78 FR 5454 - Findings of Research Misconduct

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-25

... committed research misconduct by falsifying Western blot images as well as quantitative and statistical data... DEPARTMENT OF HEALTH AND HUMAN SERVICES Office of the Secretary Findings of Research Misconduct... Research Integrity (ORI) has taken final action in the following case: Rao M. Adibhatla, Ph.D., University...

Quantitative evaluation of malignant gliomas damage induced by photoactivation of IR700 dye

NASA Astrophysics Data System (ADS)

Sakuma, Morito; Kita, Sayaka; Higuchi, Hideo

2016-01-01

The processes involved in malignant gliomas damage were quantitatively evaluated by microscopy. The near-infrared fluorescent dye IR700 that is conjugated to an anti-CD133 antibody (IR700-CD133) specifically targets malignant gliomas (U87MG) and stem cells (BT142) and is endocytosed into the cells. The gliomas are then photodamaged by the release of reactive oxygen species (ROS) and the heat induced by illumination of IR700 by a red laser, and the motility of the vesicles within these cells is altered as a result of cellular damage. To investigate these changes in motility, we developed a new method that measures fluctuations in the intensity of phase-contrast images obtained from small areas within cells. The intensity fluctuation in U87MG cells gradually decreased as cell damage progressed, whereas the fluctuation in BT142 cells increased. The endocytosed IR700 dye was co-localized in acidic organelles such as endosomes and lysosomes. The pH in U87MG cells, as monitored by a pH indicator, was decreased and then gradually increased by the illumination of IR700, while the pH in BT142 cells increased monotonically. In these experiments, the processes of cell damage were quantitatively evaluated according to the motility of vesicles and changes in pH.

Bone metabolism in oxalosis: a single-center study using new imaging techniques and biomarkers.

PubMed

Bacchetta, Justine; Fargue, Sonia; Boutroy, Stéphanie; Basmaison, Odile; Vilayphiou, Nicolas; Plotton, Ingrid; Guebre-Egziabher, Fitsum; Dohin, Bruno; Kohler, Rémi; Cochat, Pierre

2010-06-01

The deposition of calcium oxalate crystals in the kidney and bone is a hallmark of primary hyperoxaluria type 1 (PH1). We report here an evaluation of the bone status of 12 PH1 children based on bone biomarkers [parathyroid hormone, vitamin D, fibroblast growth factor 23 (FGF23)] and radiological assessments (skeletal age, three-dimensional high-resolution peripheral quantitative computed tomography, HR-pQCT) carried out within the framework of a cross-sectional single-center study. The controls consisted of healthy and children with chronic kidney disease already enrolled in local bone and mineral metabolism studies. The mean age (+ or - standard deviation) age of the patients was 99 (+ or - 63) months. Six children suffered from fracture. Bone maturation was accelerated in five patients, four of whom were <5 years. The combination of new imaging techniques and biomarkers highlighted new and unexplained features of PH1: advanced skeletal age in young PH1 patients, increased FGF23 levels and decreased total volumetric bone mineral density with bone microarchitecture alteration.

Magnetic resonance imaging using chemical exchange saturation transfer

NASA Astrophysics Data System (ADS)

Park, Jaeseok

2012-10-01

Magnetic resonance imaging (MRI) has been widely used as a valuable diagnostic imaging modality that exploits water content and water relaxation properties to provide both structural and functional information with high resolution. Chemical exchange saturation transfer (CEST) in MRI has been recently introduced as a new mechanism of image contrast, wherein exchangeable protons from mobile proteins and peptides are indirectly detected through saturation transfer and are not observable using conventional MRI. It has been demonstrated that CEST MRI can detect important tissue metabolites and byproducts such as glucose, glycogen, and lactate. Additionally, CEST MRI is sensitive to pH or temperature and can calibrate microenvironment dependent on pH or temperature. In this work, we provide an overview on recent trends in CEST MRI, introducing general principles of CEST mechanism, quantitative description of proton transfer process between water pool and exchangeable solute pool in the presence or absence of conventional magnetization transfer effect, and its applications

Nanoparticle-based luminescent probes for intracellular sensing and imaging of pH.

PubMed

Schäferling, Michael

2016-05-01

Fluorescence imaging microscopy is an essential tool in biomedical research. Meanwhile, various fluorescent probes are available for the staining of cells, cell membranes, and organelles. Though, to monitor intracellular processes and dysfunctions, probes that respond to ubiquitous chemical parameters determining the cellular function such as pH, pO2 , and Ca(2+) are required. This review is focused on the progress in the design, fabrication, and application of photoluminescent nanoprobes for sensing and imaging of pH in living cells. The advantages of using nanoprobes carrying fluorescent pH indicators compared to single molecule probes are discussed as well as their limitations due to the mostly lysosomal uptake by cells. Particular attention is paid to ratiometric dual wavelength nanosensors that enable intrinsic referenced measurements. Referencing and proper calibration procedures are basic prerequisites to carry out reliable quantitative pH determinations in complex samples such as living cells. A variety of examples will be presented that highlight the diverseness of nanocarrier materials (polymers, micelles, silica, quantum dots, carbon dots, gold, photon upconversion nanocrystals, or bacteriophages), fluorescent pH indicators for the weak acidic range, and referenced sensing mechanisms, that have been applied intracellularly up to now. WIREs Nanomed Nanobiotechnol 2016, 8:378-413. doi: 10.1002/wnan.1366 For further resources related to this article, please visit the WIREs website. © 2015 Wiley Periodicals, Inc.

Pharmacological MRI (phMRI) of the Human Central Nervous System.

PubMed

Lanfermann, H; Schindler, C; Jordan, J; Krug, N; Raab, P

2015-10-01

Pharmacological magnetic resonance imaging (phMRI) of the central nervous system (CNS) addresses the increasing demands in the biopharma industry for new methods that can accurately predict, as early as possible, whether novel CNS agents will be effective and safe. Imaging of physiological and molecular-level function can provide a more direct measure of a drug mechanism of action, enabling more predictive measures of drug activity. The availability of phMRI of the nervous system within the professional infrastructure of the Clinical Research Center (CRC) Hannover as proof of concept center ensures that advances in basic science progress swiftly into benefits for patients. Advanced standardized MRI techniques including quantitative MRI, kurtosis determination, functional MRI, and spectroscopic imaging of the entire brain are necessary for phMRI. As a result, MR scanners will evolve into high-precision measuring instruments for assessment of desirable and undesirable effects of drugs as the basic precondition for individually tailored therapy. The CRC's Imaging Unit with high-end large-scale equipment will allow the following unique opportunities: for example, identification of MR-based biomarkers to assess the effect of drugs (surrogate parameters), establishment of normal levels and reference ranges for MRI-based biomarkers, evaluation of the most relevant MRI sequences for drug monitoring in outpatient care. Another very important prerequisite for phMRI is the MHH Core Facility as the scientific and operational study unit of the CRC partner Hannover Medical School. This unit is responsible for the study coordination, conduction, complete study logistics, administration, and application of the quality assurance system based on required industry standards.

Quantitative imaging of rhizosphere pH and CO2 dynamics with planar optodes.

PubMed

Blossfeld, Stephan; Schreiber, Christina Maria; Liebsch, Gregor; Kuhn, Arnd Jürgen; Hinsinger, Philippe

2013-07-01

Live imaging methods have become extremely important for the exploration of biological processes. In particular, non-invasive measurement techniques are key to unravelling organism-environment interactions in close-to-natural set-ups, e.g. in the highly heterogeneous and difficult-to-probe environment of plant roots: the rhizosphere. pH and CO2 concentration are the main drivers of rhizosphere processes. Being able to monitor these parameters at high spatio-temporal resolution is of utmost importance for relevant interpretation of the underlying processes, especially in the complex environment of non-sterile plant-soil systems. This study introduces the application of easy-to-use planar optode systems in different set-ups to quantify plant root-soil interactions. pH- and recently developed CO2-sensors were applied to rhizobox systems to investigate roots with different functional traits, highlighting the potential of these tools. Continuous and highly resolved real-time measurements were made of the pH dynamics around Triticum turgidum durum (durum wheat) roots, Cicer arietinum (chickpea) roots and nodules, and CO2 dynamics in the rhizosphere of Viminaria juncea. Wheat root tips acidified slightly, while their root hair zone alkalized their rhizosphere by more than 1 pH unit and the effect of irrigation on soil pH could be visualized as well. Chickpea roots and nodules acidified the surrounding soil during N2 fixation and showed diurnal changes in acidification activity. A growing root of V. juncea exhibited a large zone of influence (mm) on soil CO2 content and therefore on its biogeochemical surrounding, all contributing to the extreme complexity of the root-soil interactions. This technique provides a unique tool for future root research applications and overcomes limitations of previous systems by creating quantitative maps without, for example, interpolation and time delays between single data points.

Towards pH-sensitive imaging of small animals with photon-counting difference diffuse fluorescence tomography

NASA Astrophysics Data System (ADS)

Li, Jiao; Wang, Xin; Yi, Xi; Zhang, Limin; Zhou, Zhongxing; Zhao, Huijuan; Gao, Feng

2012-09-01

The importance of cellular pH has been shown clearly in the study of cell activity, pathological feature, and drug metabolism. Monitoring pH changes of living cells and imaging the regions with abnormal pH-values, in vivo, could provide invaluable physiological and pathological information for the research of the cell biology, pharmacokinetics, diagnostics, and therapeutics of certain diseases such as cancer. Naturally, pH-sensitive fluorescence imaging of bulk tissues has been attracting great attentions from the realm of near infrared diffuse fluorescence tomography (DFT). Herein, the feasibility of quantifying pH-induced fluorescence changes in turbid medium is investigated using a continuous-wave difference-DFT technique that is based on the specifically designed computed tomography-analogous photon counting system and the Born normalized difference image reconstruction scheme. We have validated the methodology using two-dimensional imaging experiments on a small-animal-sized phantom, embedding an inclusion with varying pH-values. The results show that the proposed approach can accurately localize the target with a quantitative resolution to pH-sensitive variation of the fluorescent yield, and might provide a promising alternative method of pH-sensitive fluorescence imaging in addition to the fluorescence-lifetime imaging.

Roughness and pH changes of enamel surface induced by soft drinks in vitro-applications of stylus profilometry, focus variation 3D scanning microscopy and micro pH sensor.

PubMed

Fujii, Mie; Kitasako, Yuichi; Sadr, Alireza; Tagami, Junji

2011-01-01

This study aimed to evaluate enamel surface roughness (Ra) and pH before and after erosion by soft drinks. Enamel was exposed to a soft drink (cola, orange juice or green tea) for 1, 5 or 60 min; Ra was measured using contact-stylus surface profilometry (SSP) and non-contact focus variation 3D microscope (FVM). Surface pH was measured using a micro pH sensor. Data were analyzed at significance level of alpha=0.05. There was a significant correlation in Ra between SSP and FVM. FVM images showed no changes in the surface morphology after various periods of exposure to green tea. Unlike cola and orange juice, exposure to green tea did not significantly affect Ra or pH. A significant correlation was observed between surface pH and Ra change after exposure to the drinks. Optical surface analysis and micro pH sensor may be useful tools for non-damaging, quantitative assessment of soft drinks erosion on enamel.

Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling.

PubMed

Tsionou, Maria Iris; Knapp, Caroline E; Foley, Calum A; Munteanu, Catherine R; Cakebread, Andrew; Imberti, Cinzia; Eykyn, Thomas R; Young, Jennifer D; Paterson, Brett M; Blower, Philip J; Ma, Michelle T

2017-10-24

Gallium-68 ( 68 Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68 Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68 Ga 3+ . Ideally, the chelator will rapidly, quantitatively and stably coordinate 68 Ga 3+ at room temperature, near neutral pH and low chelator concentration, allowing for simple routine radiopharmaceutical formulation. Identification of chelators that fulfil these requirements will facilitate development of kit-based 68 Ga radiopharmaceuticals. Herein the reaction of a range of widely used macrocyclic and acyclic chelators with 68 Ga 3+ is reported. Radiochemical yields have been measured under conditions of varying chelator concentrations, pH (3.5 and 6.5) and temperature (25 and 90 °C). These chelators are: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups at the amine, bis(2-hydroxybenzyl)ethylenediaminediacetic acid (HBED), a tris(hydroxypyridinone) containing three 1,6-dimethyl-3-hydroxypyridin-4-one groups (THP) and the hexadentate tris(hydroxamate) siderophore desferrioxamine-B (DFO). Competition studies have also been undertaken to assess relative complexation efficiencies of each chelator for 68 Ga 3+ under different pH and temperature conditions. Performing radiolabelling reactions at pH 6.5, 25 °C and 5-50 μM chelator concentration resulted in near quantitative radiochemical yields for all chelators, except DOTA. Radiochemical yields either decreased or were not substantially improved when the reactions were undertaken at lower pH or at higher temperature, except in the case of DOTA. THP and DFO were the most effective 68 Ga 3+ chelators at near-neutral pH and 25 °C, rapidly providing near-quantitative radiochemical yields at very low chelator concentrations. NOTP and HBED were only slightly less effective under these conditions. In competition studies with all other chelators, THP demonstrated highest reactivity for 68 Ga 3+ complexation under all conditions. These data point to THP possessing ideal properties for rapid, one-step kit-based syntheses of 68 Ga-biomolecules for molecular PET imaging. LC-MS and 1 H, 13 C{ 1 H} and 71 Ga NMR studies of HBED complexes of Ga 3+ showed that under the analytical conditions employed in this study, multiple HBED-bound Ga complexes exist. X-ray diffraction data indicated that crystals isolated from these solutions contained octahedral [Ga(HBED)(H 2 O)], with HBED coordinated in a pentadentate N 2 O 3 mode, with only one phenolic group coordinated to Ga 3+ , and the remaining coordination site occupied by a water molecule.

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

PubMed Central

Sulis Sato, Sebastian; Artoni, Pietro; Landi, Silvia; Cozzolino, Olga; Parra, Riccardo; Pracucci, Enrico; Trovato, Francesco; Szczurkowska, Joanna; Arosio, Daniele; Beltram, Fabio; Cancedda, Laura; Kaila, Kai

2017-01-01

Intracellular chloride ([Cl−]i) and pH (pHi) are fundamental regulators of neuronal excitability. They exert wide-ranging effects on synaptic signaling and plasticity and on development and disorders of the brain. The ideal technique to elucidate the underlying ionic mechanisms is quantitative and combined two-photon imaging of [Cl−]i and pHi, but this has never been performed at the cellular level in vivo. Here, by using a genetically encoded fluorescent sensor that includes a spectroscopic reference (an element insensitive to Cl− and pH), we show that ratiometric imaging is strongly affected by the optical properties of the brain. We have designed a method that fully corrects for this source of error. Parallel measurements of [Cl−]i and pHi at the single-cell level in the mouse cortex showed the in vivo presence of the widely discussed developmental fall in [Cl−]i and the role of the K-Cl cotransporter KCC2 in this process. Then, we introduce a dynamic two-photon excitation protocol to simultaneously determine the changes of pHi and [Cl−]i in response to hypercapnia and seizure activity. PMID:28973889

Rapid and quantitative chemical exchange saturation transfer (CEST) imaging with magnetic resonance fingerprinting (MRF).

PubMed

Cohen, Ouri; Huang, Shuning; McMahon, Michael T; Rosen, Matthew S; Farrar, Christian T

2018-05-13

To develop a fast magnetic resonance fingerprinting (MRF) method for quantitative chemical exchange saturation transfer (CEST) imaging. We implemented a CEST-MRF method to quantify the chemical exchange rate and volume fraction of the N α -amine protons of L-arginine (L-Arg) phantoms and the amide and semi-solid exchangeable protons of in vivo rat brain tissue. L-Arg phantoms were made with different concentrations (25-100 mM) and pH (pH 4-6). The MRF acquisition schedule varied the saturation power randomly for 30 iterations (phantom: 0-6 μT; in vivo: 0-4 μT) with a total acquisition time of ≤2 min. The signal trajectories were pattern-matched to a large dictionary of signal trajectories simulated using the Bloch-McConnell equations for different combinations of exchange rate, exchangeable proton volume fraction, and water T 1 and T 2 relaxation times. The chemical exchange rates of the N α -amine protons of L-Arg were significantly (P < 0.0001) correlated with the rates measured with the quantitation of exchange using saturation power method. Similarly, the L-Arg concentrations determined using MRF were significantly (P < 0.0001) correlated with the known concentrations. The pH dependence of the exchange rate was well fit (R 2  = 0.9186) by a base catalyzed exchange model. The amide proton exchange rate measured in rat brain cortex (34.8 ± 11.7 Hz) was in good agreement with that measured previously with the water exchange spectroscopy method (28.6 ± 7.4 Hz). The semi-solid proton volume fraction was elevated in white (12.2 ± 1.7%) compared to gray (8.1 ± 1.1%) matter brain regions in agreement with previous magnetization transfer studies. CEST-MRF provides a method for fast, quantitative CEST imaging. © 2018 International Society for Magnetic Resonance in Medicine.

Molecular and Cellular Quantitative Microscopy: theoretical investigations, technological developments and applications to neurobiology

NASA Astrophysics Data System (ADS)

Esposito, Alessandro

2006-05-01

This PhD project aims at the development and evaluation of microscopy techniques for the quantitative detection of molecular interactions and cellular features. The primarily investigated techniques are Fαrster Resonance Energy Transfer imaging and Fluorescence Lifetime Imaging Microscopy. These techniques have the capability to quantitatively probe the biochemical environment of fluorophores. An automated microscope capable of unsupervised operation has been developed that enables the investigation of molecular and cellular properties at high throughput levels and the analysis of cellular heterogeneity. State-of-the-art Förster Resonance Energy Transfer imaging, Fluorescence Lifetime Imaging Microscopy, Confocal Laser Scanning Microscopy and the newly developed tools have been combined with cellular and molecular biology techniques for the investigation of protein-protein interactions, oligomerization and post-translational modifications of α-Synuclein and Tau, two proteins involved in Parkinson’s and Alzheimer’s disease, respectively. The high inter-disciplinarity of this project required the merging of the expertise of both the Molecular Biophysics Group at the Debye Institute - Utrecht University and the Cell Biophysics Group at the European Neuroscience Institute - Gαttingen University. This project was conducted also with the support and the collaboration of the Center for the Molecular Physiology of the Brain (Göttingen), particularly with the groups associated with the Molecular Quantitative Microscopy and Parkinson’s Disease and Aggregopathies areas. This work demonstrates that molecular and cellular quantitative microscopy can be used in combination with high-throughput screening as a powerful tool for the investigation of the molecular mechanisms of complex biological phenomena like those occurring in neurodegenerative diseases.

Improved fiber-optic chemical sensor for penicillin

DOE Office of Scientific and Technical Information (OSTI.GOV)

Healy, B.G.; Walt, D.R.

An optical penicillin biosensor is described, based on the enzyme penicillinase. The sensor is fabricated by selective photodeposition of analyte-sensitive polymer matrices on optical imaging fibers. The penicillin-sensitive matrices are fabricated by immobilizing the enzyme as micrometer-sized particles in a polymer hydrogel with a covalently bound pH indicator. An array of penicillin-sensitive and pH-sensitive matrices are fabricated on the same fiber. This array allows for the simultaneous, independent measurement of pH and penicillin. Independent measurement of the two analytes allows penicillin to be quantitated in the presence of a concurrent pH change. An analysis was conducted of enzyme kinetic parametersmore » in order to model the penicillin response of the sensor at all pH values. This analysis accounts for the varying activity of the immobilized penicillinase at different pH values. The sensor detects penicillin in the range 0.25-10.0 mM in the pH range 6.2-7.5. The sensor was used to quantify penicillin concentration produced during a Penicillium chrysogenum fermentation. 27 refs., 7 figs., 1 tab.« less

A comparison of iopromide and iopamidol, two acidoCEST MRI contrast media that measure tumor extracellular pH.

PubMed

Moon, Brianna F; Jones, Kyle M; Chen, Liu Qi; Liu, Peilu; Randtke, Edward A; Howison, Christine M; Pagel, Mark D

2015-01-01

Acidosis within tumor and kidney tissues has previously been quantitatively measured using a molecular imaging technique known as acidoCEST MRI. The previous studies used iopromide and iopamidol, two iodinated contrast agents that are approved for clinical CT diagnoses and have been repurposed for acidoCEST MRI studies. We aimed to compare the performance of the two agents for measuring pH by optimizing image acquisition conditions, correlating pH with a ratio of CEST effects from an agent, and evaluating the effects of concentration, endogenous T1 relaxation time and temperature on the pH-CEST ratio correlation for each agent. These results showed that the two agents had similar performance characteristics, although iopromide produced a pH measurement with a higher dynamic range while iopamidol produced a more precise pH measurement. We then compared the performance of the two agents to measure in vivo extracellular pH (pHe) within xenograft tumor models of Raji lymphoma and MCF-7 breast cancer. Our results showed that the pHe values measured with each agent were not significantly different. Also, iopromide consistently measured a greater region of the tumor relative to iopamidol in both tumor models. Therefore, an iodinated contrast agent for acidoCEST MRI should be selected based on the measurement properties needed for a specific biomedical study and the pharmacokinetic properties of a specific tumor model. Copyright © 2015 John Wiley & Sons, Ltd.

Flexible pH-Sensing Hydrogel Fibers for Epidermal Applications.

PubMed

Tamayol, Ali; Akbari, Mohsen; Zilberman, Yael; Comotto, Mattia; Lesha, Emal; Serex, Ludovic; Bagherifard, Sara; Chen, Yu; Fu, Guoqing; Ameri, Shideh Kabiri; Ruan, Weitong; Miller, Eric L; Dokmeci, Mehmet R; Sonkusale, Sameer; Khademhosseini, Ali

2016-03-01

Epidermal pH is an indication of the skin's physiological condition. For example, pH of wound can be correlated to angiogenesis, protease activity, bacterial infection, etc. Chronic nonhealing wounds are known to have an elevated alkaline environment, while healing process occurs more readily in an acidic environment. Thus, dermal patches capable of continuous pH measurement can be used as point-of-care systems for monitoring skin disorder and the wound healing process. Here, pH-responsive hydrogel fibers are presented that can be used for long-term monitoring of epidermal wound condition. pH-responsive dyes are loaded into mesoporous microparticles and incorporated into hydrogel fibers using a microfluidic spinning system. The fabricated pH-responsive microfibers are flexible and can create conformal contact with skin. The response of pH-sensitive fibers with different compositions and thicknesses are characterized. The suggested technique is scalable and can be used to fabricate hydrogel-based wound dressings with clinically relevant dimensions. Images of the pH-sensing fibers during real-time pH measurement can be captured with a smart phone camera for convenient readout on-site. Through image processing, a quantitative pH map of the hydrogel fibers and the underlying tissue can be extracted. The developed skin dressing can act as a point-of-care device for monitoring the wound healing process. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Real-time intravital imaging of pH variation associated with osteoclast activity.

PubMed

Maeda, Hiroki; Kowada, Toshiyuki; Kikuta, Junichi; Furuya, Masayuki; Shirazaki, Mai; Mizukami, Shin; Ishii, Masaru; Kikuchi, Kazuya

2016-08-01

Intravital imaging by two-photon excitation microscopy (TPEM) has been widely used to visualize cell functions. However, small molecular probes (SMPs), commonly used for cell imaging, cannot be simply applied to intravital imaging because of the challenge of delivering them into target tissues, as well as their undesirable physicochemical properties for TPEM imaging. Here, we designed and developed a functional SMP with an active-targeting moiety, higher photostability, and a fluorescence switch and then imaged target cell activity by injecting the SMP into living mice. The combination of the rationally designed SMP with a fluorescent protein as a reporter of cell localization enabled quantitation of osteoclast activity and time-lapse imaging of its in vivo function associated with changes in cell deformation and membrane fluctuations. Real-time imaging revealed heterogenic behaviors of osteoclasts in vivo and provided insights into the mechanism of bone resorption.

The Fab1/PIKfyve phosphoinositide phosphate kinase is not necessary to maintain the pH of lysosomes and of the yeast vacuole.

PubMed

Ho, Cheuk Y; Choy, Christopher H; Wattson, Christina A; Johnson, Danielle E; Botelho, Roberto J

2015-04-10

Lysosomes and the yeast vacuole are degradative and acidic organelles. Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a master architect of endolysosome and vacuole identity, is thought to be necessary for vacuolar acidification in yeast. There is also evidence that PtdIns(3,5)P2 may play a role in lysosomal acidification in higher eukaryotes. Nevertheless, these conclusions rely on qualitative assays of lysosome/vacuole pH. For example, quinacrine, an acidotropic fluorescent base, does not accumulate in the vacuoles of fab1Δ yeast. Fab1, along with its mammalian ortholog PIKfyve, is the lipid kinase responsible for synthesizing PtdIns(3,5)P2. In this study, we employed several assays that quantitatively assessed the lysosomal and vacuolar pH in PtdIns(3,5)P2-depleted cells. Using ratiometric imaging, we conclude that lysosomes retain a pH < 5 in PIKfyve-inhibited mammalian cells. In addition, quantitative fluorescence microscopy of vacuole-targeted pHluorin, a pH-sensitive GFP variant, indicates that fab1Δ vacuoles are as acidic as wild-type yeast. Importantly, we also employed fluorimetry of vacuoles loaded with cDCFDA, a pH-sensitive dye, to show that both wild-type and fab1Δ vacuoles have a pH < 5.0. In comparison, the vacuolar pH of the V-ATPase mutant vph1Δ or vph1Δ fab1Δ double mutant was 6.1. Although the steady-state vacuolar pH is not affected by PtdIns(3,5)P2 depletion, it may have a role in stabilizing the vacuolar pH during salt shock. Overall, we propose a model in which PtdIns(3,5)P2 does not govern the steady-state pH of vacuoles or lysosomes. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

The Fab1/PIKfyve Phosphoinositide Phosphate Kinase Is Not Necessary to Maintain the pH of Lysosomes and of the Yeast Vacuole*

PubMed Central

Ho, Cheuk Y.; Choy, Christopher H.; Wattson, Christina A.; Johnson, Danielle E.; Botelho, Roberto J.

2015-01-01

Lysosomes and the yeast vacuole are degradative and acidic organelles. Phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2), a master architect of endolysosome and vacuole identity, is thought to be necessary for vacuolar acidification in yeast. There is also evidence that PtdIns(3,5)P2 may play a role in lysosomal acidification in higher eukaryotes. Nevertheless, these conclusions rely on qualitative assays of lysosome/vacuole pH. For example, quinacrine, an acidotropic fluorescent base, does not accumulate in the vacuoles of fab1Δ yeast. Fab1, along with its mammalian ortholog PIKfyve, is the lipid kinase responsible for synthesizing PtdIns(3,5)P2. In this study, we employed several assays that quantitatively assessed the lysosomal and vacuolar pH in PtdIns(3,5)P2-depleted cells. Using ratiometric imaging, we conclude that lysosomes retain a pH < 5 in PIKfyve-inhibited mammalian cells. In addition, quantitative fluorescence microscopy of vacuole-targeted pHluorin, a pH-sensitive GFP variant, indicates that fab1Δ vacuoles are as acidic as wild-type yeast. Importantly, we also employed fluorimetry of vacuoles loaded with cDCFDA, a pH-sensitive dye, to show that both wild-type and fab1Δ vacuoles have a pH < 5.0. In comparison, the vacuolar pH of the V-ATPase mutant vph1Δ or vph1Δ fab1Δ double mutant was 6.1. Although the steady-state vacuolar pH is not affected by PtdIns(3,5)P2 depletion, it may have a role in stabilizing the vacuolar pH during salt shock. Overall, we propose a model in which PtdIns(3,5)P2 does not govern the steady-state pH of vacuoles or lysosomes. PMID:25713145

Right Ventricular Hemodynamics in Patients with Pulmonary Hypertension

NASA Astrophysics Data System (ADS)

Browning, James; Fenster, Brett; Hertzberg, Jean; Schroeder, Joyce

2012-11-01

Recent advances in cardiac magnetic resonance imaging (CMR) have allowed for characterization of blood flow in the right ventricle (RV), including calculation of vorticity and circulation, and qualitative visual assessment of coherent flow patterns. In this study, we investigate qualitative and quantitative differences in right ventricular hemodynamics between subjects with pulmonary hypertension (PH) and normal controls. Fifteen (15) PH subjects and 10 age-matched controls underwent same day 3D time resolved CMR and echocardiography. Echocardiography was used to determine right ventricular diastolic function as well as pulmonary artery systolic pressure (PASP). Velocity vectors, vorticity vectors, and streamlines in the RV were visualized in Paraview and total RV Early (E) and Atrial (A) wave diastolic vorticity was quantified. Visualizations of blood flow in the RV are presented for PH and normal subjects. The hypothesis that PH subjects exhibit different RV vorticity levels than normals during diastole is tested and the relationship between RV vorticity and PASP is explored. The mechanics of RV vortex formation are discussed within the context of pulmonary arterial pressure and right ventricular diastolic function coincident with PH.

Alterations of the cerebellum and basal ganglia in bipolar disorder mood states detected by quantitative T1ρ mapping.

PubMed

Johnson, Casey P; Christensen, Gary E; Fiedorowicz, Jess G; Mani, Merry; Shaffer, Joseph J; Magnotta, Vincent A; Wemmie, John A

2018-06-01

Quantitative mapping of T1 relaxation in the rotating frame (T1ρ) is a magnetic resonance imaging technique sensitive to pH and other cellular and microstructural factors, and is a potentially valuable tool for identifying brain alterations in bipolar disorder. Recently, this technique identified differences in the cerebellum and cerebral white matter of euthymic patients vs healthy controls that were consistent with reduced pH in these regions, suggesting an underlying metabolic abnormality. The current study built upon this prior work to investigate brain T1ρ differences across euthymic, depressed, and manic mood states of bipolar disorder. Forty participants with bipolar I disorder and 29 healthy control participants matched for age and gender were enrolled. Participants with bipolar disorder were imaged in one or more mood states, yielding 27, 12, and 13 imaging sessions in euthymic, depressed, and manic mood states, respectively. Three-dimensional, whole-brain anatomical images and T1ρ maps were acquired for all participants, enabling voxel-wise evaluation of T1ρ differences between bipolar mood state and healthy control groups. All three mood state groups had increased T1ρ relaxation times in the cerebellum compared to the healthy control group. Additionally, the depressed and manic groups had reduced T1ρ relaxation times in and around the basal ganglia compared to the control and euthymic groups. The study implicated the cerebellum and basal ganglia in the pathophysiology of bipolar disorder and its mood states, the roles of which are relatively unexplored. These findings motivate further investigation of the underlying cause of the abnormalities, and the potential role of altered metabolic activity in these regions. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hyperspectral Imaging for Predicting the Internal Quality of Kiwifruits Based on Variable Selection Algorithms and Chemometric Models.

PubMed

Zhu, Hongyan; Chu, Bingquan; Fan, Yangyang; Tao, Xiaoya; Yin, Wenxin; He, Yong

2017-08-10

We investigated the feasibility and potentiality of determining firmness, soluble solids content (SSC), and pH in kiwifruits using hyperspectral imaging, combined with variable selection methods and calibration models. The images were acquired by a push-broom hyperspectral reflectance imaging system covering two spectral ranges. Weighted regression coefficients (BW), successive projections algorithm (SPA) and genetic algorithm-partial least square (GAPLS) were compared and evaluated for the selection of effective wavelengths. Moreover, multiple linear regression (MLR), partial least squares regression and least squares support vector machine (LS-SVM) were developed to predict quality attributes quantitatively using effective wavelengths. The established models, particularly SPA-MLR, SPA-LS-SVM and GAPLS-LS-SVM, performed well. The SPA-MLR models for firmness (R pre  = 0.9812, RPD = 5.17) and SSC (R pre  = 0.9523, RPD = 3.26) at 380-1023 nm showed excellent performance, whereas GAPLS-LS-SVM was the optimal model at 874-1734 nm for predicting pH (R pre  = 0.9070, RPD = 2.60). Image processing algorithms were developed to transfer the predictive model in every pixel to generate prediction maps that visualize the spatial distribution of firmness and SSC. Hence, the results clearly demonstrated that hyperspectral imaging has the potential as a fast and non-invasive method to predict the quality attributes of kiwifruits.

Label-Free Carbon-Dots-Based Ratiometric Fluorescence pH Nanoprobes for Intracellular pH Sensing.

PubMed

Shangguan, Jingfang; He, Dinggeng; He, Xiaoxiao; Wang, Kemin; Xu, Fengzhou; Liu, Jinquan; Tang, Jinlu; Yang, Xue; Huang, Jin

2016-08-02

Measuring pH in living cells is of great importance for better understanding cellular functions as well as providing pivotal assistance for early diagnosis of diseases. In this work, we report the first use of a novel kind of label-free carbon dots for intracellular ratiometric fluorescence pH sensing. By simple one-pot hydrothermal treatment of citric acid and basic fuchsin, the carbon dots showing dual emission bands at 475 and 545 nm under single-wavelength excitation were synthesized. It is demonstrated that the fluorescence intensities of the as-synthesized carbon dots at the two emissions are pH-sensitive simultaneously. The intensity ratio (I475 nm/I545 nm) is linear against pH values from 5.2 to 8.8 in buffer solution, affording the capability as ratiometric probes for intracellular pH sensing. It also displays that the carbon dots show excellent reversibility and photostability in pH measurements. With this nanoprobe, quantitative fluorescence imaging using the ratio of two emissions (I475 nm/I545 nm) for the detection of intracellular pH were successfully applied in HeLa cells. In contrast to most of the reported nanomaterials-based ratiometric pH sensors which rely on the attachment of additional dyes, these carbon-dots-based ratiometric probes are low in toxicity, easy to synthesize, and free from labels.

TH-A-207B-00: Shear-Wave Imaging and a QIBA US Biomarker Update

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Imaging of tissue elastic properties is a relatively new and powerful approach to one of the oldest and most important diagnostic tools. Imaging of shear wave speed with ultrasound is has been added to most high-end ultrasound systems. Understanding this exciting imaging mode aiding its most effective use in medicine can be a rewarding effort for medical physicists and other medical imaging and treatment professionals. Assuring consistent, quantitative measurements across the many ultrasound systems in a typical imaging department will constitute a major step toward realizing the great potential of this technique and other quantitative imaging. This session will targetmore » these two goals with two presentations. A. Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity - Shigao Chen, Ph.D. Learning objectives-To understand: Introduction: Importance of tissue elasticity measurement Strain vs. shear wave elastography (SWE), beneficial features of SWE The link between shear wave speed and material properties, influence of viscosity Generation of shear waves External vibration (Fibroscan) ultrasound radiation force Point push Supersonic push (Aixplorer) Comb push (GE Logiq E9) Detection of shear waves Motion detection from pulse-echo ultrasound Importance of frame rate for shear wave imaging Plane wave imaging detection How to achieve high effective frame rate using line-by-line scanners Shear wave speed calculation Time to peak Random sample consensus (RANSAC) Cross correlation Sources of bias and variation in SWE Tissue viscosity Transducer compression or internal pressure of organ Reflection of shear waves at boundaries B. Elasticity Imaging System Biomarker Qualification and User Testing of Systems – Brian Garra, M.D. Learning objectives-To understand: Goals Review the need for quantitative medical imaging Provide examples of quantitative imaging biomarkers Acquaint the participant with the purpose of the RSNA Quantitative Imaging Biomarker Alliance and the need for such an organization Review the QIBA process for creating a quantitative biomarker Summarize steps needed to verify adherence of site, operators, and imaging systems to a QIBA profile Underlying Premise and Assumptions Objective, quantifiable results are needed to enhance the value of diagnostic imaging in clinical practice Reasons for quantification Evidence based medicine requires objective, not subjective observer data Computerized decision support tools (eg CAD) generally require quantitative input. Quantitative, reproducible measures are more easily used to develop personalized molecular medical diagnostic and treatment systems What is quantitative imaging? Definition from Imaging Metrology Workshop The Quantitative Imaging Biomarker Alliance Formation 2008 Mission Structure Example Imaging Biomarkers Being Explored Biomarker Selection Groundwork Draft Protocol for imaging and data evaluation QIBA Profile Drafting Equipment and Site Validation Technical Clinical Site and Equipment QA and Compliance Checking Ultrasound Elasticity Estimation Biomarker US Elasticity Estimation Background Current Status and Problems Biomarker Selection-process and outcome US SWS for Liver Fibrosis Biomarker Work Groundwork Literature search and analysis results Phase I phantom testing-Elastic phantoms Phase II phantom testing-Viscoelastic phantoms Digital Simulated Data Protocol and Profile Drafting Protocol: based on UPICT and existing literature and standards bodies protocols Profile-Current claims, Manufacturer specific appendices What comes after the profile Profile Validation Technical validation Clinical validation QA and Compliance Possible approaches Site Operator testing Site protocol re-evaluation Imaging system Manufacturer testing and attestation User acceptance testing and periodic QA Phantom Tests Digital Phantom Based Testing Standard QA Testing Remediation Schemes Profile Evolution Towards additional applications Towards higher accuracy and precision Supported in part by NIH contract HHSN268201300071C from NIBIB. Collaboration with GE Global Research, no personal support.; S. Chen, Some technologies described in this presentation have been licensed. Mayo Clinic and Dr. Chen have financial interests these technologies.« less

TH-A-207B-01: Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, S.

Imaging of tissue elastic properties is a relatively new and powerful approach to one of the oldest and most important diagnostic tools. Imaging of shear wave speed with ultrasound is has been added to most high-end ultrasound systems. Understanding this exciting imaging mode aiding its most effective use in medicine can be a rewarding effort for medical physicists and other medical imaging and treatment professionals. Assuring consistent, quantitative measurements across the many ultrasound systems in a typical imaging department will constitute a major step toward realizing the great potential of this technique and other quantitative imaging. This session will targetmore » these two goals with two presentations. A. Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity - Shigao Chen, Ph.D. Learning objectives-To understand: Introduction: Importance of tissue elasticity measurement Strain vs. shear wave elastography (SWE), beneficial features of SWE The link between shear wave speed and material properties, influence of viscosity Generation of shear waves External vibration (Fibroscan) ultrasound radiation force Point push Supersonic push (Aixplorer) Comb push (GE Logiq E9) Detection of shear waves Motion detection from pulse-echo ultrasound Importance of frame rate for shear wave imaging Plane wave imaging detection How to achieve high effective frame rate using line-by-line scanners Shear wave speed calculation Time to peak Random sample consensus (RANSAC) Cross correlation Sources of bias and variation in SWE Tissue viscosity Transducer compression or internal pressure of organ Reflection of shear waves at boundaries B. Elasticity Imaging System Biomarker Qualification and User Testing of Systems – Brian Garra, M.D. Learning objectives-To understand: Goals Review the need for quantitative medical imaging Provide examples of quantitative imaging biomarkers Acquaint the participant with the purpose of the RSNA Quantitative Imaging Biomarker Alliance and the need for such an organization Review the QIBA process for creating a quantitative biomarker Summarize steps needed to verify adherence of site, operators, and imaging systems to a QIBA profile Underlying Premise and Assumptions Objective, quantifiable results are needed to enhance the value of diagnostic imaging in clinical practice Reasons for quantification Evidence based medicine requires objective, not subjective observer data Computerized decision support tools (eg CAD) generally require quantitative input. Quantitative, reproducible measures are more easily used to develop personalized molecular medical diagnostic and treatment systems What is quantitative imaging? Definition from Imaging Metrology Workshop The Quantitative Imaging Biomarker Alliance Formation 2008 Mission Structure Example Imaging Biomarkers Being Explored Biomarker Selection Groundwork Draft Protocol for imaging and data evaluation QIBA Profile Drafting Equipment and Site Validation Technical Clinical Site and Equipment QA and Compliance Checking Ultrasound Elasticity Estimation Biomarker US Elasticity Estimation Background Current Status and Problems Biomarker Selection-process and outcome US SWS for Liver Fibrosis Biomarker Work Groundwork Literature search and analysis results Phase I phantom testing-Elastic phantoms Phase II phantom testing-Viscoelastic phantoms Digital Simulated Data Protocol and Profile Drafting Protocol: based on UPICT and existing literature and standards bodies protocols Profile-Current claims, Manufacturer specific appendices What comes after the profile Profile Validation Technical validation Clinical validation QA and Compliance Possible approaches Site Operator testing Site protocol re-evaluation Imaging system Manufacturer testing and attestation User acceptance testing and periodic QA Phantom Tests Digital Phantom Based Testing Standard QA Testing Remediation Schemes Profile Evolution Towards additional applications Towards higher accuracy and precision Supported in part by NIH contract HHSN268201300071C from NIBIB. Collaboration with GE Global Research, no personal support.; S. Chen, Some technologies described in this presentation have been licensed. Mayo Clinic and Dr. Chen have financial interests these technologies.« less

TH-A-207B-02: QIBA Ultrasound Elasticity Imaging System Biomarker Qualification and User Testing of Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garra, B.

Imaging of tissue elastic properties is a relatively new and powerful approach to one of the oldest and most important diagnostic tools. Imaging of shear wave speed with ultrasound is has been added to most high-end ultrasound systems. Understanding this exciting imaging mode aiding its most effective use in medicine can be a rewarding effort for medical physicists and other medical imaging and treatment professionals. Assuring consistent, quantitative measurements across the many ultrasound systems in a typical imaging department will constitute a major step toward realizing the great potential of this technique and other quantitative imaging. This session will targetmore » these two goals with two presentations. A. Basics and Current Implementations of Ultrasound Imaging of Shear Wave Speed and Elasticity - Shigao Chen, Ph.D. Learning objectives-To understand: Introduction: Importance of tissue elasticity measurement Strain vs. shear wave elastography (SWE), beneficial features of SWE The link between shear wave speed and material properties, influence of viscosity Generation of shear waves External vibration (Fibroscan) ultrasound radiation force Point push Supersonic push (Aixplorer) Comb push (GE Logiq E9) Detection of shear waves Motion detection from pulse-echo ultrasound Importance of frame rate for shear wave imaging Plane wave imaging detection How to achieve high effective frame rate using line-by-line scanners Shear wave speed calculation Time to peak Random sample consensus (RANSAC) Cross correlation Sources of bias and variation in SWE Tissue viscosity Transducer compression or internal pressure of organ Reflection of shear waves at boundaries B. Elasticity Imaging System Biomarker Qualification and User Testing of Systems – Brian Garra, M.D. Learning objectives-To understand: Goals Review the need for quantitative medical imaging Provide examples of quantitative imaging biomarkers Acquaint the participant with the purpose of the RSNA Quantitative Imaging Biomarker Alliance and the need for such an organization Review the QIBA process for creating a quantitative biomarker Summarize steps needed to verify adherence of site, operators, and imaging systems to a QIBA profile Underlying Premise and Assumptions Objective, quantifiable results are needed to enhance the value of diagnostic imaging in clinical practice Reasons for quantification Evidence based medicine requires objective, not subjective observer data Computerized decision support tools (eg CAD) generally require quantitative input. Quantitative, reproducible measures are more easily used to develop personalized molecular medical diagnostic and treatment systems What is quantitative imaging? Definition from Imaging Metrology Workshop The Quantitative Imaging Biomarker Alliance Formation 2008 Mission Structure Example Imaging Biomarkers Being Explored Biomarker Selection Groundwork Draft Protocol for imaging and data evaluation QIBA Profile Drafting Equipment and Site Validation Technical Clinical Site and Equipment QA and Compliance Checking Ultrasound Elasticity Estimation Biomarker US Elasticity Estimation Background Current Status and Problems Biomarker Selection-process and outcome US SWS for Liver Fibrosis Biomarker Work Groundwork Literature search and analysis results Phase I phantom testing-Elastic phantoms Phase II phantom testing-Viscoelastic phantoms Digital Simulated Data Protocol and Profile Drafting Protocol: based on UPICT and existing literature and standards bodies protocols Profile-Current claims, Manufacturer specific appendices What comes after the profile Profile Validation Technical validation Clinical validation QA and Compliance Possible approaches Site Operator testing Site protocol re-evaluation Imaging system Manufacturer testing and attestation User acceptance testing and periodic QA Phantom Tests Digital Phantom Based Testing Standard QA Testing Remediation Schemes Profile Evolution Towards additional applications Towards higher accuracy and precision Supported in part by NIH contract HHSN268201300071C from NIBIB. Collaboration with GE Global Research, no personal support.; S. Chen, Some technologies described in this presentation have been licensed. Mayo Clinic and Dr. Chen have financial interests these technologies.« less

Quantitative skeletal maturation estimation using cone-beam computed tomography-generated cervical vertebral images: a pilot study in 5- to 18-year-old Japanese children.

PubMed

Byun, Bo-Ram; Kim, Yong-Il; Yamaguchi, Tetsutaro; Maki, Koutaro; Ko, Ching-Chang; Hwang, Dea-Seok; Park, Soo-Byung; Son, Woo-Sung

2015-11-01

The purpose of this study was to establish multivariable regression models for the estimation of skeletal maturation status in Japanese boys and girls using the cone-beam computed tomography (CBCT)-based cervical vertebral maturation (CVM) assessment method and hand-wrist radiography. The analyzed sample consisted of hand-wrist radiographs and CBCT images from 47 boys and 57 girls. To quantitatively evaluate the correlation between the skeletal maturation status and measurement ratios, a CBCT-based CVM assessment method was applied to the second, third, and fourth cervical vertebrae. Pearson's correlation coefficient analysis and multivariable regression analysis were used to determine the ratios for each of the cervical vertebrae (p < 0.05). Four characteristic parameters ((OH2 + PH2)/W2, (OH2 + AH2)/W2, D2, AH3/W3), as independent variables, were used to build the multivariable regression models: for the Japanese boys, the skeletal maturation status according to the CBCT-based quantitative cervical vertebral maturation (QCVM) assessment was 5.90 + 99.11 × AH3/W3 - 14.88 × (OH2 + AH2)/W2 + 13.24 × D2; for the Japanese girls, it was 41.39 + 59.52 × AH3/W3 - 15.88 × (OH2 + PH2)/W2 + 10.93 × D2. The CBCT-generated CVM images proved very useful to the definition of the cervical vertebral body and the odontoid process. The newly developed CBCT-based QCVM assessment method showed a high correlation between the derived ratios from the second cervical vertebral body and odontoid process. There are high correlations between the skeletal maturation status and the ratios of the second cervical vertebra based on the remnant of dentocentral synchondrosis.

A tunable ratiometric pH sensor based on carbon nanodots for the quantitative measurement of the intracellular pH of whole cells.

PubMed

Shi, Wen; Li, Xiaohua; Ma, Huimin

2012-06-25

The whole picture: Carbon nanodots labeled with two fluorescent dyes have been developed as a tunable ratiometric pH sensor to measure intracellular pH. The nanosensor shows good biocompatibility and cellular dispersibility. Quantitative determinations on intact HeLa cells and pH fluctuations associated with oxidative stress were performed. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantifying heterogeneity in human tumours using MRI and PET.

PubMed

Asselin, Marie-Claude; O'Connor, James P B; Boellaard, Ronald; Thacker, Neil A; Jackson, Alan

2012-03-01

Most tumours, even those of the same histological type and grade, demonstrate considerable biological heterogeneity. Variations in genomic subtype, growth factor expression and local microenvironmental factors can result in regional variations within individual tumours. For example, localised variations in tumour cell proliferation, cell death, metabolic activity and vascular structure will be accompanied by variations in oxygenation status, pH and drug delivery that may directly affect therapeutic response. Documenting and quantifying regional heterogeneity within the tumour requires histological or imaging techniques. There is increasing evidence that quantitative imaging biomarkers can be used in vivo to provide important, reproducible and repeatable estimates of tumoural heterogeneity. In this article we review the imaging methods available to provide appropriate biomarkers of tumour structure and function. We also discuss the significant technical issues involved in the quantitative estimation of heterogeneity and the range of descriptive metrics that can be derived. Finally, we have reviewed the existing clinical evidence that heterogeneity metrics provide additional useful information in drug discovery and development and in clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

Pretreatment Blood Brain Barrier Damage and Post Treatment Intracranial Hemorrhage in Patients Receiving IV tPA

PubMed Central

Leigh, Richard; Jen, Shyian S.; Hillis, Argye E.; Krakauer, John W.; Barker, Peter B.

2014-01-01

Background and Purpose Early blood brain barrier (BBB) damage after acute ischemic stroke (AIS) has previously been qualitatively linked to subsequent intracranial hemorrhage (ICH). In this quantitative study, it was investigated whether the amount of BBB damage evident on pre-tPA MRI scans was related to the degree of post-tPA ICH in patients with AIS. Methods Analysis was performed on a database of patients with AIS provided by the STIR and VISTA Imaging Investigators. Patients with perfusion-weighted imaging (PWI) lesions >10mL and negative gradient-recalled echo (GRE) imaging prior to IV tPA were included. Post processing of the PWI source images was performed to estimate changes in BBB permeability within the perfusion deficit relative to the unaffected hemisphere. Follow-up GRE images were reviewed for evidence of ICH and divided into three groups according to ECASS criteria: no hemorrhage (NH), hemorrhagic infarction (HI), and parenchymal hematoma (PH). Results 75 patients from the database met the inclusion criteria, 28 of whom experienced ICH, of which 19 were classified as HI, and nine were classified as PH. The mean permeability (±standard deviations), expressed as an index of contrast leakage, was 17.0%±8.8 in the NH group, 19.4%±4.0 in the HI group, and 24.6%±4.5 in the PH group. Permeability was significantly correlated with ICH grade in univariate (p=0.007) and multivariate (p=0.008) linear regression modeling. Conclusions A PWI-derived index of BBB damage measured prior to IV tPA is associated with the severity of ICH after treatment in patients with AIS. PMID:24876245

Transportable and vibration-free full-field low-coherent quantitative phase microscope

NASA Astrophysics Data System (ADS)

Yamauchi, Toyohiko; Yamada, Hidenao; Goto, Kentaro; Matsui, Hisayuki; Yasuhiko, Osamu; Ueda, Yukio

2018-02-01

We developed a transportable Linnik-type full-field low-coherent quantitative phase microscope that is able to compensate for optical path length (OPL) disturbance due to environmental mechanical noises. Though two-beam interferometers such as Linnik ones suffer from unstable OPL difference, we overcame this problem with a mechanical feedback system based on digital signal-processing that controls the OPL difference in sub-nanometer resolution precisely with a feedback bandwidth of 4 kHz. The developed setup has a footprint of 200 mm by 200 mm, a height of 500 mm, and a weight of 4.5 kilograms. In the transmission imaging mode, cells were cultured on a reflection-enhanced glass-bottom dish, and we obtained interference images sequentially while performing stepwise quarter-wavelength phase-shifting. Real-time image processing, including retrieval of the unwrapped phase from interference images and its background correction, along with the acquisition of interference images, was performed on a laptop computer. Emulation of the phase contrast (PhC) images and the differential interference contrast (DIC) images was also performed in real time. Moreover, our setup was applied for full-field cell membrane imaging in the reflection mode, where the cells were cultured on an anti-reflection (AR)-coated glass-bottom dish. The phase and intensity of the light reflected by the membrane revealed the outer shape of the cells independent of the refractive index. In this paper, we show imaging results on cultured cells in both transmission and reflection modes.

Doctoral training in statistics, measurement, and methodology in psychology: replication and extension of Aiken, West, Sechrest, and Reno's (1990) survey of PhD programs in North America.

PubMed

Aiken, Leona S; West, Stephen G; Millsap, Roger E

2008-01-01

In a survey of all PhD programs in psychology in the United States and Canada, the authors documented the quantitative methodology curriculum (statistics, measurement, and research design) to examine the extent to which innovations in quantitative methodology have diffused into the training of PhDs in psychology. In all, 201 psychology PhD programs (86%) participated. This survey replicated and extended a previous survey (L. S. Aiken, S. G. West, L. B. Sechrest, & R. R. Reno, 1990), permitting examination of curriculum development. Most training supported laboratory and not field research. The median of 1.6 years of training in statistics and measurement was mainly devoted to the modally 1-year introductory statistics course, leaving little room for advanced study. Curricular enhancements were noted in statistics and to a minor degree in measurement. Additional coverage of both fundamental and innovative quantitative methodology is needed. The research design curriculum has largely stagnated, a cause for great concern. Elite programs showed no overall advantage in quantitative training. Forces that support curricular innovation are characterized. Human capital challenges to quantitative training, including recruiting and supporting young quantitative faculty, are discussed. Steps must be taken to bring innovations in quantitative methodology into the curriculum of PhD programs in psychology. PsycINFO Database Record (c) 2008 APA, all rights reserved.

Time course of pH change in plant epidermis using microscopic pH imaging system

NASA Astrophysics Data System (ADS)

Dan, Risako; Shimizu, Megumi; Kazama, Haruko; Sakaue, Hirotaka

2010-11-01

We established a microscopic pH imaging system to track the time course of pH change in plant epidermis in vivo. In the previous research, we have found out that anthocyanin containing cells have higher pH. However, it was not clear whether the anthocyanin increased the pH or anthocyanin was synthesized result from the higher pH. Therefore, we further investigated the relationship between anthocyanin and pH change. To track the time course of pH change in plant epidermis, we established a system using luminescent imaging technique. We used HPTS (8-Hydroxypyrene-1,3,6-Trisulfonate) as pH indicator and applied excitation ratio imaging method. Luminescent image was converted to a pH distribution by obtained in vitro calibration using known pH solution. Cellular level observation was enabled by merging microscopic color picture of the same region to the pH change image. The established system was applied to epidermal cells of red-tip leaf lettuce, Lactuca Sativa L. and the time course was tracked in the growth process. We would discuss about the relationship between anthocyanin and pH change in plant epidermis.

Doctoral Training in Statistics, Measurement, and Methodology in Psychology: Replication and Extension of Aiken, West, Sechrest, and Reno's (1990) Survey of PhD Programs in North America

ERIC Educational Resources Information Center

Aiken, Leona S.; West, Stephen G.; Millsap, Roger E.

2008-01-01

In a survey of all PhD programs in psychology in the United States and Canada, the authors documented the quantitative methodology curriculum (statistics, measurement, and research design) to examine the extent to which innovations in quantitative methodology have diffused into the training of PhDs in psychology. In all, 201 psychology PhD…

pH Mapping on Tooth Surfaces for Quantitative Caries Diagnosis Using Micro Ir/IrOx pH Sensor.

PubMed

Ratanaporncharoen, Chindanai; Tabata, Miyuki; Kitasako, Yuichi; Ikeda, Masaomi; Goda, Tatsuro; Matsumoto, Akira; Tagami, Junji; Miyahara, Yuji

2018-04-03

A quantitative diagnostic method for dental caries would improve oral health, which directly affects the quality of life. Here we describe the preparation and application of Ir/IrOx pH sensors, which are used to measure the surface pH of dental caries. The pH level is used as an indicator to distinguish between active and arrested caries. After a dentist visually inspected and defined 18 extracted dentinal caries at various positions as active or arrested caries, the surface pH values of sound and caries areas were directly measured with an Ir/IrOx pH sensor with a diameter of 300 μm as a dental explorer. The average pH values of the sound root, the arrested caries, and active caries were 6.85, 6.07, and 5.30, respectively. The pH obtained with an Ir/IrOx sensor was highly correlated with the inspection results by the dentist, indicating that the types of caries were successfully categorized. This caries testing technique using a micro Ir/IrOx pH sensor provides an accurate quantitative caries evaluation and has potential in clinical diagnosis.

EVALUATION OF STACHYBOTRYS CHARTARUM IN THE HOUSE OF AN INFANT WITH PULMONARY HEMORRHAGE: QUANTITATIVE ASSESSMENT BEFORE, DURING, AND AFTER REMEDIATION

EPA Science Inventory

Stachybotrys chartarum is an indoor mold that has been associated with pulmonary hemorrhage (PH) cases in the Cleveland, Ohio area. This study applied two new quantitative measurements to air samples from a home where an infant developed PH. Quantitative polymerase chain reacti...

Extracellular pH regulation in microdomains of colonic crypts: effects of short-chain fatty acids.

PubMed Central

Chu, S; Montrose, M H

1995-01-01

It has been suggested that transepithelial gradients of short-chain fatty acids (SCFAs; the major anions in the colonic lumen) generate pH gradients across the colonic epithelium. Quantitative confocal microscopy was used to study extracellular pH in mouse distal colon with intact epithelial architecture, by superfusing tissue with carboxy SNARF-1 (a pH-sensitive fluorescent dye). Results demonstrate extracellular pH regulation in two separate microdomains surrounding colonic crypts: the crypt lumen and the subepithelial tissue adjacent to crypt colonocytes. Apical superfusion with (i) a poorly metabolized SCFA (isobutyrate), (ii) an avidly metabolized SCFA (n-butyrate), or (iii) a physiologic mixture of acetate/propionate/n-butyrate produced similar results: alkalinization of the crypt lumen and acidification of subepithelial tissue. Effects were (i) dependent on the presence and orientation of a transepithelial SCFA gradient, (ii) not observed with gluconate substitution, and (iii) required activation of sustained vectorial acid/base transport by SCFAs. Results suggest that the crypt lumen functions as a pH microdomain due to slow mixing with bulk superfusates and that crypts contribute significant buffering capacity to the lumen. In conclusion, physiologic SCFA gradients cause polarized extracellular pH regulation because epithelial architecture and vectorial transport synergize to establish regulated microenvironments. Images Fig. 1 Fig. 3 PMID:7724557

Accurate Quantitative Sensing of Intracellular pH based on Self-ratiometric Upconversion Luminescent Nanoprobe

NASA Astrophysics Data System (ADS)

Li, Cuixia; Zuo, Jing; Zhang, Li; Chang, Yulei; Zhang, Youlin; Tu, Langping; Liu, Xiaomin; Xue, Bin; Li, Qiqing; Zhao, Huiying; Zhang, Hong; Kong, Xianggui

2016-12-01

Accurate quantitation of intracellular pH (pHi) is of great importance in revealing the cellular activities and early warning of diseases. A series of fluorescence-based nano-bioprobes composed of different nanoparticles or/and dye pairs have already been developed for pHi sensing. Till now, biological auto-fluorescence background upon UV-Vis excitation and severe photo-bleaching of dyes are the two main factors impeding the accurate quantitative detection of pHi. Herein, we have developed a self-ratiometric luminescence nanoprobe based on förster resonant energy transfer (FRET) for probing pHi, in which pH-sensitive fluorescein isothiocyanate (FITC) and upconversion nanoparticles (UCNPs) were served as energy acceptor and donor, respectively. Under 980 nm excitation, upconversion emission bands at 475 nm and 645 nm of NaYF4:Yb3+, Tm3+ UCNPs were used as pHi response and self-ratiometric reference signal, respectively. This direct quantitative sensing approach has circumvented the traditional software-based subsequent processing of images which may lead to relatively large uncertainty of the results. Due to efficient FRET and fluorescence background free, a highly-sensitive and accurate sensing has been achieved, featured by 3.56 per unit change in pHi value 3.0-7.0 with deviation less than 0.43. This approach shall facilitate the researches in pHi related areas and development of the intracellular drug delivery systems.

Elasticity imaging of speckle-free tissue regions with moving acoustic radiation force and phase-sensitive optical coherence tomography

NASA Astrophysics Data System (ADS)

Hsieh, Bao-Yu; Song, Shaozhen; Nguyen, Thu-Mai; Yoon, Soon Joon; Shen, Tueng; Wang, Ruikang; O'Donnell, Matthew

2016-03-01

Phase-sensitive optical coherence tomography (PhS-OCT) can be utilized for quantitative shear-wave elastography using speckle tracking. However, current approaches cannot directly reconstruct elastic properties in speckle-less or speckle-free regions, for example within the crystalline lens in ophthalmology. Investigating the elasticity of the crystalline lens could improve understanding and help manage presbyopia-related pathologies that change biomechanical properties. We propose to reconstruct the elastic properties in speckle-less regions by sequentially launching shear waves with moving acoustic radiation force (mARF), and then detecting the displacement at a specific speckle-generating position, or limited set of positions, with PhS-OCT. A linear ultrasound array (with a center frequency of 5 MHz) interfaced with a programmable imaging system was designed to launch shear waves by mARF. Acoustic sources were electronically translated to launch shear waves at laterally shifted positions, where displacements were detected by speckle tracking images produced by PhS-OCT operating in M-B mode with a 125-kHz A-line rate. Local displacements were calculated and stitched together sequentially based on the distance between the acoustic source and the detection beam. Shear wave speed, and the associated elasticity map, were then reconstructed based on a time-of-flight algorithm. In this study, moving-source shear wave elasticity imaging (SWEI) can highlight a stiff inclusion within an otherwise homogeneous phantom but with a CNR increased by 3.15 dB compared to a similar image reconstructed with moving-detector SWEI. Partial speckle-free phantoms were also investigated to demonstrate that the moving-source sequence could reconstruct the elastic properties of speckle-free regions. Results show that harder inclusions within the speckle-free region can be detected, suggesting that this imaging method may be able to detect the elastic properties of the crystalline lens.

A nanobuffer reporter library for fine-scale imaging and perturbation of endocytic organelles

PubMed Central

Wang, Chensu; Wang, Yiguang; Li, Yang; Bodemann, Brian; Zhao, Tian; Ma, Xinpeng; Huang, Gang; Hu, Zeping; DeBerardinis, Ralph J.; White, Michael A.; Gao, Jinming

2015-01-01

Endosomes, lysosomes and related catabolic organelles are a dynamic continuum of vacuolar structures that impact a number of cell physiological processes such as protein/lipid metabolism, nutrient sensing and cell survival. Here we develop a library of ultra-pH-sensitive fluorescent nanoparticles with chemical properties that allow fine-scale, multiplexed, spatio-temporal perturbation and quantification of catabolic organelle maturation at single organelle resolution to support quantitative investigation of these processes in living cells. Deployment in cells allows quantification of the proton accumulation rate in endosomes; illumination of previously unrecognized regulatory mechanisms coupling pH transitions to endosomal coat protein exchange; discovery of distinct pH thresholds required for mTORC1 activation by free amino acids versus proteins; broad-scale characterization of the consequence of endosomal pH transitions on cellular metabolomic profiles; and functionalization of a context-specific metabolic vulnerability in lung cancer cells. Together, these biological applications indicate the robustness and adaptability of this nanotechnology-enabled ‘detection and perturbation' strategy. PMID:26437053

Exploring the quantitative relationship between metabolism and enzymatic phenotype by physiological modeling of glucose metabolism and lactate oxidation in solid tumors

NASA Astrophysics Data System (ADS)

Wang, Qian; Vaupel, Peter; Ziegler, Sibylle I.; Shi, Kuangyu

2015-03-01

Molecular imaging using PET or hyperpolarized MRI can characterize tumor phenotypes by assessing the related metabolism of certain substrates. However, the interpretation of the substrate turnover in terms of a pathophysiological understanding is not straightforward and only semiquantitative. The metabolism of imaging probes is influenced by a number of factors, such as the microvascular structure or the expression of key enzymes. This study aims to use computational simulation to investigate the relationship between the metabolism behind molecular imaging and the underlying tumor phenotype. The study focused on the pathways of glucose metabolism and lactate oxidation in order to establish the quantitative relationship between the expression of several transporters (GLUT, MCT1 and MCT4), expression of the enzyme hexokinase (HK), microvasculature and the metabolism of glucose or lactate and the extracellular pH distribution. A computational model for a 2D tumor tissue phantom was constructed and the spatio-temporal evolution of related species (e.g. oxygen, glucose, lactate, protons, bicarbonate ions) was estimated by solving reaction-diffusion equations. The proposed model was tested by the verification of the simulation results using in vivo and in vitro literature data. The influences of different expression levels of GLUT, MCT1, MCT4, HK and microvessel distribution on substrate concentrations were analyzed. The major results are consistent with experimental data (e.g. GLUT is more influential to glycolytic flux than HK; extracellular pH is not correlated with MCT expressions) and provide theoretical interpretation of the co-influence of multiple factors of the tumor microenvironment. This computational simulation may assist the generation of hypotheses to bridge the discrepancy between tumor metabolism and the functions of transporters and enzymes. It has the potential to accelerate the development of multi-modal imaging strategies for assessment of tumor phenotypes.

Determination of bromhexine in plasma by reversed-phase liquid chromatography. Interference of lipoproteins on extraction.

PubMed

Johansson, M; Lenngren, S

1988-11-18

Extraction of the hydrophobic tertiary amine bromhexine from plasma using cyclohexane-heptafluorobutanol (99.5:0.5, v/v) was studied at different pH values. The extraction yield from buffer solutions was quantitative at pH greater than 4.1, but from plasma the extraction yield decreased with increasing pH. Furthermore, at pH 8.4 the extraction yield varied greatly (56-99%) in different human plasma. The addition of lipoproteins to phosphate buffer, at pH 8.1, decreased the extraction yields considerably. Quantitative extraction from plasma was obtained by using a very long extraction time at pH 8.4 or by decreasing the pH to 5.4. The chromatographic system consisted of a reversed-phase column (Nucleosil C18, 5 microns) with an acidic mobile phase (methanol-phosphate buffer, pH 2) containing an aliphatic tertiary amine. UV detection at 308 or 254 nm was used. The limit of quantitation was 5 ng/ml using 3.00 ml of plasma and detection at 254 nm. The intra-assay precision for bromhexine was better than 3.6% at 5 ng/ml.

The Effect of Recombinant Human MG53 Protein on Tourniquet-induced Ischemia Reperfusion Injury in Rat Muscle

DTIC Science & Technology

2014-06-01

blind to the treatment , and the prevalence of damaged fibers was quantitated from 10 10x images from each muscle . Approximately 800 fibers were counted...therapeutic cell membrane repair in treatment of muscular dystrophy . Sci Transl Med. 2012; 4(139):139ra185. 11. Weisleder N, Lin P, Zhao X, Orange M, Zhu H...The effect of recombinant human MG53 protein on tourniquet- induced ischemia reperfusion injury in rat muscle Benjamin T. Corona, Ph.D.1, Koyal Garg

Mechanical properties of amyloid-like fibrils defined by secondary structures

NASA Astrophysics Data System (ADS)

Bortolini, C.; Jones, N. C.; Hoffmann, S. V.; Wang, C.; Besenbacher, F.; Dong, M.

2015-04-01

Amyloid and amyloid-like fibrils represent a generic class of highly ordered nanostructures that are implicated in some of the most fatal neurodegenerative diseases. On the other hand, amyloids, by possessing outstanding mechanical robustness, have also been successfully employed as functional biomaterials. For these reasons, physical and chemical factors driving fibril self-assembly and morphology are extensively studied - among these parameters, the secondary structures and the pH have been revealed to be crucial, since a variation in pH changes the fibril morphology and net chirality during protein aggregation. It is important to quantify the mechanical properties of these fibrils in order to help the design of effective strategies for treating diseases related to the presence of amyloid fibrils. In this work, we show that by changing pH the mechanical properties of amyloid-like fibrils vary as well. In particular, we reveal that these mechanical properties are strongly related to the content of secondary structures. We analysed and estimated the Young's modulus (E) by comparing the persistence length (Lp) - measured from the observation of TEM images by using statistical mechanics arguments - with the mechanical information provided by peak force quantitative nanomechanical property mapping (PF-QNM). The secondary structure content and the chirality are investigated by means of synchrotron radiation circular dichroism (SR-CD). Results arising from this study could be fruitfully used as a protocol to investigate other medical or engineering relevant peptide fibrils.Amyloid and amyloid-like fibrils represent a generic class of highly ordered nanostructures that are implicated in some of the most fatal neurodegenerative diseases. On the other hand, amyloids, by possessing outstanding mechanical robustness, have also been successfully employed as functional biomaterials. For these reasons, physical and chemical factors driving fibril self-assembly and morphology are extensively studied - among these parameters, the secondary structures and the pH have been revealed to be crucial, since a variation in pH changes the fibril morphology and net chirality during protein aggregation. It is important to quantify the mechanical properties of these fibrils in order to help the design of effective strategies for treating diseases related to the presence of amyloid fibrils. In this work, we show that by changing pH the mechanical properties of amyloid-like fibrils vary as well. In particular, we reveal that these mechanical properties are strongly related to the content of secondary structures. We analysed and estimated the Young's modulus (E) by comparing the persistence length (Lp) - measured from the observation of TEM images by using statistical mechanics arguments - with the mechanical information provided by peak force quantitative nanomechanical property mapping (PF-QNM). The secondary structure content and the chirality are investigated by means of synchrotron radiation circular dichroism (SR-CD). Results arising from this study could be fruitfully used as a protocol to investigate other medical or engineering relevant peptide fibrils. Electronic supplementary information (ESI) available: A molecular model for the peptide studied and the charge chart associated to it. In addition, an AFM image of pH 4 fibrils is presented. See DOI: 10.1039/c4nr05109b

A review of imaging modalities in pulmonary hypertension

PubMed Central

Ascha, Mona; Renapurkar, Rahul D.; Tonelli, Adriano R.

2017-01-01

Pulmonary hypertension (PH) is defined as resting mean pulmonary artery pressure ≥25 mmHg measured by right heart catheterization. PH is a progressive, life-threatening disease with a variety of etiologies. Swift and accurate diagnosis of PH and appropriate classification in etiologic group will allow for earlier treatment and improved outcomes. A number of imaging tools are utilized in the evaluation of PH, such as chest X-ray, computed tomography (CT), ventilation/perfusion (V/Q) scan, and cardiac magnetic resonance imaging. Newer imaging tools such as dual-energy CT and single-photon emission computed tomography/computed tomography V/Q scanning have also emerged; however, their place in the diagnostic evaluation of PH remains to be determined. In general, each imaging technique provides incremental information, with varying degrees of sensitivity and specificity, which helps suspect the presence and identify the etiology of PH. The present study aims to provide a comprehensive review of the utility, advantages, and shortcomings of the imaging modalities that may be used to evaluate patients with PH. PMID:28469715

Magnetic Resonance and Computed Tomography Imaging for the Evaluation of Pulmonary Hypertension

PubMed Central

Freed, Benjamin H.; Collins, Jeremy D.; François, Christopher J.; Barker, Alex J.; Cuttica, Michael J.; Chesler, Naomi C.; Markl, Michael; Shah, Sanjiv J.

2016-01-01

Imaging plays a central role in the diagnosis and management of all forms of pulmonary hypertension (PH). While Doppler echocardiography is essential for the evaluation of PH, its ability to optimally evaluate the right ventricle (RV) and pulmonary vasculature is limited by its 2D planar capabilities. Magnetic resonance imaging (MRI) and computed tomography (CT) are capable of determining the etiology and pathophysiology of PH, and can be very useful in the management of these patients. Exciting new techniques such as RV tissue characterization with T1 mapping, 4D flow of the RV and pulmonary arteries, and CT lung perfusion imaging are paving the way for a new era of imaging in PH. These imaging modalities complement echocardiography and invasive hemodynamic testing, and may be useful as surrogate endpoints for early-phase PH clinical trials. Here we discuss the role of MRI and CT in the diagnosis and management of PH, including current uses and novel research applications, and we discuss the role of value-based imaging in PH. PMID:27282439

Quantitative Multispectral Analysis Of Discrete Subcellular Particles By Digital Imaging Fluorescence Microscopy (DIFM)

NASA Astrophysics Data System (ADS)

Dorey, C. K.; Ebenstein, David B.

1988-10-01

Subcellular localization of multiple biochemical markers is readily achieved through their characteristic autofluorescence or through use of appropriately labelled antibodies. Recent development of specific probes has permitted elegant studies in calcium and pH in living cells. However, each of these methods measured fluorescence at one wavelength; precise quantitation of multiple fluorophores at individual sites within a cell has not been possible. Using DIFM, we have achieved spectral analysis of discrete subcellular particles 1-2 gm in diameter. The fluorescence emission is broken into narrow bands by an interference monochromator and visualized through the combined use of a silicon intensified target (SIT) camera, a microcomputer based framegrabber with 8 bit resolution, and a color video monitor. Image acquisition, processing, analysis and display are under software control. The digitized image can be corrected for the spectral distortions induced by the wavelength dependent sensitivity of the camera, and the displayed image can be enhanced or presented in pseudocolor to facilitate discrimination of variation in pixel intensity of individual particles. For rapid comparison of the fluorophore composition of granules, a ratio image is produced by dividing the image captured at one wavelength by that captured at another. In the resultant ratio image, a granule which has a fluorophore composition different from the majority is selectively colored. This powerful system has been utilized to obtain spectra of endogenous autofluorescent compounds in discrete cellular organelles of human retinal pigment epithelium, and to measure immunohistochemically labelled components of the extracellular matrix associated with the human optic nerve.

A Quantitative Review and Meta-Models of the Variability and Factors Affecting Oral Drug Absorption-Part I: Gastrointestinal pH.

PubMed

Abuhelwa, Ahmad Y; Foster, David J R; Upton, Richard N

2016-09-01

This study aimed to conduct a quantitative meta-analysis for the values of, and variability in, gastrointestinal (GI) pH in the different GI segments; characterize the effect of food on the values and variability in these parameters; and present quantitative meta-models of distributions of GI pH to help inform models of oral drug absorption. The literature was systemically reviewed for the values of, and the variability in, GI pH under fed and fasted conditions. The GI tract was categorized into the following 10 distinct regions: stomach (proximal, mid-distal), duodenum (proximal, mid-distal), jejunum and ileum (proximal, mid, and distal small intestine), and colon (ascending, transverse, and descending colon). Meta-analysis used the "metafor" package of the R language. The time course of postprandial stomach pH was modeled using NONMEM. Food significantly influenced the estimated meta-mean stomach and duodenal pH but had no significant influence on small intestinal and colonic pH. The time course of postprandial pH was described using an exponential model. Increased meal caloric content increased the extent and duration of postprandial gastric pH buffering. The different parts of the small intestine had significantly different pH. Colonic pH was significantly different for descending but not for ascending and transverse colon. Knowledge of GI pH is important for the formulation design of the pH-dependent dosage forms and in understanding the dissolution and absorption of orally administered drugs. The meta-models of GI pH may also be used as part of semi-physiological pharmacokinetic models to characterize the effect of GI pH on the in vivo drug release and pharmacokinetics.

Quantitative Mapping of the Spatial Distribution of Nanoparticles in Endo-Lysosomes by Local pH.

PubMed

Wang, Jing; MacEwan, Sarah R; Chilkoti, Ashutosh

2017-02-08

Understanding the intracellular distribution and trafficking of nanoparticle drug carriers is necessary to elucidate their mechanisms of drug delivery and is helpful in the rational design of novel nanoparticle drug delivery systems. The traditional immunofluorescence method to study intracellular distribution of nanoparticles using organelle-specific antibodies is laborious and subject to artifacts. As an alternative, we developed a new method that exploits ratiometric fluorescence imaging of a pH-sensitive Lysosensor dye to visualize and quantify the spatial distribution of nanoparticles in the endosomes and lysosomes of live cells. Using this method, we compared the endolysosomal distribution of cell-penetrating peptide (CPP)-functionalized micelles to unfunctionalized micelles and found that CPP-functionalized micelles exhibited faster endosome-to-lysosome trafficking than unfunctionalized micelles. Ratiometric fluorescence imaging of pH-sensitive Lysosensor dye allows rapid quantitative mapping of nanoparticle distribution in endolysosomes in live cells while minimizing artifacts caused by extensive sample manipulation typical of alternative approaches. This new method can thus serve as an alternative to traditional immunofluorescence approaches to study the intracellular distribution and trafficking of nanoparticles within endosomes and lysosomes.

Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68

PubMed Central

Cusnir, Ruslan; Imberti, Cinzia; Hider, Robert C.; Blower, Philip J.; Ma, Michelle T.

2017-01-01

Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68Ga3+, which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68Ga3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68Ga PET radiopharmaceuticals. 68Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images. PMID:28075350

Hydroxypyridinone Chelators: From Iron Scavenging to Radiopharmaceuticals for PET Imaging with Gallium-68.

PubMed

Cusnir, Ruslan; Imberti, Cinzia; Hider, Robert C; Blower, Philip J; Ma, Michelle T

2017-01-08

Derivatives of 3,4-hydroxypyridinones have been extensively studied for in vivo Fe 3+ sequestration. Deferiprone, a 1,2-dimethyl-3,4-hydroxypyridinone, is now routinely used for clinical treatment of iron overload disease. Hexadentate tris(3,4-hydroxypyridinone) ligands (THP) complex Fe 3+ at very low iron concentrations, and their high affinities for oxophilic trivalent metal ions have led to their development for new applications as bifunctional chelators for the positron emitting radiometal, 68 Ga 3+ , which is clinically used for molecular imaging in positron emission tomography (PET). THP-peptide bioconjugates rapidly and quantitatively complex 68 Ga 3+ at ambient temperature, neutral pH and micromolar concentrations of ligand, making them amenable to kit-based radiosynthesis of 68 Ga PET radiopharmaceuticals. 68 Ga-labelled THP-peptides accumulate at target tissue in vivo, and are excreted largely via a renal pathway, providing high quality PET images.

Functional photoacoustic microscopy of pH

NASA Astrophysics Data System (ADS)

Chatni, M. Rameez; Yao, Junjie; Danielli, Amos; Favazza, Christopher P.; Maslov, Konstantin I.; Wang, Lihong V.

2012-02-01

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, imbalance of pH regulation may result from or result in serious illness. Even though the regulation system of pH is very robust, tissue pH can be altered in many diseases such as cancer, osteoporosis and diabetes mellitus. Traditional high-resolution optical imaging techniques, such as confocal microscopy, routinely image pH in cells and tissues using pH sensitive fluorescent dyes, which change their fluorescence properties with the surrounding pH. Since strong optical scattering in biological tissue blurs images at greater depths, high-resolution pH imaging is limited to penetration depths of 1mm. Here, we report photoacoustic microscopy (PAM) of commercially available pH-sensitive fluorescent dye in tissue phantoms. Using both opticalresolution photoacoustic microscopy (OR-PAM), and acoustic resolution photoacoustic microscopy (AR-PAM), we explored the possibility of recovering the pH values in tissue phantoms. In this paper, we demonstrate that PAM was capable of recovering pH values up to a depth of 2 mm, greater than possible with other forms of optical microscopy.

Image transfer properties by photonic crystal slab with negative refractive index

NASA Astrophysics Data System (ADS)

Chen, Hongbo; Chen, Xiaoshuang; Zhou, Renlong; Lu, Wei

2008-04-01

We have studied the properties of image transferred by photonic crystal (PhC) slab with negative refractive index n=-1 and confirmed the negative refractive phonomenon, but not found the saturated image properties as expected. It is found that real images will not be formed when the source distance larger than the thickness of PhC, and the transferred images are virtual images. Furthermore, comparing the quality of images transferred by a PhC slab and a cascaded stack of photonic crystal slab (CSPS), we found that the transferred images are distorted in both situations. The image resolution is good along the direction parallel to the slab interface, but bad along the direction normal to the slab interface. Simulation results show that the image formed by a CSPS is no better than a PhC slab.

