Synthesis and functionalization of NaGdF4:Yb,Er@NaGdF4 core-shell nanoparticles for possible application as multimodal contrast agents.

PubMed

Baziulyte-Paulaviciene, Dovile; Karabanovas, Vitalijus; Stasys, Marius; Jarockyte, Greta; Poderys, Vilius; Sakirzanovas, Simas; Rotomskis, Ricardas

2017-01-01

Upconverting nanoparticles (UCNPs) are promising, new imaging probes capable of serving as multimodal contrast agents. In this study, monodisperse and ultrasmall core and core-shell UCNPs were synthesized via a thermal decomposition method. Furthermore, it was shown that the epitaxial growth of a NaGdF 4 optical inert layer covering the NaGdF 4 :Yb,Er core effectively minimizes surface quenching due to the spatial isolation of the core from the surroundings. The mean diameter of the synthesized core and core-shell nanoparticles was ≈8 and ≈16 nm, respectively. Hydrophobic UCNPs were converted into hydrophilic ones using a nonionic surfactant Tween 80. The successful coating of the UCNPs by Tween 80 has been confirmed by Fourier transform infrared (FTIR) spectroscopy. Scanning electron microscopy (SEM), powder X-ray diffraction (XRD), photoluminescence (PL) spectra and magnetic resonance (MR) T1 relaxation measurements were used to characterize the size, crystal structure, optical and magnetic properties of the core and core-shell nanoparticles. Moreover, Tween 80-coated core-shell nanoparticles presented enhanced optical and MR signal intensity, good colloidal stability, low cytotoxicity and nonspecific internalization into two different breast cancer cell lines, which indicates that these nanoparticles could be applied as an efficient, dual-modal contrast probe for in vivo bioimaging.

Microbubble Sizing and Shell Characterization Using Flow Cytometry

PubMed Central

Tu, Juan; Swalwell, Jarred E.; Giraud, David; Cui, Weicheng; Chen, Weizhong; Matula, Thomas J.

2015-01-01

Experiments were performed to size, count, and obtain shell parameters for individual ultrasound contrast microbubbles using a modified flow cytometer. Light scattering was modeled using Mie theory, and applied to calibration beads to calibrate the system. The size distribution and population were measured directly from the flow cytometer. The shell parameters (shear modulus and shear viscosity) were quantified at different acoustic pressures (from 95 to 333 kPa) by fitting microbubble response data to a bubble dynamics model. The size distribution of the contrast agent microbubbles is consistent with manufacturer specifications. The shell shear viscosity increases with increasing equilibrium microbubble size, and decreases with increasing shear rate. The observed trends are independent of driving pressure amplitude. The shell elasticity does not vary with microbubble size. The results suggest that a modified flow cytometer can be an effective tool to characterize the physical properties of microbubbles, including size distribution, population, and shell parameters. PMID:21622051

Recent Advances in Molecular, Multimodal and Theranostic Ultrasound Imaging

PubMed Central

Kiessling, Fabian; Fokong, Stanley; Bzyl, Jessica; Lederle, Wiltrud; Palmowski, Moritz; Lammers, Twan

2014-01-01

Ultrasound (US) imaging is an exquisite tool for the non-invasive and real-time diagnosis of many different diseases. In this context, US contrast agents can improve lesion delineation, characterization and therapy response evaluation. US contrast agents are usually micrometer-sized gas bubbles, stabilized with soft or hard shells. By conjugating antibodies to the microbubble (MB) surface, and by incorporating diagnostic agents, drugs or nucleic acids into or onto the MB shell, molecular, multimodal and theranostic MB can be generated. We here summarize recent advances in molecular, multimodal and theranostic US imaging, and introduce concepts how such advanced MB can be generated, applied and imaged. Examples are given for their use to image and treat oncological, cardiovascular and neurological diseases. Furthermore, we discuss for which therapeutic entities incorporation into (or conjugation to) MB is meaningful, and how US-mediated MB destruction can increase their extravasation, penetration, internalization and efficacy. PMID:24316070

Ultrasound contrast agent fabricated from microbubbles containing instant adhesives, and its ultrasound imaging ability

NASA Astrophysics Data System (ADS)

Makuta, T.; Tamakawa, Y.

2012-04-01

Non-invasive surgery techniques and drug delivery system with acoustic characteristics of ultrasound contrast agent have been studied intensively in recent years. Ultrasound contrast agent collapses easily under the blood circulating and the ultrasound irradiating because it is just a stabilized bubble without solid-shell by surface adsorption of surfactant or lipid. For improving the imaging stability, we proposed the fabrication method of the hollow microcapsule with polymer shell, which can be fabricated just blowing vapor of commonly-used instant adhesive (Cyanoacrylate monomer) into water as microbubbles. Therefore, the cyanoacrylate vapor contained inside microbubble initiates polymerization on the gasliquid interface soon after microbubbles are generated in water. Consequently, hollow microspheres coated by cyanoacrylate thin film are generated. In this report, we revealed that diameter distributions of microbubbles and microcapsules were approximately same and most of them were less than 10 μm, that is, smaller than blood capillary. In addition, we also revealed that hollow microcapsules enhanced the acoustic signal especially in the harmonic contrast imaging and were broken or agglomerated under the ultrasound field. As for the yield of hollow microcapsules, we revealed that sodium dodecyl sulfate addition to water phase instead of deoxycolic acid made the fabrication yield increased.

Theoretical analysis of chirp excitation of contrast agents

NASA Astrophysics Data System (ADS)

Barlow, Euan; Mulholland, Anthony J.; Nordon, Alison; Gachagan, Anthony

2010-01-01

Analytic expressions are found for the amplitude of the first and second harmonics of the Ultrasound Contrast Agent's (UCA's) dynamics when excited by a chirp. The dependency of the second harmonic amplitude on the system parameters, the UCA shell parameters, and the insonifying signal parameters is then investigated. It is shown that optimal parameter values exist which give rise to a clear increase in the second harmonic component of the UCA's motion.

Nanocapsules of perfluorooctyl bromide for theranostics: from formulation to targeting

NASA Astrophysics Data System (ADS)

Diou, O.; Fattal, E.; Payen, T.; Bridal, S. L.; Valette, J.; Tsapis, N.

2014-03-01

The need to detect cancer at its early stages, as well as, to deliver chemotherapy to targeted site motivates many researchers to build theranostic platforms which combine diagnostic and therapy. Among imaging modalities, ultrasonography and Magnetic Resonance Imaging (MRI) are widely available, non invasive and complement each other. Both techniques often require the use of contrast agents. We have developed nanocapsules of perfluorooctyl bromide as dual contrast agent for both imaging modalities. The soft, amorphous polymer shell provides echogenicity, while the high-density perfluorinated liquid core allows detection by 19F MRI. We have used a shell of poly(lactide-co-glycolide) (PLGA) since this polymer is biodegradable, biocompatible and can be loaded with drugs. These capsules were shown to be efficient in vitro as contrast agents for both 19F MRI and ultrasonography. In addition, for in vivo applications a poly(ethyleneglycol) (PEG) coating promotes stability and prolonged circulation. Being stealth, nanocapsule can accumulate passively into implanted tumors by the EPR effect. We will present nanocapsule formulation and characterization, and will show promising in vivo results obtained for both ultrasonography and 19F MRI.

Nonlinear response of ultrasound contrast agent microbubbles: From fundamentals to applications

NASA Astrophysics Data System (ADS)

Teng, Xu-Dong; Guo, Xia-Sheng; Tu, Juan; Zhang, Dong

2016-12-01

Modelling and biomedical applications of ultrasound contrast agent (UCA) microbubbles have attracted a great deal of attention. In this review, we summarize a series of researches done in our group, including (i) the development of an all-in-one solution of characterizing coated bubble parameters based on the light scattering technique and flow cytometry; (ii) a novel bubble dynamic model that takes into consideration both nonlinear shell elasticity and viscosity to eliminate the dependences of bubble shell parameters on bubble size; (iii) the evaluation of UCA inertial cavitation threshold and its relationship with shell parameters; and (iv) the investigations of transfection efficiency and the reduction of cytotoxicity in gene delivery facilitated by UCAs excited by ultrasound exposures. Projects supported by the National Natural Science Foundation of China (Grant Nos. 81127901, 81227004, 11374155, 11274170, 11274176, 11474001, 11474161, 11474166, and 11674173), the National High-Technology Research and Development Program, China (Grant No. 2012AA022702), and Qing Lan Project of Jiangsu Province, China.

Rupture threshold characterization of polymer-shelled ultrasound contrast agents subjected to static overpressure

NASA Astrophysics Data System (ADS)

Chitnis, Parag V.; Lee, Paul; Mamou, Jonathan; Allen, John S.; Böhmer, Marcel; Ketterling, Jeffrey A.

