; Balez, Rachelle; van der Sar, Astrid M.; Ooi, Lezanne; Heeren, Ron M. A.

2018-06-01

A unique method for identification of biomolecular components in different biological specimens, while preserving the capability for high speed 2D and 3D molecular imaging, is employed to investigate cellular response to oxidative stress. The employed method enables observing the distribution of the antioxidant α-tocopherol and other molecules in cellular structures via time-of-flight secondary ion mass spectrometry (TOF-SIMS (MS1)) imaging in parallel with tandem mass spectrometry (MS2) imaging, collected simultaneously. The described method is employed to examine a network formed by neuronal cells differentiated from human induced pluripotent stem cells (iPSCs), a model for investigating human neurons in vitro. The antioxidant α-tocopherol is identified in situ within different cellular layers utilizing a 3D TOF-SIMS tandem MS imaging analysis. As oxidative stress also plays an important role in mediating inflammation, the study was expanded to whole body tissue sections of M. marinum-infected zebrafish, a model organism for tuberculosis. The TOF-SIMS tandem MS imaging results reveal an increased presence of α-tocopherol in response to the pathogen. [Figure not available: see fulltext.

Myofiber metabolic type determination by mass spectrometry imaging

OpenAIRE

Théron, Laetitia; Vénien, Annie; Pujos-Guillot, Estelle; Astruc, Thierry; Chambon, Christophe

2017-01-01

In muscle imaging, myofiber type determination is of great importance to better understand biological mechanisms related to skeletal muscle changes associated with pathologies. However, reference methods (histo-enzymology and immunohistochemistry) require serial-cross sections, and several days from the sampling to the results of image analysis. In this work, a strategy based on MALDI-Mass Spectrometry Imaging was developed as an alternative to the classical methods for myofiber metabolic typ...

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

Science.gov (United States)

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

2016-06-01

MALDI imaging mass spectrometry is a powerful analytical tool enabling the visualization of biomolecules in tissue. However, there are unique challenges associated with protein imaging experiments including the need for higher spatial resolution capabilities, improved image acquisition rates, and better molecular specificity. Here we demonstrate the capabilities of ultra-high speed MALDI-TOF and high mass resolution MALDI FTICR IMS platforms as they relate to these challenges. High spatial resolution MALDI-TOF protein images of rat brain tissue and cystic fibrosis lung tissue were acquired at image acquisition rates >25 pixels/s. Structures as small as 50 μm were spatially resolved and proteins associated with host immune response were observed in cystic fibrosis lung tissue. Ultra-high speed MALDI-TOF enables unique applications including megapixel molecular imaging as demonstrated for lipid analysis of cystic fibrosis lung tissue. Additionally, imaging experiments using MALDI FTICR IMS were shown to produce data with high mass accuracy (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. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Realistic tissue visualization using photoacoustic image

Science.gov (United States)

Cho, Seonghee; Managuli, Ravi; Jeon, Seungwan; Kim, Jeesu; Kim, Chulhong

2018-02-01

Visualization methods are very important in biomedical imaging. As a technology that understands life, biomedical imaging has the unique advantage of providing the most intuitive information in the image. This advantage of biomedical imaging can be greatly improved by choosing a special visualization method. This is more complicated in volumetric data. Volume data has the advantage of containing 3D spatial information. Unfortunately, the data itself cannot directly represent the potential value. Because images are always displayed in 2D space, visualization is the key and creates the real value of volume data. However, image processing of 3D data requires complicated algorithms for visualization and high computational burden. Therefore, specialized algorithms and computing optimization are important issues in volume data. Photoacoustic-imaging is a unique imaging modality that can visualize the optical properties of deep tissue. Because the color of the organism is mainly determined by its light absorbing component, photoacoustic data can provide color information of tissue, which is closer to real tissue color. In this research, we developed realistic tissue visualization using acoustic-resolution photoacoustic volume data. To achieve realistic visualization, we designed specialized color transfer function, which depends on the depth of the tissue from the skin. We used direct ray casting method and processed color during computing shader parameter. In the rendering results, we succeeded in obtaining similar texture results from photoacoustic data. The surface reflected rays were visualized in white, and the reflected color from the deep tissue was visualized red like skin tissue. We also implemented the CUDA algorithm in an OpenGL environment for real-time interactive imaging.

Imaging in cellular and tissue engineering

CERN Document Server

Yu, Hanry

2013-01-01

Details on specific imaging modalities for different cellular and tissue engineering applications are scattered throughout articles and chapters in the literature. Gathering this information into a single reference, Imaging in Cellular and Tissue Engineering presents both the fundamentals and state of the art in imaging methods, approaches, and applications in regenerative medicine. The book underscores the broadening scope of imaging applications in cellular and tissue engineering. It covers a wide range of optical and biological applications, including the repair or replacement of whole tiss

Visualization of metallodrugs in single cells by secondary ion mass spectrometry imaging.

Science.gov (United States)

Wu, Kui; Jia, Feifei; Zheng, Wei; Luo, Qun; Zhao, Yao; Wang, Fuyi

2017-07-01

Secondary ion mass spectrometry, including nanoscale secondary ion mass spectrometry (NanoSIMS) and time-of-flight secondary ion mass spectrometry (ToF-SIMS), has emerged as a powerful tool for biological imaging, especially for single cell imaging. SIMS imaging can provide information on subcellular distribution of endogenous and exogenous chemicals, including metallodrugs, from membrane through to cytoplasm and nucleus without labeling, and with high spatial resolution and chemical specificity. In this mini-review, we summarize recent progress in the field of SIMS imaging, particularly in the characterization of the subcellular distribution of metallodrugs. We anticipate that the SIMS imaging method will be widely applied to visualize subcellular distributions of drugs and drug candidates in single cells, exerting significant influence on early drug evaluation and metabolism in medicinal and pharmaceutical chemistry. Recent progress of SIMS applications in characterizing the subcellular distributions of metallodrugs was summarized.

Quantification of low molecular weight compounds by MALDI imaging mass spectrometry - A tutorial review.

Science.gov (United States)

Rzagalinski, Ignacy; Volmer, Dietrich A

2017-07-01

Matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry imaging (MSI) permits label-free in situ analysis of chemical compounds directly from the surface of two-dimensional biological tissue slices. It links qualitative molecular information of compounds to their spatial coordinates and distribution within the investigated tissue. MALDI-MSI can also provide the quantitative amounts of target compounds in the tissue, if proper calibration techniques are performed. Obviously, as the target molecules are embedded within the biological tissue environment and analysis must be performed at their precise locations, there is no possibility for extensive sample clean-up routines or chromatographic separations as usually performed with homogenized biological materials; ion suppression phenomena therefore become a critical side effect of MALDI-MSI. Absolute quantification by MALDI-MSI should provide an accurate value of the concentration/amount of the compound of interest in relatively small, well-defined region of interest of the examined tissue, ideally in a single pixel. This goal is extremely challenging and will not only depend on the technical possibilities and limitations of the MSI instrument hardware, but equally on the chosen calibration/standardization strategy. These strategies are the main focus of this article and are discussed and contrasted in detail in this tutorial review. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

Mass Spectrometry Imaging of Drugs of Abuse in Hair.

Science.gov (United States)

Flinders, Bryn; Cuypers, Eva; Porta, Tiffany; Varesio, Emmanuel; Hopfgartner, Gérard; Heeren, Ron M A

2017-01-01

Hair testing is a powerful tool routinely used for the detection of drugs of abuse. The analysis of hair is highly advantageous as it can provide prolonged drug detectability versus that in biological fluids and chronological information about drug intake based on the average growth of hair. However, current methodology requires large amounts of hair samples and involves complex time-consuming sample preparation followed by gas or liquid chromatography coupled with mass spectrometry. Mass spectrometry imaging is increasingly being used for the analysis of single hair samples, as it provides more accurate and visual chronological information in single hair samples.Here, two methods for the preparation of single hair samples for mass spectrometry imaging are presented.The first uses an in-house built cutting apparatus to prepare longitudinal sections, the second is a method for embedding and cryo-sectioning hair samples in order to prepare cross-sections all along the hair sample.

Ontology-based, Tissue MicroArray oriented, image centered tissue bank

Directory of Open Access Journals (Sweden)

Viti Federica

2008-04-01

Full Text Available Abstract Background Tissue MicroArray technique is becoming increasingly important in pathology for the validation of experimental data from transcriptomic analysis. This approach produces many images which need to be properly managed, if possible with an infrastructure able to support tissue sharing between institutes. Moreover, the available frameworks oriented to Tissue MicroArray provide good storage for clinical patient, sample treatment and block construction information, but their utility is limited by the lack of data integration with biomolecular information. Results In this work we propose a Tissue MicroArray web oriented system to support researchers in managing bio-samples and, through the use of ontologies, enables tissue sharing aimed at the design of Tissue MicroArray experiments and results evaluation. Indeed, our system provides ontological description both for pre-analysis tissue images and for post-process analysis image results, which is crucial for information exchange. Moreover, working on well-defined terms it is then possible to query web resources for literature articles to integrate both pathology and bioinformatics data. Conclusions Using this system, users associate an ontology-based description to each image uploaded into the database and also integrate results with the ontological description of biosequences identified in every tissue. Moreover, it is possible to integrate the ontological description provided by the user with a full compliant gene ontology definition, enabling statistical studies about correlation between the analyzed pathology and the most commonly related biological processes.

Molecular imaging of cannabis leaf tissue with MeV-SIMS method

Science.gov (United States)

Jenčič, Boštjan; Jeromel, Luka; Ogrinc Potočnik, Nina; Vogel-Mikuš, Katarina; Kovačec, Eva; Regvar, Marjana; Siketić, Zdravko; Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož

2016-03-01

To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

Molecular imaging of cannabis leaf tissue with MeV-SIMS method

Energy Technology Data Exchange (ETDEWEB)

Jenčič, Boštjan, E-mail: bostjan.jencic@ijs.si [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); Jeromel, Luka [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); Ogrinc Potočnik, Nina [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); M4I, Maastricht University, Peter Debijelaan 25A, 6229 HX Maastricht (Netherlands); Vogel-Mikuš, Katarina [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia); University of Ljubljana, Biotechnical Faculty, Dept. of Biology, Večna pot 11, SI-1000 Ljubljana (Slovenia); Kovačec, Eva; Regvar, Marjana [University of Ljubljana, Biotechnical Faculty, Dept. of Biology, Večna pot 11, SI-1000 Ljubljana (Slovenia); Siketić, Zdravko [Ruđer Bošković Institute, P.O. Box 180, 10000 Zagreb (Croatia); Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož [Jožef Stefan Institute, Jamova 39, SI-1000 Ljubljana (Slovenia)

2016-03-15

To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

Molecular imaging of cannabis leaf tissue with MeV-SIMS method

International Nuclear Information System (INIS)

Jenčič, Boštjan; Jeromel, Luka; Ogrinc Potočnik, Nina; Vogel-Mikuš, Katarina; Kovačec, Eva; Regvar, Marjana; Siketić, Zdravko; Vavpetič, Primož; Rupnik, Zdravko; Bučar, Klemen; Kelemen, Mitja; Kovač, Janez; Pelicon, Primož

2016-01-01

To broaden our analytical capabilities with molecular imaging in addition to the existing elemental imaging with micro-PIXE, a linear Time-Of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry (MeV-SIMS) was constructed and added to the existing nuclear microprobe at the Jožef Stefan Institute. We measured absolute molecular yields and damage cross-section of reference materials, without significant alteration of the fragile biological samples during the duration of measurements in the mapping mode. We explored the analytical capability of the MeV-SIMS technique for chemical mapping of the plant tissue of medicinal cannabis leaves. A series of hand-cut plant tissue slices were prepared by standard shock-freezing and freeze-drying protocol and deposited on the Si wafer. We show the measured MeV-SIMS spectra showing a series of peaks in the mass area of cannabinoids, as well as their corresponding maps. The indicated molecular distributions at masses of 345.5 u and 359.4 u may be attributed to the protonated THCA and THCA-C4 acids, and show enhancement in the areas with opened trichome morphology.

Tissues segmentation based on multi spectral medical images

Science.gov (United States)

Li, Ya; Wang, Ying

2017-11-01

Each band image contains the most obvious tissue feature according to the optical characteristics of different tissues in different specific bands for multispectral medical images. In this paper, the tissues were segmented by their spectral information at each multispectral medical images. Four Local Binary Patter descriptors were constructed to extract blood vessels based on the gray difference between the blood vessels and their neighbors. The segmented tissue in each band image was merged to a clear image.

Near-infrared spectroscopic tissue imaging for medical applications

Science.gov (United States)

Demos, Stavros [Livermore, CA; Staggs, Michael C [Tracy, CA

2006-12-12

Near infrared imaging using elastic light scattering and tissue autofluorescence are explored for medical applications. The approach involves imaging using cross-polarized elastic light scattering and tissue autofluorescence in the Near Infra-Red (NIR) coupled with image processing and inter-image operations to differentiate human tissue components.

Synthetic aperture tissue and flow ultrasound imaging

DEFF Research Database (Denmark)

Nikolov, Svetoslav

imaging applied to medical ultrasound. It is divided into two major parts: tissue and blood flow imaging. Tissue imaging using synthetic aperture algorithms has been investigated for about two decades, but has not been implemented in medical scanners yet. Among the other reasons, the conventional scanning...... and beamformation methods are adequate for the imaging modalities in clinical use - the B-mode imaging of tissue structures, and the color mapping of blood flow. The acquisition time, however, is too long, and these methods fail to perform real-time three-dimensional scans. The synthetic transmit aperture......, on the other hand, can create a Bmode image with as little as 2 emissions, thus significantly speeding-up the scan procedure. The first part of the dissertation describes the synthetic aperture tissue imaging. It starts with an overview of the efforts previously made by other research groups. A classification...

Imaging of plant materials using indirect desorption electrospray ionization mass spectrometry

DEFF Research Database (Denmark)

Janfelt, Christian

2015-01-01

Indirect desorption electrospray ionization mass spectrometry (DESI-MS) imaging is a method for imaging distributions of metabolites in plant materials, in particular leaves and petals. The challenge in direct imaging of such plant materials with DESI-MS is particularly the protective layer of cu...... of interest from parts of their matrix while preserving the spatial information in the two dimensions. The imprint can then easily be imaged by DESI-MS. The method delivers simple and robust mass spectrometry imaging of plant material with very high success ratios....... of cuticular wax present in leaves and petals. The cuticle protects the plant from drying out, but also makes it difficult for the DESI sprayer to reach the analytes of interest inside the plant material. A solution to this problem is to imprint the plant material onto a surface, thus releasing the analytes...

Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism.

Science.gov (United States)

Steinhauser, Matthew L; Bailey, Andrew P; Senyo, Samuel E; Guillermier, Christelle; Perlstein, Todd S; Gould, Alex P; Lee, Richard T; Lechene, Claude P

2012-01-15

Mass spectrometry with stable isotope labels has been seminal in discovering the dynamic state of living matter, but is limited to bulk tissues or cells. We developed multi-isotope imaging mass spectrometry (MIMS) that allowed us to view and measure stable isotope incorporation with submicrometre resolution. Here we apply MIMS to diverse organisms, including Drosophila, mice and humans. We test the 'immortal strand hypothesis', which predicts that during asymmetric stem cell division chromosomes containing older template DNA are segregated to the daughter destined to remain a stem cell, thus insuring lifetime genetic stability. After labelling mice with (15)N-thymidine from gestation until post-natal week 8, we find no (15)N label retention by dividing small intestinal crypt cells after a four-week chase. In adult mice administered (15)N-thymidine pulse-chase, we find that proliferating crypt cells dilute the (15)N label, consistent with random strand segregation. We demonstrate the broad utility of MIMS with proof-of-principle studies of lipid turnover in Drosophila and translation to the human haematopoietic system. These studies show that MIMS provides high-resolution quantification of stable isotope labels that cannot be obtained using other techniques and that is broadly applicable to biological and medical research.

Tissue Harmonic Synthetic Aperture Ultrasound Imaging

DEFF Research Database (Denmark)

Hemmsen, Martin Christian; Rasmussen, Joachim; Jensen, Jørgen Arendt

2014-01-01

Synthetic aperture sequential beamforming (SASB) and tissue har- monic imaging (THI) are combined to improve the image quality of medical ultrasound imaging. The technique is evaluated in a compar- ative study against dynamic receive focusing (DRF). The objective is to investigate if SASB combined...... with THI improves the image qual- ity compared to DRF-THI. The major benet of SASB is a reduced bandwidth between the probe and processing unit. A BK Medical 2202 Ultraview ultrasound scanner was used to acquire beamformed RF data for oine evaluation. The acquisition was made interleaved between methods......, and data were recorded with and without pulse inversion for tissue harmonic imaging. Data were acquired using a Sound Technol- ogy 192 element convex array transducer from both a wire phantom and a tissue mimicking phantom to investigate spatial resolution and pen- etration. In-vivo scans were also...

Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

Directory of Open Access Journals (Sweden)

Debasish Paul

2013-01-01

Full Text Available Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches.

Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

Science.gov (United States)

Paul, Debasish; Kumar, Avinash; Gajbhiye, Akshada; Santra, Manas K.; Srikanth, Rapole

2013-01-01

Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA) were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches. PMID:23586059

Compressed sensing in imaging mass spectrometry

International Nuclear Information System (INIS)

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

2013-01-01

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

Determination of iodine in oyster tissue by isotope dilution laser resonance ionization mass spectrometry

International Nuclear Information System (INIS)

Fassett, J.D.; Murphy, T.J.

1990-01-01

The technique of laser resonance ionization mass spectrometry has been combined with isotope dilution analysis to determine iodine in oyster tissue. The long-lived radioisotope, 129I, was used to spike the samples. Samples were equilibrated with the 129I, wet ashed under controlled conditions, and iodine separated by coprecipitation with silver chloride. The analyte was dried as silver ammonium iodide upon a tantalum filament from which iodine was thermally desorbed in the resonance ionization mass spectrometry instrument. A single-color, two-photon resonant plus one-photon ionization scheme was used to form positive iodine ions. Long-lived iodine signals were achieved from 100 ng of iodine. The precision of 127I/129I measurement has been evaluated by replicate determinations of the spike, the spike calibration samples, and the oyster tissue samples and was 1.0%. Measurement precision among samples was 1.9% for the spike calibration and 1.4% for the oyster tissue. The concentration of iodine determined in SRM 1566a, Oyster Tissue, was 4.44 micrograms/g with an estimate of the overall uncertainty for the analysis of +/- 0.12 microgram/g

Automated, feature-based image alignment for high-resolution imaging mass spectrometry of large biological samples

NARCIS (Netherlands)

Broersen, A.; Liere, van R.; Altelaar, A.F.M.; Heeren, R.M.A.; McDonnell, L.A.

2008-01-01

High-resolution imaging mass spectrometry of large biological samples is the goal of several research groups. In mosaic imaging, the most common method, the large sample is divided into a mosaic of small areas that are then analyzed with high resolution. Here we present an automated alignment

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

Science.gov (United States)

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

Determination of trimethoprim in tissues using liquid chromatography-thermospray mass spectrometry.

Science.gov (United States)

Cannavan, A; Hewitt, S A; Floyd, S D; Kennedy, D G

1997-11-01

A method is described for the determination of the antibacterial drug trimethoprim in tissues. Minced tissue is homogenised with chloroform-acetone (1 + 1 v/v), filtered, and the filtrate evaporated to an oily residue using a rotary evaporator. The residue is redissolved in methanol-water-acetic acid (50 + 48.7 + 1.3 v/v) and any fats present are partitioned into hexane. The aqueous phase is analysed by liquid chromatography-thermospray mass spectrometry in positive mode with the protonated molecular ion at m/z 291 being monitored. Recoveries ranged between 60% in liver and 79% in muscle. The limit of determination was 25 micrograms kg-1 and the limit of detection was approximately 4 micrograms kg-1. The method is suitable for monitoring tissues taken under national surveillance schemes for veterinary drug residues.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry.

Science.gov (United States)

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student'st test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Marolla, Ana Paula Cleto [Universidade Federal de São Paulo, São Paulo, SP (Brazil); Waisberg, Jaques [Hospital do Servidor Público Estadual, São Paulo, SP (Brazil); Faculdade de Medicina do ABC, Santo André, SP (Brazil); Saba, Gabriela Tognini [Faculdade de Medicina do ABC, Santo André, SP (Brazil); Waisberg, Daniel Reis [Faculdade de Medicina da Universidade de São Paulo, São Paulo, SP (Brazil); Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva [Faculdade de Medicina do ABC, Santo André, SP (Brazil)

2015-07-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues.

Glycomics expression analysis of sulfated glycosaminoglycans of human colorectal cancer tissues and non-neoplastic mucosa by electrospray ionization mass spectrometry

International Nuclear Information System (INIS)

Marolla, Ana Paula Cleto; Waisberg, Jaques; Saba, Gabriela Tognini; Waisberg, Daniel Reis; Margeotto, Fernando Beani; Pinhal, Maria Aparecida da Silva

2015-01-01

To determine the presence of glycosaminoglycans in the extracellular matrix of connective tissue from neoplastic and non-neoplastic colorectal tissues, since it has a central role in tumor development and progression. Tissue samples from neoplastic and non-neoplastic colorectal tissues were obtained from 64 operated patients who had colorectal carcinoma with no distant metastases. Expressions of heparan sulphate, chondroitin sulphate, dermatan sulphate and their fragments were analyzed by electrospray ionization mass spectrometry, with the technique for extraction and quantification of glycosaminoglycans after proteolysis and electrophoresis. The statistical analysis included mean, standard deviation, and Student’s t test. The glycosaminoglycans extracted from colorectal tissue showed three electrophoretic bands in agarose gel. Electrospray ionization mass spectrometry showed characteristic disaccharide fragments from glycosaminoglycans, indicating their structural characterization in the tissues analyzed. Some peaks in the electrospray ionization mass spectrometry were not characterized as fragments of sugars, indicating the presence of fragments of the protein structure of proteoglycans generated during the glycosaminoglycan purification. The average amount of chondroitin and dermatan increased in the neoplastic tissue compared to normal tissue (p=0.01). On the other hand, the average amount of heparan decreased in the neoplastic tissue compared to normal tissue (p= 0.03). The method allowed the determination of the glycosaminoglycans structural profile in colorectal tissue from neoplastic and non-neoplastic colorectal tissue. Neoplastic tissues showed greater amounts of chondroitin sulphate and dermatan sulphate compared to non-neoplastic tissues, while heparan sulphate was decreased in neoplastic tissues

Radionuclide imaging of soft tissue neoplasms

International Nuclear Information System (INIS)

Chew, F.S.; Hudson, T.M.; Enneking, W.F.

1981-01-01

Two classes of radiopharmaceuticals may be used for imaging tumors of the musculoskeletal system. The first is comprised of soft tissue or tumor specific agents such as gallium-67, bleomycin, and radionuclide-labeled antibodies, which may be useful for detecting and localizing these tumors. The other class of tracer is comprised of those with avidity for bone. The 99mTc-labeled-phosphate skeletal imaging compounds have been found to localize in a variety of soft tissue lesions, including benign and malignant tumors. In 1972, Enneking began to include bone scans in the preoperative evaluation of soft tissue masses. Later, he and his associates reported that these scans were useful in planning operative treatment of sarcomas by detecting involvement of bone by the tumors. Nearly all malignant soft tissue tumors take up bone-seeking radiopharmaceuticals, and bone involvement was indicated in two-thirds of the scans we reviewed. About half of benign soft tissue lesions had normal scans, but the other half showed uptake within the lesion and a few also showed bone involvement. Careful, thorough imaging technique is essential to proper evaluation. Multiple, high-resolution static gamma camera images in different projections are necessary to adequately demonstrate the presence or absence of soft tissue abnormality and to define the precise relationship of the tumor to the adjacent bone

Physics of tissue harmonic imaging by ultrasound

Science.gov (United States)

Jing, Yuan

Tissue Harmonic Imaging (THI) is an imaging modality that is currently deployed on diagnostic ultrasound scanners. In THI the amplitude of the ultrasonic pulse that is used to probe the tissue is large enough that the pulse undergoes nonlinear distortion as it propagates into the tissue. One result of the distortion is that as the pulse propagates energy is shifted from the fundamental frequency of the source pulse into its higher harmonics. These harmonics will scatter off objects in the tissue and images formed from the scattered higher harmonics are considered to have superior quality to the images formed from the fundamental frequency. Processes that have been suggested as possibly responsible for the improved imaging in THI include: (1) reduced sensitivity to reverberation, (2) reduced sensitivity to aberration, and (3) reduction in side lobes. By using a combination of controlled experiments and numerical simulations, these three reasons have been investigated. A single element transducer and a clinical ultrasound scanner with a phased array transducer were used to image a commercial tissue-mimicking phantom with calibrated targets. The higher image quality achieved with THI was quantified in terms of spatial resolution and "clutter" signals. A three-dimensional model of the forward propagation of nonlinear sound beams in media with arbitrary spatial properties (a generalized KZK equation) was developed. A time-domain code for solving the KZK equation was validated with measurements of the acoustic field generated by the single element transducer and the phased array transducer. The code was used to investigate the impact of aberration using tissue-like media with three-dimensional variations in all acoustic properties. The three-dimensional maps of tissue properties were derived from the datasets available through the Visible Female project. The experiments and simulations demonstrated that second harmonic imaging (1) suffers less clutter associated with

The Spatial Distribution of Alkaloids in Psychotria prunifolia (Kunth) Steyerm and Palicourea coriacea (Cham.) K. Schum Leaves Analysed by Desorption Electrospray Ionisation Mass Spectrometry Imaging

DEFF Research Database (Denmark)

Kato, Lucilia; Moraes, Aline Pereira; de Oliveira, Cecília Maria Alves

2018-01-01

INTRODUCTION: Species of the genera Psychotria and Palicourea are sources of indole alkaloids, however, the distribution of alkaloids within the plants is not known. Analysing the spatial distribution using desorption electrospray ionisation mass spectrometry imaging (DESI-MSI) has become...... analyses. METHODOLOGY: Based upon previous structure elucidation studies, four alkaloids targeted in this study were identified using high resolution mass spectrometry by direct infusion of plant extracts, and their distributions were imaged by DESI-MSI via tissue imprints on a porous Teflon surface....... Relative quantitation of the four alkaloids was obtained by HPLC-MS/MS analysis performed using multiple-reaction monitoring (MRM) mode on a triple quadrupole mass spectrometer. RESULTS: Alkaloids showed distinct distributions on the leaf surfaces. Prunifoleine was mainly present in the midrib, while 10...

Multi-imaging of Cytokinin and Abscisic Acid on the Roots of Rice (Oryza sativa) Using Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry.

Science.gov (United States)

Shiono, Katsuhiro; Hashizaki, Riho; Nakanishi, Toyofumi; Sakai, Tatsuko; Yamamoto, Takushi; Ogata, Koretsugu; Harada, Ken-Ichi; Ohtani, Hajime; Katano, Hajime; Taira, Shu

2017-09-06

Plant hormones act as important signaling molecules that regulate responses to abiotic stress as well as plant growth and development. Because their concentrations of hormones control the physiological responses in the target tissue, it is important to know the distributions and concentrations in the tissues. However, it is difficult to determine the hormone concentration on the plant tissue as a result of the limitations of conventional methods. Here, we report the first multi-imaging of two plant hormones, one of cytokinin [i.e., trans-zeatin (tZ)] and abscisic acid (ABA) using a new technology, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) imaging. Protonated signals of tZ (m/z 220.1) and ABA (m/z 265.3) were chosen on longitudinal sections of rice roots for MS imaging. tZ was broadly distributed about 40 mm behind the root apex but was barely detectable at the apex, whereas ABA was mainly detected at the root apex. Multi-imaging using MALDI-TOF-MS enabled the visualization of the localization and quantification of plant hormones. Thus, this tool is applicable to a wide range of plant species growing under various environmental conditions.

Molecular mass spectrometry imaging in biomedical and life science research

Czech Academy of Sciences Publication Activity Database

Pól, Jaroslav; Strohalm, Martin; Havlíček, Vladimír; Volný, Michael

2010-01-01

Roč. 134, č. 5 (2010), s. 423-443 ISSN 0948-6143 R&D Projects: GA MŠk LC545; GA ČR GPP206/10/P018 Institutional research plan: CEZ:AV0Z50200510 Keywords : Mass spectrometry * Chemical imaging * Molecular imaging Subject RIV: EE - Microbiology, Virology Impact factor: 4.727, year: 2010

Direct Analyses of Secondary Metabolites by Mass Spectrometry Imaging (MSI) from Sunflower (Helianthus annuus L.) Trichomes.

Science.gov (United States)

Brentan Silva, Denise; Aschenbrenner, Anna-Katharina; Lopes, Norberto Peporine; Spring, Otmar

2017-05-10

Helianthus annuus (sunflower) displays non-glandular trichomes (NGT), capitate glandular trichomes (CGT), and linear glandular trichomes (LGT), which reveal different chemical compositions and locations in different plant tissues. With matrix-assisted laser desorption/ionization (MALDI) and laser desorption/ionization (LDI) mass spectrometry imaging (MSI) techniques, efficient methods were developed to analyze the tissue distribution of secondary metabolites (flavonoids and sesquiterpenes) and proteins inside of trichomes. Herein, we analyzed sesquiterpene lactones, present in CGT, from leaf transversal sections using the matrix 2,5-dihydroxybenzoic acid (DHB) and α-cyano-4-hydroxycinnamic acid (CHCA) (mixture 1:1) with sodium ions added to increase the ionization in positive ion mode. The results observed for sesquiterpenes and polymethoxylated flavones from LGT were similar. However, upon desiccation, LGT changed their shape in the ionization source, complicating analyses by MSI mainly after matrix application. An alternative method could be applied to LGT regions by employing LDI (without matrix) in negative ion mode. The polymethoxylated flavones were easily ionized by LDI, producing images with higher resolution, but the sesquiterpenes were not observed in spectra. Thus, the application and viability of MALDI imaging for the analyses of protein and secondary metabolites inside trichomes were confirmed, highlighting the importance of optimization parameters.

NMR imaging of soft tissue tumors

International Nuclear Information System (INIS)

Laval-Jeantet, M.; Tobolsk, F.; Delepine, N.; Delepine, G.; Roger, B.; Cabanis, E.A.

1986-01-01

Preliminary findings on NMR imaging of 30 soft tissue tumors demonstrated the indispensable value of this examination (particularly when a surface antenna is used) for preoperative investigation and diagnosis of tumoral recurrence when compared with other radiologic techniques. The possible potential of NMR imaging for characterization of tissues, apart from lipoma or liposarcoma, cannot be evaluated at the present time [fr

MALDI (matrix assisted laser desorption ionization) Imaging Mass Spectrometry (IMS) of skin: Aspects of sample preparation.

Science.gov (United States)

de Macedo, Cristiana Santos; Anderson, David M; Schey, Kevin L

2017-11-01

MALDI (matrix assisted laser desorption ionization) Imaging Mass Spectrometry (IMS) allows molecular analysis of biological materials making possible the identification and localization of molecules in tissues, and has been applied to address many questions on skin pathophysiology, as well as on studies about drug absorption and metabolism. Sample preparation for MALDI IMS is the most important part of the workflow, comprising specimen collection and preservation, tissue embedding, cryosectioning, washing, and matrix application. These steps must be carefully optimized for specific analytes of interest (lipids, proteins, drugs, etc.), representing a challenge for skin analysis. In this review, critical parameters for MALDI IMS sample preparation of skin samples will be described. In addition, specific applications of MALDI IMS of skin samples will be presented including wound healing, neoplasia, and infection. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparison of mechanisms involved in image enhancement of Tissue Harmonic Imaging

Science.gov (United States)

Cleveland, Robin O.; Jing, Yuan

2006-05-01

Processes that have been suggested as responsible for the improved imaging in Tissue Harmonic Imaging (THI) include: 1) reduced sensitivity to reverberation, 2) reduced sensitivity to aberration, and 3) reduction in the amplitude of diffraction side lobes. A three-dimensional model of the forward propagation of nonlinear sound beams in media with arbitrary spatial properties (a generalized KZK equation) was developed and solved using a time-domain code. The numerical simulations were validated through experiments with tissue mimicking phantoms. The impact of aberration from tissue-like media was determined through simulations using three-dimensional maps of tissue properties derived from datasets available through the Visible Female Project. The experiments and simulations demonstrated that second harmonic imaging suffers less clutter from reverberation and side-lobes but is not immune to aberration effects. The results indicate that side lobe suppression is the most significant reason for the improvement of second harmonic imaging.

Imaging the hard/soft tissue interface.

Science.gov (United States)

Bannerman, Alistair; Paxton, Jennifer Z; Grover, Liam M

2014-03-01

Interfaces between different tissues play an essential role in the biomechanics of native tissues and their recapitulation is now recognized as critical to function. As a consequence, imaging the hard/soft tissue interface has become increasingly important in the area of tissue engineering. Particularly as several biotechnology based products have made it onto the market or are close to human trials and an understanding of their function and development is essential. A range of imaging modalities have been developed that allow a wealth of information on the morphological and physical properties of samples to be obtained non-destructively in vivo or via destructive means. This review summarizes the use of a selection of imaging modalities on interfaces to date considering the strengths and weaknesses of each. We will also consider techniques which have not yet been utilized to their full potential or are likely to play a role in future work in the area.

MR imaging of soft-tissue masses

International Nuclear Information System (INIS)

Fujimoto, H.; Murakami, K.; Ichikawa, T.; Matsubara, T.; Tsumurai, Y.; Masuda, S.; Terauchi, M.; Ozawa, K.; Arimizu, N.

1990-01-01

This paper evaluates the ability of T2*-weighted gradient-field-echo (T2*FE) MR imaging to image soft-tissue masses. The series included 26 cases, including 17 benign tumors, four malignant tumors, and five others. Images were obtained on a 0.5-T magnet with T2*FE imaging (300/22 [repetition time msec/echo time msec], 20 degree). Results were compared with those of T1-weighted spin-echo (SE) images (500/20--40) and T2-weighted SE (T2SE) images (2,000/80). T2*FE images were similar to T2SE images with respect to the signal intensity and internal architecture of the masses in many cases. In some instances, they were superior to T2SE images in depicting special features such as a hemosiderin deposit or in delineating the masses and adjacent fat tissues. Shorter (about one-third or two-thirds) scanning time was required to obtain T2*FE images than to obtain T2SE images

POLARIZATION IMAGING AND SCATTERING MODEL OF CANCEROUS LIVER TISSUES

Directory of Open Access Journals (Sweden)

DONGZHI LI

2013-07-01

Full Text Available We apply different polarization imaging techniques for cancerous liver tissues, and compare the relative contrasts for difference polarization imaging (DPI, degree of polarization imaging (DOPI and rotating linear polarization imaging (RLPI. Experimental results show that a number of polarization imaging parameters are capable of differentiating cancerous cells in isotropic liver tissues. To analyze the contrast mechanism of the cancer-sensitive polarization imaging parameters, we propose a scattering model containing two types of spherical scatterers and carry on Monte Carlo simulations based on this bi-component model. Both the experimental and Monte Carlo simulated results show that the RLPI technique can provide a good imaging contrast of cancerous tissues. The bi-component scattering model provides a useful tool to analyze the contrast mechanism of polarization imaging of cancerous tissues.

DETERMINATION OF TOTAL MERCURY IN FISH TISSUES USING PYROLYSIS ATOMIC ABSORPTION SPECTROMETRY WITH GOLD AMALGAMATION

Science.gov (United States)

A simple and rapid procedure for measuring total mercury in fish tissues is evaluated and compared with conventional techniques. Using an automated instrument incorporating combustion, preconcentration by amalgamation with gold, and atomic absorption spectrometry (AAS), mill...

The expression profile of phosphatidylinositol in high spatial resolution imaging mass spectrometry as a potential biomarker for prostate cancer.

Directory of Open Access Journals (Sweden)

Takayuki Goto

Full Text Available High-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS is an emerging application for the comprehensive and detailed analysis of the spatial distribution of ionized molecules in situ on tissue slides. HR-MALDI-IMS in negative mode in a mass range of m/z 500-1000 was performed on optimal cutting temperature (OCT compound-embedded human prostate tissue samples obtained from patients with prostate cancer at the time of radical prostatectomy. HR-MALDI-IMS analysis of the 14 samples in the discovery set identified 26 molecules as highly expressed in the prostate. Tandem mass spectrometry (MS/MS showed that these molecules included 14 phosphatidylinositols (PIs, 3 phosphatidylethanolamines (PEs and 3 phosphatidic acids (PAs. Among the PIs, the expression of PI(18:0/18:1, PI(18:0/20:3 and PI(18:0/20:2 were significantly higher in cancer tissue than in benign epithelium. A biomarker algorithm for prostate cancer was formulated by analyzing the expression profiles of PIs in cancer tissue and benign epithelium of the discovery set using orthogonal partial least squares discriminant analysis (OPLS-DA. The sensitivity and specificity of this algorithm for prostate cancer diagnosis in the 24 validation set samples were 87.5 and 91.7%, respectively. In conclusion, HR-MALDI-IMS identified several PIs as being more highly expressed in prostate cancer than benign prostate epithelium. These differences in PI expression profiles may serve as a novel diagnostic tool for prostate cancer.

Evaluation of multimodality imaging using image fusion with ultrasound tissue elasticity imaging in an experimental animal model.

Science.gov (United States)

Paprottka, P M; Zengel, P; Cyran, C C; Ingrisch, M; Nikolaou, K; Reiser, M F; Clevert, D A

2014-01-01

To evaluate the ultrasound tissue elasticity imaging by comparison to multimodality imaging using image fusion with Magnetic Resonance Imaging (MRI) and conventional grey scale imaging with additional elasticity-ultrasound in an experimental small-animal-squamous-cell carcinoma-model for the assessment of tissue morphology. Human hypopharynx carcinoma cells were subcutaneously injected into the left flank of 12 female athymic nude rats. After 10 days (SD ± 2) of subcutaneous tumor growth, sonographic grey scale including elasticity imaging and MRI measurements were performed using a high-end ultrasound system and a 3T MR. For image fusion the contrast-enhanced MRI DICOM data set was uploaded in the ultrasonic device which has a magnetic field generator, a linear array transducer (6-15 MHz) and a dedicated software package (GE Logic E9), that can detect transducers by means of a positioning system. Conventional grey scale and elasticity imaging were integrated in the image fusion examination. After successful registration and image fusion the registered MR-images were simultaneously shown with the respective ultrasound sectional plane. Data evaluation was performed using the digitally stored video sequence data sets by two experienced radiologist using a modified Tsukuba Elasticity score. The colors "red and green" are assigned for an area of soft tissue, "blue" indicates hard tissue. In all cases a successful image fusion and plan registration with MRI and ultrasound imaging including grey scale and elasticity imaging was possible. The mean tumor volume based on caliper measurements in 3 dimensions was ~323 mm3. 4/12 rats were evaluated with Score I, 5/12 rates were evaluated with Score II, 3/12 rates were evaluated with Score III. There was a close correlation in the fused MRI with existing small necrosis in the tumor. None of the scored II or III lesions was visible by conventional grey scale. The comparison of ultrasound tissue elasticity imaging enables a

Cryo-sectioning of mice for whole-body imaging of drugs and metabolites with desorption electrospray ionization mass spectrometry imaging - a simplified approach.