High speed all optical shear wave imaging optical coherence elastography (Conference Presentation)

NASA Astrophysics Data System (ADS)

Song, Shaozhen; Hsieh, Bao-Yu; Wei, Wei; Shen, Tueng; O'Donnell, Matthew; Wang, Ruikang K.

2016-03-01

Optical Coherence Elastography (OCE) is a non-invasive testing modality that maps the mechanical property of soft tissues with high sensitivity and spatial resolution using phase-sensitive optical coherence tomography (PhS-OCT). Shear wave OCE (SW-OCE) is a leading technique that relies on the speed of propagating shear waves to provide a quantitative elastography. Previous shear wave imaging OCT techniques are based on repeated M-B scans, which have several drawbacks such as long acquisition time and repeated wave stimulations. Recent developments of Fourier domain mode-locked high-speed swept-source OCT system has enabled enough speed to perform KHz B-scan rate OCT imaging. Here we propose ultra-high speed, single shot shear wave imaging to capture single-shot transient shear wave propagation to perform SW-OCE. The frame rate of shear wave imaging is 16 kHz, at A-line rate of ~1.62 MHz, which allows the detection of high-frequency shear wave of up to 8 kHz. The shear wave is generated photothermal-acoustically, by ultra-violet pulsed laser, which requires no contact to OCE subjects, while launching high frequency shear waves that carries rich localized elasticity information. The image acquisition and processing can be performed at video-rate, which enables real-time 3D elastography. SW-OCE measurements are demonstrated on tissue-mimicking phantoms and porcine ocular tissue. This approach opens up the feasibility to perform real-time 3D SW-OCE in clinical applications, to obtain high-resolution localized quantitative measurement of tissue biomechanical property.

1 H NMRS of carnosine combined with 31 P NMRS to better characterize skeletal muscle pH dysregulation in Duchenne muscular dystrophy.

PubMed

Reyngoudt, Harmen; Turk, Suna; Carlier, Pierre G

2018-01-01

In recent years, quantitative nuclear magnetic resonance imaging and spectroscopy (NMRI and NMRS) have been used more systematically as outcome measures in natural history and clinical trial studies for Duchenne muscular dystrophy (DMD). Whereas most of these studies have emphasized the evaluation of the fat fraction as an assessment for disease severity, less focus has been placed on metabolic indices measured by NMRS. 31 P NMRS in DMD reveals an alkaline inorganic phosphate (P i ) pool, originating from either leaky dystrophic myocytes or an increased interstitial space. 1 H NMRS, exploiting the pH-sensitive proton resonances of carnosine, an intracellular dipeptide, was used to distinguish between these two hypotheses. NMR data were obtained in 23 patients with DMD and 14 healthy subjects on a 3-T clinical NMR system. Both 31 P and 1 H NMRS data were acquired at the level of the gastrocnemius medialis muscle. A multi-slice multi-echo imaging acquisition was performed for the determination of water T 2 and fat fraction in the same region of interest. Whereas nearly all patients with DMD showed an elevated pH compared with healthy controls when using 31 P NMRS, 1 H NMRS-determined pH was not systematically increased. As expected, the carnosine-based intracellular pH was never found to be alkaline in the absence of a concurrent P i -based pH elevation. In addition, abnormal intracellular pH, based on carnosine, was never associated with normal water T 2 values. We conclude that, in one group of patients, both 1 H and 31 P NMRS showed an alkaline pH, originating from the intracellular compartment and reflecting ionic dysregulation in dystrophic myocytes. In the other patients with DMD, intracellular pH was normal, but an alkaline P i pool was still present, suggesting an extracellular origin, probably revealing an expanded interstitial volume fraction, often associated with fibrotic changes. The data demonstrate that 1 H NMRS could serve as a biomarker to assess the normalization of intramyocytic pH and sarcolemmal permeability following therapy inducing dystrophin expression in patients with DMD. Copyright © 2017 John Wiley & Sons, Ltd.

Quantitative Functional Imaging Using Dynamic Positron Computed Tomography and Rapid Parameter Estimation Techniques

NASA Astrophysics Data System (ADS)

Koeppe, Robert Allen

Positron computed tomography (PCT) is a diagnostic imaging technique that provides both three dimensional imaging capability and quantitative measurements of local tissue radioactivity concentrations in vivo. This allows the development of non-invasive methods that employ the principles of tracer kinetics for determining physiological properties such as mass specific blood flow, tissue pH, and rates of substrate transport or utilization. A physiologically based, two-compartment tracer kinetic model was derived to mathematically describe the exchange of a radioindicator between blood and tissue. The model was adapted for use with dynamic sequences of data acquired with a positron tomograph. Rapid estimation techniques were implemented to produce functional images of the model parameters by analyzing each individual pixel sequence of the image data. A detailed analysis of the performance characteristics of three different parameter estimation schemes was performed. The analysis included examination of errors caused by statistical uncertainties in the measured data, errors in the timing of the data, and errors caused by violation of various assumptions of the tracer kinetic model. Two specific radioindicators were investigated. ('18)F -fluoromethane, an inert freely diffusible gas, was used for local quantitative determinations of both cerebral blood flow and tissue:blood partition coefficient. A method was developed that did not require direct sampling of arterial blood for the absolute scaling of flow values. The arterial input concentration time course was obtained by assuming that the alveolar or end-tidal expired breath radioactivity concentration is proportional to the arterial blood concentration. The scale of the input function was obtained from a series of venous blood concentration measurements. The method of absolute scaling using venous samples was validated in four studies, performed on normal volunteers, in which directly measured arterial concentrations were compared to those predicted from the expired air and venous blood samples. The glucose analog ('18)F-3-deoxy-3-fluoro-D -glucose (3-FDG) was used for quantitating the membrane transport rate of glucose. The measured data indicated that the phosphorylation rate of 3-FDG was low enough to allow accurate estimation of the transport rate using a two compartment model.

Imaging intracellular pH in live cells with a genetically encoded red fluorescent protein sensor.

PubMed

Tantama, Mathew; Hung, Yin Pun; Yellen, Gary

2011-07-06

Intracellular pH affects protein structure and function, and proton gradients underlie the function of organelles such as lysosomes and mitochondria. We engineered a genetically encoded pH sensor by mutagenesis of the red fluorescent protein mKeima, providing a new tool to image intracellular pH in live cells. This sensor, named pHRed, is the first ratiometric, single-protein red fluorescent sensor of pH. Fluorescence emission of pHRed peaks at 610 nm while exhibiting dual excitation peaks at 440 and 585 nm that can be used for ratiometric imaging. The intensity ratio responds with an apparent pK(a) of 6.6 and a >10-fold dynamic range. Furthermore, pHRed has a pH-responsive fluorescence lifetime that changes by ~0.4 ns over physiological pH values and can be monitored with single-wavelength two-photon excitation. After characterizing the sensor, we tested pHRed's ability to monitor intracellular pH by imaging energy-dependent changes in cytosolic and mitochondrial pH.

Quantitative measurement and real-time tracking of high intensity focused ultrasound using phase-sensitive optical coherence tomography: Feasibility study.

PubMed

Le, Nhan; Song, ShaoZhen; Nabi, Ghulam; Wang, Ruikang; Huang, Zhihong

2016-09-01

Phase-sensitive optical coherence tomography (PhS-OCT) is proposed, as a new high intensity focused ultrasound (HIFU) imaging guidance to detect and track HIFU focus inside 1% agar samples in this work. The experiments studied the effect of varying HIFU power on the induction of shear wave, which can be implemented as a new technique to monitor focused ultrasound surgery (FUS). A miniature HIFU transducer (1.02 MHz, 20 mm aperture diameter, 15 mm radius of curvature) was produced in-house, pressure-field mapped, and calibrated. The transducer was then embedded inside a 1% agar phantom, which was placed under PhS-OCT for observation, under various HIFU power settings (acoustic power, and number of cycles per pulse). Shear wave was induced on the sample surface by HIFU and was captured in full under PhS-OCT. The lowest HIFU acoustic power output for the detection of shear wave was found to be 0.36 W (1.02 MHz, 100 cycles/pulse), or with the number of cycles/pulse as low as 20 (1.02 MHz, 0.98 W acoustic power output). A linear relationship between acoustic power output and the maximum shear wave displacement was found in the first study. The second study explores a non-linear correlation between the (HIFU) numbers of cycles per pulse, and the maximum shear wave displacement. PhS-OCT demonstrates excellent tracking and detection of HIFU-induced shear wave. The results could benefit other imaging techniques in tracking and guiding HIFU focus. Further studies will explore the relationship between the physical transducer characteristics and the HIFU-induced shear wave.

Bevacizumab impairs oxidative energy metabolism and shows antitumoral effects in recurrent glioblastomas: a 31P/1H MRSI and quantitative magnetic resonance imaging study.

PubMed

Hattingen, Elke; Jurcoane, Alina; Bähr, Oliver; Rieger, Johannes; Magerkurth, Jörg; Anti, Sandra; Steinbach, Joachim P; Pilatus, Ulrich

2011-12-01

Bevacizumab shows unprecedented rates of response in recurrent glioblastomas (GBM), but the detailed mechanisms are still unclear. We employed in vivo magnetic resonance spectroscopic imaging (MRSI) and quantitative magnetic resonance imaging to investigate whether bevacizumab alters oxygen and energy metabolism and whether this effect has antitumoral activity in recurrent GBM. (31)P and (1)H MRSI, apparent diffusion coefficient (ADC), and high-resolution T2 and T2' mapping (indirect marker of oxygen extraction) were investigated in 16 patients with recurrent GBM at 3 Tesla before and 1.5-2 months after initiation of therapy with bevacizumab. Changes of metabolite concentrations and of the quantitative values in the tumor and normal appearing brain tissue were calculated. The Wilcoxon signed-ranks test was used to evaluate differences for tumor/edema versus control as well as changes before versus after commencement of therapy. Survival analyses were performed for significant parameters. Tumor T2', pH, ADC, and T2 decreased significantly in patients responding to bevacizumab therapy (n = 10). Patients with at least 25% T2' decrease during treatment showed longer progression-free and overall survival durations. Levels of high-energy metabolites were lower at baseline; these persisted under therapy. Glycerophosphoethanolamine as catabolic phospholipid metabolite increased in responders. The MRSI data support the hypothesis that bevacizumab induces relative tumor hypoxia (T2' decrease) and affects energy homeostasis in recurrent GBM, suggesting that bevacizumab impairs vascular function. The antiangiogenic effect of bevacizumab is predictive of better outcome and seems to induce antitumoral activity in the responding GBMs.

Multimodality Image-Guided HDR/IMRT in Prostate Cancer: Combined Molecular Targeting Using Nanoparticle MR, 3D MRSI, and 11C Acetate PET Imaging

DTIC Science & Technology

2005-08-01

Ph.D. Panos Fatouros, Ph.D. Jerry Hirsch, MSc, PharmD Rhonda Hoyle Kristin Schmidt Dorin Tudor, Ph.D. Jie Liu CONTRACTING ORGANIZATION: Virginia...McClish, Ph.D., Panos Fatouros, Ph.D., Jerry Hirsch, MSc, PharmD, 5e. TASK NUMBER Rhonda Hoyle, Kristin Schmidt, Dorin Tudor, Ph.D., Jie Liu 5f. WORK UNIT

Multifunctional PHPMA-Derived Polymer for Ratiometric pH Sensing, Fluorescence Imaging, and Magnetic Resonance Imaging.

PubMed

Su, Fengyu; Agarwal, Shubhangi; Pan, Tingting; Qiao, Yuan; Zhang, Liqiang; Shi, Zhengwei; Kong, Xiangxing; Day, Kevin; Chen, Meiwan; Meldrum, Deirdre; Kodibagkar, Vikram D; Tian, Yanqing

2018-01-17

In this paper, we report synthesis and characterization of a novel multimodality (MRI/fluorescence) probe for pH sensing and imaging. A multifunctional polymer was derived from poly(N-(2-hydroxypropyl)methacrylamide) (PHPMA) and integrated with a naphthalimide-based-ratiometric fluorescence probe and a gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex (Gd-DOTA complex). The polymer was characterized using UV-vis absorption spectrophotometry, fluorescence spectrofluorophotometry, magnetic resonance imaging (MRI), and confocal microscopy for optical and MRI-based pH sensing and cellular imaging. In vitro labeling of macrophage J774 and esophageal CP-A cell lines shows the polymer's ability to be internalized in the cells. The transverse relaxation time (T 2 ) of the polymer was observed to be pH-dependent, whereas the spin-lattice relaxation time (T 1 ) was not. The pH probe in the polymer shows a strong fluorescence-based ratiometric pH response with emission window changes, exhibiting blue emission under acidic conditions and green emission under basic conditions, respectively. This study provides new materials with multimodalities for pH sensing and imaging.

Kinetics of Cd(ii) adsorption and desorption on ferrihydrite: experiments and modeling.

PubMed

Liang, Yuzhen; Tian, Lei; Lu, Yang; Peng, Lanfang; Wang, Pei; Lin, Jingyi; Cheng, Tao; Dang, Zhi; Shi, Zhenqing

2018-05-15

The kinetics of Cd(ii) adsorption/desorption on ferrihydrite is an important process affecting the fate, transport, and bioavailability of Cd(ii) in the environment, which was rarely systematically studied and understood at quantitative levels. In this work, a combination of stirred-flow kinetic experiments, batch adsorption equilibrium experiments, high-resolution transmission electron microscopy (HR-TEM), and mechanistic kinetic modeling were used to study the kinetic behaviors of Cd(ii) adsorption/desorption on ferrihydrite. HR-TEM images showed the open, loose, and sponge-like structure of ferrihydrite. The batch adsorption equilibrium experiments revealed that higher pH and initial metal concentration increased Cd(ii) adsorption on ferrihydrite. The stirred-flow kinetic results demonstrated the increased adsorption rate and capacity as a result of the increased pH, influent concentration, and ferrihydrite concentration. The mechanistic kinetic model successfully described the kinetic behaviors of Cd(ii) during the adsorption and desorption stages under various chemistry conditions. The model calculations showed that the adsorption rate coefficients varied as a function of solution chemistry, and the relative contributions of the weak and strong ferrihydrite sites for Cd(ii) binding varied with time at different pH and initial metal concentrations. Our model is able to quantitatively assess the contributions of each individual ferrihydrite binding site to the overall Cd(ii) adsorption/desorption kinetics. This study provided insights into the dynamic behavior of Cd(ii) and a predictive modeling tool for Cd(ii) adsorption/desorption kinetics when ferrihydrite is present, which may be helpful for the risk assessment and management of Cd contaminated sites.

Use of the pH sensitive fluorescence probe pyranine to monitor internal pH changes in Escherichia coli membrane vesicles.

PubMed

Damiano, E; Bassilana, M; Rigaud, J L; Leblanc, G

1984-01-23

Measurements of the fluorescent properties of 8-hydroxy-1,3,6-pyrenetrisulfonate (pyranine) enclosed within the internal space of Escherichia coli membrane vesicles enable recordings and quantitative analysis of: (i) changes in intravesicular pH taking place during oxidation of electron donors by the membrane respiratory chain; (ii) transient alkalization of the internal aqueous space resulting from the creation of outwardly directed acetate diffusion gradients across the vesicular membrane. Quantitation of the fluorescence variations recorded during the creation of transmembrane acetate gradients shows a close correspondence between the measured shifts in internal pH value and those expected from the amplitude of the imposed acetate gradients.

Human in vivo cardiac phosphorus NMR spectroscopy at 3.0 Tesla

NASA Astrophysics Data System (ADS)

Bruner, Angela Properzio

One of the newest methods with great potential for use in clinical diagnosis of heart disease is human, cardiac, phosphorus NMR spectroscopy (cardiac p 31 MRS). Cardiac p31 MRS is able to provide quantitative, non-invasive, functional information about the myocardial energy metabolites such as pH, phosphocreatine (PCr), and adenosinetriphosphate (ATP). In addition to the use of cardiac p3l MRS for other types of cardiac problems, studies have shown that the ratio of PCr/ATP and pH are sensitive and specific markers of ischemia at the myocardial level. In human studies, typically performed at 1.5 Tesla, PCr/ATP has been relatively easy to measure but often requires long scan times to provide adequate signal-to-noise (SNR). In addition, pH which relies on identification of inorganic phosphate (Pi), has rarely been obtained. Significant improvement in the quality of cardiac p31 MRS was achieved through the use of the General Electric SIGNATM 3.0 Tesla whole body magnet, improved coil designs and optimized pulse sequences. Phantom and human studies performed on many types of imaging and spectroscopy sequences, identified breathhold gradient-echo imaging and oblique DRESS p31 spectroscopy as the best compromises between SNR, flexibility and quality localization. Both single-turn and quadrature 10-cm diameter, p31 radiofrequency coils, were tested with the quadrature coil providing greater SNR, but at a greater depth to avoid skeletal muscle contamination. Cardiac p31 MRS obtained in just 6 to 8 minutes, gated, showed both improved SNR and discernment of Pi allowing for pH measurement. A handgrip, in-magnet exerciser was designed, created and tested at 1.5 and 3.0 Tesla on volunteers and patients. In ischemic patients, this exercise was adequate to cause a repeated drop in PCr/ATP and pH with approximately eight minutes of isometric exercise at 30% maximum effort. As expected from literature, this exercise did not cause a drop in PCr/ATP for reference volunteers.

Thiol Specific and Mitochondria Selective Fluorogenic Benzofurazan Sulfide for Live Cell Nonprotein Thiol Imaging and Quantification in Mitochondria.

PubMed

Wang, Shenggang; Yin, Huihui; Huang, Yue; Guan, Xiangming

2018-06-11

Cellular thiols are divided into two major categories: nonprotein thiols (NPSH) and protein thiols (PSH). Thiols are unevenly distributed inside the cell and compartmentalized in subcellular structures. Most of our knowledge on functions/dysfunctions of cellular/subcellular thiols is based on the quantification of cellular/subcellular thiols through homogenization of cellular/subcellular structures followed by a thiol quantification method. We would like to report a thiol-specific mitochondria-selective fluorogenic benzofurazan sulfide {7,7'-thiobis( N-rhodamine-benzo[c][1,2,5]oxadiazole-4-sulfonamide) (TBROS)} that can effectively image and quantify live cell NPSH in mitochondria through fluorescence intensity. Limited methods are available for imaging thiols in mitochondria in live cells especially in a quantitative manner. The thiol specificity of TBROS was demonstrated by its ability to react with thiols and inability to react with biologically relevant nucleophilic functional groups other than thiols. TBROS, with minimal fluorescence, formed strong fluorescent thiol adducts (λ ex = 550 nm, λ em = 580 nm) when reacting with NPSH confirming its fluorogenicity. TBROS failed to react with PSH from bovine serum albumin and cell homogenate proteins. The high mitochondrial thiol selectivity of TBROS was achieved by its mitochondria targeting structure and its higher reaction rate with NPSH at mitochondrial pH. Imaging of mitochondrial NPSH in live cells was confirmed by two colocalization methods and use of a thiol-depleting reagent. TBROS effectively imaged NPSH changes in a quantitative manner in mitochondria in live cells. The reagent will be a useful tool in exploring physiological and pathological roles of mitochondrial thiols.

Self-Assembled Fluorescent Bovine Serum Albumin Nanoprobes for Ratiometric pH Measurement inside Living Cells.

PubMed

Yang, Qiaoyu; Ye, Zhongju; Zhong, Meile; Chen, Bo; Chen, Jian; Zeng, Rongjin; Wei, Lin; Li, Hung-wing; Xiao, Lehui

2016-04-20

In this work, we demonstrated a new ratiometric method for the quantitative analysis of pH inside living cells. The structure of the nanosensor comprises a biofriendly fluorescent bovine serum albumin (BSA) matrix, acting as a pH probe, and pH-insensitive reference dye Alexa 594 enabling ratiometric quantitative pH measurement. The fluorescent BSA matrix was synthesized by cross-linking of the denatured BSA proteins in ethanol with glutaraldehyde. The size of the as-synthesized BSA nanoparticles can be readily manipulated from 30 to 90 nm, which exhibit decent fluorescence at the peak wavelength of 535 nm with a pH response range of 6-8. The potential of this pH sensor for intracellular pH monitoring was demonstrated inside living HeLa cells, whereby a significant change in fluorescence ratio was observed when the pH of the cell was switched from normal to acidic with anticancer drug treatment. The fast response of the nanosensor makes it a very powerful tool in monitoring the processes occurring within the cytosol.

PhAst: A Flexible IDL Astronomical Image Viewer

NASA Astrophysics Data System (ADS)

Rehnberg, Morgan; Crawford, R.; Trueblood, M.; Mighell, K.

2012-01-01

We present near-Earth asteroid data analyzed with PhAst, a new IDL astronomical image viewer based on the existing application ATV. PhAst opens, displays, and analyzes an arbitrary number of FITS images. Analysis packages include image calibration, photometry, and astrometry (provided through an interface with SExtractor, SCAMP, and missFITS). PhAst has been designed to generate reports for Minor Planet Center reporting. PhAst is cross platform (Linux/Mac OSX/Windows for image viewing and Linux/Mac OSX for image analysis) and can be downloaded from the following website at NOAO: http://www.noao.edu/staff/mighell/phast/. Rehnberg was supported by the NOAO/KPNO Research Experiences for Undergraduates (REU) Program which is funded by the National Science Foundation Research Experiences for Undergraduates Program and the Department of Defense ASSURE program through Scientific Program Order No. 13 (AST-0754223) of the Cooperative Agreement No. AST-0132798 between the Association of Universities for Research in Astronomy (AURA) and the NSF.

Retrievals of atmospheric variables on the gas giants from ground-based mid-infrared imaging

NASA Astrophysics Data System (ADS)

Fletcher, L. N.; Orton, G. S.; Yanamandra-Fisher, P.; Fisher, B. M.; Parrish, P. D.; Irwin, P. G. J.

2009-03-01

Thermal-infrared imaging of Jupiter and Saturn using the NASA/IRTF and Subaru observatories are quantitatively analyzed to assess the capabilities for reproducing and extending the zonal mean atmospheric results of the Cassini/CIRS experiment. We describe the development of a robust, systematic and reproducible approach to the acquisition and reduction of planetary images in the mid-infrared (7-25 μm), and perform an adaptation and validation of the optimal estimation, correlated- k retrieval algorithm described by Irwin et al. [Irwin, P., Teanby, N., de Kok, R., Fletcher, L., Howett, C., Tsang, C., Wilson, C., Calcutt, S., Nixon, C., Parrish, P., 2008. J. Quant. Spectrosc. Radiat. Trans. 109 (6), 1136-1150] for channel-integrated radiances. Synthetic spectral analyses and a comparison to Cassini results are used to verify our abilities to retrieve temperatures, haze opacities and gaseous abundances from filtered imaging. We find that ground-based imaging with a sufficiently high spatial resolution is able to reproduce the three-dimensional temperature and para-H 2 fields measured by spacecraft visiting Jupiter and Saturn, allowing us to investigate vertical wind shear, pressure and, with measured cloud-top winds, Ertel potential vorticity on potential temperature surfaces. Furthermore, by scaling vertical profiles of NH 3, PH 3, haze opacity and hydrocarbons as free parameters during thermal retrievals, we can produce meridional results comparable with CIRS spectroscopic investigations. This paper demonstrates that mid-IR imaging instruments operating at ground-based observatories have access to several dynamical and chemical diagnostics of the atmospheric state of the gas giants, offering the prospect for quantitative studies over much longer baselines and often covering much wider areas than is possible from spaceborne platforms.

X-Ray Excited Luminescence Chemical Imaging of Bacterial Growth on Surfaces Implanted in Tissue.

PubMed

Wang, Fenglin; Raval, Yash; Tzeng, Tzuen-Rong J; Anker, Jeffrey N

2015-04-22

A pH sensor film is developed that can be coated on an implant surface and imaged using a combination of X-ray excitation and visible spectroscopy to monitor bacterial infection and treatment of implanted medical devices (IMDs) through tissue. X-ray scintillators in the pH sensor film generate light when an X-ray beam irradiates them. This light first passes through a layer containing pH indicator that alters the spectrum according to pH, then passes through and out of the tissue where it is detected by a spectrometer. A reference region on the film is used to account for spectral distortion from wavelength-dependent absorption and scattering in the tissue. pH images are acquired by moving the sample relative to the X-ray beam and collecting a spectrum at each location, with a spatial resolution limited by the X-ray beam width. Using this X-ray excited luminescence chemical imaging (XELCI) to map pH through ex vivo porcine tissue, a pH drop is detected during normal bacterial growth on the sensor surface, and a restoration of the pH to the bulk value during antibiotic treatment over the course of hours with milli-meter resolution. Overall, XELCI provides a novel approach to noninvasively image surface pH for studying implant infections and treatments. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Norcyanine dyes with benzo[c,d]indolium moiety: Spectral sensitivity with pH change for fluorescence pH imaging in living cells.

PubMed

Guan, Li; Liu, Qi; Zhang, Borui; Wang, Lanying

2017-01-01

Fluorescence pH imaging in living cells is a rapidly expanding research direction, however, it relies on the development of pH-sensitive fluorescent imaging agents. Here four norcyanine dyes with benzo[c,d]indolium moiety, exhibiting high spectral sensitivity with pH changes, were synthesized for fluorescence pH imaging in living cells, and characterized by 1 H NMR, 13 C NMR, IR, UV-Vis and HRMS. The investigation of their spectral properties in methanol and water showed that the absorption and emission maxima were in the region 488-618nm and 583-651nm, respectively, and four dyes exhibited high photostability. The pH spectral titrations showed that selective dye D1 had pH-dependent absorption spectral changes within the pH range of 2.4 to 9.4, and high fluorescent spectral sensitivity at pH5.0-8.0, with a pK a of 5.0. A cell association study indicated that dye D1 exhibited no or mild cytotoxicity at the application dose and duration, and could be accumulated in cells and mainly distributed in the cytoplasm, giving red fluorescence imaging. In particular, dye D1 could achieve pH-dependent fluorescence imaging in living cells with the increase of pH from 3.0 to 8.0, at excitation wavelength of 543nm and receiving wavelength of 655-755nm, which was valuable for studying the weak acidic, neutral and weak alkaline biological tissue compartments. Copyright © 2016 Elsevier B.V. All rights reserved.

Rescue of hyperexcitability in hippocampal CA1 neurons from Mecp2 (-/y) mouse through surface potential neutralization

PubMed Central

Mironov, Sergej L.

2018-01-01

Hyperventilation is a known feature of Rett syndrome (RTT). However, how hyperventilation is related to other RTT symptoms such as hyperexcitability is unknown. Intense breathing during hyperventilation induces hypocapnia and culminates in respiratory alkalosis. Alkalinization of extracellular milieu can trigger epilepsy in patients who already have neuronal hyperexcitability. By combining patch-clamp electrophysiology and quantitative glutamate imaging, we compared excitability of CA1 neurons of WT and Mecp2 (-/y) mice, and analyzed the biophysical properties of subthreshold membrane channels. The results show that Mecp2 (-/y) CA1 neurons are hyperexcitable in normal pH (7.4) and are increasingly vulnerable to alkaline extracellular pH (8.4), during which their excitability increased further. Under normal pH conditions, an abnormal negative shift in the voltage-dependencies of HCN (hyperpolarization-activated cyclic nucleotide-gated) and calcium channels in the CA1 neurons of Mecp2 (-/y) mice was observed. Alkaline pH also enhanced excitability in wild-type (WT) CA1 neurons through modulation of the voltage dependencies of HCN- and calcium channels. Additionally alkaline pH augmented spontaneous glutamate release and burst firing in WT CA1 neurons. Conversely, acidic pH (6.4) and 8 mM Mg2+ exerted the opposite effect, and diminished hyperexcitability in Mecp2 (-/y) CA1 neurons. We propose that the observed effects of pH and Mg2+ are mediated by changes in the neuronal membrane surface potential, which consecutively modulates the gating of HCN and calcium channels. The results provide insight to pivotal cellular mechanisms that can regulate neuronal excitability and help to devise treatment strategies for hyperexcitability induced symptoms of Rett syndrome. PMID:29621262

Automated colour identification in melanocytic lesions.

PubMed

Sabbaghi, S; Aldeen, M; Garnavi, R; Varigos, G; Doliantis, C; Nicolopoulos, J

2015-08-01

Colour information plays an important role in classifying skin lesion. However, colour identification by dermatologists can be very subjective, leading to cases of misdiagnosis. Therefore, a computer-assisted system for quantitative colour identification is highly desirable for dermatologists to use. Although numerous colour detection systems have been developed, few studies have focused on imitating the human visual perception of colours in melanoma application. In this paper we propose a new methodology based on QuadTree decomposition technique for automatic colour identification in dermoscopy images. Our approach mimics the human perception of lesion colours. The proposed method is trained on a set of 47 images from NIH dataset and applied to a test set of 190 skin lesions obtained from PH2 dataset. The results of our proposed method are compared with a recently reported colour identification method using the same dataset. The effectiveness of our method in detecting colours in dermoscopy images is vindicated by obtaining approximately 93% accuracy when the CIELab1 colour space is used.

Light-Addressable Potentiometric Sensors for Quantitative Spatial Imaging of Chemical Species.

PubMed

Yoshinobu, Tatsuo; Miyamoto, Ko-Ichiro; Werner, Carl Frederik; Poghossian, Arshak; Wagner, Torsten; Schöning, Michael J

2017-06-12

A light-addressable potentiometric sensor (LAPS) is a semiconductor-based chemical sensor, in which a measurement site on the sensing surface is defined by illumination. This light addressability can be applied to visualize the spatial distribution of pH or the concentration of a specific chemical species, with potential applications in the fields of chemistry, materials science, biology, and medicine. In this review, the features of this chemical imaging sensor technology are compared with those of other technologies. Instrumentation, principles of operation, and various measurement modes of chemical imaging sensor systems are described. The review discusses and summarizes state-of-the-art technologies, especially with regard to the spatial resolution and measurement speed; for example, a high spatial resolution in a submicron range and a readout speed in the range of several tens of thousands of pixels per second have been achieved with the LAPS. The possibility of combining this technology with microfluidic devices and other potential future developments are discussed.

A sprayable luminescent pH sensor and its use for wound imaging in vivo.

PubMed

Schreml, Stephan; Meier, Robert J; Weiß, Katharina T; Cattani, Julia; Flittner, Dagmar; Gehmert, Sebastian; Wolfbeis, Otto S; Landthaler, Michael; Babilas, Philipp

2012-12-01

Non-invasive luminescence imaging is of great interest for studying biological parameters in wound healing, tumors and other biomedical fields. Recently, we developed the first method for 2D luminescence imaging of pH in vivo on humans, and a novel method for one-stop-shop visualization of oxygen and pH using the RGB read-out of digital cameras. Both methods make use of semitransparent sensor foils. Here, we describe a sprayable ratiometric luminescent pH sensor, which combines properties of both these methods. Additionally, a major advantage is that the sensor spray is applicable to very uneven tissue surfaces due to its consistency. A digital RGB image of the spray on tissue is taken. The signal of the pH indicator (fluorescein isothiocyanate) is stored in the green channel (G), while that of the reference dye [ruthenium(II)-tris-(4,7-diphenyl-1,10-phenanthroline)] is stored in the red channel (R). Images are processed by rationing luminescence intensities (G/R) to result in pseudocolor pH maps of tissues, e.g. wounds. © 2012 John Wiley & Sons A/S.

pH induced contrast in viscoelasticity imaging of biopolymers

PubMed Central

Yapp, R D; Insana, M F

2009-01-01

Understanding contrast mechanisms and identifying discriminating features is at the heart of diagnostic imaging development. This report focuses on how pH influences the viscoelastic properties of biopolymers to better understand the effects of extracellular pH on breast tumour elasticity imaging. Extracellular pH is known to decrease as much as 1 pH unit in breast tumours, thus creating a dangerous environment that increases cellular mutatation rates and therapeutic resistance. We used a gelatin hydrogel phantom to isolate the effects of pH on a polymer network with similarities to the extracellular matrix in breast stroma. Using compressive unconfined creep and stress relaxation measurements, we systematically measured the viscoelastic features sensitive to pH by way of time domain models and complex modulus analysis. These results are used to determine the sensitivity of quasi-static ultrasonic elasticity imaging to pH. We found a strong elastic response of the polymer network to pH, such that the matrix stiffness decreases as pH was reduced, however the viscous response of the medium to pH was negligible. While physiological features of breast stroma such as proteoglycans and vascular networks are not included in our hydrogel model, observations in this study provide insight into viscoelastic features specific to pH changes in the collagenous stromal network. These observations suggest that the large contrast common in breast tumours with desmoplasia may be reduced under acidic conditions, and that viscoelastic features are unlikely to improve discriminability. PMID:19174599

Phosphorus Imaging as a Tool for Studying the pH Metabolism in Living Insects

NASA Astrophysics Data System (ADS)

Skibbe, U.; Christeller, J. T.; Eccles, C. D.; Laing, W. A.; Callaghan, P. T.

1995-09-01

Comparative 31P NMR and 1H NMR imaging experiments at submillimeter pixel resolution were carried out, using a specially constructed solenoidal RF coil. Chemical-shift imaging is used to provide pH maps from the midgut of a Lepidopteran larvae and to demonstrate physiological dependence in the resulting images, The titration curve of pH versus chemical shift for inorganic phosphate is extended beyond the "normal" biological range to the strong alkaline limit.

Quantitative Chemical Exchange Saturation Transfer MRI of Intervertebral Disc in a Porcine Model

PubMed Central

Zhou, Zhengwei; Bez, Maxim; Tawackoli, Wafa; Giaconi, Joseph; Sheyn, Dmitriy; de Mel, Sandra; Maya, Marcel M.; Pressman, Barry D.; Gazit, Zulma; Pelled, Gadi; Gazit, Dan; Li, Debiao

2017-01-01

Purpose Previous studies have associated low pH in interver-tebral discs (IVDs) with discogenic back pain. The purpose of this study was to determine whether quantitative CEST (qCEST) MRI can be used to detect pH changes in IVDs in vivo. Methods The exchange rate ksw between glycosaminoglycan (GAG) protons and water protons was determined from qCEST analysis. Its dependence on pH value was investigated in GAG phantoms with varying pH and concentrations. The relationship between ksw and pH was studied further in vivo in a porcine model on a 3T MR scanner and validated using a pH meter. Sodium lactate was injected into the IVDs to induce various pH values within the discs ranging from 5 to 7. Results Phantom and animal results revealed that ksw measured using qCEST MRI is highly correlated with pH level. In the animal studies, the relationship can be described as ksw =9.2 × 106 × 10−pH + 196.9, R2 = 0.7883. Conclusion The exchange rate between GAG and water protons determined from qCEST MRI is closely correlated with pH value. This technique has the potential to noninvasively measure pH in the IVDs of patients with discogenic pain. PMID:27670140

Zonal NePhRO scoring system: a superior renal tumor complexity classification model.

PubMed

Hakky, Tariq S; Baumgarten, Adam S; Allen, Bryan; Lin, Hui-Yi; Ercole, Cesar E; Sexton, Wade J; Spiess, Philippe E

2014-02-01

Since the advent of the first standardized renal tumor complexity system, many subsequent scoring systems have been introduced, many of which are complicated and can make it difficult to accurately measure data end points. In light of these limitations, we introduce the new zonal NePhRO scoring system. The zonal NePhRO score is based on 4 anatomical components that are assigned a score of 1, 2, or 3, and their sum is used to classify renal tumors. The zonal NePhRO scoring system is made up of the (Ne)arness to collecting system, (Ph)ysical location of the tumor in the kidney, (R)adius of the tumor, and (O)rganization of the tumor. In this retrospective study, we evaluated patients exhibiting clinical stage T1a or T1b who underwent open partial nephrectomy performed by 2 genitourinary surgeons. Each renal unit was assigned both a zonal NePhRO score and a RENAL (radius, exophytic/endophytic properties, nearness of tumor to the collecting system or sinus in millimeters, anterior/posterior, location relative to polar lines) score, and a blinded reviewer used the same preoperative imaging study to obtain both scores. Additional data points gathered included age, clamp time, complication rate, urine leak rate, intraoperative blood loss, and pathologic tumor size. One hundred sixty-six patients underwent open partial nephrectomy. There were 37 perioperative complications quantitated using the validated Clavien-Dindo system; their occurrence was predicted by the NePhRO score on both univariate and multivariate analyses (P = .0008). Clinical stage, intraoperative blood loss, and tumor diameter were all correlated with the zonal NePhRO score on univariate analysis only. The zonal NePhRO scoring system is a simpler tool that accurately predicts the surgical complexity of a renal lesion. Copyright © 2014 Elsevier Inc. All rights reserved.

Skin thickness effects on in vivo LXRF

DOE Office of Scientific and Technical Information (OSTI.GOV)

Preiss, I.L.; Washington, W. II

The analysis of lead concentration in bone utilizing LXRF can be adversely effected by overlying issue. A quantitative measure of the attenuation of the 10.5 keV Pb L a x-ray signal by skin and skin equivalent plastic has been conducted. Concentration ranges in plaster of Paris and goat bone from 7 to 90 ppm with attenuators of Lucite{reg_sign} and pig skin were examined. It is concluded that no quantitative or semi quantitative analysis can be achieved if overlying sue thickness exceeds 3 mm for Ph concentrations of less than 30 porn Ph in bone.

Mitochondrial redox and pH signaling occurs in axonal and synaptic organelle clusters.

PubMed

Breckwoldt, Michael O; Armoundas, Antonis A; Aon, Miguel A; Bendszus, Martin; O'Rourke, Brian; Schwarzländer, Markus; Dick, Tobias P; Kurz, Felix T

2016-03-22

Redox switches are important mediators in neoplastic, cardiovascular and neurological disorders. We recently identified spontaneous redox signals in neurons at the single mitochondrion level where transients of glutathione oxidation go along with shortening and re-elongation of the organelle. We now have developed advanced image and signal-processing methods to re-assess and extend previously obtained data. Here we analyze redox and pH signals of entire mitochondrial populations. In total, we quantified the effects of 628 redox and pH events in 1797 mitochondria from intercostal axons and neuromuscular synapses using optical sensors (mito-Grx1-roGFP2; mito-SypHer). We show that neuronal mitochondria can undergo multiple redox cycles exhibiting markedly different signal characteristics compared to single redox events. Redox and pH events occur more often in mitochondrial clusters (medium cluster size: 34.1 ± 4.8 μm(2)). Local clusters possess higher mitochondrial densities than the rest of the axon, suggesting morphological and functional inter-mitochondrial coupling. We find that cluster formation is redox sensitive and can be blocked by the antioxidant MitoQ. In a nerve crush paradigm, mitochondrial clusters form sequentially adjacent to the lesion site and oxidation spreads between mitochondria. Our methodology combines optical bioenergetics and advanced signal processing and allows quantitative assessment of entire mitochondrial populations.

Design and performance evaluation of a 20-aperture multipinhole collimator for myocardial perfusion imaging applications.

PubMed

Bowen, Jason D; Huang, Qiu; Ellin, Justin R; Lee, Tzu-Cheng; Shrestha, Uttam; Gullberg, Grant T; Seo, Youngho

2013-10-21

Single photon emission computed tomography (SPECT) myocardial perfusion imaging remains a critical tool in the diagnosis of coronary artery disease. However, after more than three decades of use, photon detection efficiency remains poor and unchanged. This is due to the continued reliance on parallel-hole collimators first introduced in 1964. These collimators possess poor geometric efficiency. Here we present the performance evaluation results of a newly designed multipinhole collimator with 20 pinhole apertures (PH20) for commercial SPECT systems. Computer simulations and numerical observer studies were used to assess the noise, bias and diagnostic imaging performance of a PH20 collimator in comparison with those of a low energy high resolution (LEHR) parallel-hole collimator. Ray-driven projector/backprojector pairs were used to model SPECT imaging acquisitions, including simulation of noiseless projection data and performing MLEM/OSEM image reconstructions. Poisson noise was added to noiseless projections for realistic projection data. Noise and bias performance were investigated for five mathematical cardiac and torso (MCAT) phantom anatomies imaged at two gantry orbit positions (19.5 and 25.0 cm). PH20 and LEHR images were reconstructed with 300 MLEM iterations and 30 OSEM iterations (ten subsets), respectively. Diagnostic imaging performance was assessed by a receiver operating characteristic (ROC) analysis performed on a single MCAT phantom; however, in this case PH20 images were reconstructed with 75 pixel-based OSEM iterations (four subsets). Four PH20 projection views from two positions of a dual-head camera acquisition and 60 LEHR projections were simulated for all studies. At uniformly-imposed resolution of 12.5 mm, significant improvements in SNR and diagnostic sensitivity (represented by the area under the ROC curve, or AUC) were realized when PH20 collimators are substituted for LEHR parallel-hole collimators. SNR improves by factors of 1.94-2.34 for the five patient anatomies and two orbital positions studied. For the ROC analysis the PH20 AUC is larger than the LEHR AUC with a p-value of 0.0067. Bias performance, however, decreases with the use of PH20 collimators. Systematic analyses showed PH20 collimators present improved diagnostic imaging performance over LEHR collimators, requiring only collimator exchange on existing SPECT cameras for their use.

Design and performance evaluation of a 20-aperture multipinhole collimator for myocardial perfusion imaging applications

NASA Astrophysics Data System (ADS)

Bowen, Jason D.; Huang, Qiu; Ellin, Justin R.; Lee, Tzu-Cheng; Shrestha, Uttam; Gullberg, Grant T.; Seo, Youngho

2013-10-01

Single photon emission computed tomography (SPECT) myocardial perfusion imaging remains a critical tool in the diagnosis of coronary artery disease. However, after more than three decades of use, photon detection efficiency remains poor and unchanged. This is due to the continued reliance on parallel-hole collimators first introduced in 1964. These collimators possess poor geometric efficiency. Here we present the performance evaluation results of a newly designed multipinhole collimator with 20 pinhole apertures (PH20) for commercial SPECT systems. Computer simulations and numerical observer studies were used to assess the noise, bias and diagnostic imaging performance of a PH20 collimator in comparison with those of a low energy high resolution (LEHR) parallel-hole collimator. Ray-driven projector/backprojector pairs were used to model SPECT imaging acquisitions, including simulation of noiseless projection data and performing MLEM/OSEM image reconstructions. Poisson noise was added to noiseless projections for realistic projection data. Noise and bias performance were investigated for five mathematical cardiac and torso (MCAT) phantom anatomies imaged at two gantry orbit positions (19.5 and 25.0 cm). PH20 and LEHR images were reconstructed with 300 MLEM iterations and 30 OSEM iterations (ten subsets), respectively. Diagnostic imaging performance was assessed by a receiver operating characteristic (ROC) analysis performed on a single MCAT phantom; however, in this case PH20 images were reconstructed with 75 pixel-based OSEM iterations (four subsets). Four PH20 projection views from two positions of a dual-head camera acquisition and 60 LEHR projections were simulated for all studies. At uniformly-imposed resolution of 12.5 mm, significant improvements in SNR and diagnostic sensitivity (represented by the area under the ROC curve, or AUC) were realized when PH20 collimators are substituted for LEHR parallel-hole collimators. SNR improves by factors of 1.94-2.34 for the five patient anatomies and two orbital positions studied. For the ROC analysis the PH20 AUC is larger than the LEHR AUC with a p-value of 0.0067. Bias performance, however, decreases with the use of PH20 collimators. Systematic analyses showed PH20 collimators present improved diagnostic imaging performance over LEHR collimators, requiring only collimator exchange on existing SPECT cameras for their use.

Imaging of pH in vivo using hyperpolarized 13C-labelled zymonic acid

PubMed Central

Düwel, Stephan; Hundshammer, Christian; Gersch, Malte; Feuerecker, Benedikt; Steiger, Katja; Buck, Achim; Walch, Axel; Haase, Axel; Glaser, Steffen J.; Schwaiger, Markus; Schilling, Franz

2017-01-01

Natural pH regulatory mechanisms can be overruled during several pathologies such as cancer, inflammation and ischaemia, leading to local pH changes in the human body. Here we demonstrate that 13C-labelled zymonic acid (ZA) can be used as hyperpolarized magnetic resonance pH imaging sensor. ZA is synthesized from [1-13C]pyruvic acid and its 13C resonance frequencies shift up to 3.0 p.p.m. per pH unit in the physiological pH range. The long lifetime of the hyperpolarized signal enhancement enables monitoring of pH, independent of concentration, temperature, ionic strength and protein concentration. We show in vivo pH maps within rat kidneys and subcutaneously inoculated tumours derived from a mammary adenocarcinoma cell line and characterize ZA as non-toxic compound predominantly present in the extracellular space. We suggest that ZA represents a reliable and non-invasive extracellular imaging sensor to localize and quantify pH, with the potential to improve understanding, diagnosis and therapy of diseases characterized by aberrant acid-base balance. PMID:28492229

Smartphone-based quantitative measurements on holographic sensors.

PubMed

Khalili Moghaddam, Gita; Lowe, Christopher Robin

2017-01-01

The research reported herein integrates a generic holographic sensor platform and a smartphone-based colour quantification algorithm in order to standardise and improve the determination of the concentration of analytes of interest. The utility of this approach has been exemplified by analysing the replay colour of the captured image of a holographic pH sensor in near real-time. Personalised image encryption followed by a wavelet-based image compression method were applied to secure the image transfer across a bandwidth-limited network to the cloud. The decrypted and decompressed image was processed through four principal steps: Recognition of the hologram in the image with a complex background using a template-based approach, conversion of device-dependent RGB values to device-independent CIEXYZ values using a polynomial model of the camera and computation of the CIEL*a*b* values, use of the colour coordinates of the captured image to segment the image, select the appropriate colour descriptors and, ultimately, locate the region of interest (ROI), i.e. the hologram in this case, and finally, application of a machine learning-based algorithm to correlate the colour coordinates of the ROI to the analyte concentration. Integrating holographic sensors and the colour image processing algorithm potentially offers a cost-effective platform for the remote monitoring of analytes in real time in readily accessible body fluids by minimally trained individuals.

Smartphone-based quantitative measurements on holographic sensors

PubMed Central

Khalili Moghaddam, Gita

2017-01-01

The research reported herein integrates a generic holographic sensor platform and a smartphone-based colour quantification algorithm in order to standardise and improve the determination of the concentration of analytes of interest. The utility of this approach has been exemplified by analysing the replay colour of the captured image of a holographic pH sensor in near real-time. Personalised image encryption followed by a wavelet-based image compression method were applied to secure the image transfer across a bandwidth-limited network to the cloud. The decrypted and decompressed image was processed through four principal steps: Recognition of the hologram in the image with a complex background using a template-based approach, conversion of device-dependent RGB values to device-independent CIEXYZ values using a polynomial model of the camera and computation of the CIEL*a*b* values, use of the colour coordinates of the captured image to segment the image, select the appropriate colour descriptors and, ultimately, locate the region of interest (ROI), i.e. the hologram in this case, and finally, application of a machine learning-based algorithm to correlate the colour coordinates of the ROI to the analyte concentration. Integrating holographic sensors and the colour image processing algorithm potentially offers a cost-effective platform for the remote monitoring of analytes in real time in readily accessible body fluids by minimally trained individuals. PMID:29141008

Colorimetric Determination of pH.

ERIC Educational Resources Information Center

Tucker, Sheryl; And Others

1989-01-01

Presented is an activity in which the pH of a solution can be quantitatively measured using a spectrophotometer. The theory, experimental details, sample preparation and selection, instrumentation, and results are discussed. (CW)

Left Ventricular End-Systolic Eccentricity Index for Assessment of Pulmonary Hypertension in Infants.

PubMed

Abraham, Sharon; Weismann, Constance G

2016-06-01

Pulmonary hypertension (PH) is a common problem in the neonatal intensive care unit and is associated with significant morbidity and mortality. The aim of this study was to identify a quantitative echocardiographic marker of septal curvature that can be used to accurately identify PH in NICU infants with concern for PH. Echocardiograms of infants who were prematurely born and infants with persistent pulmonary hypertension of the newborn were performed using a defined protocol for evaluation of PH. Qualitative assessment by a single pediatric cardiologist was used as a reference standard. Qualitative and quantitative parameters of right ventricular (RV) size, pressure, and function were documented. Left ventricular end-systolic eccentricity index (EI) was defined as the ratio of the anterior-inferior and septal-posterolateral cavity dimensions at the mid-ventricular level. A total of 216 infants at risk for PH were included in this study. One hundred forty-three (66%) had an interpretable tricuspid regurgitation jet velocity. While systolic septal flattening was recognized at EIs ≥ 1.15, more than half-systemic RV pressure became apparent at EIs ≥ 1.3. Unlike qualitative assessment of septal flattening, there was high inter-observer agreement for EIs. Quantitative parameters of RV systolic function were impaired only at EIs ≥ 1.3. We suggest that EIs should be incorporated into routine protocols when there is a concern for PH in neonates. This may lead to a more reliable assessment of PH and may reduce inter-observer variability. Correlation of EIs with invasive hemodynamic data is needed to validate our results. © 2016, Wiley Periodicals, Inc.

pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent

PubMed Central

Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C.; Yu, Jing; Vinogradov, Elena; Lenkinski, Robert E.; Sherry, A. Dean

2015-01-01

Purpose This study explored the feasibility of using a pH responsive paraCEST agent to image the pH gradient in kidneys of healthy mice. Methods CEST signals were acquired on an Agilent 9.4 T small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. Results Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min post-injection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. Conclusion This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. PMID:26173637

Intestine pH measurements using fluorescence imaging: an in-vivo preliminary study

NASA Astrophysics Data System (ADS)

Marechal, Xavier-Marie; Mordon, Serge R.; Devoisselle, Jean-Marie; Begu, Sylvie; Mathieu, D.; Buys, Bruno; Dhelin, Guy; Lesage, Jean C.; Neviere, Remi; Chopin, Claude

1999-02-01

Measurement of gastrointestinal intramucosal pH has been recognized as an important factor in the detection of hypoxia-induced dysfunctions. However, current pH measurement techniques are limited in terms of time and spatial resolution. A major advance in accurate pH measurement was the development of the ratiometric fluorescent indicator dye, 2',7'-bis(carboxyethyl)-4,5- carboxyfluorescein (BCECF). This study aimed to demonstrate the feasibility of fluorescence imaging technique to measure in vivo the pH of intestine. The intestine was inserted in an optical chamber placed under a microscope. Animals were injected i.v. with the pH-sensitive fluorescent dye BCECF. Fluorescence was visualized by illuminating the intestine alternately at 490 and 470 nm. The emitted fluorescence was directed to an intensified camera. The ratio of emitted fluorescence at excitation wavelengths of 490 and 470 nm was measured, corrected and converted to pH by constructing a calibration curve. The pH controls were performed with a pH microelectrode correlated with venous blood gas sampling. We concluded that accurate pH measurements of rat intestine can be obtained by fluorescence imaging using BCECF. This technology could be easily adapted for endoscopic pH measurement.

Quantitative trait locus analysis of heterosis for plant height and ear height in an elite maize hybrid zhengdan 958 by design III.

PubMed

Li, Hongjian; Yang, Qingsong; Fan, Nannan; Zhang, Ming; Zhai, Huijie; Ni, Zhongfu; Zhang, Yirong

2017-04-17

Plant height (PH) and ear height (EH) are two important agronomic traits in maize selection breeding. F 1 hybrid exhibit significant heterosis for PH and EH as compared to their parental inbred lines. To understand the genetic basis of heterosis controlling PH and EH, we conducted quantitative trait locus (QTL) analysis using a recombinant inbreed line (RIL) based design III population derived from the elite maize hybrid Zhengdan 958 in five environments. A total of 14 environmentally stable QTLs were identified, and the number of QTLs for Z 1 and Z 2 populations was six and eight, respectively. Notably, all the eight environmentally stable QTLs for Z 2 were characterized by overdominance effect (OD), suggesting that overdominant QTLs were the most important contributors to heterosis for PH and EH. Furthermore, 14 environmentally stable QTLs were anchored on six genomic regions, among which four are trait-specific QTLs, suggesting that the genetic basis for PH and EH is partially different. Additionally, qPH.A-1.3, modifying about 10 centimeters of PH, was further validated in backcross populations. The genetic basis for PH and EH is partially different, and overdominant QTLs are important factors for heterosis of PH and EH. A major QTL qPH.A-1.3 may be a desired target for genetic improvement of maize plant height.

Brain Injury Lesion Imaging Using Preconditioned Quantitative Susceptibility Mapping without Skull Stripping.

PubMed

Soman, S; Liu, Z; Kim, G; Nemec, U; Holdsworth, S J; Main, K; Lee, B; Kolakowsky-Hayner, S; Selim, M; Furst, A J; Massaband, P; Yesavage, J; Adamson, M M; Spincemallie, P; Moseley, M; Wang, Y

2018-04-01

Identifying cerebral microhemorrhage burden can aid in the diagnosis and management of traumatic brain injury, stroke, hypertension, and cerebral amyloid angiopathy. MR imaging susceptibility-based methods are more sensitive than CT for detecting cerebral microhemorrhage, but methods other than quantitative susceptibility mapping provide results that vary with field strength and TE, require additional phase maps to distinguish blood from calcification, and depict cerebral microhemorrhages as bloom artifacts. Quantitative susceptibility mapping provides universal quantification of tissue magnetic property without these constraints but traditionally requires a mask generated by skull-stripping, which can pose challenges at tissue interphases. We evaluated the preconditioned quantitative susceptibility mapping MR imaging method, which does not require skull-stripping, for improved depiction of brain parenchyma and pathology. Fifty-six subjects underwent brain MR imaging with a 3D multiecho gradient recalled echo acquisition. Mask-based quantitative susceptibility mapping images were created using a commonly used mask-based quantitative susceptibility mapping method, and preconditioned quantitative susceptibility images were made using precondition-based total field inversion. All images were reviewed by a neuroradiologist and a radiology resident. Ten subjects (18%), all with traumatic brain injury, demonstrated blood products on 3D gradient recalled echo imaging. All lesions were visible on preconditioned quantitative susceptibility mapping, while 6 were not visible on mask-based quantitative susceptibility mapping. Thirty-one subjects (55%) demonstrated brain parenchyma and/or lesions that were visible on preconditioned quantitative susceptibility mapping but not on mask-based quantitative susceptibility mapping. Six subjects (11%) demonstrated pons artifacts on preconditioned quantitative susceptibility mapping and mask-based quantitative susceptibility mapping; they were worse on preconditioned quantitative susceptibility mapping. Preconditioned quantitative susceptibility mapping MR imaging can bring the benefits of quantitative susceptibility mapping imaging to clinical practice without the limitations of mask-based quantitative susceptibility mapping, especially for evaluating cerebral microhemorrhage-associated pathologies, such as traumatic brain injury. © 2018 by American Journal of Neuroradiology.

A review of optimization and quantification techniques for chemical exchange saturation transfer (CEST) MRI toward sensitive in vivo imaging

PubMed Central

Guo, Yingkun; Zheng, Hairong; Sun, Phillip Zhe

2015-01-01

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging method that probes the chemical exchange between bulk water and exchangeable protons. CEST imaging indirectly detects dilute labile protons via bulk water signal changes following selective saturation of exchangeable protons, which offers substantial sensitivity enhancement and has sparked numerous biomedical applications. Over the past decade, CEST imaging techniques have rapidly evolved due to contributions from multiple domains, including the development of CEST mathematical models, innovative contrast agent designs, sensitive data acquisition schemes, efficient field inhomogeneity correction algorithms, and quantitative CEST (qCEST) analysis. The CEST system that underlies the apparent CEST-weighted effect, however, is complex. The experimentally measurable CEST effect depends not only on parameters such as CEST agent concentration, pH and temperature, but also on relaxation rate, magnetic field strength and more importantly, experimental parameters including repetition time, RF irradiation amplitude and scheme, and image readout. Thorough understanding of the underlying CEST system using qCEST analysis may augment the diagnostic capability of conventional imaging. In this review, we provide a concise explanation of CEST acquisition methods and processing algorithms, including their advantages and limitations, for optimization and quantification of CEST MRI experiments. PMID:25641791

Differential plating medium for quantitative detection of histamine-producing bacteria.

PubMed Central

Niven, C F; Jeffrey, M B; Corlett, D A

1981-01-01

A histidine-containing agar medium has been devised for quantitative detection of histamine-producing bacteria that are alleged to be associated with scombroid fish poisoning outbreaks. The responsible bacteria produce a marked pH change in the agar, with attendant color change of pH indicator adjacent to the colonies, thus facilitating their recognition. Proteus morganii and Klebsiella pneumoniae were the two most common histidine-decarboxylating species isolated from scombroid fish and mahi mahi. PMID:7013698

Separation of thorium from lanthanides by solvent extraction with ionizable crown ethers.

PubMed

Du, H S; Wood, D J; Elshani, S; Wai, C M

1993-02-01

Thorium and the lanthanides are extracted by alpha-(sym-dibenzo-16-crown-5-oxy)acetic acid and its analogues in different pH ranges. At pH 4.5, Th is quantitatively extracted by the crown ether carboxylic acids into chloroform whereas the extraction of the lanthanides is negligible. Separation of Th from the lanthanides can be achieved by solvent extraction under this condition. The extraction does not require specific counteranions and is reversible with respect to pH. Trace amounts of Th in water can be quantitatively recovered using this extraction system for neutron activation analysis. The nature of the extracted Th complex and the mechanism of extraction are discussed.

Precision Sensing by Two Opposing Gradient Sensors: How Does Escherichia coli Find its Preferred pH Level?

PubMed Central

Hu, Bo; Tu, Yuhai

2013-01-01

It is essential for bacteria to find optimal conditions for their growth and survival. The optimal levels of certain environmental factors (such as pH and temperature) often correspond to some intermediate points of the respective gradients. This requires the ability of bacteria to navigate from both directions toward the optimum location and is distinct from the conventional unidirectional chemotactic strategy. Remarkably, Escherichia coli cells can perform such a precision sensing task in pH taxis by using the same chemotaxis machinery, but with opposite pH responses from two different chemoreceptors (Tar and Tsr). To understand bacterial pH sensing, we developed an Ising-type model for a mixed cluster of opposing receptors based on the push-pull mechanism. Our model can quantitatively explain experimental observations in pH taxis for various mutants and wild-type cells. We show how the preferred pH level depends on the relative abundance of the competing sensors and how the sensory activity regulates the behavioral response. Our model allows us to make quantitative predictions on signal integration of pH and chemoattractant stimuli. Our study reveals two general conditions and a robust push-pull scheme for precision sensing, which should be applicable in other adaptive sensory systems with opposing gradient sensors. PMID:23823247

Label-free silicon nanodots featured ratiometric fluorescent aptasensor for lysosomal imaging and pH measurement.

PubMed

Zhang, Yanan; Guo, Shan; Cheng, Shibo; Ji, Xinghu; He, Zhike

2017-08-15

The homeostasis of lysosomal pH is crucial in cell physiology. Developing small fluorescent nanosensors for lysosome imaging and ratiometric measurement of pH is highly demanded yet challenging. Herein, a pH-sensitive fluorescein tagged aptamer AS1411 has been utilized to covalently modify the label-free fluorescent silicon nanodots via a crosslinker for construction of a ratiometric pH biosensor. The established aptasensor exhibits the advantages of ultrasmall size, hypotoxicity, excellent pH reversibility and good photostability, which favors its application in an intracellular environment. Using human breast MCF-7 cancer cells and MCF-10A normal cells as the model, this aptasensor shows cell specificity for cancer cells and displays a wide pH response range of 4.5-8.0 in living cells. The results demonstrate that the pH of MCF-7 cells is 5.1, which is the expected value for acidic organelles. Lysosome imaging and accurate measurement of pH in MCF-7 cells have been successfully conducted based on this nanosensor via fluorescent microscopy and flow cytometry. Copyright © 2017 Elsevier B.V. All rights reserved.

Quantitative structure-permeability relationships at various pH values for acidic and basic drugs and drug-like compounds.

PubMed

Oja, M; Maran, U

2015-01-01

Absorption in gastrointestinal tract compartments varies and is largely influenced by pH. Therefore, considering pH in studies and analyses of membrane permeability provides an opportunity to gain a better understanding of the behaviour of compounds and to obtain good permeability estimates for prediction purposes. This study concentrates on relationships between the chemical structure and membrane permeability of acidic and basic drugs and drug-like compounds. The membrane permeability of 36 acidic and 61 basic compounds was measured using the parallel artificial membrane permeability assay (PAMPA) at pH 3, 5, 7.4 and 9. Descriptive and/or predictive single-parameter quantitative structure-permeability relationships were derived for all pH values. For acidic compounds, membrane permeability is mainly influenced by hydrogen bond donor properties, as revealed by models with r(2) > 0.8 for pH 3 and pH 5. For basic compounds, the best (r(2) > 0.7) structure-permeability relationships are obtained with the octanol-water distribution coefficient for pH 7.4 and pH 9, indicating the importance of partition properties. In addition to the validation set, the prediction quality of the developed models was tested with folic acid and astemizole, showing good matches between experimental and calculated membrane permeabilities at key pHs. Selected QSAR models are available at the QsarDB repository ( http://dx.doi.org/10.15152/QDB.166 ).

Principles of Quantitative MR Imaging with Illustrated Review of Applicable Modular Pulse Diagrams.

PubMed

Mills, Andrew F; Sakai, Osamu; Anderson, Stephan W; Jara, Hernan

2017-01-01

Continued improvements in diagnostic accuracy using magnetic resonance (MR) imaging will require development of methods for tissue analysis that complement traditional qualitative MR imaging studies. Quantitative MR imaging is based on measurement and interpretation of tissue-specific parameters independent of experimental design, compared with qualitative MR imaging, which relies on interpretation of tissue contrast that results from experimental pulse sequence parameters. Quantitative MR imaging represents a natural next step in the evolution of MR imaging practice, since quantitative MR imaging data can be acquired using currently available qualitative imaging pulse sequences without modifications to imaging equipment. The article presents a review of the basic physical concepts used in MR imaging and how quantitative MR imaging is distinct from qualitative MR imaging. Subsequently, the article reviews the hierarchical organization of major applicable pulse sequences used in this article, with the sequences organized into conventional, hybrid, and multispectral sequences capable of calculating the main tissue parameters of T1, T2, and proton density. While this new concept offers the potential for improved diagnostic accuracy and workflow, awareness of this extension to qualitative imaging is generally low. This article reviews the basic physical concepts in MR imaging, describes commonly measured tissue parameters in quantitative MR imaging, and presents the major available pulse sequences used for quantitative MR imaging, with a focus on the hierarchical organization of these sequences. © RSNA, 2017.

Teaching Plant-Soil Relationships with Color Images of Rhizosphere pH.

ERIC Educational Resources Information Center

Heckman, J. R.; Strick, J. E.

1996-01-01

Presents a laboratory exercise that uses a simple imaging technique to illustrate the profound effects that living roots exert on the pH of the surrounding soil environment. Achieves visually stimulating results that can be used to reinforce lectures on rhizosphere pH, nutrient availability, plant tolerance of soil acidity, microbial activity, and…

pH imaging of mouse kidneys in vivo using a frequency-dependent paraCEST agent.

PubMed

Wu, Yunkou; Zhang, Shanrong; Soesbe, Todd C; Yu, Jing; Vinogradov, Elena; Lenkinski, Robert E; Sherry, A Dean

2016-06-01

This study explored the feasibility of using a pH responsive paramagnetic chemical exchange saturation transfer (paraCEST) agent to image the pH gradient in kidneys of healthy mice. CEST signals were acquired on an Agilent 9.4 Tesla small animal MRI system using a steady-state gradient echo pulse sequence after a bolus injection of agent. The magnetic field inhomogeneity across each kidney was corrected using the WASSR method and pH maps were calculated by measuring the frequency of water exchange signal arising from the agent. Dynamic CEST studies demonstrated that the agent was readily detectable in kidneys only between 4 to 12 min postinjection. The CEST images showed a higher signal intensity in the pelvis and calyx regions and lower signal intensity in the medulla and cortex regions. The pH maps reflected tissue pH values spanning from 6.0 to 7.5 in kidneys of healthy mice. This study demonstrated that pH maps of the kidney can be imaged in vivo by measuring the pH-dependent chemical shift of a single water exchange CEST peak without prior knowledge of the agent concentration in vivo. The results demonstrate the potential of using a simple frequency-dependent paraCEST agent for mapping tissue pH in vivo. Magn Reson Med 75:2432-2441, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

A Soft, Wearable Microfluidic Device for the Capture, Storage, and Colorimetric Sensing of Sweat

PubMed Central

Koh, Ahyeon; Kang, Daeshik; Xue, Yeguang; Lee, Seungmin; Pielak, Rafal M.; Kim, Jeonghyun; Hwang, Taehwan; Min, Seunghwan; Banks, Anthony; Bastien, Philippe; Manco, Megan C.; Wang, Liang; Ammann, Kaitlyn R.; Jang, Kyung-In; Won, Phillip; Han, Seungyong; Ghaffari, Roozbeh; Paik, Ungyu; Slepian, Marvin J.; Balooch, Guive; Huang, Yonggang; Rogers, John A.

2017-01-01

Capabilities in health monitoring via capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH and concentration of both chloride and lactate. PMID:27881826

Quantitative imaging biomarkers: the application of advanced image processing and analysis to clinical and preclinical decision making.

PubMed

Prescott, Jeffrey William

2013-02-01

The importance of medical imaging for clinical decision making has been steadily increasing over the last four decades. Recently, there has also been an emphasis on medical imaging for preclinical decision making, i.e., for use in pharamaceutical and medical device development. There is also a drive towards quantification of imaging findings by using quantitative imaging biomarkers, which can improve sensitivity, specificity, accuracy and reproducibility of imaged characteristics used for diagnostic and therapeutic decisions. An important component of the discovery, characterization, validation and application of quantitative imaging biomarkers is the extraction of information and meaning from images through image processing and subsequent analysis. However, many advanced image processing and analysis methods are not applied directly to questions of clinical interest, i.e., for diagnostic and therapeutic decision making, which is a consideration that should be closely linked to the development of such algorithms. This article is meant to address these concerns. First, quantitative imaging biomarkers are introduced by providing definitions and concepts. Then, potential applications of advanced image processing and analysis to areas of quantitative imaging biomarker research are described; specifically, research into osteoarthritis (OA), Alzheimer's disease (AD) and cancer is presented. Then, challenges in quantitative imaging biomarker research are discussed. Finally, a conceptual framework for integrating clinical and preclinical considerations into the development of quantitative imaging biomarkers and their computer-assisted methods of extraction is presented.

Toward Quantitative Small Animal Pinhole SPECT: Assessment of Quantitation Accuracy Prior to Image Compensations

PubMed Central

Chen, Chia-Lin; Wang, Yuchuan; Lee, Jason J. S.; Tsui, Benjamin M. W.

2011-01-01

Purpose We assessed the quantitation accuracy of small animal pinhole single photon emission computed tomography (SPECT) under the current preclinical settings, where image compensations are not routinely applied. Procedures The effects of several common image-degrading factors and imaging parameters on quantitation accuracy were evaluated using Monte-Carlo simulation methods. Typical preclinical imaging configurations were modeled, and quantitative analyses were performed based on image reconstructions without compensating for attenuation, scatter, and limited system resolution. Results Using mouse-sized phantom studies as examples, attenuation effects alone degraded quantitation accuracy by up to −18% (Tc-99m or In-111) or −41% (I-125). The inclusion of scatter effects changed the above numbers to −12% (Tc-99m or In-111) and −21% (I-125), respectively, indicating the significance of scatter in quantitative I-125 imaging. Region-of-interest (ROI) definitions have greater impacts on regional quantitation accuracy for small sphere sources as compared to attenuation and scatter effects. For the same ROI, SPECT acquisitions using pinhole apertures of different sizes could significantly affect the outcome, whereas the use of different radii-of-rotation yielded negligible differences in quantitation accuracy for the imaging configurations simulated. Conclusions We have systematically quantified the influence of several factors affecting the quantitation accuracy of small animal pinhole SPECT. In order to consistently achieve accurate quantitation within 5% of the truth, comprehensive image compensation methods are needed. PMID:19048346

Candida tropicalis biofilm and human epithelium invasion is highly influenced by environmental pH.

PubMed

Ferreira, Carina; Gonçalves, Bruna; Vilas Boas, Diana; Oliveira, Hugo; Henriques, Mariana; Azeredo, Joana; Silva, Sónia

2016-11-01

The main goal of this study was to investigate the role of pH on Candida tropicalis virulence determinants, namely the ability to form biofilms and to colonize/invade reconstituted human vaginal epithelia. Biofilm formation was evaluated by enumeration of cultivable cells, total biomass quantification and structural analysis by scanning electron microscopy and confocal laser scanning microscopy. Candida tropicalis human vaginal epithelium colonization and invasiveness were examined qualitatively by epifluorescence microscopy and quantitatively by a novel quantitative real-time PCR protocol for Candida quantification in tissues. The results revealed that environmental pH influences C. tropicalis biofilm formation as well as the colonization and potential to invade human epithelium with intensification at neutral and alkaline conditions compared to acidic conditions. For the first time, we have demonstrated that C. tropicalis biofilm formation and invasion is highly influenced by environmental pH. © Crown copyright 2016.

Phase-sensitive optical coherence tomography characterization of pulse-induced trabecular meshwork displacement in ex vivo nonhuman primate eyes

NASA Astrophysics Data System (ADS)

Li, Peng; Reif, Roberto; Zhi, Zhongwei; Martin, Elizabeth; Shen, Tueng T.; Johnstone, Murray; Wang, Ruikang K.

2012-07-01

Glaucoma is a blinding disease for which intraocular pressure (IOP) is the only treatable risk factor. The mean IOP is regulated through the aqueous outflow system, which contains the trabecular meshwork (TM). Considerable evidence indicates that trabecular tissue movement regulates the aqueous outflow and becomes abnormal during glaucoma; however, such motion has thus far escaped detection. The purpose of this study is to describe anovel use of a phase-sensitive optical coherence tomography (PhS-OCT) method to assess pulse-dependent TM movement. For this study, we used enucleated monkey eyes, each mounted in an anterior segment holder. A perfusion system was used to control the mean IOP as well as to provide IOP sinusoidal transients (amplitude 3 mmHg, frequency 1 pulse/second) in all experiments. Measurements were carried out at seven graded mean IOPs (5, 8, 10, 20, 30, 40, and 50 mm Hg). We demonstrate that PhS-OCT is sensitive enough to image/visualize TM movement synchronous with the pulse-induced IOP transients, providing quantitative measurements of dynamic parameters such as velocity, displacement, and strain rate that are important for assessing the biomechanical compliance of the TM. We find that the largest TM displacement is in the area closest to Schlemm's canal (SC) endothelium. While maintaining constant ocular pulse amplitude, an increase of mean IOP results in a decrease of TM displacement and mean size of the SC. These results demonstrate that the PhS-OCT is a useful imaging technique capable of assessing functional properties necessary to maintain IOP in a healthy range, offering a new diagnostic alternative for glaucoma.

[Chemical Exchange Saturation Transfer Imaging of Creatine Metabolites: a 3.0 T MRI Pilot].

PubMed

Guo, Ying-kun; Li, Zhen-lin; Rong, Yu; Xia, Chun-chao; Zhang, Li-zhi; Peng, Wan-ling; Liu, Xi; Xu, Hua-yan; Zhang, Ti-jiang; Zuo, Pan-li; Schmitt, Benjamin

2016-03-01

To determine the feasibility of using chemical exchange saturation transfer (CEST) imaging to measure creatine (Cr) metabolites with 3.0 T MR. Phantoms containing different concentrations of Cr under various pH conditions were studied with CEST sequence on 3.0 T MR imaging. CEST effect and Z spectra were analyzed. Cr exhibited significant CEST effect (± 1.8 ppm, F = 99.08, P < 0.001) on 3.0 T MR imaging, and positive correlation was found between the signal intensity and concentration of Cr (r = 0.963, P < 0.001). The CEST effect showed pH dependency of Cr (r = 0.41, P = 0.035). Creatine CEST imaging can be performed on 3.0 T MR imaging. Creatine concentrations and pH influence CEST effect.

Pulmonary arterial pressure and right ventricular dilatation independently determine tricuspid valve insufficiency severity in pre-capillary pulmonary hypertension.

PubMed

De Meester, Pieter; Van De Bruaene, Alexander; Delcroix, Marion; Belmans, Ann; Herijgers, Paul; Voigt, Jens-Uwe; Budts, Werner

2012-11-01

Elevated pulmonary artery systolic pressure (PASP) causes functional tricuspid valve insufficiency (TI). However, the differential contribution of pressure load and right ventricular (RV) dilatation is not well established. The study aim was to evaluate both variables in relation to TI. A cross-sectional study was performed of consecutive transthoracic echocardiographic studies of patients with pre-capillary pulmonary hypertension (PH). Both, demographic data and echocardiographic RV parameters were reviewed. TI was graded semi-quantitatively with color Doppler flow imaging. Trend analyses for TI severity (TI grade 0/4, 1/4, 2/4, 3/4, or 4/4) were performed. A proportional odds logistic regression analysis was carried out to identify independent predictors of TI severity. Eighty-one patients (56 females, 25 males; mean age 60 +/- 15 years) with pre-capillary PH were evaluated. Patients with more severe TI had a significantly lower body mass index, a lower mean systemic blood pressure, a shorter pulmonary acceleration time, a higher tricuspid regurgitant gradient, and a more dilated right ventricle. From the echocardiographic parameters, RV dilatation (p = 0.0143) and the tricuspid regurgitant gradient (p = 0.0026) were independently related to the degree of TI. In patients with pre-capillary PH, PASP and RV dilatation were both related to the increasing severity of TI. When focusing on TI to improve the prognosis of patients with pre-capillary PH, both PASP and RV dimensions should be taken into consideration.

Detection of elevated right ventricular extracellular volume in pulmonary hypertension using Accelerated and Navigator-Gated Look-Locker Imaging for Cardiac T1 Estimation (ANGIE) cardiovascular magnetic resonance.

PubMed

Mehta, Bhairav B; Auger, Daniel A; Gonzalez, Jorge A; Workman, Virginia; Chen, Xiao; Chow, Kelvin; Stump, Claire J; Mazimba, Sula; Kennedy, Jamie L W; Gay, Elizabeth; Salerno, Michael; Kramer, Christopher M; Epstein, Frederick H; Bilchick, Kenneth C

2015-12-21

Assessment of diffuse right ventricular (RV) fibrosis is of particular interest in pulmonary hypertension (PH) and heart failure (HF). Current cardiovascular magnetic resonance (CMR) T1 mapping techniques such as Modified Look-Locker inversion recovery (MOLLI) imaging have limited resolution, but accelerated and navigator-gated Look-Locker imaging for cardiac T1 estimation (ANGIE) is a novel CMR sequence with spatial resolution suitable for T1 mapping of the RV. We tested the hypothesis that patients with PH would have significantly more RV fibrosis detected with MRI ANGIE compared with normal volunteers and patients having HF with reduced (LV) ejection fraction (HFrEF) without co-existing PH, independent of RV dilitation and dysfunction. Patients with World Health Organization group 1 or group 4 PH, patients with HFrEF without PH, and normal volunteers were recruited to undergo contrast-enhanced CMR. RV and LV extracellular volume fractions (RV-ECV and LV-ECV) were determined using pre-contrast and post-contrast T1 mapping using ANGIE (RV and LV) and MOLLI (LV only). Thirty-two participants (53.1% female, median age 52 years, IQR 26-65 years) were enrolled, including n = 12 with PH, n = 10 having HFrEF without co-existing PH, and n = 10 normal volunteers. ANGIE ECV imaging was of high quality, and ANGIE measurements of LV-ECV were highly correlated with those of MOLLI (r = 0.91; p < 0.001). The RV-ECV in PH patients was 27.2% greater than the RV-ECV in normal volunteers (0.341 v. 0.268; p < 0.0001) and 18.9% greater than the RV-ECV in HFrEF patients without PH (0.341 v. 0.287; p < 0.0001). RV-ECV was greater than LV-ECV in PH (RV-LV difference = 0.04), but RV-ECV was nearly equivalent to LV-ECV in normal volunteers (RV-LV difference = 0.002) (p < 0.0001 for RV-LV difference in PH versus normal volunteers). RV-ECV was linearly associated with both increasing RVEDVI (p = 0.049) and decreasing RVEF (p = 0.04) in a multivariable linear model, but PH was still associated with greater RV-ECV even after adjustment for RVEDVI and RVEF. Pre- and post-contrast ANGIE imaging provides high-resolution ECV determination for the RV. PH is independently associated with increased RV-ECV even after adjustment for RV dilatation and dysfunction, consistent with an independent effect of PH on fibrosis. ANGIE RV imaging merits further clinical evaluation in PH.

Demineralization of resin-sealed enamel by soft drinks in a clinically relevant pH cycling model.

PubMed

Bartels, Agata A; Evans, Carla A; Viana, Grace; Bedran-Russo, Ana K

2016-04-01

To compare the in vitro protective effect of orthodontic sealants on the enamel demineralization under a soft drink-induced erosive challenge. The facial surfaces of bovine incisors were sectioned into 5 mm x 4 mm x 4 mm enamel blocks. Specimens were randomly assigned to three surface protection measures: control (exposed enamel), coating with Transbond XT (unfilled resin primer), or coating with Opal Seal (filled and fluoride releasing primer). Thermocycling was used to simulate aging. The specimens were pH cycled through an acidic buffer, test beverage and a neutral buffer for a total of 7 days. Test beverages included water, Diet Mountain Dew, and Coke Classic. Quantitative light-induced fluorescence (QLF) images were taken at baseline and after aging. Final QLF images were taken to evaluate the demineralization of enamel. Data were analyzed statistically using a two-way ANOVA to compare the interaction between enamel surface protection and beverages as well as one-way ANOVA to compare surface protection and the test beverage levels. A statistically significant interaction was found between the surface protected groups and the test beverage groups (P < 0.05). Statistically significant differences were found among the test beverage groups (P < 0.05) and among the surface protection groups (P < 0.05). Coke Classic went through the sealant layer resulting in high enamel demineralization. Enamel coating with Opal Seal significantly reduced the erosive attack of beverages.

Targeting diseased tissues by pHLIP insertion at low cell surface pH.

PubMed

Andreev, Oleg A; Engelman, Donald M; Reshetnyak, Yana K

2014-01-01

The discovery of the pH Low Insertion Peptides (pHLIPs®) provides an opportunity to develop imaging and drug delivery agents targeting extracellular acidity. Extracellular acidity is associated with many pathological states, such as those in cancer, ischemic stroke, neurotrauma, infection, lacerations, and others. The metabolism of cells in injured or diseased tissues often results in the acidification of the extracellular environment, so acidosis might be useful as a general marker for the imaging and treatment of diseased states if an effective targeting method can be developed. The molecular mechanism of a pHLIP peptide is based on pH-dependent membrane-associated folding. pHLIPs, being moderately hydrophobic peptides, have high affinities for cellular membranes at normal pH, but fold and insert across membranes at low pH, allowing them to sense pH at the surfaces of cells in diseased tissues, where it is the lowest. Here we discuss the main principles of pHLIP interactions with membrane lipid bilayers at neutral and low pHs, the possibility of tuning the folding and insertion pH by peptide sequence variation, and potential applications of pHLIPs for imaging, therapy and image-guided interventions.