2011-04-01

Polymer-shelled micro-bubbles are employed as ultrasound contrast agents (UCAs) and vesicles for targeted drug delivery. UCA-based delivery of the therapeutic payload relies on ultrasound-induced shell rupture. The fragility of two polymer-shelled UCAs manufactured by Point Biomedical or Philips Research was investigated by characterizing their response to static overpressure. The nominal diameters of Point and Philips UCAs were 3 μm and 2 μm, respectively. The UCAs were subjected to static overpressure in a glycerol-filled test chamber with a microscope-reticule lid. UCAs were reconstituted in 0.1 mL of water and added over the glycerol surface in contact with the reticule. A video-microscope imaged UCAs as glycerol was injected (5 mL/h) to vary the pressure from 2 to 180 kPa over 1 h. Neither UCA population responded to overpressure until the rupture threshold was exceeded, which resulted in abrupt destruction. The rupture data for both UCAs indicated three subclasses that exhibited different rupture behavior, although their mean diameters were not statistically different. The rupture pressures provided a measure of UCA fragility; the Philips UCAs were more resilient than Point UCAs. Results were compared to theoretical models of spherical shells under compression. Observed variations in rupture pressures are attributed to shell imperfections. These results may provide means to optimize polymeric UCAs for drug delivery and elucidate associated mechanisms.

Modeling of nonlinear viscous stress in encapsulating shells of lipid-coated contrast agent microbubbles.

PubMed

Doinikov, Alexander A; Haac, Jillian F; Dayton, Paul A

2009-02-01

A general theoretical approach to the development of zero-thickness encapsulation models for contrast microbubbles is proposed. The approach describes a procedure that allows one to recast available rheological laws from the bulk form to a surface form which is used in a modified Rayleigh-Plesset equation governing the radial dynamics of a contrast microbubble. By the use of the proposed procedure, the testing of different rheological laws for encapsulation can be carried out. Challenges of existing shell models for lipid-encapsulated microbubbles, such as the dependence of shell parameters on the initial bubble radius and the "compression-only" behavior, are discussed. Analysis of the rheological behavior of lipid encapsulation is made by using experimental radius-time curves for lipid-coated microbubbles with radii in the range 1.2-2.5 microm. The curves were acquired for a research phospholipid-coated contrast agent insonified with a 20 cycle, 3.0 MHz, 100 kPa acoustic pulse. The fitting of the experimental data by a model which treats the shell as a viscoelastic solid gives the values of the shell surface viscosity increasing from 0.30 x 10(-8) kg/s to 2.63 x 10(-8) kg/s for the range of bubble radii, indicated above. The shell surface elastic modulus increases from 0.054 N/m to 0.37 N/m. It is proposed that this increase may be a result of the lipid coating possessing the properties of both a shear-thinning and a strain-softening material. We hypothesize that these complicated rheological properties do not allow the existing shell models to satisfactorily describe the dynamics of lipid encapsulation. In the existing shell models, the viscous and the elastic shell terms have the linear form which assumes that the viscous and the elastic stresses acting inside the lipid shell are proportional to the shell shear rate and the shell strain, respectively, with constant coefficients of proportionality. The analysis performed in the present paper suggests that a more general, nonlinear theory may be more appropriate. It is shown that the use of the nonlinear theory for shell viscosity allows one to model the "compression-only" behavior. As an example, the results of the simulation for a 2.03 microm radius bubble insonified with a 6 cycle, 1.8 MHz, 100 kPa acoustic pulse are given. These parameters correspond to the acoustic conditions under which the "compression-only" behavior was observed by de Jong et al. [Ultrasound Med. Biol. 33 (2007) 653-656]. It is also shown that the use of the Cross law for the modeling of the shear-thinning behavior of shell viscosity reduces the variance of experimentally estimated values of the shell viscosity and its dependence on the initial bubble radius.

Instrumentation for contrast echocardiography: technology and techniques.

PubMed

Kaul, Sanjiv

2002-11-18

Contrast echocardiography is the only clinical imaging technique in which the imaging modality (ultrasound) can cause a change in the contrast agent (microbubbles). The change in the contrast agent can range from small oscillations of the microbubbles at a low mechanical index to their disruption at a high mechanical index. The specific mechanical index required to produce these various effects may be different for each contrast agent, depending on the bubble dimension as well as shell and gas characteristics. These alterations in bubbles result in changes in ultrasound backscatter that are specific for the bubbles themselves, rather than for tissue, and are therefore exploited for imaging their presence in tissue. These signal-processing techniques have resulted in an increased signal-to-noise ratio from bubbles vis-à-vis the tissue and have made online assessment of myocardial perfusion possible.

Resonance frequencies of lipid-shelled microbubbles in the regime of nonlinear oscillations

PubMed Central

Doinikov, Alexander A.; Haac, Jillian F.; Dayton, Paul A.

2009-01-01

Knowledge of resonant frequencies of contrast microbubbles is important for the optimization of ultrasound contrast imaging and therapeutic techniques. To date, however, there are estimates of resonance frequencies of contrast microbubbles only for the regime of linear oscillation. The present paper proposes an approach for evaluating resonance frequencies of contrast agent microbubbles in the regime of nonlinear oscillation. The approach is based on the calculation of the time-averaged oscillation power of the radial bubble oscillation. The proposed procedure was verified for free bubbles in the frequency range 1–4 MHz and then applied to lipid-shelled microbubbles insonified with a single 20-cycle acoustic pulse at two values of the acoustic pressure amplitude, 100 kPa and 200 kPa, and at four frequencies: 1.5, 2.0, 2.5, and 3.0 MHz. It is shown that, as the acoustic pressure amplitude is increased, the resonance frequency of a lipid-shelled microbubble tends to decrease in comparison with its linear resonance frequency. Analysis of existing shell models reveals that models that treat the lipid shell as a linear viscoelastic solid appear may be challenged to provide the observed tendency in the behavior of the resonance frequency at increasing acoustic pressure. The conclusion is drawn that the further development of shell models could be improved by the consideration of nonlinear rheological laws. PMID:18977009

A Prussian Blue-Based Core-Shell Hollow-Structured Mesoporous Nanoparticle as a Smart Theranostic Agent with Ultrahigh pH-Responsive Longitudinal Relaxivity.

PubMed

Cai, Xiaojun; Gao, Wei; Ma, Ming; Wu, Meiying; Zhang, Linlin; Zheng, Yuanyi; Chen, Hangrong; Shi, Jianlin

2015-11-04

Novel core-shell hollow mesoporous Prussian blue @ Mn-containing Prussian blue analogue (HMPB@MnPBA) nanoparticles, designated as HMPB-Mn) as an intelligent theranostic nanoagent, are successfully constructed by coating a similarly crystal-structured MnPBA onto HMPB. This can be used as a pH-responsive T1 -weighted magnetic resonance imaging contrast agent with ultrahigh longitudinal relaxivity (r1 = 7.43 m m(-1) s(-1) ), and achieves the real-time monitoring of drug release. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Development of Microbubble Contrast Agents with Biochemical Recognition and Tunable Acoustic Response

NASA Astrophysics Data System (ADS)

Nakatsuka, Matthew Allan Masao

Microbubbles, consisting of gas-filled cores encapsulated within phospholipid or polymer shells, are the most widely used ultrasound contrast agents in the world. Because of their acoustic impedance mismatch with surrounding tissues and compressible gaseous interiors, they have high echogenicities that allow for efficient backscatter of ultrasound. They can also generate unique harmonic frequencies when insonated near their resonance frequency, depending on physical microbubble properties such as the stiffness and thickness of the encapsulating shell. Microbubbles are used to detect a number of cardiovascular diseases, but current methodologies lack the ability to detect and distinguish small, rapidly growing abnormalities that do not produce visible blockage or slowing of blood flow. This work describes the development, formulation, and validation of microbubbles with various polymer shell architectures designed to modulate their acoustic ability. We demonstrate that the addition of a thick disulfide crosslinked, poly(acrylic acid) encapsulating shell increases a bubble's resistance to cavitation and changes its resonance frequency. Modification of this shell architecture to use hybridized DNA strands to form crosslinks between the polymer chains allows for tuning of the bubble acoustic response. When the DNA crosslinks are in place, shell stiffness is increased so the bubbles do not oscillate and acoustic signal is muted. Subsequently, when these DNA strands are displaced, partial acoustic activity is restored. By using aptamer sequences with a specific affinity towards the biomolecule thrombin as the DNA crosslinking strand, this acoustic "ON/OFF" behavior can be specifically tailored towards the presence of a specific biomarker, and produces a change in acoustic signal at concentrations of thrombin consistent with acute deep venous thrombosis. Incorporation of the emulsifying agent poly(ethylene glycol) into the encapsulating shell improves microbubble yield and circulation half-life substantially, allowing for the in vivo detection of a blood clot in a rabbit model. The results presented here show a unique marriage of highly specific molecular imaging and sonography that could be tailored towards a wide variety of cardiovascular abnormalities.