Science.gov (United States)

Okutan, Seda; Hansen, Harald S; Janfelt, Christian

2016-06-01

A method is presented for whole-body imaging of drugs and metabolites in mice with desorption electrospray ionization mass spectrometry imaging (DESI-MSI). Unlike most previous approaches to whole-body imaging which are based on cryo-sectioning using a cryo-macrotome, the presented approach is based on use of the cryo-microtome which is found in any histology lab. The tissue sections are collected on tape which is analyzed directly by DESI-MSI. The method is demonstrated on mice which have been dosed intraperitoneally with the antidepressive drug amitriptyline. By combining full-scan detection with the more selective and sensitive MS/MS detection, a number of endogenous compounds (lipids) were imaged simultaneously with the drug and one of its metabolites. The sensitivity of this approach allowed for imaging of drug and the metabolite in a mouse dosed with 2.7 mg amitriptyline per kg bodyweight which is comparable to the normal prescribed human dose. The simultaneous imaging of endogenous and exogenous compounds facilitates registration of the drug images to certain organs in the body by colored-overlay of the two types of images. The method represents a relatively low-cost approach to simple, sensitive and highly selective whole-body imaging in drug distribution and metabolism studies. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Characterizing the lipid and metabolite changes associated with placental function and pregnancy complications using ion mobility spectrometry-mass spectrometry and mass spectrometry imaging

Energy Technology Data Exchange (ETDEWEB)

Burnum-Johnson, Kristin E.; Baker, Erin S.; Metz, Thomas O.

2017-12-01

Successful pregnancy is dependent upon discrete biological events, which include embryo implantation, decidualization, and placentation. Problems associated with each of these events can cause infertility or conditions such as preeclampsia. A greater understanding of the molecular changes associated with these complex processes is necessary to aid in identifying treatments for each condition. Previous nuclear magnetic resonance spectroscopy and mass spectrometry studies have been used to identify metabolites and lipids associated with pregnancy-related complications. However, due to limitations associated with conventional implementations of both techniques, novel technology developments are needed to more fully understand the initiation and development of pregnancy related problems at the molecular level. In this perspective, we describe current analytical techniques for metabolomic and lipidomic characterization of pregnancy complications and discuss the potential for new technologies such as ion mobility spectrometry-mass spectrometry and mass spectrometry imaging to contribute to a better understanding of the molecular changes that affect the placenta and pregnancy outcomes.

A comprehensive high-resolution mass spectrometry approach for characterization of metabolites by combination of ambient ionization, chromatography and imaging methods.

Science.gov (United States)

Berisha, Arton; Dold, Sebastian; Guenther, Sabine; Desbenoit, Nicolas; Takats, Zoltan; Spengler, Bernhard; Römpp, Andreas

2014-08-30

An ideal method for bioanalytical applications would deliver spatially resolved quantitative information in real time and without sample preparation. In reality these requirements can typically not be met by a single analytical technique. Therefore, we combine different mass spectrometry approaches: chromatographic separation, ambient ionization and imaging techniques, in order to obtain comprehensive information about metabolites in complex biological samples. Samples were analyzed by laser desorption followed by electrospray ionization (LD-ESI) as an ambient ionization technique, by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging for spatial distribution analysis and by high-performance liquid chromatography/electrospray ionization mass spectrometry (HPLC/ESI-MS) for quantitation and validation of compound identification. All MS data were acquired with high mass resolution and accurate mass (using orbital trapping and ion cyclotron resonance mass spectrometers). Grape berries were analyzed and evaluated in detail, whereas wheat seeds and mouse brain tissue were analyzed in proof-of-concept experiments. In situ measurements by LD-ESI without any sample preparation allowed for fast screening of plant metabolites on the grape surface. MALDI imaging of grape cross sections at 20 µm pixel size revealed the detailed distribution of metabolites which were in accordance with their biological function. HPLC/ESI-MS was used to quantify 13 anthocyanin species as well as to separate and identify isomeric compounds. A total of 41 metabolites (amino acids, carbohydrates, anthocyanins) were identified with all three approaches. Mass accuracy for all MS measurements was better than 2 ppm (root mean square error). The combined approach provides fast screening capabilities, spatial distribution information and the possibility to quantify metabolites. Accurate mass measurements proved to be critical in order to reliably combine data from different MS

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

Science.gov (United States)

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

Mass spectrometric characterization of elements and molecules in cell cultures and tissues

International Nuclear Information System (INIS)

Arlinghaus, H.F.; Kriegeskotte, C.; Fartmann, M.; Wittig, A.; Sauerwein, W.; Lipinsky, D.

2006-01-01

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) and laser post-ionization secondary neutral mass spectrometry (laser-SNMS) have been used to image and quantify targeted compounds, intrinsic elements and molecules with subcellular resolution in single cells of both cell cultures and tissues. Special preparation procedures for analyzing cell cultures and tissue materials were developed. Cancer cells type MeWo, incubated with boronated compounds, were sandwiched between two substrates, cryofixed, freeze-fractured and freeze-dried. Also, after injection with boronated compounds, different types of mouse tissues were extracted, prepared on a special specimen carrier and plunged with high velocity into LN 2 -cooled propane for cryofixation. After trimming, these tissue blocks were freeze-dried. The measurements of the K/Na ratio demonstrated that for both cell cultures and tissue materials the special preparation techniques used were appropriate for preserving the chemical and structural integrity of the living cell. The boron images show inter- and intracellular boron signals with different intensities. Molecular images show distinct features partly correlated with the cell structure. A comparison between laser-SNMS and ToF-SIMS showed that especially laser-SNMS is particularly well-suited for identifying specific cell structures and imaging ultratrace element concentrations in tissues

Biomarker discovery in high grade sarcomas by mass spectrometry imaging

OpenAIRE

Lou, S.

2017-01-01

This thesis demonstrates a detailed biomarker discovery Mass Spectrometry Imaging workflow for histologically heterogeneous high grade sarcomas. Panels of protein and metabolite signatures were discovered either distinguishing different histological subtypes or stratifying high risk patients with poor survival.

Detection of SiO2 nanoparticles in lung tissue by ToF-SIMS imaging and fluorescence microscopy.

Science.gov (United States)

Veith, Lothar; Vennemann, Antje; Breitenstein, Daniel; Engelhard, Carsten; Wiemann, Martin; Hagenhoff, Birgit

2017-07-10

The direct detection of nanoparticles in tissues at high spatial resolution is a current goal in nanotoxicology. Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) is widely used for the direct detection of inorganic and organic substances with high spatial resolution but its capability to detect nanoparticles in tissue sections is still insufficiently explored. To estimate the applicability of this technique for nanotoxicological questions, comparative studies with established techniques on the detection of nanoparticles can offer additional insights. Here, we compare ToF-SIMS imaging data with sub-micrometer spatial resolution to fluorescence microscopy imaging data to explore the usefulness of ToF-SIMS for the detection of nanoparticles in tissues. SiO 2 nanoparticles with a mean diameter of 25 nm, core-labelled with fluorescein isothiocyanate, were intratracheally instilled into rat lungs. Subsequently, imaging of lung cryosections was performed with ToF-SIMS and fluorescence microscopy. Nanoparticles were successfully detected with ToF-SIMS in 3D microanalysis mode based on the lateral distribution of SiO 3 - (m/z 75.96), which was co-localized with the distribution pattern that was obtained from nanoparticle fluorescence. In addition, the lateral distribution of protein (CN - , m/z 26.00) and phosphate based signals (PO 3 - , m/z 78.96) originating from the tissue material could be related to the SiO 3 - lateral distribution. In conclusion, ToF-SIMS is suitable to directly detect and laterally resolve SiO 2 nanomaterials in biological tissue at sufficient intensity levels. At the same time, information about the chemical environment of the nanoparticles in the lung tissue sections is obtained.

Mass Spectrometry Imaging for the Investigation of Intratumor Heterogeneity.

Science.gov (United States)

Balluff, B; Hanselmann, M; Heeren, R M A

2017-01-01

One of the big clinical challenges in the treatment of cancer is the different behavior of cancer patients under guideline therapy. An important determinant for this phenomenon has been identified as inter- and intratumor heterogeneity. While intertumor heterogeneity refers to the differences in cancer characteristics between patients, intratumor heterogeneity refers to the clonal and nongenetic molecular diversity within a patient. The deciphering of intratumor heterogeneity is recognized as key to the development of novel therapeutics or treatment regimens. The investigation of intratumor heterogeneity is challenging since it requires an untargeted molecular analysis technique that accounts for the spatial and temporal dynamics of the tumor. So far, next-generation sequencing has contributed most to the understanding of clonal evolution within a cancer patient. However, it falls short in accounting for the spatial dimension. Mass spectrometry imaging (MSI) is a powerful tool for the untargeted but spatially resolved molecular analysis of biological tissues such as solid tumors. As it provides multidimensional datasets by the parallel acquisition of hundreds of mass channels, multivariate data analysis methods can be applied for the automated annotation of tissues. Moreover, it integrates the histology of the sample, which enables studying the molecular information in a histopathological context. This chapter will illustrate how MSI in combination with statistical methods and histology has been used for the description and discovery of intratumor heterogeneity in different cancers. This will give evidence that MSI constitutes a unique tool for the investigation of intratumor heterogeneity, and could hence become a key technology in cancer research. © 2017 Elsevier Inc. All rights reserved.

Teaching the physics of medical imaging: an active learning approach involving imaging of biological tissue

DEFF Research Database (Denmark)

Wilhjelm, Jens E.; Pihl, Michael Johannes; Lonsdale, Markus Nowak

2008-01-01

Introduction to medical imaging is an experimentally oriented course in the physics of medical imaging, where the students record, process and analyse 3D data of an unknown piece of formalin fixed animal tissue embedded in agar in order to estimate the tissue types present. Planar X-ray, CT, MRI......, ultrasound and SPECT/PET images are recorded, showing the tissue in very different ways. In order for the students to estimate the tissue type, they need to study the physical principles of the imaging modalities. The “true” answer is subsequently revealed by slicing the tissue....

Gold internal standard correction for elemental imaging of soft tissue sections by LA-ICP-MS: element distribution in eye microstructures.

Science.gov (United States)

Konz, Ioana; Fernández, Beatriz; Fernández, M Luisa; Pereiro, Rosario; González, Héctor; Alvarez, Lydia; Coca-Prados, Miguel; Sanz-Medel, Alfredo

2013-04-01

Laser ablation coupled to inductively coupled plasma mass spectrometry has been developed for the elemental imaging of Mg, Fe and Cu distribution in histological tissue sections of fixed eyes, embedded in paraffin, from human donors (cadavers). This work presents the development of a novel internal standard correction methodology based on the deposition of a homogeneous thin gold film on the tissue surface and the use of the (197)Au(+) signal as internal standard. Sample preparation (tissue section thickness) and laser conditions were carefully optimized, and internal normalisation using (197)Au(+) was compared with (13)C(+) correction for imaging applications. (24)Mg(+), (56)Fe(+) and (63)Cu(+) distributions were investigated in histological sections of the anterior segment of the eye (including the iris, ciliary body, cornea and trabecular meshwork) and were shown to be heterogeneously distributed along those tissue structures. Reproducibility was assessed by imaging different human eye sections from the same donor and from ten different eyes from adult normal donors, which showed that similar spatial maps were obtained and therefore demonstrate the analytical potential of using (197)Au(+) as internal standard. The proposed analytical approach could offer a robust tool with great practical interest for clinical studies, e.g. to investigate trace element distribution of metals and their alterations in ocular diseases.

Continuous wave terahertz reflection imaging of human colorectal tissue

Science.gov (United States)

Doradla, Pallavi; Alavi, Karim; Joseph, Cecil S.; Giles, Robert H.

2013-03-01

Continuous wave terahertz (THz) imaging has the potential to offer a safe, non-ionizing, and nondestructive medical imaging modality for delineating colorectal cancer. Fresh excisions of normal colon tissue were obtained from surgeries performed at the University of Massachusetts Medical School, Worcester. Reflection measurements of thick sections of colorectal tissues, mounted in an aluminum sample holder, were obtained for both fresh and formalin fixed tissues. The two-dimensional reflection images were acquired by using an optically pumped far-infrared molecular gas laser operating at 584 GHz with liquid Helium cooled silicon bolometer detector. Using polarizers in the experiment both co-polarized and cross-polarized remittance form the samples was collected. Analysis of the images showed the importance of understanding the effects of formalin fixation while determining reflectance level of tissue response. The resulting co- and cross-polarized images of both normal and formalin fixed tissues showed uniform terahertz response over the entire sample area. Initial measurements indicated a co-polarized reflectance of 16%, and a cross-polarized reflectance of 0.55% from fresh excisions of normal colonic tissues.

Stokes polarimetry imaging of dog prostate tissue

Science.gov (United States)

Kim, Jihoon; Johnston, William K., III; Walsh, Joseph T., Jr.

2010-02-01

Prostate cancer is the second leading cause of death in the United States in 2009. Radical prostatectomy (complete removal of the prostate) is the most common treatment for prostate cancer, however, differentiating prostate tissue from adjacent bladder, nerves, and muscle is difficult. Improved visualization could improve oncologic outcomes and decrease damage to adjacent nerves and muscle important for preservation of potency and continence. A novel Stokes polarimetry imaging (SPI) system was developed and evaluated using a dog prostate specimen in order to examine the feasibility of the system to differentiate prostate from bladder. The degree of linear polarization (DOLP) image maps from linearly polarized light illumination at different visible wavelengths (475, 510, and 650 nm) were constructed. The SPI system used the polarization property of the prostate tissue. The DOLP images allowed advanced differentiation by distinguishing glandular tissue of prostate from the muscular-stromal tissue in the bladder. The DOLP image at 650 nm effectively differentiated prostate and bladder by strong DOLP in bladder. SPI system has the potential to improve surgical outcomes in open or robotic-assisted laparoscopic removal of the prostate. Further in vivo testing is warranted.

Imaging mass spectrometry (IMS) of cortical lipids from preclinical to severe stages of Alzheimer's disease.

Science.gov (United States)

Gónzalez de San Román, E; Manuel, I; Giralt, M T; Ferrer, I; Rodríguez-Puertas, R

2017-09-01

Alzheimer's disease (AD) is a progressive neurodegenerative disease affecting millions of patients worldwide. Previous studies have demonstrated alterations in the lipid composition of lipid extracts from plasma and brain samples of AD patients. However, there is no consensus regarding the qualitative and quantitative changes of lipids in brains from AD patients. In addition, the recent developments in imaging mass spectrometry methods are leading to a new stage in the in situ analysis of lipid species in brain tissue slices from human postmortem samples. The present study uses the matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS), permitting the direct anatomical analysis of lipids in postmortem brain sections from AD patients, which are compared with the intensity of the lipid signal in samples from matched subjects with no neurological diseases. The frontal cortex samples from AD patients were classified in three groups based on Braak's histochemical criteria, ranging from non-cognitively impaired patients to those severely affected. The main results indicate a depletion of different sulfatide lipid species from the earliest stages of the disease in both white and gray matter areas of the frontal cortex. Therefore, the decrease in sulfatides in cortical areas could be considered as a marker of the disease, but may also indicate neurochemical modifications related to the pathogenesis of the disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017 Elsevier B.V. All rights reserved.

Magnetic resonance imaging of pediatric soft-tissue vascular anomalies

International Nuclear Information System (INIS)

Navarro, Oscar M.

2016-01-01

Magnetic resonance (MR) imaging can be used in the management of pediatric soft-tissue vascular anomalies for diagnosing and assessing extent of lesions and for evaluating response to therapy. MR imaging studies often involve a combination of T1- and T2-weighted images in addition to MR angiography and fat-suppressed post-contrast sequences. The MR imaging features of these vascular anomalies when combined with clinical findings can aid in diagnosis. In cases of complex vascular malformations and syndromes associated with vascular anomalies, MR imaging can be used to evaluate accompanying soft-tissue and bone anomalies. This article reviews the MR imaging protocols and appearances of the most common pediatric soft-tissue vascular anomalies. (orig.)

Translational imaging mass spectrometry: From CERN to the surgeon

CERN Multimedia

CERN. Geneva

2018-01-01

A comprehensive understanding of molecular patterns of health and disease is needed to pave the way for personalized medicine and tissue regeneration. New Mass Spectrometry based chemical microscopes that target biomedical tissue analysis in various diseases as well as other chemically complex surfaces have now firmly established themselves in translational research. In concert they elucidate the way in which local environments can influence molecular signaling pathways on various scales, from molecule to man. The integration of this pathway information in a surgical setting is imminent, but innovations that push the boundaries of the technology and its application are still needed. In particular, researchers investigate comprehensive and isolated biomolecular molecular patterns of health and disease. This is a key element needed to pave the way for personalized medicine and tissue regeneration. One barrier to predictive, personalized medicine is the lack of a comprehensive molecular understanding at the ti...

Profiling the metabolic signals involved in chemical communication between microbes using imaging mass spectrometry.

Science.gov (United States)

Stasulli, Nikolas M; Shank, Elizabeth A

2016-11-01

The ability of microbes to secrete bioactive chemical signals into their environment has been known for over a century. However, it is only in the last decade that imaging mass spectrometry has provided us with the ability to directly visualize the spatial distributions of these microbial metabolites. This technology involves collecting mass spectra from multiple discrete locations across a biological sample, yielding chemical ‘maps’ that simultaneously reveal the distributions of hundreds of metabolites in two dimensions. Advances in microbial imaging mass spectrometry summarized here have included the identification of novel strain- or coculture-specific compounds, the visualization of biotransformation events (where one metabolite is converted into another by a neighboring microbe), and the implementation of a method to reconstruct the 3D subsurface distributions of metabolites, among others. Here we review the recent literature and discuss how imaging mass spectrometry has spurred novel insights regarding the chemical consequences of microbial interactions.

Image-guided urologic surgery: intraoperative optical imaging and tissue interrogation (Conference Presentation)

Science.gov (United States)

Liao, Joseph C.

2017-02-01

Emerging optical imaging technologies can be integrated in the operating room environment during minimally invasive and open urologic surgery, including oncologic surgery of the bladder, prostate, and kidney. These technologies include macroscopic fluorescence imaging that provides contrast enhancement between normal and diseased tissue and microscopic imaging that provides tissue characterization. Optical imaging technologies that have reached the clinical arena in urologic surgery are reviewed, including photodynamic diagnosis, near infrared fluorescence imaging, optical coherence tomography, and confocal laser endomicroscopy. Molecular imaging represents an exciting future arena in conjugating cancer-specific contrast agents to fluorophores to improve the specificity of disease detection. Ongoing efforts are underway to translate optimal targeting agents and imaging modalities, with the goal to improve cancer-specific and functional outcomes.

Functional imaging of small tissue volumes with diffuse optical tomography

Science.gov (United States)

Klose, Alexander D.; Hielscher, Andreas H.

2006-03-01

Imaging of dynamic changes in blood parameters, functional brain imaging, and tumor imaging are the most advanced application areas of diffuse optical tomography (DOT). When dealing with the image reconstruction problem one is faced with the fact that near-infrared photons, unlike X-rays, are highly scattered when they traverse biological tissue. Image reconstruction schemes are required that model the light propagation inside biological tissue and predict measurements on the tissue surface. By iteratively changing the tissue-parameters until the predictions agree with the real measurements, a spatial distribution of optical properties inside the tissue is found. The optical properties can be related to the tissue oxygenation, inflammation, or to the fluorophore concentration of a biochemical marker. If the model of light propagation is inaccurate, the reconstruction process will lead to an inaccurate result as well. Here, we focus on difficulties that are encountered when DOT is employed for functional imaging of small tissue volumes, for example, in cancer studies involving small animals, or human finger joints for early diagnosis of rheumatoid arthritis. Most of the currently employed image reconstruction methods rely on the diffusion theory that is an approximation to the equation of radiative transfer. But, in the cases of small tissue volumes and tissues that contain low scattering regions diffusion theory has been shown to be of limited applicability Therefore, we employ a light propagation model that is based on the equation of radiative transfer, which promises to overcome the limitations.

Combined spectroscopic imaging and chemometric approach for automatically partitioning tissue types in human prostate tissue biopsies

Science.gov (United States)

Haka, Abigail S.; Kidder, Linda H.; Lewis, E. Neil

2001-07-01

We have applied Fourier transform infrared (FTIR) spectroscopic imaging, coupling a mercury cadmium telluride (MCT) focal plane array detector (FPA) and a Michelson step scan interferometer, to the investigation of various states of malignant human prostate tissue. The MCT FPA used consists of 64x64 pixels, each 61 micrometers 2, and has a spectral range of 2-10.5 microns. Each imaging data set was collected at 16-1 resolution, resulting in 512 image planes and a total of 4096 interferograms. In this article we describe a method for separating different tissue types contained within FTIR spectroscopic imaging data sets of human prostate tissue biopsies. We present images, generated by the Fuzzy C-Means clustering algorithm, which demonstrate the successful partitioning of distinct tissue type domains. Additionally, analysis of differences in the centroid spectra corresponding to different tissue types provides an insight into their biochemical composition. Lastly, we demonstrate the ability to partition tissue type regions in a different data set using centroid spectra calculated from the original data set. This has implications for the use of the Fuzzy C-Means algorithm as an automated technique for the separation and examination of tissue domains in biopsy samples.

Spatial organization of lipids in the human retina and optic nerve by MALDI imaging mass spectrometry.

Science.gov (United States)

Zemski Berry, Karin A; Gordon, William C; Murphy, Robert C; Bazan, Nicolas G

2014-03-01

MALDI imaging mass spectrometry (IMS) was used to characterize lipid species within sections of human eyes. Common phospholipids that are abundant in most tissues were not highly localized and observed throughout the accessory tissue, optic nerve, and retina. Triacylglycerols were highly localized in accessory tissue, whereas sulfatide and plasmalogen glycerophosphoethanolamine (PE) lipids with a monounsaturated fatty acid were found enriched in the optic nerve. Additionally, several lipids were associated solely with the inner retina, photoreceptors, or retinal pigment epithelium (RPE); a plasmalogen PE lipid containing DHA (22:6), PE(P-18:0/22:6), was present exclusively in the inner retina, and DHA-containing glycerophosphatidylcholine (PC) and PE lipids were found solely in photoreceptors. PC lipids containing very long chain (VLC)-PUFAs were detected in photoreceptors despite their low abundance in the retina. Ceramide lipids and the bis-retinoid, N-retinylidene-N-retinylethanolamine, was tentatively identified and found only in the RPE. This MALDI IMS study readily revealed the location of many lipids that have been associated with degenerative retinal diseases. Complex lipid localization within retinal tissue provides a global view of lipid organization and initial evidence for specific functions in localized regions, offering opportunities to assess their significance in retinal diseases, such as macular degeneration, where lipids have been implicated in the disease process.

Metabolite localization by atmospheric pressure high-resolution scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging in whole-body sections and individual organs of the rove beetle Paederus riparius.

Science.gov (United States)

Bhandari, Dhaka Ram; Schott, Matthias; Römpp, Andreas; Vilcinskas, Andreas; Spengler, Bernhard

2015-03-01

Mass spectrometry imaging provides for non-targeted, label-free chemical imaging. In this study, atmospheric pressure high-resolution scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) was used for the first time to describe the chemical distribution of the defensive compounds pederin, pseudopederin, and pederon in tissue sections (16 μm thick) of the rove beetle Paederus riparius. The whole-insect tissue section was scanned with a 20-μm step size. Mass resolution of the orbital trapping mass spectrometer was set to 100,000 at m/z 200. Additionally, organ-specific compounds were identified for brain, nerve cord, eggs, gut, ovaries, and malpighian tubules. To confirm the distribution of the specific compounds, individual organs from the insect were dissected, and MSI experiments were performed on the dissected organs. Three ganglia of the nerve cord, with a dimension of 250-500 μm, were measured with 10-μm spatial resolution. High-quality m/z images, based on high spatial resolution and high mass accuracy were generated. These features helped to assign mass spectral peaks with high confidence. Mass accuracy of the imaging experiments was section. Without any labeling, we assigned key lipids for specific organs to describe their location in the body and to identify morphological structures with a specificity higher than with staining or immunohistology methods.

Determination of d-limonene in adipose tissue by gas chromatography-mass spectrometry

Science.gov (United States)

Miller, Jessica A.; Hakim, Iman A.; Thomson, Cynthia; Thompson, Patricia; Chow, H-H. Sherry

2008-01-01

We developed a novel method for analyzing d-limonene levels in adipose tissue. Fat samples were subjected to saponification followed by solvent extraction. d-Limonene in the sample extract was analyzed using gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring. Linear calibration curves were established over the mass range of 79.0-2,529 ng d-limonene per 0.1 grams of adipose tissue. Satisfactory within day precision (RSD 6.7 to 9.6%) and accuracy (% difference of −2.7 to 3.8%) and between day precision (RSD 6.0 to 10.7%) and accuracy (% difference of 1.8 to 2.6%) were achieved. The assay was successfully applied to human fat biopsy samples from a d-limonene feeding trial. PMID:18571481

Magnetic resonance imaging of peripheral soft tissue hemangiomas

Energy Technology Data Exchange (ETDEWEB)

Nelson, M C; Stull, M A; Patt, R H; Freedman, M T [Georgetown Univ., Washington, DC (USA). Dept. of Radiology; Teitelbaum, G P [Georgetown Univ., Washington, DC (USA). Dept. of Radiology University of Southern California, Los Angeles (USA). Dept. of Radiology; Lack, E E [Georgetown Univ., Washington, DC (USA). Dept. of Pathology; Bogumill, G P [Georgetown Univ., Washington, DC (USA). Dept. of Orthopedic Surgery

1990-10-01

Ten patients with soft tissue hemangiomas outside the central nervous system were studied with MR imaging. Eight patients were studied at 1.5 Tesla (T) with T{sub 1}-weighted and triple echo T{sub 2}-weighted sequences. Two additional patients were imaged on a 0.5-T system. The MR images were correlated with images from other modalities. It was found that prolonged T{sub 2}-weighted imaging together with standard spin echo T{sub 1} and T{sub 2} pulse sequences is a good substitute for contrast-enhanced CT and arteriographic evaluation of soft tissue hemangiomas. (orig./DG).

Spatially resolved chemical analysis of cicada wings using laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS).

Science.gov (United States)

Román, Jessica K; Walsh, Callee M; Oh, Junho; Dana, Catherine E; Hong, Sungmin; Jo, Kyoo D; Alleyne, Marianne; Miljkovic, Nenad; Cropek, Donald M

2018-03-01

Laser-ablation electrospray ionization (LAESI) imaging mass spectrometry (IMS) is an emerging bioanalytical tool for direct imaging and analysis of biological tissues. Performing ionization in an ambient environment, this technique requires little sample preparation and no additional matrix, and can be performed on natural, uneven surfaces. When combined with optical microscopy, the investigation of biological samples by LAESI allows for spatially resolved compositional analysis. We demonstrate here the applicability of LAESI-IMS for the chemical analysis of thin, desiccated biological samples, specifically Neotibicen pruinosus cicada wings. Positive-ion LAESI-IMS accurate ion-map data was acquired from several wing cells and superimposed onto optical images allowing for compositional comparisons across areas of the wing. Various putative chemical identifications were made indicating the presence of hydrocarbons, lipids/esters, amines/amides, and sulfonated/phosphorylated compounds. With the spatial resolution capability, surprising chemical distribution patterns were observed across the cicada wing, which may assist in correlating trends in surface properties with chemical distribution. Observed ions were either (1) equally dispersed across the wing, (2) more concentrated closer to the body of the insect (proximal end), or (3) more concentrated toward the tip of the wing (distal end). These findings demonstrate LAESI-IMS as a tool for the acquisition of spatially resolved chemical information from fragile, dried insect wings. This LAESI-IMS technique has important implications for the study of functional biomaterials, where understanding the correlation between chemical composition, physical structure, and biological function is critical. Graphical abstract Positive-ion laser-ablation electrospray ionization mass spectrometry coupled with optical imaging provides a powerful tool for the spatially resolved chemical analysis of cicada wings.

Interactive classification and content-based retrieval of tissue images

Science.gov (United States)

Aksoy, Selim; Marchisio, Giovanni B.; Tusk, Carsten; Koperski, Krzysztof

2002-11-01

We describe a system for interactive classification and retrieval of microscopic tissue images. Our system models tissues in pixel, region and image levels. Pixel level features are generated using unsupervised clustering of color and texture values. Region level features include shape information and statistics of pixel level feature values. Image level features include statistics and spatial relationships of regions. To reduce the gap between low-level features and high-level expert knowledge, we define the concept of prototype regions. The system learns the prototype regions in an image collection using model-based clustering and density estimation. Different tissue types are modeled using spatial relationships of these regions. Spatial relationships are represented by fuzzy membership functions. The system automatically selects significant relationships from training data and builds models which can also be updated using user relevance feedback. A Bayesian framework is used to classify tissues based on these models. Preliminary experiments show that the spatial relationship models we developed provide a flexible and powerful framework for classification and retrieval of tissue images.

The role of fat tissues in the diagnosis of musculoskeletal imaging

International Nuclear Information System (INIS)

Kim, Sue Yon; Park, Ji Seon; Ryu, Kyung Nam; Jin, Wook

2007-01-01

Fat tissue is a unique component of the soft tissue, and this fat tissue lies primarily in the spaces beneath the normal subcutaneous tissue, and within or around the organs. An entire lesion, or just a part of it, can be composed of these fat tissues. Therefore, it plays an important role in the diagnostic workup of suspected musculoskeletal diseases as well as in the differentiation between them. Fat tissue is shown as low density on plain radiographs, decreased attenuation on CT images, high signal intensity on T1-weighted images and it is hypoechoic on sonography. Because of its distinctive features, fat tissue is easy to verify on various modalities. In addition, recent image studies like fat-suppressed imaging and STIR imaging provide more precise information of the lesion that involve fat tissue. In this article, we have reviewed the differentiation of musculoskeletal diseases, including the various tumorous lesion and tumor-like lesions involving the fat tissue

Characterization of human breast cancer tissues by infrared imaging.

Science.gov (United States)

Verdonck, M; Denayer, A; Delvaux, B; Garaud, S; De Wind, R; Desmedt, C; Sotiriou, C; Willard-Gallo, K; Goormaghtigh, E

2016-01-21

Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins.

Deep learning for tumor classification in imaging mass spectrometry.

Science.gov (United States)

Behrmann, Jens; Etmann, Christian; Boskamp, Tobias; Casadonte, Rita; Kriegsmann, Jörg; Maaß, Peter

2018-04-01

Tumor classification using imaging mass spectrometry (IMS) data has a high potential for future applications in pathology. Due to the complexity and size of the data, automated feature extraction and classification steps are required to fully process the data. Since mass spectra exhibit certain structural similarities to image data, deep learning may offer a promising strategy for classification of IMS data as it has been successfully applied to image classification. Methodologically, we propose an adapted architecture based on deep convolutional networks to handle the characteristics of mass spectrometry data, as well as a strategy to interpret the learned model in the spectral domain based on a sensitivity analysis. The proposed methods are evaluated on two algorithmically challenging tumor classification tasks and compared to a baseline approach. Competitiveness of the proposed methods is shown on both tasks by studying the performance via cross-validation. Moreover, the learned models are analyzed by the proposed sensitivity analysis revealing biologically plausible effects as well as confounding factors of the considered tasks. Thus, this study may serve as a starting point for further development of deep learning approaches in IMS classification tasks. https://gitlab.informatik.uni-bremen.de/digipath/Deep_Learning_for_Tumor_Classification_in_IMS. jbehrmann@uni-bremen.de or christianetmann@uni-bremen.de. Supplementary data are available at Bioinformatics online.

Artificial neural net system for interactive tissue classification with MR imaging and image segmentation

International Nuclear Information System (INIS)

Clarke, L.P.; Silbiger, M.; Naylor, C.; Brown, K.

1990-01-01

This paper reports on the development of interactive methods for MR tissue classification that permit mathematically rigorous methods for three-dimensional image segmentation and automatic organ/tumor contouring, as required for surgical and RTP planning. The authors investigate a number of image-intensity based tissue- classification methods that make no implicit assumptions on the MR parameters and hence are not limited by image data set. Similarly, we have trained artificial neural net (ANN) systems for both supervised and unsupervised tissue classification

New methods for multimodal MS imaging of histological tissue sections

NARCIS (Netherlands)

Amstalden Van Hove, E.R.

2011-01-01

The insights derived from spatial localization of molecules in tissue sections are of great value for understanding and treating cancer and other diseases. These insights can relate to molecules linked to a disease as well as to drug molecules distributed across organs of interest. Mass spectrometry

MARS spectral molecular imaging of lamb tissue: data collection and image analysis

CERN Document Server

Aamir, R; Bateman, C.J.; Butler, A.P.H.; Butler, P.H.; Anderson, N.G.; Bell, S.T.; Panta, R.K.; Healy, J.L.; Mohr, J.L.; Rajendran, K.; Walsh, M.F.; Ruiter, N.de; Gieseg, S.P.; Woodfield, T.; Renaud, P.F.; Brooke, L.; Abdul-Majid, S.; Clyne, M.; Glendenning, R.; Bones, P.J.; Billinghurst, M.; Bartneck, C.; Mandalika, H.; Grasset, R.; Schleich, N.; Scott, N.; Nik, S.J.; Opie, A.; Janmale, T.; Tang, D.N.; Kim, D.; Doesburg, R.M.; Zainon, R.; Ronaldson, J.P.; Cook, N.J.; Smithies, D.J.; Hodge, K.

2014-01-01

Spectral molecular imaging is a new imaging technique able to discriminate and quantify different components of tissue simultaneously at high spatial and high energy resolution. Our MARS scanner is an x-ray based small animal CT system designed to be used in the diagnostic energy range (20 to 140 keV). In this paper, we demonstrate the use of the MARS scanner, equipped with the Medipix3RX spectroscopic photon-processing detector, to discriminate fat, calcium, and water in tissue. We present data collected from a sample of lamb meat including bone as an illustrative example of human tissue imaging. The data is analyzed using our 3D Algebraic Reconstruction Algorithm (MARS-ART) and by material decomposition based on a constrained linear least squares algorithm. The results presented here clearly show the quantification of lipid-like, water-like and bone-like components of tissue. However, it is also clear to us that better algorithms could extract more information of clinical interest from our data. Because we ...

Phospholipid Topography of Whole-Body Sections of the Anopheles stephensi Mosquito, Characterized by High-Resolution Atmospheric-Pressure Scanning Microprobe Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

Science.gov (United States)

Khalil, Saleh M; Römpp, Andreas; Pretzel, Jette; Becker, Katja; Spengler, Bernhard

2015-11-17

High-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) has been employed to study the molecular anatomical structure of rodent malaria vector Anopheles stephensi mosquitoes. A dedicated sample preparation method was developed which suits both, the special tissue properties of the sample and the requirements of high-resolution MALDI imaging. Embedding in 5% carboxymethylcellulose (CMC) was used to maintain the tissue integrity of the whole mosquitoes, being very soft, fragile, and difficult to handle. Individual lipid compounds, specifically representing certain cell types, tissue areas, or organs, were detected and imaged in 20 μm-thick whole-body tissue sections at a spatial resolution of 12 μm per image pixel. Mass spectrometric data and information quality were based on a mass resolution of 70,000 (at m/z 200) and a mass accuracy of better than 2 ppm in positive-ion mode on an orbital trapping mass spectrometer. A total of 67 imaged lipids were assigned by database search and, in a number of cases, identified via additional MS/MS fragmentation studies directly from tissue. This is the first MSI study at 12 μm spatial resolution of the malaria vector Anopheles. The study provides insights into the molecular anatomy of Anopheles stephensi and the distribution and localization of major classes of glycerophospholipids and sphingolipids. These data can be a basis for future experiments, investigating, e.g., the metabolism of Plasmodium-infected and -uninfected Anopheles mosquitoes.

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

Science.gov (United States)

Steinhauser, Matthew L.; Lechene, Claude P.

2014-01-01

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

Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry.

Science.gov (United States)

Shariatgorji, Mohammadreza; Strittmatter, Nicole; Nilsson, Anna; Källback, Patrik; Alvarsson, Alexandra; Zhang, Xiaoqun; Vallianatou, Theodosia; Svenningsson, Per; Goodwin, Richard J A; Andren, Per E

2016-08-01

With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyramine, serotonin, glutamate, glutamine, aspartate, γ-aminobutyric acid, adenosine) as well as neuroactive drugs (amphetamine, sibutramine, fluvoxamine) and drug metabolites in situ directly in brain tissue sections. The use of both positive and negative ionization modes increased the number of identified molecular targets. Chemical derivatization by charge-tagging the primary amines of molecules significantly increased the sensitivity, enabling the detection of low abundant neurotransmitters and other neuroactive substances previously undetectable by MSI. The sensitivity of the imaging approach of neurochemicals has a great potential in many diverse applications in fields such as neuroscience, pharmacology, drug discovery, neurochemistry, and medicine. Copyright © 2016 Elsevier Inc. All rights reserved.

Prompt gamma-ray spectrometry for measurement of B-10 concentration in brain tissue and blood

International Nuclear Information System (INIS)

Nakagawa, Yoshinobu; Kitamura, Katsuji; Kobayashi, Toru; Matsumoto, Keizo; Hatanaka, Hiroshi.

1993-01-01

Boron-10 (B-10) concentration in the brain tissue and blood was measured continuously for 24 hours after injection of the B-10 compound in live rabbits using prompt gamma-ray spectrometry. Following injection of B-10 compound (Na 2 B 12 H 11 SH, 50mg/kg) dissolved in physiological saline, B-10 concentration was continuously measured in the brain tissue. Intermittently the concentration of B-10 in blood and cerebro-spinal fluid (CSF) was also measured. In 10 minutes after the injection of B-10 compound, the level of B-10 concentration reached the peak of 400-500 ppm in blood and 20-30 ppm in the normal brain tissue. In 60 minutes the level of B-10 concentration rapidly decreased and then a gradual decline was observed. The value was 15-30 ppm at 3 hours after injection, 5-10 ppm at 6 hours and 2-5 ppm at 24 hours in the blood. The concentration in the brain tissue was 3-8 ppm at 3 hours, 2-5 ppm at 6 hours and below 1.5 ppm at 24 hours. B-10 concentration in cerebro-spinal fluid was below 1 ppm. B-10 concentration was also measured in the brain tumor and blood in the human cases at boron neutron capture therapy (BNCT). These data studied by prompt gamma-ray spectrometry are very important and useful to decide the irradiation time. (author)

Mass spectrometry-based analysis of the HLA-ligandomes of renal cell carcinoma and benign renal tissue

OpenAIRE

Rabsteyn, Armin

2018-01-01

Peptide vaccination is a promising immunotherapeutic approach for the treatment of malignancies. In this project, the unique opportunity to analyze HLA ligandomes of samples from tumor and adjacent benign tissue of renal cell carcinoma (RCC) patients by mass spectrometry was given. This allowed for the establishment of a novel approach of antigen definition by comparative profiling of malignant and benign HLA ligandomes. Analyses were performed for HLA class I and II of tumor and benign tissu...