Evaluation of acridine orange, LysoTracker Red, and quinacrine as fluorescent probes for long-term tracking of acidic vesicles.

PubMed

Pierzyńska-Mach, Agnieszka; Janowski, Paweł A; Dobrucki, Jurek W

2014-08-01

Acidic vesicles can be imaged and tracked in live cells after staining with several low molecular weight fluorescent probes, or with fluorescently labeled proteins. Three fluorescent dyes, acridine orange, LysoTracker Red DND-99, and quinacrine, were evaluated as acidic vesicle tracers for confocal fluorescence imaging and quantitative analysis. The stability of fluorescent signals, achievable image contrast, and phototoxicity were taken into consideration. The three tested tracers exhibit different advantages and pose different problems in imaging experiments. Acridine orange makes it possible to distinguish acidic vesicles with different internal pH but is fairly phototoxic and can cause spectacular bursts of the dye-loaded vesicles. LysoTracker Red is less phototoxic but its rapid photobleaching limits the range of useful applications considerably. We demonstrate that quinacrine is most suitable for long-term imaging when a high number of frames is required. This capacity made it possible to trace acidic vesicles for several hours, during a process of drug-induced apoptosis. An ability to record the behavior of acidic vesicles over such long periods opens a possibility to study processes like autophagy or long-term effects of drugs on endocytosis and exocytosis. © 2014 International Society for Advancement of Cytometry.

Near infrared fluorescence-based bacteriophage particles for ratiometric pH imaging.

PubMed

Hilderbrand, Scott A; Kelly, Kimberly A; Niedre, Mark; Weissleder, Ralph

2008-08-01

Fluorogenic imaging agents emitting in the near-infrared are becoming important research tools for disease investigation in vivo. Often pathophysiological states such as cancer and cystic fibrosis are associated with disruptions in acid/base homeostasis. The development of optical sensors for pH imaging would facilitate the investigation of these diseased conditions. In this report, the design and synthesis of a ratiometric near-infrared emitting probe for pH quantification is detailed. The pH-responsive probe is prepared by covalent attachment of pH-sensitive and pH-insensitive fluorophores to a bacteriophage particle scaffold. The pH-responsive cyanine dye, HCyC-646, used to construct the probe, has a fluorogenic pKa of 6.2, which is optimized for visualization of acidic pH often associated with tumor hypoxia and other diseased states. Incorporation of pH-insensitive reference dyes enables the ratiometric determination of pH independent of the probe concentration. With the pH-responsive construct, measurement of intracellular pH and accurate determination of pH through optically diffuse biological tissue is demonstrated.

Validity of the Medical College Admission Test for Predicting MD-PhD Student Outcomes

ERIC Educational Resources Information Center

Bills, James L.; VanHouten, Jacob; Grundy, Michelle M.; Chalkley, Roger; Dermody, Terence S.

2016-01-01

The Medical College Admission Test (MCAT) is a quantitative metric used by MD and MD-PhD programs to evaluate applicants for admission. This study assessed the validity of the MCAT in predicting training performance measures and career outcomes for MD-PhD students at a single institution. The study population consisted of 153 graduates of the…

The Benefits of Publishing Systematic Quantitative Literature Reviews for PhD Candidates and Other Early-Career Researchers

ERIC Educational Resources Information Center

Pickering, Catherine; Byrne, Jason

2014-01-01

Universities increasingly expect students to publish during a PhD candidature because it benefits the candidate, supervisor, institution, and wider community. Here, we describe a method successfully used by early-career researchers including PhD candidates to undertake and publish literature reviews--a challenge for researchers new to a field. Our…

Temporal lobe epilepsy: quantitative MR volumetry in detection of hippocampal atrophy.

PubMed

Farid, Nikdokht; Girard, Holly M; Kemmotsu, Nobuko; Smith, Michael E; Magda, Sebastian W; Lim, Wei Y; Lee, Roland R; McDonald, Carrie R

2012-08-01

To determine the ability of fully automated volumetric magnetic resonance (MR) imaging to depict hippocampal atrophy (HA) and to help correctly lateralize the seizure focus in patients with temporal lobe epilepsy (TLE). This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Volumetric MR imaging data were analyzed for 34 patients with TLE and 116 control subjects. Structural volumes were calculated by using U.S. Food and Drug Administration-cleared software for automated quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR imaging were compared with visual detection of atrophy, and, when available, with histologic specimens. Receiver operating characteristic analyses were performed to determine the optimal sensitivity and specificity of quantitative MR imaging for detecting HA and asymmetry. A linear classifier with cross validation was used to estimate the ability of quantitative MR imaging to help lateralize the seizure focus. Quantitative MR imaging-derived hippocampal asymmetries discriminated patients with TLE from control subjects with high sensitivity (86.7%-89.5%) and specificity (92.2%-94.1%). When a linear classifier was used to discriminate left versus right TLE, hippocampal asymmetry achieved 94% classification accuracy. Volumetric asymmetries of other subcortical structures did not improve classification. Compared with invasive video electroencephalographic recordings, lateralization accuracy was 88% with quantitative MR imaging and 85% with visual inspection of volumetric MR imaging studies but only 76% with visual inspection of clinical MR imaging studies. Quantitative MR imaging can depict the presence and laterality of HA in TLE with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Thus, quantitative MR imaging may enhance standard visual analysis, providing a useful and viable means for translating volumetric analysis into clinical practice.

Diagnosis of pulmonary hypertension from magnetic resonance imaging-based computational models and decision tree analysis.

PubMed

Lungu, Angela; Swift, Andrew J; Capener, David; Kiely, David; Hose, Rod; Wild, Jim M

2016-06-01

Accurately identifying patients with pulmonary hypertension (PH) using noninvasive methods is challenging, and right heart catheterization (RHC) is the gold standard. Magnetic resonance imaging (MRI) has been proposed as an alternative to echocardiography and RHC in the assessment of cardiac function and pulmonary hemodynamics in patients with suspected PH. The aim of this study was to assess whether machine learning using computational modeling techniques and image-based metrics of PH can improve the diagnostic accuracy of MRI in PH. Seventy-two patients with suspected PH attending a referral center underwent RHC and MRI within 48 hours. Fifty-seven patients were diagnosed with PH, and 15 had no PH. A number of functional and structural cardiac and cardiovascular markers derived from 2 mathematical models and also solely from MRI of the main pulmonary artery and heart were integrated into a classification algorithm to investigate the diagnostic utility of the combination of the individual markers. A physiological marker based on the quantification of wave reflection in the pulmonary artery was shown to perform best individually, but optimal diagnostic performance was found by the combination of several image-based markers. Classifier results, validated using leave-one-out cross validation, demonstrated that combining computation-derived metrics reflecting hemodynamic changes in the pulmonary vasculature with measurement of right ventricular morphology and function, in a decision support algorithm, provides a method to noninvasively diagnose PH with high accuracy (92%). The high diagnostic accuracy of these MRI-based model parameters may reduce the need for RHC in patients with suspected PH.

High-resolution Imaging of pH in Alkaline Sediments and Water Based on a New Rapid Response Fluorescent Planar Optode

NASA Astrophysics Data System (ADS)

Han, Chao; Yao, Lei; Xu, Di; Xie, Xianchuan; Zhang, Chaosheng

2016-05-01

A new dual-lumophore optical sensor combined with a robust RGB referencing method was developed for two-dimensional (2D) pH imaging in alkaline sediments and water. The pH sensor film consisted of a proton-permeable polymer (PVC) in which two dyes with different pH sensitivities and emission colors: (1) chloro phenyl imino propenyl aniline (CPIPA) and (2) the coumarin dye Macrolex® fluorescence yellow 10 GN (MFY-10 GN) were entrapped. Calibration experiments revealed the typical sigmoid function and temperature dependencies. This sensor featured high sensitivity and fast response over the alkaline working ranges from pH 7.5 to pH 10.5. Cross-sensitivity towards ionic strength (IS) was found to be negligible for freshwater when IS <0.1 M. The sensor had a spatial resolution of approximately 22 μm and aresponse time of <120 s when going from pH 7.0 to 9.0. The feasibility of the sensor was demonstrated using the pH microelectrode. An example of pH image obtained in the natrual freshwater sediment and water associated with the photosynthesis of Vallisneria spiral species was also presented, suggesting that the sensor held great promise for the field applications.

High-resolution Imaging of pH in Alkaline Sediments and Water Based on a New Rapid Response Fluorescent Planar Optode

PubMed Central

Han, Chao; Yao, Lei; Xu, Di; Xie, Xianchuan; Zhang, Chaosheng

2016-01-01

A new dual-lumophore optical sensor combined with a robust RGB referencing method was developed for two-dimensional (2D) pH imaging in alkaline sediments and water. The pH sensor film consisted of a proton-permeable polymer (PVC) in which two dyes with different pH sensitivities and emission colors: (1) chloro phenyl imino propenyl aniline (CPIPA) and (2) the coumarin dye Macrolex® fluorescence yellow 10 GN (MFY-10 GN) were entrapped. Calibration experiments revealed the typical sigmoid function and temperature dependencies. This sensor featured high sensitivity and fast response over the alkaline working ranges from pH 7.5 to pH 10.5. Cross-sensitivity towards ionic strength (IS) was found to be negligible for freshwater when IS <0.1 M. The sensor had a spatial resolution of approximately 22 μm and aresponse time of <120 s when going from pH 7.0 to 9.0. The feasibility of the sensor was demonstrated using the pH microelectrode. An example of pH image obtained in the natrual freshwater sediment and water associated with the photosynthesis of Vallisneria spiral species was also presented, suggesting that the sensor held great promise for the field applications. PMID:27199163

Precision sensing by two opposing gradient sensors: how does Escherichia coli find its preferred pH level?

PubMed

Hu, Bo; Tu, Yuhai

2013-07-02

It is essential for bacteria to find optimal conditions for their growth and survival. The optimal levels of certain environmental factors (such as pH and temperature) often correspond to some intermediate points of the respective gradients. This requires the ability of bacteria to navigate from both directions toward the optimum location and is distinct from the conventional unidirectional chemotactic strategy. Remarkably, Escherichia coli cells can perform such a precision sensing task in pH taxis by using the same chemotaxis machinery, but with opposite pH responses from two different chemoreceptors (Tar and Tsr). To understand bacterial pH sensing, we developed an Ising-type model for a mixed cluster of opposing receptors based on the push-pull mechanism. Our model can quantitatively explain experimental observations in pH taxis for various mutants and wild-type cells. We show how the preferred pH level depends on the relative abundance of the competing sensors and how the sensory activity regulates the behavioral response. Our model allows us to make quantitative predictions on signal integration of pH and chemoattractant stimuli. Our study reveals two general conditions and a robust push-pull scheme for precision sensing, which should be applicable in other adaptive sensory systems with opposing gradient sensors. Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Hyperspectral Imaging in Tandem with R Statistics and Image Processing for Detection and Visualization of pH in Japanese Big Sausages Under Different Storage Conditions.

PubMed

Feng, Chao-Hui; Makino, Yoshio; Yoshimura, Masatoshi; Thuyet, Dang Quoc; García-Martín, Juan Francisco

2018-02-01

The potential of hyperspectral imaging with wavelengths of 380 to 1000 nm was used to determine the pH of cooked sausages after different storage conditions (4 °C for 1 d, 35 °C for 1, 3, and 5 d). The mean spectra of the sausages were extracted from the hyperspectral images and partial least squares regression (PLSR) model was developed to relate spectral profiles with the pH of the cooked sausages. Eleven important wavelengths were selected based on the regression coefficient values. The PLSR model established using the optimal wavelengths showed good precision being the prediction coefficient of determination (R p 2 ) 0.909 and the root mean square error of prediction 0.035. The prediction map for illustrating pH indices in sausages was for the first time developed by R statistics. The overall results suggested that hyperspectral imaging combined with PLSR and R statistics are capable to quantify and visualize the sausages pH evolution under different storage conditions. In this paper, hyperspectral imaging is for the first time used to detect pH in cooked sausages using R statistics, which provides another useful information for the researchers who do not have the access to Matlab. Eleven optimal wavelengths were successfully selected, which were used for simplifying the PLSR model established based on the full wavelengths. This simplified model achieved a high R p 2 (0.909) and a low root mean square error of prediction (0.035), which can be useful for the design of multispectral imaging systems. © 2017 Institute of Food Technologists®.

Reperfusion-Associated Hemorrhagic Transformation in SHR Rats

PubMed Central

Henning, Erica C.; Latour, Lawrence L.; Hallenbeck, John M.; Warach, Steven

2016-01-01

Background and Purpose Symptomatic hemorrhagic transformation (HT) is the most important complicating factor after treatment with intravenous tissue plasminogen activator. In this study, we used multimodal magnetic resonance imaging to investigate the incidence and severity of reperfusion-based HT in spontaneously hypertensive rats after ischemia/reperfusion. Methods Twenty male spontaneously hypertensive rats were subjected to 30 minutes of middle cerebral artery occlusion via the suture model. Diffusion-weighted, T2-weighted, and gradient-echo imaging were performed on days 1, 2, 3, 4, and 7 for longitudinal evaluation of lesion evolution, vasogenic edema, and HT, respectively. Findings on gradient-echo images were classified according to the severity of hemorrhage: no HT; punctate or small petechial hemorrhage (HI-1); confluent petechial hemorrhage (HI-2); hematoma with absent/mild space-occupying effect (PH-1, ≤30% lesion volume); and hematoma with significant space-occupying effect and potential perihematomal edema (PH-2, >30% lesion volume). Histopathologic evaluation of HT was performed after final imaging for comparison with magnetic resonance imaging results. Results Final hemorrhage scores based on severity were as follows: HI-1 23.1%, HI-2 30.8%, PH-1 30.8%, and PH-2 15.4%. Similar to clinical observations, only PH-2 was associated with neurologic deterioration and associated weight loss. Conclusions This model has a high incidence of parenchymal hematomas (46.2%) and therefore is appropriate for the evaluation of novel therapeutics targeting blood-brain barrier integrity and the reduction of symptomatic HT events (PH-2), as well as those potentially “at risk” for neurologic deterioration (PH-1). PMID:18757286

High-Resolution pH Imaging of Living Bacterial Cells To Detect Local pH Differences

PubMed Central

Morimoto, Yusuke V.; Kami-ike, Nobunori; Miyata, Tomoko; Kawamoto, Akihiro; Kato, Takayuki

2016-01-01

ABSTRACT Protons are utilized for various biological activities such as energy transduction and cell signaling. For construction of the bacterial flagellum, a type III export apparatus utilizes ATP and proton motive force to drive flagellar protein export, but the energy transduction mechanism remains unclear. Here, we have developed a high-resolution pH imaging system to measure local pH differences within living Salmonella enterica cells, especially in close proximity to the cytoplasmic membrane and the export apparatus. The local pH near the membrane was ca. 0.2 pH unit higher than the bulk cytoplasmic pH. However, the local pH near the export apparatus was ca. 0.1 pH unit lower than that near the membrane. This drop of local pH depended on the activities of both transmembrane export components and FliI ATPase. We propose that the export apparatus acts as an H+/protein antiporter to couple ATP hydrolysis with H+ flow to drive protein export. PMID:27923921

Shedding quantitative fluorescence light on novel regulatory mechanisms in skeletal biomedicine and biodentistry.

PubMed

Lee, Ji-Won; Iimura, Tadahiro

2017-02-01

Digitalized fluorescence images contain numerical information such as color (wavelength), fluorescence intensity and spatial position. However, quantitative analyses of acquired data and their validation remained to be established. Our research group has applied quantitative fluorescence imaging on tissue sections and uncovered novel findings in skeletal biomedicine and biodentistry. This review paper includes a brief background of quantitative fluorescence imaging and discusses practical applications by introducing our previous research. Finally, the future perspectives of quantitative fluorescence imaging are discussed.

Magnetic Resonance-based Motion Correction for Quantitative PET in Simultaneous PET-MR Imaging.

PubMed

Rakvongthai, Yothin; El Fakhri, Georges

2017-07-01

Motion degrades image quality and quantitation of PET images, and is an obstacle to quantitative PET imaging. Simultaneous PET-MR offers a tool that can be used for correcting the motion in PET images by using anatomic information from MR imaging acquired concurrently. Motion correction can be performed by transforming a set of reconstructed PET images into the same frame or by incorporating the transformation into the system model and reconstructing the motion-corrected image. Several phantom and patient studies have validated that MR-based motion correction strategies have great promise for quantitative PET imaging in simultaneous PET-MR. Copyright © 2017 Elsevier Inc. All rights reserved.

Quantitative imaging biomarker ontology (QIBO) for knowledge representation of biomedical imaging biomarkers.

PubMed

Buckler, Andrew J; Liu, Tiffany Ting; Savig, Erica; Suzek, Baris E; Ouellette, M; Danagoulian, J; Wernsing, G; Rubin, Daniel L; Paik, David

2013-08-01

A widening array of novel imaging biomarkers is being developed using ever more powerful clinical and preclinical imaging modalities. These biomarkers have demonstrated effectiveness in quantifying biological processes as they occur in vivo and in the early prediction of therapeutic outcomes. However, quantitative imaging biomarker data and knowledge are not standardized, representing a critical barrier to accumulating medical knowledge based on quantitative imaging data. We use an ontology to represent, integrate, and harmonize heterogeneous knowledge across the domain of imaging biomarkers. This advances the goal of developing applications to (1) improve precision and recall of storage and retrieval of quantitative imaging-related data using standardized terminology; (2) streamline the discovery and development of novel imaging biomarkers by normalizing knowledge across heterogeneous resources; (3) effectively annotate imaging experiments thus aiding comprehension, re-use, and reproducibility; and (4) provide validation frameworks through rigorous specification as a basis for testable hypotheses and compliance tests. We have developed the Quantitative Imaging Biomarker Ontology (QIBO), which currently consists of 488 terms spanning the following upper classes: experimental subject, biological intervention, imaging agent, imaging instrument, image post-processing algorithm, biological target, indicated biology, and biomarker application. We have demonstrated that QIBO can be used to annotate imaging experiments with standardized terms in the ontology and to generate hypotheses for novel imaging biomarker-disease associations. Our results established the utility of QIBO in enabling integrated analysis of quantitative imaging data.

Role of Recurrent Hypoxia-Ischemia in Preterm White Matter Injury Severity

PubMed Central

Hagen, Matthew W.; Riddle, Art; McClendon, Evelyn; Gong, Xi; Shaver, Daniel; Srivastava, Taasin; Dean, Justin M.; Bai, Ji-Zhong; Fowke, Tania M.; Gunn, Alistair J.; Jones, Daniel F.; Sherman, Larry S.; Grafe, Marjorie R.; Hohimer, A. Roger; Back, Stephen A.

2014-01-01

Objective Although the spectrum of white matter injury (WMI) in preterm infants is shifting from cystic necrotic lesions to milder forms, the factors that contribute to this changing spectrum are unclear. We hypothesized that recurrent hypoxia-ischemia (rHI) will exacerbate the spectrum of WMI defined by markers of inflammation and molecules related to the extracellular matrix (hyaluronan (HA) and the PH20 hyaluronidase) that regulate maturation of the oligodendrocyte (OL) lineage after WMI. Methods We employed a preterm fetal sheep model of in utero moderate hypoxemia and global severe but not complete cerebral ischemia that reproduces the spectrum of human WMI. The response to rHI was compared against corresponding early or later single episodes of HI. An ordinal rating scale of WMI was compared against an unbiased quantitative image analysis protocol that provided continuous histo-pathological outcome measures for astrogliosis and microglial activation. Late oligodendrocyte progenitors (preOLs) were quantified by stereology. Analysis of hyaluronan and the hyaluronidase PH20 defined the progressive response of the extracellular matrix to WMI. Results rHI resulted in a more severe spectrum of WMI with a greater burden of necrosis, but an expanded population of preOLs that displayed reduced susceptibility to cell death. WMI from single episodes of HI or rHI was accompanied by elevated HA levels and increased labeling for PH20. Expression of PH20 in fetal ovine WMI was confirmed by RT-PCR and RNA-sequencing. Conclusions rHI is associated with an increased risk for more severe WMI with necrosis, but reduced risk for preOL degeneration compared to single episodes of HI. Expansion of the preOL pool may be linked to elevated hyaluronan and PH20. PMID:25390897

Precipitation of molybdenum(V) as the hydroxide and its separation from rhenium.

PubMed

Yatirajam, V; Ahuja, U; Kakkar, L R

1975-03-01

A study of the conditions for precipitation of molybdenum(V) hydroxide shows that for Mo concentration 1 mg ml about 97.5% of the Mo can be precipitated between pH 5 and 5.8. Lower concentrations of molybdenum(V) or molybdenum(VI) can be precipitated quantitatively by using 20 times the amount of zirconium as collector, at the same pH. On this basis, a simple method is given for quantitative separation of rhenium from large amounts of molybdenum and is attested by analysis of synthetic and molybdenite samples.

Hyperpolarized Amino Acid Derivatives as Multivalent Magnetic Resonance pH Sensor Molecules.

PubMed

Hundshammer, Christian; Düwel, Stephan; Ruseckas, David; Topping, Geoffrey; Dzien, Piotr; Müller, Christoph; Feuerecker, Benedikt; Hövener, Jan B; Haase, Axel; Schwaiger, Markus; Glaser, Steffen J; Schilling, Franz

2018-02-15

pH is a tightly regulated physiological parameter that is often altered in diseased states like cancer. The development of biosensors that can be used to non-invasively image pH with hyperpolarized (HP) magnetic resonance spectroscopic imaging has therefore recently gained tremendous interest. However, most of the known HP-sensors have only individually and not comprehensively been analyzed for their biocompatibility, their pH sensitivity under physiological conditions, and the effects of chemical derivatization on their logarithmic acid dissociation constant (p K a ). Proteinogenic amino acids are biocompatible, can be hyperpolarized and have at least two pH sensitive moieties. However, they do not exhibit a pH sensitivity in the physiologically relevant pH range. Here, we developed a systematic approach to tailor the p K a of molecules using modifications of carbon chain length and derivatization rendering these molecules interesting for pH biosensing. Notably, we identified several derivatives such as [1- 13 C]serine amide and [1- 13 C]-2,3-diaminopropionic acid as novel pH sensors. They bear several spin-1/2 nuclei ( 13 C, 15 N, 31 P) with high sensitivity up to 4.8 ppm/pH and we show that 13 C spins can be hyperpolarized with dissolution dynamic polarization (DNP). Our findings elucidate the molecular mechanisms of chemical shift pH sensors that might help to design tailored probes for specific pH in vivo imaging applications.

Comparative evaluation of two quantitative test methods for determining the efficacy of liquid sporicides and sterilants on a hard surface: a precollaborative study.

PubMed

Tomasino, Stephen F; Hamilton, Martin A

2007-01-01

Two quantitative carrier-based test methods for determining the efficacy of liquid sporicides and sterilants on a hard surface, the Standard Quantitative Carrier Test Method-ASTM E 2111-00 and an adaptation of a quantitative micro-method as reported by Sagripanti and Bonifacino, were compared in this study. The methods were selected based on their desirable characteristics (e.g., well-developed protocol, previous use with spores, fully quantitative, and use of readily available equipment) for testing liquid sporicides and sterilants on a hard surface. In this paper, the Sagripanti-Bonifacino procedure is referred to as the Three Step Method (TSM). AOAC Official Method 966.04 was included in this study as a reference method. Three laboratories participated in the evaluation. Three chemical treatments were tested: (1) 3000 ppm sodium hypochlorite with pH adjusted to 7.0, (2) a hydrogen peroxide/peroxyacetic acid product, and (3) 3000 ppm sodium hypochlorite with pH unadjusted (pH of approximately 10.0). A fourth treatment, 6000 ppm sodium hypochlorite solution with pH adjusted to 7.0, was included only for Method 966.04 as a positive control (high level of efficacy). The contact time was 10 min for all chemical treatments except the 6000 ppm sodium hypochlorite treatment which was tested at 30 min. Each chemical treatment was tested 3 times using each of the methods. Only 2 of the laboratories performed the AOAC method. Method performance was assessed by the within-laboratory variance, between-laboratory variance, and total variance associated with the log reduction (LR) estimates generated by each quantitative method. The quantitative methods performed similarly, and the LR values generated by each method were not statistically different for the 3 treatments evaluated. Based on feedback from the participating laboratories, compared to the TSM, ASTM E 2111-00 was more resource demanding and required more set-up time. The logistical and resource concerns identified for ASTM E 2111-00 were largely associated with the filtration process and counting bacterial colonies on filters. Thus, the TSM was determined to be the most suitable method.

Improving training in methodology enriches the science of psychology.

PubMed

Aiken, Leona S; West, Stephen G; Millsap, Roger E

2009-01-01

Replies to the comment Ramifications of increased training in quantitative methodology by Herbet Zimiles on the current authors original article "Doctoral training in statistics, measurement, and methodology in psychology: Replication and extension of Aiken, West, Sechrest, and Reno's (1990) survey of PhD programs in North America". The current authors state that in their recent article, they reported the results of an extensive survey of quantitative training in all PhD programs in North America. They compared these results with those of a similar survey conducted 12 years earlier (Aiken, West, Sechrest, & Reno, 1990), and raised issues for the future methodological training of substantive and quantitative researchers in psychology. The authors then respond to Zimiles three questions. PsycINFO Database Record 2009 APA.

In vivo EPR imaging of differential tumor targeting using cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl

PubMed Central

Redler, Gage; Barth, Eugene D.; Bauer, Kenneth S.; Kao, Joseph P.Y.; Rosen, Gerald M.; Halpern, Howard J.

2015-01-01

Purpose EPR spectroscopy promises quantitative images of important physiologic markers of animal tumors and normal tissues, such as pO2, pH, and thiol redox status. These parameters of tissue function are conveniently reported by tailored nitroxides. For defining tumor physiology, it is vital that nitroxides are selectively localized in tumors relative to normal tissue. Furthermore, these paramagnetic species should be specifically taken up by cells of the tumor, thereby reporting on both the site of tumor formation and the physiological status of the tissue. This study investigates the tumor localization of the novel nitroxide, cis-3,4-di(acetoxymethoxycarbonyl)-2,2,5,5-tetramethyl-1-pyrrolidinyloxyl 3 relative to the corresponding di-acid 4. Methods We obtained images of nitroxide 3 infused intravenously into C3H mice bearing 0.5-cm3 FSa fibrosarcoma on the leg, and compared these with images of similar tumors infused with nitroxide 4. Results The ratio of spectral intensity from within the tumor-bearing region to that of normal tissue was higher in the mice injected with 3 relative to 4. Conclusion This establishes the possibility of tumor imaging with a nitroxide with intracellular distribution and provides the basis for EPR images of animal models to investigate the relationship between crucial aspects of tumor microenvironment and malignancy and its response to therapy. PMID:23776127

High speed fluorescence imaging with compressed ultrafast photography

NASA Astrophysics Data System (ADS)

Thompson, J. V.; Mason, J. D.; Beier, H. T.; Bixler, J. N.

2017-02-01

Fluorescent lifetime imaging is an optical technique that facilitates imaging molecular interactions and cellular functions. Because the excited lifetime of a fluorophore is sensitive to its local microenvironment,1, 2 measurement of fluorescent lifetimes can be used to accurately detect regional changes in temperature, pH, and ion concentration. However, typical state of the art fluorescent lifetime methods are severely limited when it comes to acquisition time (on the order of seconds to minutes) and video rate imaging. Here we show that compressed ultrafast photography (CUP) can be used in conjunction with fluorescent lifetime imaging to overcome these acquisition rate limitations. Frame rates up to one hundred billion frames per second have been demonstrated with compressed ultrafast photography using a streak camera.3 These rates are achieved by encoding time in the spatial direction with a pseudo-random binary pattern. The time domain information is then reconstructed using a compressed sensing algorithm, resulting in a cube of data (x,y,t) for each readout image. Thus, application of compressed ultrafast photography will allow us to acquire an entire fluorescent lifetime image with a single laser pulse. Using a streak camera with a high-speed CMOS camera, acquisition rates of 100 frames per second can be achieved, which will significantly enhance our ability to quantitatively measure complex biological events with high spatial and temporal resolution. In particular, we will demonstrate the ability of this technique to do single-shot fluorescent lifetime imaging of cells and microspheres.

Prospects and challenges of quantitative phase imaging in tumor cell biology

NASA Astrophysics Data System (ADS)

Kemper, Björn; Götte, Martin; Greve, Burkhard; Ketelhut, Steffi

2016-03-01

Quantitative phase imaging (QPI) techniques provide high resolution label-free quantitative live cell imaging. Here, prospects and challenges of QPI in tumor cell biology are presented, using the example of digital holographic microscopy (DHM). It is shown that the evaluation of quantitative DHM phase images allows the retrieval of different parameter sets for quantification of cellular motion changes in migration and motility assays that are caused by genetic modifications. Furthermore, we demonstrate simultaneously label-free imaging of cell growth and morphology properties.

Trends in Ph.D. Productivity and Diversity in Top-50 U.S. Chemistry Departments: An Institutional Analysis

ERIC Educational Resources Information Center

Laursen, Sandra L.; Weston, Timothy J.

2014-01-01

The education of doctoral chemists contributes to the chemical research enterprise and thus to innovation as an engine of the economy. This quantitative analysis describes trends in the production and diversity of chemistry Ph.D. degrees in the top-50 U.S. Ph.D.-granting departments in the past two decades. Time series data for individual…

Quantitative comparison of 3D third harmonic generation and fluorescence microscopy images.

PubMed

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

2018-01-01

Third harmonic generation (THG) microscopy is a label-free imaging technique that shows great potential for rapid pathology of brain tissue during brain tumor surgery. However, the interpretation of THG brain images should be quantitatively linked to images of more standard imaging techniques, which so far has been done qualitatively only. We establish here such a quantitative link between THG images of mouse brain tissue and all-nuclei-highlighted fluorescence images, acquired simultaneously from the same tissue area. For quantitative comparison of a substantial pair of images, we present here a segmentation workflow that is applicable for both THG and fluorescence images, with a precision of 91.3 % and 95.8 % achieved respectively. We find that the correspondence between the main features of the two imaging modalities amounts to 88.9 %, providing quantitative evidence of the interpretation of dark holes as brain cells. Moreover, 80 % bright objects in THG images overlap with nuclei highlighted in the fluorescence images, and they are 2 times smaller than the dark holes, showing that cells of different morphologies can be recognized in THG images. We expect that the described quantitative comparison is applicable to other types of brain tissue and with more specific staining experiments for cell type identification. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Magnetic Resonance Imaging of Electrolysis.

PubMed Central

Meir, Arie; Hjouj, Mohammad; Rubinsky, Liel; Rubinsky, Boris

2015-01-01

This study explores the hypothesis that Magnetic Resonance Imaging (MRI) can image the process of electrolysis by detecting pH fronts. The study has relevance to real time control of cell ablation with electrolysis. To investigate the hypothesis we compare the following MR imaging sequences: T1 weighted, T2 weighted and Proton Density (PD), with optical images acquired using pH-sensitive dyes embedded in a physiological saline agar solution phantom treated with electrolysis and discrete measurements with a pH microprobe. We further demonstrate the biological relevance of our work using a bacterial E. Coli model, grown on the phantom. The results demonstrate the ability of MRI to image electrolysis produced pH changes in a physiological saline phantom and show that these changes correlate with cell death in the E. Coli model grown on the phantom. The results are promising and invite further experimental research. PMID:25659942

pH optimization for a reliable quantification of brain tumor cell and tissue extracts with (1)H NMR: focus on choline-containing compounds and taurine.

PubMed

Robert, O; Sabatier, J; Desoubzdanne, D; Lalande, J; Balayssac, S; Gilard, V; Martino, R; Malet-Martino, M

2011-01-01

The aim of this study was to define the optimal pH for (1)H nuclear magnetic resonance (NMR) spectroscopy analysis of perchloric acid or methanol-chloroform-water extracts from brain tumor cells and tissues. The systematic study of the proton chemical shift variations as a function of pH of 13 brain metabolites in model solutions demonstrated that recording (1)H NMR spectra at pH 10 allowed resolving resonances that are overlapped at pH 7, especially in the 3.2-3.3 ppm choline-containing-compounds region. (1)H NMR analysis of extracts at pH 7 or 10 showed that quantitative measurements of lactate, alanine, glutamate, glutamine (Gln), creatine + phosphocreatine and myo-inositol (m-Ino) can be readily performed at both pHs. The concentrations of glycerophosphocholine, phosphocholine and choline that are crucial metabolites for tumor brain malignancy grading were accurately measured at pH 10 only. Indeed, the resonances of their trimethylammonium moieties are cleared of any overlapping signal, especially those of taurine (Tau) and phosphoethanolamine. The four non-ionizable Tau protons resonating as a singlet in a non-congested spectral region permits an easier and more accurate quantitation of this apoptosis marker at pH 10 than at pH 7 where the triplet at 3.43 ppm can be overlapped with the signals of glucose or have an intensity too low to be measured. Glycine concentration was determined indirectly at both pHs after subtracting the contribution of the overlapped signals of m-Ino at pH 7 or Gln at pH 10.

Estimating weak ratiometric signals in imaging data. I. Dual-channel data.

PubMed

Broder, Josef; Majumder, Anirban; Porter, Erika; Srinivasamoorthy, Ganesh; Keith, Charles; Lauderdale, James; Sornborger, Andrew

2007-09-01

Ratiometric fluorescent indicators are becoming increasingly prevalent in many areas of biology. They are used for making quantitative measurements of intracellular free calcium both in vitro and in vivo, as well as measuring membrane potentials, pH, and other important physiological variables of interest to researchers in many subfields. Often, functional changes in the fluorescent yield of ratiometric indicators are small, and the signal-to-noise ratio (SNR) is of order unity or less. In particular, variability in the denominator of the ratio can lead to very poor ratio estimates. We present a statistical optimization method for objectively detecting and estimating ratiometric signals in dual-wavelength measurements of fluorescent, ratiometric indicators that improves on standard methods. With the use of an appropriate statistical model for ratiometric signals and by taking the pixel-pixel covariance of an imaging dataset into account, we are able to extract user-independent spatiotemporal information that retains high resolution in both space and time.

The emerging science of quantitative imaging biomarkers terminology and definitions for scientific studies and regulatory submissions.

PubMed

Kessler, Larry G; Barnhart, Huiman X; Buckler, Andrew J; Choudhury, Kingshuk Roy; Kondratovich, Marina V; Toledano, Alicia; Guimaraes, Alexander R; Filice, Ross; Zhang, Zheng; Sullivan, Daniel C

2015-02-01

The development and implementation of quantitative imaging biomarkers has been hampered by the inconsistent and often incorrect use of terminology related to these markers. Sponsored by the Radiological Society of North America, an interdisciplinary group of radiologists, statisticians, physicists, and other researchers worked to develop a comprehensive terminology to serve as a foundation for quantitative imaging biomarker claims. Where possible, this working group adapted existing definitions derived from national or international standards bodies rather than invent new definitions for these terms. This terminology also serves as a foundation for the design of studies that evaluate the technical performance of quantitative imaging biomarkers and for studies of algorithms that generate the quantitative imaging biomarkers from clinical scans. This paper provides examples of research studies and quantitative imaging biomarker claims that use terminology consistent with these definitions as well as examples of the rampant confusion in this emerging field. We provide recommendations for appropriate use of quantitative imaging biomarker terminological concepts. It is hoped that this document will assist researchers and regulatory reviewers who examine quantitative imaging biomarkers and will also inform regulatory guidance. More consistent and correct use of terminology could advance regulatory science, improve clinical research, and provide better care for patients who undergo imaging studies. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Real-time quantitative fluorescence imaging using a single snapshot optical properties technique for neurosurgical guidance

NASA Astrophysics Data System (ADS)

Valdes, Pablo A.; Angelo, Joseph; Gioux, Sylvain

2015-03-01

Fluorescence imaging has shown promise as an adjunct to improve the extent of resection in neurosurgery and oncologic surgery. Nevertheless, current fluorescence imaging techniques do not account for the heterogeneous attenuation effects of tissue optical properties. In this work, we present a novel imaging system that performs real time quantitative fluorescence imaging using Single Snapshot Optical Properties (SSOP) imaging. We developed the technique and performed initial phantom studies to validate the quantitative capabilities of the system for intraoperative feasibility. Overall, this work introduces a novel real-time quantitative fluorescence imaging method capable of being used intraoperatively for neurosurgical guidance.

TU-CD-BRB-04: Automated Radiomic Features Complement the Prognostic Value of VASARI in the TCGA-GBM Dataset

DOE Office of Scientific and Technical Information (OSTI.GOV)

Velazquez, E Rios; Narayan, V; Grossmann, P

2015-06-15

Purpose: To compare the complementary prognostic value of automated Radiomic features to that of radiologist-annotated VASARI features in TCGA-GBM MRI dataset. Methods: For 96 GBM patients, pre-operative MRI images were obtained from The Cancer Imaging Archive. The abnormal tumor bulks were manually defined on post-contrast T1w images. The contrast-enhancing and necrotic regions were segmented using FAST. From these sub-volumes and the total abnormal tumor bulk, a set of Radiomic features quantifying phenotypic differences based on the tumor intensity, shape and texture, were extracted from the post-contrast T1w images. Minimum-redundancy-maximum-relevance (MRMR) was used to identify the most informative Radiomic, VASARI andmore » combined Radiomic-VASARI features in 70% of the dataset (training-set). Multivariate Cox-proportional hazards models were evaluated in 30% of the dataset (validation-set) using the C-index for OS. A bootstrap procedure was used to assess significance while comparing the C-Indices of the different models. Results: Overall, the Radiomic features showed a moderate correlation with the radiologist-annotated VASARI features (r = −0.37 – 0.49); however that correlation was stronger for the Tumor Diameter and Proportion of Necrosis VASARI features (r = −0.71 – 0.69). After MRMR feature selection, the best-performing Radiomic, VASARI, and Radiomic-VASARI Cox-PH models showed a validation C-index of 0.56 (p = NS), 0.58 (p = NS) and 0.65 (p = 0.01), respectively. The combined Radiomic-VASARI model C-index was significantly higher than that obtained from either the Radiomic or VASARI model alone (p = <0.001). Conclusion: Quantitative volumetric and textural Radiomic features complement the qualitative and semi-quantitative annotated VASARI feature set. The prognostic value of informative qualitative VASARI features such as Eloquent Brain and Multifocality is increased with the addition of quantitative volumetric and textural features from the contrast-enhancing and necrotic tumor regions. These results should be further evaluated in larger validation cohorts.« less

Detection of low back pain using pH level-dependent imaging of the intervertebral disc using the ratio of R1ρ dispersion and -OH chemical exchange saturation transfer (RROC).

PubMed

Liu, Qi; Tawackoli, Wafa; Pelled, Gadi; Fan, Zhaoyang; Jin, Ning; Natsuaki, Yutaka; Bi, Xiaoming; Gart, Avrom; Bae, Hyun; Gazit, Dan; Li, Debiao

2015-03-01

Low pH is associated with intervertebral disc (IVD)-generated low back pain (LBP). The purpose of this work was to develop an in vivo pH level-dependent magnetic resonance imaging (MRI) method for detecting discogenic LBP, without using exogenous contrast agents. The ratio of R1ρ dispersion and chemical exchange saturation transfer (CEST) (RROC) was used for pH-level dependent imaging of the IVD while eliminating the effect of labile proton concentration. The technique was validated by numerical simulations and studies on phantoms and ex vivo porcine spines. Four male (ages 42.8 ± 18.3) and two female patients (ages 55.5 ± 2.1) with LBP and scheduled for discography were examined with the method on a 3.0 Tesla MR scanner. RROC measurements were compared with discography outcomes using paired t-test. Simulation and phantom results indicated RROC is a concentration independent and pH level-dependent technique. Porcine spine study results found higher RROC value was related to lower pH level. Painful discs based on discography had significant higher RROC values than those with negative diagnosis (P < 0.05). RROC imaging is a promising pH level dependent MRI technique that has the potential to be a noninvasive imaging tool to detect painful IVDs in vivo. © 2014 Wiley Periodicals, Inc.

Development of a fluorescence endoscopic system for pH mapping of gastric tissue

NASA Astrophysics Data System (ADS)

Rochon, Philippe; Mordon, Serge; Buys, Bruno; Dhelin, Guy; Lesage, Jean C.; Chopin, Claude

2003-10-01

Measurement of gastro intestinal intramucosal pH (pHim) has been recognized as an important factor in the detection of hypoxia induced dysfonctions. However, current pH measurements techniques are limited in terms of time and spatial resolutions. A major advance in accurate pH measurement was the development of the ratiometric fluorescent indicator dye, 2',7'-bis(carboxyethyl)-5,6-carboxyfluorescein (BCECF). BCECF which pKa is in the physiological pH range is suitable for pH tissue measurements in vivo. This study aimed to develop and evaluate an endoscopic imaging system for real time pH measurements in the stomach in order to provide to ICU a new tool for gastro intestinal intramucosal pH (pHim) measurements. This fluorescence imaging technique should allow the temporal exploration of sequential events, particularly in ICU where the pHim provides a predictive information of the patient' status. The experimental evaluations of this new and innovative endoscopic fluorescence system confirms the accuracy of pH measurement using BCECF.

Geometrical Calibration of the Photo-Spectral System and Digital Maps Retrieval

NASA Astrophysics Data System (ADS)

Bruchkouskaya, S.; Skachkova, A.; Katkovski, L.; Martinov, A.

2013-12-01

Imaging systems for remote sensing of the Earth are required to demonstrate high metric accuracy of the picture which can be provided through preliminary geometrical calibration of optical systems. Being defined as a result of the geometrical calibration, parameters of internal and external orientation of the cameras are needed while solving such problems of image processing, as orthotransformation, geometrical correction, geographical coordinate fixing, scale adjustment and image registration from various channels and cameras, creation of image mosaics of filmed territories, and determination of geometrical characteristics of objects in the images. The geometrical calibration also helps to eliminate image deformations arising due to manufacturing defects and errors in installation of camera elements and photo receiving matrices as well as those resulted from lens distortions. A Photo-Spectral System (PhSS), which is intended for registering reflected radiation spectra of underlying surfaces in a wavelength range from 350 nm to 1050 nm and recording images of high spatial resolution, has been developed at the A.N. Sevchenko Research Institute of Applied Physical Problems of the Belarusian State University. The PhSS has undergone flight tests over the territory of Belarus onboard the Antonov AN-2 aircraft with the aim to obtain visible range images of the underlying surface. Then we performed the geometrical calibration of the PhSS and carried out the correction of images obtained during the flight tests. Furthermore, we have plotted digital maps of the terrain using the stereo pairs of images acquired from the PhSS and evaluated the accuracy of the created maps. Having obtained the calibration parameters, we apply them for correction of the images from another identical PhSS device, which is located at the Russian Orbital Segment of the International Space Station (ROS ISS), aiming to retrieve digital maps of the terrain with higher accuracy.

Spectrally And Temporally Resolved Low-Light Level Video Microscopy

NASA Astrophysics Data System (ADS)

Wampler, John E.; Furukawa, Ruth; Fechheimer, Marcus

1989-12-01

The IDG law-light video microscope system was designed to aid studies of localization of subcellular luminescence sources and stimulus/response coupling in single living cells using luminescent probes. Much of the motivation for design of this instrument system came from the pioneering efforts of Dr. Reynolds (Reynolds, Q. Rev. Biophys. 5, 295-347; Reynolds and Taylor, Bioscience 30, 586-592) who showed the value of intensified video camera systems for detection and localizion of fluorescence and bioluminescence signals from biological tissues. Our instrument system has essentially two roles, 1) localization and quantitation of very weak bioluminescence signals and 2) quantitation of intracellular environmental characteristics such as pH and calcium ion concentrations using fluorescent and bioluminescent probes. The instrument system exhibits over one million fold operating range allowing visualization and enhancement of quantum limited images with quantum limited response, spectral analysis of fluorescence signals, and transmitted light imaging. The computer control of the system implements rapid switching between light regimes, spatially resolved spectral scanning, and digital data processing for spectral shape analysis and for detailed analysis of the statistical distribution of single cell measurements. The system design and software algorithms used by the system are summarized. These design criteria are illustrated with examples taken from studies of bioluminescence, applications of bioluminescence to study developmental processes and gene expression in single living cells, and applications of fluorescent probes to study stimulus/response coupling in living cells.

Development of a vision-based pH reading system

NASA Astrophysics Data System (ADS)

Hur, Min Goo; Kong, Young Bae; Lee, Eun Je; Park, Jeong Hoon; Yang, Seung Dae; Moon, Ha Jung; Lee, Dong Hoon

2015-10-01

pH paper is generally used for pH interpretation in the QC (quality control) process of radiopharmaceuticals. pH paper is easy to handle and useful for small samples such as radio-isotopes and radioisotope (RI)-labeled compounds for positron emission tomography (PET). However, pHpaper-based detecting methods may have some errors due limitations of eye sight and inaccurate readings. In this paper, we report a new device for pH reading and related software. The proposed pH reading system is developed with a vision algorithm based on the RGB library. The pH reading system is divided into two parts. First is the reading device that consists of a light source, a CCD camera and a data acquisition (DAQ) board. To improve the accuracy of the sensitivity, we utilize the three primary colors of the LED (light emission diode) in the reading device. The use of three colors is better than the use of a single color for a white LED because of wavelength. The other is a graph user interface (GUI) program for a vision interface and report generation. The GUI program inserts the color codes of the pH paper into the database; then, the CCD camera captures the pH paper and compares its color with the RGB database image in the reading mode. The software captures and reports information on the samples, such as pH results, capture images, and library images, and saves them as excel files.

A dual pH and temperature responsive polymeric fluorescent sensor and its imaging application in living cells.

PubMed

Yin, Liyan; He, Chunsheng; Huang, Chusen; Zhu, Weiping; Wang, Xin; Xu, Yufang; Qian, Xuhong

2012-05-11

A polymeric fluorescent sensor PNME, consisting of A4 and N-isopropylacrylamide (NIPAM) units, was synthesized. PNME exhibited dual responses to pH and temperature, and could be used as an intracellular pH sensor for lysosomes imaging. Moreover, it also could sense different temperature change in living cells at 25 and 37 °C, respectively. This journal is © The Royal Society of Chemistry 2012

Quantitative imaging test approval and biomarker qualification: interrelated but distinct activities.

PubMed

Buckler, Andrew J; Bresolin, Linda; Dunnick, N Reed; Sullivan, Daniel C; Aerts, Hugo J W L; Bendriem, Bernard; Bendtsen, Claus; Boellaard, Ronald; Boone, John M; Cole, Patricia E; Conklin, James J; Dorfman, Gary S; Douglas, Pamela S; Eidsaunet, Willy; Elsinger, Cathy; Frank, Richard A; Gatsonis, Constantine; Giger, Maryellen L; Gupta, Sandeep N; Gustafson, David; Hoekstra, Otto S; Jackson, Edward F; Karam, Lisa; Kelloff, Gary J; Kinahan, Paul E; McLennan, Geoffrey; Miller, Colin G; Mozley, P David; Muller, Keith E; Patt, Rick; Raunig, David; Rosen, Mark; Rupani, Haren; Schwartz, Lawrence H; Siegel, Barry A; Sorensen, A Gregory; Wahl, Richard L; Waterton, John C; Wolf, Walter; Zahlmann, Gudrun; Zimmerman, Brian

2011-06-01

Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging. http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1. RSNA, 2011

Evaluation of quantitative image analysis criteria for the high-resolution microendoscopic detection of neoplasia in Barrett's esophagus

NASA Astrophysics Data System (ADS)

Muldoon, Timothy J.; Thekkek, Nadhi; Roblyer, Darren; Maru, Dipen; Harpaz, Noam; Potack, Jonathan; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

2010-03-01

Early detection of neoplasia in patients with Barrett's esophagus is essential to improve outcomes. The aim of this ex vivo study was to evaluate the ability of high-resolution microendoscopic imaging and quantitative image analysis to identify neoplastic lesions in patients with Barrett's esophagus. Nine patients with pathologically confirmed Barrett's esophagus underwent endoscopic examination with biopsies or endoscopic mucosal resection. Resected fresh tissue was imaged with fiber bundle microendoscopy; images were analyzed by visual interpretation or by quantitative image analysis to predict whether the imaged sites were non-neoplastic or neoplastic. The best performing pair of quantitative features were chosen based on their ability to correctly classify the data into the two groups. Predictions were compared to the gold standard of histopathology. Subjective analysis of the images by expert clinicians achieved average sensitivity and specificity of 87% and 61%, respectively. The best performing quantitative classification algorithm relied on two image textural features and achieved a sensitivity and specificity of 87% and 85%, respectively. This ex vivo pilot trial demonstrates that quantitative analysis of images obtained with a simple microendoscope system can distinguish neoplasia in Barrett's esophagus with good sensitivity and specificity when compared to histopathology and to subjective image interpretation.

Quantitative phase imaging and complex field reconstruction by pupil modulation differential phase contrast

PubMed Central

Lu, Hangwen; Chung, Jaebum; Ou, Xiaoze; Yang, Changhuei

2016-01-01

Differential phase contrast (DPC) is a non-interferometric quantitative phase imaging method achieved by using an asymmetric imaging procedure. We report a pupil modulation differential phase contrast (PMDPC) imaging method by filtering a sample’s Fourier domain with half-circle pupils. A phase gradient image is captured with each half-circle pupil, and a quantitative high resolution phase image is obtained after a deconvolution process with a minimum of two phase gradient images. Here, we introduce PMDPC quantitative phase image reconstruction algorithm and realize it experimentally in a 4f system with an SLM placed at the pupil plane. In our current experimental setup with the numerical aperture of 0.36, we obtain a quantitative phase image with a resolution of 1.73μm after computationally removing system aberrations and refocusing. We also extend the depth of field digitally by 20 times to ±50μm with a resolution of 1.76μm. PMID:27828473

Analysis of airborne MAIS imaging spectrometric data for mineral exploration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang Jinnian; Zheng Lanfen; Tong Qingxi

1996-11-01

The high spectral resolution imaging spectrometric system made quantitative analysis and mapping of surface composition possible. The key issue will be the quantitative approach for analysis of surface parameters for imaging spectrometer data. This paper describes the methods and the stages of quantitative analysis. (1) Extracting surface reflectance from imaging spectrometer image. Lab. and inflight field measurements are conducted for calibration of imaging spectrometer data, and the atmospheric correction has also been used to obtain ground reflectance by using empirical line method and radiation transfer modeling. (2) Determining quantitative relationship between absorption band parameters from the imaging spectrometer data andmore » chemical composition of minerals. (3) Spectral comparison between the spectra of spectral library and the spectra derived from the imagery. The wavelet analysis-based spectrum-matching techniques for quantitative analysis of imaging spectrometer data has beer, developed. Airborne MAIS imaging spectrometer data were used for analysis and the analysis results have been applied to the mineral and petroleum exploration in Tarim Basin area china. 8 refs., 8 figs.« less

Microenvironmental pH measurement during sodium naproxenate dissolution in acidic medium by UV/vis imaging.

PubMed

Østergaard, Jesper; Jensen, Henrik; Larsen, Susan W; Larsen, Claus; Lenke, Jim

2014-11-01

Variable dissolution from sodium salts of drugs containing a carboxylic acid group after passing the acidic environment of the stomach may affect oral bioavailability. The aim of the present proof of concept study was to investigate pH effects in relation to the dissolution of sodium naproxenate in 0.01M hydrochloric acid. For this purpose a UV/vis imaging-based approach capable of measuring microenvironmental pH in the vicinity of the solid drug compact as well as monitoring drug dissolution was developed. Using a pH indicating dye real-time spatially resolved measurement of pH was achieved. Sodium naproxenate, can significantly alter the local pH of the dissolution medium, is eventually neutralized and precipitates as the acidic species naproxen. The developed approach is considered useful for detailed studies of pH dependent dissolution phenomena in dissolution testing. Copyright © 2014 Elsevier B.V. All rights reserved.

Wide-Field Imaging Using Nitrogen Vacancies

NASA Technical Reports Server (NTRS)

Englund, Dirk Robert (Inventor); Trusheim, Matthew Edwin (Inventor)

2017-01-01

Nitrogen vacancies in bulk diamonds and nanodiamonds can be used to sense temperature, pressure, electromagnetic fields, and pH. Unfortunately, conventional sensing techniques use gated detection and confocal imaging, limiting the measurement sensitivity and precluding wide-field imaging. Conversely, the present sensing techniques do not require gated detection or confocal imaging and can therefore be used to image temperature, pressure, electromagnetic fields, and pH over wide fields of view. In some cases, wide-field imaging supports spatial localization of the NVs to precisions at or below the diffraction limit. Moreover, the measurement range can extend over extremely wide dynamic range at very high sensitivity.

Temporal Lobe Epilepsy: Quantitative MR Volumetry in Detection of Hippocampal Atrophy

PubMed Central

Farid, Nikdokht; Girard, Holly M.; Kemmotsu, Nobuko; Smith, Michael E.; Magda, Sebastian W.; Lim, Wei Y.; Lee, Roland R.

2012-01-01

Purpose: To determine the ability of fully automated volumetric magnetic resonance (MR) imaging to depict hippocampal atrophy (HA) and to help correctly lateralize the seizure focus in patients with temporal lobe epilepsy (TLE). Materials and Methods: This study was conducted with institutional review board approval and in compliance with HIPAA regulations. Volumetric MR imaging data were analyzed for 34 patients with TLE and 116 control subjects. Structural volumes were calculated by using U.S. Food and Drug Administration–cleared software for automated quantitative MR imaging analysis (NeuroQuant). Results of quantitative MR imaging were compared with visual detection of atrophy, and, when available, with histologic specimens. Receiver operating characteristic analyses were performed to determine the optimal sensitivity and specificity of quantitative MR imaging for detecting HA and asymmetry. A linear classifier with cross validation was used to estimate the ability of quantitative MR imaging to help lateralize the seizure focus. Results: Quantitative MR imaging–derived hippocampal asymmetries discriminated patients with TLE from control subjects with high sensitivity (86.7%–89.5%) and specificity (92.2%–94.1%). When a linear classifier was used to discriminate left versus right TLE, hippocampal asymmetry achieved 94% classification accuracy. Volumetric asymmetries of other subcortical structures did not improve classification. Compared with invasive video electroencephalographic recordings, lateralization accuracy was 88% with quantitative MR imaging and 85% with visual inspection of volumetric MR imaging studies but only 76% with visual inspection of clinical MR imaging studies. Conclusion: Quantitative MR imaging can depict the presence and laterality of HA in TLE with accuracy rates that may exceed those achieved with visual inspection of clinical MR imaging studies. Thus, quantitative MR imaging may enhance standard visual analysis, providing a useful and viable means for translating volumetric analysis into clinical practice. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112638/-/DC1 PMID:22723496

A soft, wearable microfluidic device for the capture, storage, and colorimetric sensing of sweat.

PubMed

Koh, Ahyeon; Kang, Daeshik; Xue, Yeguang; Lee, Seungmin; Pielak, Rafal M; Kim, Jeonghyun; Hwang, Taehwan; Min, Seunghwan; Banks, Anthony; Bastien, Philippe; Manco, Megan C; Wang, Liang; Ammann, Kaitlyn R; Jang, Kyung-In; Won, Phillip; Han, Seungyong; Ghaffari, Roozbeh; Paik, Ungyu; Slepian, Marvin J; Balooch, Guive; Huang, Yonggang; Rogers, John A

2016-11-23

Capabilities in health monitoring enabled by capture and quantitative chemical analysis of sweat could complement, or potentially obviate the need for, approaches based on sporadic assessment of blood samples. Established sweat monitoring technologies use simple fabric swatches and are limited to basic analysis in controlled laboratory or hospital settings. We present a collection of materials and device designs for soft, flexible, and stretchable microfluidic systems, including embodiments that integrate wireless communication electronics, which can intimately and robustly bond to the surface of the skin without chemical and mechanical irritation. This integration defines access points for a small set of sweat glands such that perspiration spontaneously initiates routing of sweat through a microfluidic network and set of reservoirs. Embedded chemical analyses respond in colorimetric fashion to markers such as chloride and hydronium ions, glucose, and lactate. Wireless interfaces to digital image capture hardware serve as a means for quantitation. Human studies demonstrated the functionality of this microfluidic device during fitness cycling in a controlled environment and during long-distance bicycle racing in arid, outdoor conditions. The results include quantitative values for sweat rate, total sweat loss, pH, and concentration of chloride and lactate. Copyright © 2016, American Association for the Advancement of Science.

Multimodal quantitative phase and fluorescence imaging of cell apoptosis

NASA Astrophysics Data System (ADS)

Fu, Xinye; Zuo, Chao; Yan, Hao

2017-06-01

Fluorescence microscopy, utilizing fluorescence labeling, has the capability to observe intercellular changes which transmitted and reflected light microscopy techniques cannot resolve. However, the parts without fluorescence labeling are not imaged. Hence, the processes simultaneously happen in these parts cannot be revealed. Meanwhile, fluorescence imaging is 2D imaging where information in the depth is missing. Therefore the information in labeling parts is also not complete. On the other hand, quantitative phase imaging is capable to image cells in 3D in real time through phase calculation. However, its resolution is limited by the optical diffraction and cannot observe intercellular changes below 200 nanometers. In this work, fluorescence imaging and quantitative phase imaging are combined to build a multimodal imaging system. Such system has the capability to simultaneously observe the detailed intercellular phenomenon and 3D cell morphology. In this study the proposed multimodal imaging system is used to observe the cell behavior in the cell apoptosis. The aim is to highlight the limitations of fluorescence microscopy and to point out the advantages of multimodal quantitative phase and fluorescence imaging. The proposed multimodal quantitative phase imaging could be further applied in cell related biomedical research, such as tumor.

pH & Rate of Enzymatic Reactions.

ERIC Educational Resources Information Center

Clariana, Roy B.

1991-01-01

A quantitative and inexpensive way to measure the rate of enzymatic reaction is provided. The effects of different pH levels on the reaction rate of an enzyme from yeast are investigated and the results graphed. Background information, a list of needed materials, directions for preparing solutions, procedure, and results and discussion are…

Quantitative imaging methods in osteoporosis.

PubMed

Oei, Ling; Koromani, Fjorda; Rivadeneira, Fernando; Zillikens, M Carola; Oei, Edwin H G

2016-12-01

Osteoporosis is characterized by a decreased bone mass and quality resulting in an increased fracture risk. Quantitative imaging methods are critical in the diagnosis and follow-up of treatment effects in osteoporosis. Prior radiographic vertebral fractures and bone mineral density (BMD) as a quantitative parameter derived from dual-energy X-ray absorptiometry (DXA) are among the strongest known predictors of future osteoporotic fractures. Therefore, current clinical decision making relies heavily on accurate assessment of these imaging features. Further, novel quantitative techniques are being developed to appraise additional characteristics of osteoporosis including three-dimensional bone architecture with quantitative computed tomography (QCT). Dedicated high-resolution (HR) CT equipment is available to enhance image quality. At the other end of the spectrum, by utilizing post-processing techniques such as the trabecular bone score (TBS) information on three-dimensional architecture can be derived from DXA images. Further developments in magnetic resonance imaging (MRI) seem promising to not only capture bone micro-architecture but also characterize processes at the molecular level. This review provides an overview of various quantitative imaging techniques based on different radiological modalities utilized in clinical osteoporosis care and research.

Enamel demineralization and remineralization under plaque fluid-like conditions: a quantitative light-induced fluorescence study.

PubMed

Lippert, F; Butler, A; Lynch, R J M

2011-01-01

The present study investigated de- and remineralization in enamel lesions under plaque fluid (PF)-like conditions using quantitative light-induced fluorescence (QLF). Preformed lesions were exposed to partially saturated lactic acid solutions, varying in pH and fluoride concentration ([F]) based on a 5 × 3 factorial study design (0/0.1/0.5/1.5/4 ppm F; pH 4.9/5.2/5.5). Average fluorescence loss (ΔF) was monitored for 11 days. Subsequently, lesions were demineralized in a partially saturated acetic acid solution for two 24-hour periods. Data were analyzed using repeated measures analysis of covariance. Lesions exposed to PF at 4 ppm F and pH 5.5 showed not only the most remineralization (ΔΔF = 28.2 ± 14.0%) for all groups after 11 days, but also the most demineralization (ΔΔF = -19.3 ± 13.5%) after subsequent acetic acid exposure. Increased [F] resulted in more remineralization, regardless of pH. Higher pH values resulted in more remineralization. No remineralization was observed in lesions exposed to F-free solutions, regardless of pH. Remineralization was noticeable under the following conditions: pH 4.9 - [F] = 4 ppm, pH 5.2 - [F] ≥ 1.5 ppm, and pH 5.5 - [F] ≥ 0.5 ppm. Overall, [F] had a stronger effect on remineralization than pH. Subsequent demineralization showed that little protection was offered by PF-like solutions, and further demineralization compared with baseline was observed on lesions not remineralized initially. [F] had a stronger effect on net mineral change than pH. The present study has shown that QLF is a valuable tool in studying lesion de- and remineralization under PF-like conditions, where [F] was shown to be more important than pH. Copyright © 2011 S. Karger AG, Basel.

Quantitation of Fine Displacement in Echography

NASA Astrophysics Data System (ADS)

Masuda, Kohji; Ishihara, Ken; Yoshii, Ken; Furukawa, Toshiyuki; Kumagai, Sadatoshi; Maeda, Hajime; Kodama, Shinzo

1993-05-01

A High-speed Digital Subtraction Echography was developed to visualize the fine displacement of human internal organs. This method indicates differences in position through time series images of high-frame-rate echography. Fine displacement less than ultrasonic wavelength can be observed. This method, however, lacks the ability to quantitatively measure displacement length. The subtraction between two successive images was affected by displacement direction in spite of the displacement length being the same. To solve this problem, convolution of an echogram with Gaussian distribution was used. To express displacement length as brightness quantitatively, normalization using a brightness gradient was applied. The quantitation algorithm was applied to successive B-mode images. Compared to the simply subtracted images, quantitated images express more precisely the motion of organs. Expansion of the carotid artery and fine motion of ventricular walls can be visualized more easily. Displacement length can be quantitated with wavelength. Under more static conditions, this system quantitates displacement length that is much less than wavelength.

Observation of the pulp horn by swept source optical coherence tomography and cone beam computed tomography

NASA Astrophysics Data System (ADS)

Iino, Yoshiko; Yoshioka, Toshihiko; Hanada, Takahiro; Ebihara, Arata; Sunakawa, Mitsuhiro; Sumi, Yasunori; Suda, Hideaki

2015-02-01

Cone-beam computed tomography (CBCT) is one of the most useful diagnostic techniques in dentistry but it involves ionizing radiation, while swept source optical coherence tomography (SS-OCT) has been introduced recently as a nondestructive, real-time, high resolution imaging technique using low-coherence interferometry, which involves no ionizing radiation. The purpose of this study was to evaluate the ability of SS-OCT to detect the pulp horn (PH) in comparison with that of CBCT. Ten extracted human mandibular molars were used. After horizontally removing a half of the tooth crown, the distance from the cut dentin surface to PH was measured using microfocus computed tomography (Micro CT) (SL) as the gold standard, by CBCT (CL) and by SS-OCT (OL). In the SS-OCT images, only when PH was observed beneath the overlying dentin, the distance from the cut dentin surface to PH was recorded. If the pulp was exposed, it was defined as pulp exposure (PE). The results obtained by the above three methods were statistically analyzed by Spearman's rank correlation coefficient at a significance level of p < 0.01. SS-OCT detected the presence of PH when the distance from the cut dentin surface to PH determined by SL was 2.33 mm or less. Strong correlations of the measured values were found between SL and CL (r=0.87), SL and OL (r=0.96), and CL and OL (r=0.86). The results showed that SS-OCT images correlated closely with CBCT images, suggesting that SS-OCT can be a useful tool for the detection of PH.

Ratiometric, visual, dual-signal fluorescent sensing and imaging of pH/copper ions in real samples based on carbon dots-fluorescein isothiocyanate composites.

PubMed

Zhu, Xinxin; Jin, Hui; Gao, Cuili; Gui, Rijun; Wang, Zonghua

2017-01-01

In this article, a facile aqueous synthesis of carbon dots (CDs) was developed by using natural kelp as a new carbon source. Through hydrothermal carbonization of kelp juice, fluorescent CDs were prepared and the CDs' surface was modified with polyethylenimine (PEI). The PEI-modified CDs were conjugated with fluorescein isothiocyanate (FITC) to fabricate CDs-FITC composites. To exploit broad applications, the CDs-FITC composites were developed as fluorescent sensing or imaging platforms of pH and Cu 2+ . Analytical performances of the composites-based fluorescence (FL) sensors were evaluated, including visual FL imaging of pH in glass bottle, ratiometric FL sensing of pH in yogurt samples, visual FL latent fingerprint and leaf imaging detection of [Cu 2+ ], dual-signal FL sensing of [Cu 2+ ] in yogurt and human serum samples. Experimental results from ratiometric, visual, dual-signal FL sensing and imaging applications confirmed the high feasibility, accuracy, stabilization and simplicity of CDs-FITC composites-based FL sensors for the detection of pH and Cu 2+ ions in real samples. Copyright © 2016 Elsevier B.V. All rights reserved.

In vivo pH monitoring using boron doped diamond microelectrode and silver needles: Application to stomach disorder diagnosis

NASA Astrophysics Data System (ADS)

Fierro, Stéphane; Seishima, Ryo; Nagano, Osamu; Saya, Hideyuki; Einaga, Yasuaki

2013-11-01

This study presents the in vivo electrochemical monitoring of pH using boron doped diamond (BDD) microelectrode and silver needles for potential application in medical diagnosis. Accurate calibration curve for pH determination were obtained through in vitro electrochemical measurements. The increase induced in stomach pH by treatment with pantoprazole was used to demonstrate that it is possible to monitor the pH in vivo using the simple and noninvasive system proposed herein. Using the results of the in vivo and in vitro experiments, a quantitative analysis of the increase in stomach pH is also presented. It is proposed that the catheter-free pH monitoring system presented in this study could be potentially employed in any biological environment.

In vivo pH monitoring using boron doped diamond microelectrode and silver needles: application to stomach disorder diagnosis.

PubMed

Fierro, Stéphane; Seishima, Ryo; Nagano, Osamu; Saya, Hideyuki; Einaga, Yasuaki

2013-11-19

This study presents the in vivo electrochemical monitoring of pH using boron doped diamond (BDD) microelectrode and silver needles for potential application in medical diagnosis. Accurate calibration curve for pH determination were obtained through in vitro electrochemical measurements. The increase induced in stomach pH by treatment with pantoprazole was used to demonstrate that it is possible to monitor the pH in vivo using the simple and noninvasive system proposed herein. Using the results of the in vivo and in vitro experiments, a quantitative analysis of the increase in stomach pH is also presented. It is proposed that the catheter-free pH monitoring system presented in this study could be potentially employed in any biological environment.

Pharmacological imaging as a tool to visualise dopaminergic neurotoxicity.

PubMed

Schrantee, A; Reneman, L

2014-09-01

Dopamine abnormalities underlie a wide variety of psychopathologies, including ADHD and schizophrenia. A new imaging technique, pharmacological magnetic resonance imaging (phMRI), is a promising non-invasive technique to visualize the dopaminergic system in the brain. In this review we explore the clinical potential of phMRI in detecting dopamine dysfunction or neurotoxicity, assess its strengths and weaknesses and identify directions for future research. Preclinically, phMRI is able to detect severe dopaminergic abnormalities quite similar to conventional techniques such as PET and SPECT. phMRI benefits from its high spatial resolution and the possibility to visualize both local and downstream effects of dopaminergic neurotransmission. In addition, it allows for repeated measurements and assessments in vulnerable populations. The major challenge is the complex interpretation of phMRI results. Future studies in patients with dopaminergic abnormalities need to confirm the currently reviewed preclinical findings to validate the technique in a clinical setting. Eventually, based on the current review we expect that phMRI can be of use in a clinical setting involving vulnerable populations (such as children and adolescents) for diagnosis and monitoring treatment efficacy. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optical measurement of acidification of human dental plaque in vitro

NASA Astrophysics Data System (ADS)

Graham, Jasmine Y.; Nelson, Leonard Y.; Seibel, Eric J.

2018-02-01

A pH measurement of oral biofilms is helpful for monitoring the impact of acidogenic bacteria in the caries process. Demineralization of dental enamel is closely related to the time dependent pH of human plaque. Therefore, providing a means to easily measure the local pH of biofilms is a useful clinical diagnostic in the arsenal of caries prevention tools. Optical measurement methods of plaque metabolism can use intrinsic fluorescence or extrinsic fluorescence from added dyes. Autofluorescence spectral features of human oral biofilms at green (500 nm) and red (634 nm) fluorescence wavelengths using 405 nm excitation did not demonstrate a spectral or intensity shift between neutral and acidic conditions. Chlorin e6, an ingredient in chlorophyllin food supplement, exhibited a spectral and intensity shift of fluorescence emission in buffered solutions, but this quantitative pH-dependence was not transferable to a human plaque environment. Finally, a ratiometric quantitative pH measure was achieved by exciting (405 nm laser) a mixture of two dyes, fluorescein and rhodamine B. This two-dye mixture produced two strong fluorescent bands centered at 515 nm (fluorescein) and 580 nm (rhodamine B), where the 515 nm band was pH sensitive and the 580 nm band served as a pH insensitive reference. This dual-dye fluorescence ratio exhibited a linear response over pH 7 to 5 in human oral biofilms during a sugar challenge. We have explored methods to use non-contact, optical measures of local acidity levels in difficult to access dental locations such as occlusal fissures using various pH sensitive fluorescent dye systems.

pH determines the energetic efficiency of the cyanobacterial CO2 concentrating mechanism.

PubMed

Mangan, Niall M; Flamholz, Avi; Hood, Rachel D; Milo, Ron; Savage, David F

2016-09-06

Many carbon-fixing bacteria rely on a CO2 concentrating mechanism (CCM) to elevate the CO2 concentration around the carboxylating enzyme ribulose bisphosphate carboxylase/oxygenase (RuBisCO). The CCM is postulated to simultaneously enhance the rate of carboxylation and minimize oxygenation, a competitive reaction with O2 also catalyzed by RuBisCO. To achieve this effect, the CCM combines two features: active transport of inorganic carbon into the cell and colocalization of carbonic anhydrase and RuBisCO inside proteinaceous microcompartments called carboxysomes. Understanding the significance of the various CCM components requires reconciling biochemical intuition with a quantitative description of the system. To this end, we have developed a mathematical model of the CCM to analyze its energetic costs and the inherent intertwining of physiology and pH. We find that intracellular pH greatly affects the cost of inorganic carbon accumulation. At low pH the inorganic carbon pool contains more of the highly cell-permeable H2CO3, necessitating a substantial expenditure of energy on transport to maintain internal inorganic carbon levels. An intracellular pH ≈8 reduces leakage, making the CCM significantly more energetically efficient. This pH prediction coincides well with our measurement of intracellular pH in a model cyanobacterium. We also demonstrate that CO2 retention in the carboxysome is necessary, whereas selective uptake of HCO3 (-) into the carboxysome would not appreciably enhance energetic efficiency. Altogether, integration of pH produces a model that is quantitatively consistent with cyanobacterial physiology, emphasizing that pH cannot be neglected when describing biological systems interacting with inorganic carbon pools.

pH determines the energetic efficiency of the cyanobacterial CO2 concentrating mechanism

PubMed Central

Flamholz, Avi; Hood, Rachel D.; Milo, Ron

2016-01-01

Many carbon-fixing bacteria rely on a CO2 concentrating mechanism (CCM) to elevate the CO2 concentration around the carboxylating enzyme ribulose bisphosphate carboxylase/oxygenase (RuBisCO). The CCM is postulated to simultaneously enhance the rate of carboxylation and minimize oxygenation, a competitive reaction with O2 also catalyzed by RuBisCO. To achieve this effect, the CCM combines two features: active transport of inorganic carbon into the cell and colocalization of carbonic anhydrase and RuBisCO inside proteinaceous microcompartments called carboxysomes. Understanding the significance of the various CCM components requires reconciling biochemical intuition with a quantitative description of the system. To this end, we have developed a mathematical model of the CCM to analyze its energetic costs and the inherent intertwining of physiology and pH. We find that intracellular pH greatly affects the cost of inorganic carbon accumulation. At low pH the inorganic carbon pool contains more of the highly cell-permeable H2CO3, necessitating a substantial expenditure of energy on transport to maintain internal inorganic carbon levels. An intracellular pH ≈8 reduces leakage, making the CCM significantly more energetically efficient. This pH prediction coincides well with our measurement of intracellular pH in a model cyanobacterium. We also demonstrate that CO2 retention in the carboxysome is necessary, whereas selective uptake of HCO3− into the carboxysome would not appreciably enhance energetic efficiency. Altogether, integration of pH produces a model that is quantitatively consistent with cyanobacterial physiology, emphasizing that pH cannot be neglected when describing biological systems interacting with inorganic carbon pools. PMID:27551079

Multi-view approach for the diagnosis of pulmonary hypertension using transthoracic echocardiography.

PubMed

Schneider, Matthias; Pistritto, Anna Maria; Gerges, Christian; Gerges, Mario; Binder, Christina; Lang, Irene; Maurer, Gerald; Binder, Thomas; Goliasch, Georg

2018-05-01

Pulmonary hypertension (PH) is a disease with severe morbidity and mortality. Echocardiography plays an essential role in the screening of PH. The quality of the acquired continuous wave Doppler signal is the major limitation of the method and can greatly affect the accuracy of estimated pulmonary pressures. The aim of this study was to evaluate the clinical need to image from multiple ultrasound windows in patients with suspected pulmonary hypertension. We prospectively evaluated 65 patients (43% male, mean age 67.2 years) with echocardiography and right heart catheterization. 17% had invasively normal pulmonary pressures, 83% had pulmonary hypertension. Peak tricuspid regurgitation (TR) velocity was imaged in five echocardiographic views. Sufficient Doppler signal was recorded in 94% of the patients. Correlation for overall peak TR velocity with invasively measured systolic pulmonary artery pressure was r = 0.83 (p < 0.001). Considering all five imaging windows resulted in a sensitivity of 87%, and a specificity of 91% for correct diagnosis of PH with an AUC of 0.89, which was significantly better as compared to sole imaging from the right ventricular modified apical four-chamber view (AUC 0.85, p = 0.0395). Additional imaging from atypical views changed the overall peak TR velocity in 32% of the patients. A multiple-view approach changed the echocardiographic diagnosis of PH in 11% of the patients as opposed to sole imaging from an apical four-chamber view. This study comprehensively assessed the impact on clinical decision making when evaluating patients with an echocardiographic multiplane approach for suspected PH. This approach substantially increased sensitivity without a decrease in specificity.

Preoperative Cerebral Oxygen Extraction Fraction Imaging Generated from 7T MR Quantitative Susceptibility Mapping Predicts Development of Cerebral Hyperperfusion following Carotid Endarterectomy.

PubMed

Nomura, J-I; Uwano, I; Sasaki, M; Kudo, K; Yamashita, F; Ito, K; Fujiwara, S; Kobayashi, M; Ogasawara, K

2017-12-01

Preoperative hemodynamic impairment in the affected cerebral hemisphere is associated with the development of cerebral hyperperfusion following carotid endarterectomy. Cerebral oxygen extraction fraction images generated from 7T MR quantitative susceptibility mapping correlate with oxygen extraction fraction images on positron-emission tomography. The present study aimed to determine whether preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping could identify patients at risk for cerebral hyperperfusion following carotid endarterectomy. Seventy-seven patients with unilateral internal carotid artery stenosis (≥70%) underwent preoperative 3D T2*-weighted imaging using a multiple dipole-inversion algorithm with a 7T MR imager. Quantitative susceptibility mapping images were then obtained, and oxygen extraction fraction maps were generated. Quantitative brain perfusion single-photon emission CT was also performed before and immediately after carotid endarterectomy. ROIs were automatically placed in the bilateral middle cerebral artery territories in all images using a 3D stereotactic ROI template, and affected-to-contralateral ratios in the ROIs were calculated on quantitative susceptibility mapping-oxygen extraction fraction images. Ten patients (13%) showed post-carotid endarterectomy hyperperfusion (cerebral blood flow increases of ≥100% compared with preoperative values in the ROIs on brain perfusion SPECT). Multivariate analysis showed that a high quantitative susceptibility mapping-oxygen extraction fraction ratio was significantly associated with the development of post-carotid endarterectomy hyperperfusion (95% confidence interval, 33.5-249.7; P = .002). Sensitivity, specificity, and positive- and negative-predictive values of the quantitative susceptibility mapping-oxygen extraction fraction ratio for the prediction of the development of post-carotid endarterectomy hyperperfusion were 90%, 84%, 45%, and 98%, respectively. Preoperative oxygen extraction fraction imaging generated from 7T MR quantitative susceptibility mapping identifies patients at risk for cerebral hyperperfusion following carotid endarterectomy. © 2017 by American Journal of Neuroradiology.

Proton-Fueled, Reversible DNA Hybridization Chain Assembly for pH Sensing and Imaging.

PubMed

Liu, Lan; Liu, Jin-Wen; Huang, Zhi-Mei; Wu, Han; Li, Na; Tang, Li-Juan; Jiang, Jian-Hui

2017-07-05

Design of DNA self-assembly with reversible responsiveness to external stimuli is of great interest for diverse applications. We for the first time develop a pH-responsive, fully reversible hybridization chain reaction (HCR) assembly that allows sensitive sensing and imaging of pH in living cells. Our design relies on the triplex forming sequences that form DNA triplex with toehold regions under acidic conditions and then induce a cascade of strand displacement and DNA assembly. The HCR assembly has shown dynamic responses in physiological pH ranges with excellent reversibility and demonstrated the potential for in vitro detection and live-cell imaging of pH. Moreover, this method affords HCR assemblies with highly localized fluorescence responses, offering advantages of improving sensitivity and better selectivity. The proton-fueled, reversible HCR assembly may provide a useful approach for pH-related cell biology study and disease diagnostics.

Quantitative imaging biomarkers: a review of statistical methods for technical performance assessment.