Cell mechanics in biomedical cavitation

PubMed Central

Wang, Qianxi; Manmi, Kawa; Liu, Kuo-Kang

2015-01-01

Studies on the deformation behaviours of cellular entities, such as coated microbubbles and liposomes subject to a cavitation flow, become increasingly important for the advancement of ultrasonic imaging and drug delivery. Numerical simulations for bubble dynamics of ultrasound contrast agents based on the boundary integral method are presented in this work. The effects of the encapsulating shell are estimated by adapting Hoff's model used for thin-shell contrast agents. The viscosity effects are estimated by including the normal viscous stress in the boundary condition. In parallel, mechanical models of cell membranes and liposomes as well as state-of-the-art techniques for quantitative measurement of viscoelasticity for a single cell or coated microbubbles are reviewed. The future developments regarding modelling and measurement of the material properties of the cellular entities for cutting-edge biomedical applications are also discussed. PMID:26442142

In Search of the Optimal Heart Perfusion Ultrasound Imaging Platform.

PubMed

Grishenkov, Dmitry; Gonon, Adrian; Janerot-Sjoberg, Birgitta

2015-09-01

Quantification of myocardial perfusion by contrast echocardiography remains a challenge. Existing imaging phantoms used to evaluate the performance of ultrasound scanners do not comply with perfusion basics in the myocardium, where perfusion and motion are inherently coupled. To contribute toward an improvement, we developed a contrast echocardiographic perfusion imaging platform based on an isolated rat heart coupled to an ultrasound scanner. Perfusion was assessed by using 3 different types of contrast agents: dextran-based Promiten (Meda AB, Solna, Sweden), phospholipid-shelled SonoVue (Bracco Diagnostics, Inc, Princeton, NJ), and polymer-shelled MB-pH5-RT, developed in-house. The myocardial video intensity was monitored over time from contrast agent administration to peak, and 2 characteristic constants were calculated by using an exponential fit: A, representing capillary volume; and β, representing inflow velocity. Acquired experimental evidence demonstrates that the application of all 3 contrast agents allows sonographic estimation of myocardial perfusion in the isolated rat heart. Video intensity maps show that an increase in contrast concentration increases the late-plateau values, A, mimicking increased capillary volume. Estimated values of the flow, proportional to A × β, increase when the pressure of the perfusate column increases from 80 to 110 cm of water. This finding is in agreement with the true values of the coronary flow increase measured by a flowmeter attached to the aortic cannula. The contrast echocardiographic perfusion imaging platform described holds promise for standardized evaluation and optimization of contrast perfusion ultrasound imaging in which real-time inflow curves at low acoustic power semiquantitatively reflect coronary flow. © 2015 by the American Institute of Ultrasound in Medicine.

Nanoparticle imaging probes for molecular imaging with computed tomography and application to cancer imaging

NASA Astrophysics Data System (ADS)

Roeder, Ryan K.; Curtis, Tyler E.; Nallathamby, Prakash D.; Irimata, Lisa E.; McGinnity, Tracie L.; Cole, Lisa E.; Vargo-Gogola, Tracy; Cowden Dahl, Karen D.

2017-03-01

Precision imaging is needed to realize precision medicine in cancer detection and treatment. Molecular imaging offers the ability to target and identify tumors, associated abnormalities, and specific cell populations with overexpressed receptors. Nuclear imaging and radionuclide probes provide high sensitivity but subject the patient to a high radiation dose and provide limited spatiotemporal information, requiring combined computed tomography (CT) for anatomic imaging. Therefore, nanoparticle contrast agents have been designed to enable molecular imaging and improve detection in CT alone. Core-shell nanoparticles provide a powerful platform for designing tailored imaging probes. The composition of the core is chosen for enabling strong X-ray contrast, multi-agent imaging with photon-counting spectral CT, and multimodal imaging. A silica shell is used for protective, biocompatible encapsulation of the core composition, volume-loading fluorophores or radionuclides for multimodal imaging, and facile surface functionalization with antibodies or small molecules for targeted delivery. Multi-agent (k-edge) imaging and quantitative molecular imaging with spectral CT was demonstrated using current clinical agents (iodine and BaSO4) and a proposed spectral library of contrast agents (Gd2O3, HfO2, and Au). Bisphosphonate-functionalized Au nanoparticles were demonstrated to enhance sensitivity and specificity for the detection of breast microcalcifications by conventional radiography and CT in both normal and dense mammary tissue using murine models. Moreover, photon-counting spectral CT enabled quantitative material decomposition of the Au and calcium signals. Immunoconjugated Au@SiO2 nanoparticles enabled highly-specific targeting of CD133+ ovarian cancer stem cells for contrast-enhanced detection in model tumors.

Photo-cured PMMA/PEI core/shell nanoparticles surface-modified with Gd-DTPA for T1 MR imaging.

PubMed

Ratanajanchai, Montri; Lee, Don Haeng; Sunintaboon, Panya; Yang, Su-Geun

2014-02-01

Herein, we introduced amine-functionalized core-shell nanoparticles (Polymethyl methacrylate/Polyethyleneimine; PMMA/PEI) with surface primary amines (3.15×10(5) groups/particle) and uniform size distribution (150-200nm) that were prepared by one-step photo-induced emulsion polymerization. Further PEI-surface was modified with diethylenetriamine pentaacetic acid (DTPA) and introduced with Gd(III). The modified particles possessing DTPA can entrap a high content of Gd(III) ions of over 5.5×10(4)Gd/particle with stable chelation (no release of free Gd) at least 7h. The Gd-DTPA-conjugated core-shell nanoparticles (PMMA/PEI-DTPA-Gd NPs) enhanced the MRI intensity more than Primovist (a commercial hepatic contrast agent). Moreover, the PMMA/PEI-DTPA-Gd NPs showed non-cytotoxicity up to 250μM in normal liver cells. Thus, in vitro data suggested the PMMA/PEI-DTPA-Gd NPs is promising delivery system as a superior MRI contrast agent, especially for hepatic lesion targeted MR imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

Encapsulated microbubbles and echogenic liposomes for contrast ultrasound imaging and targeted drug delivery

PubMed Central

Paul, Shirshendu; Nahire, Rahul; Mallik, Sanku; Sarkar, Kausik

2014-01-01

Micron- to nanometer-sized ultrasound agents, like encapsulated microbubbles and echogenic liposomes, are being developed for diagnostic imaging and ultrasound mediated drug/gene delivery. This review provides an overview of the current state of the art of the mathematical models of the acoustic behavior of ultrasound contrast microbubbles. We also present a review of the in vitro experimental characterization of the acoustic properties of microbubble based contrast agents undertaken in our laboratory. The hierarchical two-pronged approach of modeling contrast agents we developed is demonstrated for a lipid coated (Sonazoid™) and a polymer shelled (poly D-L-lactic acid) contrast microbubbles. The acoustic and drug release properties of the newly developed echogenic liposomes are discussed for their use as simultaneous imaging and drug/gene delivery agents. Although echogenicity is conclusively demonstrated in experiments, its physical mechanisms remain uncertain. Addressing questions raised here will accelerate further development and eventual clinical approval of these novel technologies. PMID:26097272

Acoustic Characterization and Enhanced Ultrasound Imaging of Long-Circulating Lipid-Coated Microbubbles.

PubMed

Li, Hongbo; Yang, Yanye; Zhang, Meimei; Yin, Liping; Tu, Juan; Guo, Xiasheng; Zhang, Dong

2018-05-01

A long-circulating lipid-coated ultrasound (US) contrast agent was fabricated to achieve a longer wash-out time and gain more resistance against higher-mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles. By simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid-coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash-out time and higher inertial cavitation threshold. To bridge the structure-performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles. The synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 μm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue. Nano/micrometer long-circulating lipid-coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher-molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver. © 2017 by the American Institute of Ultrasound in Medicine.

Broadband attenuation measurements of phospholipid-shelled ultrasound contrast agents.