High Spatial Resolution Imaging Mass Spectrometry of Human Optic Nerve Lipids and Proteins

Science.gov (United States)

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.

Automatic tissue image segmentation based on image processing and deep learning

Science.gov (United States)

Kong, Zhenglun; Luo, Junyi; Xu, Shengpu; Li, Ting

2018-02-01

Image segmentation plays an important role in multimodality imaging, especially in fusion structural images offered by CT, MRI with functional images collected by optical technologies or other novel imaging technologies. Plus, image segmentation also provides detailed structure description for quantitative visualization of treating light distribution in the human body when incorporated with 3D light transport simulation method. Here we used image enhancement, operators, and morphometry methods to extract the accurate contours of different tissues such as skull, cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) on 5 fMRI head image datasets. Then we utilized convolutional neural network to realize automatic segmentation of images in a deep learning way. We also introduced parallel computing. Such approaches greatly reduced the processing time compared to manual and semi-automatic segmentation and is of great importance in improving speed and accuracy as more and more samples being learned. Our results can be used as a criteria when diagnosing diseases such as cerebral atrophy, which is caused by pathological changes in gray matter or white matter. We demonstrated the great potential of such image processing and deep leaning combined automatic tissue image segmentation in personalized medicine, especially in monitoring, and treatments.

Imaging of soft tissue sarcomas

International Nuclear Information System (INIS)

Vanel, D.; Le Treut, A.

1988-01-01

Modern imaging of soft tissue sarcomas now includes ultrasounds, CT and MRI. These new techniques allow a better evaluation of initial local extension, of the response to treatment and are able to detect local recurrences early [fr

Quantitative imaging of single upconversion nanoparticles in biological tissue.

Directory of Open Access Journals (Sweden)

Annemarie Nadort

Full Text Available The unique luminescent properties of new-generation synthetic nanomaterials, upconversion nanoparticles (UCNPs, enabled high-contrast optical biomedical imaging by suppressing the crowded background of biological tissue autofluorescence and evading high tissue absorption. This raised high expectations on the UCNP utilities for intracellular and deep tissue imaging, such as whole animal imaging. At the same time, the critical nonlinear dependence of the UCNP luminescence on the excitation intensity results in dramatic signal reduction at (∼1 cm depth in biological tissue. Here, we report on the experimental and theoretical investigation of this trade-off aiming at the identification of optimal application niches of UCNPs e.g. biological liquids and subsurface tissue layers. As an example of such applications, we report on single UCNP imaging through a layer of hemolyzed blood. To extend this result towards in vivo applications, we quantified the optical properties of single UCNPs and theoretically analyzed the prospects of single-particle detectability in live scattering and absorbing bio-tissue using a human skin model. The model predicts that a single 70-nm UCNP would be detectable at skin depths up to 400 µm, unlike a hardly detectable single fluorescent (fluorescein dye molecule. UCNP-assisted imaging in the ballistic regime thus allows for excellent applications niches, where high sensitivity is the key requirement.

Visualisation of abscisic acid and 12-oxo-phytodienoic acid in immature Phaseolus vulgaris L. seeds using desorption electrospray ionisation-imaging mass spectrometry

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Enomoto, Hirofumi; Sensu, Takuya; Sato, Kei; Sato, Futoshi; Paxton, Thanai; Yumoto, Emi; Miyamoto, Koji; Asahina, Masashi; Yokota, Takao; Yamane, Hisakazu

2017-02-01

The plant hormone abscisic acid (ABA) and the jasmonic acid related-compound 12-oxo-phytodienoic acid (OPDA) play crucial roles in seed development, dormancy, and germination. However, a lack of suitable techniques for visualising plant hormones has restricted the investigation of their biological mechanisms. In the present study, desorption electrospray ionisation-imaging mass spectrometry (DESI-IMS), a powerful tool for visualising metabolites in biological tissues, was used to visualise ABA and OPDA in immature Phaseolus vulgaris L. seed sections. The mass spectra, peak values and chemical formulae obtained from the analysis of seed sections were consistent with those determined for ABA and OPDA standards, as were the precursor and major fragment ions observed in tandem mass spectrometry (MS/MS) imaging. Furthermore, the precursor and fragment ion images showed similar distribution patterns. In addition, the localisation of ABA and OPDA using DESI-IMS was confirmed using liquid chromatography-MS/MS (LC-MS/MS). The results indicated that ABA was mainly distributed in the radical and cotyledon of the embryo, whereas OPDA was distributed exclusively in external structures, such as the hilum and seed coat. The present study is the first to report the visualisation of plant hormones using IMS, and demonstrates that DESI-IMS is a promising technique for future plant hormone research.

A high-resolution optical imaging system for obtaining the serial transverse section images of biologic tissue

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Wu, Li; Zhang, Bin; Wu, Ping; Liu, Qian; Gong, Hui

2007-05-01

A high-resolution optical imaging system was designed and developed to obtain the serial transverse section images of the biologic tissue, such as the mouse brain, in which new knife-edge imaging technology, high-speed and high-sensitive line-scan CCD and linear air bearing stages were adopted and incorporated with an OLYMPUS microscope. The section images on the tip of the knife-edge were synchronously captured by the reflection imaging in the microscope while cutting the biologic tissue. The biologic tissue can be sectioned at interval of 250 nm with the same resolution of the transverse section images obtained in x and y plane. And the cutting job can be automatically finished based on the control program wrote specially in advance, so we save the mass labor of the registration of the vast images data. In addition, by using this system a larger sample can be cut than conventional ultramicrotome so as to avoid the loss of the tissue structure information because of splitting the tissue sample to meet the size request of the ultramicrotome.

Preparation of Single Cells for Imaging Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

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.

A survey of clearing techniques for 3D imaging of tissues with special reference to connective tissue.

Science.gov (United States)

Azaripour, Adriano; Lagerweij, Tonny; Scharfbillig, Christina; Jadczak, Anna Elisabeth; Willershausen, Brita; Van Noorden, Cornelis J F

2016-08-01

For 3-dimensional (3D) imaging of a tissue, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1° clearing of the opaque tissue to render it transparent for microscopy, 2° fluorescence labeling of the tissues and 3° 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most clearing techniques have been applied to the central nervous system and other organs that contain relatively low amounts of connective tissue including extracellular matrix. However, tissues that contain large amounts of extracellular matrix such as dermis in skin or gingiva are difficult to clear. The present survey lists methodologies that are available for clearing of tissues for 3D imaging. We report here that the BABB method using a mixture of benzyl alcohol and benzyl benzoate and iDISCO using dibenzylether (DBE) are the most successful methods for clearing connective tissue-rich gingiva and dermis of skin for 3D histochemistry and imaging of fluorescence using light-sheet microscopy. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Influence of Desorption Conditions on Analyte Sensitivity and Internal Energy in Discrete Tissue or Whole Body Imaging by IR-MALDESI

Science.gov (United States)

Rosen, Elias P.; Bokhart, Mark T.; Ghashghaei, H. Troy; Muddiman, David C.

2015-06-01

Analyte signal in a laser desorption/postionization scheme such as infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) is strongly coupled to the degree of overlap between the desorbed plume of neutral material from a sample and an orthogonal electrospray. In this work, we systematically examine the effect of desorption conditions on IR-MALDESI response to pharmaceutical drugs and endogenous lipids in biological tissue using a design of experiments approach. Optimized desorption conditions have then been used to conduct an untargeted lipidomic analysis of whole body sagittal sections of neonate mouse. IR-MALDESI response to a wide range of lipid classes has been demonstrated, with enhanced lipid coverage received by varying the laser wavelength used for mass spectrometry imaging (MSI). Targeted MS2 imaging (MS2I) of an analyte, cocaine, deposited beneath whole body sections allowed determination of tissue-specific ion response factors, and CID fragments of cocaine were monitored to comment on wavelength-dependent internal energy deposition based on the "survival yield" method.

Pitfalls in soft tissue sarcoma imaging: chronic expanding hematomas.

Science.gov (United States)

Jahed, Kiarash; Khazai, Behnaz; Umpierrez, Monica; Subhawong, Ty K; Singer, Adam D

2018-01-01

Solid or nodular enhancement is typical of soft tissue sarcomas although high grade soft tissue sarcomas and those with internal hemorrhage often appear heterogeneous with areas of nonenhancement and solid or nodular enhancement. These MRI findings often prompt an orthopedic oncology referral, a biopsy or surgery. However, not all masses with these imaging findings are malignant. We report the multimodality imaging findings of two surgically proven chronic expanding hematomas (CEH) with imaging features that mimicked sarcomas. A third case of nonenhancing CEH of the lower extremity is also presented as a comparison. It is important that in the correct clinical scenario with typical imaging findings, the differential diagnosis of a chronic expanding hematoma be included in the workup of these patients. An image-guided biopsy of nodular tissue within such masses that proves to be negative for malignancy should not necessarily be considered discordant. A correct diagnosis may prevent a morbid unnecessary surgery and may indicate the need for a conservative noninvasive follow-up with imaging.

Imaging of single cells and tissue using MeV ions

International Nuclear Information System (INIS)

Watt, F.; Bettiol, A.A.; Kan, J.A. van; Ynsa, M.D.; Ren Minqin; Rajendran, R.; Cui Huifang; Sheu, F.-S.; Jenner, A.M.

2009-01-01

With the attainment of sub-100 nm high energy (MeV) ion beams, comes the opportunity to image cells and tissue at nano-dimensions. The advantage of MeV ion imaging is that the ions will penetrate whole cells, or relatively thick tissue sections, without any significant loss of resolution. In this paper, we demonstrate that whole cells (cultured N2A neuroblastoma cells ATCC) and tissue sections (rabbit pancreas tissue) can be imaged at sub-100 nm resolutions using scanning transmission ion microscopy (STIM), and that sub-cellular structural details can be identified. In addition to STIM imaging we have also demonstrated for the first time, that sub-cellular proton induced fluorescence imaging (on cultured N2A neuroblastoma cells ATCC) can also be carried out at resolutions of 200 nm, compared with 300-400 nm resolutions achieved by conventional optical fluorescence imaging. The combination of both techniques offers a potentially powerful tool in the quest for elucidating cell function, particularly when it should be possible in the near future to image down to sub-50 nm.

A new standard of visual data representation for imaging mass spectrometry.

Science.gov (United States)

O'Rourke, Matthew B; Padula, Matthew P

2017-03-01

MALDI imaging MS (IMS) is principally used for cancer diagnostics. In our own experience with publishing IMS data, we have been requested to modify our protocols with respect to the areas of the tissue that are imaged in order to comply with the wider literature. In light of this, we have determined that current methodologies lack effective controls and can potentially introduce bias by only imaging specific areas of the targeted tissue EXPERIMENTAL DESIGN: A previously imaged sample was selected and then cropped in different ways to show the potential effect of only imaging targeted areas. By using a model sample, we were able to effectively show how selective imaging of samples can misinterpret tissue features and by changing the areas that are acquired, according to our new standard, an effective internal control can be introduced. Current IMS sampling convention relies on the assumption that sample preparation has been performed correctly. This prevents users from checking whether molecules have moved beyond borders of the tissue due to delocalization and consequentially products of improper sample preparation could be interpreted as biological features that are of critical importance when encountered in a visual diagnostic. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three-dimensional CT imaging of soft-tissue anatomy

International Nuclear Information System (INIS)

Fishman, E.K.; Ney, D.R.; Magid, D.; Kuhlman, J.E.

1988-01-01

Three-dimensional display of computed tomographic data has been limited to skeletal structures. This was in part related to the reconstruction algorithm used, which relied on a binary classification scheme. A new algorithm, volumetric rendering with percentage classification, provides the ability to display three-dimensional images of muscle and soft tissue. A review was conducted of images in 35 cases in which muscle and/or soft tissue were part of the clinical problem. In all cases, individual muscle groups could be clearly identified and discriminated. Branching vessels in the range of 2.3 mm could be identified. Similarly, lymph nodes could be clearly defined. High-resolution three-dimensional images were found to be useful both in providing an increased understanding of complex muscle and soft tissue anatomy and in surgical planning

Clinical evaluation of Synthetic Aperture Sequential Beamforming and Tissue Harmonic Imaging

DEFF Research Database (Denmark)

Brandt, Andreas Hjelm; Hemmsen, Martin Christian; Hansen, Peter Møller

2014-01-01

This study determines if the data reduction achieved by the combination Synthetic Aperture Sequential Beamforming (SASB) and Tissue Harmonic Imaging (THI) affects image quality. SASB-THI was evaluated against the combination of Dynamic Received Focusing and Tissue Harmonic Imaging (DRF-THI). A BK...... equally good image quality although a data reduction of 64 times is achieved with SASB-THI.......This study determines if the data reduction achieved by the combination Synthetic Aperture Sequential Beamforming (SASB) and Tissue Harmonic Imaging (THI) affects image quality. SASB-THI was evaluated against the combination of Dynamic Received Focusing and Tissue Harmonic Imaging (DRF-THI). A BK...... liver pathology were scanned to set a clinical condition, where ultrasonography is often performed. A total of 114 sequences were recorded and evaluated by five radiologists. The evaluators were blinded to the imaging technique, and each sequence was shown twice with different left-right positioning...

Connecting imaging mass spectrometry and magnetic resonance imaging-based anatomical atlases for automated anatomical interpretation and differential analysis.

Science.gov (United States)

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

2017-07-01

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 and dimensionality 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. The measurements 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. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2017. Published by Elsevier B.V.

Imaging MALDI mass spectrometry using an oscillating capillary nebulizer matrix coating system and its application to analysis of lipids in brain from a mouse model of Tay-Sachs/Sandhoff disease.

Science.gov (United States)

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

2008-04-15

The quality of tissue imaging by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) depends on the effectiveness of the matrix deposition, especially for lipids that may dissolve in the solvent used for the matrix application. This article describes the use of an oscillating capillary nebulizer (OCN) to spray small droplets of matrix aerosol onto the sample surface for improved matrix homogeneity, reduced crystal size, and controlled solvent effects. This system was then applied to the analysis of histological slices of brains from mice with homozygous disruption of the hexb gene (hexb-/-), a model of Tay-Sachs and Sandhoff disease, versus the functionally normal heterozygote (hexb+/-) by imaging MALDI-MS. This allowed profiling and localization of many different lipid species, and of particular interest, ganglioside GM2, asialo-GM2 (GA2), and sulfatides (ST). The presence of these compounds was confirmed by analysis of brain extracts using electrospray ionization in conjunction with tandem mass spectrometry (MS/MS). The major fatty acid of the ceramide backbone of both GM2 and GA2 was identified as stearic acid (18:0) versus nervonic acid (24:1) for ST by both tissue-imaging MS and ESI-MS/MS. GM2 and GA2 were highly elevated in hexb-/- and were both localized in the granular cell region of the cerebellum. ST, however, was localized mainly in myelinated fiber (white matter) region of the cerebellum as well as in the brain stem with a relatively uniform distribution and had similar relative signal intensity for both hexb+/- and hexb-/- brain. It was also observed that there were distinct localizations for numerous other lipid subclasses; hence, imaging MALDI-MS could be used for "lipidomic" studies. These results illustrate the usefulness of tissue-imaging MALDI-MS with matrix deposition by OCN for histologic comparison of lipids in tissues such as brains from this mouse model of Tay-Sachs and Sandhoff disease.

Molecular identification of Mucorales in human tissues: contribution of PCR electrospray-ionization mass spectrometry.

Science.gov (United States)

Alanio, A; Garcia-Hermoso, D; Mercier-Delarue, S; Lanternier, F; Gits-Muselli, M; Menotti, J; Denis, B; Bergeron, A; Legrand, M; Lortholary, O; Bretagne, S

2015-06-01

Molecular methods are crucial for mucormycosis diagnosis because cultures are frequently negative, even if microscopy suggests the presence of hyphae in tissues. We assessed PCR/electrospray-ionization mass spectrometry (PCR/ESI-MS) for Mucorales identification in 19 unfixed tissue samples from 13 patients with proven or probable mucormycosis and compared the results with culture, quantitative real-time PCR, 16S-23S rRNA gene internal transcribed spacer region (ITS PCR) and 18S PCR sequencing. Concordance with culture identification to both genus and species levels was higher for PCR/ESI-MS than for the other techniques. Thus, PCR/ESI-MS is suitable for Mucorales identification, within 6 hours, for tissue samples for which microscopy results suggest the presence of hyphae. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Utilizing mass spectrometry imaging to map the thyroid hormones triiodothyronine and thyroxine in Xenopus tropicalis tadpoles.

Science.gov (United States)

Goto-Inoue, Naoko; Sato, Tomohiko; Morisasa, Mizuki; Kashiwagi, Akihiko; Kashiwagi, Keiko; Sugiura, Yuki; Sugiyama, Eiji; Suematsu, Makoto; Mori, Tsukasa

2018-02-01

Thyroid hormones are not only responsible for thermogenesis and energy metabolism in animals, but also have an important role in cell differentiation and development. Amphibian metamorphosis provides an excellent model for studying the remodeling of the body. This metamorphic organ remodeling is induced by thyroid hormones, and a larval body is thus converted into an adult one. The matrix-assisted laser desorption/ionization (MALDI)-mass spectrometry (MS) imaging technology is expected to be a suitable tool for investigating small bioreactive molecules. The present study describes the distribution of the thyroid hormones, i.e., triiodothyronine (T3) and thyroxine (T4) and their inactive form reverse T3 (rT3) in Xenopus tropicalis tadpoles using two different types of imaging techniques, MS/MS and Fourier transform (FT)-MS imaging. As a result of MS/MS imaging, we demonstrated that T3 was mainly distributed in the gills. T4 was faintly localized in the eyes, inner gills, and intestine during metamorphosis. The intensity of T3 in the gills and the intensity of T4 in the body fluids were increased during metamorphosis. Moreover, the localization of the inactive form rT3 was demonstrated to be separate from T3, namely in the intestine and muscles. In addition, FT-MS imaging could utilize simultaneous imaging including thyroid hormone. This is the first report to demonstrate the molecular distribution of thyroid hormones themselves and to discriminate T3, T4, and rT3 in animal tissues.

Mass-spectrometry analysis of histone post-translational modifications in pathology tissue using the PAT-H-MS approach

Directory of Open Access Journals (Sweden)

Roberta Noberini

2016-06-01

Full Text Available Aberrant histone post-translational modifications (hPTMs have been implicated with various pathologies, including cancer, and may represent useful epigenetic biomarkers. The data described here provide a mass spectrometry-based quantitative analysis of hPTMs from formalin-fixed paraffin-embedded (FFPE tissues, from which histones were extracted through the recently developed PAT-H-MS method. First, we analyzed FFPE samples from mouse spleen and liver or human breast cancer up to six years old, together with their corresponding fresh frozen tissue. We then combined the PAT-H-MS approach with a histone-focused version of the super-SILAC strategy-using a mix of histones from four breast cancer cell lines as a spike-in standard- to accurately quantify hPTMs from breast cancer specimens belonging to different subtypes. The data, which are associated with a recent publication (Pathology tissue-quantitative mass spectrometry analysis to profile histone post-translational modification patterns in patient samples (Noberini, 2015 [1], are deposited at the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier http://www.ebi.ac.uk/pride/archive/projects/PXD002669.

Exploring surface photoreaction dynamics using pixel imaging mass spectrometry (PImMS)

Science.gov (United States)

Kershis, Matthew D.; Wilson, Daniel P.; White, Michael G.; John, Jaya John; Nomerotski, Andrei; Brouard, Mark; Lee, Jason W. L.; Vallance, Claire; Turchetta, Renato

2013-08-01

A new technique for studying surface photochemistry has been developed using an ion imaging time-of-flight mass spectrometer in conjunction with a fast camera capable of multimass imaging. This technique, called pixel imaging mass spectrometry (PImMS), has been applied to the study of butanone photooxidation on TiO2(110). In agreement with previous studies of this system, it was observed that the main photooxidation pathway for butanone involves ejection of an ethyl radical into vacuum which, as confirmed by our imaging experiment, undergoes fragmentation after ionization in the mass spectrometer. This proof-of-principle experiment illustrates the usefulness and applicability of PImMS technology to problems of interest within the surface science community.

In Situ Analysis of Bacterial Lipopeptide Antibiotics by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging.

Science.gov (United States)

Debois, Delphine; Ongena, Marc; Cawoy, Hélène; De Pauw, Edwin

2016-01-01

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is a technique developed in the late 1990s enabling the two-dimensional mapping of a broad variety of biomolecules present at the surface of a sample. In many applications including pharmaceutical studies or biomarker discovery, the distribution of proteins, lipids or drugs, and metabolites may be visualized within tissue sections. More recently, MALDI MSI has become increasingly applied in microbiology where the versatility of the technique is perfectly suited to monitor the metabolic dynamics of bacterial colonies. The work described here is focused on the application of MALDI MSI to map secondary metabolites produced by Bacilli, especially lipopeptides, produced by bacterial cells during their interaction with their environment (bacteria, fungi, plant roots, etc.). This chapter addresses the advantages and challenges that the implementation of MALDI MSI to microbiological samples entails, including detailed protocols on sample preparation (from both microbiologist and mass spectrometrist points of view), matrix deposition, and data acquisition and interpretation. Lipopeptide images recorded from confrontation plates are also presented.

Blind source separation of ex-vivo aorta tissue multispectral images.

Science.gov (United States)

Galeano, July; Perez, Sandra; Montoya, Yonatan; Botina, Deivid; Garzón, Johnson

2015-05-01

Blind Source Separation methods (BSS) aim for the decomposition of a given signal in its main components or source signals. Those techniques have been widely used in the literature for the analysis of biomedical images, in order to extract the main components of an organ or tissue under study. The analysis of skin images for the extraction of melanin and hemoglobin is an example of the use of BSS. This paper presents a proof of concept of the use of source separation of ex-vivo aorta tissue multispectral Images. The images are acquired with an interference filter-based imaging system. The images are processed by means of two algorithms: Independent Components analysis and Non-negative Matrix Factorization. In both cases, it is possible to obtain maps that quantify the concentration of the main chromophores present in aortic tissue. Also, the algorithms allow for spectral absorbance of the main tissue components. Those spectral signatures were compared against the theoretical ones by using correlation coefficients. Those coefficients report values close to 0.9, which is a good estimator of the method's performance. Also, correlation coefficients lead to the identification of the concentration maps according to the evaluated chromophore. The results suggest that Multi/hyper-spectral systems together with image processing techniques is a potential tool for the analysis of cardiovascular tissue.

Whole slide imaging of unstained tissue using lensfree microscopy

Science.gov (United States)

Morel, Sophie Nhu An; Hervé, Lionel; Bordy, Thomas; Cioni, Olivier; Delon, Antoine; Fromentin, Catherine; Dinten, Jean-Marc; Allier, Cédric

2016-04-01

Pathologist examination of tissue slides provides insightful information about a patient's disease. Traditional analysis of tissue slides is performed under a binocular microscope, which requires staining of the sample and delays the examination. We present a simple cost-effective lensfree imaging method to record 2-4μm resolution wide-field (10 mm2 to 6 cm2) images of unstained tissue slides. The sample processing time is reduced as there is no need for staining. A wide field of view (10 mm2) lensfree hologram is recorded in a single shot and the image is reconstructed in 2s providing a very fast acquisition chain. The acquisition is multispectral, i.e. multiple holograms are recorded simultaneously at three different wavelengths, and a dedicated holographic reconstruction algorithm is used to retrieve both amplitude and phase. Whole tissue slides imaging is obtained by recording 130 holograms with X-Y translation stages and by computing the mosaic of a 25 x 25 mm2 reconstructed image. The reconstructed phase provides a phase-contrast-like image of the unstained specimen, revealing structures of healthy and diseased tissue. Slides from various organs can be reconstructed, e.g. lung, colon, ganglion, etc. To our knowledge, our method is the first technique that enables fast wide-field lensfree imaging of such unlabeled dense samples. This technique is much cheaper and compact than a conventional phase contrast microscope and could be made portable. In sum, we present a new methodology that could quickly provide useful information when a rapid diagnosis is needed, such as tumor margin identification on frozen section biopsies during surgery.

A novel liquid chromatography/mass spectrometry method for determination of neurotransmitters in brain tissue: Application to human tauopathies.

Science.gov (United States)

Forgacsova, Andrea; Galba, Jaroslav; Garruto, Ralph M; Majerova, Petra; Katina, Stanislav; Kovac, Andrej

2018-01-15

Neurotransmitters, small molecules widely distributed in the central nervous system are essential in transmitting electrical signals across neurons via chemical communication. Dysregulation of these chemical signaling molecules is linked to numerous neurological diseases including tauopathies. In this study, a precise and reliable liquid chromatography method was established with tandem mass spectrometry detection for the simultaneous determination of aspartic acid, asparagine, glutamic acid, glutamine, γ-aminobutyric acid, N-acetyl-l-aspartic acid, pyroglutamic acid, acetylcholine and choline in human brain tissue. The method was successfully applied to the analysis of human brain tissues from three different tauopathies; corticobasal degeneration, progressive supranuclear palsy and parkinsonism-dementia complex of Guam. Neurotransmitters were analyzed on ultra-high performance chromatography (UHPLC) using an ethylene bridged hybrid amide column coupled with tandem mass spectrometry (MS/MS). Identification and quantification of neurotransmitters was carried out by ESI+ mass spectrometry detection. We optimized sample preparation to achieve simple and fast extraction of all nine analytes. Our method exhibited an excellent linearity for all analytes (all coefficients of determination >0.99), with inter-day and intra-day precision yielding relative standard deviations 3.2%-11.2% and an accuracy was in range of 92.6%-104.3%. The present study, using the above method, is the first to demonstrate significant alterations of brain neurotransmitters caused by pathological processes in the brain tissues of patient with three different tauopathies. Copyright © 2017 Elsevier B.V. All rights reserved.

Oscillating intensity display of soft tissue lesions in MR imaging

International Nuclear Information System (INIS)

Herrmann, A.; Levin, D.N.; Beck, R.N.

1986-01-01

A computer-aided tissue characterization scheme is used to separate abnormal from normal tissues on the basis of their intensities on T1- and T2-weighted images. The intensity of an abnormal tissue on a T1-weighted image is then made to oscillate so that the amplitude (or frequency) of oscillation is directly proportional to the difference between the lesion's intensity and the intensities of normal tissues. The result is a ''movie'' in which the abnormal tissue churns or oscillates on the screen, drawing the attention because of the eye's sensitivity to motion

Using Non-Invasive Multi-Spectral Imaging to Quantitatively Assess Tissue Vasculature

Energy Technology Data Exchange (ETDEWEB)

Vogel, A; Chernomordik, V; Riley, J; Hassan, M; Amyot, F; Dasgeb, B; Demos, S G; Pursley, R; Little, R; Yarchoan, R; Tao, Y; Gandjbakhche, A H

2007-10-04

This research describes a non-invasive, non-contact method used to quantitatively analyze the functional characteristics of tissue. Multi-spectral images collected at several near-infrared wavelengths are input into a mathematical optical skin model that considers the contributions from different analytes in the epidermis and dermis skin layers. Through a reconstruction algorithm, we can quantify the percent of blood in a given area of tissue and the fraction of that blood that is oxygenated. Imaging normal tissue confirms previously reported values for the percent of blood in tissue and the percent of blood that is oxygenated in tissue and surrounding vasculature, for the normal state and when ischemia is induced. This methodology has been applied to assess vascular Kaposi's sarcoma lesions and the surrounding tissue before and during experimental therapies. The multi-spectral imaging technique has been combined with laser Doppler imaging to gain additional information. Results indicate that these techniques are able to provide quantitative and functional information about tissue changes during experimental drug therapy and investigate progression of disease before changes are visibly apparent, suggesting a potential for them to be used as complementary imaging techniques to clinical assessment.

Image-based characterization of foamed polymeric tissue scaffolds

International Nuclear Information System (INIS)

Mather, Melissa L; Morgan, Stephen P; Crowe, John A; White, Lisa J; Shakesheff, Kevin M; Tai, Hongyun; Howdle, Steven M; Kockenberger, Walter

2008-01-01

Tissue scaffolds are integral to many regenerative medicine therapies, providing suitable environments for tissue regeneration. In order to assess their suitability, methods to routinely and reproducibly characterize scaffolds are needed. Scaffold structures are typically complex, and thus their characterization is far from trivial. The work presented in this paper is centred on the application of the principles of scaffold characterization outlined in guidelines developed by ASTM International. Specifically, this work demonstrates the capabilities of different imaging modalities and analysis techniques used to characterize scaffolds fabricated from poly(lactic-co-glycolic acid) using supercritical carbon dioxide. Three structurally different scaffolds were used. The scaffolds were imaged using: scanning electron microscopy, micro x-ray computed tomography, magnetic resonance imaging and terahertz pulsed imaging. In each case two-dimensional images were obtained from which scaffold properties were determined using image processing. The findings of this work highlight how the chosen imaging modality and image-processing technique can influence the results of scaffold characterization. It is concluded that in order to obtain useful results from image-based scaffold characterization, an imaging methodology providing sufficient contrast and resolution must be used along with robust image segmentation methods to allow intercomparison of results

Nanoscale X-Ray Microscopic Imaging of Mammalian Mineralized Tissue

OpenAIRE

Andrews, Joy C.; Almeida, Eduardo; van der Meulen, Marjolein C.H.; Alwood, Joshua S.; Lee, Chialing; Liu, Yijin; Chen, Jie; Meirer, Florian; Feser, Michael; Gelb, Jeff; Rudati, Juana; Tkachuk, Andrei; Yun, Wenbing; Pianetta, Piero

2010-01-01

A novel hard transmission X-ray microscope (TXM) at the Stanford Synchrotron Radiation Light-source operating from 5 to 15 keV X-ray energy with 14 to 30 µm2 field of view has been used for high-resolution (30–40 nm) imaging and density quantification of mineralized tissue. TXM is uniquely suited for imaging of internal cellular structures and networks in mammalian mineralized tissues using relatively thick (50 µm), untreated samples that preserve tissue micro- and nanostructure. To test this...

A method to obtain reference images for evaluation of ultrasonic tissue characterization techniques

DEFF Research Database (Denmark)

Jensen, M.S.; Wilhjelm, Jens E.; Sahl, B.

2002-01-01

of the macroscopic photograph, due to the histological preparation process. The histological information was "mapped back" into the format of the ultrasound images the following way: On the macroscopic images, outlines were drawn manually which defined the border of the tissue. These outlines were superimposed...... of the various tissue types. Specifically, the macroscopic image revealed the borders between the different tissues, while the histological image identified the four tissue types. A set of 12 reference images based on modified macroscopic outlines was created. The overlap between the ultrasound images...... and the macroscopic images-which are the geometrical basis for the final reference images-was between 77% and 93%. A set of 12 reference images spaced 2.5 mm, identifying spatial location of four different tissue types in porcine muscle has been created. With the reference images, it is possible to quantitatively...

Fluorescent imaging of cancerous tissues for targeted surgery

Science.gov (United States)

Bu, Lihong; Shen, Baozhong; Cheng, Zhen

2014-01-01

To maximize tumor excision and minimize collateral damage is the primary goal of cancer surgery. Emerging molecular imaging techniques have to “image-guided surgery” developing into “molecular imaging-guided surgery”, which is termed “targeted surgery” in this review. Consequently, the precision of surgery can be advanced from tissue-scale to molecule-scale, enabling “targeted surgery” to be a component of “targeted therapy”. Evidence from numerous experimental and clinical studies has demonstrated significant benefits of fluorescent imaging in targeted surgery with preoperative molecular diagnostic screening. Fluorescent imaging can help to improve intraoperative staging and enable more radical cytoreduction, detect obscure tumor lesions in special organs, highlight tumor margins, better map lymph node metastases, and identify important normal structures intraoperatively. Though limited tissue penetration of fluorescent imaging and tumor heterogeneity are two major hurdles for current targeted surgery, multimodality imaging and multiplex imaging may provide potential solutions to overcome these issues, respectively. Moreover, though many fluorescent imaging techniques and probes have been investigated, targeted surgery remains at a proof-of-principle stage. The impact of fluorescent imaging on cancer surgery will likely be realized through persistent interdisciplinary amalgamation of research in diverse fields. PMID:25064553

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

Science.gov (United States)

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. Copyright © 2016. Published by Elsevier Ireland Ltd.

Photoacoustic imaging in both soft and hard biological tissue

International Nuclear Information System (INIS)

Li, T; Dewhurst, R J

2010-01-01

To date, most Photoacoustic (PA) imaging results have been from soft biotissues. In this study, a PA imaging system with a near-infrared pulsed laser source has been applied to obtain 2-D and 3-D images from both soft tissue and post-mortem dental samples. Imaging results showed that the PA technique has the potential to image human oral disease, such as early-stage teeth decay. For non-invasive photoacoustic imaging, the induced temperature and pressure rises within biotissues should not cause physical damage to the tissue. Several simulations based on the thermoelastic effect have been applied to predict initial temperature and pressure fields within a tooth sample. Predicted initial temperature and pressure rises are below corresponding safety limits.

MALDI Mass Spectrometry Imaging for Visualizing In Situ Metabolism of Endogenous Metabolites and Dietary Phytochemicals

Science.gov (United States)

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

Imaging Mass Spectrometry Revealed the Accumulation Characteristics of the 2-Nitroimidazole-Based Agent "Pimonidazole" in Hypoxia.

Directory of Open Access Journals (Sweden)

Yukiko Masaki

Full Text Available Hypoxia, or low oxygen concentration, is a key factor promoting tumor progression and angiogenesis and resistance of cancer to radiotherapy and chemotherapy. 2-Nitroimidazole-based agents have been widely used in pathological and nuclear medicine examinations to detect hypoxic regions in tumors; in particular, pimonidazole is used for histochemical staining of hypoxic regions. It is considered to accumulate in hypoxic cells via covalent binding with macromolecules or by forming reductive metabolites after reduction of its nitro group. However, the detailed mechanism of its accumulation remains unknown. In this study, we investigated the accumulation mechanism of pimonidazole in hypoxic tumor tissues in a mouse model by mass spectrometric analyses including imaging mass spectrometry (IMS. Pimonidazole and its reductive metabolites were observed in the tumor tissues. However, their locations in the tumor sections were not similar to the positively stained areas in pimonidazole-immunohistochemistry, an area considered hypoxic. The glutathione conjugate of reduced pimonidazole, a low-molecular-weight metabolite of pimonidazole, was found in tumor tissues by LC-MS analysis, and our IMS study determined that the intratumor localization of the glutathione conjugate was consistent with the area positively immunostained for pimonidazole. We also found complementary localization of the glutathione conjugate and reduced glutathione (GSH, implying that formation of the glutathione conjugate occurred in the tumor tissue. These results suggest that in hypoxic tumor cells, pimonidazole is reduced at its nitro group, followed by conjugation with GSH.

Microwave tomography for functional imaging of extremity soft tissues: feasibility assessment

International Nuclear Information System (INIS)

Semenov, Serguei; Kellam, James; Althausen, Peter; Williams, Thomas; Abubakar, Aria; Bulyshev, Alexander; Sizov, Yuri

2007-01-01

It is important to assess the viability of extremity soft tissues, as this component is often the determinant of the final outcome of fracture treatment. Microwave tomography (MWT) and sensing might be able to provide a fast and mobile assessment of such properties. MWT imaging of extremities possesses a complicated, nonlinear, high dielectric contrast inverse problem of diffraction tomography. There is a high dielectric contrast between bone and soft tissue in the extremities. A contrast between soft tissue abnormalities is less pronounced when compared with the high bone-soft tissue contrast. The goal of this study was to assess the feasibility of MWT for functional imaging of extremity soft tissues, i.e. to detect a relatively small contrast within soft tissues in closer proximity to high contrast boney areas. Both experimental studies and computer simulation were performed. Experiments were conducted using live pigs with compromised blood flow and compartment syndrome within an extremity. A whole 2D tomographic imaging cycle at 1 GHz was computer simulated and images were reconstructed using the Newton, MR-CSI and modified Born methods. Results of experimental studies demonstrate that microwave technology is sensitive to changes in the soft tissue blood content and elevated compartment pressure. It was demonstrated that MWT is feasible for functional imaging of extremity soft tissues, circulatory-related changes, blood flow and elevated compartment pressure

Preliminary study of synthetic aperture tissue harmonic imaging on in-vivo data

DEFF Research Database (Denmark)

Rasmussen, Joachim Hee; Hemmsen, Martin Christian; Sloth Madsen, Signe

2013-01-01

. Results from the image quality study show, that in the current configuration on the UltraView system, where no transmit apodization was applied, SASB-THI and DRF-THI produced equally good images. It is expected that given the use of transmit apodization, SASB-THI could be further improved.......A method for synthetic aperture tissue harmonic imaging is investigated. It combines synthetic aperture sequential beamforming (SASB) with tissue harmonic imaging (THI) to produce an increased and more uniform spatial resolution and improved side lobe reduction compared to conventional B......-mode imaging. Synthetic aperture sequential beamforming tissue harmonic imaging (SASB-THI) was implemented on a commercially available BK 2202 Pro Focus UltraView ultrasound system and compared to dynamic receive focused tissue harmonic imaging (DRF-THI) in clinical scans. The scan sequence...

Capillary electrophoresis - Mass spectrometry metabolomics analysis revealed enrichment of hypotaurine in rat glioma tissues.

Science.gov (United States)

Gao, Peng; Ji, Min; Fang, Xueyan; Liu, Yingyang; Yu, Zhigang; Cao, Yunfeng; Sun, Aijun; Zhao, Liang; Zhang, Yong

2017-11-15

Glioma is one of the most lethal brain malignancies with unknown etiologies. Many metabolomics analysis aiming at diverse kinds of samples had been performed. Due to the varied adopted analytical platforms, the reported disease-related metabolites were not consistent across different studies. Comparable metabolomics results are more likely to be acquired by analyzing the same sample types with identical analytical platform. For tumor researches, tissue samples metabolomics analysis own the unique advantage that it can gain more direct insight into disease-specific pathological molecules. In this light, a previous reported capillary electrophoresis - mass spectrometry human tissues metabolomics analysis method was employed to profile the metabolome of rat C6 cell implantation gliomas and the corresponding precancerous tissues. It was found that 9 metabolites increased in the glioma tissues. Of them, hypotaurine was the only metabolite that enriched in the malignant tissues as what had been reported in the relevant human tissues metabolomics analysis. Furthermore, hypotaurine was also proved to inhibit α-ketoglutarate-dependent dioxygenases (2-KDDs) through immunocytochemistry staining and in vitro enzymatic activity assays by using C6 cell cultures. This study reinforced the previous conclusion that hypotaurine acted as a competitive inhibitor of 2-KDDs and proved the value of metabolomics in oncology studies. Copyright © 2017. Published by Elsevier Inc.