PubMed

Raunig, David L; McShane, Lisa M; Pennello, Gene; Gatsonis, Constantine; Carson, Paul L; Voyvodic, James T; Wahl, Richard L; Kurland, Brenda F; Schwarz, Adam J; Gönen, Mithat; Zahlmann, Gudrun; Kondratovich, Marina V; O'Donnell, Kevin; Petrick, Nicholas; Cole, Patricia E; Garra, Brian; Sullivan, Daniel C

2015-02-01

Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers to measure changes in these features. Critical to the performance of a quantitative imaging biomarker in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method, and metrics used to assess a quantitative imaging biomarker for clinical use. It is therefore difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America and the Quantitative Imaging Biomarker Alliance with technical, radiological, and statistical experts developed a set of technical performance analysis methods, metrics, and study designs that provide terminology, metrics, and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of quantitative imaging biomarker performance studies so that results from multiple studies can be compared, contrasted, or combined. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Quantitative and simultaneous detection of four foodborne bacterial pathogens with a multi-channel SPR sensor.

PubMed

Taylor, Allen D; Ladd, Jon; Yu, Qiuming; Chen, Shengfu; Homola, Jirí; Jiang, Shaoyi

2006-12-15

We report the quantitative and simultaneous detection of four species of bacteria, Escherichia coli O157:H7, Salmonella choleraesuis serotype typhimurium, Listeria monocytogenes, and Campylobacter jejuni, using an eight-channel surface plasmon resonance (SPR) sensor based on wavelength division multiplexing. Detection curves showing SPR response versus analyte concentration were established for each species of bacteria in buffer at pH 7.4, apple juice at native pH 3.7, and apple juice at an adjusted pH of 7.4, as well as for a mixture containing all four species of bacteria in buffer. Control experiments were performed to show the non-fouling characteristics of the sensor surface as well as the specificity of the amplification antibodies used in this study. The limit of detection (LOD) for each of the four species of bacteria in the tested matrices ranges from 3.4 x 10(3) to 1.2 x 10(5) cfu/ml. Detection curves in buffer of an individual species of bacteria in a mixture of all four species of bacteria correlated well with detection curves of the individual species of bacteria alone. SPR responses were higher for bacteria in apple juice at pH 7.4 than in apple juice at pH 3.7. This difference in sensor response could be partly attributed to the pH dependence of antibody-antigen binding.

Quantitative radiomics studies for tissue characterization: a review of technology and methodological procedures.

PubMed

Larue, Ruben T H M; Defraene, Gilles; De Ruysscher, Dirk; Lambin, Philippe; van Elmpt, Wouter

2017-02-01

Quantitative analysis of tumour characteristics based on medical imaging is an emerging field of research. In recent years, quantitative imaging features derived from CT, positron emission tomography and MR scans were shown to be of added value in the prediction of outcome parameters in oncology, in what is called the radiomics field. However, results might be difficult to compare owing to a lack of standardized methodologies to conduct quantitative image analyses. In this review, we aim to present an overview of the current challenges, technical routines and protocols that are involved in quantitative imaging studies. The first issue that should be overcome is the dependency of several features on the scan acquisition and image reconstruction parameters. Adopting consistent methods in the subsequent target segmentation step is evenly crucial. To further establish robust quantitative image analyses, standardization or at least calibration of imaging features based on different feature extraction settings is required, especially for texture- and filter-based features. Several open-source and commercial software packages to perform feature extraction are currently available, all with slightly different functionalities, which makes benchmarking quite challenging. The number of imaging features calculated is typically larger than the number of patients studied, which emphasizes the importance of proper feature selection and prediction model-building routines to prevent overfitting. Even though many of these challenges still need to be addressed before quantitative imaging can be brought into daily clinical practice, radiomics is expected to be a critical component for the integration of image-derived information to personalize treatment in the future.

Validation of a method for the quantitation of ghrelin and unacylated ghrelin by HPLC.

PubMed

Staes, Edith; Rozet, Eric; Ucakar, Bernard; Hubert, Philippe; Préat, Véronique

2010-02-05

An HPLC/UV method was first optimized for the separation and quantitation of human acylated and unacylated (or des-acyl) ghrelin from aqueous solutions. This method was validated by an original approach using accuracy profiles based on tolerance intervals for the total error measurement. The concentration range that achieved adequate accuracy extended from 1.85 to 59.30microM and 1.93 to 61.60microM for acylated and unacylated ghrelin, respectively. Then, optimal temperature, pH and buffer for sample storage were determined. Unacylated ghrelin was found to be stable in all conditions tested. At 37 degrees C acylated ghrelin was stable at pH 4 but unstable at pH 7.4, the main degradation product was unacylated ghrelin. Finally, this validated HPLC/UV method was used to evaluate the binding of acylated and unacylated ghrelin to liposomes.

Educational Training and Careers of Ph.D. Holders: An Exploratory Empirical Study. Planning Paper 27.

ERIC Educational Resources Information Center

Morris, Jeffrey

This study analyzes the occupational mobility of individuals who hold the Ph.D. degree. Drawing upon data contained in the National Register of Scientific and Technical Personnel compiled by the National Science Foundation, this paper presents the quantitative relationships between educational background, occupational mobility, and salaries. Based…

Prediction of pH of fresh chicken breast fillets by VNIR hyperspectral imaging

USDA-ARS?s Scientific Manuscript database

Visible and near-infrared (VNIR) hyperspectral imaging (400–900 nm) was used to evaluate pH of fresh chicken breast fillets (pectoralis major muscle) from the bone (dorsal) side of individual fillets. After the principal component analysis (PCA), a band threshold method was applied to the first prin...

In situ fluorescence imaging of localized corrosion with a pH-sensitive imaging fiber

DOE Office of Scientific and Technical Information (OSTI.GOV)

Panova, A.A.; Pantano, P.; Walt, D.R.

1997-12-01

A fiber optic pH-sensor capable of both visualizing corrosion sites and measuring local chemical concentrations is applied to real-time corrosion monitoring. The imaging fiber`s distal face containing an immobilized pH-sensitive fluorescent dye is brought into contact with metal surfaces submerged in aqueous buffers and fluorescence images are acquired as a function of time. The observed changes in fluorescence due to increases in pH at cathodic sites and decreases in pH at anodic sites are indicative of localized corrosion rates.

Digitized hand-wrist radiographs: comparison of subjective and software-derived image quality at various compression ratios.

PubMed

McCord, Layne K; Scarfe, William C; Naylor, Rachel H; Scheetz, James P; Silveira, Anibal; Gillespie, Kevin R

2007-05-01

The objectives of this study were to compare the effect of JPEG 2000 compression of hand-wrist radiographs on observer image quality qualitative assessment and to compare with a software-derived quantitative image quality index. Fifteen hand-wrist radiographs were digitized and saved as TIFF and JPEG 2000 images at 4 levels of compression (20:1, 40:1, 60:1, and 80:1). The images, including rereads, were viewed by 13 orthodontic residents who determined the image quality rating on a scale of 1 to 5. A quantitative analysis was also performed by using a readily available software based on the human visual system (Image Quality Measure Computer Program, version 6.2, Mitre, Bedford, Mass). ANOVA was used to determine the optimal compression level (P < or =.05). When we compared subjective indexes, JPEG compression greater than 60:1 significantly reduced image quality. When we used quantitative indexes, the JPEG 2000 images had lower quality at all compression ratios compared with the original TIFF images. There was excellent correlation (R2 >0.92) between qualitative and quantitative indexes. Image Quality Measure indexes are more sensitive than subjective image quality assessments in quantifying image degradation with compression. There is potential for this software-based quantitative method in determining the optimal compression ratio for any image without the use of subjective raters.

Quantitative MR imaging of pulmonary hypertension: A practical approach to the current state of the art

PubMed Central

Swift, Andrew J.; Wild, Jim M.; Nagle, Scott K.; Roldán-Alzate, Alejandro; François, Christopher J.; Fain, Sean; Johnson, Kevin; Capener, Dave; van Beek, Edwin J. R.; Kiely, David G.; Wang, Kang; Schiebler, Mark L.

2014-01-01

Pulmonary hypertension (PH) is a condition of varied aetiology, commonly associated with a poor clinical outcome. Patients are categorised on the basis of pathophysiological, clinical, radiological and therapeutic similarities. Pulmonary arterial hypertension (PAH) is often diagnosed late in its disease course with outcome dependent on aetiology, disease severity and response to treatment. Recent advances in quantitative MR imaging allow for a better initial characterization and measurement of the morphologic and flow related changes that accompany the response of the heart-lung axis to prolonged elevation of pulmonary arterial pressure and resistance and provide a reproducible, comprehensive and non-invasive means of assessing the course of the disease and response to treatment. Typical features of pulmonary arterial hypertension (PAH) occur primarily as a result of increased pulmonary vascular resistance and resultant increased RV afterload. Several MRI derived diagnostic markers have emerged, such as ventricular mass index (VMI), interventricular septal configuration and average pulmonary artery velocity having reported diagnostic accuracy similar to Doppler echocardiography. Furthermore, prognostic markers have been identified with independent predictive value for identification of treatment failure. Such markers include: large right ventricular end-diastolic volume index (RVEDVI), low left ventricular end diastolic volume index (LVEDVI), low right ventricular ejection fraction (RVEF) and relative area change of the pulmonary trunk. MRI is ideally suited to longitudinal follow-up of patients with PAH due to its non-invasive nature, high reproducibility and has the advantage over other biomarkers in PAH due to its sensitivity to change in morphological, functional and flow related parameters. Further study the role of MR imaging as a biomarker in the clinical environment is warranted. PMID:24552882

A quantitative reconstruction software suite for SPECT imaging

NASA Astrophysics Data System (ADS)

Namías, Mauro; Jeraj, Robert

2017-11-01

Quantitative Single Photon Emission Tomography (SPECT) imaging allows for measurement of activity concentrations of a given radiotracer in vivo. Although SPECT has usually been perceived as non-quantitative by the medical community, the introduction of accurate CT based attenuation correction and scatter correction from hybrid SPECT/CT scanners has enabled SPECT systems to be as quantitative as Positron Emission Tomography (PET) systems. We implemented a software suite to reconstruct quantitative SPECT images from hybrid or dedicated SPECT systems with a separate CT scanner. Attenuation, scatter and collimator response corrections were included in an Ordered Subset Expectation Maximization (OSEM) algorithm. A novel scatter fraction estimation technique was introduced. The SPECT/CT system was calibrated with a cylindrical phantom and quantitative accuracy was assessed with an anthropomorphic phantom and a NEMA/IEC image quality phantom. Accurate activity measurements were achieved at an organ level. This software suite helps increasing quantitative accuracy of SPECT scanners.

Quantified pH imaging with hyperpolarized (13) C-bicarbonate.

PubMed

Scholz, David Johannes; Janich, Martin A; Köllisch, Ulrich; Schulte, Rolf F; Ardenkjaer-Larsen, Jan H; Frank, Annette; Haase, Axel; Schwaiger, Markus; Menzel, Marion I

2015-06-01

Because pH plays a crucial role in several diseases, it is desirable to measure pH in vivo noninvasively and in a spatially localized manner. Spatial maps of pH were quantified in vitro, with a focus on method-based errors, and applied in vivo. In vitro and in vivo (13) C mapping were performed for various flip angles for bicarbonate (BiC) and CO2 with spectral-spatial excitation and spiral readout in healthy Lewis rats in five slices. Acute subcutaneous sterile inflammation was induced with Concanavalin A in the right leg of Buffalo rats. pH and proton images were measured 2 h after induction. After optimizing the signal to noise ratio of the hyperpolarized (13) C-bicarbonate, error estimation of the spectral-spatial excited spectrum reveals that the method covers the biologically relevant pH range of 6 to 8 with low pH error (< 0.2). Quantification of pH maps shows negligible impact of the residual bicarbonate signal. pH maps reflect the induction of acute metabolic alkalosis. Inflamed, infected regions exhibit lower pH. Hyperpolarized (13) C-bicarbonate pH mapping was shown to be sensitive in the biologically relevant pH range. The mapping of pH was applied to healthy in vivo organs and interpreted within inflammation and acute metabolic alkalosis models. © 2014 Wiley Periodicals, Inc.

Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury

PubMed Central

Liu, Wei; Soderlund, Karl; Senseney, Justin S.; Joy, David; Yeh, Ping-Hong; Ollinger, John; Sham, Elyssa B.; Liu, Tian; Wang, Yi; Oakes, Terrence R.; Riedy, Gerard

2017-01-01

Purpose To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping. Materials and Methods The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient-recalled-echo MR imaging and three-dimensional flow-compensated multi-echo gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test. Results Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy-seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean ± standard deviation, 9.8 microhemorrhages ± 12.8 vs 13.7 microhemorrhages ± 16.6; P = .019). Quantitative susceptibility mapping–derived quantitative measures of microhemorrhages also decreased over time: −0.85 mm3 per day ± 1.59 for total volume (P = .039) and −0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P = .016). Conclusion The number of microhemorrhages and quantitative susceptibility mapping–derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage. PMID:26371749

Imaging Cerebral Microhemorrhages in Military Service Members with Chronic Traumatic Brain Injury.

PubMed

Liu, Wei; Soderlund, Karl; Senseney, Justin S; Joy, David; Yeh, Ping-Hong; Ollinger, John; Sham, Elyssa B; Liu, Tian; Wang, Yi; Oakes, Terrence R; Riedy, Gerard

2016-02-01

To detect cerebral microhemorrhages in military service members with chronic traumatic brain injury by using susceptibility-weighted magnetic resonance (MR) imaging. The longitudinal evolution of microhemorrhages was monitored in a subset of patients by using quantitative susceptibility mapping. The study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants underwent two-dimensional conventional gradient-recalled-echo MR imaging and three-dimensional flow-compensated multiecho gradient-recalled-echo MR imaging (processed to generate susceptibility-weighted images and quantitative susceptibility maps), and a subset of patients underwent follow-up imaging. Microhemorrhages were identified by two radiologists independently. Comparisons of microhemorrhage number, size, and magnetic susceptibility derived from quantitative susceptibility maps between baseline and follow-up imaging examinations were performed by using the paired t test. Among the 603 patients, cerebral microhemorrhages were identified in 43 patients, with six excluded for further analysis owing to artifacts. Seventy-seven percent (451 of 585) of the microhemorrhages on susceptibility-weighted images had a more conspicuous appearance than on gradient-recalled-echo images. Thirteen of the 37 patients underwent follow-up imaging examinations. In these patients, a smaller number of microhemorrhages were identified at follow-up imaging compared with baseline on quantitative susceptibility maps (mean ± standard deviation, 9.8 microhemorrhages ± 12.8 vs 13.7 microhemorrhages ± 16.6; P = .019). Quantitative susceptibility mapping-derived quantitative measures of microhemorrhages also decreased over time: -0.85 mm(3) per day ± 1.59 for total volume (P = .039) and -0.10 parts per billion per day ± 0.14 for mean magnetic susceptibility (P = .016). The number of microhemorrhages and quantitative susceptibility mapping-derived quantitative measures of microhemorrhages all decreased over time, suggesting that hemosiderin products undergo continued, subtle evolution in the chronic stage. © RSNA, 2015.

Carbon-Based Solid-State Calcium Ion-Selective Microelectrode and Scanning Electrochemical Microscopy: A Quantitative Study of pH-Dependent Release of Calcium Ions from Bioactive Glass.

PubMed

Ummadi, Jyothir Ganesh; Downs, Corey J; Joshi, Vrushali S; Ferracane, Jack L; Koley, Dipankar

2016-03-15

Solid-state ion-selective electrodes are used as scanning electrochemical microscope (SECM) probes because of their inherent fast response time and ease of miniaturization. In this study, we report the development of a solid-state, low-poly(vinyl chloride), carbon-based calcium ion-selective microelectrode (Ca(2+)-ISME), 25 μm in diameter, capable of performing an amperometric approach curve and serving as a potentiometric sensor. The Ca(2+)-ISME has a broad linear response range of 5 μM to 200 mM with a near Nernstian slope of 28 mV/log[a(Ca(2+))]. The calculated detection limit for Ca(2+)-ISME is 1 μM. The selectivity coefficients of this Ca(2+)-ISME are log K(Ca(2+),A) = -5.88, -5.54, and -6.31 for Mg(2+), Na(+), and K(+), respectively. We used this new type of Ca(2+)-ISME as an SECM probe to quantitatively map the chemical microenvironment produced by a model substrate, bioactive glass (BAG). In acidic conditions (pH 4.5), BAG was found to increase the calcium ion concentration from 0.7 mM ([Ca(2+)] in artificial saliva) to 1.4 mM at 20 μm above the surface. In addition, a solid-state dual SECM pH probe was used to correlate the release of calcium ions with the change in local pH. Three-dimensional pH and calcium ion distribution mapping were also obtained by using these solid-state probes. The quantitative mapping of pH and Ca(2+) above the BAG elucidates the effectiveness of BAG in neutralizing and releasing calcium ions in acidic conditions.

The relationship between viability and intracellular pH in the yeast Saccharomyces cerevisiae.

PubMed Central

Imai, T; Ohno, T

1995-01-01

The relationship between viability (cell proliferation activity) and intracellular pH in the yeast Saccharomyces cerevisiae was investigated by using cells that had been deactivated by low-temperature storage, ethanol treatment, or heat treatment. The intracellular pH was measured with a microscopic image processor or a spectrofluorophotometer. At first, the intracellular pH measurements of individual cells were compared with slide culture results by microscopic image processing. A clear correlation existed between the proliferation activity and intracellular pH. Moreover, by spectrofluorophotometry analysis, it was found that there was a relationship between the viability and intracellular pH of brewing yeast under conditions of low external pH (n = 15, r = 0.960, P = 0.001). This relationship was also observed in baker's yeast (n = 13, r = 0.950, P = 0.001). On the other hand, when the fluorescein staining method was used in these experiments, the relationship between viability and staining percentage was not observed. From these results, intracellular pH was found to be a sensitive factor for estimating yeast physiology. The possible role of cell deterioration is also discussed. PMID:7486996

Investigation of the optical response of photonic crystal nanocavities in ferroelectric oxide thin film

NASA Astrophysics Data System (ADS)

Lin, Pao Tai; Russin, William A.; Joshi-Imre, Alexandra; Ocola, Leonidas E.; Wessels, B. W.

2015-10-01

The optical properties of BaTiO3 two dimensional photonic crystal (PhC) nanocavities were investigated. Two types of nanocavities consisting of dopants and vacancies with PhC periodicities ranging from 200 to 550 nm were evaluated. The images from laser scanning confocal microscopy show the optical scattering of the PhC cavities is highly wavelength dependent. An optical intensity reversal is observed when the wavelength of probe light shifts by 29 nm. Meanwhile, intensity contrast between the nanocavity and its adjacent PhCs is enhanced as the PhC periodicity becomes shorter than the probe wavelength. To determine the photonic band structures fluorescence from dye covered PhCs were imaged and analyzed. A strong enhancement of fluorescence is observed for the PhC with a period of 200 nm. Upon comparison to the 2D finite difference time domain calculations, the enhancement is attributed to strong light localization within the PhC nanocavity. As a result, the in-plane lightwave propagation is prohibited that results in an increase in the vertical light scattering.

Optimization of urinary dipstick pH: Are multiple dipstick pH readings reliably comparable to commercial 24-hour urinary pH?

PubMed

Abbott, Joel E; Miller, Daniel L; Shi, William; Wenzler, David; Elkhoury, Fuad F; Patel, Nishant D; Sur, Roger L

2017-09-01

Accurate measurement of pH is necessary to guide medical management of nephrolithiasis. Urinary dipsticks offer a convenient method to measure pH, but prior studies have only assessed the accuracy of a single, spot dipstick. Given the known diurnal variation in pH, a single dipstick pH is unlikely to reflect the average daily urinary pH. Our goal was to determine whether multiple dipstick pH readings would be reliably comparable to pH from a 24-hour urine analysis. Kidney stone patients undergoing a 24-hour urine collection were enrolled and took images of dipsticks from their first 3 voids concurrently with the 24-hour collection. Images were sent to and read by a study investigator. The individual and mean pH from the dipsticks were compared to the 24-hour urine pH and considered to be accurate if the dipstick readings were within 0.5 of the 24-hour urine pH. The Bland-Altman test of agreement was used to further compare dipstick pH relative to 24-hour urine pH. Fifty-nine percent of patients had mean urinary pH values within 0.5 pH units of their 24-hour urine pH. Bland-Altman analysis showed a mean difference between dipstick pH and 24-hour urine pH of -0.22, with an upper limit of agreement of 1.02 (95% confidence interval [CI], 0.45-1.59) and a lower limit of agreement of -1.47 (95% CI, -2.04 to -0.90). We concluded that urinary dipstick based pH measurement lacks the precision required to guide medical management of nephrolithiasis and physicians should use 24-hour urine analysis to base their metabolic therapy.

Highly resolved imaging at the soil - plant root interface: A combination of fluorescence imaging and neutron radiography

NASA Astrophysics Data System (ADS)

Rudolph, N.; Oswald, S. E.; Lehmann, E.

2012-12-01

This study represents a novel experimental set up to non-invasivley map the gradients of biogeochemical parameters at the soil -root interface of plants in situ. The patterns of oxygen, pH and the soil water content distribution were mapped in high resolution with a combination of fluorescence imaging and neutron radiography. Measuring the real-time distribution of water, pH and oxygen concentration would enable us to locate the active parts of the roots in respect to water uptake, exudation and respiration. Roots performance itself is variable as a function of age and development stage and is interrelated with local soil conditions such as water and oxygen availability or nutrients and pH buffering capacity in soil. Non-destructive imaging methods such as fluorescence and neutron imaging have provided a unique opportunity to unravel some of these complex processes. Thin glass containers (inner size 10cm x 10cm x 1.5 cm) were filled with 2 different sandy soils. Sensor foil for O2 and pH were installed on the inner-sides of the containers. We grew lupine plants in the container under controlled conditions until the root system was developed. Growing plants at different stages prior to the imaging experiment, we took neutron radiographs and fluorescence images of 10-day old and 30-day old root systems of lupine plants over a range of soil water contents, and therefore a range of root activities and oxygen changes. We observed the oxygen consumption pattern, the pH changes, and the root water uptake of lupine plants over the course of several days. We observed a higher respiration activity around the lateral roots than for the tap root. The oxygen depletion zones around the roots extended to farther distances after each rewatering of the samples. Root systems of the plants were mapped from the neutron radiograps. Close association of the roots distribution and the the location of oxygen depletion patterns provided evidence that this effect was caused by roots. The oxygen deficit pattern intensified with increasing root age. Due to the high soil water content after rewatering, the aeration from atmosphere was limited. pH dynamic was closely related to the root age. Initially, the soil pH strongly decreased around the young growing tap root. This pattern changed with time to an increased pH around the tap root but a strong acidification in the vicinity of lateral roots. After each rewatering, the pH increased which might be due to the dilution of H+ in high soil water contents. With our coupled imaging set up we were able to monitor the dynamics of oxygen, pH and water content around the roots of plant with high spatial and temporal resolutions over day and night at a wide range of soil water contents. Our experimental set up provides the opportunity to simultaneousely map the dynamics of these vital parameters in the root zone of plants.

The effect of antioxidants on quantitative changes of lysine and methionine in linoleic acid emulsions at different pH conditions.

PubMed

Hęś, Marzanna; Gliszczyńska-Świgło, Anna; Gramza-Michałowska, Anna

2017-01-01

Plants are an important source of phenolic compounds. The antioxidant capacities of green tea, thyme and rosemary extracts that contain these compounds have been reported earlier. However, there is a lack of accessible information about their activity against lipid oxidation in emulsions and inhibit the interaction of lipid oxidation products with amino acids. Therefore, the influence of green tea, thyme and rosemary extracts and BHT (butylated hydroxytoluene) on quantitative changes in lysine and methionine in linoleic acid emulsions at a pH of isoelectric point and a pH lower than the isoelectric point of amino acids was investigated. Total phenolic contents in plant extracts were determined spectrophotometrically by using Folin-Ciocalteu's reagent, and individual phenols by using HPLC. The level of oxidation of emulsion was determined using the measurement of peroxides and TBARS (thiobarbituric acid reactive substances). Methionine and lysine in the system were reacted with sodium nitroprusside and trinitrobenzenesulphonic acid respectively, and the absorbance of the complexes was measured. Extract of green tea had the highest total polyphenol content. The system containing antioxidants and amino acid protected linoleic acid more efficiently than by the addition of antioxidants only. Lysine and methionine losses in samples without the addition of antioxidants were lower in their isoelectric points than below these points. Antioxidants decrease the loss of amino acids. The protective properties of antioxidants towards methionine were higher in a pH of isoelectric point whereas towards lysine in pH below this point. Green tea, thyme and rosemary extracts exhibit antioxidant activity in linoleic acid emulsions. Moreover, they can be utilized to inhibit quantitative changes in amino acids in lipid emulsions. However, the antioxidant efficiency of these extracts seems to depend on pH conditions. Further investigations should be carried out to clarify this issue.

Cancer imaging phenomics toolkit: quantitative imaging analytics for precision diagnostics and predictive modeling of clinical outcome.

PubMed

Davatzikos, Christos; Rathore, Saima; Bakas, Spyridon; Pati, Sarthak; Bergman, Mark; Kalarot, Ratheesh; Sridharan, Patmaa; Gastounioti, Aimilia; Jahani, Nariman; Cohen, Eric; Akbari, Hamed; Tunc, Birkan; Doshi, Jimit; Parker, Drew; Hsieh, Michael; Sotiras, Aristeidis; Li, Hongming; Ou, Yangming; Doot, Robert K; Bilello, Michel; Fan, Yong; Shinohara, Russell T; Yushkevich, Paul; Verma, Ragini; Kontos, Despina

2018-01-01

The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

Calibration of diatom-pH-alkalinity methodology for the interpretation of the sedimentary record in Emerald Lake Integrated watershed study. Final report, 6 May 1985-10 October 1986

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmes, R.W.

1986-10-10

The present study was designed to establish quantitative relationships between lake air-equilibrated pH, alkalinity, and diatoms occurring in the surface sediments in high-elevation Sierra Nevada Lakes. These relationships provided the necessary information to develop predictive equations relating lake pH to the composition of surface-sediment diatom assemblages in 27 study lakes. Using the Hustedt diatom pH classification system, Index B of Renberg and Hellberg, and multiple linear regression analysis, two equations were developed which predict lake pH from the relative abundance of sediment diatoms occurring in each of four diatom pH groupings.

Quantitative comparison of bright field and annular bright field imaging modes for characterization of oxygen octahedral tilts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kim, Young-Min; Pennycook, Stephen J.; Borisevich, Albina Y.

Octahedral tilt behavior is increasingly recognized as an important contributing factor to the physical behavior of perovskite oxide materials and especially their interfaces, necessitating the development of high-resolution methods of tilt mapping. There are currently two major approaches for quantitative imaging of tilts in scanning transmission electron microscopy (STEM), bright field (BF) and annular bright field (ABF). In this study, we show that BF STEM can be reliably used for measurements of oxygen octahedral tilts. While optimal conditions for BF imaging are more restricted with respect to sample thickness and defocus, we find that BF imaging with an aberration-corrected microscopemore » with the accelerating voltage of 300 kV gives us the most accurate quantitative measurement of the oxygen column positions. Using the tilted perovskite structure of BiFeO 3 (BFO) as our test sample, we simulate BF and ABF images in a wide range of conditions, identifying the optimal imaging conditions for each mode. Finally, we show that unlike ABF imaging, BF imaging remains directly quantitatively interpretable for a wide range of the specimen mistilt, suggesting that it should be preferable to the ABF STEM imaging for quantitative structure determination.« less

Quantitative comparison of bright field and annular bright field imaging modes for characterization of oxygen octahedral tilts

DOE PAGES

Kim, Young-Min; Pennycook, Stephen J.; Borisevich, Albina Y.

2017-04-29

Octahedral tilt behavior is increasingly recognized as an important contributing factor to the physical behavior of perovskite oxide materials and especially their interfaces, necessitating the development of high-resolution methods of tilt mapping. There are currently two major approaches for quantitative imaging of tilts in scanning transmission electron microscopy (STEM), bright field (BF) and annular bright field (ABF). In this study, we show that BF STEM can be reliably used for measurements of oxygen octahedral tilts. While optimal conditions for BF imaging are more restricted with respect to sample thickness and defocus, we find that BF imaging with an aberration-corrected microscopemore » with the accelerating voltage of 300 kV gives us the most accurate quantitative measurement of the oxygen column positions. Using the tilted perovskite structure of BiFeO 3 (BFO) as our test sample, we simulate BF and ABF images in a wide range of conditions, identifying the optimal imaging conditions for each mode. Finally, we show that unlike ABF imaging, BF imaging remains directly quantitatively interpretable for a wide range of the specimen mistilt, suggesting that it should be preferable to the ABF STEM imaging for quantitative structure determination.« less

A confocal microscopy based method to monitor extracellular pH in fungal biofilms.

PubMed

Schlafer, Sebastian; Kamp, Anja; Garcia, Javier E

2018-04-19

pH in fungal biofilms is important for a variety of fungal infections and industrial applications involving fungal biofilms, but to date, it has never been measured directly inside the biofilm matrix. In the present study, a new methodology was developed allowing for confocal microscopy based monitoring of extracellular pH inside fungal biofilms. Monospecies biofilms of Aspergillus fumigatus, Candida albicans, Candida dubliniensis and Cryptococcus neoformans were stained with the pH dependent ratiometric probe C-SNARF-4, imaged with a confocal microscope, and a digital image analysis procedure was developed to determine pH in the extracellular matrix. As a proof of concept, pH developments at the biofilm-substratum interface were monitored for one h after exposure to glucose. Observed pH drops differed considerably between the different species and also between replicate biofilms of the same species. C. albicans biofilms showed the highest acidogenicity, with pH drops occurring much faster than in planktonic culture. pH ratiometry with C-SNARF-4 is a valuable tool to get insight into fungal biofilm metabolism and may shed new light on both disease-related and industrially relevant processes in fungal biofilms.

Development of quantitative methods for the detection of enteroviruses in sewage sludges during activation and following land disposal.

PubMed Central

Hurst, C J; Farrah, S R; Gerba, C P; Melnick, J L

1978-01-01

The development and evaluation of methods for the quantitative recovery of enteroviruses from sewage sludge are reported. Activated sewage sludge solids were collected by centrifugation, and elution of the solid-associated virus was accomplished by mechanical agitation in glycine buffer at pH 11.0. Eluted viruses were concentrated either onto an aluminum hydroxide floc or by association with a floc which formed de novo upon adjustment of the glycine eluate to pH 3.5. Viruses which remained in the liquid phase after lowering the pH of glycine eluate were concentrated by adsorption to and elution from membrane filters. The method of choice included high pH glycine elution and subsequent low pH concentration; it yielded an efficiency of recovery from activated sludge of 80% for poliovirus type 1, 68% for echovirus type 7, and 75% for coxsackievirus B3. This method was used to study the survival of naturally occurring virus in sludge at a sewage treatment plant and after subsequent land disposal of the solids after aerobic digestion. Reduction of enterovirus titers per gram (dry weight) of solids were modest during sludge activation but increased to a rate of 2 log 10/week after land disposal. PMID:29559

Development of quantitative methods for the detection of enteroviruses in sewage sludges during activation and following land disposal.

PubMed

Hurst, C J; Farrah, S R; Gerba, C P; Melnick, J L

1978-07-01

The development and evaluation of methods for the quantitative recovery of enteroviruses from sewage sludge are reported. Activated sewage sludge solids were collected by centrifugation, and elution of the solid-associated virus was accomplished by mechanical agitation in glycine buffer at pH 11.0. Eluted viruses were concentrated either onto an aluminum hydroxide floc or by association with a floc which formed de novo upon adjustment of the glycine eluate to pH 3.5. Viruses which remained in the liquid phase after lowering the pH of glycine eluate were concentrated by adsorption to and elution from membrane filters. The method of choice included high pH glycine elution and subsequent low pH concentration; it yielded an efficiency of recovery from activated sludge of 80% for poliovirus type 1, 68% for echovirus type 7, and 75% for coxsackievirus B3. This method was used to study the survival of naturally occurring virus in sludge at a sewage treatment plant and after subsequent land disposal of the solids after aerobic digestion. Reduction of enterovirus titers per gram (dry weight) of solids were modest during sludge activation but increased to a rate of 2 log 10/week after land disposal.

Watershed scale fungal community characterization along a pH gradient in a subsurface environment co-contaminated with uranium and nitrate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jasrotia, Puja; Green, Stefan; Canion, Andy

2014-01-01

The objective of this study was to characterize fungal communities in a subsurface environment co-contaminated with uranium and nitrate at the watershed scale, and to determine the potential contribution of fungi to contaminant transformation (nitrate attenuation). The abundance, distribution and diversity of fungi in subsurface groundwater samples were determined using quantitative and semi-quantitative molecular techniques, including quantitative PCR of eukaryotic SSU rRNA genes and pyrosequencing of fungal internal transcribed spacer (ITS) regions. Potential bacterial and fungal denitrification was assessed in sediment-groundwater slurries amended with antimicrobial compounds and in fungal pure cultures isolated from subsurface. Our results demonstrate that subsurface fungalmore » communities are dominated by members of the phylum Ascomycota, and a pronounced shift in fungal community composition occurs across the groundwater pH gradient at the field site, with lower diversity observed under acidic (pH < 4.5) conditions. Fungal isolates recovered from subsurface sediments were shown to reduce nitrate to nitrous oxide, including cultures of the genus Coniochaeta that were detected in abundance in pyrosequence libraries of site groundwater samples. Denitrifying fungal isolates recovered from the site were classified, and found to be distributed broadly within the phylum Ascomycota, and within a single genus within the Basidiomycota. Potential denitrification rate assays with sediment-groundwater slurries showed the potential for subsurface fungi to reduce nitrate to nitrous oxide under in situ acidic pH conditions.« less

Improvements in Diagnostic Accuracy with Quantitative Dynamic Contrast-Enhanced MRI

DTIC Science & Technology

2011-12-01

Magnetic   Resonance   Imaging  during  the  Menstrual  Cylce:  Perfusion   Imaging  Signal   Enhanceent,  and  Influence  of...acquisition of quantitative images displaying the concentration of contrast media as well as MRI -detectable proton density. To date 21 patients have...truly  quantitative   images  of  a  dynamic  contrast-­‐enhanced  (DCE)   MRI  of  the

Developing the Quantitative Histopathology Image Ontology (QHIO): A case study using the hot spot detection problem.

PubMed

Gurcan, Metin N; Tomaszewski, John; Overton, James A; Doyle, Scott; Ruttenberg, Alan; Smith, Barry

2017-02-01

Interoperability across data sets is a key challenge for quantitative histopathological imaging. There is a need for an ontology that can support effective merging of pathological image data with associated clinical and demographic data. To foster organized, cross-disciplinary, information-driven collaborations in the pathological imaging field, we propose to develop an ontology to represent imaging data and methods used in pathological imaging and analysis, and call it Quantitative Histopathological Imaging Ontology - QHIO. We apply QHIO to breast cancer hot-spot detection with the goal of enhancing reliability of detection by promoting the sharing of data between image analysts. Copyright © 2016 Elsevier Inc. All rights reserved.

Photonic crystal resonances for sensing and imaging

NASA Astrophysics Data System (ADS)

Pitruzzello, Giampaolo; Krauss, Thomas F.

2018-07-01

This review provides an insight into the recent developments of photonic crystal (PhC)-based devices for sensing and imaging, with a particular emphasis on biosensors. We focus on two main classes of devices, namely sensors based on PhC cavities and those on guided mode resonances (GMRs). This distinction is able to capture the richness of possibilities that PhCs are able to offer in this space. We present recent examples highlighting applications where PhCs can offer new capabilities, open up new applications or enable improved performance, with a clear emphasis on the different types of structures and photonic functions. We provide a critical comparison between cavity-based devices and GMR devices by highlighting strengths and weaknesses. We also compare PhC technologies and their sensing mechanism to surface plasmon resonance, microring resonators and integrated interferometric sensors.

Genetic and Physiological Characterization of Two Clusters of Quantitative Trait Loci Associated With Seed Dormancy and Plant Height in Rice

PubMed Central

Ye, Heng; Beighley, Donn H.; Feng, Jiuhuan; Gu, Xing-You

2013-01-01

Seed dormancy and plant height have been well-studied in plant genetics, but their relatedness and shared regulatory mechanisms in natural variants remain unclear. The introgression of chromosomal segments from weedy into cultivated rice (Oryza sativa) prompted the detection of two clusters (qSD1-2/qPH1 and qSD7-2/qPH7) of quantitative trait loci both associated with seed dormancy and plant height. Together, these two clusters accounted for >96% of the variances for plant height and ~71% of the variances for germination rate in an isogenic background across two environments. On the initial introgression segments, qSD1-2/qPH1 was dissected genetically from OsVp1 for vivipary and qSD7-2/qPH7 separated from Sdr4 for seed dormancy. The narrowed qSD1-2/qPH1 region encompasses the semidwarf1 (sd1) locus for gibberellin (GA) biosynthesis. The qSD1-2/qPH1 allele from the cultivar reduced germination and stem elongation and the mutant effects were recovered by exogenous GA, suggesting that sd1 is a candidate gene of the cluster. In contrast, the effect-reducing allele at qSD7-2/qPH7 was derived from the weedy line; this allele was GA-insensitive and blocked GA responses of qSD1-2/qPH1, including the transcription of a GA-inducible α-amylase gene in imbibed endosperm, suggesting that qSD7-2/qPH7 may work downstream from qSD1-2/qPH1 in GA signaling. Thus, this research established the seed dormancy-plant height association that is likely mediated by GA biosynthesis and signaling pathways in natural populations. The detected association contributed to weed mimicry for the plant stature in the agro-ecosystem dominated by semidwarf cultivars and revealed the potential benefit of semidwarf genes in resistance to preharvest sprouting. PMID:23390608

Genetic and physiological characterization of two clusters of quantitative trait Loci associated with seed dormancy and plant height in rice.

PubMed

Ye, Heng; Beighley, Donn H; Feng, Jiuhuan; Gu, Xing-You

2013-02-01

Seed dormancy and plant height have been well-studied in plant genetics, but their relatedness and shared regulatory mechanisms in natural variants remain unclear. The introgression of chromosomal segments from weedy into cultivated rice (Oryza sativa) prompted the detection of two clusters (qSD1-2/qPH1 and qSD7-2/qPH7) of quantitative trait loci both associated with seed dormancy and plant height. Together, these two clusters accounted for >96% of the variances for plant height and ~71% of the variances for germination rate in an isogenic background across two environments. On the initial introgression segments, qSD1-2/qPH1 was dissected genetically from OsVp1 for vivipary and qSD7-2/qPH7 separated from Sdr4 for seed dormancy. The narrowed qSD1-2/qPH1 region encompasses the semidwarf1 (sd1) locus for gibberellin (GA) biosynthesis. The qSD1-2/qPH1 allele from the cultivar reduced germination and stem elongation and the mutant effects were recovered by exogenous GA, suggesting that sd1 is a candidate gene of the cluster. In contrast, the effect-reducing allele at qSD7-2/qPH7 was derived from the weedy line; this allele was GA-insensitive and blocked GA responses of qSD1-2/qPH1, including the transcription of a GA-inducible α-amylase gene in imbibed endosperm, suggesting that qSD7-2/qPH7 may work downstream from qSD1-2/qPH1 in GA signaling. Thus, this research established the seed dormancy-plant height association that is likely mediated by GA biosynthesis and signaling pathways in natural populations. The detected association contributed to weed mimicry for the plant stature in the agro-ecosystem dominated by semidwarf cultivars and revealed the potential benefit of semidwarf genes in resistance to preharvest sprouting.

A novel iris transillumination grading scale allowing flexible assessment with quantitative image analysis and visual matching.

PubMed

Wang, Chen; Brancusi, Flavia; Valivullah, Zaheer M; Anderson, Michael G; Cunningham, Denise; Hedberg-Buenz, Adam; Power, Bradley; Simeonov, Dimitre; Gahl, William A; Zein, Wadih M; Adams, David R; Brooks, Brian

2018-01-01

To develop a sensitive scale of iris transillumination suitable for clinical and research use, with the capability of either quantitative analysis or visual matching of images. Iris transillumination photographic images were used from 70 study subjects with ocular or oculocutaneous albinism. Subjects represented a broad range of ocular pigmentation. A subset of images was subjected to image analysis and ranking by both expert and nonexpert reviewers. Quantitative ordering of images was compared with ordering by visual inspection. Images were binned to establish an 8-point scale. Ranking consistency was evaluated using the Kendall rank correlation coefficient (Kendall's tau). Visual ranking results were assessed using Kendall's coefficient of concordance (Kendall's W) analysis. There was a high degree of correlation among the image analysis, expert-based and non-expert-based image rankings. Pairwise comparisons of the quantitative ranking with each reviewer generated an average Kendall's tau of 0.83 ± 0.04 (SD). Inter-rater correlation was also high with Kendall's W of 0.96, 0.95, and 0.95 for nonexpert, expert, and all reviewers, respectively. The current standard for assessing iris transillumination is expert assessment of clinical exam findings. We adapted an image-analysis technique to generate quantitative transillumination values. Quantitative ranking was shown to be highly similar to a ranking produced by both expert and nonexpert reviewers. This finding suggests that the image characteristics used to quantify iris transillumination do not require expert interpretation. Inter-rater rankings were also highly similar, suggesting that varied methods of transillumination ranking are robust in terms of producing reproducible results.

Direct Estimation of Local pH Change at Infection Sites of Fungi in Potato Tubers.

PubMed

Tardi-Ovadia, R; Linker, R; Tsror Lahkim, L

2017-01-01

Fungi can modify the pH in or around the infected site via alkalization or acidification, and pH monitoring may provide valuable information on host-fungus interactions. The objective of the present study was to examine the ability of two fungi, Colletotrichum coccodes and Helminthosporium solani, to modify the pH of potato tubers during artificial inoculation in situ. Both fungi cause blemishes on potato tubers, which downgrades tuber quality and yield. Direct visualization and estimation of pH changes near the inoculation area were achieved using pH indicators and image analysis. The results showed that the pH of the area infected by either fungus increased from potato native pH of approximately 6.0 to 7.4 to 8.0. By performing simple analysis of the images, it was also possible to derive the growth curve of each fungus and estimate the lag phase of the radial growth: 10 days for C. coccodes and 17 days H. solani. In addition, a distinctive halo (an edge area with increased pH) was observed only during the lag phase of H. solani infection. pH modulation is a major factor in pathogen-host interaction and the proposed method offers a simple and rapid way to monitor these changes.

Dual-Emitting Fluorescent Metal-Organic Framework Nanocomposites as a Broad-Range pH Sensor for Fluorescence Imaging.

PubMed

Chen, Haiyong; Wang, Jing; Shan, Duoliang; Chen, Jing; Zhang, Shouting; Lu, Xiaoquan

2018-05-15

pH plays an important role in understanding physiological/pathologic processes, and abnormal pH is a symbol of many common diseases such as cancer, stroke, and Alzheimer's disease. In this work, an effective dual-emission fluorescent metal-organic framework nanocomposite probe (denoted as RB-PCN) has been constructed for sensitive and broad-range detection of pH. RB-PCN was prepared by encapsulating the DBI-PEG-NH 2 -functionalized Fe 3 O 4 into Zr-MOFs and then further reacting it with rhodamine B isothiocyanates (RBITC). In RB-PCN, RBITC is capable of sensing changes in pH in acidic solutions. Zr-MOFs not only enrich the target analyte but also exhibit a fluorescence response to pH changes in alkaline solutions. Based on the above structural and compositional features, RB-PCN could detect a wide range of pH changes. Importantly, such a nanoprobe could "see" the intracellular pH changes by fluorescence confocal imaging as well as "measure" the wider range of pH in actual samples by fluorescence spectroscopy. To the best of our knowledge, this is the first time a MOF-based dual-emitting fluorescent nanoprobe has been used for a wide range of pH detection.

The cassava (Manihot esculenta Crantz) root proteome: protein identification and differential expression.

PubMed

Sheffield, Jeanne; Taylor, Nigel; Fauquet, Claude; Chen, Sixue

2006-03-01

Using high-resolution 2-DE, we resolved proteins extracted from fibrous and tuberous root tissues of 3-month-old cassava plants. Gel image analysis revealed an average of 1467 electrophoretically resolved spots on the fibrous gels and 1595 spots on the tuberous gels in pH 3-10 range. Protein spots from both sets of gels were digested with trypsin. The digests were subjected to nanoelectrospray quadrupole TOF tandem mass analysis. Currently, we have obtained 299 protein identifications for 292 gel spots corresponding to 237 proteins. The proteins span various functional categories from energy, primary and secondary metabolism, disease and defense, destination and storage, transport, signal transduction, protein synthesis, cell structure, and transcription to cell growth and division. Gel image analysis has shown unique, as well as up- and down-regulated proteins, present in the tuberous and the fibrous tissues. Quantitative and qualitative analysis of the cassava root proteome is an important step towards further characterization of differentially expressed proteins and the elucidation of the mechanisms underlying the development and biological functions of the two types of roots.

A Dual-Mode Large-Arrayed CMOS ISFET Sensor for Accurate and High-Throughput pH Sensing in Biomedical Diagnosis.

PubMed

Huang, Xiwei; Yu, Hao; Liu, Xu; Jiang, Yu; Yan, Mei; Wu, Dongping

2015-09-01

The existing ISFET-based DNA sequencing detects hydrogen ions released during the polymerization of DNA strands on microbeads, which are scattered into microwell array above the ISFET sensor with unknown distribution. However, false pH detection happens at empty microwells due to crosstalk from neighboring microbeads. In this paper, a dual-mode CMOS ISFET sensor is proposed to have accurate pH detection toward DNA sequencing. Dual-mode sensing, optical and chemical modes, is realized by integrating a CMOS image sensor (CIS) with ISFET pH sensor, and is fabricated in a standard 0.18-μm CIS process. With accurate determination of microbead physical locations with CIS pixel by contact imaging, the dual-mode sensor can correlate local pH for one DNA slice at one location-determined microbead, which can result in improved pH detection accuracy. Moreover, toward a high-throughput DNA sequencing, a correlated-double-sampling readout that supports large array for both modes is deployed to reduce pixel-to-pixel nonuniformity such as threshold voltage mismatch. The proposed CMOS dual-mode sensor is experimentally examined to show a well correlated pH map and optical image for microbeads with a pH sensitivity of 26.2 mV/pH, a fixed pattern noise (FPN) reduction from 4% to 0.3%, and a readout speed of 1200 frames/s. A dual-mode CMOS ISFET sensor with suppressed FPN for accurate large-arrayed pH sensing is proposed and demonstrated with state-of-the-art measured results toward accurate and high-throughput DNA sequencing. The developed dual-mode CMOS ISFET sensor has great potential for future personal genome diagnostics with high accuracy and low cost.

[Quantitative data analysis for live imaging of bone.

PubMed

Seno, Shigeto

Bone tissue is a hard tissue, it was difficult to observe the interior of the bone tissue alive. With the progress of microscopic technology and fluorescent probe technology in recent years, it becomes possible to observe various activities of various cells forming bone society. On the other hand, the quantitative increase in data and the diversification and complexity of the images makes it difficult to perform quantitative analysis by visual inspection. It has been expected to develop a methodology for processing microscopic images and data analysis. In this article, we introduce the research field of bioimage informatics which is the boundary area of biology and information science, and then outline the basic image processing technology for quantitative analysis of live imaging data of bone.

The Use of Quantitative SPECT/CT Imaging to Assess Residual Limb Health

DTIC Science & Technology

2016-10-01

AWARD NUMBER: W81XWH-15-1-0669 TITLE: The Use of Quantitative SPECT/CT Imaging to Assess Residual Limb Health PRINCIPAL INVESTIGATOR...3. DATES COVERED 30 Sep 2015 - 29 Sep 2016 4. TITLE AND SUBTITLE The Use of Quantitative SPECT/CT Imaging to Assess Residual Limb Health 5a...amputation and subsequently evaluate the utility of non-invasive imaging for evaluating the impact of next-generation socket technologies on the health of

Quantitative fractography by digital image processing: NIH Image macro tools for stereo pair analysis and 3-D reconstruction.

PubMed

Hein, L R

2001-10-01

A set of NIH Image macro programs was developed to make qualitative and quantitative analyses from digital stereo pictures produced by scanning electron microscopes. These tools were designed for image alignment, anaglyph representation, animation, reconstruction of true elevation surfaces, reconstruction of elevation profiles, true-scale elevation mapping and, for the quantitative approach, surface area and roughness calculations. Limitations on time processing, scanning techniques and programming concepts are also discussed.

Comparison of qualitative and quantitative evaluation of diffusion-weighted MRI and chemical-shift imaging in the differentiation of benign and malignant vertebral body fractures.

PubMed

Geith, Tobias; Schmidt, Gerwin; Biffar, Andreas; Dietrich, Olaf; Dürr, Hans Roland; Reiser, Maximilian; Baur-Melnyk, Andrea

2012-11-01

The objective of our study was to compare the diagnostic value of qualitative diffusion-weighted imaging (DWI), quantitative DWI, and chemical-shift imaging in a single prospective cohort of patients with acute osteoporotic and malignant vertebral fractures. The study group was composed of patients with 26 osteoporotic vertebral fractures (18 women, eight men; mean age, 69 years; age range, 31 years 6 months to 86 years 2 months) and 20 malignant vertebral fractures (nine women, 11 men; mean age, 63.4 years; age range, 24 years 8 months to 86 years 4 months). T1-weighted, STIR, and T2-weighted sequences were acquired at 1.5 T. A DW reverse fast imaging with steady-state free precession (PSIF) sequence at different delta values was evaluated qualitatively. A DW echo-planar imaging (EPI) sequence and a DW single-shot turbo spin-echo (TSE) sequence at different b values were evaluated qualitatively and quantitatively using the apparent diffusion coefficient. Opposed-phase sequences were used to assess signal intensity qualitatively. The signal loss between in- and opposed-phase images was determined quantitatively. Two-tailed Fisher exact test, Mann-Whitney test, and receiver operating characteristic analysis were performed. Sensitivities, specificities, and accuracies were determined. Qualitative DW-PSIF imaging (delta = 3 ms) showed the best performance for distinguishing between benign and malignant fractures (sensitivity, 100%; specificity, 88.5%; accuracy, 93.5%). Qualitative DW-EPI (b = 50 s/mm(2) [p = 1.00]; b = 250 s/mm(2) [p = 0.50]) and DW single-shot TSE imaging (b = 100 s/mm(2) [p = 1.00]; b = 250 s/mm(2) [p = 0.18]; b = 400 s/mm(2) [p = 0.18]; b = 600 s/mm(2) [p = 0.39]) did not indicate significant differences between benign and malignant fractures. DW-EPI using a b value of 500 s/mm(2) (p = 0.01) indicated significant differences between benign and malignant vertebral fractures. Quantitative DW-EPI (p = 0.09) and qualitative opposed-phase imaging (p = 0.06) did not exhibit significant differences, quantitative DW single-shot TSE imaging (p = 0.002) and quantitative chemical-shift imaging (p = 0.01) showed significant differences between benign and malignant fractures. The DW-PSIF sequence (delta = 3 ms) had the highest accuracy in differentiating benign from malignant vertebral fractures. Quantitative chemical-shift imaging and quantitative DW single-shot TSE imaging had a lower accuracy than DW-PSIF imaging because of a large overlap. Qualitative assessment of opposed-phase, DW-EPI, and DW single-shot TSE sequences and quantitative assessment of the DW-EPI sequence were not suitable for distinguishing between benign and malignant vertebral fractures.

Magnetic resonance imaging (MRI) and relaxation spectrum analysis as methods to investigate swelling in whey protein gels.

PubMed

Oztop, Mecit H; Rosenberg, Moshe; Rosenberg, Yael; McCarthy, Kathryn L; McCarthy, Michael J

2010-10-01

Effective means for controlled delivery of nutrients and nutraceuticals are needed. Whey protein-based gels, as a model system and as a potential delivery system, exhibit pH-dependent swelling when placed in aqueous solutions. Understanding the physics that govern gel swelling is thus important when designing gel-based delivery platforms. The extent of swelling over time was monitored gravimetrically. In addition to gravimetric measurements, magnetic resonance imaging (MRI) a real-time noninvasive imaging technique that quantified changes in geometry and water content of these gels was utilized. Heat-set whey protein gels were prepared at pH 7 and swelling was monitored in aqueous solutions with pH values of 2.5, 7, and 10. Changes in dimension over time, as characterized by the number of voxels in an image, were correlated to gravimetric measurements. Excellent correlations between mass uptake and volume change (R(2)= 0.99) were obtained for the gels in aqueous solutions at pH 7 and 10, but not for gels in the aqueous solution at pH 2.5. To provide insight into the mechanisms for water uptake, nuclear magnetic resonance (NMR) relaxation times were measured in independent experiments. The relaxation spectrum for the spin-spin relaxation time (T(2)) showed the presence of 3 proton pools for pH 7 and 10 trials and 4 proton pools for pH 2.5 trials. Results demonstrate that MRI and NMR relaxation measurements provided information about swelling in whey protein gels that can constitute a new means for investigating and developing effective delivery systems for foods.

Spectroscopic analysis and in vitro imaging applications of a pH responsive AIE sensor with a two-input inhibit function.

PubMed

Zhou, Zhan; Gu, Fenglong; Peng, Liang; Hu, Ying; Wang, Qianming

2015-08-04

A novel terpyridine derivative formed stable aggregates in aqueous media (DMSO/H2O = 1/99) with dramatically enhanced fluorescence compared to its organic solution. Moreover, the ultra-violet absorption spectra also demonstrated specific responses to the incorporation of water. The yellow emission at 557 nm changed to a solution with intense greenish luminescence only in the presence of protons and it conformed to a molecular logic gate with a two-input INHIBIT function. This molecular-based material could permeate into live cells and remain undissociated in the cytoplasm. The new aggregation induced emission (AIE) pH type bio-probe permitted easy collection of yellow luminescence images on a fluorescent microscope. As designed, it displayed striking green emission in organelles at low internal pH. This feature enabled the self-assembled structure to have a whole new function for the pH detection within the field of cell imaging.

Semi-quantitative methods yield greater inter- and intraobserver agreement than subjective methods for interpreting 99m technetium-hydroxymethylene-diphosphonate uptake in equine thoracic processi spinosi.

PubMed

van Zadelhoff, Claudia; Ehrle, Anna; Merle, Roswitha; Jahn, Werner; Lischer, Christoph

2018-05-09

Scintigraphy is a standard diagnostic method for evaluating horses with back pain due to suspected thoracic processus spinosus pathology. Lesion detection is based on subjective or semi-quantitative assessments of increased uptake. This retrospective, analytical study is aimed to compare semi-quantitative and subjective methods in the evaluation of scintigraphic images of the processi spinosi in the equine thoracic spine. Scintigraphic images of 20 Warmblood horses, presented for assessment of orthopedic conditions between 2014 and 2016, were included in the study. Randomized, blinded image evaluation was performed by 11 veterinarians using subjective and semi-quantitative methods. Subjective grading was performed for the analysis of red-green-blue and grayscale scintigraphic images, which were presented in full-size or as masked images. For the semi-quantitative assessment, observers placed regions of interest over each processus spinosus. The uptake ratio of each processus spinosus in comparison to a reference region of interest was determined. Subsequently, a modified semi-quantitative calculation was developed whereby only the highest counts-per-pixel for a specified number of pixels was processed. Inter- and intraobserver agreement was calculated using intraclass correlation coefficients. Inter- and intraobserver intraclass correlation coefficients were 41.65% and 71.39%, respectively, for the subjective image assessment. Additionally, a correlation between intraobserver agreement, experience, and grayscale images was identified. The inter- and intraobserver agreement was significantly increased when using semi-quantitative analysis (97.35% and 98.36%, respectively) or the modified semi-quantitative calculation (98.61% and 98.82%, respectively). The proposed modified semi-quantitative technique showed a higher inter- and intraobserver agreement when compared to other methods, which makes it a useful tool for the analysis of scintigraphic images. The association of the findings from this study with clinical and radiological examinations requires further investigation. © 2018 American College of Veterinary Radiology.

Respiratory trace feature analysis for the prediction of respiratory-gated PET quantification.

PubMed

Wang, Shouyi; Bowen, Stephen R; Chaovalitwongse, W Art; Sandison, George A; Grabowski, Thomas J; Kinahan, Paul E

2014-02-21

The benefits of respiratory gating in quantitative PET/CT vary tremendously between individual patients. Respiratory pattern is among many patient-specific characteristics that are thought to play an important role in gating-induced imaging improvements. However, the quantitative relationship between patient-specific characteristics of respiratory pattern and improvements in quantitative accuracy from respiratory-gated PET/CT has not been well established. If such a relationship could be estimated, then patient-specific respiratory patterns could be used to prospectively select appropriate motion compensation during image acquisition on a per-patient basis. This study was undertaken to develop a novel statistical model that predicts quantitative changes in PET/CT imaging due to respiratory gating. Free-breathing static FDG-PET images without gating and respiratory-gated FDG-PET images were collected from 22 lung and liver cancer patients on a PET/CT scanner. PET imaging quality was quantified with peak standardized uptake value (SUV(peak)) over lesions of interest. Relative differences in SUV(peak) between static and gated PET images were calculated to indicate quantitative imaging changes due to gating. A comprehensive multidimensional extraction of the morphological and statistical characteristics of respiratory patterns was conducted, resulting in 16 features that characterize representative patterns of a single respiratory trace. The six most informative features were subsequently extracted using a stepwise feature selection approach. The multiple-regression model was trained and tested based on a leave-one-subject-out cross-validation. The predicted quantitative improvements in PET imaging achieved an accuracy higher than 90% using a criterion with a dynamic error-tolerance range for SUV(peak) values. The results of this study suggest that our prediction framework could be applied to determine which patients would likely benefit from respiratory motion compensation when clinicians quantitatively assess PET/CT for therapy target definition and response assessment.

Respiratory trace feature analysis for the prediction of respiratory-gated PET quantification

NASA Astrophysics Data System (ADS)

Wang, Shouyi; Bowen, Stephen R.; Chaovalitwongse, W. Art; Sandison, George A.; Grabowski, Thomas J.; Kinahan, Paul E.

2014-02-01

The benefits of respiratory gating in quantitative PET/CT vary tremendously between individual patients. Respiratory pattern is among many patient-specific characteristics that are thought to play an important role in gating-induced imaging improvements. However, the quantitative relationship between patient-specific characteristics of respiratory pattern and improvements in quantitative accuracy from respiratory-gated PET/CT has not been well established. If such a relationship could be estimated, then patient-specific respiratory patterns could be used to prospectively select appropriate motion compensation during image acquisition on a per-patient basis. This study was undertaken to develop a novel statistical model that predicts quantitative changes in PET/CT imaging due to respiratory gating. Free-breathing static FDG-PET images without gating and respiratory-gated FDG-PET images were collected from 22 lung and liver cancer patients on a PET/CT scanner. PET imaging quality was quantified with peak standardized uptake value (SUVpeak) over lesions of interest. Relative differences in SUVpeak between static and gated PET images were calculated to indicate quantitative imaging changes due to gating. A comprehensive multidimensional extraction of the morphological and statistical characteristics of respiratory patterns was conducted, resulting in 16 features that characterize representative patterns of a single respiratory trace. The six most informative features were subsequently extracted using a stepwise feature selection approach. The multiple-regression model was trained and tested based on a leave-one-subject-out cross-validation. The predicted quantitative improvements in PET imaging achieved an accuracy higher than 90% using a criterion with a dynamic error-tolerance range for SUVpeak values. The results of this study suggest that our prediction framework could be applied to determine which patients would likely benefit from respiratory motion compensation when clinicians quantitatively assess PET/CT for therapy target definition and response assessment.

pH measurement of tubular vacuoles of an arbuscular mycorrhizal fungus, Gigaspora margarita.

PubMed

Funamoto, Rintaro; Saito, Katsuharu; Oyaizu, Hiroshi; Aono, Toshihiro; Saito, Masanori

2015-01-01

Arbuscular mycorrhizal fungi play an important role in phosphate supply to the host plants. The fungal hyphae contain tubular vacuoles where phosphate compounds such as polyphosphate are accumulated. Despite their importance for the phosphate storage, little is known about the physiological properties of the tubular vacuoles in arbuscular mycorrhizal fungi. As an indicator of the physiological state in vacuoles, we measured pH of tubular vacuoles in living hyphae of arbuscular mycorrhizal fungus Gigaspora margarita using ratio image analysis with pH-dependent fluorescent probe, 6-carboxyfluorescein. Fluorescent images of the fine tubular vacuoles were obtained using a laser scanning confocal microscope, which enabled calculation of vacuolar pH with high spatial resolution. The tubular vacuoles showed mean pH of 5.6 and a pH range of 5.1-6.3. These results suggest that the tubular vacuoles of arbuscular mycorrhizal fungi have a mildly acidic pH just like vacuoles of other fungal species including yeast and ectomycorrhizal fungi.

Fine Substituent Effects in Sandwich Complexes: A Threshold Ionization Study of Monosubstituted Chromium Bisarene Compounds.

PubMed

Ketkov, Sergey Yu; Markin, Gennady V; Tzeng, Sheng Y; Tzeng, Wen B

2016-03-24

Mass-analyzed threshold ionization spectra of jet-cooled [(η(6) -PhMe)(η(6) -PhH)Cr] and [(η(6) -Ph2 )(η(6) -PhH)Cr] reveal with unprecedented accuracy the effects of methyl and phenyl groups on the electronic structure of bis(η(6) -benzene)chromium. These "pure" substituent effects allow quantitative experimental determination of the ionization energy changes caused by the mutual substituent influence in bisarene systems. Two types of such influence have been revealed for the first time in bis(η(6) -toluene)chromium. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative comparison of OSEM and penalized likelihood image reconstruction using relative difference penalties for clinical PET

NASA Astrophysics Data System (ADS)

Ahn, Sangtae; Ross, Steven G.; Asma, Evren; Miao, Jun; Jin, Xiao; Cheng, Lishui; Wollenweber, Scott D.; Manjeshwar, Ravindra M.

2015-08-01

Ordered subset expectation maximization (OSEM) is the most widely used algorithm for clinical PET image reconstruction. OSEM is usually stopped early and post-filtered to control image noise and does not necessarily achieve optimal quantitation accuracy. As an alternative to OSEM, we have recently implemented a penalized likelihood (PL) image reconstruction algorithm for clinical PET using the relative difference penalty with the aim of improving quantitation accuracy without compromising visual image quality. Preliminary clinical studies have demonstrated visual image quality including lesion conspicuity in images reconstructed by the PL algorithm is better than or at least as good as that in OSEM images. In this paper we evaluate lesion quantitation accuracy of the PL algorithm with the relative difference penalty compared to OSEM by using various data sets including phantom data acquired with an anthropomorphic torso phantom, an extended oval phantom and the NEMA image quality phantom; clinical data; and hybrid clinical data generated by adding simulated lesion data to clinical data. We focus on mean standardized uptake values and compare them for PL and OSEM using both time-of-flight (TOF) and non-TOF data. The results demonstrate improvements of PL in lesion quantitation accuracy compared to OSEM with a particular improvement in cold background regions such as lungs.

Evaluation of Parallel and Fan-Beam Data Acquisition Geometries and Strategies for Myocardial SPECT Imaging

NASA Astrophysics Data System (ADS)

Qi, Yujin; Tsui, B. M. W.; Gilland, K. L.; Frey, E. C.; Gullberg, G. T.

2004-06-01

This study evaluates myocardial SPECT images obtained from parallel-hole (PH) and fan-beam (FB) collimator geometries using both circular-orbit (CO) and noncircular-orbit (NCO) acquisitions. A newly developed 4-D NURBS-based cardiac-torso (NCAT) phantom was used to simulate the /sup 99m/Tc-sestamibi uptakes in human torso with myocardial defects in the left ventricular (LV) wall. Two phantoms were generated to simulate patients with thick and thin body builds. Projection data including the effects of attenuation, collimator-detector response and scatter were generated using SIMSET Monte Carlo simulations. A large number of photon histories were generated such that the projection data were close to noise free. Poisson noise fluctuations were then added to simulate the count densities found in clinical data. Noise-free and noisy projection data were reconstructed using the iterative OS-EM reconstruction algorithm with attenuation compensation. The reconstructed images from noisy projection data show that the noise levels are lower for the FB as compared to the PH collimator due to increase in detected counts. The NCO acquisition method provides slightly better resolution and small improvement in defect contrast as compared to the CO acquisition method in noise-free reconstructed images. Despite lower projection counts the NCO shows the same noise level as the CO in the attenuation corrected reconstruction images. The results from the channelized Hotelling observer (CHO) study show that FB collimator is superior to PH collimator in myocardial defect detection, but the NCO shows no statistical significant difference from the CO for either PH or FB collimator. In conclusion, our results indicate that data acquisition using NCO makes a very small improvement in the resolution over CO for myocardial SPECT imaging. This small improvement does not make a significant difference on myocardial defect detection. However, an FB collimator provides better defect detection than a PH collimator with similar spatial resolution for myocardial SPECT imaging.

Combining inkjet printing and sol-gel chemistry for making pH-sensitive surfaces.

PubMed

Orsi, Gianni; De Maria, Carmelo; Montemurro, Francesca; Chauhan, Veeren M; Aylott, Jonathan W; Vozzi, Giovanni

2015-01-01

Today biomedical sciences are experiencing the importance of imaging biological parameters with luminescence methods. Studying 2D pH distribution with those methods allows building knowledge about complex cellular processes. Immobilizing pH sensitive nanoparticles inside hydrogel matrixes, in order to guarantee a proper SNR, could easily make stable and biocompatible 2D sensors. Inkjet printing is also well known as tool for printing images onto porous surfaces. Recently it has been used as a free-form fabrication method for building three-dimensional parts, and now is being explored as a way of printing electrical and optical devices. Inkjet printing was used either as a rapid prototyping method for custom biosensors. Sol-gel method is naturally bound with inkjet, because the picoliter-sized ink droplets evaporate quickly, thus allowing quick sol-gel transitions on the printed surface. In this work will be shown how to merge those technologies, in order to make a nanoparticles doped printable hydrogel, which could be used for making 2D/3D smart scaffolds able to monitor cell activities. An automated image analysis system was developed in order to quickly have the pH measurements from pH nanosensors fluorescence images.

In vivo imaging of the morphology and changes in pH along the gastrointestinal tract of Japanese medaka by photonic band-gap hydrogel microspheres.

PubMed

Du, Xuemin; Lei, Ngai-Yu; Hu, Peng; Lei, Zhang; Ong, Daniel Hock-Chun; Ge, Xuewu; Zhang, Zhicheng; Lam, Michael Hon-Wah

2013-07-17

Colloidal crystalline microspheres with photonic band-gap properties responsive to media pH have been developed for in vivo imaging purposes. These colloidal crystalline microspheres were constructed from monodispersed core-shell nano-size particles with poly(styrene-co-acrylic acid) (PS-co-PAA) cores and poly(acrylic acid-co-N-isopropylacrylamide) (PAA-co-PNIPAM) hydrogel shells cross-linked by N,N'-methylenebisacrylamide. A significant shift in the photonic band-gap properties of these colloidal crystalline microspheres was observed in the pH range of 4-5. This was caused by the discontinuous volume phase transition of the hydrogel coating, due to the protonation/deprotonation of its acrylic acid moieties, on the core-shell nano-sized particles within the microspheres. The in vivo imaging capability of these pH-responsive photonic microspheres was demonstrated on a test organism - Japanese medaka, Oryzia latipes - in which the morphology and change in pH along their gastrointestinal (GI) tracts were revealed under an ordinary optical microscope. This work illustrates the potential of stimuli-responsive photonic band-gap materials in tissue-/organ-level in vivo bio-imaging. Copyright © 2013 Elsevier B.V. All rights reserved.

Informatics methods to enable sharing of quantitative imaging research data.

PubMed

Levy, Mia A; Freymann, John B; Kirby, Justin S; Fedorov, Andriy; Fennessy, Fiona M; Eschrich, Steven A; Berglund, Anders E; Fenstermacher, David A; Tan, Yongqiang; Guo, Xiaotao; Casavant, Thomas L; Brown, Bartley J; Braun, Terry A; Dekker, Andre; Roelofs, Erik; Mountz, James M; Boada, Fernando; Laymon, Charles; Oborski, Matt; Rubin, Daniel L

2012-11-01

The National Cancer Institute Quantitative Research Network (QIN) is a collaborative research network whose goal is to share data, algorithms and research tools to accelerate quantitative imaging research. A challenge is the variability in tools and analysis platforms used in quantitative imaging. Our goal was to understand the extent of this variation and to develop an approach to enable sharing data and to promote reuse of quantitative imaging data in the community. We performed a survey of the current tools in use by the QIN member sites for representation and storage of their QIN research data including images, image meta-data and clinical data. We identified existing systems and standards for data sharing and their gaps for the QIN use case. We then proposed a system architecture to enable data sharing and collaborative experimentation within the QIN. There are a variety of tools currently used by each QIN institution. We developed a general information system architecture to support the QIN goals. We also describe the remaining architecture gaps we are developing to enable members to share research images and image meta-data across the network. As a research network, the QIN will stimulate quantitative imaging research by pooling data, algorithms and research tools. However, there are gaps in current functional requirements that will need to be met by future informatics development. Special attention must be given to the technical requirements needed to translate these methods into the clinical research workflow to enable validation and qualification of these novel imaging biomarkers. Copyright © 2012 Elsevier Inc. All rights reserved.

Calibration of Wide-Field Deconvolution Microscopy for Quantitative Fluorescence Imaging

PubMed Central

Lee, Ji-Sook; Wee, Tse-Luen (Erika); Brown, Claire M.

2014-01-01

Deconvolution enhances contrast in fluorescence microscopy images, especially in low-contrast, high-background wide-field microscope images, improving characterization of features within the sample. Deconvolution can also be combined with other imaging modalities, such as confocal microscopy, and most software programs seek to improve resolution as well as contrast. Quantitative image analyses require instrument calibration and with deconvolution, necessitate that this process itself preserves the relative quantitative relationships between fluorescence intensities. To ensure that the quantitative nature of the data remains unaltered, deconvolution algorithms need to be tested thoroughly. This study investigated whether the deconvolution algorithms in AutoQuant X3 preserve relative quantitative intensity data. InSpeck Green calibration microspheres were prepared for imaging, z-stacks were collected using a wide-field microscope, and the images were deconvolved using the iterative deconvolution algorithms with default settings. Afterwards, the mean intensities and volumes of microspheres in the original and the deconvolved images were measured. Deconvolved data sets showed higher average microsphere intensities and smaller volumes than the original wide-field data sets. In original and deconvolved data sets, intensity means showed linear relationships with the relative microsphere intensities given by the manufacturer. Importantly, upon normalization, the trend lines were found to have similar slopes. In original and deconvolved images, the volumes of the microspheres were quite uniform for all relative microsphere intensities. We were able to show that AutoQuant X3 deconvolution software data are quantitative. In general, the protocol presented can be used to calibrate any fluorescence microscope or image processing and analysis procedure. PMID:24688321

Detecting activity-evoked pH changes in human brain

PubMed Central

Magnotta, Vincent A.; Heo, Hye-Young; Dlouhy, Brian J.; Dahdaleh, Nader S.; Follmer, Robin L.; Thedens, Daniel R.; Welsh, Michael J.; Wemmie, John A.

2012-01-01

Localized pH changes have been suggested to occur in the brain during normal function. However, the existence of such pH changes has also been questioned. Lack of methods for noninvasively measuring pH with high spatial and temporal resolution has limited insight into this issue. Here we report that a magnetic resonance imaging (MRI) strategy, T1 relaxation in the rotating frame (T1ρ), is sufficiently sensitive to detect widespread pH changes in the mouse and human brain evoked by systemically manipulating carbon dioxide or bicarbonate. Moreover, T1ρ detected a localized acidosis in the human visual cortex induced by a flashing checkerboard. Lactate measurements and pH-sensitive 31P spectroscopy at the same site also identified a localized acidosis. Consistent with the established role for pH in blood flow recruitment, T1ρ correlated with blood oxygenation level-dependent contrast commonly used in functional MRI. However, T1ρ was not directly sensitive to blood oxygen content. These observations indicate that localized pH fluctuations occur in the human brain during normal function. Furthermore, they suggest a unique functional imaging strategy based on pH that is independent of traditional functional MRI contrast mechanisms. PMID:22566645

Quantitative analysis of single-molecule superresolution images

PubMed Central

Coltharp, Carla; Yang, Xinxing; Xiao, Jie

2014-01-01

This review highlights the quantitative capabilities of single-molecule localization-based superresolution imaging methods. In addition to revealing fine structural details, the molecule coordinate lists generated by these methods provide the critical ability to quantify the number, clustering, and colocalization of molecules with 10 – 50 nm resolution. Here we describe typical workflows and precautions for quantitative analysis of single-molecule superresolution images. These guidelines include potential pitfalls and essential control experiments, allowing critical assessment and interpretation of superresolution images. PMID:25179006

NeuronRead, an open source semi-automated tool for morphometric analysis of phase contrast and fluorescence neuronal images.

PubMed

Dias, Roberto A; Gonçalves, Bruno P; da Rocha, Joana F; da Cruz E Silva, Odete A B; da Silva, Augusto M F; Vieira, Sandra I

2017-12-01

Neurons are specialized cells of the Central Nervous System whose function is intricately related to the neuritic network they develop to transmit information. Morphological evaluation of this network and other neuronal structures is required to establish relationships between neuronal morphology and function, and may allow monitoring physiological and pathophysiologic alterations. Fluorescence-based microphotographs are the most widely used in cellular bioimaging, but phase contrast (PhC) microphotographs are easier to obtain, more affordable, and do not require invasive, complicated and disruptive techniques. Despite the various freeware tools available for fluorescence-based images analysis, few exist that can tackle the more elusive and harder-to-analyze PhC images. To surpass this, an interactive semi-automated image processing workflow was developed to easily extract relevant information (e.g. total neuritic length, average cell body area) from both PhC and fluorescence neuronal images. This workflow, named 'NeuronRead', was developed in the form of an ImageJ macro. Its robustness and adaptability were tested and validated on rat cortical primary neurons under control and differentiation inhibitory conditions. Validation included a comparison to manual determinations and to a golden standard freeware tool for fluorescence image analysis. NeuronRead was subsequently applied to PhC images of neurons at distinct differentiation days and exposed or not to DAPT, a pharmacological inhibitor of the γ-secretase enzyme, which cleaves the well-known Alzheimer's amyloid precursor protein (APP) and the Notch receptor. Data obtained confirms a neuritogenic regulatory role for γ-secretase products and validates NeuronRead as a time- and cost-effective useful monitoring tool. Copyright © 2017. Published by Elsevier Inc.

A far-field-viewing sensor for making analytical measurements in remote locations.

PubMed

Michael, K L; Taylor, L C; Walt, D R

1999-07-15

We demonstrate a far-field-viewing GRINscope sensor for making analytical measurements in remote locations. The GRINscope was fabricated by permanently affixing a micro-Gradient index (GRIN) lens on the distal face of a 350-micron-diameter optical imaging fiber. The GRINscope can obtain both chemical and visual information. In one application, a thin, pH-sensitive polymer layer was immobilized on the distal end of the GRINscope. The ability of the GRINscope to visually image its far-field surroundings and concurrently detect pH changes in a flowing stream was demonstrated. In a different application, the GRINscope was used to image pH- and O2-sensitive particles on a remote substrate and simultaneously measure their fluorescence intensity in response to pH or pO2 changes.

Digital Imaging

NASA Technical Reports Server (NTRS)

1986-01-01

Digital Imaging is the computer processed numerical representation of physical images. Enhancement of images results in easier interpretation. Quantitative digital image analysis by Perceptive Scientific Instruments, locates objects within an image and measures them to extract quantitative information. Applications are CAT scanners, radiography, microscopy in medicine as well as various industrial and manufacturing uses. The PSICOM 327 performs all digital image analysis functions. It is based on Jet Propulsion Laboratory technology, is accurate and cost efficient.

Can You Earn a Ph.D. in Economics in Five Years?

ERIC Educational Resources Information Center

Stock, Wendy A.; Finegan, T. Aldrich; Siegfried, John J.

2009-01-01

We investigate graduate school outcomes for students who entered economics Ph.D. programs in Fall 2002. Students in Top-15 ranked programs and those with higher verbal and quantitative GRE scores are less likely to have dropped out, but no more likely to have graduated. Those with undergraduate degrees from Top-60 U.S. liberal arts colleges and…

An in vivo quantitative Raman-pH sensor of arterial blood based on laser trapping of erythrocytes.

PubMed

Lin, Manman; Xu, Bin; Yao, Huilu; Shen, Aiguo; Hu, Jiming

2016-05-10

We report on a continuous and non-invasive approach in vivo to monitor arterial blood pH based on the laser trapping and Raman detection of single live erythrocytes. A home-built confocal laser tweezers Raman system (LTRS) is applied to trace the live erythrocytes at different pH values of the extracellular environment to record their corresponding Raman changes in vitro and in vivo. The analysis results in vitro show that when the extracellular environment pH changes from 6.5 to 9.0, the Raman intensity ratio (R1603, 1616 = I1603/I1616) of single erythrocytes decrease regularly; what is more, there is a good linear relationship between these two variables, and the linearity is 0.985, which is also verified successfully via in vivo Raman measurements. These results demonstrate that the Raman signal of single live erythrocytes is possible as a marker of the extracellular pH value. This in vivo and quantitative Raman-pH sensor of arterial blood will be an important candidate for monitoring the acid-base status during the treatment of ill patients and in some major surgeries because of its continuous and non-invasive characters.

Quantitative color measurement of pH indicator paper using trichromatic LEDs and TCS230 color sensor

NASA Astrophysics Data System (ADS)

Ghorude, T. N.; Chaudhari, A. L.; Shaligram, A. D.

2008-11-01

Quantitative analysis of pH indicator paper color is needed in the various fields. An indigenously developed Tristimulus colorimeter is used in this work for pH Indicator paper color measurement. The colorimeter uses Trichromatic RGB LEDs and a programmable color light to frequency converter (TCS230), combining configurable silicon photodiodes and a current to frequency converter on a single monolithic CMOS integrated circuit. The output is a square wave (50% duty cycle) with frequency directly proportional to light intensity. Digital input and digital output allow directly to a microcontroller. The light to frequency converter reads an 8*8 array of photodiodes. Sixteen photodiodes have red filters, 16 photodiodes have green filters, 16 photodiodes have blue filters, and 16 photodiodes are clear with no filters. All 16 photodiodes of the same colors are connected in parallel and type of photodiode the device uses during operation is pin selectable. Solutions having different standard pH were prepared and indicator paper was dipped in solution, it shows change in color. Using the developed RGB colorimeter chromaticity coordinates were measured and compared with the chromaticity coordinates measured using Ocean Optics HR-4000 high resolution spectrophotometer.

A FRET-Based Ratiometric Chemosensor for in Vitro Cellular Fluorescence Analyses of pH

PubMed Central

Zhou, Xianfeng; Su, Fengyu; Lu, Hongguang; Senechal-Willis, Patti; Tian, Yanqing; Johnson, Roger H.; Meldrum, Deirdre R.

