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Sample records for imaging targeting myeloperoxidase

  1. Myeloperoxidase: a target for new drug development?

    PubMed Central

    Malle, E; Furtmüller, P G; Sattler, W; Obinger, C

    2007-01-01

    Myeloperoxidase (MPO), a member of the haem peroxidase-cyclooxygenase superfamily, is abundantly expressed in neutrophils and to a lesser extent in monocytes and certain type of macrophages. MPO participates in innate immune defence mechanism through formation of microbicidal reactive oxidants and diffusible radical species. A unique activity of MPO is its ability to use chloride as a cosubstrate with hydrogen peroxide to generate chlorinating oxidants such as hypochlorous acid, a potent antimicrobial agent. However, evidence has emerged that MPO-derived oxidants contribute to tissue damage and the initiation and propagation of acute and chronic vascular inflammatory disease. The fact that circulating levels of MPO have been shown to predict risks for major adverse cardiac events and that levels of MPO-derived chlorinated compounds are specific biomarkers for disease progression, has attracted considerable interest in the development of therapeutically useful MPO inhibitors. Today, detailed information on the structure of ferric MPO and its complexes with low- and high-spin ligands is available. This, together with a thorough understanding of reaction mechanisms including redox properties of intermediates, enables a rationale attempt in developing specific MPO inhibitors that still maintain MPO activity during host defence and bacterial killing but interfere with pathophysiologically persistent activation of MPO. The various approaches to inhibit enzyme activity of MPO and to ameliorate adverse effects of MPO-derived oxidants will be discussed. Emphasis will be put on mechanism-based inhibitors and high-throughput screening of compounds as well as the discussion of physiologically useful HOCl scavengers. PMID:17592500

  2. MR Imaging of Myeloperoxidase Activity in a Model of the Inflamed Aneurysm Wall

    PubMed Central

    Gounis, M.J.; van der Bom, I.M.J.; Wakhloo, A.K.; Zheng, S.; Chueh, J.-Y.; Kühn, A.L.; Bogdanov, A.A.

    2014-01-01

    Background and Purpose Although myeloperoxidase (MPO) activity in vivo can be visualized using non-invasive imaging, successful clinical translation requires further optimization of the imaging approach. We report a motion-sensitized-driven-equilibrium (MSDE) for the detection of an MPO activity-specific gadolinium (Gd)-containing imaging agent (IA) in experimental aneurysm models that compensates for irregular blood flow enabling vascular wall imaging in the aneurysm. Materials and Methods We deployed a phantom model to optimize a MSDE MR sequence that suppresses complex flow patterns within the aneurysm for detection of an MPO-specific Gd-chelate. The phantom was built from rotational angiography of a rabbit elastase aneurysm model and connected to a cardiac pulse duplicator mimicking rabbit-specific flow conditions. Thereafter, we further refined the MSDE sequence and applied it in vivo to rabbit aneurysm models with and without inflammation in the aneurysmal wall. Under each condition, the aneurysms were imaged before and after intravenous administration of the IA. The signal-to-noise ratio (SNR) of each MR slice through the aneurysm was calculated. Results The MSDE sequence was optimized to reduce flow signal enabling detection of the MPO-IA in the phantom. The optimized imaging protocol in the rabbit model of saccular aneurysms revealed a significant increase in the change of SNR pre- to postcontrast MR signal intensities in the inflamed aneurysms as compared to naïve aneurysms and the adjacent carotid artery (p<0.0001). Conclusion A diagnostic MR protocol was optimized for molecular imaging of an MPO-specific molecular imaging agent in an animal model of brain aneurysms. PMID:25273534

  3. Integrin Targeted MR Imaging.

    PubMed

    Tan, Mingqian; Lu, Zheng-Rong

    2011-01-19

    Magnetic resonance imaging (MRI) is a powerful medical diagnostic imaging modality for integrin targeted imaging, which uses the magnetic resonance of tissue water protons to display tissue anatomic structures with high spatial resolution. Contrast agents are often used in MRI to highlight specific regions of the body and make them easier to visualize. There are four main classes of MRI contrast agents based on their different contrast mechanisms, including T(1), T(2), chemical exchange saturation transfer (CEST) agents, and heteronuclear contrast agents. Integrins are an important family of heterodimeric transmembrane glycoproteins that function as mediators of cell-cell and cell-extracellular matrix interactions. The overexpressed integrins can be used as the molecular targets for designing suitable integrin targeted contrast agents for MR molecular imaging. Integrin targeted contrast agent includes a targeting agent specific to a target integrin, a paramagnetic agent and a linker connecting the targeting agent with the paramagnetic agent. Proper selection of targeting agents is critical for targeted MRI contrast agents to effectively bind to integrins for in vivo imaging. An ideal integrin targeted MR contrast agent should be non-toxic, provide strong contrast enhancement at the target sites and can be completely excreted from the body after MR imaging. An overview of integrin targeted MR contrast agents based on small molecular and macromolecular Gd(III) complexes, lipid nanoparticles and superparamagnetic nanoparticles is provided for MR molecular imaging. By using proper delivery systems for loading sufficient Gd(III) chelates or superparamagnetic nanoparticles, effective molecular imaging of integrins with MRI has been demonstrated in animal models.

  4. Myeloperoxidase Stimulates Neutrophil Degranulation.

    PubMed

    Grigorieva, D V; Gorudko, I V; Sokolov, A V; Kostevich, V A; Vasilyev, V B; Cherenkevich, S N; Panasenko, O M

    2016-08-01

    Myeloperoxidase, heme enzyme of azurophilic granules in neutrophils, is released into the extracellular space in the inflammation foci. In neutrophils, it stimulates a dose-dependent release of lactoferrin (a protein of specific granules), lysozyme (a protein of specific and azurophilic granules), and elastase (a protein of azurophilic granules). 4-Aminobenzoic acid hydrazide, a potent inhibitor of peroxidase activity of myeloperoxidase, produced no effect on neutrophil degranulation. Using signal transduction inhibitors (genistein, methoxyverapamil, wortmannin, and NiCl2), we demonstrated that myeloperoxidase-induced degranulation of neutrophils resulted from enzyme interaction with the plasma membrane and depends on activation of tyrosine kinases, phosphatidylinositol 3-kinases (PI3K), and calcium signaling. Myeloperoxidase modified by oxidative/halogenation stress (chlorinated and monomeric forms of the enzyme) lost the potency to activate neutrophil degranulation. PMID:27597056

  5. Therapeutic targeting of naturally presented myeloperoxidase-derived HLA peptide ligands on myeloid leukemia cells by TCR-transgenic T cells.

    PubMed

    Klar, R; Schober, S; Rami, M; Mall, S; Merl, J; Hauck, S M; Ueffing, M; Admon, A; Slotta-Huspenina, J; Schwaiger, M; Stevanović, S; Oostendorp, R A J; Busch, D H; Peschel, C; Krackhardt, A M

    2014-12-01

    T cells have been proven to be therapeutically effective in patients with relapsed leukemias, although target antigens on leukemic cells as well as T-cell receptors (TCRs), potentially recognizing those antigens, are mostly unknown. We have applied an immunopeptidomic approach and isolated human leukocyte antigen (HLA) ligands from primary leukemia cells. We identified a number of ligands derived from different genes that are restrictedly expressed in the hematopoietic system. We exemplarily selected myeloperoxidase (MPO) as a potential target and isolated a high-avidity TCR with specificity for a HLA-B*07:02-(HLA-B7)-restricted epitope of MPO in the single HLA-mismatched setting. T cells transgenic for this TCR demonstrated high peptide and antigen specificity as well as leukemia reactivity in vitro and in vivo. In contrast, no significant on- and off-target toxicity could be observed. In conclusion, we here demonstrate, exemplarily for MPO, that leukemia-derived HLA ligands can be selected for specific effector tool development to redirect T cells to be used for graft manipulation or adoptive T-cell therapies in diverse transplant settings. This approach can be extended to other HLA ligands and HLA molecules in order to provide better treatment options for this life-threatening disease.

  6. Myeloperoxidase is synthesized as larger phosphorylated precursor.

    PubMed Central

    Hasilik, A; Pohlmann, R; Olsen, R L; von Figura, K

    1984-01-01

    Synthesis and processing of myeloperoxidase were examined in metabolically labeled cells of the human promyelocyte line HL-60 and in an in vitro rabbit reticulocyte lysate system directed with HL-60 mRNA. Radioactivity labeled products were isolated by immunoprecipitation and analyzed by gel electrophoresis and fluorography. In vivo, myeloperoxidase was labeled initially as a 85-K glycosylated polypeptide (75 K after treatment with endo-beta-N-acetylglucosaminidase H). This polypeptide was soon processed to an 81-K intermediate and to smaller mature fragments of 60 K and 13 K within approximately 1 day. A minor portion of the precursor was converted to fragments of 40 K and 43 K. The pattern of labeled polypeptides of mature myeloperoxidase was similar to that of the enzyme purified from human leucocytes. The modifications of the polypeptide and of the oligosaccharide side chains in myeloperoxidase resembled those known to occur during the processing of lysosomal enzymes. In the absence or presence of dog pancreas membranes, myeloperoxidase was synthesized in vitro as a 76-K polypeptide or a 87-K glycosylated polypeptide, respectively. In HL-60 cells [32P]phosphate was incorporated into endo-beta-N-acetylglucosaminidase H-sensitive oligosaccharides. The presence of phosphorylated oligosaccharides was inferred from the fact that endocytosis of leucocyte myeloperoxidase in fibroblasts was sensitive to mannose 6-phosphate. It is suggested that myeloperoxidase is synthesized in the rough endoplasmic reticulum as a precursor of larger molecular mass and that the oligosaccharide side chains in the precursor are modified to contain mannose 6-phosphate residues which may be involved in the segregation and transport of the precursor. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. PMID:6096138

  7. Targeted Endoscopic Imaging

    PubMed Central

    Li, Meng; Wang, Thomas D

    2011-01-01

    Summary Endoscopy has undergone explosive technological growth in over recent years, and with the emergence of targeted imaging, its truly transformative power and impact in medicine lies just over the horizon. Today, our ability to see inside the digestive tract with medical endoscopy is headed toward exciting crossroads. The existing paradigm of making diagnostic decisions based on observing structural changes and identifying anatomical landmarks may soon be replaced by visualizing functional properties and imaging molecular expression. In this novel approach, the presence of intracellular and cell surface targets unique to disease are identified and used to predict the likelihood of mucosal transformation and response to therapy. This strategy can result in the development of new methods for early cancer detection, personalized therapy, and chemoprevention. This targeted approach will require further development of molecular probes and endoscopic instruments, and will need support from the FDA for streamlined regulatory oversight. Overall, this molecular imaging modality promises to significantly broaden the capabilities of the gastroenterologist by providing a new approach to visualize the mucosa of the digestive tract in a manner that has never been seen before. PMID:19423025

  8. Targeted Nanotechnology for Cancer Imaging

    PubMed Central

    Toy, Randall; Bauer, Lisa; Hoimes, Christopher; Ghaghada, Ketan B.; Karathanasis, Efstathios

    2014-01-01

    Targeted nanoparticle imaging agents provide many benefits and new opportunities to facilitate accurate diagnosis of cancer and significantly impact patient outcome. Due to the highly engineerable nature of nanotechnology, targeted nanoparticles exhibit significant advantages including increased contrast sensitivity, binding avidity and targeting specificity. Considering the various nanoparticle designs and their adjustable ability to target a specific site and generate detectable signals, nanoparticles can be optimally designed in terms of biophysical interactions (i.e., intravascular and interstitial transport) and biochemical interactions (i.e., targeting avidity towards cancer-related biomarkers) for site-specific detection of very distinct microenvironments. This review seeks to illustrate that the design of a nanoparticle dictates its in vivo journey and targeting of hard-to-reach cancer sites, facilitating early and accurate diagnosis and interrogation of the most aggressive forms of cancer. We will report various targeted nanoparticles for cancer imaging using X-ray computed tomography, ultrasound, magnetic resonance imaging, nuclear imaging and optical imaging. Finally, to realize the full potential of targeted nanotechnology for cancer imaging, we will describe the challenges and opportunities for the clinical translation and widespread adaptation of targeted nanoparticles imaging agents. PMID:25116445

  9. Myeloperoxidase levels predict executive function.

    PubMed

    Haslacher, H; Perkmann, T; Lukas, I; Barth, A; Ponocny-Seliger, E; Michlmayr, M; Scheichenberger, V; Wagner, O; Winker, R

    2012-12-01

    The main purpose of the study was to investigate whether baseline myeloperoxidase (MPO) levels are associated with executive cognitive function in individuals with high physical activity. Baseline serum MPO levels of 56 elderly marathon runners and 58 controls were assessed by ELISA. Standardized tests were applied to survey domain-specific cognitive functions. Changes in brain morphology were visualized by magnetic resonance imaging (MRI). High baseline serum MPO levels correlated with worse outcome in tests assessing executive cognitive function in athletes but not in the control group (NAI maze test p<0.05, Trail Making Test ratio p<0.01). In control participants, subcortical white matter hyperintensities were associated with higher scores on the Geriatric Depression Scale (p<0.05), whereas athletes seem to be protected from this effect. During strenuous exercising, MPO as well as its educts may be elevated due to increased oxygen intake and excretion of pro-inflammatory mediators inducing host tissue damage via oxidative stress. This outweighs the potential benefits of physical activity on cognitive function.

  10. Myeloperoxidase levels predict executive function.

    PubMed

    Haslacher, H; Perkmann, T; Lukas, I; Barth, A; Ponocny-Seliger, E; Michlmayr, M; Scheichenberger, V; Wagner, O; Winker, R

    2012-12-01

    The main purpose of the study was to investigate whether baseline myeloperoxidase (MPO) levels are associated with executive cognitive function in individuals with high physical activity. Baseline serum MPO levels of 56 elderly marathon runners and 58 controls were assessed by ELISA. Standardized tests were applied to survey domain-specific cognitive functions. Changes in brain morphology were visualized by magnetic resonance imaging (MRI). High baseline serum MPO levels correlated with worse outcome in tests assessing executive cognitive function in athletes but not in the control group (NAI maze test p<0.05, Trail Making Test ratio p<0.01). In control participants, subcortical white matter hyperintensities were associated with higher scores on the Geriatric Depression Scale (p<0.05), whereas athletes seem to be protected from this effect. During strenuous exercising, MPO as well as its educts may be elevated due to increased oxygen intake and excretion of pro-inflammatory mediators inducing host tissue damage via oxidative stress. This outweighs the potential benefits of physical activity on cognitive function. PMID:22855218

  11. Target identification using laser imaging

    SciTech Connect

    Jennings, J.; Baker, M.; Barrett, J.; Ellis, B.N.; Kacerek, J.; Yee, J.

    1994-12-31

    Solid state lasers have been utilized for many varied applications. This application describes how the high peak power, short pulse capability of an alexandrite laser, in combination with a generation 3 image intensified receiver can solve the problem of very long range target identification. Applications have relevance to both commercial and military uses where day/night all weather imaging is required. Wavelength diversity provides single and multispectral system capability, therefore allowing discrimination of targets against varied backgrounds.

  12. Targeted molecular imaging in oncology.

    PubMed

    Yang, David J; Kim, E Edmund; Inoue, Tomio

    2006-01-01

    Improvement of scintigraphic tumor imaging is extensively determined by the development of more tumor specific radiopharmaceuticals. Thus, to improve the differential diagnosis, prognosis, planning and monitoring of cancer treatment, several functional pharmaceuticals have been developed. Application of molecular targets for cancer imaging, therapy and prevention using generator-produced isotopes is the major focus of ongoing research projects. Radionuclide imaging modalities (positron emission tomography, PET; single photon emission computed tomography, SPECT) are diagnostic cross-sectional imaging techniques that map the location and concentration of radionuclide-labeled radiotracers. 99mTc- and 68Ga-labeled agents using ethylenedicysteine (EC) as a chelator were synthesized and their potential uses to assess tumor targets were evaluated. 99mTc (t1/2 = 6 hr, 140 keV) is used for SPECT and 68Ga (t1/2 = 68 min, 511 keV) for PET. Molecular targets labeled with Tc-99m and Ga-68 can be utilized for prediction of therapeutic response, monitoring tumor response to treatment and differential diagnosis. Molecular targets for oncological research in (1) cell apoptosis, (2) gene and nucleic acid-based approach, (3) angiogenesis (4) tumor hypoxia, and (5) metabolic imaging are discussed. Numerous imaging ligands in these categories have been developed and evaluated in animals and humans. Molecular targets were imaged and their potential to redirect optimal cancer diagnosis and therapeutics were demonstrated. PMID:16485568

  13. Target identification by image analysis.

    PubMed

    Fetz, V; Prochnow, H; Brönstrup, M; Sasse, F

    2016-05-01

    Covering: 1997 to the end of 2015Each biologically active compound induces phenotypic changes in target cells that are characteristic for its mode of action. These phenotypic alterations can be directly observed under the microscope or made visible by labelling structural elements or selected proteins of the cells with dyes. A comparison of the cellular phenotype induced by a compound of interest with the phenotypes of reference compounds with known cellular targets allows predicting its mode of action. While this approach has been successfully applied to the characterization of natural products based on a visual inspection of images, recent studies used automated microscopy and analysis software to increase speed and to reduce subjective interpretation. In this review, we give a general outline of the workflow for manual and automated image analysis, and we highlight natural products whose bacterial and eucaryotic targets could be identified through such approaches. PMID:26777141

  14. Coherent Communications, Imaging and Targeting

    SciTech Connect

    Stappaerts, E; Baker, K; Gavel, D; Wilks, S; Olivier, S; Brase, J; Olivier, S; Brase, J

    2003-10-03

    Laboratory and field demonstration results obtained as part of the DARPA-sponsored Coherent Communications, Imaging and Targeting (CCIT) program are reviewed. The CCIT concept uses a Phase Conjugation Engine based on a quadrature receiver array, a hologram processor and a spatial light modulator (SLM) for high-speed, digital beam control. Progress on the enabling MEMS SLM, being developed by a consortium consisting of LLNL, academic institutions and small businesses, is presented.

  15. Seismoelectric imaging of shallow targets

    USGS Publications Warehouse

    Haines, S.S.; Pride, S.R.; Klemperer, S.L.; Biondi, B.

    2007-01-01

    We have undertaken a series of controlled field experiments to develop seismoelectric experimental methods for near-surface applications and to improve our understanding of seismoelectric phenomena. In a set of off-line geometry surveys (source separated from the receiver line), we place seismic sources and electrode array receivers on opposite sides of a man-made target (two sand-filled trenches) to record separately two previously documented seismoelectric modes: (1) the electromagnetic interface response signal created at the target and (2) the coseismic electric fields located within a compressional seismic wave. With the seismic source point in the center of a linear electrode array, we identify the previously undocumented seismoelectric direct field, and the Lorentz field of the metal hammer plate moving in the earth's magnetic field. We place the seismic source in the center of a circular array of electrodes (radial and circumferential orientations) to analyze the source-related direct and Lorentz fields and to establish that these fields can be understood in terms of simple analytical models. Using an off-line geometry, we create a multifold, 2D image of our trenches as dipping layers, and we also produce a complementary synthetic image through numerical modeling. These images demonstrate that off-line geometry (e.g., crosswell) surveys offer a particularly promising application of the seismoelectric method because they effectively separate the interface response signal from the (generally much stronger) coseismic and source-related fields. ?? 2007 Society of Exploration Geophysicists.

  16. Integrin Targeting for Tumor Optical Imaging

    PubMed Central

    Ye, Yunpeng; Chen, Xiaoyuan

    2011-01-01

    Optical imaging has emerged as a powerful modality for studying molecular recognitions and molecular imaging in a noninvasive, sensitive, and real-time way. Some advantages of optical imaging include cost-effectiveness, convenience, and non-ionization safety as well as complementation with other imaging modalities such as positron emission tomography (PET), single-photon emission computed tomography (SPECT), and magnetic resonance imaging (MRI). Over the past decade, considerable advances have been made in tumor optical imaging by targeting integrin receptors in preclinical studies. This review has emphasized the construction and evaluation of diverse integrin targeting agents for optical imaging of tumors in mouse models. They mainly include some near-infrared fluorescent dye-RGD peptide conjugates, their multivalent analogs, and nanoparticle conjugates for targeting integrin αvβ3. Some compounds targeting other integrin subtypes such as α4β1 and α3 for tumor optical imaging have also been included. Both in vitro and in vivo studies have revealed some promising integrin-targeting optical agents which have further enhanced our understanding of integrin expression and targeting in cancer biology as well as related anticancer drug discovery. Especially, some integrin-targeted multifunctional optical agents including nanoparticle-based optical agents can multiplex optical imaging with other imaging modalities and targeted therapy, serving as an attractive type of theranostics for simultaneous imaging and targeted therapy. Continued efforts to discover and develop novel, innovative integrin-based optical agents with improved targeting specificity and imaging sensitivity hold great promises for improving cancer early detection, diagnosis, and targeted therapy in clinic. PMID:21546996

  17. Myeloperoxidase in chronic kidney disease.

    PubMed

    Madhusudhana Rao, A; Anand, Usha; Anand, C V

    2011-01-01

    Numerous lines of evidence implicate a role of myeloperoxidase (MPO) in the pathogenesis of cardiovascular disease (CVD). It is a well accepted fact that patients with chronic kidney disease (CKD) are at an increased risk for CVD. MPO is a pro-oxidant enzyme which could be involved in the increased susceptibility of these patients to CVD. Hence, the levels of plasma MPO was determined in healthy controls as well as in patients with CKD [stratified with the level of their kidney failure as CKD stages II-V (end stage renal disease)]. Plasma MPO was assayed by a spectrophotometric method. Serum urea and creatinine were estimated on a clinical chemistry analyzer using standard laboratory procedures. The mean plasma MPO levels were significantly lower with advancing stages of renal failure (P < 0.001). There was a positive correlation between MPO and GFR (r = +0.89, P < 0.001) and a negative correlation with urea (r = -0.85, P < 0.001) and creatinine (r = -0.82, P < 0.001). While an inverse association was observed between plasma MPO and urea in CKD patients, such an association was not observed in control subjects (P = 0.43). In conclusion, the decline in plasma MPO levels may be due to the inhibitory effect of uraemic toxins on the enzyme.

  18. Spacecraft Images Comet Target's Jets

    NASA Video Gallery

    The Deep Impact spacecraft's High- and Medium-Resolution Imagers (HRI and MRI) have captured multiple jets turning on and off while the spacecraft is 8 million kilometers (5 million miles) away fro...

  19. Detecting slow moving targets in SAR images

    NASA Astrophysics Data System (ADS)

    Linnehan, Robert; Perlovsky, Leonid; Mutz, Chris W.; Schindler, John

    2004-08-01

    Ground moving target indication (GMTI) radars can detect slow-moving targets if their velocities are high enough to produce distinguishable Doppler frequencies. However, no reliable technique is currently available to detect targets that fall below the minimum detectable velocity (MDV) of GMTI radars. In synthetic aperture radar (SAR) images, detection of moving targets is difficult because of target smear due to motion, which could make low-RCS targets fall below stationary ground clutter. Several techniques for SAR imaging of moving targets have been discussed in the literature. These techniques require sufficient signal-to-clutter ratio (SCR) and adequate MDV for pre-detection. Other techniques require complex changes in hardware. Extracting the maximum information from SAR image data is possible using adaptive, model-based approaches. However, these approaches lead to computational complexity, which exceeds current processing power for more than a single object in an image. This combinatorial complexity is due to the need for having to consider a large number of combinations between multiple target models and the data, while estimating unknown parameters of the target models. We are developing a technique for detecting slow-moving targets in SAR images with low signal-to-clutter ratio, without minimal velocity requirements, and without combinatorial complexity. This paper briefly summarizes the difficulties related to current model-based detection algorithms. A new concept, dynamic logic, is introduced along with an algorithm suitable for the detection of very slow-moving targets in SAR images. This new mathematical technique is inspired by the analysis of biological systems, like the human brain, which combines conceptual understanding with emotional evaluation and overcomes the combinatorial complexity of model-based techniques.

  20. A Targeting Microbubble for Ultrasound Molecular Imaging

    PubMed Central

    Yeh, James Shue-Min; Sennoga, Charles A.; McConnell, Ellen; Eckersley, Robert; Tang, Meng-Xing; Nourshargh, Sussan; Seddon, John M.; Haskard, Dorian O.; Nihoyannopoulos, Petros

    2015-01-01

    Rationale Microbubbles conjugated with targeting ligands are used as contrast agents for ultrasound molecular imaging. However, they often contain immunogenic (strept)avidin, which impedes application in humans. Although targeting bubbles not employing the biotin-(strept)avidin conjugation chemistry have been explored, only a few reached the stage of ultrasound imaging in vivo, none were reported/evaluated to show all three of the following properties desired for clinical applications: (i) low degree of non-specific bubble retention in more than one non-reticuloendothelial tissue; (ii) effective for real-time imaging; and (iii) effective for acoustic quantification of molecular targets to a high degree of quantification. Furthermore, disclosures of the compositions and methodologies enabling reproduction of the bubbles are often withheld. Objective To develop and evaluate a targeting microbubble based on maleimide-thiol conjugation chemistry for ultrasound molecular imaging. Methods and Results Microbubbles with a previously unreported generic (non-targeting components) composition were grafted with anti-E-selectin F(ab’)2 using maleimide-thiol conjugation, to produce E-selectin targeting microbubbles. The resulting targeting bubbles showed high specificity to E-selectin in vitro and in vivo. Non-specific bubble retention was minimal in at least three non-reticuloendothelial tissues with inflammation (mouse heart, kidneys, cremaster). The bubbles were effective for real-time ultrasound imaging of E-selectin expression in the inflamed mouse heart and kidneys, using a clinical ultrasound scanner. The acoustic signal intensity of the targeted bubbles retained in the heart correlated strongly with the level of E-selectin expression (|r|≥0.8), demonstrating a high degree of non-invasive molecular quantification. Conclusions Targeting microbubbles for ultrasound molecular imaging, based on maleimide-thiol conjugation chemistry and the generic composition described

  1. THz polarization difference imaging of aqueous targets

    NASA Astrophysics Data System (ADS)

    Sung, Shijun; Bajwa, Neha; Ramirez, Lucia; Grundfest, Warren; Taylor, Zachary

    2015-08-01

    This paper describes the basic design, implementation, and testing of a polarization difference imaging system for use on aqueous targets. The ultimate performance limitation of THz imaging in many active areas of research is clutter from surface geometry. While the signal to nose ratio (SNR) of standard THz imaging systems is quite large, the signal to clutter ratio (SCR) often faced in an imaging application is orders of magnitude lower and, in many cases, lower than the contrast to noise (CNR) resulting in imagery where the contrast mechanism of interest does not significantly contribute to the overall observed contrast. To overcome these limitations we develop a system that uses a circularly polarized source and linearly polarized detectors to acquire images of transverse electric (TE) and transverse magnetic (TM) reflectivities of the target over the same field of view. Geletin based tissue mimicking phantoms are fabricated with spatially varying water content and modified with a range of surface topologies and surface roughness. TE and TM images are combined to yield self-calibrated clutter-suppressed images. The resulting image indicates that the imaging field clutter affected both polarization channels nearly equally allowing the system to resolve differences in phantom water content. This design is a step toward windowless THz imaging capability critical for clinical translation where patient imaging is dominated by clutter.

  2. Automatic target detection in cluttered IR images

    NASA Astrophysics Data System (ADS)

    Mueller, Markus; Korn, Axel

    1998-07-01

    Automatic target detection (ATR) generally refers to the localization of potential targets by computer processing of data from a variety of sensors. Automatic detection is applicable for data reduction purposes in the reconnaissance domain and is therefore aimed at reducing the workload on human operators. ATR covers activities such as the localization of individual objects in large areas or volumes for assessing the battlefield simulation. An increase of reliability and efficiency of the overall reconnaissance process is expected. The results of automatic image evaluation are offered to the image analyst as hypotheses. In this paper cluttered images from an infrared sensor are analyzed with the aim of finding Regions of Interest (ROIs), where hints for man-made objects have to be found. This analysis uses collateral data from acquisition time and location (e.g. day time, weather condition, resolution, sensor specification and orientation etc.). The assumed target size in the image is also compared by using collateral data. Based on the collateral data, the algorithm adjusts its parameters in order to find ROIs and to detect targets. Low contrast conditions can be successfully tackled if the directions of the grey value gradient are considered, which are nearly independent of the contrast. Blobs are generated by applying adaptive thresholds in the ROIs. Here the evaluation of histograms is very important for the extraction of structured features. The height, aspect angle, and camera parameters are approximately known for an estimation of target sizes in the image domain out of the collateral data.

  3. Target plane imager for inertial confinement fusion

    SciTech Connect

    Swift, C.D.; Bliss, E.S.; Jones, W.A.; Seppala, L.G.

    1985-01-30

    The Nova laser, completed in December 1984 at Lawrence Livermore National Laboratory, is being used to conduct inertial confinement fusion experiments. It is capable of focusing more than 100 kJ of energy on small fusion targets. This paper discusses an optical system called the target plane imager that is used during the beam alignment phase of these experiments. The TPI includes a three meter long periscope with a wide field of view, F/3 objective. The telescope relays images of the target focal plane to viewing optics and a video sensor located outside the target chamber. Operation of the system is possible at three wavelengths: 1.05..mu.., 0.527..mu.., and 0.351..mu... These are the three wavelengths at which the ten Nova laser beams can irradiate targets. Both nearfield and farfield images of the ten beams can be viewed with the TPI. This instrument is used to properly align the laser to the target before each target irradiation.

  4. Imaging efficacy of a targeted imaging agent for fluorescence endoscopy

    NASA Astrophysics Data System (ADS)

    Healey, A. J.; Bendiksen, R.; Attramadal, T.; Bjerke, R.; Waagene, S.; Hvoslef, A. M.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. A significant unmet clinical need exists in the area of screening for earlier and more accurate diagnosis and treatment. We have identified a fluorescence imaging agent targeted to an early stage molecular marker for colorectal cancer. The agent is administered intravenously and imaged in a far red imaging channel as an adjunct to white light endoscopy. There is experimental evidence of preclinical proof of mechanism for the agent. In order to assess potential clinical efficacy, imaging was performed with a prototype fluorescence endoscope system designed to produce clinically relevant images. A clinical laparoscope system was modified for fluorescence imaging. The system was optimised for sensitivity. Images were recorded at settings matching those expected with a clinical endoscope implementation (at video frame rate operation). The animal model was comprised of a HCT-15 xenograft tumour expressing the target at concentration levels expected in early stage colorectal cancer. Tumours were grown subcutaneously. The imaging agent was administered intravenously at a dose of 50nmol/kg body weight. The animals were killed 2 hours post administration and prepared for imaging. A 3-4mm diameter, 1.6mm thick slice of viable tumour was placed over the opened colon and imaged with the laparoscope system. A receiver operator characteristic analysis was applied to imaging results. An area under the curve of 0.98 and a sensitivity of 87% [73, 96] and specificity of 100% [93, 100] were obtained.

  5. Improved target identification using synthetic infrared images

    NASA Astrophysics Data System (ADS)

    Weber, Bruce A.; Penn, Joseph A.

    2002-07-01

    The performance of infrared (IR) target identification classifiers, trained on randomly selected subsets of target chips taken from larger databases of either synthetic or measured data, is shown to improve rapidly with increasing subset size. This increase continues until the new data no longer provides additional information, or the classifier can not handle the information, at which point classifier performance levels off. It will also be shown that subsets of data selected with advanced knowledge can significantly outperform randomly selected sets, suggesting that classifier training-sets must be carefully selected if optimal performance is desired. Performance will also be shown to be subject to the quality of data used to train the classifier. Thus while increasing training set size generally improves classifier performance, the level to which the classifier performance can be raised will be shown to depend on the similarity between the training data and testing data. In fact, if the training data to be added to a given set of training data is unlike the testing data, performance will often not improve and may possibly diminish. Having too much data can reduce performance as much as having too little. Our results again demonstrate that an infrared (IR) target-identification classifier, trained on synthetic images of targets and tested on measured images, can perform as well as a classifier trained on measured images alone. We also demonstrate that the combination of the measured and the synthetic image databases can be used to train a classifier whose performance exceeds that of classifiers trained on either database alone. Results suggest that it may be possible to select data subsets from image databases that can optimize target classifiers performance for specific locations and operational scenarios.

  6. Neutrophil myeloperoxidase and its substrates: formation of specific markers and reactive compounds during inflammation

    PubMed Central

    Kato, Yoji

    2016-01-01

    Myeloperoxidase is an inflammatory enzyme that generates reactive hypochlorous acid in the presence of hydrogen peroxide and chloride ion. However, this enzyme also uses bromide ion or thiocyanate as a substrate to form hypobromous or hypothiocyanous acid, respectively. These species play important roles in host defense against the invasion of microorganisms. In contrast, these enzyme products modify biomolecules in hosts during excess inflammation, indicating that the action of myeloperoxidase is both beneficial and harmful. Myeloperoxidase uses other endogenous compounds, such as serotonin, urate, and l-tyrosine, as substrates. This broad-range specificity may have some biological implications. Target molecules of this enzyme and its products vary, including low-molecular weight thiols, proteins, nucleic acids, and lipids. The modified products represent biomarkers of myeloperoxidase action. Moderate inhibition of this enzyme might be critical for the prevention/modulation of excess, uncontrolled inflammatory events. Some phytochemicals inhibit myeloperoxidase, which might explain the reductive effect caused by the intake of vegetables and fruits on cardiovascular diseases. PMID:27013775

  7. Design of Targeted Cardiovascular Molecular Imaging Probes

    PubMed Central

    Anderson, Carolyn J.; Bulte, Jeff W.M.; Chen, Kai; Chen, Xiaoyuan; Khaw, Ban-An; Shokeen, Monica; Wooley, Karen L.; VanBrocklin, Henry F.

    2013-01-01

    Molecular imaging relies on the development of sensitive and specific probes coupled with imaging hardware and software to provide information about the molecular status of a disease and its response to therapy, which are important aspects of disease management. As genomic and proteomic information from a variety of cardiovascular diseases becomes available, new cellular and molecular targets will provide an imaging readout of fundamental disease processes. A review of the development and application of several cardiovascular probes is presented here. Strategies for labeling cells with superparamagnetic iron oxide nanoparticles enable monitoring of the delivery of stem cell therapies. Small molecules and biologics (e.g., proteins and antibodies) with high affinity and specificity for cell surface receptors or cellular proteins as well as enzyme substrates or inhibitors may be labeled with single-photon–emitting or positron-emitting isotopes for nuclear molecular imaging applications. Labeling of bispecific antibodies with single-photon–emitting isotopes coupled with a pretargeting strategy may be used to enhance signal accumulation in small lesions. Emerging nanomaterials will provide platforms that have various sizes and structures and that may be used to develop multimeric, multimodal molecular imaging agents to probe one or more targets simultaneously. These platforms may be chemically manipulated to afford molecules with specific targeting and clearance properties. These examples of molecular imaging probes are characteristic of the multidisciplinary nature of the extraction of advanced biochemical information that will enhance diagnostic evaluation and drug development and predict clinical outcomes, fulfilling the promise of personalized medicine and improved patient care. PMID:20395345

  8. Stroma Targeting Nuclear Imaging and Radiopharmaceuticals

    PubMed Central

    Shetty, Dinesh; Jeong, Jae-Min; Shim, Hyunsuk

    2012-01-01

    Malignant transformation of tumor accompanies profound changes in the normal neighboring tissue, called tumor stroma. The tumor stroma provides an environment favoring local tumor growth, invasion, and metastatic spreading. Nuclear imaging (PET/SPECT) measures biochemical and physiologic functions in the human body. In oncology, PET/SPECT is particularly useful for differentiating tumors from postsurgical changes or radiation necrosis, distinguishing benign from malignant lesions, identifying the optimal site for biopsy, staging cancers, and monitoring the response to therapy. Indeed, PET/SPECT is a powerful, proven diagnostic imaging modality that displays information unobtainable through other anatomical imaging, such as CT or MRI. When combined with coregistered CT data, [18F]fluorodeoxyglucose ([18F]FDG)-PET is particularly useful. However, [18F]FDG is not a target-specific PET tracer. This paper will review the tumor microenvironment targeting oncologic imaging such as angiogenesis, invasion, hypoxia, growth, and homing, and also therapeutic radiopharmaceuticals to provide a roadmap for additional applications of tumor imaging and therapy. PMID:22685650

  9. Image understanding research for automatic target recognition

    SciTech Connect

    Bhanu, B. ); Jones, T.L. )

    1993-10-01

    Automatic Target Recognition (ATR) is an extremely important capability for defense applications. Many aspects of Image Understanding (IU) research are traditionally used to solve ATR problems. In this paper, the authors discuss ATR applications and problems in developing real-world ATR systems, and present the status of technology for these systems. They identify several IU problems that need to be resolved in order to enhance the effectiveness of ATR-based weapon systems. Finally, they conclude that technological gains in developing robust ATR systems will also lead to significant advances in many other areas of applications of image understanding.

  10. Multiresolution target discrimination during image formation

    NASA Astrophysics Data System (ADS)

    Kaplan, Lance M.; Oh, Seung-Mok; McClellan, James H.

    2000-08-01

    This paper presents a novel scheme to detect and discriminate landmines from other clutter objects during the image formation process for ultra-wideband (UWB) synthetic aperture radar (SAR) systems. By identifying likely regions containing the targets of interest, i.e., landmines, it is possible to speed up the overall formation time by pruning the processing to resolve regions that do not contain targets. The image formation algorithm is a multiscale approximation to standard backprojection known as the quadtree that uses a 'divide-and- conquer' strategy. The intermediate quadtree data admits multiresolution representations of the scene, and we develop a contrast statistic to discriminate structured/diffuse regions and an aperture diversity statistic to discriminate between regions containing mines and desert scrub. The potential advantages of this technique are illustrated using data collected at Yuma, AZ by the ARL BoomSAR system.

  11. Target image search using fMRI signals

    NASA Astrophysics Data System (ADS)

    Xiong, Shi; Song, Sutao; Zhan, Yu; Zhang, Jiacai

    2014-03-01

    Recent neural signal decoding studies based on functional magnetic resonance imaging (fMRI) have identified the specific image presenting to the subject from a set of potential images, and some studies extend neural decoding into image reconstruction, i.e. image contents that the subject perceived were decoded from the fMRI signals recorded during the subject looking at images. In this paper, we decoded the target images using fMRI signals and described a target image searching method based on the relationship between target image stimuli and fMRI activity. We recorded fMRI data during a serial visual stimuli image presentation task, some of the stimuli images were target images and the rest images were non-target ones. Our fMRI data analysis results showed that in the serial visual presentation task, target images elicited a stereotypical response in the fMRI, which can be detected by multi-voxel pattern analysis (MVPA). Classifiers designed with support vector machine (SVM) used this response to decipher target images from non-target images. The leave-one-run-out cross-validation showed that we can pick out the target images with a possibility far above the chance level, which indicate that there's a neural signatures correlated with the target image recognition process in the human systems.

  12. Specific Sequence Motifs Direct the Oxygenation and Chlorination of Tryptophan by Myeloperoxidase

    PubMed Central

    Fu, Xiaoyun; Wang, Yi; Kao, Jeffery; Irwin, Angela; d’Avignon, André; Mecham, Robert P.; Parks, William C.; Heinecke, Jay W.

    2008-01-01

    Most studies of protein oxidation have typically focused on the reactivity of single amino acid side chains while ignoring the potential importance of adjacent sequences in directing the reaction pathway. We previously showed that hypochlorous acid (HOCl), a specific product of myeloperoxidase, inactivates matrilysin by modifying adjacent tryptophan and glycine (WG) residues in the catalytic domain. Here, we use model peptides that mimic the region of matrilysin involved in this reaction, VVWGTA, VVWATA and the library VVWXTA, to determine whether specific sequence motifs are targeted for chlorination or oxygenation by myeloperoxidase. Our results demonstrate that HOCl generated by myeloperoxidase or activated neutrophils converts the peptide VVWGTA to a chlorinated product, WG+32(Cl). Tandem mass spectrometry in concert with high resolution 1H and two-dimensional NMR analysis revealed that the modification required cross-linking of the tryptophan to the amide of glycine followed by chlorination of the indole ring of tryptophan. In contrast, when glycine in the peptide was replaced with alanine, the major products were mono- and di-oxygenated tryptophan residues. When the peptide library VVWXTA (where X represents all 20 common amino acids) was exposed to HOCl, only WG produced a high yield of the chloroindolenine derivative. However, when glycine was replaced by other amino acids, oxygenated tryptophan derivatives were the major products. Our observations indicate that WG may represent a specific sequence motif in proteins that is targeted for chlorination by myeloperoxidase. PMID:16548523

  13. Flash trajectory imaging of target 3D motion

    NASA Astrophysics Data System (ADS)

    Wang, Xinwei; Zhou, Yan; Fan, Songtao; He, Jun; Liu, Yuliang

    2011-03-01

    We present a flash trajectory imaging technique which can directly obtain target trajectory and realize non-contact measurement of motion parameters by range-gated imaging and time delay integration. Range-gated imaging gives the range of targets and realizes silhouette detection which can directly extract targets from complex background and decrease the complexity of moving target image processing. Time delay integration increases information of one single frame of image so that one can directly gain the moving trajectory. In this paper, we have studied the algorithm about flash trajectory imaging and performed initial experiments which successfully obtained the trajectory of a falling badminton. Our research demonstrates that flash trajectory imaging is an effective approach to imaging target trajectory and can give motion parameters of moving targets.

  14. Neutrophil myeloperoxidase destruction by ultraviolet irradiation

    SciTech Connect

    Hanker, J.; Giammara, B.; Strauss, G.

    1988-01-01

    The peroxidase activity of enriched leukocyte preparations on coverslips was determined cytochemically with a newly developed method. The techniques utilizes diaminobenzidine medium and cupric nitrate intensification and is suitable for analysis with light microscopy, SEM, and TEM. Blood specimens from control individuals were studied with and without in vitro UV irradiation and compared with those from psoriasis patients exposed therapeutically to various types of UV in phototherapy. All UV irradiated samples showed diminished neutrophil myeloperoxidase (MP) activity although that of the principal eosinophil peroxidase was unaffected. The SEMs supported the contention that decreased neutrophil MP activity might be related to UV induced degranulation. It is believed to be possible, eventually, to equate the observed MP degranulation effect after UV irradiation with diminished ability to fight bacterial infections.

  15. Target detection in hyperspectral Imaging using logistic regression

    NASA Astrophysics Data System (ADS)

    Lo, Edisanter; Ientilucci, Emmett

    2016-05-01

    Target detection is an important application in hyperspectral imaging. Conventional algorithms for target detection assume that the pixels have a multivariate normal distribution. The pixels in most images do not have multivariate normal distributions. The logistic regression model, which does not require the assumption of multivariate normal distribution, is proposed in this paper as a target detection algorithm. Experimental results show that the logistic regression model can work well in target detection.

  16. Potent Reversible Inhibition of Myeloperoxidase by Aromatic Hydroxamates*

    PubMed Central

    Forbes, Louisa V.; Sjögren, Tove; Auchère, Françoise; Jenkins, David W.; Thong, Bob; Laughton, David; Hemsley, Paul; Pairaudeau, Garry; Turner, Rufus; Eriksson, Håkan; Unitt, John F.; Kettle, Anthony J.

    2013-01-01

    The neutrophil enzyme myeloperoxidase (MPO) promotes oxidative stress in numerous inflammatory pathologies by producing hypohalous acids. Its inadvertent activity is a prime target for pharmacological control. Previously, salicylhydroxamic acid was reported to be a weak reversible inhibitor of MPO. We aimed to identify related hydroxamates that are good inhibitors of the enzyme. We report on three hydroxamates as the first potent reversible inhibitors of MPO. The chlorination activity of purified MPO was inhibited by 50% by a 5 nm concentration of a trifluoromethyl-substituted aromatic hydroxamate, HX1. The hydroxamates were specific for MPO in neutrophils and more potent toward MPO compared with a broad range of redox enzymes and alternative targets. Surface plasmon resonance measurements showed that the strength of binding of hydroxamates to MPO correlated with the degree of enzyme inhibition. The crystal structure of MPO-HX1 revealed that the inhibitor was bound within the active site cavity above the heme and blocked the substrate channel. HX1 was a mixed-type inhibitor of the halogenation activity of MPO with respect to both hydrogen peroxide and halide. Spectral analyses demonstrated that hydroxamates can act variably as substrates for MPO and convert the enzyme to a nitrosyl ferrous intermediate. This property was unrelated to their ability to inhibit MPO. We propose that aromatic hydroxamates bind tightly to the active site of MPO and prevent it from producing hypohalous acids. This mode of reversible inhibition has potential for blocking the activity of MPO and limiting oxidative stress during inflammation. PMID:24194519

  17. INACTIVATION OF MYELOPEROXIDASE BY BENZOIC ACID HYDRAZIDE*

    PubMed Central

    Huang, Jiansheng; Smith, Forrest; Panizzi, Jennifer R.; Goodwin, Douglas C.; Panizzi, Peter

    2015-01-01

    Myeloperoxidase (MPO) is expressed by myeloid cells for the purpose of catalyzing the formation of hypochlorous acid, from chloride ions and reaction with a hydrogen peroxide-charged heme covalently bound to the enzyme. Most peroxidase enzymes both plant and mammalian are inhibited by benzoic acid hydrazide (BAH)-containing compounds, but the mechanism underlying MPO inhibition by BAH compounds is largely unknown. Recently, we reported MPO inhibition by BAH and 4-(trifluoromethyl)-BAH was due to hydrolysis of the ester bond between MPO heavy chain glutamate 242 (Glu242) residue and the heme pyrrole A ring, freeing the heme linked light chain MPO subunit from the larger remaining heavy chain portion. Here we probed the structure and function relationship behind this ester bond cleavage using a panel of BAH analogs to gain insight into the constraints imposed by the MPO active site and channel leading to the buried protoporphyrin IX ring. In addition, we show evidence that destruction of the heme ring does not occur by tracking the heme prosthetic group and provide evidence that the mechanism of hydrolysis follows a potential attack of the Glu242 carbonyl leading to a rearrangement causing the release of the vinyl-sulfonium linkage between HC-Met243 and the pyrrole A ring. PMID:25688920

  18. Metrics for image-based modeling of target acquisition

    NASA Astrophysics Data System (ADS)

    Fanning, Jonathan D.

    2012-06-01

    This paper presents an image-based system performance model. The image-based system model uses an image metric to compare a given degraded image of a target, as seen through the modeled system, to the set of possible targets in the target set. This is repeated for all possible targets to generate a confusion matrix. The confusion matrix is used to determine the probability of identifying a target from the target set when using a particular system in a particular set of conditions. The image metric used in the image-based model should correspond closely to human performance. The image-based model performance is compared to human perception data on Contrast Threshold Function (CTF) tests, naked eye Triangle Orientation Discrimination (TOD), and TOD including an infrared camera system. Image-based system performance modeling is useful because it allows modeling of arbitrary image processing. Modern camera systems include more complex image processing, much of which is nonlinear. Existing linear system models, such as the TTP metric model implemented in NVESD models such as NV-IPM, assume that the entire system is linear and shift invariant (LSI). The LSI assumption makes modeling nonlinear processes difficult, such as local area processing/contrast enhancement (LAP/LACE), turbulence reduction, and image fusion.

  19. Fluorescent imaging of cancerous tissues for targeted surgery

    PubMed Central

    Bu, Lihong; Shen, Baozhong; Cheng, Zhen

    2014-01-01

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

  20. Superoxide-dependent oxidation of melatonin by myeloperoxidase.

    PubMed

    Ximenes, Valdecir F; Silva, Sueli de O; Rodrigues, Maria R; Catalani, Luiz H; Maghzal, Ghassan J; Kettle, Anthony J; Campa, Ana

    2005-11-18

    Myeloperoxidase uses hydrogen peroxide to oxidize numerous substrates to hypohalous acids or reactive free radicals. Here we show that neutrophils oxidize melatonin to N(1)-acetyl-N(2)-formyl-5-methoxykynuramine (AFMK) in a reaction that is catalyzed by myeloperoxidase. Production of AFMK was highly dependent on superoxide but not hydrogen peroxide. It did not require hypochlorous acid, singlet oxygen, or hydroxyl radical. Purified myeloperoxidase and a superoxide-generating system oxidized melatonin to AFMK and a dimer. The dimer would result from coupling of melatonin radicals. Oxidation of melatonin was partially inhibited by catalase or superoxide dismutase. Formation of AFMK was almost completely eliminated by superoxide dismutase but weakly inhibited by catalase. In contrast, production of melatonin dimer was enhanced by superoxide dismutase and blocked by catalase. We propose that myeloperoxidase uses superoxide to oxidize melatonin by two distinct pathways. One pathway involves the classical peroxidation mechanism in which hydrogen peroxide is used to oxidize melatonin to radicals. Superoxide adds to these radicals to form an unstable peroxide that decays to AFMK. In the other pathway, myeloperoxidase uses superoxide to insert dioxygen into melatonin to form AFMK. This novel activity expands the types of oxidative reactions myeloperoxidase can catalyze. It should be relevant to the way neutrophils use superoxide to kill bacteria and how they metabolize xenobiotics. PMID:16148002

  1. Camouflage target reconnaissance based on hyperspectral imaging technology

    NASA Astrophysics Data System (ADS)

    Hua, Wenshen; Guo, Tong; Liu, Xun

    2015-08-01

    Efficient camouflaged target reconnaissance technology makes great influence on modern warfare. Hyperspectral images can provide large spectral range and high spectral resolution, which are invaluable in discriminating between camouflaged targets and backgrounds. Hyperspectral target detection and classification technology are utilized to achieve single class and multi-class camouflaged targets reconnaissance respectively. Constrained energy minimization (CEM), a widely used algorithm in hyperspectral target detection, is employed to achieve one class camouflage target reconnaissance. Then, support vector machine (SVM), a classification method, is proposed to achieve multi-class camouflage target reconnaissance. Experiments have been conducted to demonstrate the efficiency of the proposed method.

  2. Insights into myeloperoxidase biosynthesis from its inherited deficiency.

    PubMed

    Nauseef, W M

    1998-09-01

    Myeloperoxidase (MPO) is a heme protein present in the granules of neutrophils and monocytes. The activated neutrophil releases MPO into the phagolysosome or into the extracellular space in response to a variety of agonists. During concomitant activation of the NADPH-dependent oxidase, the stimulated neutrophil also generates hydrogen peroxide, and in this way the MPO-hydrogen peroxide-halide system exerts its potent microbicidal activity. Recent interest in MPO has extended well beyond the domain of innate host defense against infection and includes generalized inflammatory diseases, atherosclerosis, and degenerative neurologic diseases. Search of the various data banks using the cDNA sequence for MPO has uncovered previously unsuspected relationships among peroxidatively active proteins in widely different species. In addition, application of the analytical tools of cell and molecular biology has allowed definition of specific genotypes underlying MPO deficiency and the impact of particular mutations on the fate of MPO precursors along the biosynthetic pathway. In parallel, such studies have allowed significant advances in understanding of the normal steps in MPO biosynthesis and intracellular targeting.

  3. Target model and simulation for laser imaging fuze

    NASA Astrophysics Data System (ADS)

    Li, Weiheng; Song, Chengtian

    2013-09-01

    Image detection is an important direction of fuze development nowadays, and laser imaging fuze is one of the main technologies. This paper carries out the research in simulation technology of the process with detection, scan and imaging, which is used in laser imaging fuze for tank target, and get the simulation images information of different intersection conditions, including tank spot information,distance information and power information. The target coordinate system is established with the movement characteristics,physical characteristics and existing coordinate system of tank target. And through transferring missile coordinates to the target coordinate system as well as the relative movement between the different time intervals, the model of missile-target in time and space is build up. The model is build up according to the tank target and diffusion properties of different background, including desert, soil, vegetation, and buildings. The relations of scattering power and bidirectional reflectance distribution function deduced the laser echo power calculation formula, which can calculate the echoes incidence to each surface of the laser.The design of laser imaging fuze simulation system is complicated ,which contains the technology of the process with detection, scan and imaging used in laser imaging fuze for tank target. The simulation system products the tank spot picture, the distance gradation picture, and the power gradation picture. The latter two contains two-dimensional information, the scanning distance as well as the value of echo power to meet the expected design effects.

  4. Advance of Molecular Imaging Technology and Targeted Imaging Agent in Imaging and Therapy

    PubMed Central

    Chen, Zhi-Yi; Wang, Yi-Xiang; Lin, Yan; Zhang, Jin-Shan; Yang, Feng; Zhou, Qiu-Lan; Liao, Yang-Ying

    2014-01-01

    Molecular imaging is an emerging field that integrates advanced imaging technology with cellular and molecular biology. It can realize noninvasive and real time visualization, measurement of physiological or pathological process in the living organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. Molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imaging signal with molecular event. Recently, the application of new emerging chemical technology and nanotechnology has stimulated the development of imaging agents. Nanoparticles modified with small molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. Therapeutic drug or gene is incorporated into nanoparticles to construct multifunctional imaging agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imaging, the novel imaging agent including targeted imaging agent and multifunctional imaging agent, as well as cite some examples of their application in molecular imaging and therapy. PMID:24689058

  5. Detecting and tracking small moving target in infrared image sequence

    NASA Astrophysics Data System (ADS)

    Yan, Hong-lei; Huang, Geng-hua; Wang, Hai-wei; Shu, Rong

    2013-09-01

    Nowadays, infrared imaging systems play important roles in the field of civil and military. Especially small infrared target detecting and recognizing is one of the most widely use. The capability of target-detection algorithm is an important index of the system. This paper presents a novel algorithm for detecting a small moving target in infrared (IR) image sequences and finding its mass center, and recording the target moving track. In the target searching and recognizing algorithm of infrared image sequences, infrared image sequence is broken into frames, filtered by spatial filter algorithm, which helped to reduce granular noise. We use the Canny algorithm factor to find the edge of the target, and the result of detecting target edge is process by ecological open-loop filter method, including erosion and dilation algorithm with a same scale. Then, the candidate targets are recognized and saved temporarily. In order to get the mass centers of the candidate targets, the valid area of the candidate targets is defined by different weight valves, and then the mass centers are calculated by weighted average algorithm, and record per frame. After got several frames mass centers of the candidate targets, we get rid of the non-target mass centers by frame difference algorithm, and get the real mass center of the small moving infrared target. If the background is observed for enough time, the effect of frame difference algorithm is more efficiency. Finally, the moving track of the target is found out. The infrared (IR) image sequences used here are obtained through an IR camera in the laboratory, which uses a 288*384 silicon infrared image sensor produced by ULIS company. The methods referred above are realized and simulated on compute with Matlab. Theory analysis and experiments prove the method is reasonable and efficient.

  6. Target recognition for ladar range image using slice image

    NASA Astrophysics Data System (ADS)

    Xia, Wenze; Han, Shaokun; Wang, Liang

    2015-12-01

    A shape descriptor and a complete shape-based recognition system using slice images as geometric feature descriptor for ladar range images are introduced. A slice image is a two-dimensional image generated by three-dimensional Hough transform and the corresponding mathematical transformation. The system consists of two processes, the model library construction and recognition. In the model library construction process, a series of range images are obtained after the model object is sampled at preset attitude angles. Then, all the range images are converted into slice images. The number of slice images is reduced by clustering analysis and finding a representation to reduce the size of the model library. In the recognition process, the slice image of the scene is compared with the slice image in the model library. The recognition results depend on the comparison. Simulated ladar range images are used to analyze the recognition and misjudgment rates, and comparison between the slice image representation method and moment invariants representation method is performed. The experimental results show that whether in conditions without noise or with ladar noise, the system has a high recognition rate and low misjudgment rate. The comparison experiment demonstrates that the slice image has better representation ability than moment invariants.

  7. Molecular Targeted Viral Nanoparticles as Tools for Imaging Cancer

    PubMed Central

    Cho, C.F.; Sourabh, S.; Simpson, E.J.; Steinmetz, N.F.; Luyt, L.G.; Lewis, J.D.

    2015-01-01

    Viral nanoparticles (VNPs) are a novel class of bionanomaterials that harness the natural biocompatibility of viruses for the development of therapeutics, vaccines, and imaging tools. The plant virus, cowpea mosaic virus (CPMV), has been successfully engineered to create novel cancer-targeted imaging agents by incorporating fluorescent dyes, polyethylene glycol (PEG) polymers, and targeting moieties. Using straightforward conjugation strategies, VNPs with high selectivity for cancer-specific molecular targets can be synthesized for in vivo imaging of tumors. Here we describe the synthesis and purification of CPMV-based VNPs, the functionalization of these VNPs using click chemistry, and their use for imaging xenograft tumors in animal models. VNPs decorated with fluorescent dyes, PEG, and targeting ligands can be synthesized in one day, and imaging studies can be performed over hours, days, or weeks, depending on the application. PMID:24243252

  8. Improved target detection by IR dual-band image fusion

    NASA Astrophysics Data System (ADS)

    Adomeit, U.; Ebert, R.

    2009-09-01

    Dual-band thermal imagers acquire information simultaneously in both the 8-12 μm (long-wave infrared, LWIR) and the 3-5 μm (mid-wave infrared, MWIR) spectral range. Compared to single-band thermal imagers they are expected to have several advantages in military applications. These advantages include the opportunity to use the best band for given atmospheric conditions (e. g. cold climate: LWIR, hot and humid climate: MWIR), the potential to better detect camouflaged targets and an improved discrimination between targets and decoys. Most of these advantages have not yet been verified and/or quantified. It is expected that image fusion allows better exploitation of the information content available with dual-band imagers especially with respect to detection of targets. We have developed a method for dual-band image fusion based on the apparent temperature differences in the two bands. This method showed promising results in laboratory tests. In order to evaluate its performance under operational conditions we conducted a field trial in an area with high thermal clutter. In such areas, targets are hardly to detect in single-band images because they vanish in the clutter structure. The image data collected in this field trial was used for a perception experiment. This perception experiment showed an enhanced target detection range and reduced false alarm rate for the fused images compared to the single-band images.

  9. 3-D Target Location from Stereoscopic SAR Images

    SciTech Connect

    DOERRY,ARMIN W.

    1999-10-01

    SAR range-Doppler images are inherently 2-dimensional. Targets with a height offset lay over onto offset range and azimuth locations. Just which image locations are laid upon depends on the imaging geometry, including depression angle, squint angle, and target bearing. This is the well known layover phenomenon. Images formed with different aperture geometries will exhibit different layover characteristics. These differences can be exploited to ascertain target height information, in a stereoscopic manner. Depending on the imaging geometries, height accuracy can be on the order of horizontal position accuracies, thereby rivaling the best IFSAR capabilities in fine resolution SAR images. All that is required for this to work are two distinct passes with suitably different geometries from any plain old SAR.

  10. Snapshot spectral and polarimetric imaging; target identification with multispectral video

    NASA Astrophysics Data System (ADS)

    Bartlett, Brent D.; Rodriguez, Mikel D.

    2013-05-01

    As the number of pixels continue to grow in consumer and scientific imaging devices, it has become feasible to collect the incident light field. In this paper, an imaging device developed around light field imaging is used to collect multispectral and polarimetric imagery in a snapshot fashion. The sensor is described and a video data set is shown highlighting the advantage of snapshot spectral imaging. Several novel computer vision approaches are applied to the video cubes to perform scene characterization and target identification. It is shown how the addition of spectral and polarimetric data to the video stream allows for multi-target identification and tracking not possible with traditional RGB video collection.

  11. Size-varying small target detection for infrared image processing

    NASA Astrophysics Data System (ADS)

    Li, Miao; Zhu, Ran; Long, Yunli; An, Wei; Zhou, Yiyu

    2015-10-01

    IRST (Infrared Search and Track) has been applied to many military or civil fields such as precise guidance, aerospace, early warning. As a key technique, small target detection based on infrared image plays an important role. However, infrared targets have their own characteristics, such as target size variation, which make the detection work quite difficult. In practical application, the target size may vary due to many reasons, such as optic angle of sensors, imaging distance, environment and so on. For conventional detection methods, it is difficult to detect such size-varying targets, especially when the backgrounds have strong clutters. This paper presents a novel method to detect size-varying infrared targets in a cluttered background. It is easy to find that the target region is salient in infrared images. It means that target region have a signature of discontinuity with its neighboring regions and concentrates in a relatively small region, which can be considered as a homogeneous compact region, and the background is consistent with its neighboring regions. Motivated by the saliency feature and gradient feature, we introduce minimum target intensity (MTI) to measure the dissimilarity between different scales, and use mean gradient to restrict the target scale in a reasonable range. They are integrated to be multiscale MTI filter. The proposed detection method is designed based on multiscale MTI filter. Firstly, salient region is got by morphological low-pass filtering, where the potential target exists in. Secondly, the candidate target regions are extracted by multiscale minimum target intensity filter, which can effectively give the optimal target size. At last, signal-to-clutter ratio (SCR) is used to segment targets, which is computed based on optimal scale of candidate targets. The experimental results indicate that the proposed method can achieve both higher detection precision and robustness in complex background.

  12. Target recognition in passive terahertz image of human body

    NASA Astrophysics Data System (ADS)

    Zhao, Ran; Zhao, Yuan-meng; Deng, Chao; Zhang, Cun-lin; Li, Yue

    2014-11-01

    THz radiation can penetrate through many nonpolar dielectric materials and can be used for nondestructive/noninvasive sensing and imaging of targets under nonpolar, nonmetallic covers or containers. Thus using THz systems to "see through" concealing barriers (i.e. packaging, corrugated cardboard, clothing) has been proposed as a new security screening method. Objects that can be detected by THz include concealed weapons, explosives, and chemical agents under clothing. Passive THz imaging system can detect THz wave from human body without transmit any electromagnetic wave, and the suspicious objects will become visible because the THz wave is blocked by this items. We can find out whether or not someone is carrying dangerous objects through this image. In this paper, the THz image enhancement, segmentation and contour extraction algorithms were studied to achieve effective target image detection. First, the terahertz images are enhanced and their grayscales are stretched. Then we apply global threshold segmentation to extract the target, and finally the targets are marked on the image. Experimental results showed that the algorithm proposed in this paper can extract and mark targets effectively, so that people can identify suspicious objects under clothing quickly. The algorithm can significantly improve the usefulness of the terahertz security apparatus.

  13. Feature-aided multiple target tracking in the image plane

    NASA Astrophysics Data System (ADS)

    Brown, Andrew P.; Sullivan, Kevin J.; Miller, David J.

    2006-05-01

    Vast quantities of EO and IR data are collected on airborne platforms (manned and unmanned) and terrestrial platforms (including fixed installations, e.g., at street intersections), and can be exploited to aid in the global war on terrorism. However, intelligent preprocessing is required to enable operator efficiency and to provide commanders with actionable target information. To this end, we have developed an image plane tracker which automatically detects and tracks multiple targets in image sequences using both motion and feature information. The effects of platform and camera motion are compensated via image registration, and a novel change detection algorithm is applied for accurate moving target detection. The contiguous pixel blob on each moving target is segmented for use in target feature extraction and model learning. Feature-based target location measurements are used for tracking through move-stop-move maneuvers, close target spacing, and occlusion. Effective clutter suppression is achieved using joint probabilistic data association (JPDA), and confirmed target tracks are indicated for further processing or operator review. In this paper we describe the algorithms implemented in the image plane tracker and present performance results obtained with video clips from the DARPA VIVID program data collection and from a miniature unmanned aerial vehicle (UAV) flight.

  14. Passive synthetic aperture radar imaging of ground moving targets

    NASA Astrophysics Data System (ADS)

    Wacks, Steven; Yazici, Birsen

    2012-05-01

    In this paper we present a method for imaging ground moving targets using passive synthetic aperture radar. A passive radar imaging system uses small, mobile receivers that do not radiate any energy. For these reasons, passive imaging systems result in signicant cost, manufacturing, and stealth advantages. The received signals are obtained by multiple airborne receivers collecting scattered waves due to illuminating sources of opportunity such as commercial television, radio, and cell phone towers. We describe a novel forward model and a corresponding ltered-backprojection type image reconstruction method combined with entropy optimization. Our method determines the location and velocity of multiple targets moving at dierent velocities. Furthermore, it can accommodate arbitrary imaging geometries. we present numerical simulations to verify the imaging method.

  15. Molecular imaging of macrophage enzyme activity in cardiac inflammation

    PubMed Central

    Ali, Muhammad; Pulli, Benjamin; Chen, John W.

    2014-01-01

    Molecular imaging is highly advantageous as various insidious inflammatory events can be imaged in a serial and quantitative fashion. Combined with the conventional imaging modalities like computed tomography (CT), magnetic resonance (MR) and nuclear imaging, it helps us resolve the extent of ongoing pathology, quantify inflammation and predict outcome. Macrophages are increasingly gaining importance as an imaging biomarker in inflammatory cardiovascular diseases. Macrophages, recruited to the site of injury, internalize necrotic or foreign material. Along with phagocytosis, activated macrophages release proteolytic enzymes like matrix metalloproteinases (MMPs) and cathepsins into the extracellular environment. Pro-inflammatory monocytes and macrophages also induce tissue oxidative damage through the inflammatory enzyme myeloperoxidase (MPO). In this review we will highlight recent advances in molecular macrophage imaging. Particular stress will be given to macrophage functional and enzymatic activity imaging which targets phagocytosis, proteolysis and myeloperoxidase activity imaging. PMID:24729833

  16. Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase.

    PubMed

    Morgan, P E; Laura, R P; Maki, R A; Reynolds, W F; Davies, M J

    2015-06-01

    Elevated levels of the heme enzyme myeloperoxidase (MPO) are associated with adverse cardiovascular outcomes. MPO predominantly catalyzes formation of the oxidants hypochlorous acid (HOCl) from Cl(-), and hypothiocyanous acid (HOSCN) from SCN(-), with these anions acting as competitive substrates. HOSCN is a less powerful and more specific oxidant than HOCl, and selectively targets thiols; such damage is largely reversible, unlike much HOCl-induced damage. We hypothesized that increased plasma SCN(-), and hence HOSCN formation instead of HOCl, may decrease artery wall damage. This was examined using high-fat fed atherosclerosis-prone LDLR(-/-) mice transgenic for human MPO, with and without SCN(-) (10 mM) added to drinking water. Serum samples, collected fortnightly, were analyzed for cholesterol, triglycerides, thiols, MPO, and SCN(-); study-long exposure was calculated by area under the curve (AUC). Mean serum SCN(-) concentrations were elevated in the supplemented mice (200-320 μM) relative to controls (< 120 μM). Normalized aortic root plaque areas at sacrifice were 26% lower in the SCN(-)-supplemented mice compared with controls (P = 0.0417), but plaque morphology was not appreciably altered. Serum MPO levels steadily increased in mice on the high-fat diet, however, comparison of SCN(-)-supplemented versus control mice showed no significant changes in MPO protein, cholesterol, or triglyceride levels; thiol levels were decreased in supplemented mice at one time-point. Plaque areas increased with higher cholesterol AUC (r = 0.4742; P = 0.0468), and decreased with increasing SCN(-) AUC (r = - 0.5693; P = 0.0134). These data suggest that increased serum SCN(-) levels, which can be achieved in humans by dietary manipulation, may decrease atherosclerosis burden.

  17. Thiocyanate supplementation decreases atherosclerotic plaque in mice expressing human myeloperoxidase

    PubMed Central

    Morgan, P. E.; Laura, R. P.; Maki, R. A.; Reynolds, W. F.; Davies, M. J.

    2015-01-01

    Elevated levels of the heme enzyme myeloperoxidase (MPO) are associated with adverse cardiovascular outcomes. MPO predominantly catalyzes formation of the oxidants hypochlorous acid (HOCl) from Cl−, and hypothiocyanous acid (HOSCN) from SCN−, with these anions acting as competitive substrates. HOSCN is a less powerful and more specific oxidant than HOCl, and selectively targets thiols; such damage is largely reversible, unlike much HOCl-induced damage. We hypothesized that increased plasma SCN−, and hence HOSCN formation instead of HOCl, may decrease artery wall damage. This was examined using high-fat fed atherosclerosis-prone LDLR−/− mice transgenic for human MPO, with and without SCN− (10 mM) added to drinking water. Serum samples, collected fortnightly, were analyzed for cholesterol, triglycerides, thiols, MPO and SCN−; study-long exposure was calculated by area under the curve (AUC). Mean serum SCN− concentrations were elevated in the supplemented mice (200-320 μM) relative to controls (<120 μM). Normalized aortic root plaque areas at sacrifice were 26% lower in the SCN−-supplemented mice compared to controls (P=0.0417), but plaque morphology was not appreciably altered. Serum MPO levels steadily increased in mice on the high-fat diet, however, comparison of SCN−- supplemented vs. control mice showed no significant changes in MPO protein, cholesterol or triglyceride levels; thiol levels were decreased in supplemented mice at one time-point. Plaque areas increased with higher cholesterol AUC (r=0.4742; P=0.0468), and decreased with increasing SCN− AUC (r=−0.5693; P=0.0134). These data suggest that increased serum SCN− levels, which can be achieved in humans by dietary manipulation, may decrease atherosclerosis burden. PMID:25812586

  18. Applications of Aptamers in Targeted Imaging: State of the Art

    PubMed Central

    Dougherty, Casey A.; Cai, Weibo; Hong, Hao

    2015-01-01

    Aptamers are single-stranded oligonucleotides with high affinity and specificity to the target molecules or cells, thus they can serve as an important category of molecular targeting ligand. Since their discove1y, aptamers have been rapidly translated into clinical practice. The strong target affinity/selectivity, cost-effectivity, chemical versatility and safety of aptamers are superior to traditional peptides- or proteins-based ligands which make them unique choices for molecular imaging. Therefore, aptamers are considered to be extremely useful to guide various imaging contrast agents to the target tissues or cells for optical, magnetic resonance, nuclear, computed tomography, ultra sound and multimodality imaging. This review aims to provide an overview of aptamers' advantages as targeting ligands and their application in targeted imaging. Further research in synthesis of new types of aptamers and their conjugation with new categories of contrast agents is required to develop clinically translatable aptamer-based imaging agents which will eventually result in improved patient care. PMID:25866268

  19. Automatic target locating system through cooperative dual-field imaging

    NASA Astrophysics Data System (ADS)

    Huang, Kun; He, Yuqing; Hou, Boyan; Wei, Shan; Wang, Siyuan

    2015-04-01

    This paper proposes an automatic targeting locating system based on dual-field imaging to improve the stability of light weapons. The system consists of a wide field of view (WFOV) camera and a narrow field of view (NFOV) camera. The WFOV camera searches the pedestrian in the scenery, the other camera tracks the pedestrian and aims it accurately. Video signal is send to the processing unit PC and control signal is send back to the imaging system. This automatic target tracking algorithm is integrated by Adaboost and Median-Flow algorithm. It is used to track the pedestrians and locate the head of the target. Experiment results show that the dual-field imaging system and proposed algorithm has robust target tracking performance.