Impact of Computed Tomography Image Quality on Image-Guided Radiation Therapy Based on Soft Tissue Registration

International Nuclear Information System (INIS)

Morrow, Natalya V.; Lawton, Colleen A.; Qi, X. Sharon; Li, X. Allen

2012-01-01

Purpose: In image-guided radiation therapy (IGRT), different computed tomography (CT) modalities with varying image quality are being used to correct for interfractional variations in patient set-up and anatomy changes, thereby reducing clinical target volume to the planning target volume (CTV-to-PTV) margins. We explore how CT image quality affects patient repositioning and CTV-to-PTV margins in soft tissue registration-based IGRT for prostate cancer patients. Methods and Materials: Four CT-based IGRT modalities used for prostate RT were considered in this study: MV fan beam CT (MVFBCT) (Tomotherapy), MV cone beam CT (MVCBCT) (MVision; Siemens), kV fan beam CT (kVFBCT) (CTVision, Siemens), and kV cone beam CT (kVCBCT) (Synergy; Elekta). Daily shifts were determined by manual registration to achieve the best soft tissue agreement. Effect of image quality on patient repositioning was determined by statistical analysis of daily shifts for 136 patients (34 per modality). Inter- and intraobserver variability of soft tissue registration was evaluated based on the registration of a representative scan for each CT modality with its corresponding planning scan. Results: Superior image quality with the kVFBCT resulted in reduced uncertainty in soft tissue registration during IGRT compared with other image modalities for IGRT. The largest interobserver variations of soft tissue registration were 1.1 mm, 2.5 mm, 2.6 mm, and 3.2 mm for kVFBCT, kVCBCT, MVFBCT, and MVCBCT, respectively. Conclusions: Image quality adversely affects the reproducibility of soft tissue-based registration for IGRT and necessitates a careful consideration of residual uncertainties in determining different CTV-to-PTV margins for IGRT using different image modalities.

Impact of Computed Tomography Image Quality on Image-Guided Radiation Therapy Based on Soft Tissue Registration

Energy Technology Data Exchange (ETDEWEB)

Morrow, Natalya V.; Lawton, Colleen A. [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States); Qi, X. Sharon [Department of Radiation Oncology, University of Colorado Denver, Denver, Colorado (United States); Li, X. Allen, E-mail: ali@mcw.edu [Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, Wisconsin (United States)

2012-04-01

Purpose: In image-guided radiation therapy (IGRT), different computed tomography (CT) modalities with varying image quality are being used to correct for interfractional variations in patient set-up and anatomy changes, thereby reducing clinical target volume to the planning target volume (CTV-to-PTV) margins. We explore how CT image quality affects patient repositioning and CTV-to-PTV margins in soft tissue registration-based IGRT for prostate cancer patients. Methods and Materials: Four CT-based IGRT modalities used for prostate RT were considered in this study: MV fan beam CT (MVFBCT) (Tomotherapy), MV cone beam CT (MVCBCT) (MVision; Siemens), kV fan beam CT (kVFBCT) (CTVision, Siemens), and kV cone beam CT (kVCBCT) (Synergy; Elekta). Daily shifts were determined by manual registration to achieve the best soft tissue agreement. Effect of image quality on patient repositioning was determined by statistical analysis of daily shifts for 136 patients (34 per modality). Inter- and intraobserver variability of soft tissue registration was evaluated based on the registration of a representative scan for each CT modality with its corresponding planning scan. Results: Superior image quality with the kVFBCT resulted in reduced uncertainty in soft tissue registration during IGRT compared with other image modalities for IGRT. The largest interobserver variations of soft tissue registration were 1.1 mm, 2.5 mm, 2.6 mm, and 3.2 mm for kVFBCT, kVCBCT, MVFBCT, and MVCBCT, respectively. Conclusions: Image quality adversely affects the reproducibility of soft tissue-based registration for IGRT and necessitates a careful consideration of residual uncertainties in determining different CTV-to-PTV margins for IGRT using different image modalities.

Direct tissue oxygen monitoring by in vivo photoacoustic lifetime imaging (PALI)

Science.gov (United States)

Shao, Qi; Morgounova, Ekaterina; Ashkenazi, Shai

2014-03-01

Tissue oxygen plays a critical role in maintaining tissue viability and in various diseases, including response to therapy. Images of oxygen distribution provide the history of tissue hypoxia and evidence of oxygen availability in the circulatory system. Currently available methods of direct measuring or imaging tissue oxygen all have significant limitations. Previously, we have reported a non-invasive in vivo imaging modality based on photoacoustic lifetime. The technique maps the excited triplet state of oxygen-sensitive dye, thus reflects the spatial and temporal distribution of tissue oxygen. We have applied PALI on tumor hypoxia in small animals, and the hypoxic region imaged by PALI is consistent with the site of the tumor imaged by ultrasound. Here, we present two studies of applying PALI to monitor changes of tissue oxygen by modulations. The first study involves an acute ischemia model using a thin thread tied around the hind limb of a normal mouse to reduce the blood flow. PALI images were acquired before, during, and after the restriction. The drop of muscle pO2 and recovery from hypoxia due to reperfusion were observed by PALI tracking the same region. The second study modulates tissue oxygen by controlling the percentage of oxygen the mouse inhales. We demonstrate that PALI is able to reflect the change of oxygen level with respect to both hyperbaric and hypobaric conditions. We expect this technique to be very attractive for a range of clinical applications in which tissue oxygen mapping would improve therapy decision making and treatment planning.

Meet interesting abbreviations in clinical mass spectrometry: from compound classification by REIMS to multimodal and mass spectrometry imaging (MSI)

Czech Academy of Sciences Publication Activity Database

Luptáková, Dominika; Pluháček, Tomáš; Palyzová, Andrea; Přichystal, Jakub; Balogh, J.; Lemr, Karel; Juránek, I.; Havlíček, Vladimír

2017-01-01

Roč. 61, č. 3 (2017), s. 353-360 ISSN 0001-723X R&D Projects: GA MŠk(CZ) LO1509; GA ČR(CZ) GA16-20229S Institutional support: RVO:61388971 Keywords : REIMS * multimodal * mass spectrometry imaging Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 0.673, year: 2016

Endeavors in micro-imaging spectrometry

Energy Technology Data Exchange (ETDEWEB)

Rosen, M.M.

1995-10-19

The goal of this apparatus is to better enable characterization of tissue samples both on a microscopic scale and across the visible spectrum. The set-up consists of a phase-contrast inverted Nikon microscope, a single-grating imaging spectrometer, a CCD camera, and a computer potentially controlling all three of the previous devices, The computer uses an object-oriented program development environment called LabVIEW to run the three devices. This apparatus will hopefully enable better, less invasive surgical procedures, as well as permitting higher-resolution, more up-close observation of cellular dynamics.

Imaging mass spectrometry tackles interfacial challenges in electrochemistry

Energy Technology Data Exchange (ETDEWEB)

Yu, Xiao-Ying

2017-12-01

Electrochemistry has played a significant role in many research fields. Owing to its sensitivity and selectivity, in situ electroanalysis has been widely used as a fast and economical means for achieving outstanding results. Although many spectroscopic techniques have been used in electrochemistry, the challenges to capture short-lived intermediate species as a result of electron transfer in the buried solid electrode and electrolyte solution interface remains a grand challenge. In situ imaging mass spectrometry (IMS) recently has been extended to capture transient species in electrochemistry. This review intends to summarize newest development of IMS and its applications in advancing fundamental electrochemistry.

In vivo multiphoton tomography and fluorescence lifetime imaging of human brain tumor tissue.

Science.gov (United States)

Kantelhardt, Sven R; Kalasauskas, Darius; König, Karsten; Kim, Ella; Weinigel, Martin; Uchugonova, Aisada; Giese, Alf

2016-05-01

High resolution multiphoton tomography and fluorescence lifetime imaging differentiates glioma from adjacent brain in native tissue samples ex vivo. Presently, multiphoton tomography is applied in clinical dermatology and experimentally. We here present the first application of multiphoton and fluorescence lifetime imaging for in vivo imaging on humans during a neurosurgical procedure. We used a MPTflex™ Multiphoton Laser Tomograph (JenLab, Germany). We examined cultured glioma cells in an orthotopic mouse tumor model and native human tissue samples. Finally the multiphoton tomograph was applied to provide optical biopsies during resection of a clinical case of glioblastoma. All tissues imaged by multiphoton tomography were sampled and processed for conventional histopathology. The multiphoton tomograph allowed fluorescence intensity- and fluorescence lifetime imaging with submicron spatial resolution and 200 picosecond temporal resolution. Morphological fluorescence intensity imaging and fluorescence lifetime imaging of tumor-bearing mouse brains and native human tissue samples clearly differentiated tumor and adjacent brain tissue. Intraoperative imaging was found to be technically feasible. Intraoperative image quality was comparable to ex vivo examinations. To our knowledge we here present the first intraoperative application of high resolution multiphoton tomography and fluorescence lifetime imaging of human brain tumors in situ. It allowed in vivo identification and determination of cell density of tumor tissue on a cellular and subcellular level within seconds. The technology shows the potential of rapid intraoperative identification of native glioma tissue without need for tissue processing or staining.

Optical redox imaging indices discriminate human breast cancer from normal tissues

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2016-01-01

Abstract. Our long-term goal was to investigate the potential of incorporating redox imaging technique as a breast cancer (BC) diagnosis component to increase the positive predictive value of suspicious imaging finding and to reduce unnecessary biopsies and overdiagnosis. We previously found that precancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. We also revealed abnormal mitochondrial redox state in cancerous specimens from three BC patients. Here, we extend our study to include biopsies of 16 patients. Tissue aliquots were collected from both apparently normal and cancerous tissues from the affected cancer-bearing breasts shortly after surgical resection. All specimens were snap-frozen and scanned with the Chance redox scanner, i.e., the three-dimensional cryogenic NADH/Fp (reduced nicotinamide adenine dinucleotide/oxidized flavoproteins) fluorescence imager. We found both Fp and NADH in the cancerous tissues roughly tripled that in the normal tissues (predox ratio Fp/(NADH + Fp) was ∼27% higher in the cancerous tissues (predox ratio alone could predict cancer with reasonable sensitivity and specificity. Our findings suggest that the optical redox imaging technique can provide parameters independent of clinical factors for discriminating cancer from noncancer breast tissues in human patients. PMID:27896360

Chromatic confocal microscopy for multi-depth imaging of epithelial tissue

Science.gov (United States)

Olsovsky, Cory; Shelton, Ryan; Carrasco-Zevallos, Oscar; Applegate, Brian E.; Maitland, Kristen C.

2013-01-01

We present a novel chromatic confocal microscope capable of volumetric reflectance imaging of microstructure in non-transparent tissue. Our design takes advantage of the chromatic aberration of aspheric lenses that are otherwise well corrected. Strong chromatic aberration, generated by multiple aspheres, longitudinally disperses supercontinuum light onto the sample. The backscattered light detected with a spectrometer is therefore wavelength encoded and each spectrum corresponds to a line image. This approach obviates the need for traditional axial mechanical scanning techniques that are difficult to implement for endoscopy and susceptible to motion artifact. A wavelength range of 590-775 nm yielded a >150 µm imaging depth with ~3 µm axial resolution. The system was further demonstrated by capturing volumetric images of buccal mucosa. We believe these represent the first microstructural images in non-transparent biological tissue using chromatic confocal microscopy that exhibit long imaging depth while maintaining acceptable resolution for resolving cell morphology. Miniaturization of this optical system could bring enhanced speed and accuracy to endomicroscopic in vivo volumetric imaging of epithelial tissue. PMID:23667789

Imaging of connective tissue diseases of the head and neck

Science.gov (United States)

2016-01-01

We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren’s syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still’s disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders. PMID:26988082

Role of tissue harmonic imaging in characterization of cystic renallesions

International Nuclear Information System (INIS)

Mohammed, A.; Sandhu, Manavjit S.; Lal, A.; Sodhi, Kushaljit S.; Sud, K.; Kohli, Harbir S.

2008-01-01

Objective was to determine the utility of tissue harmonic imaging inevaluating cystic renal lesions and to compare these findings withconventional ultrasound guidance (USG) and CT. Thirty patients, detected withcystic renal lesions on routine USG (over a period of 18 months from July2004 to December 2005) at the Postgraduate Institute of Medical Education andResearch Chandigarh, Chandigarh, India) were included in this study. Allpatients underwent a conventional gray scale ultrasound study (GSI), followedby tissue harmonic imaging (THI) sonography on the same machine (advancetechnology limited high definition imaging 5000). Computed tomography ofabdomen was carried out within one week of the ultrasound examinations. Allimages were evaluated for size, number and location of lesions. The findingsof THI sonography, conventional USG and CT of abdomen were recorded in theirrespective proformas. The images obtained by GSI, THI and contrast enhancedCT were also evaluated for image, quality, lesion conspicuity and fluid-soliddifferentiation. Tissue harmonic imaging showed better image quality in 27 of34 lesions, improvement in lesion conspicuity was found in 27 of 34 cysticlesions and an improved solid-fluid differentiation in 30 of 34 lesions whencompared to GSI. The THI provided additional information as compared to GSIin 8 patients. The grading of CT scan was significantly higher in overallimage quality (p=0.007) and lesion conspicuity (p=0.004), but wasnon-significant for fluid-solid differentiation (p=0.23). Tissue harmonicimaging provides better image quality, lesion delineation and superiorcharacterization than conventional gray scale sonography. (author)

Imaging of elements in leaves of tobacco by solid sampling–electrothermal vaporization–inductively coupled plasma-optical emission spectrometry

Energy Technology Data Exchange (ETDEWEB)

Masson, Pierre, E-mail: masson@bordeaux.inra.fr

2014-12-01

Plants take up and store elements according to the environment in which they are growing. Because plants are at the base of the food chain, the determination of essential elements or toxic elements in plant materials is of importance. However, it is assumed that the element content determined on selected tissues may provide more specific information than that derived from the whole plant analysis. In this work, we assessed the feasibility of solid sampling–electrothermal vaporization–inductively coupled plasma-optical emission spectrometry analyses for quantitative imaging of Cd and Mg in plant leaves. Leaves of tobacco (Nicotiana tabacum) were selected to be used as samples. To produce a two dimensional image, sections cut from leaf samples were analyzed. Cellulose doped with multi-element solution standards was used as calibration samples. Two certified reference materials (NIST SRM 1547 Peach Leaves and NIST SRM 1573a Tomato leaves) were used to verify the accuracy of measurements with good agreement between the measured concentrations and the certified values. Quantitative imaging revealed the inhomogeneous distribution of the selected elements. Excess of Cd and Mg tended to be focused on peripheral regions and the tip of the leaf.

Hippocampal lipid differences in Alzheimer's disease: a human brain study using matrix-assisted laser desorption/ionization-imaging mass spectrometry.

Science.gov (United States)

Mendis, Lakshini H S; Grey, Angus C; Faull, Richard L M; Curtis, Maurice A

2016-10-01

Alzheimer's disease (AD), the leading cause of dementia, is pathologically characterized by β-amyloid plaques and tau tangles. However, there is also evidence of lipid dyshomeostasis-mediated AD pathology. Given the structural diversity of lipids, mass spectrometry is a useful tool for studying lipid changes in AD. Although there have been a few studies investigating lipid changes in the human hippocampus in particular, there are few reports on how lipids change in each hippocampal subfield (e.g., Cornu Ammonis [CA] 1-4, dentate gyrus [DG] etc.). Since each subfield has its own function, we postulated that there could be lipid changes that are unique to each. We used matrix-assisted laser desorption/ionization-imaging mass spectrometry to investigate specific lipid changes in each subfield in AD. Data from the hippocampus region of six age- and gender-matched normal and AD pairs were analyzed with SCiLS lab 2015b software (SCiLS GmbH, Germany; RRID:SCR_014426), using an analysis workflow developed in-house. Hematoxylin, eosin, and luxol fast blue staining were used to precisely delineate each anatomical hippocampal subfield. Putative lipid identities, which were consistent with published data, were assigned using MS/MS. Both positively and negatively charged lipid ion species were abundantly detected in normal and AD tissue. While the distribution pattern of lipids did not change in AD, the abundance of some lipids changed, consistent with trends that have been previously reported. However, our results indicated that the majority of these lipid changes specifically occur in the CA1 region. Additionally, there were many lipid changes that were specific to the DG. Matrix-assisted laser desorption/ionization-imaging mass spectrometry and our analysis workflow provide a novel method to investigate specific lipid changes in hippocampal subfields. Future work will focus on elucidating the role that specific lipid differences in each subfield play in AD pathogenesis.

First cosmic-ray images of bone and soft tissue

Science.gov (United States)

Mrdja, Dusan; Bikit, Istvan; Bikit, Kristina; Slivka, Jaroslav; Hansman, Jan; Oláh, László; Varga, Dezső

2016-11-01

More than 120 years after Roentgen's first X-ray image, the first cosmic-ray muon images of bone and soft tissue are created. The pictures, shown in the present paper, represent the first radiographies of structures of organic origin ever recorded by cosmic rays. This result is achieved by a uniquely designed, simple and versatile cosmic-ray muon-imaging system, which consists of four plastic scintillation detectors and a muon tracker. This system does not use scattering or absorption of muons in order to deduct image information, but takes advantage of the production rate of secondaries in the target materials, detected in coincidence with muons. The 2D image slices of cow femur bone are obtained at several depths along the bone axis, together with the corresponding 3D image. Real organic soft tissue, polymethyl methacrylate and water, never seen before by any other muon imaging techniques, are also registered in the images. Thus, similar imaging systems, placed around structures of organic or inorganic origin, can be used for tomographic imaging using only the omnipresent cosmic radiation.

The challenge of on-tissue digestion for MALDI MSI- a comparison of different protocols to improve imaging experiments.

Science.gov (United States)

Diehl, Hanna C; Beine, Birte; Elm, Julian; Trede, Dennis; Ahrens, Maike; Eisenacher, Martin; Marcus, Katrin; Meyer, Helmut E; Henkel, Corinna

2015-03-01

Mass spectrometry imaging (MSI) has become a powerful and successful tool in the context of biomarker detection especially in recent years. This emerging technique is based on the combination of histological information of a tissue and its corresponding spatial resolved mass spectrometric information. The identification of differentially expressed protein peaks between samples is still the method's bottleneck. Therefore, peptide MSI compared to protein MSI is closer to the final goal of identification since peptides are easier to measure than proteins. Nevertheless, the processing of peptide imaging samples is challenging due to experimental complexity. To address this issue, a method development study for peptide MSI using cryoconserved and formalin-fixed paraffin-embedded (FFPE) rat brain tissue is provided. Different digestion times, matrices, and proteases were tested to define an optimal workflow for peptide MSI. All practical experiments were done in triplicates and analyzed by the SCiLS Lab software, using structures derived from myelin basic protein (MBP) peaks, principal component analysis (PCA) and probabilistic latent semantic analysis (pLSA) to rate the experiments' quality. Blinded experimental evaluation in case of defining countable structures in the datasets was performed by three individuals. Such an extensive method development for peptide matrix-assisted laser desorption/ionization (MALDI) imaging experiments has not been performed so far, and the resulting problems and consequences were analyzed and discussed.

Distribution of erlotinib in rash and normal skin in cancer patients receiving erlotinib visualized by matrix assisted laser desorption/ionization mass spectrometry imaging.

Science.gov (United States)

Nishimura, Meiko; Hayashi, Mitsuhiro; Mizutani, Yu; Takenaka, Kei; Imamura, Yoshinori; Chayahara, Naoko; Toyoda, Masanori; Kiyota, Naomi; Mukohara, Toru; Aikawa, Hiroaki; Fujiwara, Yasuhiro; Hamada, Akinobu; Minami, Hironobu

2018-04-06

The development of skin rashes is the most common adverse event observed in cancer patients treated with epidermal growth factor receptor-tyrosine kinase inhibitors such as erlotinib. However, the pharmacological evidence has not been fully revealed. Erlotinib distribution in the rashes was more heterogeneous than that in the normal skin, and the rashes contained statistically higher concentrations of erlotinib than adjacent normal skin in the superficial skin layer (229 ± 192 vs. 120 ± 103 ions/mm 2 ; P = 0.009 in paired t -test). LC-MS/MS confirmed that the concentration of erlotinib in the skin rashes was higher than that in normal skin in the superficial skin layer (1946 ± 1258 vs. 1174 ± 662 ng/cm 3 ; P = 0.028 in paired t -test). The results of MALDI-MSI and LC-MS/MS were well correlated (coefficient of correlation 0.879, P distribution of erlotinib in the skin tissue was visualized using non-labeled MALDI-MSI. Erlotinib concentration in the superficial layer of the skin rashes was higher than that in the adjacent normal skin. We examined patients with advanced pancreatic cancer who developed skin rashes after treatment with erlotinib and gemcitabine. We biopsied both the rash and adjacent normal skin tissues, and visualized and compared the distribution of erlotinib within the skin using matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI). The tissue concentration of erlotinib was also measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) with laser microdissection.

Excitation-scanning hyperspectral imaging as a means to discriminate various tissues types

Science.gov (United States)

Deal, Joshua; Favreau, Peter F.; Lopez, Carmen; Lall, Malvika; Weber, David S.; Rich, Thomas C.; Leavesley, Silas J.

2017-02-01

Little is currently known about the fluorescence excitation spectra of disparate tissues and how these spectra change with pathological state. Current imaging diagnostic techniques have limited capacity to investigate fluorescence excitation spectral characteristics. This study utilized excitation-scanning hyperspectral imaging to perform a comprehensive assessment of fluorescence spectral signatures of various tissues. Immediately following tissue harvest, a custom inverted microscope (TE-2000, Nikon Instruments) with Xe arc lamp and thin film tunable filter array (VersaChrome, Semrock, Inc.) were used to acquire hyperspectral image data from each sample. Scans utilized excitation wavelengths from 340 nm to 550 nm in 5 nm increments. Hyperspectral images were analyzed with custom Matlab scripts including linear spectral unmixing (LSU), principal component analysis (PCA), and Gaussian mixture modeling (GMM). Spectra were examined for potential characteristic features such as consistent intensity peaks at specific wavelengths or intensity ratios among significant wavelengths. The resultant spectral features were conserved among tissues of similar molecular composition. Additionally, excitation spectra appear to be a mixture of pure endmembers with commonalities across tissues of varied molecular composition, potentially identifiable through GMM. These results suggest the presence of common autofluorescent molecules in most tissues and that excitationscanning hyperspectral imaging may serve as an approach for characterizing tissue composition as well as pathologic state. Future work will test the feasibility of excitation-scanning hyperspectral imaging as a contrast mode for discriminating normal and pathological tissues.

Technological Development of High-Performance MALDI Mass Spectrometry Imaging for the Study of Metabolic Biology

Energy Technology Data Exchange (ETDEWEB)

Feenstra, Adam D. [Iowa State Univ., Ames, IA (United States)

2016-12-17

This thesis represents efforts made in technological developments for the study of metabolic biology in plants, specifically maize, using matrix-assisted laser desorption/ ionization-mass spectrometry imaging.

Direct microCT imaging of non-mineralized connective tissues at high resolution.

Science.gov (United States)

Naveh, Gili R S; Brumfeld, Vlad; Dean, Mason; Shahar, Ron; Weiner, Steve

2014-01-01

The 3D imaging of soft tissues in their native state is challenging, especially when high resolution is required. An X-ray-based microCT is, to date, the best choice for high resolution 3D imaging of soft tissues. However, since X-ray attenuation of soft tissues is very low, contrasting enhancement using different staining materials is needed. The staining procedure, which also usually involves tissue fixation, causes unwanted and to some extent unknown tissue alterations. Here, we demonstrate that a method that enables 3D imaging of soft tissues without fixing and staining using an X-ray-based bench-top microCT can be applied to a variety of different tissues. With the sample mounted in a custom-made loading device inside a humidity chamber, we obtained soft tissue contrast and generated 3D images of fresh, soft tissues with a resolution of 1 micron voxel size. We identified three critical conditions which make it possible to image soft tissues: humidified environment, mechanical stabilization of the sample and phase enhancement. We demonstrate the capability of the technique using different specimens: an intervertebral disc, the non-mineralized growth plate, stingray tessellated radials (calcified cartilage) and the collagenous network of the periodontal ligament. Since the scanned specimen is fresh an interesting advantage of this technique is the ability to scan a specimen under load and track the changes of the different structures. This method offers a unique opportunity for obtaining valuable insights into 3D structure-function relationships of soft tissues.

Segmentation of Multi-Isotope Imaging Mass Spectrometry Data for Semi-Automatic Detection of Regions of Interest

Science.gov (United States)

Poczatek, J. Collin; Turck, Christoph W.; Lechene, Claude

2012-01-01

Multi-isotope imaging mass spectrometry (MIMS) associates secondary ion mass spectrometry (SIMS) with detection of several atomic masses, the use of stable isotopes as labels, and affiliated quantitative image-analysis software. By associating image and measure, MIMS allows one to obtain quantitative information about biological processes in sub-cellular domains. MIMS can be applied to a wide range of biomedical problems, in particular metabolism and cell fate [1], [2], [3]. In order to obtain morphologically pertinent data from MIMS images, we have to define regions of interest (ROIs). ROIs are drawn by hand, a tedious and time-consuming process. We have developed and successfully applied a support vector machine (SVM) for segmentation of MIMS images that allows fast, semi-automatic boundary detection of regions of interests. Using the SVM, high-quality ROIs (as compared to an expert's manual delineation) were obtained for 2 types of images derived from unrelated data sets. This automation simplifies, accelerates and improves the post-processing analysis of MIMS images. This approach has been integrated into “Open MIMS,” an ImageJ-plugin for comprehensive analysis of MIMS images that is available online at http://www.nrims.hms.harvard.edu/NRIMS_ImageJ.php. PMID:22347386

Imaging mass spectrometry visualizes ceramides and the pathogenesis of dorfman-chanarin syndrome due to ceramide metabolic abnormality in the skin.

Directory of Open Access Journals (Sweden)

Naoko Goto-Inoue

Full Text Available Imaging mass spectrometry (IMS is a useful cutting edge technology used to investigate the distribution of biomolecules such as drugs and metabolites, as well as to identify molecular species in tissues and cells without labeling. To protect against excess water loss that is essential for survival in a terrestrial environment, mammalian skin possesses a competent permeability barrier in the stratum corneum (SC, the outermost layer of the epidermis. The key lipids constituting this barrier in the SC are the ceramides (Cers comprising of a heterogeneous molecular species. Alterations in Cer composition have been reported in several skin diseases that display abnormalities in the epidermal permeability barrier function. Not only the amounts of different Cers, but also their localizations are critical for the barrier function. We have employed our new imaging system, capable of high-lateral-resolution IMS with an atmospheric-pressure ionization source, to directly visualize the distribution of Cers. Moreover, we show an ichthyotic disease pathogenesis due to abnormal Cer metabolism in Dorfman-Chanarin syndrome, a neutral lipid storage disorder with ichthyosis in human skin, demonstrating that IMS is a novel diagnostic approach for assessing lipid abnormalities in clinical setting, as well as for investigating physiological roles of lipids in cells/tissues.

A photoacoustic tomography system for imaging of biological tissues

International Nuclear Information System (INIS)

Su Yixiong; Zhang Fan; Xu Kexin; Yao Jianquan; Wang, Ruikang K

2005-01-01

Non-invasive laser-induced photoacoustic tomography (PAT) is a promising imaging modality in the biomedical optical imaging field. This technology, based on the intrinsic optical properties of tissue and ultrasonic detection, overcomes the resolution disadvantage of pure-optical imaging caused by strong light scattering and the contrast and speckle disadvantages of pure ultrasonic imaging. Here, we report a PAT experimental system constructed in our laboratory. In our system, a Q-switched Nd : YAG pulse laser operated at 532 nm with a 8 ns pulse width is used to generate a photoacoustic signal. By using this system, the two-dimensional distribution of optical absorption in the tissue-mimicking phantom is reconstructed and has an excellent agreement with the original ones. The spatial resolution of the imaging system approaches 100 μm through about 4 cm of highly scattering medium

Synchronous ultrasonic Doppler imaging of magnetic microparticles in biological tissues

Energy Technology Data Exchange (ETDEWEB)

Pyshnyi, Michael Ph. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Kuznetsov, Oleg A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)], E-mail: kuznetsov_oa@yahoo.com; Pyshnaya, Svetlana V.; Nechitailo, Galina S.; Kuznetsov, Anatoly A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)

2009-05-15

We considered applicability of acoustic imaging technology for the detection of magnetic microparticles and nanoparticles inside soft biological tissues. Such particles are widely used for magnetically targeted drug delivery and magnetic hyperthermia. We developed a new method of ultrasonic synchronous tissue Doppler imaging with magnetic modulation for in vitro and in vivo detection and visualization of magnetic ultradisperse objects in soft tissues. Prototype hardware with appropriate software was produced and the method was successfully tested on magnetic microparticles injected into an excised pig liver.

Synchronous ultrasonic Doppler imaging of magnetic microparticles in biological tissues

International Nuclear Information System (INIS)

Pyshnyi, Michael Ph.; Kuznetsov, Oleg A.; Pyshnaya, Svetlana V.; Nechitailo, Galina S.; Kuznetsov, Anatoly A.

2009-01-01

We considered applicability of acoustic imaging technology for the detection of magnetic microparticles and nanoparticles inside soft biological tissues. Such particles are widely used for magnetically targeted drug delivery and magnetic hyperthermia. We developed a new method of ultrasonic synchronous tissue Doppler imaging with magnetic modulation for in vitro and in vivo detection and visualization of magnetic ultradisperse objects in soft tissues. Prototype hardware with appropriate software was produced and the method was successfully tested on magnetic microparticles injected into an excised pig liver.

Depth determination of low-energy photon emitter deposits in tissue by means of high-resolution X-ray spectrometry

International Nuclear Information System (INIS)

Schlueter, W.

1982-01-01

A method has been developed for ascertaining the depth of low-energy photon emitters deposited in wounds. It is based on the determination of the energy-dependent absorption of the emitted photons by the tissue separating source and detector. The method is applicable to counting for low-energy photon-emitting nuclides that can be characterized by more than one quantum energy. Attenuation coefficients were given for lard, beef, and five tissue- equivalent materials. For spectrometry, a planar Ge(Li) detector proved most suitable. (author)

Mass Spectrometry Imaging in Nanomedicine: Unraveling the Potential of MSI for the Detection of Nanoparticles in Neuroscience.

Science.gov (United States)

Barre, Florian P Y; Heeren, Ron M A; Potocnik, Nina Ogrinc

2017-01-01

Mass spectrometry imaging (MSI) can uniquely detect thousands of compounds allowing both their identification and localization within biological tissue samples. MSI is an interdisciplinary science that crosses the borders of physics, chemistry and biology, and enables local molecular analysis at a broad range of length scales: From the subcellular level to whole body tissue sections. The spatial resolution of some mass spectrometers now allows nano-scale research, crucial for studies in nanomedicine. Recent developments in MSI have enabled the optimization and localization of drug delivery with nanoparticles within the body and in specific organs such as kidney, liver and brain. Combining MSI with nanomedicine has vast potential, specifically in the treatment of neurological disorders, where effective drug delivery has been hampered by the blood-brain barrier. This review provides an introduction to MSI and its different technologies, with the application of MSI to nanomedicine and the different possibilities that MSI offers to study molecular signals in the brain. Finally, we provide an outlook for the future and exciting potential of MSI in nanoparticle-related research. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Imaging of oral pathological tissue using optical coherence tomography

Science.gov (United States)

Canjau, Silvana; Todea, Carmen; Sinescu, Cosmin; Duma, Virgil-Florin; Topala, Florin I.; Podoleanu, Adrian G.

2014-01-01

Oral squamous cell carcinoma (OSCC) constitutes 90% of oral cancer. Early detection is a cornerstone to improve survival. Interaction of light with tissues may highlight changes in tissue structure and metabolism. We propose optical coherence tomography (OCT), as a non-invasive diagnosis method, being a new high-resolution optical technique that permits tri-dimensional (3-D), real-time imaging of near surface abnormalities in complex tissues. In this study half of the excisional biopsy was directed to the pathologist and the other half was assigned for OCT investigation. Histopathology validated the results. Areas of OSCC of the buccal mucosa were identified in the OCT images. The elements obserced included extensive epithelial down-growth, the disruption of the basement membrane, with areas of erosion, an epithelial layer that was highly variable in thickness and invasion into the sub-epithelial layers. Therefore, OCT appears to be a highly promising imaging modality.

MR imaging of skeletal soft tissue infection: utility of diffusion-weighted imaging in detecting abscess formation

International Nuclear Information System (INIS)

Harish, Srinivasan; Rebello, Ryan; Chiavaras, Mary M.; Kotnis, Nikhil

2011-01-01

Our objectives were to assess if diffusion-weighted imaging (DWI) can help identify abscess formation in the setting of soft tissue infection and to assess whether abscess formation can be diagnosed confidently with a combination of DWI and other unenhanced sequences. Eight cases of soft tissue infection imaged with MRI including DWI were retrospectively reviewed. Two male and six female patients were studied (age range 23-50 years). Unenhanced MRI including DWI was performed in all patients. Post-contrast images were obtained in seven patients. All patients had clinically or surgically confirmed abscesses. Abscesses demonstrated restricted diffusion. DWI in conjunction with other unenhanced imaging showed similar confidence levels as post-contrast images in diagnosing abscess formation in four cases. In two cases, although the combined use of DWI and other unenhanced imaging yielded the same confidence levels as post-contrast imaging, DWI was more definitive for demonstrating abscess formation. In one case, post-contrast images had a better confidence for suggesting abscess. In one case, DWI helped detected the abscess, where gadolinium could not be administered because of a contraindication. This preliminary study suggests that DWI is a useful adjunct in the diagnosis of skeletal soft tissue abscesses. (orig.)

Hard X-ray Microscopic Imaging Of Human Breast Tissues

Science.gov (United States)

Park, Sung H.; Kim, Hong T.; Kim, Jong K.; Jheon, Sang H.; Youn, Hwa S.

2007-01-01

X-ray microscopy with synchrotron radiation will be a useful tool for innovation of x-ray imaging in clinical and laboratory settings. It helps us observe detailed internal structure of material samples non-invasively in air. And, it also has the potential to solve some tough problems of conventional breast imaging if it could evaluate various conditions of breast tissue effectively. A new hard x-ray microscope with a spatial resolution better than 100 nm was installed at Pohang Light Source, a third generation synchrotron radiation facility in Pohang, Korea. The x-ray energy was set at 6.95 keV, and the x-ray beam was monochromatized by W/B4C monochromator. Condenser and objective zone plates were used as x-ray lenses. Zernike phase plate next to condenser zone plate was introduced for improved contrast imaging. The image of a sample was magnified 30 times by objective zone plate and 20 times by microscope objective, respectively. After additional 10 times digital magnification, the total magnifying power was up to 6000 times in the end. Phase contrast synchrotron images of 10-μm-thick female breast tissue of the normal, fibroadenoma, fibrocystic change and carcinoma cases were obtained. By phase contrast imaging, hard x-rays enable us to observe many structures of breast tissue without sample preparations such as staining or fixation.

Hard X-ray Microscopic Imaging Of Human Breast Tissues

International Nuclear Information System (INIS)

Park, Sung H.; Kim, Hong T.; Kim, Jong K.; Jheon, Sang H.; Youn, Hwa S.

2007-01-01

X-ray microscopy with synchrotron radiation will be a useful tool for innovation of x-ray imaging in clinical and laboratory settings. It helps us observe detailed internal structure of material samples non-invasively in air. And, it also has the potential to solve some tough problems of conventional breast imaging if it could evaluate various conditions of breast tissue effectively. A new hard x-ray microscope with a spatial resolution better than 100 nm was installed at Pohang Light Source, a third generation synchrotron radiation facility in Pohang, Korea. The x-ray energy was set at 6.95 keV, and the x-ray beam was monochromatized by W/B4C monochromator. Condenser and objective zone plates were used as x-ray lenses. Zernike phase plate next to condenser zone plate was introduced for improved contrast imaging. The image of a sample was magnified 30 times by objective zone plate and 20 times by microscope objective, respectively. After additional 10 times digital magnification, the total magnifying power was up to 6000 times in the end. Phase contrast synchrotron images of 10-μm-thick female breast tissue of the normal, fibroadenoma, fibrocystic change and carcinoma cases were obtained. By phase contrast imaging, hard x-rays enable us to observe many structures of breast tissue without sample preparations such as staining or fixation

Experimental and numerical investigation of tissue harmonic imaging (THI)

Science.gov (United States)

Jing, Yuan; Yang, Xinmai; Cleveland, Robin O.

2003-04-01

In THI the probing ultrasonic pulse has enough amplitude that it undergoes nonlinear distortion and energy shifts from the fundamental frequency of the pulse into its higher harmonics. Images generated from the second harmonic (SH) have superior quality to the images formed from the fundamental frequency. Experiments with a single element focused ultrasound transducer were used to compare a line target embedded in a tissue phantom using either fundamental or SH imaging. SH imaging showed an improvement in both the axial resolution (0.70 mm vs 0.92 mm) and the lateral resolution (1.02 mm vs 2.70 mm) of the target. In addition, the contrast-to-tissue ratio of the target was 2 dB higher with SH imaging. A three-dimensional model of the forward propagation has been developed to simulate the experimental system. The model is based on a time-domain code for solving the KZK equation and accounts for arbitrary spatial variations in all tissue properties. The code was used to determine the impact of a nearfield layer of fat on the fundamental and second harmonic signals. For a 15 mm thick layer the SH side-lobes remained the same but the fundamental side-lobes increased by 2 dB. [Work supported by the NSF through the Center for Subsurface Sensing and Imaging Systems.

Energy-Looping Nanoparticles: Harnessing Excited-State Absorption for Deep-Tissue Imaging.

Science.gov (United States)

Levy, Elizabeth S; Tajon, Cheryl A; Bischof, Thomas S; Iafrati, Jillian; Fernandez-Bravo, Angel; Garfield, David J; Chamanzar, Maysamreza; Maharbiz, Michel M; Sohal, Vikaas S; Schuck, P James; Cohen, Bruce E; Chan, Emory M

2016-09-27

Near infrared (NIR) microscopy enables noninvasive imaging in tissue, particularly in the NIR-II spectral range (1000-1400 nm) where attenuation due to tissue scattering and absorption is minimized. Lanthanide-doped upconverting nanocrystals are promising deep-tissue imaging probes due to their photostable emission in the visible and NIR, but these materials are not efficiently excited at NIR-II wavelengths due to the dearth of lanthanide ground-state absorption transitions in this window. Here, we develop a class of lanthanide-doped imaging probes that harness an energy-looping mechanism that facilitates excitation at NIR-II wavelengths, such as 1064 nm, that are resonant with excited-state absorption transitions but not ground-state absorption. Using computational methods and combinatorial screening, we have identified Tm(3+)-doped NaYF4 nanoparticles as efficient looping systems that emit at 800 nm under continuous-wave excitation at 1064 nm. Using this benign excitation with standard confocal microscopy, energy-looping nanoparticles (ELNPs) are imaged in cultured mammalian cells and through brain tissue without autofluorescence. The 1 mm imaging depths and 2 μm feature sizes are comparable to those demonstrated by state-of-the-art multiphoton techniques, illustrating that ELNPs are a promising class of NIR probes for high-fidelity visualization in cells and tissue.

High Definition Confocal Imaging Modalities for the Characterization of Tissue-Engineered Substitutes.