2011-01-01

Ratiometric fluorescence sensing is an important technique for precise and quantitative analysis of biological events occurring under complex conditions by simultaneously recording fluorescence intensities at two wavelengths and calculating their ratios. Herein, we design a ratiometric chemosensor for pH that is based on photo-induced electron transfer (PET) and binding-induced modulation of fluorescence resonance energy transfer (FRET) mechanisms. This ratiometric chemosensor was constructed by introduction of a pH-insensitive coumarin fluorophore as a FRET donor into a pH-sensitive amino-naphthalimide derivative as the FRET acceptor. The sensor exhibited clear dual-mission signal changes in blue and green spectral windows upon pH changes. The pH sensor was applied for not only measuring cellular pH, but also for visualizing stimulus-responsive changes of intracellular pH values. PMID:21982292

Quantitative magnetic resonance imaging phantoms: A review and the need for a system phantom.

PubMed

Keenan, Kathryn E; Ainslie, Maureen; Barker, Alex J; Boss, Michael A; Cecil, Kim M; Charles, Cecil; Chenevert, Thomas L; Clarke, Larry; Evelhoch, Jeffrey L; Finn, Paul; Gembris, Daniel; Gunter, Jeffrey L; Hill, Derek L G; Jack, Clifford R; Jackson, Edward F; Liu, Guoying; Russek, Stephen E; Sharma, Samir D; Steckner, Michael; Stupic, Karl F; Trzasko, Joshua D; Yuan, Chun; Zheng, Jie

2018-01-01

The MRI community is using quantitative mapping techniques to complement qualitative imaging. For quantitative imaging to reach its full potential, it is necessary to analyze measurements across systems and longitudinally. Clinical use of quantitative imaging can be facilitated through adoption and use of a standard system phantom, a calibration/standard reference object, to assess the performance of an MRI machine. The International Society of Magnetic Resonance in Medicine AdHoc Committee on Standards for Quantitative Magnetic Resonance was established in February 2007 to facilitate the expansion of MRI as a mainstream modality for multi-institutional measurements, including, among other things, multicenter trials. The goal of the Standards for Quantitative Magnetic Resonance committee was to provide a framework to ensure that quantitative measures derived from MR data are comparable over time, between subjects, between sites, and between vendors. This paper, written by members of the Standards for Quantitative Magnetic Resonance committee, reviews standardization attempts and then details the need, requirements, and implementation plan for a standard system phantom for quantitative MRI. In addition, application-specific phantoms and implementation of quantitative MRI are reviewed. Magn Reson Med 79:48-61, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Chiral separation and quantitation of cetirizine and hydroxyzine by maltodextrin-mediated CE in human plasma: effect of zwitterionic property of cetirizine on enantioseparation.

PubMed

Nojavan, Saeed; Fakhari, Ali Reza

2011-03-01

In the present study, a very simple CE method for chiral separation and quantitation of zwitterionic cetirizine (CTZ), as the main metabolite of hydroxyzine (HZ), and HZ has been developed. In addition, the effect of zwitterionic property of CTZ on enantioseparation was investigated. Maltodextrin, a linear polysaccharide, as a chiral selector was used and several parameters affecting the separation such as pH of BGE, concentration of chiral selector and applied voltage were studied. The best BGE conditions for CTZ and HZ enantiomers were optimized as 75 mM sodium phosphate solution at pH of 2.0, containing 5% w/v maltodextrin. Results showed that, compared to HZ, pH of BGE was an effective parameter in enantioseparation of CTZ due to the zwitterionic property of CTZ. The linear range of the method was over 30-1200 ng/mL for all enantiomers of CTZ and HZ. The quantification and detection limits (S/N=3) of all enantiomers were 30 and 10 ng/mL, respectively. The method was used to quantitative enantioseparation of CTZ and HZ in spiked human plasma. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Does Late Gadolinium Enhancement still have Value? Right Ventricular Internal Mechanical Work, Ea/Emax and Late Gadolinium Enhancement as Prognostic Markers in Patients with Advanced Pulmonary Hypertension via Cardiac MRI.

PubMed

Abouelnour, Amr Ei; Doyle, Mark; Thompson, Diane V; Yamrozik, June; Williams, Ronald B; Shah, Moneal B; Soma, Siva Kr; Murali, Srinivas; Benza, Raymond L; Biederman, Robert Ww

2017-01-01

Investigate the impact of Right Ventricular (RV) Internal Work (IW), ratio of arterial to ventricular end-systolic elastance (E a /E max ), and RV Insertion Point (IP) Late Gadolinium Enhancement (LGE) on outcome in Pulmonary Hypertension (PH) patients. LGE is well known to be present within the RVIPs and Inter Ventricular Septum (IVS) in PH patients, but its prognostic role remains complex and potentially overestimated via 2D qualitative relative to the 3D quantitative measures now available. However, E a /E max , a measure of ventricular-arterial coupling and IW, when added to external cardiac work i.e. the P-V loop area as correlates to the heart's energy demands, might fundamentally improve measures of prognosis as they interrogate physiology beyond just the RV. Cardiac Magnetic Resonance Imaging (CMR) of 124 PH patients (age = 60±13, 85F) referred to a large tertiary PH center, was retrospectively examined for RV volumetric and functional indices and RVIP LGE%. Right Heart Catheterizations (RHC) performed within 1±2 months of the CMR were reviewed. E a /E max was derived as RV End-Systolic Volume (ESV/RVSV). IW was estimated as RVESV ×(RV end-systolic pressure-RV diastolic pressure). Patients were followed from date of CMR for up to 5 years for MACE (death, hospitalized RV failure, initiation of parenteral prostacyclin, sustained ventricular arrhythmia or referral for lung transplantation). MACE was high; 48/124 (39%) patients had MACE by 1.6±1.3 years. Neither RVIP nor IVS LGE using visual assessment or even 3D quantization predicted MACE. The strongest predictor of MACE was RVIW (OR=1.00013, p<0.002), vs. mPAP, RV mass, RV EF and IP LGE. Surprisingly, neither a single time-point RVIP nor whole IVS LGE% can predict outcome in the largest cohort of PH patients studied to date when compared with conventional or contemporary metrics of disease progression. CMR-LGE appears to lose its' prognostic value in PH patients in stark contradistinction to all other left and right-sided human myocardial pathologies.

Quantitative, spectrally-resolved intraoperative fluorescence imaging

PubMed Central

Valdés, Pablo A.; Leblond, Frederic; Jacobs, Valerie L.; Wilson, Brian C.; Paulsen, Keith D.; Roberts, David W.

2012-01-01

Intraoperative visual fluorescence imaging (vFI) has emerged as a promising aid to surgical guidance, but does not fully exploit the potential of the fluorescent agents that are currently available. Here, we introduce a quantitative fluorescence imaging (qFI) approach that converts spectrally-resolved data into images of absolute fluorophore concentration pixel-by-pixel across the surgical field of view (FOV). The resulting estimates are linear, accurate, and precise relative to true values, and spectral decomposition of multiple fluorophores is also achieved. Experiments with protoporphyrin IX in a glioma rodent model demonstrate in vivo quantitative and spectrally-resolved fluorescence imaging of infiltrating tumor margins for the first time. Moreover, we present images from human surgery which detect residual tumor not evident with state-of-the-art vFI. The wide-field qFI technique has broad implications for intraoperative surgical guidance because it provides near real-time quantitative assessment of multiple fluorescent biomarkers across the operative field. PMID:23152935

[Phospholipase and proteinase production by Malassezia pachydermatis isolated in dogs with and without otitis].

PubMed

Ortiz, Gustavo; Martín, M Carmen; Carrillo-Muñoz, Alfonso J; Payá, M Jesús

2013-01-01

Malassezia pachydermatis is part of the skin microbiota of dogs and cats. M. pachydermatis has been associated with external otitis and seborrhoeic dermatitis, reported more often in dogs than in cats. When the physical, chemical or immunological mechanisms of the skin are altered, M. pachydermatis could act as a pathogen. Thus, several virulence factors, such as the ability to produce esterase, lipase, lipoxygenase, protease, chondroitin sulphatase, and hyaluronidase, have been studied. In the present study, we aim to identify the phospholipase activity measured at pH 6.3, and the proteinase activity measured at pH 6.3 and pH 6.8 (pH from ears of dogs with external otitis) of M. pachydermatis strains isolated from dogs with and without external otitis. The phospholipase activity was measured using a semi-quantitative method with egg yolk, and the proteinase activity with a semi-quantitative method using bovine serum albumin agar. The study was performed on 96 isolates of M. pachydermatis, 43 isolated from dogs without clinical symptoms of otitis, and 52 isolated from dogs with otitis. In our study, 75.8% of the isolates showed phospholipase activity at pH 6.3, and 81 and 97.9% of them showed proteinase activity measured at pH 6.3 and 6.8, respectively. A higher phospholipase activity was detected in strains isolated from dogs with otitis. The proteinase activity was increased at a pH of 6.8 (97.9%) in comparison to a pH of 6.3 (81%). Our results suggest that the phospholipase activity may play an important role in the invasion of host tissues in chronic canine otitis cases. The proteinase activity results obtained in this study suggest that a reduction in the pH of the treatment may improve its efficacy in the resolution of M. pachydermatis otitis. Copyright © 2012 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

A novel method to visually determine the intracellular pH of xenografted tumor in vivo by utilizing fluorescent protein as an indicator.

PubMed

Tanaka, Shotaro; Harada, Hiroshi; Hiraoka, Masahiro

2015-09-04

The alkalization of intracellular pH (pHin) advances together with enhancement of aerobic glycolysis within tumor cells (the Warburg effect), and that is responsible for the progression of tumor malignancy together with hypoxia and angiogenesis. But how they correlate each other during tumor growth is poorly understood, partly due to the lack of suitable imaging methods. In present study, we propose a novel method to visually determine the pHin of tumor xenograft model from fluorescent image ratios. We utilized tandemly-linked two fluorescent proteins as a pH indicator; yellow fluorescent protein (YFP, pH sensitive) as an indicator, and red fluorescent protein (RFP, pH insensitive) as a reference. This method can eliminate the influence of optical factors from tissue as well as of the diverse expression level of pH indicator in the grafted cells. In addition, that can be operated by filter-based fluorescent imagers that are generally used in small animal study. The efficacy of the pH indicator, RFP-YFP, was confirmed by studies using recombinant protein in vitro and HeLa cells expressing RFP-YFP in vivo. Furthermore, we prepared nude mice subcutaneously xenografted HeLa cells expressing RFP-YFP cells as tumor model. The image ratios (YFP/RFP) of the tumor at the day 5 after surgery clearly showed the heterogeneous distribution of diverse pHin cells in the tumor tissue. Concomitantly acquired angiography using near-infrared fluorescence (680 nm for emission) also indicated that the relative alkaline pHin cells located in the region far from tumor vessels in which tumor aerobic glycolysis would be facilitated by progression of hypoxia and nutrient starvation. Applying the present method for a multi-wavelength imaging concerning pO2 and/or nutrient starvation states in addition to pHin and angiogenesis would provide valuable information about complicated alteration of tumoral cell states during tumorigenesis. Copyright © 2015 Elsevier Inc. All rights reserved.

A general quantitative pH sensor developed with dicyandiamide N-doped high quantum yield graphene quantum dots.

PubMed

Wu, Zhu Lian; Gao, Ming Xuan; Wang, Ting Ting; Wan, Xiao Yan; Zheng, Lin Ling; Huang, Cheng Zhi

2014-04-07

A general quantitative pH sensor for environmental and intracellular applications was developed by the facile hydrothermal preparation of dicyandiamide (DCD) N-doped high quantum yield (QY) graphene quantum dots (GQDs) using citric acid (CA) as the carbon source. The obtained N-doped GQDs have excellent photoluminesence (PL) properties with a relatively high QY of 36.5%, suggesting that N-doped chemistry could promote the QY of carbon nanomaterials. The possible mechanism for the formation of the GQDs involves the CA self-assembling into a nanosheet structure through intermolecular H-bonding at the initial stage of the reaction, and then the pure graphene core with many function groups formed through the dehydration between the carboxyl and hydroxyl of the intermolecules under hydrothermal conditions. These N-doped GQDs have low toxicity, and are photostable and pH-sensitive between 1.81 to 8.96, giving a general pH sensor with a wide range of applications from real water to intracellular contents.

Minimizing target interference in PK immunoassays: new approaches for low-pH-sample treatment.

PubMed

Partridge, Michael A; Pham, John; Dziadiv, Olena; Luong, Onson; Rafique, Ashique; Sumner, Giane; Torri, Albert

2013-08-01

Quantitating total levels of monoclonal antibody (mAb) biotherapeutics in serum using ELISA may be hindered by soluble targets. We developed two low-pH-sample-pretreatment techniques to minimize target interference. The first procedure involves sample pretreatment at pH <3.0 before neutralization and analysis in a target capture ELISA. Careful monitoring of acidification time is required to minimize potential impact on mAb detection. The second approach involves sample dilution into mild acid (pH ∼4.5) before transferring to an anti-human capture-antibody-coated plate without neutralization. Analysis of target-drug and drug-capture antibody interactions at pH 4.5 indicated that the capture antibody binds to the drug, while the drug and the target were dissociated. Using these procedures, total biotherapeutic levels were accurately measured when soluble target was >30-fold molar excess. These techniques provide alternatives for quantitating mAb biotherapeutics in the presence of a target when standard acid-dissociation procedures are ineffective.

CCR researchers identify pathway critical for preventing premature aging | Center for Cancer Research

Cancer.gov

Hutchinson-Gilford progeria syndrome (HGPS) is a rare, fatal disease in which patients age prematurely. To identify primary HGPS driver mechanisms, Nard Kubben, Ph.D., a Research Fellow in the laboratory of Tom Misteli, Ph.D., in CCR’s Laboratory of Receptor Biology and Gene Expression, and colleagues in the NCI High-throughput Imaging Facility developed an imaging-based

Can we understand, control and use the blinking of quantum dots in biological surroundings?

NASA Astrophysics Data System (ADS)

Durisic, Nela

Semiconductor nanocrystals, also known as quantum dots (QDs), are evoking remarkable technological and scientific interest due to their fascinating size-dependent electronic and optical properties. Many biophysical studies to date have used effectively as brighter and more photostable replacement of organic dyes. In this thesis we focus on the most prominent feature of their photophysical properties, a random switching between emitting and non-emitting states, also known as fluorescence intermittency, or "blinking," in order to better understand the mechanism of quantum dot emission and how it reflects interaction with their immediate environment. We first designed and built a total internal reflection florescent microscope (TIRFM) with single molecule detection capabilities and determined optimal conditions for single QD studies. We then used image correlation techniques to show that the change in blinking dynamics could be detected and that it could complicate interpretation of the commonly used analytical techniques that rely on intensity fluctuations as reporters of particle mobility. In particular, we demonstrated that the transport coefficients recovered from fluorescence fluctuation analysis of diffusional mobility using temporal image correlation spectroscopy (TICS) had significant systematic errors due to blinking of the nanoparticles. We then performed a thorough, systematic study of the effects of protons on QDs' photochemical stability by varying the pH of their aqueous environment and related the single particle properties to properties of an ensemble of QDs. As pH was lowered, shorter "on" times and longer "off" times were observed, brightness of single QDs decreased and the number of permanently non-emitting QDs (dark fraction) increased. Based on these results, we proposed a coupled role for H+ ions by which they first reduced the intensity of the emitting state as well as affected probabilities of the QD to switch between the "on" and "off" states and eventually trapped the QD in a permanent dark state. We discussed and extended theoretical blinking models to account for the effect of the H+ ions as well as to highlight a common mechanism governing blinking and the dark fraction formation. Results presented in this thesis are particularly important for developing a more complete theory of QD blinking, but are also relevant in various applications of QDs, especially for quantitative biological imaging applications where pH variations exist between the cytoplasmic and extra cellular spaces and within cellular organelles.

3D Slicer as an Image Computing Platform for the Quantitative Imaging Network

PubMed Central

Fedorov, Andriy; Beichel, Reinhard; Kalpathy-Cramer, Jayashree; Finet, Julien; Fillion-Robin, Jean-Christophe; Pujol, Sonia; Bauer, Christian; Jennings, Dominique; Fennessy, Fiona; Sonka, Milan; Buatti, John; Aylward, Stephen; Miller, James V.; Pieper, Steve; Kikinis, Ron

2012-01-01

Quantitative analysis has tremendous but mostly unrealized potential in healthcare to support objective and accurate interpretation of the clinical imaging. In 2008, the National Cancer Institute began building the Quantitative Imaging Network (QIN) initiative with the goal of advancing quantitative imaging in the context of personalized therapy and evaluation of treatment response. Computerized analysis is an important component contributing to reproducibility and efficiency of the quantitative imaging techniques. The success of quantitative imaging is contingent on robust analysis methods and software tools to bring these methods from bench to bedside. 3D Slicer is a free open source software application for medical image computing. As a clinical research tool, 3D Slicer is similar to a radiology workstation that supports versatile visualizations but also provides advanced functionality such as automated segmentation and registration for a variety of application domains. Unlike a typical radiology workstation, 3D Slicer is free and is not tied to specific hardware. As a programming platform, 3D Slicer facilitates translation and evaluation of the new quantitative methods by allowing the biomedical researcher to focus on the implementation of the algorithm, and providing abstractions for the common tasks of data communication, visualization and user interface development. Compared to other tools that provide aspects of this functionality, 3D Slicer is fully open source and can be readily extended and redistributed. In addition, 3D Slicer is designed to facilitate the development of new functionality in the form of 3D Slicer extensions. In this paper, we present an overview of 3D Slicer as a platform for prototyping, development and evaluation of image analysis tools for clinical research applications. To illustrate the utility of the platform in the scope of QIN, we discuss several use cases of 3D Slicer by the existing QIN teams, and we elaborate on the future directions that can further facilitate development and validation of imaging biomarkers using 3D Slicer. PMID:22770690

Biomarkers and Surrogate Endpoints in Uveitis: The Impact of Quantitative Imaging.

PubMed

Denniston, Alastair K; Keane, Pearse A; Srivastava, Sunil K

2017-05-01

Uveitis is a major cause of sight loss across the world. The reliable assessment of intraocular inflammation in uveitis ('disease activity') is essential in order to score disease severity and response to treatment. In this review, we describe how 'quantitative imaging', the approach of using automated analysis and measurement algorithms across both standard and emerging imaging modalities, can develop objective instrument-based measures of disease activity. This is a narrative review based on searches of the current world literature using terms related to quantitative imaging techniques in uveitis, supplemented by clinical trial registry data, and expert knowledge of surrogate endpoints and outcome measures in ophthalmology. Current measures of disease activity are largely based on subjective clinical estimation, and are relatively insensitive, with poor discrimination and reliability. The development of quantitative imaging in uveitis is most established in the use of optical coherence tomographic (OCT) measurement of central macular thickness (CMT) to measure severity of macular edema (ME). The transformative effect of CMT in clinical assessment of patients with ME provides a paradigm for the development and impact of other forms of quantitative imaging. Quantitative imaging approaches are now being developed and validated for other key inflammatory parameters such as anterior chamber cells, vitreous haze, retinovascular leakage, and chorioretinal infiltrates. As new forms of quantitative imaging in uveitis are proposed, the uveitis community will need to evaluate these tools against the current subjective clinical estimates and reach a new consensus for how disease activity in uveitis should be measured. The development, validation, and adoption of sensitive and discriminatory measures of disease activity is an unmet need that has the potential to transform both drug development and routine clinical care for the patient with uveitis.

Quantitative SIMS Imaging of Agar-Based Microbial Communities.

PubMed

Dunham, Sage J B; Ellis, Joseph F; Baig, Nameera F; Morales-Soto, Nydia; Cao, Tianyuan; Shrout, Joshua D; Bohn, Paul W; Sweedler, Jonathan V

2018-05-01

After several decades of widespread use for mapping elemental ions and small molecular fragments in surface science, secondary ion mass spectrometry (SIMS) has emerged as a powerful analytical tool for molecular imaging in biology. Biomolecular SIMS imaging has primarily been used as a qualitative technique; although the distribution of a single analyte can be accurately determined, it is difficult to map the absolute quantity of a compound or even to compare the relative abundance of one molecular species to that of another. We describe a method for quantitative SIMS imaging of small molecules in agar-based microbial communities. The microbes are cultivated on a thin film of agar, dried under nitrogen, and imaged directly with SIMS. By use of optical microscopy, we show that the area of the agar is reduced by 26 ± 2% (standard deviation) during dehydration, but the overall biofilm morphology and analyte distribution are largely retained. We detail a quantitative imaging methodology, in which the ion intensity of each analyte is (1) normalized to an external quadratic regression curve, (2) corrected for isomeric interference, and (3) filtered for sample-specific noise and lower and upper limits of quantitation. The end result is a two-dimensional surface density image for each analyte. The sample preparation and quantitation methods are validated by quantitatively imaging four alkyl-quinolone and alkyl-quinoline N-oxide signaling molecules (including Pseudomonas quinolone signal) in Pseudomonas aeruginosa colony biofilms. We show that the relative surface densities of the target biomolecules are substantially different from values inferred through direct intensity comparison and that the developed methodologies can be used to quantitatively compare as many ions as there are available standards.

Quantitative analysis of γ-oryzanol content in cold pressed rice bran oil by TLC-image analysis method.

PubMed

Sakunpak, Apirak; Suksaeree, Jirapornchai; Monton, Chaowalit; Pathompak, Pathamaporn; Kraisintu, Krisana

2014-02-01

To develop and validate an image analysis method for quantitative analysis of γ-oryzanol in cold pressed rice bran oil. TLC-densitometric and TLC-image analysis methods were developed, validated, and used for quantitative analysis of γ-oryzanol in cold pressed rice bran oil. The results obtained by these two different quantification methods were compared by paired t-test. Both assays provided good linearity, accuracy, reproducibility and selectivity for determination of γ-oryzanol. The TLC-densitometric and TLC-image analysis methods provided a similar reproducibility, accuracy and selectivity for the quantitative determination of γ-oryzanol in cold pressed rice bran oil. A statistical comparison of the quantitative determinations of γ-oryzanol in samples did not show any statistically significant difference between TLC-densitometric and TLC-image analysis methods. As both methods were found to be equal, they therefore can be used for the determination of γ-oryzanol in cold pressed rice bran oil.

Quantitative analysis of γ-oryzanol content in cold pressed rice bran oil by TLC-image analysis method

PubMed Central

Sakunpak, Apirak; Suksaeree, Jirapornchai; Monton, Chaowalit; Pathompak, Pathamaporn; Kraisintu, Krisana

2014-01-01

Objective To develop and validate an image analysis method for quantitative analysis of γ-oryzanol in cold pressed rice bran oil. Methods TLC-densitometric and TLC-image analysis methods were developed, validated, and used for quantitative analysis of γ-oryzanol in cold pressed rice bran oil. The results obtained by these two different quantification methods were compared by paired t-test. Results Both assays provided good linearity, accuracy, reproducibility and selectivity for determination of γ-oryzanol. Conclusions The TLC-densitometric and TLC-image analysis methods provided a similar reproducibility, accuracy and selectivity for the quantitative determination of γ-oryzanol in cold pressed rice bran oil. A statistical comparison of the quantitative determinations of γ-oryzanol in samples did not show any statistically significant difference between TLC-densitometric and TLC-image analysis methods. As both methods were found to be equal, they therefore can be used for the determination of γ-oryzanol in cold pressed rice bran oil. PMID:25182282

Research in Image Understanding as Applied to 3-D Microwave Tomographic Imaging with Near Optical Resolution.

DTIC Science & Technology

1987-03-01

Oct. 1985. 28. D.L. Jaggard, K. Schultz, Y. Kim and P. Frangos , "Inverse Scattering for Dielectric Media", Annual OSA Meeting, Wash. D.C., Oct. 1985...T.H. Chu - Graduate Student (50%) C.Y. Ho - Graduate Student (50%) Y. Kim - Graduate Student (50%) K S. Lee - Graduate Student (50%) P. Frangos ...1982. 3. P. Frangos (Ph.D.) - "One-Dimensional Inverse Scattering: Exact Methods and Applications". 4. C.L. Werner (Ph.D.) - ŗ-D Imaging of Coherent and

Detection of Prostate Cancer: Quantitative Multiparametric MR Imaging Models Developed Using Registered Correlative Histopathology.

PubMed

Metzger, Gregory J; Kalavagunta, Chaitanya; Spilseth, Benjamin; Bolan, Patrick J; Li, Xiufeng; Hutter, Diane; Nam, Jung W; Johnson, Andrew D; Henriksen, Jonathan C; Moench, Laura; Konety, Badrinath; Warlick, Christopher A; Schmechel, Stephen C; Koopmeiners, Joseph S

2016-06-01

Purpose To develop multiparametric magnetic resonance (MR) imaging models to generate a quantitative, user-independent, voxel-wise composite biomarker score (CBS) for detection of prostate cancer by using coregistered correlative histopathologic results, and to compare performance of CBS-based detection with that of single quantitative MR imaging parameters. Materials and Methods Institutional review board approval and informed consent were obtained. Patients with a diagnosis of prostate cancer underwent multiparametric MR imaging before surgery for treatment. All MR imaging voxels in the prostate were classified as cancer or noncancer on the basis of coregistered histopathologic data. Predictive models were developed by using more than one quantitative MR imaging parameter to generate CBS maps. Model development and evaluation of quantitative MR imaging parameters and CBS were performed separately for the peripheral zone and the whole gland. Model accuracy was evaluated by using the area under the receiver operating characteristic curve (AUC), and confidence intervals were calculated with the bootstrap procedure. The improvement in classification accuracy was evaluated by comparing the AUC for the multiparametric model and the single best-performing quantitative MR imaging parameter at the individual level and in aggregate. Results Quantitative T2, apparent diffusion coefficient (ADC), volume transfer constant (K(trans)), reflux rate constant (kep), and area under the gadolinium concentration curve at 90 seconds (AUGC90) were significantly different between cancer and noncancer voxels (P < .001), with ADC showing the best accuracy (peripheral zone AUC, 0.82; whole gland AUC, 0.74). Four-parameter models demonstrated the best performance in both the peripheral zone (AUC, 0.85; P = .010 vs ADC alone) and whole gland (AUC, 0.77; P = .043 vs ADC alone). Individual-level analysis showed statistically significant improvement in AUC in 82% (23 of 28) and 71% (24 of 34) of patients with peripheral-zone and whole-gland models, respectively, compared with ADC alone. Model-based CBS maps for cancer detection showed improved visualization of cancer location and extent. Conclusion Quantitative multiparametric MR imaging models developed by using coregistered correlative histopathologic data yielded a voxel-wise CBS that outperformed single quantitative MR imaging parameters for detection of prostate cancer, especially when the models were assessed at the individual level. (©) RSNA, 2016 Online supplemental material is available for this article.

Quantitative imaging biomarkers: Effect of sample size and bias on confidence interval coverage.

PubMed

Obuchowski, Nancy A; Bullen, Jennifer

2017-01-01

Introduction Quantitative imaging biomarkers (QIBs) are being increasingly used in medical practice and clinical trials. An essential first step in the adoption of a quantitative imaging biomarker is the characterization of its technical performance, i.e. precision and bias, through one or more performance studies. Then, given the technical performance, a confidence interval for a new patient's true biomarker value can be constructed. Estimating bias and precision can be problematic because rarely are both estimated in the same study, precision studies are usually quite small, and bias cannot be measured when there is no reference standard. Methods A Monte Carlo simulation study was conducted to assess factors affecting nominal coverage of confidence intervals for a new patient's quantitative imaging biomarker measurement and for change in the quantitative imaging biomarker over time. Factors considered include sample size for estimating bias and precision, effect of fixed and non-proportional bias, clustered data, and absence of a reference standard. Results Technical performance studies of a quantitative imaging biomarker should include at least 35 test-retest subjects to estimate precision and 65 cases to estimate bias. Confidence intervals for a new patient's quantitative imaging biomarker measurement constructed under the no-bias assumption provide nominal coverage as long as the fixed bias is <12%. For confidence intervals of the true change over time, linearity must hold and the slope of the regression of the measurements vs. true values should be between 0.95 and 1.05. The regression slope can be assessed adequately as long as fixed multiples of the measurand can be generated. Even small non-proportional bias greatly reduces confidence interval coverage. Multiple lesions in the same subject can be treated as independent when estimating precision. Conclusion Technical performance studies of quantitative imaging biomarkers require moderate sample sizes in order to provide robust estimates of bias and precision for constructing confidence intervals for new patients. Assumptions of linearity and non-proportional bias should be assessed thoroughly.

Generalized PSF modeling for optimized quantitation in PET imaging.

PubMed

Ashrafinia, Saeed; Mohy-Ud-Din, Hassan; Karakatsanis, Nicolas A; Jha, Abhinav K; Casey, Michael E; Kadrmas, Dan J; Rahmim, Arman

2017-06-21

Point-spread function (PSF) modeling offers the ability to account for resolution degrading phenomena within the PET image generation framework. PSF modeling improves resolution and enhances contrast, but at the same time significantly alters image noise properties and induces edge overshoot effect. Thus, studying the effect of PSF modeling on quantitation task performance can be very important. Frameworks explored in the past involved a dichotomy of PSF versus no-PSF modeling. By contrast, the present work focuses on quantitative performance evaluation of standard uptake value (SUV) PET images, while incorporating a wide spectrum of PSF models, including those that under- and over-estimate the true PSF, for the potential of enhanced quantitation of SUVs. The developed framework first analytically models the true PSF, considering a range of resolution degradation phenomena (including photon non-collinearity, inter-crystal penetration and scattering) as present in data acquisitions with modern commercial PET systems. In the context of oncologic liver FDG PET imaging, we generated 200 noisy datasets per image-set (with clinically realistic noise levels) using an XCAT anthropomorphic phantom with liver tumours of varying sizes. These were subsequently reconstructed using the OS-EM algorithm with varying PSF modelled kernels. We focused on quantitation of both SUV mean and SUV max , including assessment of contrast recovery coefficients, as well as noise-bias characteristics (including both image roughness and coefficient of-variability), for different tumours/iterations/PSF kernels. It was observed that overestimated PSF yielded more accurate contrast recovery for a range of tumours, and typically improved quantitative performance. For a clinically reasonable number of iterations, edge enhancement due to PSF modeling (especially due to over-estimated PSF) was in fact seen to lower SUV mean bias in small tumours. Overall, the results indicate that exactly matched PSF modeling does not offer optimized PET quantitation, and that PSF overestimation may provide enhanced SUV quantitation. Furthermore, generalized PSF modeling may provide a valuable approach for quantitative tasks such as treatment-response assessment and prognostication.

Evaluation of a web based informatics system with data mining tools for predicting outcomes with quantitative imaging features in stroke rehabilitation clinical trials

NASA Astrophysics Data System (ADS)

Wang, Ximing; Kim, Bokkyu; Park, Ji Hoon; Wang, Erik; Forsyth, Sydney; Lim, Cody; Ravi, Ragini; Karibyan, Sarkis; Sanchez, Alexander; Liu, Brent

2017-03-01

Quantitative imaging biomarkers are used widely in clinical trials for tracking and evaluation of medical interventions. Previously, we have presented a web based informatics system utilizing quantitative imaging features for predicting outcomes in stroke rehabilitation clinical trials. The system integrates imaging features extraction tools and a web-based statistical analysis tool. The tools include a generalized linear mixed model(GLMM) that can investigate potential significance and correlation based on features extracted from clinical data and quantitative biomarkers. The imaging features extraction tools allow the user to collect imaging features and the GLMM module allows the user to select clinical data and imaging features such as stroke lesion characteristics from the database as regressors and regressands. This paper discusses the application scenario and evaluation results of the system in a stroke rehabilitation clinical trial. The system was utilized to manage clinical data and extract imaging biomarkers including stroke lesion volume, location and ventricle/brain ratio. The GLMM module was validated and the efficiency of data analysis was also evaluated.

Ptychography: use of quantitative phase information for high-contrast label free time-lapse imaging of living cells

NASA Astrophysics Data System (ADS)

Suman, Rakesh; O'Toole, Peter

2014-03-01

Here we report a novel label free, high contrast and quantitative method for imaging live cells. The technique reconstructs an image from overlapping diffraction patterns using a ptychographical algorithm. The algorithm utilises both amplitude and phase data from the sample to report on quantitative changes related to the refractive index (RI) and thickness of the specimen. We report the ability of this technique to generate high contrast images, to visualise neurite elongation in neuronal cells, and to provide measure of cell proliferation.

Ultra-fast quantitative imaging using ptychographic iterative engine based digital micro-mirror device

NASA Astrophysics Data System (ADS)

Sun, Aihui; Tian, Xiaolin; Kong, Yan; Jiang, Zhilong; Liu, Fei; Xue, Liang; Wang, Shouyu; Liu, Cheng

2018-01-01

As a lensfree imaging technique, ptychographic iterative engine (PIE) method can provide both quantitative sample amplitude and phase distributions avoiding aberration. However, it requires field of view (FoV) scanning often relying on mechanical translation, which not only slows down measuring speed, but also introduces mechanical errors decreasing both resolution and accuracy in retrieved information. In order to achieve high-accurate quantitative imaging with fast speed, digital micromirror device (DMD) is adopted in PIE for large FoV scanning controlled by on/off state coding by DMD. Measurements were implemented using biological samples as well as USAF resolution target, proving high resolution in quantitative imaging using the proposed system. Considering its fast and accurate imaging capability, it is believed the DMD based PIE technique provides a potential solution for medical observation and measurements.

Congenital hypothyroidism: diagnostic scintigraphic evaluation of an organification defect

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cone, L.; Oates, E.; Vazquez, R.

1988-06-01

Quantitative Tc-99m pertechnetate thyroid imaging was performed on a hypothyroid neonate. The image revealed markedly increased trapping in an enlarged, bilobed, eutopic gland. A perchlorate washout test using quantitative imaging with I-123 confirmed an organification problem.

Phase-sensitive optical coherence tomography-based vibrometry using a highly phase-stable akinetic swept laser source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Applegate, Brian E.; Park, Jesung; Carbajal, Esteban

Phase-sensitive Optical Coherence Tomography (PhOCT) is an emerging tool for in vivo investigation of the vibratory function of the intact middle and inner ear. PhOCT is able to resolve micron scale tissue morphology in three dimensions as well as measure picometer scale motion at each spatial position. Most PhOCT systems to date have relied upon the phase stability offered by spectrometer detection. On the other hand swept laser source based PhOCT offers a number of advantages including balanced detection, long imaging depths, and high imaging speeds. Unfortunately the inherent phase instability of traditional swept laser sources has necessitated complex usermore » developed hardware/software solutions to restore phase sensitivity. Here we present recent results using a prototype swept laser that overcomes these issues. The akinetic swept laser is electronically tuned and precisely controls sweeps without any mechanical movement, which results in high phase stability. We have developed an optical fiber based PhOCT system around the akinetic laser source that had a 1550 nm center wavelength and a sweep rate of 140 kHz. The stability of the system was measured to be 4.4 pm with a calibrated reflector, thus demonstrating near shot noise limited performance. Using this PhOCT system, we have acquired structural and vibratory measurements of the middle ear in a mouse model, post mortem. The quality of the results suggest that the akinetic laser source is a superior laser source for PhOCT with many advantages that greatly reduces the required complexity of the imaging system.« less

Cotton growth modeling and assessment using unmanned aircraft system visual-band imagery

NASA Astrophysics Data System (ADS)

Chu, Tianxing; Chen, Ruizhi; Landivar, Juan A.; Maeda, Murilo M.; Yang, Chenghai; Starek, Michael J.

2016-07-01

This paper explores the potential of using unmanned aircraft system (UAS)-based visible-band images to assess cotton growth. By applying the structure-from-motion algorithm, the cotton plant height (ph) and canopy cover (cc) information were retrieved from the point cloud-based digital surface models (DSMs) and orthomosaic images. Both UAS-based ph and cc follow a sigmoid growth pattern as confirmed by ground-based studies. By applying an empirical model that converts the cotton ph to cc, the estimated cc shows strong correlation (R2=0.990) with the observed cc. An attempt for modeling cotton yield was carried out using the ph and cc information obtained on June 26, 2015, the date when sigmoid growth curves for both ph and cc tended to decline in slope. In a cross-validation test, the correlation between the ground-measured yield and the estimated equivalent derived from the ph and/or cc was compared. Generally, combining ph and cc, the performance of the yield estimation is most comparable against the observed yield. On the other hand, the observed yield and cc-based estimation produce the second strongest correlation, regardless of the complexity of the models.

Subsurface imaging and cell refractometry using quantitative phase/ shear-force feedback microscopy

NASA Astrophysics Data System (ADS)

Edward, Kert; Farahi, Faramarz

2009-10-01

Over the last few years, several novel quantitative phase imaging techniques have been developed for the study of biological cells. However, many of these techniques are encumbered by inherent limitations including 2π phase ambiguities and diffraction limited spatial resolution. In addition, subsurface information in the phase data is not exploited. We hereby present a novel quantitative phase imaging system without 2 π ambiguities, which also allows for subsurface imaging and cell refractometry studies. This is accomplished by utilizing simultaneously obtained shear-force topography information. We will demonstrate how the quantitative phase and topography data can be used for subsurface and cell refractometry analysis and will present results for a fabricated structure and a malaria infected red blood cell.

Widefield quantitative multiplex surface enhanced Raman scattering imaging in vivo

NASA Astrophysics Data System (ADS)

McVeigh, Patrick Z.; Mallia, Rupananda J.; Veilleux, Israel; Wilson, Brian C.

2013-04-01

In recent years numerous studies have shown the potential advantages of molecular imaging in vitro and in vivo using contrast agents based on surface enhanced Raman scattering (SERS), however the low throughput of traditional point-scanned imaging methodologies have limited their use in biological imaging. In this work we demonstrate that direct widefield Raman imaging based on a tunable filter is capable of quantitative multiplex SERS imaging in vivo, and that this imaging is possible with acquisition times which are orders of magnitude lower than achievable with comparable point-scanned methodologies. The system, designed for small animal imaging, has a linear response from (0.01 to 100 pM), acquires typical in vivo images in <10 s, and with suitable SERS reporter molecules is capable of multiplex imaging without compensation for spectral overlap. To demonstrate the utility of widefield Raman imaging in biological applications, we show quantitative imaging of four simultaneous SERS reporter molecules in vivo with resulting probe quantification that is in excellent agreement with known quantities (R2>0.98).

Quantitative photoacoustic elasticity and viscosity imaging for cirrhosis detection

NASA Astrophysics Data System (ADS)

Wang, Qian; Shi, Yujiao; Yang, Fen; Yang, Sihua

2018-05-01

Elasticity and viscosity assessments are essential for understanding and characterizing the physiological and pathological states of tissue. In this work, by establishing a photoacoustic (PA) shear wave model, an approach for quantitative PA elasticity imaging based on measurement of the rise time of the thermoelastic displacement was developed. Thus, using an existing PA viscoelasticity imaging method that features a phase delay measurement, quantitative PA elasticity imaging and viscosity imaging can be obtained in a simultaneous manner. The method was tested and validated by imaging viscoelastic agar phantoms prepared at different agar concentrations, and the imaging data were in good agreement with rheometry results. Ex vivo experiments on liver pathological models demonstrated the capability for cirrhosis detection, and the results were consistent with the corresponding histological results. This method expands the scope of conventional PA imaging and has potential to become an important alternative imaging modality.

Quantitative Image Restoration in Bright Field Optical Microscopy.

PubMed

Gutiérrez-Medina, Braulio; Sánchez Miranda, Manuel de Jesús

2017-11-07

Bright field (BF) optical microscopy is regarded as a poor method to observe unstained biological samples due to intrinsic low image contrast. We introduce quantitative image restoration in bright field (QRBF), a digital image processing method that restores out-of-focus BF images of unstained cells. Our procedure is based on deconvolution, using a point spread function modeled from theory. By comparing with reference images of bacteria observed in fluorescence, we show that QRBF faithfully recovers shape and enables quantify size of individual cells, even from a single input image. We applied QRBF in a high-throughput image cytometer to assess shape changes in Escherichia coli during hyperosmotic shock, finding size heterogeneity. We demonstrate that QRBF is also applicable to eukaryotic cells (yeast). Altogether, digital restoration emerges as a straightforward alternative to methods designed to generate contrast in BF imaging for quantitative analysis. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Standardizing Quality Assessment of Fused Remotely Sensed Images

NASA Astrophysics Data System (ADS)

Pohl, C.; Moellmann, J.; Fries, K.

2017-09-01

The multitude of available operational remote sensing satellites led to the development of many image fusion techniques to provide high spatial, spectral and temporal resolution images. The comparison of different techniques is necessary to obtain an optimized image for the different applications of remote sensing. There are two approaches in assessing image quality: 1. Quantitatively by visual interpretation and 2. Quantitatively using image quality indices. However an objective comparison is difficult due to the fact that a visual assessment is always subject and a quantitative assessment is done by different criteria. Depending on the criteria and indices the result varies. Therefore it is necessary to standardize both processes (qualitative and quantitative assessment) in order to allow an objective image fusion quality evaluation. Various studies have been conducted at the University of Osnabrueck (UOS) to establish a standardized process to objectively compare fused image quality. First established image fusion quality assessment protocols, i.e. Quality with No Reference (QNR) and Khan's protocol, were compared on varies fusion experiments. Second the process of visual quality assessment was structured and standardized with the aim to provide an evaluation protocol. This manuscript reports on the results of the comparison and provides recommendations for future research.

Three RNases in Senescent and Nonsenescent Wheat Leaves 1

PubMed Central

Blank, A.; McKeon, Thomas A.

1991-01-01

We have described three RNases in wheat leaves (Triticum aestivum L. cv Chinese Spring) and developed assays for measuring each RNase individually in crude leaf extracts. We initially used activity staining in sodium dodecyl sulfate-polyacrylamide gels to characterize RNases in extracts of primary and flag leaves. We thus identified acid RNase (EC 3.1.27.1, here designated RNase WLA), and two apparently novel enzymes, designated RNases WLB and WLC. RNase WLB activity displays a distinctive isozyme pattern, a molecular mass of 26 kilodaltons (major species), a broad pH range with an optimum near neutrality, insensitivity to EDTA, and stimulation by moderate concentrations of KCl and by MgCl2. RNase WLC activity exhibits a molecular mass of 27 kilodaltons, a neutral pH optimum, insensitivity to EDTA, and inhibition by KCl, MgCl2, and tri-(hydroxymethyl)aminomethane. Based on distinctive catalytic properties established in gels, we designed conventional solution assays for selective quantitation of each RNase activity. We used the assays to monitor the individual RNases after gel filtration chromatography and native gel electrophoresis of extracts. In accompanying work, we used the assays to monitor RNases WLA, WLB, and WLC, which are present in senescent and nonsenescent leaves, during the course of leaf senescence. ImagesFigure 1Figure 3Figure 4 PMID:16668563

Fish Viruses: Buffers and Methods for Plaquing Eight Agents Under Normal Atmosphere

PubMed Central

Wolf, Ken; Quimby, M. C.

1973-01-01

A universal procedure was sought for plaque assay of eight fish viruses (bluegill myxovirus, channel catfish virus, eel virus, Egtved virus, infectious hematopoietic necrosis virus, infectious pancreatic necrosis virus, lymphocystis virus, and the agent of spring viremia of carp (Rhabdovirus carpio), in dish cultures of various fish cells. Eagle minimal essential medium with sodium bicarbonate-CO2 buffer (Earle’s salt solution) was compared with minimal essential medium buffered principally with tris (hydroxymethyl)aminomethane or N-2-hydroxyethylpiperazine-N′-2′-ethanesulfonic acid at a pH or in the range of 7.6 to 8.0 depending upon temperature. Five fish cell lines collectively capable of replicating all fish viruses thus far isolated were tested and quantitatively found to grow comparably well in the three media. Two-phase (gel-liquid) media incorporating the various buffer systems allowed plaquing at 15 to 33 C either in partial pressures of CO2 or in normal atmosphere, but greater efficiency and sensitivity were obtained with the organic buffers, and, overall, the best results were obtained with tris(hydroxymethyl)aminomethane. Epizootiological data, specific fish cell line response, and plaque morphology permit presumptive identification of most of the agents. At proper pH, use of organic buffers obviates the need for CO2 incubators. Images PMID:4349252

Simple and fast spectral domain algorithm for quantitative phase imaging of living cells with digital holographic microscopy

NASA Astrophysics Data System (ADS)

Min, Junwei; Yao, Baoli; Ketelhut, Steffi; Kemper, Björn

2017-02-01

The modular combination of optical microscopes with digital holographic microscopy (DHM) has been proven to be a powerful tool for quantitative live cell imaging. The introduction of condenser and different microscope objectives (MO) simplifies the usage of the technique and makes it easier to measure different kinds of specimens with different magnifications. However, the high flexibility of illumination and imaging also causes variable phase aberrations that need to be eliminated for high resolution quantitative phase imaging. The existent phase aberrations compensation methods either require add additional elements into the reference arm or need specimen free reference areas or separate reference holograms to build up suitable digital phase masks. These inherent requirements make them unpractical for usage with highly variable illumination and imaging systems and prevent on-line monitoring of living cells. In this paper, we present a simple numerical method for phase aberration compensation based on the analysis of holograms in spatial frequency domain with capabilities for on-line quantitative phase imaging. From a single shot off-axis hologram, the whole phase aberration can be eliminated automatically without numerical fitting or pre-knowledge of the setup. The capabilities and robustness for quantitative phase imaging of living cancer cells are demonstrated.

Cardiac imaging: working towards fully-automated machine analysis & interpretation.

PubMed

Slomka, Piotr J; Dey, Damini; Sitek, Arkadiusz; Motwani, Manish; Berman, Daniel S; Germano, Guido

2017-03-01

Non-invasive imaging plays a critical role in managing patients with cardiovascular disease. Although subjective visual interpretation remains the clinical mainstay, quantitative analysis facilitates objective, evidence-based management, and advances in clinical research. This has driven developments in computing and software tools aimed at achieving fully automated image processing and quantitative analysis. In parallel, machine learning techniques have been used to rapidly integrate large amounts of clinical and quantitative imaging data to provide highly personalized individual patient-based conclusions. Areas covered: This review summarizes recent advances in automated quantitative imaging in cardiology and describes the latest techniques which incorporate machine learning principles. The review focuses on the cardiac imaging techniques which are in wide clinical use. It also discusses key issues and obstacles for these tools to become utilized in mainstream clinical practice. Expert commentary: Fully-automated processing and high-level computer interpretation of cardiac imaging are becoming a reality. Application of machine learning to the vast amounts of quantitative data generated per scan and integration with clinical data also facilitates a move to more patient-specific interpretation. These developments are unlikely to replace interpreting physicians but will provide them with highly accurate tools to detect disease, risk-stratify, and optimize patient-specific treatment. However, with each technological advance, we move further from human dependence and closer to fully-automated machine interpretation.

Dependence of quantitative accuracy of CT perfusion imaging on system parameters

NASA Astrophysics Data System (ADS)

Li, Ke; Chen, Guang-Hong

2017-03-01

Deconvolution is a popular method to calculate parametric perfusion parameters from four dimensional CT perfusion (CTP) source images. During the deconvolution process, the four dimensional space is squeezed into three-dimensional space by removing the temporal dimension, and a prior knowledge is often used to suppress noise associated with the process. These additional complexities confound the understanding about deconvolution-based CTP imaging system and how its quantitative accuracy depends on parameters and sub-operations involved in the image formation process. Meanwhile, there has been a strong clinical need in answering this question, as physicians often rely heavily on the quantitative values of perfusion parameters to make diagnostic decisions, particularly during an emergent clinical situation (e.g. diagnosis of acute ischemic stroke). The purpose of this work was to develop a theoretical framework that quantitatively relates the quantification accuracy of parametric perfusion parameters with CTP acquisition and post-processing parameters. This goal was achieved with the help of a cascaded systems analysis for deconvolution-based CTP imaging systems. Based on the cascaded systems analysis, the quantitative relationship between regularization strength, source image noise, arterial input function, and the quantification accuracy of perfusion parameters was established. The theory could potentially be used to guide developments of CTP imaging technology for better quantification accuracy and lower radiation dose.

Quantitative phase imaging of arthropods

PubMed Central

Sridharan, Shamira; Katz, Aron; Soto-Adames, Felipe; Popescu, Gabriel

2015-01-01

Abstract. Classification of arthropods is performed by characterization of fine features such as setae and cuticles. An unstained whole arthropod specimen mounted on a slide can be preserved for many decades, but is difficult to study since current methods require sample manipulation or tedious image processing. Spatial light interference microscopy (SLIM) is a quantitative phase imaging (QPI) technique that is an add-on module to a commercial phase contrast microscope. We use SLIM to image a whole organism springtail Ceratophysella denticulata mounted on a slide. This is the first time, to our knowledge, that an entire organism has been imaged using QPI. We also demonstrate the ability of SLIM to image fine structures in addition to providing quantitative data that cannot be obtained by traditional bright field microscopy. PMID:26334858

Ultrasonography for diagnosis, monitoring and treatment of tenosynovitis in patients with rheumatoid arthritis.

PubMed

Danielsen, Mads Ammitzbøll

2018-03-01

Rheumatod arthritis is a chronic systemic autoimmune disease, characterized by inflammation in joints and tendon sheaths, which frequently leads to permanent and serious disability due to joint destruction, but also tendon and ligament ruptures. Clinical management of rheumatoid arthritis has traditionally been supported by biochemical and radiographic findings. However, imaging modalities like ultrasound and magnetic resonance imaging (MRI) have improved the possibility for better management of rheumatoid arthritis patients, due to higher sensitivity and specificity for detecting ongoing inflammation, this thesis is focusing on tenosynovitis as recent studies have shown that inflammation in tendon sheaths, i.e. tenosynovitis, is a very common manifestation of rheumatoid arthritis and may often be mistaken for synovitis. Furthermore, presence of ultrasonographic tenosynovitis may predict clinical flare and erosive progression. 
The main aim of this PhD thesis was to further develop and validate ultrasound as a tool for diagnosis, monitoring and treatment of tenosynovitis. This was investigated in four studies: 
Study I: 3D Doppler Ultrasound findings in healthy wrist and finger tendon sheaths - Can feeding vessels lead to misinterpretation in Doppler-detected tenosynovitis? 
Study II: Image fusion of Ultrasound and MRI and B-flow evaluation of tenosynovitis - A pilot study on new imaging techniques in rheumatoid arthritis patients. 
Study III: Validity and sensitivity to change of the semi-quantitative Outcome Measures in Rheumatology Clinical Trials (OMERACT) ultrasound scoring system for tenosynovitis in patients with rheumatoid arthritis and for the quantitative scoring system, pixel index. 
Study IV: Intramuscular versus ultrasound guided intratenosynovial glucocorticoid injection for tenosynovitis in patients with rheumatoid arthritis - A randomised, double-blind, controlled study with ultrasound and clinical follow up at 4 and 12 weeks. 
From the studies presented in the PhD thesis the following was concluded:
 Doppler findings in or in close proximity to the tendon sheaths were common in wrists and fingers in healthy participants. These feeding vessels may be a source of misinterpretation, i.e .wrong diagnosis of a low degree of tenosynovitis, not only due to their presence but also because they may be interpreted as being inside the tendon sheath due to blooming and reverberations artefacts.
 Ultrasound and MRI had high agreement using image fusion for assessment of tenosynovitis when MRI partial volume artefacts were taken into account. In contrast, the agreement between B-flow and ultrasound was poor, since the quality of the b-flow images and the flow sensitivity were low.
 The OMERACT ultrasound scoring system for tenosynovitis had an excellent intra- and interreader agreement between trained investigators and a high ability to detect change over time, similarly, the quantitative tenosynovitis assessment by pixel index had a very good intrareader agreement and moderate to good interreader agreement, but only a moderate ability to detect change over time. The ultrasound scores had a high responsiveness, indicating that the OMERACT ultrasound scoring system was useful for diagnosing and monitoring tenosynovitis in rheumatoid arthritis patients in clinical trials and practice. For treatment of tenosynovitis in rheumatoid arthritis patients, remission (ultrasound tenosynovitis grey scale score ≤1 and Doppler score = 0) was achieved significantly more frequently in the ultrasound guided intratenosynovial glucocorticoid injection group than in the intramuscular glucocorticoid injection group, both at 4 and 12 week follow-ups. Furthermore, tenosynovitis responded significantly better clinically and by ultrasound assessment when treated with ultrasound guided intratenosynovial glucocorticoid injection com-pared to intramuscular glucocorticoid injection, both at 4 and 12 week follow-ups. Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Quantitative Metrics in Clinical Radiology Reporting: A Snapshot Perspective from a Single Mixed Academic-Community Practice

PubMed Central

Abramson, Richard G.; Su, Pei-Fang; Shyr, Yu

2012-01-01

Quantitative imaging has emerged as a leading priority on the imaging research agenda, yet clinical radiology has traditionally maintained a skeptical attitude toward numerical measurement in diagnostic interpretation. To gauge the extent to which quantitative reporting has been incorporated into routine clinical radiology practice, and to offer preliminary baseline data against which the evolution of quantitative imaging can be measured, we obtained all clinical computed tomography (CT) and magnetic resonance imaging (MRI) reports from two randomly selected weekdays in 2011 at a single mixed academic-community practice and evaluated those reports for the presence of quantitative descriptors. We found that 44% of all reports contained at least one “quantitative metric” (QM), defined as any numerical descriptor of a physical property other than quantity, but only 2% of reports contained an “advanced quantitative metric” (AQM), defined as a numerical parameter reporting on lesion function or composition, excluding simple size and distance measurements. Possible reasons for the slow translation of AQMs into routine clinical radiology reporting include perceptions that the primary clinical question may be qualitative in nature or that a qualitative answer may be sufficient; concern that quantitative approaches may obscure important qualitative information, may not be adequately validated, or may not allow sufficient expression of uncertainty; the feeling that “gestalt” interpretation may be superior to quantitative paradigms; and practical workflow limitations. We suggest that quantitative imaging techniques will evolve primarily as dedicated instruments for answering specific clinical questions requiring precise and standardized interpretation. Validation in real-world settings, ease of use, and reimbursement economics will all play a role in determining the rate of translation of AQMs into broad practice. PMID:22795791

Applying quantitative benefit-risk analysis to aid regulatory decision making in diagnostic imaging: methods, challenges, and opportunities.

PubMed

Agapova, Maria; Devine, Emily Beth; Bresnahan, Brian W; Higashi, Mitchell K; Garrison, Louis P

2014-09-01

Health agencies making regulatory marketing-authorization decisions use qualitative and quantitative approaches to assess expected benefits and expected risks associated with medical interventions. There is, however, no universal standard approach that regulatory agencies consistently use to conduct benefit-risk assessment (BRA) for pharmaceuticals or medical devices, including for imaging technologies. Economics, health services research, and health outcomes research use quantitative approaches to elicit preferences of stakeholders, identify priorities, and model health conditions and health intervention effects. Challenges to BRA in medical devices are outlined, highlighting additional barriers in radiology. Three quantitative methods--multi-criteria decision analysis, health outcomes modeling and stated-choice survey--are assessed using criteria that are important in balancing benefits and risks of medical devices and imaging technologies. To be useful in regulatory BRA, quantitative methods need to: aggregate multiple benefits and risks, incorporate qualitative considerations, account for uncertainty, and make clear whose preferences/priorities are being used. Each quantitative method performs differently across these criteria and little is known about how BRA estimates and conclusions vary by approach. While no specific quantitative method is likely to be the strongest in all of the important areas, quantitative methods may have a place in BRA of medical devices and radiology. Quantitative BRA approaches have been more widely applied in medicines, with fewer BRAs in devices. Despite substantial differences in characteristics of pharmaceuticals and devices, BRA methods may be as applicable to medical devices and imaging technologies as they are to pharmaceuticals. Further research to guide the development and selection of quantitative BRA methods for medical devices and imaging technologies is needed. Copyright © 2014 AUR. Published by Elsevier Inc. All rights reserved.

Phase calibration target for quantitative phase imaging with ptychography.

PubMed

Godden, T M; Muñiz-Piniella, A; Claverley, J D; Yacoot, A; Humphry, M J

2016-04-04

Quantitative phase imaging (QPI) utilizes refractive index and thickness variations that lead to optical phase shifts. This gives contrast to images of transparent objects. In quantitative biology, phase images are used to accurately segment cells and calculate properties such as dry mass, volume and proliferation rate. The fidelity of the measured phase shifts is of critical importance in this field. However to date, there has been no standardized method for characterizing the performance of phase imaging systems. Consequently, there is an increasing need for protocols to test the performance of phase imaging systems using well-defined phase calibration and resolution targets. In this work, we present a candidate for a standardized phase resolution target, and measurement protocol for the determination of the transfer of spatial frequencies, and sensitivity of a phase imaging system. The target has been carefully designed to contain well-defined depth variations over a broadband range of spatial frequencies. In order to demonstrate the utility of the target, we measure quantitative phase images on a ptychographic microscope, and compare the measured optical phase shifts with Atomic Force Microscopy (AFM) topography maps and surface profile measurements from coherence scanning interferometry. The results show that ptychography has fully quantitative nanometer sensitivity in optical path differences over a broadband range of spatial frequencies for feature sizes ranging from micrometers to hundreds of micrometers.

An Improved Method for Measuring Quantitative Resistance to the Wheat Pathogen Zymoseptoria tritici Using High-Throughput Automated Image Analysis.

PubMed

Stewart, Ethan L; Hagerty, Christina H; Mikaberidze, Alexey; Mundt, Christopher C; Zhong, Ziming; McDonald, Bruce A

2016-07-01

Zymoseptoria tritici causes Septoria tritici blotch (STB) on wheat. An improved method of quantifying STB symptoms was developed based on automated analysis of diseased leaf images made using a flatbed scanner. Naturally infected leaves (n = 949) sampled from fungicide-treated field plots comprising 39 wheat cultivars grown in Switzerland and 9 recombinant inbred lines (RIL) grown in Oregon were included in these analyses. Measures of quantitative resistance were percent leaf area covered by lesions, pycnidia size and gray value, and pycnidia density per leaf and lesion. These measures were obtained automatically with a batch-processing macro utilizing the image-processing software ImageJ. All phenotypes in both locations showed a continuous distribution, as expected for a quantitative trait. The trait distributions at both sites were largely overlapping even though the field and host environments were quite different. Cultivars and RILs could be assigned to two or more statistically different groups for each measured phenotype. Traditional visual assessments of field resistance were highly correlated with quantitative resistance measures based on image analysis for the Oregon RILs. These results show that automated image analysis provides a promising tool for assessing quantitative resistance to Z. tritici under field conditions.

Ratiometric photoluminescence sensing based on Ti3C2 MXene quantum dots as an intracellular pH sensor.

PubMed

Chen, Xu; Sun, Xueke; Xu, Wen; Pan, Gencai; Zhou, Donglei; Zhu, Jinyang; Wang, He; Bai, Xue; Dong, Biao; Song, Hongwei

2018-01-18

Intracellular pH sensing is of importance and can be used as an indicator for monitoring the evolution of various diseases and the health of cells. Here, we developed a new class of surface-functionalized MXene quantum dots (QDs), Ti 3 C 2 , by the sonication cutting and hydrothermal approach and further explored their intracellular pH sensing. The functionalized Ti 3 C 2 QDs exhibit bright excitation-dependent blue photoluminescence (PL) originating from the size effect and surface defects. Meanwhile, Ti 3 C 2 QDs demonstrate a high PL response induced by the deprotonation of the surface defects. Furthermore, combining the highly pH sensitive Ti 3 C 2 QDs with the pH insensitive [Ru(dpp) 3 ]Cl 2 , we developed a ratiometric pH sensor to quantitatively monitor the intracellular pH values. These novel MXene quantum dots can serve as a promising platform for developing practical fluorescent nanosensors.

Magnetic Field Gradient Calibration as an Experiment to Illustrate Magnetic Resonance Imaging

ERIC Educational Resources Information Center

Seedhouse, Steven J.; Hoffmann, Markus M.

2008-01-01

A nuclear magnetic resonance (NMR) spectroscopy experiment for the undergraduate physical chemistry laboratory is described that encompasses both qualitative and quantitative pedagogical goals. Qualitatively, the experiment illustrates how images are obtained in magnetic resonance imaging (MRI). Quantitatively, students experience the…

A scanning tunneling microscopy study of PH 3 adsorption on Si(1 1 1)-7 × 7 surfaces, P-segregation and thermal desorption

NASA Astrophysics Data System (ADS)

Ji, Jeong-Young; Shen, T.-C.

2007-04-01

PH 3 adsorption on Si(1 1 1)-7 × 7 was studied after various exposures between 0.3 and 60 L at room temperature by means of scanning tunneling microscopy (STM). PH 3-, PH 2-, H-reacted, and unreacted adatoms can be identified by analyzing empty-state STM images at different sample biases. PH x-reacted rest-atoms can be observed in empty-state STM images if neighboring adatoms are hydrogen terminated. Most of the PH 3 adsorbs dissociatively on the surface, generating H- and PH 2-adsorbed rest-atom and adatom sites. Dangling-bonds at rest-atom sites are more reactive than adatom sites and the faulted half of the 7 × 7 unit cell is more reactive than the unfaulted half. Center adatoms are overwhelmingly preferred over corner adatoms for PH 2 adsorption. The saturation P coverage is ˜0.18 ML. Annealing of PH 3-reacted 7 × 7 surfaces at 900 K generates disordered, partially P-covered surfaces, but dosing PH 3 at 900 K forms P/Si(1 1 1)- 6√{3} surfaces. Si deposition at 510 K leaves disordered clusters on the surface, which cannot be reordered by annealing up to 800 K. However, annealing above 900 K recreates P/Si(1 1 1)- 6√{3} surfaces. Surface morphologies formed by sequential rapid thermal annealing are also presented.

A Colorimetric Analysis Experiment Not Requiring a Spectrophotometer: Quantitative Determination of Albumin in Powdered Egg White

ERIC Educational Resources Information Center

Charlton, Amanda K.; Sevcik, Richard S.; Tucker, Dorie A.; Schultz, Linda D.

2007-01-01

A general science experiment for high school chemistry students might serve as an excellent review of the concepts of solution preparation, solubility, pH, and qualitative and quantitative analysis of a common food product. The students could learn to use safe laboratory techniques, collect and analyze data using proper scientific methodology and…

Urban College Graduates: Their Investments in and Returns for Strong Quantitative Skills, Social Capital Skills, and Soft Skills

ERIC Educational Resources Information Center

Haynes, Marie Ellen

2010-01-01

This case study examined strong quantitative skills, social capital skills, and soft skills of urban college graduates using data from the Multi-City Study of Urban Inequality Household Survey. The urban college graduates lived in Atlanta, Boston, or Los Angeles and had bachelor's, master's, PhD, and professional degrees. Among the three skills…

Qualitative and quantitative effects of harmonic echocardiographic imaging on endocardial edge definition and side-lobe artifacts

NASA Technical Reports Server (NTRS)

Rubin, D. N.; Yazbek, N.; Garcia, M. J.; Stewart, W. J.; Thomas, J. D.

2000-01-01

Harmonic imaging is a new ultrasonographic technique that is designed to improve image quality by exploiting the spontaneous generation of higher frequencies as ultrasound propagates through tissue. We studied 51 difficult-to-image patients with blinded side-by-side cineloop evaluation of endocardial border definition by harmonic versus fundamental imaging. In addition, quantitative intensities from cavity versus wall were compared for harmonic versus fundamental imaging. Harmonic imaging improved left ventricular endocardial border delineation over fundamental imaging (superior: harmonic = 71.1%, fundamental = 18.7%; similar: 10.2%; P <.001). Quantitative analysis of 100 wall/cavity combinations demonstrated brighter wall segments and more strikingly darker cavities during harmonic imaging (cavity intensity on a 0 to 255 scale: fundamental = 15.6 +/- 8.6; harmonic = 6.0 +/- 5.3; P <.0001), which led to enhanced contrast between the wall and cavity (1.89 versus 1.19, P <.0001). Harmonic imaging reduces side-lobe artifacts, resulting in a darker cavity and brighter walls, thereby improving image contrast and endocardial delineation.

Quantitative cervical vertebral maturation assessment in adolescents with normal occlusion: a mixed longitudinal study.

PubMed

Chen, Li-Li; Xu, Tian-Min; Jiang, Jiu-Hui; Zhang, Xing-Zhong; Lin, Jiu-Xiang

2008-12-01

The purpose of this study was to establish a quantitative cervical vertebral maturation (CVM) system for adolescents with normal occlusion. Mixed longitudinal data were used. The subjects included 87 children and adolescents from 8 to 18 years old with normal occlusion (32 boys, 55 girls) selected from 901 candidates. Sequential lateral cephalograms and hand-wrist films were taken once a year for 6 years. The lateral cephalograms of all subjects were divided into 11 maturation groups according to the Fishman skeletal maturity indicators. The morphologic characteristics of the second, third, and fourth cervical vertebrae at 11 developmental stages were measured and analyzed. Three characteristic parameters (H4/W4, AH3/PH3, @2) were selected to determine the classification of CVM. With 3 morphologic variables, the quantitative CVM system including 4 maturational stages was established. An equation that can accurately estimate the maturation of the cervical vertebrae was established: CVM stage=-4.13+3.57xH4/W4+4.07xAH3/PH3+0.03x@2. The quantitative CVM method is an efficient, objective, and relatively simple approach to assess the level of skeletal maturation during adolescence.

Full skin quantitative optical coherence elastography achieved by combining vibration and surface acoustic wave methods

NASA Astrophysics Data System (ADS)

Li, Chunhui; Guan, Guangying; Huang, Zhihong; Wang, Ruikang K.; Nabi, Ghulam

2015-03-01

By combining with the phase sensitive optical coherence tomography (PhS-OCT), vibration and surface acoustic wave (SAW) methods have been reported to provide elastography of skin tissue respectively. However, neither of these two methods can provide the elastography in full skin depth in current systems. This paper presents a feasibility study on an optical coherence elastography method which combines both vibration and SAW in order to give the quantitative mechanical properties of skin tissue with full depth range, including epidermis, dermis and subcutaneous fat. Experiments are carried out on layered tissue mimicking phantoms and in vivo human forearm and palm skin. A ring actuator generates vibration while a line actuator were used to excited SAWs. A PhS-OCT system is employed to provide the ultrahigh sensitive measurement of the generated waves. The experimental results demonstrate that by the combination of vibration and SAW method the full skin bulk mechanical properties can be quantitatively measured and further the elastography can be obtained with a sensing depth from ~0mm to ~4mm. This method is promising to apply in clinics where the quantitative elasticity of localized skin diseases is needed to aid the diagnosis and treatment.

TH-AB-209-09: Quantitative Imaging of Electrical Conductivity by VHF-Induced Thermoacoustics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patch, S; Hull, D; See, W

Purpose: To demonstrate that very high frequency (VHF) induced thermoacoustics has the potential to provide quantitative images of electrical conductivity in Siemens/meter, much as shear wave elastography provides tissue stiffness in kPa. Quantitatively imaging a large organ requires exciting thermoacoustic pulses throughout the volume and broadband detection of those pulses because tomographic image reconstruction preserves frequency content. Applying the half-wavelength limit to a 200-micron inclusion inside a 7.5 cm diameter organ requires measurement sensitivity to frequencies ranging from 4 MHz down to 10 kHz, respectively. VHF irradiation provides superior depth penetration over near infrared used in photoacoustics. Additionally, VHF signalmore » production is proportional to electrical conductivity, and prostate cancer is known to suppress electrical conductivity of prostatic fluid. Methods: A dual-transducer system utilizing a P4-1 array connected to a Verasonics V1 system augmented by a lower frequency focused single element transducer was developed. Simultaneous acquisition of VHF-induced thermoacoustic pulses by both transducers enabled comparison of transducer performance. Data from the clinical array generated a stack of 96-images with separation of 0.3 mm, whereas the single element transducer imaged only in a single plane. In-plane resolution and quantitative accuracy were measured at isocenter. Results: The array provided volumetric imaging capability with superior resolution whereas the single element transducer provided superior quantitative accuracy. Combining axial images from both transducers preserved resolution of the P4-1 array and improved image contrast. Neither transducer was sensitive to frequencies below 50 kHz, resulting in a DC offset and low-frequency shading over fields of view exceeding 15 mm. Fresh human prostates were imaged ex vivo and volumetric reconstructions reveal structures rarely seen in diagnostic images. Conclusion: Quantitative whole-organ thermoacoustic tomography will be feasible by sparsely interspersing transducer elements sensitive to the low end of the ultrasonic range.« less

Quantitative analysis for peripheral vascularity assessment based on clinical photoacoustic and ultrasound images

NASA Astrophysics Data System (ADS)

Murakoshi, Dai; Hirota, Kazuhiro; Ishii, Hiroyasu; Hashimoto, Atsushi; Ebata, Tetsurou; Irisawa, Kaku; Wada, Takatsugu; Hayakawa, Toshiro; Itoh, Kenji; Ishihara, Miya

2018-02-01

Photoacoustic (PA) imaging technology is expected to be applied to clinical assessment for peripheral vascularity. We started a clinical evaluation with the prototype PA imaging system we recently developed. Prototype PA imaging system was composed with in-house Q-switched Alexandrite laser system which emits short-pulsed laser with 750 nm wavelength, handheld ultrasound transducer where illumination optics were integrated and signal processing for PA image reconstruction implemented in the clinical ultrasound (US) system. For the purpose of quantitative assessment of PA images, an image analyzing function has been developed and applied to clinical PA images. In this analyzing function, vascularity derived from PA signal intensity ranged for prescribed threshold was defined as a numerical index of vessel fulfillment and calculated for the prescribed region of interest (ROI). Skin surface was automatically detected by utilizing B-mode image acquired simultaneously with PA image. Skinsurface position is utilized to place the ROI objectively while avoiding unwanted signals such as artifacts which were imposed due to melanin pigment in the epidermal layer which absorbs laser emission and generates strong PA signals. Multiple images were available to support the scanned image set for 3D viewing. PA images for several fingers of patients with systemic sclerosis (SSc) were quantitatively assessed. Since the artifact region is trimmed off in PA images, the visibility of vessels with rather low PA signal intensity on the 3D projection image was enhanced and the reliability of the quantitative analysis was improved.

Imaging Lysosomal pH Alteration in Stressed Cells with a Sensitive Ratiometric Fluorescence Sensor.

PubMed

Xue, Zhongwei; Zhao, Hu; Liu, Jian; Han, Jiahuai; Han, Shoufa

2017-03-24

The organelle-specific pH is crucial for cell homeostasis. Aberrant pH of lysosomes has been manifested in myriad diseases. To probe lysosome responses to cell stress, we herein report the detection of lysosomal pH changes with a dual colored probe (CM-ROX), featuring a coumarin domain with "always-on" blue fluorescence and a rhodamine-lactam domain activatable to lysosomal acidity to give red fluorescence. With sensitive ratiometric signals upon subtle pH changes, CM-ROX enables discernment of lysosomal pH changes in cells undergoing autophagy, cell death, and viral infection.

Body Image

MedlinePlus

... Lumley, Ph.D., Professor and Director of Clinical Psychology Training, Department of Psychology, Wayne State University, and his Stress and Health ... Jennifer J. Thomas, Ph.D., Associate Professors of Psychology, Department of Psychiatry, Harvard Medical School; Co-Directors ...

Quantitative Analysis of Rat Dorsal Root Ganglion Neurons Cultured on Microelectrode Arrays Based on Fluorescence Microscopy Image Processing.

PubMed

Mari, João Fernando; Saito, José Hiroki; Neves, Amanda Ferreira; Lotufo, Celina Monteiro da Cruz; Destro-Filho, João-Batista; Nicoletti, Maria do Carmo

2015-12-01

Microelectrode Arrays (MEA) are devices for long term electrophysiological recording of extracellular spontaneous or evocated activities on in vitro neuron culture. This work proposes and develops a framework for quantitative and morphological analysis of neuron cultures on MEAs, by processing their corresponding images, acquired by fluorescence microscopy. The neurons are segmented from the fluorescence channel images using a combination of segmentation by thresholding, watershed transform, and object classification. The positioning of microelectrodes is obtained from the transmitted light channel images using the circular Hough transform. The proposed method was applied to images of dissociated culture of rat dorsal root ganglion (DRG) neuronal cells. The morphological and topological quantitative analysis carried out produced information regarding the state of culture, such as population count, neuron-to-neuron and neuron-to-microelectrode distances, soma morphologies, neuron sizes, neuron and microelectrode spatial distributions. Most of the analysis of microscopy images taken from neuronal cultures on MEA only consider simple qualitative analysis. Also, the proposed framework aims to standardize the image processing and to compute quantitative useful measures for integrated image-signal studies and further computational simulations. As results show, the implemented microelectrode identification method is robust and so are the implemented neuron segmentation and classification one (with a correct segmentation rate up to 84%). The quantitative information retrieved by the method is highly relevant to assist the integrated signal-image study of recorded electrophysiological signals as well as the physical aspects of the neuron culture on MEA. Although the experiments deal with DRG cell images, cortical and hippocampal cell images could also be processed with small adjustments in the image processing parameter estimation.

A NBD-based simple but effective fluorescent pH probe for imaging of lysosomes in living cells.

PubMed

Cao, Xiang-Jian; Chen, Li-Na; Zhang, Xuan; Liu, Jin-Ting; Chen, Ming-Yu; Wu, Qiu-Rong; Miao, Jun-Ying; Zhao, Bao-Xiang

2016-05-12

NBDlyso with lysosome-locating morpholine moiety has been developed as a high selective and sensitive fluorescent pH probe. This probe can respond to acidic pH (2.0-7.0) in a short time (less than 1 min) and not almost change after continuously illuminated for an extended period by ultraviolet light. The fluorescence intensity of NBDlyso enhanced 100-fold in acidic solution, with very good linear relationship (R(2) = 0.996). The pKa of probe NBDlyso is 4.10. Therefore, NBDlyso was used to detect lysosomal pH changes successfully. Besides, X-ray crystallography was used to verify the structure of NBDlyso, and the recognition mechanism involving photo-induced electron transfer was interpreted theoretically by means of DFT and TDDFT calculations skillfully when NBDlyso comes into play under the acidic condition. This probe showed good ability to sense pH change in living cell image. Copyright © 2016 Elsevier B.V. All rights reserved.

Pulmonary hypertension associated with left-sided heart disease.

PubMed

Maeder, Micha Tobias; Schoch, Otto D; Kleiner, Rebekka; Joerg, Lucas; Weilenmann, Daniel; Swiss Society For Pulmonary Hypertension

2017-01-19

Pulmonary hypertension associated with left-sided heart disease (PH-LHD) is the most common type of pulmonary hypertension. In patients with left-sided heart disease, the presence of pulmonary hypertension is typically a marker of more advanced disease, more severe symptoms, and worse prognosis. In contrast to pulmonary arterial hypertension, PH-LHD is characterised by an elevated pulmonary artery wedge pressure (postcapillary pulmonary hypertension) without or with an additional precapillary component (isolated postcapillary versus combined postcapillary and precapillary pulmonary hypertension). Transthoracic echocardiography is the primary nonin-vasive imaging tool to estimate the probability of pulmonary hypertension and to establish a working diagnosis on the mechanism of pulmonary hyperten-sion. However, right heart catheterisation is always required if significant pulmonary hypertension is sus-pected and exact knowledge of the haemodynamic constellation is necessary. The haemodynamic con-stellation (mean pulmonary artery pressure, mean pulmonary artery wedge pressure, left ventricular end-diastolic pressure) in combination with clinical infor-mation and imaging findings (mainly echocardiog-raphy, coronary angiography and cardiac magnetic resonance imaging) will usually allow the exact mech-anism underlying PH-LHD to be defined, which is a prerequisite for appropriate treatment. The general principle for the management of PH-LHD is to treat the underlying left-sided heart disease in an optimal man-ner using drugs and/or interventional or surgical ther-apy. There is currently no established indication for pulmonary arterial hypertension-specific therapies in PH-LHD, and specific therapies may even cause harm in patients with PH-LHD.

Spin-lock imaging of exogenous exchange-based contrast agents to assess tissue pH.

PubMed

Zu, Zhongliang; Li, Hua; Jiang, Xiaoyu; Gore, John C

2018-01-01

Some X-ray contrast agents contain exchangeable protons that give rise to exchange-based effects on MRI, including chemical exchange saturation transfer (CEST). However, CEST has poor specificity to explicit exchange parameters. Spin-lock sequences at high field are also sensitive to chemical exchange. Here, we evaluate whether spin-locking techniques can detect the contrast agent iohexol in vivo after intravenous administration, and their potential for measuring changes in tissue pH. Two metrics of contrast based on R 1ρ , the spin lattice relaxation rate in the rotating frame, were derived from the behavior of R 1ρ at different locking fields. Solutions containing iohexol at different concentrations and pH were used to evaluate the ability of the two metrics to quantify exchange effects. Images were also acquired from rat brains bearing tumors before and after intravenous injections of iohexol to evaluate the potential of spin-lock techniques for detecting the agent and pH variations. The two metrics were found to depend separately on either agent concentration or pH. Spin-lock imaging may therefore provide specific quantification of iohexol concentration and the iohexol-water exchange rate, which reports on pH. Spin-lock techniques may be used to assess the dynamics of intravenous contrast agents and detect extracellular acidification. Magn Reson Med 79:298-305, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Quantitative Imaging in Cancer Clinical Trials

PubMed Central

Yankeelov, Thomas E.; Mankoff, David A.; Schwartz, Lawrence H.; Lieberman, Frank S.; Buatti, John M.; Mountz, James M.; Erickson, Bradley J.; Fennessy, Fiona M.M.; Huang, Wei; Kalpathy-Cramer, Jayashree; Wahl, Richard L.; Linden, Hannah M.; Kinahan, Paul; Zhao, Binsheng; Hylton, Nola M.; Gillies, Robert J.; Clarke, Laurence; Nordstrom, Robert; Rubin, Daniel L.

2015-01-01

As anti-cancer therapies designed to target specific molecular pathways have been developed, it has become critical to develop methods to assess the response induced by such agents. While traditional, anatomic CT and MRI exams are useful in many settings, there is increasing evidence that these methods cannot answer the fundamental biological and physiological questions essential for assessment and, eventually, prediction of treatment response in the clinical trial setting, especially in the critical period soon after treatment is initiated. To optimally apply advances in quantitative imaging methods to trials of targeted cancer therapy, new infrastructure improvements are needed that incorporate these emerging techniques into the settings where they are most likely to have impact. In this review, we first elucidate the needs for therapeutic response assessment in the era of molecularly targeted therapy and describe how quantitative imaging can most effectively provide scientifically and clinically relevant data. We then describe the tools and methods required to apply quantitative imaging and provide concrete examples of work making these advances practically available for routine application in clinical trials. We conclude by proposing strategies to surmount barriers to wider incorporation of these quantitative imaging methods into clinical trials and, eventually, clinical practice. Our goal is to encourage and guide the oncology community to deploy standardized quantitative imaging techniques in clinical trials to further personalize care for cancer patients, and to provide a more efficient path for the development of improved targeted therapies. PMID:26773162

Adaptive response due to changes in gene regulation: a study with Drosophila.