  20. Preparation of a Versatile Bifunctional Zeolite for Targeted Imaging Applications

    PubMed Central

    Ndiege, Nicholas; Raidoo, Renugan; Schultz, Michael K.; Larsen, Sarah

    2011-01-01

    Bifunctional zeolite Y was prepared for use in targeted in vivo molecular imaging applications. The strategy involved functionalization of the external surface of zeolite Y with chloropropyltriethoxysilane followed by reaction with sodium azide to form azide-functionalized NaY, which is amenable to copper(1) catalyzed click chemistry. In this study, a model alkyne (4-pentyn-1-ol) was attached to the azide-terminated surface via click chemistry to demonstrate feasibility for attachment of molecular targeting vectors (e.g., peptides, aptamers) to the zeolite surface. The modified particle efficiently incorporates the imaging radioisotope gallium-68 (68Ga) into the pores of the azide-functionalized NaY zeolite to form a stable bifunctional molecular targeting vector. The result is a versatile “clickable” zeolite platform that can be tailored for future in vivo molecular targeting and imaging modalities. PMID:21306141

  1. Recent advances in image-guided targeted prostate biopsy.

    PubMed

    Brown, Anna M; Elbuluk, Osama; Mertan, Francesca; Sankineni, Sandeep; Margolis, Daniel J; Wood, Bradford J; Pinto, Peter A; Choyke, Peter L; Turkbey, Baris

    2015-08-01

    Prostate cancer is a common malignancy in the United States that results in over 30,000 deaths per year. The current state of prostate cancer diagnosis, based on PSA screening and sextant biopsy, has been criticized for both overdiagnosis of low-grade tumors and underdiagnosis of clinically significant prostate cancers (Gleason score ≥7). Recently, image guidance has been added to perform targeted biopsies of lesions detected on multi-parametric magnetic resonance imaging (mpMRI) scans. These methods have improved the ability to detect clinically significant cancer, while reducing the diagnosis of low-grade tumors. Several approaches have been explored to improve the accuracy of image-guided targeted prostate biopsy, including in-bore MRI-guided, cognitive fusion, and MRI/transrectal ultrasound fusion-guided biopsy. This review will examine recent advances in these image-guided targeted prostate biopsy techniques. PMID:25596716

  2. Enhanced sensitivity carbon nanotubes as targeted photoacoustic molecular imaging agents

    NASA Astrophysics Data System (ADS)

    de la Zerda, Adam; Liu, Zhuang; Zavaleta, Cristina; Bodapati, Sunil; Teed, Robert; Vaithilingam, Srikant; Ma, Te-Jen; Oralkan, Omer; Chen, Xiaoyuan; Khuri-Yakub, Butrus T.; Dai, Hongjie; Gambhir, Sanjiv S.

    2009-02-01

    Photoacoustic imaging of living subjects offers high spatial resolution at increased tissue depths compared to purely optical imaging techniques. We have recently shown that intravenously injected single walled carbon nanotubes (SWNTs) can be used as targeted photoacoustic imaging agents in living mice using RGD peptides to target αvβ3 integrins. We have now developed a new targeted photoacoustic imaging agent based on SWNTs and Indocyanine Green (SWNT-ICG) with absorption peak at 780nm. The photoacoustic signal of the new imaging agent is enhanced by ~20 times as compared to plain SWNTs. The particles are synthesized from SWNT-RGD that noncovalently attach to multiple ICG molecules through pi-pi stacking interactions. Negative control particles had RAD peptide instead of RGD. We measured the serum stability of the particles and verified that the RGD/RAD conjugation did not alter the particle's absorbance spectrum. Finally, through cell uptake studies with U87MG cells we verified that the particles bind selectively to αvβ3 integrin. In conclusion, the extremely high absorption of the SWNT-ICG particles shows great promise for high sensitivity photoacoustic imaging of molecular targets in-vivo. This work lays the foundations for future in-vivo studies that will use the SWNT-ICG particles as imaging agents administered systemically.

  3. Phase calibration target for quantitative phase imaging with ptychography.

    PubMed

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

    2016-04-01

    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. PMID:27137054

  4. Targeting Apolipoproteins in Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Sriram, Renuka; Lagerstedt, Jens O.; Samardzic, Haris; Kreutzer, Ulrike; Petrolova, Jitka; Xie, Hongtao; Kaysen, George A.; Voss, John C.; Desreux, Jean F.; Jue, Thomas

    Maintaining normal physiological homeostasis depends upon a coordinated metabolism of both water-soluble and -insoluble substrates. In humans the body derives these molecules — such as glucose, amino acids, and fatty acids — from complex food matter. Water-soluble substrates can circulate readily in blood, while water-insoluble molecules — such as fatty acid, triacylglycerol, and cholesterol — require ampiphathic carriers to transport them from the site of biosynthesis (liver and intestine) to the target tissue. For fatty acid, albumin serves as the major transporter. For triacylglycerol and cholesterol, however, macromolecular complexes aggregate the hydrophobic molecules into the core and cover the surface with amphiphatic proteins and phospholipids to solubilize the particles in the lymphatic and circulatory systems. These macromolecules belong to a class of proteins, plasma lipoproteins, with specific functions and cellular targets. In the clinic these lipoproteins prognosticate the risk of cardiovascular disease (CVD). Lipoproteins divide usually into five major types: chylomicron, very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Each lipoprotein type exhibits characteristic density, size, and composition. As implied in the name, the density varies from the low-density chylomicron (<0.95 g/ml) to the high-density HDL (1.2 g/ml). Size also varies. The chylomicron has the largest diameter (75-1,200 nm), and HDL has the smallest (5-12 nm). The physical property variation arises from each lipoprotein's distinct composition. In a chylomicron, cholesterol, triacylglycerol, and phospholipid predominate and constitute about 90% of the particle. Protein constitutes only about 10%. In contrast, the smaller HDL has less cholesterol, triacylglycerol, and phospholipid (65% of the particle) but more protein (over 30%).

  5. Molecular targeting of the lymphovascular system for imaging and therapy.

    PubMed

    Schöder, Heiko; Glass, Edwin C; Pecking, Alain P; Harness, Jay K; Wallace, Anne M; Hirnle, Peter; Alberini, Jean L; Vilain, Didier; Larson, Steven M; Hoh, Carl K; Vera, David R

    2006-06-01

    Progress toward targeting cancer cells is a multi-disciplinary endeavor. In addition to the surgical and oncology specialties, radiologists collaborate with mathematicians, computer scientists, and physicists, in a constant effort to incrementally improve upon the current imaging modalities. Recently, radiologists have formed collaborations with molecular biologists and chemists in order to develop molecular agents that target cancer cells via receptor-substrate or specific physiochemical interactions. In this review, we summarize selected efforts toward molecular targeting of the lymphovascular system. Standard imaging modalities, positron emission tomography, single photon emission tomography, and ultrasound, are reviewed as well as, the targeted introduction of substances for endolymphatic therapy. We also review the current status of sentinel lymph node mapping with radiocolloids and the application of molecular targeting for the development of a radiopharmaceutical specifically designed for sentinel lymph node mapping.

  6. Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

    NASA Astrophysics Data System (ADS)

    Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

    2015-11-01

    Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging.

  7. Multimodal targeted high relaxivity thermosensitive liposome for in vivo imaging

    PubMed Central

    Kuijten, Maayke M. P.; Hannah Degeling, M.; Chen, John W.; Wojtkiewicz, Gregory; Waterman, Peter; Weissleder, Ralph; Azzi, Jamil; Nicolay, Klaas; Tannous, Bakhos A.

    2015-01-01

    Liposomes are spherical, self-closed structures formed by lipid bilayers that can encapsulate drugs and/or imaging agents in their hydrophilic core or within their membrane moiety, making them suitable delivery vehicles. We have synthesized a new liposome containing gadolinium-DOTA lipid bilayer, as a targeting multimodal molecular imaging agent for magnetic resonance and optical imaging. We showed that this liposome has a much higher molar relaxivities r1 and r2 compared to a more conventional liposome containing gadolinium-DTPA-BSA lipid. By incorporating both gadolinium and rhodamine in the lipid bilayer as well as biotin on its surface, we used this agent for multimodal imaging and targeting of tumors through the strong biotin-streptavidin interaction. Since this new liposome is thermosensitive, it can be used for ultrasound-mediated drug delivery at specific sites, such as tumors, and can be guided by magnetic resonance imaging. PMID:26610702

  8. Slant path range gated imaging of static and moving targets

    NASA Astrophysics Data System (ADS)

    Steinvall, Ove; Elmqvist, Magnus; Karlsson, Kjell; Gustafsson, Ove; Chevalier, Tomas

    2012-06-01

    This paper will report experiments and analysis of slant path imaging using 1.5 μm and 0.8 μm gated imaging. The investigation is a follow up on the measurement reported last year at the laser radar conference at SPIE Orlando. The sensor, a SWIR camera was collecting both passive and active images along a 2 km long path over an airfield. The sensor was elevated by a lift in steps from 1.6-13.5 meters. Targets were resolution charts and also human targets. The human target was holding various items and also performing certain tasks some of high of relevance in defence and security. One of the main purposes with this investigation was to compare the recognition of these human targets and their activities with the resolution information obtained from conventional resolution charts. The data collection of human targets was also made from out roof top laboratory at about 13 m height above ground. The turbulence was measured along the path with anemometers and scintillometers. The camera was collecting both passive and active images in the SWIR region. We also included the Obzerv camera working at 0.8 μm in some tests. The paper will present images for both passive and active modes obtained at different elevations and discuss the results from both technical and system perspectives.

  9. Hyperspectral Image Target Detection Improvement Based on Total Variation.

    PubMed

    Yang, Shuo; Shi, Zhenwei

    2016-05-01

    For the hyperspectral target detection, the neighbors of a target pixel are very likely to be target pixels, and those of a background pixel are very likely to be background pixels. In order to utilize this spatial homogeneity or smoothness, based on total variation (TV), we propose a novel supervised target detection algorithm which uses a single target spectrum as the prior knowledge. TV can make the image smooth, and has been widely used in image denoising and restoration. The proposed algorithm uses TV to keep the spatial homogeneity or smoothness of the detection output. Meanwhile, a constraint is used to guarantee the spectral signature of the target unsuppressed. The final formulated detection model is an ℓ1-norm convex optimization problem. The split Bregman algorithm is used to solve our optimization problem, as it can solve the ℓ1-norm optimization problem efficiently. Two synthetic and two real hyperspectral images are used to do experiments. The experimental results demonstrate that the proposed algorithm outperforms the other algorithms for the experimental data sets. The experimental results also show that even when the target occupies only one pixel, the proposed algorithm can still obtain good results. This is because in such a case, the background is kept smooth, but at the same time, the algorithm allows for sharp edges in the detection output. PMID:27019489

  10. Identifying radiotherapy target volumes in brain cancer by image analysis

    PubMed Central

    Cheng, Kun; Montgomery, Dean; Feng, Yang; Steel, Robin; Liao, Hanqing; McLaren, Duncan B.; Erridge, Sara C.; McLaughlin, Stephen

    2015-01-01

    To establish the optimal radiotherapy fields for treating brain cancer patients, the tumour volume is often outlined on magnetic resonance (MR) images, where the tumour is clearly visible, and mapped onto computerised tomography images used for radiotherapy planning. This process requires considerable clinical experience and is time consuming, which will continue to increase as more complex image sequences are used in this process. Here, the potential of image analysis techniques for automatically identifying the radiation target volume on MR images, and thereby assisting clinicians with this difficult task, was investigated. A gradient-based level set approach was applied on the MR images of five patients with grades II, III and IV malignant cerebral glioma. The relationship between the target volumes produced by image analysis and those produced by a radiation oncologist was also investigated. The contours produced by image analysis were compared with the contours produced by an oncologist and used for treatment. In 93% of cases, the Dice similarity coefficient was found to be between 60 and 80%. This feasibility study demonstrates that image analysis has the potential for automatic outlining in the management of brain cancer patients, however, more testing and validation on a much larger patient cohort is required. PMID:26609418

  11. Multi-point sources and imaging compound infrared target simulator

    NASA Astrophysics Data System (ADS)

    Shi, Rui; Xu, Rui; Wang, Hongjie; Wang, Xin; Wu, Di; Li, Zhuo

    2014-11-01

    Infrared target simulator is an important unit in guidance hardware-in-the-loop simulation systems. It is used to simulate the radiation and motion characteristics of target, decoy and background. This paper proposed a multi-channel IR target simulator. It could generate one IR point target, two pairs of IR decoys and background respectively in the same field of view of the seeker's optical system simultaneously. An IR imaging fiber bundle as the focal plane of the projection optical system was used to compound the target, decoys and background. The compound scene was projected to the seeker by the projection optical system. In IR imaging channel, IR scene was generated by an optical film chip as a visible to thermal transducer which was placed in a vacuum cell. The simulated temperature range of IR scene could be from room temperature to 430K.The thin film transducer had 512×512 pixels. Its frame rate could reach to 100Hz. Light sources with high equivalent black body temperature were adopted in IR target and decoy channels. The size and the radiation intensity of the IR point target and decoys could be controlled by pin holes and attenuators. The point target and decoys driven by high precise motors could travel through the whole instantaneous field of view of the seeker's optical system. Two pairs of decoys could move away from the center to the edge of the instantaneous field of view. The highest simulated black body temperature of the point source was 1200K.

  12. Video rate multispectral imaging for camouflaged target detection

    NASA Astrophysics Data System (ADS)

    Henry, Sam

    2015-05-01

    The ability to detect and identify camouflaged targets is critical in combat environments. Hyperspectral and Multispectral cameras allow a soldier to identify threats more effectively than traditional RGB cameras due to both increased color resolution and ability to see beyond visible light. Static imagers have proven successful, however the development of video rate imagers allows for continuous real time target identification and tracking. This paper presents an analysis of existing anomaly detection algorithms and how they can be adopted to video rates, and presents a general purpose semisupervised real time anomaly detection algorithm using multiple frame sampling.

  13. Sequential Superresolution Imaging of Multiple Targets Using a Single Fluorophore

    PubMed Central

    Lidke, Diane S.; Lidke, Keith A.

    2015-01-01

    Fluorescence superresolution (SR) microscopy, or fluorescence nanoscopy, provides nanometer scale detail of cellular structures and allows for imaging of biological processes at the molecular level. Specific SR imaging methods, such as localization-based imaging, rely on stochastic transitions between on (fluorescent) and off (dark) states of fluorophores. Imaging multiple cellular structures using multi-color imaging is complicated and limited by the differing properties of various organic dyes including their fluorescent state duty cycle, photons per switching event, number of fluorescent cycles before irreversible photobleaching, and overall sensitivity to buffer conditions. In addition, multiple color imaging requires consideration of multiple optical paths or chromatic aberration that can lead to differential aberrations that are important at the nanometer scale. Here, we report a method for sequential labeling and imaging that allows for SR imaging of multiple targets using a single fluorophore with negligible cross-talk between images. Using brightfield image correlation to register and overlay multiple image acquisitions with ~10 nm overlay precision in the x-y imaging plane, we have exploited the optimal properties of AlexaFluor647 for dSTORM to image four distinct cellular proteins. We also visualize the changes in co-localization of the epidermal growth factor (EGF) receptor and clathrin upon EGF addition that are consistent with clathrin-mediated endocytosis. These results are the first to demonstrate sequential SR (s-SR) imaging using direct stochastic reconstruction microscopy (dSTORM), and this method for sequential imaging can be applied to any superresolution technique. PMID:25860558

  14. Real Time Target Tracking in a Phantom Using Ultrasonic Imaging

    NASA Astrophysics Data System (ADS)

    Xiao, X.; Corner, G.; Huang, Z.

    In this paper we present a real-time ultrasound image guidance method suitable for tracking the motion of tumors. A 2D ultrasound based motion tracking system was evaluated. A robot was used to control the focused ultrasound and position it at the target that has been segmented from a real-time ultrasound video. Tracking accuracy and precision were investigated using a lesion mimicking phantom. Experiments have been conducted and results show sufficient efficiency of the image guidance algorithm. This work could be developed as the foundation for combining the real time ultrasound imaging tracking and MRI thermometry monitoring non-invasive surgery.

  15. STATUS OF BEAM IMAGING DEVELOPMENTS FOR THE SNS TARGET

    SciTech Connect

    Shea, Thomas J; McManamy, Thomas J; Maxey, L Curt; Shkvarunets, A; Feldman, D; Fiorito, R

    2009-01-01

    The Spallation Neutron Source (SNS) continues a ramp up in proton beam power toward the design goal of 1.4 MW on target. At Megawatt levels, US and Japanese studies have shown that cavitation in the Mercury target could lead to dramatically shortened target lifetime. Therefore, it will be critical to measure and control the proton beam distribution on the target, in a region of extremely high radiation and limited accessibility. Several sources of photons have been considered for imaging the beam on or near the target. These include a freestanding temporary screen, a scintillating coating, Helium gas scintillation, optical transition radiation, and a beam- heated wire mesh. This paper will outline the selection process that led to the current emphasis on coating development. In this harsh environment, the optics design presented significant challenges. The optical system has been constructed and characterized in preparation for installation. Optical test results will be described along with predictions of overall system performance.

  16. Automatic target detection in UAV imagery using image formation conditions

    NASA Astrophysics Data System (ADS)

    Lin, Huibao; Si, Jennie; Abousleman, Glen P.

    2003-09-01

    This paper is about automatic target detection (ATD) in unmanned aerial vehicle (UAV) imagery. Extracting reliable features under all conditions from a 2D projection of a target in UAV imagery is a difficult problem. However, since the target size information is usually invariant to the image formation proces, we propose an algorithm for automatically estimating the size of a 3D target by using its 2D projection. The size information in turn becomes an important feature to be used in a knowledge-driven, multi-resolution-based algorithm for automatically detecting targets in UAV imagery. Experimental results show that our proposed ATD algorithm provides outstanding detection performance, while significantly reducing the false alarm rate and the computational complexity.

  17. HuntIR thermal imagers for reconnaissance and targeting applications

    NASA Astrophysics Data System (ADS)

    Breiter, Rainer; Cabanski, Wolfgang A.; Ihle, Tobias; Mauk, Karl-Heinz; Rode, Werner

    2004-08-01

    A new family of light handheld military thermal imagers for reconnaissance and targeting applications was developed based on AIM's IR components like IR detection modules, command and control electronics and image processing units. Three different types of imagers provide solutions for different requirements in identification ranges of targets. The highest performance device makes use of a FPA MCT 384x288 MWIR detector with a motorized double field of view optics. An identification range up to 2400m for the NATO standard target was proven according to the FGAN-FOM TRM3 range model. The device provides a mechanical adaptation to weapon systems and provides target markers for common hand weapons of the German army. A single field of view MCT device for 1000m ranges and an uncooled device on the lower performance end complete the imager family. Electronics for intelligent power management from batteries and display electronics were developed to provide stand alone operation. The modular concept allows the use of the same image processing unit for all devices providing special features for best performance like scene-based non-uniformity correction together with an optical calibration element and dynamic reduction including automatic histogram equalization for optimized scene display and text or graphics overlay. Due to the modular concept the components like the image processing unit are already used and validated in programs like the thermal sight for the self defense gun of the reconnaissance vehicle FENNEK together with a 320x240 LWIR uncooled microbolometer detector or with the MCT 384x288 MWIR detection module in a thermal imager for the German army UAV Luna.

  18. PIRATE: pediatric imaging response assessment and targeting environment

    NASA Astrophysics Data System (ADS)

    Glenn, Russell; Zhang, Yong; Krasin, Matthew; Hua, Chiaho

    2010-02-01

    By combining the strengths of various imaging modalities, the multimodality imaging approach has potential to improve tumor staging, delineation of tumor boundaries, chemo-radiotherapy regime design, and treatment response assessment in cancer management. To address the urgent needs for efficient tools to analyze large-scale clinical trial data, we have developed an integrated multimodality, functional and anatomical imaging analysis software package for target definition and therapy response assessment in pediatric radiotherapy (RT) patients. Our software provides quantitative tools for automated image segmentation, region-of-interest (ROI) histogram analysis, spatial volume-of-interest (VOI) analysis, and voxel-wise correlation across modalities. To demonstrate the clinical applicability of this software, histogram analyses were performed on baseline and follow-up 18F-fluorodeoxyglucose (18F-FDG) PET images of nine patients with rhabdomyosarcoma enrolled in an institutional clinical trial at St. Jude Children's Research Hospital. In addition, we combined 18F-FDG PET, dynamic-contrast-enhanced (DCE) MR, and anatomical MR data to visualize the heterogeneity in tumor pathophysiology with the ultimate goal of adaptive targeting of regions with high tumor burden. Our software is able to simultaneously analyze multimodality images across multiple time points, which could greatly speed up the analysis of large-scale clinical trial data and validation of potential imaging biomarkers.

  19. Processing infrared images for target detection: A literature study

    NASA Astrophysics Data System (ADS)

    Alblas, B. P.

    1988-07-01

    Methods of image processing applied to IR images to obtain better detection and/or recognition of military targets, particularly vehicles, are reviewed. The following subjects are dealt with: histogram specification, scanline degradation, correlation, clutter and noise. Only a few studies deal with the effects of image processing on human performance. Most of the literature concerns computer vision. Local adaptive and image dependent techniques appear to be the most promising methods of obtaining higher observation performance. In particular the size-contrast box filter and histogram specification methods seem to be suitable. There is a need for a generally applicable definition of image quality and clutter level to evaluate the utility of a specified algorithm. Proposals for further research are given.

  20. A targeted molecular probe for colorectal cancer imaging

    NASA Astrophysics Data System (ADS)

    Attramadal, T.; Bjerke, R.; Indrevoll, B.; Moestue, S.; Rogstad, A.; Bendiksen, R.; Healey, A.; Johannesen, E.

    2008-02-01

    Colorectal cancer is a major cause of cancer death. Morbidity, mortality and healthcare costs can be reduced if the disease can be detected at an early stage. Screening is a viable approach as there is a clear link to risk factors such as age. We have developed a fluorescent contrast agent for use during colonoscopy. The agent is administered intravenously and is targeted to an early stage molecular marker for colorectal cancer. The agent consists of a targeting section comprising a peptide, and a fluorescent reporter molecule. Clinical imaging of the agent is to be performed with a far red fluorescence imaging channel (635 nm excitation/660-700 nm emission) as an adjunct to white light colonoscopy. Preclinical proof of mechanism results are presented. The compound has a K d of ~3nM. Two human xenograft tumour models were used. Tumour cells were implanted and grown subcutaneously in nude mice. Imaging using a fluorescence reflectance imaging system and quantitative biodistribution studies were performed. Substances tested include the targeted agent, and a scrambled sequence of the peptide (no binding) used as a negative control. Competition studies were also performed by co-administration of 180 times excess unlabelled peptide. Positive imaging contrast was shown in the tumours, with a clear relationship to expression levels (confirmed with quantitative biodistribution data). There was a significant difference between the positive and negative control substances, and a significant reduction in contrast in the competition experiment.

  1. Target plane imaging system for the Nova laser

    SciTech Connect

    Swift, C.D.; Bliss, E.S.; Jones, W.A.; Reeves, R.J.; Seppala, L.G.; Shelton, R.T.; VanArsdall, P.J.

    1985-12-12

    The Nova laser, in operation since December 1984, is capable of irradiating targets with light at 1.05 ..mu..m, 0.53 ..mu..m, and 0.35 ..mu..m. Correct alignment of these harmonic beams uses a system called a target plane imager (TPI). It is a large microscope (four meters long, weighing one thousand kilograms) that relays images from the target chamber center to a video optics module located on the outside of the chamber. Several modes of operation are possible including: near-field viewing and far-field viewing at three magnifications and three wavelengths. In addition, the entire instrument can be scanned in X,Y,Z to examine various planes near chamber center. Performance of this system and its computer controls will be described.

  2. Time-reversal MUSIC imaging of extended targets.

    PubMed

    Marengo, Edwin A; Gruber, Fred K; Simonetti, Francesco

    2007-08-01

    This paper develops, within a general framework that is applicable to rather arbitrary electromagnetic and acoustic remote sensing systems, a theory of time-reversal "MUltiple Signal Classification" (MUSIC)-based imaging of extended (nonpoint-like) scatterers (targets). The general analysis applies to arbitrary remote sensing geometry and sheds light onto how the singular system of the scattering matrix relates to the geometrical and propagation characteristics of the entire transmitter-target-receiver system and how to use this effect for imaging. All the developments are derived within exact scattering theory which includes multiple scattering effects. The derived time-reversal MUSIC methods include both interior sampling, as well as exterior sampling (or enclosure) approaches. For presentation simplicity, particular attention is given to the time-harmonic case where the informational wave modes employed for target interrogation are purely spatial, but the corresponding generalization to broadband fields is also given. This paper includes computer simulations illustrating the derived theory and algorithms.

  3. Targeting Strategies for Multifunctional Nanoparticles in Cancer Imaging and Therapy

    PubMed Central

    Yu, Mi Kyung; Park, Jinho; Jon, Sangyong

    2012-01-01

    Nanomaterials offer new opportunities for cancer diagnosis and treatment. Multifunctional nanoparticles harboring various functions including targeting, imaging, therapy, and etc have been intensively studied aiming to overcome limitations associated with conventional cancer diagnosis and therapy. Of various nanoparticles, magnetic iron oxide nanoparticles with superparamagnetic property have shown potential as multifunctional nanoparticles for clinical translation because they have been used asmagnetic resonance imaging (MRI) constrast agents in clinic and their features could be easily tailored by including targeting moieties, fluorescence dyes, or therapeutic agents. This review summarizes targeting strategies for construction of multifunctional nanoparticles including magnetic nanoparticles-based theranostic systems, and the various surface engineering strategies of nanoparticles for in vivo applications. PMID:22272217

  4. Mitochondrial Nitroreductase Activity Enables Selective Imaging and Therapeutic Targeting.

    PubMed

    Chevalier, Arnaud; Zhang, Yanmin; Khdour, Omar M; Kaye, Justin B; Hecht, Sidney M

    2016-09-21

    Nitroreductase (NTR) activities have been known for decades, studied extensively in bacteria and also in systems as diverse as yeast, trypanosomes, and hypoxic tumors. The putative bacterial origin of mitochondria prompted us to explore the possible existence of NTR activity within this organelle and to probe its behavior in a cellular context. Presently, by using a profluorescent near-infrared (NIR) dye, we characterize the nature of NTR activity localized in mammalian cell mitochondria. Further, we demonstrate that this mitochondrially localized enzymatic activity can be exploited both for selective NIR imaging of mitochondria and for mitochondrial targeting by activating a mitochondrial poison specifically within that organelle. This constitutes a new mechanism for mitochondrial imaging and targeting. These findings represent the first use of mitochondrial enzyme activity to unmask agents for mitochondrial fluorescent imaging and therapy, which may prove to be more broadly applicable.

  5. Evaluation of the Efficacy of Targeted Imaging Agents.

    PubMed

    Graham, Michael M; Weber, Wolfgang A

    2016-04-01

    This paper presents our adaptation of Fryback and Thornbury's hierarchical scheme for modeling the efficacy of diagnostic imaging systems. The original scheme was designed to evaluate new medical imaging systems but is less successful when applied to evaluate new radiopharmaceuticals. The proposed adaptation, which is specifically directed toward evaluating targeted imaging agents, has 6 levels: in vitro characterization, in vivo animal studies, initial human studies, impact on clinical care (change in management), impact on patient outcome, and societal efficacy. These levels, particularly the first four, implicitly define the sequence of studies needed to move an agent from the radiochemistry synthesis laboratory to the clinic. Completion of level 4 (impact on clinical care) should be sufficient for initial approval and reimbursement. We hope that the adapted scheme will help streamline the process and assist in bringing new targeted radiopharmaceuticals to approval over the next few years. PMID:26769867

  6. Preparation of Monoclonal Antibodies and a Simple Myeloperoxidase-Immunosorbent Assay for Detecting Human Myeloperoxidase.

    PubMed

    Bian, Zhi-Ping; Li, Xiong-Zhi; Wu, Heng-Fang; Xu, Jin-Dan; Gu, Chun-Rong; Chen, Xiang-Jian; Yang, Di

    2016-04-01

    Myeloperoxidase (MPO), a leukocyte hemoprotein released from neutrophils, is thought to be a potential participant in plaque formation and plaque rupture. Therefore, MPO is regarded as an early marker predicting the risk for atherosclerosis, especially for coronary artery disease and acute coronary syndrome. We generated hybridoma clones 1E3 and 3E8 secreting monoclonal antibodies (mAbs) specific to human MPO. BALB/c mice were immunized with MPO protein purified from human neutrophils. Splenocytes from these mice were fused with the mouse myeloma cell line SP2/0. Based on isotyping of the mAbs, both clones 1E3 and 3E8 were referred to the IgG1 subclass. The specificities of 1E3 and 3E8 were assessed by enzyme-linked immunosorbent assay (ELISA), and only 3E8 was confirmed by western blot. We developed a simple MPO-immunosorbent assay (MPO-ISA) on microplate based on both the immune activity and peroxidase activity of MPO. The mAb secreted by clone 3E8 was chosen as coating antibody to capture the plasma MPO without interfering with the peroxidase activity of MPO. Then, tetramethylbenzidine substrate was added to the microwell directly, catalyzed by captured MPO, and a colored product was formed. The simple MPO-ISA test has a sensitivity of 3.68 ng/mL. The linear concentration of MPO-ISA for commercial MPO standard ranged to 250 ng/mL. The average recovery rate is 101.02%. The imprecision within-day was <10% at three different MPO levels. The imprecision between-day was <10% at low and middle MPO levels and varied to 14.61% at the high MPO level. We found that the established MPO-ISA can detect the plasma MPO from human and cavy, but not from mouse and rat. Compared with the commercial human MPO ELISA assay, the MPO-ISA can be used to detect the natural human MPO protein, but not recombinant MPO polypeptides. The generated mAbs and MPO-ISA test may be useful tools to assess risk for inflammation and cardiac events.

  7. Maximum margin metric learning based target detection for hyperspectral images

    NASA Astrophysics Data System (ADS)

    Dong, Yanni; Zhang, Liangpei; Zhang, Lefei; Du, Bo

    2015-10-01

    Target detection is one of the most important problems in hyperspectral image (HSI) processing. However, the classical algorithms depend on the specific statistical hypothesis test, and the algorithms may only perform well under certain conditions, e.g., the adaptive matched subspace detector algorithm assumes that the background covariance matrices do not include the target signatures, which seldom happens in the real world. How to develop a proper metric for measuring the separability between targets and backgrounds becomes the key in target detection. This paper proposes an efficient maximum margin metric learning (MMML) based target detection algorithm, which aims at exploring the limited samples in metric learning and transfers the metric learning problem for hyperspectral target detection into a maximum margin problem which can be optimized via a cutting plane method, and maximally separates the target samples from the background ones. The extensive experimental results with different HSIs demonstrate that the proposed method outperforms both the state-of-the-art target detection algorithms and the other classical metric learning methods.

  8. The combinative analysis of spraying target image based on chroma

    NASA Astrophysics Data System (ADS)

    Huang, Jingyao; Zhang, Fajun

    2009-10-01

    Recently, intelligent spray system with vision is a research hotspot due to its application security. This paper propose the design of a novel spraying target extraction system, which is capable of identifying crown of a tree structures that are mainly used in the prevention and treatment of the plant's diseases and insects in the urban tree lawn. But how to differentiate the billboard on the both sides of the streets, especially the green overhead structure billboard, the chroma parameters(three primary colors factor's) of spray-targets, and the character of combination were analyzed by normalization experiment in this paper. In comparative studies, the experiment verified effectively the performance of the chroma combination operation by 2G-R-B processing, and showed this method can effectively strategy that the normalization combination arithmetic preceded the simplification operator for eliminating no spray-target image and divide the crown target effectively from the background.

  9. Luminol-dependent photoemission from single neutrophil stimulated by phorbol ester and calcium ionophore--role of degranulation and myeloperoxidase

    SciTech Connect

    Suematsu, M.; Oshio, C.; Miura, S.; Suzuki, M.; Houzawa, S.; Tsuchiya, M.

    1988-08-30

    Luminol-dependent photonic burst from phorbol ester-treated single neutrophil was visually investigated by using an ultrasensitive photonic image intensifier microscope. Neutrophils stimulated by phorbol myristate acetate (0.1 microgram/ml) alone produced a negligible level of photonic activities in the presence of luminol (10 micrograms/ml). The additional application of 0.1 microM Ca2+ ionophore A23187 induced explosive changes of photonic burst corresponding to the distribution of neutrophils, and these photonic activities were gradually spread to extracellular space. Sodium azide, which prevents myeloperoxidase activity, inhibited Ca2+ ionophore-induced photonic burst from phorbol ester-treated neutrophil. These findings suggest a prerequisite role of degranulation and myeloperoxidase release in luminol-dependent photoemission from stimulated neutrophils.

  10. Myeloperoxidase-dependent Lipid Peroxidation Promotes the Oxidative Modification of Cytosolic Proteins in Phagocytic Neutrophils*

    PubMed Central

    Wilkie-Grantham, Rachel P.; Magon, Nicholas J.; Harwood, D. Tim; Kettle, Anthony J.; Vissers, Margreet C.; Winterbourn, Christine C.; Hampton, Mark B.

    2015-01-01

    Phagocytic neutrophils generate reactive oxygen species to kill microbes. Oxidant generation occurs within an intracellular phagosome, but diffusible species can react with the neutrophil and surrounding tissue. To investigate the extent of oxidative modification, we assessed the carbonylation of cytosolic proteins in phagocytic neutrophils. A 4-fold increase in protein carbonylation was measured within 15 min of initiating phagocytosis. Carbonylation was dependent on NADPH oxidase and myeloperoxidase activity and was inhibited by butylated hydroxytoluene and Trolox, indicating a role for myeloperoxidase-dependent lipid peroxidation. Proteomic analysis of target proteins revealed significant carbonylation of the S100A9 subunit of calprotectin, a truncated form of Hsp70, actin, and hemoglobin from contaminating erythrocytes. The addition of the reactive aldehyde 4-hydroxynonenal (HNE) caused carbonylation, and HNE-glutathione adducts were detected in the cytosol of phagocytic neutrophils. The post-translational modification of neutrophil proteins will influence the functioning and fate of these immune cells in the period following phagocytic activation, and provides a marker of neutrophil activation during infection and inflammation. PMID:25697357

  11. An aqueous pomegranate peel extract inhibits neutrophil myeloperoxidase in vitro and attenuates lung inflammation in mice.

    PubMed

    Bachoual, Rafik; Talmoudi, Wifak; Boussetta, Tarek; Braut, Françoise; El-Benna, Jamel

    2011-06-01

    Punica granatum peel aqueous extract (PGE) is widely used to treat disorders such as inflammation, ulcers and infections, but its pharmacological target is not known. In this study we investigated the effect of PGE on human neutrophil reactive oxygen species (ROS) production in vitro and on LPS-induced lung inflammation in vivo in mice. Neutrophils were isolated and ROS generation was measured by luminol-amplified chemiluminescence. Superoxide anion generation was detected by the cytochrome c reduction assay. H(2)O(2) was detected by DCFH fluorescence assay. Myeloperoxidase (MPO) activity was measured by the tetramethyl benzidine oxidation method. Lung inflammation was induced in mice by LPS instillation. PGE inhibited luminol-amplified chemiluminescence of resting neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLF)- or phorbol myristate acetate (PMA)-stimulated neutrophils, in a concentration-dependent manner. PGE had no effect on superoxide anion generation, suggesting that it does not directly inhibit NADPH oxidase activity or activation pathways, or scavenge superoxide anions. PGE did not scavenge H(2)O(2) but directly inhibited myeloperoxidase activity in vitro. In vivo studies showed that PGE also attenuated LPS-induced lung inflammation in mice. So this study reveals that PGE inhibits neutrophil MPO activity and attenuates LPS-induced lung inflammation in mice. Inhibition of MPO activity by PGE could explain its anti-inflammatory action. PMID:21376769

  12. An aqueous pomegranate peel extract inhibits neutrophil myeloperoxidase in vitro and attenuates lung inflammation in mice.

    PubMed

    Bachoual, Rafik; Talmoudi, Wifak; Boussetta, Tarek; Braut, Françoise; El-Benna, Jamel

    2011-06-01

    Punica granatum peel aqueous extract (PGE) is widely used to treat disorders such as inflammation, ulcers and infections, but its pharmacological target is not known. In this study we investigated the effect of PGE on human neutrophil reactive oxygen species (ROS) production in vitro and on LPS-induced lung inflammation in vivo in mice. Neutrophils were isolated and ROS generation was measured by luminol-amplified chemiluminescence. Superoxide anion generation was detected by the cytochrome c reduction assay. H(2)O(2) was detected by DCFH fluorescence assay. Myeloperoxidase (MPO) activity was measured by the tetramethyl benzidine oxidation method. Lung inflammation was induced in mice by LPS instillation. PGE inhibited luminol-amplified chemiluminescence of resting neutrophils and N-formyl-methionyl-leucyl-phenylalanine (fMLF)- or phorbol myristate acetate (PMA)-stimulated neutrophils, in a concentration-dependent manner. PGE had no effect on superoxide anion generation, suggesting that it does not directly inhibit NADPH oxidase activity or activation pathways, or scavenge superoxide anions. PGE did not scavenge H(2)O(2) but directly inhibited myeloperoxidase activity in vitro. In vivo studies showed that PGE also attenuated LPS-induced lung inflammation in mice. So this study reveals that PGE inhibits neutrophil MPO activity and attenuates LPS-induced lung inflammation in mice. Inhibition of MPO activity by PGE could explain its anti-inflammatory action.

  13. Target information enhancement using polarized component of infrared images

    NASA Astrophysics Data System (ADS)

    Qiu, Tiaowen; Zhang, Yan; Li, Jicheng; Yang, Weiping

    2014-11-01

    After a deep study of the principle of infrared polarization imaging detection, the infrared polarization information of target and background is modeled. Considering the partial polarized light can be obtained by the superposition of natural light (unpolarized light) and linearly polarized component while ignoring the component of circularly polarized light, and combing with the degree of polarization (DOLP) and the angle of polarization (AOP), the infrared polarization information is expressed by the multiplying of an intensity factor by a polarization factor. What we have modeled not only can be used to analyze the infrared polarization information visually and profoundly, but also make the extraction of polarized features convenient. Then, faced with different application fields and based on the model, a target information enhancement program is proposed, which is achieved by extracting a linear polarization component in a certain polarized direction. This program greatly improves the contrast between target and background, and can be applied in target detection or identification, especially for camouflage or stealth target. At last, we preliminarily tested the proposed enhancement method exploiting infrared polarization images obtained indoor and outdoor, which demonstrates the effectiveness of the enhancement program.

  14. Multifunctional magnetic nanoparticles for targeted imaging and therapy

    PubMed Central

    McCarthy, Jason R.; Weissleder, Ralph

    2008-01-01

    Magnetic nanoparticles have become important tools for the imaging of prevalent diseases, such as cancer, atherosclerosis, diabetes, and others. While first generation nanoparticles were fairly nonspecific, newer generations have been targeted to specific cell types and molecular targets via affinity ligands. Commonly, these ligands emerge from phage or small molecule screens, or are based on antibodies or aptamers. Secondary reporters and combined therapeutic molecules have further opened potential clinical applications of these materials. This review summarizes some of the recent biomedical applications of these newer magnetic nanomaterials. PMID:18508157

  15. Digital image fusion systems: color imaging and low-light targets

    NASA Astrophysics Data System (ADS)

    Estrera, Joseph P.

    2009-05-01

    This paper presents digital image fusion (enhanced A+B) systems in color imaging and low light target applications. This paper will discuss first the digital sensors that are utilized in the noted image fusion applications which is a 1900x1086 (high definition format) CMOS imager coupled to a Generation III image intensifier for the visible/near infrared (NIR) digital sensor and 320x240 or 640x480 uncooled microbolometer thermal imager for the long wavelength infrared (LWIR) digital sensor. Performance metrics for these digital imaging sensors will be presented. The digital image fusion (enhanced A+B) process will be presented in context of early fused night vision systems such as the digital image fused system (DIFS) and the digital enhanced night vision goggle and later, the long range digitally fused night vision sighting system. Next, this paper will discuss the effects of user display color in a dual color digital image fusion system. Dual color image fusion schemes such as Green/Red, Cyan/Yellow, and White/Blue for image intensifier and thermal infrared sensor color representation, respectively, are discussed. Finally, this paper will present digitally fused imagery and image analysis of long distance targets in low light from these digital fused systems. The result of this image analysis with enhanced A+B digital image fusion systems is that maximum contrast and spatial resolution is achieved in a digital fusion mode as compared to individual sensor modalities in low light, long distance imaging applications. Paper has been cleared by DoD/OSR for Public Release under Ref: 08-S-2183 on August 8, 2008.

  16. Clearance Pathways and Tumor Targeting of Imaging Nanoparticles

    PubMed Central

    Yu, Mengxiao; Zheng, Jie

    2016-01-01

    A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs via kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies. PMID:26149184

  17. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma.

    PubMed

    Wachsmann, Jason; Peng, Fangyu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

  18. MR Molecular Imaging of Tumor Vasculature and Vascular Targets

    PubMed Central

    Pathak, Arvind P.; Penet, Marie-France; Bhujwalla, Zaver M.

    2016-01-01

    Tumor angiogenesis and the ability of cancer cells to induce neovasculature continue to be a fascinating area of research. As the delivery network that provides substrates and nutrients, as well as chemotherapeutic agents to cancer cells, but allows cancer cells to disseminate, the tumor vasculature is richly primed with targets and mechanisms that can be exploited for cancer cure or control. The spatial and temporal heterogeneity of tumor vasculature, and the heterogeneity of response to targeting, make noninvasive imaging essential for understanding the mechanisms of tumor angiogenesis, tracking vascular targeting, and detecting the efficacy of antiangiogenic therapies. With its noninvasive characteristics, exquisite spatial resolution and range of applications, magnetic resonance imaging (MRI) techniques have provided a wealth of functional and molecular information on tumor vasculature in applications spanning from “bench to bedside”. The integration of molecular biology and chemistry to design novel imaging probes ensures the continued evolution of the molecular capabilities of MRI. In this review, we have focused on developments in the characterization of tumor vasculature with functional and molecular MRI. PMID:20807600

  19. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

    PubMed Central

    Wachsmann, Jason; Peng, Fangyu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC. PMID:26755872

  20. Targeted diagnostic magnetic nanoparticles for medical imaging of pancreatic cancer.

    PubMed

    Rosenberger, I; Strauss, A; Dobiasch, S; Weis, C; Szanyi, S; Gil-Iceta, L; Alonso, E; González Esparza, M; Gómez-Vallejo, V; Szczupak, B; Plaza-García, S; Mirzaei, S; Israel, L L; Bianchessi, S; Scanziani, E; Lellouche, J-P; Knoll, P; Werner, J; Felix, K; Grenacher, L; Reese, T; Kreuter, J; Jiménez-González, M

    2015-09-28

    Highly aggressive cancer types such as pancreatic cancer possess a mortality rate of up to 80% within the first 6months after diagnosis. To reduce this high mortality rate, more sensitive diagnostic tools allowing an early stage medical imaging of even very small tumours are needed. For this purpose, magnetic, biodegradable nanoparticles prepared using recombinant human serum albumin (rHSA) and incorporated iron oxide (maghemite, γ-Fe2O3) nanoparticles were developed. Galectin-1 has been chosen as target receptor as this protein is upregulated in pancreatic cancer and its precursor lesions but not in healthy pancreatic tissue nor in pancreatitis. Tissue plasminogen activator derived peptides (t-PA-ligands), that have a high affinity to galectin-1 have been chosen as target moieties and were covalently attached onto the nanoparticle surface. Improved targeting and imaging properties were shown in mice using single photon emission computed tomography-computer tomography (SPECT-CT), a handheld gamma camera, and magnetic resonance imaging (MRI).

  1. Targeting SR-BI for Cancer Diagnostics, Imaging and Therapy

    PubMed Central

    Rajora, Maneesha A.; Zheng, Gang

    2016-01-01

    Scavenger receptor class B type I (SR-BI) plays an important role in trafficking cholesteryl esters between the core of high density lipoprotein and the liver. Interestingly, this integral membrane protein receptor is also implicated in the metabolism of cholesterol by cancer cells, whereby overexpression of SR-BI has been observed in a number of tumors and cancer cell lines, including breast and prostate cancers. Consequently, SR-BI has recently gained attention as a cancer biomarker and exciting target for the direct cytosolic delivery of therapeutic agents. This brief review highlights these key developments in SR-BI-targeted cancer therapies and imaging probes. Special attention is given to the exploration of high density lipoprotein nanomimetic platforms that take advantage of upregulated SR-BI expression to facilitate targeted drug-delivery and cancer diagnostics, and promising future directions in the development of these agents. PMID:27729859

  2. Target-oriented Marchenko imaging of a North Sea field

    NASA Astrophysics Data System (ADS)

    Ravasi, Matteo; Vasconcelos, Ivan; Kritski, Alexander; Curtis, Andrew; Filho, Carlos Alberto da Costa; Meles, Giovanni Angelo

    2016-04-01

    Seismic imaging provides much of our information about the Earth's crustal structure. The principal source of imaging errors derives from simplicistically modeled predictions of the complex, scattered wavefields that interact with each subsurface point to be imaged. A new method of wavefield extrapolation based on inverse scattering theory produces accurate estimates of these subsurface scattered wavefields, while still using relatively little information about the Earth's properties. We use it for the first time to create real target-oriented seismic images of a North Sea field. We synthesize underside illumination from surface reflection data, and use it to reveal subsurface features that are not present in an image from conventional migration of surface data. To reconstruct underside reflections, we rely on the so-called downgoing focusing function, whose coda consists entirely of transmission-born multiple scattering. As such, we provide the first field data example of reconstructing underside reflections with contributions from transmitted multiples, without the need to first locate or image any reflectors in order to reconstruct multiple scattering effects.

  3. Imaging of Brain Tumors With Paramagnetic Vesicles Targeted to Phosphatidylserine

    PubMed Central

    Winter, Patrick M.; Pearce, John; Chu, Zhengtao; McPherson, Christopher M.; Takigiku, Ray; Lee, Jing-Huei; Qi, Xiaoyang

    2014-01-01

    Purpose To investigate paramagnetic saposin C and dioleylphosphatidylserine (SapC-DOPS) vesicles as a targeted contrast agent for imaging phosphatidylserine (PS) expressed by glioblastoma multiforme (GBM) tumors. Materials and Methods Gd-DTPA-BSA/SapC-DOPS vesicles were formulated, and the vesicle diameter and relaxivity were measured. Targeting of Gd-DTPA-BSA/ SapC-DOPS vesicles to tumor cells in vitro and in vivo was compared with nontargeted paramagnetic vesicles (lacking SapC). Mice with GBM brain tumors were imaged at 3, 10, 20, and 24 h postinjection to measure the relaxation rate (R1) in the tumor and the normal brain. Results The mean diameter of vesicles was 175 nm, and the relaxivity at 7 Tesla was 3.32 (s*mM)−1 relative to the gadolinium concentration. Gd-DTPA-BSA/SapC-DOPS vesicles targeted cultured cancer cells, leading to an increased R1 and gadolinium level in the cells. In vivo, Gd-DTPA-BSA/SapC-DOPS vesicles produced a 9% increase in the R1 of GBM brain tumors in mice 10 h postinjection, but only minimal changes (1.2% increase) in the normal brain. Nontargeted paramagnetic vesicles yielded minimal change in the tumor R1 at 10 h postinjection (1.3%). Conclusion These experiments demonstrate that Gd-DTPA-BSA/SapC-DOPS vesicles can selectively target implanted brain tumors in vivo, providing noninvasive mapping of the cancer biomarker PS. PMID:24797437

  4. Synthetic aperture radar target detection, feature extraction, and image formation techniques

    NASA Technical Reports Server (NTRS)

    Li, Jian

    1994-01-01

    This report presents new algorithms for target detection, feature extraction, and image formation with the synthetic aperture radar (SAR) technology. For target detection, we consider target detection with SAR and coherent subtraction. We also study how the image false alarm rates are related to the target template false alarm rates when target templates are used for target detection. For feature extraction from SAR images, we present a computationally efficient eigenstructure-based 2D-MODE algorithm for two-dimensional frequency estimation. For SAR image formation, we present a robust parametric data model for estimating high resolution range signatures of radar targets and for forming high resolution SAR images.

  5. Thyroid microsomal/thyroid peroxidase autoantibodies show discrete patterns of cross-reactivity to myeloperoxidase, lactoperoxidase and horseradish peroxidase.

    PubMed Central

    Banga, J P; Tomlinson, R W; Doble, N; Odell, E; McGregor, A M

    1989-01-01

    The recent cloning of the thyroid peroxidase (TPO) has shown that it is identical to the thyroid microsomal antigen (TMA), a potent antigen involved in autoimmune thyroid disease (ATD), which shares significant sequence homology with myeloperoxidase. The present study shows that autoantibodies (aAb) to the TMA/TPO antigen cross-react with human leucocyte myeloperoxidase, bovine lactoperoxidase and horseradish peroxidase. Cross-reactivity to myeloperoxidase was only apparent by ELISA using reduced and alkylated antigen preparations or by immunoblotting following denaturation with SDS. Sequential absorption of sera on SDS-denatured thyroid microsomes immobilized on Sepharose-4B followed by absorption on native microsomes removed all aAb specificities to TMA/TPO and the three peroxidase preparations, giving compelling evidence on the genuine cross-reactive nature of these aAbs. Sera from different patients contain different qualitative and quantitative specificities of aAb to the TMA/TPO antigen, confirming the polyclonal nature of this autoimmune response. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2546881

  6. Small Multifunctional Nanoclusters (Nanoroses) for Targeted Cellular Imaging and Therapy

    PubMed Central

    Ma, Li Leo; Feldman, Marc D.; Tam, Jasmine M.; Paranjape, Amit S.; Cheruku, Kiran K.; Larson, Timothy A.; Tam, Justina O.; Ingram, Davis R.; Paramita, Vidia; Villard, Joseph W.; Jenkins, James T.; Wang, Tianyi; Clarke, Geoffrey D.; Asmis, Reto; Sokolov, Konstantin; Chandrasekar, Bysani; Milner, Thomas E.; Johnston, Keith P.

    2010-01-01

    The ability of 20–50 nm nanoparticles to target and modulate the biology of specific types of cells will enable major advancements in cellular imaging and therapy in cancer and atherosclerosis. A key challenge is to load an extremely high degree of targeting, imaging, and therapeutic functionality into small, yet stable particles. Herein we report ~30 nm stable uniformly sized near-infrared (NIR) active, superparamagnetic nanoclusters formed by kinetically controlled self-assembly of gold-coated iron oxide nanoparticles. The controlled assembly of nanocomposite particles into clusters with small primary particle spacings produces collective responses of the electrons that shift the absorbance into the NIR region. The nanoclusters of ~70 iron oxide primary particles with thin gold coatings display intense NIR (700–850 nm) absorbance with a cross section of ~10−14 m2. Because of the thin gold shells with an average thickness of only 2 nm, the r2 spin–spin magnetic relaxivity is 219 mM−1 s−1, an order of magnitude larger than observed for typical iron oxide particles with thicker gold shells. Despite only 12% by weight polymeric stabilizer, the particle size and NIR absorbance change very little in deionized water over 8 months. High uptake of the nanoclusters by macrophages is facilitated by the dextran coating, producing intense NIR contrast in dark field and hyperspectral microscopy, both in cell culture and an in vivo rabbit model of atherosclerosis. Small nanoclusters with optical, magnetic, and therapeutic functionality, designed by assembly of nanoparticle building blocks, offer broad opportunities for targeted cellular imaging, therapy, and combined imaging and therapy. PMID:19711944

  7. External calibration of polarimetric radar images using distributed targets

    NASA Technical Reports Server (NTRS)

    Yueh, Simon H.; Nghiem, S. V.; Kwok, R.

    1992-01-01

    A new technique is presented for calibrating polarimetric synthetic aperture radar (SAR) images using only the responses from natural distributed targets. The model for polarimetric radars is assumed to be X = cRST where X is the measured scattering matrix corresponding to the target scattering matrix S distorted by the system matrices T and R (in general T does not equal R(sup t)). To allow for the polarimetric calibration using only distributed targets and corner reflectors, van Zyl assumed a reciprocal polarimetric radar model with T = R(sup t); when applied for JPL SAR data, a heuristic symmetrization procedure is used by POLCAL to compensate the phase difference between the measured HV and VH responses and then take the average of both. This heuristic approach causes some non-removable cross-polarization responses for corner reflectors, which can be avoided by a rigorous symmetrization method based on reciprocity. After the radar is made reciprocal, a new algorithm based on the responses from distributed targets with reflection symmetry is developed to estimate the cross-talk parameters. The new algorithm never experiences problems in convergence and is also found to converge faster than the existing routines implemented for POLCAL. When the new technique is implemented for the JPL polarimetric data, symmetrization and cross-talk removal are performed on a line-by-line (azimuth) basis. After the cross-talks are removed from the entire image, phase and amplitude calibrations are carried out by selecting distributed targets either with azimuthal symmetry along the looking direction or with some well-known volume and surface scattering mechanisms to estimate the relative phases and amplitude responses of the horizontal and vertical channels.

  8. Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes.

    PubMed

    Ruggiero, Alessandro; Villa, Carlos H; Holland, Jason P; Sprinkle, Shanna R; May, Chad; Lewis, Jason S; Scheinberg, David A; McDevitt, Michael R

    2010-10-05

    Single wall carbon nanotube (SWCNT) constructs were covalently appended with radiometal-ion chelates (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA] or desferrioxamine B [DFO]) and the tumor neovascular-targeting antibody E4G10. The E4G10 antibody specifically targeted the monomeric vascular endothelial-cadherin (VE-cad) epitope expressed in the tumor angiogenic vessels. The construct specific activity and blood compartment clearance kinetics were significantly improved relative to corresponding antibodyalone constructs. We performed targeted radioimmunotherapy with a SWCNT-([(225)Ac]DOTA) (E4G10) construct directed at the tumor vasculature in a murine xenograft model of human colon adenocarcinoma (LS174T). The specific construct reduced tumor volume and improved median survival relative to controls. We also performed positron emission tomographic (PET) radioimmunoimaging of the tumor vessels with a SWCNT-([(89)Zr]DFO)(E4G10) construct in the same murine LS174T xenograft model and compared the results to appropriate controls. Dynamic and longitudinal PET imaging of LS174T tumor-bearing mice demonstrated rapid blood clearance (<1 hour) and specific tumor accumulation of the specific construct. Incorporation of the SWCNT scaffold into the construct design permitted us to amplify the specific activity to improve the signal-to-noise ratio without detrimentally impacting the immunoreactivity of the targeting antibody moiety. Furthermore, we were able to exploit the SWCNT pharmacokinetic (PK) profile to favorably alter the blood clearance and provide an advantage for rapid imaging. Near-infrared three-dimensional fluorescent-mediated tomography was used to image the LS174T tumor model, collect antibody-alone PK data, and calculate the number of copies of VE-cad epitope per cell. All of these studies were performed as a single administration of construct and were found to be safe and well tolerated by the murine model. These data have implications that

  9. Imaging and treating tumor vasculature with targeted radiolabeled carbon nanotubes.

    PubMed

    Ruggiero, Alessandro; Villa, Carlos H; Holland, Jason P; Sprinkle, Shanna R; May, Chad; Lewis, Jason S; Scheinberg, David A; McDevitt, Michael R

    2010-01-01

    Single wall carbon nanotube (SWCNT) constructs were covalently appended with radiometal-ion chelates (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid [DOTA] or desferrioxamine B [DFO]) and the tumor neovascular-targeting antibody E4G10. The E4G10 antibody specifically targeted the monomeric vascular endothelial-cadherin (VE-cad) epitope expressed in the tumor angiogenic vessels. The construct specific activity and blood compartment clearance kinetics were significantly improved relative to corresponding antibodyalone constructs. We performed targeted radioimmunotherapy with a SWCNT-([(225)Ac]DOTA) (E4G10) construct directed at the tumor vasculature in a murine xenograft model of human colon adenocarcinoma (LS174T). The specific construct reduced tumor volume and improved median survival relative to controls. We also performed positron emission tomographic (PET) radioimmunoimaging of the tumor vessels with a SWCNT-([(89)Zr]DFO)(E4G10) construct in the same murine LS174T xenograft model and compared the results to appropriate controls. Dynamic and longitudinal PET imaging of LS174T tumor-bearing mice demonstrated rapid blood clearance (<1 hour) and specific tumor accumulation of the specific construct. Incorporation of the SWCNT scaffold into the construct design permitted us to amplify the specific activity to improve the signal-to-noise ratio without detrimentally impacting the immunoreactivity of the targeting antibody moiety. Furthermore, we were able to exploit the SWCNT pharmacokinetic (PK) profile to favorably alter the blood clearance and provide an advantage for rapid imaging. Near-infrared three-dimensional fluorescent-mediated tomography was used to image the LS174T tumor model, collect antibody-alone PK data, and calculate the number of copies of VE-cad epitope per cell. All of these studies were performed as a single administration of construct and were found to be safe and well tolerated by the murine model. These data have implications that

  10. Highly selective luminescent nanostructures for mitochondrial imaging and targeting

    NASA Astrophysics Data System (ADS)

    Fanizza, E.; Iacobazzi, R. M.; Laquintana, V.; Valente, G.; Caliandro, G.; Striccoli, M.; Agostiano, A.; Cutrignelli, A.; Lopedota, A.; Curri, M. L.; Franco, M.; Depalo, N.; Denora, N.

    2016-02-01

    Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents.Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino

  11. Imaging the inside of a tumour: a review of radionuclide imaging and theranostics targeting intracellular epitopes.

    PubMed

    Cornelissen, Bart

    2014-04-01

    Molecular imaging of tumour tissue focusses mainly on extracellular epitopes such as tumour angiogenesis or signal transduction receptors expressed on the cell membrane. However, most biological processes that define tumour phenotype occur within the cell. In this mini-review, an overview is given of the various techniques to interrogate intracellular events using molecular imaging with radiolabelled compounds. Additionally, similar targeting techniques can be employed for radionuclide therapy using Auger electron emitters, and recent advances in Auger electron therapy are discussed.

  12. IGF1 Receptor Targeted Theranostic Nanoparticles for Targeted and Image-Guided Therapy of Pancreatic Cancer.

    PubMed

    Zhou, Hongyu; Qian, Weiping; Uckun, Fatih M; Wang, Liya; Wang, Y Andrew; Chen, Hongyu; Kooby, David; Yu, Qian; Lipowska, Malgorzata; Staley, Charles A; Mao, Hui; Yang, Lily

    2015-08-25

    Overcoming resistance to chemotherapy is a major and unmet medical challenge in the treatment of pancreatic cancer. Poor drug delivery due to stromal barriers in the tumor microenvironment and aggressive tumor biology are additional impediments toward a more successful treatment of pancreatic cancer. In attempts to address these challenges, we developed IGF1 receptor (IGF1R)-directed, multifunctional theranostic nanoparticles for targeted delivery of therapeutic agents into IGF1R-expressing drug-resistant tumor cells and tumor-associated stromal cells. These nanoparticles were prepared by conjugating recombinant human IGF1 to magnetic iron oxide nanoparticles (IONPs) carrying the anthracycline doxorubicin (Dox) as the chemotherapeutic payload. Intravenously administered IGF1-IONPs exhibited excellent tumor targeting and penetration in an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer featuring enriched tumor stroma and heterogeneous cancer cells. IGF1R-targeted therapy using the theranostic IGF1-IONP-Dox significantly inhibited the growth of pancreatic PDX tumors. The effects of the intratumoral nanoparticle delivery and therapeutic responses in the orthotopic pancreatic PDX tumors could be detected by magnetic resonance imaging (MRI) with IONP-induced contrasts. Histological analysis showed that IGF1R-targeted delivery of Dox significantly inhibited cell proliferation and induced apoptotic cell death of pancreatic cancer cells. Therefore, further development of IGF1R-targeted theranostic IONPs and MRI-guided cancer therapy as a precision nanomedicine may provide the basis for more effective treatment of pancreatic cancer.

  13. Targeting Villages for Rural Development Using Satellite Image Analysis.

    PubMed

    Varshney, Kush R; Chen, George H; Abelson, Brian; Nowocin, Kendall; Sakhrani, Vivek; Xu, Ling; Spatocco, Brian L

    2015-03-01

    Satellite imagery is a form of big data that can be harnessed for many social good applications, especially those focusing on rural areas. In this article, we describe the common problem of selecting sites for and planning rural development activities as informed by remote sensing and satellite image analysis. Effective planning in poor rural areas benefits from information that is not available and is difficult to obtain at any appreciable scale by any means other than algorithms for estimation and inference from remotely sensed images. We discuss two cases in depth: the targeting of unconditional cash transfers to extremely poor villages in sub-Saharan Africa and the siting and planning of solar-powered microgrids in remote villages in India. From these cases, we draw out some common lessons broadly applicable to informed rural development.

  14. Self-induced thermal distortion effects on target image quality.

    PubMed

    Gebhardt, F G

    1972-06-01

    Experimental results are reported that show the effects of the self-induced thermal lens due to a high power laser beam on imaging or tracking systems viewing along the same propagation path. The thermal distortion effects of a wind are simulated with a low power ( less, similar 3-W) CO(2) laser beam propagating through a cell of liquid CS(2) moving across the beam. The resulting image distortion includes a warping effect analogous to the deflection of the CO(2) beam, together with a pronounced demagnification of the central portion of the object. An active optical tracker is simulated with a He-Ne laser beam propagating collinearly with the CO(2) beam. The He-Ne beam pattern returned from a specular target is distorted and sharply confined to the outline of the crescent shaped CO(2) beam. Simple ray optics models are used to provide qualitative explanations for the experimental results.

  15. Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging.

    PubMed

    Pandey, Mukesh K; DeGrado, Timothy R

    2016-01-01

    Glycogen synthase kinase-3 (GSK-3) is associated with various key biological processes, including glucose regulation, apoptosis, protein synthesis, cell signaling, cellular transport, gene transcription, proliferation, and intracellular communication. Accordingly, GSK-3 has been implicated in a wide variety of diseases and specifically targeted for both therapeutic and imaging applications by a large number of academic laboratories and pharmaceutical companies. Here, we review the structure, function, expression levels, and ligand-binding properties of GSK-3 and its connection to various diseases. A selected list of highly potent GSK-3 inhibitors, with IC50 <20 nM for adenosine triphosphate (ATP)-competitive inhibitors and IC50 <5 μM for non-ATP-competitive inhibitors, were analyzed for structure activity relationships. Furthermore, ubiquitous expression of GSK-3 and its possible impact on therapy and imaging are also highlighted. Finally, a rational perspective and possible route to selective and effective GSK-3 inhibitors is discussed. PMID:26941849

  16. Targeting Villages for Rural Development Using Satellite Image Analysis.

    PubMed

    Varshney, Kush R; Chen, George H; Abelson, Brian; Nowocin, Kendall; Sakhrani, Vivek; Xu, Ling; Spatocco, Brian L

    2015-03-01

    Satellite imagery is a form of big data that can be harnessed for many social good applications, especially those focusing on rural areas. In this article, we describe the common problem of selecting sites for and planning rural development activities as informed by remote sensing and satellite image analysis. Effective planning in poor rural areas benefits from information that is not available and is difficult to obtain at any appreciable scale by any means other than algorithms for estimation and inference from remotely sensed images. We discuss two cases in depth: the targeting of unconditional cash transfers to extremely poor villages in sub-Saharan Africa and the siting and planning of solar-powered microgrids in remote villages in India. From these cases, we draw out some common lessons broadly applicable to informed rural development. PMID:27442844

  17. Glycogen Synthase Kinase-3 (GSK-3)-Targeted Therapy and Imaging

    PubMed Central

    Pandey, Mukesh K.; DeGrado, Timothy R.

    2016-01-01

    Glycogen synthase kinase-3 (GSK-3) is associated with various key biological processes, including glucose regulation, apoptosis, protein synthesis, cell signaling, cellular transport, gene transcription, proliferation, and intracellular communication. Accordingly, GSK-3 has been implicated in a wide variety of diseases and specifically targeted for both therapeutic and imaging applications by a large number of academic laboratories and pharmaceutical companies. Here, we review the structure, function, expression levels, and ligand-binding properties of GSK-3 and its connection to various diseases. A selected list of highly potent GSK-3 inhibitors, with IC50 <20 nM for adenosine triphosphate (ATP)-competitive inhibitors and IC50 <5 μM for non-ATP-competitive inhibitors, were analyzed for structure activity relationships. Furthermore, ubiquitous expression of GSK-3 and its possible impact on therapy and imaging are also highlighted. Finally, a rational perspective and possible route to selective and effective GSK-3 inhibitors is discussed. PMID:26941849

  18. (-)-Epicatechin enhances the chlorinating activity of human myeloperoxidase.

    PubMed

    Kirchner, Tina; Flemmig, Jörg; Furtmüller, Paul Georg; Obinger, Christian; Arnhold, Jürgen

    2010-03-01

    The heme-containing enzyme myeloperoxidase (MPO) accumulates at inflammatory sites and is able to catalyse one- and two-electron oxidation reactions. Here it is shown that (-)-epicatechin, which is known to have numerous beneficial health effects, in low micromolar concentration enhances the degradation of monochlorodimedon (MCD) or the chlorination of taurine in a concentration-dependent bell-shaped manner whereas at higher concentrations it sufficiently suppresses the release of hypochlorous acid. Presented reaction mechanisms demonstrate the efficiency of micromolar concentrations of the flavan-3-ol in overcoming the accumulation of compound II that does not participate in the chlorination cycle. In case of MCD the mechanism is more complicated since it also acts as peroxidase substrate with very different reactivity towards compound I (3 x 10(5) M(-1) s(-1)) and compound II (8.8M(-1)s(-1)) at pH 7. By affecting the chlorinating activity of myeloperoxidase (-)-epicatechin may participate in regulation of immune responses at inflammatory sites.

  19. Axl-Targeted Cancer Imaging with Humanized Antibody h173

    PubMed Central

    Li, Dan; Liu, Shuanglong; Liu, Ren; Park, Ryan; Yu, Haiyang; Krasnoperov, Valery; Gill, Parkash S.; Li, Zibo; Shan, Hong; Conti, Peter S.

    2014-01-01

    Purpose The tyrosine kinase receptor Axl is overexpressed in various types of cancer and correlated with cancer malignancy. Selective Axl blockade reduces tumor growth and metastasis. The purpose of this study was to examine whether the humanized anti-Axl antibody humanized 173 (h173) labeled with near-infrared fluorescence (NIRF) dye Cy5.5 could be applied as a molecular imaging probe for NIRF imaging of Axl expression in tumor models. Procedures NIRF dye Cy5.5 was conjugated to h173 or human normal immunoglobulin G (hIgG) control through amino groups. The resulting probes were evaluated in both A549 (Axl positive) and NCI-H249 (Axl negative) lung cancer xenografts through in vivo NIRF imaging. Ex vivo imaging and probe distribution assay were also carried out to confirm the in vivo imaging results. Results After conjugation, binding activity of h173-Cy5.5 was determined to be 97.75 %± 2.09 % of the unmodified h173. In vitro fluorescence-activated cell sorting (FACS) and fluorescence microscopy analysis validated the specific binding of h173 toward Axl-positive A549 cells. h173-Cy5.5 was then applied to image Axl expression in vivo. In A549 (Axl positive) cancer xenografts, the tumor uptake of h173-Cy5.5 was significantly higher than that of the hIgG-Cy5.5 control (P<0.05) at late time points (1, 2, 3, 4, and 7 days). On the contrary, in NCI-H249 (Axl negative) cancer xenografts, the tumor uptake of both hIgG-Cy5.5 and h173-Cy5.5 was low and showed no significant difference (P>0.05) at all time points examined. Ex vivo imaging and immunofluorescence staining analysis further validated the in vivo imaging results. Conclusions Collectively, all in vitro, in vivo, and ex vivo data suggested that h173-Cy5.5 could serve as a valid probe for Axl-targeted cancer imaging, which could therefore aid in tumor diagnosis, prognosis, and treatment monitoring. PMID:24424460

  20. Advances in target imaging of deep Earth structure

    NASA Astrophysics Data System (ADS)

    Masson, Y.; Romanowicz, B. A.; Clouzet, P.

    2015-12-01

    A new generation of global tomographic models (Lekić and Romanowicz, 2011; French et al, 2013, 2014) has emerged with the development of accurate numerical wavefield computations in a 3D earth combined with access to enhanced HPC capabilities. These models have sharpened up mantle images and unveiled relatively small scale structures that were blurred out in previous generation models. Fingerlike structures have been found at the base of the oceanic asthenosphere, and vertically oriented broad low velocity plume conduits extend throughout the lower mantle beneath those major hotspots that are located within the perimeter of the deep mantle large low shear velocity provinces (LLSVPs). While providing new insights into our understanding of mantle dynamics, the detailed morphology of these features, requires further efforts to obtain higher resolution images. The focus of our ongoing effort is to develop advanced tomographic methods to image remote regions of the Earth at fine scales. We have developed an approach in which distant sources (located outside of the target region) are replaced by an equivalent set of local sources located at the border of the computational domain (Masson et al., 2014). A limited number of global simulations in a reference 3D earth model is then required. These simulations are computed prior to the regional inversion, while iterations of the model need to be performed only within the region of interest, potentially allowing us to include shorter periods at limited additional computational cost. Until now, the application was limited to a distribution of receivers inside the target region. This is particularly suitable for studies of upper mantle structure in regions with dense arrays (e.g. see our companion presentation Clouzet et al., this Fall AGU). Here we present our latest development that now can include teleseismic data recorded outside the imaged region. This allows us to perform regional waveform tomography in the situation where

  1. Exogenous Molecular Probes for Targeted Imaging in Cancer: Focus on Multi-modal Imaging

    PubMed Central

    Joshi, Bishnu P.; Wang, Thomas D.