Science.gov (United States)

Mayrand, Dominique; Fradette, Julie

2018-01-01

Optimal imaging methods are necessary in order to perform a detailed characterization of thick tissue samples from either native or engineered tissues. Tissue-engineered substitutes are featuring increasing complexity including multiple cell types and capillary-like networks. Therefore, technical approaches allowing the visualization of the inner structural organization and cellular composition of tissues are needed. This chapter describes an optical clearing technique which facilitates the detailed characterization of whole-mount samples from skin and adipose tissues (ex vivo tissues and in vitro tissue-engineered substitutes) when combined with spectral confocal microscopy and quantitative analysis on image renderings.

Preliminary study of synthetic aperture tissue harmonic imaging on in-vivo data

Science.gov (United States)

Rasmussen, Joachim H.; Hemmsen, Martin C.; Madsen, Signe S.; Hansen, Peter M.; Nielsen, Michael B.; Jensen, Jørgen A.

2013-03-01

A method for synthetic aperture tissue harmonic imaging is investigated. It combines synthetic aperture sequen- tial beamforming (SASB) with tissue harmonic imaging (THI) to produce an increased and more uniform spatial resolution and improved side lobe reduction compared to conventional B-mode imaging. Synthetic aperture sequential beamforming tissue harmonic imaging (SASB-THI) was implemented on a commercially available BK 2202 Pro Focus UltraView ultrasound system and compared to dynamic receive focused tissue harmonic imag- ing (DRF-THI) in clinical scans. The scan sequence that was implemented on the UltraView system acquires both SASB-THI and DRF-THI simultaneously. Twenty-four simultaneously acquired video sequences of in-vivo abdominal SASB-THI and DRF-THI scans on 3 volunteers of 4 different sections of liver and kidney tissues were created. Videos of the in-vivo scans were presented in double blinded studies to two radiologists for image quality performance scoring. Limitations to the systems transmit stage prevented user defined transmit apodization to be applied. Field II simulations showed that side lobes in SASB could be improved by using Hanning transmit apodization. Results from the image quality study show, that in the current configuration on the UltraView system, where no transmit apodization was applied, SASB-THI and DRF-THI produced equally good images. It is expected that given the use of transmit apodization, SASB-THI could be further improved.

Surface analysis by imaging mass spectrometry

Czech Academy of Sciences Publication Activity Database

Vidová, Veronika; Volný, Michael; Lemr, Karel; Havlíček, Vladimír

2009-01-01

Roč. 74, 7-8 (2009), s. 1101-1116 ISSN 0010-0765 Institutional research plan: CEZ:AV0Z50200510 Keywords : secondary ion mass spectrometry * matrix assisted laser desorption ionization * mass spectrometry Subject RIV: CB - Analytical Chemistry, Separation Impact factor: 0.856, year: 2009

Extracting morphologies from third harmonic generation images of structurally normal human brain tissue

NARCIS (Netherlands)

Zhang, Zhiqing; Kuzmin, Nikolay V.; Groot, Marie Louise; de Munck, Jan C.

2017-01-01

Motivation: The morphologies contained in 3D third harmonic generation (THG) images of human brain tissue can report on the pathological state of the tissue. However, the complexity of THG brain images makes the usage of modern image processing tools, especially those of image filtering,

Correcting mass shifts: A lock mass-free recalibration procedure for mass spectrometry imaging data

Czech Academy of Sciences Publication Activity Database

Kulkarni, P.; Kaftan, F.; Kynast, P.; Svatoš, Aleš; Böcker, S.

2015-01-01

Roč. 407, č. 25 (2015), s. 7603-7613 ISSN 1618-2642 Institutional support: RVO:61388963 Keywords : mass spectrometry imaging * recalibration * mass shift correction * data processing Subject RIV: CB - Analytical Chemistry , Separation Impact factor: 3.125, year: 2015

Investigation of Figopitant and Its Metabolites in Rat Tissue by Combining Whole-Body Autoradiography with Liquid Extraction Surface Analysis Mass Spectrometry

DEFF Research Database (Denmark)

Schadt, S.; Kallbach, S.; Almeida, R.

2012-01-01

tissue extraction, sample cleanup, and high-performance liquid chromatography analysis. The parent drug and the N-dealkylated metabolite M474(1) (BIIF 1148) in varying ratios were the predominant compounds in all tissues investigated. In addition, several metabolites formed by oxygenation, dealkylation......This article describes the combination of whole-body autoradiography with liquid extraction surface analysis (LESA) and mass spectrometry (MS) to study the distribution of the tachykinin neurokinin-1 antagonist figopitant and its metabolites in tissue sections of rats after intravenous...

Segmentation of the tissues from MR images using basic anatomical information

International Nuclear Information System (INIS)

Yamazaki, Nobutoshi; Notoya, Yoshiaki; Nakamura, Toshiyasu; Mochimaru, Masaaki.

1994-01-01

Automatic segmentation methods of MR images have been developed for the cardiac surgery and the brain surgery. In these fields, Region Growing method has been used mainly. In this method, the core was inserted manually, and the pixel adjoining the core was judged whether it was homogeneous or not from its features based on image information. The core grew adding the homogeneous pixels, and the region of interest was obtained as the grown core. It is available for orthopedic surgery and biomechanics to obtain the location and the orientation of bones and soft tissues in vivo. However, MR images including them could not be segmented by the former region growing method based on only image information. This is because those tissues had fuzzy boundaries on the image. Thus, we used not only intensity and spatial gradient as image information but also location, size and complexity of the tissue to segment the MR images. The pixel adjoining the core was judged from three local features of the pixel ; its intensity, gradient and location, and two global features of the core region ; its size and complexity. Judgment was performed by Fuzzy Reasoning to allow their fuzzy boundaries. The homogeneous pixel was added into the core region. It grew into normal size and smooth shape under constraint of global anatomical features. Using the present method, as an example, radius, ulna and interosseous membrane were segmented from the multi-sliced MR images of forearm. Segmented tissues agreed with the shape inserted manually by a medical doctor. As s result, three tissues containing different features on the MR image could be segmented by a single algorithm. It takes about 10 sec per slice by using an engineering workstation. (author)

Segmentation of the tissues from MR images using basic anatomical information

Energy Technology Data Exchange (ETDEWEB)

Yamazaki, Nobutoshi; Notoya, Yoshiaki [Keio Univ., Yokohama (Japan). Faculty of Science and Technology; Nakamura, Toshiyasu; Mochimaru, Masaaki

1994-11-01

Automatic segmentation methods of MR images have been developed for the cardiac surgery and the brain surgery. In these fields, Region Growing method has been used mainly. In this method, the core was inserted manually, and the pixel adjoining the core was judged whether it was homogeneous or not from its features based on image information. The core grew adding the homogeneous pixels, and the region of interest was obtained as the grown core. It is available for orthopedic surgery and biomechanics to obtain the location and the orientation of bones and soft tissues in vivo. However, MR images including them could not be segmented by the former region growing method based on only image information. This is because those tissues had fuzzy boundaries on the image. Thus, we used not only intensity and spatial gradient as image information but also location, size and complexity of the tissue to segment the MR images. The pixel adjoining the core was judged from three local features of the pixel ; its intensity, gradient and location, and two global features of the core region ; its size and complexity. Judgment was performed by Fuzzy Reasoning to allow their fuzzy boundaries. The homogeneous pixel was added into the core region. It grew into normal size and smooth shape under constraint of global anatomical features. Using the present method, as an example, radius, ulna and interosseous membrane were segmented from the multi-sliced MR images of forearm. Segmented tissues agreed with the shape inserted manually by a medical doctor. As s result, three tissues containing different features on the MR image could be segmented by a single algorithm. It takes about 10 sec per slice by using an engineering workstation. (author).

MR imaging of soft tissue tumors and tumor-like lesions

Energy Technology Data Exchange (ETDEWEB)

Laor, Tal [Department of Radiology, Cincinnati Children' s Hospital Medical Center, 3333 Burnet Avenue, 45229, Cincinnati, OH (United States)

2004-01-01

The evaluation of a soft tissue mass in a child should proceed with a differential diagnosis in mind, based on the clinical history, age of the child, and location of the abnormality. Small, superficial masses can be initially evaluated with sonography. More extensive or deep lesions usually require cross-sectional imaging. With the exception of myositis ossificans, magnetic resonance (MR) imaging has largely replaced the use of computed tomography. MR imaging is used to delineate the extent of a lesion, to evaluate response to therapy, and to monitor postoperative complications. There is great overlap in the MR imaging characteristics of benign and malignant lesions, making tissue sampling imperative for diagnosis. (orig.)

Miniaturized side-viewing imaging probe for fluorescence lifetime imaging (FLIM): validation with fluorescence dyes, tissue structural proteins and tissue specimens

OpenAIRE

Elson, DS; Jo, JA; Marcu, L

2007-01-01

We report a side viewing fibre-based endoscope that is compatible with intravascular imaging and fluorescence lifetime imaging microscopy (FLIM). The instrument has been validated through testing with fluorescent dyes and collagen and elastin powders using the Laguerre expansion deconvolution technique to calculate the fluorescence lifetimes. The instrument has also been tested on freshly excised unstained animal vascular tissues.

Raman molecular imaging of brain frozen tissue sections.

Science.gov (United States)

Kast, Rachel E; Auner, Gregory W; Rosenblum, Mark L; Mikkelsen, Tom; Yurgelevic, Sally M; Raghunathan, Aditya; Poisson, Laila M; Kalkanis, Steven N

2014-10-01

Raman spectroscopy provides a molecular signature of the region being studied. It is ideal for neurosurgical applications because it is non-destructive, label-free, not impacted by water concentration, and can map an entire region of tissue. The objective of this paper is to demonstrate the meaningful spatial molecular information provided by Raman spectroscopy for identification of regions of normal brain, necrosis, diffusely infiltrating glioma and solid glioblastoma (GBM). Five frozen section tissues (1 normal, 1 necrotic, 1 GBM, and 2 infiltrating glioma) were mapped in their entirety using a 300-µm-square step size. Smaller regions of interest were also mapped using a 25-µm step size. The relative concentrations of relevant biomolecules were mapped across all tissues and compared with adjacent hematoxylin and eosin-stained sections, allowing identification of normal, GBM, and necrotic regions. Raman peaks and peak ratios mapped included 1003, 1313, 1431, 1585, and 1659 cm(-1). Tissue maps identified boundaries of grey and white matter, necrosis, GBM, and infiltrating tumor. Complementary information, including relative concentration of lipids, protein, nucleic acid, and hemoglobin, was presented in a manner which can be easily adapted for in vivo tissue mapping. Raman spectroscopy can successfully provide label-free imaging of tissue characteristics with high accuracy. It can be translated to a surgical or laboratory tool for rapid, non-destructive imaging of tumor margins.

TH-AB-209-12: Tissue Equivalent Phantom with Excised Human Tissue for Assessing Clinical Capabilities of Coherent Scatter Imaging Applications

Energy Technology Data Exchange (ETDEWEB)

Albanese, K; Morris, R; Spencer, J [Medical Physics Graduate Program, Duke University, Durham, NC (United States); Greenberg, J [Dept. of Electrical and Computer Engineering, Duke University, Durham, NC (United States); Kapadia, A [Carl E Ravin Advanced Imaging Laboratories, Durham, NC (United States)

2016-06-15

Purpose: Previously we reported the development of anthropomorphic tissue-equivalent scatter phantoms of the human breast. Here we present the first results from the scatter imaging of the tissue equivalent breast phantoms for breast cancer diagnosis. Methods: A breast phantom was designed to assess the capability of coded aperture coherent x-ray scatter imaging to classify different types of breast tissue (adipose, fibroglandular, tumor). The phantom geometry was obtained from a prone breast geometry scanned on a dedicated breast CT system. The phantom was 3D printed using the segmented DICOM breast CT data. The 3D breast phantom was filled with lard (as a surrogate for adipose tissue) and scanned in different geometries alongside excised human breast tissues (obtained from lumpectomy and mastectomy procedures). The raw data were reconstructed using a model-based reconstruction algorithm and yielded the location and form factor (i.e., momentum transfer (q) spectrum) of the materials that were imaged. The measured material form factors were then compared to the ground truth measurements acquired by x-ray diffraction (XRD) imaging. Results: Our scatter imaging system was able to define the location and composition of the various materials and tissues within the phantom. Cancerous breast tissue was detected and classified through automated spectral matching and an 86% correlation threshold. The total scan time for the sample was approximately 10 minutes and approaches workflow times for clinical use in intra-operative or other diagnostic tasks. Conclusion: This work demonstrates the first results from an anthropomorphic tissue equivalent scatter phantom to characterize a coherent scatter imaging system. The functionality of the system shows promise in applications such as intra-operative margin detection or virtual biopsy in the diagnosis of breast cancer. Future work includes using additional patient-derived tissues (e.g., human fat), and modeling additional organs

Image processing can cause some malignant soft-tissue lesions to be missed in digital mammography images.

Science.gov (United States)

Warren, L M; Halling-Brown, M D; Looney, P T; Dance, D R; Wallis, M G; Given-Wilson, R M; Wilkinson, L; McAvinchey, R; Young, K C

2017-09-01

To investigate the effect of image processing on cancer detection in mammography. An observer study was performed using 349 digital mammography images of women with normal breasts, calcification clusters, or soft-tissue lesions including 191 subtle cancers. Images underwent two types of processing: FlavourA (standard) and FlavourB (added enhancement). Six observers located features in the breast they suspected to be cancerous (4,188 observations). Data were analysed using jackknife alternative free-response receiver operating characteristic (JAFROC) analysis. Characteristics of the cancers detected with each image processing type were investigated. For calcifications, the JAFROC figure of merit (FOM) was equal to 0.86 for both types of image processing. For soft-tissue lesions, the JAFROC FOM were better for FlavourA (0.81) than FlavourB (0.78); this difference was significant (p=0.001). Using FlavourA a greater number of cancers of all grades and sizes were detected than with FlavourB. FlavourA improved soft-tissue lesion detection in denser breasts (p=0.04 when volumetric density was over 7.5%) CONCLUSIONS: The detection of malignant soft-tissue lesions (which were primarily invasive) was significantly better with FlavourA than FlavourB image processing. This is despite FlavourB having a higher contrast appearance often preferred by radiologists. It is important that clinical choice of image processing is based on objective measures. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Antigen retrieval prior to on-tissue digestion of formalin-fixed paraffin-embedded tumour tissue sections yields oxidation of proline residues.

Science.gov (United States)

Djidja, Marie-Claude; Claude, Emmanuelle; Scriven, Peter; Allen, David W; Carolan, Vikki A; Clench, Malcolm R

2017-07-01

MALDI-mass spectrometry imaging (MALDI-MSI) has been shown to allow the study of protein distribution and identification directly within formalin-fixed paraffin-embedded (FFPE) tissue sections. However, direct protein identification from tissue sections remains challenging due to signal interferences and/or existing post-translational or other chemical modifications. The use of antigen retrieval (AR) has been demonstrated for unlocking proteins prior to in situ enzymatic digestion and MALDI-MSI analysis of FFPE tissue sections. In the work reported here, the identification of proline oxidation, which may occur when performing the AR protocol, is described. This facilitated and considerably increased the number of identified peptides when adding proline oxidation as a variable modification to the MASCOT search criteria. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann. Copyright © 2016 Elsevier B.V. All rights reserved.

Applications of two-photon fluorescence microscopy in deep-tissue imaging

Science.gov (United States)

Dong, Chen-Yuan; Yu, Betty; Hsu, Lily L.; Kaplan, Peter D.; Blankschstein, D.; Langer, Robert; So, Peter T. C.

2000-07-01

Based on the non-linear excitation of fluorescence molecules, two-photon fluorescence microscopy has become a significant new tool for biological imaging. The point-like excitation characteristic of this technique enhances image quality by the virtual elimination of off-focal fluorescence. Furthermore, sample photodamage is greatly reduced because fluorescence excitation is limited to the focal region. For deep tissue imaging, two-photon microscopy has the additional benefit in the greatly improved imaging depth penetration. Since the near- infrared laser sources used in two-photon microscopy scatter less than their UV/glue-green counterparts, in-depth imaging of highly scattering specimen can be greatly improved. In this work, we will present data characterizing both the imaging characteristics (point-spread-functions) and tissue samples (skin) images using this novel technology. In particular, we will demonstrate how blind deconvolution can be used further improve two-photon image quality and how this technique can be used to study mechanisms of chemically-enhanced, transdermal drug delivery.

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

Science.gov (United States)

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. © 2013 The Authors. Journal of Mass Spectrometry published by John Wiley & Sons, Ltd.

Automated detection of regions of interest for tissue microarray experiments: an image texture analysis

International Nuclear Information System (INIS)

Karaçali, Bilge; Tözeren, Aydin

2007-01-01

Recent research with tissue microarrays led to a rapid progress toward quantifying the expressions of large sets of biomarkers in normal and diseased tissue. However, standard procedures for sampling tissue for molecular profiling have not yet been established. This study presents a high throughput analysis of texture heterogeneity on breast tissue images for the purpose of identifying regions of interest in the tissue for molecular profiling via tissue microarray technology. Image texture of breast histology slides was described in terms of three parameters: the percentage of area occupied in an image block by chromatin (B), percentage occupied by stroma-like regions (P), and a statistical heterogeneity index H commonly used in image analysis. Texture parameters were defined and computed for each of the thousands of image blocks in our dataset using both the gray scale and color segmentation. The image blocks were then classified into three categories using the texture feature parameters in a novel statistical learning algorithm. These categories are as follows: image blocks specific to normal breast tissue, blocks specific to cancerous tissue, and those image blocks that are non-specific to normal and disease states. Gray scale and color segmentation techniques led to identification of same regions in histology slides as cancer-specific. Moreover the image blocks identified as cancer-specific belonged to those cell crowded regions in whole section image slides that were marked by two pathologists as regions of interest for further histological studies. These results indicate the high efficiency of our automated method for identifying pathologic regions of interest on histology slides. Automation of critical region identification will help minimize the inter-rater variability among different raters (pathologists) as hundreds of tumors that are used to develop an array have typically been evaluated (graded) by different pathologists. The region of interest

A novel ion imager for secondary ion mass spectrometry

International Nuclear Information System (INIS)

Matsumoto, Kazuya; Miyata, Kenji; Nakamura, Tsutomu

1993-01-01

This paper describes a new area detector for secondary ion mass spectrometry (SIMS) ion microscope, and its performance. The operational principle is based on detecting the change in potential of a floating photodiode caused by the ion-induced secondary-electron emission and the incoming ion itself. The experiments demonstrated that 10 1 -10 5 aluminum ions per pixel can be detected with good linear response. Moreover, relative ion sensitivities from hydrogen to lead were constant within a factor of 2. The performance of this area detector provides the potential for detection of kiloelectronvolt ion images with current ion microscopy

Use of synchrotron-based diffraction-enhanced imaging for visualization of soft tissues in invertebrates

International Nuclear Information System (INIS)

Rao, Donepudi V.; Swapna, Medasani; Cesareo, Roberto; Brunetti, Antonio; Zhong, Zhong; Akatsuka, Takao; Yuasa, Tetsuya; Takeda, Tohoru; Gigante, Giovanni E.

2010-01-01

Images of terrestrial and marine invertebrates (snails and bivalves) have been obtained by using an X-ray phase-contrast imaging technique, namely, synchrotron-based diffraction-enhanced imaging. Synchrotron X-rays of 20, 30 and 40 keV were used, which penetrate deep enough into animal soft tissues. The phase of X-ray photons shifts slightly as they traverse an object, such as animal soft tissue, and interact with its atoms. Biological features, such as shell morphology and animal physiology, have been visualized. The contrast of the images obtained at 40 keV is the best. This optimum energy provided a clear view of the internal structural organization of the soft tissue with better contrast. The contrast is higher at edges of internal soft-tissue structures. The image improvements achieved with the diffraction-enhanced imaging technique are due to extinction, i.e., elimination of ultra-small-angle scattering. They enabled us to identify a few embedded internal shell features, such as the origin of the apex, which is the firmly attached region of the soft tissue connecting the umbilicus to the external morphology. Diffraction-enhanced imaging can provide high-quality images of soft tissues valuable for biology.

Use of synchrotron-based diffraction-enhanced imaging for visualization of soft tissues in invertebrates

Energy Technology Data Exchange (ETDEWEB)

Rao, Donepudi V., E-mail: donepudi_venkateswararao@rediffmail.co [Istituto di Matematica e Fisica, Universita degli Studi di Sassari, Via Vienna 2, 07100 Sassari (Italy); Swapna, Medasani, E-mail: medasanisw@gmail.co [Istituto di Matematica e Fisica, Universita degli Studi di Sassari, Via Vienna 2, 07100 Sassari (Italy); Cesareo, Roberto; Brunetti, Antonio [Istituto di Matematica e Fisica, Universita degli Studi di Sassari, Via Vienna 2, 07100 Sassari (Italy); Zhong, Zhong [National Synchrotron Light Source, Brookhaven National Laboratory, Upton, NY 11973 (United States); Akatsuka, Takao; Yuasa, Tetsuya [Department of Bio-System Engineering, Faculty of Engineering, Yamagata University, Yonezawa-shi, Yamagata-992-8510 (Japan); Takeda, Tohoru [Allied Health Science, Kitasato University 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555 (Japan); Gigante, Giovanni E. [Dipartimento di Fisica, Universita di Roma, La Sapienza, 00185 Roma (Italy)

2010-09-15

Images of terrestrial and marine invertebrates (snails and bivalves) have been obtained by using an X-ray phase-contrast imaging technique, namely, synchrotron-based diffraction-enhanced imaging. Synchrotron X-rays of 20, 30 and 40 keV were used, which penetrate deep enough into animal soft tissues. The phase of X-ray photons shifts slightly as they traverse an object, such as animal soft tissue, and interact with its atoms. Biological features, such as shell morphology and animal physiology, have been visualized. The contrast of the images obtained at 40 keV is the best. This optimum energy provided a clear view of the internal structural organization of the soft tissue with better contrast. The contrast is higher at edges of internal soft-tissue structures. The image improvements achieved with the diffraction-enhanced imaging technique are due to extinction, i.e., elimination of ultra-small-angle scattering. They enabled us to identify a few embedded internal shell features, such as the origin of the apex, which is the firmly attached region of the soft tissue connecting the umbilicus to the external morphology. Diffraction-enhanced imaging can provide high-quality images of soft tissues valuable for biology.

Tissue Equivalent Phantom Design for Characterization of a Coherent Scatter X-ray Imaging System

Science.gov (United States)

Albanese, Kathryn Elizabeth

Scatter in medical imaging is typically cast off as image-related noise that detracts from meaningful diagnosis. It is therefore typically rejected or removed from medical images. However, it has been found that every material, including cancerous tissue, has a unique X-ray coherent scatter signature that can be used to identify the material or tissue. Such scatter-based tissue-identification provides the advantage of locating and identifying particular materials over conventional anatomical imaging through X-ray radiography. A coded aperture X-ray coherent scatter spectral imaging system has been developed in our group to classify different tissue types based on their unique scatter signatures. Previous experiments using our prototype have demonstrated that the depth-resolved coherent scatter spectral imaging system (CACSSI) can discriminate healthy and cancerous tissue present in the path of a non-destructive x-ray beam. A key to the successful optimization of CACSSI as a clinical imaging method is to obtain anatomically accurate phantoms of the human body. This thesis describes the development and fabrication of 3D printed anatomical scatter phantoms of the breast and lung. The purpose of this work is to accurately model different breast geometries using a tissue equivalent phantom, and to classify these tissues in a coherent x-ray scatter imaging system. Tissue-equivalent anatomical phantoms were designed to assess the capability of the CACSSI system to classify different types of breast tissue (adipose, fibroglandular, malignant). These phantoms were 3D printed based on DICOM data obtained from CT scans of prone breasts. The phantoms were tested through comparison of measured scatter signatures with those of adipose and fibroglandular tissue from literature. Tumors in the phantom were modeled using a variety of biological tissue including actual surgically excised benign and malignant tissue specimens. Lung based phantoms have also been printed for future

Dobutamine Stress Echocardiography and Tissue Synchronization Imaging

Science.gov (United States)

Tas, Hakan; Gundogdu, Fuat; Gurlertop, Yekta; Karakelleoglu, Sule

2008-01-01

Dobutamine stress echocardiography has emerged as a reliable method for the diagnosis of coronary artery disease and the management of its treatment. Several studies have shown that that this technique works with 80–85% accuracy in comparison with other imaging methods. There are few studies aimed at developing the clinical utility of dobutamine stress echocardiography for the evaluation of normal and abnormal segments that result from dobutamine stress with Tissue Synchronization Imaging. PMID:25610034

Fourier Transform Infrared (FT-IR) and Laser Ablation Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) Imaging of Cerebral Ischemia: Combined Analysis of Rat Brain Thin Cuts Toward Improved Tissue Classification.

Science.gov (United States)

Balbekova, Anna; Lohninger, Hans; van Tilborg, Geralda A F; Dijkhuizen, Rick M; Bonta, Maximilian; Limbeck, Andreas; Lendl, Bernhard; Al-Saad, Khalid A; Ali, Mohamed; Celikic, Minja; Ofner, Johannes

2018-02-01

Microspectroscopic techniques are widely used to complement histological studies. Due to recent developments in the field of chemical imaging, combined chemical analysis has become attractive. This technique facilitates a deepened analysis compared to single techniques or side-by-side analysis. In this study, rat brains harvested one week after induction of photothrombotic stroke were investigated. Adjacent thin cuts from rats' brains were imaged using Fourier transform infrared (FT-IR) microspectroscopy and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The LA-ICP-MS data were normalized using an internal standard (a thin gold layer). The acquired hyperspectral data cubes were fused and subjected to multivariate analysis. Brain regions affected by stroke as well as unaffected gray and white matter were identified and classified using a model based on either partial least squares discriminant analysis (PLS-DA) or random decision forest (RDF) algorithms. The RDF algorithm demonstrated the best results for classification. Improved classification was observed in the case of fused data in comparison to individual data sets (either FT-IR or LA-ICP-MS). Variable importance analysis demonstrated that both molecular and elemental content contribute to the improved RDF classification. Univariate spectral analysis identified biochemical properties of the assigned tissue types. Classification of multisensor hyperspectral data sets using an RDF algorithm allows access to a novel and in-depth understanding of biochemical processes and solid chemical allocation of different brain regions.

Detection of light images by simple tissues as visualized by photosensitized magnetic resonance imaging.

Directory of Open Access Journals (Sweden)

Catherine Tempel-Brami

Full Text Available In this study, we show how light can be absorbed by the body of a living rat due to an injected pigment circulating in the blood stream. This process is then physiologically translated in the tissue into a chemical signature that can be perceived as an image by magnetic resonance imaging (MRI. We previously reported that illumination of an injected photosynthetic bacteriochlorophyll-derived pigment leads to a generation of reactive oxygen species, upon oxygen consumption in the blood stream. Consequently, paramagnetic deoxyhemoglobin accumulating in the illuminated area induces changes in image contrast, detectable by a Blood Oxygen Level Dependent (BOLD-MRI protocol, termed photosensitized (psMRI. Here, we show that laser beam pulses synchronously trigger BOLD-contrast transients in the tissue, allowing representation of the luminous spatiotemporal profile, as a contrast map, on the MR monitor. Regions with enhanced BOLD-contrast (7-61 fold were deduced as illuminated, and were found to overlap with the anatomical location of the incident light. Thus, we conclude that luminous information can be captured and translated by typical oxygen exchange processes in the blood of ordinary tissues, and made visible by psMRI (Fig. 1. This process represents a new channel for communicating environmental light into the body in certain analogy to light absorption by visual pigments in the retina where image perception takes place in the central nervous system. Potential applications of this finding may include: non-invasive intra-operative light guidance and follow-up of photodynamic interventions, determination of light diffusion in opaque tissues for optical imaging and possible assistance to the blind.

Combined Mass Spectrometry Imaging and Top-down Microproteomics Reveals Evidence of a Hidden Proteome in Ovarian Cancer.

Science.gov (United States)

Delcourt, Vivian; Franck, Julien; Leblanc, Eric; Narducci, Fabrice; Robin, Yves-Marie; Gimeno, Jean-Pascal; Quanico, Jusal; Wisztorski, Maxence; Kobeissy, Firas; Jacques, Jean-François; Roucou, Xavier; Salzet, Michel; Fournier, Isabelle

2017-07-01

Recently, it was demonstrated that proteins can be translated from alternative open reading frames (altORFs), increasing the size of the actual proteome. Top-down mass spectrometry-based proteomics allows the identification of intact proteins containing post-translational modifications (PTMs) as well as truncated forms translated from reference ORFs or altORFs. Top-down tissue microproteomics was applied on benign, tumor and necrotic-fibrotic regions of serous ovarian cancer biopsies, identifying proteins exhibiting region-specific cellular localization and PTMs. The regions of interest (ROIs) were determined by MALDI mass spectrometry imaging and spatial segmentation. Analysis with a customized protein sequence database containing reference and alternative proteins (altprots) identified 15 altprots, including alternative G protein nucleolar 1 (AltGNL1) found in the tumor, and translated from an altORF nested within the GNL1 canonical coding sequence. Co-expression of GNL1 and altGNL1 was validated by transfection in HEK293 and HeLa cells with an expression plasmid containing a GNL1-FLAG (V5) construct. Western blot and immunofluorescence experiments confirmed constitutive co-expression of altGNL1-V5 with GNL1-FLAG. Taken together, our approach provides means to evaluate protein changes in the case of serous ovarian cancer, allowing the detection of potential markers that have never been considered. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Confocal multispot microscope for fast and deep imaging in semicleared tissues

Science.gov (United States)

Adam, Marie-Pierre; Müllenbroich, Marie Caroline; Di Giovanna, Antonino Paolo; Alfieri, Domenico; Silvestri, Ludovico; Sacconi, Leonardo; Pavone, Francesco Saverio

2018-02-01

Although perfectly transparent specimens are imaged faster with light-sheet microscopy, less transparent samples are often imaged with two-photon microscopy leveraging its robustness to scattering; however, at the price of increased acquisition times. Clearing methods that are capable of rendering strongly scattering samples such as brain tissue perfectly transparent specimens are often complex, costly, and time intensive, even though for many applications a slightly lower level of tissue transparency is sufficient and easily achieved with simpler and faster methods. Here, we present a microscope type that has been geared toward the imaging of semicleared tissue by combining multispot two-photon excitation with rolling shutter wide-field detection to image deep and fast inside semicleared mouse brain. We present a theoretical and experimental evaluation of the point spread function and contrast as a function of shutter size. Finally, we demonstrate microscope performance in fixed brain slices by imaging dendritic spines up to 400-μm deep.

Histology and imaging of soft tissue sarcomas.

Science.gov (United States)

Kind, Michèle; Stock, Nathalie; Coindre, Jean Michel

2009-10-01

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Histology and imaging of soft tissue sarcomas

International Nuclear Information System (INIS)

Kind, Michele; Stock, Nathalie; Coindre, Jean Michel

2009-01-01

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Histology and imaging of soft tissue sarcomas

Energy Technology Data Exchange (ETDEWEB)

Kind, Michele [Departement d' Imagerie Medicale, Institut Bergonie, 229 cours de l' Argonne, 33076 Bordeaux Cedex (France)], E-mail: kind@bergonie.org; Stock, Nathalie; Coindre, Jean Michel [Departement de Pathologie, Institut Bergonie, 229 cours de l' Argonne, 33076 Bordeaux Cedex (France); Universite Victor Segalen Bordeaux 2, 146 rue Leo Saignat, 33076 Bordeaux Cedex (France)

2009-10-15

Imaging and histology are two complementary morphological techniques which play a fundamental role in the diagnosis and management of soft tissue sarcomas. Imaging allows to identify some pseudosarcomatous benign lesions such as myositis ossificans, intramuscular hemangioma, angiomyolipoma, intramuscular lipoma, giant cell tumour of tendon sheath, desmoid tumour and elastofibroma. There is no formal criterion for diagnosing a sarcoma on magnetic resonance imaging (MRI) but malignancy is strongly suspected with the presence of necrosis and vascular, bone or joint invasion. Imaging may also suggest some histological types of sarcoma such as well-differentiated liposarcoma, dedifferentiated liposarcoma, synovial sarcoma or extraskeletal osteosarcoma. Imaging is also extremely helpful in determining the appropriate kind of sampling to carry out and in guiding the performance of a microbiopsy. The appearance observed on imaging should always be taken into consideration for the interpretation of the microbiopsy by the pathologist.

Regional differences in brain glucose metabolism determined by imaging mass spectrometry

OpenAIRE

André Kleinridders; Heather A. Ferris; Michelle L. Reyzer; Michaela Rath; Marion Soto; M. Lisa Manier; Jeffrey Spraggins; Zhihong Yang; Robert C. Stanton; Richard M. Caprioli; C. Ronald Kahn

2018-01-01

Objective: Glucose is the major energy substrate of the brain and crucial for normal brain function. In diabetes, the brain is subject to episodes of hypo- and hyperglycemia resulting in acute outcomes ranging from confusion to seizures, while chronic metabolic dysregulation puts patients at increased risk for depression and Alzheimer's disease. In the present study, we aimed to determine how glucose is metabolized in different regions of the brain using imaging mass spectrometry (IMS). Metho...

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

Science.gov (United States)

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

Multispectral imaging of acute wound tissue oxygenation

Directory of Open Access Journals (Sweden)

Audrey Huong

2017-05-01

Full Text Available This paper investigates the appropriate range of values for the transcutaneous blood oxygen saturation (StO2 of granulating tissues and the surrounding tissue that can ensure timely wound recovery. This work has used a multispectral imaging system to collect wound images at wavelengths ranging between 520nm and 600nm with a resolution of 10nm. As part of this research, a pilot study was conducted on three injured individuals with superficial wounds of different wound ages at different skin locations. The StO2 value predicted for the examined wounds using the Extended Modified Lambert–Beer model revealed a mean StO2 of 61±10.3% compared to 41.6±6.2% at the surrounding tissues, and 50.1±1.53% for control sites. These preliminary results contribute to the existing knowledge on the possible range and variation of wound bed StO2 that are to be used as indicators of the functioning of the vasomotion system and wound health. This study has concluded that a high StO2 of approximately 60% and a large fluctuation in this value should precede a good progression in wound healing.

Biochemical imaging of tissues by SIMS for biomedical applications

International Nuclear Information System (INIS)

Lee, Tae Geol; Park, Ji-Won; Shon, Hyun Kyong; Moon, Dae Won; Choi, Won Woo; Li, Kapsok; Chung, Jin Ho

2008-01-01

With the development of optimal surface cleaning techniques by cluster ion beam sputtering, certain applications of SIMS for analyzing cells and tissues have been actively investigated. For this report, we collaborated with bio-medical scientists to study bio-SIMS analyses of skin and cancer tissues for biomedical diagnostics. We pay close attention to the setting up of a routine procedure for preparing tissue specimens and treating the surface before obtaining the bio-SIMS data. Bio-SIMS was used to study two biosystems, skin tissues for understanding the effects of photoaging and colon cancer tissues for insight into the development of new cancer diagnostics for cancer. Time-of-flight SIMS imaging measurements were taken after surface cleaning with cluster ion bombardment by Bi n or C 60 under varying conditions. The imaging capability of bio-SIMS with a spatial resolution of a few microns combined with principal component analysis reveal biologically meaningful information, but the lack of high molecular weight peaks even with cluster ion bombardment was a problem. This, among other problems, shows that discourse with biologists and medical doctors are critical to glean any meaningful information from SIMS mass spectrometric and imaging data. For SIMS to be accepted as a routine, daily analysis tool in biomedical laboratories, various practical sample handling methodology such as surface matrix treatment, including nano-metal particles and metal coating, in addition to cluster sputtering, should be studied

Quantitative analysis of drug distribution by ambient mass spectrometry imaging method with signal extinction normalization strategy and inkjet-printing technology.

Science.gov (United States)

Luo, Zhigang; He, Jingjing; He, Jiuming; Huang, Lan; Song, Xiaowei; Li, Xin; Abliz, Zeper

2018-03-01

Quantitative mass spectrometry imaging (MSI) is a robust approach that provides both quantitative and spatial information for drug candidates' research. However, because of complicated signal suppression and interference, acquiring accurate quantitative information from MSI data remains a challenge, especially for whole-body tissue sample. Ambient MSI techniques using spray-based ionization appear to be ideal for pharmaceutical quantitative MSI analysis. However, it is more challenging, as it involves almost no sample preparation and is more susceptible to ion suppression/enhancement. Herein, based on our developed air flow-assisted desorption electrospray ionization (AFADESI)-MSI technology, an ambient quantitative MSI method was introduced by integrating inkjet-printing technology with normalization of the signal extinction coefficient (SEC) using the target compound itself. The method utilized a single calibration curve to quantify multiple tissue types. Basic blue 7 and an antitumor drug candidate (S-(+)-deoxytylophorinidine, CAT) were chosen to initially validate the feasibility and reliability of the quantitative MSI method. Rat tissue sections (heart, kidney, and brain) administered with CAT was then analyzed. The quantitative MSI analysis results were cross-validated by LC-MS/MS analysis data of the same tissues. The consistency suggests that the approach is able to fast obtain the quantitative MSI data without introducing interference into the in-situ environment of the tissue sample, and is potential to provide a high-throughput, economical and reliable approach for drug discovery and development. Copyright © 2017 Elsevier B.V. All rights reserved.

Progress in reflectance confocal microscopy for imaging oral tissues in vivo

Science.gov (United States)

Peterson, Gary; Zanoni, Daniella K.; Migliacci, Jocelyn; Cordova, Miguel; Rajadhyaksha, Milind; Patel, Snehal

2016-02-01

We report progress in development and feasibility testing of reflectance confocal microscopy (RCM) for imaging in the oral cavity of humans. We adapted a small rigid relay telescope (120mm long x 14mm diameter) and a small water immersion objective lens (12mm diameter, NA 0.7) to a commercial handheld RCM scanner (Vivascope 3000, Caliber ID, Rochester NY). This scanner is designed for imaging skin but we adapted the front end (the objective lens and the stepper motor that axially translates) for intra-oral use. This adaption required a new approach to address the loss of the automated stepper motor for acquisition of images in depth. A helical spring-like cap (with a coverslip to contact tissue) was designed for approximately 150 um of travel. Additionally other methods for focusing optics were designed and evaluated. The relay telescope optics is being tested in a clinical setting. With the capture of video and "video-mosaicing", extended areas can be imaged. The feasibility of imaging oral tissues was initially investigated in volunteers. RCM imaging in buccal mucosa in vivo shows nuclear and cellular detail in the epithelium and epithelial junction, and connective tissue and blood flow in the underlying lamina propria. Similar detail, including filiform and fungiform papillae, can be seen on the tongue in vivo. Clinical testing during head and neck surgery is now in progress and patients are being imaged for both normal tissue and cancerous margins in lip and tongue mucosa.

Quantum dots versus organic fluorophores in fluorescent deep-tissue imaging--merits and demerits.