PubMed Central

McDonald, J F; Chambers, G K; David, J; Ayala, F J

1977-01-01

In spite of the critical role of the process of adaptation in evolution, there are few detailed studies of the genotypic and molecular basis of the process. Drosophila melanogaster flies selected for increased tolerance to ethanol exhibited higher levels of alcohol dehydrogenase (alcohol:NAD+ oxidoreductase; EC 1.1.1.1) activity than unselected controls. A series of tests (electrophoresis, product inhibition, temperature stability, pH optima, substrate specificity, and Michaelis constants) gave no evidence of structural differences in the enzyme of the selected and the control flies. However, quantitative immunological assays showed that the selected flies contained significantly higher amounts of alcohol dehydrogenase. Adaptation of the selected flies to higher alcohol tolerance has most likely taken place by changes not in the structural gene locus coding for the enzyme, but by regulatory changes affecting the amount of gene product. Images PMID:412190

Determine precipitation rates from visible and infrared satellite images of clouds by pattern recognition technique. Progress Report, 1 Jul. 1985 - 31 Mar. 1987 Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Weinman, James A.; Garan, Louis

1987-01-01

A more advanced cloud pattern analysis algorithm was subsequently developed to take the shape and brightness of the various clouds into account in a manner that is more consistent with the human analyst's perception of GOES cloud imagery. The results of that classification scheme were compared with precipitation probabilities observed from ships of opportunity off the U.S. east coast to derive empirical regressions between cloud types and precipitation probability. The cloud morphology was then quantitatively and objectively used to map precipitation probabilities during two winter months during which severe cold air outbreaks were observed over the northwest Atlantic. Precipitation probabilities associated with various cloud types are summarized. Maps of precipitation probability derived from the cloud morphology analysis program for two months and the precipitation probability derived from thirty years of ship observation were observed.

Listening to light scattering in turbid media: quantitative optical scattering imaging using photoacoustic measurements with one-wavelength illumination

NASA Astrophysics Data System (ADS)

Yuan, Zhen; Li, Xiaoqi; Xi, Lei

2014-06-01

Biomedical photoacoustic tomography (PAT), as a potential imaging modality, can visualize tissue structure and function with high spatial resolution and excellent optical contrast. It is widely recognized that the ability of quantitatively imaging optical absorption and scattering coefficients from photoacoustic measurements is essential before PAT can become a powerful imaging modality. Existing quantitative PAT (qPAT), while successful, has been focused on recovering absorption coefficient only by assuming scattering coefficient a constant. An effective method for photoacoustically recovering optical scattering coefficient is presently not available. Here we propose and experimentally validate such a method for quantitative scattering coefficient imaging using photoacoustic data from one-wavelength illumination. The reconstruction method developed combines conventional PAT with the photon diffusion equation in a novel way to realize the recovery of scattering coefficient. We demonstrate the method using various objects having scattering contrast only or both absorption and scattering contrasts embedded in turbid media. The listening-to-light-scattering method described will be able to provide high resolution scattering imaging for various biomedical applications ranging from breast to brain imaging.

Low Medium pH Value Enhances Anthocyanin Accumulation in Malus Crabapple Leaves

PubMed Central

Tian, Ji; Jin, Kaina; Yao, Yuncong

2014-01-01

Anthocyanin is a critical factor involved in coloration of plant tissues, but the mechanism how medium pH values affect anthocyanin accumulation in woody plants is unknown. We analyzed anthocyanin composition and the expression of elements encoding anthocyanin and flavonols biosynthesis underlying different medium pH values by using three different leave color type cultivars. HPLC analysis demonstrated that high medium pH values treatment induced a dramatic decrease in the concentration of cyaniding in crabapple leaves. Conversely, the high medium pH values induced up-regulation of the content of flavones and flavonols, suggesting that low pH treatment-induced anthocyanin accumulation. Quantitative real time PCR experiment showed the expression level of anthocyanidin synthase (McANS) and uridine diphosphate glucose flavonoid 3-O-glucosyltransferase (McUFGT) was up-regulated by low pH values treatment, and high medium pH value treatment up-regulate the transcription level of flavonol synthase (McFLS). Meanwhile, several MYB TFs have been suggested in the regulation of pH responses. These results strongly indicate that the low pH treatment-induced anthocyanin accumulation is mediated by the variation of mRNA transcription of the anthocyanin biosynthetic genes. PMID:24914811

[Role of the medium acidity in the complexes formation of pyropheophorbide a with albumin and lipoproteins].

PubMed

Golovina, G V; Ol'shevskaia, V A; Kalinina, V N; Shtil', A A; Kuz'min, V A

2011-01-01

The spectral characteristics of the photosensitizer pyropheophorbide a (PPP) complexes with its carriers, that is, serum albumin and low density lipoproteins, were investigated in aqueous solutions at pH 7.4 and 5.0. The acidic pH had no effect on the quantitative parameters of PPP binding to lipoproteins but reduces its affinity for albumin. Differential role of acidification in the binding of PPP to biomacromolecules should be considered in the design of PPP-based drugs given that pH is frequently lowered in the sites of the disease.

Electrophoretic separation of proteins in space

NASA Technical Reports Server (NTRS)

Brown, R. K.

1976-01-01

Commercially available and synthetic wide range and short range ampholytes used in the isoelectric focusing of proteins was analyzed by ion exchange chromatography. A pH gradient over the pH range 3.8 to 11.0 was used to elute the ampholytes from a column of a sulfonated polystyrene resin. The wide range ampholytes were resolved into some 60 to 70 ninhydrin positive components. The recovery obtained with the method was quantitative. Acid short range ampholytes have approximately 35 components which elute readily from the ion exchange resin. Basic short range ampholytes gave about 50 components, most of which eluted at alkaline pH.

Quantitative iTRAQ secretome analysis of Aspergillus niger reveals novel hydrolytic enzymes.

PubMed

Adav, Sunil S; Li, An A; Manavalan, Arulmani; Punt, Peter; Sze, Siu Kwan

2010-08-06

The natural lifestyle of Aspergillus niger made them more effective secretors of hydrolytic proteins and becomes critical when this species were exploited as hosts for the commercial secretion of heterologous proteins. The protein secretion profile of A. niger and its mutant at different pH was explored using iTRAQ-based quantitative proteomics approach coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). This study characterized 102 highly confident unique proteins in the secretome with zero false discovery rate based on decoy strategy. The iTRAQ technique identified and relatively quantified many hydrolyzing enzymes such as cellulases, hemicellulases, glycoside hydrolases, proteases, peroxidases, and protein translocating transporter proteins during fermentation. The enzymes have potential application in lignocellulosic biomass hydrolysis for biofuel production, for example, the cellulolytic and hemicellulolytic enzymes glucan 1,4-alpha-glucosidase, alpha-glucosidase C, endoglucanase, alpha l-arabinofuranosidase, beta-mannosidase, glycosyl hydrolase; proteases such as tripeptidyl-peptidase, aspergillopepsin, and other enzymes including cytochrome c oxidase, cytochrome c oxidase, glucose oxidase were highly expressed in A. niger and its mutant secretion. In addition, specific enzyme production can be stimulated by controlling pH of the culture medium. Our results showed comprehensive unique secretory protein profile of A. niger, its regulation at different pH, and the potential application of iTRAQ-based quantitative proteomics for the microbial secretome analysis.

Quantitative Imaging in Laboratory: Fast Kinetics and Fluorescence Quenching

ERIC Educational Resources Information Center

Cumberbatch, Tanya; Hanley, Quentin S.

2007-01-01

The process of quantitative imaging, which is very commonly used in laboratory, is shown to be very useful for studying the fast kinetics and fluorescence quenching of many experiments. The imaging technique is extremely cheap and hence can be used in many absorption and luminescence experiments.

Quantitative models for predicting adsorption of oxytetracycline, ciprofloxacin and sulfamerazine to swine manures with contrasting properties.

PubMed

Cheng, Dengmiao; Feng, Yao; Liu, Yuanwang; Li, Jinpeng; Xue, Jianming; Li, Zhaojun

2018-09-01

Understanding antibiotic adsorption in livestock manures is crucial to assess the fate and risk of antibiotics in the environment. In this study, three quantitative models developed with swine manure-water distribution coefficients (LgK d ) for oxytetracycline (OTC), ciprofloxacin (CIP) and sulfamerazine (SM1) in swine manures. Physicochemical parameters (n=12) of the swine manure were used as independent variables using partial least-squares (PLSs) analysis. The cumulative cross-validated regression coefficients (Q 2 cum ) values, standard deviations (SDs) and external validation coefficient (Q 2 ext ) ranged from 0.761 to 0.868, 0.027 to 0.064, and 0.743 to 0.827 for the three models; as such, internal and external predictability of the models were strong. The pH, soluble organic carbon (SOC) and nitrogen (SON), and Ca were important explanatory variables for the OTC-Model, pH, SOC, and SON for the CIP-model, and pH, total organic nitrogen (TON), and SOC for the SM1-model. The high VIPs (variable importance in the projections) of pH (1.178-1.396), SOC (0.968-1.034), and SON (0.822 and 0.865) established these physicochemical parameters as likely being dominant (associatively) in affecting transport of antibiotics in swine manures. Copyright © 2018 Elsevier B.V. All rights reserved.

High-Sensitivity Surface-Enhanced Raman Scattering (SERS) Substrate Based on a Gold Colloid Solution with a pH Change for Detection of Trace-Level Polycyclic Aromatic Hydrocarbons in Aqueous Solution.

PubMed

Shi, Xiaofeng; Liu, Shu; Han, Xiaohong; Ma, Jun; Jiang, Yongchao; Yu, Guifeng

2015-05-01

In this study, a gold colloid solution whose parameters were optimized, and without any surfactants, was developed as a surface-enhanced Raman scattering (SERS) substrate for the detection of trace-level polycyclic aromatic hydrocarbons (PAHs). A gold colloid solution with 57 nm gold particles and pH 13 was prepared to be the SERS substrate. It had impressive enhancement that was two orders of magnitude higher than that of a gold colloid solution with 57 nm gold particles and without pH change (pH 6). Even with a compact field-based Raman spectrometer, naphthalene, phenanthrene, anthracene, fluoranthene, and pyrene were detected, with limits of detection at 6.8 nM, 3.4 nM, 1.8 nM, 0.68 nM (680 pM), and 0.44 nM (440 pM), respectively. The significant enhancement was ascribed to an electromagnetic mechanism and a charge-transfer mechanism. Quantitative analyses for these five PAHs in water were also performed. The SERS intensities of PAHs were found to have good linear dependence relations with the concentrations in low concentration. This high-sensitivity, easily prepared substrate offers a promising technology for the quantitative detection of trace-level PAHs.

qF-SSOP: real-time optical property corrected fluorescence imaging

PubMed Central

Valdes, Pablo A.; Angelo, Joseph P.; Choi, Hak Soo; Gioux, Sylvain

2017-01-01

Fluorescence imaging is well suited to provide image guidance during resections in oncologic and vascular surgery. However, the distorting effects of tissue optical properties on the emitted fluorescence are poorly compensated for on even the most advanced fluorescence image guidance systems, leading to subjective and inaccurate estimates of tissue fluorophore concentrations. Here we present a novel fluorescence imaging technique that performs real-time (i.e., video rate) optical property corrected fluorescence imaging. We perform full field of view simultaneous imaging of tissue optical properties using Single Snapshot of Optical Properties (SSOP) and fluorescence detection. The estimated optical properties are used to correct the emitted fluorescence with a quantitative fluorescence model to provide quantitative fluorescence-Single Snapshot of Optical Properties (qF-SSOP) images with less than 5% error. The technique is rigorous, fast, and quantitative, enabling ease of integration into the surgical workflow with the potential to improve molecular guidance intraoperatively. PMID:28856038

Performance evaluation of photoacoustic oximetry imaging systems using a dynamic blood flow phantom with tunable oxygen saturation

NASA Astrophysics Data System (ADS)

Vogt, William C.; Zhou, Xuewen; Andriani, Rudy; Wear, Keith A.; Garra, Brian S.; Pfefer, Joshua

2018-02-01

Photoacoustic Imaging (PAI) is an emerging technology with strong potential for broad clinical applications from breast cancer detection to cerebral monitoring due to its ability to compute maps of blood oxygen saturation (SO2) distribution in deep tissues using multispectral imaging. However, no well-validated consensus test methods currently exist for evaluating oximetry-specific performance characteristics of PAI devices. We have developed a phantombased flow system capable of rapid SO2 adjustment to serve as a test bed for elucidation of factors impacting SO2 measurement and quantitative characterization of device performance. The flow system is comprised of a peristaltic pump, membrane oxygenator, oxygen and nitrogen gas, and in-line oxygen, pH, and temperature sensors that enable real-time estimation of SO2 reference values. Bovine blood was delivered through breast-relevant tissue phantoms containing vessel-mimicking fluid channels, which were imaged using a custom multispectral PAI system. Blood was periodically drawn for SO2 measurement in a clinical-grade CO-oximeter. We used this flow phantom system to evaluate the impact of device parameters (e.g.,wavelength-dependent fluence corrections) and tissue parameters (e.g. fluid channel depth, blood SO2, spectral coloring artifacts) on oximetry measurement accuracy. Results elucidated key challenges in PAI oximetry and device design trade-offs, which subsequently allowed for optimization of system performance. This approach provides a robust benchtop test platform that can support PAI oximetry device optimization, performance validation, and clinical translation, and may inform future development of consensus test methods for performance assessment of photoacoustic oximetry imaging systems.

Non-invasive Optical Molecular Imaging for Cancer Detection

NASA Astrophysics Data System (ADS)

Luo, Zhen

Cancer is a leading cause of death worldwide. It remains the second most common cause of death in the US, accounting for nearly 1 out of every 4 deaths. Improved fundamental understanding of molecular processes and pathways resulting in cancer development has catalyzed a shift towards molecular analysis of cancer using imaging technologies. It is expected that the non-invasive or minimally invasive molecular imaging analysis of cancer can significantly aid in improving the early detection of cancer and will result in reduced mortality and morbidity associated with the disease. The central hypothesis of the proposed research is that non-invasive imaging of changes in metabolic activity of individual cells, and extracellular pH within a tissue will improve early stage detection of cancer. The specific goals of this research project were to: (a) develop novel optical imaging probes to image changes in choline metabolism and tissue pH as a function of progression of cancer using clinically isolated tissue biopsies; (b) correlate changes in tissue extracellular pH and metabolic activity of tissues as a function of disease state using clinically isolated tissue biopsies; (c) provide fundamental understanding of relationship between tumor hypoxia, acidification of the extracellular space and altered cellular metabolism with progression of cancer. Three novel molecular imaging probes were developed to detect changes in choline and glucose metabolism and extracellular pH in model systems and clinically isolated cells and biopsies. Glucose uptake and metabolism was measured using a fluorescence analog of glucose, 2-NBDG (2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose), while choline metabolism was measured using a click chemistry analog of choline, propargyl choline, which can be in-situ labeled with a fluorophore Alexa-488 azide via a click chemistry reaction. Extracellular pH in tissue were measured by Alexa-647 labeled pHLIP (pH low insertion peptide), which can selectively target plasma membrane of cells based on lower extracellular pH. 20 pairs of clinically normal and abnormal biopsies were obtained from consenting patients at UCDMC. Fluorescence intensity of tissue biopsies before and after topical delivery of 2-NBDG and Alexa-647 labeled pHLIP was measured non-invasively by widefield imaging and confocal microscope. Uptake of propargyl choline was measured after topical delivery using confocal microscope. The results of all three molecular imagine probes were further correlated with pathological diagnosis. The imaging results of clinical biopsies demonstrated that 2-NBDG, propargyl choline and pHLIP peptide can accurately distinguish the pathologically normal and abnormal biopsies. Topical application of the contrast agents generated significantly higher fluorescence signal intensity in all neoplastic tissues as compared to clinically normal biopsies irrespective of the anatomic location or patient. This unpaired comparison across all the cancer patients in this study highlights the specificity of the imaging approach. Furthermore, the results indicated that changes in intracellular glucose, choline metabolism and cancer acidosis are initiated in the early stages of cancer and these changes are correlated with the progression of the disease. In conclusion, these novel optical molecular imaging approaches to measure multiple biomarkers in cancer have significant potential to be a useful tool for improving early detection and prognostic evaluation of oral neoplasia.

Clinical MRS studies of the brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hubesch, B.; Marinier, D.S.; Hetherington, H.P.

1989-12-01

Image-guided {sup 31}P and 1H magnetic resonance localized spectroscopy was performed on patients with brain tumors, temporal lobe epilepsy, chronic brain stroke, and deep white matter lesions. Absolute molar concentrations of metabolites, peak area ratios, and pH were obtained. The important findings were that {sup 31}P metabolite concentrations were significantly reduced in tumors, infarcts, and deep white matter lesions. Similarly, {sup 1}H metabolite intensities were reduced in chronic stroke. In the seizure foci of epilepsy patients, in tumors, and in chronic stroke, the pH was more alkaline than the normal pH. Peak area ratios were altered in tumors (reduction ofmore » phosphocreatine/inorganic phosphate) and in chronic stroke (large increases in Cr/NAA and Cho/NAA). Finally, the spectroscopic imaging technique offers a versatile alternative to the single point techniques, producing spectra or images of the spatial distribution of individual {sup 31}P metabolites.« less

An Ibm PC/AT-Based Image Acquisition And Processing System For Quantitative Image Analysis

NASA Astrophysics Data System (ADS)

Kim, Yongmin; Alexander, Thomas

1986-06-01

In recent years, a large number of applications have been developed for image processing systems in the area of biological imaging. We have already finished the development of a dedicated microcomputer-based image processing and analysis system for quantitative microscopy. The system's primary function has been to facilitate and ultimately automate quantitative image analysis tasks such as the measurement of cellular DNA contents. We have recognized from this development experience, and interaction with system users, biologists and technicians, that the increasingly widespread use of image processing systems, and the development and application of new techniques for utilizing the capabilities of such systems, would generate a need for some kind of inexpensive general purpose image acquisition and processing system specially tailored for the needs of the medical community. We are currently engaged in the development and testing of hardware and software for a fairly high-performance image processing computer system based on a popular personal computer. In this paper, we describe the design and development of this system. Biological image processing computer systems have now reached a level of hardware and software refinement where they could become convenient image analysis tools for biologists. The development of a general purpose image processing system for quantitative image analysis that is inexpensive, flexible, and easy-to-use represents a significant step towards making the microscopic digital image processing techniques more widely applicable not only in a research environment as a biologist's workstation, but also in clinical environments as a diagnostic tool.

Non-interferometric quantitative phase imaging of yeast cells

NASA Astrophysics Data System (ADS)

Poola, Praveen K.; Pandiyan, Vimal Prabhu; John, Renu

2015-12-01

Real-time imaging of live cells is quite difficult without the addition of external contrast agents. Various methods for quantitative phase imaging of living cells have been proposed like digital holographic microscopy and diffraction phase microscopy. In this paper, we report theoretical and experimental results of quantitative phase imaging of live yeast cells with nanometric precision using transport of intensity equations (TIE). We demonstrate nanometric depth sensitivity in imaging live yeast cells using this technique. This technique being noninterferometric, does not need any coherent light sources and images can be captured through a regular bright-field microscope. This real-time imaging technique would deliver the depth or 3-D volume information of cells and is highly promising in real-time digital pathology applications, screening of pathogens and staging of diseases like malaria as it does not need any preprocessing of samples.

A Quantitative Three-Dimensional Image Analysis Tool for Maximal Acquisition of Spatial Heterogeneity Data.

PubMed

Allenby, Mark C; Misener, Ruth; Panoskaltsis, Nicki; Mantalaris, Athanasios

2017-02-01

Three-dimensional (3D) imaging techniques provide spatial insight into environmental and cellular interactions and are implemented in various fields, including tissue engineering, but have been restricted by limited quantification tools that misrepresent or underutilize the cellular phenomena captured. This study develops image postprocessing algorithms pairing complex Euclidean metrics with Monte Carlo simulations to quantitatively assess cell and microenvironment spatial distributions while utilizing, for the first time, the entire 3D image captured. Although current methods only analyze a central fraction of presented confocal microscopy images, the proposed algorithms can utilize 210% more cells to calculate 3D spatial distributions that can span a 23-fold longer distance. These algorithms seek to leverage the high sample cost of 3D tissue imaging techniques by extracting maximal quantitative data throughout the captured image.

Quantitative radiomic profiling of glioblastoma represents transcriptomic expression.

PubMed

Kong, Doo-Sik; Kim, Junhyung; Ryu, Gyuha; You, Hye-Jin; Sung, Joon Kyung; Han, Yong Hee; Shin, Hye-Mi; Lee, In-Hee; Kim, Sung-Tae; Park, Chul-Kee; Choi, Seung Hong; Choi, Jeong Won; Seol, Ho Jun; Lee, Jung-Il; Nam, Do-Hyun

2018-01-19

Quantitative imaging biomarkers have increasingly emerged in the field of research utilizing available imaging modalities. We aimed to identify good surrogate radiomic features that can represent genetic changes of tumors, thereby establishing noninvasive means for predicting treatment outcome. From May 2012 to June 2014, we retrospectively identified 65 patients with treatment-naïve glioblastoma with available clinical information from the Samsung Medical Center data registry. Preoperative MR imaging data were obtained for all 65 patients with primary glioblastoma. A total of 82 imaging features including first-order statistics, volume, and size features, were semi-automatically extracted from structural and physiologic images such as apparent diffusion coefficient and perfusion images. Using commercially available software, NordicICE, we performed quantitative imaging analysis and collected the dataset composed of radiophenotypic parameters. Unsupervised clustering methods revealed that the radiophenotypic dataset was composed of three clusters. Each cluster represented a distinct molecular classification of glioblastoma; classical type, proneural and neural types, and mesenchymal type. These clusters also reflected differential clinical outcomes. We found that extracted imaging signatures does not represent copy number variation and somatic mutation. Quantitative radiomic features provide a potential evidence to predict molecular phenotype and treatment outcome. Radiomic profiles represents transcriptomic phenotypes more well.

Ratiometric spectral imaging for fast tumor detection and chemotherapy monitoring in vivo

PubMed Central

Hwang, Jae Youn; Gross, Zeev; Gray, Harry B.; Medina-Kauwe, Lali K.; Farkas, Daniel L.

2011-01-01

We report a novel in vivo spectral imaging approach to cancer detection and chemotherapy assessment. We describe and characterize a ratiometric spectral imaging and analysis method and evaluate its performance for tumor detection and delineation by quantitatively monitoring the specific accumulation of targeted gallium corrole (HerGa) into HER2-positive (HER2 +) breast tumors. HerGa temporal accumulation in nude mice bearing HER2 + breast tumors was monitored comparatively by a. this new ratiometric imaging and analysis method; b. established (reflectance and fluorescence) spectral imaging; c. more commonly used fluorescence intensity imaging. We also tested the feasibility of HerGa imaging in vivo using the ratiometric spectral imaging method for tumor detection and delineation. Our results show that the new method not only provides better quantitative information than typical spectral imaging, but also better specificity than standard fluorescence intensity imaging, thus allowing enhanced in vivo outlining of tumors and dynamic, quantitative monitoring of targeted chemotherapy agent accumulation into them. PMID:21721808

Quantitative magnetic resonance imaging in traumatic brain injury.

PubMed

Bigler, E D

2001-04-01

Quantitative neuroimaging has now become a well-established method for analyzing magnetic resonance imaging in traumatic brain injury (TBI). A general review of studies that have examined quantitative changes following TBI is presented. The consensus of quantitative neuroimaging studies is that most brain structures demonstrate changes in volume or surface area after injury. The patterns of atrophy are consistent with the generalized nature of brain injury and diffuse axonal injury. Various clinical caveats are provided including how quantitative neuroimaging findings can be used clinically and in predicting rehabilitation outcome. The future of quantitative neuroimaging also is discussed.

Quantitative DIC microscopy using an off-axis self-interference approach.

PubMed

Fu, Dan; Oh, Seungeun; Choi, Wonshik; Yamauchi, Toyohiko; Dorn, August; Yaqoob, Zahid; Dasari, Ramachandra R; Feld, Michael S

2010-07-15

Traditional Normarski differential interference contrast (DIC) microscopy is a very powerful method for imaging nonstained biological samples. However, one of its major limitations is the nonquantitative nature of the imaging. To overcome this problem, we developed a quantitative DIC microscopy method based on off-axis sample self-interference. The digital holography algorithm is applied to obtain quantitative phase gradients in orthogonal directions, which leads to a quantitative phase image through a spiral integration of the phase gradients. This method is practically simple to implement on any standard microscope without stringent requirements on polarization optics. Optical sectioning can be obtained through enlarged illumination NA.

Anniversary Paper: History and status of CAD and quantitative image analysis: The role of Medical Physics and AAPM

PubMed Central

Giger, Maryellen L.; Chan, Heang-Ping; Boone, John

2008-01-01

The roles of physicists in medical imaging have expanded over the years, from the study of imaging systems (sources and detectors) and dose to the assessment of image quality and perception, the development of image processing techniques, and the development of image analysis methods to assist in detection and diagnosis. The latter is a natural extension of medical physicists’ goals in developing imaging techniques to help physicians acquire diagnostic information and improve clinical decisions. Studies indicate that radiologists do not detect all abnormalities on images that are visible on retrospective review, and they do not always correctly characterize abnormalities that are found. Since the 1950s, the potential use of computers had been considered for analysis of radiographic abnormalities. In the mid-1980s, however, medical physicists and radiologists began major research efforts for computer-aided detection or computer-aided diagnosis (CAD), that is, using the computer output as an aid to radiologists—as opposed to a completely automatic computer interpretation—focusing initially on methods for the detection of lesions on chest radiographs and mammograms. Since then, extensive investigations of computerized image analysis for detection or diagnosis of abnormalities in a variety of 2D and 3D medical images have been conducted. The growth of CAD over the past 20 years has been tremendous—from the early days of time-consuming film digitization and CPU-intensive computations on a limited number of cases to its current status in which developed CAD approaches are evaluated rigorously on large clinically relevant databases. CAD research by medical physicists includes many aspects—collecting relevant normal and pathological cases; developing computer algorithms appropriate for the medical interpretation task including those for segmentation, feature extraction, and classifier design; developing methodology for assessing CAD performance; validating the algorithms using appropriate cases to measure performance and robustness; conducting observer studies with which to evaluate radiologists in the diagnostic task without and with the use of the computer aid; and ultimately assessing performance with a clinical trial. Medical physicists also have an important role in quantitative imaging, by validating the quantitative integrity of scanners and developing imaging techniques, and image analysis tools that extract quantitative data in a more accurate and automated fashion. As imaging systems become more complex and the need for better quantitative information from images grows, the future includes the combined research efforts from physicists working in CAD with those working on quantitative imaging systems to readily yield information on morphology, function, molecular structure, and more—from animal imaging research to clinical patient care. A historical review of CAD and a discussion of challenges for the future are presented here, along with the extension to quantitative image analysis. PMID:19175137

Anniversary Paper: History and status of CAD and quantitative image analysis: The role of Medical Physics and AAPM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giger, Maryellen L.; Chan, Heang-Ping; Boone, John

2008-12-15

The roles of physicists in medical imaging have expanded over the years, from the study of imaging systems (sources and detectors) and dose to the assessment of image quality and perception, the development of image processing techniques, and the development of image analysis methods to assist in detection and diagnosis. The latter is a natural extension of medical physicists' goals in developing imaging techniques to help physicians acquire diagnostic information and improve clinical decisions. Studies indicate that radiologists do not detect all abnormalities on images that are visible on retrospective review, and they do not always correctly characterize abnormalities thatmore » are found. Since the 1950s, the potential use of computers had been considered for analysis of radiographic abnormalities. In the mid-1980s, however, medical physicists and radiologists began major research efforts for computer-aided detection or computer-aided diagnosis (CAD), that is, using the computer output as an aid to radiologists--as opposed to a completely automatic computer interpretation--focusing initially on methods for the detection of lesions on chest radiographs and mammograms. Since then, extensive investigations of computerized image analysis for detection or diagnosis of abnormalities in a variety of 2D and 3D medical images have been conducted. The growth of CAD over the past 20 years has been tremendous--from the early days of time-consuming film digitization and CPU-intensive computations on a limited number of cases to its current status in which developed CAD approaches are evaluated rigorously on large clinically relevant databases. CAD research by medical physicists includes many aspects--collecting relevant normal and pathological cases; developing computer algorithms appropriate for the medical interpretation task including those for segmentation, feature extraction, and classifier design; developing methodology for assessing CAD performance; validating the algorithms using appropriate cases to measure performance and robustness; conducting observer studies with which to evaluate radiologists in the diagnostic task without and with the use of the computer aid; and ultimately assessing performance with a clinical trial. Medical physicists also have an important role in quantitative imaging, by validating the quantitative integrity of scanners and developing imaging techniques, and image analysis tools that extract quantitative data in a more accurate and automated fashion. As imaging systems become more complex and the need for better quantitative information from images grows, the future includes the combined research efforts from physicists working in CAD with those working on quantitative imaging systems to readily yield information on morphology, function, molecular structure, and more--from animal imaging research to clinical patient care. A historical review of CAD and a discussion of challenges for the future are presented here, along with the extension to quantitative image analysis.« less

Measurement of pH micro-heterogeneity in natural cheese matrices by fluorescence lifetime imaging

PubMed Central

Burdikova, Zuzana; Svindrych, Zdenek; Pala, Jan; Hickey, Cian D.; Wilkinson, Martin G.; Panek, Jiri; Auty, Mark A. E.; Periasamy, Ammasi; Sheehan, Jeremiah J.

2015-01-01

Cheese, a product of microbial fermentation may be defined as a protein matrix entrapping fat, moisture, minerals and solutes as well as dispersed bacterial colonies. The growth and physiology of bacterial cells in these colonies may be influenced by the microenvironment around the colony, or alternatively the cells within the colony may modify the microenvironment (e.g., pH, redox potential) due to their metabolic activity. While cheese pH may be measured at macro level there remains a significant knowledge gap relating to the degree of micro-heterogeneity of pH within the cheese matrix and its relationship with microbial, enzymatic and physiochemical parameters and ultimately with cheese quality, consistency and ripening patterns. The pH of cheese samples was monitored both at macroscopic scale and at microscopic scale, using a non-destructive microscopic technique employing C-SNARF-4 and Oregon Green 488 fluorescent probes. The objectives of this work were to evaluate the suitability of these dyes for microscale pH measurements in natural cheese matrices and to enhance the sensitivity and extend the useful pH range of these probes using fluorescence lifetime imaging (FLIM). In particular, fluorescence lifetime of Oregon Green 488 proved to be sensitive probe to map pH micro heterogeneity within cheese matrices. Good agreement was observed between macroscopic scale pH measurement by FLIM and by traditional pH methods, but in addition considerable localized microheterogeneity in pH was evident within the curd matrix with pH range between 4.0 and 5.5. This technique provides significant potential to further investigate the relationship between cheese matrix physico-chemistry and bacterial metabolism during cheese manufacture and ripening. PMID:25798136

Measurement of pH micro-heterogeneity in natural cheese matrices by fluorescence lifetime imaging.

PubMed

Burdikova, Zuzana; Svindrych, Zdenek; Pala, Jan; Hickey, Cian D; Wilkinson, Martin G; Panek, Jiri; Auty, Mark A E; Periasamy, Ammasi; Sheehan, Jeremiah J

2015-01-01

Cheese, a product of microbial fermentation may be defined as a protein matrix entrapping fat, moisture, minerals and solutes as well as dispersed bacterial colonies. The growth and physiology of bacterial cells in these colonies may be influenced by the microenvironment around the colony, or alternatively the cells within the colony may modify the microenvironment (e.g., pH, redox potential) due to their metabolic activity. While cheese pH may be measured at macro level there remains a significant knowledge gap relating to the degree of micro-heterogeneity of pH within the cheese matrix and its relationship with microbial, enzymatic and physiochemical parameters and ultimately with cheese quality, consistency and ripening patterns. The pH of cheese samples was monitored both at macroscopic scale and at microscopic scale, using a non-destructive microscopic technique employing C-SNARF-4 and Oregon Green 488 fluorescent probes. The objectives of this work were to evaluate the suitability of these dyes for microscale pH measurements in natural cheese matrices and to enhance the sensitivity and extend the useful pH range of these probes using fluorescence lifetime imaging (FLIM). In particular, fluorescence lifetime of Oregon Green 488 proved to be sensitive probe to map pH micro heterogeneity within cheese matrices. Good agreement was observed between macroscopic scale pH measurement by FLIM and by traditional pH methods, but in addition considerable localized microheterogeneity in pH was evident within the curd matrix with pH range between 4.0 and 5.5. This technique provides significant potential to further investigate the relationship between cheese matrix physico-chemistry and bacterial metabolism during cheese manufacture and ripening.

Quantitative analysis of rib movement based on dynamic chest bone images: preliminary results

NASA Astrophysics Data System (ADS)

Tanaka, R.; Sanada, S.; Oda, M.; Mitsutaka, M.; Suzuki, K.; Sakuta, K.; Kawashima, H.

2014-03-01

Rib movement during respiration is one of the diagnostic criteria in pulmonary impairments. In general, the rib movement is assessed in fluoroscopy. However, the shadows of lung vessels and bronchi overlapping ribs prevent accurate quantitative analysis of rib movement. Recently, an image-processing technique for separating bones from soft tissue in static chest radiographs, called "bone suppression technique", has been developed. Our purpose in this study was to evaluate the usefulness of dynamic bone images created by the bone suppression technique in quantitative analysis of rib movement. Dynamic chest radiographs of 10 patients were obtained using a dynamic flat-panel detector (FPD). Bone suppression technique based on a massive-training artificial neural network (MTANN) was applied to the dynamic chest images to create bone images. Velocity vectors were measured in local areas on the dynamic bone images, which formed a map. The velocity maps obtained with bone and original images for scoliosis and normal cases were compared to assess the advantages of bone images. With dynamic bone images, we were able to quantify and distinguish movements of ribs from those of other lung structures accurately. Limited rib movements of scoliosis patients appeared as reduced rib velocity vectors. Vector maps in all normal cases exhibited left-right symmetric distributions, whereas those in abnormal cases showed nonuniform distributions. In conclusion, dynamic bone images were useful for accurate quantitative analysis of rib movements: Limited rib movements were indicated as a reduction of rib movement and left-right asymmetric distribution on vector maps. Thus, dynamic bone images can be a new diagnostic tool for quantitative analysis of rib movements without additional radiation dose.

Quantitative Imaging Biomarkers of NAFLD

PubMed Central

Kinner, Sonja; Reeder, Scott B.

2016-01-01

Conventional imaging modalities, including ultrasonography (US), computed tomography (CT), and magnetic resonance (MR), play an important role in the diagnosis and management of patients with nonalcoholic fatty liver disease (NAFLD) by allowing noninvasive diagnosis of hepatic steatosis. However, conventional imaging modalities are limited as biomarkers of NAFLD for various reasons. Multi-parametric quantitative MRI techniques overcome many of the shortcomings of conventional imaging and allow comprehensive and objective evaluation of NAFLD. MRI can provide unconfounded biomarkers of hepatic fat, iron, and fibrosis in a single examination—a virtual biopsy has become a clinical reality. In this article, we will review the utility and limitation of conventional US, CT, and MR imaging for the diagnosis NAFLD. Recent advances in imaging biomarkers of NAFLD are also discussed with an emphasis in multi-parametric quantitative MRI. PMID:26848588

Smartphone-based multispectral imaging: system development and potential for mobile skin diagnosis.

PubMed

Kim, Sewoong; Cho, Dongrae; Kim, Jihun; Kim, Manjae; Youn, Sangyeon; Jang, Jae Eun; Je, Minkyu; Lee, Dong Hun; Lee, Boreom; Farkas, Daniel L; Hwang, Jae Youn

2016-12-01

We investigate the potential of mobile smartphone-based multispectral imaging for the quantitative diagnosis and management of skin lesions. Recently, various mobile devices such as a smartphone have emerged as healthcare tools. They have been applied for the early diagnosis of nonmalignant and malignant skin diseases. Particularly, when they are combined with an advanced optical imaging technique such as multispectral imaging and analysis, it would be beneficial for the early diagnosis of such skin diseases and for further quantitative prognosis monitoring after treatment at home. Thus, we demonstrate here the development of a smartphone-based multispectral imaging system with high portability and its potential for mobile skin diagnosis. The results suggest that smartphone-based multispectral imaging and analysis has great potential as a healthcare tool for quantitative mobile skin diagnosis.

Quantitative analyses for elucidating mechanisms of cell fate commitment in the mouse blastocyst

NASA Astrophysics Data System (ADS)

Saiz, Néstor; Kang, Minjung; Puliafito, Alberto; Schrode, Nadine; Xenopoulos, Panagiotis; Lou, Xinghua; Di Talia, Stefano; Hadjantonakis, Anna-Katerina

2015-03-01

In recent years we have witnessed a shift from qualitative image analysis towards higher resolution, quantitative analyses of imaging data in developmental biology. This shift has been fueled by technological advances in both imaging and analysis software. We have recently developed a tool for accurate, semi-automated nuclear segmentation of imaging data from early mouse embryos and embryonic stem cells. We have applied this software to the study of the first lineage decisions that take place during mouse development and established analysis pipelines for both static and time-lapse imaging experiments. In this paper we summarize the conclusions from these studies to illustrate how quantitative, single-cell level analysis of imaging data can unveil biological processes that cannot be revealed by traditional qualitative studies.

Quantitative photothermal phase imaging of red blood cells using digital holographic photothermal microscope.

PubMed

Vasudevan, Srivathsan; Chen, George C K; Lin, Zhiping; Ng, Beng Koon

2015-05-10

Photothermal microscopy (PTM), a noninvasive pump-probe high-resolution microscopy, has been applied as a bioimaging tool in many biomedical studies. PTM utilizes a conventional phase contrast microscope to obtain highly resolved photothermal images. However, phase information cannot be extracted from these photothermal images, as they are not quantitative. Moreover, the problem of halos inherent in conventional phase contrast microscopy needs to be tackled. Hence, a digital holographic photothermal microscopy technique is proposed as a solution to obtain quantitative phase images. The proposed technique is demonstrated by extracting phase values of red blood cells from their photothermal images. These phase values can potentially be used to determine the temperature distribution of the photothermal images, which is an important study in live cell monitoring applications.

Quantitative Phase Imaging in a Volume Holographic Microscope

NASA Astrophysics Data System (ADS)

Waller, Laura; Luo, Yuan; Barbastathis, George

2010-04-01

We demonstrate a method for quantitative phase imaging in a Volume Holographic Microscope (VHM) from a single exposure, describe the properties of the system and show experimental results. The VHM system uses a multiplexed volume hologram (VH) to laterally separate images from different focal planes. This 3D intensity information is then used to solve the transport of intensity (TIE) equation and recover phase quantitatively. We discuss the modifications to the technique that were made in order to give accurate results.

Limited diagnostic value of Dual-Time-Point (18)F-FDG PET/CT imaging for classifying solitary pulmonary nodules in granuloma-endemic regions both at visual and quantitative analyses.

PubMed

Chen, Song; Li, Xuena; Chen, Meijie; Yin, Yafu; Li, Na; Li, Yaming

2016-10-01

This study is aimed to compare the diagnostic power of using quantitative analysis or visual analysis with single time point imaging (STPI) PET/CT and dual time point imaging (DTPI) PET/CT for the classification of solitary pulmonary nodules (SPN) lesions in granuloma-endemic regions. SPN patients who received early and delayed (18)F-FDG PET/CT at 60min and 180min post-injection were retrospectively reviewed. Diagnoses are confirmed by pathological results or follow-ups. Three quantitative metrics, early SUVmax, delayed SUVmax and retention index(the percentage changes between the early SUVmax and delayed SUVmax), were measured for each lesion. Three 5-point scale score was given by blinded interpretations performed by physicians based on STPI PET/CT images, DTPI PET/CT images and CT images, respectively. ROC analysis was performed on three quantitative metrics and three visual interpretation scores. One-hundred-forty-nine patients were retrospectively included. The areas under curve (AUC) of the ROC curves of early SUVmax, delayed SUVmax, RI, STPI PET/CT score, DTPI PET/CT score and CT score are 0.73, 0.74, 0.61, 0.77 0.75 and 0.76, respectively. There were no significant differences between the AUCs in visual interpretation of STPI PET/CT images and DTPI PET/CT images, nor in early SUVmax and delayed SUVmax. The differences of sensitivity, specificity and accuracy between STPI PET/CT and DTPI PET/CT were not significantly different in either quantitative analysis or visual interpretation. In granuloma-endemic regions, DTPI PET/CT did not offer significant improvement over STPI PET/CT in differentiating malignant SPNs in both quantitative analysis and visual interpretation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Real-time label-free quantitative fluorescence microscopy-based detection of ATP using a tunable fluorescent nano-aptasensor platform

NASA Astrophysics Data System (ADS)

Shrivastava, Sajal; Sohn, Il-Yung; Son, Young-Min; Lee, Won-Il; Lee, Nae-Eung

2015-11-01

Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (rGO) surfaces, thereby providing cytotoxicity assessment. Compared with conventional fluorescence spectrometry methods, our highly efficient, universally applicable, and rational approach will facilitate broader implementation of imaging-based biosensing platforms for the quantitative evaluation of a range of target molecules.Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (rGO) surfaces, thereby providing cytotoxicity assessment. Compared with conventional fluorescence spectrometry methods, our highly efficient, universally applicable, and rational approach will facilitate broader implementation of imaging-based biosensing platforms for the quantitative evaluation of a range of target molecules. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr05839b

Quantitative assessment on coronary computed tomography angiography (CCTA) image quality: comparisons between genders and different tube voltage settings.

PubMed

Chian, Teo Chee; Nassir, Norziana Mat; Ibrahim, Mohd Izuan; Yusof, Ahmad Khairuddin Md; Sabarudin, Akmal

2017-02-01

This study was carried out to quantify and compare the quantitative image quality of coronary computed tomography angiography (CCTA) between genders as well as between different tube voltages scan protocols. Fifty-five cases of CCTA were collected retrospectively and all images including reformatted axial images at systolic and diastolic phases as well as images with curved multi planar reformation (cMPR) were obtained. Quantitative image quality including signal intensity, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of right coronary artery (RCA), left anterior descending artery (LAD), left circumflex artery (LCx) and left main artery (LM) were quantified using Analyze 12.0 software. Six hundred and fifty-seven coronary arteries were evaluated. There were no significant differences in any quantitative image quality parameters between genders. 100 kilovoltage peak (kVp) scanning protocol produced images with significantly higher signal intensity compared to 120 kVp scanning protocol (P<0.001) in all coronary arteries in all types of images. Higher SNR was also observed in 100 kVp scan protocol in all coronary arteries except in LCx where 120 kVp showed better SNR than 100 kVp. There were no significant differences in image quality of CCTA between genders and different tube voltages. Lower tube voltage (100 kVp) scanning protocol is recommended in clinical practice to reduce the radiation dose to patient.

Quantitative fluorescence microscopy and image deconvolution.

PubMed

Swedlow, Jason R

2013-01-01

Quantitative imaging and image deconvolution have become standard techniques for the modern cell biologist because they can form the basis of an increasing number of assays for molecular function in a cellular context. There are two major types of deconvolution approaches--deblurring and restoration algorithms. Deblurring algorithms remove blur but treat a series of optical sections as individual two-dimensional entities and therefore sometimes mishandle blurred light. Restoration algorithms determine an object that, when convolved with the point-spread function of the microscope, could produce the image data. The advantages and disadvantages of these methods are discussed in this chapter. Image deconvolution in fluorescence microscopy has usually been applied to high-resolution imaging to improve contrast and thus detect small, dim objects that might otherwise be obscured. Their proper use demands some consideration of the imaging hardware, the acquisition process, fundamental aspects of photon detection, and image processing. This can prove daunting for some cell biologists, but the power of these techniques has been proven many times in the works cited in the chapter and elsewhere. Their usage is now well defined, so they can be incorporated into the capabilities of most laboratories. A major application of fluorescence microscopy is the quantitative measurement of the localization, dynamics, and interactions of cellular factors. The introduction of green fluorescent protein and its spectral variants has led to a significant increase in the use of fluorescence microscopy as a quantitative assay system. For quantitative imaging assays, it is critical to consider the nature of the image-acquisition system and to validate its response to known standards. Any image-processing algorithms used before quantitative analysis should preserve the relative signal levels in different parts of the image. A very common image-processing algorithm, image deconvolution, is used to remove blurred signal from an image. There are two major types of deconvolution approaches, deblurring and restoration algorithms. Deblurring algorithms remove blur, but treat a series of optical sections as individual two-dimensional entities, and therefore sometimes mishandle blurred light. Restoration algorithms determine an object that, when convolved with the point-spread function of the microscope, could produce the image data. The advantages and disadvantages of these methods are discussed. Copyright © 1998 Elsevier Inc. All rights reserved.

Cartilage Repair Surgery: Outcome Evaluation by Using Noninvasive Cartilage Biomarkers Based on Quantitative MRI Techniques?

PubMed Central

Jungmann, Pia M.; Baum, Thomas; Bauer, Jan S.; Karampinos, Dimitrios C.; Link, Thomas M.; Li, Xiaojuan; Trattnig, Siegfried; Rummeny, Ernst J.; Woertler, Klaus; Welsch, Goetz H.

2014-01-01

Background. New quantitative magnetic resonance imaging (MRI) techniques are increasingly applied as outcome measures after cartilage repair. Objective. To review the current literature on the use of quantitative MRI biomarkers for evaluation of cartilage repair at the knee and ankle. Methods. Using PubMed literature research, studies on biochemical, quantitative MR imaging of cartilage repair were identified and reviewed. Results. Quantitative MR biomarkers detect early degeneration of articular cartilage, mainly represented by an increasing water content, collagen disruption, and proteoglycan loss. Recently, feasibility of biochemical MR imaging of cartilage repair tissue and surrounding cartilage was demonstrated. Ultrastructural properties of the tissue after different repair procedures resulted in differences in imaging characteristics. T2 mapping, T1rho mapping, delayed gadolinium-enhanced MRI of cartilage (dGEMRIC), and diffusion weighted imaging (DWI) are applicable on most clinical 1.5 T and 3 T MR scanners. Currently, a standard of reference is difficult to define and knowledge is limited concerning correlation of clinical and MR findings. The lack of histological correlations complicates the identification of the exact tissue composition. Conclusions. A multimodal approach combining several quantitative MRI techniques in addition to morphological and clinical evaluation might be promising. Further investigations are required to demonstrate the potential for outcome evaluation after cartilage repair. PMID:24877139

The quantitative control and matching of an optical false color composite imaging system

NASA Astrophysics Data System (ADS)

Zhou, Chengxian; Dai, Zixin; Pan, Xizhe; Li, Yinxi

1993-10-01

Design of an imaging system for optical false color composite (OFCC) capable of high-precision density-exposure time control and color balance is presented. The system provides high quality FCC image data that can be analyzed using a quantitative calculation method. The quality requirement to each part of the image generation system is defined, and the distribution of satellite remote sensing image information is analyzed. The proposed technology makes it possible to present the remote sensing image data more effectively and accurately.

Vessel wall characterization using quantitative MRI: what's in a number?

PubMed

Coolen, Bram F; Calcagno, Claudia; van Ooij, Pim; Fayad, Zahi A; Strijkers, Gustav J; Nederveen, Aart J

2018-02-01

The past decade has witnessed the rapid development of new MRI technology for vessel wall imaging. Today, with advances in MRI hardware and pulse sequences, quantitative MRI of the vessel wall represents a real alternative to conventional qualitative imaging, which is hindered by significant intra- and inter-observer variability. Quantitative MRI can measure several important morphological and functional characteristics of the vessel wall. This review provides a detailed introduction to novel quantitative MRI methods for measuring vessel wall dimensions, plaque composition and permeability, endothelial shear stress and wall stiffness. Together, these methods show the versatility of non-invasive quantitative MRI for probing vascular disease at several stages. These quantitative MRI biomarkers can play an important role in the context of both treatment response monitoring and risk prediction. Given the rapid developments in scan acceleration techniques and novel image reconstruction, we foresee the possibility of integrating the acquisition of multiple quantitative vessel wall parameters within a single scan session.

A comparison study of image features between FFDM and film mammogram images

PubMed Central

Jing, Hao; Yang, Yongyi; Wernick, Miles N.; Yarusso, Laura M.; Nishikawa, Robert M.

2012-01-01

Purpose: This work is to provide a direct, quantitative comparison of image features measured by film and full-field digital mammography (FFDM). The purpose is to investigate whether there is any systematic difference between film and FFDM in terms of quantitative image features and their influence on the performance of a computer-aided diagnosis (CAD) system. Methods: The authors make use of a set of matched film-FFDM image pairs acquired from cadaver breast specimens with simulated microcalcifications consisting of bone and teeth fragments using both a GE digital mammography system and a screen-film system. To quantify the image features, the authors consider a set of 12 textural features of lesion regions and six image features of individual microcalcifications (MCs). The authors first conduct a direct comparison on these quantitative features extracted from film and FFDM images. The authors then study the performance of a CAD classifier for discriminating between MCs and false positives (FPs) when the classifier is trained on images of different types (film, FFDM, or both). Results: For all the features considered, the quantitative results show a high degree of correlation between features extracted from film and FFDM, with the correlation coefficients ranging from 0.7326 to 0.9602 for the different features. Based on a Fisher sign rank test, there was no significant difference observed between the features extracted from film and those from FFDM. For both MC detection and discrimination of FPs from MCs, FFDM had a slight but statistically significant advantage in performance; however, when the classifiers were trained on different types of images (acquired with FFDM or SFM) for discriminating MCs from FPs, there was little difference. Conclusions: The results indicate good agreement between film and FFDM in quantitative image features. While FFDM images provide better detection performance in MCs, FFDM and film images may be interchangeable for the purposes of training CAD algorithms, and a single CAD algorithm may be applied to either type of images. PMID:22830771

Cardiac imaging: working towards fully-automated machine analysis & interpretation

PubMed Central

Slomka, Piotr J; Dey, Damini; Sitek, Arkadiusz; Motwani, Manish; Berman, Daniel S; Germano, Guido

2017-01-01

Introduction Non-invasive imaging plays a critical role in managing patients with cardiovascular disease. Although subjective visual interpretation remains the clinical mainstay, quantitative analysis facilitates objective, evidence-based management, and advances in clinical research. This has driven developments in computing and software tools aimed at achieving fully automated image processing and quantitative analysis. In parallel, machine learning techniques have been used to rapidly integrate large amounts of clinical and quantitative imaging data to provide highly personalized individual patient-based conclusions. Areas covered This review summarizes recent advances in automated quantitative imaging in cardiology and describes the latest techniques which incorporate machine learning principles. The review focuses on the cardiac imaging techniques which are in wide clinical use. It also discusses key issues and obstacles for these tools to become utilized in mainstream clinical practice. Expert commentary Fully-automated processing and high-level computer interpretation of cardiac imaging are becoming a reality. Application of machine learning to the vast amounts of quantitative data generated per scan and integration with clinical data also facilitates a move to more patient-specific interpretation. These developments are unlikely to replace interpreting physicians but will provide them with highly accurate tools to detect disease, risk-stratify, and optimize patient-specific treatment. However, with each technological advance, we move further from human dependence and closer to fully-automated machine interpretation. PMID:28277804

Optical imaging of tumor microenvironment

PubMed Central

Wu, Yihan; Zhang, Wenjie; Li, Jinbo; Zhang, Yan

2013-01-01

Tumor microenvironment plays important roles in tumor development and metastasis. Features of the tumor microenvironment that are significantly different from normal tissues include acidity, hypoxia, overexpressed proteases and so on. Therefore, these features can serve as not only biomarkers for tumor diagnosis but also theraputic targets for tumor treatment. Imaging modalities such as optical, positron emission tomography (PET) and magnetic resonance imaging (MRI) have been intensively applied to investigate tumor microenvironment. Various imaging probes targeting pH, hypoxia and proteases in tumor microenvironment were thus well developed. In this review, we will focus on recent examples on fluorescent probes for optical imaging of tumor microenvironment. Construction of these fluorescent probes were based on characteristic feature of pH, hypoxia and proteases in tumor microenvironment. Strategies for development of these fluorescent probes and applications of these probes in optical imaging of tumor cells or tissues will be discussed in this review paper. PMID:23342297

Selective imaging of cancer cells with a pH-activatable lysosome-targeting fluorescent probe.

PubMed

Shi, Rongguang; Huang, Lu; Duan, Xiaoxue; Sun, Guohao; Yin, Gui; Wang, Ruiyong; Zhu, Jun-Jie

2017-10-02

Fluorescence imaging with tumor-specific fluorescent probe has emerged as a tool to aid surgeons in the identification and removal of tumor tissue. We report here a new lysosome-targeting fluorescent probe (NBOH) with BODIPY fluorephore to distinguish tumor tissue out of normal tissue based on different pH environment. The probe exhibited remarkable pH-dependent fluorescence behavior in a wide pH range from 3.0 to 11.0, especially a sensitive pH-dependent fluorescence change at pH range between 3.5 and 5.5, corresponding well to the acidic microenvironment of tumor cells, in aqueous solution. The response time of NBOH was extremely short and the photostability was proved to be good. Toxicity test and fluorescence cell imaging together with a sub-cellular localization study were carried out revealing its low biotoxicity and good cell membrane permeability. And NBOH was successfully applied to the imaging of tumor tissue in tumor-bearing mice suggesting potential application to surgery as a tumor-specific probe. Copyright © 2017 Elsevier B.V. All rights reserved.

A novel approach for rapidly and cost-effectively assessing toxicity of toxic metals in acidic water using an acidophilic iron-oxidizing biosensor.

PubMed

Yang, Shih-Hung; Cheng, Kuo-Chih; Liao, Vivian Hsiu-Chuan

2017-11-01

Contamination by heavy metals and metalloids is a serious environmental and health concern. Acidic wastewaters are often associated with toxic metals which may enter and spread into agricultural soils. Several biological assays have been developed to detect toxic metals; however, most of them can only detect toxic metals in a neutral pH, not in an acidic environment. In this study, an acidophilic iron-oxidizing bacterium (IOB) Strain Y10 was isolated, characterized, and used to detect toxic metals toxicity in acidic water at pH 2.5. The colorimetric acidophilic IOB biosensor was based on the inhibition of the iron oxidizing ability of Strain Y10, an acidophilic iron-oxidizing bacterium, by metals toxicity. Our results showed that Strain Y10 is acidophilic iron-oxidizing bacterium. Thiobacillus caldus medium (TCM) (pH 2.5) supplied with both S 4 O 6 2- and glucose was the optimum growth medium for Strain Y10. The optimum temperature and pH for the growth of Strain Y10 was 45 °C and pH 2.5, respectively. Our study demonstrates that the color-based acidophilic IOB biosensor can be semi-quantitatively observed by eye or quantitatively measured by spectrometer to detect toxicity from multiple toxic metals at pH 2.5 within 45 min. Our study shows that monitoring toxic metals in acidic water is possible by using the acidophilic IOB biosensor. Our study thus provides a novel approach for rapid and cost-effective detection of toxic metals in acidic conditions that can otherwise compromise current methods of chemical analysis. This method also allows for increased efficiency when screening large numbers of environmental samples. Copyright © 2017 Elsevier Ltd. All rights reserved.

Self-assembly of BODIPY based pH-sensitive near-infrared polymeric micelles for drug controlled delivery and fluorescence imaging applications

NASA Astrophysics Data System (ADS)

Liu, Xiaodong; Chen, Bizheng; Li, Xiaojun; Zhang, Lifen; Xu, Yujie; Liu, Zhuang; Cheng, Zhenping; Zhu, Xiulin

2015-10-01

Responsive block copolymer micelles emerging as promising imaging and drug delivery systems show high stability and on-demand drug release activities. Herein, we developed self-assembled pH-responsive NIR emission micelles entrapped with doxorubicin (DOX) within the cores by the electrostatic interactions for fluorescence imaging and chemotherapy applications. The block copolymer, poly(methacrylic acid)-block-poly[(poly(ethylene glycol) methyl ether methacrylate)-co-boron dipyrromethene derivatives] (PMAA-b-P(PEGMA-co-BODIPY)), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the molecular weight distribution of this copolymer was narrow (Mw/Mn = 1.31). The NIR fluorescence enhancement induced by the phenol/phenolate interconversion equilibrium works as a switch in response to the intracellular pH fluctuations. DOX-loaded PMAA-b-P(PEGMA-co-BODIPY) micelles can detect the physiological pH fluctuations with a pKa near physiological conditions (~7.52), and showed pH-responsive collapse and an obvious acid promoted anticancer drug release behavior (over 58.8-62.8% in 10 h). Real-time imaging of intracellular pH variations was performed and a significant chemotherapy effect was demonstrated against HeLa cells.Responsive block copolymer micelles emerging as promising imaging and drug delivery systems show high stability and on-demand drug release activities. Herein, we developed self-assembled pH-responsive NIR emission micelles entrapped with doxorubicin (DOX) within the cores by the electrostatic interactions for fluorescence imaging and chemotherapy applications. The block copolymer, poly(methacrylic acid)-block-poly[(poly(ethylene glycol) methyl ether methacrylate)-co-boron dipyrromethene derivatives] (PMAA-b-P(PEGMA-co-BODIPY)), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the molecular weight distribution of this copolymer was narrow (Mw/Mn = 1.31). The NIR fluorescence enhancement induced by the phenol/phenolate interconversion equilibrium works as a switch in response to the intracellular pH fluctuations. DOX-loaded PMAA-b-P(PEGMA-co-BODIPY) micelles can detect the physiological pH fluctuations with a pKa near physiological conditions (~7.52), and showed pH-responsive collapse and an obvious acid promoted anticancer drug release behavior (over 58.8-62.8% in 10 h). Real-time imaging of intracellular pH variations was performed and a significant chemotherapy effect was demonstrated against HeLa cells. Electronic supplementary information (ESI) available: GPC, UV/vis, fluorescence, and MTT data of the as-prepared polymers; 1H NMR, 13C NMR, HRMS and FT-IR of organic molecules and polymers. See DOI: 10.1039/c5nr04655f

Coastal Imaging Spectroscopy

DTIC Science & Technology

2006-09-30

Year, Semi-Finalist, Florida Environmental Research Institute, W. Paul Bissett, Ph.D., Executive Director, Greater Tampa Chamber of Commerce . 2004...Small Business of the Year, -Finalist, Florida Environmental Research Institute, W. Paul Bissett, Ph.D., Executive Director, Greater Tampa Chamber of Commerce .

Quantitative analysis of biological tissues using Fourier transform-second-harmonic generation imaging

NASA Astrophysics Data System (ADS)

Ambekar Ramachandra Rao, Raghu; Mehta, Monal R.; Toussaint, Kimani C., Jr.

2010-02-01

We demonstrate the use of Fourier transform-second-harmonic generation (FT-SHG) imaging of collagen fibers as a means of performing quantitative analysis of obtained images of selected spatial regions in porcine trachea, ear, and cornea. Two quantitative markers, preferred orientation and maximum spatial frequency are proposed for differentiating structural information between various spatial regions of interest in the specimens. The ear shows consistent maximum spatial frequency and orientation as also observed in its real-space image. However, there are observable changes in the orientation and minimum feature size of fibers in the trachea indicating a more random organization. Finally, the analysis is applied to a 3D image stack of the cornea. It is shown that the standard deviation of the orientation is sensitive to the randomness in fiber orientation. Regions with variations in the maximum spatial frequency, but with relatively constant orientation, suggest that maximum spatial frequency is useful as an independent quantitative marker. We emphasize that FT-SHG is a simple, yet powerful, tool for extracting information from images that is not obvious in real space. This technique can be used as a quantitative biomarker to assess the structure of collagen fibers that may change due to damage from disease or physical injury.

Quantitative Analysis of the Cervical Texture by Ultrasound and Correlation with Gestational Age.

PubMed

Baños, Núria; Perez-Moreno, Alvaro; Migliorelli, Federico; Triginer, Laura; Cobo, Teresa; Bonet-Carne, Elisenda; Gratacos, Eduard; Palacio, Montse

2017-01-01

Quantitative texture analysis has been proposed to extract robust features from the ultrasound image to detect subtle changes in the textures of the images. The aim of this study was to evaluate the feasibility of quantitative cervical texture analysis to assess cervical tissue changes throughout pregnancy. This was a cross-sectional study including singleton pregnancies between 20.0 and 41.6 weeks of gestation from women who delivered at term. Cervical length was measured, and a selected region of interest in the cervix was delineated. A model to predict gestational age based on features extracted from cervical images was developed following three steps: data splitting, feature transformation, and regression model computation. Seven hundred images, 30 per gestational week, were included for analysis. There was a strong correlation between the gestational age at which the images were obtained and the estimated gestational age by quantitative analysis of the cervical texture (R = 0.88). This study provides evidence that quantitative analysis of cervical texture can extract features from cervical ultrasound images which correlate with gestational age. Further research is needed to evaluate its applicability as a biomarker of the risk of spontaneous preterm birth, as well as its role in cervical assessment in other clinical situations in which cervical evaluation might be relevant. © 2016 S. Karger AG, Basel.

Development of a Hampton University Program for Novel Breast Cancer Imaging and Therapy Research

DTIC Science & Technology

2014-04-01

Award Number: W81XWH-09-1-0111 TITLE: “Development of a Hampton University Program for Novel Breast Cancer Imaging and Therapy Research...a Hampton University Program for Novel Breast Cancer Imaaging and Therapy Research Nicholas Kenney, PhD Drew Weisenberger PhD Christopher Sinesci...cosmetic outcome of women with early stage breast cancers treated with MSB applicator and the spacing between the MammoSite balloon surface and the

Imaging of dynamic ion signaling during root gravitropism.

PubMed

Monshausen, Gabriele B

2015-01-01

Gravitropic signaling is a complex process that requires the coordinated action of multiple cell types and tissues. Ca(2+) and pH signaling are key components of gravitropic signaling cascades and can serve as useful markers to dissect the molecular machinery mediating plant gravitropism. To monitor dynamic ion signaling, imaging approaches combining fluorescent ion sensors and confocal fluorescence microscopy are employed, which allow the visualization of pH and Ca(2+) changes at the level of entire tissues, while also providing high spatiotemporal resolution. Here, I describe procedures to prepare Arabidopsis seedlings for live cell imaging and to convert a microscope for vertical stage fluorescence microscopy. With this imaging system, ion signaling can be monitored during all phases of the root gravitropic response.

Quantitative label-free sperm imaging by means of transport of intensity

NASA Astrophysics Data System (ADS)

Poola, Praveen Kumar; Pandiyan, Vimal Prabhu; Jayaraman, Varshini; John, Renu

2016-03-01

Most living cells are optically transparent which makes it difficult to visualize them under bright field microscopy. Use of contrast agents or markers and staining procedures are often followed to observe these cells. However, most of these staining agents are toxic and not applicable for live cell imaging. In the last decade, quantitative phase imaging has become an indispensable tool for morphological characterization of the phase objects without any markers. In this paper, we report noninterferometric quantitative phase imaging of live sperm cells by solving transport of intensity equations with recorded intensity measurements along optical axis on a commercial bright field microscope.

Measurements of morphology and refractive indexes on human downy hairs using three-dimensional quantitative phase imaging.

PubMed

Lee, SangYun; Kim, Kyoohyun; Lee, Yuhyun; Park, Sungjin; Shin, Heejae; Yang, Jongwon; Ko, Kwanhong; Park, HyunJoo; Park, YongKeun

2015-01-01

We present optical measurements of morphology and refractive indexes (RIs) of human downy arm hairs using three-dimensional (3-D) quantitative phase imaging techniques. 3-D RI tomograms and high-resolution two-dimensional synthetic aperture images of individual downy arm hairs were measured using a Mach–Zehnder laser interferometric microscopy equipped with a two-axis galvanometer mirror. From the measured quantitative images, the RIs and morphological parameters of downy hairs were noninvasively quantified including the mean RI, volume, cylinder, and effective radius of individual hairs. In addition, the effects of hydrogen peroxide on individual downy hairs were investigated.

Open Science CBS Neuroimaging Repository: Sharing ultra-high-field MR images of the brain.

PubMed

Tardif, Christine Lucas; Schäfer, Andreas; Trampel, Robert; Villringer, Arno; Turner, Robert; Bazin, Pierre-Louis

2016-01-01

Magnetic resonance imaging at ultra high field opens the door to quantitative brain imaging at sub-millimeter isotropic resolutions. However, novel image processing tools to analyze these new rich datasets are lacking. In this article, we introduce the Open Science CBS Neuroimaging Repository: a unique repository of high-resolution and quantitative images acquired at 7 T. The motivation for this project is to increase interest for high-resolution and quantitative imaging and stimulate the development of image processing tools developed specifically for high-field data. Our growing repository currently includes datasets from MP2RAGE and multi-echo FLASH sequences from 28 and 20 healthy subjects respectively. These datasets represent the current state-of-the-art in in-vivo relaxometry at 7 T, and are now fully available to the entire neuroimaging community. Copyright © 2015 Elsevier Inc. All rights reserved.

Longitudinal and transverse right ventricular function in pulmonary hypertension: cardiovascular magnetic resonance imaging study from the ASPIRE registry

PubMed Central

Rajaram, Smitha; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M.; Kiely, David G.

2015-01-01

Abstract Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of <20 mmHg, cardiovascular magnetic resonance imaging was performed within 24 hours of right heart catheterization. In patients with PH, fractional longitudinal motion (fractional tricuspid annulus to apex distance [f-TAAD]) was significantly greater than fractional transverse motion (fractional septum to free wall distance [f-SFD]; P = 0.002). In patients without PH, no significant difference between f-SFD and f-TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH. PMID:26401257

Longitudinal and transverse right ventricular function in pulmonary hypertension: cardiovascular magnetic resonance imaging study from the ASPIRE registry.

PubMed

Swift, Andrew J; Rajaram, Smitha; Capener, Dave; Elliot, Charlie; Condliffe, Robin; Wild, Jim M; Kiely, David G

2015-09-01

Right ventricular (RV) function is a strong predictor of outcome in cardiovascular diseases. Two components of RV function, longitudinal and transverse motion, have been investigated in pulmonary hypertension (PH). However, their individual clinical significance remains uncertain. The aim of this study was to determine the factors associated with transverse and longitudinal RV motion in patients with PH. In 149 treatment-naive patients with PH and 16 patients with suspected PH found to have mean pulmonary arterial pressure of <20 mmHg, cardiovascular magnetic resonance imaging was performed within 24 hours of right heart catheterization. In patients with PH, fractional longitudinal motion (fractional tricuspid annulus to apex distance [f-TAAD]) was significantly greater than fractional transverse motion (fractional septum to free wall distance [f-SFD]; P = 0.002). In patients without PH, no significant difference between f-SFD and f-TAAD was identified (P = 0.442). Longitudinal RV motion was singularly associated with RV ejection fraction independent of age, invasive hemodynamics, and cardiac magnetic resonance measurements (P = 0.024). In contrast, transverse RV motion was independently associated with left ventricular eccentricity (P = 0.036) in addition to RV ejection fraction (P = 0.014). In conclusion, RV motion is significantly greater in the longitudinal direction in patients with PH, whereas patients without PH have equal contributions of transverse and longitudinal motion. Longitudinal RV motion is primarily associated with global RV pump function in PH. Transverse RV motion not only reflects global pump function but is independently influenced by ventricular interaction in patients with PH.

Application of Optical Imaging Techniques for Quantification of pH and O2 Dynamicsin Porous Media

NASA Astrophysics Data System (ADS)

Li, B.; Seliman, A. F.; Pales, A. R.; Liang, W.; Sams, A.; Darnault, C. J. G.; DeVol, T. A.

2016-12-01

Understanding the spatial and temporal distribution of physical and chemical parameters (e.g. pH, O2) is imperative to characterize the behavior of contaminants in a natural environment. The objectives of this research are to calibrate pH and O2 sensor foils, to develop a dual pH/O2 sensor foil, and to apply them into flow and transport experiments, in order to understand the physical and chemical parameters that control contaminant fate and transport in an unsaturated sandy porous medium. In addition, demonstration of a sensor foil that quantifies aqueous uranium concentration will be presented. Optical imaging techniques will be conducted with 2D tanks to investigate the influence of microbial exudates and plant roots on pH and O2 parameters and radionuclides transport. As a non-invasive method, the optical imaging technique utilizes optical chemical sensor films and either a digital camera or a spectrometer to capture the changes with high temporal and spatial resolutions. Sensor foils are made for different parameters by applying dyes to generate favorable fluorescence that is proportional to the parameter of interest. Preliminary results suggested that this method could detect pH ranging from 4.5 to 7.5. The result from uranium foil test with different concentrations in the range of 2 to 8 ppm indicated that a higher concentration of uranium resulted in a greater color intensity.

Smartphone-based simultaneous pH and nitrite colorimetric determination for paper microfluidic devices.

PubMed

Lopez-Ruiz, Nuria; Curto, Vincenzo F; Erenas, Miguel M; Benito-Lopez, Fernando; Diamond, Dermot; Palma, Alberto J; Capitan-Vallvey, Luis F

2014-10-07

In this work, an Android application for measurement of nitrite concentration and pH determination in combination with a low-cost paper-based microfluidic device is presented. The application uses seven sensing areas, containing the corresponding immobilized reagents, to produce selective color changes when a sample solution is placed in the sampling area. Under controlled conditions of light, using the flash of the smartphone as a light source, the image captured with the built-in camera is processed using a customized algorithm for multidetection of the colored sensing areas. The developed image-processing allows reducing the influence of the light source and the positioning of the microfluidic device in the picture. Then, the H (hue) and S (saturation) coordinates of the HSV color space are extracted and related to pH and nitrite concentration, respectively. A complete characterization of the sensing elements has been carried out as well as a full description of the image analysis for detection. The results show good use of a mobile phone as an analytical instrument. For the pH, the resolution obtained is 0.04 units of pH, 0.09 of accuracy, and a mean squared error of 0.167. With regard to nitrite, 0.51% at 4.0 mg L(-1) of resolution and 0.52 mg L(-1) as the limit of detection was achieved.

Intracellular pH measurements made simple by fluorescent protein probes and the phasor approach to fluorescence lifetime imaging†

PubMed Central

Digman, Michelle A.; Gratton, Enrico; Storti, Barbara; Beltram, Fabio

2013-01-01

A versatile pH-dependent fluorescent protein was applied to intracellular pH measurements by means of the phasor approach to fluorescence lifetime imaging. By this fit-less method we obtain intracellular pH maps under resting or altered physiological conditions by single-photon confocal or two-photon microscopy. PMID:22517076

Imaging of Intracellular pH in Tumor Spheroids Using Genetically Encoded Sensor SypHer2.

PubMed

Zagaynova, Elena V; Druzhkova, Irina N; Mishina, Natalia M; Ignatova, Nadezhda I; Dudenkova, Varvara V; Shirmanova, Marina V

2017-01-01

Intracellular pH (pHi) is one of the most important parameters that regulate the physiological state of cells and tissues. pHi homeostasis is crucial for normal cell functioning. Cancer cells are characterized by having a higher (neutral to slightly alkaline) pHi and lower (acidic) extracellular pH (pHe) compared to normal cells. This is referred to as a "reversed" pH gradient, and is essential in supporting their accelerated growth rate, invasion and migration, and in suppressing anti-tumor immunity, the promotion of metabolic coupling with fibroblasts and in preventing apoptosis. Moreover, abnormal pH, both pHi and pHe, contribute to drug resistance in cancers. Therefore, the development of methods for measuring pH in living tumor cells is likely to lead to better understanding of tumor biology and to open new ways for cancer treatment. Genetically encoded, fluorescent, pH-sensitive probes represent promising instruments enabling the subcellular measurement of pHi with unrivaled specificity and high accuracy. Here, we describe a protocol for pHi imaging at a microscopic level in HeLa tumor spheroids, using the genetically encoded ratiometric (dual-excitation) pHi indicator, SypHer2.

Quantitative chemical imaging with background-free multiplex coherent anti-Stokes Raman scattering by dual-soliton Stokes pulses

PubMed Central

Chen, Kun; Wu, Tao; Wei, Haoyun; Zhou, Tian; Li, Yan

2016-01-01

Coherent anti-Stokes Raman microscopy (CARS) is a quantitative, chemically specific, and label-free optical imaging technique for studying inhomogeneous systems. However, the complicating influence of the nonresonant response on the CARS signal severely limits its sensitivity and specificity and especially limits the extent to which CARS microscopy has been used as a fully quantitative imaging technique. On the basis of spectral focusing mechanism, we establish a dual-soliton Stokes based CARS microspectroscopy and microscopy scheme capable of quantifying the spatial information of densities and chemical composition within inhomogeneous samples, using a single fiber laser. Dual-soliton Stokes scheme not only removes the nonresonant background but also allows robust acquisition of multiple characteristic vibrational frequencies. This all-fiber based laser source can cover the entire fingerprint (800-2200 cm−1) region with a spectral resolution of 15 cm−1. We demonstrate that quantitative degree determination of lipid-chain unsaturation in the fatty acids mixture can be achieved by the characterization of C = C stretching and CH2 deformation vibrations. For microscopy purposes, we show that the spatially inhomogeneous distribution of lipid droplets can be further quantitatively visualized using this quantified degree of lipid unsaturation in the acyl chain for contrast in the hyperspectral CARS images. The combination of compact excitation source and background-free capability to facilitate extraction of quantitative composition information with multiplex spectral peaks will enable wider applications of quantitative chemical imaging in studying biological and material systems. PMID:27867704

MapX: An In Situ, Full-Frame X-Ray Spectroscopic Imager for the Biogenic Elements

NASA Technical Reports Server (NTRS)

Blake, David; Sarrazin, Philippe; Thompson, Kathy; Bristow, Thomas

2016-01-01

Microbial life exploits microscale disequilibria at boundaries where valence, chemical potential, pH, Eh, etc. vary on a length scale commensurate with the organisms themselves - tens to hundreds of micrometers. These disequilibria can exist within cracks or veins in rocks and ice, at inter- or intra-crystalline boundaries, at sediment/water or sediment/atmosphere interfaces, or even within fluid inclusions trapped inside minerals. The detection of accumulations of the biogenic elements C,N,O,P,S at appropriate concentrations on or in a mineral/ice substrate would constitute permissive evidence of extant life, but context is also required. Does the putative biosignature exist in a habitable environment? Under what conditions of P, T, and chemical potential was the host mineralogy formed? MapX is an arm-deployed contact instrument that directly images the biogenic elements C, N, O, P, S, as well as the cations of the rock-forming minerals (Na, Mg, Al, Si, K, Ca, Ti, Cr, Mn, Fe) and important anions such as Cl, Fl. The instrument provides element images having =100 micron lateral spatial resolution over a 2.5 cm X 2.5 cm area, as well as quantitative XRF spectra from ground-selected or instrument-selected Regions of Interest (ROI) on the sample. Quantitative XRF spectra from ROI can be translated into mineralogies using ground- or instrument-based algorithms. Either an X-ray tube source (X-ray fluorescence) or a radioisotope source such as 244-Cm (alpha-particle and gamma-ray fluorescence) can be used, and characteristic X-rays emitted from the sample are imaged onto an X-ray sensitive CCD through an X-ray MicroPore Optic (MPO). As a fluorescent source, 244-Cm is highly desirable in a MapX instrument intended for life detection since high-energy alpha-particles are unrivaled in fluorescence yield for the low-Z elements. The MapX design as well as baseline performance requirements for a MapX instrument intended for life detection/identification of habitable environments will be presented.

Comparison of clinical and physics scoring of PET images when image reconstruction parameters are varied.

PubMed

Walsh, C; Johnston, C; Sheehy, N; O' Reilly, G

2013-02-01

In this study the quantitative and qualitative image quality (IQ) measurements with clinical judgement of IQ in positron emission tomography (PET) were compared. The limitations of IQ metrics and the proposed criteria of acceptability for PET scanners are discussed. Phantom and patient images were reconstructed using seven different iterative reconstruction protocols. For each reconstructed set of images, IQ was scored based both on the visual analysis and on the quantitative metrics. The quantitative physics metrics did not rank the reconstruction protocols in the same order as the clinicians' scoring of perceived IQ (R(s)=-0.54). Better agreement was achieved when comparing the clinical perception of IQ to the physicist's visual assessment of IQ in the phantom images (R(s)=+0.59). The closest agreement was seen between the quantitative physics metrics and the measurement of the standard uptake values (SUVs) in small tumours (R(s)=+0.92). Given the disparity between the clinical perception of IQ and the physics metrics a cautious approach to use of IQ measurements for determining suspension levels is warranted.

Multimodal computational microscopy based on transport of intensity equation

NASA Astrophysics Data System (ADS)

Li, Jiaji; Chen, Qian; Sun, Jiasong; Zhang, Jialin; Zuo, Chao

2016-12-01

Transport of intensity equation (TIE) is a powerful tool for phase retrieval and quantitative phase imaging, which requires intensity measurements only at axially closely spaced planes without a separate reference beam. It does not require coherent illumination and works well on conventional bright-field microscopes. The quantitative phase reconstructed by TIE gives valuable information that has been encoded in the complex wave field by passage through a sample of interest. Such information may provide tremendous flexibility to emulate various microscopy modalities computationally without requiring specialized hardware components. We develop a requisite theory to describe such a hybrid computational multimodal imaging system, which yields quantitative phase, Zernike phase contrast, differential interference contrast, and light field moment imaging, simultaneously. It makes the various observations for biomedical samples easy. Then we give the experimental demonstration of these ideas by time-lapse imaging of live HeLa cell mitosis. Experimental results verify that a tunable lens-based TIE system, combined with the appropriate postprocessing algorithm, can achieve a variety of promising imaging modalities in parallel with the quantitative phase images for the dynamic study of cellular processes.

Quantitative magnetic resonance micro-imaging methods for pharmaceutical research.

PubMed

Mantle, M D

2011-09-30

The use of magnetic resonance imaging (MRI) as a tool in pharmaceutical research is now well established and the current literature covers a multitude of different pharmaceutically relevant research areas. This review focuses on the use of quantitative magnetic resonance micro-imaging techniques and how they have been exploited to extract information that is of direct relevance to the pharmaceutical industry. The article is divided into two main areas. The first half outlines the theoretical aspects of magnetic resonance and deals with basic magnetic resonance theory, the effects of nuclear spin-lattice (T(1)), spin-spin (T(2)) relaxation and molecular diffusion upon image quantitation, and discusses the applications of rapid magnetic resonance imaging techniques. In addition to the theory, the review aims to provide some practical guidelines for the pharmaceutical researcher with an interest in MRI as to which MRI pulse sequences/protocols should be used and when. The second half of the article reviews the recent advances and developments that have appeared in the literature concerning the use of quantitative micro-imaging methods to pharmaceutically relevant research. Copyright © 2010 Elsevier B.V. All rights reserved.