    2010-01-01

    Cancer is one of the major causes of mortality and morbidity in our healthcare system. Molecular imaging is an emerging methodology for the early detection of cancer, guidance of therapy, and monitoring of response. The development of new instruments and exogenous molecular probes that can be labeled for multi-modality imaging is critical to this process. Today, molecular imaging is at a crossroad, and new targeted imaging agents are expected to broadly expand our ability to detect and manage cancer. This integrated imaging strategy will permit clinicians to not only localize lesions within the body but also to manage their therapy by visualizing the expression and activity of specific molecules. This information is expected to have a major impact on drug development and understanding of basic cancer biology. At this time, a number of molecular probes have been developed by conjugating various labels to affinity ligands for targeting in different imaging modalities. This review will describe the current status of exogenous molecular probes for optical, scintigraphic, MRI and ultrasound imaging platforms. Furthermore, we will also shed light on how these techniques can be used synergistically in multi-modal platforms and how these techniques are being employed in current research. PMID:22180839

  2. Potential Role of Plasma Myeloperoxidase Level in Predicting Long-Term Outcome of Acute Myocardial Infarction

    PubMed Central

    Kaya, Mehmet Gungor; Yalcin, Ridvan; Okyay, Kaan; Poyraz, Fatih; Bayraktar, Nilufer; Pasaoglu, Hatice; Boyaci, Bulent; Cengel, Atiye

    2012-01-01

    We investigated the prognostic importance of plasma myeloperoxidase levels in patients with ST-elevation myocardial infarction (STEMI) at long-term follow-up, and we analyzed the correlations between plasma myeloperoxidase levels and other biochemical values. We evaluated 73 consecutive patients (56 men; mean age, 56 ±11 yr) diagnosed with acute STEMI and 46 age- and sex-matched healthy control participants. Patients were divided into 2 groups according to the median myeloperoxidase level (Group 1: plasma myeloperoxidase ≤68 ng/mL; and Group 2: plasma myeloperoxidase >68 ng/mL). Patients were monitored for the occurrence of major adverse cardiovascular events (MACE), which were defined as cardiac death; reinfarction; new hospital admission for angina; heart failure; and revascularization procedures. The mean follow-up period was 25 ± 16 months. Plasma myeloperoxidase levels were higher in STEMI patients than in control participants (82 ± 34 vs 20 ±12 ng/mL; P=0.001). Composite MACE occurred in 12 patients with high myeloperoxidase levels (33%) and in 4 patients with low myeloperoxidase levels (11%) (P=0.02). The incidences of nonfatal recurrent myocardial infarction and verified cardiac death were higher in the high-mye-loperoxidase group. In multivariate analysis, high plasma myeloperoxidase levels were independent predictors of MACE (odds ratio = 3.843; <95% confidence interval, 1.625–6.563; P=0.003). High plasma myeloperoxidase levels identify patients with a worse prognosis after acute STEMI at 2-year follow-up. Evaluation of plasma myeloperoxidase levels might be useful in determining patients at high risk of death and MACE who can benefit from further aggressive treatment and closer follow-up. PMID:22949765

  3. Autoradiography Imaging in Targeted Alpha Therapy with Timepix Detector

    PubMed Central

    AL Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

    2015-01-01

    There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy. PMID:25688285

  4. Autoradiography imaging in targeted alpha therapy with Timepix detector.

    PubMed

    A L Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

    2015-01-01

    There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy.

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

    PubMed Central

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

    2015-01-01

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

  6. Autoradiography imaging in targeted alpha therapy with Timepix detector.

    PubMed

    A L Darwish, Ruqaya; Staudacher, Alexander Hugo; Bezak, Eva; Brown, Michael Paul

    2015-01-01

    There is a lack of data related to activity uptake and particle track distribution in targeted alpha therapy. These data are required to estimate the absorbed dose on a cellular level as alpha particles have a limited range and traverse only a few cells. Tracking of individual alpha particles is possible using the Timepix semiconductor radiation detector. We investigated the feasibility of imaging alpha particle emissions in tumour sections from mice treated with Thorium-227 (using APOMAB), with and without prior chemotherapy and Timepix detector. Additionally, the sensitivity of the Timepix detector to monitor variations in tumour uptake based on the necrotic tissue volume was also studied. Compartmental analysis model was used, based on the obtained imaging data, to assess the Th-227 uptake. Results show that alpha particle, photon, electron, and muon tracks were detected and resolved by Timepix detector. The current study demonstrated that individual alpha particle emissions, resulting from targeted alpha therapy, can be visualised and quantified using Timepix detector. Furthermore, the variations in the uptake based on the tumour necrotic volume have been observed with four times higher uptake for tumours pretreated with chemotherapy than for those without chemotherapy. PMID:25688285

  7. Constrain static target kinetic iterative image reconstruction for 4D cardiac CT imaging

    NASA Astrophysics Data System (ADS)

    Alessio, Adam M.; La Riviere, Patrick J.

    2011-03-01

    Iterative image reconstruction offers improved signal to noise properties for CT imaging. A primary challenge with iterative methods is the substantial computation time. This computation time is even more prohibitive in 4D imaging applications, such as cardiac gated or dynamic acquisition sequences. In this work, we propose only updating the time-varying elements of a 4D image sequence while constraining the static elements to be fixed or slowly varying in time. We test the method with simulations of 4D acquisitions based on measured cardiac patient data from a) a retrospective cardiac-gated CT acquisition and b) a dynamic perfusion CT acquisition. We target the kinetic elements with one of two methods: 1) position a circular ROI on the heart, assuming area outside ROI is essentially static throughout imaging time; and 2) select varying elements from the coefficient of variation image formed from fast analytic reconstruction of all time frames. Targeted kinetic elements are updated with each iteration, while static elements remain fixed at initial image values formed from the reconstruction of data from all time frames. Results confirm that the computation time is proportional to the number of targeted elements; our simulations suggest that <30% of elements need to be updated in each frame leading to >3 times reductions in reconstruction time. The images reconstructed with the proposed method have matched mean square error with full 4D reconstruction. The proposed method is amenable to most optimization algorithms and offers the potential for significant computation improvements, which could be traded off for more sophisticated system models or penalty terms.

  8. Evaluation of automated target detection using image fusion

    NASA Astrophysics Data System (ADS)

    Irvine, John M.; Abramson, Susan; Mossing, John

    2003-09-01

    Reliance on Automated Target Recognition (ATR) technology is essential to the future success of Intelligence, Surveillance, and Reconnaissance (ISR) missions. Although benefits may be realized through ATR processing of a single data source, fusion of information across multiple images and multiple sensors promises significant performance gains. A major challenge, as ATR fusion technologies mature, is the establishment of sound methods for evaluating ATR performance in the context of data fusion. The Deputy Under Secretary of Defense for Science and Technology (DUSD/S&T), as part of their ongoing ATR Program, has sponsored an effort to develop and demonstrate methods for evaluating ATR algorithms that utilize multiple data source, i.e., fusion-based ATR. This paper presents results from this program, focusing on the target detection and cueing aspect of the problem. The first step in assessing target detection performance is to relate the ground truth to the ATR decisions. Once the ATR decisions have been mapped to ground truth, the second step in the evaluation is to characterize ATR performance. A common approach is to vary the confidence threshold of the ATR and compute the Probability of Detection (PD) and the False Alarm Rate (FAR) associated with each threshold. Varying the threshold, therefore, produces an empirical performance curve relating detection performance to false alarms. Various statistical methods have been developed, largely in the medical imaging literature, to model this curve so that statistical inferences are possible. One approach, based on signal detection theory, generalizes the Receiver Operator Characteristic (ROC) curve. Under this approach, the Free Response Operating Characteristic (FROC) curve models performance for search problems. The FROC model is appropriate when multiple detections are possible and the number of false alarms is unconstrained. The parameterization of the FROC model provides a natural method for characterizing both

  9. Multimodality Imaging with Silica-Based Targeted Nanoparticle Platforms

    SciTech Connect

    Jason S. Lewis

    2012-04-09

    Objectives: To synthesize and characterize a C-Dot silica-based nanoparticle containing 'clickable' groups for the subsequent attachment of targeting moieties (e.g., peptides) and multiple contrast agents (e.g., radionuclides with high specific activity) [1,2]. These new constructs will be tested in suitable tumor models in vitro and in vivo to ensure maintenance of target-specificity and high specific activity. Methods: Cy5 dye molecules are cross-linked to a silica precursor which is reacted to form a dye-rich core particle. This core is then encapsulated in a layer of pure silica to create the core-shell C-Dot (Figure 1) [2]. A 'click' chemistry approach has been used to functionalize the silica shell with radionuclides conferring high contrast and specific activity (e.g. 64Cu and 89Zr) and peptides for tumor targeting (e.g. cRGD and octreotate) [3]. Based on the selective Diels-Alder reaction between tetrazine and norbornene, the reaction is bioorthogonal, highyielding, rapid, and water-compatible. This radiolabeling approach has already been employed successfully with both short peptides (e.g. octreotate) and antibodies (e.g. trastuzumab) as model systems for the ultimate labeling of the nanoparticles [1]. Results: PEGylated C-Dots with a Cy5 core and labeled with tetrazine have been synthesized (d = 55 nm, zeta potential = -3 mV) reliably and reproducibly and have been shown to be stable under physiological conditions for up to 1 month. Characterization of the nanoparticles revealed that the immobilized Cy5 dye within the C-Dots exhibited fluorescence intensities over twice that of the fluorophore alone. The nanoparticles were successfully radiolabeled with Cu-64. Efforts toward the conjugation of targeting peptides (e.g. cRGD) are underway. In vitro stability, specificity, and uptake studies as well as in vivo imaging and biodistribution investigations will be presented. Conclusions: C-Dot silica-based nanoparticles offer a robust, versatile, and multi

  10. Role of Myeloperoxidase in Patients with Chronic Kidney Disease

    PubMed Central

    Kisic, Bojana; Miric, Dijana; Dragojevic, Ilija; Rasic, Julijana; Popovic, Ljiljana

    2016-01-01

    Chronic kidney disease (CKD) is a worldwide public health problem. Patients with CKD have a number of disorders in the organism, and the presence of oxidative stress and systemic inflammation in these patients is the subject of numerous studies. Chronic inflammation joined with oxidative stress contributes to the development of numerous complications: accelerated atherosclerosis process and cardiovascular disease, emergence of Type 2 diabetes mellitus, development of malnutrition, anaemia, hyperparathyroidism, and so forth, affecting the prognosis and quality of life of patients with CKD. In this review we presented the potential role of the myeloperoxidase enzyme in the production of reactive/chlorinating intermediates and their role in oxidative damage to biomolecules in the body of patients with chronic kidney disease and end-stage renal disease. In addition, we discussed the role of modified lipoprotein particles under the influence of prooxidant MPO intermediates in the development of endothelial changes and cardiovascular complications in renal failure. PMID:27127544

  11. Myeloperoxidase-antineutrophil cytoplasmic antibody-associated sensorineural hearing loss.

    PubMed

    Maguchi, S; Fukuda, S; Chida, E; Terayama, Y

    2001-05-01

    A 36-year-old female with hyperthyroidism that had been treated with propilthiouracil (PTU) complained of tinnitus and hearing loss in both ears. She was treated with steroid administration by an otolaryngologist; however, hearing continued to fluctuate when the steroids were tapered. Laboratory evaluation revealed a decreased complement level and elevated levels of immunoglobulin M (IgM) and myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA). With the withdrawal of PTU and high-dose methylprednisolone, she had excellent return of right-sided hearing. In recent years, there have been many reports about MPO-ANCA-associated small vessel vasculitis. Although any organ may be affected by this disease, there are no reports about MPO-ANCA-associated progressive hearing loss without any other organ involvement. The present case suggests the possibility that inner ear blood flow impairment due to ANCA-associated small vessel vasculitis induces the so-called autoimmune sensorineural hearing loss.

  12. Quantum Dot-Based Nanoprobes for In Vivo Targeted Imaging

    PubMed Central

    Zhu, Yian; Hong, Hao; Xu, Zhi Ping; Li, Zhen; Cai, Weibo

    2013-01-01

    Fluorescent semiconductor quantum dots (QDs) have attracted tremendous attention over the last decade. The superior optical properties of QDs over conventional organic dyes make them attractive labels for a wide variety of biomedical applications, whereas their potential toxicity and instability in biological environment has puzzled scientific researchers. Much research effort has been devoted to surface modification and functionalization of QDs to make them versatile probes for biomedical applications, and significant progress has been made over the last several years. This review article aims to describe the current state-of-the-art of the synthesis, modification, bioconjugation, and applications of QDs for in vivo targeted imaging. In addition, QD-based multifunctional nanoprobes are also summarized. PMID:24206136

  13. Localized harmonic motion imaging for focused ultrasound surgery targeting.

    PubMed

    Curiel, Laura; Hynynen, Kullervo

    2011-08-01

    Recently, an in vivo real-time ultrasound-based monitoring technique that uses localized harmonic motion (LHM) to detect changes in tissues during focused ultrasound surgery (FUS) has been proposed to control the exposure. This technique can potentially be used as well for targeting imaging. In the present study, we evaluated the potential of using LHM to detect changes in stiffness and the feasibility of using it for imaging purposes in phantoms and in vivo tumor detection. A single-element FUS transducer (80 mm focal length, 100 mm diameter, 1.485 MHz) was used for inducing a localized harmonic motion and a separate ultrasound diagnostic transducer excited by a pulser/receiver (5 kHz PRF, 5 MHz) was used to track motion. The motion was estimated using cross-correlation techniques on the acquired radio-frequency (RF) signal. Silicon phantom studies were performed to determine the size of inclusion that was possible to detect using this technique. Inclusions were discerned from the surroundings as a reduction on LHM amplitude and it was possible to depict inclusions as small as 4 mm. The amplitude of the induced LHM was always lower at the inclusions compared with the one obtained at the surroundings. Ten New Zealand rabbits had VX2 tumors implanted on their thighs and LHM was induced and measured at the tumor region. Tumors (as small as 10 mm in length and 4 mm in width) were discerned from the surroundings as a reduction on LHM amplitude.

  14. Research on the intelligent control simulation target with IR imaging target for hardware-in-the-loop simulation test

    NASA Astrophysics Data System (ADS)

    Dong, Key-an; Gu, Ye; An, Yan; Meng, Xiang-kai; Lou, Yan; Zhang, Ya-lin; Zhan, Juntong; Song, Yan-song; Dong, Yan; Tong, Shou-feng

    2014-11-01

    The intelligent control of simulation target with infrared imaging target in the indoor and outdoor environment can effectively and quantitatively evaluated the parameters such as the minimum resolution temperature difference (MRTD) and spatial resolution of airborne forward looking infrared, infrared detection and tracking, infrared alarm, and etc. This paper focused on introducing the working principles of the intelligent control simulation target of Infrared imaging target, studying the thermal radiation characteristics of the infrared target surface material, analyzing the influences of the infrared radiation energy distribution, and developing the intelligent control simulation target with IR imaging target for hardware-in-the-loop simulation test. The intelligent control simulation target which area was 5 m2 and concluded 44 infrared targets including two kinds of infrared targets ,0.25m×0.25m;, and 0.25m×0.5m, achieved 1°~10° temperature simulation of target and the background, and temperature control precision better than 0.5°. Field test requirements were achieved by actual test.

  15. Evolution of bombesin conjugates for targeted PET imaging of tumors.

    PubMed

    Zhang, Hanwen; Abiraj, Keelara; Thorek, Daniel L J; Waser, Beatrice; Smith-Jones, Peter M; Honer, Michael; Reubi, Jean Claude; Maecke, Helmut R

    2012-01-01

    Bombesin receptors are under intense investigation as molecular targets since they are overexpressed in several prevalent solid tumors. We rationally designed and synthesized a series of modified bombesin (BN) peptide analogs to study the influence of charge and spacers at the N-terminus, as well as amino acid substitutions, on both receptor binding affinity and pharmacokinetics. This enabled development of a novel (64/67)Cu-labeled BN peptide for PET imaging and targeted radiotherapy of BN receptor-positive tumors. Our results show that N-terminally positively charged peptide ligands had significantly higher affinity to human gastrin releasing peptide receptor (GRPr) than negatively charged or uncharged ligands (IC(50): 3.2±0.5 vs 26.3±3.5 vs 41.5±2.5 nM). The replacement of Nle(14) by Met, and deletion of D-Tyr(6), further resulted in 8-fold higher affinity. Contrary to significant changes to human GRPr binding, modifications at the N-terminal and at the 6(th), 11(th), and 14(th) position of BN induced only slight influences on affinity to mouse GRPr. [Cu(II)]-CPTA-[βAla(11)] BN(7-14) ([Cu(II)]-BZH7) showed the highest internalization rate into PC-3 cells with relatively slow efflux because of its subnanomolar affinity to GRPr. Interestingly, [(64/67)Cu]-BZH7 also displayed similar affinities to the other 2 human BN receptor subtypes. In vivo studies showed that [(64/67)Cu]-BZH7 had a high accumulation in PC-3 xenografts and allowed for clear-cut visualization of the tumor in PET imaging. In addition, a CPTA-glycine derivative, forming a hippurane-type spacer, enhanced kidney clearance of the radiotracer. These data indicate that the species variation of BN receptor plays an important role in screening radiolabeled BN. As well, the positive charge from the metallated complex at the N-terminal significantly increases affinity to human GRPr. Application of these observations enabled the novel ligand [(64/67)Cu]-BZH7 to clearly visualize PC-3 tumors in vivo

  16. Non-Cooperative Target Imaging and Parameter Estimation with Narrowband Radar Echoes.

    PubMed

    Yeh, Chun-mao; Zhou, Wei; Lu, Yao-bing; Yang, Jian

    2016-01-20

    This study focuses on the rotating target imaging and parameter estimation with narrowband radar echoes, which is essential for radar target recognition. First, a two-dimensional (2D) imaging model with narrowband echoes is established in this paper, and two images of the target are formed on the velocity-acceleration plane at two neighboring coherent processing intervals (CPIs). Then, the rotating velocity (RV) is proposed to be estimated by utilizing the relationship between the positions of the scattering centers among two images. Finally, the target image is rescaled to the range-cross-range plane with the estimated rotational parameter. The validity of the proposed approach is confirmed using numerical simulations.

  17. Night vision image fusion for target detection with improved 2D maximum entropy segmentation

    NASA Astrophysics Data System (ADS)

    Bai, Lian-fa; Liu, Ying-bin; Yue, Jiang; Zhang, Yi

    2013-08-01

    Infrared and LLL image are used for night vision target detection. In allusion to the characteristics of night vision imaging and lack of traditional detection algorithm for segmentation and extraction of targets, we propose a method of infrared and LLL image fusion for target detection with improved 2D maximum entropy segmentation. Firstly, two-dimensional histogram was improved by gray level and maximum gray level in weighted area, weights were selected to calculate the maximum entropy for infrared and LLL image segmentation by using the histogram. Compared with the traditional maximum entropy segmentation, the algorithm had significant effect in target detection, and the functions of background suppression and target extraction. And then, the validity of multi-dimensional characteristics AND operation on the infrared and LLL image feature level fusion for target detection is verified. Experimental results show that detection algorithm has a relatively good effect and application in target detection and multiple targets detection in complex background.

  18. High Precision Imaging of Microscopic Spread of Glioblastoma with a Targeted Ultrasensitive SERRS Molecular Imaging Probe

    PubMed Central

    Huang, Ruimin; Harmsen, Stefan; Samii, Jason M.; Karabeber, Hazem; Pitter, Kenneth L.; Holland, Eric C.; Kircher, Moritz F.

    2016-01-01

    The dismal prognosis of patients with malignant brain tumors such as glioblastoma multiforme (GBM) is attributed mostly to their diffuse growth pattern and early microscopic tumor spread to distant regions of the brain. Because the microscopic tumor foci cannot be visualized with current imaging modalities, it remains impossible to direct treatments optimally. Here we explored the ability of integrin-targeted surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles to depict the true tumor extent in a GBM mouse model that closely mimics the pathology in humans. The recently developed SERRS-nanoparticles have a sensitivity of detection in the femtomolar range. An RGD-peptide-conjugated version for integrin-targeting (RGD-SERRS) was compared directly to its non-targeted RAD-SERRS control in the same mice via Raman multiplexing. Pre-blocking with RGD peptide before injection of RGD-SERRS nanoparticles was used to verify the specificity of integrin-targeting. In contrast to the current belief that the enhanced permeability and retention (EPR) effect results in a baseline uptake of nanoparticles regardless of their surface chemistry, integrin-targeting was shown to be highly specific, with markedly lower accumulation after pre-blocking. While the non-targeted SERRS particles enabled delineation of the main tumor, the RGD-SERRS nanoparticles afforded a major improvement in visualization of the true extent and the diffuse margins of the main tumor. This included the detection of unexpected tumor areas distant to the main tumor, tracks of migrating cells of 2-3 cells in diameter, and even isolated distant tumor cell clusters of less than 5 cells. This Raman spectroscopy-based nanoparticle-imaging technology holds promise to allow high precision visualization of the true extent of malignant brain tumors. PMID:27279902

  19. VHDL Modeling and Simulation for a Digital Target Imaging Architecture for Multiple Large Targets Generation

    NASA Astrophysics Data System (ADS)

    Bergoen, Halkan

    2002-09-01

    The subject of this thesis is to model and verify the correctness of the architecture of the Digital Image Synthesizer (DIS). The DIS, a system-on-a-chip, is especially useful as a counter-targeting repeater. It synthesizes the characteristic echo signature of a pre-selected target. The VHDL (VHSIC (Very High Speed Integrated Circuit) Hardware Description Language) description of the DIS architecture was exported from Tanner S-Edit, modified, and simulated. Different software oriented verification approaches were researched and a White-box approach to functional verification was adopted. An algorithm based on the hardware functionality was developed to compare expected and simulated results. Initially, the architecture of one Range Bin Modulator was exported. Modifications to the VHDL source code included modeling of the behavior of the N-FET and P-FET (Positive Channel Field Effect Transistor) transistors as well as Ground and Vdd (the voltages connected to the drains of the FETs). It also included renaming of entities to comply with VHDL naming conventions. Simulation results were compared to manual calculations and Matlab programs to verify the architecture. The procedure was repeated for the architecture of an Eight-Range Bin Modulator with equally successful results. VHDL was then used to create a super class of a 32-Range Bin Modulator. Test vectors developed in Matlab were used to yet again verify correct functionality.

  20. Impact of 4D image quality on the accuracy of target definition.

    PubMed

    Nielsen, Tine Bjørn; Hansen, Christian Rønn; Westberg, Jonas; Hansen, Olfred; Brink, Carsten

    2016-03-01

    Delineation accuracy of target shape and position depends on the image quality. This study investigates whether the image quality on standard 4D systems has an influence comparable to the overall delineation uncertainty. A moving lung target was imaged using a dynamic thorax phantom on three different 4D computed tomography (CT) systems and a 4D cone beam CT (CBCT) system using pre-defined clinical scanning protocols. Peak-to-peak motion and target volume were registered using rigid registration and automatic delineation, respectively. A spatial distribution of the imaging uncertainty was calculated as the distance deviation between the imaged target and the true target shape. The measured motions were smaller than actual motions. There were volume differences of the imaged target between respiration phases. Imaging uncertainties of >0.4 cm were measured in the motion direction which showed that there was a large distortion of the imaged target shape. Imaging uncertainties of standard 4D systems are of similar size as typical GTV-CTV expansions (0.5-1 cm) and contribute considerably to the target definition uncertainty. Optimising and validating 4D systems is recommended in order to obtain the most optimal imaged target shape.

  1. Inactivation of transferrin iron binding capacity by the neutrophil myeloperoxidase system

    SciTech Connect

    Clark, R.A.; Pearson, D.W.

    1989-06-05

    Human serum apotransferrin was exposed to the isolated myeloperoxidase-H2O2-halide system or to phorbol ester-activated human neutrophils. Such treatment resulted in a marked loss in transferrin iron binding capacity as well as concomitant iodination of transferrin. Each component of the cell-free system (myeloperoxidase, H2O2, iodide) or neutrophil system (neutrophils, phorbol ester, iodide) was required in order to observe these changes. In the cell-free system, the H2O2 requirement was fulfilled by either reagent H2O2 or the peroxide-generating system glucose oxidase plus glucose. Both loss of iron binding capacity and transferrin iodination by either the myeloperoxidase system or activated neutrophils were blocked by azide or catalase. The isolated peroxidase system had an acidic pH optimum, whereas the intact cell system was more efficient at neutral pH. The kinetics of changes in iron binding capacity and iodination closely paralleled one another, exhibiting t1/2 values of less than 1 min for the myeloperoxidase-H2O2 system, 3-4 min for the myeloperoxidase-glucose oxidase system, and 8 min for the neutrophil system. That the occupied binding site is protected from the myeloperoxidase system was suggested by (1) a failure to mobilize iron from iron-loaded transferrin, (2) an inverse correlation between initial iron saturation and myeloperoxidase-mediated loss of iron binding capacity, and (3) decreased myeloperoxidase-mediated iodination of iron-loaded versus apotransferrin. Since as little as 1 atom of iodide bound per molecule of transferrin was associated with substantial losses in iron binding capacity, there appears to be a high specificity of myeloperoxidase-catalyzed iodination for residues at or near the iron binding sites. Amino acid analysis of iodinated transferrin (approximately 2 atoms/molecule) demonstrated that iodotyrosine was the predominant iodinated species.

  2. A targeted approach to cancer imaging and therapy

    NASA Astrophysics Data System (ADS)

    Li, Chun

    2014-02-01

    Nanoparticle-based imaging plays a crucial role in cancer diagnosis and treatment. Here, we discuss the modalities used for molecular imaging of the tumour microenvironment and image-guided interventions including drug delivery, surgery and ablation therapy.

  3. Targeted contrast agents--an adjunct to whole-body imaging: current concepts.

    PubMed

    Foran, Paul; Bolster, Ferdia; Crosbie, Ian; MacMahon, Peter; O'Kennedy, Richard; Eustace, Stephen J

    2010-03-01

    This article reviews the potential use of a combination of whole-body imaging and targeted contrast agents in improving diagnostics, with a particular focus on oncology imaging. It looks at the rationale for nanoparticles and their development as targeted contrast agents. It subsequently describes many of the advances made thus far in developing tissue-specific contrast agents capable of targeting tumors that combined with whole-body imaging may enable superior cancer detection and characterization.

  4. Parameter Estimation of a Ground Moving Target Using Image Sharpness Optimization.

    PubMed

    Yu, Jing; Li, Yaan

    2016-06-30

    Motion parameter estimation of a ground moving target is an important issue in synthetic aperture radar ground moving target indication (SAR-GMTI) which has significant applications for civilian and military. The SAR image of a moving target may be displaced and defocused due to the radial and along-track velocity components, respectively. The sharpness cost function presents a measure of the degree of focus of the image. In this work, a new ground moving target parameter estimation algorithm based on the sharpness optimization criterion is proposed. The relationships between the quadratic phase errors and the target's velocity components are derived. Using two-dimensional searching of the sharpness cost function, we can obtain the velocity components of the target and the focused target image simultaneously. The proposed moving target parameter estimation method and image sharpness metrics are analyzed in detail. Finally, numerical results illustrate the effective and superior velocity estimation performance of the proposed method when compared to existing algorithms.

  5. Imaging of multiple mRNA targets using quantum dot based in situ hybridization and spectral deconvolution in clinical biopsies

    SciTech Connect

    Tholouli, Eleni; Hoyland, Judith A.; Di Vizio, Dolores; O'Connell, Fionnuala; MacDermott, Sarah A.; Twomey, David; Levenson, Richard; Yin, John A. Liu; Golub, Todd R.; Loda, Massimo; Byers, Richard . E-mail: r.byers@manchester.ac.uk

    2006-09-22

    Gene expression mapping using microarray analysis has identified useful gene signatures for predicting outcome. However, little of this has been translated into clinically effective diagnostic tools as microarrays require high quality fresh-frozen tissue samples. We describe a methodology of multiplexed in situ hybridization (ISH) using a novel combination of quantum dot (QD)-labeled oligonucleotide probes and spectral imaging analysis in routinely processed, formalin-fixed paraffin embedded human biopsies. The conditions for QD-ISH were optimized using a poly d(T) oligonucleotide in decalcified bone marrow samples. Single and multiplex QD-ISH was performed in samples with acute leukemia and follicular lymphoma using oligonucleotide probes for myeloperoxidase, bcl-2, survivin, and XIAP. Spectral imaging was used for post hybridization tissue analysis, enabling separation of spatially colocalized signals. The method allows quantitative characterization of multiple gene expression using non-bleaching fluorochromes. This is expected to facilitate multiplex in situ transcript detection in routinely processed human clinical tissue.

  6. Intracellular imaging of targeted proteins labeled with quantum dots

    SciTech Connect

    Yoo, Jungwoo; Kambara, Taketoshi; Gonda, Kohsuke; Higuchi, Hideo

    2008-11-15

    We developed a new method for imaging the movement of targeted proteins in living cancer cells with photostable and bright quantum dots (QDs). QDs were conjugated with various molecules and proteins, such as phalloidin, anti-tubulin antibody and kinesin. These bioconjugated QDs were mixed with a transfection reagent and successfully internalized into living cells. The movements of individual QDs were tracked for long periods of time. Phalloidin conjugated QDs bound to actin filaments and showed almost no movement. In contrast, anti-tubulin antibody conjugated QDs bound to microtubules and revealed dynamic movement of microtubules. Kinesin showed an interesting behavior whereby kinesin came to be almost paused briefly for a few seconds and then moved once again. This is in direct contrast to the smoothly continuous movement of kinesin in an in vitro assay. The maximum velocity of kinesin in cells was faster than that in the in vitro assay. These results suggest that intracellular movement of kinesin is different from that in the in vitro assay. This newly described method will be a powerful tool for investigating the functions of proteins in living cells.

  7. [Influence of human body target's spectral characteristics on visual range of low light level image intensifiers].

    PubMed

    Zhang, Jun-Ju; Yang, Wen-Bin; Xu, Hui; Liu, Lei; Tao, Yuan-Yaun

    2013-11-01

    To study the effect of different human target's spectral reflective characteristic on low light level (LLL) image intensifier's distance, based on the spectral characteristics of the night-sky radiation and the spectral reflective coefficients of common clothes, we established a equation of human body target's spectral reflective distribution, and analyzed the spectral reflective characteristics of different human targets wearing the clothes of different color and different material, and from the actual detection equation of LLL image intensifier distance, discussed the detection capability of LLL image intensifier for different human target. The study shows that the effect of different human target's spectral reflective characteristic on LLL image intensifier distance is mainly reflected in the average reflectivity rho(-) and the initial contrast of the target and the background C0. Reflective coefficient and spectral reflection intensity of cotton clothes are higher than polyester clothes, and detection capability of LLL image intensifier is stronger for the human target wearing cotton clothes. Experimental results show that the LLL image intensifiers have longer visual ranges for targets who wear cotton clothes than targets who wear same color but polyester clothes, and have longer visual ranges for targets who wear light-colored clothes than targets who wear dark-colored clothes. And in the full moon illumination conditions, LLL image intensifiers are more sensitive to the clothes' material.

  8. Simulation of target interpretation based on infrared image features and psychology principle

    NASA Astrophysics Data System (ADS)

    Lin, Wei; Chen, Yu-hua; Gao, Hong-sheng; Wang, Zhan-feng; Wang, Ji-jun; Su, Rong-hua; Huang, Yan-ping

    2009-07-01

    It's an important and complicated process in target interpretation that target features extraction and identification, which effect psychosensorial quantity of interpretation person to target infrared image directly, and decide target viability finally. Using statistical decision theory and psychology principle, designing four psychophysical experiment, the interpretation model of the infrared target is established. The model can get target detection probability by calculating four features similarity degree between target region and background region, which were plotted out on the infrared image. With the verification of a great deal target interpretation in practice, the model can simulate target interpretation and detection process effectively, get the result of target interpretation impersonality, which can provide technique support for target extraction, identification and decision-making.

  9. Effect of Patient Set-up and Respiration motion on Defining Biological Targets for Image-Guided Targeted Radiotherapy

    NASA Astrophysics Data System (ADS)

    McCall, Keisha C.

    Identification and monitoring of sub-tumor targets will be a critical step for optimal design and evaluation of cancer therapies in general and biologically targeted radiotherapy (dose-painting) in particular. Quantitative PET imaging may be an important tool for these applications. Currently radiotherapy planning accounts for tumor motion by applying geometric margins. These margins create a motion envelope to encompass the most probable positions of the tumor, while also maintaining the appropriate tumor control and normal tissue complication probabilities. This motion envelope is effective for uniform dose prescriptions where the therapeutic dose is conformed to the external margins of the tumor. However, much research is needed to establish the equivalent margins for non-uniform fields, where multiple biological targets are present and each target is prescribed its own dose level. Additionally, the size of the biological targets and close proximity make it impractical to apply planning margins on the sub-tumor level. Also, the extent of high dose regions must be limited to avoid excessive dose to the surrounding tissue. As such, this research project is an investigation of the uncertainty within quantitative PET images of moving and displaced dose-painting targets, and an investigation of the residual errors that remain after motion management. This included characterization of the changes in PET voxel-values as objects are moved relative to the discrete sampling interval of PET imaging systems (SPECIFIC AIM 1). Additionally, the repeatability of PET distributions and the delineating dose-painting targets were measured (SPECIFIC AIM 2). The effect of imaging uncertainty on the dose distributions designed using these images (SPECIFIC AIM 3) has also been investigated. This project also included analysis of methods to minimize motion during PET imaging and reduce the dosimetric impact of motion/position-induced imaging uncertainty (SPECIFIC AIM 4).

  10. Kinetic evidence for rapid oxidation of (-)-epicatechin by human myeloperoxidase

    SciTech Connect

    Spalteholz, Holger; Furtmueller, Paul Georg; Jakopitsch, Christa; Obinger, Christian; Schewe, Tankred; Sies, Helmut; Arnhold, Juergen

    2008-07-11

    Apocynin has been reported to require dimerization by myeloperoxidase (MPO) to inhibit leukocyte NADPH oxidase. (-)-Epicatechin, a dietary flavan-3-ol, has been identified as a 'prodrug' of apocynin-like metabolites that inhibit endothelial NADPH oxidase activity and elevate the cellular level of nitric oxide. Since (-)-epicatechin has tentatively been identified as substrate of MPO, we studied the one-electron oxidation of (-)-epicatechin by MPO. By using multi-mixing stopped-flow technique, we demonstrate that (-)-epicatechin is one of the most efficient electron donors for heme peroxidases investigated so far. Second order rate constants for the (-)-epicatechin-mediated conversion of MPO-compound I to compound II and compound II to resting enzyme were estimated to be 1.9 x 10{sup 7} and 4.5 x 10{sup 6} M{sup -1} s{sup -1}, respectively (pH 7, 25 deg. C). The data indicate that (-)-epicatechin is capable of undergoing fast MPO-mediated one-electron oxidation.

  11. Cyanate-mediated inhibition of neutrophil myeloperoxidase activity.

    PubMed Central

    Qian, M; Eaton, J W; Wolff, S P

    1997-01-01

    Cyanate (CNO-) forms spontaneously in solutions containing urea, and is present in urine and the body fluids of uraemic patients. We have explored the possibility that CNO- might be one of the unknown substances responsible for the reported impairment, by urine and uraemic plasma, of neutrophil oxidative metabolism (especially as measured by luminol-enhanced chemiluminescence). Luminol-enhanced chemiluminescence generated by human neutrophils derives predominantly from the activity of myeloperoxidase (MPO) which produces hypochlorous acid from H2O2 and Cl-. We hypothesized that CNO- (which resembles the 'pseudohalide' thiocyanate, an alternative substrate for MPO) might somehow interfere with the activity of MPO. In support of this, we find: (i) CNO- inhibits both peroxidative and halogenating activities of MPO and also inhibits the enzyme within intact human neutrophils; (ii) the inhibition is H2O2-dependent, irreversible, accompanied by covalent addition of [14C]CNO- (or a carbon-containing fragment thereof) to the enzyme; (iii) CNO- also inhibits Cl-/H2O2/MPO-mediated bacterial killing. Impairment of this arm of neutrophil bactericidal activity by CNO- formed from urea may be one factor in the risk of urinary-tract infection associated with urinary stasis and perhaps in the generalized increase in susceptibility to infection in uraemic patients. PMID:9337863

  12. Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis

    PubMed Central

    Hilhorst, Marc; van Paassen, Pieter

    2015-01-01

    In patients with GN or vasculitis, ANCAs are directed against proteinase 3 (PR3) or myeloperoxidase (MPO). The differences between PR3-ANCA-associated vasculitis (AAV) and MPO-AAV described in the past have been supplemented during the last decade. In this review, we discuss the differences between these two small-vessel vasculitides, focusing especially on possible etiologic and pathophysiologic differences. PR3-AAV is more common in northern parts of the world, whereas MPO-AAV is more common in southern regions of Europe, Asia, and the Pacific, with the exception of New Zealand and Australia. A genetic contribution has been extensively studied, and there is a high prevalence of the HLA-DPB1*04:01 allele in patients with PR3-AAV as opposed to patients with MPO-AAV and/or healthy controls. Histologically, MPO-AAV and PR3-AAV are similar but show qualitative differences when analyzed carefully. Clinically, both serotypes are difficult to distinguish, but quantitative differences are present. More organs are affected in PR3-AAV, whereas renal limited vasculitis occurs more often in patients with MPO-AAV. For future clinical trials, we advocate classifying patients by ANCA serotype as opposed to the traditional disease type classification. PMID:25956510

  13. Inhibition of myeloperoxidase and antioxidative activity of Gentiana lutea extracts.

    PubMed

    Nastasijević, Branislav; Lazarević-Pašti, Tamara; Dimitrijević-Branković, Suzana; Pašti, Igor; Vujačić, Ana; Joksić, Gordana; Vasić, Vesna

    2012-07-01

    The aim of this study was to investigate the inhibitory activity of Gentiana lutea extracts on the enzyme myeloperoxidase (MPO), as well as the antioxidant activity of these extracts and their correlation with the total polyphenol content. Extracts were prepared using methanol (100%), water and ethanol aqueous solutions (96, 75, 50 and 25%v/v) as solvents for extraction. Also, isovitexin, amarogentin and gentiopicroside, pharmacologically active constituents of G. lutea were tested as potential inhibitors of MPO. Antioxidant activity of extracts was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging test and also using cyclic voltammetry (CV). Among all extracts, the antioxidant capacity of 50% ethanol aqueous extract was the highest, both when measured using the DPPH test, with IC(50)=20.6 μg/ml, and when using CV. Also, 50% ethanol extract, showed the best inhibition of MPO activity in comparison with other extracts. In the group of the selected G. lutea constituents, gentiopicroside has proved to be the strongest inhibitor of MPO, with IC(50)=0.8 μg/ml. Also, the concentration of G. lutea constituents were determined in all extracts, using Ultra Performance Liquid Chromatography (UPLC).

  14. Myeloperoxidase in human peripheral blood lymphocytes: Production and subcellular localization.

    PubMed

    Okada, Sabrina Sayori; de Oliveira, Edson Mendes; de Araújo, Tomaz Henrique; Rodrigues, Maria Rita; Albuquerque, Renata Chaves; Mortara, Renato Arruda; Taniwaki, Noemi Nosomi; Nakaya, Helder Imoto; Campa, Ana; Moreno, Ana Carolina Ramos

    2016-02-01

    Myeloperoxidase (MPO) is an important enzyme in the front-line protection against microorganisms. In peripheral blood, it is accepted that MPO is only produced by myeloid-lineage cells. Thus, MPO presence is unexpected in lymphocytes. We showed recently that B1-lymphocytes from mice have MPO. Here, we showed that subsets of human peripheral B, CD4(+) and CD8(+) T lymphocytes express MPO. The content of MPO in lymphocytes was very low compared to neutrophils/monocytes with a preferential distribution in the nucleus and perinuclear region. Also, we performed a MPO mRNA expression analysis from human blood cells derived from microarray raw data publicly available, showing that MPO is modulated in infectious disease. MPO was increased in CD4(+) T lymphocytes from HIV chronic infection and in CD8(+) T lymphocytes from HCV-positive patients. Our study points out MPO as a multifunctional protein due to its subcellular localization and expression modulation in lymphocytes indicating alternative unknown functions for MPO in lymphocytes. PMID:26632272

  15. Megavoltage image contrast with low-atomic number target materials and amorphous silicon electronic portal imagers

    NASA Astrophysics Data System (ADS)

    Orton, E. J.; Robar, J. L.

    2009-03-01

    Low-atomic number (Z) targets have been shown to improve contrast in megavoltage (MV) images when using film-screen detection systems. This research aims to quantify the effect of low-Z targets on MV image contrast using an amorphous silicon electronic portal image detector (a-Si EPID) through both experimental measurement and Monte Carlo (MC) simulation. Experimental beams were produced with the linac running in the 6 MeV electron mode and with a 1.0 cm aluminum (Al, Z = 13) target replacing flattening filtration in the carousel, (6 MeV/Al). A 2100EX Varian linac equipped with an aS500 EPID was used with the QC3 MV phantom for the majority of contrast measurements. The BEAMnrc/EGSnrc MC package was used to build a model of the full imaging system including beam generation (linac head), the a-Si detector and the contrast phantom. The model accurately reproduces contrast measurements to within 2.5% for both the standard 6 MV therapy beam and the 6 MeV/Al beam. The contrast advantage of 6 MeV/Al over 6 MV, as quantified with the QC3 phantom, ranged from a factor increase of 1.6 ± 0.1 to 2.8 ± 0.2. Only a modest improvement in contrast was seen when the incident electron energy was reduced to 4 MeV (up to factor of 1.2 ± 0.1 over 6 MeV/Al) or with removal of the copper build-up layer in the detector, (up to factor of 1.2 ± 0.1 over 6 MeV/Al). Further decreasing the target Z, to beryllium (Be, Z = 4), at 4 MeV showed no significant improvement over 4 MeV/Al. Experimentally, the contrast advantage of 6 MeV/Al over 6 MV was found to decrease with increasing patient thickness, as can be expected due to selective attenuation of low-energy photons. At head and neck-like thicknesses, the low-Z advantage is a factor increase of 1.7 ± 0.1.

  16. Immunomodulation by neutrophil myeloperoxidase and hydrogen peroxide: differential susceptibility of human lymphocyte functions.

    PubMed

    el-Hag, A; Lipsky, P E; Bennett, M; Clark, R A

    1986-05-01

    The coexistence of activated polymorphonuclear leukocytes and lymphocytes in tumor masses and inflammatory tissues suggests the possibility of interaction between secreted neutrophil products and nearby lymphocytes. To test this hypothesis, we examined the effects of neutrophil myeloperoxidase and H2O2 on lymphocytes. Human peripheral blood mononuclear leukocytes were exposed to myeloperoxidase, an H2O2-generating system (glucose + glucose oxidase), and a halide, and were then tested for functional activities. Natural killer activity against K562 cells, lymphocyte proliferation in response to mitogens, and generation of immunoglobulin-secreting cells were all susceptible to oxidative injury by myeloperoxidase and H2O2. The degree as well as the mechanism of suppression was dependent on the glucose oxidase concentration (i.e., the rate of H2O2 delivery). At low H2O2 flux, myeloperoxidase was essential for induction of lymphocyte suppression; as the rate of H2O2 generation increased, suppression became myeloperoxidase-independent and was mediated by H2O2 alone. Various lymphocyte functions were differentially susceptible to oxidative injury by myeloperoxidase and H2O2. The proliferative response to poke-weed mitogen was the least sensitive, whereas antibody formation was the most sensitive. Proliferative responses to concanavalin A and phytohemagglutinin as well as natural killer activity displayed intermediate degrees of susceptibility. In all assays, lymphocyte viability was greater than 90%. Removal of monocytes from mononuclear leukocytes by adherence to glass increased susceptibility of lymphocytes to oxidative injury. Monocytes in proportions within the range present in peripheral blood mononuclear leukocytes protected lymphocyte functions against oxidative injury by myeloperoxidase and H2O2. This study demonstrates a differential susceptibility of various immune functions to oxidative injury by the neutrophil products myeloperoxidase and H2O2, and shows, in

  17. Sulfite-mediated oxidation of myeloperoxidase to a free radical: immuno-spin trapping detection in human neutrophils.

    PubMed

    Ranguelova, Kalina; Rice, Annette B; Lardinois, Olivier M; Triquigneaux, Mathilde; Steinckwich, Natacha; Deterding, Leesa J; Garantziotis, Stavros; Mason, Ronald P

    2013-07-01

    Previous studies focused on catalyzed oxidation of (bi)sulfite, leading to the formation of the reactive sulfur trioxide ((•)SO3(-)), peroxymonosulfate ((-)O3SOO(•)), and sulfate (SO4(•-)) anion radicals, which can damage target proteins and oxidize them to protein radicals. It is known that these very reactive sulfur- and oxygen-centered radicals can be formed by oxidation of (bi)sulfite by peroxidases. Myeloperoxidase (MPO), an abundant heme protein secreted from activated neutrophils that play a central role in host defense mechanisms, allergic reactions, and asthma, is a likely candidate for initiating the respiratory damage caused by sulfur dioxide. The objective of this study was to examine the oxidative damage caused by (bi)sulfite-derived free radicals in human neutrophils through formation of protein radicals. We used immuno-spin trapping and confocal microscopy to study the protein oxidations driven by sulfite-derived radicals. We found that the presence of sulfite can cause MPO-catalyzed oxidation of MPO to a protein radical in phorbol 12-myristate 13-acetate-activated human neutrophils. We trapped the MPO-derived radicals in situ using the nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide and detected them immunologically as nitrone adducts in cells. Our present study demonstrates that myeloperoxidase initiates (bi)sulfite oxidation leading to MPO radical damage, possibly leading to (bi)sulfite-exacerbated allergic reactions.

  18. Eccentricity in Images of Circular and Spherical Targets and its Impact to 3D Object Reconstruction

    NASA Astrophysics Data System (ADS)

    Luhmann, T.

    2014-06-01

    This paper discusses a feature of projective geometry which causes eccentricity in the image measurement of circular and spherical targets. While it is commonly known that flat circular targets can have a significant displacement of the elliptical image centre with respect to the true imaged circle centre, it can also be shown that the a similar effect exists for spherical targets. Both types of targets are imaged with an elliptical contour. As a result, if measurement methods based on ellipses are used to detect the target (e.g. best-fit ellipses), the calculated ellipse centre does not correspond to the desired target centre in 3D space. This paper firstly discusses the use and measurement of circular and spherical targets. It then describes the geometrical projection model in order to demonstrate the eccentricity in image space. Based on numerical simulations, the eccentricity in the image is further quantified and investigated. Finally, the resulting effect in 3D space is estimated for stereo and multi-image intersections. It can be stated that the eccentricity is larger than usually assumed, and must be compensated for high-accuracy applications. Spherical targets do not show better results than circular targets. The paper is an updated version of Luhmann (2014) new experimental investigations on the effect of length measurement errors.

  19. Myeloperoxidase-dependent effect of amines on functions of isolated neutrophils.

    PubMed Central

    Thomas, E L; Grisham, M B; Jefferson, M M

    1983-01-01

    Isolated neutrophilic leukocytes were incubated with primary amines and related nitrogenous compounds. Stimulation of neutrophil oxygen (O2) metabolism with phorbol myristate acetate or opsonized zymosan resulted in production of hydrogen peroxide (H2O2), myeloperoxidase-catalyzed oxidation of chloride (C1-) to hypochlorous acid (HOC1), and the reaction of HOC1 with the added compounds to yield nitrogen-chlorine (N-C1) derivatives. Formation of N-C1 derivatives of low lipid solubility resulted in accumulation of the derivatives in the extracellular medium. These oxidizing agents were identified and measured on the basis of their absorption spectra and their ability to oxidize 5-thio-2-nitrobenzoic acid to the disulfide form. The yield of N-Cl derivatives was in the order: taurine greater than Tris greater than spermidine greater than spermine greater than glucosamine greater than putrescine greater than guanidinoacetate. Accumulation of N-C1 derivatives was also observed in the absence of added amines, owing to the reaction of HOC1 with endogenous taurine and other amines that were released from the cells into the medium. In the presence of compounds that yield lipophilic N-C1 derivatives, little or no accumulation of oxidizing agents was observed. Instead, these compounds inhibited the accumulation of N-C1 derivatives that was obtained with taurine, and their effect was competitive with taurine. Inhibition was in the order: methylamine greater than ethanolamine greater than phenylethylamine greater than p-toluenesulfonamide greater than ammonia greater than guanidine. Formation of lipophilic N-C1 derivatives also resulted in inhibition of O2 uptake and glucose metabolism. Inhibition was prevented by adding catalase to eliminate H2O2, dapsone to inhibit myeloperoxidase, taurine to compete for reaction with HOC1, or compounds that are rapidly oxidized by HOC1 or N-C1 derivatives, to reduce these oxidizing agents. The results indicate that: (a) formation of N-C1

  20. Evaluation of a targeted nanobubble ultrasound contrast agent for potential tumor imaging

    NASA Astrophysics Data System (ADS)

    Li, Chunfang; Shen, Chunxu; Liu, Haijuan; Wu, Kaizhi; Zhou, Qibing; Ding, Mingyue

    2015-03-01

    Targeted nanobubbles have been reported to improve the contrast effect of ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, the contrast enhancement abilities and the tumor targeting potential of a self-made VEGFR2-targeted nanobubble ultrasound contrast agent was evaluated in-vitro and in-vivo. Size distribution and zeta potential were assessed. Then the contrast-enhanced ultrasound imaging of the VEGFR2 targeted nanobubbles were evaluated with a custom-made experimental apparatus and in normal Wistar rats. Finally, the in-vivo tumor-targeting ability was evaluated on nude mice with subcutaneous tumor. The results showed that the target nanobubbles had uniform distribution with the average diameter of 208.1 nm, polydispersity index (PDI) of 0.411, and zeta potential of -13.21 mV. Significant contrast enhancement was observed in both in-vitro and in-vivo ultrasound imaging, demonstrating that the self-made target nanobubbles can enhance the contrast effect of ultrasound imaging efficiently. Targeted tumor imaging showed less promising result, due to the fact that the targeted nanobubbles arriving and permeating through tumor vessels were not many enough to produce significant enhancement. Future work will focus on exploring new imaging algorithm which is sensitive to targeted nanobubbles, so as to correctly detect the contrast agent, particularly at a low bubble concentration.

  1. Myeloperoxidase genotype, fruit and vegetable consumption, and breast cancer risk.

    PubMed

    Ahn, Jiyoung; Gammon, Marilie D; Santella, Regina M; Gaudet, Mia M; Britton, Julie A; Teitelbaum, Susan L; Terry, Mary Beth; Neugut, Alfred I; Josephy, P David; Ambrosone, Christine B

    2004-10-15

    Myeloperoxidase (MPO), an antimicrobial enzyme in the breast, generates reactive oxygen species (ROS) endogenously. An MPO G463A polymorphism exists in the promoter region, with the variant A allele conferring lower transcription activity than the common G allele. Because oxidative stress may play a role in breast carcinogenesis, we evaluated MPO genotypes in relation to breast cancer risk among 1,011 cases and 1,067 controls from the Long Island Breast Cancer Study Project (1996-1997). We also assessed the potential modifying effects of dietary antioxidants and hormonally related risk factors on these relationships. Women over 20 years with incident breast cancer who were residents of Nassau and Suffolk Counties, NY, were identified as potential cases. Population-based controls were frequency matched by 5-year age groups. Genotyping was performed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) technology, and suspected breast cancer risk factors and usual dietary intake were assessed during an in-person interview. Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals. Having at least one A allele was associated with an overall 13% reduction in breast cancer risk. When consumption of fruits and vegetables and specific dietary antioxidants were dichotomized at the median, inverse associations with either GA or AA genotypes were most pronounced among women who consumed higher amounts of total fruits and vegetables (odds ratio, 0.75; 95% confidence interval, 0.58-0.97); this association was not noted among the low-consumption group (P for interaction = 0.04). Relationships were strongest among premenopausal women. Results from this first study of MPO genotypes and breast cancer risk indicate that MPO variants, related to reduced generation of ROS, are associated with decreased breast cancer risk, and emphasize the importance of fruit and vegetable consumption in reduction of breast

  2. Myeloperoxidase deficiency ameliorates progression of chronic kidney disease in mice.

    PubMed

    Lehners, Alexander; Lange, Sascha; Niemann, Gianina; Rosendahl, Alva; Meyer-Schwesinger, Catherine; Oh, Jun; Stahl, Rolf; Ehmke, Heimo; Benndorf, Ralf; Klinke, Anna; Baldus, Stephan; Wenzel, Ulrich Otto

    2014-08-15

    Myeloperoxidase (MPO) is an enzyme expressed in neutrophils and monocytes/macrophages. Beside its well-defined role in innate immune defence, it may also be responsible for tissue damage. To identify the role of MPO in the progression of chronic kidney disease (CKD), we investigated CKD in a model of renal ablation in MPO knockout and wild-type mice. CKD was induced by 5/6 nephrectomy. Mice were followed for 10 wk to evaluate the impact of MPO deficiency on renal morbidity. Renal ablation induced CKD in wild-type mice with increased plasma levels of MPO compared with controls. No difference was found between MPO-deficient and wild-type mice regarding albuminuria 1 wk after renal ablation, indicating similar acute responses to renal ablation. Over the next 10 wk, however, MPO-deficient mice developed significantly less albuminuria and glomerular injury than wild-type mice. This was accompanied by a significantly lower renal mRNA expression of the fibrosis marker genes plasminogen activator inhibitor-I, collagen type III, and collagen type IV as well as matrix metalloproteinase-2 and matrix metalloproteinase-9. MPO-deficient mice also developed less renal inflammation after renal ablation, as indicated by a lower infiltration of CD3-positive T cells and F4/80-positive monocytes/macrophages compared with wild-type mice. In vitro chemotaxis of monocyte/macrophages isolated from MPO-deficient mice was impaired compared with wild-type mice. No significant differences were observed for mortality and blood pressure after renal ablation. In conclusion, these results demonstrate that MPO deficiency ameliorates renal injury in the renal ablation model of CKD in mice.

  3. The molecular mechanism for interaction of ceruloplasmin and myeloperoxidase

    NASA Astrophysics Data System (ADS)

    Bakhautdin, Bakytzhan; Bakhautdin, Esen Göksöy

    2016-04-01

    Ceruloplasmin (Cp) is a copper-containing ferroxidase with potent antioxidant activity. Cp is expressed by hepatocytes and activated macrophages and has been known as physiologic inhibitor of myeloperoxidase (MPO). Enzymatic activity of MPO produces anti-microbial agents and strong prooxidants such as hypochlorous acid and has a potential to damage host tissue at the sites of inflammation and infection. Thus Cp-MPO interaction and inhibition of MPO has previously been suggested as an important control mechanism of excessive MPO activity. Our aim in this study was to identify minimal Cp domain or peptide that interacts with MPO. We first confirmed Cp-MPO interaction by ELISA and surface plasmon resonance (SPR). SPR analysis of the interaction yielded 30 nM affinity between Cp and MPO. We then designed and synthesized 87 overlapping peptides spanning the entire amino acid sequence of Cp. Each of the peptides was tested whether it binds to MPO by direct binding ELISA. Two of the 87 peptides, P18 and P76 strongly interacted with MPO. Amino acid sequence analysis of identified peptides revealed high sequence and structural homology between them. Further structural analysis of Cp's crystal structure by PyMOL software unfolded that both peptides represent surface-exposed sites of Cp and face nearly the same direction. To confirm our finding we raised anti-P18 antisera in rabbit and demonstrated that this antisera disrupts Cp-MPO binding and rescues MPO activity. Collectively, our results confirm Cp-MPO interaction and identify two nearly identical sites on Cp that specifically bind MPO. We propose that inhibition of MPO by Cp requires two nearly identical sites on Cp to bind homodimeric MPO simultaneously and at an angle of at least 120 degrees, which, in turn, exerts tension on MPO and results in conformational change.

  4. Bioactivation of myelotoxic xenobiotics by human neutrophil myeloperoxidase

    SciTech Connect

    Roy, R.R.

    1989-01-01

    Many environmental pollutants and drugs are toxic to the bone marrow. Some of these xenobiotics may initiate toxicity after undergoing bioactivation to free radicals and/or other reactive electrophiles. Peroxidases are a group of enzymes that catalyze the one-electron oxidative bioactivation of a variety of xenobiotics in vitro. Myeloperoxidase (MPO) is a peroxidative enzyme found in very high concentration in the neutrophils of human bone marrow. In this study, human MPO was evaluated to determine its ability to catalyze the in vitro bioactivation of known bone marrow toxicants that contain the aromatic hydroxyl (Ar-OH), aromatic amine (Ar-N-R{sub 2}), or heterocyclic tertiary amine ({double bond}N-R) moieties. The formation of free radical metabolites during the MPO-catalyzed bioactivation of hydroquinone and catechol (benzene metabolites), mitoxantrone and ametantrone (antitumor drugs), and chlorpromazine and promazine (antipsychotic drugs) was demonstrated by EPR spectroscopy. The reactivity of the products formed during the MPO catalyzed bioactivation of ({sup 14}C)hydroquinone and ({sup 14}C)catechol was shown by their covalent binding to protein and DNA in vitro. The covalently binding metabolite in each case is postulated to be the quinone form of the xenobiotic. In addition, both GSH and NADH were oxidized by the reactive intermediate(s) formed during the MPO-catalyzed bioactivation of many of the bone marrow toxicants tested. It was also shown that p,p-biphenol stimulated the MPO catalyzed bioactivation of both hydroquinone and catechol, while p-cresol stimulated the MPO-catalyzed bioactivation of catechol.

  5. Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

    PubMed Central

    Vanhamme, Luc; Roumeguère, Thierry; Zouaoui Boudjeltia, Karim

    2013-01-01

    Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFα and IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis. PMID:23983406

  6. Extreme Ultraviolet Imaging of Electron Heated Targets in Petawatt Laser Experiments

    SciTech Connect

    Ma, T; MacPhee, A; Key, M; Akli, K; Mackinnon, A; Chen, C; Barbee, T; Freeman, R; King, J; Link, A; Offermann, D; Ovchinnikov, V; Patel, P; Stephens, R; VanWoerkom, L; Zhang, B; Beg, F

    2007-11-29

    The study of the transport of electrons, and the flow of energy into a solid target or dense plasma, is instrumental in the development of fast ignition inertial confinement fusion. An extreme ultraviolet (XUV) imaging diagnostic at 256 eV and 68 eV provides information about heating and energy deposition within petawatt laser-irradiated targets. XUV images of several irradiated solid targets are presented.

  7. Advances in targeting strategies for nanoparticles in cancer imaging and therapy

    NASA Astrophysics Data System (ADS)

    YheeThese Authors Contributed The Same., Ji Young; Lee, Sangmin; Kim, Kwangmeyung

    2014-10-01

    In the last decade, nanoparticles have offered great advances in diagnostic imaging and targeted drug delivery. In particular, nanoparticles have provided remarkable progress in cancer imaging and therapy based on materials science and biochemical engineering technology. Researchers constantly attempted to develop the nanoparticles which can deliver drugs more specifically to cancer cells, and these efforts brought the advances in the targeting strategy of nanoparticles. This minireview will discuss the progress in targeting strategies for nanoparticles focused on the recent innovative work for nanomedicine.

  8. Clinical applications of perfluorocarbon nanoparticles for molecular imaging and targeted therapeutics

    PubMed Central

    Tran, Trung D; Caruthers, Shelton D; Hughes, Michael; Marsh, John N; Cyrus, Tillmann; Winter, Patrick M; Neubauer, Anne M; Wickline, Samuel A; Lanza, Gregory M

    2007-01-01

    Molecular imaging is a novel tool that has allowed non-invasive diagnostic imaging to transition from gross anatomical description to identification of specific tissue epitopes and observation of biological processes at the cellular level. This technique has been confined to the field of nuclear imaging; however, recent advances in nanotechnology have extended this research to include ultrasound (US) and magnetic resonance (MR) imaging. The exploitation of nanotechnology for MR and US molecular imaging has generated several candidate contrast agents. One multimodality platform, targeted perfluorocarbon (PFC) nanoparticles, is useful for noninvasive detection with US and MR, targeted drug delivery, and quantification. PMID:18203420

  9. Target azimuth estimation for automatic tracking in range-gated imaging

    NASA Astrophysics Data System (ADS)

    Cao, Yinan; Wang, Xinwei; Zhou, Yan

    2012-11-01

    Target tracking is of great importance in imaging system, which can be applied in surveillance, as well as salvage and rescue where 3D spatial coordinates are used to locate the target. Range-gated imaging system is capable of acquiring range information of targets. However, azimuth is also necessary to provide the spatial coordinates to achieve target tracking. This paper presents a target azimuth estimation method for range-gated imaging system, aiming at obtaining essential information for vision-based automatic tracking. Due to the noise and low contrast of range-gated image, median filter and histogram equalization are used. Then the Otsu method is performed to make the segmentation of target and background. After segmentation, morphologic transformation methods will be taken in order to delete false targets. With pixels of target extracted from the image, the centoid will be derived. Next the pinhole camera model is applied to work out the azimuth coordinate. Since the focus length of camera is needed in the formula, an NC (Numerical Control) zoom module is developed. In this module, a sliding potentiometer is connected to the focus motor in camera, which serves as a feedback of the focus. To read the focus length and control the focus motor, an MCU (with AD converter) is used. Once the target azimuth information is obtained, the pan-tilt control unit can track the target bit by bit automatically.

  10. Spectral imaging of neurosurgical target tissues through operation microscope

    NASA Astrophysics Data System (ADS)

    Antikainen, Jukka; von Und Zu Fraunberg, Mikael; Orava, Joni; Jaaskelainen, Juha E.; Hauta-Kasari, Markku

    2011-11-01

    It has been noticed that spectral information can be used for analyzing and separating different biological tissues. However, most of the studies for spectral image acquisitions are mainly done in vitro. Usually the main restrictions for in vivo measurements are the size or the weight of the spectral camera. If the camera weights too much, the surgery microscope cannot be stabilized. If the size of the camera is too big, it will disturb the surgeon or even risk the safety of the patient. The main goal of this study was to develop an independent spectral imaging device which can be used for collecting spectral information from the neurosurgeries without any previously described restrictions. Size of the imaging system is small enough not to disturb the surgeon during the surgery. The developed spectral imaging system is used for collecting a spectral database which can be used for the future imaging systems.

  11. Passive synthetic aperture hitchhiker imaging of ground moving targets--Part 1: image formation and velocity estimation.

    PubMed

    Wacks, Steven; Yazici, Birsen

    2014-06-01

    In the Part 1 of this two-part study, we present a method of imaging and velocity estimation of ground moving targets using passive synthetic aperture radar. Such a system uses a network of small, mobile receivers that collect scattered waves due to transmitters of opportunity, such as commercial television, radio, and cell phone towers. Therefore, passive imaging systems have significant cost, manufacturing, and stealth advantages over active systems. We describe a novel generalized Radon transform-type forward model and a corresponding filtered-backprojection-type image formation and velocity estimation method. We form a stack of position images over a range of hypothesized velocities, and show that the targets can be reconstructed at the correct position whenever the hypothesized velocity is equal to the true velocity of targets. We then use entropy to determine the most accurate velocity and image pair for each moving target. We present extensive numerical simulations to verify the reconstruction method. Our method does not require a priori knowledge of transmitter locations and transmitted waveforms. It can determine the location and velocity of multiple targets moving at different velocities. Furthermore, it can accommodate arbitrary imaging geometries. In Part 2, we present the resolution analysis and analysis of positioning errors in passive SAR images due to erroneous velocity estimation. PMID:24815619

  12. Passive synthetic aperture hitchhiker imaging of ground moving targets--Part 1: image formation and velocity estimation.

    PubMed

    Wacks, Steven; Yazici, Birsen

    2014-06-01

    In the Part 1 of this two-part study, we present a method of imaging and velocity estimation of ground moving targets using passive synthetic aperture radar. Such a system uses a network of small, mobile receivers that collect scattered waves due to transmitters of opportunity, such as commercial television, radio, and cell phone towers. Therefore, passive imaging systems have significant cost, manufacturing, and stealth advantages over active systems. We describe a novel generalized Radon transform-type forward model and a corresponding filtered-backprojection-type image formation and velocity estimation method. We form a stack of position images over a range of hypothesized velocities, and show that the targets can be reconstructed at the correct position whenever the hypothesized velocity is equal to the true velocity of targets. We then use entropy to determine the most accurate velocity and image pair for each moving target. We present extensive numerical simulations to verify the reconstruction method. Our method does not require a priori knowledge of transmitter locations and transmitted waveforms. It can determine the location and velocity of multiple targets moving at different velocities. Furthermore, it can accommodate arbitrary imaging geometries. In Part 2, we present the resolution analysis and analysis of positioning errors in passive SAR images due to erroneous velocity estimation.

  13. Spmk and Grabcut Based Target Extraction from High Resolution Remote Sensing Images

    NASA Astrophysics Data System (ADS)

    Cui, Weihong; Wang, Guofeng; Feng, Chenyi; Zheng, Yiwei; Li, Jonathan; Zhang, Yi

    2016-06-01

    Target detection and extraction from high resolution remote sensing images is a basic and wide needed application. In this paper, to improve the efficiency of image interpretation, we propose a detection and segmentation combined method to realize semi-automatic target extraction. We introduce the dense transform color scale invariant feature transform (TC-SIFT) descriptor and the histogram of oriented gradients (HOG) & HSV descriptor to characterize the spatial structure and color information of the targets. With the k-means cluster method, we get the bag of visual words, and then, we adopt three levels' spatial pyramid (SP) to represent the target patch. After gathering lots of different kinds of target image patches from many high resolution UAV images, and using the TC-SIFT-SP and the multi-scale HOG & HSV feature, we constructed the SVM classifier to detect the target. In this paper, we take buildings as the targets. Experiment results show that the target detection accuracy of buildings can reach to above 90%. Based on the detection results which are a series of rectangle regions of the targets. We select the rectangle regions as candidates for foreground and adopt the GrabCut based and boundary regularized semi-auto interactive segmentation algorithm to get the accurate boundary of the target. Experiment results show its accuracy and efficiency. It can be an effective way for some special targets extraction.

  14. Automatic target recognition algorithm based on statistical dispersion of infrared multispectral image

    NASA Astrophysics Data System (ADS)

    Zhang, Wei; Cao, Le-lin; Wu, Chun-feng; Hou, Qing-yu

    2009-07-01

    A novel automatic target recognition algorithm based on statistical dispersion of infrared multispectral images(SDOIMI) is proposed. Firstly, infrared multispectral characteristic matrix of the scenario is constructed based on infrared multispectral characteristic information (such as radiation intensity and spectral distribution etc.) of targets, background and decoys. Then the infrared multispectral characteristic matrix of targets is reconstructed after segmenting image by maximum distance method and fusing spatial and spectral information. Finally, an statistical dispersion of infrared multispectral images(SDOIMI) recognition criteria is formulated in terms of spectral radiation difference of interesting targets. In simulation, nine sub-bands multispectral images of real ship target and shipborne aerosol infrared decoy modulated by laser simulating ship geometry appearance are obtained via using spectral radiation curves. Digital simulation experiment result verifies that the algorithm is effective and feasible.

  15. Study of target tracking techniques based on non-scanning imaging lidar

    NASA Astrophysics Data System (ADS)

    Chen, Sui; Wang, Qianqian; Zhang, Shuhao; Shan, Bin; Li, Xiaoyang; Peng, Zhong

    2015-08-01

    Non-scanning imaging lidar, as a sensor, is applied in target tracking system to acquire distance image, intensity image and amplitude image, which makes it possible to achieve information fusion of the target. This system applies ARM as a hardware development platform which makes it easy to carry and achieve the system miniaturization. Target characteristics are extracted by the method combines codebook model and connected domain denoising to improve the accuracy of target characteristics extraction. Qt/Embedded development platform applied in building graphical user interface has a good architecture and programming mode which improves man-machine interaction and control efficiency. The results show the high accuracy of the target tracking, excellent man-machine interaction and perfect interface functions of the designed system.

  16. Target detection technology based on polarization imaging in the complex environment

    NASA Astrophysics Data System (ADS)

    Fu, Qiang; Jiang, Hui-lin; Duan, Jin; Mo, Chun-he; Zhuang, Shu-ming; Yang, Yong-he

    2013-09-01

    The polarization imaging detection technology has some advantages in revealling targets in complex background, identify stealthy, camouflage, dim, false target, and "penetrating smoke". This article summarizes foreign polarization imaging detection technology development process, the status and development trends, and discusses the foreign technical level, further research on key technology of polarization imaging detection, put forward a scheme of the detection system based on polarization imaging in complex environment, through increasing the polarization dimension information based on intensity imaging , on which intensity and spectrum cannot reflect, and can significantly enhance the difference between target and background, increase influencing distance in the haze, smoke and dust environment , through the analysis, we elucidated the feasibility and availability of the system, in order to enhance the future of the target detection and recognition ability of photoelectric equipment.

  17. Non-Cooperative Target Imaging and Parameter Estimation with Narrowband Radar Echoes

    PubMed Central

    Yeh, Chun-mao; Zhou, Wei; Lu, Yao-bing; Yang, Jian

    2016-01-01

    This study focuses on the rotating target imaging and parameter estimation with narrowband radar echoes, which is essential for radar target recognition. First, a two-dimensional (2D) imaging model with narrowband echoes is established in this paper, and two images of the target are formed on the velocity-acceleration plane at two neighboring coherent processing intervals (CPIs). Then, the rotating velocity (RV) is proposed to be estimated by utilizing the relationship between the positions of the scattering centers among two images. Finally, the target image is rescaled to the range-cross-range plane with the estimated rotational parameter. The validity of the proposed approach is confirmed using numerical simulations. PMID:26805836

  18. On combining spectral and spatial information of hyperspectral image for camouflaged target detecting

    NASA Astrophysics Data System (ADS)

    Hua, Wenshen; Liu, Xun; Yang, Jia

    2013-12-01

    Detecting enemy's targets and being undetectable play increasingly important roles in modern warfare. Hyperspectral images can provide large spectral range and high spectral resolution, which are invaluable in discriminating between camouflaged targets and backgrounds. As supervised classification requires prior knowledge which cannot be acquired easily, unsupervised classification usually is adopted to process hyperspectral images to detect camouflaged target. But one of its drawbacks—low detecting accuracy confines its application for camouflaged target detecting. Most research on the processing of hyperspectral image tends to focus exclusively on spectral domain and ignores spatial domain. However current hyperspectral image provides high spatial resolution which contains useful information for camouflaged target detecting. A new method combining spectral and spatial information is proposed to increase the detecting accuracy using unsupervised classification. The method has two steps. In the first step, a traditional unsupervised classifier (i.e. K-MEANS, ISODATA) is adopted to classify the hyperspectral image to acquire basic classifications or clusters. During the second step, a 3×3 model and spectral angle mapping are utilized to test the spatial character of the hyperspectral image. The spatial character is defined as spatial homogeneity and calculated by spectral angle mapping. Theory analysis and experiment shows the method is reasonable and efficient. Camouflaged targets are extracted from the background and different camouflaged targets are also recognized. And the proposed algorithm outperforms K-MEANS in terms of detecting accuracy, robustness and edge's distinction. This paper demonstrates the new method is meaningful to camouflaged targets detecting.