Science.gov (United States)

Bakalova, Rumiana; Zhelev, Zhivko; Gadjeva, Veselina

2008-12-01

The use of fluorescence in deep-tissue imaging is rapidly expanding in last several years. The progress in fluorescent molecular probes and fluorescent imaging techniques gives an opportunity to detect single cells and even molecular targets in live organisms. The highly sensitive and high-speed fluorescent molecular sensors and detection devices allow the application of fluorescence in functional imaging. With the development of novel bright fluorophores based on nanotechnologies and 3D fluorescence scanners with high spatial and temporal resolution, the fluorescent imaging has a potential to become an alternative of the other non-invasive imaging techniques as magnetic resonance imaging, positron-emission tomography, X-ray, computing tomography. The fluorescent imaging has also a potential to give a real map of human anatomy and physiology. The current review outlines the advantages of fluorescent nanoparticles over conventional organic dyes in deep-tissue imaging in vivo and defines the major requirements to the "perfect fluorophore". The analysis proceeds from the basic principles of fluorescence and major characteristics of fluorophores, light-tissue interactions, and major limitations of fluorescent deep-tissue imaging. The article is addressed to a broad readership - from specialists in this field to university students.

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

Science.gov (United States)

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.

Proteomics with Mass Spectrometry Imaging: Beyond Amyloid Typing.

Science.gov (United States)

Lavatelli, Francesca; Merlini, Giampaolo

2018-04-01

Detection and typing of amyloid deposits in tissues are two crucial steps in the management of systemic amyloidoses. The presence of amyloid deposits is routinely evaluated through Congo red staining, whereas proteomics is now a mainstay in the identification of the deposited proteins. In article number 1700236, Winter et al. [Proteomics 2017, 17, Issue 22] describe a novel method based on MALDI-MS imaging coupled to ion mobility separation and peptide filtering, to detect the presence of amyloid in histology samples and to identify its composition, while preserving the spatial distribution of proteins in tissues. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Determination of thyroid hormones in mouse tissues by isotope-dilution microflow liquid chromatography-mass spectrometry method.

Science.gov (United States)

De Angelis, Meri; Giesert, Florian; Finan, Brian; Clemmensen, Christoffer; Müller, Timo D; Vogt-Weisenhorn, Daniela; Tschöp, Matthias H; Schramm, Karl-Werner

2016-10-15

Thyroid hormones (THs) play a critical role in the regulation of many biological processes such as growth, metabolism and development both in humans and wildlife. In general, TH levels are measured by immunoassay (IA) methods but the specificity of the antibodies used in these assays limits selectivity. In the last decade, several analytical methods using liquid chromatography-mass spectrometry (LC-MS) and tandem mass spectrometry (LC-MS/MS) have been developed to measure THs. These new techniques proved to be more accurate than the IA analysis and they were widely used for the determination of TH level in different human and animal tissues. A large part of LC-MS/MS methods described in literature employed between 200 and 500mg of sample, however this quantity can be considered too high especially when preclinical studies are conducted using mice as test subjects. Thus an analytical method that reduces the amount of tissue is essential. In this study, we developed a procedure for the analysis of six THs; L-thyroxine (T4), 3,3',5-triiodo-l-thyronine (T3), 3,3',5'-triiodo-l-thyronine (rT3), 3,5-diiodo-l-thyronine (rT2), 3,3'-diiodo-l-thyronine (T2), 3-iodo-l-thyronine (T1) using isotope ((13)C6-T4, (13)C6-T3, (13)C6-rT3, (13)C6-T2) dilution liquid chromatography-mass spectrometry. The major difference with previously described methods lies in the utilization of a nano-UPLC (Ultra Performance Liquid Chromatography) system in micro configuration. This approach leads to a reduction compared to the published methods, of column internal diameter, flow rate, and injected volume. The result of all these improvements is a decrease in the amount of sample necessary for the analysis. The method was tested on six different mouse tissues: liver, heart, kidney, muscle, lung and brown adipose tissue (BAT). The nano-UPLC system was interfaced with a quadrupole time-of-flight mass spectrometer (Q-TOF2-MS) using the positive ion mode electrospray ionization. In our analytical method

Prevalence of Soft Tissue Calcifications in CBCT Images of Mandibular Region.

Science.gov (United States)

Khojastepour, Leila; Haghnegahdar, Abdolaziz; Sayar, Hamed

2017-06-01

Most of the soft tissue calcifications within the head and neck region might not be accompanied by clinical symptoms but may indicate some pathological conditions. The aim of this research was to determine the prevalence of soft tissue calcifications in cone beam computed tomography (CBCT) images of mandibular region. In this cross sectional study the CBCT images of 602 patients including 294 men and 308 women with mean age 41.38±15.18 years were evaluated regarding the presence, anatomical location; type (single or multiple) and size of soft tissue calcification in mandibular region. All CBCT images were acquired by NewTom VGi scanner. Odds ratio and chi-square tests were used for data analysis and p < 0.05 was considered to be statistically significant. 156 out of 602 patients had at least one soft tissue calcification in their mandibular region (25.9%. of studied population with mean age 51.7±18.03 years). Men showed significantly higher rate of soft tissue calcification than women (30.3% vs. 21.8%). Soft tissue calcification was predominantly seen at posterior region of the mandible (88%) and most of them were single (60.7%). The prevalence of soft tissue calcification increased with age. Most of the detected soft tissue calcifications were smaller than 3mm (90%). Soft tissue calcifications in mandibular area were a relatively common finding especially in posterior region and more likely to happen in men and in older age group.

Added soft tissue contrast using signal attenuation and the fractal dimension for optical coherence tomography images of porcine arterial tissue

International Nuclear Information System (INIS)

Flueraru, C; Mao, Y; Chang, S; Popescu, D P; Sowa, M G

2010-01-01

Optical coherence tomography (OCT) images of left-descending coronary tissues harvested from three porcine specimens were acquired with a home-build swept-source OCT setup. Despite the fact that OCT is capable of acquiring high resolution circumferential images of vessels, many distinct histological features of a vessel have comparable optical properties leading to poor contrast in OCT images. Two classification methods were tested in this report for the purpose of enhancing contrast between soft-tissue components of porcine coronary vessels. One method involved analyzing the attenuation of the OCT signal as a function of light penetration into the tissue. We demonstrated that by analyzing the signal attenuation in this manner we were able to differentiate two media sub-layers with different orientations of the smooth muscle cells. The other classification method used in our study was fractal analysis. Fractal analysis was implemented in a box-counting (fractal dimension) image-processing code and was used as a tool to differentiate and quantify variations in tissue texture at various locations in the OCT images. The calculated average fractal dimensions had different values in distinct regions of interest (ROI) within the imaged coronary samples. When compared to the results obtained by using the attenuation of the OCT signal, the method of fractal analysis demonstrated better classification potential for distinguishing amongst the tissue ROI.

Texture analysis of speckle in optical coherence tomography images of tissue phantoms

International Nuclear Information System (INIS)

Gossage, Kirk W; Smith, Cynthia M; Kanter, Elizabeth M; Hariri, Lida P; Stone, Alice L; Rodriguez, Jeffrey J; Williams, Stuart K; Barton, Jennifer K

2006-01-01

Optical coherence tomography (OCT) is an imaging modality capable of acquiring cross-sectional images of tissue using back-reflected light. Conventional OCT images have a resolution of 10-15 μm, and are thus best suited for visualizing tissue layers and structures. OCT images of collagen (with and without endothelial cells) have no resolvable features and may appear to simply show an exponential decrease in intensity with depth. However, examination of these images reveals that they display a characteristic repetitive structure due to speckle.The purpose of this study is to evaluate the application of statistical and spectral texture analysis techniques for differentiating living and non-living tissue phantoms containing various sizes and distributions of scatterers based on speckle content in OCT images. Statistically significant differences between texture parameters and excellent classification rates were obtained when comparing various endothelial cell concentrations ranging from 0 cells/ml to 25 million cells/ml. Statistically significant results and excellent classification rates were also obtained using various sizes of microspheres with concentrations ranging from 0 microspheres/ml to 500 million microspheres/ml. This study has shown that texture analysis of OCT images may be capable of differentiating tissue phantoms containing various sizes and distributions of scatterers

Comparison of tissue viability imaging and colorimetry: skin blanching.

Science.gov (United States)

Zhai, Hongbo; Chan, Heidi P; Farahmand, Sara; Nilsson, Gert E; Maibach, Howard I

2009-02-01

Operator-independent assessment of skin blanching is important in the development and evaluation of topically applied steroids. Spectroscopic instruments based on hand-held probes, however, include elements of operator dependence such as difference in applied pressure and probe misalignment, while laser Doppler-based methods are better suited for demonstration of skin vasodilatation than for vasoconstriction. To demonstrate the potential of the emerging technology of Tissue Viability Imaging (TiVi) in the objective and operator-independent assessment of skin blanching. The WheelsBridge TiVi600 Tissue Viability Imager was used for quantification of human skin blanching with the Minolta chromameter CR 200 as an independent colorimeter reference method. Desoximetasone gel 0.05% was applied topically on the volar side of the forearm under occlusion for 6 h in four healthy adults. In a separate study, the induction of blanching in the occlusion phase was mapped using a transparent occlusion cover. The relative uncertainty in the blanching estimate produced by the Tissue Viability Imager was about 5% and similar to that of the chromameter operated by a single user and taking the a(*) parameter as a measure of blanching. Estimation of skin blanching could also be performed in the presence of a transient paradoxical erythema, using the integrated TiVi software. The successive induction of skin blanching during the occlusion phase could readily be mapped by the Tissue Viability Imager. TiVi seems to be suitable for operator-independent and remote mapping of human skin blanching, eliminating the main disadvantages of methods based on hand-held probes.

Accurate determination of silver nanoparticles in animal tissues by inductively coupled plasma mass spectrometry

Energy Technology Data Exchange (ETDEWEB)

Veverková, Lenka [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Hradilová, Šárka [Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Milde, David, E-mail: david.mlde@upol.cz [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Panáček, Aleš [Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Skopalová, Jana [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Kvítek, Libor [Regional Centre of Advanced Technologies and Materials, Department of Physical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); Petrželová, Kamila [Regional Centre of Advanced Technologies and Materials, Department of Analytical Chemistry, Faculty of Science, Palacky University, 17.listopadu 12, CZ 771 46 Olomouc (Czech Republic); National Reference Laboratory for Chemical Elements, Department of Residues in Kroměříž, State Veterinary Institute Olomouc, Hulínská 2286, CZ 767 60 Kroměříž (Czech Republic); and others

2014-12-01

This study examined recoveries of silver determination in animal tissues after wet digestion by inductively coupled plasma mass spectrometry. The composition of the mineralization mixture for microwave assisted digestion was optimized and the best recoveries were obtained for mineralization with HNO{sub 3} and addition of HCl promptly after digestion. The optimization was performed on model samples of chicken meat spiked with silver nanoparticles and a solution of ionic silver. Basic calculations of theoretical distribution of Ag among various silver-containing species were implemented and the results showed that most of the silver is in the form of soluble complexes AgCl{sub 2}{sup −} and AgCl{sub 3}{sup 2−} for the optimized composition of the mineralization mixture. Three animal tissue certified reference materials were then analyzed to verify the trueness and precision of the results. - Highlights: • We performed detailed optimization of microwave assisted digestion procedure of animal tissue used prior to Ag determination by ICP-MS. • We provide basic equilibrium calculations to give theoretical explanation of results from optimization of tested mineralization mixtures. • Results from method validation that was done by analysis of several matrix CRMs are presented.

Feasibility of full-field optical coherence microscopy in ultra-structural imaging of human colon tissues

Energy Technology Data Exchange (ETDEWEB)

Choi, Eun Seo [Chosun University, Gwangju (Korea, Republic of); Choi, Woo June; Ryu, Seon Young; Lee, Byeong Ha [Gwangju Institute of Science and Technology, Gwangju (Korea, Republic of); Lee, Jae Hyuk; Bom, Hee Seung; Lee, Byeong Il [Chonnam National University Hospital, Gwangju (Korea, Republic of)

2010-06-15

We demonstrated the imaging feasibility of full-field optical coherence microscopy (FF-OCM) in pathological diagnosis of human colon tissues. FF-OCM images with high transverse resolution were obtained at different depths of the samples without any dye staining or physical slicing, and detailed microstructures of human colon tissues were visualized. Morphological differences in normal tissues, cancer tissues, and tissues under transition were observed and matched with results seen in conventional optical microscope images. The optical biopsy based on FF-OCM could overcome the limitations on the number of physical cuttings of tissues and could perform high-throughput mass diagnosis of diseased tissues. The proved utility of FF-OCM as a comprehensive and efficient imaging modality of human tissues showed it to be a good alternative to conventional biopsy.

Feasibility of full-field optical coherence microscopy in ultra-structural imaging of human colon tissues

International Nuclear Information System (INIS)

Choi, Eun Seo; Choi, Woo June; Ryu, Seon Young; Lee, Byeong Ha; Lee, Jae Hyuk; Bom, Hee Seung; Lee, Byeong Il

2010-01-01

We demonstrated the imaging feasibility of full-field optical coherence microscopy (FF-OCM) in pathological diagnosis of human colon tissues. FF-OCM images with high transverse resolution were obtained at different depths of the samples without any dye staining or physical slicing, and detailed microstructures of human colon tissues were visualized. Morphological differences in normal tissues, cancer tissues, and tissues under transition were observed and matched with results seen in conventional optical microscope images. The optical biopsy based on FF-OCM could overcome the limitations on the number of physical cuttings of tissues and could perform high-throughput mass diagnosis of diseased tissues. The proved utility of FF-OCM as a comprehensive and efficient imaging modality of human tissues showed it to be a good alternative to conventional biopsy.

A Proof of Concept to Bridge the Gap between Mass Spectrometry Imaging, Protein Identification and Relative Quantitation: MSI~LC-MS/MS-LF

Directory of Open Access Journals (Sweden)

Laëtitia Théron

2016-10-01

Full Text Available Mass spectrometry imaging (MSI is a powerful tool to visualize the spatial distribution of molecules on a tissue section. The main limitation of MALDI-MSI of proteins is the lack of direct identification. Therefore, this study focuses on a MSI~LC-MS/MS-LF workflow to link the results from MALDI-MSI with potential peak identification and label-free quantitation, using only one tissue section. At first, we studied the impact of matrix deposition and laser ablation on protein extraction from the tissue section. Then, we did a back-correlation of the m/z of the proteins detected by MALDI-MSI to those identified by label-free quantitation. This allowed us to compare the label-free quantitation of proteins obtained in LC-MS/MS with the peak intensities observed in MALDI-MSI. We managed to link identification to nine peaks observed by MALDI-MSI. The results showed that the MSI~LC-MS/MS-LF workflow (i allowed us to study a representative muscle proteome compared to a classical bottom-up workflow; and (ii was sparsely impacted by matrix deposition and laser ablation. This workflow, performed as a proof-of-concept, suggests that a single tissue section can be used to perform MALDI-MSI and protein extraction, identification, and relative quantitation.

Imaging the spectral reflectance properties of bipolar radiofrequency-fused bowel tissue

Science.gov (United States)

Clancy, Neil T.; Arya, Shobhit; Stoyanov, Danail; Du, Xiaofei; Hanna, George B.; Elson, Daniel S.

2015-07-01

Delivery of radiofrequency (RF) electrical energy is used during surgery to heat and seal tissue, such as vessels, allowing resection without blood loss. Recent work has suggested that this approach may be extended to allow surgical attachment of larger tissue segments for applications such as bowel anastomosis. In a large series of porcine surgical procedures bipolar RF energy was used to resect and re-seal the small bowel in vivo with a commercial tissue fusion device (Ligasure; Covidien PLC, USA). The tissue was then imaged with a multispectral imaging laparoscope to obtain a spectral datacube comprising both fused and healthy tissue. Maps of blood volume, oxygen saturation and scattering power were derived from the measured reflectance spectra using an optimised light-tissue interaction model. A 60% increase in reflectance of visible light (460-700 nm) was observed after fusion, with the tissue taking on a white appearance. Despite this the distinctive shape of the haemoglobin absorption spectrum was still noticeable in the 460-600 nm wavelength range. Scattering power increased in the fused region in comparison to normal serosa, while blood volume and oxygen saturation decreased. Observed fusion-induced changes in the reflectance spectrum are consistent with the biophysical changes induced through tissue denaturation and increased collagen cross-linking. The multispectral imager allows mapping of the spatial extent of these changes and classification of the zone of damaged tissue. Further analysis of the spectral data in parallel with histopathological examination of excised specimens will allow correlation of the optical property changes with microscopic alterations in tissue structure.

Differentiating cancerous from normal breast tissue by redox imaging

Science.gov (United States)

Xu, He N.; Tchou, Julia; Feng, Min; Zhao, Huaqing; Li, Lin Z.

2015-02-01

Abnormal metabolism can be a hallmark of cancer occurring early before detectable histological changes and may serve as an early detection biomarker. The current gold standard to establish breast cancer (BC) diagnosis is histological examination of biopsy. Previously we have found that pre-cancer and cancer tissues in animal models displayed abnormal mitochondrial redox state. Our technique of quantitatively measuring the mitochondrial redox state has the potential to be implemented as an early detection tool for cancer and may provide prognostic value. We therefore in this present study, investigated the feasibility of quantifying the redox state of tumor samples from 16 BC patients. Tumor tissue aliquots were collected from both normal and cancerous tissue from the affected cancer-bearing breasts of 16 female patients (5 TNBC, 9 ER+, 2 ER+/Her2+) shortly after surgical resection. All specimens were snap-frozen with liquid nitrogen on site and scanned later with the Chance redox scanner, i.e., the 3D cryogenic NADH/oxidized flavoprotein (Fp) fluorescence imager. Our preliminary results showed that both NADH and Fp (including FAD, i.e., flavin adenine dinucleotide) signals in the cancerous tissues roughly tripled to quadrupled those in the normal tissues (pcancerous tissues than in the normal ones (pcancer and non-cancer breast tissues in human patients and this novel redox scanning procedure may assist in tissue diagnosis in freshly procured biopsy samples prior to tissue fixation. We are in the process of evaluating the prognostic value of the redox imaging indices for BC.

Microwave non-contact imaging of subcutaneous human body tissues.

Science.gov (United States)

Kletsov, Andrey; Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

2015-10-01

A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated.

Imaging of the most frequent superficial soft-tissue sarcomas

International Nuclear Information System (INIS)

Morel, Melanie; Taieb, Sophie; Ceugnart, Luc; Penel, Nicolas; Mortier, Laurent; Vanseymortier, Luc; Robin, Y.M.; Gosset, Pierre; Cotten, Anne

2011-01-01

Superficial soft-tissue sarcomas are malignant mesenchymal tumors located within the cutaneous and/or subcutaneous layers. Most superficial soft-tissue sarcomas are low-grade tumors; yet, the risk of local recurrence is high, and initial wide surgery is the main prognostic factor. Some of these superficial sarcomas may grow, following an infiltrative pattern, and their real extent may be underestimated clinically. Imaging techniques are useful to determine precisely the real margins of the tumor, especially in cases of clinically doubtful or recurrent or large superficial lesions. Imaging tools enable one to determine the relationship with the superficial fascia separating the subcutaneous layer from the underlying muscle. In our institution ultrasonographic examination is followed by magnetic resonance (MR) imaging when the size of the lesion exceeds 3-5 cm. Imaging assessment is performed prior to biopsy, enabling optimal surgical management. Imaging features of the main superficial sarcomas are detailed in the following article, according to their major locations: those arising in the epidermis and/or dermis, which are most often diagnosed by dermatologists, and the subcutaneous sarcomas. (orig.)

Imaging of the most frequent superficial soft-tissue sarcomas

Energy Technology Data Exchange (ETDEWEB)

Morel, Melanie; Taieb, Sophie; Ceugnart, Luc [Centre Oscar Lambret, Department of Radiology, Lille (France); Penel, Nicolas [Centre Oscar Lambret, Department of Oncology, Lille (France); Mortier, Laurent [Centre Hospitalier Universitaire de Lille, Department of Dermatology, Hopital Claude Huriez, Lille (France); Vanseymortier, Luc [Centre Oscar Lambret, Department of Surgery, Lille (France); Robin, Y.M. [Centre Oscar Lambret, Departement of Pathology, Lille (France); Gosset, Pierre [Groupement Hospitalier de l' Institut Catholique-Faculte Libre de Medecine de Lille, Department of Pathology, Hopital Saint-Philibert, Lomme (France); Cotten, Anne [Centre Hospitalier Universitaire de Lille, Department of Musculoskeletal Radiology, Centre Hopital Roger Salengro, Lille (France)

2011-03-15

Superficial soft-tissue sarcomas are malignant mesenchymal tumors located within the cutaneous and/or subcutaneous layers. Most superficial soft-tissue sarcomas are low-grade tumors; yet, the risk of local recurrence is high, and initial wide surgery is the main prognostic factor. Some of these superficial sarcomas may grow, following an infiltrative pattern, and their real extent may be underestimated clinically. Imaging techniques are useful to determine precisely the real margins of the tumor, especially in cases of clinically doubtful or recurrent or large superficial lesions. Imaging tools enable one to determine the relationship with the superficial fascia separating the subcutaneous layer from the underlying muscle. In our institution ultrasonographic examination is followed by magnetic resonance (MR) imaging when the size of the lesion exceeds 3-5 cm. Imaging assessment is performed prior to biopsy, enabling optimal surgical management. Imaging features of the main superficial sarcomas are detailed in the following article, according to their major locations: those arising in the epidermis and/or dermis, which are most often diagnosed by dermatologists, and the subcutaneous sarcomas. (orig.)

Simultaneous determination of β-agonists and monitoring in bovine tissues by liquid chromatography-tandem mass spectrometry

Directory of Open Access Journals (Sweden)

Kyunghun Jeong

2018-01-01

Full Text Available The misuse of β-agonists leads to a potential risk to public health and is forbidden in many countries. We developed a rapid, sensitive and reliable multi-residue detection method for zilpaterol, ractopamine, and clenbuterol in bovine tissues by liquid chromatography–tandem mass spectrometry. Residues were extracted in ethyl acetate after protein precipitation, and then analyzed by the developed method. Good linearities (R2 > 0.99 were observed, and the recoveries of zilpaterol, ractopamine, and clenbuterol were 99%, 74%, and 102%, respectively. The limits of quantitation for zilpaterol, ractopamine, and clenbuterol were 1.3, 5.0, and 1.7 ng/g, respectively. The method is also applied successfully to bovine tissues within the Korean National Residue Programme. None of the 3 β-agonists were detected from 50 domestic samples. However, zilpaterol (6.3 ng/g was quantified in one out of the 50 imported samples. The application of this method will be helpful in quality control analysis of β-agonists residues in bovine tissues.

The Assessment of Left Ventricular Time-Varying Radius Using Tissue Doppler Imaging

Directory of Open Access Journals (Sweden)

Fardin Mirbolouk

2012-03-01

Full Text Available Background: Left ventricular twist/torsion is believed to be a sensitive indicator of systolic and diastolic performance. To obtain circumferential rotation using tissue Doppler imaging, we need to estimate the time-varying radius of the left ventricle throughout the cardiac cycle to convert the tangential velocity into angular velocity. Objectives: The aim of this study was to investigate accuracy of measured LV radius using tissue Doppler imaging throughout the cardiac cycle compared to two-dimensional (2D imaging. Methods: A total of 35 subjects (47±12 years old underwent transthoracic echocardiographic standard examinations. Left ventricular radius during complete cardiac cycle measured using tissue Doppler and 2D-imaging at basal and apical short axis levels. For this reason, the 2D-images and velocity-time data derived and transferred to a personal computer for off-line analysis. 2D image frames analyzed via a program written in the MATLAB software. Velocity-time data from anteroseptal at basal level (or anterior wall at apical level and posterior walls transferred to a spreadsheet Excel program for the radius calculations. Linear correlation and Bland-Altman analysis were calculated to assess the relationships and agreements between the tissue Doppler and 2D-measured radii throughout the cardiac cycle. Results: There was significant correlation between tissue Doppler and 2D-measured radii and the Pearson correlation coefficients were 0.84 to 0.97 (P<0.05. Bland-Altman analysis by constructing the 95% limits of agreement showed that the good agreements existed between the two methods. Conclusion: It can be concluded from our experience that the tissue Doppler imaging can reasonably estimate radius of the left ventricle throughout the cardiac cycle.

Molecular imaging needles: dual-modality optical coherence tomography and fluorescence imaging of labeled antibodies deep in tissue

Science.gov (United States)

Scolaro, Loretta; Lorenser, Dirk; Madore, Wendy-Julie; Kirk, Rodney W.; Kramer, Anne S.; Yeoh, George C.; Godbout, Nicolas; Sampson, David D.; Boudoux, Caroline; McLaughlin, Robert A.

2015-01-01

Molecular imaging using optical techniques provides insight into disease at the cellular level. In this paper, we report on a novel dual-modality probe capable of performing molecular imaging by combining simultaneous three-dimensional optical coherence tomography (OCT) and two-dimensional fluorescence imaging in a hypodermic needle. The probe, referred to as a molecular imaging (MI) needle, may be inserted tens of millimeters into tissue. The MI needle utilizes double-clad fiber to carry both imaging modalities, and is interfaced to a 1310-nm OCT system and a fluorescence imaging subsystem using an asymmetrical double-clad fiber coupler customized to achieve high fluorescence collection efficiency. We present, to the best of our knowledge, the first dual-modality OCT and fluorescence needle probe with sufficient sensitivity to image fluorescently labeled antibodies. Such probes enable high-resolution molecular imaging deep within tissue. PMID:26137379

Multispectral fluorescence imaging of human ovarian and Fallopian tube tissue for early stage cancer detection

Science.gov (United States)

Tate, Tyler; Baggett, Brenda; Rice, Photini; Watson, Jennifer; Orsinger, Gabe; Nymeyer, Ariel C.; Welge, Weston A.; Keenan, Molly; Saboda, Kathylynn; Roe, Denise J.; Hatch, Kenneth; Chambers, Setsuko; Black, John; Utzinger, Urs; Barton, Jennifer

2015-03-01

With early detection, five year survival rates for ovarian cancer are over 90%, yet no effective early screening method exists. Emerging consensus suggests that perhaps over 50% of the most lethal form of the disease, high grade serous ovarian cancer, originates in the Fallopian tube. Cancer changes molecular concentrations of various endogenous fluorophores. Using specific excitation wavelengths and emissions bands on a Multispectral Fluorescence Imaging (MFI) system, spatial and spectral data over a wide field of view can be collected from endogenous fluorophores. Wavelength specific reflectance images provide additional information to normalize for tissue geometry and blood absorption. Ratiometric combination of the images may create high contrast between neighboring normal and abnormal tissue. Twenty-six women undergoing oophorectomy or debulking surgery consented the use of surgical discard tissue samples for MFI imaging. Forty-nine pieces of ovarian tissue and thirty-two pieces of Fallopian tube tissue were collected and imaged with excitation wavelengths between 280 nm and 550 nm. After imaging, each tissue sample was fixed, sectioned and HE stained for pathological evaluation. Comparison of mean intensity values between normal, benign, and cancerous tissue demonstrate a general trend of increased fluorescence of benign tissue and decreased fluorescence of cancerous tissue when compared to normal tissue. The predictive capabilities of the mean intensity measurements are tested using multinomial logistic regression and quadratic discriminant analysis. Adaption of the system for in vivo Fallopian tube and ovary endoscopic imaging is possible and is briefly described.

An imaging colorimeter for noncontact tissue color mapping.

Science.gov (United States)

Balas, C

1997-06-01

There has been a considerable effort in several medical fields, for objective color analysis and characterization of biological tissues. Conventional colorimeters have proved inadequate for this purpose, since they do not provide spatial color information and because the measuring procedure randomly affects the color of the tissue. In this paper an imaging colorimeter is presented, where the nonimaging optical photodetector of colorimeters is replaced with the charge-coupled device (CCD) sensor of a color video camera, enabling the independent capturing of the color information for any spatial point within its field-of-view. Combining imaging and colorimetry methods, the acquired image is calibrated and corrected, under several ambient light conditions, providing noncontact reproducible color measurements and mapping, free of the errors and the limitations present in conventional colorimeters. This system was used for monitoring of blood supply changes of psoriatic plaques, that have undergone Psoralens and ultraviolet-A radiation (PUVA) therapy, where reproducible and reliable measurements were demonstrated. These features highlight the potential of the imaging colorimeters as clinical and research tools for the standardization of clinical diagnosis and for the objective evaluation of treatment effectiveness.

Measurement of facial soft tissues thickness using 3D computed tomographic images

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Jeong, Ho Gul; Kim, Kee Deog; Shin, Dong Won; Hu, Kyung Seok; Lee, Jae Bum; Park, Hyok; Park, Chang Seo [Yonsei Univ. Hospital, Seoul (Korea, Republic of); Han, Seung Ho [Catholic Univ. of Korea, Seoul (Korea, Republic of)

2006-03-15

To evaluate accuracy and reliability of program to measure facial soft tissue thickness using 3D computed tomographic images by comparing with direct measurement. One cadaver was scanned with a Helical CT with 3 mm slice thickness and 3 mm/sec table speed. The acquired data was reconstructed with 1.5 mm reconstruction interval and the images were transferred to a personal computer. The facial soft tissue thickness were measured using a program developed newly in 3D image. For direct measurement, the cadaver was cut with a bone cutter and then a ruler was placed above the cut side. The procedure was followed by taking pictures of the facial soft tissues with a high-resolution digital camera. Then the measurements were done in the photographic images and repeated for ten times. A repeated measure analysis of variance was adopted to compare and analyze the measurements resulting from the two different methods. Comparison according to the areas was analyzed by Mann-Whitney test. There were no statistically significant differences between the direct measurements and those using the 3D images(p>0.05). There were statistical differences in the measurements on 17 points but all the points except 2 points showed a mean difference of 0.5 mm or less. The developed software program to measure the facial soft tissue thickness using 3D images was so accurate that it allows to measure facial soft tissue thickness more easily in forensic science and anthropology.

Measurement of facial soft tissues thickness using 3D computed tomographic images

International Nuclear Information System (INIS)

Jeong, Ho Gul; Kim, Kee Deog; Shin, Dong Won; Hu, Kyung Seok; Lee, Jae Bum; Park, Hyok; Park, Chang Seo; Han, Seung Ho

2006-01-01

To evaluate accuracy and reliability of program to measure facial soft tissue thickness using 3D computed tomographic images by comparing with direct measurement. One cadaver was scanned with a Helical CT with 3 mm slice thickness and 3 mm/sec table speed. The acquired data was reconstructed with 1.5 mm reconstruction interval and the images were transferred to a personal computer. The facial soft tissue thickness were measured using a program developed newly in 3D image. For direct measurement, the cadaver was cut with a bone cutter and then a ruler was placed above the cut side. The procedure was followed by taking pictures of the facial soft tissues with a high-resolution digital camera. Then the measurements were done in the photographic images and repeated for ten times. A repeated measure analysis of variance was adopted to compare and analyze the measurements resulting from the two different methods. Comparison according to the areas was analyzed by Mann-Whitney test. There were no statistically significant differences between the direct measurements and those using the 3D images(p>0.05). There were statistical differences in the measurements on 17 points but all the points except 2 points showed a mean difference of 0.5 mm or less. The developed software program to measure the facial soft tissue thickness using 3D images was so accurate that it allows to measure facial soft tissue thickness more easily in forensic science and anthropology

Visualization and tissue classification of human breast cancer images using ultrahigh-resolution OCT (Conference Presentation)

Science.gov (United States)

Yao, Xinwen; Gan, Yu; Chang, Ernest W.; Hibshoosh, Hanina; Feldman, Sheldon; Hendon, Christine P.

2017-02-01

We employed a home-built ultrahigh resolution (UHR) OCT system at 800nm to image human breast cancer sample ex vivo. The system has an axial resolution of 2.72µm and a lateral resolution of 5.52µm with an extended imaging range of 1.78mm. Over 900 UHR OCT volumes were generated on specimens from 23 breast cancer cases. With better spatial resolution, detailed structures in the breast tissue were better defined. Different types of breast cancer as well as healthy breast tissue can be well delineated from the UHR OCT images. To quantitatively evaluate the advantages of UHR OCT imaging of breast cancer, features derived from OCT intensity images were used as inputs to a machine learning model, the relevance vector machine. A trained machine learning model was employed to evaluate the performance of tissue classification based on UHR OCT images for differentiating tissue types in the breast samples, including adipose tissue, healthy stroma and cancerous region. For adipose tissue, grid-based local features were extracted from OCT intensity data, including standard deviation, entropy, and homogeneity. We showed that it was possible to enhance the classification performance on distinguishing fat tissue from non-fat tissue by using the UHR images when compared with the results based on OCT images from a commercial 1300 nm OCT system. For invasive ductal carcinoma (IDC) and normal stroma differentiation, the classification was based on frame-based features that portray signal penetration depth and tissue reflectivity. The confusing matrix indicated a sensitivity of 97.5% and a sensitivity of 77.8%.

Image standards in Tissue-Based Diagnosis (Diagnostic Surgical Pathology

Directory of Open Access Journals (Sweden)

Vollmer Ekkehard

2008-04-01

Full Text Available Abstract Background Progress in automated image analysis, virtual microscopy, hospital information systems, and interdisciplinary data exchange require image standards to be applied in tissue-based diagnosis. Aims To describe the theoretical background, practical experiences and comparable solutions in other medical fields to promote image standards applicable for diagnostic pathology. Theory and experiences Images used in tissue-based diagnosis present with pathology – specific characteristics. It seems appropriate to discuss their characteristics and potential standardization in relation to the levels of hierarchy in which they appear. All levels can be divided into legal, medical, and technological properties. Standards applied to the first level include regulations or aims to be fulfilled. In legal properties, they have to regulate features of privacy, image documentation, transmission, and presentation; in medical properties, features of disease – image combination, human – diagnostics, automated information extraction, archive retrieval and access; and in technological properties features of image acquisition, display, formats, transfer speed, safety, and system dynamics. The next lower second level has to implement the prescriptions of the upper one, i.e. describe how they are implemented. Legal aspects should demand secure encryption for privacy of all patient related data, image archives that include all images used for diagnostics for a period of 10 years at minimum, accurate annotations of dates and viewing, and precise hardware and software information. Medical aspects should demand standardized patients' files such as DICOM 3 or HL 7 including history and previous examinations, information of image display hardware and software, of image resolution and fields of view, of relation between sizes of biological objects and image sizes, and of access to archives and retrieval. Technological aspects should deal with image

Tissue types (image)

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... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

Mass spectrometry protein expression profiles in colorectal cancer tissue associated with clinico-pathological features of disease

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Liao Christopher CL

2010-08-01

Full Text Available Abstract Background Studies of several tumour types have shown that expression profiling of cellular protein extracted from surgical tissue specimens by direct mass spectrometry analysis can accurately discriminate tumour from normal tissue and in some cases can sub-classify disease. We have evaluated the potential value of this approach to classify various clinico-pathological features in colorectal cancer by employing matrix-assisted laser desorption ionisation time of-flight-mass spectrometry (MALDI-TOF MS. Methods Protein extracts from 31 tumour and 33 normal mucosa specimens were purified, subjected to MALDI-Tof MS and then analysed using the 'GenePattern' suite of computational tools (Broad Institute, MIT, USA. Comparative Gene Marker Selection with either a t-test or a signal-to-noise ratio (SNR test statistic was used to identify and rank differentially expressed marker peaks. The k-nearest neighbours algorithm was used to build classification models either using separate training and test datasets or else by using an iterative, 'leave-one-out' cross-validation method. Results 73 protein peaks in the mass range 1800-16000Da were differentially expressed in tumour verses adjacent normal mucosa tissue (P ≤ 0.01, false discovery rate ≤ 0.05. Unsupervised hierarchical cluster analysis classified most tumour and normal mucosa into distinct cluster groups. Supervised prediction correctly classified the tumour/normal mucosa status of specimens in an independent test spectra dataset with 100% sensitivity and specificity (95% confidence interval: 67.9-99.2%. Supervised prediction using 'leave-one-out' cross validation algorithms for tumour spectra correctly classified 10/13 poorly differentiated and 16/18 well/moderately differentiated tumours (P = P = P = 0.001; ROC error, 0.212. Conclusions Protein expression profiling of surgically resected CRC tissue extracts by MALDI-TOF MS has potential value in studies aimed at improved molecular

Imaging of tissue sections with very slow electrons

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Frank, L., E-mail: ludek@isibrno.cz [Institute of Scientific Instruments AS CR, v.v.i., Královopolská 147, 61264 Brno (Czech Republic); Nebesářová, J.; Vancová, M. [Biology Centre AS CR, v.v.i., Branišovská 31, 37005 České Budějovice (Czech Republic); Paták, A.; Müllerová, I. [Institute of Scientific Instruments AS CR, v.v.i., Královopolská 147, 61264 Brno (Czech Republic)

2015-01-15

The examination of thin sections of tissues with electron microscopes is an indispensable tool. Being composed of light elements, samples of living matter illuminated with electrons at the usual high energies of tens or even hundreds of kiloelectronvolts provide very low image contrasts in transmission or scanning transmission electron microscopes. Therefore, heavy metal salts are added to the specimen during preparation procedures (post-fixation with osmium tetroxide or staining). However, these procedures can modify or obscure the ultrastructural details of cells. Here we show that the energy of electrons used for the scanned transmission imaging of tissue sections can be reduced to mere hundreds or even tens of electronvolts and can produce extremely high contrast even for samples free of any metal salts. We found that when biasing a sufficiently thin tissue section sample to a high negative potential in a scanning transmission electron microscope, thereby reducing the energy of the electrons landing on the sample, and collecting the transmitted electrons with a grounded detector, we obtain a high contrast revealing structure details not enhanced by heavy atoms. Moreover, bombardment with slow electrons sensitively depolymerises the resin in which the tissue is embedded, thereby enhancing the transmitted signal with no observable loss of structure details. The use of low-energy electrons requires ultrathin sections of a thickness of less than 10 nm, but their preparation is now possible. Ultralow energy STEM provides a tool enabling the observation of very thin biological samples without any staining. This method should also be advantageous for examination of 2D crystals, thin films of polymers, polymer blends, etc. - Highlights: • Sections of a thickness below 10 nm were imaged in STEM at hundreds and tens of eV. • Image contrast grows steeply with decreasing electron energy in the STEM. • Very slow electrons provide high contrast for samples free of

A comparative study of three tissue-cultured Dendrobium species and their wild correspondences by headspace gas chromatography-mass spectrometry combined with chemometric methods.

Science.gov (United States)

Chen, Nai-Dong; You, Tao; Li, Jun; Bai, Li-Tao; Hao, Jing-Wen; Xu, Xiao-Yuan

2016-10-01

Plant tissue culture technique is widely used in the conservation and utilization of rare and endangered medicinal plants and it is crucial for tissue culture stocks to obtain the ability to produce similar bioactive components as their wild correspondences. In this paper, a headspace gas chromatography-mass spectrometry method combined with chemometric methods was applied to analyze and evaluate the volatile compounds in tissue-cultured and wild Dendrobium huoshanense Cheng and Tang, Dendrobium officinale Kimura et Migo and Dendrobium moniliforme (Linn.) Sw. In total, 63 volatile compounds were separated, with 53 being identified from the three Dendrobium spp. Different provenances of Dendrobiums had characteristic chemicals and showed remarkable quantity discrepancy of common compositions. The similarity evaluation disclosed that the accumulation of volatile compounds in Dendrobium samples might be affected by their provenance. Principal component analysis showed that the first three components explained 85.9% of data variance, demonstrating a good discrimination between samples. Gas chromatography-mass spectrometry techniques, combined with chemometrics, might be an effective strategy for identifying the species and their provenance, especially in the assessment of tissue-cultured Dendrobium quality for use in raw herbal medicines. Copyright © 2016. Published by Elsevier B.V.