Iterative optimization method for design of quantitative magnetization transfer imaging experiments.

PubMed

Levesque, Ives R; Sled, John G; Pike, G Bruce

2011-09-01

Quantitative magnetization transfer imaging (QMTI) using spoiled gradient echo sequences with pulsed off-resonance saturation can be a time-consuming technique. A method is presented for selection of an optimum experimental design for quantitative magnetization transfer imaging based on the iterative reduction of a discrete sampling of the Z-spectrum. The applicability of the technique is demonstrated for human brain white matter imaging at 1.5 T and 3 T, and optimal designs are produced to target specific model parameters. The optimal number of measurements and the signal-to-noise ratio required for stable parameter estimation are also investigated. In vivo imaging results demonstrate that this optimal design approach substantially improves parameter map quality. The iterative method presented here provides an advantage over free form optimal design methods, in that pragmatic design constraints are readily incorporated. In particular, the presented method avoids clustering and repeated measures in the final experimental design, an attractive feature for the purpose of magnetization transfer model validation. The iterative optimal design technique is general and can be applied to any method of quantitative magnetization transfer imaging. Copyright © 2011 Wiley-Liss, Inc.

Comparison among Reconstruction Algorithms for Quantitative Analysis of 11C-Acetate Cardiac PET Imaging.

PubMed

Shi, Ximin; Li, Nan; Ding, Haiyan; Dang, Yonghong; Hu, Guilan; Liu, Shuai; Cui, Jie; Zhang, Yue; Li, Fang; Zhang, Hui; Huo, Li

2018-01-01

Kinetic modeling of dynamic 11 C-acetate PET imaging provides quantitative information for myocardium assessment. The quality and quantitation of PET images are known to be dependent on PET reconstruction methods. This study aims to investigate the impacts of reconstruction algorithms on the quantitative analysis of dynamic 11 C-acetate cardiac PET imaging. Suspected alcoholic cardiomyopathy patients ( N = 24) underwent 11 C-acetate dynamic PET imaging after low dose CT scan. PET images were reconstructed using four algorithms: filtered backprojection (FBP), ordered subsets expectation maximization (OSEM), OSEM with time-of-flight (TOF), and OSEM with both time-of-flight and point-spread-function (TPSF). Standardized uptake values (SUVs) at different time points were compared among images reconstructed using the four algorithms. Time-activity curves (TACs) in myocardium and blood pools of ventricles were generated from the dynamic image series. Kinetic parameters K 1 and k 2 were derived using a 1-tissue-compartment model for kinetic modeling of cardiac flow from 11 C-acetate PET images. Significant image quality improvement was found in the images reconstructed using iterative OSEM-type algorithms (OSME, TOF, and TPSF) compared with FBP. However, no statistical differences in SUVs were observed among the four reconstruction methods at the selected time points. Kinetic parameters K 1 and k 2 also exhibited no statistical difference among the four reconstruction algorithms in terms of mean value and standard deviation. However, for the correlation analysis, OSEM reconstruction presented relatively higher residual in correlation with FBP reconstruction compared with TOF and TPSF reconstruction, and TOF and TPSF reconstruction were highly correlated with each other. All the tested reconstruction algorithms performed similarly for quantitative analysis of 11 C-acetate cardiac PET imaging. TOF and TPSF yielded highly consistent kinetic parameter results with superior image quality compared with FBP. OSEM was relatively less reliable. Both TOF and TPSF were recommended for cardiac 11 C-acetate kinetic analysis.

Dynamic measurement of the optical properties of bovine enamel demineralization models using four-dimensional optical coherence tomography

NASA Astrophysics Data System (ADS)

Aden, Abdirahman; Anthony, Arthi; Brigi, Carel; Merchant, Muhammad Sabih; Siraj, Huda; Tomlins, Peter H.

2017-07-01

Dental enamel mineral loss is multifactorial and is consequently explored using a variety of in vitro models. Important factors include the presence of acidic pH and its specific ionic composition, which can both influence lesion characteristics. Optical coherence tomography (OCT) has been demonstrated as a promising tool for studying dental enamel demineralization. However, OCT-based characterization and comparison of demineralization model dynamics are challenging without a consistent experimental environment. Therefore, an automated four-dimensional OCT system was integrated with a multispecimen flow cell to measure and compare the optical properties of subsurface enamel demineralization in different models. This configuration was entirely automated, thus mitigating any need to disturb the specimens and ensuring spatial registration of OCT image volumes at multiple time points. Twelve bovine enamel disks were divided equally among three model groups. The model demineralization solutions were citric acid (pH 3.8), acetic acid (pH 4.0), and acetic acid with added calcium and phosphate (pH 4.4). Bovine specimens were exposed to the solution continuously for 48 h. Three-dimensional OCT data were obtained automatically from each specimen at a minimum of 1-h intervals from the same location within each specimen. Lesion dynamics were measured in terms of the depth below the surface to which the lesion extended and the attenuation coefficient. The net loss of surface enamel was also measured for comparison. Similarities between the dynamics of each model were observed, although there were also distinct characteristic differences. Notably, the attenuation coefficients showed a systematic offset and temporal shift with respect to the different models. Furthermore, the lesion depth curves displayed a discontinuous increase several hours after the initial acid challenge. This work demonstrated the capability of OCT to distinguish between different enamel demineralization models by making dynamic quantitative measurements of lesion properties. This has important implications for future applications in clinical dentistry.

Monitoring of internal pH gradients within multi-layer tablets by optical methods and EPR imaging.

PubMed

Eisenächer, Friederike; Schädlich, Andreas; Mäder, Karsten

2011-09-30

The high variability of gastrointestinal pH is a general challenge regarding constant release from oral drug delivery systems, especially for ionisable drugs. These drugs often show a pH-dependent solubility and therewith associated intra- and inter-individual variability of emerging drug plasma levels. Several strategies have been investigated with the intention to influence the microenvironmental pH (pH(M)) within solid formulations and therefore achieve pH-independent release profiles. Because of the heterogeneity of solid systems, a precise prediction of the occurring pH(M) is rather difficult. It is therefore important to monitor the pH(M) within the formulations to achieve requested release as well as to minimise pH-dependent degradation processes of the active compound. The purpose of the current study was the analysis of pH(M) gradients within 2- and 3-layer tablets during hydration using 3 different techniques for comparison intensions, in particular a pH indicator dye, fluorescence imaging and EPR imaging. The influence of the presence or absence of pH modifying substances and of an additional lipophilic inter layer on the pH(M) was investigated as well as the variation of matrix forming excipient and buffer pH. The influence of the pH(M) on drug release was analysed as well. In addition, benchtop MRI was accomplished to gain a deeper insight on the hydration and erosion behaviour of 2- and 3-layer tablets. Copyright © 2010 Elsevier B.V. All rights reserved.

Smartphone-based multispectral imaging: system development and potential for mobile skin diagnosis

PubMed Central

Kim, Sewoong; Cho, Dongrae; Kim, Jihun; Kim, Manjae; Youn, Sangyeon; Jang, Jae Eun; Je, Minkyu; Lee, Dong Hun; Lee, Boreom; Farkas, Daniel L.; Hwang, Jae Youn

2016-01-01

We investigate the potential of mobile smartphone-based multispectral imaging for the quantitative diagnosis and management of skin lesions. Recently, various mobile devices such as a smartphone have emerged as healthcare tools. They have been applied for the early diagnosis of nonmalignant and malignant skin diseases. Particularly, when they are combined with an advanced optical imaging technique such as multispectral imaging and analysis, it would be beneficial for the early diagnosis of such skin diseases and for further quantitative prognosis monitoring after treatment at home. Thus, we demonstrate here the development of a smartphone-based multispectral imaging system with high portability and its potential for mobile skin diagnosis. The results suggest that smartphone-based multispectral imaging and analysis has great potential as a healthcare tool for quantitative mobile skin diagnosis. PMID:28018743

Quantitative single-molecule imaging by confocal laser scanning microscopy.

PubMed

Vukojevic, Vladana; Heidkamp, Marcus; Ming, Yu; Johansson, Björn; Terenius, Lars; Rigler, Rudolf

2008-11-25

A new approach to quantitative single-molecule imaging by confocal laser scanning microscopy (CLSM) is presented. It relies on fluorescence intensity distribution to analyze the molecular occurrence statistics captured by digital imaging and enables direct determination of the number of fluorescent molecules and their diffusion rates without resorting to temporal or spatial autocorrelation analyses. Digital images of fluorescent molecules were recorded by using fast scanning and avalanche photodiode detectors. In this way the signal-to-background ratio was significantly improved, enabling direct quantitative imaging by CLSM. The potential of the proposed approach is demonstrated by using standard solutions of fluorescent dyes, fluorescently labeled DNA molecules, quantum dots, and the Enhanced Green Fluorescent Protein in solution and in live cells. The method was verified by using fluorescence correlation spectroscopy. The relevance for biological applications, in particular, for live cell imaging, is discussed.

Identification of ginseng root using quantitative X-ray microtomography.

PubMed

Ye, Linlin; Xue, Yanling; Wang, Yudan; Qi, Juncheng; Xiao, Tiqiao

2017-07-01

The use of X-ray phase-contrast microtomography for the investigation of Chinese medicinal materials is advantageous for its nondestructive, in situ , and three-dimensional quantitative imaging properties. The X-ray phase-contrast microtomography quantitative imaging method was used to investigate the microstructure of ginseng, and the phase-retrieval method is also employed to process the experimental data. Four different ginseng samples were collected and investigated; these were classified according to their species, production area, and sample growth pattern. The quantitative internal characteristic microstructures of ginseng were extracted successfully. The size and position distributions of the calcium oxalate cluster crystals (COCCs), important secondary metabolites that accumulate in ginseng, are revealed by the three-dimensional quantitative imaging method. The volume and amount of the COCCs in different species of the ginseng are obtained by a quantitative analysis of the three-dimensional microstructures, which shows obvious difference among the four species of ginseng. This study is the first to provide evidence of the distribution characteristics of COCCs to identify four types of ginseng, with regard to species authentication and age identification, by X-ray phase-contrast microtomography quantitative imaging. This method is also expected to reveal important relationships between COCCs and the occurrence of the effective medicinal components of ginseng.

Real time quantitative phase microscopy based on single-shot transport of intensity equation (ssTIE) method

NASA Astrophysics Data System (ADS)

Yu, Wei; Tian, Xiaolin; He, Xiaoliang; Song, Xiaojun; Xue, Liang; Liu, Cheng; Wang, Shouyu

2016-08-01

Microscopy based on transport of intensity equation provides quantitative phase distributions which opens another perspective for cellular observations. However, it requires multi-focal image capturing while mechanical and electrical scanning limits its real time capacity in sample detections. Here, in order to break through this restriction, real time quantitative phase microscopy based on single-shot transport of the intensity equation method is proposed. A programmed phase mask is designed to realize simultaneous multi-focal image recording without any scanning; thus, phase distributions can be quantitatively retrieved in real time. It is believed the proposed method can be potentially applied in various biological and medical applications, especially for live cell imaging.

Spectro-refractometry of individual microscopic objects using swept-source quantitative phase imaging.

PubMed

Jung, Jae-Hwang; Jang, Jaeduck; Park, Yongkeun

2013-11-05

We present a novel spectroscopic quantitative phase imaging technique with a wavelength swept-source, referred to as swept-source diffraction phase microscopy (ssDPM), for quantifying the optical dispersion of microscopic individual samples. Employing the swept-source and the principle of common-path interferometry, ssDPM measures the multispectral full-field quantitative phase imaging and spectroscopic microrefractometry of transparent microscopic samples in the visible spectrum with a wavelength range of 450-750 nm and a spectral resolution of less than 8 nm. With unprecedented precision and sensitivity, we demonstrate the quantitative spectroscopic microrefractometry of individual polystyrene beads, 30% bovine serum albumin solution, and healthy human red blood cells.

Differential diagnosis of breast cancer using quantitative, label-free and molecular vibrational imaging

PubMed Central

Yang, Yaliang; Li, Fuhai; Gao, Liang; Wang, Zhiyong; Thrall, Michael J.; Shen, Steven S.; Wong, Kelvin K.; Wong, Stephen T. C.

2011-01-01

We present a label-free, chemically-selective, quantitative imaging strategy to identify breast cancer and differentiate its subtypes using coherent anti-Stokes Raman scattering (CARS) microscopy. Human normal breast tissue, benign proliferative, as well as in situ and invasive carcinomas, were imaged ex vivo. Simply by visualizing cellular and tissue features appearing on CARS images, cancerous lesions can be readily separated from normal tissue and benign proliferative lesion. To further distinguish cancer subtypes, quantitative disease-related features, describing the geometry and distribution of cancer cell nuclei, were extracted and applied to a computerized classification system. The results show that in situ carcinoma was successfully distinguished from invasive carcinoma, while invasive ductal carcinoma (IDC) and invasive lobular carcinoma were also distinguished from each other. Furthermore, 80% of intermediate-grade IDC and 85% of high-grade IDC were correctly distinguished from each other. The proposed quantitative CARS imaging method has the potential to enable rapid diagnosis of breast cancer. PMID:21833355

Issues in Quantitative Analysis of Ultraviolet Imager (UV) Data: Airglow

NASA Technical Reports Server (NTRS)

Germany, G. A.; Richards, P. G.; Spann, J. F.; Brittnacher, M. J.; Parks, G. K.

1999-01-01

The GGS Ultraviolet Imager (UVI) has proven to be especially valuable in correlative substorm, auroral morphology, and extended statistical studies of the auroral regions. Such studies are based on knowledge of the location, spatial, and temporal behavior of auroral emissions. More quantitative studies, based on absolute radiometric intensities from UVI images, require a more intimate knowledge of the instrument behavior and data processing requirements and are inherently more difficult than studies based on relative knowledge of the oval location. In this study, UVI airglow observations are analyzed and compared with model predictions to illustrate issues that arise in quantitative analysis of UVI images. These issues include instrument calibration, long term changes in sensitivity, and imager flat field response as well as proper background correction. Airglow emissions are chosen for this study because of their relatively straightforward modeling requirements and because of their implications for thermospheric compositional studies. The analysis issues discussed here, however, are identical to those faced in quantitative auroral studies.

Quantitative x-ray phase-contrast imaging using a single grating of comparable pitch to sample feature size.

PubMed

Morgan, Kaye S; Paganin, David M; Siu, Karen K W

2011-01-01

The ability to quantitatively retrieve transverse phase maps during imaging by using coherent x rays often requires a precise grating or analyzer-crystal-based setup. Imaging of live animals presents further challenges when these methods require multiple exposures for image reconstruction. We present a simple method of single-exposure, single-grating quantitative phase contrast for a regime in which the grating period is much greater than the effective pixel size. A grating is used to create a high-visibility reference pattern incident on the sample, which is distorted according to the complex refractive index and thickness of the sample. The resolution, along a line parallel to the grating, is not restricted by the grating spacing, and the detector resolution becomes the primary determinant of the spatial resolution. We present a method of analysis that maps the displacement of interrogation windows in order to retrieve a quantitative phase map. Application of this analysis to the imaging of known phantoms shows excellent correspondence.

How do directors of public health perceive leadership?

PubMed

McAreav, M J; Alimo-Metcalfe, B; Connelly, J

2001-01-01

This study examines how directors of public health (DsPH) perceive effective leadership. Kelly's repertory grid technique is used. A total of 13 out of a possible 14 DsPH in one NHS region of England were interviewed. Qualitative and quantitative analysis were carried out. The findings show that male DsPH (n = 8) rate their leadership ability more highly than do female DsPH (n = 5). Qualitative analysis produced a number of categories of constructs, some of which are perceived to be indicative of effective leadership, these being "working for others", "personal attributes", "vision and innovation" and "courage and integrity" Some categories appear to be applicable only to the UK (or to public health) and not to the existing dominant US models of leadership. In general, DsPH perceptions of effective leadership converge with current theories; most specifically the UK-based theories. This study therefore refutes any simple extrapolation of US theories of leadership to UK health organisations.

Nonlinear optical microscopy: use of second harmonic generation and two-photon microscopy for automated quantitative liver fibrosis studies.

PubMed

Sun, Wanxin; Chang, Shi; Tai, Dean C S; Tan, Nancy; Xiao, Guangfa; Tang, Huihuan; Yu, Hanry

2008-01-01

Liver fibrosis is associated with an abnormal increase in an extracellular matrix in chronic liver diseases. Quantitative characterization of fibrillar collagen in intact tissue is essential for both fibrosis studies and clinical applications. Commonly used methods, histological staining followed by either semiquantitative or computerized image analysis, have limited sensitivity, accuracy, and operator-dependent variations. The fibrillar collagen in sinusoids of normal livers could be observed through second-harmonic generation (SHG) microscopy. The two-photon excited fluorescence (TPEF) images, recorded simultaneously with SHG, clearly revealed the hepatocyte morphology. We have systematically optimized the parameters for the quantitative SHG/TPEF imaging of liver tissue and developed fully automated image analysis algorithms to extract the information of collagen changes and cell necrosis. Subtle changes in the distribution and amount of collagen and cell morphology are quantitatively characterized in SHG/TPEF images. By comparing to traditional staining, such as Masson's trichrome and Sirius red, SHG/TPEF is a sensitive quantitative tool for automated collagen characterization in liver tissue. Our system allows for enhanced detection and quantification of sinusoidal collagen fibers in fibrosis research and clinical diagnostics.

Sub-band denoising and spline curve fitting method for hemodynamic measurement in perfusion MRI

NASA Astrophysics Data System (ADS)

Lin, Hong-Dun; Huang, Hsiao-Ling; Hsu, Yuan-Yu; Chen, Chi-Chen; Chen, Ing-Yi; Wu, Liang-Chi; Liu, Ren-Shyan; Lin, Kang-Ping

2003-05-01

In clinical research, non-invasive MR perfusion imaging is capable of investigating brain perfusion phenomenon via various hemodynamic measurements, such as cerebral blood volume (CBV), cerebral blood flow (CBF), and mean trasnit time (MTT). These hemodynamic parameters are useful in diagnosing brain disorders such as stroke, infarction and periinfarct ischemia by further semi-quantitative analysis. However, the accuracy of quantitative analysis is usually affected by poor signal-to-noise ratio image quality. In this paper, we propose a hemodynamic measurement method based upon sub-band denoising and spline curve fitting processes to improve image quality for better hemodynamic quantitative analysis results. Ten sets of perfusion MRI data and corresponding PET images were used to validate the performance. For quantitative comparison, we evaluate gray/white matter CBF ratio. As a result, the hemodynamic semi-quantitative analysis result of mean gray to white matter CBF ratio is 2.10 +/- 0.34. The evaluated ratio of brain tissues in perfusion MRI is comparable to PET technique is less than 1-% difference in average. Furthermore, the method features excellent noise reduction and boundary preserving in image processing, and short hemodynamic measurement time.

Comparative analysis of time-scaling properties about water pH in Poyang Lake Inlet and Outlet on the basis of fractal methods.

PubMed

Shi, K; Liu, C Q; Huang, Z W; Zhang, B; Su, Y

2010-01-01

Detrended fluctuation analysis (DFA) and multifractal methods are applied to the time-scaling properties analysis of water pH series in Poyang Lake Inlet and Outlet in China. The results show that these pH series are characterised by long-term memory and multifractal scaling, and these characteristics have obvious differences between the Lake Inlet and Outlet. The comparison results suggest that monofractal and multifractal parameters can be quantitative dynamical indexes reflecting the capability of anti-acidification of Poyang Lake. Furthermore, we investigated the frequency-size distribution of pH series in Poyang Lake Inlet and Outlet. Our findings suggest that water pH is an example of a self-organised criticality (SOC) process. The results show that it is different SOC behaviours that result in the differences of power-law relations between pH series in Poyang Lake Inlet and Outlet. This work can be helpful to improvement of modelling of lake water quality.

Application of quartz crystal microbalance to study the impact of pH and ionic strength on protein-silicone oil interactions.

PubMed

Dixit, Nitin; Maloney, Kevin M; Kalonia, Devendra S

2011-06-30

In this study, we have used quartz crystal microbalance (QCM) to quantitate the adsorption of a protein on silicone oil coated surfaces as a function of protein concentration, pH and ionic strength using a 5 MHz quartz crystal. Protein adsorption isotherms were generated at different solution pH and ionic strengths. Surface saturation concentrations were selected from adsorption isotherms and used to generate adsorption profiles from pH 3.0 to 9.0, and at ionic strengths of 10 mM and 150 mM. At low ionic strength (10mM) and pH 5.0 (close to the isoelectric point of the protein), maximum adsorption of protein to the silicone oil surface was observed. At higher ionic strength (150 mM), no significant pH influence on adsorption was observed. QCM could be used as a reliable technique to study the binding of proteins to silicone oil coated surfaces. Copyright © 2011 Elsevier B.V. All rights reserved.

Polyamine/salt-assembled microspheres coated with hyaluronic acid for targeting and pH sensing.

PubMed

Zhang, Pan; Yang, Hui; Wang, Guojun; Tong, Weijun; Gao, Changyou

2016-06-01

The poly(allylamine hydrochloride)/trisodium citrate aggregates were fabricated and further covalently crosslinked via the coupling reaction of carboxylic sites on trisodium citrate with the amine groups on polyamine, onto which poly-L-lysine and hyaluronic acid were sequentially assembled, forming stable microspheres. The pH sensitive dye and pH insensitive dye were further labeled to enable the microspheres with pH sensing property. Moreover, these microspheres could be specifically targeted to HeLa tumor cells, since hyaluronic acid can specifically recognize and bind to CD44, a receptor overexpressed on many tumor cells. Quantitative pH measurement by confocal laser scanning microscopy demonstrated that the microspheres were internalized into HeLa cells, and accumulated in acidic compartments. By contrast, only a few microspheres were adhered on the NIH 3T3 cells surface. The microspheres with combined pH sensing property and targeting ability can enhance the insight understanding of the targeted drug vehicles trafficking after cellular internalization. Copyright © 2016 Elsevier B.V. All rights reserved.

Functional photoacoustic microscopy of pH.

PubMed

Chatni, Muhammad Rameez; Yao, Junjie; Danielli, Amos; Favazza, Christopher P; Maslov, Konstantin I; Wang, Lihong V

2011-10-01

pH is a tightly regulated indicator of metabolic activity. In mammalian systems, an imbalance of pH regulation may result from or result in serious illness. In this paper, we report photoacoustic microscopy (PAM) of a commercially available pH-sensitive fluorescent dye (SNARF-5F carboxylic acid) in tissue phantoms. We demonstrated that PAM is capable of pH imaging in absolute values at tissue depths of up to 2.0 mm, greater than possible with other forms of optical microscopy.

Quantitative assessment of cervical vertebral maturation using cone beam computed tomography in Korean girls.

PubMed

Byun, Bo-Ram; Kim, Yong-Il; Yamaguchi, Tetsutaro; Maki, Koutaro; Son, Woo-Sung

2015-01-01

This study was aimed to examine the correlation between skeletal maturation status and parameters from the odontoid process/body of the second vertebra and the bodies of third and fourth cervical vertebrae and simultaneously build multiple regression models to be able to estimate skeletal maturation status in Korean girls. Hand-wrist radiographs and cone beam computed tomography (CBCT) images were obtained from 74 Korean girls (6-18 years of age). CBCT-generated cervical vertebral maturation (CVM) was used to demarcate the odontoid process and the body of the second cervical vertebra, based on the dentocentral synchondrosis. Correlation coefficient analysis and multiple linear regression analysis were used for each parameter of the cervical vertebrae (P < 0.05). Forty-seven of 64 parameters from CBCT-generated CVM (independent variables) exhibited statistically significant correlations (P < 0.05). The multiple regression model with the greatest R (2) had six parameters (PH2/W2, UW2/W2, (OH+AH2)/LW2, UW3/LW3, D3, and H4/W4) as independent variables with a variance inflation factor (VIF) of <2. CBCT-generated CVM was able to include parameters from the second cervical vertebral body and odontoid process, respectively, for the multiple regression models. This suggests that quantitative analysis might be used to estimate skeletal maturation status.

Ratiometric Near-Infrared Fluorescent Probes Based On Through-Bond Energy Transfer and π-Conjugation Modulation between Tetraphenylethene and Hemicyanine Moieties for Sensitive Detection of pH Changes in Live Cells.

PubMed

Wang, Jianbo; Xia, Shuai; Bi, Jianheng; Fang, Mingxi; Mazi, Wafa; Zhang, Yibin; Conner, Nathan; Luo, Fen-Tair; Lu, H Peter; Liu, Haiying

2018-04-18

In this paper, we present three ratiometric near-infrared fluorescent probes (A-C) for accurate, ratiometric detection of intracellular pH changes in live cells. Probe A consists of a tetraphenylethene (TPE) donor and near-infrared hemicyanine acceptor in a through-bond energy transfer (TBET) strategy, while probes B and C are composed of TPE and hemicyanine moieties through single and double sp 2 carbon-carbon bond connections in a π-conjugation modulation strategy. The specific targeting of the probes to lysosomes in live cells was achieved by introducing morpholine residues to the hemicyanine moieties to form closed spirolactam ring structures. Probe A shows aggregation-induced emission (AIE) property at neutral or basic pH, while probes B and C lack AIE properties. At basic or neutral pH, the probes only show fluorescence of TPE moieties with closed spirolactam forms of hemicyanine moieties, and effectively avoid blind fluorescence imaging spots, an issue which typical intensity-based pH fluorescent probes encounter. Three probes show ratiometric fluorescence responses to pH changes from 7.0 to 3.0 with TPE fluorescence decreases and hemicyanine fluorescence increases, because acidic pH makes the spirolactam rings open to enhance π-conjugation of hemicyanine moieties. However, probe A shows much more sensitive ratiometric fluorescence responses to pH changes from 7.0 to 3.0 with remarkable ratio increase of TPE fluorescence to hemicyanine fluorescence up to 238-fold than probes B and C because of its high efficiency of energy transfer from TPE donor to the hemicyanine acceptor in the TBET strategy. The probe offers dual Stokes shifts with a large pseudo-Stokes shift of 361 nm and well-defined dual emissions, and allows for colocalization of the imaging readouts of visible and near-infrared fluorescence channels to achieve more precisely double-checked ratiometric fluorescence imaging. These platforms could be employed to develop a variety of novel ratiometric fluorescent probes for accurate detection of different analytes in applications of chemical and biological sensing, imaging, and diagnostics by introducing appropriate sensing ligands to hemicyanine moieties to form on-off spirolactam switches.

Quantitative Imaging of Single Unstained Magnetotactic Bacteria by Coherent X-ray Diffraction Microscopy.

PubMed

Fan, Jiadong; Sun, Zhibin; Zhang, Jian; Huang, Qingjie; Yao, Shengkun; Zong, Yunbing; Kohmura, Yoshiki; Ishikawa, Tetsuya; Liu, Hong; Jiang, Huaidong

2015-06-16

Novel coherent diffraction microscopy provides a powerful lensless imaging method to obtain a better understanding of the microorganism at the nanoscale. Here we demonstrated quantitative imaging of intact unstained magnetotactic bacteria using coherent X-ray diffraction microscopy combined with an iterative phase retrieval algorithm. Although the signal-to-noise ratio of the X-ray diffraction pattern from single magnetotactic bacterium is weak due to low-scattering ability of biomaterials, an 18.6 nm half-period resolution of reconstructed image was achieved by using a hybrid input-output phase retrieval algorithm. On the basis of the quantitative reconstructed images, the morphology and some intracellular structures, such as nucleoid, polyβ-hydroxybutyrate granules, and magnetosomes, were identified, which were also confirmed by scanning electron microscopy and energy dispersive spectroscopy. With the benefit from the quantifiability of coherent diffraction imaging, for the first time to our knowledge, an average density of magnetotactic bacteria was calculated to be ∼1.19 g/cm(3). This technique has a wide range of applications, especially in quantitative imaging of low-scattering biomaterials and multicomponent materials at nanoscale resolution. Combined with the cryogenic technique or X-ray free electron lasers, the method could image cells in a hydrated condition, which helps to maintain their natural structure.

Quantitative Ultrasound for Nondestructive Characterization of Engineered Tissues and Biomaterials

PubMed Central

Dalecki, Diane; Mercado, Karla P.; Hocking, Denise C.

2015-01-01

Non-invasive, non-destructive technologies for imaging and quantitatively monitoring the development of artificial tissues are critical for the advancement of tissue engineering. Current standard techniques for evaluating engineered tissues, including histology, biochemical assays and mechanical testing, are destructive approaches. Ultrasound is emerging as a valuable tool for imaging and quantitatively monitoring the properties of engineered tissues and biomaterials longitudinally during fabrication and post-implantation. Ultrasound techniques are rapid, non-invasive, non-destructive and can be easily integrated into sterile environments necessary for tissue engineering. Furthermore, high-frequency quantitative ultrasound techniques can enable volumetric characterization of the structural, biological, and mechanical properties of engineered tissues during fabrication and post-implantation. This review provides an overview of ultrasound imaging, quantitative ultrasound techniques, and elastography, with representative examples of applications of these ultrasound-based techniques to the field of tissue engineering. PMID:26581347

[Ph-Sensor Properties of a Fluorescent Protein from Dendronephthya sp].

PubMed

Pakhomov, A A; Chertkova, R V; Martynov, V I

2015-01-01

Genetically encoded biosensors based on fluorescent proteins are now widely applicable for monitoring pH changes in live cells. Here, we have shown that a fluorescent protein from Dendronephthya sp. (DendFP) exhibits a pronounced pH-sensitivity. Unlike most of known genetically encoded pH-sensors, fluorescence of the protein is not quenched upon medium acidification, but is shifting from the red to green spectral range. Therefore, quantitative measurements of intracellular pH are feasible by ratiometric comparison of emission intensities in the red and green spectral ranges, which makes DendFP advantageous compared with other genetically encoded pH-sensors.

Quantitative assessment on coronary computed tomography angiography (CCTA) image quality: comparisons between genders and different tube voltage settings

PubMed Central

Chian, Teo Chee; Nassir, Norziana Mat; Ibrahim, Mohd Izuan; Yusof, Ahmad Khairuddin Md

2017-01-01

Background This study was carried out to quantify and compare the quantitative image quality of coronary computed tomography angiography (CCTA) between genders as well as between different tube voltages scan protocols. Methods Fifty-five cases of CCTA were collected retrospectively and all images including reformatted axial images at systolic and diastolic phases as well as images with curved multi planar reformation (cMPR) were obtained. Quantitative image quality including signal intensity, image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of right coronary artery (RCA), left anterior descending artery (LAD), left circumflex artery (LCx) and left main artery (LM) were quantified using Analyze 12.0 software. Results Six hundred and fifty-seven coronary arteries were evaluated. There were no significant differences in any quantitative image quality parameters between genders. 100 kilovoltage peak (kVp) scanning protocol produced images with significantly higher signal intensity compared to 120 kVp scanning protocol (P<0.001) in all coronary arteries in all types of images. Higher SNR was also observed in 100 kVp scan protocol in all coronary arteries except in LCx where 120 kVp showed better SNR than 100 kVp. Conclusions There were no significant differences in image quality of CCTA between genders and different tube voltages. Lower tube voltage (100 kVp) scanning protocol is recommended in clinical practice to reduce the radiation dose to patient. PMID:28275559

Compressive hyperspectral time-resolved wide-field fluorescence lifetime imaging

NASA Astrophysics Data System (ADS)

Pian, Qi; Yao, Ruoyang; Sinsuebphon, Nattawut; Intes, Xavier

2017-07-01

Spectrally resolved fluorescence lifetime imaging and spatial multiplexing have offered information content and collection-efficiency boosts in microscopy, but efficient implementations for macroscopic applications are still lacking. An imaging platform based on time-resolved structured light and hyperspectral single-pixel detection has been developed to perform quantitative macroscopic fluorescence lifetime imaging (MFLI) over a large field of view (FOV) and multiple spectral bands simultaneously. The system makes use of three digital micromirror device (DMD)-based spatial light modulators (SLMs) to generate spatial optical bases and reconstruct N by N images over 16 spectral channels with a time-resolved capability (∼40 ps temporal resolution) using fewer than N2 optical measurements. We demonstrate the potential of this new imaging platform by quantitatively imaging near-infrared (NIR) Förster resonance energy transfer (FRET) both in vitro and in vivo. The technique is well suited for quantitative hyperspectral lifetime imaging with a high sensitivity and paves the way for many important biomedical applications.

Using the phase-space imager to analyze partially coherent imaging systems: bright-field, phase contrast, differential interference contrast, differential phase contrast, and spiral phase contrast

NASA Astrophysics Data System (ADS)

Mehta, Shalin B.; Sheppard, Colin J. R.

2010-05-01

Various methods that use large illumination aperture (i.e. partially coherent illumination) have been developed for making transparent (i.e. phase) specimens visible. These methods were developed to provide qualitative contrast rather than quantitative measurement-coherent illumination has been relied upon for quantitative phase analysis. Partially coherent illumination has some important advantages over coherent illumination and can be used for measurement of the specimen's phase distribution. However, quantitative analysis and image computation in partially coherent systems have not been explored fully due to the lack of a general, physically insightful and computationally efficient model of image formation. We have developed a phase-space model that satisfies these requirements. In this paper, we employ this model (called the phase-space imager) to elucidate five different partially coherent systems mentioned in the title. We compute images of an optical fiber under these systems and verify some of them with experimental images. These results and simulated images of a general phase profile are used to compare the contrast and the resolution of the imaging systems. We show that, for quantitative phase imaging of a thin specimen with matched illumination, differential phase contrast offers linear transfer of specimen information to the image. We also show that the edge enhancement properties of spiral phase contrast are compromised significantly as the coherence of illumination is reduced. The results demonstrate that the phase-space imager model provides a useful framework for analysis, calibration, and design of partially coherent imaging methods.

Selection and Presentation of Imaging Figures in the Medical Literature

PubMed Central

Siontis, George C. M.; Patsopoulos, Nikolaos A.; Vlahos, Antonios P.; Ioannidis, John P. A.

2010-01-01

Background Images are important for conveying information, but there is no empirical evidence on whether imaging figures are properly selected and presented in the published medical literature. We therefore evaluated the selection and presentation of radiological imaging figures in major medical journals. Methodology/Principal Findings We analyzed articles published in 2005 in 12 major general and specialty medical journals that had radiological imaging figures. For each figure, we recorded information on selection, study population, provision of quantitative measurements, color scales and contrast use. Overall, 417 images from 212 articles were analyzed. Any comment/hint on image selection was made in 44 (11%) images (range 0–50% across the 12 journals) and another 37 (9%) (range 0–60%) showed both a normal and abnormal appearance. In 108 images (26%) (range 0–43%) it was unclear whether the image came from the presented study population. Eighty-three images (20%) (range 0–60%) had any quantitative or ordered categorical value on a measure of interest. Information on the distribution of the measure of interest in the study population was given in 59 cases. For 43 images (range 0–40%), a quantitative measurement was provided for the depicted case and the distribution of values in the study population was also available; in those 43 cases there was no over-representation of extreme than average cases (p = 0.37). Significance The selection and presentation of images in the medical literature is often insufficiently documented; quantitative data are sparse and difficult to place in context. PMID:20526360

Three-dimensional quantitative flow diagnostics

NASA Technical Reports Server (NTRS)

Miles, Richard B.; Nosenchuck, Daniel M.

1989-01-01

The principles, capabilities, and practical implementation of advanced measurement techniques for the quantitative characterization of three-dimensional flows are reviewed. Consideration is given to particle, Rayleigh, and Raman scattering; fluorescence; flow marking by H2 bubbles, photochromism, photodissociation, and vibrationally excited molecules; light-sheet volume imaging; and stereo imaging. Also discussed are stereo schlieren methods, holographic particle imaging, optical tomography, acoustic and magnetic-resonance imaging, and the display of space-filling data. Extensive diagrams, graphs, photographs, sample images, and tables of numerical data are provided.

Molecule-Specific Imaging Analysis of Carcinogens in Breast Cancer Cells Using Time-of-Flight Secondary Ion Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Quong, J N; Knize, M G; Kulp, K S

2003-08-19

Imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) is used to study the localization of heterocyclic amines in MCF7 line of human breast cancer cells. The detection sensitivities of a model rodent mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were determined. Following an established criteria for the determination of status of freeze-fracture cells, the distribution of PhIP in the MCF7 cells are reported.

A pH-sensitive red fluorescent protein compatible with hydrophobic resin embedding

NASA Astrophysics Data System (ADS)

Guo, Wenyan; Gang, Yadong; Liu, Xiuli; Zhou, Hongfu; Zeng, Shaoqun

2017-02-01

pH sensitive fluorescent proteins enabling chemical reactivation in resin are useful tools for fluorescence microimaging. EYFP or EGFP improved from GFP in jellyfish are good for such applications. For simultaneous two-color imaging, a suitable red fluorescent protein is of urgent need. Here a pH sensitive red fluorescent protein, pHuji, is selected and verified to be compatible with hydrophobic resin embedding and thus may be promising for dual-colour chemical reactivation imaging in conjunction with EGFP or EYFP.

Synchronous Bioimaging of Intracellular pH and Chloride Based on LSS Fluorescent Protein.

PubMed

Paredes, Jose M; Idilli, Aurora I; Mariotti, Letizia; Losi, Gabriele; Arslanbaeva, Lyaysan R; Sato, Sebastian Sulis; Artoni, Pietro; Szczurkowska, Joanna; Cancedda, Laura; Ratto, Gian Michele; Carmignoto, Giorgio; Arosio, Daniele

2016-06-17

Ion homeostasis regulates critical physiological processes in the living cell. Intracellular chloride concentration not only contributes in setting the membrane potential of quiescent cells but it also plays a role in modulating the dynamic voltage changes during network activity. Dynamic chloride imaging demands new tools, allowing faster acquisition rates and correct accounting of concomitant pH changes. Joining a long-Stokes-shift red-fluorescent protein to a GFP variant with high sensitivity to pH and chloride, we obtained LSSmClopHensor, a genetically encoded fluorescent biosensor optimized for the simultaneous chloride and pH imaging and requiring only two excitation wavelengths (458 and 488 nm). LSSmClopHensor allowed us to monitor the dynamic changes of intracellular pH and chloride concentration during seizure like discharges in neocortical brain slices. Only cells with tightly controlled resting potential revealed a narrow distribution of chloride concentration peaking at about 5 and 8 mM, in neocortical neurons and SK-N-SH cells, respectively. We thus showed that LSSmClopHensor represents a new versatile tool for studying the dynamics of chloride and proton concentration in living systems.

Quantitative X-ray mapping, scatter diagrams and the generation of correction maps to obtain more information about your material

NASA Astrophysics Data System (ADS)

Wuhrer, R.; Moran, K.

2014-03-01

Quantitative X-ray mapping with silicon drift detectors and multi-EDS detector systems have become an invaluable analysis technique and one of the most useful methods of X-ray microanalysis today. The time to perform an X-ray map has reduced considerably with the ability to map minor and trace elements very accurately due to the larger detector area and higher count rate detectors. Live X-ray imaging can now be performed with a significant amount of data collected in a matter of minutes. A great deal of information can be obtained from X-ray maps. This includes; elemental relationship or scatter diagram creation, elemental ratio mapping, chemical phase mapping (CPM) and quantitative X-ray maps. In obtaining quantitative x-ray maps, we are able to easily generate atomic number (Z), absorption (A), fluorescence (F), theoretical back scatter coefficient (η), and quantitative total maps from each pixel in the image. This allows us to generate an image corresponding to each factor (for each element present). These images allow the user to predict and verify where they are likely to have problems in our images, and are especially helpful to look at possible interface artefacts. The post-processing techniques to improve the quantitation of X-ray map data and the development of post processing techniques for improved characterisation are covered in this paper.

Quantitative imaging of protein targets in the human brain with PET

NASA Astrophysics Data System (ADS)

Gunn, Roger N.; Slifstein, Mark; Searle, Graham E.; Price, Julie C.

2015-11-01

PET imaging of proteins in the human brain with high affinity radiolabelled molecules has a history stretching back over 30 years. During this period the portfolio of protein targets that can be imaged has increased significantly through successes in radioligand discovery and development. This portfolio now spans six major categories of proteins; G-protein coupled receptors, membrane transporters, ligand gated ion channels, enzymes, misfolded proteins and tryptophan-rich sensory proteins. In parallel to these achievements in radiochemical sciences there have also been significant advances in the quantitative analysis and interpretation of the imaging data including the development of methods for image registration, image segmentation, tracer compartmental modeling, reference tissue kinetic analysis and partial volume correction. In this review, we analyze the activity of the field around each of the protein targets in order to give a perspective on the historical focus and the possible future trajectory of the field. The important neurobiology and pharmacology is introduced for each of the six protein classes and we present established radioligands for each that have successfully transitioned to quantitative imaging in humans. We present a standard quantitative analysis workflow for these radioligands which takes the dynamic PET data, associated blood and anatomical MRI data as the inputs to a series of image processing and bio-mathematical modeling steps before outputting the outcome measure of interest on either a regional or parametric image basis. The quantitative outcome measures are then used in a range of different imaging studies including tracer discovery and development studies, cross sectional studies, classification studies, intervention studies and longitudinal studies. Finally we consider some of the confounds, challenges and subtleties that arise in practice when trying to quantify and interpret PET neuroimaging data including motion artifacts, partial volume effects, age effects, image registration and normalization, input functions and metabolites, parametric imaging, receptor internalization and genetic factors.

[Quantitative mineralogical analyzes of kidney stones and diagnosing metabolic disorders in female patients with calcium oxalate urolithiasis].

PubMed

Kustov, A V; Moryganov, M A; Strel'nikov, A I; Zhuravleva, N I; Airapetyan, A O

2016-02-01

To conduct a complex examination of female patients with calcium oxalate urolithiasis to detect metabolic disorders, leading to stone formation. The study was carried out using complex physical and chemical methods, including quantitative X-ray phase analysis of urinary stones, pH measurement, volumetry, urine and blood spectrophotometry. Quantitative mineralogical composition of stones, daily urine pH profile, daily urinary excretion of ions of calcium, magnesium, oxalate, phosphate, citrate and uric acid were determined in 20 female patients with calcium oxalate stones. We have shown that most of the stones comprised calcium oxalate monohydrate or mixtures of calcium oxalate dihydrate and hydroxyapatite. Among the identified abnormalities, the most frequent were hypocitraturia and hypercalciuria - 90 and 45%, respectively. Our findings revealed that the daily secretion of citrate and oxalate in patients older than 50 years was significantly lower than in younger patients. In conclusion, daily urinary citrate excretion should be measured in female patients with calcium oxalate stones. This is necessary both to determine the causes of stone formation, and to monitor the effectiveness of citrate therapy.

Global combined precursor isotopic labeling and isobaric tagging (cPILOT) approach with selective MS(3) acquisition.

PubMed

Evans, Adam R; Robinson, Renã A S

2013-11-01

Recently, we reported a novel proteomics quantitation scheme termed "combined precursor isotopic labeling and isobaric tagging (cPILOT)" that allows for the identification and quantitation of nitrated peptides in as many as 12-16 samples in a single experiment. cPILOT offers enhanced multiplexing and posttranslational modification specificity, however excludes global quantitation for all peptides present in a mixture and underestimates reporter ion ratios similar to other isobaric tagging methods due to precursor co-isolation. Here, we present a novel chemical workflow for cPILOT that can be used for global tagging of all peptides in a mixture. Specifically, through low pH precursor dimethylation of tryptic or LysC peptides followed by high pH tandem mass tags, the same reporter ion can be used twice in a single experiment. Also, to improve triple-stage mass spectrometry (MS(3) ) data acquisition, a selective MS(3) method that focuses on product selection of the y1 fragment of lysine-terminated peptides is incorporated into the workflow. This novel cPILOT workflow has potential for global peptide quantitation that could lead to enhanced sample multiplexing and increase the number of quantifiable spectra obtained from MS(3) acquisition methods. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

FLIM-FRET image analysis of tryptophan in prostate cancer cells

NASA Astrophysics Data System (ADS)

Periasamy, Ammasi; Alam, Shagufta R.; Svindrych, Zdenek; Wallrabe, Horst

2017-07-01

A region of interest (ROI) based quantitative FLIM-FRET image analysis is developed to quantitate the autofluorescence signals of the essential amino acid tryptophan as a biomarker to investigate the metabolism in prostate cancer cells.

Hyperpolarized 15N-pyridine Derivatives as pH-Sensitive MRI Agents

PubMed Central

Jiang, Weina; Lumata, Lloyd; Chen, Wei; Zhang, Shanrong; Kovacs, Zoltan; Sherry, A. Dean; Khemtong, Chalermchai

2015-01-01

Highly sensitive MR imaging agents that can accurately and rapidly monitor changes in pH would have diagnostic and prognostic value for many diseases. Here, we report an investigation of hyperpolarized 15N-pyridine derivatives as ultrasensitive pH-sensitive imaging probes. These molecules are easily polarized to high levels using standard dynamic nuclear polarization (DNP) techniques and their 15N chemical shifts were found to be highly sensitive to pH. These probes displayed sharp 15N resonances and large differences in chemical shifts (Δδ >90 ppm) between their free base and protonated forms. These favorable features make these agents highly suitable candidates for the detection of small changes in tissue pH near physiological values. PMID:25774436

Spotsizer: High-throughput quantitative analysis of microbial growth.

PubMed

Bischof, Leanne; Převorovský, Martin; Rallis, Charalampos; Jeffares, Daniel C; Arzhaeva, Yulia; Bähler, Jürg

2016-10-01

Microbial colony growth can serve as a useful readout in assays for studying complex genetic interactions or the effects of chemical compounds. Although computational tools for acquiring quantitative measurements of microbial colonies have been developed, their utility can be compromised by inflexible input image requirements, non-trivial installation procedures, or complicated operation. Here, we present the Spotsizer software tool for automated colony size measurements in images of robotically arrayed microbial colonies. Spotsizer features a convenient graphical user interface (GUI), has both single-image and batch-processing capabilities, and works with multiple input image formats and different colony grid types. We demonstrate how Spotsizer can be used for high-throughput quantitative analysis of fission yeast growth. The user-friendly Spotsizer tool provides rapid, accurate, and robust quantitative analyses of microbial growth in a high-throughput format. Spotsizer is freely available at https://data.csiro.au/dap/landingpage?pid=csiro:15330 under a proprietary CSIRO license.

Quantitative multimodality imaging in cancer research and therapy.

PubMed

Yankeelov, Thomas E; Abramson, Richard G; Quarles, C Chad

2014-11-01

Advances in hardware and software have enabled the realization of clinically feasible, quantitative multimodality imaging of tissue pathophysiology. Earlier efforts relating to multimodality imaging of cancer have focused on the integration of anatomical and functional characteristics, such as PET-CT and single-photon emission CT (SPECT-CT), whereas more-recent advances and applications have involved the integration of multiple quantitative, functional measurements (for example, multiple PET tracers, varied MRI contrast mechanisms, and PET-MRI), thereby providing a more-comprehensive characterization of the tumour phenotype. The enormous amount of complementary quantitative data generated by such studies is beginning to offer unique insights into opportunities to optimize care for individual patients. Although important technical optimization and improved biological interpretation of multimodality imaging findings are needed, this approach can already be applied informatively in clinical trials of cancer therapeutics using existing tools. These concepts are discussed herein.

Diagnosis of breast cancer biopsies using quantitative phase imaging

NASA Astrophysics Data System (ADS)

Majeed, Hassaan; Kandel, Mikhail E.; Han, Kevin; Luo, Zelun; Macias, Virgilia; Tangella, Krishnarao; Balla, Andre; Popescu, Gabriel

2015-03-01

The standard practice in the histopathology of breast cancers is to examine a hematoxylin and eosin (H&E) stained tissue biopsy under a microscope. The pathologist looks at certain morphological features, visible under the stain, to diagnose whether a tumor is benign or malignant. This determination is made based on qualitative inspection making it subject to investigator bias. Furthermore, since this method requires a microscopic examination by the pathologist it suffers from low throughput. A quantitative, label-free and high throughput method for detection of these morphological features from images of tissue biopsies is, hence, highly desirable as it would assist the pathologist in making a quicker and more accurate diagnosis of cancers. We present here preliminary results showing the potential of using quantitative phase imaging for breast cancer screening and help with differential diagnosis. We generated optical path length maps of unstained breast tissue biopsies using Spatial Light Interference Microscopy (SLIM). As a first step towards diagnosis based on quantitative phase imaging, we carried out a qualitative evaluation of the imaging resolution and contrast of our label-free phase images. These images were shown to two pathologists who marked the tumors present in tissue as either benign or malignant. This diagnosis was then compared against the diagnosis of the two pathologists on H&E stained tissue images and the number of agreements were counted. In our experiment, the agreement between SLIM and H&E based diagnosis was measured to be 88%. Our preliminary results demonstrate the potential and promise of SLIM for a push in the future towards quantitative, label-free and high throughput diagnosis.

Dual function microscope for quantitative DIC and birefringence imaging

NASA Astrophysics Data System (ADS)

Li, Chengshuai; Zhu, Yizheng

2016-03-01

A spectral multiplexing interferometry (SXI) method is presented for integrated birefringence and phase gradient measurement on label-free biological specimens. With SXI, the retardation and orientation of sample birefringence are simultaneously encoded onto two separate spectral carrier waves, generated by a crystal retarder oriented at a specific angle. Thus sufficient information for birefringence determination can be obtained from a single interference spectrum, eliminating the need for multiple acquisitions with mechanical rotation or electrical modulation. In addition, with the insertion of a Nomarski prism, the setup can then acquire quantitative differential interference contrast images. Red blood cells infected by malaria parasites are imaged for birefringence retardation as well as phase gradient. The results demonstrate that the SXI approach can achieve both quantitative phase imaging and birefringence imaging with a single, high-sensitivity system.

Scanning tunneling microscopy study of low temperature silicon epitaxy on hydrogen/silicon(001) and phosphine adsorption on silicon(111)-7x7

NASA Astrophysics Data System (ADS)

Ji, Jeong-Young

A three-chamber ultra-high-vacuum (UHV) system with preparation, scanning tunneling microscopy (STM), and chemical vapor deposition (CVD) chambers was designed and built. Here, one can perform surface preparation, STM e-beam lithography, precursor gas dosing, ion sputtering, silicon epitaxy, and various measurements such as reflection high energy electron diffraction (RHEED), low energy electron diffraction (LEED), and Auger electron spectroscopy (AES). Processes performed in the ultra-clean preparation and gas-filled CVD chambers can be monitored by transferring the samples back to the STM chamber to take topographical images. Si deposition on H-terminated Si(001)-2x1 surfaces at temperatures 300--530 K was studied by scanning tunneling microscopy. Hydrogen apparently hinders Si adatom diffusion and enhances surface roughening. Post-growth annealing transfers the top layer atoms downward to fill in vacancies in the lower layer, restoring the crystallinity of the thin film. Hydrogen is shown to remain on the growth front up to at least 10 ML. Si deposition onto the H/Si(001)-3x1 surface at 530 K suggests that dihydride units further suppress Si adatom diffusion and increase surface roughness. PH3 adsorption on Si(111)-7x7 was studied for various exposures between 0.3--60 L at room temperature by means of the scanning-tunneling-microscopy (STM). PH3-, PH2-, H-reacted, and unreacted adatoms can be identified by analyzing STM images at different sample biases. Most of PH3 adsorbs dissociatively on the surface at initial exposure, generating H and PH2 adsorption sites, followed by molecular adsorption of PH3. Rest atoms are more reactive than the adatoms and PH 2-reacted rest atom sites are also observed in STM images. Statistical analysis shows that center adatoms are more reactive than corner adatoms and the saturation P coverage is ˜0.22 ML. Finally, 900 K annealing of a PH 3 dosed surface results in a disordered, partially P-covered surface and PH3 dosing at 900 K forms the same surface reconstruction as a P2-adsorbed surface at similar temperature.

SNPs detection in DHPS-WDR83 overlapping genes mapping on porcine chromosome 2 in a QTL region for meat pH.

PubMed

Zambonelli, Paolo; Davoli, Roberta; Bigi, Mila; Braglia, Silvia; De Paolis, Luigi Francesco; Buttazzoni, Luca; Gallo, Maurizio; Russo, Vincenzo

2013-10-08

The pH is an important parameter influencing technological quality of pig meat, a trait affected by environmental and genetic factors. Several quantitative trait loci associated to meat pH are described on PigQTL database but only two genes influencing this parameter have been so far detected: Ryanodine receptor 1 and Protein kinase, AMP-activated, gamma 3 non-catalytic subunit. To search for genes influencing meat pH we analyzed genomic regions with quantitative effect on this trait in order to detect SNPs to use for an association study. The expressed sequences mapping on porcine chromosomes 1, 2, 3 in regions associated to pork pH were searched in silico to find SNPs. 356 out of 617 detected SNPs were used to genotype Italian Large White pigs and to perform an association analysis with meat pH values recorded in semimembranosus muscle at about 1 hour (pH1) and 24 hours (pHu) post mortem.The results of the analysis showed that 5 markers mapping on chromosomes 1 or 3 were associated with pH1 and 10 markers mapping on chromosomes 1 or 2 were associated with pHu. After False Discovery Rate correction only one SNP mapping on chromosome 2 was confirmed to be associated to pHu. This polymorphism was located in the 3'UTR of two partly overlapping genes, Deoxyhypusine synthase (DHPS) and WD repeat domain 83 (WDR83). The overlapping of the 3'UTRs allows the co-regulation of mRNAs stability by a cis-natural antisense transcript method of regulation. DHPS catalyzes the first step in hypusine formation, a unique amino acid formed by the posttranslational modification of the protein eukaryotic translation initiation factor 5A in a specific lysine residue. WDR83 has an important role in the modulation of a cascade of genes involved in cellular hypoxia defense by intensifying the glycolytic pathway and, theoretically, the meat pH value. The involvement of the SNP detected in the DHPS/WDR83 genes on meat pH phenotypic variability and their functional role are suggestive of molecular and biological processes related to glycolysis increase during post-mortem phase. This finding, after validation, can be applied to identify new biomarkers to be used to improve pig meat quality.

Richard Mazurchuk, PhD | Division of Cancer Prevention

Cancer.gov

Dr. Richard Mazurchuk received a BS in Physics and MS and PhD in Biophysics from SUNY Buffalo. His research focused on developing novel multi-modality imaging techniques, contrast (enhancing) agents and methods to assess the efficacy of experimental therapeutics. |

Automatic pH Control and Soluble and Insoluble Substrate Input for Continuous Culture of Rumen Microorganisms

PubMed Central

Slyter, Leonard L.

1975-01-01

An artifical rumen continuous culture with pH control, automated input of water-soluble and water-insoluble substrates, controlled mixing of contents, and a collection system for gas is described. Images PMID:16350029

Quantitative and qualitative comparison of MR imaging of the temporomandibular joint at 1.5 and 3.0 T using an optimized high-resolution protocol

PubMed Central

Spinner, Georg; Wyss, Michael; Erni, Stefan; Ettlin, Dominik A; Nanz, Daniel; Ulbrich, Erika J; Gallo, Luigi M; Andreisek, Gustav

2016-01-01

Objectives: To quantitatively and qualitatively compare MRI of the temporomandibular joint (TMJ) using an optimized high-resolution protocol at 3.0 T and a clinical standard protocol at 1.5 T. Methods: A phantom and 12 asymptomatic volunteers were MR imaged using a 2-channel surface coil (standard TMJ coil) at 1.5 and 3.0 T (Philips Achieva and Philips Ingenia, respectively; Philips Healthcare, Best, Netherlands). Imaging protocol consisted of coronal and oblique sagittal proton density-weighted turbo spin echo sequences. For quantitative evaluation, a spherical phantom was imaged. Signal-to-noise ratio (SNR) maps were calculated on a voxelwise basis. For qualitative evaluation, all volunteers underwent MRI of the TMJ with the jaw in closed position. Two readers independently assessed visibility and delineation of anatomical structures of the TMJ and overall image quality on a 5-point Likert scale. Quantitative and qualitative measurements were compared between field strengths. Results: The quantitative analysis showed similar SNR for the high-resolution protocol at 3.0 T compared with the clinical protocol at 1.5 T. The qualitative analysis showed significantly better visibility and delineation of clinically relevant anatomical structures of the TMJ, including the TMJ disc and pterygoid muscle as well as better overall image quality at 3.0 T than at 1.5 T. Conclusions: The presented results indicate that expected gains in SNR at 3.0 T can be used to increase the spatial resolution when imaging the TMJ, which translates into increased visibility and delineation of anatomical structures of the TMJ. Therefore, imaging at 3.0 T should be preferred over 1.5 T for imaging the TMJ. PMID:26371077

Quantitative and qualitative comparison of MR imaging of the temporomandibular joint at 1.5 and 3.0 T using an optimized high-resolution protocol.

PubMed

Manoliu, Andrei; Spinner, Georg; Wyss, Michael; Erni, Stefan; Ettlin, Dominik A; Nanz, Daniel; Ulbrich, Erika J; Gallo, Luigi M; Andreisek, Gustav

2016-01-01

To quantitatively and qualitatively compare MRI of the temporomandibular joint (TMJ) using an optimized high-resolution protocol at 3.0 T and a clinical standard protocol at 1.5 T. A phantom and 12 asymptomatic volunteers were MR imaged using a 2-channel surface coil (standard TMJ coil) at 1.5 and 3.0 T (Philips Achieva and Philips Ingenia, respectively; Philips Healthcare, Best, Netherlands). Imaging protocol consisted of coronal and oblique sagittal proton density-weighted turbo spin echo sequences. For quantitative evaluation, a spherical phantom was imaged. Signal-to-noise ratio (SNR) maps were calculated on a voxelwise basis. For qualitative evaluation, all volunteers underwent MRI of the TMJ with the jaw in closed position. Two readers independently assessed visibility and delineation of anatomical structures of the TMJ and overall image quality on a 5-point Likert scale. Quantitative and qualitative measurements were compared between field strengths. The quantitative analysis showed similar SNR for the high-resolution protocol at 3.0 T compared with the clinical protocol at 1.5 T. The qualitative analysis showed significantly better visibility and delineation of clinically relevant anatomical structures of the TMJ, including the TMJ disc and pterygoid muscle as well as better overall image quality at 3.0 T than at 1.5 T. The presented results indicate that expected gains in SNR at 3.0 T can be used to increase the spatial resolution when imaging the TMJ, which translates into increased visibility and delineation of anatomical structures of the TMJ. Therefore, imaging at 3.0 T should be preferred over 1.5 T for imaging the TMJ.

Qualitative and quantitative mass spectrometry imaging of drugs and metabolites.

PubMed

Lietz, Christopher B; Gemperline, Erin; Li, Lingjun

2013-07-01

Mass spectrometric imaging (MSI) has rapidly increased its presence in the pharmaceutical sciences. While quantitative whole-body autoradiography and microautoradiography are the traditional techniques for molecular imaging of drug delivery and metabolism, MSI provides advantageous specificity that can distinguish the parent drug from metabolites and modified endogenous molecules. This review begins with the fundamentals of MSI sample preparation/ionization, and then moves on to both qualitative and quantitative applications with special emphasis on drug discovery and delivery. Cutting-edge investigations on sub-cellular imaging and endogenous signaling peptides are also highlighted, followed by perspectives on emerging technology and the path for MSI to become a routine analysis technique. Copyright © 2013 Elsevier B.V. All rights reserved.

Qualitative and quantitative mass spectrometry imaging of drugs and metabolites

PubMed Central

Lietz, Christopher B.; Gemperline, Erin; Li, Lingjun

2013-01-01

Mass spectrometric imaging (MSI) has rapidly increased its presence in the pharmaceutical sciences. While quantitative whole-body autoradiography and microautoradiography are the traditional techniques for molecular imaging of drug delivery and metabolism, MSI provides advantageous specificity that can distinguish the parent drug from metabolites and modified endogenous molecules. This review begins with the fundamentals of MSI sample preparation/ionization, and then moves on to both qualitative and quantitative applications with special emphasis on drug discovery and delivery. Cutting-edge investigations on sub-cellular imaging and endogenous signaling peptides are also highlighted, followed by perspectives on emerging technology and the path for MSI to become a routine analysis technique. PMID:23603211

End-to-end deep neural network for optical inversion in quantitative photoacoustic imaging.

PubMed

Cai, Chuangjian; Deng, Kexin; Ma, Cheng; Luo, Jianwen

2018-06-15

An end-to-end deep neural network, ResU-net, is developed for quantitative photoacoustic imaging. A residual learning framework is used to facilitate optimization and to gain better accuracy from considerably increased network depth. The contracting and expanding paths enable ResU-net to extract comprehensive context information from multispectral initial pressure images and, subsequently, to infer a quantitative image of chromophore concentration or oxygen saturation (sO 2 ). According to our numerical experiments, the estimations of sO 2 and indocyanine green concentration are accurate and robust against variations in both optical property and object geometry. An extremely short reconstruction time of 22 ms is achieved.

Algorithm of pulmonary emphysema extraction using thoracic 3D CT images

NASA Astrophysics Data System (ADS)

Saita, Shinsuke; Kubo, Mitsuru; Kawata, Yoshiki; Niki, Noboru; Nakano, Yasutaka; Ohmatsu, Hironobu; Tominaga, Keigo; Eguchi, Kenji; Moriyama, Noriyuki

2007-03-01

Recently, due to aging and smoking, emphysema patients are increasing. The restoration of alveolus which was destroyed by emphysema is not possible, thus early detection of emphysema is desired. We describe a quantitative algorithm for extracting emphysematous lesions and quantitatively evaluate their distribution patterns using low dose thoracic 3-D CT images. The algorithm identified lung anatomies, and extracted low attenuation area (LAA) as emphysematous lesion candidates. Applying the algorithm to thoracic 3-D CT images and then by follow-up 3-D CT images, we demonstrate its potential effectiveness to assist radiologists and physicians to quantitatively evaluate the emphysematous lesions distribution and their evolution in time interval changes.

Algorithm of pulmonary emphysema extraction using low dose thoracic 3D CT images

NASA Astrophysics Data System (ADS)

Saita, S.; Kubo, M.; Kawata, Y.; Niki, N.; Nakano, Y.; Omatsu, H.; Tominaga, K.; Eguchi, K.; Moriyama, N.

2006-03-01

Recently, due to aging and smoking, emphysema patients are increasing. The restoration of alveolus which was destroyed by emphysema is not possible, thus early detection of emphysema is desired. We describe a quantitative algorithm for extracting emphysematous lesions and quantitatively evaluate their distribution patterns using low dose thoracic 3-D CT images. The algorithm identified lung anatomies, and extracted low attenuation area (LAA) as emphysematous lesion candidates. Applying the algorithm to 100 thoracic 3-D CT images and then by follow-up 3-D CT images, we demonstrate its potential effectiveness to assist radiologists and physicians to quantitatively evaluate the emphysematous lesions distribution and their evolution in time interval changes.

Determining fluoride ions in ammonium desulfurization slurry using an ion selective electrode method

NASA Astrophysics Data System (ADS)

Luo, Zhengwei; Guo, Mulin; Chen, Huihui; Lian, Zhouyang; Wei, Wuji

2018-02-01

Determining fluoride ions in ammonia desulphurization slurry using a fluoride ion selective electrode (ISE) is investigated. The influence of pH was studied and the appropriate total ionic strength adjustment buffer and its dosage were optimized. The impact of Fe3+ concentration on the detection results was analyzed under preferable conditions, and the error analysis of the ISE method’s accuracy and precision for measuring fluoride ion concentration in the range of 0.5-2000 mg/L was conducted. The quantitative recovery of F- in ammonium sulfate slurry was assessed. The results showed that when pH ranged from 5.5˜6 and the Fe3+ concentration was less than 750 mg/L, the accuracy and precision test results with quantitative recovery rates of 92.0%-104.2% were obtained.

Rapid quantitative analysis of individual anthocyanin content based on high-performance liquid chromatography with diode array detection with the pH differential method.

PubMed

Wang, Huayin

2014-09-01

A new quantitative technique for the simultaneous quantification of the individual anthocyanins based on the pH differential method and high-performance liquid chromatography with diode array detection is proposed in this paper. The six individual anthocyanins (cyanidin 3-glucoside, cyanidin 3-rutinoside, petunidin 3-glucoside, petunidin 3-rutinoside, and malvidin 3-rutinoside) from mulberry (Morus rubra) and Liriope platyphylla were used for demonstration and validation. The elution of anthocyanins was performed using a C18 column with stepwise gradient elution and individual anthocyanins were identified by high-performance liquid chromatography with tandem mass spectrometry. Based on the pH differential method, the high-performance liquid chromatography peak areas of maximum and reference absorption wavelengths of anthocyanin extracts were conducted to quantify individual anthocyanins. The calibration curves for these anthocyanins were linear within the range of 10-5500 mg/L. The correlation coefficients (r(2)) all exceeded 0.9972, and the limits of detection were in the range of 1-4 mg/L at a signal-to-noise ratio ≥5 for these anthocyanins. The proposed quantitative analysis was reproducible with good accuracy of all individual anthocyanins ranging from 96.3 to 104.2% and relative recoveries were in the range 98.4-103.2%. The proposed technique is performed without anthocyanin standards and is a simple, rapid, accurate, and economical method to determine individual anthocyanin contents. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development and validation of a generic high-performance liquid chromatography for the simultaneous separation and determination of six cough ingredients: Robustness study on core-shell particles.

PubMed

Yehia, Ali Mohamed; Essam, Hebatallah Mohamed

2016-09-01

A generally applicable high-performance liquid chromatographic method for the qualitative and quantitative determination of pharmaceutical preparations containing phenylephrine hydrochloride, paracetamol, ephedrine hydrochloride, guaifenesin, doxylamine succinate, and dextromethorphan hydrobromide is developed. Optimization of chromatographic conditions was performed for the gradient elution using different buffer pH values, flow rates and two C18 stationary phases. The method was developed using a Kinetex® C18 column as a core-shell stationary phase with a gradient profile using buffer pH 5.0 and acetonitrile at 2.0 mL/min flow rate. Detection was carried out at 220 nm and linear calibrations were obtained for all components within the studied ranges. The method was fully validated in agreement with ICH guidelines. The proposed method is specific, accurate and precise (RSD% < 3%). Limits of detection are lower than 2.0 μg/mL. Qualitative and quantitative responses were evaluated using experimental design to assist the method robustness. The method was proved to be highly robust against 10% change in buffer pH and flow rate (RSD% < 10%), however, the flow rate may significantly influence the quantitative responses of phenylephrine, paracetamol, and doxylamine (RSD% > 10%). Satisfactory results were obtained for commercial combinations analyses. Statistical comparison between the proposed chromatographic and official methods revealed no significant difference. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative analysis of zopiclone, N-desmethylzopiclone, zopiclone N-oxide and 2-amino-5-chloropyridine in urine using LC-MS-MS.

PubMed

Nilsson, Gunnel H; Kugelberg, Fredrik C; Ahlner, Johan; Kronstrand, Robert

2014-01-01

A simple liquid chromatography-tandem mass spectrometry method was validated to allow determination of zopiclone (ZOP), N-desmethylzopiclone (NDZOP), zopiclone N-oxide (ZOPNO) and 2-amino-5-chloropyridine (ACP) in urine at concentrations up to 3,000 ng/mL within 3.5 min. This method was used for quantitative analysis of the analytes in authentic urine samples obtained 10 h after oral administration of zopiclone (Imovane(®)) and in aliquots of the same urine samples after different storage conditions. In addition, pH of each studied urine sample was measured over time. The results showed that formation of ACP occurred at elevated pH and/or temperature by degradation of ZOP, NDZOP and ZOPNO. This method was also applied to samples obtained from two female victims of drug-facilitated assault. One sample had been exposed to long-term storage conditions at different temperatures and at pH >8.2, which resulted in high concentrations of ACP. The other sample, which was exposed to pH <6.5, showed no formation of ACP. ACP is formed both from ZOP and from its metabolites NDZOP and ZOPNO depending on the pH of the urine, time of storage and/or the temperature conditions. For correct interpretation in forensic cases, ZOP, its major metabolites and ACP should be analyzed. When ACP is identified in urine, the concentrations of ZOP, NDZOP and ZOPNO should be interpreted with great caution. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'.

PubMed

Simpson, Elizabeth

2015-04-19

'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

In situ detection of tree root distribution and biomass by multi-electrode resistivity imaging.

PubMed

Amato, Mariana; Basso, Bruno; Celano, Giuseppe; Bitella, Giovanni; Morelli, Gianfranco; Rossi, Roberta

2008-10-01

Traditional methods for studying tree roots are destructive and labor intensive, but available nondestructive techniques are applicable only to small scale studies or are strongly limited by soil conditions and root size. Soil electrical resistivity measured by geoelectrical methods has the potential to detect belowground plant structures, but quantitative relationships of these measurements with root traits have not been assessed. We tested the ability of two-dimensional (2-D) DC resistivity tomography to detect the spatial variability of roots and to quantify their biomass in a tree stand. A high-resolution resistivity tomogram was generated along a 11.75 m transect under an Alnus glutinosa (L.) Gaertn. stand based on an alpha-Wenner configuration with 48 electrodes spaced 0.25 m apart. Data were processed by a 2-D finite-element inversion algorithm, and corrected for soil temperature. Data acquisition, inversion and imaging were completed in the field within 60 min. Root dry mass per unit soil volume (root mass density, RMD) was measured destructively on soil samples collected to a depth of 1.05 m. Soil sand, silt, clay and organic matter contents, electrical conductivity, water content and pH were measured on a subset of samples. The spatial pattern of soil resistivity closely matched the spatial distribution of RMD. Multiple linear regression showed that only RMD and soil water content were related to soil resistivity along the transect. Regression analysis of RMD against soil resistivity revealed a highly significant logistic relationship (n = 97), which was confirmed on a separate dataset (n = 67), showing that soil resistivity was quantitatively related to belowground tree root biomass. This relationship provides a basis for developing quick nondestructive methods for detecting root distribution and quantifying root biomass, as well as for optimizing sampling strategies for studying root-driven phenomena.

Determination of Peroxisomal pH in Living Mammalian Cells Using pHRed.

PubMed

Godinho, Luis F; Schrader, Michael

2017-01-01

Organelle pH homeostasis is crucial for maintaining proper cellular function. The nature of the peroxisomal pH remains somewhat controversial, with several studies reporting conflicting results. Here, we describe in detail a rapid and accurate method for the measurement of peroxisomal pH, using the pHRed sensor protein and confocal microscopy of living mammalian cells. pHRed, a ratiometric sensor of pH, is targeted to the peroxisomes by virtue of a C-terminal targeting sequence. The probe has a maximum fluorescence emission at 610 nm while exhibiting dual excitation peaks at 440 and 585 nm, allowing for ratiometric imaging and determination of intracellular pH in live cell microscopy.

A water-soluble rhodamine B-derived fluorescent probe for pH monitoring and imaging in acidic regions

NASA Astrophysics Data System (ADS)

Cui, Peng; Jiang, Xuekai; Sun, Junyong; Zhang, Qiang; Gao, Feng

2017-06-01

A structurally simple, water-soluble rhodamine-derivatived fluorescent probe, which is responsive to acidic pH, was conveniently synthesized via a one-step condensation reaction of rhodamine B hydrazide and 4-formybenzene-1,3-disulfonate. As a stable and highly sensitive pH sensor, the probe displays an approximately 50-fold fluorescence enhancement over the pH range of 7.16-4.89 as the structure of probe changes from spirocyclic (weak fluorescent) to ring-open (strong fluorescent) with decreasing pH. The synthesized fluorescent probe is applied to the detection of pH changes in vitro and in vivo bioimaging of immortalized gastric cancer cells, with satisfactory results.

Quantitative geomorphologic studies from spaceborne platforms

NASA Technical Reports Server (NTRS)

Williams, R. S., Jr.

1985-01-01

Although LANDSAT images of our planet represent a quantum improvement in the availability of a global image-data set for independent or comparative regional geomorphic studies of landforms, such images have several limitations which restrict their suitability for quantitative geomorphic investigations. The three most serious deficiencies are: (1) photogrammetric inaccuracies, (2) two-dimensional nature of the data, and (3) spatial resolution. These deficiencies are discussed, as well as the use of stereoscopic images and laser altimeter data.

In Vivo Proton–Electron Double-Resonance Imaging of Extracellular Tumor pH Using an Advanced Nitroxide Probe

PubMed Central

Samouilov, Alexandre; Efimova, Olga V.; Bobko, Andrey A.; Sun, Ziqi; Petryakov, Sergey; Eubank, Timothy D.; Trofimov, Dmitrii G.; Kirilyuk, Igor A.; Grigor’ev, Igor A.; Takahashi, Wataru; Zweier, Jay L.; Khramtsov, Valery V.

2014-01-01

A variable radio frequency proton–electron double-resonance imaging (VRF PEDRI) approach for pH mapping of aqueous samples has been recently developed (Efimova et al. J. Magn. Reson. 2011, 209, 227–232). A pH map is extracted from two PEDRI acquisitions performed at electron paramagnetic resonance (EPR) frequencies of protonated and unprotonated forms of a pH-sensitive probe. To translate VRF PEDRI to an in vivo setting, an advanced pH probe was synthesized. Probe deuteration resulted in a narrow spectral line of 1.2 G compared to a nondeuterated analogue line width of 2.1 G allowing for an increase of Overhauser enhancements and reduction in rf power deposition. Binding of the probe to the cell-impermeable tripeptide, glutathione (GSH), allows for targeting to extracellular tissue space for monitoring extracellular tumor acidosis, a prognostic factor in tumor pathophysiology. The probe demonstrated pH sensitivity in the 5.8–7.8 range, optimum for measurement of acidic extracellular tumor pH (pHe). In vivo VRF PEDRI was performed on Met-1 tumor-bearing mice. Compared to normal mammary glands with a neutral mean pHe (7.1 ± 0.1), we observed broader pH distribution with acidic mean pHe (6.8 ± 0.1) in tumor tissue. In summary, VRF PEDRI in combination with a newly developed pH probe provides an analytical approach for spatially resolved noninvasive pHe monitoring, in vivo. PMID:24372284

Real-time monitoring of pH-dependent intracellular trafficking of ovarian cancer G protein-coupled receptor 1 in living leukocytes.

PubMed

Tan, Modong; Yamaguchi, Satoshi; Nakamura, Motonao; Nagamune, Teruyuki

2018-04-11

G-protein coupled receptors (GPCRs) are involved in many diseases and important biological phenomena; elucidating the mechanisms underlying regulation of their signal transduction potentially provides both novel targets for drug discovery and insight into living systems. A proton-sensing GPCR, ovarian cancer G protein-coupled receptor 1 (OGR1), has been reported to be related to acidosis and diseases that cause tissue acidification, but the mechanism of proton-induced activation of OGR1-mediated signal transduction in acidic conditions remains unclear. Here, pH-dependent intracellular trafficking of OGR1 was visualized in living leukocytes by a real-time fluorescence microscopic method based on sortase A-mediated pulse labeling of OGR1. OGR1 labeled on the cell surface with a small fluorescent dye was clearly observed to remain in the plasma membrane during incubation in mildly acidic medium (pH 6.6) and to be internalized to the intracellular compartments on changing the medium to slightly basic pH (7.7). Quantitative single-cell image analysis showed that most of the internalized OGR1s were then recycled to the plasma membrane for signal transduction if the extracellular pH was returned to the mildly acidic state. However, in a minor population of cells (40%), the internalized OGR1s were retained in endosomes or transported to lysosomes and degraded, leading to low efficiency of their recycling to the plasma membrane. Thus, the present live-cell monitoring strongly suggests that the signal transduction activity of OGR1 is regulated by pH-dependent internalization and recycling to the plasma membrane. Copyright © 2018 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Quantitative Evaluation of a Planetary Renderer for Terrain Relative Navigation

NASA Astrophysics Data System (ADS)

Amoroso, E.; Jones, H.; Otten, N.; Wettergreen, D.; Whittaker, W.

2016-11-01

A ray-tracing computer renderer tool is presented based on LOLA and LROC elevation models and is quantitatively compared to LRO WAC and NAC images for photometric accuracy. We investigated using rendered images for terrain relative navigation.

pH triggered in vivo photothermal therapy and fluorescence nanoplatform of cancer based on responsive polymer-indocyanine green integrated reduced graphene oxide.

PubMed

Sharker, Shazid Md; Lee, Jung Eun; Kim, Sung Han; Jeong, Ji Hoon; In, Insik; Lee, Haeshin; Park, Sung Young

2015-08-01

We have synthesized a pH-dependent, NIR-sensitive, reduced graphene oxide (rGO) hybrid nano-composite via electrostatic interaction with indocyanine green (ICG) which is designed not only to destroy localized cancer cells but also be minimally invasive to surrounding normal cells. The near-infrared (NIR) irradiated hybrid nano-composites showed pH dependent photo-thermal heat generation capability from pH 5.0 to 7.4 due to the pH response relief and quenching effects of poly(2-dimethyl amino ethyl methacrylate) [poly(PDMAEMA)] with ICG on a single rGO sheet. This pH-triggered relief and quenching mechanism regulated in vitro photo-thermolysis as the pH changed from 5.0 to 7.4. The in vitro cellular uptake and confocal laser scan microscopic (CLSM) images at different pH values show promise for environment sensitive bio-imaging. The NIR-absorbing hybrid nanomaterials showed a remarkably improved in vitro cancer cell targeted photothermal destruction compared to free ICG. Upon local NIR irradiation, these hybrid nano-composites-treated tumors showed necrotic, shrunken, ablation of malignant cells and totally healed after 18 days treatment. Our finding regarding the acidic pH stimulus of cancer cellular environment has proven to be a wining platform for the fight against cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

MR morphology of triangular fibrocartilage complex: correlation with quantitative MR and biomechanical properties.

PubMed

Bae, Won C; Ruangchaijatuporn, Thumanoon; Chang, Eric Y; Biswas, Reni; Du, Jiang; Statum, Sheronda; Chung, Christine B

2016-04-01

To evaluate pathology of the triangular fibrocartilage complex (TFCC) using high-resolution morphologic magnetic resonance (MR) imaging, and compare with quantitative MR and biomechanical properties. Five cadaveric wrists (22-70 years) were imaged at 3 T using morphologic (proton density weighted spin echo, PD FS, and 3D spoiled gradient echo, 3D SPGR) and quantitative MR sequences to determine T2 and T1rho properties. In eight geographic regions, morphology of TFC disc and laminae were evaluated for pathology and quantitative MR values. Samples were disarticulated and biomechanical indentation testing was performed on the distal surface of the TFC disc. On morphologic PD SE images, TFC disc pathology included degeneration and tears, while that of the laminae included degeneration, degeneration with superimposed tear, mucinous transformation, and globular calcification. Punctate calcifications were highly visible on 3D SPGR images and found only in pathologic regions. Disc pathology occurred more frequently in proximal regions of the disc than distal regions. Quantitative MR values were lowest in normal samples, and generally higher in pathologic regions. Biomechanical testing demonstrated an inverse relationship, with indentation modulus being high in normal regions with low MR values. The laminae studied were mostly pathologic, and additional normal samples are needed to discern quantitative changes. These results show technical feasibility of morphologic MR, quantitative MR, and biomechanical techniques to characterize pathology of the TFCC. Quantitative MRI may be a suitable surrogate marker of soft tissue mechanical properties, and a useful adjunct to conventional morphologic MR techniques.