  19. Accuracy of positioning and irradiation targeting for multiple targets in intracranial image-guided radiation therapy: a phantom study

    NASA Astrophysics Data System (ADS)

    Tominaga, Hirofumi; Araki, Fujio; Shimohigashi, Yoshinobu; Ishihara, Terunobu; Kawasaki, Keiichi; Kanetake, Nagisa; Sakata, Junichi; Iwashita, Yuki

    2014-12-01

    This study investigated the accuracy of positioning and irradiation targeting for multiple off-isocenter targets in intracranial image-guided radiation therapy (IGRT). A phantom with nine circular targets was created to evaluate both accuracies. First, the central point of the isocenter target was positioned with a combination of an ExacTrac x-ray (ETX) and a 6D couch. The positioning accuracy was determined from the deviations of coordinates of the central point in each target obtained from the kV-cone beam computed tomography (kV-CBCT) for IGRT and the planning CT. Similarly, the irradiation targeting accuracy was evaluated from the deviations of the coordinates between the central point of each target and the central point of each multi-leaf collimator (MLC) field for multiple targets. Secondly, the 6D couch was intentionally rotated together with both roll and pitch angles of 0.5° and 1° at the isocenter and similarly the deviations were evaluated. The positioning accuracy for all targets was less than 1 mm after 6D positioning corrections. The irradiation targeting accuracy was up to 1.3 mm in the anteroposterior (AP) direction for a target 87 mm away from isocenter. For the 6D couch rotations with both roll and pitch angles of 0.5° and 1°, the positioning accuracy was up to 1.0 mm and 2.3 mm in the AP direction for the target 87 mm away from the isocenter, respectively. The irradiation targeting accuracy was up to 2.1 mm and 2.6 mm in the AP direction for the target 87 mm away from the isocenter, respectively. The off-isocenter irradiation targeting accuracy became worse than the positioning accuracy. Both off-isocenter accuracies worsened in proportion to rotation angles and the distance from the isocenter to the targets. It is necessary to examine the set-up margin for off-isocenter multiple targets at each institution because irradiation targeting accuracy is peculiar to the linac machine.

  20. Fluorescence imaging of tumors with "smart" pH-activatable targeted probes.

    PubMed

    Asanuma, Daisuke; Kobayashi, Hisataka; Nagano, Tetsuo; Urano, Yasuteru

    2009-01-01

    One goal of molecular imaging is to establish a widely applicable technique for specific detection of tumors with minimal background originated from non-target tissues. In this study, a "smart" activatable strategy for specific tumor imaging is proposed in which pH-activatable targeted probes specifically detect tumors after binding to the target cell surface proteins, internalization, and eventual acidic pH activation within the acidic organelles. We successfully visualized submillimeter-sized tumors using this strategy in two different tumor mouse models. Since the design of pH-activatable targeted probes can be applied to any target molecules on the cell surface that are to be internalized after ligand binding, this imaging strategy can afford a general and powerful method to diagnose and monitor the target tumors.

  1. Nanomedicine strategies for molecular targets with MRI and optical imaging

    PubMed Central

    Pan, Dipanjan; Caruthers, Shelton D; Chen, Junjie; Winter, Patrick M; SenPan, Angana; Schmieder, Anne H; Wickline, Samuel A

    2010-01-01

    The science of ‘theranostics’ plays a crucial role in personalized medicine, which represents the future of patient management. Over the last decade an increasing research effort has focused on the development of nanoparticle-based molecular-imaging and drug-delivery approaches, emerging as a multidisciplinary field that shows promise in understanding the components, processes, dynamics and therapies of a disease at a molecular level. The potential of nanometer-sized agents for early detection, diagnosis and personalized treatment of diseases is extraordinary. They have found applications in almost all clinically relevant biomedical imaging modality. In this review, a number of these approaches will be presented with a particular emphasis on MRI and optical imaging-based techniques. We have discussed both established molecular-imaging approaches and recently developed innovative strategies, highlighting the seminal studies and a number of successful examples of theranostic nanomedicine, especially in the areas of cardiovascular and cancer therapy. PMID:20485473

  2. Occluded target viewing and identification high-resolution 2D imaging laser radar

    NASA Astrophysics Data System (ADS)

    Grasso, Robert J.; Dippel, George F.; Cecchetti, Kristen D.; Wikman, John C.; Drouin, David P.; Egbert, Paul I.

    2007-09-01

    BAE SYSTEMS has developed a high-resolution 2D imaging laser radar (LADAR) system that has proven its ability to detect and identify hard targets in occluded environments, through battlefield obscurants, and through naturally occurring image-degrading atmospheres. Limitations of passive infrared imaging for target identification using medium wavelength infrared (MWIR) and long wavelength infrared (LWIR) atmospheric windows are well known. Of particular concern is that as wavelength is increased the aperture must be increased to maintain resolution, hence, driving apertures to be very larger for long-range identification; impractical because of size, weight, and optics cost. Conversely, at smaller apertures and with large f-numbers images may become photon starved with long integration times. Here, images are most susceptible to distortion from atmospheric turbulence, platform vibration, or both. Additionally, long-range identification using passive thermal imaging is clutter limited arising from objects in close proximity to the target object.

  3. Preliminary Quantification of Image Color Gradient on Genesis Concentrator Silicon Carbine Target 60001

    NASA Technical Reports Server (NTRS)

    Allton, J. H.; Calaway, M. J.; Rodriquez, M. C.

    2008-01-01

    The Genesis spacecraft concentrator was a device to focus solar wind ions onto a 6-cm diameter target area, thus concentrating the solar wind by 20X [1]. The target area was comprised of 4 quadrants held in place by a gold-coated stainless steel "cross" (Fig. 1). To date, two SiC and one chemical vapor deposited (CVD) quadrants have been imaged at 5X using a Leica DM-6000M in autoscan mode. Complete imaging of SiC sample 60001 required 1036 images. The mosaic of images is shown in Fig. 2 and position of analyzed areas in Fig. 3. This mosaic imaging is part of the curatorial documentation of surface condition and mapping of contamination. Higher magnification (50X) images of selected areas of the target and individual contaminant particles are compiled into reports which may be requested from the Genesis Curator [2].

  4. Survey of evaluation methods in image complexity of target and background

    NASA Astrophysics Data System (ADS)

    Xiao, Bo; Duan, Jin; Zhu, Yong; Chen, Yanqin; Li, Guangming

    2015-10-01

    In the domain of target recognition, the image complexity of target and background is used to describe the difficult degree of extracting and recognizing target from complex background, which has important guiding significance and widely application prospect in a lot of domains such as biological medical, information encrypt, image compression, meteorological analysis, automatic target recognition. This paper comprehensively took the innate characteristics of target and the target local background characteristic into consideration, which affected the algorithm performance of target extraction and recognition, then made generalizations of three classes of evaluation methods: methods based on the target characteristic, including the target shape characteristic, the gray standard deviation of target pixels, the target Local background entropy difference, etc; methods based on the target similitude, including the edge profile and structural characteristic similitude between target and phony target; methods based on the background characteristic, including texture characteristic edge ratio, etc. And on this basis, we made research on the relationship of structural features and evaluation parameters, and analyzed the foundation and properties of each method by contrast. Thoughts and foresights of this field are given at the end of this paper.

  5. Relationship between the lipophilicity of gallic acid n-alquil esters' derivatives and both myeloperoxidase activity and HOCl scavenging.

    PubMed

    Rosso, Rober; Vieira, Tiago O; Leal, Paulo C; Nunes, Ricardo J; Yunes, Rosendo A; Creczynski-Pasa, Tânia B

    2006-09-15

    The gallic acid and several n-alkyl gallates, with the same number of hydroxyl substituents, varying only in the side carbonic chain length, with respective lipophilicity defined through the C log P, were studied. It evidenced the structure-activity relationship of the myeloperoxidase activity inhibition and the hypochlorous acid scavenger property, as well as its low toxicity in rat hepatic tissue. The gallates with C log P below 3.0 (compounds 2-7) were more active against the enzyme activity, what means that the addition of 1-6 carbons (C log P between 0.92 and 2.92) at the side chain increased approximately 50% the gallic acid effect. However, a relationship between the HOCl scavenging capability and the lipophilicity was not observed. With these results it is possible to suggest that the gallates protect the HOCl targets through two mechanisms: inhibiting its production by the enzyme and scavenging the reactive specie.

  6. Clustered targets imaged by optical tomography guided by ultrasound

    NASA Astrophysics Data System (ADS)

    Xu, Yan; Xu, Chen; Zhu, Quing

    2011-07-01

    Clustered small breast lesions may be present in the neighboring areas and are difficult to accurately resolve and quantify in diffuse optical tomography. In addition, larger cancers are often accompanied by clustered satellite lesions in the neighboring areas, which are also difficult to resolve and quantify. To improve the light quantification of clustered lesions, a new multi-zone reconstruction algorithm guided by co-registered ultrasound (US) was investigated using simulations, phantoms, and clinical examples. This method separated one larger region-of-interest (ROI) into several ROIs based on the location information provided by co-registered US. In general, the single-ROI method cannot resolve two smaller targets when their separations were less than 2.5 cm and the depth was greater than 2.0 cm. The multi-zone reconstruction method improved the resolving ability and reconstruction accuracy. As a result, two targets located at 2.5 cm depth with separation greater than 2.0 cm could be distinguished, and reconstruction improved by more than 20% as compared with that of the single-ROI method. When two targets, one larger and one smaller, were located closer to each other, the location of the reconstructed absorption mass was shifted toward the larger target and the quantification of the smaller target was limited.

  7. A system for the real-time display of radar and video images of targets

    NASA Technical Reports Server (NTRS)

    Allen, W. W.; Burnside, W. D.

    1990-01-01

    Described here is a software and hardware system for the real-time display of radar and video images for use in a measurement range. The main purpose is to give the reader a clear idea of the software and hardware design and its functions. This system is designed around a Tektronix XD88-30 graphics workstation, used to display radar images superimposed on video images of the actual target. The system's purpose is to provide a platform for tha analysis and documentation of radar images and their associated targets in a menu-driven, user oriented environment.

  8. Target detection during image formation for ultrawideband radar

    NASA Astrophysics Data System (ADS)

    Kaplan, Lance M.; Oh, Seung-Mok; McClellan, James H.; Murenzi, Romain; Namuduri, Kameswara R.

    1999-09-01

    In this work, we introduce a detection scheme that is able to identify regions of interest during the intermediate stages of an image formation process for ultra-wideband (UWB) synthetic aperture radar. Traditional detection methods manipulate the data after image formation. However, this approach wastes computational resources by resolving to completion the entire scene including area dominated by benign clutter. As an alternative, we introduce a multiscale focus of attention (FOA) algorithm that processes intermediate radar data from a quadtree-based backprojection image formation algorithm. As the stages of the quadtree algorithm progress, the FOA thresholds a detection statistic that estimates the signal-to-background ratio for increasingly smaller subpatches. Whenever a subpatch fails a detection, the FOA cues the image formation processor to terminate further processing of that subpatch. We demonstrate that the FOA is able to decrease the overall computational load of the image formation process by a factor of two. We also show that the new FOA method provides fewer false alarms than the two-parameter CFAR FOA over a small database of UWB radar data.

  9. uPAR-targeted Optical Imaging Contrasts as Theranostic Agents for Tumor Margin Detection

    PubMed Central

    Yang, Lily; Sajja, Hari Krishna; Cao, Zehong; Qian, Weiping; Bender, Laura; Marcus, Adam I.; Lipowska, Malgorzata; Wood, William C.; Wang, Y. Andrew

    2014-01-01

    Complete removal of tumors by surgery is the most important prognostic factor for cancer patients with the early stage cancers. The ability to identify invasive tumor edges of the primary tumor, locally invaded small tumor lesions, and drug resistant residual tumors following neoadjuvant therapy during surgery should significantly reduce the incidence of local tumor recurrence and improve survival of cancer patients. In this study, we report that urokinase plasminogen activator (uPA) and its receptor (uPAR) are the ligand/cell surface target pair for the development of targeted optical imaging probes for enhancing imaging contrasts in the tumor border. Recombinant peptides of the amino terminal fragment (ATF) of the receptor binding domain of uPA were labeled with near infrared fluorescence (NIR) dye molecules either as peptide-imaging or peptide-conjugated nanoparticle imaging probes. Systemic delivery of the uPAR-targeted imaging probes in mice bearing orthotopic human breast or pancreatic tumor xenografts or mouse mammary tumors led to the accumulation of the probes in the tumor and stromal cells, resulting in strong signals for optical imaging of tumors and identification of tumor margins. Histological analysis showed that a high level of uPAR-targeted nanoparticles was present in the tumor edge or active tumor stroma immediately adjacent to the tumor cells. Furthermore, following targeted therapy using uPAR-targeted theranostic nanoparticles, residual tumors were detectable by optical imaging through the imaging contrasts produced by NIR-dye-labeled theranostic nanoparticles in drug resistant tumor cells. Therefore, results of our study support the potential of the development of uPAR-targeted imaging and theranostic agents for image-guided surgery. PMID:24396518

  10. Noise suppression in reconstruction of low-Z target megavoltage cone-beam CT images

    SciTech Connect

    Wang Jing; Robar, James; Guan Huaiqun

    2012-08-15

    Purpose: To improve the image contrast-to-noise (CNR) ratio for low-Z target megavoltage cone-beam CT (MV CBCT) using a statistical projection noise suppression algorithm based on the penalized weighted least-squares (PWLS) criterion. Methods: Projection images of a contrast phantom, a CatPhan{sup Registered-Sign} 600 phantom and a head phantom were acquired by a Varian 2100EX LINAC with a low-Z (Al) target and low energy x-ray beam (2.5 MeV) at a low-dose level and at a high-dose level. The projections were then processed by minimizing the PWLS objective function. The weighted least square (WLS) term models the noise of measured projection and the penalty term enforces the smoothing constraints of the projection image. The variance of projection data was chosen as the weight for the PWLS objective function and it determined the contribution of each measurement. An anisotropic quadratic form penalty that incorporates the gradient information of projection image was used to preserve edges during noise reduction. Low-Z target MV CBCT images were reconstructed by the FDK algorithm after each projection was processed by the PWLS smoothing. Results: Noise in low-Z target MV CBCT images were greatly suppressed after the PWLS projection smoothing, without noticeable sacrifice of the spatial resolution. Depending on the choice of smoothing parameter, the CNR of selected regions of interest in the PWLS processed low-dose low-Z target MV CBCT image can be higher than the corresponding high-dose image.Conclusion: The CNR of low-Z target MV CBCT images was substantially improved by using PWLS projection smoothing. The PWLS projection smoothing algorithm allows the reconstruction of high contrast low-Z target MV CBCT image with a total dose of as low as 2.3 cGy.

  11. Imaging of Isotopically Enhanced Molecular Targeting Agents Final Report

    SciTech Connect

    Quong, J N

    2004-02-19

    The goal of this project is to develop experimental and computational protocols to use SIMS to image the chemical composition of biological samples, focusing on optimizing sample preparation protocols and developing multivariate data analysis methods. Our results on sample preparation, molecular imaging, and multivariate analysis have been presented at several meeting abstracts (UCRL151797ABS, UCRL151797ABSREV1, UCRL151426ABS, UCRL201277, UCRL154757). A refereed paper describing our results for sample preparation and molecular imaging of various endogenous biomolecules as well as the mutagen PhIP has been accepted for publication (UCRL-JC-151797). We are also preparing two additional papers describing our multivariate analysis methods to analyze spectral data. As these papers have not been submitted, their content is included in this final report.

  12. Lead sulfide near-infrared quantum dot bioconjugates for targeted molecular imaging.

    PubMed

    Sun, Jiantang; Zhu, Ming-Qiang; Fu, Kun; Lewinski, Nastassja; Drezek, Rebekah A

    2007-01-01

    In this paper, we report the use of lead sulfide quantum dot (PbS QD) bioconjugates as near infrared (NIR) contrast agents for targeted molecular imaging with expanded emission wavelengths beyond 1000 nm. The red-shifted emission band, coupled with the small particle size, which will facilitate clearance, both afford PbS QDs unique properties for noninvasive, high resolution in vivo NIR imaging applications. We have performed imaging experiments at the molecular level using surface-modified PbS NIR QDs, together with our lab-built NIR imaging system. This novel instrumentation and fluorescent contrast agent have enabled us to study the relatively unexplored NIR biomedical imaging spectral region of 900-1200 nm. Preliminary experimental results indicate that PbS-QD/antibody bioconjugates are promising candidates for targeted NIR molecular imaging and future in vivo NIR tissue imaging applications.

  13. OPTICAL correlation identification technology applied in underwater laser imaging target identification

    NASA Astrophysics Data System (ADS)

    Yao, Guang-tao; Zhang, Xiao-hui; Ge, Wei-long

    2012-01-01

    The underwater laser imaging detection is an effective method of detecting short distance target underwater as an important complement of sonar detection. With the development of underwater laser imaging technology and underwater vehicle technology, the underwater automatic target identification has gotten more and more attention, and is a research difficulty in the area of underwater optical imaging information processing. Today, underwater automatic target identification based on optical imaging is usually realized with the method of digital circuit software programming. The algorithm realization and control of this method is very flexible. However, the optical imaging information is 2D image even 3D image, the amount of imaging processing information is abundant, so the electronic hardware with pure digital algorithm will need long identification time and is hard to meet the demands of real-time identification. If adopt computer parallel processing, the identification speed can be improved, but it will increase complexity, size and power consumption. This paper attempts to apply optical correlation identification technology to realize underwater automatic target identification. The optics correlation identification technology utilizes the Fourier transform characteristic of Fourier lens which can accomplish Fourier transform of image information in the level of nanosecond, and optical space interconnection calculation has the features of parallel, high speed, large capacity and high resolution, combines the flexibility of calculation and control of digital circuit method to realize optoelectronic hybrid identification mode. We reduce theoretical formulation of correlation identification and analyze the principle of optical correlation identification, and write MATLAB simulation program. We adopt single frame image obtained in underwater range gating laser imaging to identify, and through identifying and locating the different positions of target, we can improve

  14. OPTICAL correlation identification technology applied in underwater laser imaging target identification

    NASA Astrophysics Data System (ADS)

    Yao, Guang-Tao; Zhang, Xiao-Hui; Ge, Wei-Long

    2011-11-01

    The underwater laser imaging detection is an effective method of detecting short distance target underwater as an important complement of sonar detection. With the development of underwater laser imaging technology and underwater vehicle technology, the underwater automatic target identification has gotten more and more attention, and is a research difficulty in the area of underwater optical imaging information processing. Today, underwater automatic target identification based on optical imaging is usually realized with the method of digital circuit software programming. The algorithm realization and control of this method is very flexible. However, the optical imaging information is 2D image even 3D image, the amount of imaging processing information is abundant, so the electronic hardware with pure digital algorithm will need long identification time and is hard to meet the demands of real-time identification. If adopt computer parallel processing, the identification speed can be improved, but it will increase complexity, size and power consumption. This paper attempts to apply optical correlation identification technology to realize underwater automatic target identification. The optics correlation identification technology utilizes the Fourier transform characteristic of Fourier lens which can accomplish Fourier transform of image information in the level of nanosecond, and optical space interconnection calculation has the features of parallel, high speed, large capacity and high resolution, combines the flexibility of calculation and control of digital circuit method to realize optoelectronic hybrid identification mode. We reduce theoretical formulation of correlation identification and analyze the principle of optical correlation identification, and write MATLAB simulation program. We adopt single frame image obtained in underwater range gating laser imaging to identify, and through identifying and locating the different positions of target, we can improve

  15. Functionalized Hollow Mesoporous Silica Nanoparticles for Tumor Vasculature Targeting and PET Image-Guided Drug Delivery

    PubMed Central

    Chakravarty, Rubel; Goel, Shreya; Hong, Hao; Chen, Feng; Valdovinos, Hector F.; Hernandez, Reinier; Barnhart, Todd E.; Cai, Weibo

    2014-01-01

    Aim Development of multifunctional and well-dispersed hollow mesoporous silica nanoparticles (HMSNs) for tumor vasculature targeted drug delivery and positron emission tomography (PET) imaging. Materials and Methods Amine functionalized HMSNs (150–250 nm) were conjugated with a macrocyclic chelator, NOTA, PEGylated and loaded with anti-angiogenesis drug, Sunitinib. Cyclo(Arg-Gly-Asp-D-Tyr-Lys) (cRGDyK) peptide was attached to the nanoconjugate and radiolabeled with 64Cu for PET imaging. Results 64Cu-NOTA-HMSN-PEG-cRGDyK exhibited integrin specific uptake both in vitro and in vivo. PET results indicated ~ 8 %ID/g uptake of targeted nanoconjugates in U87MG tumors, which correlated well with ex vivo and histological analyses. Enhanced tumor targeted delivery of sunitinib was also observed. Conclusions We successfully developed tumor vasculature targeted HMSNs for PET imaging and image guided drug delivery. PMID:25955122

  16. Target-acquisition performance in undersampled infrared imagers: static imagery to motion video.

    PubMed

    Krapels, Keith; Driggers, Ronald G; Teaney, Brian

    2005-11-20

    In this research we show that the target-acquisition performance of an undersampled imager improves with sensor or target motion. We provide an experiment designed to evaluate the improvement in observer performance as a function of target motion rate in the video. We created the target motion by mounting a thermal imager on a precision two-axis gimbal and varying the sensor motion rate from 0.25 to 1 instantaneous field of view per frame. A midwave thermal imager was used to permit short integration times and remove the effects of motion blur. It is shown that the human visual system performs a superresolution reconstruction that mitigates some aliasing and provides a higher (than static imagery) effective resolution. This process appears to be relatively independent of motion velocity. The results suggest that the benefits of superresolution reconstruction techniques as applied to imaging systems with motion may be limited. PMID:16318174

  17. Domain adaptation of image classification based on collective target nearest-neighbor representation

    NASA Astrophysics Data System (ADS)

    Tang, Song; Ye, Mao; Liu, Qihe; Li, Fan

    2016-05-01

    In many practical applications, we frequently face the awkward problem in which an image classifier trained in a scenario is difficult to use in a new scenario. Traditionally, the probability inference-based methods are used to solve this problem. From the point of image representation, we propose an approach for domain adaption of image classification. First, all source samples are supposed to form the dictionary. Then, we encode the target sample by combining this dictionary and the local geometric information. Based on this new representation, called target nearest-neighbor representation, image classification can obtain good performance in the target domain. Our core contribution is that the nearest-neighbor information of the target sample is technically exploited to form more robust representation. Experimental results confirm the effectiveness of our method.

  18. Extraction of Target Scatterings from Received Transients on Target Detection Trial of Ambient Noise Imaging with Acoustic Lens

    NASA Astrophysics Data System (ADS)

    Mori, Kazuyoshi; Ogasawara, Hanako; Nakamura, Toshiaki; Tsuchiya, Takenobu; Endoh, Nobuyuki

    2012-07-01

    We have already designed and fabricated an aspherical lens with an aperture diameter of 1.0 m to develop a prototype system for ambient noise imaging (ANI). It has also been verified that this acoustic lens realizes a directional resolution, which is a beam width of 1° at the center frequency of 120 kHz over the field of view from -7 to +7°. In this study, a sea trial of silent target detection using the prototype ANI system was conducted under only natural ocean ambient noise at Uchiura Bay, in November of 2010. There were many transients in the received sound. These transients were classified roughly into directly received noises and target scatterings. We proposed a classification method to extract transients of only target scatterings. By analyzing transients extracted as target scatterings, it was verified that the power spectrum density levels of the on-target directions were greater than those of the off-target directions in the higher frequency band over 60 kHz. These results showed that the targets are successfully detected under natural ocean ambient noise, mainly generated by snapping shrimps.

  19. Bone as an imaging biomarker and treatment target in OA

    PubMed Central

    Neogi, Tuhina; Felson, David T.

    2016-01-01

    Radiographic joint-space width is the standard structural outcome for trials in knee osteoarthritis (OA), but MRI provides comprehensive 3D insights into the multi-tissue pathology of OA and could provide a superior means of monitoring disease progression and response to treatment. A new study highlights bone as an imaging biomarker. PMID:27383914

  20. Adaptive target detection in foliage-penetrating SAR images using alpha-stable models.

    PubMed

    Banerjee, A; Burlina, P; Chellappa, R

    1999-01-01

    Detecting targets occluded by foliage in foliage-penetrating (FOPEN) ultra-wideband synthetic aperture radar (UWB SAR) images is an important and challenging problem. Given the different nature of target returns in foliage and nonfoliage regions and very low signal-to-clutter ratio in UWB imagery, conventional detection algorithms fail to yield robust target detection results. A new target detection algorithm is proposed that (1) incorporates symmetric alpha-stable (SalphaS) distributions for accurate clutter modeling, (2) constructs a two-dimensional (2-D) site model for deriving local context, and (3) exploits the site model for region-adaptive target detection. Theoretical and empirical evidence is given to support the use of the SalphaS model for image segmentation and constant false alarm rate (CFAR) detection. Results of our algorithm on real FOPEN images collected by the Army Research Laboratory are provided.

  1. The study of target damage assessment system based on image change detection

    NASA Astrophysics Data System (ADS)

    Zhao, Ping; Yang, Fan; Feng, Xinxi

    2009-10-01

    Target Damage Assessment (TDA) system is an important component of the intelligent command and control system. The method of building TDA based on Image Change Detection can greatly improve the system efficiency and accuracy, thus get a fast and precise assessment results. This paper firstly analyzes the structure of TDA system. Then studies the key technology in this system. Finally, gives an evaluation criteria based on image change detection of the target damage assessment system.

  2. Synthesis of a Targeted Biarsenical Cy3-Cy5 Affinity Probe for Superresolution Fluorescence Imaging

    SciTech Connect

    Fu, Na; Xiong, Yijia; Squier, Thomas C.

    2012-11-01

    Photoswitchable fluorescent probes capable of the targeted labeling of tagged proteins are of significant interest due to their ability to enable in situ imaging of protein complexes within native biomolecular assemblies. Here we describe the synthesis of a fluorescent probe (AsCy3Cy5), and demonstrate the targeted labeling and super-resolution imaging of a tagged protein within a supramolecular protein complex.

  3. Correlated imaging for a reflective target with a smooth or rough surface

    NASA Astrophysics Data System (ADS)

    Gong, Wenlin

    2016-08-01

    Correlated imaging for a reflective target with a smooth or rough surface is investigated. Our analytical results, which are backed up by numerical simulations, demonstrate that for a reflective target with a smooth surface, the quality of ghost imaging is related with the transverse sizes of both the source and the detector in the object path, and the target’s information can also be obtained by the technique of Fourier-transform ghost diffraction. However, for a reflective target with a rough surface, the target’s whole image can be reconstructed by ghost imaging even using a single point-like detector but Fourier-transform ghost diffraction is invalid. The application of correlated imaging in remote sensing is also discussed based on the above results.

  4. The research of multi-frame target recognition based on laser active imaging

    NASA Astrophysics Data System (ADS)

    Wang, Can-jin; Sun, Tao; Wang, Tin-feng; Chen, Juan

    2013-09-01

    Laser active imaging is fit to conditions such as no difference in temperature between target and background, pitch-black night, bad visibility. Also it can be used to detect a faint target in long range or small target in deep space, which has advantage of high definition and good contrast. In one word, it is immune to environment. However, due to the affect of long distance, limited laser energy and atmospheric backscatter, it is impossible to illuminate the whole scene at the same time. It means that the target in every single frame is unevenly or partly illuminated, which make the recognition more difficult. At the same time the speckle noise which is common in laser active imaging blurs the images . In this paper we do some research on laser active imaging and propose a new target recognition method based on multi-frame images . Firstly, multi pulses of laser is used to obtain sub-images for different parts of scene. A denoising method combined homomorphic filter with wavelet domain SURE is used to suppress speckle noise. And blind deconvolution is introduced to obtain low-noise and clear sub-images. Then these sub-images are registered and stitched to combine a completely and uniformly illuminated scene image. After that, a new target recognition method based on contour moments is proposed. Firstly, canny operator is used to obtain contours. For each contour, seven invariant Hu moments are calculated to generate the feature vectors. At last the feature vectors are input into double hidden layers BP neural network for classification . Experiments results indicate that the proposed algorithm could achieve a high recognition rate and satisfactory real-time performance for laser active imaging.

  5. Myeloperoxidase and crystalline bodies in the granules of DMBA-induced rat chloroma cells.

    PubMed

    Ioachim, H L; Keller, S; Sabbath, M; Andersson, B; Dorsett, B; Essner, E

    1972-01-01

    Chloroma (chloroleukemia) was induced in a splenectomized rat by repeatedly administering dimethylbenz(a)anthracene (DMBA) and was serially transplanted thereafter. Composed of immature myeloid cells, the tumor imparted a green discoloration to the tissues that it infiltrated extensively. Chloroma cells fluoresced red in ultraviolet light, produced a characteristic curve in spectrophotometry, and contained large amounts of myeloperoxidase. They included numerous intracytoplasmic granules of both types A and B, which contained occasional crystalline bars. Permanent lines of chloroma cells were established in tissue culture. These cells, while maintaining their initial morphology, ceased producing myeloperoxidase and subsequently induced white tumors when they were isotransplanted.

  6. Human myeloperoxidase activity is inhibited in vitro by quercetin. Comparison with three related compounds.

    PubMed

    Pincemail, J; Deby, C; Thirion, A; de Bruyn-Dister, M; Goutier, R

    1988-05-15

    Quercetin is an effective inhibitor of human myeloperoxidase (MPO) activity, both with purified enzyme (IC50 = 3.5 microM) and in a system using stimulated human neutrophils. Quercetin is significantly more potent than three other related compounds (rutin, rutin sulfate and troxerutin) and than methimazole, a previously-known myeloperoxidase inhibitor. The inhibitory activity of quercetin is of the competitive type. Moreover, quercetin is directly able to scavenge hypochlorous acid (HOCl), a chlorinated species generated by the MPO/H2O2/Cl- system.

  7. Fluorescent non-conjugated polymer dots for targeted cell imaging

    NASA Astrophysics Data System (ADS)

    Sun, Bin; Zhao, Bin; Wang, Dandan; Wang, Yibo; Tang, Qi; Zhu, Shoujun; Yang, Bai; Sun, Hongchen

    2016-05-01

    Through the chemical crosslinking of the sub-fluorophore, linear non-conjugated polymers can possess strong photoluminescence (PL), which is a very important fluorescence behavior and the non-conjugated polymer dots (PDs) are efficient bio-fluorophores for bio-based applications. Herein, the new type of non-conjugated polyethyleneimine (PEI) PDs was further modified by targeting molecules (folic acid) for a new generation of bio-fluorophores. The free folic acid can quench the PL of PDs by energy transfer, while the conjugated folic acid@PDs (FA@PDs) can still maintain their PL properties to a certain degree. The FA@PDs also possess lower toxicity compared with free PDs, which is possibly due to blocking of the amino groups. Moreover, we investigated the targeted bioimaging applications of the FA@PDs, which gave a very important direction for application of these types of materials.Through the chemical crosslinking of the sub-fluorophore, linear non-conjugated polymers can possess strong photoluminescence (PL), which is a very important fluorescence behavior and the non-conjugated polymer dots (PDs) are efficient bio-fluorophores for bio-based applications. Herein, the new type of non-conjugated polyethyleneimine (PEI) PDs was further modified by targeting molecules (folic acid) for a new generation of bio-fluorophores. The free folic acid can quench the PL of PDs by energy transfer, while the conjugated folic acid@PDs (FA@PDs) can still maintain their PL properties to a certain degree. The FA@PDs also possess lower toxicity compared with free PDs, which is possibly due to blocking of the amino groups. Moreover, we investigated the targeted bioimaging applications of the FA@PDs, which gave a very important direction for application of these types of materials. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01909a

  8. Ultrasound imaging of extended targets using a windowed time-reversal MUSIC method

    NASA Astrophysics Data System (ADS)

    Labyed, Yassin; Huang, Lianjie

    2012-03-01

    Time-reversal with Multiple Signal Classification (TR-MUSIC) is an ultrasound imaging algorithm for detecting small targets embedded in a medium. This technique can produce images with subwavelength resolution when the targets are pointlike, and when the number of targets is fewer than the number of transducer elements used to image the medium. In this experimental study, we evaluate the performance of the TR-MUSIC algorithm when the interrogated medium contains extended targets that cannot be considered as point scatterers. We construct tissue-mimicking phantoms embedded with distributed glass spheres. We show that the quality of the phantom images obtained using the TR-MUSIC algorithm decreases with increasing sphere size. However, significant improvement is achieved when the image plane is divided into sub-regions, where each sub-region is imaged separately. The windowed TR-MUSIC algorithm accurately locates the spheres (extended targets), but the images do not provide quantitative information about the shape and reflectivity of the spheres.

  9. Multimode optical imaging for translational chemotherapy: in vivo tumor detection and delineation by targeted gallium corroles

    NASA Astrophysics Data System (ADS)

    Hwang, Jae Youn; Gross, Zeev; Gray, Harry B.; Medina-Kauwe, Lali K.; Farkas, Daniel L.

    2011-02-01

    We report the feasibility of tumor detection and delineation in vivo using multimode optical imaging of targeted gallium corrole (HerGa). HerGa is highly effective for targeted HER2+ tumor elimination in vivo, and it emits intense fluorescence. These unique characteristics of HerGa prompted us to investigate the potential of HerGa for tumor detection and delineation, by performing multimode optical imaging ex vivo and in vivo; the imaging modes included fluorescence intensity, spectral (including ratiometric), lifetime, and two-photon excited fluorescence, using our custombuilt imaging system. While fluorescence intensity imaging provided information about tumor targeting capacity and tumor retention of HerGa, ratiometric spectral imaging offered more quantitative and specific information about HerGa location and accumulation. Most importantly, the fluorescence lifetime imaging of HerGa allowed us to discriminate between tumor and non-tumor regions by fluorescence lifetime differences. Finally, two-photon excited fluorescence images provided highly resolved and thus topologically detailed information around the tumor regions where HerGa accumulates. Taken together, the results shown in this report suggest the feasibility of tumor detection and delineation by multimode optical imaging of HerGa, and fluorescent chemotherapy agents in general. Specifically, the multimode optical imaging can offer complementary and even synergetic information simultaneously in the tumor detection and delineation by HerGa, thus enhancing contrast.

  10. Effects of asymmetry and target location on microwave imaging reflectometry

    SciTech Connect

    Ignatenko, M.; Mase, A.; Bruskin, L.G.; Kogi, Y.; Hojo, H.

    2004-10-01

    In this article we perform a numerical study of microwave imaging reflectometry (MIR) and compare it with conventional reflectometry system. As an approximation to the reflections by real plasma fluctuations, a corrugated wheel is used. As far as general performance is concerned, our simulations confirm the results by Munsat et al. [Plasma Phys. Controlled Fusion 45, 469 (2003)] that the MIR system reproduces shape of corrugation far from the wheel while conventional systems fail to do so. We addressed the effects of asymmetry and defocusing of the wheel-reflectometer system as well as spectral sensitivity of the imaging reflectometer. For a particular geometry we estimated the deterioration of the MIR performance due to misalignments and existence of broadband fluctuation000.

  11. Parameter Estimation of a Ground Moving Target Using Image Sharpness Optimization.

    PubMed

    Yu, Jing; Li, Yaan

    2016-01-01

    Motion parameter estimation of a ground moving target is an important issue in synthetic aperture radar ground moving target indication (SAR-GMTI) which has significant applications for civilian and military. The SAR image of a moving target may be displaced and defocused due to the radial and along-track velocity components, respectively. The sharpness cost function presents a measure of the degree of focus of the image. In this work, a new ground moving target parameter estimation algorithm based on the sharpness optimization criterion is proposed. The relationships between the quadratic phase errors and the target's velocity components are derived. Using two-dimensional searching of the sharpness cost function, we can obtain the velocity components of the target and the focused target image simultaneously. The proposed moving target parameter estimation method and image sharpness metrics are analyzed in detail. Finally, numerical results illustrate the effective and superior velocity estimation performance of the proposed method when compared to existing algorithms. PMID:27376294

  12. M13-templated magnetic nanoparticles for targeted in vivo imaging of prostate cancer

    NASA Astrophysics Data System (ADS)

    Ghosh, Debadyuti; Lee, Youjin; Thomas, Stephanie; Kohli, Aditya G.; Yun, Dong Soo; Belcher, Angela M.; Kelly, Kimberly A.

    2012-10-01

    Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and would improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

  13. Imaging of a targeted PDT drug with fluorescence tomography

    NASA Astrophysics Data System (ADS)

    Muffoletto, Dan; Gupta, Anurag; Xu, Zhiqiang; Mahrer, Chris; Bauer, Gretchen; Galas, Scott; Pandey, Ravindra K.; Sunar, Ulas

    2009-02-01

    We constructed a whole-body fluorescence tomography instrument to monitor novel bifunctional phototherapeutic drugs (e.g., HPPH-Cyanine dye conjugate) in small animals. The instrument allows dense source and detector sampling with a fast galvo scanner and a CCD detector for improved resolution and sensitivity (Patwardhan et al., 2005). Here we report tissue phantom measurements to evaluate the imaging performance with a newly constructed tomography instrument. Phantom measurements showed that strong fluorescence generated by HPPH-Cyanine dye (HPPH-CD), having high fluorescence quantum yield and long wavelength fluorescence emission, allowed deep tissue imaging. We also report in vivo fluorescence measurements of the conjugate in Nude mice bearing A549 human non-small cell lung carcinoma (NSCLC) tumors at 24 hr post injection to evaluate tumor detection ability of the conjugate. Our results indicate that the HPPH-CD shows preferential uptake in tumors compared to surrounding normal tissue at 24 hr post injection. This study demonstrates a potential use of HPPH-CD in detection (fluorescence imaging) and treatment (PDT) of deeply seated tumors.

  14. Myeloperoxidase-derived oxidants rapidly oxidize and disrupt zinc-cysteine/histidine clusters in proteins.

    PubMed

    Cook, Naomi L; Pattison, David I; Davies, Michael J

    2012-12-01

    Zinc is an abundant cellular transition metal ion, which binds avidly to protein cysteine (Cys) and histidine (His) residues to form zinc-Cys/His clusters; these play a key role in the function of many proteins (e.g., DNA binding and repair enzymes, transcription factors, nitric oxide synthase). Leukocyte-derived myeloperoxidase generates powerful oxidants including hypochlorous (HOCl), hypobromous (HOBr), and hypothiocyanous (HOSCN) acids from H(2)O(2) and (pseudo)halide ions. Excessive or misplaced formation of these species is associated with cellular dysfunction, apoptosis and necrosis, and multiple inflammatory diseases. HOCl and HOBr react rapidly with sulfur-containing compounds, and HOSCN reacts specifically with thiols. Consequently, we hypothesized that zinc-Cys/His clusters would be targets for these oxidants, and the activity of such enzymes would be perturbed. This hypothesis has been tested using yeast alcohol dehydrogenase (YADH), which contains a well-characterized Zn(1)Cys(2)His(1) cluster. Incubation of YADH with pathologically relevant concentrations of HOSCN, HOCl, and HOBr resulted in rapid oxidation of the protein (rate constants, determined by competition kinetics, for reaction of HOCl and HOSCN with YADH being (3.3±0.9)×10(8) and (2.9±0.4)×10(4) M(-1) s(-1) per YADH monomer, respectively), loss of enzyme activity, Zn(2+) release, changes in protein structure (particularly formation of disulfide cross-links), and oxidation of Cys residues. The loss of enzyme activity correlated with Zn(2+) release, loss of thiols, and changes in protein structure. We conclude that exposure of zinc-Cys/His clusters to inflammatory oxidants can result in impaired protein activity, thiol oxidation, and Zn(2+) release. These reactions may contribute to inflammation-induced tissue damage.

  15. Myeloperoxidase-derived oxidants rapidly oxidize and disrupt zinc-cysteine/histidine clusters in proteins.

    PubMed

    Cook, Naomi L; Pattison, David I; Davies, Michael J

    2012-12-01

    Zinc is an abundant cellular transition metal ion, which binds avidly to protein cysteine (Cys) and histidine (His) residues to form zinc-Cys/His clusters; these play a key role in the function of many proteins (e.g., DNA binding and repair enzymes, transcription factors, nitric oxide synthase). Leukocyte-derived myeloperoxidase generates powerful oxidants including hypochlorous (HOCl), hypobromous (HOBr), and hypothiocyanous (HOSCN) acids from H(2)O(2) and (pseudo)halide ions. Excessive or misplaced formation of these species is associated with cellular dysfunction, apoptosis and necrosis, and multiple inflammatory diseases. HOCl and HOBr react rapidly with sulfur-containing compounds, and HOSCN reacts specifically with thiols. Consequently, we hypothesized that zinc-Cys/His clusters would be targets for these oxidants, and the activity of such enzymes would be perturbed. This hypothesis has been tested using yeast alcohol dehydrogenase (YADH), which contains a well-characterized Zn(1)Cys(2)His(1) cluster. Incubation of YADH with pathologically relevant concentrations of HOSCN, HOCl, and HOBr resulted in rapid oxidation of the protein (rate constants, determined by competition kinetics, for reaction of HOCl and HOSCN with YADH being (3.3±0.9)×10(8) and (2.9±0.4)×10(4) M(-1) s(-1) per YADH monomer, respectively), loss of enzyme activity, Zn(2+) release, changes in protein structure (particularly formation of disulfide cross-links), and oxidation of Cys residues. The loss of enzyme activity correlated with Zn(2+) release, loss of thiols, and changes in protein structure. We conclude that exposure of zinc-Cys/His clusters to inflammatory oxidants can result in impaired protein activity, thiol oxidation, and Zn(2+) release. These reactions may contribute to inflammation-induced tissue damage. PMID:23032100

  16. Modification of High Density Lipoprotein by Myeloperoxidase Generates a Pro-inflammatory Particle*

    PubMed Central

    Undurti, Arundhati; Huang, Ying; Lupica, Joseph A.; Smith, Jonathan D.; DiDonato, Joseph A.; Hazen, Stanley L.

    2009-01-01

    High density lipoprotein (HDL) is the major atheroprotective particle in plasma. Recent studies demonstrate that myeloperoxidase (MPO) binds to HDL in vivo, selectively targeting apolipoprotein A1 (apoA1) of HDL for oxidative modification and concurrent loss in cholesterol efflux and lecithin cholesterol acyl transferase activating activities, generating a “dysfunctional HDL” particle. We now show that (patho)physiologically relevant levels of MPO-catalyzed oxidation result in loss of non-cholesterol efflux activities of HDL including anti-apoptotic and anti-inflammatory functions. One mechanism responsible is shown to involve the loss of modified HDL binding to the HDL receptor, scavenger receptor B1, and concurrent acquisition of saturable and specific binding to a novel unknown receptor independent of scavenger receptors CD36 and SR-A1. HDL modification by MPO is further shown to confer pro-inflammatory gain of function activities as monitored by NF-κB activation and surface vascular cell adhesion molecule levels on aortic endothelial cells exposed to MPO-oxidized HDL. The loss of non-cholesterol efflux activities and the gain of pro-inflammatory functions requires modification of the entire particle and can be recapitulated by oxidation of reconstituted HDL particles comprised of apoA1 and nonoxidizable phosphatidylcholine species. Multiple site-directed mutagenesis studies of apoA1 suggest that the pro-inflammatory activity of MPO-modified HDL does not involve methionine, tyrosine, or tryptophan, oxidant-sensitive residues previously mapped as sites of apoA1 oxidation within human atheroma. Thus, MPO-catalyzed oxidation of HDL results not only in the loss of classic atheroprotective reverse cholesterol transport activities of the lipoprotein but also both the loss of non-cholesterol efflux related activities and the gain of pro-inflammatory functions. PMID:19726691

  17. Infrared small moving target detection using sparse representation-based image decomposition

    NASA Astrophysics Data System (ADS)

    Qin, Hanlin; Han, Jiaojiao; Yan, Xiang; Zeng, Qingjie; Zhou, Huixin; Li, Jia; Chen, Zhimin

    2016-05-01

    Infrared small moving target detection is one of the crucial techniques in infrared search and tracking systems. This paper presents a novel small moving target detection method for infrared image sequence with complicated background. The key points are given as follows: (1) since target detection mainly depends on the incoherence between target and background, the proposed method separate the target from the background according to the morphological feature diversity between target and background; (2) considering the continuity of target motion in time domain, the target trajectory is extracted by the RX filter in random projection. The experiments on various clutter background sequences have validated the detection capability of the proposed method. The experimental results show that the proposed method can robustly provide a higher detection probability and a lower false alarm rate than baseline methods.

  18. Gold nano-rods as a targeting contrast agent for photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Agarwal, A.; Huang, S.-W.; Day, K. C.; O'Donnell, M.; Day, M.; Kotov, N.; Ashkenazi, S.

    2007-02-01

    We have studied the potential of gold nanorods to target cancer cells and provide contrast for photoacoustic imaging. The elongated "rod" shape of these nanoparticles provides a mechanism to tune their plasmon peak absorption wavelength. The absorption peak is shifted to longer wavelengths by increasing the aspect ratio of the rods. Particles 15 nm in diameter and 45 nm long were prepared using a seed mediated growth method. Their plasmon absorption peak was designed to be at 800 nm for increased penetration depth into biological tissue. They were conjugated with a specific antibody to target prostate cancer cells. We have applied photoacoustics to image a prostate cell culture targeted by conjugated gold particles. Images confirm the efficiency of conjugated particle binding to the targeted cell membranes. Photoacoustic detection of a single cell layer is demonstrated. To evaluate the applicability of the technique to clinical prostate cancer detection, we have imaged phantom objects mimicking a real tissue with small (2 mm size) inclusions of nanoparticle gel solution. Our photoacoustic imaging setup is based on a modified commercial ultrasonic scanner which makes it attractive for fast implementation in cancer diagnosis in clinical application. In addition, the setup allows for dual mode operation where a photoacoustic image is superimposed on a conventional B-mode ultrasound image. Dual mode operation is demonstrated by imaging a mouse with gold nanorod gel solution implanted in its hind limb.

  19. [Myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis with acute pancreatitis: a case report].

    PubMed

    Iida, Takeshi; Amari, Yoshifumi; Yurugi, Takatomi; Nakajima, Fumitaka

    2015-01-01

    We report here a case of a 64-year-old woman with myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) -associated glomerulonephritis who developed acute pancreatitis. The patient was admitted to our hospital because of abnormal urinalysis findings, edema, and progressive renal failure. Laboratory studies showed a high white blood cell count (11,570/μL), anemia (hemoglobin 7.8 g/dL), and elevated serum creatinine (2.36 mg/dL) and C-reactive protein (12.20 mg/dL) levels. Furthermore, the MPO-ANCA titer was very high (1,625 U/mL, normal range < 10 U/mL). Histopathological findings of the renal biopsy were consistent with microscopic polyangiitis. Accordingly, we diagnosed MPO-ANCA-associated glomerulonephritis. On the day after the renal biopsy, the patient complained of low back pain. Computed tomography (CT) revealed postbiopsy hemorrhage. Thereafter, the patient's symptoms and laboratory studies gradually worsened. A repeat CT performed a few days later revealed no changes in the perirenal hematoma; however, an enlarged pancreas head was incidentally observed. There was no obvious cause of acute pancreatitis, and MPO-ANCA-associated vasculitis, although rare, was suspected as the cause. We initiated prednisolone pulse therapy for vasculitis along with the administration of nafamostat mesilate and ulinastatin for acute pancreatitis. Subsequently, the levels of pancreatic enzymes gradually increased, but several days later, abdominal magnetic resonance imaging showed improvement in the pancreas head. The pancreatitis gradually resolved over time. Acute pancreatitis occurring concurrently with MPO-ANCA-associated glomerulonephritis is extremely rare. To our knowledge, only a few such cases have been reported and have suggested that steroid therapy may play a role in triggering pancreatic involvement. In our case, however, an enlarged pancreas head was observed before steroid therapy was initiated. Therefore, we consider our case to be very rare. PMID

  20. Polychromatic in vivo imaging of multiple targets using visible and near infrared light

    PubMed Central

    Kobayashi, Hisataka; Longmire, Michelle R.; Choyke, Peter L.

    2013-01-01

    Conventional diagnostic imaging methods such as X-ray CT, MRI, and nuclear medicine are inherently monochromatic meaning that they can depict only one molecular target at a time. Optical imaging has the unique ability to be polychromatic and therefore multi-color imaging employing targeted agents conjugated to fluorophores of varying wavelength enables multiple simultaneous readouts thus providing greater multiplexed information. Numerous successful multicolor imaging techniques have recently been reported using optical imaging in vivo animal disease models, thus adding to a growing body of research supporting the clinical viability and applicability of these technologies. Herein, we review multicolor optical imaging from the basic chemistry and physics perspective and then extend this to biological and medical applications. PMID:23220327

  1. Feasibility of Image-Based Simulation to Estimate Ablation Target in Human Ventricular Arrhythmia

    PubMed Central

    Ashikaga, Hiroshi; Arevalo, Hermenegild; Vadakkumpadan, Fijoy; Blake, Robert C.; Bayer, Jason D.; Nazarian, Saman; Zviman, M. Muz; Tandri, Harikrishna; Berger, Ronald D.; Calkins, Hugh; Herzka, Daniel A.; Trayanova, Natalia A.; Halperin, Henry R.

    2013-01-01

    Background Previous studies suggest that MRI with late gadolinium enhancement (LGE) may identify slowly conducting tissues in scar-related ventricular tachycardia (VT). Objective We tested the feasibility of image-based simulation based on LGE to estimate ablation targets in VT. Methods We conducted a retrospective study in 13 patients who had pre-ablation MRI for scar-related VT ablation. We used image-based simulation to induce VT and estimate target regions according to the simulated VT circuit. The estimated target regions were co-registered with the LGE scar map and the ablation sites from the electroanatomical map in the standard ablation approach. Results In image-based simulation, VT was inducible in 12 patients (92.3%). All VTs showed macro-reentrant propagation patterns, and the narrowest width of estimated target region that an ablation line should span to prevent VT recurrence was 5.0 ± 3.4 mm. Out of 11 patients who underwent ablation, the results of image-based simulation and the standard approach were consistent in 9 patients (82%), where ablation within the estimated target region was associated with acute success (n=8) and ablation outside the estimated target region was associated with failure (n=1). In one case (9%), the results of image-based simulation and the standard approach were inconsistent, where ablation outside the estimated target region was associated with acute success. Conclusions The image-based simulation can be used to estimate potential ablation targets of scar-related VT. The image-based simulation may be a powerful noninvasive tool for pre-procedural planning of ablation procedures to potentially reduce the procedure time and complication rates. PMID:23608593

  2. Morphological operators for enhanced polarimetric image target detection

    NASA Astrophysics Data System (ADS)

    Romano, João. M.; Rosario, Dalton S.

    2015-09-01

    We introduce an algorithm based on morphological filters with the Stokes parameters that augments the daytime and nighttime detection of weak-signal manmade objects immersed in a predominant natural background scene. The approach features a tailored sequence of signal-enhancing filters, consisting of core morphological operators (dilation, erosion) and higher level morphological operations (e.g., spatial gradient, opening, closing) to achieve a desired overarching goal. Using representative data from the SPICE database, the results show that the approach was able to automatically and persistently detect with a high confidence level the presence of three mobile military howitzer surrogates (targets) in natural clutter.

  3. Target Detection in SAR Images Based on a Level Set Approach

    SciTech Connect

    Marques, Regis C.P.; Medeiros, Fatima N.S.; Ushizima, Daniela M.

    2008-09-01

    This paper introduces a new framework for point target detection in synthetic aperture radar (SAR) images. We focus on the task of locating reflective small regions using alevel set based algorithm. Unlike most of the approaches in image segmentation, we address an algorithm which incorporates speckle statistics instead of empirical parameters and also discards speckle filtering. The curve evolves according to speckle statistics, initially propagating with a maximum upward velocity in homogeneous areas. Our approach is validated by a series of tests on synthetic and real SAR images and compared with three other segmentation algorithms, demonstrating that it configures a novel and efficient method for target detection purpose.

  4. A novel targeted enhancement technique for decimation and interpolation of images

    NASA Astrophysics Data System (ADS)

    Prabhakaran, P. Joy; Poonacha, P. G.

    2015-12-01

    In this paper we give an efficient method for obtaining interpolated images with much better PSNR compared to Bicubic interpolation scheme using a new technique called targeted image enhancement (TIE) to improve PSNR. Study of typical images decimated by a factor of 2 and regenerated with Bicubic interpolation, leads to significant PSNR degradation and the significant errors are seen around the object edges as all interpolation techniques lead to some form of smoothing of the interpolated images. Our targeted image enhancement technique compensates for the losses in the distorted pixels in the interpolated image. One of the challenges in such an approach is to determine locations of pixels in the interpolated image which are subjected to high distortion. We have given a technique which extracts a location map of the pixels which face high distortion in the interpolated image. This location map can be generated by both the decoder and the encoder without the need for sending location information. Information needed for correcting the distorted pixels is sent as additional information along with the decimated image. Simulation studies indicate that an average PSNR of 28 dB after standard bicubic can be improved to 32 dB, on an average, with targeted enhancement. This improvement is attained with a data over head of only 3%.

  5. Simulation of a new 3D imaging sensor for identifying difficult military targets

    NASA Astrophysics Data System (ADS)

    Harvey, Christophe; Wood, Jonathan; Randall, Peter; Watson, Graham; Smith, Gordon

    2008-04-01

    This paper reports the successful application of automatic target recognition and identification (ATR/I) algorithms to simulated 3D imagery of 'difficult' military targets. QinetiQ and Selex S&AS are engaged in a joint programme to build a new 3D laser imaging sensor for UK MOD. The sensor is a 3D flash system giving an image containing range and intensity information suitable for targeting operations from fast jet platforms, and is currently being integrated with an ATR/I suite for demonstration and testing. The sensor has been extensively modelled and a set of high fidelity simulated imagery has been generated using the CAMEO-SIM scene generation software tool. These include a variety of different scenarios (varying range, platform altitude, target orientation and environments), and some 'difficult' targets such as concealed military vehicles. The ATR/I algorithms have been tested on this image set and their performance compared to 2D passive imagery from the airborne trials using a Wescam MX-15 infrared sensor and real-time ATR/I suite. This paper outlines the principles behind the sensor model and the methodology of 3D scene simulation. An overview of the 3D ATR/I programme and algorithms is presented, and the relative performance of the ATR/I against the simulated image set is reported. Comparisons are made to the performance of typical 2D sensors, confirming the benefits of 3D imaging for targeting applications.

  6. Disease-specific target gene expression profiling of molecular imaging probes: database development and clinical validation.

    PubMed

    Chan, Lawrence Wing-Chi; Ngo, Connie Hiu-Ching; Wang, Fengfeng; Zhao, Moss Y; Zhao, Mengying; Law, Helen Ka-Wai; Wong, Sze Chuen Cesar; Yung, Benjamin Yat-Ming

    2014-01-01

    Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2-deoxy-2-d-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/. PMID:25022454

  7. Adapting high-resolution speckle imaging to moving targets and platforms

    SciTech Connect

    Carrano, C J; Brase, J M

    2004-02-05

    High-resolution surveillance imaging with apertures greater than a few inches over horizontal or slant paths at optical or infrared wavelengths will typically be limited by atmospheric aberrations. With static targets and static platforms, we have previously demonstrated near-diffraction limited imaging of various targets including personnel and vehicles over horizontal and slant paths ranging from less than a kilometer to many tens of kilometers using adaptations to bispectral speckle imaging techniques. Nominally, these image processing methods require the target to be static with respect to its background during the data acquisition since multiple frames are required. To obtain a sufficient number of frames and also to allow the atmosphere to decorrelate between frames, data acquisition times on the order of one second are needed. Modifications to the original imaging algorithm will be needed to deal with situations where there is relative target to background motion. In this paper, we present an extension of these imaging techniques to accommodate mobile platforms and moving targets.

  8. Optical imaging of targeted β-galactosidase in brain tumors to detect EGFR levels.

    PubMed

    Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari; Liggett, Alexander; Kinstlinger, Ian; Basilion, James

    2015-04-15

    A current limitation in molecular imaging is that it often requires genetic manipulation of cancer cells for noninvasive imaging. Other methods to detect tumor cells in vivo using exogenously delivered and functionally active reporters, such as β-gal, are required. We report the development of a platform system for linking β-gal to any number of different ligands or antibodies for in vivo targeting to tissue or cells, without the requirement for genetic engineering of the target cells prior to imaging. Our studies demonstrate significant uptake in vitro and in vivo of an EGFR-targeted β-gal complex. We were then able to image orthotopic brain tumor accumulation and localization of the targeted enzyme when a fluorophore was added to the complex, as well as validate the internalization of the intravenously administered β-gal reporter complex ex vivo. After fluorescence imaging localized the β-gal complexes to the brain tumor, we topically applied a bioluminescent β-gal substrate to serial sections of the brain to evaluate the delivery and integrity of the enzyme. Finally, robust bioluminescence of the EGFR-targeted β-gal complex was captured within the tumor during noninvasive in vivo imaging.

  9. An innovative pre-targeting strategy for tumor cell specific imaging and therapy

    NASA Astrophysics Data System (ADS)

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

    2015-08-01

    A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging

  10. Design and fabrication of magnetic nanoparticles for targeted drug delivery and imaging

    PubMed Central

    Veiseh, Omid; Gunn, Jonathan; Zhang, Miqin

    2009-01-01

    Magnetic nanoparticles (MNPs) represent a class of non-invasive imaging agents that have been developed for magnetic resonance (MR) imaging. These MNPs have traditionally been used for disease imaging via passive targeting, but recent advances have opened the door to cellular-specific targeting, drug delivery, and multi-modal imaging by these nanoparticles. As more elaborate MNPs are envisioned, adherence to proper design criteria (e.g. size, coating, molecular functionalization) becomes even more essential. This review summarizes the design parameters that affect MNP performance in vivo, including the physicochemical properties and nanoparticle surface modifications, such as MNP coating and targeting ligand functionalizations that can enhance MNP management of biological barriers. A careful review of the chemistries used to modify the surfaces of MNPs is also given, with attention paid to optimizing the activity of bound ligands while maintaining favorable physicochemical properties. PMID:19909778

  11. Polarimetric imaging and retrieval of target polarization characteristics in underwater environment.

    PubMed

    Gu, Yalong; Carrizo, Carlos; Gilerson, Alexander A; Brady, Parrish C; Cummings, Molly E; Twardowski, Michael S; Sullivan, James M; Ibrahim, Amir I; Kattawar, George W

    2016-01-20

    Polarized light fields contain more information than simple irradiance and such capabilities provide an advanced tool for underwater imaging. The concept of the beam spread function (BSF) for analysis of scalar underwater imaging was extended to a polarized BSF which considers polarization. The following studies of the polarized BSF in an underwater environment through Monte Carlo simulations and experiments led to a simplified underwater polarimetric imaging model. With the knowledge acquired in the analysis of the polarimetric imaging formation process of a manmade underwater target with known polarization properties, a method to extract the inherent optical properties of the water and to retrieve polarization characteristics of the target was explored. The proposed method for retrieval of underwater target polarization characteristics should contribute to future efforts to reveal the underlying mechanism of polarization camouflage possessed by marine animals and finally to generalize guidelines for creating engineered surfaces capable of similar polarization camouflage abilities in an underwater environment. PMID:26835939

  12. Polarimetric imaging and retrieval of target polarization characteristics in underwater environment.

    PubMed

    Gu, Yalong; Carrizo, Carlos; Gilerson, Alexander A; Brady, Parrish C; Cummings, Molly E; Twardowski, Michael S; Sullivan, James M; Ibrahim, Amir I; Kattawar, George W

    2016-01-20

    Polarized light fields contain more information than simple irradiance and such capabilities provide an advanced tool for underwater imaging. The concept of the beam spread function (BSF) for analysis of scalar underwater imaging was extended to a polarized BSF which considers polarization. The following studies of the polarized BSF in an underwater environment through Monte Carlo simulations and experiments led to a simplified underwater polarimetric imaging model. With the knowledge acquired in the analysis of the polarimetric imaging formation process of a manmade underwater target with known polarization properties, a method to extract the inherent optical properties of the water and to retrieve polarization characteristics of the target was explored. The proposed method for retrieval of underwater target polarization characteristics should contribute to future efforts to reveal the underlying mechanism of polarization camouflage possessed by marine animals and finally to generalize guidelines for creating engineered surfaces capable of similar polarization camouflage abilities in an underwater environment.

  13. Analysis and exploitation of multipath ghosts in radar target image classification.

    PubMed

    Smith, Graeme E; Mobasseri, Bijan G

    2014-04-01

    An analysis of the relationship between multipath ghosts and the direct target image for radar imaging is presented. A multipath point spread function (PSF) is defined that allows for specular reflections in the local environment and can allow the ghost images to be localized. Analysis of the multipath PSF shows that certain ghosts can only be focused for the far field synthetic aperture radar case and not the full array case. Importantly, the ghosts are shown to be equivalent to direct target images taken from different observation angles. This equivalence suggests that exploiting the ghosts would improve target classification performance, and this improvement is demonstrated using experimental data and a naïve Bayesian classifer. The maximum performance gain achieved is 32%.

  14. Parameter Estimation of a Ground Moving Target Using Image Sharpness Optimization

    PubMed Central

    Yu, Jing; Li, Yaan

    2016-01-01

    Motion parameter estimation of a ground moving target is an important issue in synthetic aperture radar ground moving target indication (SAR-GMTI) which has significant applications for civilian and military. The SAR image of a moving target may be displaced and defocused due to the radial and along-track velocity components, respectively. The sharpness cost function presents a measure of the degree of focus of the image. In this work, a new ground moving target parameter estimation algorithm based on the sharpness optimization criterion is proposed. The relationships between the quadratic phase errors and the target’s velocity components are derived. Using two-dimensional searching of the sharpness cost function, we can obtain the velocity components of the target and the focused target image simultaneously. The proposed moving target parameter estimation method and image sharpness metrics are analyzed in detail. Finally, numerical results illustrate the effective and superior velocity estimation performance of the proposed method when compared to existing algorithms. PMID:27376294

  15. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes.

    PubMed

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  16. In vivo photoacoustic molecular imaging of breast carcinoma with folate receptor-targeted indocyanine green nanoprobes

    NASA Astrophysics Data System (ADS)

    Wang, Huina; Liu, Chengbo; Gong, Xiaojing; Hu, Dehong; Lin, Riqiang; Sheng, Zonghai; Zheng, Cuifang; Yan, Meng; Chen, Jingqin; Cai, Lintao; Song, Liang

    2014-11-01

    As an optical-acoustic hybrid imaging technology, photoacoustic imaging uniquely combines the advantages of rich optical contrast with high ultrasonic resolution in depth, opening up many new possibilities not attainable with conventional pure optical imaging technologies. To perform photoacoustic molecular imaging, optically absorbing exogenous contrast agents are needed to enhance the signals from specifically targeted disease activity. In this work, we designed and developed folate receptor targeted, indocyanine green dye doped poly(d,l-lactide-co-glycolide) lipid nanoparticles (FA-ICG-PLGA-lipid NPs) for molecular photoacoustic imaging of tumor. The fabricated FA-ICG-PLGA-lipid NPs exhibited good aqueous stability, a high folate-receptor targeting efficiency, and remarkable optical absorption in near-infrared wavelengths, providing excellent photoacoustic signals in vitro. Furthermore, after intravenous administration of FA-ICG-PLGA-lipid NPs, mice bearing MCF-7 breast carcinomas showed significantly enhanced photoacoustic signals in vivo in the tumor regions, compared with those using non-targeted ICG-PLGA-lipid NPs. Given the existing wide clinical use of ICG and PLGA, the developed FA-ICG-PLGA-lipid NPs, in conjunction with photoacoustic imaging technology, offer a great potential to be translated into the clinic for non-ionizing molecular imaging of breast cancer in vivo.

  17. Frequency-spatial cues based sea-surface salient target detection from UAV image

    NASA Astrophysics Data System (ADS)

    Sun, Xiaoliang; Liu, Xiaolin; Yu, Qifeng; Liu, Yan

    2015-05-01

    This paper proposes an algorithm for salient target detection from Unmanned Aerial Vehicles (UAV) sea surface image using frequency and spatial cues. The algorithm is consisted of three parts: background suppression in the frequency domain, adaptive smoothing of the background suppressed image and salient target detection via adaptive thresholding, region growth and cluster. The sea surface background in UAV image is modeled as non-salient components which correspond to the spikes of the amplitude spectrum in the frequency domain. The background suppression is achieved by removing the spikes using a low pass Gaussian kernel of proper scale. In order to eliminate the negative effects brought by the complex textures, a Gaussian blur kernel is introduced to process the background suppressed image and its scale is determined by the entropy of the background suppressed image. The salient target is detected using adaptive thresholding, region growth and cluster performed on the blurred background suppressed image. Experiments on a large number of images indicate that the algorithm proposed in this paper can detected the sea surface salient target accurately and efficiently.

  18. Tumor targeting and imaging with dual-peptide conjugated multifunctional liposomal nanoparticles

    PubMed Central

    Rangger, Christine; Helbok, Anna; Sosabowski, Jane; Kremser, Christian; Koehler, Gottfried; Prassl, Ruth; Andreae, Fritz; Virgolini, Irene J; von Guggenberg, Elisabeth; Decristoforo, Clemens

    2013-01-01

    Background The significant progress in nanotechnology provides a wide spectrum of nanosized material for various applications, including tumor targeting and molecular imaging. The aim of this study was to evaluate multifunctional liposomal nanoparticles for targeting approaches and detection of tumors using different imaging modalities. The concept of dual-targeting was tested in vitro and in vivo using liposomes derivatized with an arginine-glycine-aspartic acid (RGD) peptide binding to αvβ3 integrin receptors and a substance P peptide binding to neurokinin-1 receptors. Methods For liposome preparation, lipids, polyethylene glycol building blocks, DTPA-derivatized lipids for radiolabeling, lipid-based RGD and substance P building blocks and imaging labels were combined in defined molar ratios. Liposomes were characterized by photon correlation spectroscopy and zeta potential measurements, and in vitro binding properties were tested using fluorescence microscopy. Standardized protocols for radiolabeling were developed to perform biodistribution and micro-single photon emission computed tomography/computed tomography (SPECT/CT) studies in nude mice bearing glioblastoma and/or melanoma tumor xenografts. Additionally, an initial magnetic resonance imaging study was performed. Results Liposomes were radiolabeled with high radiochemical yields. Fluorescence microscopy showed specific cellular interactions with RGD-liposomes and substance P-liposomes. Biodistribution and micro-SPECT/CT imaging of 111In-labeled liposomal nanoparticles revealed low tumor uptake, but in a preliminary magnetic resonance imaging study with a single-targeted RGD-liposome, uptake in the tumor xenografts could be visualized. Conclusion The present study shows the potential of liposomes as multifunctional targeted vehicles for imaging of tumors combining radioactive, fluorescent, and magnetic resonance signaling. Specific in vitro tumor targeting by fluorescence microscopy and radioactivity was

  19. Genetically targeted fluorogenic macromolecules for subcellular imaging and cellular perturbation.

    PubMed

    Magenau, Andrew J D; Saurabh, Saumya; Andreko, Susan K; Telmer, Cheryl A; Schmidt, Brigitte F; Waggoner, Alan S; Bruchez, Marcel P

    2015-10-01

    The alteration of cellular functions by anchoring macromolecules to specified organelles may reveal a new area of therapeutic potential and clinical treatment. In this work, a unique phenotype was evoked by influencing cellular behavior through the modification of subcellular structures with genetically targetable macromolecules. These fluorogen-functionalized polymers, prepared via controlled radical polymerization, were capable of exclusively decorating actin, cytoplasmic, or nuclear compartments of living cells expressing localized fluorgen-activating proteins. The macromolecular fluorogens were optimized by establishing critical polymer architecture-biophysical property relationships which impacted binding rates, binding affinities, and the level of internalization. Specific labeling of subcellular structures was realized at nanomolar concentrations of polymer, in the absence of membrane permeabilization or transduction domains, and fluorogen-modified polymers were found to bind to protein intact after delivery to the cytosol. Cellular motility was found to be dependent on binding of macromolecular fluorogens to actin structures causing rapid cellular ruffling without migration.

  20. Genetically Targeted Fluorogenic Macromolecules for Subcellular Imaging and Cellular Perturbation

    PubMed Central

    Magenau, Andrew J. D.; Saurabh, Saumya; Andreko, Susan K.; Telmer, Cheryl A.; Schmidt, Brigitte F.; Waggoner, Alan S.; Bruchez, Marcel P.