Metabolomic profiling of lung and prostate tumor tissues by capillary electrophoresis time-of-flight mass spectrometry.

Science.gov (United States)

Kami, Kenjiro; Fujimori, Tamaki; Sato, Hajime; Sato, Mutsuko; Yamamoto, Hiroyuki; Ohashi, Yoshiaki; Sugiyama, Naoyuki; Ishihama, Yasushi; Onozuka, Hiroko; Ochiai, Atsushi; Esumi, Hiroyasu; Soga, Tomoyoshi; Tomita, Masaru

2013-04-01

Metabolic microenvironment of tumor cells is influenced by oncogenic signaling and tissue-specific metabolic demands, blood supply, and enzyme expression. To elucidate tumor-specific metabolism, we compared the metabolomics of normal and tumor tissues surgically resected pairwise from nine lung and seven prostate cancer patients, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Phosphorylation levels of enzymes involved in central carbon metabolism were also quantified. Metabolomic profiles of lung and prostate tissues comprised 114 and 86 metabolites, respectively, and the profiles not only well distinguished tumor from normal tissues, but also squamous cell carcinoma from the other tumor types in lung cancer and poorly differentiated tumors from moderately differentiated tumors in prostate cancer. Concentrations of most amino acids, especially branched-chain amino acids, were significantly higher in tumor tissues, independent of organ type, but of essential amino acids were particularly higher in poorly differentiated than moderately differentiated prostate cancers. Organ-dependent differences were prominent at the levels of glycolytic and tricarboxylic acid cycle intermediates and associated energy status. Significantly high lactate concentrations and elevated activating phosphorylation levels of phosphofructokinase and pyruvate kinase in lung tumors confirmed hyperactive glycolysis. We highlighted the potential of CE-TOFMS-based metabolomics combined with phosphorylated enzyme analysis for understanding tissue-specific tumor microenvironments, which may lead to the development of more effective and specific anticancer therapeutics.

Opto-ultrasound imaging in vivo in deep tissue

International Nuclear Information System (INIS)

Si, Ke; YanXu; Zheng, Yao; Zhu, Xinpei; Gong, Wei

2016-01-01

It is of keen importance of deep tissue imaging with high resolution in vivo. Here we present an opto-ultrasound imaging method which utilizes an ultrasound to confine the laser pulse in a very tiny spot as a guide star. The results show that the imaging depth is 2mm with a resolution of 10um. Meanwhile, the excitation power we used is less than 2mW, which indicates that our methods can be applied in vivo without optical toxicity and optical bleaching due to the excitation power. (paper)

Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

International Nuclear Information System (INIS)

Ahlawat, Shivani; Fayad, Laura M.

2018-01-01

Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

Diffusion weighted imaging demystified. The technique and potential clinical applications for soft tissue imaging

Energy Technology Data Exchange (ETDEWEB)

Ahlawat, Shivani [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); Fayad, Laura M. [The Johns Hopkins Medical Institutions, The Russell H. Morgan Department of Radiology and Radiological Science, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Oncology, Baltimore, MD (United States); The Johns Hopkins Medical Institutions, Department of Orthopaedic Surgery, Baltimore, MD (United States)

2018-03-15

Diffusion-weighted imaging (DWI) is a fast, non-contrast technique that is readily available and easy to integrate into an existing imaging protocol. DWI with apparent diffusion coefficient (ADC) mapping offers a quantitative metric for soft tissue evaluation and provides information regarding the cellularity of a region of interest. There are several available methods of performing DWI, and artifacts and pitfalls must be considered when interpreting DWI studies. This review article will review the various techniques of DWI acquisition and utility of qualitative as well as quantitative methods of image interpretation, with emphasis on optimal methods for ADC measurement. The current clinical applications for DWI are primarily related to oncologic evaluation: For the assessment of de novo soft tissue masses, ADC mapping can serve as a useful adjunct technique to routine anatomic sequences for lesion characterization as cyst or solid and, if solid, benign or malignant. For treated soft tissue masses, the role of DWI/ADC mapping in the assessment of treatment response as well as recurrent or residual neoplasm in the setting of operative management is discussed, especially when intravenous contrast medium cannot be given. Emerging DWI applications for non-neoplastic clinical indications are also reviewed. (orig.)

Breast tissue classification in digital tomosynthesis images based on global gradient minimization and texture features

Science.gov (United States)

Qin, Xulei; Lu, Guolan; Sechopoulos, Ioannis; Fei, Baowei

2014-03-01

Digital breast tomosynthesis (DBT) is a pseudo-three-dimensional x-ray imaging modality proposed to decrease the effect of tissue superposition present in mammography, potentially resulting in an increase in clinical performance for the detection and diagnosis of breast cancer. Tissue classification in DBT images can be useful in risk assessment, computer-aided detection and radiation dosimetry, among other aspects. However, classifying breast tissue in DBT is a challenging problem because DBT images include complicated structures, image noise, and out-of-plane artifacts due to limited angular tomographic sampling. In this project, we propose an automatic method to classify fatty and glandular tissue in DBT images. First, the DBT images are pre-processed to enhance the tissue structures and to decrease image noise and artifacts. Second, a global smooth filter based on L0 gradient minimization is applied to eliminate detailed structures and enhance large-scale ones. Third, the similar structure regions are extracted and labeled by fuzzy C-means (FCM) classification. At the same time, the texture features are also calculated. Finally, each region is classified into different tissue types based on both intensity and texture features. The proposed method is validated using five patient DBT images using manual segmentation as the gold standard. The Dice scores and the confusion matrix are utilized to evaluate the classified results. The evaluation results demonstrated the feasibility of the proposed method for classifying breast glandular and fat tissue on DBT images.

Polarization image segmentation of radiofrequency ablated porcine myocardial tissue.

Directory of Open Access Journals (Sweden)

Iftikhar Ahmad

Full Text Available Optical polarimetry has previously imaged the spatial extent of a typical radiofrequency ablated (RFA lesion in myocardial tissue, exhibiting significantly lower total depolarization at the necrotic core compared to healthy tissue, and intermediate values at the RFA rim region. Here, total depolarization in ablated myocardium was used to segment the total depolarization image into three (core, rim and healthy zones. A local fuzzy thresholding algorithm was used for this multi-region segmentation, and then compared with a ground truth segmentation obtained from manual demarcation of RFA core and rim regions on the histopathology image. Quantitative comparison of the algorithm segmentation results was performed with evaluation metrics such as dice similarity coefficient (DSC = 0.78 ± 0.02 and 0.80 ± 0.02, sensitivity (Sn = 0.83 ± 0.10 and 0.91 ± 0.08, specificity (Sp = 0.76 ± 0.17 and 0.72 ± 0.17 and accuracy (Acc = 0.81 ± 0.09 and 0.71 ± 0.10 for RFA core and rim regions, respectively. This automatic segmentation of parametric depolarization images suggests a novel application of optical polarimetry, namely its use in objective RFA image quantification.

Optoacoustic multispectral imaging of radiolucent foreign bodies in tissue.

Science.gov (United States)

Page, Leland; Maswadi, Saher; Glickman, Randolph D

2013-01-01

Optoacoustic imaging is an emerging medical technology that uniquely combines the absorption contrast of optical imaging and the penetration depth of ultrasound. While it is not currently employed as a clinical imaging modality, the results of current research strongly support the use of optoacoustic-based methods in medical imaging. One such application is the diagnosis of the presence of soft tissue foreign bodies. Because many radiolucent foreign bodies have sufficient contrast for imaging in the optical domain, laser-induced optoacoustic imaging could be advantageous for the detection of such objects. Common foreign bodies have been scanned over a range of visible and near infrared wavelengths by using an optoacoustic method to obtain the spectroscopic properties of the materials commonly associated with these foreign bodies. The derived optical absorption spectra compared quite closely to the absorption spectra generated when using a conventional spectrophotometer. By using the probe-beam deflection technique, a novel, pressure-wave detection method, we successfully generated optoacoustic spectroscopic plots of a wooden foreign body embedded in a tissue phantom, which closely resembled the spectrum of the same object obtained in isolation. A practical application of such spectra is to assemble a library of spectroscopic data for radiolucent materials, from which specific characteristic wavelengths can be selected for use in optimizing imaging instrumentation and provide a basis for the identification of the material properties of particular foreign bodies.

Frequency-locked pulse sequencer for high-frame-rate monochromatic tissue motion imaging.

Science.gov (United States)

Azar, Reza Zahiri; Baghani, Ali; Salcudean, Septimiu E; Rohling, Robert

2011-04-01

To overcome the inherent low frame rate of conventional ultrasound, we have previously presented a system that can be implemented on conventional ultrasound scanners for high-frame-rate imaging of monochromatic tissue motion. The system employs a sector subdivision technique in the sequencer to increase the acquisition rate. To eliminate the delays introduced during data acquisition, a motion phase correction algorithm has also been introduced to create in-phase displacement images. Previous experimental results from tissue- mimicking phantoms showed that the system can achieve effective frame rates of up to a few kilohertz on conventional ultrasound systems. In this short communication, we present a new pulse sequencing strategy that facilitates high-frame-rate imaging of monochromatic motion such that the acquired echo signals are inherently in-phase. The sequencer uses the knowledge of the excitation frequency to synchronize the acquisition of the entire imaging plane to that of an external exciter. This sequencing approach eliminates any need for synchronization or phase correction and has applications in tissue elastography, which we demonstrate with tissue-mimicking phantoms. © 2011 IEEE

Quantitative breast tissue characterization using grating-based x-ray phase-contrast imaging

Science.gov (United States)

Willner, M.; Herzen, J.; Grandl, S.; Auweter, S.; Mayr, D.; Hipp, A.; Chabior, M.; Sarapata, A.; Achterhold, K.; Zanette, I.; Weitkamp, T.; Sztrókay, A.; Hellerhoff, K.; Reiser, M.; Pfeiffer, F.

2014-04-01

X-ray phase-contrast imaging has received growing interest in recent years due to its high capability in visualizing soft tissue. Breast imaging became the focus of particular attention as it is considered the most promising candidate for a first clinical application of this contrast modality. In this study, we investigate quantitative breast tissue characterization using grating-based phase-contrast computed tomography (CT) at conventional polychromatic x-ray sources. Different breast specimens have been scanned at a laboratory phase-contrast imaging setup and were correlated to histopathology. Ascertained tumor types include phylloides tumor, fibroadenoma and infiltrating lobular carcinoma. Identified tissue types comprising adipose, fibroglandular and tumor tissue have been analyzed in terms of phase-contrast Hounsfield units and are compared to high-quality, high-resolution data obtained with monochromatic synchrotron radiation, as well as calculated values based on tabulated tissue properties. The results give a good impression of the method’s prospects and limitations for potential tumor detection and the associated demands on such a phase-contrast breast CT system. Furthermore, the evaluated quantitative tissue values serve as a reference for simulations and the design of dedicated phantoms for phase-contrast mammography.

Thick tissue diffusion model with binding to optimize topical staining in fluorescence breast cancer margin imaging

Science.gov (United States)

Xu, Xiaochun; Kang, Soyoung; Navarro-Comes, Eric; Wang, Yu; Liu, Jonathan T. C.; Tichauer, Kenneth M.

2018-03-01

Intraoperative tumor/surgical margin assessment is required to achieve higher tumor resection rate in breast-conserving surgery. Though current histology provides incomparable accuracy in margin assessment, thin tissue sectioning and the limited field of view of microscopy makes histology too time-consuming for intraoperative applications. If thick tissue, wide-field imaging can provide an acceptable assessment of tumor cells at the surface of resected tissues, an intraoperative protocol can be developed to guide the surgery and provide immediate feedback for surgeons. Topical staining of margins with cancer-targeted molecular imaging agents has the potential to provide the sensitivity needed to see microscopic cancer on a wide-field image; however, diffusion and nonspecific retention of imaging agents in thick tissue can significantly diminish tumor contrast with conventional methods. Here, we present a mathematical model to accurately simulate nonspecific retention, binding, and diffusion of imaging agents in thick tissue topical staining to guide and optimize future thick tissue staining and imaging protocol. In order to verify the accuracy and applicability of the model, diffusion profiles of cancer targeted and untargeted (control) nanoparticles at different staining times in A431 tumor xenografts were acquired for model comparison and tuning. The initial findings suggest the existence of nonspecific retention in the tissue, especially at the tissue surface. The simulator can be used to compare the effect of nonspecific retention, receptor binding and diffusion under various conditions (tissue type, imaging agent) and provides optimal staining and imaging protocols for targeted and control imaging agent.

Feasibility of Imaging Tissue Electrical Conductivity by Switching Field Gradients with MRI.

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Gibbs, Eric; Liu, Chunlei

2015-12-01

Tissue conductivity is a biophysical marker of tissue structure and physiology. Present methods of measuring tissue conductivity are limited. Electrical impedance tomography, and magnetic resonance electrical impedance tomography rely on passing external current through the object being imaged, which prevents its use in most human imaging. Recently, the RF field used for MR excitation has been used to non-invasively measure tissue conductivity. This technique is promising, but conductivity at higher frequencies is less sensitive to tissue structure. Measuring tissue conductivity non-invasively at low frequencies remains elusive. It has been proposed that eddy currents generated during the rise and decay of gradient pulses could act as a current source to map low-frequency conductivity. This work centers on a gradient echo pulse sequence that uses large gradients prior to excitation to create eddy currents. The electric and magnetic fields during a gradient pulse are simulated by a finite-difference time-domain simulation. The sequence is also tested with a phantom and an animal MRI scanner equipped with gradients of high gradient strengths and slew rate. The simulation demonstrates that eddy currents in materials with conductivity similar to biological tissue decay with a half-life on the order of nanoseconds and any eddy currents generated prior to excitation decay completely before influencing the RF signal. Gradient-induced eddy currents can influence phase accumulation after excitation but the effect is too small to image. The animal scanner images show no measurable phase accumulation. Measuring low-frequency conductivity by gradient-induced eddy currents is presently unfeasible.

Tissue clearing for confocal imaging of native and bio-artificial skeletal muscle.

Science.gov (United States)

Decroix, L; Van Muylder, V; Desender, L; Sampaolesi, M; Thorrez, L

2015-01-01

Novel clearing techniques have revolutionized three-dimensional confocal imaging of the brain without the need for physical tissue sectioning. We evaluated three clearing methods, ScaleA2, Clear(T2), and 3DISCO for visualizing native and tissue engineered muscle by confocal microscopy. We found that Clear(T2) treatment improved the depth of visualization of immunohistochemical staining slightly, but did not improve depth of visualization of endogenous green fluorescent protein (GFP). ScaleA2 preserved endogenous GFP signal better and permitted significantly deeper GFP imaging, but it was incompatible with tropomyosin immunohistochemical staining. 3DISCO treatment preserved both endogenous GFP and immunohistochemical staining, and permitted significantly deeper imaging. Clearing time for the 3DISCO procedure is short compared to ScaleA2 and Clear(T2). We suggest that 3DISCO is the preferable clearing method for native and tissue engineered skeletal muscle tissue.

Observation of endoplasmic reticulum tubules via TOF-SIMS tandem mass spectrometry imaging of transfected cells.

Science.gov (United States)

Chini, Corryn E; Fisher, Gregory L; Johnson, Ben; Tamkun, Michael M; Kraft, Mary L

2018-02-26

Advances in three-dimensional secondary ion mass spectrometry (SIMS) imaging have enabled visualizing the subcellular distributions of various lipid species within individual cells. However, the difficulty of locating organelles using SIMS limits efforts to study their lipid compositions. Here, the authors have assessed whether endoplasmic reticulum (ER)-Tracker Blue White DPX ® , which is a commercially available stain for visualizing the endoplasmic reticulum using fluorescence microscopy, produces distinctive ions that can be used to locate the endoplasmic reticulum using SIMS. Time-of-flight-SIMS tandem mass spectrometry (MS 2 ) imaging was used to identify positively and negatively charged ions produced by the ER-Tracker stain. Then, these ions were used to localize the stain and thus the endoplasmic reticulum, within individual human embryonic kidney cells that contained higher numbers of endoplasmic reticulum-plasma membrane junctions on their surfaces. By performing MS 2 imaging of selected ions in parallel with the precursor ion (MS 1 ) imaging, the authors detected a chemical interference native to the cell at the same nominal mass as the pentafluorophenyl fragment from the ER-Tracker stain. Nonetheless, the fluorine secondary ions produced by the ER-Tracker stain provided a distinctive signal that enabled locating the endoplasmic reticulum using SIMS. This simple strategy for visualizing the endoplasmic reticulum in individual cells using SIMS could be combined with existing SIMS methodologies for imaging intracellular lipid distribution and to study the lipid composition within the endoplasmic reticulum.

In Vivo Deep Tissue Fluorescence and Magnetic Imaging Employing Hybrid Nanostructures.

Science.gov (United States)

Ortgies, Dirk H; de la Cueva, Leonor; Del Rosal, Blanca; Sanz-Rodríguez, Francisco; Fernández, Nuria; Iglesias-de la Cruz, M Carmen; Salas, Gorka; Cabrera, David; Teran, Francisco J; Jaque, Daniel; Martín Rodríguez, Emma

2016-01-20

Breakthroughs in nanotechnology have made it possible to integrate different nanoparticles in one single hybrid nanostructure (HNS), constituting multifunctional nanosized sensors, carriers, and probes with great potential in the life sciences. In addition, such nanostructures could also offer therapeutic capabilities to achieve a wider variety of multifunctionalities. In this work, the encapsulation of both magnetic and infrared emitting nanoparticles into a polymeric matrix leads to a magnetic-fluorescent HNS with multimodal magnetic-fluorescent imaging abilities. The magnetic-fluorescent HNS are capable of simultaneous magnetic resonance imaging and deep tissue infrared fluorescence imaging, overcoming the tissue penetration limits of classical visible-light based optical imaging as reported here in living mice. Additionally, their applicability for magnetic heating in potential hyperthermia treatments is assessed.

ATMAD: robust image analysis for Automatic Tissue MicroArray De-arraying.

Science.gov (United States)

Nguyen, Hoai Nam; Paveau, Vincent; Cauchois, Cyril; Kervrann, Charles

2018-04-19

Over the last two decades, an innovative technology called Tissue Microarray (TMA), which combines multi-tissue and DNA microarray concepts, has been widely used in the field of histology. It consists of a collection of several (up to 1000 or more) tissue samples that are assembled onto a single support - typically a glass slide - according to a design grid (array) layout, in order to allow multiplex analysis by treating numerous samples under identical and standardized conditions. However, during the TMA manufacturing process, the sample positions can be highly distorted from the design grid due to the imprecision when assembling tissue samples and the deformation of the embedding waxes. Consequently, these distortions may lead to severe errors of (histological) assay results when the sample identities are mismatched between the design and its manufactured output. The development of a robust method for de-arraying TMA, which localizes and matches TMA samples with their design grid, is therefore crucial to overcome the bottleneck of this prominent technology. In this paper, we propose an Automatic, fast and robust TMA De-arraying (ATMAD) approach dedicated to images acquired with brightfield and fluorescence microscopes (or scanners). First, tissue samples are localized in the large image by applying a locally adaptive thresholding on the isotropic wavelet transform of the input TMA image. To reduce false detections, a parametric shape model is considered for segmenting ellipse-shaped objects at each detected position. Segmented objects that do not meet the size and the roundness criteria are discarded from the list of tissue samples before being matched with the design grid. Sample matching is performed by estimating the TMA grid deformation under the thin-plate model. Finally, thanks to the estimated deformation, the true tissue samples that were preliminary rejected in the early image processing step are recognized by running a second segmentation step. We

Breast tissue classification in digital breast tomosynthesis images using texture features: a feasibility study

Science.gov (United States)

Kontos, Despina; Berger, Rachelle; Bakic, Predrag R.; Maidment, Andrew D. A.

2009-02-01

Mammographic breast density is a known breast cancer risk factor. Studies have shown the potential to automate breast density estimation by using computerized texture-based segmentation of the dense tissue in mammograms. Digital breast tomosynthesis (DBT) is a tomographic x-ray breast imaging modality that could allow volumetric breast density estimation. We evaluated the feasibility of distinguishing between dense and fatty breast regions in DBT using computer-extracted texture features. Our long-term hypothesis is that DBT texture analysis can be used to develop 3D dense tissue segmentation algorithms for estimating volumetric breast density. DBT images from 40 women were analyzed. The dense tissue area was delineated within each central source projection (CSP) image using a thresholding technique (Cumulus, Univ. Toronto). Two (2.5cm)2 ROIs were manually selected: one within the dense tissue region and another within the fatty region. Corresponding (2.5cm)3 ROIs were placed within the reconstructed DBT images. Texture features, previously used for mammographic dense tissue segmentation, were computed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate feature classification performance. Different texture features appeared to perform best in the 3D reconstructed DBT compared to the 2D CSP images. Fractal dimension was superior in DBT (AUC=0.90), while contrast was best in CSP images (AUC=0.92). We attribute these differences to the effects of tissue superimposition in CSP and the volumetric visualization of the breast tissue in DBT. Our results suggest that novel approaches, different than those conventionally used in projection mammography, need to be investigated in order to develop DBT dense tissue segmentation algorithms for estimating volumetric breast density.

Hyperspectral Imaging and SPA-LDA Quantitative Analysis for Detection of Colon Cancer Tissue

Science.gov (United States)

Yuan, X.; Zhang, D.; Wang, Ch.; Dai, B.; Zhao, M.; Li, B.

2018-05-01

Hyperspectral imaging (HSI) has been demonstrated to provide a rapid, precise, and noninvasive method for cancer detection. However, because HSI contains many data, quantitative analysis is often necessary to distill information useful for distinguishing cancerous from normal tissue. To demonstrate that HSI with our proposed algorithm can make this distinction, we built a Vis-NIR HSI setup and made many spectral images of colon tissues, and then used a successive projection algorithm (SPA) to analyze the hyperspectral image data of the tissues. This was used to build an identification model based on linear discrimination analysis (LDA) using the relative reflectance values of the effective wavelengths. Other tissues were used as a prediction set to verify the reliability of the identification model. The results suggest that Vis-NIR hyperspectral images, together with the spectroscopic classification method, provide a new approach for reliable and safe diagnosis of colon cancer and could lead to advances in cancer diagnosis generally.

Imaging of oxygenation in 3D tissue models with multi-modal phosphorescent probes

Science.gov (United States)

Papkovsky, Dmitri B.; Dmitriev, Ruslan I.; Borisov, Sergei

2015-03-01

Cell-penetrating phosphorescence based probes allow real-time, high-resolution imaging of O2 concentration in respiring cells and 3D tissue models. We have developed a panel of such probes, small molecule and nanoparticle structures, which have different spectral characteristics, cell penetrating and tissue staining behavior. The probes are compatible with conventional live cell imaging platforms and can be used in different detection modalities, including ratiometric intensity and PLIM (Phosphorescence Lifetime IMaging) under one- or two-photon excitation. Analytical performance of these probes and utility of the O2 imaging method have been demonstrated with different types of samples: 2D cell cultures, multi-cellular spheroids from cancer cell lines and primary neurons, excised slices from mouse brain, colon and bladder tissue, and live animals. They are particularly useful for hypoxia research, ex-vivo studies of tissue physiology, cell metabolism, cancer, inflammation, and multiplexing with many conventional fluorophors and markers of cellular function.

Hyperspectral imaging based on compressive sensing to determine cancer margins in human pancreatic tissue ex vivo

Science.gov (United States)

Peller, Joseph; Thompson, Kyle J.; Siddiqui, Imran; Martinie, John; Iannitti, David A.; Trammell, Susan R.

2017-02-01

Pancreatic cancer is the fourth leading cause of cancer death in the US. Currently, surgery is the only treatment that offers a chance of cure, however, accurately identifying tumor margins in real-time is difficult. Research has demonstrated that optical spectroscopy can be used to distinguish between healthy and diseased tissue. The design of a single-pixel imaging system for cancer detection is discussed. The system differentiates between healthy and diseased tissue based on differences in the optical reflectance spectra of these regions. In this study, pancreatic tissue samples from 6 patients undergoing Whipple procedures are imaged with the system (total number of tissue sample imaged was N=11). Regions of healthy and unhealthy tissue are determined based on SAM analysis of these spectral images. Hyperspectral imaging results are then compared to white light imaging and histological analysis. Cancerous regions were clearly visible in the hyperspectral images. Margins determined via spectral imaging were in good agreement with margins identified by histology, indicating that hyperspectral imaging system can differentiate between healthy and diseased tissue. After imaging the system was able to detect cancerous regions with a sensitivity of 74.50±5.89% and a specificity of 75.53±10.81%. Possible applications of this imaging system include determination of tumor margins during surgery/biopsy and assistance with cancer diagnosis and staging.

Visualizing fungal metabolites during mycoparasitic interaction by MALDI mass spectrometry imaging

Science.gov (United States)

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

2016-01-01

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

Analysis of Chloroquine and Metabolites Directly from Whole-body Animal Tissue Sections by Liquid Extraction Surface Analysis (LESA) and Tandem Mass Spectrometry

Energy Technology Data Exchange (ETDEWEB)

Parson, Whitney B [ORNL; Koeniger, Stormy L [Abbott Laboratories; Johnson, Robert W [Abbott Laboratories; Erickson, Jamie [Abbott Laboratories; Tian, Yu [Abbott Laboratories; Stedman, Christopher A. [Abbott Laboratories; Schwartz, Annette [Abbott Laboratories; Tarcsa, Edit [Abbott Laboratories; Cole, Roderic [ORNL; Van Berkel, Gary J [ORNL

2012-01-01

The rapid and direct analysis of the amount and spatial distribution of exogenous chloroquine and chloroquine metabolites from tissue sections by liquid extraction surface sampling analysis coupled with tandem mass spectrometry (LESA-MS) was demonstrated. LESA-MS results compared well with previously published chloroquine quantification data collected by organ excision, extraction and fluorescent detection. The ability to directly sample and analyze spatially-resolved exogenous molecules from tissue sections with minimal sample preparation and analytical method development has the potential to facilitate the assessment of target tissue penetration of pharmaceutical compounds, to establish pharmacokinetic/pharmacodynamic (PK/PD) relationships, and to complement established pharmacokinetic methods used in the drug discovery process during tissue distribution assessment.

Effects on MR images compression in tissue classification quality

International Nuclear Information System (INIS)

Santalla, H; Meschino, G; Ballarin, V

2007-01-01

It is known that image compression is required to optimize the storage in memory. Moreover, transmission speed can be significantly improved. Lossless compression is used without controversy in medicine, though benefits are limited. If we compress images lossy, where image can not be totally recovered; we can only recover an approximation. In this point definition of 'quality' is essential. What we understand for 'quality'? How can we evaluate a compressed image? Quality in images is an attribute whit several definitions and interpretations, which actually depend on the posterior use we want to give them. This work proposes a quantitative analysis of quality for lossy compressed Magnetic Resonance (MR) images, and their influence in automatic tissue classification, accomplished with these images

Simultaneous imaging of multiple neurotransmitters and neuroactive substances in the brain by desorption electrospray ionization mass spectrometry

OpenAIRE

Shariatgorji, Mohammadreza; Strittmatter, Nicole; Nilsson, Anna; Kallbäck, Patrik; Alvarsson, Alexandra; Zhang, Xiaoqun; Vallianatou, Theodosia; Svenningsson, Per; Goodwin, Richard J. A.; Andrén, Per E.

2016-01-01

With neurological processes involving multiple neurotransmitters and neuromodulators, it is important to have the ability to directly map and quantify multiple signaling molecules simultaneously in a single analysis. By utilizing a molecular-specific approach, namely desorption electrospray ionization mass spectrometry imaging (DESI-MSI), we demonstrated that the technique can be used to image multiple neurotransmitters and their metabolites (dopamine, dihydroxyphenylacetic acid, 3-methoxytyr...

Chondro-osseous differentiation in fat tissue tumors: magnetic resonance imaging with pathological correlation

International Nuclear Information System (INIS)

Orui, Hiroshi; Ishikawa, Akira; Tsuchiya, Takashi; Takahara, Masatoshi; Ogino, Toshihiko; Ito, Masafumi

2000-01-01

Chondro-osseous differentiation of three benign or malignant fat tissue tumors - two chondrolipomas and a liposarcoma with cartilaginous metaplasia - was studied with magnetic resonance (MR) imaging and compared with their pathological findings. The results suggest that demarcation of cartilage tisssue can be clearly defined on MR imaging when the size of the cartilaginous area is large. Myxoid matrix, degenerative fat tissue and lipodystrophic change may decrease the delineation of the cartilage tissue. (orig.)

Chondro-osseous differentiation in fat tissue tumors: magnetic resonance imaging with pathological correlation

Energy Technology Data Exchange (ETDEWEB)

Orui, Hiroshi; Ishikawa, Akira; Tsuchiya, Takashi; Takahara, Masatoshi; Ogino, Toshihiko [Dept. of Orthopaedic Surgery, Yamagata University School of Medicine (Japan); Ito, Masafumi [1. Dept. of Pathology, Yamagata University School of Medicine, Yamagata (Japan)

2000-08-01

Chondro-osseous differentiation of three benign or malignant fat tissue tumors - two chondrolipomas and a liposarcoma with cartilaginous metaplasia - was studied with magnetic resonance (MR) imaging and compared with their pathological findings. The results suggest that demarcation of cartilage tisssue can be clearly defined on MR imaging when the size of the cartilaginous area is large. Myxoid matrix, degenerative fat tissue and lipodystrophic change may decrease the delineation of the cartilage tissue. (orig.)

Characterization of Soft Tissue Tumors by Diffusion-Weighted Imaging

International Nuclear Information System (INIS)

Pekcevik, Yeliz; Kahya, Mehmet Onur; Kaya, Ahmet

2015-01-01

Diffusion-weighted imaging (DWI) is a noninvasive method for investigation of tumor histological content. It has been applied for some musculoskeletal tumors and reported to be useful. The aim of the present study was to prospectively evaluate the apparent diffusion coefficient (ADC) values of benign and malignant soft tissue tumors and to determine if ADC can help differentiate these tumors. DWI was performed on 25 histologically proven soft tissue masses. It was obtained with a single-shot echo-planar imaging technique using a 1.5T magnetic resonance (MR) machine. The mean ADC values were calculated. We grouped soft tissue tumors as benign cystic, benign solid or mixed, malignant cystic and malignant solid or mixed tumors and compared mean ADC values between these groups. There was only one patient with a malignant cystic tumor and was not included in the statistical analysis. The median ADC values of benign and malignant tumors were 2.31 ± 1.29 and 0.90 ± 0.70 (median ± interquartile range), respectively. The mean ADC values were different between benign and malignant tumors (P = 0.031). Benign cystic tumors had significantly higher ADC values than benign solid or mixed tumors and malignant solid or mixed tumors (p values were < 0.001 and 0.003, respectively). Malignant solid or mixed tumors had lower ADC values than benign solid or mixed tumors (P = 0.02). Our preliminary results have shown that although there is some overlap between benign and malignant tumors, adding DWI, MR imaging to routine soft tissue tumor protocols may improve diagnostic accuracy

Imaging of human breast tissue using polarization sensitive optical coherence tomography

Science.gov (United States)

Verma, Y.; Gautam, M.; Divakar Rao, K.; Swami, M. K.; Gupta, P. K.

2011-12-01

We report a study on the use of polarization sensitive optical coherence tomography (PSOCT) for discriminating malignant (invasive ductal carcinoma), benign (fibroadenoma) and normal (adipocytes) breast tissue sites. The results show that while conventional OCT, that utilizes only the intensity of light back-scattered from tissue microstructures, is able to discriminate breast tissues as normal (adipocytes) and abnormal (malignant and benign) tissues, PS-OCT helps in discriminating between malignant and benign tissue sites also. The estimated values of birefringence obtained from the PSOCT imaging show that benign breast tissue samples have significantly higher birefringence as compared to the malignant tissue samples.

Multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures

Science.gov (United States)

Shin, Kwangsoo; Choi, Jin Woo; Ko, Giho; Baik, Seungmin; Kim, Dokyoon; Park, Ok Kyu; Lee, Kyoungbun; Cho, Hye Rim; Han, Sang Ihn; Lee, Soo Hong; Lee, Dong Jun; Lee, Nohyun; Kim, Hyo-Cheol; Hyeon, Taeghwan

2017-07-01

Tissue adhesives have emerged as an alternative to sutures and staples for wound closure and reconnection of injured tissues after surgery or trauma. Owing to their convenience and effectiveness, these adhesives have received growing attention particularly in minimally invasive procedures. For safe and accurate applications, tissue adhesives should be detectable via clinical imaging modalities and be highly biocompatible for intracorporeal procedures. However, few adhesives meet all these requirements. Herein, we show that biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) exhibit not only high contrast effects for real-time imaging but also strong adhesive properties. Furthermore, the biocompatible TSNs cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (that is, a mixture of cyanoacrylate and Lipiodol). Because of their multifunctional imaging and adhesive property, the TSNs are successfully applied as a hemostatic adhesive for minimally invasive procedures and as an immobilized marker for image-guided procedures.

3D imaging of optically cleared tissue using a simplified CLARITY method and on-chip microscopy

KAUST Repository

Zhang, Yibo; Shin, Yoonjung; Sung, Kevin; Yang, Sam; Chen, Harrison; Wang, Hongda; Teng, Da; Rivenson, Yair; Kulkarni, Rajan P.; Ozcan, Aydogan

2017-01-01

High-throughput sectioning and optical imaging of tissue samples using traditional immunohistochemical techniques can be costly and inaccessible in resource-limited areas. We demonstrate three-dimensional (3D) imaging and phenotyping in optically transparent tissue using lens-free holographic on-chip microscopy as a low-cost, simple, and high-throughput alternative to conventional approaches. The tissue sample is passively cleared using a simplified CLARITY method and stained using 3,3′-diaminobenzidine to target cells of interest, enabling bright-field optical imaging and 3D sectioning of thick samples. The lens-free computational microscope uses pixel super-resolution and multi-height phase recovery algorithms to digitally refocus throughout the cleared tissue and obtain a 3D stack of complex-valued images of the sample, containing both phase and amplitude information. We optimized the tissue-clearing and imaging system by finding the optimal illumination wavelength, tissue thickness, sample preparation parameters, and the number of heights of the lens-free image acquisition and implemented a sparsity-based denoising algorithm to maximize the imaging volume and minimize the amount of the acquired data while also preserving the contrast-to-noise ratio of the reconstructed images. As a proof of concept, we achieved 3D imaging of neurons in a 200-μm-thick cleared mouse brain tissue over a wide field of view of 20.5 mm2. The lens-free microscope also achieved more than an order-of-magnitude reduction in raw data compared to a conventional scanning optical microscope imaging the same sample volume. Being low cost, simple, high-throughput, and data-efficient, we believe that this CLARITY-enabled computational tissue imaging technique could find numerous applications in biomedical diagnosis and research in low-resource settings.

3D imaging of optically cleared tissue using a simplified CLARITY method and on-chip microscopy

KAUST Repository

Zhang, Yibo

2017-08-12

High-throughput sectioning and optical imaging of tissue samples using traditional immunohistochemical techniques can be costly and inaccessible in resource-limited areas. We demonstrate three-dimensional (3D) imaging and phenotyping in optically transparent tissue using lens-free holographic on-chip microscopy as a low-cost, simple, and high-throughput alternative to conventional approaches. The tissue sample is passively cleared using a simplified CLARITY method and stained using 3,3′-diaminobenzidine to target cells of interest, enabling bright-field optical imaging and 3D sectioning of thick samples. The lens-free computational microscope uses pixel super-resolution and multi-height phase recovery algorithms to digitally refocus throughout the cleared tissue and obtain a 3D stack of complex-valued images of the sample, containing both phase and amplitude information. We optimized the tissue-clearing and imaging system by finding the optimal illumination wavelength, tissue thickness, sample preparation parameters, and the number of heights of the lens-free image acquisition and implemented a sparsity-based denoising algorithm to maximize the imaging volume and minimize the amount of the acquired data while also preserving the contrast-to-noise ratio of the reconstructed images. As a proof of concept, we achieved 3D imaging of neurons in a 200-μm-thick cleared mouse brain tissue over a wide field of view of 20.5 mm2. The lens-free microscope also achieved more than an order-of-magnitude reduction in raw data compared to a conventional scanning optical microscope imaging the same sample volume. Being low cost, simple, high-throughput, and data-efficient, we believe that this CLARITY-enabled computational tissue imaging technique could find numerous applications in biomedical diagnosis and research in low-resource settings.

Imaging of alkaline phosphatase activity in bone tissue.

Directory of Open Access Journals (Sweden)

Terence P Gade

Full Text Available The purpose of this study was to develop a paradigm for quantitative molecular imaging of bone cell activity. We hypothesized the feasibility of non-invasive imaging of the osteoblast enzyme alkaline phosphatase (ALP using a small imaging molecule in combination with (19Flourine magnetic resonance spectroscopic imaging ((19FMRSI. 6, 8-difluoro-4-methylumbelliferyl phosphate (DiFMUP, a fluorinated ALP substrate that is activatable to a fluorescent hydrolysis product was utilized as a prototype small imaging molecule. The molecular structure of DiFMUP includes two Fluorine atoms adjacent to a phosphate group allowing it and its hydrolysis product to be distinguished using (19Fluorine magnetic resonance spectroscopy ((19FMRS and (19FMRSI. ALP-mediated hydrolysis of DiFMUP was tested on osteoblastic cells and bone tissue, using serial measurements of fluorescence activity. Extracellular activation of DiFMUP on ALP-positive mouse bone precursor cells was observed. Concurringly, DiFMUP was also activated on bone derived from rat tibia. Marked inhibition of the cell and tissue activation of DiFMUP was detected after the addition of the ALP inhibitor levamisole. (19FMRS and (19FMRSI were applied for the non-invasive measurement of DiFMUP hydrolysis. (19FMRS revealed a two-peak spectrum representing DiFMUP with an associated chemical shift for the hydrolysis product. Activation of DiFMUP by ALP yielded a characteristic pharmacokinetic profile, which was quantifiable using non-localized (19FMRS and enabled the development of a pharmacokinetic model of ALP activity. Application of (19FMRSI facilitated anatomically accurate, non-invasive imaging of ALP concentration and activity in rat bone. Thus, (19FMRSI represents a promising approach for the quantitative imaging of bone cell activity during bone formation with potential for both preclinical and clinical applications.