Optofluidic time-stretch quantitative phase microscopy.

PubMed

Guo, Baoshan; Lei, Cheng; Wu, Yi; Kobayashi, Hirofumi; Ito, Takuro; Yalikun, Yaxiaer; Lee, Sangwook; Isozaki, Akihiro; Li, Ming; Jiang, Yiyue; Yasumoto, Atsushi; Di Carlo, Dino; Tanaka, Yo; Yatomi, Yutaka; Ozeki, Yasuyuki; Goda, Keisuke

2018-03-01

Innovations in optical microscopy have opened new windows onto scientific research, industrial quality control, and medical practice over the last few decades. One of such innovations is optofluidic time-stretch quantitative phase microscopy - an emerging method for high-throughput quantitative phase imaging that builds on the interference between temporally stretched signal and reference pulses by using dispersive properties of light in both spatial and temporal domains in an interferometric configuration on a microfluidic platform. It achieves the continuous acquisition of both intensity and phase images with a high throughput of more than 10,000 particles or cells per second by overcoming speed limitations that exist in conventional quantitative phase imaging methods. Applications enabled by such capabilities are versatile and include characterization of cancer cells and microalgal cultures. In this paper, we review the principles and applications of optofluidic time-stretch quantitative phase microscopy and discuss its future perspective. Copyright © 2017 Elsevier Inc. All rights reserved.

Real-time label-free quantitative fluorescence microscopy-based detection of ATP using a tunable fluorescent nano-aptasensor platform.

PubMed

Shrivastava, Sajal; Sohn, Il-Yung; Son, Young-Min; Lee, Won-Il; Lee, Nae-Eung

2015-12-14

Although real-time label-free fluorescent aptasensors based on nanomaterials are increasingly recognized as a useful strategy for the detection of target biomolecules with high fidelity, the lack of an imaging-based quantitative measurement platform limits their implementation with biological samples. Here we introduce an ensemble strategy for a real-time label-free fluorescent graphene (Gr) aptasensor platform. This platform employs aptamer length-dependent tunability, thus enabling the reagentless quantitative detection of biomolecules through computational processing coupled with real-time fluorescence imaging data. We demonstrate that this strategy effectively delivers dose-dependent quantitative readouts of adenosine triphosphate (ATP) concentration on chemical vapor deposited (CVD) Gr and reduced graphene oxide (rGO) surfaces, thereby providing cytotoxicity assessment. Compared with conventional fluorescence spectrometry methods, our highly efficient, universally applicable, and rational approach will facilitate broader implementation of imaging-based biosensing platforms for the quantitative evaluation of a range of target molecules.

Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for the detection of Barrett’s-associated neoplasia

PubMed Central

Thekkek, Nadhi; Lee, Michelle H.; Polydorides, Alexandros D.; Rosen, Daniel G.; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

2015-01-01

Abstract. Current imaging tools are associated with inconsistent sensitivity and specificity for detection of Barrett’s-associated neoplasia. Optical imaging has shown promise in improving the classification of neoplasia in vivo. The goal of this pilot study was to evaluate whether in vivo vital dye fluorescence imaging (VFI) has the potential to improve the accuracy of early-detection of Barrett’s-associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites in 14 patients with confirmed Barrett’s esophagus (BE), dysplasia, or esophageal adenocarcinoma using a modular video endoscope and a high-resolution microendoscope (HRME). Qualitative image features were compared to histology; VFI and HRME images show changes in glandular structure associated with neoplastic progression. Quantitative image features in VFI images were identified for objective image classification of metaplasia and neoplasia, and a diagnostic algorithm was developed using leave-one-out cross validation. Three image features extracted from VFI images were used to classify tissue as neoplastic or not with a sensitivity of 87.8% and a specificity of 77.6% (AUC=0.878). A multimodal approach incorporating VFI and HRME imaging can delineate epithelial changes present in Barrett’s-associated neoplasia. Quantitative analysis of VFI images may provide a means for objective interpretation of BE during surveillance. PMID:25950645

Quantitative evaluation of in vivo vital-dye fluorescence endoscopic imaging for the detection of Barrett's-associated neoplasia.

PubMed

Thekkek, Nadhi; Lee, Michelle H; Polydorides, Alexandros D; Rosen, Daniel G; Anandasabapathy, Sharmila; Richards-Kortum, Rebecca

2015-05-01

Current imaging tools are associated with inconsistent sensitivity and specificity for detection of Barrett's-associated neoplasia. Optical imaging has shown promise in improving the classification of neoplasia in vivo. The goal of this pilot study was to evaluate whether in vivo vital dye fluorescence imaging (VFI) has the potential to improve the accuracy of early-detection of Barrett's-associated neoplasia. In vivo endoscopic VFI images were collected from 65 sites in 14 patients with confirmed Barrett's esophagus (BE), dysplasia, oresophageal adenocarcinoma using a modular video endoscope and a high-resolution microendoscope(HRME). Qualitative image features were compared to histology; VFI and HRME images show changes in glandular structure associated with neoplastic progression. Quantitative image features in VFI images were identified for objective image classification of metaplasia and neoplasia, and a diagnostic algorithm was developed using leave-one-out cross validation. Three image features extracted from VFI images were used to classify tissue as neoplastic or not with a sensitivity of 87.8% and a specificity of 77.6% (AUC = 0.878). A multimodal approach incorporating VFI and HRME imaging can delineate epithelial changes present in Barrett's-associated neoplasia. Quantitative analysis of VFI images may provide a means for objective interpretation of BE during surveillance.

Archaeal Abundance across a pH Gradient in an Arable Soil and Its Relationship to Bacterial and Fungal Growth Rates

PubMed Central

Sterngren, Anna E.; Rousk, Johannes

2012-01-01

Soil pH is one of the most influential factors for the composition of bacterial and fungal communities, but the influence of soil pH on the distribution and composition of soil archaeal communities has yet to be systematically addressed. The primary aim of this study was to determine how total archaeal abundance (quantitative PCR [qPCR]-based estimates of 16S rRNA gene copy numbers) is related to soil pH across a pH gradient (pH 4.0 to 8.3). Secondarily, we wanted to assess how archaeal abundance related to bacterial and fungal growth rates across the same pH gradient. We identified two distinct and opposite effects of pH on the archaeal abundance. In the lowest pH range (pH 4.0 to 4.7), the abundance of archaea did not seem to correspond to pH. Above this pH range, there was a sharp, almost 4-fold decrease in archaeal abundance, reaching a minimum at pH 5.1 to 5.2. The low abundance of archaeal 16S rRNA gene copy numbers at this pH range then sharply increased almost 150-fold with pH, resulting in an increase in the ratio between archaeal and bacterial copy numbers from a minimum of 0.002 to more than 0.07 at pH 8. The nonuniform archaeal response to pH could reflect variation in the archaeal community composition along the gradient, with some archaea adapted to acidic conditions and others to neutral to slightly alkaline conditions. This suggestion is reinforced by observations of contrasting outcomes of the (competitive) interactions between archaea, bacteria, and fungi toward the lower and higher ends of the examined pH gradient. PMID:22706045

Archaeal abundance across a pH gradient in an arable soil and its relationship to bacterial and fungal growth rates.

PubMed

Bengtson, Per; Sterngren, Anna E; Rousk, Johannes

2012-08-01

Soil pH is one of the most influential factors for the composition of bacterial and fungal communities, but the influence of soil pH on the distribution and composition of soil archaeal communities has yet to be systematically addressed. The primary aim of this study was to determine how total archaeal abundance (quantitative PCR [qPCR]-based estimates of 16S rRNA gene copy numbers) is related to soil pH across a pH gradient (pH 4.0 to 8.3). Secondarily, we wanted to assess how archaeal abundance related to bacterial and fungal growth rates across the same pH gradient. We identified two distinct and opposite effects of pH on the archaeal abundance. In the lowest pH range (pH 4.0 to 4.7), the abundance of archaea did not seem to correspond to pH. Above this pH range, there was a sharp, almost 4-fold decrease in archaeal abundance, reaching a minimum at pH 5.1 to 5.2. The low abundance of archaeal 16S rRNA gene copy numbers at this pH range then sharply increased almost 150-fold with pH, resulting in an increase in the ratio between archaeal and bacterial copy numbers from a minimum of 0.002 to more than 0.07 at pH 8. The nonuniform archaeal response to pH could reflect variation in the archaeal community composition along the gradient, with some archaea adapted to acidic conditions and others to neutral to slightly alkaline conditions. This suggestion is reinforced by observations of contrasting outcomes of the (competitive) interactions between archaea, bacteria, and fungi toward the lower and higher ends of the examined pH gradient.

Image guided drug release from pH-sensitive Ion channel-functionalized stealth liposomes into an in vivo glioblastoma model.

PubMed

Pacheco-Torres, Jesus; Mukherjee, Nobina; Walko, Martin; López-Larrubia, Pilar; Ballesteros, Paloma; Cerdan, Sebastian; Kocer, Armagan

2015-08-01

Liposomal drug delivery vehicles are promising nanomedicine tools for bringing cytotoxic drugs to cancerous tissues selectively. However, the triggered cargo release from liposomes in response to a target-specific stimulus has remained elusive. We report on functionalizing stealth-liposomes with an engineered ion channel and using these liposomes in vivo for releasing an imaging agent into a cerebral glioma rodent model. If the ambient pH drops below a threshold value, the channel generates temporary pores on the liposomes, thus allowing leakage of the intraluminal medicines. By using magnetic resonance spectroscopy and imaging, we show that engineered liposomes can detect the mildly acidic pH of the tumor microenvironment with 0.2 pH unit precision and they release their content into C6 glioma tumors selectively, in vivo. A drug delivery system with this level of sensitivity and selectivity to environmental stimuli may well serve as an optimal tool for environmentally-triggered and image-guided drug release. Cancer remains a leading cause of mortality worldwide. With advances in science, delivery systems of anti-cancer drugs have also become sophisticated. In this article, the authors designed and characterized functionalized liposomal vehicles, which would release the drug payload in a highly sensitive manner in response to a change in pH environment in an animal glioma model. The novel data would enable better future designs of drug delivery systems. Copyright © 2015 Elsevier Inc. All rights reserved.

Modification by protons of frog skeletal muscle KATP channels: effects on ion conduction and nucleotide inhibition.

PubMed Central

Vivaudou, M; Forestier, C

1995-01-01

1. The molecular mechanisms underlying pH regulation of skeletal muscle ATP-sensitive K+ (KATP) channels were studied using the patch clamp technique in the inside-out configuration. Two effects of intracellular protons were studied in detail: the decrease in magnitude of single-channel currents and the increase in open probability (Po) of nucleotide-inhibited channels. 2. The pH dependence of inward unit currents under different ionic conditions was in poor agreement with either a direct block of the pore by protons or an indirect proton-induced conformational change, but was compatible with the protonation of surface charges located near the cytoplasmic entrance of the pore. This latter electrostatic mechanism was modelled using Gouy-Chapman-Stern theory, which predicted the data accurately with a surface charge density of about 0.1 negative elementary charges per square nanometre and a pK (pH value for 50% effect) value for protonation of these charges of 6.25. The same mechanism, i.e. neutralization of negative surface charges by cation binding, could also account for the previously reported reduction of inward unit currents by Mg2+. 3. Intracellular alkalization did not affect Po of the KATP channels. Acidification increased Po. In the presence of 0.1 mM ATP (no Mg2+), the channel activation vs. pH relationship could be fitted with a sigmoid curve with a Hill coefficient slightly above 2 and a pK value of 6. This latter value was dependent on the ATP concentration, decreasing from 6.3 in 30 microM ATP to 5.3 in 1 microM ATP. 4. Conversely, the channel inhibition vs. ATP concentration curve was shifted to the right when the pH was lowered. At pH 7.1, the ATP concentration causing half-maximal inhibition was about 10 microM. At pH 5.4, it was about 400 microM. The Hill coefficient values remained slightly below 2. Similar effects were observed when ADP was used as the inhibitory nucleotide. 5. These results confirm that a reciprocal competitive link exists between proton and nucleotide binding sites. Quantitatively, they are in full agreement with a steady-state model of a KATP channel possessing four identical protonation sites (microscopic pK, 6) allosterically connected to the channel open state and two identical nucleotide sites (microscopic ATP dissociation constant, approximately 30 microM) connected to the closed state. Images Figure 13 PMID:7473225

Recombinant albumin monolayers on latex particles.

PubMed

Sofińska, Kamila; Adamczyk, Zbigniew; Kujda, Marta; Nattich-Rak, Małgorzata

2014-01-14

The adsorption of recombinant human serum albumin (rHSA) on negatively charged polystyrene latex micro-particles was studied at pH 3.5 and the NaCl concentration range of 10(-3) to 0.15 M. The electrophoretic mobility of latex monotonically increased with the albumin concentration in the suspension. The coverage of adsorbed albumin was quantitatively determined using the depletion method, where the residual protein concentration was determined by electrokinetic measurements and AFM imaging. It was shown that albumin adsorption was irreversible. Its maximum coverage on latex varied between 0.7 mg m(-2) for 10(-3) M NaCl to 1.3 mg m(-2) for 0.15 M NaCl. The latter value matches the maximum coverage previously determined for human serum albumin on mica using the streaming potential method. The increase in the maximum coverage was interpreted in terms of reduced electrostatic repulsion among adsorbed molecules. These facts confirm that albumin adsorption at pH 3.5 is governed by electrostatic interactions and proceeds analogously to colloid particle deposition. The stability of albumin monolayers was measured in additional experiments where changes in the latex electrophoretic mobility and the concentration of free albumin in solutions were monitored over prolonged time periods. Based on these experimental data, a robust procedure of preparing albumin monolayers on latex particles of well-controlled coverage and molecule distribution was proposed.

Modeling sickle cell vasoocclusion in the rat leg: quantification of trapped sickle cells and correlation with 31P metabolic and 1H magnetic resonance imaging changes.

PubMed Central

Fabry, M E; Rajanayagam, V; Fine, E; Holland, S; Gore, J C; Nagel, R L; Kaul, D K

1989-01-01

We have developed an animal model to elucidate the acute effects of perfusion abnormalities on muscle metabolism induced by different density-defined classes of erythrocytes isolated from sickle cell anemia patients. Technetium-99m (99mTc)-labeled, saline-washed normal (AA), homozygous sickle (SS), or high-density SS (SS4) erythrocytes were injected into the femoral artery of the rat and quantitative 99mTc imaging, 31P magnetic resonance spectroscopy by surface coil at 2 teslas, and 1H magnetic resonance imaging at 0.15 tesla were performed. Between 5 and 25 microliters of SS4 cells was trapped in the microcirculation of the thigh (or 1-6 x 10(7) cells per cubic centimeter of tissue). In contrast, fewer SS discocytes (SS2) or AA cells were trapped (an equivalent packed cell volume of less than 6.7 microliters and 0.3 microliters, respectively). After injection of SS4 cells an initial increase in inorganic phosphate was observed in the region of the thigh served by the femoral artery, intracellular pH decreased, and subsequently the proton relaxation time T1 reached a broad maximum at 18-28 hr. When T1 obtained at this time was plotted against the volume of cells trapped, an increase of T1 over the control value of 411 +/- 48 msec was found that was proportional to the number of cells trapped. We conclude that the densest SS cells are most effective at producing vasoocclusion. The extent of the change detected by 1H magnetic resonance imaging is dependent on the amount of cells trapped in the microcirculation and the magnitude of the initial increase of inorganic phosphate. Images PMID:2726752

Computer system for definition of the quantitative geometry of musculature from CT images.

PubMed

Daniel, Matej; Iglic, Ales; Kralj-Iglic, Veronika; Konvicková, Svatava

2005-02-01

The computer system for quantitative determination of musculoskeletal geometry from computer tomography (CT) images has been developed. The computer system processes series of CT images to obtain three-dimensional (3D) model of bony structures where the effective muscle fibres can be interactively defined. Presented computer system has flexible modular structure and is suitable also for educational purposes.

Quantitative imaging assay for NF-κB nuclear translocation in primary human macrophages

PubMed Central

Noursadeghi, Mahdad; Tsang, Jhen; Haustein, Thomas; Miller, Robert F.; Chain, Benjamin M.; Katz, David R.

2008-01-01

Quantitative measurement of NF-κB nuclear translocation is an important research tool in cellular immunology. Established methodologies have a number of limitations, such as poor sensitivity, high cost or dependence on cell lines. Novel imaging methods to measure nuclear translocation of transcriptionally active components of NF-κB are being used but are also partly limited by the need for specialist imaging equipment or image analysis software. Herein we present a method for quantitative detection of NF-κB rel A nuclear translocation, using immunofluorescence microscopy and the public domain image analysis software ImageJ that can be easily adopted for cellular immunology research without the need for specialist image analysis expertise and at low cost. The method presented here is validated by demonstrating the time course and dose response of NF-κB nuclear translocation in primary human macrophages stimulated with LPS, and by comparison with a commercial NF-κB activation reporter cell line. PMID:18036607

Accuracy and Precision of Radioactivity Quantification in Nuclear Medicine Images

PubMed Central

Frey, Eric C.; Humm, John L.; Ljungberg, Michael

2012-01-01

The ability to reliably quantify activity in nuclear medicine has a number of increasingly important applications. Dosimetry for targeted therapy treatment planning or for approval of new imaging agents requires accurate estimation of the activity in organs, tumors, or voxels at several imaging time points. Another important application is the use of quantitative metrics derived from images, such as the standard uptake value commonly used in positron emission tomography (PET), to diagnose and follow treatment of tumors. These measures require quantification of organ or tumor activities in nuclear medicine images. However, there are a number of physical, patient, and technical factors that limit the quantitative reliability of nuclear medicine images. There have been a large number of improvements in instrumentation, including the development of hybrid single-photon emission computed tomography/computed tomography and PET/computed tomography systems, and reconstruction methods, including the use of statistical iterative reconstruction methods, which have substantially improved the ability to obtain reliable quantitative information from planar, single-photon emission computed tomography, and PET images. PMID:22475429

Quantitative endoscopy: initial accuracy measurements.

PubMed

Truitt, T O; Adelman, R A; Kelly, D H; Willging, J P

2000-02-01

The geometric optics of an endoscope can be used to determine the absolute size of an object in an endoscopic field without knowing the actual distance from the object. This study explores the accuracy of a technique that estimates absolute object size from endoscopic images. Quantitative endoscopy involves calibrating a rigid endoscope to produce size estimates from 2 images taken with a known traveled distance between the images. The heights of 12 samples, ranging in size from 0.78 to 11.80 mm, were estimated with this calibrated endoscope. Backup distances of 5 mm and 10 mm were used for comparison. The mean percent error for all estimated measurements when compared with the actual object sizes was 1.12%. The mean errors for 5-mm and 10-mm backup distances were 0.76% and 1.65%, respectively. The mean errors for objects <2 mm and > or =2 mm were 0.94% and 1.18%, respectively. Quantitative endoscopy estimates endoscopic image size to within 5% of the actual object size. This method remains promising for quantitatively evaluating object size from endoscopic images. It does not require knowledge of the absolute distance of the endoscope from the object, rather, only the distance traveled by the endoscope between images.

Informatics in radiology: automated structured reporting of imaging findings using the AIM standard and XML.

PubMed

Zimmerman, Stefan L; Kim, Woojin; Boonn, William W

2011-01-01

Quantitative and descriptive imaging data are a vital component of the radiology report and are frequently of paramount importance to the ordering physician. Unfortunately, current methods of recording these data in the report are both inefficient and error prone. In addition, the free-text, unstructured format of a radiology report makes aggregate analysis of data from multiple reports difficult or even impossible without manual intervention. A structured reporting work flow has been developed that allows quantitative data created at an advanced imaging workstation to be seamlessly integrated into the radiology report with minimal radiologist intervention. As an intermediary step between the workstation and the reporting software, quantitative and descriptive data are converted into an extensible markup language (XML) file in a standardized format specified by the Annotation and Image Markup (AIM) project of the National Institutes of Health Cancer Biomedical Informatics Grid. The AIM standard was created to allow image annotation data to be stored in a uniform machine-readable format. These XML files containing imaging data can also be stored on a local database for data mining and analysis. This structured work flow solution has the potential to improve radiologist efficiency, reduce errors, and facilitate storage of quantitative and descriptive imaging data for research. Copyright © RSNA, 2011.

Molecularly Characterized Solvent Extracts and Saponins from Polygonum hydropiper L. Show High Anti-Angiogenic, Anti-Tumor, Brine Shrimp, and Fibroblast NIH/3T3 Cell Line Cytotoxicity

PubMed Central

Ayaz, Muhammad; Junaid, Muhammad; Ullah, Farhat; Sadiq, Abdul; Subhan, Fazal; Khan, Mir Azam; Ahmad, Waqar; Ali, Gowhar; Imran, Muhammad; Ahmad, Sajjad

2016-01-01

Polygonum hydropiper is used as anti-cancer and anti-rheumatic agent in folk medicine. This study was designed to investigate the anti-angiogenic, anti-tumor, and cytotoxic potentials of different solvent extracts and isolated saponins. Samples were analyzed using GC, Gas Chromatography–Mass Spectrometry (GC–MS) to identify major and bioactive compounds. Quantitation of antiangiogenesis for the plant's samples including methanolic extract (Ph.Cr), its subsequent fractions; n-hexane (Ph.Hex), chloroform (Ph.Chf), ethyl acetate (Ph.EtAc), n-Butanol (Ph.Bt), aqueous (Ph.Aq), saponins (Ph.Sp) were performed using the chick embryo chorioallantoic membrane (CAM) assay. Potato disc anti-tumor assay was performed on Agrobacterium tumefaciens containing tumor inducing plasmid. Cytotoxicity was performed against Artemia salina and mouse embryonic fibroblast NIH/3T3 cell line following contact toxicity and MTT cells viability assays, respectively. The GC–MS analysis of Ph.Cr, Ph.Hex, Ph.Chf, Ph.Bt, and Ph.EtAc identified 126, 124, 153, 131, and 164 compounds, respectively. In anti-angiogenic assay, Ph.Chf, Ph.Sp, Ph.EtAc, and Ph.Cr exhibited highest activity with IC50 of 28.65, 19.21, 88.75, and 461.53 μg/ml, respectively. In anti-tumor assay, Ph.Sp, Ph.Chf, Ph.EtAc, and Ph.Cr were most potent with IC50 of 18.39, 73.81, 217.19, and 342.53 μg/ml, respectively. In MTT cells viability assay, Ph.Chf, Ph.EtAc, Ph.Sp were most active causing 79.00, 72.50, and 71.50% cytotoxicity, respectively, at 1000 μg/ml with the LD50 of 140, 160, and 175 μg/ml, respectively. In overall study, Ph.Chf and Ph.Sp have shown overwhelming results which signifies their potentials as sources of therapeutic agents against cancer. PMID:27065865

Dynamic PCr and pH imaging of human calf muscles during exercise and recovery using (31) P gradient-Echo MRI at 7 Tesla.

PubMed

Schmid, Albrecht Ingo; Meyerspeer, Martin; Robinson, Simon Daniel; Goluch, Sigrun; Wolzt, Michael; Fiedler, Georg Bernd; Bogner, Wolfgang; Laistler, Elmar; Krššák, Martin; Moser, Ewald; Trattnig, Siegfried; Valkovič, Ladislav

2016-06-01

Simultaneous acquisition of spatially resolved (31) P-MRI data for evaluation of muscle specific energy metabolism, i.e., PCr and pH kinetics. A three-dimensional (3D) gradient-echo sequence for multiple frequency-selective excitations of the PCr and Pi signals in an interleaved sampling scheme was developed and tested at 7 Tesla (T). The pH values were derived from the chemical shift-induced phase difference between the resonances. The achieved spatial resolution was ∼2 mL with image acquisition time below 6 s. Ten healthy volunteers were studied performing plantar flexions during the delay between (31) P-MRI acquisitions, yielding a temporal resolution of 9-10 s. Signal from anatomically matched regions of interest had sufficient signal-to-noise ratio to allow single-acquisition PCr and pH quantification. The Pi signal was clearly detected in voxels of actively exercising muscles. The PCr depletions were in gastrocnemius 42 ± 14% (medialis), 48 ± 17% (lateralis) and in soleus 20 ± 11%. The end exercise pH values were 6.74 ± 0.18 and 6.65 ± 0.27 for gastrocnemius medialis and lateralis, respectively, and 6.96 ± 0.12 for soleus muscle. Simultaneous acquisition of PCr and Pi images with high temporal resolution, suitable for measuring PCr and pH kinetics in exercise-recovery experiments, was demonstrated at 7T. This study presents a fast alternative to MRS for quantifying energy metabolism of posterior muscle groups of the lower leg. Magn Reson Med 75:2324-2331, 2016. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Self-assembly of BODIPY based pH-sensitive near-infrared polymeric micelles for drug controlled delivery and fluorescence imaging applications.

PubMed

Liu, Xiaodong; Chen, Bizheng; Li, Xiaojun; Zhang, Lifen; Xu, Yujie; Liu, Zhuang; Cheng, Zhenping; Zhu, Xiulin

2015-10-21

Responsive block copolymer micelles emerging as promising imaging and drug delivery systems show high stability and on-demand drug release activities. Herein, we developed self-assembled pH-responsive NIR emission micelles entrapped with doxorubicin (DOX) within the cores by the electrostatic interactions for fluorescence imaging and chemotherapy applications. The block copolymer, poly(methacrylic acid)-block-poly[(poly(ethylene glycol) methyl ether methacrylate)-co-boron dipyrromethene derivatives] (PMAA-b-P(PEGMA-co-BODIPY), was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, and the molecular weight distribution of this copolymer was narrow (Mw/Mn = 1.31). The NIR fluorescence enhancement induced by the phenol/phenolate interconversion equilibrium works as a switch in response to the intracellular pH fluctuations. DOX-loaded PMAA-b-P(PEGMA-co-BODIPY) micelles can detect the physiological pH fluctuations with a pKa near physiological conditions (∼7.52), and showed pH-responsive collapse and an obvious acid promoted anticancer drug release behavior (over 58.8-62.8% in 10 h). Real-time imaging of intracellular pH variations was performed and a significant chemotherapy effect was demonstrated against HeLa cells.

Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

PubMed

Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

2016-05-05

Molecular imaging agent design involves simultaneously optimizing multiple probe properties. While several desired characteristics are straightforward, including high affinity and low non-specific background signal, in practice there are quantitative trade-offs between these properties. These include plasma clearance, where fast clearance lowers background signal but can reduce target uptake, and binding, where high affinity compounds sometimes suffer from lower stability or increased non-specific interactions. Further complicating probe development, many of the optimal parameters vary depending on both target tissue and imaging agent properties, making empirical approaches or previous experience difficult to translate. Here, we focus on low molecular weight compounds targeting extracellular receptors, which have some of the highest contrast values for imaging agents. We use a mechanistic approach to provide a quantitative framework for weighing trade-offs between molecules. Our results show that specific target uptake is well-described by quantitative simulations for a variety of targeting agents, whereas non-specific background signal is more difficult to predict. Two in vitro experimental methods for estimating background signal in vivo are compared - non-specific cellular uptake and plasma protein binding. Together, these data provide a quantitative method to guide probe design and focus animal work for more cost-effective and time-efficient development of molecular imaging agents.

Quantitative MRI of kidneys in renal disease.

PubMed

Kline, Timothy L; Edwards, Marie E; Garg, Ishan; Irazabal, Maria V; Korfiatis, Panagiotis; Harris, Peter C; King, Bernard F; Torres, Vicente E; Venkatesh, Sudhakar K; Erickson, Bradley J

2018-03-01

To evaluate the reproducibility and utility of quantitative magnetic resonance imaging (MRI) sequences for the assessment of kidneys in young adults with normal renal function (eGFR ranged from 90 to 130 mL/min/1.73 m 2 ) and patients with early renal disease (autosomal dominant polycystic kidney disease). This prospective case-control study was performed on ten normal young adults (18-30 years old) and ten age- and sex-matched patients with early renal parenchymal disease (autosomal dominant polycystic kidney disease). All subjects underwent a comprehensive kidney MRI protocol, including qualitative imaging: T1w, T2w, FIESTA, and quantitative imaging: 2D cine phase contrast of the renal arteries, and parenchymal diffusion weighted imaging (DWI), magnetization transfer imaging (MTI), blood oxygen level dependent (BOLD) imaging, and magnetic resonance elastography (MRE). The normal controls were imaged on two separate occasions ≥24 h apart (range 24-210 h) to assess reproducibility of the measurements. Quantitative MR imaging sequences were found to be reproducible. The mean ± SD absolute percent difference between quantitative parameters measured ≥24 h apart were: MTI-derived ratio = 4.5 ± 3.6%, DWI-derived apparent diffusion coefficient (ADC) = 6.5 ± 3.4%, BOLD-derived R2* = 7.4 ± 5.9%, and MRE-derived tissue stiffness = 7.6 ± 3.3%. Compared with controls, the ADPKD patient's non-cystic renal parenchyma (NCRP) had statistically significant differences with regard to quantitative parenchymal measures: lower MTI percent ratios (16.3 ± 4.4 vs. 23.8 ± 1.2, p < 0.05), higher ADCs (2.46 ± 0.20 vs. 2.18 ± 0.10 × 10 -3  mm 2 /s, p < 0.05), lower R2*s (14.9 ± 1.7 vs. 18.1 ± 1.6 s -1 , p < 0.05), and lower tissue stiffness (3.2 ± 0.3 vs. 3.8 ± 0.5 kPa, p < 0.05). Excellent reproducibility of the quantitative measurements was obtained in all cases. Significantly different quantitative MR parenchymal measurement parameters between ADPKD patients and normal controls were obtained by MT, DWI, BOLD, and MRE indicating the potential for detecting and following renal disease at an earlier stage than the conventional qualitative imaging techniques.

Diffraction enhance x-ray imaging for quantitative phase contrast studies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Agrawal, A. K.; Singh, B., E-mail: balwants@rrcat.gov.in; Kashyap, Y. S.

2016-05-23

Conventional X-ray imaging based on absorption contrast permits limited visibility of feature having small density and thickness variations. For imaging of weakly absorbing material or materials possessing similar densities, a novel phase contrast imaging techniques called diffraction enhanced imaging has been designed and developed at imaging beamline Indus-2 RRCAT Indore. The technique provides improved visibility of the interfaces and show high contrast in the image forsmall density or thickness gradients in the bulk. This paper presents basic principle, instrumentation and analysis methods for this technique. Initial results of quantitative phase retrieval carried out on various samples have also been presented.

Technique to quantitatively measure magnetic properties of thin structures at <10 NM spatial resolution

DOEpatents

Bajt, Sasa

2003-07-08

A highly sensitive and high resolution magnetic microscope images magnetic properties quantitatively. Imaging is done with a modified transmission electron microscope that allows imaging of the sample in a zero magnetic field. Two images from closely spaced planes, one in focus and one slightly out of focus, are sufficient to calculate the absolute values of the phase change imparted to the electrons, and hence obtain the magnetization vector field distribution.

Quantitative Image Informatics for Cancer Research (QIICR) | Informatics Technology for Cancer Research (ITCR)

Cancer.gov

Imaging has enormous untapped potential to improve cancer research through software to extract and process morphometric and functional biomarkers. In the era of non-cytotoxic treatment agents, multi- modality image-guided ablative therapies and rapidly evolving computational resources, quantitative imaging software can be transformative in enabling minimally invasive, objective and reproducible evaluation of cancer treatment response. Post-processing algorithms are integral to high-throughput analysis and fine- grained differentiation of multiple molecular targets.

High resolution quantitative phase imaging of live cells with constrained optimization approach

NASA Astrophysics Data System (ADS)

Pandiyan, Vimal Prabhu; Khare, Kedar; John, Renu

2016-03-01

Quantitative phase imaging (QPI) aims at studying weakly scattering and absorbing biological specimens with subwavelength accuracy without any external staining mechanisms. Use of a reference beam at an angle is one of the necessary criteria for recording of high resolution holograms in most of the interferometric methods used for quantitative phase imaging. The spatial separation of the dc and twin images is decided by the reference beam angle and Fourier-filtered reconstructed image will have a very poor resolution if hologram is recorded below a minimum reference angle condition. However, it is always inconvenient to have a large reference beam angle while performing high resolution microscopy of live cells and biological specimens with nanometric features. In this paper, we treat reconstruction of digital holographic microscopy images as a constrained optimization problem with smoothness constraint in order to recover only complex object field in hologram plane even with overlapping dc and twin image terms. We solve this optimization problem by gradient descent approach iteratively and the smoothness constraint is implemented by spatial averaging with appropriate size. This approach will give excellent high resolution image recovery compared to Fourier filtering while keeping a very small reference angle. We demonstrate this approach on digital holographic microscopy of live cells by recovering the quantitative phase of live cells from a hologram recorded with nearly zero reference angle.

Qualitative and quantitative interpretation of SEM image using digital image processing.

PubMed

Saladra, Dawid; Kopernik, Magdalena

2016-10-01

The aim of the this study is improvement of qualitative and quantitative analysis of scanning electron microscope micrographs by development of computer program, which enables automatic crack analysis of scanning electron microscopy (SEM) micrographs. Micromechanical tests of pneumatic ventricular assist devices result in a large number of micrographs. Therefore, the analysis must be automatic. Tests for athrombogenic titanium nitride/gold coatings deposited on polymeric substrates (Bionate II) are performed. These tests include microshear, microtension and fatigue analysis. Anisotropic surface defects observed in the SEM micrographs require support for qualitative and quantitative interpretation. Improvement of qualitative analysis of scanning electron microscope images was achieved by a set of computational tools that includes binarization, simplified expanding, expanding, simple image statistic thresholding, the filters Laplacian 1, and Laplacian 2, Otsu and reverse binarization. Several modifications of the known image processing techniques and combinations of the selected image processing techniques were applied. The introduced quantitative analysis of digital scanning electron microscope images enables computation of stereological parameters such as area, crack angle, crack length, and total crack length per unit area. This study also compares the functionality of the developed computer program of digital image processing with existing applications. The described pre- and postprocessing may be helpful in scanning electron microscopy and transmission electron microscopy surface investigations. © 2016 The Authors Journal of Microscopy © 2016 Royal Microscopical Society.

Promote quantitative ischemia imaging via myocardial perfusion CT iterative reconstruction with tensor total generalized variation regularization

NASA Astrophysics Data System (ADS)

Gu, Chengwei; Zeng, Dong; Lin, Jiahui; Li, Sui; He, Ji; Zhang, Hao; Bian, Zhaoying; Niu, Shanzhou; Zhang, Zhang; Huang, Jing; Chen, Bo; Zhao, Dazhe; Chen, Wufan; Ma, Jianhua

2018-06-01

Myocardial perfusion computed tomography (MPCT) imaging is commonly used to detect myocardial ischemia quantitatively. A limitation in MPCT is that an additional radiation dose is required compared to unenhanced CT due to its repeated dynamic data acquisition. Meanwhile, noise and streak artifacts in low-dose cases are the main factors that degrade the accuracy of quantifying myocardial ischemia and hamper the diagnostic utility of the filtered backprojection reconstructed MPCT images. Moreover, it is noted that the MPCT images are composed of a series of 2/3D images, which can be naturally regarded as a 3/4-order tensor, and the MPCT images are globally correlated along time and are sparse across space. To obtain higher fidelity ischemia from low-dose MPCT acquisitions quantitatively, we propose a robust statistical iterative MPCT image reconstruction algorithm by incorporating tensor total generalized variation (TTGV) regularization into a penalized weighted least-squares framework. Specifically, the TTGV regularization fuses the spatial correlation of the myocardial structure and the temporal continuation of the contrast agent intake during the perfusion. Then, an efficient iterative strategy is developed for the objective function optimization. Comprehensive evaluations have been conducted on a digital XCAT phantom and a preclinical porcine dataset regarding the accuracy of the reconstructed MPCT images, the quantitative differentiation of ischemia and the algorithm’s robustness and efficiency.

Automated high resolution full-field spatial coherence tomography for quantitative phase imaging of human red blood cells

NASA Astrophysics Data System (ADS)

Singla, Neeru; Dubey, Kavita; Srivastava, Vishal; Ahmad, Azeem; Mehta, D. S.

2018-02-01

We developed an automated high-resolution full-field spatial coherence tomography (FF-SCT) microscope for quantitative phase imaging that is based on the spatial, rather than the temporal, coherence gating. The Red and Green color laser light was used for finding the quantitative phase images of unstained human red blood cells (RBCs). This study uses morphological parameters of unstained RBCs phase images to distinguish between normal and infected cells. We recorded the single interferogram by a FF-SCT microscope for red and green color wavelength and average the two phase images to further reduced the noise artifacts. In order to characterize anemia infected from normal cells different morphological features were extracted and these features were used to train machine learning ensemble model to classify RBCs with high accuracy.

Histological Image Processing Features Induce a Quantitative Characterization of Chronic Tumor Hypoxia

PubMed Central

Grabocka, Elda; Bar-Sagi, Dafna; Mishra, Bud

2016-01-01

Hypoxia in tumors signifies resistance to therapy. Despite a wealth of tumor histology data, including anti-pimonidazole staining, no current methods use these data to induce a quantitative characterization of chronic tumor hypoxia in time and space. We use image-processing algorithms to develop a set of candidate image features that can formulate just such a quantitative description of xenographed colorectal chronic tumor hypoxia. Two features in particular give low-variance measures of chronic hypoxia near a vessel: intensity sampling that extends radially away from approximated blood vessel centroids, and multithresholding to segment tumor tissue into normal, hypoxic, and necrotic regions. From these features we derive a spatiotemporal logical expression whose truth value depends on its predicate clauses that are grounded in this histological evidence. As an alternative to the spatiotemporal logical formulation, we also propose a way to formulate a linear regression function that uses all of the image features to learn what chronic hypoxia looks like, and then gives a quantitative similarity score once it is trained on a set of histology images. PMID:27093539

Quantitative oxygen concentration imaging in toluene atmospheres using Dual Imaging with Modeling Evaluation

NASA Astrophysics Data System (ADS)

Ehn, Andreas; Jonsson, Malin; Johansson, Olof; Aldén, Marcus; Bood, Joakim

2013-01-01

Fluorescence lifetimes of toluene as a function of oxygen concentration in toluene/nitrogen/oxygen mixtures have been measured at room temperature using picosecond-laser excitation of the S1-S0 transition at 266 nm. The data satisfy the Stern-Volmer relation with high accuracy, providing an updated value of the Stern-Volmer slope. A newly developed fluorescence lifetime imaging scheme, called Dual Imaging with Modeling Evaluation (DIME), is evaluated and successfully demonstrated for quantitative oxygen concentration imaging in toluene-seeded O2/N2 gas mixtures.

Quantitative oxygen concentration imaging in toluene atmospheres using Dual Imaging with Modeling Evaluation

NASA Astrophysics Data System (ADS)

Ehn, Andreas; Jonsson, Malin; Johansson, Olof; Aldén, Marcus; Bood, Joakim

2012-12-01

Fluorescence lifetimes of toluene as a function of oxygen concentration in toluene/nitrogen/oxygen mixtures have been measured at room temperature using picosecond-laser excitation of the S1-S0 transition at 266 nm. The data satisfy the Stern-Volmer relation with high accuracy, providing an updated value of the Stern-Volmer slope. A newly developed fluorescence lifetime imaging scheme, called Dual Imaging with Modeling Evaluation (DIME), is evaluated and successfully demonstrated for quantitative oxygen concentration imaging in toluene-seeded O2/N2 gas mixtures.

Detection of blur artifacts in histopathological whole-slide images of endomyocardial biopsies.

PubMed

Hang Wu; Phan, John H; Bhatia, Ajay K; Cundiff, Caitlin A; Shehata, Bahig M; Wang, May D

2015-01-01

Histopathological whole-slide images (WSIs) have emerged as an objective and quantitative means for image-based disease diagnosis. However, WSIs may contain acquisition artifacts that affect downstream image feature extraction and quantitative disease diagnosis. We develop a method for detecting blur artifacts in WSIs using distributions of local blur metrics. As features, these distributions enable accurate classification of WSI regions as sharp or blurry. We evaluate our method using over 1000 portions of an endomyocardial biopsy (EMB) WSI. Results indicate that local blur metrics accurately detect blurry image regions.

A Method for Qualitative Mapping of Thick Oil Spills Using Imaging Spectroscopy

USGS Publications Warehouse

Clark, Roger N.; Swayze, Gregg A.; Leifer, Ira; Livo, K. Eric; Lundeen, Sarah; Eastwood, Michael; Green, Robert O.; Kokaly, Raymond F.; Hoefen, Todd; Sarture, Charles; McCubbin, Ian; Roberts, Dar; Steele, Denis; Ryan, Thomas; Dominguez, Roseanne; Pearson, Neil; ,

2010-01-01

A method is described to create qualitative images of thick oil in oil spills on water using near-infrared imaging spectroscopy data. The method uses simple 'three-point-band depths' computed for each pixel in an imaging spectrometer image cube using the organic absorption features due to chemical bonds in aliphatic hydrocarbons at 1.2, 1.7, and 2.3 microns. The method is not quantitative because sub-pixel mixing and layering effects are not considered, which are necessary to make a quantitative volume estimate of oil.

In vivo two-dimensional NMR correlation spectroscopy

NASA Astrophysics Data System (ADS)

Kraft, Robert A.

1999-10-01

The poor resolution of in-vivo one- dimensional nuclear magnetic resonance spectroscopy (NMR) has limited its clinical potential. Currently, only the large singlet methyl resonances arising from N-acetyl aspartate (NAA), choline, and creatine are quantitated in a clinical setting. Other metabolites such as myo- inositol, glutamine, glutamate, lactate, and γ- amino butyric acid (GABA) are of clinical interest but quantitation is difficult due to the overlapping resonances and limited spectral resolution. To improve the spectral resolution and distinguish between overlapping resonances, a series of two- dimensional chemical shift correlation spectroscopy experiments were developed for a 1.5 Tesla clinical imaging magnet. Two-dimensional methods are attractive for in vivo spectroscopy due to their ability to unravel overlapping resonances with the second dimension, simplifying the interpretation and quantitation of low field NMR spectra. Two-dimensional experiments acquired with mix-mode line shape negate the advantages of the second dimension. For this reason, a new experiment, REVOLT, was developed to achieve absorptive mode line shape in both dimensions. Absorptive mode experiments were compared to mixed mode experiments with respect to sensitivity, resolution, and water suppression. Detailed theoretical and experimental calculations of the optimum spin lock and radio frequency power deposition were performed. Two-dimensional spectra were acquired from human bone marrow and human brain tissue. The human brain tissue spectra clearly reveal correlations among the coupled spins of NAA, glutamine, glutamate, lactate, GABA, aspartate and myo-inositol obtained from a single experiment of 23 minutes from a volume of 59 mL. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)

New Therapeutic Approaches and Prognostic Assays for Breast Cancer: Radiolabeled Ligands and Antibodies and Quantitative PCR..

DTIC Science & Technology

1997-11-01

and Quantitative PCR PRINCIPAL INVESTIGATOR: Indra Poola, Ph.D. CONTRACTING ORGANIZATION: Howard university Washington, DC 20059 REPORT DATE... Howard University Washington, DC 20059 8. PERFORMING ORGANIZATION REPORT NUMBER 8. SPONSORING f MONITORING AGENCY NAME(S) AND ADDRESS(ES) U.S...Stollar J.A. Hanover B.L. Vallee C.B. Hirschberg November 21, 1997 Indra Poola Dept. of Pharmacology Howard University School of Medicine 520 W

AUTOMATED ANALYSIS OF QUANTITATIVE IMAGE DATA USING ISOMORPHIC FUNCTIONAL MIXED MODELS, WITH APPLICATION TO PROTEOMICS DATA.

PubMed

Morris, Jeffrey S; Baladandayuthapani, Veerabhadran; Herrick, Richard C; Sanna, Pietro; Gutstein, Howard

2011-01-01

Image data are increasingly encountered and are of growing importance in many areas of science. Much of these data are quantitative image data, which are characterized by intensities that represent some measurement of interest in the scanned images. The data typically consist of multiple images on the same domain and the goal of the research is to combine the quantitative information across images to make inference about populations or interventions. In this paper, we present a unified analysis framework for the analysis of quantitative image data using a Bayesian functional mixed model approach. This framework is flexible enough to handle complex, irregular images with many local features, and can model the simultaneous effects of multiple factors on the image intensities and account for the correlation between images induced by the design. We introduce a general isomorphic modeling approach to fitting the functional mixed model, of which the wavelet-based functional mixed model is one special case. With suitable modeling choices, this approach leads to efficient calculations and can result in flexible modeling and adaptive smoothing of the salient features in the data. The proposed method has the following advantages: it can be run automatically, it produces inferential plots indicating which regions of the image are associated with each factor, it simultaneously considers the practical and statistical significance of findings, and it controls the false discovery rate. Although the method we present is general and can be applied to quantitative image data from any application, in this paper we focus on image-based proteomic data. We apply our method to an animal study investigating the effects of opiate addiction on the brain proteome. Our image-based functional mixed model approach finds results that are missed with conventional spot-based analysis approaches. In particular, we find that the significant regions of the image identified by the proposed method frequently correspond to subregions of visible spots that may represent post-translational modifications or co-migrating proteins that cannot be visually resolved from adjacent, more abundant proteins on the gel image. Thus, it is possible that this image-based approach may actually improve the realized resolution of the gel, revealing differentially expressed proteins that would not have even been detected as spots by modern spot-based analyses.

Accurate single-shot quantitative phase imaging of biological specimens with telecentric digital holographic microscopy.

PubMed

Doblas, Ana; Sánchez-Ortiga, Emilio; Martínez-Corral, Manuel; Saavedra, Genaro; Garcia-Sucerquia, Jorge

2014-04-01

The advantages of using a telecentric imaging system in digital holographic microscopy (DHM) to study biological specimens are highlighted. To this end, the performances of nontelecentric DHM and telecentric DHM are evaluated from the quantitative phase imaging (QPI) point of view. The evaluated stability of the microscope allows single-shot QPI in DHM by using telecentric imaging systems. Quantitative phase maps of a section of the head of the drosophila melanogaster fly and of red blood cells are obtained via single-shot DHM with no numerical postprocessing. With these maps we show that the use of telecentric DHM provides larger field of view for a given magnification and permits more accurate QPI measurements with less number of computational operations.

UK audit of quantitative thyroid uptake imaging.

PubMed

Taylor, Jonathan C; Murray, Anthony W; Hall, David O; Barnfield, Mark C; O'Shaugnessy, Emma R; Carson, Kathryn J; Cullis, James; Towey, David J; Kenny, Bob

2017-07-01

A national audit of quantitative thyroid uptake imaging was conducted by the Nuclear Medicine Software Quality Group of the Institute of Physics and Engineering in Medicine in 2014/2015. The aims of the audit were to measure and assess the variability in thyroid uptake results across the UK and to compare local protocols with British Nuclear Medicine Society (BNMS) guidelines. Participants were invited through a combination of emails on a public mailbase and targeted invitations from regional co-ordinators. All participants were given a set of images from which to calculate quantitative measures and a spreadsheet for capturing results. The image data consisted of two sets of 10 anterior thyroid images, half of which were acquired after administration of Tc-pertechnetate and the other half after administration of I-iodide. Images of the administration syringes or thyroid phantoms were also included. In total, 54 participants responded to the audit. The median number of scans conducted per year was 50. A majority of centres had at least one noncompliance in comparison with BNMS guidelines. Of most concern was the widespread lack of injection-site imaging. Quantitative results showed that both intersite and intrasite variability were low for the Tc dataset. The coefficient of quartile deviation was between 0.03 and 0.13 for measurements of overall percentage uptake. Although the number of returns for the I dataset was smaller, the level of variability between participants was greater (the coefficient of quartile deviation was between 0.17 and 0.25). A UK-wide audit showed that thyroid uptake imaging is still a common test in the UK. It was found that most centres do not adhere to all aspects of the BNMS practice guidelines but that quantitative results are reasonably consistent for Tc-based scans.

MO-DE-303-03: Session on quantitative imaging for assessment of tumor response to radiation therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bowen, S.

This session will focus on quantitative imaging for assessment of tumor response to radiation therapy. This is a technically challenging method to translate to practice in radiation therapy. In the new era of precision medicine, however, delivering the right treatment, to the right patient, and at the right time, can positively impact treatment choices and patient outcomes. Quantitative imaging provides the spatial sensitivity required by radiation therapy for precision medicine that is not available by other means. In this Joint ESTRO -AAPM Symposium, three leading-edge investigators will present specific motivations for quantitative imaging biomarkers in radiation therapy of esophageal, headmore » and neck, locally advanced non-small cell lung cancer, and hepatocellular carcinoma. Experiences with the use of dynamic contrast enhanced (DCE) MRI, diffusion- weighted (DW) MRI, PET/CT, and SPECT/CT will be presented. Issues covered will include: response prediction, dose-painting, timing between therapy and imaging, within-therapy biomarkers, confounding effects, normal tissue sparing, dose-response modeling, and association with clinical biomarkers and outcomes. Current information will be presented from investigational studies and clinical practice. Learning Objectives: Learn motivations for the use of quantitative imaging biomarkers for assessment of response to radiation therapy Review the potential areas of application in cancer therapy Examine the challenges for translation, including imaging confounds and paucity of evidence to date Compare exemplary examples of the current state of the art in DCE-MRI, DW-MRI, PET/CT and SPECT/CT imaging for assessment of response to radiation therapy Van der Heide: Research grants from the Dutch Cancer Society and the European Union (FP7) Bowen: RSNA Scholar grant.« less

Use of local noise power spectrum and wavelet analysis in quantitative image quality assurance for EPIDs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Soyoung

Purpose: To investigate the use of local noise power spectrum (NPS) to characterize image noise and wavelet analysis to isolate defective pixels and inter-subpanel flat-fielding artifacts for quantitative quality assurance (QA) of electronic portal imaging devices (EPIDs). Methods: A total of 93 image sets including custom-made bar-pattern images and open exposure images were collected from four iViewGT a-Si EPID systems over three years. Global quantitative metrics such as modulation transform function (MTF), NPS, and detective quantum efficiency (DQE) were computed for each image set. Local NPS was also calculated for individual subpanels by sampling region of interests within each subpanelmore » of the EPID. The 1D NPS, obtained by radially averaging the 2D NPS, was fitted to a power-law function. The r-square value of the linear regression analysis was used as a singular metric to characterize the noise properties of individual subpanels of the EPID. The sensitivity of the local NPS was first compared with the global quantitative metrics using historical image sets. It was then compared with two commonly used commercial QA systems with images collected after applying two different EPID calibration methods (single-level gain and multilevel gain). To detect isolated defective pixels and inter-subpanel flat-fielding artifacts, Haar wavelet transform was applied on the images. Results: Global quantitative metrics including MTF, NPS, and DQE showed little change over the period of data collection. On the contrary, a strong correlation between the local NPS (r-square values) and the variation of the EPID noise condition was observed. The local NPS analysis indicated image quality improvement with the r-square values increased from 0.80 ± 0.03 (before calibration) to 0.85 ± 0.03 (after single-level gain calibration) and to 0.96 ± 0.03 (after multilevel gain calibration), while the commercial QA systems failed to distinguish the image quality improvement between the two calibration methods. With wavelet analysis, defective pixels and inter-subpanel flat-fielding artifacts were clearly identified as spikes after thresholding the inversely transformed images. Conclusions: The proposed local NPS (r-square values) showed superior sensitivity to the noise level variations of individual subpanels compared with global quantitative metrics such as MTF, NPS, and DQE. Wavelet analysis was effective in detecting isolated defective pixels and inter-subpanel flat-fielding artifacts. The proposed methods are promising for the early detection of imaging artifacts of EPIDs.« less

Tumor cell membrane-targeting pH-dependent electron donor-acceptor fluorescence systems with low background signals.

PubMed

Han, Liang; Liu, Mingming; Ye, Deyong; Zhang, Ning; Lim, Ed; Lu, Jing; Jiang, Chen

2014-03-01

Minimizing the background signal is crucial for developing tumor-imaging techniques with sufficient specificity and sensitivity. Here we use pH difference between healthy tissues and tumor and tumor targeting delivery to achieve this goal. We synthesize fluorophore-dopamine conjugate as pH-dependent electron donor-acceptor fluorescence system. Fluorophores are highly sensitive to electron-transfer processes, which can alter their optical properties. The intrinsic redox properties of dopamine are oxidation of hydroquinone to quinone at basic pH and reduction of quinone to hydroquinone at acidic pH. Quinone can accept electron then quench fluorescence. We design tumor cell membrane-targeting carrier for delivery. We demonstrate quenched fluorophore-quinone can be specially transferred to tumor extracellular environment and tumor-accumulated fluorophore can be activated by acidic pH. These tumor-targeting pH-dependent electron donor-acceptor fluorescence systems may offer new opportunity for developing tumor-imaging techniques. Copyright © 2014 Elsevier Ltd. All rights reserved.

Non-invasive imaging of global and regional cardiac function in pulmonary hypertension

PubMed Central

Crowe, Tim; Jayasekera, Geeshath

2017-01-01

Pulmonary hypertension (PH) is a progressive illness characterized by elevated pulmonary artery pressure; however, the main cause of mortality in PH patients is right ventricular (RV) failure. Historically, improving the hemodynamics of pulmonary circulation was the focus of treatment; however, it is now evident that cardiac response to a given level of pulmonary hemodynamic overload is variable but plays an important role in the subsequent prognosis. Non-invasive tests of RV function to determine prognosis and response to treatment in patients with PH is essential. Although the right ventricle is the focus of attention, it is clear that cardiac interaction can cause left ventricular dysfunction, thus biventricular assessment is paramount. There is also focus on the atrial chambers in their contribution to cardiac function in PH. Furthermore, there is evidence of regional dysfunction of the two ventricles in PH, so it would be useful to understand both global and regional components of dysfunction. In order to understand global and regional cardiac function in PH, the most obvious non-invasive imaging techniques are echocardiography and cardiac magnetic resonance imaging (CMRI). Both techniques have their advantages and disadvantages. Echocardiography is widely available, relatively inexpensive, provides information regarding RV function, and can be used to estimate RV pressures. CMRI, although expensive and less accessible, is the gold standard of biventricular functional measurements. The advent of 3D echocardiography and techniques including strain analysis and stress echocardiography have improved the usefulness of echocardiography while new CMRI technology allows the measurement of strain and measuring cardiac function during stress including exercise. In this review, we have analyzed the advantages and disadvantages of the two techniques and discuss pre-existing and novel forms of analysis where echocardiography and CMRI can be used to examine atrial, ventricular, and interventricular function in patients with PH at rest and under stress. PMID:29064323

In-vivo and ex-vivo spectrofluorometric and imaging study of liposome uptake by the liver using a pH-sensitive probe

NASA Astrophysics Data System (ADS)

Soulie-Begu, Sylvie; Devoisselle, Jean-Marie; Mordon, Serge R.

1995-04-01

Liposomes are known to be uptaken by the liver cells after intraveinous injection. Only few techniques are available to follow this process in vivo like nuclear magnetic resonance spectroscopy or scintigraphy. Intracellular pathway and liposomes localization in the different liver cells require sacrifice of the animals, cells separation and electronic microscopy, then little is known about liposomes kinetic uptake by the acidic intracellular compartments in vivo. We propose in this study a new method to follow liposomes uptake in the liver in vivo using a fluorescent pH sensitive probe 5,6-carboxyfluorescein and two different composition of liposomes: phospholipids DSPC/Chol and DMPC in order to evaluate the influence of the formulation on the release characteristics of liposomes in the lysosomes. We have already demonstrated the ability of the fluorescence spectroscopy and imaging using a pH dependent probe to monitor pH in living tissues. As pH of lysosomes is very low, the kinetic liposomes uptake in this intracellular acidic compartment is followed by monitoring the pH of the whole liver in vivo and ex vivo. Carboxyfluorescein is used at high concentration (100 mM) in order to quench its fluorescence. Liposomes are injected to Wistar rats into the penil vein. After laparotomy, fluorescence spectra and images are recorded during two hours. Results show a clear relationship between formulation of liposomes and stability in the acidic compartments of hepatic cells. After sacrifice and flush with cold saline solution, pH of the liver ex vivo is found to be 5.0-5.5. Data show a rapid clearance of release dye and an uptake of liposomes by the liver cells and, as liposomes penetrate in the acidic compartment, dye is released from liposomes and is delivered in lysosomes leading to the decrease of the pH.

A custom-built PET phantom design for quantitative imaging of printed distributions.

PubMed

Markiewicz, P J; Angelis, G I; Kotasidis, F; Green, M; Lionheart, W R; Reader, A J; Matthews, J C

2011-11-07

This note presents a practical approach to a custom-made design of PET phantoms enabling the use of digital radioactive distributions with high quantitative accuracy and spatial resolution. The phantom design allows planar sources of any radioactivity distribution to be imaged in transaxial and axial (sagittal or coronal) planes. Although the design presented here is specially adapted to the high-resolution research tomograph (HRRT), the presented methods can be adapted to almost any PET scanner. Although the presented phantom design has many advantages, a number of practical issues had to be overcome such as positioning of the printed source, calibration, uniformity and reproducibility of printing. A well counter (WC) was used in the calibration procedure to find the nonlinear relationship between digital voxel intensities and the actual measured radioactive concentrations. Repeated printing together with WC measurements and computed radiography (CR) using phosphor imaging plates (IP) were used to evaluate the reproducibility and uniformity of such printing. Results show satisfactory printing uniformity and reproducibility; however, calibration is dependent on the printing mode and the physical state of the cartridge. As a demonstration of the utility of using printed phantoms, the image resolution and quantitative accuracy of reconstructed HRRT images are assessed. There is very good quantitative agreement in the calibration procedure between HRRT, CR and WC measurements. However, the high resolution of CR and its quantitative accuracy supported by WC measurements made it possible to show the degraded resolution of HRRT brain images caused by the partial-volume effect and the limits of iterative image reconstruction.

Putting tools in the toolbox: Development of a free, open-source toolbox for quantitative image analysis of porous media.

NASA Astrophysics Data System (ADS)

Iltis, G.; Caswell, T. A.; Dill, E.; Wilkins, S.; Lee, W. K.

2014-12-01

X-ray tomographic imaging of porous media has proven to be a valuable tool for investigating and characterizing the physical structure and state of both natural and synthetic porous materials, including glass bead packs, ceramics, soil and rock. Given that most synchrotron facilities have user programs which grant academic researchers access to facilities and x-ray imaging equipment free of charge, a key limitation or hindrance for small research groups interested in conducting x-ray imaging experiments is the financial cost associated with post-experiment data analysis. While the cost of high performance computing hardware continues to decrease, expenses associated with licensing commercial software packages for quantitative image analysis continue to increase, with current prices being as high as $24,000 USD, for a single user license. As construction of the Nation's newest synchrotron accelerator nears completion, a significant effort is being made here at the National Synchrotron Light Source II (NSLS-II), Brookhaven National Laboratory (BNL), to provide an open-source, experiment-to-publication toolbox that reduces the financial and technical 'activation energy' required for performing sophisticated quantitative analysis of multidimensional porous media data sets, collected using cutting-edge x-ray imaging techniques. Implementation focuses on leveraging existing open-source projects and developing additional tools for quantitative analysis. We will present an overview of the software suite that is in development here at BNL including major design decisions, a demonstration of several test cases illustrating currently available quantitative tools for analysis and characterization of multidimensional porous media image data sets and plans for their future development.

Molecular imaging of melanin distribution in vivo and quantitative differential diagnosis of human pigmented lesions using label-free harmonic generation biopsy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Sun, Chi-Kuang; Wei, Ming-Liang; Su, Yu-Hsiang; Weng, Wei-Hung; Liao, Yi-Hua

2017-02-01

Harmonic generation microscopy is a noninvasive repetitive imaging technique that provides real-time 3D microscopic images of human skin with a sub-femtoliter resolution and high penetration down to the reticular dermis. In this talk, we show that with a strong resonance effect, the third-harmonic-generation (THG) modality provides enhanced contrast on melanin and allows not only differential diagnosis of various pigmented skin lesions but also quantitative imaging for longterm tracking. This unique capability makes THG microscopy the only label-free technique capable of identifying the active melanocytes in human skin and to image their different dendriticity patterns. In this talk, we will review our recent efforts to in vivo image melanin distribution and quantitatively diagnose pigmented skin lesions using label-free harmonic generation biopsy. This talk will first cover the spectroscopic study on the melanin enhanced THG effect in human cells and the calibration strategy inside human skin for quantitative imaging. We will then review our recent clinical trials including: differential diagnosis capability study on pigmented skin tumors; as well as quantitative virtual biopsy study on pre- and post- treatment evaluation on melasma and solar lentigo. Our study indicates the unmatched capability of harmonic generation microscopy to perform virtual biopsy for noninvasive histopathological diagnosis of various pigmented skin tumors, as well as its unsurpassed capability to noninvasively reveal the pathological origin of different hyperpigmentary diseases on human face as well as to monitor the efficacy of laser depigmentation treatments. This work is sponsored by National Health Research Institutes.

Image segmentation evaluation for very-large datasets

NASA Astrophysics Data System (ADS)

Reeves, Anthony P.; Liu, Shuang; Xie, Yiting

2016-03-01

With the advent of modern machine learning methods and fully automated image analysis there is a need for very large image datasets having documented segmentations for both computer algorithm training and evaluation. Current approaches of visual inspection and manual markings do not scale well to big data. We present a new approach that depends on fully automated algorithm outcomes for segmentation documentation, requires no manual marking, and provides quantitative evaluation for computer algorithms. The documentation of new image segmentations and new algorithm outcomes are achieved by visual inspection. The burden of visual inspection on large datasets is minimized by (a) customized visualizations for rapid review and (b) reducing the number of cases to be reviewed through analysis of quantitative segmentation evaluation. This method has been applied to a dataset of 7,440 whole-lung CT images for 6 different segmentation algorithms designed to fully automatically facilitate the measurement of a number of very important quantitative image biomarkers. The results indicate that we could achieve 93% to 99% successful segmentation for these algorithms on this relatively large image database. The presented evaluation method may be scaled to much larger image databases.

Quantitative Imaging with a Mobile Phone Microscope

PubMed Central

Skandarajah, Arunan; Reber, Clay D.; Switz, Neil A.; Fletcher, Daniel A.

2014-01-01

Use of optical imaging for medical and scientific applications requires accurate quantification of features such as object size, color, and brightness. High pixel density cameras available on modern mobile phones have made photography simple and convenient for consumer applications; however, the camera hardware and software that enables this simplicity can present a barrier to accurate quantification of image data. This issue is exacerbated by automated settings, proprietary image processing algorithms, rapid phone evolution, and the diversity of manufacturers. If mobile phone cameras are to live up to their potential to increase access to healthcare in low-resource settings, limitations of mobile phone–based imaging must be fully understood and addressed with procedures that minimize their effects on image quantification. Here we focus on microscopic optical imaging using a custom mobile phone microscope that is compatible with phones from multiple manufacturers. We demonstrate that quantitative microscopy with micron-scale spatial resolution can be carried out with multiple phones and that image linearity, distortion, and color can be corrected as needed. Using all versions of the iPhone and a selection of Android phones released between 2007 and 2012, we show that phones with greater than 5 MP are capable of nearly diffraction-limited resolution over a broad range of magnifications, including those relevant for single cell imaging. We find that automatic focus, exposure, and color gain standard on mobile phones can degrade image resolution and reduce accuracy of color capture if uncorrected, and we devise procedures to avoid these barriers to quantitative imaging. By accommodating the differences between mobile phone cameras and the scientific cameras, mobile phone microscopes can be reliably used to increase access to quantitative imaging for a variety of medical and scientific applications. PMID:24824072

Quantitative image processing in fluid mechanics

NASA Technical Reports Server (NTRS)

Hesselink, Lambertus; Helman, James; Ning, Paul

1992-01-01

The current status of digital image processing in fluid flow research is reviewed. In particular, attention is given to a comprehensive approach to the extraction of quantitative data from multivariate databases and examples of recent developments. The discussion covers numerical simulations and experiments, data processing, generation and dissemination of knowledge, traditional image processing, hybrid processing, fluid flow vector field topology, and isosurface analysis using Marching Cubes.

Influence of sample preparation and reliability of automated numerical refocusing in stain-free analysis of dissected tissues with quantitative phase digital holographic microscopy

NASA Astrophysics Data System (ADS)

Kemper, Björn; Lenz, Philipp; Bettenworth, Dominik; Krausewitz, Philipp; Domagk, Dirk; Ketelhut, Steffi

2015-05-01

Digital holographic microscopy (DHM) has been demonstrated to be a versatile tool for high resolution non-destructive quantitative phase imaging of surfaces and multi-modal minimally-invasive monitoring of living cell cultures in-vitro. DHM provides quantitative monitoring of physiological processes through functional imaging and structural analysis which, for example, gives new insight into signalling of cellular water permeability and cell morphology changes due to toxins and infections. Also the analysis of dissected tissues quantitative DHM phase contrast prospects application fields by stain-free imaging and the quantification of tissue density changes. We show that DHM allows imaging of different tissue layers with high contrast in unstained tissue sections. As the investigation of fixed samples represents a very important application field in pathology, we also analyzed the influence of the sample preparation. The retrieved data demonstrate that the quality of quantitative DHM phase images of dissected tissues depends strongly on the fixing method and common staining agents. As in DHM the reconstruction is performed numerically, multi-focus imaging is achieved from a single digital hologram. Thus, we evaluated the automated refocussing feature of DHM for application on different types of dissected tissues and revealed that on moderately stained samples highly reproducible holographic autofocussing can be achieved. Finally, it is demonstrated that alterations of the spatial refractive index distribution in murine and human tissue samples represent a reliable absolute parameter that is related of different degrees of inflammation in experimental colitis and Crohn's disease. This paves the way towards the usage of DHM in digital pathology for automated histological examinations and further studies to elucidate the translational potential of quantitative phase microscopy for the clinical management of patients, e.g., with inflammatory bowel disease.

Development of CD3 cell quantitation algorithms for renal allograft biopsy rejection assessment utilizing open source image analysis software.

PubMed

Moon, Andres; Smith, Geoffrey H; Kong, Jun; Rogers, Thomas E; Ellis, Carla L; Farris, Alton B Brad

2018-02-01

Renal allograft rejection diagnosis depends on assessment of parameters such as interstitial inflammation; however, studies have shown interobserver variability regarding interstitial inflammation assessment. Since automated image analysis quantitation can be reproducible, we devised customized analysis methods for CD3+ T-cell staining density as a measure of rejection severity and compared them with established commercial methods along with visual assessment. Renal biopsy CD3 immunohistochemistry slides (n = 45), including renal allografts with various degrees of acute cellular rejection (ACR) were scanned for whole slide images (WSIs). Inflammation was quantitated in the WSIs using pathologist visual assessment, commercial algorithms (Aperio nuclear algorithm for CD3+ cells/mm 2 and Aperio positive pixel count algorithm), and customized open source algorithms developed in ImageJ with thresholding/positive pixel counting (custom CD3+%) and identification of pixels fulfilling "maxima" criteria for CD3 expression (custom CD3+ cells/mm 2 ). Based on visual inspections of "markup" images, CD3 quantitation algorithms produced adequate accuracy. Additionally, CD3 quantitation algorithms correlated between each other and also with visual assessment in a statistically significant manner (r = 0.44 to 0.94, p = 0.003 to < 0.0001). Methods for assessing inflammation suggested a progression through the tubulointerstitial ACR grades, with statistically different results in borderline versus other ACR types, in all but the custom methods. Assessment of CD3-stained slides using various open source image analysis algorithms presents salient correlations with established methods of CD3 quantitation. These analysis techniques are promising and highly customizable, providing a form of on-slide "flow cytometry" that can facilitate additional diagnostic accuracy in tissue-based assessments.

77 FR 2987 - National Institute of Biomedical Imaging and Bioengineering; Notice of Closed Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-01-20

... Biomedical Imaging and Bioengineering; Notice of Closed Meeting Pursuant to section 10(d) of the Federal... clearly unwarranted invasion of personal privacy. Name of Committee: National Institute of Biomedical..., Ph.D., Scientific Review Officer, National Institute of Biomedical Imaging and Bioengineering...

Ultrasound introscopic image quantitative characteristics for medical diagnosis

NASA Astrophysics Data System (ADS)

Novoselets, Mikhail K.; Sarkisov, Sergey S.; Gridko, Alexander N.; Tcheban, Anatoliy K.

1993-09-01

The results on computer aided extraction of quantitative characteristics (QC) of ultrasound introscopic images for medical diagnosis are presented. Thyroid gland (TG) images of Chernobil Accident sufferers are considered. It is shown that TG diseases can be associated with some values of selected QCs of random echo distribution in the image. The possibility of these QCs usage for TG diseases recognition in accordance with calculated values is analyzed. The role of speckle noise elimination in the solution of the problem on TG diagnosis is considered too.

Simultaneous off-axis multiplexed holography and regular fluorescence microscopy of biological cells.

PubMed

Nygate, Yoav N; Singh, Gyanendra; Barnea, Itay; Shaked, Natan T

2018-06-01

We present a new technique for obtaining simultaneous multimodal quantitative phase and fluorescence microscopy of biological cells, providing both quantitative phase imaging and molecular specificity using a single camera. Our system is based on an interferometric multiplexing module, externally positioned at the exit of an optical microscope. In contrast to previous approaches, the presented technique allows conventional fluorescence imaging, rather than interferometric off-axis fluorescence imaging. We demonstrate the presented technique for imaging fluorescent beads and live biological cells.

Analysis of chronic aortic regurgitation by 2D and 3D echocardiography and cardiac MRI

PubMed Central

Stoebe, Stephan; Metze, Michael; Jurisch, Daniel; Tayal, Bhupendar; Solty, Kilian; Laufs, Ulrich; Pfeiffer, Dietrich; Hagendorff, Andreas

2018-01-01

Purpose The study compares the feasibility of the quantitative volumetric and semi-quantitative approach for quantification of chronic aortic regurgitation (AR) using different imaging modalities. Methods Left ventricular (LV) volumes, regurgitant volumes (RVol) and regurgitant fractions (RF) were assessed retrospectively by 2D, 3D echocardiography and cMRI in 55 chronic AR patients. Semi-quantitative parameters were assessed by 2D echocardiography. Results 22 (40%) patients had mild, 25 (46%) moderate and 8 (14%) severe AR. The quantitative volumetric approach was feasible using 2D, 3D echocardiography and cMRI, whereas the feasibility of semi-quantitative parameters varied considerably. LV volume (LVEDV, LVESV, SVtot) analyses showed good correlations between the different imaging modalities, although significantly increased LV volumes were assessed by cMRI. RVol was significantly different between 2D/3D echocardiography and 2D echocardiography/cMRI but was not significantly different between 3D echocardiography/cMRI. RF was not statistically different between 2D echocardiography/cMRI and 3D echocardiography/cMRI showing poor correlations (r < 0.5) between the different imaging modalities. For AR grading by RF, moderate agreement was observed between 2D/3D echocardiography and 2D echocardiography/cMRI and good agreement was observed between 3D echocardiography/cMRI. Conclusion Semi-quantitative parameters are difficult to determine by 2D echocardiography in clinical routine. The quantitative volumetric RF assessment seems to be feasible and can be discussed as an alternative approach in chronic AR. However, RVol and RF did not correlate well between the different imaging modalities. The best agreement for grading of AR severity by RF was observed between 3D echocardiography and cMRI. LV volumes can be verified by different approaches and different imaging modalities. PMID:29519957

Objective evaluation of reconstruction methods for quantitative SPECT imaging in the absence of ground truth.

PubMed

Jha, Abhinav K; Song, Na; Caffo, Brian; Frey, Eric C

2015-04-13

Quantitative single-photon emission computed tomography (SPECT) imaging is emerging as an important tool in clinical studies and biomedical research. There is thus a need for optimization and evaluation of systems and algorithms that are being developed for quantitative SPECT imaging. An appropriate objective method to evaluate these systems is by comparing their performance in the end task that is required in quantitative SPECT imaging, such as estimating the mean activity concentration in a volume of interest (VOI) in a patient image. This objective evaluation can be performed if the true value of the estimated parameter is known, i.e. we have a gold standard. However, very rarely is this gold standard known in human studies. Thus, no-gold-standard techniques to optimize and evaluate systems and algorithms in the absence of gold standard are required. In this work, we developed a no-gold-standard technique to objectively evaluate reconstruction methods used in quantitative SPECT when the parameter to be estimated is the mean activity concentration in a VOI. We studied the performance of the technique with realistic simulated image data generated from an object database consisting of five phantom anatomies with all possible combinations of five sets of organ uptakes, where each anatomy consisted of eight different organ VOIs. Results indicate that the method provided accurate ranking of the reconstruction methods. We also demonstrated the application of consistency checks to test the no-gold-standard output.

Analytical robustness of quantitative NIR chemical imaging for Islamic paper characterization

NASA Astrophysics Data System (ADS)

Mahgoub, Hend; Gilchrist, John R.; Fearn, Thomas; Strlič, Matija

2017-07-01

Recently, spectral imaging techniques such as Multispectral (MSI) and Hyperspectral Imaging (HSI) have gained importance in the field of heritage conservation. This paper explores the analytical robustness of quantitative chemical imaging for Islamic paper characterization by focusing on the effect of different measurement and processing parameters, i.e. acquisition conditions and calibration on the accuracy of the collected spectral data. This will provide a better understanding of the technique that can provide a measure of change in collections through imaging. For the quantitative model, special calibration target was devised using 105 samples from a well-characterized reference Islamic paper collection. Two material properties were of interest: starch sizing and cellulose degree of polymerization (DP). Multivariate data analysis methods were used to develop discrimination and regression models which were used as an evaluation methodology for the metrology of quantitative NIR chemical imaging. Spectral data were collected using a pushbroom HSI scanner (Gilden Photonics Ltd) in the 1000-2500 nm range with a spectral resolution of 6.3 nm using a mirror scanning setup and halogen illumination. Data were acquired at different measurement conditions and acquisition parameters. Preliminary results showed the potential of the evaluation methodology to show that measurement parameters such as the use of different lenses and different scanning backgrounds may not have a great influence on the quantitative results. Moreover, the evaluation methodology allowed for the selection of the best pre-treatment method to be applied to the data.

Comparison of clinical semi-quantitative assessment of muscle fat infiltration with quantitative assessment using chemical shift-based water/fat separation in MR studies of the calf of post-menopausal women.

PubMed

Alizai, Hamza; Nardo, Lorenzo; Karampinos, Dimitrios C; Joseph, Gabby B; Yap, Samuel P; Baum, Thomas; Krug, Roland; Majumdar, Sharmila; Link, Thomas M

2012-07-01

The goal of this study was to compare the semi-quantitative Goutallier classification for fat infiltration with quantitative fat-fraction derived from a magnetic resonance imaging (MRI) chemical shift-based water/fat separation technique. Sixty-two women (age 61 ± 6 years), 27 of whom had diabetes, underwent MRI of the calf using a T1-weighted fast spin-echo sequence and a six-echo spoiled gradient-echo sequence at 3 T. Water/fat images and fat fraction maps were reconstructed using the IDEAL algorithm with T2* correction and a multi-peak model for the fat spectrum. Two radiologists scored fat infiltration on the T1-weighted images using the Goutallier classification in six muscle compartments. Spearman correlations between the Goutallier grades and the fat fraction were calculated; in addition, intra-observer and inter-observer agreement were calculated. A significant correlation between the clinical grading and the fat fraction values was found for all muscle compartments (P < 0.0001, R values ranging from 0.79 to 0.88). Goutallier grades 0-4 had a fat fraction ranging from 3.5 to 19%. Intra-observer and inter-observer agreement values of 0.83 and 0.81 were calculated for the semi-quantitative grading. Semi-quantitative grading of intramuscular fat and quantitative fat fraction were significantly correlated and both techniques had excellent reproducibility. However, the clinical grading was found to overestimate muscle fat. Fat infiltration of muscle commonly occurs in many metabolic and neuromuscular diseases. • Image-based semi-quantitative classifications for assessing fat infiltration are not well validated. • Quantitative MRI techniques provide an accurate assessment of muscle fat.

Comparison of quantitative Y-90 SPECT and non-time-of-flight PET imaging in post-therapy radioembolization of liver cancer

PubMed Central

Yue, Jianting; Mauxion, Thibault; Reyes, Diane K.; Lodge, Martin A.; Hobbs, Robert F.; Rong, Xing; Dong, Yinfeng; Herman, Joseph M.; Wahl, Richard L.; Geschwind, Jean-François H.; Frey, Eric C.

2016-01-01

Purpose: Radioembolization with yttrium-90 microspheres may be optimized with patient-specific pretherapy treatment planning. Dose verification and validation of treatment planning methods require quantitative imaging of the post-therapy distribution of yttrium-90 (Y-90). Methods for quantitative imaging of Y-90 using both bremsstrahlung SPECT and PET have previously been described. The purpose of this study was to compare the two modalities quantitatively in humans. Methods: Calibration correction factors for both quantitative Y-90 bremsstrahlung SPECT and a non-time-of-flight PET system without compensation for prompt coincidences were developed by imaging three phantoms. The consistency of these calibration correction factors for the different phantoms was evaluated. Post-therapy images from both modalities were obtained from 15 patients with hepatocellular carcinoma who underwent hepatic radioembolization using Y-90 glass microspheres. Quantitative SPECT and PET images were rigidly registered and the total liver activities and activity distributions estimated for each modality were compared. The activity distributions were compared using profiles, voxel-by-voxel correlation and Bland–Altman analyses, and activity-volume histograms. Results: The mean ± standard deviation of difference in the total activity in the liver between the two modalities was 0% ± 9% (range −21%–18%). Voxel-by-voxel comparisons showed a good agreement in regions corresponding roughly to treated tumor and treated normal liver; the agreement was poorer in regions with low or no expected activity, where PET appeared to overestimate the activity. The correlation coefficients between intrahepatic voxel pairs for the two modalities ranged from 0.86 to 0.94. Cumulative activity volume histograms were in good agreement. Conclusions: These data indicate that, with appropriate reconstruction methods and measured calibration correction factors, either Y-90 SPECT/CT or Y-90 PET/CT can be used for quantitative post-therapy monitoring of Y-90 activity distribution following hepatic radioembolization. PMID:27782730