PubMed

Raymond, Jason L; Haworth, Kevin J; Bader, Kenneth B; Radhakrishnan, Kirthi; Griffin, Joseph K; Huang, Shao-Ling; McPherson, David D; Holland, Christy K

2014-02-01

The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of transducers. Viscoelastic shell parameters of the UCAs were estimated using a linearized model developed by N. de Jong, L. Hoff, T. Skotland and N. Bom (Ultrasonics 1992; 30:95-103). The effect of diluent on the attenuation of these UCA suspensions was evaluated by performing attenuation measurements in 0.5% (w/v) bovine serum albumin and whole blood. Changes in attenuation and shell parameters of the UCAs were investigated at room temperature (25°C) and physiologic temperature (37°C). The attenuation of the UCAs diluted in 0.5% (w/v) bovine serum albumin was found to be identical to the attenuation of UCAs in whole blood. For each UCA, attenuation was higher at 37°C than at 25°C, underscoring the importance of conducting characterization studies at physiologic temperature. Echogenic liposomes exhibited a larger increase in attenuation at 37°C versus 25°C than either Definity or MicroMarker. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Gold nanoparticles for photoacoustic imaging

PubMed Central

Li, Wanwan; Chen, Xiaoyuan

2015-01-01

Photoacoustic (PA) imaging is a biomedical imaging modality that provides functional information regarding the cellular and molecular signatures of tissue by using endogenous and exogenous contrast agents. There has been tremendous effort devoted to the development of PA imaging agents, and gold nanoparticles as exogenous contrast agents have great potential for PA imaging due to their inherent and geometrically induced optical properties. The gold-based nanoparticles that are most commonly employed for PA imaging include spheres, rods, shells, prisms, cages, stars and vesicles. This article provides an overview of the current state of research in utilizing these gold nanomaterials for PA imaging of cancer, atherosclerotic plaques, brain function and image-guided therapy. PMID:25600972

Effect of Anesthesia Carrier Gas on In-Vivo Circulation Times of Ultrasound Microbubble Contrast Agents in Rats

PubMed Central

Mullin, Lee; Gessner, Ryan; Kwan, James; Kaya, Mehmet; Borden, Mark A.; Dayton, Paul A.

2012-01-01

Purpose Microbubble contrast agents are currently implemented in a variety of both clinical and preclinical ultrasound imaging studies. The therapeutic and diagnostic capabilities of these contrast agents are limited by their short in-vivo lifetimes, and research to lengthen their circulation times is ongoing. In this manuscript, observations are presented from a controlled experiment performed to evaluate differences in circulation times for lipid shelled perfluorocarbon-filled contrast agents circulating within rodents as a function of inhaled anesthesia carrier gas. Methods The effects of two common anesthesia carrier gas selections - pure oxygen and medical air – were observed within five rats. Contrast agent persistence within the kidney was measured and compared for oxygen and air anesthesia carrier gas for six bolus contrast injections in each animal. Simulations were performed to examine microbubble behavior with changes in external environment gases. Results A statistically significant extension of contrast circulation time was observed for animals breathing medical air compared to breathing pure oxygen. Simulations support experimental observations and indicate that enhanced contrast persistence may be explained by reduced ventilation/perfusion mismatch and classical diffusion, in which nitrogen plays a key role by contributing to the volume and diluting other gas species in the microbubble gas core. Conclusion: Using medical air in place of oxygen as the carrier gas for isoflurane anesthesia can increase the circulation lifetime of ultrasound microbubble contrast agents. PMID:21246710

Modeling of nonlinear viscous stress in encapsulating shells of lipid-coated contrast agent microbubbles

PubMed Central

Doinikov, Alexander A.; Haac, Jillian F.; Dayton, Paul A.

2009-01-01

A general theoretical approach to the development of zero-thickness encapsulation models for contrast microbubbles is proposed. The approach describes a procedure that allows one to recast available rheological laws from the bulk form to a surface form which is used in a modified Rayleigh-Plesset equation governing the radial dynamics of a contrast microbubble. By the use of the proposed procedure, the testing of different rheological laws for encapsulation can be carried out. Challenges of existing shell models for lipid-encapsulated microbubbles, such as the dependence of shell parameters on the initial bubble radius and the “compression-only” behavior, are discussed. Analysis of the rheological behavior of lipid encapsulation is made by using experimental radius-time curves for lipid-coated microbubbles with radii in the range 1.2 – 2.5 μm. The curves were acquired for a research phospholipid-coated contrast agent insonified with a 20-cycle, 3.0 MHz, 100 kPa acoustic pulse. The fitting of the experimental data by a model which treats the shell as a viscoelastic solid gives the values of the shell surface viscosity increasing from 0.30×10-8 kg/s to 2.63×10-8 kg/s for the range of bubble radii indicated above. The shell surface elastic modulus increases from 0.054 N/m to 0.37 N/m. It is proposed that this increase may be a result of the lipid coating possessing the properties of both a shear-thinning and a strain-softening material. We hypothesize that these complicated rheological properties do not allow the existing shell models to satisfactorily describe the dynamics of lipid encapsulation. In the existing shell models, the viscous and the elastic shell terms have the linear form which assumes that the viscous and the elastic stresses acting inside the lipid shell are proportional to the shell shear rate and the shell strain, respectively, with constant coefficients of proportionality. The analysis performed in the present paper suggests that a more general, nonlinear theory may be more appropriate. It is shown that the use of the nonlinear theory for shell viscosity allows one to model the “compression-only” behavior. As an example, the results of the simulation for a 2.03- μm-radius bubble insonified with a 6-cycle, 1.8 MHz, 100 kPa acoustic pulse are given. These parameters correspond to the acoustic conditions under which the “compression-only” behavior was observed by de Jong et al. [Ultrasound Med. Biol. 33 (2007) 653–656]. It is also shown that the use of the Cross law for the modeling of the shear-thinning behavior of shell viscosity reduces the variance of experimentally estimated values of the shell viscosity and its dependence on the initial bubble radius. PMID:18990417

Magnetic hybrid magnetite/metal organic framework nanoparticles: facile preparation, post-synthetic biofunctionalization and tracking in vivo with magnetic methods

NASA Astrophysics Data System (ADS)

Tregubov, A. A.; Sokolov, I. L.; Babenyshev, A. V.; Nikitin, P. I.; Cherkasov, V. R.; Nikitin, M. P.

2018-03-01

Multifunctional hybrid nanocomposites remain to be of great interest in biomedicine as a universal tool in a number of applications. As a promising example, the nanoparticles with magnetic core and porous shell have a potential as theranostic agents combining both the diagnostics probe and drug delivery vehicle properties. However, reported methods of the nanostructure preparation are complex and include tedious time-consuming growth of porous shell by means of layer by layer assembly technique. In this study, we develop new way of fabrication of the superparamagnetic magnetite core @ porous metal organic framework shell nanoparticles and demonstrate their application both as a multimodal (MRI contrasting, magnetometric and optical labeling) and multifunctional (in vivo bioimaging, biotargeting by coupled receptors, lateral flow assay) agents. The easiness of fabrication, controllable bioconjugation properties and low level of non-specific binding indicate high potential of the nanoparticles to be employed as multifunctional agents in theranostics, advanced biosensing and bioimaging.

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

Bazalova, M; Ahmad, M; Fahrig, R

Purpose: To evaluate x-ray fluorescence computed tomography induced with proton beams (pXFCT) for imaging of gold contrast agent. Methods: Proton-induced x-ray fluorescence was studied by means of Monte Carlo (MC) simulations using TOPAS, a MC code based on GEANT4. First, proton-induced K-shell and L-shell fluorescence was studied as a function of proton beam energy and 1) depth in water and 2) size of contrast object. Second, pXFCT images of a 2-cm diameter cylindrical phantom with four 5- mm diameter contrast vials and of a 20-cm diameter phantom with 1-cm diameter vials were simulated. Contrast vials were filled with water andmore » water solutions with 1-5% gold per weight. Proton beam energies were varied from 70-250MeV. pXFCT sinograms were generated based on the net number of gold K-shell or L-shell x-rays determined by interpolations from the neighboring 0.5keV energy bins of spectra collected with an idealized 4π detector. pXFCT images were reconstructed with filtered-back projection, and no attenuation correction was applied. Results: Proton induced x-ray fluorescence spectra showed very low background compared to x-ray induced fluorescence. Proton induced L-shell fluorescence had a higher cross-section compared to K-shell fluorescence. Excitation of L-shell fluorescence was most efficient for low-energy protons, i.e. at the Bragg peak. K-shell fluorescence increased with increasing proton beam energy and object size. The 2% and 5% gold contrast vials were accurately reconstructed in K-shell pXFCT images of both the 2-cm and 20-cm diameter phantoms. Small phantom L-shell pXFCT image required attenuation correction and had a higher sensitivity for 70MeV protons compared to 250MeV protons. With attenuation correction, L-shell pXFCT might be a feasible option for imaging of small size (∼2cm) objects. Imaging doses for all simulations were 5-30cGy. Conclusion: Proton induced x-ray fluorescence CT promises to be an alternative quantitative imaging technique to the commonly considered XFCT imaging with x-ray beams.« less