Magnetic resonance imaging appearance of soft-tissue metastases: our experience at an orthopedic oncology center

International Nuclear Information System (INIS)

Sammon, Jennifer; Jain, Abhishek; Bleakney, Robert; Mohankumar, Rakesh

2017-01-01

To assess the prevalence and magnetic resonance imaging appearance of metastasis presenting as a soft-tissue mass. A retrospective chart review was performed on 51 patients who presented to an orthopedic oncology center with soft-tissue masses, with a histology-proven diagnosis of soft-tissue metastasis, over a 14-year period. Their magnetic resonance imaging, primary origin, and follow-up have been assessed. Soft-tissue metastasis was identified in patients ranging from 18 to 85 years old. Most (80%) of the masses were located deep to the deep fascia. In our cohort of patients, melanoma was the most common primary malignancy contributing to soft-tissue metastasis (21.8%). Among soft-tissue metastasis from solid organs, breast and lung were the most frequent (9.1% each). Five patients had soft-tissue metastases from an unknown primary. Imaging diagnosis of soft-tissue metastases is challenging as it can demonstrate imaging appearances similar to primary soft-tissue sarcoma. The presence of a known malignancy may not be evident in everyone, and even if available, histopathology will be necessary for diagnosis if this is the only site of recurrence/metastasis to differentiate from a primary soft-tissue sarcoma. Moreover, soft-tissue metastasis may be the initial presentation of a malignancy. Primary malignancies with soft-tissue metastasis carry a poor prognosis; hence, prompt diagnosis and management in essential. (orig.)

Magnetic resonance imaging appearance of soft-tissue metastases: our experience at an orthopedic oncology center

Energy Technology Data Exchange (ETDEWEB)

Sammon, Jennifer; Jain, Abhishek; Bleakney, Robert; Mohankumar, Rakesh [Mount Sinai Hospital and University of Toronto, Division of Musculoskeletal Imaging, Joint Department of Medical Imaging, Toronto, Ontario (Canada)

2017-04-15

To assess the prevalence and magnetic resonance imaging appearance of metastasis presenting as a soft-tissue mass. A retrospective chart review was performed on 51 patients who presented to an orthopedic oncology center with soft-tissue masses, with a histology-proven diagnosis of soft-tissue metastasis, over a 14-year period. Their magnetic resonance imaging, primary origin, and follow-up have been assessed. Soft-tissue metastasis was identified in patients ranging from 18 to 85 years old. Most (80%) of the masses were located deep to the deep fascia. In our cohort of patients, melanoma was the most common primary malignancy contributing to soft-tissue metastasis (21.8%). Among soft-tissue metastasis from solid organs, breast and lung were the most frequent (9.1% each). Five patients had soft-tissue metastases from an unknown primary. Imaging diagnosis of soft-tissue metastases is challenging as it can demonstrate imaging appearances similar to primary soft-tissue sarcoma. The presence of a known malignancy may not be evident in everyone, and even if available, histopathology will be necessary for diagnosis if this is the only site of recurrence/metastasis to differentiate from a primary soft-tissue sarcoma. Moreover, soft-tissue metastasis may be the initial presentation of a malignancy. Primary malignancies with soft-tissue metastasis carry a poor prognosis; hence, prompt diagnosis and management in essential. (orig.)

Comparison study among conventional, tissue harmonic and pulse inversion harmonic images to evaluate pleural effusion and ascites

International Nuclear Information System (INIS)

Chung, Hwan Hoon; Kim, Yun Hwan; Kang, Chang Ho; Park, Bum Jin; Chung, Kyoo Byung; Suh, Won Hyuck

2000-01-01

To determine the most useful sonographic technique to evaluate pleural effusion and ascites by comparing conventional, tissue harmonic and pulse inversion harmonic images. 12 patients having pleural effusion and 14 patients having ascites were included in this study. 18 patients were male and 8 patients were female. Average age was 54.8 yrs (25-77). We compared images which had been taken at the same section with 3 above mentioned sonographic techniques. Evaluation was done by 3 radiologists in consensus and grades were given to 3 techniques from 1 to 3. Evaluating points were 1) normal structures that border the fluid such as liver, peritoneal lining, pleura, 2) septation in fluid, 3) debris floating in fluid, and 4) artifacts. Pulse inversion harmonic image was the best in image quality for normal structures, followed by tissue harmonic and conventional image (p<0.05). Pulse inversion harmonic image was better than conventional image to evaluate septation in fluid (p<0.05), but there were no statistically significant difference between pulse inversion and tissue harmonic images, and tissue harmonic and conventional images. Tissue harmonic image was better than pulse inversion harmonic and conventional images to evaluate debris floating in fluid (p<0.05) but there was no statistically significant difference between these two latter techniques. Artifacts were most prominent on conventional image followed by tissue harmonic and pulse inversion harmonic image (p<0.05). Pulse inversion harmonic image was the best sonographic technique to evaluate pleural effusion or ascites, However, Tissue harmonic image was the best for evaluation of debris.

Comparison study among conventional, tissue harmonic and pulse inversion harmonic images to evaluate pleural effusion and ascites

Energy Technology Data Exchange (ETDEWEB)

Chung, Hwan Hoon; Kim, Yun Hwan; Kang, Chang Ho; Park, Bum Jin; Chung, Kyoo Byung; Suh, Won Hyuck [Korea University College of Medicine, Seoul (Korea, Republic of)

2000-12-15

To determine the most useful sonographic technique to evaluate pleural effusion and ascites by comparing conventional, tissue harmonic and pulse inversion harmonic images. 12 patients having pleural effusion and 14 patients having ascites were included in this study. 18 patients were male and 8 patients were female. Average age was 54.8 yrs (25-77). We compared images which had been taken at the same section with 3 above mentioned sonographic techniques. Evaluation was done by 3 radiologists in consensus and grades were given to 3 techniques from 1 to 3. Evaluating points were 1) normal structures that border the fluid such as liver, peritoneal lining, pleura, 2) septation in fluid, 3) debris floating in fluid, and 4) artifacts. Pulse inversion harmonic image was the best in image quality for normal structures, followed by tissue harmonic and conventional image (p<0.05). Pulse inversion harmonic image was better than conventional image to evaluate septation in fluid (p<0.05), but there were no statistically significant difference between pulse inversion and tissue harmonic images, and tissue harmonic and conventional images. Tissue harmonic image was better than pulse inversion harmonic and conventional images to evaluate debris floating in fluid (p<0.05) but there was no statistically significant difference between these two latter techniques. Artifacts were most prominent on conventional image followed by tissue harmonic and pulse inversion harmonic image (p<0.05). Pulse inversion harmonic image was the best sonographic technique to evaluate pleural effusion or ascites, However, Tissue harmonic image was the best for evaluation of debris.

Determination of spatial distribution of melamine-cyanuric acid crystals in rat kidney tissue by histology and imaging matrix-assisted laser desorption/ionization quadrupole time-of-flight mass spectrometry.

Science.gov (United States)

Kim, Chae-Wook; Yun, Jun-Won; Bae, Il-Hong; Lee, Joon-Seok; Kang, Hyun-Jin; Joo, Kyung-Mi; Jeong, Hye-Jin; Chung, Jin-Ho; Park, Young-Ho; Lim, Kyung-Min

2010-01-01

After the outbreak of acute renal failure associated with melamine-contaminated pet food, many attempts have been made to uncover the mechanism underlying the renal toxicity caused by melamine and melamine-related compounds. Using rat models, we investigated the renal crystal formation following the ingestion of a melamine-cyanuric acid mixture (M+CA, 1:1) to gain insight into the M+CA-induced renal toxicity. M+CA did not induce toxicity in precision-cut kidney slices, suggesting that M+CA does not have a direct nephrotoxicity. On the contrary, oral administration of M+CA for 3 days induced nephrotoxicity as determined by increased serum blood urea nitrogen and creatinine, reduced creatinine clearance, and enlarged kidneys in the animals treated with 50 mg/kg M+CA (melamine, 25 mg/kg, and cyanuric acid, 25 mg/kg; 2 of 10 animals) and 100 mg/kg M+CA (9 of 9 animals). While urine crystals were found in all animals treated with M+CA (25-100 mg/kg), histological examination revealed that renal crystals could be observed only in the kidneys of animals showing signs of nephrotoxicity. Remarkably, at 50 mg/kg M+CA, crystals were observed mainly in the medulla region of the kidney, while at 100 mg/kg, crystals were disseminated throughout the cortex and medulla regions. To further investigate the crystal formation by M+CA, matrix-assisted laser desorption/ionization quadrupole time-of-flight (MALDI-Q-TOF) imaging mass spectrometry detecting melamine distribution through monitoring the product ion (m/z 85, M + H) from melamine (m/z 127, M + H) was developed to directly obtain the image of melamine distribution in the kidney. The distribution image of melamine in kidney tissue confirmed that dense points of melamine were located only in the medulla region at 50 mg/kg M+CA, while at 100 mg/kg, they were disseminated widely from the cortex to medulla. These results demonstrated that M+CA ingestion could lead to crystal formation in kidney tubules along the osmotic gradient and

An approach for quantification of platinum distribution in tissues by LA-ICP-MS imaging using isotope dilution analysis.

Science.gov (United States)

Moraleja, I; Mena, M L; Lázaro, A; Neumann, B; Tejedor, A; Jakubowski, N; Gómez-Gómez, M M; Esteban-Fernández, D

2018-02-01

Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been revealed as a convenient technique for trace elemental imaging in tissue sections, providing elemental 2D distribution at a quantitative level. For quantification purposes, in the last years several approaches have been proposed in the literature such as the use of CRMs or matrix matched standards. The use of Isotope Dilution (ID) for quantification by LA-ICP-MS has been also described, being mainly useful for bulk analysis but not feasible for spatial measurements so far. In this work, a quantification method based on ID analysis was developed by printing isotope-enriched inks onto kidney slices from rats treated with antitumoral Pt-based drugs using a commercial ink-jet device, in order to perform an elemental quantification in different areas from bio-images. For the ID experiments 194 Pt enriched platinum was used. The methodology was validated by deposition of natural Pt standard droplets with a known amount of Pt onto the surface of a control tissue, where could be quantified even 50pg of Pt, with recoveries higher than 90%. The amount of Pt present in the whole kidney slices was quantified for cisplatin, carboplatin and oxaliplatin-treated rats. The results obtained were in accordance with those previously reported. The amount of Pt distributed between the medullar and cortical areas was also quantified, observing different behavior for the three drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues

Science.gov (United States)

Tzoumas, Stratis; Nunes, Antonio; Olefir, Ivan; Stangl, Stefan; Symvoulidis, Panagiotis; Glasl, Sarah; Bayer, Christine; Multhoff, Gabriele; Ntziachristos, Vasilis

2016-06-01

Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation, an effect that causes spectral corruption. Spectral corruption has limited the quantification accuracy of optical and optoacoustic spectroscopic methods, and impeded the goal of imaging blood oxygen saturation (sO2) deep in tissues; a critical goal for the assessment of oxygenation in physiological processes and disease. Here we describe light fluence in the spectral domain and introduce eigenspectra multispectral optoacoustic tomography (eMSOT) to account for wavelength-dependent light attenuation, and estimate blood sO2 within deep tissue. We validate eMSOT in simulations, phantoms and animal measurements and spatially resolve sO2 in muscle and tumours, validating our measurements with histology data. eMSOT shows substantial sO2 accuracy enhancement over previous optoacoustic methods, potentially serving as a valuable tool for imaging tissue pathophysiology.

Eigenspectra optoacoustic tomography achieves quantitative blood oxygenation imaging deep in tissues.

Science.gov (United States)

Tzoumas, Stratis; Nunes, Antonio; Olefir, Ivan; Stangl, Stefan; Symvoulidis, Panagiotis; Glasl, Sarah; Bayer, Christine; Multhoff, Gabriele; Ntziachristos, Vasilis

2016-06-30

Light propagating in tissue attains a spectrum that varies with location due to wavelength-dependent fluence attenuation, an effect that causes spectral corruption. Spectral corruption has limited the quantification accuracy of optical and optoacoustic spectroscopic methods, and impeded the goal of imaging blood oxygen saturation (sO2) deep in tissues; a critical goal for the assessment of oxygenation in physiological processes and disease. Here we describe light fluence in the spectral domain and introduce eigenspectra multispectral optoacoustic tomography (eMSOT) to account for wavelength-dependent light attenuation, and estimate blood sO2 within deep tissue. We validate eMSOT in simulations, phantoms and animal measurements and spatially resolve sO2 in muscle and tumours, validating our measurements with histology data. eMSOT shows substantial sO2 accuracy enhancement over previous optoacoustic methods, potentially serving as a valuable tool for imaging tissue pathophysiology.

Hyperspectral microscope for in vivo imaging of microstructures and cells in tissues

Science.gov (United States)

Demos,; Stavros, G [Livermore, CA

2011-05-17

An optical hyperspectral/multimodal imaging method and apparatus is utilized to provide high signal sensitivity for implementation of various optical imaging approaches. Such a system utilizes long working distance microscope objectives so as to enable off-axis illumination of predetermined tissue thereby allowing for excitation at any optical wavelength, simplifies design, reduces required optical elements, significantly reduces spectral noise from the optical elements and allows for fast image acquisition enabling high quality imaging in-vivo. Such a technology provides a means of detecting disease at the single cell level such as cancer, precancer, ischemic, traumatic or other type of injury, infection, or other diseases or conditions causing alterations in cells and tissue micro structures.

Quantitative segmentation of fluorescence microscopy images of heterogeneous tissue: Approach for tuning algorithm parameters

Science.gov (United States)

Mueller, Jenna L.; Harmany, Zachary T.; Mito, Jeffrey K.; Kennedy, Stephanie A.; Kim, Yongbaek; Dodd, Leslie; Geradts, Joseph; Kirsch, David G.; Willett, Rebecca M.; Brown, J. Quincy; Ramanujam, Nimmi

2013-02-01

The combination of fluorescent contrast agents with microscopy is a powerful technique to obtain real time images of tissue histology without the need for fixing, sectioning, and staining. The potential of this technology lies in the identification of robust methods for image segmentation and quantitation, particularly in heterogeneous tissues. Our solution is to apply sparse decomposition (SD) to monochrome images of fluorescently-stained microanatomy to segment and quantify distinct tissue types. The clinical utility of our approach is demonstrated by imaging excised margins in a cohort of mice after surgical resection of a sarcoma. Representative images of excised margins were used to optimize the formulation of SD and tune parameters associated with the algorithm. Our results demonstrate that SD is a robust solution that can advance vital fluorescence microscopy as a clinically significant technology.

Laser-induced fluorescence imaging of subsurface tissue structures with a volume holographic spatial-spectral imaging system.

Science.gov (United States)

Luo, Yuan; Gelsinger-Austin, Paul J; Watson, Jonathan M; Barbastathis, George; Barton, Jennifer K; Kostuk, Raymond K

2008-09-15

A three-dimensional imaging system incorporating multiplexed holographic gratings to visualize fluorescence tissue structures is presented. Holographic gratings formed in volume recording materials such as a phenanthrenquinone poly(methyl methacrylate) photopolymer have narrowband angular and spectral transmittance filtering properties that enable obtaining spatial-spectral information within an object. We demonstrate this imaging system's ability to obtain multiple depth-resolved fluorescence images simultaneously.

Magnetic resonance imaging of local soft tissue inflammation using gadolinium-DTPA

International Nuclear Information System (INIS)

Paajanen, H.; Brasch, R.C.; Schmiedl, U.; Ogan, M.

1987-01-01

Chemical inflammation was induced subcutaneously in 10 rats using carrageenan mucopolysaccharide. Dual spin echo (SE) imaging of inflammatory loci was performed employing a 0.35 tesla resistive magnet. In addition, gadolinium-DTPA was administrated intravenously into 5 rats to evaluate the potential benefits of paramagnetic contrast medium for the detection and characterization of inflammatory loci. T2 weighted SE images demonstrated the edematous lesions as zones of high intensity. This was attributed to the increased relaxation times of lesions when compared to the adjacent soft tissue. The inflammation was also delineated on T1 weighted SE images, but only after injection of paramagnetic Gd-DTPA. Carrageenan mucopolysaccharide-induced lesions provide a useful experimental model for in viva evaluation of soft tissue inflammation using magnetic resonance imaging. No special benefit of paramagnetic contrast enhancement was demonstrated in this model of local edema. (orig.)

Identification and imaging of modern paints using Secondary Ion Mass Spectrometry with MeV ions

Science.gov (United States)

Bogdanović Radović, Iva; Siketić, Zdravko; Jembrih-Simbürger, Dubravka; Marković, Nikola; Anghelone, Marta; Stoytschew, Valentin; Jakšić, Milko

2017-09-01

Secondary Ion Mass Spectrometry using MeV ion excitation was applied to analyse modern paint materials containing synthetic organic pigments and binders. It was demonstrated that synthetic organic pigments and binder components with molecular masses in the m/z range from 1 to 1200 could be identified in different paint samples with a high efficiency and in a single measurement. Different ways of mounting of mostly insulating paint samples were tested prior to the analysis in order to achieve the highest possible yield of pigment main molecular ions. As Time-of-Flight mass spectrometer for MeV Secondary Ion Mass Spectrometry is attached to the heavy ion microprobe, molecular imaging on cross-sections of small paint fragments was performed using focused ions. Due to the fact that molecules are extracted from the uppermost layer of the sample and to avoid surface contamination, the paint samples were not embedded in the resin as is usually done when imaging of paint samples using different techniques in the field of cultural heritage.

3D Multi-isotope Imaging Mass Spectrometry Reveals Penetration of 18O-Trehalose in Mouse Sperm Nucleus

OpenAIRE

Lechene, Claude P.; Lee, Gloria Y.; Poczatek, J. Collin; Toner, Mehmet; Biggers, John D.

2012-01-01

The prevalence of genetically engineered mice in medical research has led to ever increasing storage costs. Trehalose has a significant beneficial effect in preserving the developmental potential of mouse sperm following partial desiccation and storage at temperatures above freezing. Using multi-isotope imaging mass spectrometry, we are able to image and measure trehalose in individual spermatozoa. We provide the first evidence that trehalose penetrates the nucleus of a mammalian cell, permit...

Cell and Tissue Imaging with Molecularly Imprinted Polymers.

Science.gov (United States)

Panagiotopoulou, Maria; Kunath, Stephanie; Haupt, Karsten; Tse Sum Bui, Bernadette

2017-01-01

Advanced tools for cell imaging are of particular interest as they can detect, localize and quantify molecular targets like abnormal glycosylation sites that are biomarkers of cancer and infection. Targeting these biomarkers is often challenging due to a lack of receptor materials. Molecularly imprinted polymers (MIPs) are promising artificial receptors; they can be tailored to bind targets specifically, be labeled easily, and are physically and chemically stable. Herein, we demonstrate the application of MIPs as artificial antibodies for selective labeling and imaging of cellular targets, on the example of hyaluronan and sialylation moieties on fixated human skin cells and tissues. Thus, fluorescently labeled MIP nanoparticles templated with glucuronic acid (MIPGlcA) and N-acetylneuraminic acid (MIPNANA) are respectively applied. Two different fluorescent probes are used: (1) MIPGlcA particles, ~400 nm in size are labeled with the dye rhodamine that target the extracellular hyaluronan on cells and tissue specimens and (2) MIP-coated InP/ZnS quantum dots (QDs) of two different colors, ~125 nm in size that target the extracellular and intracellular hyaluronan and sialylation sites. Green and red emitting QDs are functionalized with MIPGlcA and MIPNANA respectively, enabling multiplexed cell imaging. This is a general approach that can also be adapted to other target molecules on and in cells.

Mass Spectrometry-Based Biomarker Discovery.

Science.gov (United States)

Zhou, Weidong; Petricoin, Emanuel F; Longo, Caterina

2017-01-01

The discovery of candidate biomarkers within the entire proteome is one of the most important and challenging goals in proteomic research. Mass spectrometry-based proteomics is a modern and promising technology for semiquantitative and qualitative assessment of proteins, enabling protein sequencing and identification with exquisite accuracy and sensitivity. For mass spectrometry analysis, protein extractions from tissues or body fluids and subsequent protein fractionation represent an important and unavoidable step in the workflow for biomarker discovery. Following extraction of proteins, the protein mixture must be digested, reduced, alkylated, and cleaned up prior to mass spectrometry. The aim of our chapter is to provide comprehensible and practical lab procedures for sample digestion, protein fractionation, and subsequent mass spectrometry analysis.

Use of high-intensity sonication for pre-treatment of biological tissues prior to multielemental analysis by total reflection X-ray fluorescence spectrometry

International Nuclear Information System (INIS)

De La Calle, Inmaculada; Costas, Marta; Cabaleiro, Noelia; Lavilla, Isela; Bendicho, Carlos

2012-01-01

In this work, two ultrasound-based procedures are developed for sample preparation prior to determination of P, K, Ca, Cr, Mn, Fe, Ni, Cu, Zn, As, Se and Sr in biological tissues by total reflection X-ray fluorescence spectrometry. Ultrasound-assisted extraction by means of a cup-horn sonoreactor and ultrasonic-probe slurry sampling were compared with a well-established procedure such as magnetic agitation slurry sampling. For that purpose, seven certified reference materials and different real samples of animal tissue were used. Similar accuracy and precision is obtained with the three sample preparation approaches tried. Limits of detection were dependent on both the sample matrix and the sample pre-treatment used, best values being achieved with ultrasound-assisted extraction. Advantages of ultrasound-assisted extraction include reduced sample handling, decreased contamination risks (neither addition of surfactants nor use of foreign objects inside the extraction vial), simpler background (no solid particles onto the sample carrier) and improved recovery for some elements such as P. A mixture of 10% v/v HNO 3 + 20–40% v/v HCl was suitable for extraction from biological tissues. - Highlights: ► We implement high-intensity sonication for pre-treatment of biological tissues. ► Multielemental analysis is performed by total reflection X-ray spectrometry. ► Ultrasound-based procedures are developed and compared to conventional slurry preparation. ► Features such as background, recovery and sample handling are favored by using ultrasonic extraction.

Ultrasound Imaging Techniques for Spatiotemporal Characterization of Composition, Microstructure, and Mechanical Properties in Tissue Engineering.

Science.gov (United States)

Deng, Cheri X; Hong, Xiaowei; Stegemann, Jan P

2016-08-01

Ultrasound techniques are increasingly being used to quantitatively characterize both native and engineered tissues. This review provides an overview and selected examples of the main techniques used in these applications. Grayscale imaging has been used to characterize extracellular matrix deposition, and quantitative ultrasound imaging based on the integrated backscatter coefficient has been applied to estimating cell concentrations and matrix morphology in tissue engineering. Spectral analysis has been employed to characterize the concentration and spatial distribution of mineral particles in a construct, as well as to monitor mineral deposition by cells over time. Ultrasound techniques have also been used to measure the mechanical properties of native and engineered tissues. Conventional ultrasound elasticity imaging and acoustic radiation force imaging have been applied to detect regions of altered stiffness within tissues. Sonorheometry and monitoring of steady-state excitation and recovery have been used to characterize viscoelastic properties of tissue using a single transducer to both deform and image the sample. Dual-mode ultrasound elastography uses separate ultrasound transducers to produce a more potent deformation force to microscale characterization of viscoelasticity of hydrogel constructs. These ultrasound-based techniques have high potential to impact the field of tissue engineering as they are further developed and their range of applications expands.

The Effect of Collimating Lens Focusing on Laser Beam Shape in Matrix Assisted Laser Desorption/Ionization Mass Spectrometry (MALDI-MS).

Science.gov (United States)

O'Rourke, Matthew B; Raymond, Benjamin B A; Djordjevic, Steven P; Padula, Matthew P

2018-03-01

Tissue imaging using matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a well-established technique that, in recent years, has seen wider adoption and novel application. Applications such imaging mass spectrometry (IMS) and biotyping are beginning to gain greater exposure and use; however, with limitations in optimization methods, producing the best result often relies on the ability to customize the physical characteristics of the instrumentation, a task that is challenging for most mass spectrometry laboratories. With this in mind, we have described the effect of making simple adjustments to the laser optics at the final collimating lens area, to adjust the laser beam size and shape in order to allow greater customization of the instrument for improving techniques such as IMS. We have therefore been able to demonstrate that improvements can be made without requiring the help of an electrical engineer or external funding in a way that only costs a small amount of time. Graphical Abstract ᅟ.

Magnetoacoustic Imaging of Electrical Conductivity of Biological Tissues at a Spatial Resolution Better than 2 mm

OpenAIRE

Hu, Gang; He, Bin

2011-01-01

Magnetoacoustic tomography with magnetic induction (MAT-MI) is an emerging approach for noninvasively imaging electrical impedance properties of biological tissues. The MAT-MI imaging system measures ultrasound waves generated by the Lorentz force, having been induced by magnetic stimulation, which is related to the electrical conductivity distribution in tissue samples. MAT-MI promises to provide fine spatial resolution for biological tissue imaging as compared to ultrasound resolution. In t...

Soft-tissue imaging with C-arm cone-beam CT using statistical reconstruction

International Nuclear Information System (INIS)

Wang, Adam S; Stayman, J Webster; Otake, Yoshito; Siewerdsen, Jeffrey H; Kleinszig, Gerhard; Vogt, Sebastian; Gallia, Gary L; Khanna, A Jay

2014-01-01

The potential for statistical image reconstruction methods such as penalized-likelihood (PL) to improve C-arm cone-beam CT (CBCT) soft-tissue visualization for intraoperative imaging over conventional filtered backprojection (FBP) is assessed in this work by making a fair comparison in relation to soft-tissue performance. A prototype mobile C-arm was used to scan anthropomorphic head and abdomen phantoms as well as a cadaveric torso at doses substantially lower than typical values in diagnostic CT, and the effects of dose reduction via tube current reduction and sparse sampling were also compared. Matched spatial resolution between PL and FBP was determined by the edge spread function of low-contrast (∼40–80 HU) spheres in the phantoms, which were representative of soft-tissue imaging tasks. PL using the non-quadratic Huber penalty was found to substantially reduce noise relative to FBP, especially at lower spatial resolution where PL provides a contrast-to-noise ratio increase up to 1.4–2.2× over FBP at 50% dose reduction across all objects. Comparison of sampling strategies indicates that soft-tissue imaging benefits from fully sampled acquisitions at dose above ∼1.7 mGy and benefits from 50% sparsity at dose below ∼1.0 mGy. Therefore, an appropriate sampling strategy along with the improved low-contrast visualization offered by statistical reconstruction demonstrates the potential for extending intraoperative C-arm CBCT to applications in soft-tissue interventions in neurosurgery as well as thoracic and abdominal surgeries by overcoming conventional tradeoffs in noise, spatial resolution, and dose. (paper)

Deep-tissue reporter-gene imaging with fluorescence and optoacoustic tomography: a performance overview.

Science.gov (United States)

Deliolanis, Nikolaos C; Ale, Angelique; Morscher, Stefan; Burton, Neal C; Schaefer, Karin; Radrich, Karin; Razansky, Daniel; Ntziachristos, Vasilis

2014-10-01

A primary enabling feature of near-infrared fluorescent proteins (FPs) and fluorescent probes is the ability to visualize deeper in tissues than in the visible. The purpose of this work is to find which is the optimal visualization method that can exploit the advantages of this novel class of FPs in full-scale pre-clinical molecular imaging studies. Nude mice were stereotactically implanted with near-infrared FP expressing glioma cells to from brain tumors. The feasibility and performance metrics of FPs were compared between planar epi-illumination and trans-illumination fluorescence imaging, as well as to hybrid Fluorescence Molecular Tomography (FMT) system combined with X-ray CT and Multispectral Optoacoustic (or Photoacoustic) Tomography (MSOT). It is shown that deep-seated glioma brain tumors are possible to visualize both with fluorescence and optoacoustic imaging. Fluorescence imaging is straightforward and has good sensitivity; however, it lacks resolution. FMT-XCT can provide an improved rough resolution of ∼1 mm in deep tissue, while MSOT achieves 0.1 mm resolution in deep tissue and has comparable sensitivity. We show imaging capacity that can shift the visualization paradigm in biological discovery. The results are relevant not only to reporter gene imaging, but stand as cross-platform comparison for all methods imaging near infrared fluorescent contrast agents.

The reliability of a segmentation methodology for assessing intramuscular adipose tissue and other soft-tissue compartments of lower leg MRI images.

Science.gov (United States)

Karampatos, Sarah; Papaioannou, Alexandra; Beattie, Karen A; Maly, Monica R; Chan, Adrian; Adachi, Jonathan D; Pritchard, Janet M

2016-04-01

Determine the reliability of a magnetic resonance (MR) image segmentation protocol for quantifying intramuscular adipose tissue (IntraMAT), subcutaneous adipose tissue, total muscle and intermuscular adipose tissue (InterMAT) of the lower leg. Ten axial lower leg MRI slices were obtained from 21 postmenopausal women using a 1 Tesla peripheral MRI system. Images were analyzed using sliceOmatic™ software. The average cross-sectional areas of the tissues were computed for the ten slices. Intra-rater and inter-rater reliability were determined and expressed as the standard error of measurement (SEM) (absolute reliability) and intraclass coefficient (ICC) (relative reliability). Intra-rater and inter-rater reliability for IntraMAT were 0.991 (95% confidence interval [CI] 0.978-0.996, p soft tissue compartments, the ICCs were all >0.90 (p soft-tissue compartments of the lower leg. A standard operating procedure manual is provided to assist users, and SEM values can be used to estimate sample size and determine confidence in repeated measurements in future research.

Effect of inter-tissue inductive coupling on multi-frequency imaging of intracranial hemorrhage by magnetic induction tomography

Science.gov (United States)

Xiao, Zhili; Tan, Chao; Dong, Feng

2017-08-01

Magnetic induction tomography (MIT) is a promising technique for continuous monitoring of intracranial hemorrhage due to its contactless nature, low cost and capacity to penetrate the high-resistivity skull. The inter-tissue inductive coupling increases with frequency, which may lead to errors in multi-frequency imaging at high frequency. The effect of inter-tissue inductive coupling was investigated to improve the multi-frequency imaging of hemorrhage. An analytical model of inter-tissue inductive coupling based on the equivalent circuit was established. A set of new multi-frequency decomposition equations separating the phase shift of hemorrhage from other brain tissues was derived by employing the coupling information to improve the multi-frequency imaging of intracranial hemorrhage. The decomposition error and imaging error are both decreased after considering the inter-tissue inductive coupling information. The study reveals that the introduction of inter-tissue inductive coupling can reduce the errors of multi-frequency imaging, promoting the development of intracranial hemorrhage monitoring by multi-frequency MIT.

Helical 3D-CT images of soft tissue tumors in the hand

Energy Technology Data Exchange (ETDEWEB)

Otani, Kazuhiro; Kikuchi, Hiraku; Tan, Akihiro; Hamanishi, Chiaki; Tanaka, Seisuke [Kinki Univ., Osaka-Sayama (Japan). School of Medicine

2000-02-01

X-ray, ultrasonograph CT, MRI and angiography are used to detect tumoral lesions. Recently, helical CT has been revealed to be a useful method for the diagnosis and preoperative evaluation of soft tissue tumors, by which high quality and accurate three dimensional (3D) images can be obtained quickly. We analyzed the preoperative 3D-CT images of soft tissue tumors in the hands of 11 cases (hemangioma in 6 cases, giant cell tumor, lipoma, angiofibroma, chondrosarcoma and malignant fibro-histiocytoma in one case each). Enhanced 3D-CT clearly visualized hemangiomas and solid tumors from the surrounding tissues. The tumors could easily be observed from any direction and color-coded according to the CT number. Helical 3D-CT was thus confirmed to be useful for the diagnosis and preoperative planning by indicating the details of tumor expansion into surrounding tissues. (author)

Molecular imaging of brown adipose tissue in health and disease

International Nuclear Information System (INIS)

Bauwens, Matthias; Wierts, Roel; Brans, Boudewijn; Royen, Bart van; Backes, Walter; Bucerius, Jan; Mottaghy, Felix

2014-01-01

Brown adipose tissue (BAT) has transformed from an interfering tissue in oncological 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to an independent imaging research field. This review takes the perspective from the imaging methodology on which human BAT research has come to rely on heavily. This review analyses relevant PubMed-indexed publications that discuss molecular imaging methods of BAT. In addition, reported links between BAT and human diseases such as obesity are discussed, and the possibilities for imaging in these fields are highlighted. Radiopharmaceuticals aiming at several different biological mechanisms of BAT are discussed and evaluated. Prospective, dedicated studies allow visualization of BAT function in a high percentage of human subjects. BAT dysfunction has been implicated in obesity, linked with diabetes and associated with cachexia and atherosclerosis. Presently, 18 F-FDG PET/CT is the most useful tool for evaluating therapies aiming at BAT activity. In addition to 18 F-FDG, other radiopharmaceuticals such as 99m Tc-sestamibi, 123 I-metaiodobenzylguanidine (MIBG), 18 F-fluorodopa and 18 F-14(R,S)-[ 18 F]fluoro-6-thia-heptadecanoic acid (FTHA) may have a potential for visualizing other aspects of BAT activity. MRI methods are under continuous development and provide the prospect of functional imaging without ionizing radiation. Molecular imaging of BAT can be used to quantitatively assess different aspects of BAT metabolic activity. (orig.)

Imaging AMS

Energy Technology Data Exchange (ETDEWEB)

Freeman, S.P.H.T. [Univ. of Oxford (United Kingdom)]|[Lawrence Livermore National Lab., CA (United States); Ramsey, C.B.; Hedges, R.E.M. [Univ. of Oxford (United Kingdom)

1993-12-01

The benefits of simultaneous high effective mass resolution and large spectrometer acceptance that accelerator mass spectrometry has afforded the bulk analysis of material samples by secondary ion mass spectrometry may also be applied to imaging SIMS. The authors are exploring imaging AMS with the addition to the Oxford {sup 14}C-AMS system of a scanning secondary ion source. It employs a sub micron probe and a separate Cs flood to further increase the useful ion yield. The source has been accommodated on the system by directly injecting sputtered ions into the accelerator without mass analysis. They are detected with a range of devices including new high-bandwidth detectors. Qualitative mass spectra may be easily generated by varying only the post-accelerator analysis magnet. Selected ion signals may be used for imaging. In developing the instrument for bioscience research the authors are establishing its capability for measuring the lighter elements prevalent in biological tissue. Importantly, the machine can map the distributions of radiocarbon labeled compounds with an efficiency of about 1{per_thousand}. A background due to misidentification of non-{sup 14}C ions as a result of the reduced ion mass filtering is too small to hinder high magnification microscopy.

Comparison of quality of ultrasonographic image of the pancreas: Tissue harmonic image vs. Fundamental image

International Nuclear Information System (INIS)

Seo, Young Lan; Choi, Chul Soon; Kim, Ho Chul; Yoon, Dae Young; Han, Dae Hee; Bae, Sang Hoon

2002-01-01

To compare the quality of ultrasonographic (US) images, tissue harmonic image (THI) versus fundamental image (FI), of the pancreas. During a recent 2 month period, forty one patients with the normal pancreas on US were included. All of them were free of abnormal clinical and laboratory findings suggestive of pancreatic disease, US was performed by an abdominal radiologist with a 2.5-5 MHz convex-array transducer (Sequoia 512: Acuson, Mountain View, Calif.U.S.A.). Comparison of THI and FI of the pancreas was done for the following parameters:conspicuity, intermal architecture, and delineation range. Grading was made by the consensus of two abdominal radiologist witha three-point scale. Statistical analysis was done using Wilcox signed rank sum test. For the evaluation of the US image quality of the pancreas THI showed better conspicuity (p=0.0130), clearer internal architecture (p=0.0029) and superior delineation range (p=0.0191) than those of FI. THI appears to show a superior image quality than FI in evaluation of the pancreas.

Real time analysis of brain tissue by direct combination of ultrasonic surgical aspiration and sonic spray mass spectrometry.

Science.gov (United States)

Schäfer, Karl-Christian; Balog, Júlia; Szaniszló, Tamás; Szalay, Dániel; Mezey, Géza; Dénes, Júlia; Bognár, László; Oertel, Matthias; Takáts, Zoltán

2011-10-15

Direct combination of cavitron ultrasonic surgical aspirator (CUSA) and sonic spray ionization mass spectrometry is presented. A commercially available ultrasonic surgical device was coupled to a Venturi easy ambient sonic-spray ionization (V-EASI) source by directly introducing liquified tissue debris into the Venturi air jet pump. The Venturi air jet pump was found to efficiently nebulize the suspended tissue material for gas phase ion production. The ionization mechanism involving solely pneumatic spraying was associated with that of sonic spray ionization. Positive and negative ionization spectra were obtained from brain and liver samples reflecting the primary application areas of the surgical device. Mass spectra were found to feature predominantly complex lipid-type constituents of tissues in both ion polarity modes. Multiply charged peptide anions were also detected. The influence of instrumental settings was characterized in detail. Venturi pump geometry and flow parameters were found to be critically important in ionization efficiency. Standard solutions of phospholipids and peptides were analyzed in order to test the dynamic range, sensitivity, and suppression effects. The spectra of the intact tissue specimens were found to be highly specific to the histological tissue type. The principal component analysis (PCA) and linear discriminant analysis (LDA) based data analysis method was developed for real-time tissue identification in a surgical environment. The method has been successfully tested on post-mortem and ex vivo human samples including astrocytomas, meningeomas, metastatic brain tumors, and healthy brain tissue. © 2011 American Chemical Society

Tissue harmonic imaging in the evaluation of acute pancreatitis

International Nuclear Information System (INIS)

Garg, Mandeep; Sandhu, Manavjit; Sood, Bimal; Lal, Anupam; Suri, Sudha; Bhasin, Deepak

2004-01-01

To evaluate the role of tissue harmonic imaging (THI) in acute pancreatitis, and to compare its findings with conventional grey-scale sonography and contrast-enhanced computed tomography (CECT) scan, we evaluated 25 patients diagnosed with acute pancreatitis on clinical examination and laboratory findings. Conventional grey-scale ultrasound followed by tissue harmonic sonography was done on the same machine followed by a CECT within 12 h of the ultrasound examination. The present study showed that sonograms obtained with THI were of much better quality than those obtained conventionally, especially for the pancreatic tail. The benefits of harmonic imaging were more apparent in obese patients and in others whose body habitus was unfavourable for sonography. In the assessment of pancreatic image quality, grey-scale imaging had an accuracy of 60, 80 and 28% in relation to the head, body and tail, respectively. In comparison, THI had a far higher accuracy of 80, 92 and 60% in relation to the head, body and tail, respectively, with the superiority being most obvious in the pancreatic tail region. There were no cases in which tissue harmonic sonography provided less information than conventional sonography. However, CECT scan remained the best modality in all patients for the evaluation of acute pancreatitis. It showed superior demonstration of all the morphological changes, ranging from minimal pancreatic oedema to extensive fluid collections, necrosis and the haemorrhage that developed in fulminant severe pancreatitis. Our experience thus suggests that THI cannot replace CT scan as the gold standard in the assessment of acute pancreatitis, as it is poor in evaluating the pancreatic tail, cannot clearly distinguish phlegmon from necrosis, and is inferior to CT in the assessment of the complications of acute pancreatitis Copyright (2004) Blackwell Publishing Asia Pty Ltd

Tissue discrimination in magnetic resonance imaging of the rotator cuff

International Nuclear Information System (INIS)

Meschino, G J; Comas, D S; González, M A; Ballarin, V L; Capiel, C