    2015-01-01

    The alteration of cellular functions by anchoring macromolecules to specified organelles may reveal a new area of therapeutic potential and clinical treatment. In this work, a unique phenotype was evoked by influencing cellular behavior through the modification of subcellular structures with genetically targetable macromolecules. These fluorogen-functionalized polymers, prepared via controlled radical polymerization, were capable of exclusively decorating actin, cytoplasmic, or nuclear compartments of living cells expressing localized fluorgen-activating proteins. The macromolecular fluorogens were optimized by establishing critical polymer architecture-biophysical property relationships which impacted binding rates, binding affinities, and the level of internalization. Specific labeling of subcellular structures was realized at nanomolar concentrations of polymer, in the absence of membrane permeabilization or transduction domains, and fluorogen-modified polymers were found to bind to protein intact after delivery to the cytosol. Cellular motility was found to be dependent on binding of macromolecular fluorogens to actin structures causing rapid cellular ruffling without migration. PMID:26183934

  1. Imaging Diagnostic and Therapeutic Targets - Steroid Receptors in Breast Cancer

    PubMed Central

    Fowler, Amy M.; Clark, Amy S.; Katzenellenbogen, John A; Linden, Hannah M.; Dehdashti, Farrokh

    2016-01-01

    Estrogen receptor-alpha (ERα) and progesterone receptor (PR) are important steroid hormone receptor biomarkers used to determine prognosis and predict benefit from endocrine therapies for breast cancer patients. Receptor expression is routinely measured in biopsy specimens using immunohistochemistry, although such testing can be challenging particularly in the setting of metastatic disease. ERα and PR can be quantitatively assayed non-invasively with positron emission tomography (PET). This approach provides the opportunity to assess receptor expression and function in “real-time”, within the entire tumor, and across distant sites of metastatic disease. This article reviews the current evidence of ERα and PR PET imaging as predictive and early response biomarkers for endocrine therapy. PMID:26834106

  2. The spectral analysis and information extraction for small geological target detection using hyperion image

    NASA Astrophysics Data System (ADS)

    Li, Qingting; Wei, Xinxin; Zhang, Bing; Yan, Shouxun; Liu, Xiang

    2008-12-01

    Imaging spectroscopic technique has been used for the mineral and rock geological mapping and alteration information extraction successfully with many reasonable results, but it is mainly used in arid and semi-arid land with low vegetation covering. In the case of the high vegetation covering, the outcrop of the altered rocks is small and distributes sparsely, the altered rocks is difficult to be identified directly. The target detection technique using imaging spectroscopic data should be introduced to the extraction of small geological targets under high vegetation covering area. In the paper, we take Ding-Ma gold deposit as the study area which located in Zhenan country, Shanxi province, the spectral features of the targets and the backgrounds are studied and analyzed using the field reflectance spectra, in addition to the study of the principle of the algorithms, some target detection algorithms which is appropriate to the small geological target detection are introduced. At last, the small altered rock targets under the covering of vegetation in forest are detected and discriminated in imaging spectroscopy data with the methods of spectral angle mapper (SAM), Constrained Energy Minimization (CEM) and Adaptive Cosine Estimator (ACE). The detection results are reasonable and indicate the ability of target detection algorithms in geological target detection in the forest area.

  3. Propylthiouracil (PTU)-induced vasculitis associated with antineutrophil antibody against myeloperoxidase (MPO-ANCA).

    PubMed

    Nakamori, Yoshitaka; Tominaga, Takayuki; Inoue, Yasushi; Shinohara, Kenji

    2003-06-01

    A 54-year-old woman had been administered propylthiouracil (PTU) for Graves' disease for 4 years. Recently, she complained of hemoptysis due to pulmonary alveolar hemorrhage causing anemia, and also had microhematuria. Antineutrophil cytoplasmic antibody against myeloperoxidase (MPO-ANCA) was positive, and she was diagnosed with PTU-induced vasculitis. Cessation of PTU and the administration of corticosteroids ameliorated these manifestations.

  4. Myeloperoxidase-produced Genomic DNA-centered Radicals and Protection by Resveratrol

    EPA Science Inventory

    Myeloperoxidase (MPO) released by activated neutrophils, production of hypochlorous acid (HOCI) and oxidation of the genomic DNA in epithelial cells is thought to initiate and promote carcinogenesis. In this study we applied the 5,5-dimethyl-l-pyrroline N-oxide (DMPO)-based i;nmu...

  5. Research on spatial-variant property of bistatic ISAR imaging plane of space target

    NASA Astrophysics Data System (ADS)

    Guo, Bao-Feng; Wang, Jun-Ling; Gao, Mei-Guo

    2015-04-01

    The imaging plane of inverse synthetic aperture radar (ISAR) is the projection plane of the target. When taking an image using the range-Doppler theory, the imaging plane may have a spatial-variant property, which causes the change of scatter’s projection position and results in migration through resolution cells. In this study, we focus on the spatial-variant property of the imaging plane of a three-axis-stabilized space target. The innovative contributions are as follows. 1) The target motion model in orbit is provided based on a two-body model. 2) The instantaneous imaging plane is determined by the method of vector analysis. 3) Three Euler angles are introduced to describe the spatial-variant property of the imaging plane, and the image quality is analyzed. The simulation results confirm the analysis of the spatial-variant property. The research in this study is significant for the selection of the imaging segment, and provides the evidence for the following data processing and compensation algorithm. Project supported by the National Natural Science Foundation of China (Grant No. 61401024), the Shanghai Aerospace Science and Technology Innovation Foundation, China (Grant No. SAST201240), and the Basic Research Foundation of Beijing Institute of Technology (Grant No. 20140542001).

  6. Adaptive sparse reconstruction with joint parametric estimation for high-speed uniformly moving targets in coincidence imaging radar

    NASA Astrophysics Data System (ADS)

    Zha, Guofeng; Wang, Hongqiang; Yang, Zhaocheng; Cheng, Yongqiang; Qin, Yuliang

    2016-04-01

    As a complementary imaging technology, coincidence imaging radar (CIR) achieves high resolution for stationary or low-speed targets under the assumption of ignoring the influence of the original position mismatching. As to high-speed moving targets moving from the original imaging cell to other imaging cells during imaging, it is inaccurate to reconstruct the target using the previous imaging plane. We focus on the recovery problem for high-speed moving targets in the CIR system based on the intrapulse frequency random modulation signal in a single pulse. The effects induced by the motion on the imaging performance are analyzed. Because the basis matrix in the CIR imaging equation is determined by the unknown velocity parameter of the moving target, both the target images and basis matrix should be estimated jointly. We propose an adaptive joint parametric estimation recovery algorithm based on the Tikhonov regularization method to update the target velocity and basis matrix adaptively and recover the target images synchronously. Finally, the target velocity and target images are obtained in an iterative manner. Simulation results are presented to demonstrate the efficiency of the proposed algorithm.

  7. Galactosylated manganese ferrite nanoparticles for targeted MR imaging of asialoglycoprotein receptor.

    PubMed

    Yang, Seung-Hyun; Heo, Dan; Lee, Eugene; Kim, Eunjung; Lim, Eun-Kyung; Lee, Young Han; Haam, Seungjoo; Suh, Jin-Suck; Huh, Yong-Min; Yang, Jaemoon; Park, Sahng Wook

    2013-11-29

    Cancer cells can express specific biomarkers, such as cell membrane proteins and signaling factors. Thus, finding biomarkers and delivering diagnostic agents are important in the diagnosis of cancer. In this study, we investigated a biomarker imaging agent for the diagnosis of hepatic cancers. The asialoglycoprotein receptor (ASGPr) was selected as a biomarker for hepatoma cells and the ASGPr-targetable imaging agent bearing a galactosyl group was prepared using manganese ferrite nanoparticles (MFNP) and galactosylgluconic acid. The utility of the ASGPr-targetable imaging agent, galactosylated MFNP (G-MFNP) was assessed by several methods in ASGPr-expressing HepG2 cells as target cells and ASGPr-deficient MCF7 cells. Physical and chemical properties of G-MFNP were examined using Fourier-transform infrared spectroscopy, dynamic light scattering, zeta potential analysis, and transmission electron microscopy. No significant cytotoxicity was observed in either cell line. Targeting ability was assessed using flow cytometry, magnetic resonance imaging, inductively coupled plasma atomic emission spectroscopy, absorbance analysis, dark-field microscopy, Prussian blue staining, and transmission electron microscopy. We demonstrated that G-MFNP target successfully and bind to ASGPr-expressing HepG2 cells specifically. We suggest that these results will be useful in strategies for cancer diagnoses based on magnetic resonance imaging.

  8. Evaluation of super-resolution imager with binary fractal test target

    NASA Astrophysics Data System (ADS)

    Landeau, Stéphane

    2014-10-01

    Today, new generation of powerful non-linear image processing are used for real time super-resolution or noise reduction. Optronic imagers with such features are becoming difficult to assess, because spatial resolution and sensitivity are now related to scene content. Many algorithms include regularization process, which usually reduces image complexity to enhance spread edges or contours. Small important scene details can be then deleted by this kind of processing. In this paper, a binary fractal test target is presented, with a structured clutter pattern and an interesting autosimilarity multi-scale property. The apparent structured clutter of this test target gives a trade-off between a white noise, unlikely in real scenes, and very structured targets like MTF targets. Together with the fractal design of the target, an assessment method has been developed to evaluate automatically the non-linear effects on the acquired and processed image of the imager. The calculated figure of merit is to be directly comparable to the linear Fourier MTF. For this purpose the Haar wavelet elements distributed spatially and at different scales on the target are assimilated to the sine Fourier cycles at different frequencies. The probability of correct resolution indicates the ability to read correct Haar contrast among all Haar wavelet elements with a position constraint. For the method validation, a simulation of two different imager types has been done, a well-sampled linear system and an under-sampled one, coupled with super-resolution or noise reduction algorithms. The influence of the target contrast on the figures of merit is analyzed. Finally, the possible introduction of this new figure of merit in existing analytical range performance models, such as TRM4 (Fraunhofer IOSB) or NVIPM (NVESD) is discussed. Benefits and limitations of the method are also compared to the TOD (TNO) evaluation method.

  9. Installation and Initial Operation of an On-line Target Imaging System for SNS

    SciTech Connect

    McManamy, Thomas J; Banke, Glenn; Blokland, Willem; Brunson, Aly; Dayton, Michael J; Goetz, Kathleen C; Janney, Jim G; Lance, Michael J; Maxey, L Curt; Montgomery, Fred C; Rosenblad, Peter M; Sampath, Sanjay; Simpson, Marc Livingstone; Shea, Thomas J

    2010-01-01

    After several years of operation, the SNS now enters an era of megawatt class operation. At this intensity level, the target will be operating closer to its engineering limits and the beam profile on target must be carefully controlled. During commissioning and early operations, a temporary imaging system was used to measure the proton density on target. This system was not designed to survive the increasing power levels and it had to be removed in the second half of 2006. Since then, no direct measurement of beam properties at the target has been available. A collaboration was forged to remedy this situation, and has resulted in a new imaging system consisting of three major components: a thermal-sprayed luminescent coating deposited on the target nose, a radiation-tolerant optical system installed upstream of the target, and an image acquisition system integrated with the accelerator controls network. The design, installation, and integration of these components will be described. Initial beam measurements and image analysis results will be presented. Lessons learned during this initial operating experience have been documented and will guide the collaboration s future plans.

  10. Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging.

    PubMed

    Fan, Xiaozhou; Wang, Luofu; Guo, Yanli; Tu, Zhui; Li, Lang; Tong, Haipeng; Xu, Yang; Li, Rui; Fang, Kejing

    2015-01-01

    To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The "targeted" nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles. PMID:26111008

  11. Compound algorithm for restoration of heavy turbulence-degraded image for space target

    NASA Astrophysics Data System (ADS)

    Wang, Liang-liang; Wang, Ru-jie; Li, Ming; Kang, Zi-qian; Xu, Xiao-qin; Gao, Xin

    2012-11-01

    Restoration of atmospheric turbulence degraded image is needed to be solved as soon as possible in the field of astronomical space technology. Owing to the fact that the point spread function of turbulence is unknown, changeable with time, hard to be described by mathematics models, withal, kinds of noises would be brought during the imaging processes (such as sensor noise), the image for space target is edge blurred and heavy noised, which making a single restoration algorithm to reach the requirement of restoration difficult. Focusing the fact that the image for space target which was fetched during observation by ground-based optical telescopes is heavy noisy turbulence degraded, this paper discusses the adjustment and reformation of various algorithm structures as well as the selection of various parameters, after the combination of the nonlinear filter algorithm based on noise spatial characteristics, restoration algorithm of heavy turbulence degrade image for space target based on regularization, and the statistics theory based EM restoration algorithm. In order to test the validity of the algorithm, a series of restoration experiments are performed on the heavy noisy turbulence-degraded images for space target. The experiment results show that the new compound algorithm can achieve noise restriction and detail preservation simultaneously, which is effective and practical. Withal, the definition measures and relative definition measures show that the new compound algorithm is better than the traditional algorithms.

  12. Altered visual experience and acute visual deprivation affect predatory targeting by infrared-imaging Boid snakes.

    PubMed

    Grace, M S; Woodward, O M

    2001-11-23

    Boid and Crotaline snakes use both their eyes and infrared-imaging facial pit organs to target homeothermic prey. These snakes can target in complete darkness, but the eyes can also effectively direct predatory strikes. We investigated the behavioral correlates of boid snakes' simultaneous use of two imaging systems by testing whether congenital unilateral visual deprivation affects targeting performance. Normally sighted Burmese pythons exhibited average targeting angle of zero (on the midline axis of the head), but three unilaterally anophthalmic Burmese pythons targeted preferentially on the sighted side. A unilaterally anophthalmic amethystine python also targeted on the sighted side, and a unilaterally anophthalmic Brazilian rainbow boa tended to target on the sighted side, though its mean targeting angle was not significantly different from zero. When unilaterally anophthalmic Burmese pythons were temporarily blinded, mean strike angle changed to that of normally sighted snakes. These results show that while infrared-imaging snakes can shift between visual and infrared information under acute experimental conditions, loss of part of the visual field during development results in abnormal predatory targeting behavior. In contrast, normally sighted snakes subjected to temporary unilateral blinding do not target preferentially on the sighted side. Therefore, while loss of part of the visual field may be compensated for by infrared input in normal snakes, partial absence of visual input during development may alter central organization of visual information. Conversely, absence of half the visual field during development does not alter targeting performance based upon infrared input alone, suggesting that organization of the central infrared map does not depend upon normal organization of visual input.

  13. Why Integrin as a Primary Target for Imaging and Therapy

    PubMed Central

    Niu, Gang; Chen, Xiaoyuan

    2011-01-01

    Integrin-mediated cell adhesion is involved in many essential normal cellular and pathological functions including cell survival, growth, differentiation, migration, inflammatory responses, platelet aggregation, tissue repair and tumor invasion. 24 different heterodimerized transmembrane integrin receptors are combined from 18 different α and 8 different β subunits. Each integrin subunit contains a large extracellular domain, a single transmembrane domain and a usually short cytoplasmic domain. Integrins bind extracellular matrix (ECM) proteins through their large extracellular domain, and engage the cytoskeleton via their short cytoplasmic tails. These integrin-mediated linkages on either side of the plasma membrane are dynamically linked. Thus, integrins communicate over the plasma membrane in both directions, i.e., outside-in and inside-out signaling. In outside-in signaling through integrins, conformational changes of integrin induced by ligand binding on the extracellular domain altered the cytoplasmic domain structures to elicit various intracellular signaling pathways. Inside-out signaling originates from non-integrin cell surface receptors or cytoplasmic molecules and it activates signaling pathways inside the cells, ultimately resulting in the activation/deactivation of integrins. Integrins are one of key family proteins for cell adhesion regulation through binding to a large number of ECM molecules and cell membrane proteins. Lack of expression of integrins may result in a wide variety of effects ranging from blockage in pre-implantation to embryonic or perinatal lethality and developmental defects. Based on both the key role they played in angiogenesis, leukocytes function and tumor development and easy accessibility as cell surface receptors interacting with extracellular ligands, the integrin superfamily represents the best opportunity of targeting both antibodies and small-molecule antagonists for both therapeutic and diagnostic utility in various

  14. Effects of residual target motion for image-tracked spine radiosurgery

    SciTech Connect

    Chuang, Cynthia; Sahgal, Arjun; Lee, Letitia; Larson, David; Huang, Kim; Petti, Paula; Verhey, Lynn; Ma Lijun

    2007-11-15

    A quality assurance method was developed to investigate the effects of residual target motion for hypofractionated spine radiosurgery. The residual target motion (target movement between successive image-guided corrections) was measured on-line via dual x-ray imagers for patients treated with CyberKnife (Accuray, Inc., Sunnyvale, CA), a robotic linear accelerator with intrafractional image-tracking capability. The six degree-of-freedom characteristics of the residual target motion were analyzed, the effects of such motion on patient treatment delivery were investigated by incorporating the probability distribution of the residual motion into the treatment planning dose calculations, and deviations of the doses from those originally planned were calculated. Measurements using a programmable motion phantom were also carried out and compared with the static treatment plan calculations. It was found that the residual target motions were patient specific and typically on the order of 2 mm. The measured dose distributions incorporating the residual target motion also exhibited 2.0 mm discrepancy at the prescription isodose level when compared with the static treatment plan calculations. For certain patients, residual errors introduced significant uncertainties ({approx}1 Gy) for the dose delivered to the spinal cord, especially at the high dose levels covering a small volume of the spinal cord (e.g., 0.1 cc). In such cases, stringent cord constraints and frequent monitoring of the target position should be implemented.

  15. Targeting of deep-brain structures in nonhuman primates using MR and CT Images

    NASA Astrophysics Data System (ADS)

    Chen, Antong; Hines, Catherine; Dogdas, Belma; Bone, Ashleigh; Lodge, Kenneth; O'Malley, Stacey; Connolly, Brett; Winkelmann, Christopher T.; Bagchi, Ansuman; Lubbers, Laura S.; Uslaner, Jason M.; Johnson, Colena; Renger, John; Zariwala, Hatim A.

    2015-03-01

    In vivo gene delivery in central nervous systems of nonhuman primates (NHP) is an important approach for gene therapy and animal model development of human disease. To achieve a more accurate delivery of genetic probes, precise stereotactic targeting of brain structures is required. However, even with assistance from multi-modality 3D imaging techniques (e.g. MR and CT), the precision of targeting is often challenging due to difficulties in identification of deep brain structures, e.g. the striatum which consists of multiple substructures, and the nucleus basalis of meynert (NBM), which often lack clear boundaries to supporting anatomical landmarks. Here we demonstrate a 3D-image-based intracranial stereotactic approach applied toward reproducible intracranial targeting of bilateral NBM and striatum of rhesus. For the targeting we discuss the feasibility of an atlas-based automatic approach. Delineated originally on a high resolution 3D histology-MR atlas set, the NBM and the striatum could be located on the MR image of a rhesus subject through affine and nonrigid registrations. The atlas-based targeting of NBM was compared with the targeting conducted manually by an experienced neuroscientist. Based on the targeting, the trajectories and entry points for delivering the genetic probes to the targets could be established on the CT images of the subject after rigid registration. The accuracy of the targeting was assessed quantitatively by comparison between NBM locations obtained automatically and manually, and finally demonstrated qualitatively via post mortem analysis of slices that had been labelled via Evan Blue infusion and immunohistochemistry.

  16. Study of image matching algorithm and sub-pixel fitting algorithm in target tracking

    NASA Astrophysics Data System (ADS)

    Yang, Ming-dong; Jia, Jianjun; Qiang, Jia; Wang, Jian-yu

    2015-03-01

    Image correlation matching is a tracking method that searched a region most approximate to the target template based on the correlation measure between two images. Because there is no need to segment the image, and the computation of this method is little. Image correlation matching is a basic method of target tracking. This paper mainly studies the image matching algorithm of gray scale image, which precision is at sub-pixel level. The matching algorithm used in this paper is SAD (Sum of Absolute Difference) method. This method excels in real-time systems because of its low computation complexity. The SAD method is introduced firstly and the most frequently used sub-pixel fitting algorithms are introduced at the meantime. These fitting algorithms can't be used in real-time systems because they are too complex. However, target tracking often requires high real-time performance, we put forward a fitting algorithm named paraboloidal fitting algorithm based on the consideration above, this algorithm is simple and realized easily in real-time system. The result of this algorithm is compared with that of surface fitting algorithm through image matching simulation. By comparison, the precision difference between these two algorithms is little, it's less than 0.01pixel. In order to research the influence of target rotation on precision of image matching, the experiment of camera rotation was carried on. The detector used in the camera is a CMOS detector. It is fixed to an arc pendulum table, take pictures when the camera rotated different angles. Choose a subarea in the original picture as the template, and search the best matching spot using image matching algorithm mentioned above. The result shows that the matching error is bigger when the target rotation angle is larger. It's an approximate linear relation. Finally, the influence of noise on matching precision was researched. Gaussian noise and pepper and salt noise were added in the image respectively, and the image

  17. Assessments of image-based and scatterometry-based overlay targets

    NASA Astrophysics Data System (ADS)

    Koay, Chiew-seng; Felix, Nelson; Hamieh, Bassem; Halle, Scott; Zheng, Chumeng; Sieg, Stuart

    2016-03-01

    Having a well designed overlay metrology target is one of the ways to improve on-product overlay performance. The traditional screening method in which multiple targets types are added to successive reticle tape outs and then evaluated by trial-and-error may not suffice for the 7nm node and beyond. For instance, although segmentation of image-based overlay target has been reported by many as a means for improving overlay measurement, we find that segmentation does not guarantee improvement. In fact it can be undesirable. Fundamental understandings of metrology and wafer process are required to properly design the targets and carefully optimize them for a given process stack involving multilevel measurement. This paper investigates the Blossom, AIM, and scatterometry targets at the FEOL, MOL, and BEOL patterning levels in 7nm node to gain knowledge needed in order to comprehensively map out the overlay target solutions for future nodes.

  18. Ground target detection based on discrete cosine transform and Rényi entropy for imaging ladar

    NASA Astrophysics Data System (ADS)

    Xu, Yuannan; Chen, Weili; Li, Junwei; Dong, Yanbing

    2016-01-01

    The discrete cosine transform (DCT) due to its excellent properties that the images can be represented in spatial/spatial-frequency domains, has been applied in sequence data analysis and image fusion. For intensity and range images of ladar, through the DCT using one dimension window, the statistical property of Rényi entropy for images is studied. We also analyzed the change of Rényi entropy's statistical property in the ladar intensity and range images when the man-made objects appear. From this foundation, a novel method for generating saliency map based on DCT and Rényi entropy is proposed. After that, ground target detection is completed when the saliency map is segmented using a simple and convenient threshold method. For the ladar intensity and range images, experimental results show the proposed method can effectively detect the military vehicles from complex earth background with low false alarm.

  19. Chlorotoxin-conjugated nanoparticles for targeted imaging and therapy of glioma.

    PubMed

    Zhao, Lingzhou; Shi, Xiangyang; Zhao, Jinhua

    2015-01-01

    This review reports the recent advances in chlorotoxin (CTX)-targeted nanoparticles (NPs) for imaging and therapy of glioma. CTX has been identified as a targeting ligand to specifically bind to glioma. Through different conjugation approaches, CTX can be conjugated onto iron oxide NPs, quantum dots, and rare-earth upconversion NPs for targeted magnetic resonance and fluorescence imaging of glioma. Likewise, CTX-conjugated NPs can also be used as a carrier system to load anticancer drugs or therapeutic genes for targeted chemotherapy or gene therapy of glioma, respectively. Some of the key developments in this area of research will be introduced in detail. Challenges and future perspectives in the development of CTX-conjugated NPs will be discussed.

  20. Early recognition of lung cancer by integrin targeted imaging in K-ras mouse model.

    PubMed

    Ermolayev, Vladimir; Mohajerani, Pouyan; Ale, Angelique; Sarantopoulos, Athanasios; Aichler, Michaela; Kayser, Gian; Walch, Axel; Ntziachristos, Vasilis

    2015-09-01

    Non-small cell lung cancer is characterized by slow progression and high heterogeneity of tumors. Integrins play an important role in lung cancer development and metastasis and were suggested as a tumor marker; however their role in anticancer therapy remains controversial. In this work, we demonstrate the potential of integrin-targeted imaging to recognize early lesions in transgenic mouse model of lung cancer based on spontaneous introduction of mutated human gene bearing K-ras mutation. We conducted ex vivo and fluorescence molecular tomography-X-ray computed tomography (FMT-XCT) in vivo imaging and analysis for specific targeting of early lung lesions and tumors in rodent preclinical model for lung cancer. The lesions and tumors were characterized by histology, immunofluorescence and immunohistochemistry using a panel of cancer markers. Ex vivo, the integrin-targeted fluorescent signal significantly differed between wild type lung tissue and K-ras pulmonary lesions (PL) at all ages studied. The panel of immunofluorescence experiments demonstrated that PL, which only partially show cancer cell features were detected by αvβ3-integrin targeted imaging. Human patient material analysis confirmed the specificity of target localization in different lung cancer types. Most importantly, small tumors in the lungs of 4-week-old animals could be noninvasively detected in vivo on the fluorescence channel of FMT-XCT. Our findings demonstrated αvβ3-integrin targeted fluorescent imaging to specifically detect premalignant pleural lesions in K-ras mice. Integrin targeted imaging may find application areas in preclinical research and clinical practice, such as early lung cancer diagnostics, intraoperative assistance or therapy monitoring.

  1. Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy

    PubMed Central

    Harpel, Kaitlin; Baker, Robert Dawson; Amirsolaimani, Babak; Mehravar, Soroush; Vagner, Josef; Matsunaga, Terry O.; Banerjee, Bhaskar; Kieu, Khanh

    2016-01-01

    The use of receptor-targeted lipid microbubbles imaged by ultrasound is an innovative method of detecting and localizing disease. However, since ultrasound requires a medium between the transducer and the object being imaged, it is impractical to apply to an exposed surface in a surgical setting where sterile fields need be maintained and ultrasound gel may cause the bubbles to collapse. Multiphoton microscopy (MPM) is an emerging tool for accurate, label-free imaging of tissues and cells with high resolution and contrast. We have recently determined a novel application of MPM to be used for detecting targeted microbubble adherence to the upregulated plectin-receptor on pancreatic tumor cells. Specifically, the third-harmonic generation response can be used to detect bound microbubbles to various cell types presenting MPM as an alternative and useful imaging method. This is an interesting technique that can potentially be translated as a diagnostic tool for the early detection of cancer and inflammatory disorders. PMID:27446711

  2. Opti-acoustic stereo imaging: on system calibration and 3-D target reconstruction.

    PubMed

    Negahdaripour, Shahriar; Sekkati, Hicham; Pirsiavash, Hamed

    2009-06-01

    Utilization of an acoustic camera for range measurements is a key advantage for 3-D shape recovery of underwater targets by opti-acoustic stereo imaging, where the associated epipolar geometry of optical and acoustic image correspondences can be described in terms of conic sections. In this paper, we propose methods for system calibration and 3-D scene reconstruction by maximum likelihood estimation from noisy image measurements. The recursive 3-D reconstruction method utilized as initial condition a closed-form solution that integrates the advantages of two other closed-form solutions, referred to as the range and azimuth solutions. Synthetic data tests are given to provide insight into the merits of the new target imaging and 3-D reconstruction paradigm, while experiments with real data confirm the findings based on computer simulations, and demonstrate the merits of this novel 3-D reconstruction paradigm.

  3. Imaging of targeted lipid microbubbles to detect cancer cells using third harmonic generation microscopy.

    PubMed

    Harpel, Kaitlin; Baker, Robert Dawson; Amirsolaimani, Babak; Mehravar, Soroush; Vagner, Josef; Matsunaga, Terry O; Banerjee, Bhaskar; Kieu, Khanh

    2016-07-01

    The use of receptor-targeted lipid microbubbles imaged by ultrasound is an innovative method of detecting and localizing disease. However, since ultrasound requires a medium between the transducer and the object being imaged, it is impractical to apply to an exposed surface in a surgical setting where sterile fields need be maintained and ultrasound gel may cause the bubbles to collapse. Multiphoton microscopy (MPM) is an emerging tool for accurate, label-free imaging of tissues and cells with high resolution and contrast. We have recently determined a novel application of MPM to be used for detecting targeted microbubble adherence to the upregulated plectin-receptor on pancreatic tumor cells. Specifically, the third-harmonic generation response can be used to detect bound microbubbles to various cell types presenting MPM as an alternative and useful imaging method. This is an interesting technique that can potentially be translated as a diagnostic tool for the early detection of cancer and inflammatory disorders. PMID:27446711

  4. Opti-acoustic stereo imaging: on system calibration and 3-D target reconstruction.

    PubMed

    Negahdaripour, Shahriar; Sekkati, Hicham; Pirsiavash, Hamed

    2009-06-01

    Utilization of an acoustic camera for range measurements is a key advantage for 3-D shape recovery of underwater targets by opti-acoustic stereo imaging, where the associated epipolar geometry of optical and acoustic image correspondences can be described in terms of conic sections. In this paper, we propose methods for system calibration and 3-D scene reconstruction by maximum likelihood estimation from noisy image measurements. The recursive 3-D reconstruction method utilized as initial condition a closed-form solution that integrates the advantages of two other closed-form solutions, referred to as the range and azimuth solutions. Synthetic data tests are given to provide insight into the merits of the new target imaging and 3-D reconstruction paradigm, while experiments with real data confirm the findings based on computer simulations, and demonstrate the merits of this novel 3-D reconstruction paradigm. PMID:19380272

  5. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design.

    PubMed

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M

    2016-01-01

    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. PMID:27147293

  6. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design

    NASA Astrophysics Data System (ADS)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M.

    2016-05-01

    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.

  7. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design

    NASA Astrophysics Data System (ADS)

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M.

    2016-05-01

    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.

  8. Ultrasonic Nanobubbles Carrying Anti-PSMA Nanobody: Construction and Application in Prostate Cancer-Targeted Imaging

    PubMed Central

    Guo, Yanli; Tu, Zhui; Li, Lang; Tong, Haipeng; Xu, Yang; Li, Rui; Fang, Kejing

    2015-01-01

    To facilitate prostate cancer imaging using targeted molecules, we constructed ultrasonic nanobubbles coupled with specific anti-PSMA (prostate specific membrane antigen) nanobodies, and evaluated their in vitro binding capacity and in vivo imaging efficacy. The “targeted” nanobubbles, which were constructed via a biotin-streptavidin system, had an average diameter of 487.60 ± 33.55 nm and carried the anti-PSMA nanobody as demonstrated by immunofluorescence. Microscopy revealed targeted binding of nanobubbles in vitro to PSMA-positive cells. Additionally, ultrasonography indicators of nanobubble imaging (including arrival time, peak time, peak intensity and enhanced duration) were evaluated for the ultrasound imaging in three kinds of animal xenografts (LNCaP, C4-2 and MKN45), and showed that these four indicators of targeted nanobubbles exhibited significant differences from blank nanobubbles. Therefore, this study not only presents a novel approach to target prostate cancer ultrasonography, but also provides the basis and methods for constructing small-sized and high-efficient targeted ultrasound nanobubbles. PMID:26111008

  9. Mechanistic and quantitative insight into cell surface targeted molecular imaging agent design

    PubMed Central

    Zhang, Liang; Bhatnagar, Sumit; Deschenes, Emily; Thurber, Greg M.

    2016-01-01

    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. PMID:27147293

  10. 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.

  11. Numerical Simulation of Target Range Estimation Using Ambient Noise Imaging with Acoustic Lens

    NASA Astrophysics Data System (ADS)

    Mori, Kazuyoshi; Ogasawara, Hanako; Nakamura, Toshiaki; Tsuchiya, Takenobu; Endoh, Nobuyuki

    2010-07-01

    In ambient noise imaging (ANI), each pixel of a target image is mapped by either monochrome or pseudo color to represent its acoustic intensity in each direction. This intensity is obtained by measuring the target object's reflecting or scattering wave, with ocean background noise serving as the sound source. In the case of using an acoustic lens, the ANI system creates a C-mode-like image, where receivers are arranged on a focal plane and each pixel's color corresponds to the intensity of each receiver output. There is no consideration for estimating a target range by this method, because it is impossible to measure the traveling time between a transducer and a target by a method like an active imaging sonar. In this study, we tried to estimate a target range using the ANI system with an acoustic lens. Here, we conducted a numerical simulation of sound propagation based on the principle of the time reversal mirror. First, instead of actual ocean measurements in the forward propagation, we calculated the scattering wave from a rigid target object in an acoustic noise field generated by a large number of point sources using the two-dimensional (2D) finite difference time domain (FDTD) method. The time series of the scattering wave converged by the lens was then recorded on each receiver. The sound pressure distribution assuming that the time-reversed wave of the scattering wave was reradiated from each receiver position was also calculated using the 2D FDTD method in the backward propagation. It was possible to estimate a target range using the ANI system with an acoustic lens, because the maximum position of the reradiated sound pressure field was close to the target position.

  12. Numerical Simulation of Target Range Estimation Using Ambient Noise Imaging with Acoustic Lens

    NASA Astrophysics Data System (ADS)

    Kazuyoshi Mori,; Hanako Ogasawara,; Toshiaki Nakamura,; Takenobu Tsuchiya,; Nobuyuki Endoh,

    2010-07-01

    In ambient noise imaging (ANI), each pixel of a target image is mapped by either monochrome or pseudo color to represent its acoustic intensity in each direction. This intensity is obtained by measuring the target object’s reflecting or scattering wave, with ocean background noise serving as the sound source. In the case of using an acoustic lens, the ANI system creates a C-mode-like image, where receivers are arranged on a focal plane and each pixel’s color corresponds to the intensity of each receiver output. There is no consideration for estimating a target range by this method, because it is impossible to measure the traveling time between a transducer and a target by a method like an active imaging sonar. In this study, we tried to estimate a target range using the ANI system with an acoustic lens. Here, we conducted a numerical simulation of sound propagation based on the principle of the time reversal mirror. First, instead of actual ocean measurements in the forward propagation, we calculated the scattering wave from a rigid target object in an acoustic noise field generated by a large number of point sources using the two-dimensional (2D) finite difference time domain (FDTD) method. The time series of the scattering wave converged by the lens was then recorded on each receiver. The sound pressure distribution assuming that the time-reversed wave of the scattering wave was reradiated from each receiver position was also calculated using the 2D FDTD method in the backward propagation. It was possible to estimate a target range using the ANI system with an acoustic lens, because the maximum position of the reradiated sound pressure field was close to the target position.

  13. Targeted Molecular Imaging of Cancer Cells Using MS2-Based (129)Xe NMR.

    PubMed

    Jeong, Keunhong; Netirojjanakul, Chawita; Munch, Henrik K; Sun, Jinny; Finbloom, Joel A; Wemmer, David E; Pines, Alexander; Francis, Matthew B

    2016-08-17

    We have synthesized targeted, selective, and highly sensitive (129)Xe NMR nanoscale biosensors using a spherical MS2 viral capsid, Cryptophane A molecules, and DNA aptamers. The biosensors showed strong binding specificity toward targeted lymphoma cells (Ramos line). Hyperpolarized (129)Xe NMR signal contrast and hyper-CEST (129)Xe MRI image contrast indicated its promise as highly sensitive hyperpolarized (129)Xe NMR nanoscale biosensor for future applications in cancer detection in vivo. PMID:27454679

  14. Tensor Fukunaga-Koontz transform for small target detection in infrared images

    NASA Astrophysics Data System (ADS)

    Liu, Ruiming; Wang, Jingzhuo; Yang, Huizhen; Gong, Chenglong; Zhou, Yuanshen; Liu, Lipeng; Zhang, Zhen; Shen, Shuli

    2016-09-01

    Infrared small targets detection plays a crucial role in warning and tracking systems. Some novel methods based on pattern recognition technology catch much attention from researchers. However, those classic methods must reshape images into vectors with the high dimensionality. Moreover, vectorizing breaks the natural structure and correlations in the image data. Image representation based on tensor treats images as matrices and can hold the natural structure and correlation information. So tensor algorithms have better classification performance than vector algorithms. Fukunaga-Koontz transform is one of classification algorithms and it is a vector version method with the disadvantage of all vector algorithms. In this paper, we first extended the Fukunaga-Koontz transform into its tensor version, tensor Fukunaga-Koontz transform. Then we designed a method based on tensor Fukunaga-Koontz transform for detecting targets and used it to detect small targets in infrared images. The experimental results, comparison through signal-to-clutter, signal-to-clutter gain and background suppression factor, have validated the advantage of the target detection based on the tensor Fukunaga-Koontz transform over that based on the Fukunaga-Koontz transform.

  15. Validation of a target acquisition model for active imager using perception experiments

    NASA Astrophysics Data System (ADS)

    Lapaz, Frédéric; Canevet, Loïc

    2007-10-01

    Active night vision systems based on laser diodes emitters have now reached a technology level allowing military applications. In order to predict the performance of observers using such systems, we built an analytic model including sensor, atmosphere, visualization and eye effects. The perception task has been modelled using the Targeting Task Performance metric (TTP metric) developed by R. Vollmerhausen from the Night Vision and Electronic Sensors Directorate (NVESD). Sensor and atmosphere models have been validated separately. In order to validate the whole model, two identification tests have been set up. The first set submitted to trained observers was made of hybrid images. The target to background contrast, the blur and the noise were added to armoured vehicles signatures in accordance to sensor and atmosphere models. The second set of images was made with the same targets, sensed by a real active sensor during field trials. Images were recorded, showing different vehicles, at different ranges and orientations, under different illumination and acquisition configurations. Indeed, this set of real images was built with three different types of gating: wide illumination, illumination of the background and illumination of the target. Analysis of the perception experiments results showed a good concordance between the two sets of images. The calculation of an identification criterion, related to this set of vehicles in the near infrared, gave the same results in both cases. The impact of gating on observer's performance was also evaluated.

  16. Targeted Imaging of Damaged Bone in Vivo with Gemstone Spectral Computed Tomography.

    PubMed

    Wang, Ying; Jiang, Chunhuan; He, Wenhui; Ai, Kelong; Ren, Xiaoyan; Liu, Lin; Zhang, Mengchao; Lu, Lehui

    2016-04-26

    Achieving high-resolution imaging of bone-cracks and even monitoring them in live organisms are of great significance for understanding their extreme biological effects but remain quite challenging, especially for adopting commercial imaging systems. Herein, we explore the use of the clinical gemstone spectral computed tomography (GSCT) technique as a powerful tool for targeted imaging of bone-cracks in rats via intramuscularly administrating crack-targeted ytterbium-based contrast agents (CAs). Material density images of GSCT reveal that bone-cracks targeted with CAs can be successfully differentiated from healthy bone based on their different X-ray attenuation characteristics, giving GSCT a distinct advantage over conventional CT. More importantly, the superior imaging capability of GSCT allows us to real-time monitor the targeting and accumulation of CAs toward bone-crack in vivo. These results highlight that clinical GSCT, combined with ytterbium-based CAs, provides a promising opportunity for understanding bone-related diseases in the future. PMID:27043072

  17. In vivo targeted cancer imaging, sentinel lymph node mapping and multi-channel imaging with biocompatible silicon nanocrystals.

    PubMed

    Erogbogbo, Folarin; Yong, Ken-Tye; Roy, Indrajit; Hu, Rui; Law, Wing-Cheung; Zhao, Weiwei; Ding, Hong; Wu, Fang; Kumar, Rajiv; Swihart, Mark T; Prasad, Paras N

    2011-01-25

    Quantum dots (QDs) have size-dependent optical properties that make them uniquely advantageous for in vivo targeted fluorescence imaging, traceable delivery, and therapy. The use of group II-VI (e.g., CdSe) QDs for these applications is advancing rapidly. However, group II-VI QDs contain toxic heavy metals that limit their in vivo applications. Thus, replacing these with QDs of a biocompatible semiconductor, such as silicon (Si), is desirable. Here, we demonstrate that properly encapsulated biocompatible Si QDs can be used in multiple cancer-related in vivo applications, including tumor vasculature targeting, sentinel lymph node mapping, and multicolor NIR imaging in live mice. This work overcomes dispersibility and functionalization challenges to in vivo imaging with Si QDs through a unique nanoparticle synthesis, surface functionalization, PEGylated micelle encapsulation, and bioconjugation process that produces bright, targeted nanospheres with stable luminescence and long (>40 h) tumor accumulation time in vivo. Upon the basis of this demonstration, we anticipate that Si QDs can play an important role in more sophisticated in vivo models, by alleviating QD toxicity concerns while maintaining the key advantages of QD-based imaging methods.

  18. Tomographic diffractive microscopy with agile illuminations for imaging targets in a noisy background.

    PubMed

    Zhang, T; Godavarthi, C; Chaumet, P C; Maire, G; Giovannini, H; Talneau, A; Prada, C; Sentenac, A; Belkebir, K

    2015-02-15

    Tomographic diffractive microscopy is a marker-free optical digital imaging technique in which three-dimensional samples are reconstructed from a set of holograms recorded under different angles of incidence. We show experimentally that, by processing the holograms with singular value decomposition, it is possible to image objects in a noisy background that are invisible with classical wide-field microscopy and conventional tomographic reconstruction procedure. The targets can be further characterized with a selective quantitative inversion.

  19. A multiple constrained signal subspace projection for target detection in hyperspectral images

    NASA Astrophysics Data System (ADS)

    Chang, Lena; Wu, Yen-Ting; Tang, Zay-Shing; Chang, Yang-Lang

    2015-05-01

    In the study, we develop a multiple constrained signal subspace projection (SSP) approach to target detection. Instead of using single constraint on target detection, we design an optimal filter with multiple constraints on desired targets by using SSP. The proposed SSP approach fully exploits the orthogonal property of two orthogonal subspaces: one denoted signal subspace containing desired and undesired/background targets; the other denoted noise subspace, which is orthogonal to signal subspace. By projecting the weights of the detection filter on the signal subspace, the proposed SSP can reduces some estimation errors in target signatures and alleviate the performance degradation caused by uncertainty of target signature. The SSP approach can detect desired targets, suppress undesired targets and minimize the interference effects. In experiments, we provide three methods in selecting multiple constraints of the desired target: Kmeans, principal eigenvectors and endmenber extracting techniques. Simulation results show that the proposed SSP with multiple constraints selected by K-means has better detection performance. Furthermore, the proposed SSP with multiple constraints is a robust detection approach which could overcome the uncertainty of desired target signature in real image data.

  20. Toward prediction of hyperspectral target detection performance after lossy image compression

    NASA Astrophysics Data System (ADS)

    Kaufman, Jason R.; Vongsy, Karmon M.; Dill, Jeffrey C.

    2016-05-01

    Hyperspectral imagery (HSI) offers numerous advantages over traditional sensing modalities with its high spectral content that allows for classification, anomaly detection, target discrimination, and change detection. However, this imaging modality produces a huge amount of data, which requires transmission, processing, and storage resources; hyperspectral compression is a viable solution to these challenges. It is well known that lossy compression of hyperspectral imagery can impact hyperspectral target detection. Here we examine lossy compressed hyperspectral imagery from data-centric and target-centric perspectives. The compression ratio (CR), root mean square error (RMSE), the signal to noise ratio (SNR), and the correlation coefficient are computed directly from the imagery and provide insight to how the imagery has been affected by the lossy compression process. With targets present in the imagery, we perform target detection with the spectral angle mapper (SAM) and adaptive coherence estimator (ACE) and evaluate the change in target detection performance by examining receiver operating characteristic (ROC) curves and the target signal-to-clutter ratio (SCR). Finally, we observe relationships between the data- and target-centric metrics for selected visible/near-infrared to shortwave infrared (VNIR/SWIR) HSI data, targets, and backgrounds that motivate potential prediction of change in target detection performance as a function of compression ratio.

  1. Toward prediction of hyperspectral target detection performance after lossy image compression

    NASA Astrophysics Data System (ADS)

    Kaufman, Jason R.; Vongsy, Karmon M.; Dill, Jeffrey C.

    2016-05-01

    Hyperspectral imagery (HSI) offers numerous advantages over traditional sensing modalities with its high spectral content that allows for classification, anomaly detection, target discrimination, and change detection. However, this imaging modality produces a huge amount of data, which requires transmission, processing, and storage resources; hyperspectral compression is a viable solution to these challenges. It is well known that lossy compression of hyperspectral imagery can impact hyperspectral target detection. Here we examine lossy compressed hyperspectral imagery from data-centric and target-centric perspectives. The compression ratio (CR), root mean square error (RMSE), the signal to noise ratio (SNR), and the correlation coefficient are computed directly from the imagery and provide insight to how the imagery has been affected by the lossy compression process. With targets present in the imagery, we perform target detection with the spectral angle mapper (SAM) and adaptive coherence estimator (ACE) and evaluate the change in target detection performance by examining receiver operating characteristic (ROC) curves and the target signal-to-clutter ratio (SCR). Finally, we observe relationships between the data- and target-centric metrics for selected visible/near-infrared to shortwave infrared (VNIR/SWIR) HSI data, targets, and backgrounds that motivate potential prediction of change in target detection performance as a function of compression ratio.

  2. Targeting accurate object extraction from an image: a comprehensive study of natural image matting.

    PubMed

    Zhu, Qingsong; Shao, Ling; Li, Xuelong; Wang, Lei

    2015-02-01

    With the development of digital multimedia technologies, image matting has gained increasing interests from both academic and industrial communities. The purpose of image matting is to precisely extract the foreground objects with arbitrary shapes from an image or a video frame for further editing. It is generally known that image matting is inherently an ill-posed problem because we need to output three images out of only one input image. In this paper, we provide a comprehensive survey of the existing image matting algorithms and evaluate their performance. In addition to the blue screen matting, we systematically divide all existing natural image matting methods into four categories: 1) color sampling-based; 2) propagation-based; 3) combination of sampling-based and propagation-based; and 4) learning-based approaches. Sampling-based methods assume that the foreground and background colors of an unknown pixel can be explicitly estimated by examining nearby pixels. Propagation-based methods are instead based on the assumption that foreground and background colors are locally smooth. Learning-based methods treat the matting process as a supervised or semisupervised learning problem. Via the learning process, users can construct a linear or nonlinear model between the alpha mattes and the image colors using a training set to estimate the alpha matte of an unknown pixel without any assumption about the characteristics of the testing image. With three benchmark data sets, the various matting algorithms are evaluated and compared using several metrics to demonstrate the strengths and weaknesses of each method both quantitatively and qualitatively. Finally, we conclude this paper by outlining the research trends and suggesting a number of promising directions for future development. PMID:25423658

  3. Target Definition in Salvage Radiotherapy for Recurrent Prostate Cancer: The Role of Advanced Molecular Imaging

    PubMed Central

    Amzalag, Gaël; Rager, Olivier; Tabouret-Viaud, Claire; Wissmeyer, Michael; Sfakianaki, Electra; de Perrot, Thomas; Ratib, Osman; Miralbell, Raymond; Giovacchini, Giampiero; Garibotto, Valentina; Zilli, Thomas

    2016-01-01

    Salvage radiotherapy (SRT) represents the main treatment option for relapsing prostate cancer in patients after radical prostatectomy. Several open questions remain unanswered in terms of target volumes definition and delivered doses for SRT: the effective dose necessary to achieve biochemical control in the SRT setting may be different if the tumor recurrence is micro- or macroscopic. At the same time, irradiation of only the prostatic bed or of the whole pelvis will depend on the localization of the recurrence, local or locoregional. In the “theragnostic imaging” era, molecular imaging using positron emission tomography (PET) constitutes a useful tool for clinicians to define the site of the recurrence, the extent of disease, and individualize salvage treatments. The best option currently available in clinical routine is the combination of radiolabeled choline PET imaging and multiparametric magnetic resonance imaging (MRI), associating the nodal and distant metastases identification based on PET with the local assessment by MRI. A new generation of targeted tracers, namely, prostate-specific membrane antigen, show promising results, with a contrast superior to choline imaging and a higher detection rate even for low prostate-specific antigen levels; validation studies are ongoing. Finally, imaging targeting bone remodeling, using whole-body SPECT–CT, is a relevant complement to molecular/metabolic PET imaging when bone involvement is suspected. PMID:27065024

  4. Predicting range performance of sampled imagers by treating aliased signal as target-dependent noise.

    PubMed

    Vollmerhausen, Richard H; Driggers, Ronald G; Wilson, David L

    2008-08-01

    This paper presents a new theory to predict the impact of sampling on target acquisition. The aliased signal that results from sampling is treated as noise. The aliased signal is different from detector noise in two ways. First, aliasing disappears as the target contrast decreases. Second, the image corruption due to aliasing gets worse with increased range. This is because sampling is constant in angle space, and targets become poorly sampled as range increases. The theory is presented, along with the results of three experiments. The match between model and experiment is excellent.

  5. 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

  6. Quantitative imaging of protein targets in the human brain with PET.

    PubMed

    Gunn, Roger N; Slifstein, Mark; Searle, Graham E; Price, Julie C

    2015-11-21

    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

  7. Automatic Extraction of Closed Pixel Clusters for Target Cueing in Hyperspectral Images

    SciTech Connect

    Paglieroni, D W; Perkins, D E

    2001-06-05

    Traditional algorithms for automatic target cueing (ATC) in hyperspectral images, such as the RX algorithm, treat anomaly detection as a simple hypothesis testing problem. Each decision threshold gives rise to a different set of anomalous pixels. The clustered Rx algorithm generates target cues by grouping anomalous pixels into spatial clusters, and retaining only those clusters that satisfy target specific spatial constraints. It produces one set of target cues for each of several decision thresholds, and conservatively requires {Omicron}(K{sup 2}) operations per pixel, where K is the number of spectral bands (which varies from hundreds to thousands in hyperspectral images). A novel ATC algorithm, known as ''Pixel Cluster Cueing'' (PCC), is discussed. PCC groups pixels into clusters based on spectral similarity and spatial proximity, and then selects only those clusters that satisfy target-specific spatial constraints as target cues. PCC requires only {Omicron}(K) operations per pixel, and it produces only one set of target cues because it is not an anomaly detection algorithm, i.e., it does not use a decision threshold to classify individual pixels as anomalies. PCC is compared both computationally and statistically to the RX algorithm.

  8. Target identification and navigation performance modeling of a passive millimeter wave imager.

    PubMed

    Jacobs, Eddie L; Furxhi, Orges

    2010-07-01

    Human task performance using a passive interferometric millimeter wave imaging sensor is modeled using a task performance modeling approach developed by the U.S. Army Night Vision and Electronic Sensors Directorate. The techniques used are illustrated for an imaging system composed of an interferometric antenna array, optical upconversion, and image formation using a shortwave infrared focal plane array. Two tasks, target identification and pilotage, are modeled. The effects of sparse antenna arrays on task performance are considered. Applications of this model include system trade studies for concealed weapon identification, navigation in fog, and brownout conditions. PMID:20648126

  9. Target identification and navigation performance modeling of a passive millimeter wave imager.

    PubMed

    Jacobs, Eddie L; Furxhi, Orges

    2010-07-01

    Human task performance using a passive interferometric millimeter wave imaging sensor is modeled using a task performance modeling approach developed by the U.S. Army Night Vision and Electronic Sensors Directorate. The techniques used are illustrated for an imaging system composed of an interferometric antenna array, optical upconversion, and image formation using a shortwave infrared focal plane array. Two tasks, target identification and pilotage, are modeled. The effects of sparse antenna arrays on task performance are considered. Applications of this model include system trade studies for concealed weapon identification, navigation in fog, and brownout conditions.

  10. Small-Protein-Stabilized Semiconductor Nanoprobe for Targeted Imaging of Cancer Cells.

    PubMed

    Zhao, Ning; Liu, Siyu; Jiang, Qike; Lan, Tian; Cheng, Zhen; Liu, Hongguang

    2016-07-01

    Recently, semiconductor nanoparticles such as quantum dots (QDs) have attracted significant attention for bioimaging. Complex chemical functionalization, surface modification, and bioconjugation chemistry are generally required to tag biomolecules to QDs for imaging of different biomarkers. In this study, we report a simple method for production of QDs stabilized by the small protein, Affibody (AF-QDs) for fluorescent imaging of the human epidermal growth factor receptor type 2 (HER2) in human A549 lung cancer cells. This one-pot synthesis of AF-QDs avoids complex chemical conjugation procedures and demonstrates a promising approach for the preparation of fluorescent nanoprobes for imaging of cancer targets. PMID:27123671

  11. Moving target detection by nonlinear adaptive filtering on temporal profiles in infrared image sequences

    NASA Astrophysics Data System (ADS)

    Liu, Delian; Li, Zhaohui; Wang, Xiaorui; Zhang, Jianqi

    2015-11-01

    Target detection is of great importance both in civil and military fields. Here a new moving target detection approach is proposed, which employs a nonlinear adaptive filter to remove large fluctuations on temporal profiles that are produced by evolving clutters. Initially, this paper discusses the temporal behaviors of different pixels in infrared sequences. Then, the new nonlinear adaptive filter that is a variation of the median-modified Wiener filter is given to extract pulse signals on temporal profiles that relate to moving targets. Next, the variance of each temporal profile is estimated by segmenting each temporal profile into several segments to normalize the amplitude of the pulse signals. Finally, the proposed approach is tested via two infrared image sequences and compared with several conventional target detection algorithms. The results show our approach has a high effectiveness in extracting target temporal profiles amidst heavy and slowly evolving clutters.

  12. Targeted Multifunctional Multimodal Protein-Shell Microspheres as Cancer Imaging Contrast Agents

    PubMed Central

    John, Renu; Nguyen, Freddy T.; Kolbeck, Kenneth J.; Chaney, Eric J.; Marjanovic, Marina; Suslick, Kenneth S.; Boppart, Stephen A.

    2012-01-01

    Purpose In this study, protein-shell microspheres filled with a suspension of iron oxide nanoparticles in oil are demonstrated as multimodal contrast agents in magnetic resonance imaging (MRI), magnetomotive optical coherence tomography (MM-OCT), and ultrasound imaging. The development, characterization, and use of multifunctional multimodal microspheres are described for targeted contrast and therapeutic applications. Procedures A preclinical rat model was used to demonstrate the feasibility of the multimodal multifunctional microspheres as contrast agents in ultrasound, MM-OCT and MRI. Microspheres were functionalized with the RGD peptide ligand, which is targeted to αvβ3 integrin receptors that are over-expressed in tumors and atherosclerotic lesions. Results These microspheres, which contain iron oxide nanoparticles in their cores, can be modulated externally using a magnetic field to create dynamic contrast in MM-OCT. With the presence of iron oxide nanoparticles, these agents also show significant negative T2 contrast in MRI. Using ultrasound B-mode imaging at a frequency of 30 MHz, a marked enhancement of scatter intensity from in vivo rat mammary tumor tissue was observed for these targeted protein microspheres. Conclusions Preliminary results demonstrate multimodal contrast-enhanced imaging of these functionalized microsphere agents with MRI, MM-OCT, ultrasound imaging, and fluorescence microscopy, including in vivo tracking of the dynamics of these microspheres in real-time using a high-frequency ultrasound imaging system. These targeted oil-filled protein microspheres with the capacity for high drug-delivery loads offer the potential for local delivery of lipophilic drugs under image guidance. PMID:21298354

  13. Triple-Modal Imaging of Magnetically-Targeted Nanocapsules in Solid Tumours In Vivo

    PubMed Central

    Bai, Jie; Wang, Julie T.-W.; Rubio, Noelia; Protti, Andrea; Heidari, Hamed; Elgogary, Riham; Southern, Paul; Al-Jamal, Wafa' T.; Sosabowski, Jane; Shah, Ajay M.; Bals, Sara; Pankhurst, Quentin A.; Al-Jamal, Khuloud T.

    2016-01-01

    Triple-modal imaging magnetic nanocapsules, encapsulating hydrophobic superparamagnetic iron oxide nanoparticles, are formulated and used to magnetically target solid tumours after intravenous administration in tumour-bearing mice. The engineered magnetic polymeric nanocapsules m-NCs are ~200 nm in size with negative Zeta potential and shown to be spherical in shape. The loading efficiency of superparamagnetic iron oxide nanoparticles in the m-NC was ~100%. Up to ~3- and ~2.2-fold increase in tumour uptake at 1 and 24 h was achieved, when a static magnetic field was applied to the tumour for 1 hour. m-NCs, with multiple imaging probes (e.g. indocyanine green, superparamagnetic iron oxide nanoparticles and indium-111), were capable of triple-modal imaging (fluorescence/magnetic resonance/nuclear imaging) in vivo. Using triple-modal imaging is to overcome the intrinsic limitations of single modality imaging and provides complementary information on the spatial distribution of the nanocarrier within the tumour. The significant findings of this study could open up new research perspectives in using novel magnetically-responsive nanomaterials in magnetic-drug targeting combined with multi-modal imaging. PMID:26909110

  14. Triple-Modal Imaging of Magnetically-Targeted Nanocapsules in Solid Tumours In Vivo.

    PubMed

    Bai, Jie; Wang, Julie T-W; Rubio, Noelia; Protti, Andrea; Heidari, Hamed; Elgogary, Riham; Southern, Paul; Al-Jamal, Wafa' T; Sosabowski, Jane; Shah, Ajay M; Bals, Sara; Pankhurst, Quentin A; Al-Jamal, Khuloud T

    2016-01-01

    Triple-modal imaging magnetic nanocapsules, encapsulating hydrophobic superparamagnetic iron oxide nanoparticles, are formulated and used to magnetically target solid tumours after intravenous administration in tumour-bearing mice. The engineered magnetic polymeric nanocapsules m-NCs are ~200 nm in size with negative Zeta potential and shown to be spherical in shape. The loading efficiency of superparamagnetic iron oxide nanoparticles in the m-NC was ~100%. Up to ~3- and ~2.2-fold increase in tumour uptake at 1 and 24 h was achieved, when a static magnetic field was applied to the tumour for 1 hour. m-NCs, with multiple imaging probes (e.g. indocyanine green, superparamagnetic iron oxide nanoparticles and indium-111), were capable of triple-modal imaging (fluorescence/magnetic resonance/nuclear imaging) in vivo. Using triple-modal imaging is to overcome the intrinsic limitations of single modality imaging and provides complementary information on the spatial distribution of the nanocarrier within the tumour. The significant findings of this study could open up new research perspectives in using novel magnetically-responsive nanomaterials in magnetic-drug targeting combined with multi-modal imaging.

  15. Sorting for storage in myeloid cells of nonmyeloid proteins and chimeras with the propeptide of myeloperoxidase precursor.

    PubMed

    Bülow, E; Nauseef, W M; Goedken, M; McCormick, S; Calafat, J; Gullberg, U; Olsson, I

    2002-02-01

    During formation of polymorphonuclear neutrophils, proteins are synthesized for storage in granules. Whereas sorting of proteins into distinct subtypes of cytoplasmic granules may reflect the coordinated expression of the proteins contained in them, still the mechanism(s) for the retrieval of proteins from the constitutive secretion is unknown. To investigate the mechanisms of retrieval, nonmyeloid secretory proteins were expressed in myeloid cell lines, and their subcellular fate was assessed. The contribution of the propeptide (MPOpro) of the myeloperoxidase (MPO) precursor was investigated by determining the fate of chimeras containing MPOpro. The nonmyeloid protein alpha(1)-microglobulin (alpha(1)-m) was targeted to storage organelles in 32D cells and colocalized with the lysosomal marker LAMP-1, whereas soluble TNF receptor 1 (sTNFR1) was secreted without granule targeting. Fusion of MPOpro to alpha(1)-m delayed exit from endoplasmic reticulum (ER), but subsequent targeting to dense organelles was indistinguishable from that of alpha(1)-m alone. Fusion proteins between MPOpro and sTNFR1 or green fluorescent protein expressed in myeloid 32D, K562, or PLB-985 cells did not associate stably with calreticulin or calnexin, molecular chaperones that normally interact transiently with the MPO precursor, but were still efficiently retained in the ER followed by degradation. We conclude that normally secreted, nonmyeloid proteins can be targeted efficiently to storage organelles in myeloid cells, that myeloid cells selectively target some proteins for storage but not others, and that MPOpro may contribute to the prolonged ER retention of the MPO precursor independent of the ER-molecular chaperones calreticulin and calnexin.

  16. Enzymatic activatable self-assembled peptide nanowire for targeted therapy and fluorescence imaging of tumors.

    PubMed

    Tang, Ying; Wu, Zhan; Zhang, Chong-Hua; Zhang, Xiao-Li; Jiang, Jian-Hui

    2016-03-01

    We developed novel activatable probe using self-assembled peptide nanowires with low affinity and toxicity to tumor cells in the absence of matrix metalloproteinase that showed activated high affinity and toxicity and provided a highly selective and efficient platform for targeted therapy and tumor imaging. PMID:26854263

  17. Enabling automated magnetic resonance imaging-based targeting assessment during dipole field navigation

    NASA Astrophysics Data System (ADS)

    Latulippe, Maxime; Felfoul, Ouajdi; Dupont, Pierre E.; Martel, Sylvain

    2016-02-01

    The magnetic navigation of drugs in the vascular network promises to increase the efficacy and reduce the secondary toxicity of cancer treatments by targeting tumors directly. Recently, dipole field navigation (DFN) was proposed as the first method achieving both high field and high navigation gradient strengths for whole-body interventions in deep tissues. This is achieved by introducing large ferromagnetic cores around the patient inside a magnetic resonance imaging (MRI) scanner. However, doing so distorts the static field inside the scanner, which prevents imaging during the intervention. This limitation constrains DFN to open-loop navigation, thus exposing the risk of a harmful toxicity in case of a navigation failure. Here, we are interested in periodically assessing drug targeting efficiency using MRI even in the presence of a core. We demonstrate, using a clinical scanner, that it is in fact possible to acquire, in specific regions around a core, images of sufficient quality to perform this task. We show that the core can be moved inside the scanner to a position minimizing the distortion effect in the region of interest for imaging. Moving the core can be done automatically using the gradient coils of the scanner, which then also enables the core to be repositioned to perform navigation to additional targets. The feasibility and potential of the approach are validated in an in vitro experiment demonstrating navigation and assessment at two targets.

  18. Adaptive chirp-Fourier transform for chirp estimation with applications in ISAR imaging of maneuvering targets

    NASA Astrophysics Data System (ADS)

    Xia, Xiang-Gen; Wang, Genyuan; Chen, Victor C.

    2001-03-01

    This paper first reviews some basic properties of the discrete chirp-Fourier transform and then present an adaptive chirp- Fourier transform, a generalization of the amplitude and phase estimation of sinusoids (APES) algorithm proposed by Li and Stoica for sinusoidal signals. We finally applied it to the ISAR imaging of maneuvering targets.

  19. Advances in molecular imaging: targeted optical contrast agents for cancer diagnostics

    PubMed Central

    Hellebust, Anne; Richards-Kortum, Rebecca

    2012-01-01

    Over the last three decades, our understanding of the molecular changes associated with cancer development and progression has advanced greatly. This has led to new cancer therapeutics targeted against specific molecular pathways; such therapies show great promise to reduce mortality, in part by enabling physicians to tailor therapy for patients based on a molecular profile of their tumor. Unfortunately, the tools for definitive cancer diagnosis – light microscopic examination of biopsied tissue stained with nonspecific dyes – remain focused on the analysis of tissue ex vivo. There is an important need for new clinical tools to support the molecular diagnosis of cancer. Optical molecular imaging is emerging as a technique to help meet this need. Targeted, optically active contrast agents can specifically label extra-and intracellular biomarkers of cancer. Optical images can be acquired in real time with high spatial resolution to image-specific molecular targets, while still providing morphologic context. This article reviews recent advances in optical molecular imaging, highlighting the advances in technology required to improve early cancer detection, guide selection of targeted therapy and rapidly evaluate therapeutic efficacy. PMID:22385200

  20. Theranostic Protein Targeting ErbB2 for Bioluminescence Imaging and Therapy for Cancer

    PubMed Central

    Han, Xiao-Jian; Sun, Ling-Fei; Nishiyama, Yuki; Feng, Bin; Michiue, Hiroyuki; Seno, Masaharu; Matsui, Hideki; Tomizawa, Kazuhito

    2013-01-01

    A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy. PMID:24069396

  1. Hohlraum Target Alignment from X-ray Detector Images using Starburst Design Patterns

    SciTech Connect

    Leach, R R; Conder, A; Edwards, O; Kroll, J; Kozioziemski, B; Mapoles, E; McGuigan, D; Wilhelmsen, K

    2010-12-14

    National Ignition Facility (NIF) is a high-energy laser facility comprised of 192 laser beams focused with enough power and precision on a hydrogen-filled spherical, cryogenic target to initiate a fusion reaction. The target container, or hohlraum, must be accurately aligned to an x-ray imaging system to allow careful monitoring of the frozen fuel layer in the target. To achieve alignment, x-ray images are acquired through starburst-shaped windows cut into opposite sides of the hohlraum. When the hohlraum is in alignment, the starburst pattern pairs match nearly exactly and allow a clear view of the ice layer formation on the edge of the target capsule. During the alignment process, x-ray image analysis is applied to determine the direction and magnitude of adjustment required. X-ray detector and source are moved in concert during the alignment process. The automated pointing alignment system described here is both accurate and efficient. In this paper, we describe the control and associated image processing that enables automation of the starburst pointing alignment.

  2. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

    PubMed

    Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-02-16

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407

  3. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release.

    PubMed

    Hosoya, Hitomi; Dobroff, Andrey S; Driessen, Wouter H P; Cristini, Vittorio; Brinker, Lina M; Staquicini, Fernanda I; Cardó-Vila, Marina; D'Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R; Dogra, Prashant; Melancon, Marites P; Stafford, R Jason; Miyazono, Kohei; Gelovani, Juri G; Kataoka, Kazunori; Brinker, C Jeffrey; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-02-16

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.

  4. Development of multifunctional nanoparticles for targeted drug delivery and noninvasive imaging of therapeutic effect.

    PubMed

    Sajja, Hari Krishna; East, Michael P; Mao, Hui; Wang, Y Andrew; Nie, Shuming; Yang, Lily

    2009-03-01

    Nanotechnology is a multidisciplinary scientific field undergoing explosive development. Nanometer-sized particles offer novel structural, optical and electronic properties that are not attainable with individual molecules or bulk solids. Advances in nanomedicine can be made by engineering biodegradable nanoparticles such as magnetic iron oxide nanoparticles, polymers, dendrimers and liposomes that are capable of targeted delivery of both imaging agents and anticancer drugs. This leads toward the concept and possibility of personalized medicine for the potential of early detection of cancer lesions, determination of molecular signatures of the tumor by noninvasive imaging and, most importantly, molecular targeted cancer therapy. Increasing evidence suggests that the nanoparticles, whose surface contains a targeting molecule that binds to receptors highly expressed in tumor cells, can serve as cancer image contrast agents to increase sensitivity and specificity in tumor detection. In comparison with other small molecule contrast agents, the advantage of using nanoparticles is their large surface area and the possibility of surface modifications for further conjugation or encapsulation of large amounts of therapeutic agents. Targeted nanoparticles ferry large doses of therapeutic agents into malignant cells while sparing the normal healthy cells. Such multifunctional nanodevices hold the promise of significant improvement of current clinical management of cancer patients. This review explores the development of nanoparticles for enabling and improving the targeted delivery of therapeutic agents, the potential of nanomedicine, and the development of novel and more effective diagnostic and screening techniques to extend the limits of molecular diagnostics providing point-of-care diagnosis and more personalized medicine.

  5. Targeted Multifunctional Nanoparticles cure and image Brain Tumors: Selective MRI Contrast Enhancement and Photodynamic Therapy

    NASA Astrophysics Data System (ADS)

    Kopelman, Raoul

    2008-03-01

    Aimed at targeted therapy and imaging of brain tumors, our approach uses targeted, multi-functional nano-particles (NP). A typical nano-particle contains a biologically inert, non-toxic matrix, biodegradable and bio-eliminable over a long time period. It also contains active components, such as fluorescent chemical indicators, photo-sensitizers, MRI contrast enhancement agents and optical imaging dyes. In addition, its surface contains molecular targeting units, e.g. peptides or antibodies, as well as a cloaking agent, to prevent uptake by the immune system, i.e. enabling control of the plasma residence time. These dynamic nano-platforms (DNP) contain contrast enhancement agents for the imaging (MRI, optical, photo-acoustic) of targeted locations, i.e. tumors. Added to this are targeted therapy agents, such as photosensitizers for photodynamic therapy (PDT). A simple protocol, for rats implanted with human brain cancer, consists of tail injection with DNPs, followed by 5 min red light illumination of the tumor region. It resulted in excellent cure statistics for 9L glioblastoma.

  6. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    PubMed Central

    Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; Lin, Yu-Shen; Dunphy, Darren R.; Dogra, Prashant; Melancon, Marites P.; Stafford, R. Jason; Miyazono, Kohei; Gelovani, Juri G.; Kataoka, Kazunori; Brinker, C. Jeffrey; Sidman, Richard L.; Arap, Wadih; Pasqualini, Renata

    2016-01-01

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared, thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. These results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications. PMID:26839407

  7. Integrated nanotechnology platform for tumor-targeted multimodal imaging and therapeutic cargo release

    DOE PAGESBeta

    Hosoya, Hitomi; Dobroff, Andrey S.; Driessen, Wouter H. P.; Cristini, Vittorio; Brinker, Lina M.; Staquicini, Fernanda I.; Cardó-Vila, Marina; D’Angelo, Sara; Ferrara, Fortunato; Proneth, Bettina; et al

    2016-02-02

    A major challenge of targeted molecular imaging and drug delivery in cancer is establishing a functional combination of ligand-directed cargo with a triggered release system. Here we develop a hydrogel-based nanotechnology platform that integrates tumor targeting, photon-to-heat conversion, and triggered drug delivery within a single nanostructure to enable multimodal imaging and controlled release of therapeutic cargo. In proof-of-concept experiments, we show a broad range of ligand peptide-based applications with phage particles, heat-sensitive liposomes, or mesoporous silica nanoparticles that self-assemble into a hydrogel for tumor-targeted drug delivery. Because nanoparticles pack densely within the nanocarrier, their surface plasmon resonance shifts to near-infrared,more » thereby enabling a laser-mediated photothermal mechanism of cargo release. We demonstrate both noninvasive imaging and targeted drug delivery in preclinical mouse models of breast and prostate cancer. Finally, we applied mathematical modeling to predict and confirm tumor targeting and drug delivery. We conclude that these results are meaningful steps toward the design and initial translation of an enabling nanotechnology platform with potential for broad clinical applications.« less

  8. Passive Synthetic Aperture Hitchhiker Imaging of Ground Moving Targets - Part 2: Performance Analysis.

    PubMed

    Wacks, Steven; Yazici, Birsen

    2014-07-01

    In Part 1 of this work, we present a passive synthetic aperture imaging and velocity estimation method for ground moving targets using a network of passive receivers. The method involves inversion of a Radon transform type forward model via a novel filtered backprojection approach combined with entropy optimization. The method is applicable to noncooperative transmitters of opportunity where the transmitter locations and transmitted waveforms are unknown. Furthermore, it can image multiple targets moving at different velocities in arbitrary imaging geometries. In this paper, we present a detailed analysis of the performance of our method. First the resolution analysis in position and velocity spaces is presented. The analysis identifies several factors that contribute positively or negativity towards position and velocity resolution. Next, we present a novel theory to analyze and predict smearing artifacts in position images due to error in velocity estimation of moving targets. Specifically, we show that small errors in the velocity estimation result in small positioning errors. We present extensive numerical simulations to demonstrate the theoretical results. While our primary interest lies in radar, the theory, methods and algorithms introduced in our work are also applicable to passive acoustic, seismic, and microwave imaging. PMID:25020091

  9. Passive Synthetic Aperture Hitchhiker Imaging of Ground Moving Targets - Part 2: Performance Analysis.

    PubMed

    Wacks, Steven; Yazici, Birsen

    2014-07-01

    In Part 1 of this work, we present a passive synthetic aperture imaging and velocity estimation method for ground moving targets using a network of passive receivers. The method involves inversion of a Radon transform type forward model via a novel filtered backprojection approach combined with entropy optimization. The method is applicable to noncooperative transmitters of opportunity where the transmitter locations and transmitted waveforms are unknown. Furthermore, it can image multiple targets moving at different velocities in arbitrary imaging geometries. In this paper, we present a detailed analysis of the performance of our method. First the resolution analysis in position and velocity spaces is presented. The analysis identifies several factors that contribute positively or negativity towards position and velocity resolution. Next, we present a novel theory to analyze and predict smearing artifacts in position images due to error in velocity estimation of moving targets. Specifically, we show that small errors in the velocity estimation result in small positioning errors. We present extensive numerical simulations to demonstrate the theoretical results. While our primary interest lies in radar, the theory, methods and algorithms introduced in our work are also applicable to passive acoustic, seismic, and microwave imaging.