In vivo magnetic resonance and fluorescence dual imaging of tumor sites by using dye-doped silica-coated iron oxide nanoparticles

NASA Astrophysics Data System (ADS)

Jang, Haeyun; Lee, Chaedong; Nam, Gi-Eun; Quan, Bo; Choi, Hyuck Jae; Yoo, Jung Sun; Piao, Yuanzhe

2016-02-01

The difficulty in delineating tumor is a major obstacle for better outcomes in cancer treatment of patients. The use of single-imaging modality is often limited by inadequate sensitivity and resolution. Here, we present the synthesis and the use of monodisperse iron oxide nanoparticles coated with fluorescent silica nano-shells for fluorescence and magnetic resonance dual imaging of tumor. The as-synthesized core-shell nanoparticles were designed to improve the accuracy of diagnosis via simultaneous tumor imaging with dual imaging modalities by a single injection of contrast agent. The iron oxide nanocrystals ( 11 nm) were coated with Rhodamine B isothiocyanate-doped silica shells via reverse microemulsion method. Then, the core-shell nanoparticles ( 54 nm) were analyzed to confirm their size distribution by transmission electron microscopy and dynamic laser scattering. Photoluminescence spectroscopy was used to characterize the fluorescent property of the dye-doped silica shell-coated nanoparticles. The cellular compatibility of the as-prepared nanoparticles was confirmed by a trypan blue dye exclusion assay and the potential as a dual-imaging contrast agent was verified by in vivo fluorescence and magnetic resonance imaging. The experimental results show that the uniform-sized core-shell nanoparticles are highly water dispersible and the cellular toxicity of the nanoparticles is negligible. In vivo fluorescence imaging demonstrates the capability of the developed nanoparticles to selectively target tumors by the enhanced permeability and retention effects and ex vivo tissue analysis was corroborated this. Through in vitro phantom test, the core/shell nanoparticles showed a T2 relaxation time comparable to Feridex® with smaller size, indicating that the as-made nanoparticles are suitable for imaging tumor. This new dual-modality-nanoparticle approach has promised for enabling more accurate tumor imaging.

Investigation on the inertial cavitation threshold and shell properties of commercialized ultrasound contrast agent microbubbles.

PubMed

Guo, Xiasheng; Li, Qian; Zhang, Zhe; Zhang, Dong; Tu, Juan

2013-08-01

The inertial cavitation (IC) activity of ultrasound contrast agents (UCAs) plays an important role in the development and improvement of ultrasound diagnostic and therapeutic applications. However, various diagnostic and therapeutic applications have different requirements for IC characteristics. Here through IC dose quantifications based on passive cavitation detection, IC thresholds were measured for two commercialized UCAs, albumin-shelled KangRun(®) and lipid-shelled SonoVue(®) microbubbles, at varied UCA volume concentrations (viz., 0.125 and 0.25 vol. %) and acoustic pulse lengths (viz., 5, 10, 20, 50, and 100 cycles). Shell elastic and viscous coefficients of UCAs were estimated by fitting measured acoustic attenuation spectra with Sarkar's model. The influences of sonication condition (viz., acoustic pulse length) and UCA shell properties on IC threshold were discussed based on numerical simulations. Both experimental measurements and numerical simulations indicate that IC thresholds of UCAs decrease with increasing UCA volume concentration and acoustic pulse length. The shell interfacial tension and dilatational viscosity estimated for SonoVue (0.7 ± 0.11 N/m, 6.5 ± 1.01 × 10(-8) kg/s) are smaller than those of KangRun (1.05 ± 0.18 N/m, 1.66 ± 0.38 × 10(-7) kg/s); this might result in lower IC threshold for SonoVue. The current results will be helpful for selecting and utilizing commercialized UCAs for specific clinical applications, while minimizing undesired IC-induced bioeffects.

Influence of nesting shell size on brightness longevity and resistance to ultrasound-induced dissolution during enhanced B-mode contrast imaging.

PubMed

Wallace, N; Dicker, S; Lewin, P; Wrenn, S P

2014-12-01

This study aims to bridge the gap between transport mechanisms of an improved ultrasound contrast agent (UCA) and its resulting behavior in a clinical imaging study. Phospholipid-shelled microbubbles nested within the aqueous core of a polymer microcapsule are examined for their use and feasibility as an improved UCA. The nested formulation provides contrast comparable to traditional formulations, specifically an SF6 microbubble coated by a DSPC PEG-3000 monolayer, with the advantage that contrast persists at least nine times longer in a mock clinical, in vitro setting. The effectiveness of the sample was measured using a contrast ratio in units of decibels (dB) which compares the brightness of the nested microbubbles to a reference value of a phantom tissue mimic. During a 40min imaging study, six nesting formulations with average outer capsule diameters of 1.95, 2.53, 5.55, 9.95, 14.95, and 20.51μm reached final contrast ratio values of 0.25, 2.35, 3.68, 4.51, 5.93, and 8.00dB, respectively. The starting contrast ratio in each case was approximately 8dB and accounts for the brightness attributed to the nesting shell. As compared with empty microcapsules (no microbubbles nested within), enhancement of the initial contrast ratio increased systematically with decreasing microcapsule size. The time required to reach a steady state in the temporal contrast ratio profile also varied with microcapsule diameter and was found to be 420s for each of the four smallest shell diameters and 210s and 150s, respectively, for the largest two shell diameters. All nested formulations were longer-lived and gave higher final contrast ratios than a control sample comprising un-nested, but otherwise equivalent, microbubbles. Specifically, the contrast ratio of the un-nested microbubbles decreased to a negative value after 4min of continuous ultrasound exposure with complete disappearance of the microbubbles after 15min whereas all nested formulations maintained positive contrast ratio values for the duration of the 40min trial. The results are consistent with two distinct stages of gas transport: in the first stage, passive diffusion occurs under ambient conditions across the microbubble monolayer within the first few minutes after formulation until the aqueous interior of the microcapsule is saturated with gas; in the second stage ultrasound drives additional gas dissolution even further due to pressure modulation. It is important to understand the chemistry and transport mechanisms of this contrast agent under the influence of ultrasound to attain better perspicacity for enhanced applications in imaging. Results from this study will facilitate future preclinical studies and clinical applications of nested microbubbles for therapeutic and diagnostic imaging. Copyright © 2014 Elsevier B.V. All rights reserved.

In vivo ultrasound visualization of non-occlusive blood clots with thrombin-sensitive contrast agents.

PubMed

Nakatsuka, Matthew A; Barback, Christopher V; Fitch, Kirsten R; Farwell, Alexander R; Esener, Sadik C; Mattrey, Robert F; Cha, Jennifer N; Goodwin, Andrew P

2013-12-01

The use of microbubbles as ultrasound contrast agents is one of the primary methods to diagnose deep venous thrombosis. However, current microbubble imaging strategies require either a clot sufficiently large to produce a circulation filling defect or a clot with sufficient vascularization to allow for targeted accumulation of contrast agents. Previously, we reported the design of a microbubble formulation that modulated its ability to generate ultrasound contrast from interaction with thrombin through incorporation of aptamer-containing DNA crosslinks in the encapsulating shell, enabling the measurement of a local chemical environment by changes in acoustic activity. However, this contrast agent lacked sufficient stability and lifetime in blood to be used as a diagnostic tool. Here we describe a PEG-stabilized, thrombin-activated microbubble (PSTA-MB) with sufficient stability to be used in vivo in circulation with no change in biomarker sensitivity. In the presence of actively clotting blood, PSTA-MBs showed a 5-fold increase in acoustic activity. Specificity for the presence of thrombin and stability under constant shear flow were demonstrated in a home-built in vitro model. Finally, PSTA-MBs were able to detect the presence of an active clot within the vena cava of a rabbit sufficiently small as to not be visible by current non-specific contrast agents. By activating in non-occlusive environments, these contrast agents will be able to detect clots not diagnosable by current contrast agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Photoacoustic/ultrasound dual-modality contrast agent and its application to thermotherapy.

PubMed

Wang, Yu-Hsin; Liao, Ai-Ho; Chen, Jui-Hao; Wang, Churng-Ren Chris; Li, Pai-Chi

2012-04-01

This study investigates a photoacoustic/ultrasound dual-modality contrast agent, including extending its applications from image-contrast enhancement to combined diagnosis and therapy with site-specific targeting. The contrast agent comprises albumin-shelled microbubbles with encapsulated gold nanorods (AuMBs). The gas-filled microbubbles, whose diameters range from submicrometer to several micrometers, are not only echogenic but also can serve as drug-delivery vehicles. The gold nanorods are used to enhance the generation of both photoacoustic and photothermal signals. The optical absorption peak of the gold nanorods is tuned to 760 nm and is invariant after microbubble encapsulation. Dual-modality contrast enhancement is first described here, and the applications to cellular targeting and laser-induced thermotherapy in a phantom are demonstrated. Photoacoustic imaging can be used to monitor temperature increases during the treatment. The targeting capability of AuMBs was verified, and the temperature increased by 26°C for a laser power of 980 mW, demonstrating the potential of combined diagnosis and therapy with the dual-modality agent. Targeted photo- or acoustic-mediated delivery is also possible.