  10. Folic acid-functionalized mesoporous silica nanospheres hybridized with AIE luminogens for targeted cancer cell imaging

    NASA Astrophysics Data System (ADS)

    Wang, Zilong; Xu, Bin; Zhang, Lei; Zhang, Jibo; Ma, Tenghe; Zhang, Jiabao; Fu, Xueqi; Tian, Wenjing

    2013-02-01

    Fluorescent nanoparticles (FNPs) have been found to be useful as visualization tools for biological sensing, probing, imaging, and monitoring. Applied to targeted cancer cell imaging, FNPs are highly desirable for early stage cancer diagnosis and treatment. However, the light emission from most of the FNPs reported is severely limited because of the aggregation-caused quenching (ACQ) effect. Herein, we present highly emissive inorganic-organic nanoparticles with core-shell structures for targeted cancer cell imaging. Coated with a folate-functionalized silica shell, 9,10-distyrylanthracene (DSA) fluorogens with aggregation-induced emission (AIE) properties served as the fluorescent core, affording folate-functionalized fluorescent silica nanoparticles (FFSNPs) with a high fluorescence quantum yield (up to 20%). The FFSNPs are of small size (diameter ~60 nm), monodispersed, stable in aqueous suspension, and pose little toxicity to living cells and thus can be utilized for targeted HeLa cell imaging. In addition, the FFSNPs are mesoporous and therefore can potentially be used as vehicles for controlled, externally activated release of anticancer drugs.Fluorescent nanoparticles (FNPs) have been found to be useful as visualization tools for biological sensing, probing, imaging, and monitoring. Applied to targeted cancer cell imaging, FNPs are highly desirable for early stage cancer diagnosis and treatment. However, the light emission from most of the FNPs reported is severely limited because of the aggregation-caused quenching (ACQ) effect. Herein, we present highly emissive inorganic-organic nanoparticles with core-shell structures for targeted cancer cell imaging. Coated with a folate-functionalized silica shell, 9,10-distyrylanthracene (DSA) fluorogens with aggregation-induced emission (AIE) properties served as the fluorescent core, affording folate-functionalized fluorescent silica nanoparticles (FFSNPs) with a high fluorescence quantum yield (up to 20%). The

  11. Payload drug vs. nanocarrier biodegradation by myeloperoxidase- and peroxynitrite-mediated oxidations: pharmacokinetic implications

    NASA Astrophysics Data System (ADS)

    Seo, Wanji; Kapralov, Alexandr A.; Shurin, Galina V.; Shurin, Michael R.; Kagan, Valerian E.; Star, Alexander

    2015-05-01

    With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation.With the advancement of nanocarriers for drug delivery into biomedical practice, assessments of drug susceptibility to oxidative degradation by enzymatic mechanisms of inflammatory cells become important. Here, we investigate oxidative degradation of a carbon nanotube-based drug carrier loaded with Doxorubicin. We employed myeloperoxidase-catalysed and peroxynitrite-mediated oxidative conditions to mimic the respiratory burst of neutrophils and macrophages, respectively. In addition, we revealed that the cytostatic and cytotoxic effects of free Doxorubicin, but not nanotube-carried drug, on melanoma and lung carcinoma cell lines were abolished in the presence of tumor-activated myeloid regulatory cells that create unique myeloperoxidase- and peroxynitrite-induced oxidative conditions. Both ex vivo and in vitro studies demonstrate that the nanocarrier protects the drug against oxidative biodegradation. Electronic supplementary information (ESI) available: Experimental details and data from characterization of materials synthesis and degradation studies. See DOI: 10

  12. Facile Synthesis of Biocompatible Fluorescent Nanoparticles for Cellular Imaging and Targeted Detection of Cancer Cells.

    PubMed

    Tang, Fu; Wang, Chun; Wang, Xiaoyu; Li, Lidong

    2015-11-18

    In this work, we report the facile synthesis of functional core-shell structured nanoparticles with fluorescence enhancement, which show specific targeting of cancer cells. Biopolymer poly-l-lysine was used to coat the silver core with various shell thicknesses. Then, the nanoparticles were functionalized with folic acid as a targeting agent for folic acid receptor. The metal-enhanced fluorescence effect was observed when the fluorophore (5-(and-6)-carboxyfluorescein-succinimidyl ester) was conjugated to the modified nanoparticle surface. Cellular imaging assay of the nanoparticles in folic acid receptor-positive cancer cells showed their excellent biocompatibility and selectivity. The as-prepared functional nanoparticles demonstrate the efficiency of the metal-enhanced fluorescence effect and provide an alternative approach for the cellular imaging and targeting of cancer cells.

  13. Multifunctional nanoparticles for upconversion luminescence/MR multimodal imaging and magnetically targeted photothermal therapy.

    PubMed

    Cheng, Liang; Yang, Kai; Li, Yonggang; Zeng, Xiao; Shao, Mingwang; Lee, Shuit-Tong; Liu, Zhuang

    2012-03-01

    Theranostics, the combination of diagnostics and therapies, has become a new concept in the battles with various major diseases such as cancer. Herein, we develop multifunctional nanoparticles (MFNPs) with highly integrated functionalities including upconversion luminescence, superparamagnetism, and strong optical absorption in the near-infrared (NIR) region with high photostability. In vivo dual modal optical/magnetic resonance imaging of mice uncovers that by placing a magnet nearby the tumor, MFNPs tend to migrate toward the tumor after intravenous injection and show high tumor accumulation, which is ~8 folds higher than that without magnetic targeting. NIR laser irradiation is then applied to the tumors grown on MFNP-injected mice under magnetic tumor-targeting, obtaining an outstanding photothermal therapeutic efficacy with 100% of tumor elimination in a murine breast cancer model. We present here a strategy for multimodal imaging-guided, magnetically targeted physical cancer therapy and highlight the promise of using multifunctional nanostructures for cancer theranostics.

  14. Gastric cancer target detection using near-infrared hyperspectral imaging with chemometrics

    NASA Astrophysics Data System (ADS)

    Yi, Weisong; Zhang, Jian; Jiang, Houmin; Zhang, Niya

    2014-09-01

    Gastric cancer is one of the leading causes of cancer death in the world due to its high morbidity and mortality. Hyperspectral imaging (HSI) is an emerging, non-destructive, cutting edge analytical technology that combines conventional imaging and spectroscopy in one single system. The manuscript has investigated the application of near-infrared hyperspectral imaging (900-1700 nm) (NIR-HSI) for gastric cancer detection with algorithms. Major spectral differences were observed in three regions (950-1050, 1150-1250, and 1400-1500 nm). By inspecting cancerous mean spectrum three major absorption bands were observed around 975, 1215 and 1450 nm. Furthermore, the cancer target detection results are consistent and conformed with histopathological examination results. These results suggest that NIR-HSI is a simple, feasible and sensitive optical diagnostic technology for gastric cancer target detection with chemometrics.

  15. New Radiotracers for Imaging of Vascular Targets in Angiogenesis-related Diseases

    PubMed Central

    Hong, Hao; Chen, Feng; Zhang, Yin; Cai, Weibo

    2014-01-01

    Tremendous advances over the last several decades in positron emission tomography (PET) and single photon emission computed tomography (SPECT) allow for targeted imaging of molecular and cellular events in the living systems. Angiogenesis, a multistep process regulated by the network of different angiogenic factors, has attracted world-wide interests, due to its pivotal role in the formation and progression of different diseases including cancer, cardiovascular diseases (CVD), and inflammation. In this review article, we will summarize the recent progress in PET or SPECT imaging of a wide variety of vascular targets in three major angiogenesis-related diseases: cancer, cardiovascular diseases, and inflammation. Faster drug development and patient stratification for a specific therapy will become possible with the facilitation of PET or SPECT imaging and it will be critical for the maximum benefit of patients. PMID:25086372

  16. The registration of dual-modality ship target images based on edge extraction

    NASA Astrophysics Data System (ADS)

    Zhang, Weimin; Wang, Risheng; Zhou, Fugen

    2014-11-01

    In this paper, we study the problem of visible and IR(infrared) ship target image registration with scale changes. We mainly focus on the infrared and visible image feature extraction and matching method. A method based on Force Field Transformation is used to determine the ship target contour area. Canny edge detection method is applied to obtain the edge features. During the process of image registration, we take the cross-correlation as the similarity measure and propose an improved Powell algorithm based on multi-scale searching to optimize the registration parameters. Through the edge fusion results, we can see the corresponding edges are almost overlapped, indicating that the method could achieve satisfying results. Also the average error distance of match is less than one pixel.

  17. The inextricable axis of targeted diagnostic imaging and therapy: An immunological natural history approach.

    PubMed

    Cope, Frederick O; Abbruzzese, Bonnie; Sanders, James; Metz, Wendy; Sturms, Kristyn; Ralph, David; Blue, Michael; Zhang, Jane; Bracci, Paige; Bshara, Wiam; Behr, Spencer; Maurer, Toby; Williams, Kenneth; Walker, Joshua; Beverly, Allison; Blay, Brooke; Damughatla, Anirudh; Larsen, Mark; Mountain, Courtney; Neylon, Erin; Parcel, Kaeli; Raghuraman, Kapil; Ricks, Kevin; Rose, Lucas; Sivakumar, Akhilesh; Streck, Nicholas; Wang, Bryan; Wasco, Christopher; Williams, Amifred; McGrath, Michael

    2016-03-01

    In considering the challenges of approaches to clinical imaging, we are faced with choices that sometimes are impacted by rather dogmatic notions about what is a better or worse technology to achieve the most useful diagnostic image for the patient. For example, is PET or SPECT most useful in imaging any particular disease dissemination? The dictatorial approach would be to choose PET, all other matters being equal. But is such a totalitarian attitude toward imaging selection still valid? In the face of new receptor targeted SPECT agents one must consider the remarkable specificity and sensitivity of these agents. (99m)Tc-Tilmanocept is one of the newest of these agents, now approved for guiding sentinel node biopsy (SLNB) in several solid tumors. Tilmanocept has a Kd of 3×10(-11)M, and it specificity for the CD206 receptor is unlike any other agent to date. This coupled with a number of facts, that specific disease-associated macrophages express this receptor (100 to 150 thousand receptors), that the receptor has multiple binding sites for tilmanocept (>2 sites per receptor) and that these receptors are recycled every 15 min to bind more tilmanocept (acting as intracellular "drug compilers" of tilmanocept into non-degraded vesicles), gives serious pause as to how we select our approaches to diagnostic imaging. Clinically, the size of SLNs varies greatly, some, anatomically, below the machine resolution of SPECT. Yet, with tilmanocept targeting, the SLNs are highly visible with macrophages stably accruing adequate (99m)Tc-tilmanocept counting statistics, as high target-to-background ratios can compensate for spatial resolution blurring. Importantly, it may be targeted imaging agents per se, again such as tilmanocept, which may significantly shrink any perceived chasm between the imaging technologies and anchor the diagnostic considerations in the targeting and specificity of the agent rather than any lingering dogma about the hardware as the basis for imaging

  18. Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques.

    PubMed

    Li, Xiao; Wang, Cong; Tan, Hui; Cheng, Leilei; Liu, Guobing; Yang, Yi; Zhao, Yanzhao; Zhang, Yiqiu; Li, Yanli; Zhang, Chunfu; Xiu, Yan; Cheng, Dengfeng; Shi, Hongcheng

    2016-11-01

    In order to realize accurate localization and precise evaluation of vulnerability of atherosclerotic plaques via dual-modal imaging, gold nanoparticles (GNPs) were firstly caped with a thin amino-PEGs cover and then conjugated with the targeting molecular Annexin V and radionuclide Tc-99m simultaneously to form SPECT/CT imaging probe targeting apoptotic macrophages. The as-synthesized (99m)Tc-GNPs-Annexin V was with uniform size (30.2 ± 2.9 nm) and high labeling rate (98.9 ± 0.5%) and stability. Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced. For macrophages with 30% apoptosis, cellular uptakes of 3.52 ± 0.35% for (99m)Tc-GNPs-Annexin V, 2.41 ± 0.53% for (99m)Tc-GNPs and 1.68 ± 0.36% for (99m)Tc-Annexin V were achieved after 2 h incubation. ApoE knock out mice with high fat diet-induced atherosclerosis were scanned via (99m)Tc-GNPs-Annexin V SPECT/CT. With the introduction of targeting molecules, imaging probe was more efficient in accumulating in apoptotic macrophages. In practical evaluation, CT helps to restrict the lesions depiction more accurately, meanwhile, SPECT imaging intensity correlated with pathological changes tightly. In conclusion, Annexin V-modified hybrid gold nanoparticles were successfully synthesized, and this imaging system helped to better localize and diagnose those vulnerable AS plaques via specific targeting the apoptotic macrophages.

  19. Gold nanoparticles-based SPECT/CT imaging probe targeting for vulnerable atherosclerosis plaques.

    PubMed

    Li, Xiao; Wang, Cong; Tan, Hui; Cheng, Leilei; Liu, Guobing; Yang, Yi; Zhao, Yanzhao; Zhang, Yiqiu; Li, Yanli; Zhang, Chunfu; Xiu, Yan; Cheng, Dengfeng; Shi, Hongcheng

    2016-11-01

    In order to realize accurate localization and precise evaluation of vulnerability of atherosclerotic plaques via dual-modal imaging, gold nanoparticles (GNPs) were firstly caped with a thin amino-PEGs cover and then conjugated with the targeting molecular Annexin V and radionuclide Tc-99m simultaneously to form SPECT/CT imaging probe targeting apoptotic macrophages. The as-synthesized (99m)Tc-GNPs-Annexin V was with uniform size (30.2 ± 2.9 nm) and high labeling rate (98.9 ± 0.5%) and stability. Targeting ability of Annexin V for apoptotic macrophages was kept and enhanced. For macrophages with 30% apoptosis, cellular uptakes of 3.52 ± 0.35% for (99m)Tc-GNPs-Annexin V, 2.41 ± 0.53% for (99m)Tc-GNPs and 1.68 ± 0.36% for (99m)Tc-Annexin V were achieved after 2 h incubation. ApoE knock out mice with high fat diet-induced atherosclerosis were scanned via (99m)Tc-GNPs-Annexin V SPECT/CT. With the introduction of targeting molecules, imaging probe was more efficient in accumulating in apoptotic macrophages. In practical evaluation, CT helps to restrict the lesions depiction more accurately, meanwhile, SPECT imaging intensity correlated with pathological changes tightly. In conclusion, Annexin V-modified hybrid gold nanoparticles were successfully synthesized, and this imaging system helped to better localize and diagnose those vulnerable AS plaques via specific targeting the apoptotic macrophages. PMID:27619241

  20. High concentrations of myeloperoxidase in the equine uterus as an indicator of endometritis.

    PubMed

    Parrilla-Hernandez, Sonia; Ponthier, Jérôme; Franck, Thierry Y; Serteyn, Didier D; Deleuze, Stéfan C

    2014-04-15

    Intraluminal fluid and excessive abnormal hyperedema are regularly used for the diagnosis of endometritis in the mare, which is routinely confirmed by the presence of neutrophils on endometrial smears. Studies show a relation between neutrophils and myeloperoxidase (MPO), an enzyme contained in and released by neutrophils during degranulation or after cell lysis. This enzyme has been found in many fluids and tissues, and associated with different inflammatory pathologies in the horse. The aims of this study were to assess the presence and concentration of MPO in the equine uterus, and to investigate its relation with neutrophils, and other clinical signs of endometritis. Mares (n = 51) were evaluated for the presence of intraluminal fluid and excessive endometrial edema before breeding, and a small volume lavage and cytology samples were obtained. From 69 cycles, supernatant of the uterine flushes was analyzed with a specific equine MPO ELISA assay to measure MPO concentration. Cytology samples were used for the diagnosis of endometritis. Myeloperoxidase was present in the uterus of all estrus mares in highly variable concentrations. Myeloperoxidase concentrations were significantly (P < 0.05) higher in samples with positive cytologies and in the presence of intraluminal fluid. Occasionally, some samples with negative cytologies showed high MPO concentration, but the opposite was never observed. Cycles presenting hyperedema weren't associated with high concentration of MPO, intraluminal fluid, or positive cytology, making it a poor diagnostic tool of endometritis. PMID:24565475

  1. Target-to-background enhancement in multispectral endoscopy with background autofluorescence mitigation for quantitative molecular imaging

    NASA Astrophysics Data System (ADS)

    Yang, Chenying; Hou, Vivian W.; Girard, Emily J.; Nelson, Leonard Y.; Seibel, Eric J.

    2014-07-01

    Fluorescence molecular imaging with exogenous probes improves specificity for the detection of diseased tissues by targeting unambiguous molecular signatures. Additionally, increased diagnostic sensitivity is expected with the application of multiple molecular probes. We developed a real-time multispectral fluorescence-reflectance scanning fiber endoscope (SFE) for wide-field molecular imaging of fluorescent dye-labeled molecular probes at nanomolar detection levels. Concurrent multichannel imaging with the wide-field SFE also allows for real-time mitigation of the background autofluorescence (AF) signal, especially when fluorescein, a U.S. Food and Drug Administration approved dye, is used as the target fluorophore. Quantitative tissue AF was measured for the ex vivo porcine esophagus and murine brain tissues across the visible and near-infrared spectra. AF signals were then transferred to the unit of targeted fluorophore concentration to evaluate the SFE detection sensitivity for sodium fluorescein and cyanine. Next, we demonstrated a real-time AF mitigation algorithm on a tissue phantom, which featured molecular probe targeted cells of high-grade dysplasia on a substrate containing AF species. The target-to-background ratio was enhanced by more than one order of magnitude when applying the real-time AF mitigation algorithm. Furthermore, a quantitative estimate of the fluorescein photodegradation (photobleaching) rate was evaluated and shown to be insignificant under the illumination conditions of SFE. In summary, the multichannel laser-based flexible SFE has demonstrated the capability to provide sufficient detection sensitivity, image contrast, and quantitative target intensity information for detecting small precancerous lesions in vivo.

  2. Targeted magnetic delivery and tracking of cells using a magnetic resonance imaging system.

    PubMed

    Riegler, Johannes; Wells, Jack A; Kyrtatos, Panagiotis G; Price, Anthony N; Pankhurst, Quentin A; Lythgoe, Mark F

    2010-07-01

    The success of cell therapies depends on the ability to deliver the cells to the site of injury. Targeted magnetic cell delivery is an emergent technique for localised cell transplantation therapy. The use of permanent magnets limits such a treatment to organs close to the body surface or an implanted magnetic source. A possible alternative method for magnetic cell delivery is magnetic resonance targeting (MRT), which uses magnetic field gradients inherent to all magnetic resonance imaging system, to steer ferromagnetic particles to their target region. In this study we have assessed the feasibility of such an approach for cell targeting, using a range of flow rates and different super paramagnetic iron oxide particles in a vascular bifurcation phantom. Using MRT we have demonstrated that 75% of labelled cells could be guided within the vascular bifurcation. Furthermore we have demonstrated the ability to image the labelled cells before and after magnetic targeting, which may enable interactive manipulation and assessment of the distribution of cellular therapy. This is the first demonstration of cellular MRT and these initial findings support the potential value of MRT for improved targeting of intravascular cell therapies.

  3. Technique for Targeting Arteriovenous Malformations Using Frameless Image-Guided Robotic Radiosurgery

    SciTech Connect

    Hristov, Dimitre; Liu, Lina; Adler, John R.; Gibbs, Iris C.; Moore, Teri; Sarmiento, Marily; Chang, Steve D.; Dodd, Robert; Marks, Michael; Do, Huy M.

    2011-03-15

    Purpose: To integrate three-dimensional (3D) digital rotation angiography (DRA) and two-dimensional (2D) digital subtraction angiography (DSA) imaging into a targeting methodology enabling comprehensive image-guided robotic radiosurgery of arteriovenous malformations (AVMs). Methods and Materials: DRA geometric integrity was evaluated by imaging a phantom with embedded markers. Dedicated DSA acquisition modes with preset C-arm positions were configured. The geometric reproducibility of the presets was determined, and its impact on localization accuracy was evaluated. An imaging protocol composed of anterior-posterior and lateral DSA series in combination with a DRA run without couch displacement between acquisitions was introduced. Software was developed for registration of DSA and DRA (2D-3D) images to correct for: (a) small misalignments of the C-arm with respect to the estimated geometry of the set positions and (b) potential patient motion between image series. Within the software, correlated navigation of registered DRA and DSA images was incorporated to localize AVMs within a 3D image coordinate space. Subsequent treatment planning and delivery followed a standard image-guided robotic radiosurgery process. Results: DRA spatial distortions were typically smaller than 0.3 mm throughout a 145-mm x 145-mm x 145-mm volume. With 2D-3D image registration, localization uncertainties resulting from the achievable reproducibility of the C-arm set positions could be reduced to about 0.2 mm. Overall system-related localization uncertainty within the DRA coordinate space was 0.4 mm. Image-guided frameless robotic radiosurgical treatments with this technique were initiated. Conclusions: The integration of DRA and DSA into the process of nidus localization increases the confidence with which radiosurgical ablation of AVMs can be performed when using only an image-guided technique. Such an approach can increase patient comfort, decrease time pressure on clinical and

  4. Modularly assembled magnetite nanoparticles enhance in vivo targeting for magnetic resonance cancer imaging.

    PubMed

    Wu, Ping-Ching; Su, Chia-Hao; Cheng, Fong-Yu; Weng, Jun-Cheng; Chen, Jyh-Horng; Tsai, Tsung-Lin; Yeh, Chen-Sheng; Su, Wu-Chou; Hwu, Jih Ru; Tzeng, Yonhua; Shieh, Dar-Bin

    2008-10-01

    Modularly assembled targeting nanoparticles were synthesized through self-assembly of targeting moieties on surfaces of functional nanoparticles. Specific molecular recognition of nickel nitrilotriacetate on Fe3O4 nanoparticles with hexahistidine tag on RGD4C peptides results in precisely controlled orientation of the targeting peptides. Better selectivity of the self-assembled RGD4C-Fe3O4 nanoparticles targeting oral cancer cells than that achievable through a conventional chemical cross-link strategy was demonstrated by means of atomic absorption spectrometry (AAS). An oral cancer hamster model was applied to reveal specific in vivo targeting and MR molecular imaging contrast in cancer lesions expressing alphavbeta3 integrin. Both AAS and MRI revealed that the self-assembled nanoparticles improved the targeting efficiency and reduced the hepatic uptake as compared with the conventional chemical cross-link particles. We investigated the biosafety, biodistribution, and kinetics of the nanoparticles and found that the nanoparticles were significantly cleared from the liver and kidneys after one week. By recombining the desired targeting moiety and various functional nanoparticles through self-assembly, this new modularly designed platform has the capability of enhancing the efficiency of targeted diagnosis and therapies for a wide spectrum of biomedical applications.

  5. Ultrasound Molecular Imaging of Tumor Angiogenesis with an Integrin Targeted Microbubble Contrast Agent

    PubMed Central

    Anderson, Christopher R.; Hu, Xiaowen; Tlaxca, Jose; Decleves, Anne-Emilie; Houghtaling, Robert; Sharma, Kumar; Lawrence, Michael; Ferrara, Katherine; Rychak, Joshua J.

    2010-01-01

    Rationale and Objectives Ultrasound molecular imaging is an emerging technique for sensitive detection of intravascular targets. Molecular imaging of angiogenesis has strong potential for both clinical use and as a research tool in tumor biology and the development of anti-angiogenic therapies. Our objective is to develop a robust microbubble (MB) ultrasound contrast agent platform to which targeting ligands can be conjugated by biocompatible, covalent conjugation chemistry, and to develop a pure low mechanical index imaging processing method and corresponding quantifying method. The microbubbles and the imaging methods were evaluated in a mouse model of breast cancer in vivo. Materials and Methods We utilized a cyclic RGD (cRGD) pentapeptide containing a terminal cysteine group conjugated to the surface of MB bearing pyridyldithio-propionate (PDP) for targeting αvβ3 integrins. As negative controls, MB without a ligand or MB bearing a scrambled sequence (cRAD) were prepared. To enable characterization of peptides bound to MB surfaces, the cRGD peptide was labeled with FITC and detected by plate fluorometry, flow cytometry, and fluorescence microscopy. Targeted adhesion of cRGD-MB was demonstrated in an in vitro flow adhesion assay against recombinant murine αvβ3 integrin protein and αvβ3 integrin-expressing endothelial cells (bEnd.3). The specificity of cRGD-MB for αvβ3 integrin was demonstrated by treating bEnd.3 EC with a blocking antibody. A murine model of mammary carcinoma was used to assess targeted adhesion and ultrasound molecular imaging in vivo. The targeted microbubbles were visualized using a low mechanical index contrast imaging pulse sequence, and quantified by intensity normalization and two-dimensional Fourier transform analysis, Results The cRGD ligand concentration on the MB surface was ~8.2 × 106 molecules/MB. At a wall shear stress of 1.0 dynes/cm2, cRGD-MB exhibited 5-fold higher adhesion to immobilized recombinant αvβ3 integrin

  6. Targeted imaging of cancer by fluorocoxib C, a near-infrared cyclooxygenase-2 probe

    NASA Astrophysics Data System (ADS)

    Uddin, Md. Jashim; Crews, Brenda C.; Ghebreselasie, Kebreab; Daniel, Cristina K.; Kingsley, Philip J.; Xu, Shu; Marnett, Lawrence J.

    2015-05-01

    Cyclooxygenase-2 (COX-2) is a promising target for the imaging of cancer in a range of diagnostic and therapeutic settings. We report a near-infrared COX-2-targeted probe, fluorocoxib C (FC), for visualization of solid tumors by optical imaging. FC exhibits selective and potent COX-2 inhibition in both purified protein and human cancer cell lines. In vivo optical imaging shows selective accumulation of FC in COX-2-overexpressing human tumor xenografts [1483 head and neck squamous cell carcinoma (HNSCC)] implanted in nude mice, while minimal uptake is detectable in COX-2-negative tumor xenografts (HCT116) or 1483 HNSCC xenografts preblocked with the COX-2-selective inhibitor celecoxib. Time course imaging studies conducted from 3 h to 7-day post-FC injection revealed a marked reduction in nonspecific fluorescent signals with retention of fluorescence in 1483 HNSCC tumors. Thus, use of FC in a delayed imaging protocol offers an approach to improve imaging signal-to-noise that should improve cancer detection in multiple preclinical and clinical settings.

  7. Structural colour printing from a reusable generic nanosubstrate masked for the target image.

    PubMed

    Rezaei, M; Jiang, H; Kaminska, B

    2016-02-26

    Structural colour printing has advantages over traditional pigment-based colour printing. However, the high fabrication cost has hindered its applications in printing large-area images because each image requires patterning structural pixels in nanoscale resolution. In this work, we present a novel strategy to print structural colour images from a pixelated substrate which is called a nanosubstrate. The nanosubstrate is fabricated only once using nanofabrication tools and can be reused for printing a large quantity of structural colour images. It contains closely packed arrays of nanostructures from which red, green, blue and infrared structural pixels can be imprinted. To print a target colour image, the nanosubstrate is first covered with a mask layer to block all the structural pixels. The mask layer is subsequently patterned according to the target colour image to make apertures of controllable sizes on top of the wanted primary colour pixels. The masked nanosubstrate is then used as a stamp to imprint the colour image onto a separate substrate surface using nanoimprint lithography. Different visual colours are achieved by properly mixing the red, green and blue primary colours into appropriate ratios controlled by the aperture sizes on the patterned mask layer. Such a strategy significantly reduces the cost and complexity of printing a structural colour image from lengthy nanoscale patterning into high throughput micro-patterning and makes it possible to apply structural colour printing in personalized security features and data storage. In this paper, nanocone array grating pixels were used as the structural pixels and the nanosubstrate contains structures to imprint the nanocone arrays. Laser lithography was implemented to pattern the mask layer with submicron resolution. The optical properties of the nanocone array gratings are studied in detail. Multiple printed structural colour images with embedded covert information are demonstrated. PMID:26820913

  8. Structural colour printing from a reusable generic nanosubstrate masked for the target image

    NASA Astrophysics Data System (ADS)

    Rezaei, M.; Jiang, H.; Kaminska, B.

    2016-02-01

    Structural colour printing has advantages over traditional pigment-based colour printing. However, the high fabrication cost has hindered its applications in printing large-area images because each image requires patterning structural pixels in nanoscale resolution. In this work, we present a novel strategy to print structural colour images from a pixelated substrate which is called a nanosubstrate. The nanosubstrate is fabricated only once using nanofabrication tools and can be reused for printing a large quantity of structural colour images. It contains closely packed arrays of nanostructures from which red, green, blue and infrared structural pixels can be imprinted. To print a target colour image, the nanosubstrate is first covered with a mask layer to block all the structural pixels. The mask layer is subsequently patterned according to the target colour image to make apertures of controllable sizes on top of the wanted primary colour pixels. The masked nanosubstrate is then used as a stamp to imprint the colour image onto a separate substrate surface using nanoimprint lithography. Different visual colours are achieved by properly mixing the red, green and blue primary colours into appropriate ratios controlled by the aperture sizes on the patterned mask layer. Such a strategy significantly reduces the cost and complexity of printing a structural colour image from lengthy nanoscale patterning into high throughput micro-patterning and makes it possible to apply structural colour printing in personalized security features and data storage. In this paper, nanocone array grating pixels were used as the structural pixels and the nanosubstrate contains structures to imprint the nanocone arrays. Laser lithography was implemented to pattern the mask layer with submicron resolution. The optical properties of the nanocone array gratings are studied in detail. Multiple printed structural colour images with embedded covert information are demonstrated.

  9. Dual-mode ultrasound arrays for image-guided targeting of atheromatous plaques

    NASA Astrophysics Data System (ADS)

    Ballard, John R.; Casper, Andrew J.; Liu, Dalong; Haritonova, Alyona; Shehata, Islam A.; Troutman, Mitchell; Ebbini, Emad S.

    2012-11-01

    A feasibility study was undertaken in order to investigate alternative noninvasive treatment options for atherosclerosis. In particular, the aim of this study was to investigate the potential use of Dual-Mode Ultrasound Arrays (DMUAs) for image guided treatment of atheromatous plaques. DMUAs offer a unique treatment paradigm for image-guided surgery allowing for robust image-based identification of tissue targets for localized application of HIFU. In this study we present imaging and therapeutic results form a 3.5 MHz, 64-element fenestrated prototype DMUA for targeting lesions in the femoral artery of familial hypercholesterolemic (FH) swine. Before treatment, diagnostic ultrasound was used to verify the presence of plaque in the femoral artery of the swine. Images obtained with the DMUA and a diagnostic (HST 15-8) transducer housed in the fenestration were analyzed and used for guidance in targeting of the plaque. Discrete therapeutic shots with an estimated focal intensity of 4000-5600 W/cm2 and 500-2000 msec duration were performed at several planes in the plaque. During therapy, pulsed HIFU was interleaved with single transmit focus imaging from the DMUA and M2D imaging from the diagnostic transducer for further analysis of lesion formation. After therapy, the swine's were recovered and later sacrificed after 4 and 7 days for histological analysis of lesion formation. At sacrifice, the lower half of the swine was perfused and the femoral artery with adjoining muscle was fixed and stained with H&E to characterize HIFU-induced lesions. Histology has confirmed that localized thermal lesion formation within the plaque was achieved according to the planned lesion maps. Furthermore, the damage was confined to the plaque tissue without damage to the intima. These results offer the promise of a new treatment potentially suited for vulnerable plaques. The results also provide the first real-time demonstration of DMUA technology in targeting fine tissue structures for

  10. Target recognition using HRR profile-based incoherent SAR (InSAR) image formation

    NASA Astrophysics Data System (ADS)

    O'Donoughue, Nicholas A.; Kuklinski, Walter S.; Arabadjis, Constantine

    2008-04-01

    Feature-aided target verification is a challenging field of research, with the potential to yield significant increases in the confidence of re-established target tracks after kinematic confusion events. Using appropriate control algorithms airborne multi-mode radars can acquire a library of HRR (High Range Resolution) profiles for targets as they are tracked. When a kinematic confusion event occurs, such as a vehicle dropping below MDV (Minimum Detectable Velocity) for some period of time, or two target tracks crossing, it is necessary to utilize feature-aided tracking methods to correctly associate post-confusion tracks with pre-confusion tracks. Many current HRR profile target recognition methods focus on statistical characteristics of either individual profiles or sets of profiles taken over limited viewing angles. These methods have not proven to be very effective when the pre- and post- confusion libraries do not overlap in azimuth angle. To address this issue we propose a new approach to target recognition from HRR profiles. We present an algorithm that generates 2-D imagery of targets from the pre- and post-confusion libraries. These images are subsequently used as the input to a target recognition/classifier process. Since, center-aligned HRR Profiles, while ideal for processing, are not easily computed in field systems, as they require the airborne platform's center of rotation to line up with the geometric center of the moving target (this is impossible when multiple targets are being tracked), our algorithm is designed to work with HRR profiles that are aligned to the leading edge (the first detection above a threshold, commonly referred to as Edge-Aligned HRR profiles). Our simulated results demonstrate the effectiveness of this method for classifying target vehicles based on simulations using both overlapping and non-overlapping HRR profile sets. The algorithm was tested on several test cases using an input set of .28 m resolution XPATCH generated HRR

  11. Targeted radionuclide and fluorescence dual-modality imaging of cancer: preclinical advances and clinical translation.

    PubMed

    Lütje, S; Rijpkema, M; Helfrich, W; Oyen, W J G; Boerman, O C

    2014-12-01

    In oncology, sensitive and reliable detection tumor tissue is crucial to prevent recurrences and to improve surgical outcome. Currently, extensive research is focused on the use of radionuclides as well as fluorophores to provide real-time guidance during surgery to aid the surgeon in the identification of malignant tissue. Particularly, dual-modality approaches combining radionuclide and near-infrared fluorescence (NIRF) imaging have shown promising results in preclinical studies. Radionuclide imaging allows sensitive intra-operative localization of tumor lesions using a gamma probe, whereas NIRF imaging allows more accurate real-time tumor delineation. Consequently, both radionuclide and NIRF imaging might complement each other, and dual-modality image-guided surgery may overcome limitations of the currently used single-modality imaging techniques. In this review, a comprehensive overview on recent preclinical advances in tumor-targeted radionuclide and fluorescence dual-modality imaging is provided. Subsequently, the clinical applicability of dual-modality image-guided surgery is discussed.

  12. FISST based method for multi-target tracking in the image plane of optical sensors.

    PubMed

    Xu, Yang; Xu, Hui; An, Wei; Xu, Dan

    2012-01-01

    A finite set statistics (FISST)-based method is proposed for multi-target tracking in the image plane of optical sensors. The method involves using signal amplitude information in probability hypothesis density (PHD) filter which is derived from FISST to improve multi-target tracking performance. The amplitude of signals generated by the optical sensor is modeled first, from which the amplitude likelihood ratio between target and clutter is derived. An alternative approach is adopted for the situations where the signal noise ratio (SNR) of target is unknown. Then the PHD recursion equations incorporated with signal information are derived and the Gaussian mixture (GM) implementation of this filter is given. Simulation results demonstrate that the proposed method achieves significantly better performance than the generic PHD filter. Moreover, our method has much lower computational complexity in the scenario with high SNR and dense clutter. PMID:22736984

  13. FISST Based Method for Multi-Target Tracking in the Image Plane of Optical Sensors

    PubMed Central

    Xu, Yang; Xu, Hui; An, Wei; Xu, Dan

    2012-01-01

    A finite set statistics (FISST)-based method is proposed for multi-target tracking in the image plane of optical sensors. The method involves using signal amplitude information in probability hypothesis density (PHD) filter which is derived from FISST to improve multi-target tracking performance. The amplitude of signals generated by the optical sensor is modeled first, from which the amplitude likelihood ratio between target and clutter is derived. An alternative approach is adopted for the situations where the signal noise ratio (SNR) of target is unknown. Then the PHD recursion equations incorporated with signal information are derived and the Gaussian mixture (GM) implementation of this filter is given. Simulation results demonstrate that the proposed method achieves significantly better performance than the generic PHD filter. Moreover, our method has much lower computational complexity in the scenario with high SNR and dense clutter. PMID:22736984

  14. In vivo imaging of specific drug target binding at subcellular resolution

    PubMed Central

    Dubach, J.M.; Vinegoni, C.; Mazitschek, R.; Fumene Feruglio, P.; Cameron, L.A.; Weissleder, R.

    2015-01-01

    The possibility to measure binding of small molecule drugs to desired targets in live cells could provide a better understanding of drug action. However, current approaches mostly yield static data, require lysis or rely on indirect assays and thus often provide an incomplete understanding of drug action. Here, we present a multiphoton fluorescence anisotropy microscopy live cell imaging technique to measure and map drug-target interaction in real time at subcellular resolution. This approach is generally applicable using any fluorescently labeled drug and enables high resolution spatial and temporal mapping of bound and unbound drug distribution. To illustrate our approach we measure intracellular target engagement of the chemotherapeutic Olaparib, a poly(ADP-ribose) polymerase inhibitor, in live cells and within a tumor in vivo. These results are the first generalizable approach to directly measure drug-target binding in vivo and present a promising tool to enhance understanding of drug activity. PMID:24867710

  15. FISST based method for multi-target tracking in the image plane of optical sensors.

    PubMed

    Xu, Yang; Xu, Hui; An, Wei; Xu, Dan

    2012-01-01

    A finite set statistics (FISST)-based method is proposed for multi-target tracking in the image plane of optical sensors. The method involves using signal amplitude information in probability hypothesis density (PHD) filter which is derived from FISST to improve multi-target tracking performance. The amplitude of signals generated by the optical sensor is modeled first, from which the amplitude likelihood ratio between target and clutter is derived. An alternative approach is adopted for the situations where the signal noise ratio (SNR) of target is unknown. Then the PHD recursion equations incorporated with signal information are derived and the Gaussian mixture (GM) implementation of this filter is given. Simulation results demonstrate that the proposed method achieves significantly better performance than the generic PHD filter. Moreover, our method has much lower computational complexity in the scenario with high SNR and dense clutter.

  16. Facile synthesis and functionalization of manganese oxide nanoparticles for targeted T1-weighted tumor MR imaging.

    PubMed

    Luo, Yu; Yang, Jia; Li, Jingchao; Yu, Zhibo; Zhang, Guixiang; Shi, Xiangyang; Shen, Mingwu

    2015-12-01

    We report the polyethyleneimine (PEI)-enabled synthesis and functionalization of manganese oxide (Mn3O4) nanoparticles (NPs) for targeted tumor magnetic resonance (MR) imaging in vivo. In this work, monodispersed PEI-coated Mn3O4 NPs were formed by decomposition of acetylacetone manganese via a solvothermal approach. The Mn3O4 NPs with PEI coating were sequentially conjugated with fluorescein isothiocyanate, folic acid (FA)-linked polyethylene glycol (PEG), and PEG monomethyl ether. Followed by final acetylation of the remaining PEI surface amines, multifunctional Mn3O4 NPs were formed and well characterized. We show that the formed multifunctional Mn3O4 NPs with a mean diameter of 8.0 nm possess good water-dispersibility, colloidal stability, and cytocompatibility and hemocompatibility in the given concentration range. Flow cytometry and confocal microscopic observation reveal that the multifunctional Mn3O4 NPs are able to target FA receptor-overexpressing cancer cells in vitro. Importantly, the FA-targeted Mn3O4 NPs can be used as a nanoprobe for efficient T1-weighted MR imaging of cancer cells in vitro and the xenografted tumor model in vivo via an active FA-mediated targeting pathway. With the facile PEI-enabled formation and functionalization, the developed PEI-coated Mn3O4 NPs may be modified with other biomolecules for different biomedical imaging applications. PMID:26454057

  17. In vivo photoacoustic imaging of breast cancer tumor with HER2-targeted nanodiamonds

    NASA Astrophysics Data System (ADS)

    Zhang, Ti; Cui, Huizhong; Fang, Chia-Yi; Jo, Janggun; Yang, Xinmai; Chang, Huan-Cheng; Forrest, M. Laird

    2013-09-01

    Radiation-damaged nanodiamonds (NDs) are ideal optical contrast agents for photoacoustic (PA) imaging in biological tissues due to their good biocompatibility and high optical absorbance in the near-infrared (NIR) range. Acid treated NDs are oxidized to form carboxyl groups on the surface, functionalized with polyethylene glycol (PEG) and human epidermal growth factor receptor 2 (HER2) targeting ligand for breast cancer tumor imaging. Because of the specific binding of the ligand conjugated NDs to the HER2-overexpressing murine breast cancer cells (4T1.2 neu), the tumor tissues are significantly delineated from the surrounding normal tissue at wavelength of 820 nm under the PA imaging modality. Moreover, HER2 targeted NDs (HER2-PEG-NDs) result in higher accumulation in HER2 positive breast tumors as compared to non-targeted NDs after intravenous injection (i.v.). Longer retention time of HER-PEG-NDs is observed in HER2 overexpressing tumor model than that in negative tumor model (4T1.2). This demonstrates that targeting moiety conjugated NDs have great potential for the sensitive detection of cancer tumors and provide an attractive delivery strategy for anti-cancer drugs.

  18. Radionuclide (131)I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors.

    PubMed

    Zhu, Jingyi; Zhao, Lingzhou; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Shen, Mingwu; Zhao, Jinhua; Shi, Xiangyang

    2015-11-21

    We report the synthesis, characterization, and utilization of radioactive (131)I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 ((131)I). The generated multifunctional (131)I-G5·NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to (131)I labeling, the G5·NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive (131)I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.

  19. Real-time imaging systems' combination of methods to achieve automatic target recognition

    NASA Astrophysics Data System (ADS)

    Maraviglia, Carlos G.; Williams, Elmer F.; Pezzulich, Alan Z.

    1998-03-01

    Using a combination of strategies real time imaging weapons systems are achieving their goals of detecting their intended targets. The demands of acquiring a target in a cluttered environment in a timely manner with a high degree of confidence demands compromise be made as to having a truly automatic system. A combination of techniques such as dedicated image processing hardware, real time operating systems, mixes of algorithmic methods, and multi-sensor detectors are a forbearance of the unleashed potential of future weapons system and their incorporation in truly autonomous target acquisition. Elements such as position information, sensor gain controls, way marks for mid course correction, and augmentation with different imaging spectrums as well as future capabilities such as neural net expert systems and decision processors over seeing a fusion matrix architecture may be considered tools for a weapon system's achievement of its ultimate goal. Currently, acquiring a target in a cluttered environment in a timely manner with a high degree of confidence demands compromises be made as to having a truly automatic system. It is now necessary to include a human in the track decision loop, a system feature that may be long lived. Automatic Track Recognition will still be the desired goal in future systems due to the variability of military missions and desirability of an expendable asset. Furthermore, with the increasing incorporation of multi-sensor information into the track decision the human element's real time contribution must be carefully engineered.

  20. EGFR Targeted Theranostic Nanoemulsion For Image-Guided Ovarian Cancer Therapy

    PubMed Central

    Ganta, Srinivas; Singh, Amit; Kulkarni, Praveen; Keeler, Amanda W.; Piroyan, Aleksandr; Sawant, Rupa R.; Patel, Niravkumar R.; Davis, Barbara; Ferris, Craig; O’Neal, Sara; Zamboni, William; Amiji, Mansoor M.; Coleman, Timothy P.

    2015-01-01

    Purpose Platinum-based therapies are the first line treatments for most types of cancer including ovarian cancer. However, their use is associated with dose-limiting toxicities and resistance. We report initial translational studies of a theranostic nanoemulsion loaded with a cisplatin derivative, myrisplatin and pro-apoptotic agent, C6-ceramide. Methods The surface of the nanoemulsion is annotated with an endothelial growth factor receptor (EGFR) binding peptide to improve targeting ability and gadolinium to provide diagnostic capability for image-guided therapy of EGFR overexpressing ovarian cancers. A high shear microfludization process was employed to produce the formulation with particle size below 150 nm. Results Pharmacokinetic study showed a prolonged blood platinum and gadolinium levels with nanoemulsions in nu/nu mice. The theranostic nanoemulsions also exhibited less toxicity and enhanced the survival time of mice as compared to an equivalent cisplatin treatment. Conclusions Magnetic resonance imaging (MRI) studies indicate the theranostic nanoemulsions were effective contrast agents and could be used to track accumulation in a tumor. The MRI study additionally indicate that significantly more EGFR-targeted theranostic nanoemulsion accumulated in a tumor than non-targeted nanoemulsuion providing the feasibility of using a targeted theranostic agent in conjunction with MRI to image disease loci and quantify the disease progression. PMID:25732960

  1. One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging

    PubMed Central

    Kukreja, Aastha; Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Lee, Taeksu; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

    2014-01-01

    In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease. PMID:24904209

  2. ISAR Imaging of Maneuvering Targets Based on the Modified Discrete Polynomial-Phase Transform.

    PubMed

    Wang, Yong; Abdelkader, Ali Cherif; Zhao, Bin; Wang, Jinxiang

    2015-01-01

    Inverse synthetic aperture radar (ISAR) imaging of a maneuvering target is a challenging task in the field of radar signal processing. The azimuth echo can be characterized as a multi-component polynomial phase signal (PPS) after the translational compensation, and the high quality ISAR images can be obtained by the parameters estimation of it combined with the Range-Instantaneous-Doppler (RID) technique. In this paper, a novel parameters estimation algorithm of the multi-component PPS with order three (cubic phase signal-CPS) based on the modified discrete polynomial-phase transform (MDPT) is proposed, and the corresponding new ISAR imaging algorithm is presented consequently. This algorithm is efficient and accurate to generate a focused ISAR image, and the results of real data demonstrate the effectiveness of it. PMID:26404299

  3. ISAR Imaging of Maneuvering Targets Based on the Modified Discrete Polynomial-Phase Transform

    PubMed Central

    Wang, Yong; Abdelkader, Ali Cherif; Zhao, Bin; Wang, Jinxiang

    2015-01-01

    Inverse synthetic aperture radar (ISAR) imaging of a maneuvering target is a challenging task in the field of radar signal processing. The azimuth echo can be characterized as a multi-component polynomial phase signal (PPS) after the translational compensation, and the high quality ISAR images can be obtained by the parameters estimation of it combined with the Range-Instantaneous-Doppler (RID) technique. In this paper, a novel parameters estimation algorithm of the multi-component PPS with order three (cubic phase signal-CPS) based on the modified discrete polynomial-phase transform (MDPT) is proposed, and the corresponding new ISAR imaging algorithm is presented consequently. This algorithm is efficient and accurate to generate a focused ISAR image, and the results of real data demonstrate the effectiveness of it. PMID:26404299

  4. One-pot synthesis of magnetic nanoclusters enabling atherosclerosis-targeted magnetic resonance imaging.

    PubMed

    Kukreja, Aastha; Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Lee, Taeksu; Suh, Jin-Suck; Huh, Yong-Min; Haam, Seungjoo

    2014-01-01

    In this study, dextran-encrusted magnetic nanoclusters (DMNCs) were synthesized using a one-pot solution phase method for detection of atherosclerosis by magnetic resonance imaging. Pyrenyl dextran was used as a surfactant because of its electron-stabilizing effect and its amphiphilic nature, rendering the DMNCs stable and water-dispersible. The DMNCs were 65.6±4.3 nm, had a narrow size distribution, and were superparamagnetic with a high magnetization value of 60.1 emu/g. Further, they showed biocompatibility and high cellular uptake efficiency, as indicated by a strong interaction between dextran and macrophages. In vivo magnetic resonance imaging demonstrated the ability of DMNCs to act as an efficient magnetic resonance imaging contrast agent capable of targeted detection of atherosclerosis. In view of these findings, it is concluded that DMNCs can be used as magnetic resonance imaging contrast agents to detect inflammatory disease.

  5. Soft nanomaterial-based targeting polymersomes for near-infrared fluorescence multispectral in vivo imaging.

    PubMed

    Li, Zuhong; Wu, Liyuan; Hu, Peiran; Han, Sihai; Zhang, Tao; Fan, Hongliang; Jin, Wei; Jin, Qinhan; Mu, Ying

    2012-11-21

    We report here the soft nanomaterial-based targeting polymersomes for near-infrared (NIR) fluorescence imaging to carry out in vivo tumor detection. Two polymersome-based NIR fluorescent probes were prepared through the self-assembly of amphiphilic block copolymers, poly(butadiene-b-ethylene oxide) (PEO-b-PBD). Each of them was encapsulated with distinct hydrophobic near-infrared dyes (DiD and DiR) and modified with different targeting ligands (anti-CEA antibody and anti-EGFR antibody), respectively. After simultaneous injection of these two probes into the tumor-bearing mice via tail vein, multispectral near-infrared fluorescence images were obtained. The results indicate that both probes are successfully directed to the tumor foci, where two distinguishable fluorescent signals were detected through the unmixed fluorescence images. By taking advantage of two targeting polymersome-based probes with distinct fluorescent features, the proposed multispectral near-infrared fluorescence imaging method can greatly improve the specificity and accuracy for in vivo tumor detection.

  6. Fluorescent-Guided Surgical Resection of Glioma with Targeted Molecular Imaging Agents: A Literature Review.

    PubMed

    Craig, Sonya E L; Wright, James; Sloan, Andrew E; Brady-Kalnay, Susann M

    2016-06-01

    The median life expectancy after a diagnosis of glioblastoma is 15 months. Although chemotherapeutics may someday cure glioblastoma by killing the highly dispersive malignant cells, the most important contribution that clinicians can currently offer to improve survival is by maximizing the extent of resection and providing concurrent chemo-radiation, which has become standard. Strides have been made in this area with the advent and implementation of methods of improved intraoperative tumor visualization. One of these techniques, optical fluorescent imaging with targeted molecular imaging agents, allows the surgeon to view fluorescently labeled tumor tissue during surgery with the use of special microscopy, thereby highlighting where to resect and indicating when tumor-free margins have been obtained. This advantage is especially important at the difficult-to-observe margins where tumor cells infiltrate normal tissue. Targeted fluorescent agents also may be valuable for identifying tumor versus nontumor tissue. In this review, we briefly summarize nontargeted fluorescent tumor imaging agents before discussing several novel targeted fluorescent agents being developed for glioma imaging in the context of fluorescent-guided surgery or live molecular navigation. Many of these agents are currently undergoing preclinical testing. As the agents become available, however, it is necessary to understand the strengths and weaknesses of each. PMID:26915698

  7. Soft nanomaterial-based targeting polymersomes for near-infrared fluorescence multispectral in vivo imaging

    NASA Astrophysics Data System (ADS)

    Li, Zuhong; Wu, Liyuan; Hu, Peiran; Han, Sihai; Zhang, Tao; Fan, Hongliang; Jin, Wei; Jin, Qinhan; Mu, Ying

    2012-10-01

    We report here the soft nanomaterial-based targeting polymersomes for near-infrared (NIR) fluorescence imaging to carry out in vivo tumor detection. Two polymersome-based NIR fluorescent probes were prepared through the self-assembly of amphiphilic block copolymers, poly(butadiene-b-ethylene oxide) (PEO-b-PBD). Each of them was encapsulated with distinct hydrophobic near-infrared dyes (DiD and DiR) and modified with different targeting ligands (anti-CEA antibody and anti-EGFR antibody), respectively. After simultaneous injection of these two probes into the tumor-bearing mice via tail vein, multispectral near-infrared fluorescence images were obtained. The results indicate that both probes are successfully directed to the tumor foci, where two distinguishable fluorescent signals were detected through the unmixed fluorescence images. By taking advantage of two targeting polymersome-based probes with distinct fluorescent features, the proposed multispectral near-infrared fluorescence imaging method can greatly improve the specificity and accuracy for in vivo tumor detection.

  8. Target detection: magnetic resonance imaging-ultrasound fusion-guided prostate biopsy.

    PubMed

    Sonn, Geoffrey A; Margolis, Daniel J; Marks, Leonard S

    2014-08-01

    Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance. PMID:24239473

  9. Imaging exoplanets with the WFIRST Coronagraph: A background check of high priority targets

    NASA Astrophysics Data System (ADS)

    Fu, Guangwei; Turnbull, Margaret C.; Gallagher, John S.; Kotulla, Ralf C.; Merrelli, Aronne; L'Ecuyer, Tristan; Hu, Renyu

    2016-01-01

    The WFIRST coronagraph is envisioned to achieve a limiting contrast for exoplanet detection of 10e-9. This revolutionary mission will enable the direct detection of known and newly discovered exoplanets amongst the nearest stars, from super-Earths to giants. However, at this contrast the coronagraph will essentially see a Hubble Ultra Deep Field (HUDF) in every image. For targets near the Galactic Plane on the sky, distant stars with varying levels of extinction and reddening will dominate the background. Away from the plane, we then expect extragalactic sources to dominate. What impact will these background sources have on the WFIRST exoplanet imaging program? How can we efficiently distinguish background sources from exoplanet targets in a single image? To have a comprehensive understanding of the distribution of background sources across the sky, we have used the HUDF to model extragalactic faint sources, and "Trilegal" simulations to model galactic background sources. Through some preliminary color and point source analysis, we offer a statistical estimation of expected background contamination and the probability of false positive background sources. In this poster we show plots relating number of extragalactic sources versus magnitude in HUDF and "Trilegal" simulation. We present a table of high priority WFIRST exoplanet imaging targets, with an assessment of the "background threat" due to background stars, galaxies, and binary companions.

  10. Target detection: Magnetic resonance imaging-ultrasound fusion–guided prostate biopsy

    PubMed Central

    Sonn, Geoffrey A.; Margolis, Daniel J.; Marks, Leonard S.

    2014-01-01

    Recent advances in multiparametric magnetic resonance imaging (MRI) have enabled image-guided detection of prostate cancer. Fusion of MRI with real-time ultrasound (US) allows the information from MRI to be used to direct biopsy needles under US guidance in an office-based procedure. Fusion can be performed either cognitively or electronically, using a fusion device. Fusion devices allow superimposition (coregistration) of stored MRI images on real-time US images; areas of suspicion found on MRI can then serve as targets during US-guided biopsy. Currently available fusion devices use a variety of technologies to perform coregistration: robotic tracking via a mechanical arm with built-in encoders (Artemis/Eigen, BioJet/Geoscan); electromagnetic tracking (UroNav/Philips-Invivo, Hi-RVS/Hitachi); or tracking with a 3D US probe (Urostation/Koelis). Targeted fusion biopsy has been shown to identify more clinically significant cancers and fewer insignificant cancers than conventional biopsy. Fusion biopsy appears to be a major advancement over conventional biopsy because it allows (1) direct targeting of suspicious areas not seen on US and (2) follow-up biopsy of specific cancerous sites in men undergoing active surveillance. PMID:24239473

  11. Nonlinear techniques in optical synthetic aperture radar image generation and target recognition.

    PubMed

    Weaver, S; Wagner, K

    1995-07-10

    One of the most successful optical signal-processing applications to date has been the use of optical processors to convert synthetic aperture radar (SAR) data into images of the radar reflectivity of the ground. We have demonstrated real-time input to a high-space-bandwidth optical SAR imagegeneration system by using a dynamic organic holographic recording medium and SAR phase-history data. Real-time speckle reduction in optically processed SAR imagery has been accomplished by the use of multilook averaging to achieve nonlinear modulus-squared accumulation of subaperture images. We designed and assembled an all-optical system that accomplished real-time target recognition in SAR imagery. This system employed a simple square-law nonlinearity in the form of an optically addressed spatial light modulator at the SAR image plane to remove the effects of speckle phase profiles returned from complex SAR targets. The detection stage enabled the creation of an optical SAR automatic target recognition system as a nonlinear cascade of an optical SAR image generator and an optical correlator.

  12. A strategy to objectively evaluate the necessity of correcting detected target deviations in image guided radiotherapy

    SciTech Connect

    Yue, Ning J.; Kim, Sung; Jabbour, Salma; Narra, Venkat; Haffty, Bruce G.

    2007-11-15

    Image guided radiotherapy technologies are being increasingly utilized in the treatment of various cancers. These technologies have enhanced the ability to detect temporal and spatial deviations of the target volume relative to planned radiation beams. Correcting these detected deviations may, in principle, improve the accuracy of dose delivery to the target. However, in many situations, a clinical decision has to be made as to whether it is necessary to correct some of the deviations since the relevant dosimetric impact may or may not be significant, and the corresponding corrective action may be either impractical or time consuming. Ideally this decision should be based on objective and reproducible criteria rather than subjective judgment. In this study, a strategy is proposed for the objective evaluation of the necessity of deviation correction during the treatment verification process. At the treatment stage, without any alteration from the planned beams, the treatment beams should provide the desired dose coverage to the geometric volume identical to the planning target volume (PTV). Given this fact, the planned dose distribution and PTV geometry were used to compute the dose coverage and PTV enclosure of the clinical target volume (CTV) that was detected from imaging during the treatment setup verification. The spatial differences between the detected CTV and the planning CTV are essentially the target deviations. The extent of the PTV enclosure of the detected CTV as well as its dose coverage were used as criteria to evaluate the necessity of correcting any of the target deviations. This strategy, in principle, should be applicable to any type of target deviations, including both target deformable and positional changes and should be independent of how the deviations are detected. The proposed strategy was used on two clinical prostate cancer cases. In both cases, gold markers were implanted inside the prostate for the purpose of treatment setup

  13. Non-rigid target tracking in 2D ultrasound images using hierarchical grid interpolation

    NASA Astrophysics Data System (ADS)

    Royer, Lucas; Babel, Marie; Krupa, Alexandre

    2014-03-01

    In this paper, we present a new non-rigid target tracking method within 2D ultrasound (US) image sequence. Due to the poor quality of US images, the motion tracking of a tumor or cyst during needle insertion is considered as an open research issue. Our approach is based on well-known compression algorithm in order to make our method work in real-time which is a necessary condition for many clinical applications. Toward that end, we employed a dedicated hierarchical grid interpolation algorithm (HGI) which can represent a large variety of deformations compared to other motion estimation algorithms such as Overlapped Block Motion Compensation (OBMC), or Block Motion Algorithm (BMA). The sum of squared difference of image intensity is selected as similarity criterion because it provides a good trade-off between computation time and motion estimation quality. Contrary to the others methods proposed in the literature, our approach has the ability to distinguish both rigid and non-rigid motions which are observed in ultrasound image modality. Furthermore, this technique does not take into account any prior knowledge about the target, and limits the user interaction which usually complicates the medical validation process. Finally, a technique aiming at identifying the main phases of a periodic motion (e.g. breathing motion) is introduced. The new approach has been validated from 2D ultrasound images of real human tissues which undergo rigid and non-rigid deformations.

  14. Using a targeting metric to predict the utility of an EO imager as a pilotage aid

    NASA Astrophysics Data System (ADS)

    Vollmerhausen, Richard H.; Bui, Trang

    2006-05-01

    Army aviators use both image intensified goggles and thermal imagers as night vision aids when flying helicopters at night. The Targeting Task Performance (TTP) metric can be used to predict how well these imagers support the pilotage task under different illumination and thermal contrast conditions. The TTP metric predicts the field performance of the Aviator's Night Vision Imaging System, the Apache Helicopter Pilot's Night Vision System, and the Advanced Helicopter Pilotage system. These three systems represent diverse technologies: image intensified goggles, a first generation thermal imager, and a second-generation thermal imager. The ability of the TTP metric to predict the behavior of these diverse systems is evidence of its suitability as a pilotage metric. This paper discusses the application of the TTP metric to helicopter pilotage. Data from field surveys of Army aviators are used to validate the use of the TTP metric to predict pilotage system performance. Since knowledge of scene contrast is necessary to make sensor design trades using the TTP metric, a discussion of the terrain thermal contrast available in the mid-wave and long-wave infrared is also provided.

  15. Simultaneous SPECT imaging of multi-targets to assist in identifying hepatic lesions

    PubMed Central

    Guo, Zhide; Gao, Mengna; Zhang, Deliang; Li, Yesen; Song, Manli; Zhuang, Rongqiang; Su, Xinhui; Chen, Guibing; Liu, Ting; Liu, Pingguo; Wu, Hua; Du, Jin; Zhang, Xianzhong

    2016-01-01

    Molecular imaging technique is an attractive tool to detect liver disease at early stage. This study aims to develop a simultaneous dual-isotope single photon emission computed tomography (SPECT)/CT imaging method to assist diagnosis of hepatic tumor and liver fibrosis. Animal models of liver fibrosis and orthotopic human hepatocellular carcinoma (HCC) were established. The tracers of 131I-NGA and 99mTc-3P-RGD2 were selected to target asialoglycoprotein receptor (ASGPR) on the hepatocytes and integrin αvβ3 receptor in tumor or fibrotic liver, respectively. SPECT imaging and biodistribution study were carried out to verify the feasibility and superiority. As expected, 99mTc-3P-RGD2 had the ability to evaluate liver fibrosis and detect tumor lesions. 131I-NGA showed that it was effective in assessing the anatomy and function of the liver. In synchronized dual-isotope SPECT/CT imaging, clear fusion images can be got within 30 minutes for diagnosing liver fibrosis and liver cancer. This new developed imaging approach enables the acquisition of different physiological information for diagnosing liver fibrosis, liver cancer and evaluating residual functional liver volume simultaneously. So synchronized dual-isotope SPECT/CT imaging with 99mTc-3P-RGD2 and 131I-NGA is an effective approach to detect liver disease, especially liver fibrosis and liver cancer. PMID:27377130

  16. Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma

    PubMed Central

    Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene’s expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment. PMID:27468205

  17. Alpha-fetoprotein-targeted reporter gene expression imaging in hepatocellular carcinoma.

    PubMed

    Kim, Kwang Il; Chung, Hye Kyung; Park, Ju Hui; Lee, Yong Jin; Kang, Joo Hyun

    2016-07-21

    Hepatocellular carcinoma (HCC) is one of the most common cancers in Eastern Asia, and its incidence is increasing globally. Numerous experimental models have been developed to better our understanding of the pathogenic mechanism of HCC and to evaluate novel therapeutic approaches. Molecular imaging is a convenient and up-to-date biomedical tool that enables the visualization, characterization and quantification of biologic processes in a living subject. Molecular imaging based on reporter gene expression, in particular, can elucidate tumor-specific events or processes by acquiring images of a reporter gene's expression driven by tumor-specific enhancers/promoters. In this review, we discuss the advantages and disadvantages of various experimental HCC mouse models and we present in vivo images of tumor-specific reporter gene expression driven by an alpha-fetoprotein (AFP) enhancer/promoter system in a mouse model of HCC. The current mouse models of HCC development are established by xenograft, carcinogen induction and genetic engineering, representing the spectrum of tumor-inducing factors and tumor locations. The imaging analysis approach of reporter genes driven by AFP enhancer/promoter is presented for these different HCC mouse models. Such molecular imaging can provide longitudinal information about carcinogenesis and tumor progression. We expect that clinical application of AFP-targeted reporter gene expression imaging systems will be useful for the detection of AFP-expressing HCC tumors and screening of increased/decreased AFP levels due to disease or drug treatment. PMID:27468205

  18. Carrier-free, water dispersible and highly luminescent dye nanoparticles for targeted cell imaging

    NASA Astrophysics Data System (ADS)

    Diao, Xiaojun; Li, Wei; Yu, Jia; Wang, Xiaojing; Zhang, Xiujuan; Yang, Yinlong; An, Feifei; Liu, Zhuang; Zhang, Xiaohong

    2012-08-01

    We develop a new strategy of using surface functionalized small molecule organic dye nanoparticles (NPs) for targeted cell imaging. Organic dye (2-tert-butyl-9,10-di(naphthalen-2-yl)anthracene, TBADN) was fabricated into NPs and this was followed by surface modification with an amphipathic surfactant poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG) through hydrophobic interactions to achieve good water dispersibility and bio-environmental stability. It should be noted that no additional inert materials were added as carriers, thus the dye-loading capacity of the resulting TBADN NPs is obviously higher than those of previously reported carrier-based structures. This would lead to much larger absorption and then much higher brightness. The resulting TBADN NPs possess comparable, if not higher, brightness than CdSe/ZnS quantum dots under the same conditions, with favorable biocompatibility. Significantly, TBADN NPs are readily conjugated with folic acid, and successfully applied in targeted cell imaging. These results show that water dispersible and highly stable organic NPs would be a promising new class of fluorescent probe for bioapplications in cellular imaging and labeling. This strategy may be straightforwardly extended to other organic dyes to achieve water dispersible NPs for cell imaging and drug delivery.We develop a new strategy of using surface functionalized small molecule organic dye nanoparticles (NPs) for targeted cell imaging. Organic dye (2-tert-butyl-9,10-di(naphthalen-2-yl)anthracene, TBADN) was fabricated into NPs and this was followed by surface modification with an amphipathic surfactant poly(maleic anhydride-alt-1-octadecene)-polyethylene glycol (C18PMH-PEG) through hydrophobic interactions to achieve good water dispersibility and bio-environmental stability. It should be noted that no additional inert materials were added as carriers, thus the dye-loading capacity of the resulting TBADN NPs is obviously higher than

  19. Automatic target classification of man-made objects in synthetic aperture radar images using Gabor wavelet and neural network

    NASA Astrophysics Data System (ADS)

    Vasuki, Perumal; Roomi, S. Mohamed Mansoor

    2013-01-01

    Processing of synthetic aperture radar (SAR) images has led to the development of automatic target classification approaches. These approaches help to classify individual and mass military ground vehicles. This work aims to develop an automatic target classification technique to classify military targets like truck/tank/armored car/cannon/bulldozer. The proposed method consists of three stages via preprocessing, feature extraction, and neural network (NN). The first stage removes speckle noise in a SAR image by the identified frost filter and enhances the image by histogram equalization. The second stage uses a Gabor wavelet to extract the image features. The third stage classifies the target by an NN classifier using image features. The proposed work performs better than its counterparts, like K-nearest neighbor (KNN). The proposed work performs better on databases like moving and stationary target acquisition and recognition against the earlier methods by KNN.

  20. Effective and robust infrared small target detection with the fusion of polydirectional first order derivative images under facet model

    NASA Astrophysics Data System (ADS)

    Zhu, Bing; Xin, Yunhong

    2015-03-01

    The robust detection of IR small target acts as one of the key techniques in the infrared search and tracking system (IRSTS). This paper presents a new method of small-target detection which formulates the problem as the detection of Gaussian-like spot. Initially, the amendatory first-order directional derivative (AFODD) based on facet model is applied to get the polydirectional derivative IR images, and the direction information of targets is reserved in these images. Then, the AFODD images are fused together to ensure the robustness and effectiveness of target detection. At last, the Principal Component Analysis (PCA) method is carried out to make targets in the fusion image more prominent, so that they can be extracted out by a simple threshold segmentation. Experiment results show that the presented method performs well even in the IR images with complex backgrounds.

  1. Intracellular protein target detection by quantum dots optimized for live cell imaging.

    PubMed

    Choi, Youngseon; Kim, Keumhyun; Hong, Sukmin; Kim, Hichul; Kwon, Yong-Jun; Song, Rita

    2011-08-17

    Imaging of specific intracellular target proteins in living cells has been of great challenge and importance for understanding intracellular events and elucidating various biological phenomena. Highly photoluminescent and water-soluble semiconductor nanocrystal quantum dots (QDs) have been extensively applied to various cellular imaging applications due to the long-term photostability and the tunable narrow emission spectra with broad excitation. Despite the great success of various bioimaging and diagnostic applications, visualization of intracellular targets in live cells still has been of great challenge. Nonspecific binding, difficulty of intracellular delivery, or endosomal trapping of nanosized QDs are the main reasons to hamper specific target binding in live cells. In this context, we prepared the polymer-coated QDs (pcQD) of which the surface was optimized for specific intracellular targeting in live cells. Efficient intracellular delivery was achieved through PEGylation and subsequent cell penetrating peptide (i.e., TAT) conjugation to the pcQD in order to avoid significant endosomal sequestration and to facilitate internalization of the QDs, respectively. In this study, we employed HEK293 cell line overexpressing endothelin A receptor (ET(A)R), a family of G-protein coupled receptor (GPCR), of which the cytosolic c-terminal site is genetically engineered to possess green fluorescent protein (GFP) as our intracellular protein target. The fluorescence signal of the target protein and the well-defined intracellular behavior of the GPCR help to evaluate the targeting specificity of QDs in living cells. To test the hypothesis that the TAT-QDs conjugated with antibody against intracellular target of interest can find the target, we conjugated anti-GFP antibody to TAT-PEG-pcQD using heterobifunctional linkers. Compared to the TAT-PEG-pcQD, which was distributed throughout the cytoplasm, the antiGFP-functionalized TAT-PEG-pcQD could penetrate the cell membrane

  2. Dual targeting luminescent gold nanoclusters for tumor imaging and deep tissue therapy.

    PubMed

    Chen, Dan; Li, Bowen; Cai, Songhua; Wang, Peng; Peng, Shuwen; Sheng, Yuanzhi; He, Yuanyuan; Gu, Yueqing; Chen, Haiyan

    2016-09-01

    Dual targeting towards both extracellular and intracellular receptors specific to tumor is a significant approach for cancer diagnosis and therapy. In the present study, a novel nano-platform (AuNC-cRGD-Apt) with dual targeting function was initially established by conjugating gold nanocluster (AuNC) with cyclic RGD (cRGD) that is specific to αvβ3integrins over-expressed on the surface of tumor tissues and aptamer AS1411 (Apt) that is of high affinity to nucleolin over-expressed in the cytoplasm and nucleus of tumor cells. Then, AuNC-cRGD-Apt was further functionalized with near infrared (NIR) fluorescence dye (MPA), giving a NIR fluorescent dual-targeting probe AuNC-MPA-cRGD-Apt. AuNC-MPA-cRGD-Apt displays low cytotoxicity and favorable tumor-targeting capability at both in vitro and in vivo level, suggesting its clinical potential for tumor imaging. Additionally, Doxorubicin (DOX), a widely used clinical chemotherapeutic drug that kill cancer cells by intercalating DNA in cellular nucleus, was immobilized onto AuNC-cRGD-Apt forming a pro-drug, AuNC-DOX-cRGD-Apt. The enhanced tumor affinity, deep tumor penetration and improved anti-tumor activity of this pro-drug were demonstrated in different tumor cell lines, tumor spheroid and tumor-bearing mouse models. Results in this study suggest not only the prospect of non-toxic AuNC modified with two targeting ligands for tumor targeted imaging, but also confirm the promising future of dual targeting AuNC as a core for the design of prodrug in the field of cancer therapy.