Jetting of a ultrasound contrast microbubble near a rigid wall

NASA Astrophysics Data System (ADS)

Sarkar, Kausik; Mobadersany, Nima

2017-11-01

Micron sized gas-bubbles coated with a stabilizing shell of lipids or proteins, are used as contrast enhancing agents for ultrasound imaging. However, they are increasingly being explored for novel applications in drug delivery through a process called sonoporation, the reversible permeabilization of the cell membrane. Under sufficiently strong acoustic excitations, bubbles form a jet and collapse near a wall. The jetting of free bubbles has been extensively studied by boundary element method (BEM). Here, for the first time, we implemented a rigorous interfacial rheological model of the shell into BEM and investigated the jet formation. The code has been carefully validated against past results. Increasing shell elasticity decreases the maximum bubble volume and the collapse time, while the jet velocity increases. The shear stress on the wall is computed and analyzed. A phase diagram as functions of excitation pressure and wall separation describes jet formation. Effects of shell elasticity and frequency on the phase diagram are investigated. Partially supported by National Science Foundation.

Enhanced near-infrared photoacoustic imaging of silica-coated rare-earth doped nanoparticles.

PubMed

Sheng, Yang; Liao, Lun-De; Bandla, Aishwarya; Liu, Yu-Hang; Yuan, Jun; Thakor, Nitish; Tan, Mei Chee

2017-01-01

Near-infrared photoacoustic (PA) imaging is an emerging diagnostic technology that utilizes the tissue transparent window to achieve improved contrast and spatial resolution for deep tissue imaging. In this study, we investigated the enhancement effect of the SiO 2 shell on the PA property of our core/shell rare-earth nanoparticles (REs) consisting of an active rare-earth doped core of NaYF 4 :Yb,Er (REDNPs) and an undoped NaYF 4 shell. We observed that the PA signal amplitude increased with SiO 2 shell thickness. Although the SiO 2 shell caused an observed decrease in the integrated fluorescence intensity due to the dilution effect, fluorescence quenching of the rare earth emitting ions within the REDNPs cores was successfully prevented by the undoped NaYF 4 shell. Therefore, our multilayer structure consisting of an active core with successive functional layers was demonstrated to be an effective design for dual-modal fluorescence and PA imaging probes with improved PA property. The result from this work addresses a critical need for the development of dual-modal contrast agent that advances deep tissue imaging with high resolution and signal-to-noise ratio. Copyright © 2016 Elsevier B.V. All rights reserved.

Dynamics and fragmentation of thick-shelled microbubbles.

PubMed

May, Donovan J; Allen, John S; Ferrara, Katherine W

2002-10-01

Localized delivery could decrease the systemic side effects of toxic chemotherapy drugs. The unique delivery agents we examine consist of microbubbles with an outer lipid coating, an oil layer, and a perfluorobutane gas core. These structures are 0.5-12 microm in radius at rest. Oil layers of these acoustically active lipospheres (AALs) range from 0.3-1.5 microm in thickness and thus the agents can carry a large payload compared to nano-scale drug delivery systems. We show that triacetin-based drug-delivery vehicles can be fragmented using ultrasound. Compared with a lipid-shelled contrast agent, the expansion of the drug-delivery vehicle within the first cycle is similar, and a subharmonic component is demonstrated at an equivalent radius, frequency, and driving pressure. For the experimental conditions explored here, the pulse length required for destruction of the drug-delivery vehicle is significantly greater, with at least five cycles required, compared with one cycle for the contrast agent. For the drug-delivery vehicle, the observed destruction mechanism varies with the initial radius, with microbubbles smaller than resonance size undergoing a symmetric collapse and producing a set of small, equal-sized fragments. Between resonance size and twice resonance size, surface waves become visible, and the oscillations become asymmetrical. For agents larger than twice the resonance radius, the destruction mechanism changes to a pinch-off, with one fragment containing a large fraction of the original volume.

Chitosan-Gated Magnetic-Responsive Nanocarrier for Dual-Modal Optical Imaging, Switchable Drug Release, and Synergistic Therapy

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

Wang, Hui; Mu, Qingxin; Revia, Richard

In this study, we present a multifunctional yet structurally simple nanocarrier that has a high drug loading capacity, releases drug in response to onset of an AC magnetic field, and can serve as a long-term imaging contrast agent and effectively kills cancer cells by synergistic action. This nanocarrier (HMMC-NC) has a spherical shell structure with a center cavity of 80 nm in diameter. The shell is comprised of two layers: an inner layer of magnetite that exhibits superparamagnetism and an outer layer of mesoporous carbon embedded with carbon dots that exhibit photoluminescence property. Thus in addition to being a drugmore » carrier, HMMC-NC is also a contrast agent for bioimaging. The switchable drug release is enabled by the chitosan molecules attached on the nanocarrier as the switching material which turns on or off the drug release in response to the application or withdrawal of an AC magnetic field.« less

Nanobubble Ultrasound Contrast Agents for Enhanced Delivery of Thermal Sensitizer to Tumors Undergoing Radiofrequency Ablation

PubMed Central

Perera, Reshani H.; Solorio, Luis; Wu, Hanping; Gangolli, Mihika; Silverman, Eric; Hernandez, Christopher; Peiris, Pubudu M.; Broome, Ann-Marie

2013-01-01

Purpose Pluronic has been shown to sensitize various tumor cell lines to chemotherapy and hyperthermia by altering the membrane fluidity, depleting ATP, and modulating the heat shock protein 70 expression. In our prior work, Pluronic was also used to formulate nanosized ultrasound contrast agents. In the current study we evaluate the use of these contrast agents as vehicles for image-guided delivery of Pluronic to improve outcomes of tumor radiofrequency (RF) ablation. Methods Lipid-shelled Pluronic nanobubbles were prepared and examined for size distribution, zeta potential, stability, biodistribution, accumulation of nanobubbles in the tumor, and treatment efficacy. LS174-T xenograft tumor-bearing mice were used to evaluate tumor growth suppression and measure treatment efficacy after RF ablation. Results The average diameter of Pluronic bubbles was 230 nm, and initial bubble echogenicity was 16 dB. In vitro, cells exposed to Pluronic nanobubbles exhibited low cytotoxicity in the absence of ultrasound, even if heat (43°C) was applied. When the cells were exposed to Pluronic nanobubbles, heat, and ultrasound; viability was significantly reduced. In vivo, tumors treated with ultrasound-modulated nanobubbles prior to RF ablation showed a significant reduction in growth compared to the RF alone (P<0.05). Conclusion Lipid and Pluronic-shelled, echogenic nanobubbles combined with ultrasound modulation can serve as an effective theranostic method for sensitization of tumors to RF ablation. PMID:23943542

Nanobubble ultrasound contrast agents for enhanced delivery of thermal sensitizer to tumors undergoing radiofrequency ablation.

PubMed

Perera, Reshani H; Solorio, Luis; Wu, Hanping; Gangolli, Mihika; Silverman, Eric; Hernandez, Christopher; Peiris, Pubudu M; Broome, Ann-Marie; Exner, Agata A

2014-06-01

Pluronic has been shown to sensitize various tumor cell lines to chemotherapy and hyperthermia by altering the membrane fluidity, depleting ATP, and modulating the heat shock protein 70 expression. In our prior work, Pluronic was also used to formulate nanosized ultrasound contrast agents. In the current study we evaluate the use of these contrast agents as vehicles for image-guided delivery of Pluronic to improve outcomes of tumor radiofrequency (RF) ablation. Lipid-shelled Pluronic nanobubbles were prepared and examined for size distribution, zeta potential, stability, biodistribution, accumulation of nanobubbles in the tumor, and treatment efficacy. LS174-T xenograft tumor-bearing mice were used to evaluate tumor growth suppression and measure treatment efficacy after RF ablation. The average diameter of Pluronic bubbles was 230 nm, and initial bubble echogenicity was 16 dB. In vitro, cells exposed to Pluronic nanobubbles exhibited low cytotoxicity in the absence of ultrasound, even if heat (43 ºC) was applied. When the cells were exposed to Pluronic nanobubbles, heat, and ultrasound; viability was significantly reduced. In vivo, tumors treated with ultrasound-modulated nanobubbles prior to RF ablation showed a significant reduction in growth compared to the RF alone (P<0.05). Lipid and Pluronic-shelled, echogenic nanobubbles combined with ultrasound modulation can serve as an effective theranostic method for sensitization of tumors to RF ablation.

A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy.

PubMed

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Wu, Hailiang; Terada, Yasuko; Saga, Tsuneo; Aoki, Ichio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2016-08-01

Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn(2+) within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn(2+) ions. Binding to proteins increases the relaxivity of Mn(2+) and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver.

Novel DiR and SPIO nanoparticles embedded PEG-PLGA nanobubbles as a multimodalimaging contrast agent.

PubMed

Luo, Binhua; Zhang, Huajie; Liu, Xuhan; Rao, Rong; Wu, Yun; Liu, Wei

2015-01-01

Fluorescence dye DiR and superparamagnetic iron oxide nanoparticles (SPIONs) embedded in PEG-PLGA nanobubbles (DiR-SPIO-NBs) were produced using double emulsion method on a membrane of Shirasu porous glass (SPG). The nanobubbles encapsulated with DiR and SPIONs had a liquid core (perfluoropentane) and a PEG-PLGA shell. DiR-SPIO-NBs showed biocompatibility based on MTT cytotoxicity and hemolysis studies. The PFP encapsulated in the nanobubbles experienced phase transition under ultrasonic irradation. Nanobubbles dispersed well in saline over 3 months, and the relaxivity was 127.9 mM(-1)s(-1), suggesting that it could be used as a contrast agent in MRI. The MR and fluorescence images in vivo demonstrated that the signal intensity in the spleen and liver was significantly enhanced with the treatment of nanobubbles. In addition, results of ultrasound images suggested that the nanobubbles had persistent contrast ability. In conclusion, nanobubbles could be utilized as an US/MRI/fluorescence contrast agent.

A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy

NASA Astrophysics Data System (ADS)

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Wu, Hailiang; Terada, Yasuko; Saga, Tsuneo; Aoki, Ichio; Nishiyama, Nobuhiro; Kataoka, Kazunori

2016-08-01

Engineered nanoparticles that respond to pathophysiological parameters, such as pH or redox potential, have been developed as contrast agents for the magnetic resonance imaging (MRI) of tumours. However, beyond anatomic assessment, contrast agents that can sense these pathological parameters and rapidly amplify their magnetic resonance signals are desirable because they could potentially be used to monitor the biological processes of tumours and improve cancer diagnosis. Here, we report an MRI contrast agent that rapidly amplifies magnetic resonance signals in response to pH. We confined Mn2+ within pH-sensitive calcium phosphate (CaP) nanoparticles comprising a poly(ethylene glycol) shell. At a low pH, such as in solid tumours, the CaP disintegrates and releases Mn2+ ions. Binding to proteins increases the relaxivity of Mn2+ and enhances the contrast. We show that these nanoparticles could rapidly and selectively brighten solid tumours, identify hypoxic regions within the tumour mass and detect invisible millimetre-sized metastatic tumours in the liver.

Gold-silver alloy nanoshells: a new candidate for nanotherapeutics and diagnostics

NASA Astrophysics Data System (ADS)

Gheorghe, Dana E.; Cui, Lili; Karmonik, Christof; Brazdeikis, Audrius; Penaloza, Jose M.; Young, Joseph K.; Drezek, Rebekah A.; Bikram, Malavosklish

2011-10-01

We have developed novel gold-silver alloy nanoshells as magnetic resonance imaging (MRI) dual T 1 (positive) and T 2 (negative) contrast agents as an alternative to typical gadolinium (Gd)-based contrast agents. Specifically, we have doped iron oxide nanoparticles with Gd ions and sequestered the ions within the core by coating the nanoparticles with an alloy of gold and silver. Thus, these nanoparticles are very innovative and have the potential to overcome toxicities related to renal clearance of contrast agents such as nephrogenic systemic fibrosis. The morphology of the attained nanoparticles was characterized by XRD which demonstrated the successful incorporation of Gd(III) ions into the structure of the magnetite, with no major alterations of the spinel structure, as well as the growth of the gold-silver alloy shells. This was supported by TEM, ICP-AES, and SEM/EDS data. The nanoshells showed a saturation magnetization of 38 emu/g because of the presence of Gd ions within the crystalline structure with r 1 and r 2 values of 0.0119 and 0.9229 mL mg-1 s-1, respectively (Au:Ag alloy = 1:1). T 1- and T 2-weighted images of the nanoshells showed that these agents can both increase the surrounding water proton signals in the T 1-weighted image and reduce the signal in T 2-weighted images. The as-synthesized nanoparticles exhibited strong absorption in the range of 600-800 nm, their optical properties being strongly dependent upon the thickness of the gold-silver alloy shell. Thus, these nanoshells have the potential to be utilized for tumor cell ablation because of their absorption as well as an imaging agent.

Triple-functional core-shell structured upconversion luminescent nanoparticles covalently grafted with photosensitizer for luminescent, magnetic resonance imaging and photodynamic therapy in vitro

NASA Astrophysics Data System (ADS)

Qiao, Xiao-Fei; Zhou, Jia-Cai; Xiao, Jia-Wen; Wang, Ye-Fu; Sun, Ling-Dong; Yan, Chun-Hua

2012-07-01

Upconversion luminescent nanoparticles (UCNPs) have been widely used in many biochemical fields, due to their characteristic large anti-Stokes shifts, narrow emission bands, deep tissue penetration and minimal background interference. UCNPs-derived multifunctional materials that integrate the merits of UCNPs and other functional entities have also attracted extensive attention. Here in this paper we present a core-shell structured nanomaterial, namely, NaGdF4:Yb,Er@CaF2@SiO2-PS, which is multifunctional in the fields of photodynamic therapy (PDT), magnetic resonance imaging (MRI) and fluorescence/luminescence imaging. The NaGdF4:Yb,Er@CaF2 nanophosphors (10 nm in diameter) were prepared via sequential thermolysis, and mesoporous silica was coated as shell layer, in which photosensitizer (PS, hematoporphyrin and silicon phthalocyanine dihydroxide) was covalently grafted. The silica shell improved the dispersibility of hydrophobic PS molecules in aqueous environments, and the covalent linkage stably anchored the PS molecules in the silica shell. Under excitation at 980 nm, the as-fabricated nanomaterial gave luminescence bands at 550 nm and 660 nm. One luminescent peak could be used for fluorescence imaging and the other was suitable for the absorption of PS to generate singlet oxygen for killing cancer cells. The PDT performance was investigated using a singlet oxygen indicator, and was investigated in vitro in HeLa cells using a fluorescent probe. Meanwhile, the nanomaterial displayed low dark cytotoxicity and near-infrared (NIR) image in HeLa cells. Further, benefiting from the paramagnetic Gd3+ ions in the core, the nanomaterial could be used as a contrast agent for magnetic resonance imaging (MRI). Compared with the clinical commercial contrast agent Gd-DTPA, the as-fabricated nanomaterial showed a comparable longitudinal relaxivities value (r1) and similar imaging effect.Upconversion luminescent nanoparticles (UCNPs) have been widely used in many biochemical fields, due to their characteristic large anti-Stokes shifts, narrow emission bands, deep tissue penetration and minimal background interference. UCNPs-derived multifunctional materials that integrate the merits of UCNPs and other functional entities have also attracted extensive attention. Here in this paper we present a core-shell structured nanomaterial, namely, NaGdF4:Yb,Er@CaF2@SiO2-PS, which is multifunctional in the fields of photodynamic therapy (PDT), magnetic resonance imaging (MRI) and fluorescence/luminescence imaging. The NaGdF4:Yb,Er@CaF2 nanophosphors (10 nm in diameter) were prepared via sequential thermolysis, and mesoporous silica was coated as shell layer, in which photosensitizer (PS, hematoporphyrin and silicon phthalocyanine dihydroxide) was covalently grafted. The silica shell improved the dispersibility of hydrophobic PS molecules in aqueous environments, and the covalent linkage stably anchored the PS molecules in the silica shell. Under excitation at 980 nm, the as-fabricated nanomaterial gave luminescence bands at 550 nm and 660 nm. One luminescent peak could be used for fluorescence imaging and the other was suitable for the absorption of PS to generate singlet oxygen for killing cancer cells. The PDT performance was investigated using a singlet oxygen indicator, and was investigated in vitro in HeLa cells using a fluorescent probe. Meanwhile, the nanomaterial displayed low dark cytotoxicity and near-infrared (NIR) image in HeLa cells. Further, benefiting from the paramagnetic Gd3+ ions in the core, the nanomaterial could be used as a contrast agent for magnetic resonance imaging (MRI). Compared with the clinical commercial contrast agent Gd-DTPA, the as-fabricated nanomaterial showed a comparable longitudinal relaxivities value (r1) and similar imaging effect. Electronic supplementary information (ESI) available: More TEM, emission spectra, longitudinal and transverse relaxation times, t2-weighted MR images of the as-prepared nanomaterial, and confocal fluorescent images of HeLa cells. See DOI: 10.1039/c2nr30938f

Monodisperse core-shell particles composed of magnetite and dye-functionalized mesoporous silica

NASA Astrophysics Data System (ADS)

Eurov, D. A.; Kurdyukov, D. A.; Medvedev, A. V.; Kirilenko, D. A.; Yakovlev, D. R.; Golubev, V. G.