  3. In situ recognition of cell-surface glycans and targeted imaging of cancer cells

    PubMed Central

    Xu, Xiao-Ding; Cheng, Han; Chen, Wei-Hai; Cheng, Si-Xue; Zhuo, Ren-Xi; Zhang, Xian-Zheng

    2013-01-01

    Fluorescent sensors capable of recognizing cancer-associated glycans, such as sialyl Lewis X (sLex) tetrasaccharide, have great potential for cancer diagnosis and therapy. Studies on water-soluble and biocompatible sensors for in situ recognition of cancer-associated glycans in live cells and targeted imaging of cancer cells are very limited at present. Here we report boronic acid-functionalized peptide-based fluorescent sensors (BPFSs) for in situ recognition and differentiation of cancer-associated glycans, as well as targeted imaging of cancer cells. By screening BPFSs with different structures, it was demonstrated that BPFS1 with a FRGDF peptide could recognize cell-surface glycan of sLex with high specificity and thereafter fluorescently label and discriminate cancer cells through the cooperation with the specific recognition between RGD and integrins. The newly developed peptide-based sensor will find great potential as a fluorescent probe for cancer diagnosis. PMID:24042097

  4. Magnetic Nanoparticles for Targeting and Imaging of Stem Cells in Myocardial Infarction

    PubMed Central

    2016-01-01

    Stem cell therapy has broad applications in regenerative medicine and increasingly within cardiovascular disease. Stem cells have emerged as a leading therapeutic option for many diseases and have broad applications in regenerative medicine. Injuries to the heart are often permanent due to the limited proliferation and self-healing capability of cardiomyocytes; as such, stem cell therapy has become increasingly important in the treatment of cardiovascular diseases. Despite extensive efforts to optimize cardiac stem cell therapy, challenges remain in the delivery and monitoring of cells injected into the myocardium. Other fields have successively used nanoscience and nanotechnology for a multitude of biomedical applications, including drug delivery, targeted imaging, hyperthermia, and tissue repair. In particular, superparamagnetic iron oxide nanoparticles (SPIONs) have been widely employed for molecular and cellular imaging. In this mini-review, we focus on the application of superparamagnetic iron oxide nanoparticles in targeting and monitoring of stem cells for the treatment of myocardial infarctions. PMID:27127519

  5. Atherosclerotic Plaque Targeting Mechanism of Long-Circulating Nanoparticles Established by Multimodal Imaging

    PubMed Central

    Lobatto, Mark E.; Calcagno, Claudia; Millon, Antoine; Senders, Max L.; Fay, Francois; Robson, Philip M.; Ramachandran, Sarayu; Binderup, Tina; Paridaans, Maarten P.M.; Sensarn, Steven; Rogalla, Stephan; Gordon, Ronald E.; Cardoso, Luis; Storm, Gert; Metselaar, Josbert M.; Contag, Christopher H.; Stroes, Erik S. G.; Fayad, Zahi A.; Mulder, Willem J.M.

    2015-01-01

    Atherosclerosis is a major cause of global morbidity and mortality that could benefit from novel targeted therapeutics. Recent studies have shown efficient and local drug delivery with nanoparticles, although the nanoparticle targeting mechanism for atherosclerosis has not yet been fully elucidated. Here we used in vivo and ex vivo multimodal imaging to examine permeability of the vessel wall and atherosclerotic plaque accumulation of fluorescently labeled liposomal nanoparticles in a rabbit model. We found a strong correlation between permeability as established by in vivo dynamic contrast enhanced magnetic resonance imaging and nanoparticle plaque accumulation with subsequent nanoparticle distribution throughout the vessel wall. These key observations will enable the development of nanotherapeutic strategies for atherosclerosis. PMID:25619964

  6. MULTIDISCIPLINARY IMAGING OF ROCK PROPERTIES IN CARBONATE RESERVOIRS FOR FLOW-UNIT TARGETING

    SciTech Connect

    Stephen C. Ruppel

    2005-02-01

    Despite declining production rates, existing reservoirs in the US contain large quantities of remaining oil and gas that constitute a huge target for improved diagnosis and imaging of reservoir properties. The resource target is especially large in carbonate reservoirs, where conventional data and methodologies are normally insufficient to resolve critical scales of reservoir heterogeneity. The objectives of the research described in this report were to develop and test such methodologies for improved imaging, measurement, modeling, and prediction of reservoir properties in carbonate hydrocarbon reservoirs. The focus of the study is the Permian-age Fullerton Clear Fork reservoir of the Permian Basin of West Texas. This reservoir is an especially appropriate choice considering (a) the Permian Basin is the largest oil-bearing basin in the US, and (b) as a play, Clear Fork reservoirs have exhibited the lowest recovery efficiencies of all carbonate reservoirs in the Permian Basin.

  7. Conjugation of iron oxide nanoparticles with RGD-modified dendrimers for targeted tumor MR imaging.

    PubMed

    Yang, Jia; Luo, Yu; Xu, Yanhong; Li, Jingchao; Zhang, Zaixian; Wang, Han; Shen, Mingwu; Shi, Xiangyang; Zhang, Guixiang

    2015-03-11

    This article reports a new approach for the synthesis of ultrasmall iron oxide nanoparticles (NPs) conjugated with Arg-Gly-Asp (RGD)-modified dendrimers (G5.NHAc-RGD-Fe3O4 NPs) as a platform for targeted magnetic resonance (MR) imaging of C6 glioma cells. Ultrasmall Fe3O4 NPs synthesized via a solvothermal route were conjugated with RGD peptide-modified generation-5 poly(amidoamine) dendrimers (G5.NH2-RGD). The final G5.NHAc-RGD-Fe3O4 NPs were formed following the acetylation of the remaining dendrimer terminal amines. The as-prepared multifunctional Fe3O4 NPs were characterized using various techniques. The results of a cell viability assay, cell morphological observation, and hemolysis assay indicated that the G5.NHAc-RGD-Fe3O4 NPs exhibit excellent cytocompatibility and hemocompatibility over the studied concentration range. In addition, RGD conjugated onto the Fe3O4 NPs allows for the efficient targeting of the particles to C6 cells that overexpress αvβ3 receptors, which was confirmed via in vitro cell MR imaging and cellular uptake. Finally, the G5.NHAc-RGD-Fe3O4 NPs were used in the targeted MR imaging of C6 glioma cells in mice. The results obtained from the current study indicate that the developed G5.NHAc-RGD-Fe3O4 NPs offer significant potential for use as contrast agents in the targeted MR imaging of different types of tumors.

  8. Folatereceptor targeted, carboxymethyl chitosan functionalized iron oxide nanoparticles: a novel ultradispersed nanoconjugates for bimodal imaging

    NASA Astrophysics Data System (ADS)

    Bhattacharya, Dipsikha; Das, Manasmita; Mishra, Debashis; Banerjee, Indranil; Sahu, Sumanta K.; Maiti, Tapas K.; Pramanik, Panchanan

    2011-04-01

    This article delineates the design and synthesis of a novel, bio-functionalized, magneto-fluorescent multifunctional nanoparticles suitable for cancer-specific targeting, detection and imaging. Biocompatible, hydrophilic, magneto-fluorescent nanoparticles with surface-pendant amine, carboxyl and aldehyde groups were designed using o-carboxymethyl chitosan (OCMC). The free aminegroups of OCMC stabilized magnetite nanoparticles on the surface allow for the covalent attachment of a fluorescent dye such as rhodamine isothiocyanate (RITC) with the aim to develop a magneto-fluorescent nanoprobe for optical imaging. In order to impart specific cancer cell targeting properties, folic acid and its aminated derivative was conjugated onto these magneto-fluorescent nanoparticles using different pendant groups (-NH2, -COOH, -CHO). These newly synthesized iron-oxide folate nanoconjugates (FA-RITC-OCMC-SPIONs) showed excellent dispersibility, biocompatibility and good hydrodynamic sizes under physiological conditions which were extensively studied by a variety of complementary techniques. The cellular internalization efficacy of these folate-targeted and its non-targeted counterparts were studied using a folate-overexpressed (HeLa) and a normal (L929fibroblast) cells by fluorescence microscopy and magnetically activated cell sorting (MACS). Cell-uptake behaviors of nanoparticles clearly demonstrate that cancer cells over-expressing the human folatereceptor internalized a higher level of these nanoparticle-folate conjugates than normal cells. These folate targeted nanoparticles possess specific magnetic properties in the presence of an external magnetic field and the potential of these nanoconjugates as T2-weighted negative contrast MR imaging agent were evaluated in folate-overexpressed HeLa and normal L929fibroblastcells.

  9. Development of Multifunctional Nanoparticles for Targeted Drug Delivery and Non-invasive Imaging of Therapeutic Effect

    PubMed Central

    Sajja, Hari Krishna; East, Michael P.; Mao, Hui; Wang, Andrew Y.; Nie, Shuming; Yang, Lily

    2011-01-01

    Nanotechnology is a multidisciplinary scientific field undergoing explosive development. Nanometer-sized particles offer novel structural, optical and electronic properties that are not attainable with individual molecules or bulk solids. Advances in nanomedicine can be made by engineering biodegradable nanoparticles such as magnetic iron oxide nanoparticles, polymers, dendrimers and liposomes that are capable of targeted delivery of both imaging agents and anticancer drugs. This leads toward the concept and possibility of personalized medicine for the potential of early detection of cancer lesions, determination of molecular signatures of the tumor by non-invasive imaging and, most importantly, molecular targeted cancer therapy. Increasing evidence suggests that the nanoparticles, whose surface contains a targeting molecule that binds to receptors highly expressed in tumor cells, can serve as cancer image contrast agents to increase sensitivity and specificity in tumor detection. In comparison with other small molecule contrast agents, the advantage of using nanoparticles is their large surface area and the possibility of surface modifications for further conjugation or encapsulation of large amounts of therapeutic agents. Targeted nanoparticles ferry large doses of therapeutic agents into malignant cells while sparing the normal healthy cells. Such multifunctional nanodevices hold the promise of significant improvement of current clinical management of cancer patients. This review explores the development of nanoparticles for enabling and improving the targeted delivery of therapeutic agents, the potential of nanomedicine, and the development of novel and more effective diagnostic and screening techniques to extend the limits of molecular diagnostics providing point-of-care diagnosis and more personalized medicine. PMID:19275541

  10. Novel 3-D laparoscopic magnetic ultrasound image guidance for lesion targeting

    PubMed Central

    Sindram, David; McKillop, Iain H; Martinie, John B; Iannitti, David A

    2010-01-01

    Objectives: Accurate laparoscopic liver lesion targeting for biopsy or ablation depends on the ability to merge laparoscopic and ultrasound images with proprioceptive instrument positioning, a skill that can be acquired only through extensive experience. The aim of this study was to determine whether using magnetic positional tracking to provide three-dimensional, real-time guidance improves accuracy during laparoscopic needle placement. Methods: Magnetic sensors were embedded into a needle and laparoscopic ultrasound transducer. These sensors interrupted the magnetic fields produced by an electromagnetic field generator, allowing for real-time, 3-D guidance on a stereoscopic monitor. Targets measuring 5 mm were embedded 3–5 cm deep in agar and placed inside a laparoscopic trainer box. Two novices (a college student and an intern) and two experts (hepatopancreatobiliary surgeons) targeted the lesions out of the ultrasound plane using either traditional or 3-D guidance. Results: Each subject targeted 22 lesions, 11 with traditional and 11 with the novel guidance (n = 88). Hit rates of 32% (14/44) and 100% (44/44) were observed with the traditional approach and the 3-D magnetic guidance approach, respectively. The novices were essentially unable to hit the targets using the traditional approach, but did not miss using the novel system. The hit rate of experts improved from 59% (13/22) to 100% (22/22) (P < 0.0001). Conclusions: The novel magnetic 3-D laparoscopic ultrasound guidance results in perfect targeting of 5-mm lesions, even by surgical novices. PMID:21083797

  11. Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins

    PubMed Central

    Boonstra, Martin C.; de Geus, Susanna W.L.; Prevoo, Hendrica A.J.M.; Hawinkels, Lukas J.A.C.; van de Velde, Cornelis J.H.; Kuppen, Peter J.K.; Vahrmeijer, Alexander L.; Sier, Cornelis F.M.

    2016-01-01

    Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than $78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications. PMID:27721658

  12. Target error for image-to-physical space registration: preliminary clinical results using laser range scanning

    NASA Astrophysics Data System (ADS)

    Cao, Aize; Miga, Michael I.; Dumpuri, P.; Ding, S.; Dawant, B. M.; Thompson, R. C.

    2007-03-01

    In this paper, preliminary results from an image-to-physical space registration platform are presented. The current platform employs traditional and novel methods of registration which use a variety of data sources to include: traditional synthetic skin-fiducial point-based registration, surface registration based on facial contours, brain feature point-based registration, brain vessel-to-vessel registration, and a more comprehensive cortical surface registration method that utilizes both geometric and intensity information from both the image volume and physical patient. The intraoperative face and cortical surfaces were digitized using a laser range scanner (LRS) capable of producing highly resolved textured point clouds. In two in vivo cases, a series of registrations were performed using these techniques and compared within the context of a true target error. One of the advantages of using a textured point cloud data stream is that true targets among the physical cortical surface and the preoperative image volume can be identified and used to assess image-to-physical registration methods. The results suggest that iterative closest point (ICP) method for intraoperative face surface registration is equivalent to point-based registration (PBR) method of skin fiducial markers. With regard to the initial image and physical space registration, for patient 1, mean target registration error (TRE) were 3.1+/-0.4 mm and 3.6 +/-0.9 mm for face ICP and skin fiducial PBR, respectively. For patient 2, the mean TRE were 5.7 +/-1.3 mm, and 6.6 +/-0.9 mm for face ICP and skin fiducial PBR, respectively. With regard to intraoperative cortical surface registration, SurfaceMI outperformed feature based PBR and vessel ICP with 1.7+/-1.8 mm for patient 1. For patient 2, the best result was achieved by using vessel ICP with 1.9+/-0.5 mm.

  13. Nanobubble-Affibody: Novel ultrasound contrast agents for targeted molecular ultrasound imaging of tumor.

    PubMed

    Yang, Hengli; Cai, Wenbin; Xu, Lei; Lv, Xiuhua; Qiao, Youbei; Li, Pan; Wu, Hong; Yang, Yilin; Zhang, Li; Duan, Yunyou

    2015-01-01

    Nanobubbles (NBs), as novel ultrasound contrast agents (UCAs), have attracted increasing attention in the field of molecular ultrasound imaging for tumors. However, the preparation of uniform-sized NBs is considered to be controversial, and poor tumor selectivity in in vivo imaging has been reported. In this study, we fabricated uniform nano-sized NBs (478.2 ± 29.7 nm with polydispersity index of 0.164 ± 0.044, n = 3) using a thin-film hydration method by controlling the thickness of phospholipid films; we then conjugated the NBs with Affibody molecules to produce nano-sized UCAs referred to as NB-Affibody with specific affinity to human epidermal growth factor receptor type 2 (HER2)-overexpressing tumors. NB-Affibody presented good ultrasound enhancement, demonstrating a peak intensity of 104.5 ± 2.1 dB under ultrasound contrast scanning. Ex vivo experiments further confirmed that the NB-Affibody conjugates were capable of targeting HER2-expressing tumor cells in vivo with high affinity. The newly prepared nano-sized NB-Affibody conjugates were observed to be novel targeted UCAs for efficient and safe specific molecular imaging and may have potential applications in early cancer quantitative diagnosis and targeted therapy in the future.

  14. Quantum dot surface chemistry and functionalization for cell targeting and imaging.

    PubMed

    Bilan, Regina; Fleury, Fabrice; Nabiev, Igor; Sukhanova, Alyona

    2015-04-15

    Quantum dots (QDs) are highly fluorescent nanoscale crystals with size-dependent emission spectra. Due to their excellent photophysical properties, QDs are a promising alternative to organic fluorescent dyes and fluorescent proteins for cell targeting, imaging, and drug delivery. For biomedical applications, QDs should be chemically modified to be stable in aqueous solutions and tagged with the recognition molecules or drugs. Here, we review surface modification approaches to, and strategies for, conjugation of bioactive molecules with QDs. There are a variety of methods of QD surface modification and QD incorporation into larger delivery systems that yield fluorescent nanocarriers from 10 nm to several micrometers. Conjugates of QDs with peptides, proteins, antibodies, oligonucleotides, and small molecules have been used for fluorescent targeting, tracking, and imaging both in vitro and in vivo. Due to an extremely high stability to photobleaching, QDs were used for long-term visualization. QD applications pave the way for new generations of ultrasensitive detection, diagnostic systems, as well as drug delivery approaches, combining accurate targeting, delivery, and imaging in a single assay.

  15. Breast Cancer Detection by B7-H3 Targeted Ultrasound Molecular Imaging

    PubMed Central

    Bachawal, Sunitha V.; Jensen, Kristin C.; Wilson, Katheryne E.; Tian, Lu; Lutz, Amelie M.; Willmann, Jürgen K.

    2015-01-01

    Ultrasound complements mammography as an imaging modality for breast cancer detection, especially in patients with dense breast tissue, but its utility is limited by low diagnostic accuracy. One emerging molecular tool to address this limitation involves contrast-enhanced ultrasound using microbubbles targeted to molecular signatures on tumor neovasculature. In this study, we illustrate how tumor vascular expression of B7-H3 (CD276), a member of the B7 family of ligands for T cell co-regulatory receptors, can be incorporated into an ultrasound method that can distinguish normal, benign, precursor and malignant breast pathologies for diagnostic purposes. Through an immunohistochemical analysis of 248 human breast specimens, we found that vascular expression of B7-H3 was selectively and significantly higher in breast cancer tissues. B7-H3 immunostaining on blood vessels distinguished benign/precursors from malignant lesions with high diagnostic accuracy in human specimens. In a transgenic mouse model of cancer, the B7-H3-targeted ultrasound imaging signal was increased significantly in breast cancer tissues and highly correlated with ex vivo expression levels of B7-H3 on quantitative immunofluorescence. Our findings offer a preclinical proof of concept for the use of B7-H3-targeted ultrasound molecular imaging as a tool to improve the diagnostic accuracy of breast cancer detection in patients. PMID:25899053

  16. Multifunctional Nanoprobes for Cancer Cell Targeting, Imaging and Anticancer Drug Delivery

    NASA Astrophysics Data System (ADS)

    Linkov, Pavel; Laronze-Cochard, Marie; Sapi, Janos; Sidorov, Lev N.; Nabiev, Igor

    The diagnosis and treatment of cancer have been greatly improved with recent developments in bio-nanotechnology, including engineering of multifunctional probes. One of the promising nanoscale tools for cancer imaging is fluorescent quantum dots (QDs), whose small size and unique optical properties allow them to penetrate into cells and ensure highly sensitive optical diagnosis of cancer at the cellular level. Furthermore, novel multi-functional probes have been developed in which QDs are conjugated with one or several functional molecules, including targeting moieties and therapeutic agents. Here, the strategy for engineering novel nanocarriers for controlled nucleus-targeted antitumor drug delivery and real-time imaging by single- or two-photon microscopy is described. A triple multifunctional nanoprobe is being developed that consists of a nitrogen-based heterocyclic derivative, an anticancer agent interacting with a DNA in living cells; a recognized molecule serving as a vector responsible for targeted delivery of the probe into cancer cells; and photoluminescent QDs providing the imaging capability of the probe. Subsequent optimization of the multifunctional nanoprobe will offer new possibilities for cancer diagnosis and treatment.

  17. Prostate-specific membrane antigen as a target for cancer imaging and therapy

    PubMed Central

    KIESS, A. P.; BANERJEE, S. R.; MEASE, R. C.; ROWE, S. P.; RAO, A.; FOSS, C. A.; CHEN, Y.; YANG, X.; CHO, S. Y.; NIMMAGADDA, S.; POMPER, M. G.

    2016-01-01

    The prostate-specific membrane antigen (PSMA) is a molecular target whose use has resulted in some of the most productive work toward imaging and treating prostate cancer over the past two decades. A wide variety of imaging agents extending from intact antibodies to low-molecular-weight compounds permeate the literature. In parallel there is a rapidly expanding pool of antibody-drug conjugates, radiopharmaceutical therapeutics, small-molecule drug conjugates, theranostics and nanomedicines targeting PSMA. Such productivity is motivated by the abundant expression of PSMA on the surface of prostate cancer cells and within the neovasculature of other solid tumors, with limited expression in most normal tissues. Animating the field is a variety of small-molecule scaffolds upon which the radionuclides, drugs, MR-detectable species and nanoparticles can be placed with relative ease. Among those, the urea-based agents have been most extensively leveraged, with expanding clinical use for detection and more recently for radiopharmaceutical therapy of prostate cancer, with surprisingly little toxicity. PSMA imaging of other cancers is also appearing in the clinical literature, and may overtake FDG for certain indications. Targeting PSMA may provide a viable alternative or first-line approach to managing prostate and other cancers. PMID:26213140

  18. Advanced hyperspectral imaging solutions for near real-time target detection

    NASA Astrophysics Data System (ADS)

    Weatherbee, Oliver; Janaskie, Justin; Hyvärinen, Timo

    2012-09-01

    AISA hyperspectral imagers have been utilized in airborne applications for various defense related Intelligence, Surveillance and Reconnaissance (ISR) applications. In expanding the utility and capabilities of hyperspectral imagers for defense related applications, the implementation in a ground scanning configuration for check-point and forensic purposes has been achieved. System specifications, design, and operational considerations for a fully automated, near real-time target detection capability are presented. The system utilizes modularized software architecture, combining C++ command, capture, calibration, and messaging functions with drop-in IDL exploitation module for detection algorithm and target set flexibility. Performance capability against known defense related targets of interest have been tested, verified, and are presented utilizing full 400-2450nm spectral range provided by combined AisaEAGLE and AisaHAWK hyperspectral imagers. Initial results are also described for a new extended InGaAs system, covering 585-1630nm to provide a similar capability for integrations which have size, weight, and power restrictions.

  19. Target-cell-specific fluorescence silica nanoprobes for imaging and theranostics of cancer cells.

    PubMed

    Li, Henan; Mu, Yawen; Lu, Jusheng; Wei, Wei; Wan, Yakun; Liu, Songqin

    2014-04-01

    MicroRNAs (miRNAs) has been identified as diagnostic and prognostic biomarkers and predictors of drug response for many diseases, including a broad range of cancers, heart disease, and neurological diseases. The noninvasive theranostics system for miRNAs is very important for diagnosis and therapy of the cellular disease. Herein, a target-cell-specific theranostics nanoprobe for target-cell-specific delivery, cancer cells and intracellular miRNA-21 imaging, and cancer cell growth inhibition was proposed. The nanoprobe (FS-AS/MB) was prepared by simultaneously coupling of the AS1411 aptamer and miRNA-21 molecular beacon (miR-21-MB) onto the surface of Ru(bpy)₃²⁺-encapsulated silica (FS) nanoparticles. The FS nanoparticles synthesized by a facile reverse microemulsion method showed nearly monodisperse spherical shape with a smooth surface, good colloidal stability, a fluorescence quantum yield of ~21%, and low cytotoxicity. The antibiofouling polymer PEG grafted onto a silica shell reduced nonspecific uptake of cells. The ability of FS-AS/MB for target-specific cells delivery, simultaneous cancer cells, intracellular miRNA-21 imaging, and inhibition of miRNA-21 function and suppression of cell growth in vitro, were also demonstrated. The results of the present study suggested that the proposed nanoprobes would be a promising theranostics for different cancers by imaging and inhibiting other intracellular genes.

  20. Gold nanorods for target selective SPECT/CT imaging and photothermal therapy in vivo

    PubMed Central

    Jang, Boseung; Park, Seonhwa; Kang, Se Hun; Kim, Joa Kyum; Kim, Seok-Ki; Kim, In-Hoo; Choi, Yongdoo

    2012-01-01

    The development of theranostic agents with high detection sensitivity and antitumor efficacy at low concentration is a challenging task for target selective imaging and therapy of cancers. In this study, folate-conjugated and radioactive-iodine-labeled gold nanorods (GNRs) were designed and synthesized for target selective SPECT/CT imaging and subsequent thermal ablation of folate-receptor-overexpressing cancers. Both (ortho-pyridyl) disulfide-poly(ethylene glycol)-folate and a short peptide, H2N-Tyr-Asn-Asn-Leu-Ala-Cys-OH, were conjugated on the surface of the GNRs through thiol chemistry. The tyrosine in the peptide sequence was introduced for radioactive-iodine labeling through an iodine-tyrosine interaction. The labeling efficiency of radioactive iodine was more than 99%. Radiochemical stability tests on iodine-125-labeled GNRs in human serum showed that 91% of the iodine-125 remained intact on the GNRs after incubation for 24 h. In vitro and in vivo results in this study confirmed the potential utility of folate-conjugated and iodine-125-labeled GNRs as smart theranostic agents. This type of platform may also be useful for the targeted SPECT/CT imaging and photothermal therapy of inflammatory diseases such as atherosclerosis and arthritis, in which folate-receptor-overexpressing macrophages play pivotal roles. PMID:23256055

  1. Recent Developments in Active Tumor Targeted Multifunctional Nanoparticles for Combination Chemotherapy in Cancer Treatment and Imaging

    PubMed Central

    Glasgow, Micah D. K.; Chougule, Mahavir B.

    2016-01-01

    Nanotechnology and combination therapy are two major fields that show great promise in the treatment of cancer. The delivery of drugs via nanoparticles helps to improve drug’s therapeutic effectiveness while reducing adverse side effects associated with high dosage by improving their pharmacokinetics. Taking advantage of molecular markers over-expressing on tumor tissues compared to normal cells, an “active” molecular marker targeted approach would be beneficial for cancer therapy. These actively targeted nanoparticles would increase drug concentration at the tumor site, improving efficacy while further reducing chemo-resistance. The multidisciplinary approach may help to improve the overall efficacy in cancer therapy. This review article summarizes recent developments of targeted multifunctional nanoparticles in the delivery of various drugs for a combinational chemotherapy approach to cancer treatment and imaging. PMID:26554150

  2. HER2 Targeting Peptides Screening and Applications in Tumor Imaging and Drug Delivery

    PubMed Central

    Geng, Lingling; Wang, Zihua; Jia, Xiangqian; Han, Qiuju; Xiang, Zhichu; Li, Dan; Yang, Xiaoliang; Zhang, Di; Bu, Xiangli; Wang, Weizhi; Hu, Zhiyuan; Fang, Qiaojun

    2016-01-01

    Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery. PMID:27279916

  3. HER2 Targeting Peptides Screening and Applications in Tumor Imaging and Drug Delivery.

    PubMed

    Geng, Lingling; Wang, Zihua; Jia, Xiangqian; Han, Qiuju; Xiang, Zhichu; Li, Dan; Yang, Xiaoliang; Zhang, Di; Bu, Xiangli; Wang, Weizhi; Hu, Zhiyuan; Fang, Qiaojun

    2016-01-01

    Herein, computational-aided one-bead-one-compound (OBOC) peptide library design combined with in situ single-bead sequencing microarray methods were successfully applied in screening peptides targeting at human epidermal growth factor receptor-2 (HER2), a biomarker of human breast cancer. As a result, 72 novel peptides clustered into three sequence motifs which are PYL***NP, YYL***NP and PPL***NP were acquired. Particularly one of the peptides, P51, has nanomolar affinity and high specificity for HER2 in ex vivo and in vivo tests. Moreover, doxorubicin (DOX)-loaded liposome nanoparticles were modified with peptide P51 or P25 and demonstrated to improve the targeted delivery against HER2 positive cells. Our study provides an efficient peptide screening method with a combination of techniques and the novel screened peptides with a clear binding site on HER2 can be used as probes for tumor imaging and targeted drug delivery. PMID:27279916

  4. Potential of activatable FAP-targeting immunoliposomes in intraoperative imaging of spontaneous metastases.

    PubMed

    Tansi, Felista L; Rüger, Ronny; Böhm, Claudia; Kontermann, Roland E; Teichgraeber, Ulf K; Fahr, Alfred; Hilger, Ingrid

    2016-05-01

    Despite intensive research and medical advances met, metastatic disease remains the most common cause of death in cancer patients. This results from late diagnosis, poor therapeutic response and undetected micrometastases and tumor margins during surgery. One approach to overcome these challenges involves fluorescence imaging, which exploits the properties of fluorescent probes for diagnostic detection of molecular structures at the onset of transformation and for intraoperative detection of metastases and tumor margins in real time. Considering these benefits, many contrast agents suitable for fluorescence imaging have been reported. However, most reports only demonstrate the detection of primary tumors and not the detection of metastases or their application in models of image-guided surgery. In this work, we demonstrate the influence of fibroblast activation protein (FAP) on the metastatic potential of fibrosarcoma cells and elucidate the efficacy of activatable FAP-targeting immunoliposomes (FAP-IL) for image-guided detection of the spontaneous metastases in mice models. Furthermore, we characterized the biodistribution and cellular localization of the liposomal fluorescent components in mice organs and traced their excretion over time in urine and feces. Taken together, activatable FAP-IL enhances intraoperative imaging of metastases. Their high accumulation in metastases, subsequent localization in the bile canaliculi and liver kupffer cells and suitable excretion in feces substantiates their potency as contrast agents for intraoperative imaging.

  5. Small flexible structure for targeted delivery of therapeutic and imaging moieties in precision medicine

    PubMed Central

    Li, Bingjie; Qiu, Xiuchun; Zou, Chaoxia; Ran, Henry; Zhang, Fujun; Ke, Shi

    2016-01-01

    The goals of precision medicine are to link diagnostic and therapeutic agents, improve clinical outcomes, and minimize side effects. We present a simple, small, flexible three-armed core structure that can be conjugated to targeting, imaging, and therapeutic moieties. The targeting molecule can be a peptide, protein, or chemical compound. The diagnostic reporter can be optical and/or nuclear in nature, and can be replaced by chemo- and/or radiotherapeutic compounds for treatment using a single targeting molecule. Imaging components can be used to detect disease biomarkers, monitor treatment response, and guide surgery in real-time to create a tumor-free margin. Isotope impurity can be exploited to visualize whole-body distribution of therapeutic agents. The one-to-one ratio of targeting component to therapeutic agents facilitates dose calculation. The simple synthesis and flexible, modular nature of the agent facilitate high-purity, large-scale production. The core capacity to “seek, treat, and see” may advance precision medicine in the future. PMID:27027441

  6. A new look at drugs targeting malignant melanoma--an application for mass spectrometry imaging.

    PubMed

    Sugihara, Yutaka; Végvári, Akos; Welinder, Charlotte; Jönsson, Göran; Ingvar, Christian; Lundgren, Lotta; Olsson, Håkan; Breslin, Thomas; Wieslander, Elisabet; Laurell, Thomas; Rezeli, Melinda; Jansson, Bo; Nishimura, Toshihide; Fehniger, Thomas E; Baldetorp, Bo; Marko-Varga, György

    2014-09-01

    Malignant melanoma (MM) patients are being treated with an increasing number of personalized medicine (PM) drugs, several of which are small molecule drugs developed to treat patients with specific disease genotypes and phenotypes. In particular, the clinical application of protein kinase inhibitors has been highly effective for certain subsets of MM patients. Vemurafenib, a protein kinase inhibitor targeting BRAF-mutated protein, has shown significant efficacy in slowing disease progression. In this paper, we provide an overview of this new generation of targeted drugs, and demonstrate the first data on localization of PM drugs within tumor compartments. In this study, we have introduced MALDI-MS imaging to provide new information on one of the drugs currently used in the PM treatment of MM, vemurafenib. In a proof-of-concept in vitro study, MALDI-MS imaging was used to identify vemurafenib applied to metastatic lymph nodes tumors of subjects attending the regional hospital network of Southern Sweden. The paper provides evidence of BRAF overexpression in tumors isolated from MM patients and localization of the specific drug targeting BRAF, vemurafenib, using MS fragment ion signatures. Our ability to determine drug uptake at the target sites of directed therapy provides important opportunity for increasing our understanding about the mode of action of drug activity within the disease environment. PMID:25044963

  7. Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles.

    PubMed

    Guo, Jintang; Hong, Hao; Chen, Guojun; Shi, Sixiang; Zheng, Qifeng; Zhang, Yin; Theuer, Charles P; Barnhart, Todd E; Cai, Weibo; Gong, Shaoqin

    2013-11-01

    Unimolecular micelles formed by dendritic amphiphilic block copolymers poly(amidoamine)-poly(L-lactide)-b-poly(ethylene glycol) conjugated with anti-CD105 monoclonal antibody (TRC105) and 1,4,7-triazacyclononane-N, N', N-triacetic acid (NOTA, a macrocyclic chelator for (64)Cu) (abbreviated as PAMAM-PLA-b-PEG-TRC105) were synthesized and characterized. Doxorubicin (DOX), a model anti-cancer drug, was loaded into the hydrophobic core of the unimolecular micelles formed by PAMAM and PLA via physical encapsulation. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. TRC105-conjugated unimolecular micelles showed a CD105-associated cellular uptake in human umbilical vein endothelial cells (HUVEC) compared with non-targeted unimolecular micelles, which was further validated by cellular uptake in CD105-negative MCF-7 cells. In 4T1 murine breast tumor-bearing mice, (64)Cu-labeled targeted micelles exhibited a much higher level of tumor accumulation than (64)Cu-labeled non-targeted micelles, measured by serial non-invasive positron emission tomography (PET) imaging and confirmed by biodistribution studies. These unimolecular micelles formed by dendritic amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics. PMID:23932288

  8. ULTRASONIC AND RADIOGRAPHIC IMAGING OF NIOBIUM TARGET CAPSULES FOR RADIOISOTOPE PRODUCTION

    SciTech Connect

    Bach, H. T.; Claytor, T. N.; Hunter, J. F.; Dozier, B. E.; Nortier, F. M.; Smith, D. M.; Lenz, J. W.; Moddrell, C.; Smith, P. A.

    2009-03-03

    In the case of proton-irradiated radioisotope production, niobium target capsules containing gallium are exposed to intense radiation, thermally induced stress, for extended periods. The structural integrity of the target capsules is of crucial importance for containing the accelerator-produced radioisotopes and target material. The capsule window should be as thin and transparent to the proton beam as possible, and preferably should not become significantly activated under proton irradiation. In addition, the material for the capsule needs to be as defect-free as possible. Niobium encapsulated gallium targets have a history of unpredictable failure under intense irradiation with 100 MeV protons. This study illustrates the utility of non-destructive testing in order to detect defects that may result in mechanical failure of the capsules during irradiation. Prior to this work, it was not known if the gallium initially wets the niobium capsule that encapsulates it, and if it does, it is not known to what degree. However, the imaging techniques used in this work show that local areas of wetting do occur. We used ultrasonic images from various lots of niobium capsule material to assess the integrity of the capsules. Digital radiography is also used to detect any voids in the gallium that will tend to cause local heating in the capsules.

  9. Image-guided and tumor-targeted drug delivery with radiolabeled unimolecular micelles

    PubMed Central

    Chen, Guojun; Shi, Sixiang; Zheng, Qifeng; Zhang, Yin; Theuer, Charles P.; Barnhart, Todd E.; Cai, Weibo; Gong, Shaoqin

    2013-01-01

    Unimolecular micelles formed by dendritic amphiphilic block copolymers poly(amidoamine)–poly(l-lactide)-b-poly(ethylene glycol) conjugated with anti-CD105 monoclonal antibody (TRC105) and 1,4,7-triazacyclononane-N, N’, N-triacetic acid (NOTA, a macrocyclic chelator for 64Cu) (abbreviated as PAMAM–PLA-b-PEG–TRC105) were synthesized and characterized. Doxorubicin (DOX), a model anti-cancer drug, was loaded into the hydrophobic core of the unimolecular micelles formed by PAMAM and PLA via physical encapsulation. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. TRC105-conjugated unimolecular micelles showed a CD105-associated cellular uptake in human umbilical vein endothelial cells (HUVEC) compared with non-targeted unimolecular micelles, which was further validated by cellular uptake in CD105-negative MCF-7 cells. In 4T1 murine breast tumor-bearing mice, 64Cu-labeled targeted micelles exhibited a much higher level of tumor accumulation than 64Cu-labeled non-targeted micelles, measured by serial non-invasive positron emission tomography (PET) imaging and confirmed by biodistribution studies. These unimolecular micelles formed by dendritic amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics. PMID:23932288

  10. Targeting and Imaging of Cancer Cells via Monosaccharide-Imprinted Fluorescent Nanoparticles

    NASA Astrophysics Data System (ADS)

    Wang, Shuangshou; Yin, Danyang; Wang, Wenjing; Shen, Xiaojing; Zhu, Jun-Jie; Chen, Hong-Yuan; Liu, Zhen

    2016-03-01

    The recognition of cancer cells is a key for cancer diagnosis and therapy, but the specificity highly relies on the use of biorecognition molecules particularly antibodies. Because biorecognition molecules suffer from some apparent disadvantages, such as hard to prepare and poor storage stability, novel alternatives that can overcome these disadvantages are highly important. Here we present monosaccharide-imprinted fluorescent nanoparticles (NPs) for targeting and imaging of cancer cells. The molecularly imprinted polymer (MIP) probe was fluorescein isothiocyanate (FITC) doped silica NPs with a shell imprinted with sialic acid, fucose or mannose as the template. The monosaccharide-imprinted NPs exhibited high specificity toward the target monosaccharides. As the template monosaccharides used are over-expressed on cancer cells, these monosaccharide-imprinted NPs allowed for specific targeting cancer cells over normal cells. Fluorescence imaging of human hepatoma carcinoma cells (HepG-2) over normal hepatic cells (L-02) and mammary cancer cells (MCF-7) over normal mammary epithelial cells (MCF-10A) by these NPs was demonstrated. As the imprinting approach employed herein is generally applicable and highly efficient, monosaccharide-imprinted NPs can be promising probes for targeting cancer cells.

  11. Cancer Nanotheranostics: Improving Imaging and Therapy by Targeted Delivery across Biological Barriers

    PubMed Central

    Kievit, Forrest M.; Zhang, Miqin

    2012-01-01

    Cancer nanotheranostics aims to combine imaging and therapy of cancer through use of nanotechnology. The ability to engineer nanomaterials to interact with cancer cells at the molecular level can significantly improve the effectiveness and specificity of therapy to cancers that are currently difficult to treat. In particular, metastatic cancers, drug-resistant cancers, and cancer stem cells impose the greatest therapeutic challenge that requires targeted therapy to treat effectively. Targeted therapy can be achieved with appropriate designed drug delivery vehicles such as nanoparticles, adult stem cells, or T cells in immunotherapy. In this article, we first review the different types of materials commonly used to synthesize nanotheranostic particles and their use in imaging. We then discuss biological barriers that these nanoparticles encounter and must bypass to reach the target cancer cells, including the blood, liver, kidneys, spleen, and particularly the blood-brain barrier. We then review how nanotheranostics can be used to improve targeted delivery and treatment of cancer cells using nanoparticles, adult stem cells, and T cells in immunotherapy. Finally, we discuss development of nanoparticles to overcome current limitations in cancer therapy. PMID:21842473

  12. HIGH SPATIAL RESOLUTION IMAGING OF INERTIAL FUSION TARGET PLASMAS USING BUBBLE NEWTRON DETECTORS

    SciTech Connect

    FISHER,RK

    2002-10-01

    OAK B202 HIGH SPATIAL RESOLUTION IMAGING OF INERTIAL FUSION TARGET PLASMAS USING BUBBLE NEWTRON DETECTORS. Bubble detectors, which can detect neutrons with a spatial resolution of 5 to 30 {micro}, are a promising approach to high-resolution imaging of NIF target plasmas. Gel bubble detectors were used in successful proof-of-principle imaging experiments on OMEGA. Until recently, bubble detectors appeared to be the only approach capable of achieving neutron images of NIF targets with the desired 5 {micro} spatial resolution in the target plane. In 2001, NIF reduced the required standoff distance from the target, so that diagnostic components can now be placed as close as 10 cm to the target plasma. This will allow neutron imaging with higher magnification and may make it possible to obtain 5 {micro}m resolution images on NIF using deuterated scintillators. Having accomplished all that they can hope to on OMEGA using gel detectors, they suggested that the 2002 NLUF shots be used to allow experimental tests of the spatial resolution of the CEA-built deuterated scintillators. The preliminary CEA data from the June 2002 run appears to show the spatial resolution using the deuterated scintillator detector array is improved over that obtained in earlier experiments using the proton-based scintillators. Gel detectors, which consist of {approx} 10 {micro}m diameter drops of bubble detector liquid suspended in an inactive support gel that occupies {approx} 99% of the detector volume, were chosen for the initial tests on OMEGA since they are easy to use. The bubbles could be photographed several hours after the neutron exposure. Imaging NIF target plasmas at neutron yields of 10{sup 15} will require a higher detection efficiency detector. Using a liquid bubble chamber detector should result in {approx} 1000 times higher neutron detection efficiency which is comparable to that possible using scintillation detectors. A pressure-cycled liquid bubble detector will require a light

  13. Paramagnetic hollow silica nanospheres for in vivo targeted ultrasound and magnetic resonance imaging.

    PubMed

    An, Lu; Hu, He; Du, Jing; Wei, Jie; Wang, Li; Yang, Hong; Wu, Dongmei; Shi, Haili; Li, Fenghua; Yang, Shiping

    2014-07-01

    A series of hollow silica nanospheres (HSNSs) with sizes ranging from 100 to 400 nm were synthesized and used for primary ultrasound imaging (US) efficiency assessment. The 400 nm HSNSs were chosen as platform for conjugation with Gd-DTPA and cyclo-arginine-glycine-aspartic acid c(RGD) peptide to construct US and magnetic resonance imaging (MRI) dual-modal contrast agents (CAs): [HSNSs@(DTPA-Gd)-RGD]. The obtained CAs displayed good physiological stability, low cytotoxicity and negligible hemolytic activity in vitro. Furthermore, the passive accumulation and active-targeting of the HSNSs in the tumor site of mice was demonstrated by US and MR imaging, respectively. The qualitative and quantitative biodistribution of the HSNSs showed that they mainly accumulated in the tissues of liver, lung, tumor after intravenous administration and then be excreted from feces. In addition, histological, hematological, blood and biochemical analysis were used to further study toxicity of the HSNSs, and all results indicated that there were no covert toxicity of HSNSs in mice after long exposure times. Findings from this study indicated that the silica-based paramagnetic HSNSs can be used as a platform for long-term targeted imaging and therapy studies safely in vivo.

  14. Photo-acoustic imaging of blue nanoparticle targeted brain tumor for intra-operative glioma delineation

    NASA Astrophysics Data System (ADS)

    Ray, Aniruddha; Wang, Xueding; Koo Lee, Yong-Eun; Hah, HoeJin; Kim, Gwangseong; Chen, Thomas; Orrienger, Daniel; Sagher, Oren; Kopelman, Raoul

    2011-07-01

    Distinguishing the tumor from the background neo-plastic tissue is challenging for cancer surgery such as surgical resection of glioma. Attempts have been made to use visible or fluorescent markers to delineate the tumors during surgery. However, the systemic injection of the dyes requires high dose, resulting in negative side effects. A novel method to delineate rat brain tumors intra-operatively, as well as post-operatively, using a highly sensitive photoacoustic imaging technique enhanced by tumor targeting blue nanoparticle as contrast agent is demonstrated. The nanoparticles are made of polyacrylamide (PAA) matrix with covalently linked Coomassie-Blue dye. They contain 7.0% dye and the average size is 80nm. Their surface was conjugated with F3 peptide for active tumor targeting. These nanoparticles are nontoxic, chemically inert and have long plasma circulation lifetime, making them suitable as nanodevices for imaging using photoacoustics. Experiments on phantoms and rat brains tumors ex-vivo demonstrate the high sensitivity of photoacoustic imaging in delineating the tumor, containing contrast agent at concentrations too low to be visualized by eye. The control tumors without nanoparticles did not show any enhanced signal. This study shows that photoacoustic imaging facilitated with the nanoparticle contrast agent could contribute to future surgical procedures for glioma.

  15. Research on the image fusion and target extraction based on bionic compound eye system

    NASA Astrophysics Data System (ADS)

    Zhang, Shaowei; Hao, Qun; Song, Yong; Wang, Zihan; Zhang, Kaiyu; Zhang, Shiyu

    2015-08-01

    People attach more and more importance to bionic compound eye due to its advantages such as small volume, large field of view and sensitivity to high-speed moving objects. Small field of view and large volume are the disadvantages of traditional image sensor and in order to avoid these defects, this paper intends to build a set of compound eye system based on insect compound eye structure and visual processing mechanism. In the center of this system is the primary sensor which has high resolution ratio. The primary sensor is surrounded by the other six sensors which have low resolution ratio. Based on this system, this paper will study the target image fusion and extraction method by using plane compound eye structure. This paper designs a control module which can combine the distinguishing features of high resolution image with local features of low resolution image so as to conduct target detection, recognition and location. Compared with traditional ways, the way of high resolution in the center and low resolution around makes this system own the advantages of high resolution and large field of view and enables the system to detect the object quickly and recognize the object accurately.

  16. Molecular imaging of hepatocellular carcinoma xenografts with epidermal growth factor receptor targeted affibody probes.

    PubMed

    Zhao, Ping; Yang, Xiaoyang; Qi, Shibo; Liu, Hongguang; Jiang, Han; Hoppmann, Susan; Cao, Qizhen; Chua, Mei-Sze; So, Samuel K; Cheng, Zhen

    2013-01-01

    Hepatocellular carcinoma (HCC) is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%-20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR) has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET) or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo. PMID:23710458

  17. Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia

    PubMed Central

    Herhaus, Peter; Habringer, Stefan; Philipp-Abbrederis, Kathrin; Vag, Tibor; Gerngross, Carlos; Schottelius, Margret; Slotta-Huspenina, Julia; Steiger, Katja; Altmann, Torben; Weißer, Tanja; Steidle, Sabine; Schick, Markus; Jacobs, Laura; Slawska, Jolanta; Müller-Thomas, Catharina; Verbeek, Mareike; Subklewe, Marion; Peschel, Christian; Wester, Hans-Jürgen; Schwaiger, Markus; Götze, Katharina; Keller, Ulrich

    2016-01-01

    Acute myeloid leukemia originates from leukemia-initiating cells that reside in the protective bone marrow niche. CXCR4/CXCL12 interaction is crucially involved in recruitment and retention of leukemia-initiating cells within this niche. Various drugs targeting this pathway have entered clinical trials. To evaluate CXCR4 imaging in acute myeloid leukemia, we first tested CXCR4 expression in patient-derived primary blasts. Flow cytometry revealed that high blast counts in patients with acute myeloid leukemia correlate with high CXCR4 expression. The wide range of CXCR4 surface expression in patients was reflected in cell lines of acute myeloid leukemia. Next, we evaluated the CXCR4-specific peptide Pentixafor by positron emission tomography imaging in mice harboring CXCR4 positive and CXCR4 negative leukemia xenografts, and in 10 patients with active disease. [68Ga]Pentixafor-positron emission tomography showed specific measurable disease in murine CXCR4 positive xenografts, but not when CXCR4 was knocked out with CRISPR/Cas9 gene editing. Five of 10 patients showed tracer uptake correlating well with leukemia infiltration assessed by magnetic resonance imaging. The mean maximal standard uptake value was significantly higher in visually CXCR4 positive patients compared to CXCR4 negative patients. In summary, in vivo molecular CXCR4 imaging by means of positron emission tomography is feasible in acute myeloid leukemia. These data provide a framework for future diagnostic and theranostic approaches targeting the CXCR4/CXCL12-defined leukemia-initiating cell niche. PMID:27175029

  18. An automatic ellipse and line targets detection method from synthetic aperture sonar images

    NASA Astrophysics Data System (ADS)

    Liu, Wei; Li, Bao-Li; Liu, Ji-Yuan; Zhang, Chun-Hua

    2009-10-01

    Detection of ellipse and line targets is important for the analysis of Synthetic Aperture Sonar (SAS) images. An automatic ellipse and line targets detection method from synthetic aperture sonar images is presented. The method mainly has three procedures: preprocessing of SAS images, Zernike Orthogonal Moment Edge Detection Algorithm (ZOMEDA), line and ellipse detection. The guidance is presented firstly on how to perform the preprocessing of SAS images. Then, ZOMEDA is utilized to produce edge points with both the direction and position information. Principles of ZOMEDA with the 7x7 template are analyzed and the coefficients to carry out the ZOMEDA are calculated and listed. The idea of Random Sample Consensus (RANSAC) is applied to the Line and ellipse detection procedure to improve the robustness and the computing efficiency. Detail procedures of RANSAC are analyzed in the article. Calculating of line and ellipse parameters is pivotal to carry out the idea of RANSAC. Principles are analyzed on how to calculate the parameters of the line and ellipse based on the direction and position information. Another important procedure, parameters refinement, is also discussed. At last, the line and ellipse detection method is applied to simulated datasets and lake-trial datasets for validation.

  19. Aggregation-Induced Emission Luminogen-Embedded Silica Nanoparticles Containing DNA Aptamers for Targeted Cell Imaging.

    PubMed

    Wang, Xiaoyan; Song, Panshu; Peng, Lu; Tong, Aijun; Xiang, Yu

    2016-01-13

    Conventional fluorophores usually undergo aggregation-caused quenching (ACQ), which limits the loading amount of these fluorophores in nanoparticles for bright fluorescence imaging. On the contrary, fluorophores with aggregation-induced emission (AIE) characteristics are strongly fluorescent in their aggregate states and have been an ideal platform for developing highly fluorescent nanomaterials, such as fluorescent silica nanoparticles (FSNPs). In this work, AIE luminogens based on salicylaldehyde hydrazones were embedded in silica nanoparticles through a facile noncovalent approach, which afforded AIE-FSNPs emitting much brighter fluorescence than that of some commercial fluorescein-doped silica and polystyrene nanoparticles. These AIE-FSNPs displaying multiple fluorescence colors were fabricated by a general method, and they underwent much less fluorescence variation due to environmental pH changes compared with fluorescein-hybridized FSNPs. In addition, a DNA aptamer specific to nucleolin was functionalized on the surface of AIE-FSNPs for targeted cell imaging. Fluorescent microscopy and flow cytometry studies both revealed highly selective fluorescence staining of MCF-7 (a cancer cell line with nucleolin overexpression) over MCF-10A (normal) cells by the aptamer-functionalized AIE-FSNPs. The fluorescence imaging in different color channels was achieved using AIE-FSNPs containing each of the AIE luminogens, as well as photoactivatable fluorescent imaging of target cells by the caged AIE fluorophore. PMID:26653325

  20. Optical and nuclear imaging of glioblastoma with phosphatidylserine-targeted nanovesicles

    PubMed Central

    Blanco, Víctor M.; Chu, Zhengtao; LaSance, Kathleen; Gray, Brian D.; Pak, Koon Yan; Rider, Therese; Greis, Kenneth D.; Qi, Xiaoyang

    2016-01-01

    Multimodal tumor imaging with targeted nanoparticles potentially offers both enhanced specificity and sensitivity, leading to more precise cancer diagnosis and monitoring. We describe the synthesis and characterization of phenol-substituted, lipophilic orange and far-red fluorescent dyes and a simple radioiodination procedure to generate a dual (optical and nuclear) imaging probe. MALDI-ToF analyses revealed high iodination efficiency of the lipophilic reporters, achieved by electrophilic aromatic substitution using the chloramide 1,3,4,6-tetrachloro-3α,6α-diphenyl glycoluril (Iodogen) as the oxidizing agent in an organic/aqueous co-solvent mixture. Upon conjugation of iodine-127 or iodine-124-labeled reporters to tumor-targeting SapC-DOPS nanovesicles, optical (fluorescent) and PET imaging was performed in mice bearing intracranial glioblastomas. In addition, tumor vs non-tumor (normal brain) uptake was compared using iodine-125. These data provide proof-of-principle for the potential value of SapC-DOPS for multimodal imaging of glioblastoma, the most aggressive primary brain tumor. PMID:27096954

  1. Locality Preserving Projection Based on Endmember Extraction for Hyperspectral Image Dimensionality Reduction and Target Detection.

    PubMed

    Wang, Yiting; Huang, Shiqi; Liu, Zhigang; Wang, Hongxia; Liu, Daizhi

    2016-09-01

    In order to reduce the effect of spectral variability on calculation precision for the weighted matrix in the locality preserving projection (LPP) algorithm, an improved dimensionality reduction method named endmember extraction-based locality preserving projection (EE-LPP) is proposed in this paper. The method primarily uses the vertex component analysis (VCA) method to extract endmember spectra from hyperspectral imagery. It then calculates the similarity between pixel spectra and the endmember spectra by using the spectral angle distance, and uses it as the basis for selecting neighboring pixels in the image and constructs a weighted matrix between pixels. Finally, based on the weighted matrix, the idea of the LPP algorithm is applied to reduce the dimensions of hyperspectral image data. Experimental results of real hyperspectral data demonstrate that the low-dimensional features acquired by the proposed methods can fully reflect the characteristics of the original image and further improve target detection accuracy. PMID:27566254

  2. Targeted lipid–polyaniline hybrid nanoparticles for photoacoustic imaging guided photothermal therapy of cancer

    NASA Astrophysics Data System (ADS)

    Wang, Jinping; Yan, Ran; Guo, Fang; Yu, Meng; Tan, Fengping; Li, Nan

    2016-07-01

    Designing a targeted and versatile photothermal agent for the integration of precise diagnosis and effective photothermal treatment of tumors is desirable but remains a great challenge. In this study, folic acid ligand conjugated lipid-coated polyaniline hybrid nanoparticles (FA–Lipid–PANI NPs) were successfully fabricated by a distinctive technology. The obtained hybrid FA–Lipid–PANI NPs with small size exhibited not only significant photoacoustic (PA) imaging signals, but also a remarkable photothermal effect for tumor treatment. With PA imaging and photothermal therapy (PTT), the tumor could be accurately positioned and thoroughly eradicated in vivo after intravenous injection of FA–Lipid–PANI NPs. These multifunctional nanoparticles could play an important role in simultaneously facilitating imaging and PTT to achieve better therapeutic efficacy.

  3. Targeted lipid-polyaniline hybrid nanoparticles for photoacoustic imaging guided photothermal therapy of cancer

    NASA Astrophysics Data System (ADS)

    Wang, Jinping; Yan, Ran; Guo, Fang; Yu, Meng; Tan, Fengping; Li, Nan

    2016-07-01

    Designing a targeted and versatile photothermal agent for the integration of precise diagnosis and effective photothermal treatment of tumors is desirable but remains a great challenge. In this study, folic acid ligand conjugated lipid-coated polyaniline hybrid nanoparticles (FA-Lipid-PANI NPs) were successfully fabricated by a distinctive technology. The obtained hybrid FA-Lipid-PANI NPs with small size exhibited not only significant photoacoustic (PA) imaging signals, but also a remarkable photothermal effect for tumor treatment. With PA imaging and photothermal therapy (PTT), the tumor could be accurately positioned and thoroughly eradicated in vivo after intravenous injection of FA-Lipid-PANI NPs. These multifunctional nanoparticles could play an important role in simultaneously facilitating imaging and PTT to achieve better therapeutic efficacy.

  4. Cucurbit[8]uril Regulated Activatable Supramolecular Photosensitizer for Targeted Cancer Imaging and Photodynamic Therapy.

    PubMed

    Wang, Xiao-Qiang; Lei, Qi; Zhu, Jing-Yi; Wang, Wen-Jing; Cheng, Qian; Gao, Fan; Sun, Yun-Xia; Zhang, Xian-Zheng

    2016-09-01

    Activatable photosensitizers (aPSs) have emerged as promising photodynamic therapy (PDT) agents for simultaneous imaging and selective ablation of cancer. However, traditional synthetic aPSs are limited by complex design and tedious synthesis. Here, aPS regulated by cucurbit[8]uril (CB[8]) for targeted cancer imaging and PDT is reported. This system is based on the host-guest interaction between biotinylated toluidine blue (TB-B) and CB[8] to form 2TB-B@CB[8]. Moreover, a facile strategy to turn off/on the fluorescence and photodynamic activity of TB-B is developed through the reversible assembly/disassembly of 2TB-B@CB[8]. This established system can achieve selective accumulation in tumor, light-up cancer imaging, and enhanced anticancer behavior. Therefore, this work provides a novel and promising strategy for the aPS build via simple and facile regulation of supramolecular chemistry. PMID:27513690

  5. A low-noise laser-gated imaging system for long-range target identification

    NASA Astrophysics Data System (ADS)

    Baker, Ian M.; Duncan, Stuart S.; Copley, Jeremy W.

    2004-08-01

    BAE SYSTEMS has developed a laser-illuminated, gated imaging system for long range target identification which has generated bright images at ranges in excess of 10km from modest laser energies. The system is based on a short pulsewidth laser and a custom detector for sensing the return pulse. The source is a Nd YAG laser converted by an optical parametric oscillator (OPO) to 1571nm and producing 20ns pulses at 15Hz. The detector (named SWIFT) is a 320x256 array of HgCdTe photodiodes operating with high avalanche gain to achieve sensitivities as low as 10 photon rms. A custom silicon multiplexer performs the signal injection and temporal gating function, and adds additional electronic gain. Trials show that the current detectors have gate edges equivalent to 1.5m in range and complete extinction of signals outside of the gated range. The detector is encapsulated in an integrated-detector-cooler-assembly and utilises standard productionised thermal imaging electronics to perform non-uniformity correction and grey scale images. Imaging trials using the camera have shown little excess noise, crosstalk or non-uniformity due to the use of avalanching in the HgCdTe photodiodes up to gains of over 100. The images have shown high spatial resolution arising from the use of solid state focal plane array technology. The imagery, collected both in the laboratory and in field trials, has been used to explore the phenomenology unique to laser-illuminated targets and to verify system models.

  6. Molecularly-Targeted Gold-Based Nanoparticles for Cancer Imaging and Near-Infrared Photothermal Therapy

    NASA Astrophysics Data System (ADS)

    Day, Emily Shannon

    2011-12-01

    This thesis advances the use of nanoparticles as multifunctional agents for molecularly-targeted cancer imaging and photothermal therapy. Cancer mortality has remained relatively unchanged for several decades, indicating a significant need for improvements in care. Researchers are evaluating strategies incorporating nanoparticles as exogenous energy absorbers to deliver heat capable of inducing cell death selectively to tumors, sparing normal tissue. Molecular targeting of nanoparticles is predicted to improve photothermal therapy by enhancing tumor retention. This hypothesis is evaluated with two types of nanoparticles. The nanoparticles utilized, silica-gold nanoshells and gold-gold sulfide nanoparticles, can convert light energy into heat to damage cancerous cells. For in vivo applications nanoparticles are usually coated with poly(ethylene glycol) (PEG) to increase blood circulation time. Here, heterobifunctional PEG links nanoparticles to targeting agents (antibodies and growth factors) to provide cell-specific binding. This approach is evaluated through a series of experiments. In vitro, antibody-coated nanoparticles can bind breast carcinoma cells expressing the targeted receptor and act as contrast agents for multiphoton microscopy prior to inducing cell death via photoablation. Furthermore, antibody-coated nanoparticles can bind tissue ex vivo at levels corresponding to receptor expression, suggesting they should bind their target even in the complex biological milieu. This is evaluated by comparing the accumulation of antibody-coated and PEG-coated nanoparticles in subcutaneous glioma tumors in mice. Contrary to expectations, antibody targeting did not yield more nanoparticles within tumors. Nevertheless, these studies established the sensitivity of glioma to photothermal therapy; mice treated with PEG-coated nanoshells experienced 57% complete tumor regression versus no regression in control mice. Subsequent experiments employed intracranial tumors to

  7. Neutrophil-Mediated Regulation of Innate and Adaptive Immunity: The Role of Myeloperoxidase

    PubMed Central

    Odobasic, Dragana; Kitching, A. Richard; Holdsworth, Stephen R.

    2016-01-01

    Neutrophils are no longer seen as leukocytes with a sole function of being the essential first responders in the removal of pathogens at sites of infection. Being armed with numerous pro- and anti-inflammatory mediators, these phagocytes can also contribute to the development of various autoimmune diseases and can positively or negatively regulate the generation of adaptive immune responses. In this review, we will discuss how myeloperoxidase, the most abundant neutrophil granule protein, plays a key role in the various functions of neutrophils in innate and adaptive immunity. PMID:26904693

  8. Radionuclide 131I-labeled multifunctional dendrimers for targeted SPECT imaging and radiotherapy of tumors

    NASA Astrophysics Data System (ADS)

    Zhu, Jingyi; Zhao, Lingzhou; Cheng, Yongjun; Xiong, Zhijuan; Tang, Yueqin; Shen, Mingwu; Zhao, Jinhua; Shi, Xiangyang

    2015-10-01

    We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 (131I). The generated multifunctional 131I-G5.NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to 131I labeling, the G5.NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive 131I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.We report the synthesis, characterization, and utilization of radioactive 131I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and

  9. RGD-functionalized ultrasmall iron oxide nanoparticles for targeted T1-weighted MR imaging of gliomas

    NASA Astrophysics Data System (ADS)

    Luo, Yu; Yang, Jia; Yan, Yu; Li, Jingchao; Shen, Mingwu; Zhang, Guixiang; Mignani, Serge; Shi, Xiangyang

    2015-08-01

    We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration range, and display targeting specificity to glioma cells overexpressing αvβ3 integrin in vitro. With the relatively high r1 relaxivity (r1 = 1.4 mM-1 s-1), the Fe3O4-PEG-RGD particles can be used as an efficient nanoprobe for targeted T1-weighted positive MR imaging of glioma cells in vitro and the xenografted tumor model in vivo via an active RGD-mediated targeting pathway. The developed RGD-functionalized Fe3O4 NPs may hold great promise to be used as a nanoprobe for targeted T1-weighted MR imaging of different αvβ3 integrin-overexpressing cancer cells or biological systems.We report a convenient approach to prepare ultrasmall Fe3O4 nanoparticles (NPs) functionalized with an arginylglycylaspartic acid (RGD) peptide for in vitro and in vivo magnetic resonance (MR) imaging of gliomas. In our work, stable sodium citrate-stabilized Fe3O4 NPs were prepared by a solvothermal route. Then, the carboxylated Fe3O4 NPs stabilized with sodium citrate were conjugated with polyethylene glycol (PEG)-linked RGD. The formed ultrasmall RGD-functionalized nanoprobe (Fe3O4-PEG-RGD) was fully characterized using different techniques. We show that these Fe3O4-PEG-RGD particles with a size of 2.7 nm are water-dispersible, stable, cytocompatible and hemocompatible in a given concentration

  10. A novel neural network based image reconstruction model with scale and rotation invariance for target identification and classification for Active millimetre wave imaging

    NASA Astrophysics Data System (ADS)

    Agarwal, Smriti; Bisht, Amit Singh; Singh, Dharmendra; Pathak, Nagendra Prasad

    2014-12-01

    Millimetre wave imaging (MMW) is gaining tremendous interest among researchers, which has potential applications for security check, standoff personal screening, automotive collision-avoidance, and lot more. Current state-of-art imaging techniques viz. microwave and X-ray imaging suffers from lower resolution and harmful ionizing radiation, respectively. In contrast, MMW imaging operates at lower power and is non-ionizing, hence, medically safe. Despite these favourable attributes, MMW imaging encounters various challenges as; still it is very less explored area and lacks suitable imaging methodology for extracting complete target information. Keeping in view of these challenges, a MMW active imaging radar system at 60 GHz was designed for standoff imaging application. A C-scan (horizontal and vertical scanning) methodology was developed that provides cross-range resolution of 8.59 mm. The paper further details a suitable target identification and classification methodology. For identification of regular shape targets: mean-standard deviation based segmentation technique was formulated and further validated using a different target shape. For classification: probability density function based target material discrimination methodology was proposed and further validated on different dataset. Lastly, a novel artificial neural network based scale and rotation invariant, image reconstruction methodology has been proposed to counter the distortions in the image caused due to noise, rotation or scale variations. The designed neural network once trained with sample images, automatically takes care of these deformations and successfully reconstructs the corrected image for the test targets. Techniques developed in this paper are tested and validated using four different regular shapes viz. rectangle, square, triangle and circle.

  11. Fluorescence imaging of vascular endothelial growth factor in mice tumors using targeted liposome ICG probe

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Xu, Yan; Backer, Marina V.; Backer, Joseph M.; Zhu, Quing

    2013-03-01

    Indocyanine Green encapsulating liposomes (Lip/ICG) and scVEGF-Lip/ICG liposomes, decorated with site-specifically lipidated engineered single-chain vascular endothelial growth factor (scVEGF) for targeting VEGF receptors were tested as potential tracers for fluorescent tomography. Two groups of experiments were conducted with tumor-bearing mice (n=4 to 6 per group) with tumors placed in a scattering medium at the imaging depths of 1.5 and 2.0 cm. Lip/ICG and scVEGF-Lip/ICG were injected intravenously in the amounts corresponding to 5 nmol of ICG/mouse. We detected kinetics of increase and decline in fluorescent signals in tumors for both imaging depths and for both targeted and untargeted Lip/ICG. Maximum fluorescent signals were approximately 2-fold higher at 1.5 cm vs. 2.0 cm imaging. A signal from untargeted Lip/ICG reached maximum at 15 min post-injection and then rapidly declined with t1/2 ~15 min. In contrast, a signal from targeted scVEGF-Lip/ICG reached maximum at 30 min post-injection and then slow declined with t1/2 ~60-90 min. Preferential retention of scVEGF-Lip(ICG) vs. Lip(ICG) was confirmed by the analysis of fluorescence in cryosections of corresponding tumors, harvested at 400 min post-injection. Our results suggest that targeted scVEGF-Lip/ICG can provide for significantly better post-injection time window for detection of relatively deeply seated tumors.

  12. Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles

    PubMed Central

    Kim, Jeong-Yeon; Ryu, Ju Hee; Schellingerhout, Dawid; Sun, In-Cheol; Lee, Su-Kyoung; Jeon, Sangmin; Kim, Jiwon; Kwon, Ick Chan; Nahrendorf, Matthias; Ahn, Cheol-Hee; Kim, Kwangmeyung; Kim, Dong-Eog

    2015-01-01

    Computed tomography (CT) is the current standard for time-critical decision-making in stroke patients, informing decisions on thrombolytic therapy with tissue plasminogen activator (tPA), which has a narrow therapeutic index. We aimed to develop a CT-based method to directly visualize cerebrovascular thrombi and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib-GC-AuNP. This targeted imaging agent and non-targeted control agent were characterized in vitro and in vivo in C57Bl/6 mice (n = 107) with FeCl3-induced carotid thrombosis and/or embolic ischemic stroke. Fibrin-binding capacity was superior with fib-GC-AuNPs compared to GC-AuNPs, with thrombi visualized as high density on microCT (mCT). mCT imaging using fib-GC-AuNP allowed the prompt detection and quantification of cerebral thrombi, and monitoring of tPA-mediated thrombolytic effect, which reflected histological stroke outcome. Furthermore, recurrent thrombosis could be diagnosed by mCT without further nanoparticle administration for up to 3 weeks. fib-GC-AuNP-based direct cerebral thrombus imaging greatly enhance the value and information obtainable by regular CT, has multiple uses in basic / translational vascular research, and will likely allow personalized thrombolytic therapy in clinic by a) optimizing tPA-dosing to match thrombus burden, b) enabling the rational triage of patients to more radical therapies such as endovascular clot-retrieval, and c) potentially serving as a theranostic platform for targeted delivery of concurrent thrombolysis. PMID:26199648

  13. Molecular photoacoustic imaging of breast cancer using an actively targeted conjugated polymer

    PubMed Central

    Balasundaram, Ghayathri; Ho, Chris Jun Hui; Li, Kai; Driessen, Wouter; Dinish, US; Wong, Chi Lok; Ntziachristos, Vasilis; Liu, Bin; Olivo, Malini

    2015-01-01

    Conjugated polymers (CPs) are upcoming optical contrast agents in view of their unique optical properties and versatile synthetic chemistry. Biofunctionalization of these polymer-based nanoparticles enables molecular imaging of biological processes. In this work, we propose the concept of using a biofunctionalized CP for noninvasive photoacoustic (PA) molecular imaging of breast cancer. In particular, after verifying the PA activity of a CP nanoparticle (CP dots) in phantoms and the targeting efficacy of a folate-functionalized version of the same (folate-CP dots) in vitro, we systemically administered the probe into a folate receptor-positive (FR+ve) MCF-7 breast cancer xenograft model to demonstrate the possible application of folate-CP dots for imaging FR+ve breast cancers in comparison to CP dots with no folate moieties. We observed a strong PA signal at the tumor site of folate-CP dots-administered mice as early as 1 hour after administration as a result of the active targeting of the folate-CP dots to the FR+ve tumor cells but a weak PA signal at the tumor site of CP-dots-administered mice as a result of the passive accumulation of the probe by enhanced permeability and retention effect. We also observed that folate-CP dots produced ~4-fold enhancement in the PA signal in the tumor, when compared to CP dots. These observations demonstrate the great potential of this active-targeting CP to be used as a contrast agent for molecular PA diagnostic imaging in various biomedical applications. PMID:25609951

  14. A new target ligand Ser–Glu for PEPT1-overexpressing cancer imaging

    PubMed Central

    Dai, Tongcheng; Li, Na; Zhang, Lingzhi; Zhang, Yuanxing; Liu, Qin

    2016-01-01

    Nanoparticles functionalized with active target ligands have been widely used for tumor-specific diagnosis and therapy. The target ligands include antibodies, peptides, proteins, small molecules, and nucleic acid aptamers. Here, we utilize dipeptide Ser–Glu (DIP) as a new ligand to functionalize polymer-based fluorescent nanoparticles (NPs) for pancreatic cancer target imaging. We demonstrate that in the first step, Ser–Glu-conjugated NPs (NPs-DIP) efficiently bind to AsPC-1 and in the following NPs-DIP are internalized into AsPC-1 in vitro. The peptide transporter 1 inhibition experiment reveals that the targeting effects mainly depend on the specific binding of DIP to peptide transporter 1, which is remarkably upregulated in pancreatic cancer cells compared with varied normal cells. Furthermore, NPs-DIP specifically accumulate in the site of pancreatic tumor xenograft and are further internalized into the tumor cells in vivo after intravenous administration, indicating that DIP successfully enhanced nanoparticles internalization efficacy into tumor cells in vivo. This work establishes Ser–Glu to be a new tumor-targeting ligand and provides a promising tool for future tumor diagnostic or therapeutic applications. PMID:26811678

  15. Targeted in-vivo computed tomography (CT) imaging of tissue ACE using concentrated lisinopril-capped gold nanoparticle solutions

    NASA Astrophysics Data System (ADS)

    Daniel, Marie-Christine; Aras, Omer; Smith, Mark F.; Nan, Anjan; Fleiter, Thorsten

    2010-04-01

    The development of cardiac and pulmonary fibrosis have been associated with overexpression of angiotensin-converting enzyme (ACE). Moreover, ACE inhibitors, such as lisinopril, have shown a benificial effect for patients diagnosed with heart failure or systemic hypertension. Thus targeted imaging of the ACE is of crucial importance for monitoring of the tissue ACE activity as well as the treatment efficacy in heart failure. In this respect, lisinopril-capped gold nanoparticles were prepared to provide a new type of probe for targeted molecular imaging of ACE by tuned K-edge computed tomography (CT) imaging. Concentrated solutions of these modified gold nanoparticles, with a diameter around 16 nm, showed high contrast in CT imaging. These new targeted imaging agents were thus used for in vivo imaging on rat models.

  16. Advances in image compression and automatic target recognition; Proceedings of the Meeting, Orlando, FL, Mar. 30, 31, 1989

    NASA Technical Reports Server (NTRS)

    Tescher, Andrew G. (Editor)

    1989-01-01

    Various papers on image compression and automatic target recognition are presented. Individual topics addressed include: target cluster detection in cluttered SAR imagery, model-based target recognition using laser radar imagery, Smart Sensor front-end processor for feature extraction of images, object attitude estimation and tracking from a single video sensor, symmetry detection in human vision, analysis of high resolution aerial images for object detection, obscured object recognition for an ATR application, neural networks for adaptive shape tracking, statistical mechanics and pattern recognition, detection of cylinders in aerial range images, moving object tracking using local windows, new transform method for image data compression, quad-tree product vector quantization of images, predictive trellis encoding of imagery, reduced generalized chain code for contour description, compact architecture for a real-time vision system, use of human visibility functions in segmentation coding, color texture analysis and synthesis using Gibbs random fields.

  17. Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent

    PubMed Central

    Kossatz, Susanne; Brand, Christian; Gutiontov, Stanley; Liu, Jonathan T. C.; Lee, Nancy Y.; Gönen, Mithat; Weber, Wolfgang A.; Reiner, Thomas

    2016-01-01

    Earlier and more accurate detection of oral squamous cell carcinoma (OSCC) is essential to improve the prognosis of patients and to reduce the morbidity of surgical therapy. Here, we demonstrate that the nuclear enzyme Poly(ADP-ribose)Polymerase 1 (PARP1) is a promising target for optical imaging of OSCC with the fluorescent dye PARPi-FL. In patient-derived OSCC specimens, PARP1 expression was increased 7.8 ± 2.6-fold when compared to normal tissue. Intravenous injection of PARPi-FL allowed for high contrast in vivo imaging of human OSCC models in mice with a surgical fluorescence stereoscope and high-resolution imaging systems. The emitted signal was specific for PARP1 expression and, most importantly, PARPi-FL can be used as a topical imaging agent, spatially resolving the orthotopic tongue tumors in vivo. Collectively, our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve as a screening tool and help to guide surgical resections. PMID:26900125

  18. Polymer encapsulated upconversion nanoparticle/iron oxide nanocomposites for multimodal imaging and magnetic targeted drug delivery.

    PubMed

    Xu, Huan; Cheng, Liang; Wang, Chao; Ma, Xinxing; Li, Yonggang; Liu, Zhuang

    2011-12-01

    Multimodal imaging and imaging-guided therapies have become a new trend in the current development of cancer theranostics. In this work, we encapsulate hydrophobic upconversion nanoparticles (UCNPs) together with iron oxide nanoparticles (IONPs) by using an amphiphilic block copolymer, poly (styrene-block-allyl alcohol) (PS(16)-b-PAA(10)), via a microemulsion method, obtaining an UC-IO@Polymer multi-functional nanocomposite system. Fluorescent dye and anti-cancer drug molecules can be further loaded inside the UC-IO@Polymer nanocomposite for additional functionalities. Utilizing the Squaraine (SQ) dye loaded nanocomposite (UC-IO@Polymer-SQ), triple-modal upconversion luminescence (UCL)/down-conversion fluorescence (FL)/magnetic resonance (MR) imaging is demonstrated in vitro and in vivo, and also applied for in vivo cancer cell tracking in mice. On the other hand, a chemotherapy drug, doxorubicin, is also loaded into the nanocomposite, forming an UC-IO@Polymer-DOX complex, which enables novel imaging-guided and magnetic targeted drug delivery. Our work provides a method to fabricate a nanocomposite system with highly integrated functionalities for multimodal biomedical imaging and cancer therapy.

  19. Tunable and amplified Raman gold nanoprobes for effective tracking (TARGET): in vivo sensing and imaging

    NASA Astrophysics Data System (ADS)

    Gandra, Naveen; Hendargo, Hansford C.; Norton, Stephen J.; Fales, Andrew M.; Palmer, Gregory M.; Vo-Dinh, Tuan

    2016-04-01

    We describe the development of a highly tunable, physiologically stable, and ultra-bright Raman probe, named as TARGET (Tunable and Amplified Raman Gold Nanoprobes for Effective Tracking), for in vitro and in vivo surface-enhanced Raman scattering (SERS) applications. The TARGET structure consists of a gold core inside a larger gold shell with a tunable interstitial gap similar to a ``nanorattle'' structure. The combination of galvanic replacement and the seed mediated growth method was employed to load Raman reporter molecules and subsequently close the pores to prevent leaking and degradation of reporters under physiologically extreme conditions. Precise tuning of the core-shell gap width, core size, and shell thickness allows us to modulate the plasmonic effect and achieve a maximum electric-field (E-field) intensity. The interstitial gap of TARGET nanoprobes can be designed to exhibit a plasmon absorption band at 785 nm, which is in resonance with the dye absorption maximum and lies in the ``tissue optical window'', resulting in ultra-bright SERS signals for in vivo studies. The results of in vivo measurements of TARGETs in laboratory mice illustrated the usefulness of these nanoprobes for medical sensing and imaging.We describe the development of a highly tunable, physiologically stable, and ultra-bright Raman probe, named as TARGET (Tunable and Amplified Raman Gold Nanoprobes for Effective Tracking), for in vitro and in vivo surface-enhanced Raman scattering (SERS) applications. The TARGET structure consists of a gold core inside a larger gold shell with a tunable interstitial gap similar to a ``nanorattle'' structure. The combination of galvanic replacement and the seed mediated growth method was employed to load Raman reporter molecules and subsequently close the pores to prevent leaking and degradation of reporters under physiologically extreme conditions. Precise tuning of the core-shell gap width, core size, and shell thickness allows us to modulate the

  20. Multifunctional unimolecular micelles for cancer-targeted drug delivery and positron emission tomography imaging.

    PubMed

    Xiao, Yuling; Hong, Hao; Javadi, Alireza; Engle, Jonathan W; Xu, Wenjin; Yang, Yunan; Zhang, Yin; Barnhart, Todd E; Cai, Weibo; Gong, Shaoqin

    2012-04-01

    A multifunctional unimolecular micelle made of a hyperbranched amphiphilic block copolymer was designed, synthesized, and characterized for cancer-targeted drug delivery and non-invasive positron emission tomography (PET) imaging in tumor-bearing mice. The hyperbranched amphiphilic block copolymer, Boltorn(®) H40-poly(L-glutamate-hydrazone-doxorubicin)-b-poly(ethylene glycol) (i.e., H40-P(LG-Hyd-DOX)-b-PEG), was conjugated with cyclo(Arg-Gly-Asp-D-Phe-Cys) peptides (cRGD, for integrin α(v)β(3) targeting) and macrocyclic chelators (1,4,7-triazacyclononane-N, N', N''-triacetic acid [NOTA], for (64)Cu-labeling and PET imaging) (i.e., H40-P(LG-Hyd-DOX)-b-PEG-OCH(3)/cRGD/NOTA, also referred to as H40-DOX-cRGD). The anti-cancer drug, doxorubicin (DOX) was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms (i.e., PLG) via a pH-labile hydrazone linkage to enable pH-controlled drug release. The unimolecular micelles exhibited a uniform size distribution and pH-sensitive drug release behavior. cRGD-conjugated unimolecular micelles (i.e., H40-DOX-cRGD) exhibited a much higher cellular uptake in U87MG human glioblastoma cells due to integrin α(v)β(3)-mediated endocytosis than non-targeted unimolecular micelles (i.e., H40-DOX), thereby leading to a significantly higher cytotoxicity. In U87MG tumor-bearing mice, H40-DOX-cRGD-(64)Cu also exhibited a much higher level of tumor accumulation than H40-DOX-(64)Cu, measured by non-invasive PET imaging and confirmed by biodistribution studies and ex vivo fluorescence imaging. We believe that unimolecular micelles formed by hyperbranched amphiphilic block copolymers that synergistically integrate passive and active tumor-targeting abilities with pH-controlled drug release and PET imaging capabilities provide the basis for future cancer theranostics.

  1. In Vivo Fluorescence Resonance Energy Transfer Imaging for Targeted Anti-Cancer Drug Delivery Kinetics

    NASA Astrophysics Data System (ADS)

    Webb, Kevin; Gaind, Vaibhav; Tsai, Hsiaorho; Bentz, Brian; Chelvam, Venkatesh; Low, Philip

    2012-02-01

    We describe an approach for the evaluation of targeted anti-cancer drug delivery in vivo. The method emulates the drug release and activation process through acceptor release from a targeted donor-acceptor pair that exhibits fluorescence resonance energy transfer (FRET). In this case, folate targeting of the cancer cells is used - 40 % of all human cancers, including ovarian, lung, breast, kidney, brain and colon cancer, over-express folate receptors. We demonstrate the reconstruction of the spatially-dependent FRET parameters in a mouse model and in tissue phantoms. The FRET parameterization is incorporated into a source for a diffusion equation model for photon transport in tissue, in a variant of optical diffusion tomography (ODT) called FRET-ODT. In addition to the spatially-dependent tissue parameters in the diffusion model (absorption and diffusion coefficients), the FRET parameters (donor-acceptor distance and yield) are imaged as a function of position. Modulated light measurements are made with various laser excitation positions and a gated camera. More generally, our method provides a new vehicle for studying disease at the molecular level by imaging FRET parameters in deep tissue, and allows the nanometer FRET ruler to be utilized in deep tissue.

  2. A new look at spotlight mode synthetic aperture radar as tomography: imaging 3-D targets.

    PubMed

    Jakowatz, C V; Thompson, P A

    1995-01-01

    A new 3D tomographic formulation of spotlight mode synthetic aperture radar (SAR) is developed. This extends the pioneering work of Munson et al. (1983), who first formally described SAR in terms of tomography but who made the simplifying assumption that the target scene was 2D. The present authors treat the more general and practical case in which the radar target reflectivities comprise a 3D function. The main goal is to demonstrate that the demodulated radar return data from a spotlight mode collection represent a certain set of samples of the 3D Fourier transform of the target reflectivity function and to do so using a tomographic paradigm instead of traditional range-Doppler analysis. They also show that the tomographic approach is useful in interpreting the reconstructed 2D SAR image corresponding to a 3D scene. Specifically, the well-known SAR phenomenon of layover is easily explained in terms of tomographic projections and is shown to be analogous to the projection effect in conventional optical imaging.

  3. Cat-eye target imaging system research and dual-channel DSP implementation

    NASA Astrophysics Data System (ADS)

    Zheng, Zheng; Zhang, Haiyang; Shi, Guang; Han, Lei; Zhao, Changming

    2013-09-01

    In modern warfare, well-equipped and trained snipers have become a mortal malady for the combat troops. How to accurately, timely and quickly find and destroy snipers becomes a research focus of national military experts. In order to effectively detect faint echo signal of cat-eye target and get the snipers' position information in the detection area, a small size of dual-channel active laser detection system with monochrome and color Charge-couple Devices(CCD) is designed, which is based on the laser imaging principle of cat-eye effect, associated tests are also conducted. The dual-channel video capture can obtain more information of target area, while taking advantage of the high sensitivity of monochrome CCD will also provide more accurate grayscale information for the video image processing. In order to achieve the miniaturization of system, we choose a video processing board whose size is only 54mm*90mm as hardware platform to complete the algorithm. For verifying the feasibility and accuracy of algorithm, we ultimately build a full set of experimental detection system. The test results show that the system can accurately detect and mark typical cat-eye target from background under different distances, which verifies the rationality and validity of the proposed system and has certain practicality and promotion in the active laser detection system research areas.

  4. ISAR imaging of maneuvering targets based on the range centroid Doppler technique.

    PubMed

    Lv, Xiaolei; Xing, Mengdao; Wan, Chunru; Zhang, Shouhong

    2010-01-01

    A new inverse synthetic aperture radar (ISAR) imaging approach is presented for application in situations where the maneuverability of noncooperative target is not too severe and the Doppler variation of subechoes from scatterers can be approximated as a first-order polynomial. The proposed algorithm is referred to as the range centroid Doppler (RCD) ISAR imaging technique and is based on the stretch Keystone-Wigner transform (SKWT). The SKWT introduces a stretch weight factor containing a range of chirp rate into the autocorrelation function of each cross-range profile and uses a 1-D interpolation of the phase history which we call stretch keystone formatting. The processing simultaneously eliminates the effects of linear frequency migration for all signal components regardless of their unknown chirp rate in time-frequency plane, but not for the noise or for the cross terms. By utilizing this novel technique, clear ISAR imaging can be achieved for maneuvering targets without an exhaustive search procedure for the motion parameters. Performance comparison is carried out to evaluate the improvement of the RCD technique versus other methods such as the conventional range Doppler (RD) technique, the range instantaneous Doppler (RID) technique, and adaptive joint time-frequency (AJTF) technique. Examples provided demonstrate the effectiveness of the RCD technique with both simulated and experimental ISAR data.

  5. Integrin αvβ3-Targeted Imaging of Lung Cancer1

    PubMed Central

    Chen, Xiaoyuan; Sievers, Eric; Hou, Yingping; Park, Ryan; Tohme, Michel; Bart, Robert; Bremner, Ross; Bading, James R; Conti, Peter S

    2005-01-01

    Abstract A series of radiolabeled cyclic arginine-glycine-aspartic acid (RGD) peptide ligands for cell adhesion molecule integrin αvβ3-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter 64Cu-labeled PEGylated dimeric RGD peptide radiotracer 64Cu-DOTA-PEG-E[c(RGDyK)]2 for lung cancer imaging. The PEGylated RGD peptide indicated integrin αvβ3 avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, and diaphragm. As a comparison, fluorodeoxyglucose (FDG) scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. 64Cu-DOTA-PEG-E[c(RGDyK)]2 is an excellent positron emission tomography (PET) tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress. PMID:15799827

  6. Lactoferrin conjugated iron oxide nanoparticles for targeting brain glioma cells in magnetic particle imaging

    NASA Astrophysics Data System (ADS)

    Tomitaka, Asahi; Arami, Hamed; Gandhi, Sonu; Krishnan, Kannan M.

    2015-10-01

    Magnetic Particle Imaging (MPI) is a new real-time imaging modality, which promises high tracer mass sensitivity and spatial resolution directly generated from iron oxide nanoparticles. In this study, monodisperse iron oxide nanoparticles with median core diameters ranging from 14 to 26 nm were synthesized and their surface was conjugated with lactoferrin to convert them into brain glioma targeting agents. The conjugation was confirmed with the increase of the hydrodynamic diameters, change of zeta potential, and Bradford assay. Magnetic particle spectrometry (MPS), performed to evaluate the MPI performance of these nanoparticles, showed no change in signal after lactoferrin conjugation to nanoparticles for all core diameters, suggesting that the MPI signal is dominated by Néel relaxation and thus independent of hydrodynamic size difference or presence of coating molecules before and after conjugations. For this range of core sizes (14-26 nm), both MPS signal intensity and spatial resolution improved with increasing core diameter of nanoparticles. The lactoferrin conjugated iron oxide nanoparticles (Lf-IONPs) showed specific cellular internalization into C6 cells with a 5-fold increase in MPS signal compared to IONPs without lactoferrin, both after 24 h incubation. These results suggest that Lf-IONPs can be used as tracers for targeted brain glioma imaging using MPI.

  7. Cisplatin Prodrug-Conjugated Gold Nanocluster for Fluorescence Imaging and Targeted Therapy of the Breast Cancer

    PubMed Central

    Zhou, Fangyuan; Feng, Bing; Yu, Haijun; Wang, Dangge; Wang, Tingting; Liu, Jianping; Meng, Qingshuo; Wang, Siling; Zhang, Pengcheng; Zhang, Zhiwen; Li, Yaping

    2016-01-01

    Theranostic nanomedicine has emerged as a promising modality for cancer diagnosis and treatment. In this study, we report the fabrication of fluorescence gold nanoclusters (GNC) conjugated with a cisplatin prodrug and folic acid (FA) (FA-GNC-Pt) for fluorescence imaging and targeted chemotherapy of breast cancer. The physio-chemical properties of FA-GNC-Pt nanoparticles are thoroughly characterized by fluorescence/UV-Vis spectroscopic measurement, particle size and zeta-potential examination. We find that FA-modification significantly accelerated the cellular uptake and increased the cytotoxicity of GNC-Pt nanoparticles in murine 4T1 breast cancer cells. Fluorescence imaging in vivo using 4T1 tumor bearing nude mouse model shows that FA-GNC-Pt nanoparticles selectively accumulate in the orthotopic 4T1 tumor and generate strong fluorescence signal due to the tumor targeting effect of FA. Moreover, we demonstrate that FA-GNC-Pt nanoparticles significantly inhibit the growth and lung metastasis of the orthotopically implanted 4T1 breast tumors. All these data imply a good potential of the GNC-based theranostic nanoplatform for fluorescence tumor imaging and cancer therapy. PMID:27022415

  8. Selective Visualization of Cyclooxygenase-2 in Inflammation and Cancer by Targeted Fluorescent Imaging Agents†

    PubMed Central

    Uddin, Md. Jashim; Crews, Brenda C.; Blobaum, Anna L.; Kingsley, Philip J.; Gorden, D. Lee; McIntyre, J. Oliver; Matrisian, Lynn M.; Subbaramaiah, Kotha; Dannenberg, Andrew J.; Piston, David W.; Marnett, Lawrence J.

    2010-01-01

    Effective diagnosis of inflammation and cancer by molecular imaging is challenging because of interference from non-selective accumulation of the contrast agents in normal tissues. Here we report a series of novel fluorescence imaging agents that efficiently target cyclooxygenase-2 (COX-2), which is normally absent from cells, but is found at high levels in inflammatory lesions, and in many premalignant and malignant tumors. After either intraperitoneal or intravenous injection, these reagents become highly enriched in inflamed or tumor tissue compared to normal tissue and this accumulation provides sufficient signal for in vivo fluorescence imaging. Further, we show that only the intact parent compound is found in the region of interest. COX-2-specific delivery was unambiguously confirmed using animals bearing targeted deletions of COX-2 and by blocking the COX-2 active site with high affinity inhibitors in both in vitro and in vivo models. Because of their high specificity, contrast, and detectability, these COX-2 beacons are ideal candidates for detection of inflammatory lesions or early-stage COX-2-expressing human cancers, such as those in the esophagus, oropharynx, and colon. PMID:20430759

  9. Mechanism of interferon-gamma production by monocytes stimulated with myeloperoxidase and neutrophil extracellular traps.

    PubMed

    Yamaguchi, Rui; Kawata, Jin; Yamamoto, Toshitaka; Ishimaru, Yasuji; Sakamoto, Arisa; Ono, Tomomichi; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

    2015-08-01

    Neutrophil extracellular traps (NETs) have an important role in antimicrobial innate immunity and release substances that may modulate the immune response. We investigated the effects of soluble factors from NETs and neutrophil granule proteins on human monocyte function by using the Transwell system to prevent cell-cell contact. NET formation was induced by exposing human neutrophils to phorbol myristate acetate (PMA). When monocytes were incubated with PMA alone, expression of interleukin (IL)-4, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha mRNA was upregulated, but IL-10, IL-12, and interferon (IFN)-gamma mRNA were not detected. Incubation of monocytes with NETs enhanced the expression of IL-10 and IFN-gamma mRNA, but not IL-12 mRNA. Myeloperoxidase stimulated IFN-gamma production by monocytes in a dose-dependent manner. Both a nuclear factor-kappaB inhibitor (PDTC) and an intracellular calcium antagonist (TMB-8) prevented upregulation of IFN-gamma production. Neither a combined p38alpha and p38beta inhibitor (SB203580) nor an extracellular signal-regulated kinase inhibitor (PD98059) suppressed IFN-gamma production. Interestingly, a combined p38gamma and p38delta inhibitor (BIRB796) significantly decreased IFN-gamma production. These findings suggest that myeloperoxidase induces IFN-gamma production by monocytes via p38gamma/delta mitogen-activated protein kinase.

  10. A comparative study of automatic image segmentation algorithms for target tracking in MR-IGRT.

    PubMed

    Feng, Yuan; Kawrakow, Iwan; Olsen, Jeff; Parikh, Parag J; Noel, Camille; Wooten, Omar; Du, Dongsu; Mutic, Sasa; Hu, Yanle

    2016-01-01

    On-board magnetic resonance (MR) image guidance during radiation therapy offers the potential for more accurate treatment delivery. To utilize the real-time image information, a crucial prerequisite is the ability to successfully segment and track regions of interest (ROI). The purpose of this work is to evaluate the performance of different segmentation algorithms using motion images (4 frames per second) acquired using a MR image-guided radiotherapy (MR-IGRT) system. Manual con-tours of the kidney, bladder, duodenum, and a liver tumor by an experienced radiation oncologist were used as the ground truth for performance evaluation. Besides the manual segmentation, images were automatically segmented using thresholding, fuzzy k-means (FKM), k-harmonic means (KHM), and reaction-diffusion level set evolution (RD-LSE) algorithms, as well as the tissue tracking algorithm provided by the ViewRay treatment planning and delivery system (VR-TPDS). The performance of the five algorithms was evaluated quantitatively by comparing with the manual segmentation using the Dice coefficient and target registration error (TRE) measured as the distance between the centroid of the manual ROI and the centroid of the automatically segmented ROI. All methods were able to successfully segment the bladder and the kidney, but only FKM, KHM, and VR-TPDS were able to segment the liver tumor and the duodenum. The performance of the thresholding, FKM, KHM, and RD-LSE algorithms degraded as the local image contrast decreased, whereas the performance of the VP-TPDS method was nearly independent of local image contrast due to the reference registration algorithm. For segmenting high-contrast images (i.e., kidney), the thresholding method provided the best speed (< 1 ms) with a satisfying accuracy (Dice = 0.95). When the image contrast was low, the VR-TPDS method had the best automatic contour. Results suggest an image quality determination procedure before segmentation and a combination of

  11. Convergence of temporal and spectral information into acoustic images of complex sonar targets perceived by the echolocating bat, Eptesicus fuscus.

    PubMed

    Simmons, J A; Moss, C F; Ferragamo, M

    1990-02-01

    1. FM echolocating bats (Eptesicus fuscus) were trained to discriminate between a two-component complex target and a one-component simple target simulated by electronically-returned echoes in a series of experiments that explore the composition of the image of the two-component target. In Experiment I, echoes for each target were presented sequentially, and the bats had to compare a stored image of one target with that of the other. The bats made errors when the range of the simple target corresponded to the range of either glint in the complex target, indicating that some trace of the parts of one image interfered with perception of the other image. In Experiment II, echoes were presented simultaneously as well as sequentially, permitting direct masking of echoes from one target to the other. Changes in echo amplitude produced shifts in apparent range whose pattern depended upon the mode of echo presentation. 2. Eptesicus perceives images of complex sonar targets that explicitly represent the location and spacing of discrete glints located at different ranges. The bat perceives the target's structure in terms of its range profile along a psychological range axis using a combination of echo delay and echo spectral representations that together resemble a spectrogram of the FM echoes. The image itself is expressed entirely along a range scale that is defined with reference to echo delay. Spectral information contributes to the image by providing estimates of the range separation of glints, but it is transformed into these estimates. 3. Perceived absolute range is encoded by the timing of neural discharges and is vulnerable to shifts caused by neural amplitude-latency trading, which was estimated at 13 to 18 microseconds per dB from N1 and N4 auditory evoked potentials in Eptesicus. Spectral cues representing the separation of glints within the target are transformed into estimates of delay separations before being incorporated into the image. However, because they

  12. High-resolution ISAR imaging of maneuvering targets by means of the range instantaneous Doppler technique: modeling and performance analysis.

    PubMed

    Berizzi, F; Mese, E D; Diani, M; Martorella, M

    2001-01-01

    Very high resolution inverse synthetic aperture radar (ISAR) imaging of maneuvering targets is a complicated task. In fact, the conventional range Doppler (RD) ISAR technique does not work properly when target motions generate terms higher than the first order in the phase of the received signal relative to each scatterer. This effect typically happens when at least one of these situations occur: (1) very high resolution images are required; (2) the target maneuvers; and (3) the target undergoes significant angular motions (roll, pitch, and yaw). A novel ISAR technique, named range instantaneous Doppler (RID), has been proposed for the reconstruction of very high resolution images of maneuvering targets. In this paper, we analytically show that the RID technique works properly when high-resolution ISAR images are required of maneuvering and/or rolling, pitching, and yawing targets; we also quantify the performance improvement of the RID technique with respect to the RD technique. The problem is tackled from an analytical point of view. First, we define a new model of the ISAR received signal that is valid for maneuvering targets, then we derive and compare the analytical expression of the point spread function (PSF) for the two techniques. Furthermore, we perform a statistical analysis to evaluate the improvement of the RID technique versus the RD technique in terms of spatial resolution. Finally, we prove the effectiveness of the RID technique by simulating the imaging process for two different targets: (1) a ship that undergoes roll, pitch and yaw motions and (2) a fast maneuvering airplane.

  13. Multifunctional quantum dot-polypeptide hybrid nanogel for targeted imaging and drug delivery

    NASA Astrophysics Data System (ADS)

    Yang, Jie; Yao, Ming-Hao; Wen, Lang; Song, Ji-Tao; Zhang, Ming-Zhen; Zhao, Yuan-Di; Liu, Bo

    2014-09-01

    A new type of multifunctional quantum dot (QD)-polypeptide hybrid nanogel with targeted imaging and drug delivery properties has been developed by metal-affinity driven self-assembly between artificial polypeptides and CdSe-ZnS core-shell QDs. On the surface of QDs, a tunable sandwich-like microstructure consisting of two hydrophobic layers and one hydrophilic layer between them was verified by capillary electrophoresis, transmission electron microscopy, and dynamic light scattering measurements. Hydrophobic and hydrophilic drugs can be simultaneously loaded in a QD-polypeptide nanogel. In vitro drug release of drug-loaded QD-polypeptide nanogels varies strongly with temperature, pH, and competitors. A drug-loaded QD-polypeptide nanogel with an arginine-glycine-aspartic acid (RGD) motif exhibited efficient receptor-mediated endocytosis in αvβ3 overexpressing HeLa cells but not in the control MCF-7 cells as analyzed by confocal microscopy and flow cytometry. In contrast, non-targeted QD-polypeptide nanogels revealed minimal binding and uptake in HeLa cells. Compared with the original QDs, the QD-polypeptide nanogels showed lower in vitro cytotoxicity for both HeLa cells and NIH 3T3 cells. Furthermore, the cytotoxicity of the targeted QD-polypeptide nanogel was lower for normal NIH 3T3 cells than that for HeLa cancer cells. These results demonstrate that the integration of imaging and drug delivery functions in a single QD-polypeptide nanogel has the potential for application in cancer diagnosis, imaging, and therapy.A new type of multifunctional quantum dot (QD)-polypeptide hybrid nanogel with targeted imaging and drug delivery properties has been developed by metal-affinity driven self-assembly between artificial polypeptides and CdSe-ZnS core-shell QDs. On the surface of QDs, a tunable sandwich-like microstructure consisting of two hydrophobic layers and one hydrophilic layer between them was verified by capillary electrophoresis, transmission electron

  14. Iodine-125-labeled cRGD-gold nanoparticles as tumor-targeted radiosensitizer and imaging agent

    NASA Astrophysics Data System (ADS)

    Su, Ning; Dang, Yajie; Liang, Guangli; Liu, Guizhi

    2015-04-01

    Research interests on radiosensitive property of gold nanoparticles (GNPs) are rapidly raised because of the extensively proved in vitro effectiveness and clinical necessity. However, the issue of targeted accumulation of GNPs in tumor tissues hindered the transference to in vivo applications. In this study, hybrid nano-sized cyclic Arg-Gly-Asp-conjugated GNPs (cRGD-GNPs) integrated with radioactive iodine-125 was fabricated as tumor-targeted radiosensitizer. Therapeutic effects, including acute apoptosis (2 days post treatment) and long-term influence (up to 21 days), were investigated on NCI-H446 tumor-bearing mice via Tc-99 m-Annexin V SPECT and volume measurements, respectively. Apoptosis and volume loss were consistent in showing that tumor growth was effectively suppressed via the treatment of 125I-cRGD-GNP sensitized radiotherapy (RT), a more significantly radiosensitive effect than the treatment of non-targeted GNPs with RT, RT treatment alone, and no treatment. SPECT/CT images showed that the uptake of cRGD-GNPs by tumor tissues reached the peak target/non-target value of 4.76 at around 2 h post injection, and dynamic radioactivity monitoring showed that 125I-cRGD-GNPs maintained about 2.5% of injected dosage at 55 h post injection. For long-term influence, a significant radiosensitized RT-induced volume loss was observed. Hence, cyclic RGD conjugation makes the GNP-based radiosensitizer tumor targeting, offering a new modality for enhancing radiotherapeutic efficacy. Additionally, the introduction of I-125 serves as both a therapeutic factor and a radiotracer for in vivo tracking of GNPs.

  15. Characterizing EPR-Mediated Passive Drug Targeting using Contrast-Enhanced Functional Ultrasound Imaging

    PubMed Central

    Theek, Benjamin; Gremse, Felix; Kunjachan, Sijumon; Fokong, Stanley; Pola, Robert; Pechar, Michal; Deckers, Roel; Storm, Gert; Ehling, Josef; Kiessling, Fabian; Lammers, Twan

    2014-01-01

    The Enhanced Permeability and Retention (EPR) effect is extensively used in drug delivery research. Taking into account that EPR is a highly variable phenomenon, we have here set out to evaluate if contrast-enhanced functional ultrasound (ceUS) imaging can be employed to characterize EPR-mediated passive drug targeting to tumors. Using standard fluorescence molecular tomography (FMT) and two different protocols for hybrid computed tomography-fluorescence molecular tomography (CT-FMT), the tumor accumulation of a ~10 nm-sized near-infrared-fluorophore-labeled polymeric drug carrier (pHPMA-Dy750) was evaluated in CT26 tumor-bearing mice. In the same set of animals, two different ceUS techniques (2D MIOT and 3D B-mode imaging) were employed to assess tumor vascularization. Subsequently, the degree of tumor vascularization was correlated with the degree of EPR-mediated drug targeting. Depending on the optical imaging protocol used, the tumor accumulation of the polymeric drug carrier ranged from 5-12% of the injected dose. The degree of tumor vascularization, determined using ceUS, varied from 4-11%. For both hybrid CT-FMT protocols, a good correlation between the degree of tumor vascularization and the degree of tumor accumulation was observed, with in the case of reconstructed CT-FMT, correlation coefficients of ~0.8 and p-values of <0.02. These findings indicate that ceUS can be used to characterize and predict EPR, and potentially also to pre-selecting patients likely to respond to passively tumor-targeted nanomedicine treatments. PMID:24631862

  16. Urban-area extraction from polarimetric SAR image using combination of target decomposition and orientation angle

    NASA Astrophysics Data System (ADS)

    Zou, Bin; Lu, Da; Wu, Zhilu; Qiao, Zhijun G.

    2016-05-01

    The results of model-based target decomposition are the main features used to discriminate urban and non-urban area in polarimetric synthetic aperture radar (PolSAR) application. Traditional urban-area extraction methods based on modelbased target decomposition usually misclassified ground-trunk structure as urban-area or misclassified rotated urbanarea as forest. This paper introduces another feature named orientation angle to improve urban-area extraction scheme for the accurate mapping in urban by PolSAR image. The proposed method takes randomness of orientation angle into account for restriction of urban area first and, subsequently, implements rotation angle to improve results that oriented urban areas are recognized as double-bounce objects from volume scattering. ESAR L-band PolSAR data of the Oberpfaffenhofen Test Site Area was used to validate the proposed algorithm.

  17. Automatic target recognition and tracking using an acousto-optic image correlator

    SciTech Connect

    Molley, P.A.; Kast, B.A. )

    1992-05-01

    This paper discusses a hybrid electro-optic image processor, developed for automatic target recognition and tracking using an acousto-optic correlator and digital electronics. The optical system performs the computationally intensive correlation operation on the large 2-D input scenes. The electronics provide the decision-making capability and also perform part of the postprocessing needed for increasing the peak-to-clutter ratio in cluttered scenes. The system is able to analyze each correlation plane and apply a real-time template selection algorithm to accommodate scale or rotation changes of the target. A demonstration of the current system capabilities is presented using a terrain board with several different types of stationary and moving model vehicles.

  18. Tunable and amplified Raman gold nanoprobes for effective tracking (TARGET): in vivo sensing and imaging.

    PubMed

    Gandra, Naveen; Hendargo, Hansford C; Norton, Stephen J; Fales, Andrew M; Palmer, Gregory M; Vo-Dinh, Tuan

    2016-04-28

    We describe the development of a highly tunable, physiologically stable, and ultra-bright Raman probe, named as TARGET (Tunable and Amplified Raman Gold Nanoprobes for Effective Tracking), for in vitro and in vivo surface-enhanced Raman scattering (SERS) applications. The TARGET structure consists of a gold core inside a larger gold shell with a tunable interstitial gap similar to a "nanorattle" structure. The combination of galvanic replacement and the seed mediated growth method was employed to load Raman reporter molecules and subsequently close the pores to prevent leaking and degradation of reporters under physiologically extreme conditions. Precise tuning of the core-shell gap width, core size, and shell thickness allows us to modulate the plasmonic effect and achieve a maximum electric-field (E-field) intensity. The interstitial gap of TARGET nanoprobes can be designed to exhibit a plasmon absorption band at 785 nm, which is in resonance with the dye absorption maximum and lies in the "tissue optical window", resulting in ultra-bright SERS signals for in vivo studies. The results of in vivo measurements of TARGETs in laboratory mice illustrated the usefulness of these nanoprobes for medical sensing and imaging. PMID:27064259

  19. TSPO 18 kDa (PBR) Targeted Photosensitizers for Cancer Imaging (PET) and PDT.

    PubMed

    Chen, Yihui; Sajjad, Munawwar; Wang, Yanfang; Batt, Carrie; Nabi, Hani A; Pandey, Ravindra K

    2011-02-10

    Translocator protein (TSPO) 18 kDa overexpression has been observed in a large variety of human cancers, especially breast cancers. PK 11195, an isoquinoline analogue, is one of the ligands of highest TSPO binding affinity. Due to the long biological half life of our photosensitizers, there is a need to label them with a long lived radioisotope, for example I-124. Our objectives are to find translocator protein targeted photosensitizers for both tumor imaging (PET) and photodynamic therapy (PDT). I-PK 11195 is conjugated with the tumor avid photosensitizer HPPH. We find that those two tumor avid components complement each other and make the conjugate molecule even more tumor avid; compared to the photosensitizer itself, the conjugate is found to show improved PDT efficacy. It is concluded that I-PK 11195 can be a good vehicle to deliver radionuclide and photosensitizer to TSPO overexpressed tumor regions. Such conjugates could be useful for both tumor imaging (PET) and PDT.

  20. The Dark Energy Spectroscopic Instrument (DESI): The NOAO DECam Legacy Imaging Survey and DESI Target Selection

    NASA Astrophysics Data System (ADS)

    Schlegel, David J.; Blum, Robert D.; Castander, Francisco Javier; Dey, Arjun; Finkbeiner, Douglas P.; Foucaud, Sebastien; Honscheid, Klaus; James, David; Lang, Dustin; Levi, Michael; Moustakas, John; Myers, Adam D.; Newman, Jeffrey; Nord, Brian; Nugent, Peter E.; Patej, Anna; Reil, Kevin; Rudnick, Gregory; Rykoff, Eli S.; Ford Schlafly, Eddie; Stark, Casey; Valdes, Francisco; Walker, Alistair R.; Weaver, Benjamin; DECam Legacy Survey Collaboration

    2015-01-01

    The DECam Legacy Survey will conduct a 3-band imaging survey of the Sloan Digital Sky Survey (SDSS) extragalactic footprint. The Dark Energy Camera (DECam) will be used to image the 6700 square degree footprint overlapping SDSS in the region -20 < Dec < +30 deg, to depths of g=24.7, r=23.9, z=23.0. The survey will be conducted from Fall 2014 through Spring 2017, with periodic data releases beginning in March 2015. These releases will include catalogs constructed with the Tractor-based multi-wavelength forced photometry applied to the DECam and WISE satellite data.The Dark Energy Spectroscopic Instrument (DESI) will observe 24 million galaxies and quasars in a 14,000 square degree extragalactic footprint. The targeting in that footprint will be provided by a combination of these DECam data, the MOSAIC camera on the Mayall 4-meter, and the 90Prime camera on the Bok Telescope.

  1. Effects of window size and shape on accuracy of subpixel centroid estimation of target images

    NASA Technical Reports Server (NTRS)

    Welch, Sharon S.

    1993-01-01

    A new algorithm is presented for increasing the accuracy of subpixel centroid estimation of (nearly) point target images in cases where the signal-to-noise ratio is low and the signal amplitude and shape vary from frame to frame. In the algorithm, the centroid is calculated over a data window that is matched in width to the image distribution. Fourier analysis is used to explain the dependency of the centroid estimate on the size of the data window, and simulation and experimental results are presented which demonstrate the effects of window size for two different noise models. The effects of window shape were also investigated for uniform and Gaussian-shaped windows. The new algorithm was developed to improve the dynamic range of a close-range photogrammetric tracking system that provides feedback for control of a large gap magnetic suspension system (LGMSS).

  2. Mn-doped near-infrared quantum dots as multimodal targeted probes for pancreatic cancer imaging.

    PubMed

    Yong, Ken-Tye

    2009-01-01

    This work presents a novel approach to producing manganese (Mn)-doped quantum dots (Mnd-QDs) emitting in the near-infrared (NIR). Surface functionalization of Mnd-QDs with lysine makes them stably disperse in aqueous media and able to conjugate with targeting molecules. The nanoparticles were structurally and compositionally characterized and maintained a high photoluminescence quantum yield and displayed paramagnetism in water. The receptor-mediated delivery of bioconjugated Mnd-QDs into pancreatic cancer cells was demonstrated using the confocal microscopy technique. Cytotoxicity of Mnd-QDs on live cells has been evaluated. The NIR-emitting characteristic of the QDs has been exploited to acquire whole animal body imaging with high contrast signals. In addition, histological and blood analysis of mice have revealed that no long-term toxic effects arise from MnD-QDs. These studies suggest multimodal Mnd-QDs have the potentials as probes for early pancreatic cancer imaging and detection.

  3. Aptamer-mediated indirect quantum dot labeling and fluorescent imaging of target proteins in living cells

    NASA Astrophysics Data System (ADS)

    Liu, Jianbo; Zhang, Pengfei; Yang, Xiaohai; Wang, Kemin; Guo, Qiuping; Huang, Jin; Li, Wei

    2014-12-01

    Protein labeling for dynamic living cell imaging plays a significant role in basic biological research, as well as in clinical diagnostics and therapeutics. We have developed a novel strategy in which the dynamic visualization of proteins within living cells is achieved by using aptamers as mediators for indirect protein labeling of quantum dots (QDs). With this strategy, the target protein angiogenin was successfully labeled with fluorescent QDs in a minor intactness model, which was mediated by the aptamer AL6-B. Subsequent living cell imaging analyses indicated that the QDs nanoprobes were selectively bound to human umbilical vein endothelial cells, gradually internalized into the cytoplasm, and mostly localized in the lysosome organelle, indicating that the labeled protein retained high activity. Compared with traditional direct protein labeling methods, the proposed aptamer-mediated strategy is simple, inexpensive, and provides a highly selective, stable, and intact labeling platform that has shown great promise for future biomedical labeling and intracellular protein dynamic analyses.

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

    NASA Astrophysics Data System (ADS)

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

    2012-10-01

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

  5. Correction: Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy

    NASA Astrophysics Data System (ADS)

    Kim, Kyoung Sub; Kim, Jiyoung; Lee, Joo Young; Matsuda, Shofu; Hideshima, Sho; Mori, Yasurou; Osaka, Tetsuya; Na, Kun

    2016-06-01

    Correction for `Stimuli-responsive magnetic nanoparticles for tumor-targeted bimodal imaging and photodynamic/hyperthermia combination therapy' by Kyoung Sub Kim, et al., Nanoscale, 2016, DOI: 10.1039/c6nr02273a.

  6. Estimation of Cn² based on scintillation of fixed targets imaged through atmospheric turbulence.

    PubMed

    Gulich, Damián; Funes, Gustavo; Pérez, Darío; Zunino, Luciano

    2015-12-01

    We define a pixel-based scintillation index for dynamic incoherent imaging of fixed high-contrast targets through atmospheric turbulence. We propose a simple setup to study this parameter varying the Cn(2) constant in controlled laboratory conditions (weak fluctuation regime). We find the semi-empirical relationship between the pixel-based scintillation index and the index of refraction structure constant, which we then employ to estimate Cn(2) successfully in an independent case in which this value was not known beforehand.

  7. Design of an integrated hardware interface for AOSLO image capture and cone-targeted stimulus delivery

    PubMed Central

    Yang, Qiang; Arathorn, David W.; Tiruveedhula, Pavan; Vogel, Curtis R.; Roorda, Austin

    2010-01-01

    We demonstrate an integrated FPGA solution to project highly stabilized, aberration-corrected stimuli directly onto the retina by means of real-time retinal image motion signals in combination with high speed modulation of a scanning laser. By reducing the latency between target location prediction and stimulus delivery, the stimulus location accuracy, in a subject with good fixation, is improved to 0.15 arcminutes from 0.26 arcminutes in our earlier solution. We also demonstrate the new FPGA solution is capable of delivering stabilized large stimulus pattern (up to 256x256 pixels) to the retina. PMID:20721171

  8. High-resolution imaging and target designation through clouds or smoke

    SciTech Connect

    Perry, Michael D.

    2003-01-01

    A method and system of combining gated intensifiers and advances in solid-state, short-pulse laser technology, compact systems capable of producing high resolution (i.e., approximately less than 20 centimeters) optical images through a scattering medium such as dense clouds, fog, smoke, etc. may be achieved from air or ground based platforms. Laser target designation through a scattering medium is also enabled by utilizing a short pulse illumination laser and a relatively minor change to the detectors on laser guided munitions.

  9. Targeted thiazole orange derivative with folate: synthesis, fluorescence and in vivo fluorescence imaging.

    PubMed

    Fei, Xuening; Gu, Yingchun; Wang, Yiqi; Meng, Qingyang; Zhang, Baolian

    2010-10-11

    A Thiazole Orange conjugated with folate derivative was synthesized in two steps. Firstly, folate was coupled with 1-(3-aminopropyl)-4-methylquinolinium bromide to afford folate-methylquinolinium bromide, which then reacted with benzothiazolium to obtain the title folate-conjugated compound. The compound was evaluated by ¹H-NMR MS, TG/DTA and fluorescence spectroscopic methods. The title compound could selectively target folate receptor expressing tumors according to the in vivo fluorescence imaging preliminarily performed on nude mice with breast tumors.

  10. Targeted near-IR QDs-loaded micelles for cancer therapy and imaging.

    PubMed

    Nurunnabi, Md; Cho, Kwang Jae; Choi, Joon Sig; Huh, Kang Moo; Lee, Yong-kyu

    2010-07-01

    The use of water-soluble, functionalized quantum dots (QDs) that are highly stable against oxidation for biological and biomedical applications is currently one of the fastest growing fields of nanotechnology. Polymer-based nanoparticles are now widely used for drug delivery and targeted therapy. We modified the surface of near Infrared QDs by the solid dispersion method using PEG-PCDA and PCDA-Herceptin conjugates to demonstrate water-solubility and target-specific properties. Upon UV irradiation, QD cores located within nanoprobes were further stabilized by intramicellar cross-linking between neighboring PCDA-Herceptin moieties. These cross-linked nanoprobes showed higher stability and less toxicity. Near-IR QDs-loaded micelles were spherical with diameters of around 130-150 nm. The anti-tumor effect of near-IR QDs-loaded micelles against MDA-MB-231 tumors was remarkably better than that of control. Mice treated with the near-IR QDs-loaded micelles had a tumor volume of about 285 mm(3), indicating shrinkage in initial tumor volume and inhibition of tumor growth by 77.3% compared to that of control group (saline injection). In addition, near-IR QDs-loaded micelles were injected intravenously into tumor-bearing nude mice for simultaneous tumor therapy and imaging. We observed that the targeted near-IR QDs-loaded micelles distributed rapidly throughout the animal body including the tumor in real time. These multi-functional nanoprobes could therefore be used for both active and passive targeting, imaging and treatment of cancers in the early stage. PMID:20409581

  11. Classification on the monogenic scale space: application to target recognition in SAR image.

    PubMed

    Ganggang Dong; Gangyao Kuang

    2015-08-01

    This paper introduces a novel classification strategy based on the monogenic scale space for target recognition in Synthetic Aperture Radar (SAR) image. The proposed method exploits monogenic signal theory, a multidimensional generalization of the analytic signal, to capture the characteristics of SAR image, e.g., broad spectral information and simultaneous spatial localization. The components derived from the monogenic signal at different scales are then applied into a recently developed framework, sparse representation-based classification (SRC). Moreover, to deal with the data set, whose target classes are not linearly separable, the classification via kernel combination is proposed, where the multiple components of the monogenic signal are jointly considered into a unifying framework for target recognition. The novelty of this paper comes from: the development of monogenic feature via uniformly downsampling, normalization, and concatenation of the components at various scales; the development of score-level fusion for SRCs; and the development of composite kernel learning for classification. In particular, the comparative experimental studies under nonliteral operating conditions, e.g., structural modifications, random noise corruption, and variations in depression angle, are performed. The comparative experimental studies of various algorithms, including the linear support vector machine and the kernel version, the SRC and the variants, kernel SRC, kernel linear representation, and sparse representation of monogenic signal, are performed too. The feasibility of the proposed method has been successfully verified using Moving and Stationary Target Acquiration and Recognition database. The experimental results demonstrate that significant improvement for recognition accuracy can be achieved by the proposed method in comparison with the baseline algorithms.

  12. Investigating the photosensitizer-potential of targeted gallium corrole using multimode optical imaging

    NASA Astrophysics Data System (ADS)

    Hwang, Jae Youn; Lubow, Jay; Chu, David; Gross, Zeev; Gray, Harry B.; Farkas, Daniel L.; Medina-Kauwe, Lali K.

    2011-02-01

    We recently developed a novel therapeutic particle, HerGa, for breast cancer treatment and detection. HerGa consists of a tumor-targeted cell penetration protein noncovalently assembled with a gallium-metallated corrole. The corrole is structurally similar to porphyrin, emits intense fluorescence, and has proven highly effective for breast tumor treatment preclinically, without light exposure. Here, we tested HerGa as a photosensitizer for photodynamic therapy and investigated its mechanism of action using multimode optical imaging. Using confocal fluorescence imaging, we observed that HerGa disrupts the mitochondrial membrane potential in situ, and this disruption is substantially augmented by light exposure. In addition, spectral and fluorescence lifetime imaging were utilized to both validate the mitochondrial membrane potential disruption and investigate HerGa internalization, allowing us to optimize the timing for light dosimetry. We observed, using advanced multimode optical imaging, that light at a specific wavelength promotes HerGa cytotoxicity, which is likely to cause disruption of mitochondrial function. Thus, we can identify for the first time the capacity of HerGa as a photosensitizer for photodynamic therapy and reveal its mechanism of action, opening possibilities for therapeutic intervention in human breast cancer management.

  13. Framed X-Ray Imaging of Cryogenic Target Implosion Cores on Omega

    NASA Astrophysics Data System (ADS)

    Marshall, F. J.; Goncharov, V. N.; Glebov, V. Yu.; Regan, S. P.; Sangster, T. C.; Stoeckl, C.

    2015-11-01

    Cryogenic DT target implosions being performed on the OMEGA Laser System are now being diagnosed by two high-speed x-ray framing cameras (~ 30-ps frame times) able to time- and space-resolve the evolving high-pressure stagnating plasma core. One high-speed framing camera is coupled to a pinhole array and is able to image the core emission every 15 ps with ~ 16- μm spatial resolution. It can accurately measure the time of x-ray emission peak and duration. The other framing camera is coupled to a novel 16-image Kirkpatrick-Baez (KB)-type x-ray optic providing ~ 7- μm spatial resolution and can also sample the emission with images spaced in time by as little as ~ 15 ps. The core emission size determined from the framed KB images at the peak of stagnation allows for inferences of core pressure when combined with measurements of the ion temperature, burnwidth, and neutron yield. This material is based upon work supported by the Department of Energy National Nuclear Security Administration under Award Number DE-NA0001944.

  14. Automatic geocoding of high-value targets using structural image analysis and GIS data

    NASA Astrophysics Data System (ADS)

    Soergel, Uwe; Thoennessen, Ulrich

    1999-12-01

    Geocoding based merely on navigation data and sensor model is often not possible or precise enough. In these cases an improvement of the preregistration through image-based approaches is a solution. Due to the large amount of data in remote sensing automatic geocoding methods are necessary. For geocoding purposes appropriate tie points, which are present in image and map, have to be detected and matched. The tie points are base of the transformation function. Assigning the tie points is combinatorial problem depending on the number of tie points. This number can be reduced using structural tie points like corners or crossings of prominent extended targets (e.g. harbors, airfields). Additionally the reliability of the tie points is improved. Our approach extracts structural tie points independently in the image and in the vector map by a model-based image analysis. The vector map is provided by a GIS using ATKIS data base. The model parameters are extracted from maps or collateral information of the scenario. The two sets of tie points are automatically matched with a Geometric Hashing algorithm. The algorithm was successfully applied to VIS, IR and SAR data.

  15. Intracellular bottom-up generation of targeted nanosensors for single-molecule imaging

    NASA Astrophysics Data System (ADS)

    Hou, Yanyan; Arai, Satoshi; Kitaguchi, Tetsuya; Suzuki, Madoka

    2016-02-01

    Organic dyes are useful tools for sensing cellular activities but unfavorable in single-molecule imaging, whereas quantum dots (QDs) are widely applied in single-molecule imaging but with few sensing applications. Here, to visualize cellular activities by monitoring the response of a single probe in living cells, we propose a bottom-up approach to generate nanoprobes where four organic dyes are conjugated to tetravalent single-chain avidin (scAVD) proteins via an intracellular click reaction. We demonstrate that the nanoprobes, exhibiting increased brightness and enhanced photostability, were detectable as single dots in living cells. The ease of intracellular targeting allowed the tracking of endoplasmic reticulum (ER) remodeling with nanometer spatial resolution. Conjugating thermosensitive dyes generated temperature-sensitive nanoprobes on ER membranes that successfully monitored local temperature changes in response to external heat pulses. Our approach is potentially a suitable tool for visualizing localized cellular activities with single probe sensitivity in living cells.Organic dyes are useful tools for sensing cellular activities but unfavorable in single-molecule imaging, whereas quantum dots (QDs) are widely applied in single-molecule imaging but with few sensing applications. Here, to visualize cellular activities by monitoring the response of a single probe in living cells, we propose a bottom-up approach to generate nanoprobes where four organic dyes are conjugated to tetravalent single-chain avidin (scAVD) proteins via an intracellular click reaction. We demonstrate that the nanoprobes, exhibiting increased brightness and enhanced photostability, were detectable as single dots in living cells. The ease of intracellular targeting allowed the tracking of endoplasmic reticulum (ER) remodeling with nanometer spatial resolution. Conjugating thermosensitive dyes generated temperature-sensitive nanoprobes on ER membranes that successfully monitored local

  16. Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer.

    PubMed

    Sun, Yao; Ma, Xiaowei; Zhang, Zhe; Sun, Ziyan; Loft, Mathias; Ding, Bingbing; Liu, Changhao; Xu, Liying; Yang, Meng; Jiang, Yuxin; Liu, Jianfeng; Xiao, Yuling; Cheng, Zhen; Hong, Xuechuan

    2016-08-17

    Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients.

  17. Direct Imaging of ER Calcium with Targeted-Esterase Induced Dye Loading (TED)

    PubMed Central

    Samtleben, Samira; Jaepel, Juliane; Fecher, Caroline; Andreska, Thomas; Rehberg, Markus; Blum, Robert

    2013-01-01

    Visualization of calcium dynamics is important to understand the role of calcium in cell physiology. To examine calcium dynamics, synthetic fluorescent Ca2+ indictors have become popular. Here we demonstrate TED (= targeted-esterase induced dye loading), a method to improve the release of Ca2+ indicator dyes in the ER lumen of different cell types. To date, TED was used in cell lines, glial cells, and neurons in vitro. TED bases on efficient, recombinant targeting of a high carboxylesterase activity to the ER lumen using vector-constructs that express Carboxylesterases (CES). The latest TED vectors contain a core element of CES2 fused to a red fluorescent protein, thus enabling simultaneous two-color imaging. The dynamics of free calcium in the ER are imaged in one color, while the corresponding ER structure appears in red. At the beginning of the procedure, cells are transduced with a lentivirus. Subsequently, the infected cells are seeded on coverslips to finally enable live cell imaging. Then, living cells are incubated with the acetoxymethyl ester (AM-ester) form of low-affinity Ca2+ indicators, for instance Fluo5N-AM, Mag-Fluo4-AM, or Mag-Fura2-AM. The esterase activity in the ER cleaves off hydrophobic side chains from the AM form of the Ca2+ indicator and a hydrophilic fluorescent dye/Ca2+ complex is formed and trapped in the ER lumen. After dye loading, the cells are analyzed at an inverted confocal laser scanning microscope. Cells are continuously perfused with Ringer-like solutions and the ER calcium dynamics are directly visualized by time-lapse imaging. Calcium release from the ER is identified by a decrease in fluorescence intensity in regions of interest, whereas the refilling of the ER calcium store produces an increase in fluorescence intensity. Finally, the change in fluorescent intensity over time is determined by calculation of ΔF/F0. PMID:23685703

  18. Preclinical Study on GRPR-Targeted (68)Ga-Probes for PET Imaging of Prostate Cancer.

    PubMed

    Sun, Yao; Ma, Xiaowei; Zhang, Zhe; Sun, Ziyan; Loft, Mathias; Ding, Bingbing; Liu, Changhao; Xu, Liying; Yang, Meng; Jiang, Yuxin; Liu, Jianfeng; Xiao, Yuling; Cheng, Zhen; Hong, Xuechuan

    2016-08-17

    Gastrin-releasing peptide receptor (GRPR) targeted positron emission tomography (PET) is a highly promising approach for imaging of prostate cancer (PCa) in small animal models and patients. Developing a GRPR-targeted PET probe with excellent in vivo performance such as high tumor uptake, high contrast, and optimal pharmacokinetics is still very challenging. Herein, a novel bombesin (BBN) analogue (named SCH1) based on JMV594 peptide modified with an 8-amino octanoic acid spacer (AOC) was thus designed and conjugated with the metal chelator 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA). The resulting NODAGA-SCH1 was then radiolabeled with (68)Ga and evaluated for PET imaging of PCa. Compared with (68)Ga-NODAGA-JMV594 probe, (68)Ga-NODAGA-SCH1 exhibited excellent PET/CT imaging properties on PC-3 tumor-bearing nude mice, such as high tumor uptake (5.80 ± 0.42 vs 3.78 ± 0.28%ID/g, 2 h) and high tumor/muscle contrast (16.6 ± 1.50 vs 8.42 ± 0.61%ID/g, 2 h). Importantly, biodistribution data indicated a relatively similar accumulation of (68)Ga-NODAGA-SCH1 was observed in the liver (4.21 ± 0.42%ID/g) and kidney (3.41 ± 0.46%ID/g) suggesting that the clearance is through both the kidney and the liver. Overall, (68)Ga-NODAGA-SCH1 showed promising in vivo properties and is a promising candidate for translation into clinical PET-imaging of PCa patients. PMID:27399868

  19. AOTF-based near-infrared imaging spectrometer for rapid identification of camouflaged target

    NASA Astrophysics Data System (ADS)

    Gao, Zhifan; Zeng, Libo; Wu, Qiongshui

    2014-11-01

    camouflaged target from complex backgrounds. In addition, only the objective lens and its accessories are required to be replaced for its use in microscopic spectral imaging system, which may be popularized to a large number of other possible applications.

  20. Exploration of target molecules for molecular imaging of inflammatory bowel disease

    SciTech Connect

    Higashikawa, Kei; Akada, Naoki; Yagi, Katsuharu; Watanabe, Keiko; Kamino, Shinichiro; Kanayama, Yousuke; Hiromura, Makoto; Enomoto, Shuichi

    2011-07-08

    Highlights: {sup {yields}18}F-FDG PET could discriminate each inflamed area of IBD model mice clearly. {sup {yields}18}F-FDG PET could not discriminate the difference of pathogenic mechanism. {yields} Cytokines and cytokine receptors expression was different by pathogenic mechanism. {yields} Cytokines and cytokine receptors would be new target molecules for IBD imaging. -- Abstract: Molecular imaging technology is a powerful tool for the diagnosis of inflammatory bowel disease (IBD) and the efficacy evaluation of various drug therapies for it. However, it is difficult to elucidate directly the relationships between the responsible molecules and IBD using existing probes. Therefore, the development of an alternative probe that is able to elucidate the pathogenic mechanism and provide information on the appropriate guidelines for treatment is earnestly awaited. In this study, we investigated pathognomonic molecules in the intestines of model mice. The accumulation of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) in the inflamed area of the intestines of dextran sulfate sodium (DSS)- or indomethacin (IND)-induced IBD model mice was measured by positron emission tomography (PET) and autoradiography to confirm the inflamed area. The results suggested that the inflammation was selectively induced in the colons of mice by the administration of DSS, whereas it was induced mainly in the ilea and the proximal colons of mice by the administration of IND. To explore attractive target molecules for the molecular imaging of IBD, we evaluated the gene expression levels of cytokines and cytokine receptors in the inflamed area of the intestines of both model mice. We found that the expression levels of cytokines and cytokine receptors were significantly increased during the progression of IBD, whereas the expression levels were decreased as the mucosa began to heal. In particular, the expression levels of these molecules had already changed before the symptoms of IBD appeared. In

  1. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction.

    PubMed

    Thackeray, James T; Bankstahl, Jens P; Wang, Yong; Wollert, Kai C; Bengel, Frank M

    2016-01-01

    Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid (11)C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with (11)C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher (11)C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001). C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery. Serial (11)C-methionine PET was performed 3, 5 and 7d later. MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV). PET detected increased (11)C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/g vs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy). Increased (11)C-methionine uptake was associated with macrophage infiltration of damaged myocardium. Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and (11)C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and early reperfusion confirmed elevated (11)C-methionine uptake in the hypoperfused myocardial region. Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. (11)C-methionine-based molecular imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549

  2. Targeting Amino Acid Metabolism for Molecular Imaging of Inflammation Early After Myocardial Infarction

    PubMed Central

    Thackeray, James T.; Bankstahl, Jens P.; Wang, Yong; Wollert, Kai C.; Bengel, Frank M.

    2016-01-01

    Acute tissue inflammation after myocardial infarction influences healing and remodeling and has been identified as a target for novel therapies. Molecular imaging holds promise for guidance of such therapies. The amino acid 11C-methionine is a clinically approved agent which is thought to accumulate in macrophages, but not in healthy myocytes. We assessed the suitability of positron emission tomography (PET) with 11C-methionine for imaging post-MI inflammation, from cell to mouse to man. Uptake assays demonstrated 7-fold higher 11C-methionine uptake by polarized pro-inflammatory M1 macrophages over anti-inflammatory M2 subtypes (p<0.001). C57Bl/6 mice (n=27) underwent coronary artery ligation or no surgery. Serial 11C-methionine PET was performed 3, 5 and 7d later. MI mice exhibited a perfusion defect in 32-50% of the left ventricle (LV). PET detected increased 11C-methionine accumulation in the infarct territory at 3d (5.9±0.9%ID/g vs 4.7±0.9 in remote myocardium, and 2.6±0.5 in healthy mice; p<0.05 and <0.01 respectively), which declined by d7 post-MI (4.3±0.6 in infarct, 3.4±0.8 in remote; p=0.03 vs 3d, p=0.08 vs healthy). Increased 11C-methionine uptake was associated with macrophage infiltration of damaged myocardium. Treatment with anti-integrin antibodies (anti-CD11a, -CD11b, -CD49d; 100µg) lowered macrophage content by 56% and 11C-methionine uptake by 46% at 3d post-MI. A patient study at 3d after ST-elevation MI and early reperfusion confirmed elevated 11C-methionine uptake in the hypoperfused myocardial region. Targeting of elevated amino acid metabolism in pro-inflammatory M1 macrophages enables PET imaging-derived demarcation of tissue inflammation after MI. 11C-methionine-based molecular imaging may assist in the translation of novel image-guided, inflammation-targeted regenerative therapies. PMID:27570549

  3. Bioinspired Gold Nanorod Functionalization Strategies for MUC1-Targeted Imaging and Photothermal Therapy

    NASA Astrophysics Data System (ADS)

    Zelasko-Leon, Daria Cecylia

    The majority of cancers diagnosed in 2016 are epithelial in origin, constituting 85% of all new cases and predicted to account for 78% of all cancer deaths this year. Given these statistics, improving patient outcomes by providing personalized, multimodal, and minimally invasive medical interventions is critically needed. Mucin 1 (MUC1), a transmembrane glycoprotein, extends over 100 nm from cell membranes and is a key marker promoting epithelial carcinogenesis. Due to its antenna-like manifestation, MUC1 is a unique yet underexplored candidate for targeted cancer therapy, with overexpression in >64% of epithelial cancers. To overcome the limitations of existing treatment strategies for epithelial cancer, this dissertation describes a novel platform for nanomedicine, highlighting bioinspired modifications of gold nanorod (AuNR) surfaces for diagnostic cancer imaging and photothermal therapy. An ongoing challenge in the field of nanomedicine is the need for simple and effective strategies for simple surface modification of nanoparticles to facilitate targeting and enhance efficacy. Here, biofunctionalization of AuNRs was achieved with polydopamine (PD) and tannic acid (TA), polyphenolic compounds found in the marine mussel and throughout the plant kingdom that exhibit promiscuous interfacial binding properties. AuNR stabilization was achieved via PD or TA coatings followed by secondary modification with the serum protein, bovine serum albumin (BSA), or glycoprotein-mimetic polymers. The resultant constructs demonstrated good biocompatibility, enabled diagnostic imaging, and facilitated MUC1-specific photothermal treatment of breast and oral cancer cells. The in vivo performance of BSA and PD modified AuNRs was evaluated in two orthotopic animal models of breast cancer. Clinically relevant hyperthermia and high response rates with MUC1-targeted formulations were found, with significant enhancement of progression-free survival and several complete tumor regressions

  4. Imaging-guided preclinical trials of vascular targeting in prostate cancer

    NASA Astrophysics Data System (ADS)

    Kalmuk, James

    Purpose: Prostate cancer is the most common non-cutaneous malignancy in American men and is characterized by dependence on androgens (Testosterone/Dihydrotestosterone) for growth and survival. Although reduction of serum testosterone levels by surgical or chemical castration transiently inhibits neoplastic growth, tumor adaptation to castrate levels of androgens results in the generation of castration-resistant prostate cancer (CRPC). Progression to CRPC following androgen deprivation therapy (ADT) has been associated with changes in vascular morphology and increased angiogenesis. Based on this knowledge, we hypothesized that targeting tumor vasculature in combination with ADT would result in enhanced therapeutic efficacy against prostate cancer. Methods: To test this hypothesis, we examined the therapeutic activity of a tumor-vascular disrupting agent (tumor-VDA), EPC2407 (Crolibulin(TM)), alone and in combination with ADT in a murine model of prostate cancer (Myc-CaP). A non-invasive multimodality imaging approach based on magnetic resonance imaging (MRI), bioluminescence imaging (BLI), and ultrasound (US) was utilized to characterize tumor response to therapy and to guide preclinical trial design. Imaging results were correlated with histopathologic (H&E) and immunohistochemical (CD31) assessment as well as tumor growth inhibition and survival analyses. Results: Our imaging techniques were able to capture an acute reduction (within 24 hours) in tumor perfusion following castration and VDA monotherapy. BLI revealed onset of recurrent disease 5-7 days post castration prior to visible tumor regrowth suggestive of vascular recovery. Administration of VDA beginning 1 week post castration for 3 weeks resulted in sustained vascular suppression, inhibition of tumor regrowth, and conferred a more pronounced survival benefit compared to either monotherapy. Conclusion: The high mortality rate associated with CRPC underscores the need for investigating novel treatment

  5. Quality Assurance of Ultrasound Imaging Systems for Target Localization and Online Setup Corrections

    SciTech Connect

    Tome, Wolfgang A. Orton, Nigel P.

    2008-05-01

    We describe quality assurance paradigms for ultrasound imaging systems for target localization (UISTL). To determine the absolute localization accuracy of a UISTL, an absolute coordinate system can be established in the treatment room and spherical targets at various depths can be localized. To test the ability of such a system to determine the magnitude of internal organ motion, a phantom that mimics the human male pelvic anatomy can be used to simulate different organ motion ranges. To assess the interuser variability of ultrasound (US) guidance, different experienced users can independently determine the daily organ shifts for the same patients for a number of consecutive fractions. The average accuracy for a UISTL for the localization of spherical targets at various depths has been found to be 0.57 {+-} 0.47 mm in each spatial dimension for various focal depths. For the phantom organ motion test it was found that the true organ motion could be determined to within 1.0 mm along each axis. The variability between different experienced users who localized the same 5 patients for five consecutive fractions was small in comparison to the indicated shifts. In addition to the quality assurance tests that address the ability of a UISTL to accurately localize a target, a thorough quality assurance program should also incorporate the following two aspects to ensure consistent and accurate localization in daily clinical use: (1) adequate training and performance monitoring of users of the US target localization system, and (2) prescreening of patients who may not be good candidates for US localization.

  6. Targeted Iron-Oxide Nanoparticle for Photodynamic Therapy and Imaging of Head and Neck Cancer

    PubMed Central

    2015-01-01

    Photodynamic therapy (PDT) is a highly specific anticancer treatment modality for various cancers, particularly for recurrent cancers that no longer respond to conventional anticancer therapies. PDT has been under development for decades, but light-associated toxicity limits its clinical applications. To reduce the toxicity of PDT, we recently developed a targeted nanoparticle (NP) platform that combines a second-generation PDT drug, Pc 4, with a cancer targeting ligand, and iron oxide (IO) NPs. Carboxyl functionalized IO NPs were first conjugated with a fibronectin-mimetic peptide (Fmp), which binds integrin β1. Then the PDT drug Pc 4 was successfully encapsulated into the ligand-conjugated IO NPs to generate Fmp-IO-Pc 4. Our study indicated that both nontargeted IO-Pc 4 and targeted Fmp-IO-Pc 4 NPs accumulated in xenograft tumors with higher concentrations than nonformulated Pc 4. As expected, both IO-Pc 4 and Fmp-IO-Pc 4 reduced the size of HNSCC xenograft tumors more effectively than free Pc 4. Using a 10-fold lower dose of Pc 4 than that reported in the literature, the targeted Fmp-IO-Pc 4 NPs demonstrated significantly greater inhibition of tumor growth than nontargeted IO-Pc 4 NPs. These results suggest that the delivery of a PDT agent Pc 4 by IO NPs can enhance treatment efficacy and reduce PDT drug dose. The targeted IO-Pc 4 NPs have great potential to serve as both a magnetic resonance imaging (MRI) agent and PDT drug in the clinic. PMID:24923902

  7. Non-invasive in vivo imaging of early metabolic tumor response to therapies targeting choline metabolism.

    PubMed

    Mignion, Lionel; Danhier, Pierre; Magat, Julie; Porporato, Paolo E; Masquelier, Julien; Gregoire, Vincent; Muccioli, Giulio G; Sonveaux, Pierre; Gallez, Bernard; Jordan, Bénédicte F

    2016-04-15

    The cholinic phenotype, characterized by elevated phosphocholine and a high production of total-choline (tCho)-containing metabolites, is a metabolic hallmark of cancer. It can be exploited for targeted therapy. Non-invasive imaging biomarkers are required to evaluate an individual's response to targeted anticancer agents that usually do not rapidly cause tumor shrinkage. Because metabolic changes can manifest at earlier stages of therapy than changes in tumor size, the aim of the current study was to evaluate (1)H-MRS and diffusion-weighted MRI (DW-MRI) as markers of tumor response to the modulation of the choline pathway in mammary tumor xenografts. Inhibition of choline kinase activity was achieved with the direct pharmacological inhibitor H-89, indirect inhibitor sorafenib and down-regulation of choline-kinase α (ChKA) expression using specific short-hairpin RNA (shRNA). While all three strategies significantly decreased tCho tumor content in vivo, only sorafenib and anti-ChKA shRNA significantly repressed tumor growth. The increase of apparent-diffusion-coefficient of water (ADCw) measured by DW-MRI, was predictive of the induced necrosis and inhibition of the tumor growth in sorafenib treated mice, while the absence of change in ADC values in H89 treated mice predicted the absence of effect in terms of tumor necrosis and tumor growth. In conclusion, (1)H-choline spectroscopy can be useful as a pharmacodynamic biomarker for choline targeted agents, while DW-MRI can be used as an early marker of effective tumor response to choline targeted therapies. DW-MRI combined to chol