2017-08-01

Hybrid particles with a core-shell structure have been obtained in the form of monodisperse spherical mesoporous silica particles filled with magnetite and covered with a mesoporous silica shell functionalized with a luminescent dye. The particles have a small root-mean-square size deviation (at most 10%), possess a specific surface area and specific pore volume of up to 250 m2/g and 0.15 cm3/g, respectively, and exhibit visible luminescence peaked at a wavelength of 530 nm. The particles can be used in diagnostics of cancerous diseases, serving simultaneously for therapeutic (magnetic hyperthermia and targeted drug delivery) and diagnostic (contrast agent for magnetic-resonance tomography and luminescent marker) purposes.

A model for large amplitude oscillations of coated bubbles accounting for buckling and rupture

NASA Astrophysics Data System (ADS)

Marmottant, Philippe; van der Meer, Sander; Emmer, Marcia; Versluis, Michel; de Jong, Nico; Hilgenfeldt, Sascha; Lohse, Detlef

2005-12-01

We present a model applicable to ultrasound contrast agent bubbles that takes into account the physical properties of a lipid monolayer coating on a gas microbubble. Three parameters describe the properties of the shell: a buckling radius, the compressibility of the shell, and a break-up shell tension. The model presents an original non-linear behavior at large amplitude oscillations, termed compression-only, induced by the buckling of the lipid monolayer. This prediction is validated by experimental recordings with the high-speed camera Brandaris 128, operated at several millions of frames per second. The effect of aging, or the resultant of repeated acoustic pressure pulses on bubbles, is predicted by the model. It corrects a flaw in the shell elasticity term previously used in the dynamical equation for coated bubbles. The break-up is modeled by a critical shell tension above which gas is directly exposed to water.

The Subharmonic Behavior and Thresholds of High Frequency Ultrasound Contrast Agents

NASA Astrophysics Data System (ADS)

Allen, John

2016-11-01

Ultrasound contrast agents are encapsulated micro-bubbles used for diagnostic and therapeutic biomedical ultrasound. The agents oscillate nonlinearly about their equilibrium radii upon sufficient acoustic forcing and produce unique acoustic signatures that allow them to be distinguished from scattering from the surrounding tissue. The subharmonic response occurs below the fundamental and is associated with an acoustic pressure threshold. Subharmonic imaging using ultrasound contrast agents has been established for clinical applications at standard diagnostic frequencies typically below 20 MHz. However, for emerging applications of high frequency applications (above 20 MHz) subharmonic imaging is an area of on-going research. The effects of attenuation from tissue are more significant and the characterization of agents is not as well understood. Due to specificity and control production, polymer agents are useful for high frequency applications. In this study, we highlight novel measurement techniques to measure and characterize the mechanical properties of the shell of polymer contrast agents. The definition of the subharmonic threshold is investigated with respect to mono-frequency and chirp forcing waveforms which have been used to achieve optimal subharmonic content in the backscattered signal. Time frequency analysis using the Empirical Mode Decomposition (EMD) and the Hilbert-Huang transform facilitates a more sensitive and robust methodology for characterization of subharmonic content with respect to non-stationary forcing. A new definition of the subharmonic threshold is proposed with respect to the energy content of the associated adaptive basis decomposition. Additional studies with respect to targeted agent behavior and cardiovascular disease are discussed. NIH, ONR.

Synthesis and characterization of Na(Gd0.5Lu0.5)F4: Nd3+,a core-shell free multifunctional contrast agent.

PubMed

Mimun, L Christopher; Ajithkumar, G; Rightsell, Chris; Langloss, Brian W; Therien, Michael J; Sardar, Dhiraj K

2017-02-25

Compared to conventional core-shell structures, core-shell free nanoparticles with multiple functionalities offer several advantages such as minimal synthetic complexity and low production cost. In this paper, we present the synthesis and characterization of Nd 3+ doped Na(Gd 0.5 Lu 0.5 )F 4 as a core-shell free nanoparticle system with three functionalities. Nanocrystals with 20 nm diameter, high crystallinity and a narrow particle size distributions were synthesized by the solvothermal method and characterized by various analytical techniques to understand their phase and morphology. Fluorescence characteristics under near infrared (NIR) excitation at 808 nm as well as X-ray excitation were studied to explore their potential in NIR optical and X-ray imaging. At 1.0 mol% Nd concentration, we observed a quantum yield of 25% at 1064 nm emission with 13 W/cm 2 excitation power density which is sufficiently enough for imaging applications. Under 130 kVp (5 mA) power of X-ray excitation, Nd 3+ doped Na(Gd 0.5 Lu 0.5 )F 4 shows the characteristic emission bands of Gd 3+ and Nd 3+ with the strongest emission peak at 1064 nm due to Nd 3+ . Furthermore, magnetization measurements show that the nanocrystals are paramagnetic in nature with a calculated magnetic moment per particle of ~570 μB at 2T. These preliminary results support the suitability of the present nanophosphor as a multimodal contrast agent with three imaging features viz. optical, magnetic and X-ray.

A theranostic dental pulp capping agent with improved MRI and CT contrast and biological properties.

PubMed

Mastrogiacomo, S; Güvener, N; Dou, W; Alghamdi, H S; Camargo, W A; Cremers, J G O; Borm, P J A; Heerschap, A; Oosterwijk, E; Jansen, J A; Walboomers, X F

2017-10-15

Different materials have been used for vital dental pulp treatment. Preferably a pulp capping agent should show appropriate biological performance, excellent handling properties, and a good imaging contrast. These features can be delivered into a single material through the combination of therapeutic and diagnostic agents (i.e. theranostic). Calcium phosphate based composites (CPCs) are potentially ideal candidate for pulp treatment, although poor imaging contrast and poor dentino-inductive properties are limiting their clinical use. In this study, a theranostic dental pulp capping agent was developed. First, imaging properties of the CPC were improved by using a core-shell structured dual contrast agent (csDCA) consisting of superparamagnetic iron oxide (SPIO) and colloidal gold, as MRI and CT contrast agent respectively. Second, biological properties were implemented by using a dentinogenic factor (i.e. bone morphogenetic protein 2, BMP-2). The obtained CPC/csDCA/BMP-2 composite was tested in vivo, as direct pulp capping agent, in a male Habsi goat incisor model. Our outcomes showed no relevant alteration of the handling and mechanical properties (e.g. setting time, injectability, and compressive strength) by the incorporation of csDCA particles. In vivo results proved MRI contrast enhancement up to 7weeks. Incisors treated with BMP-2 showed improved tertiary dentin deposition as well as faster cement degradation as measured by µCT assessment. In conclusion, the presented theranostic agent matches the imaging and regenerative requirements for pulp capping applications. In this study, we combined diagnostic and therapeutic agents in order to developed a theranostic pulp capping agent with enhanced MRI and CT contrast and improved dentin regeneration ability. In our study we cover all the steps from material preparation, mechanical and in vitro characterization, to in vivo study in a goat dental model. To the best of our knowledge, this is the first time that a theranostic pulp capping material have been developed and tested in an in vivo animal model. Our promising results in term of imaging contrast enhancement and of induction of new dentin formation, open a new scenario in the development of innovative dental materials. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Inertial cavitation threshold of nested microbubbles.

PubMed

Wallace, N; Dicker, S; Lewin, Peter; Wrenn, S P

2015-04-01

Cavitation of ultrasound contrast agents (UCAs) promotes both beneficial and detrimental bioeffects in vivo (Radhakrishnan et al., 2013) [1]. The ability to determine the inertial cavitation threshold of UCA microbubbles has potential application in contrast imaging, development of therapeutic agents, and evaluation of localized effects on the body (Ammi et al., 2006) [2]. This study evaluates a novel UCA and its inertial cavitation behavior as determined by a home built cavitation detection system. Two 2.25 MHz transducers are placed at a 90° angle to one another where one transducer is driven by a high voltage pulser and the other transducer receives the signal from the oscillating microbubble. The sample chamber is placed in the overlap of the focal region of the two transducers where the microbubbles are exposed to a pulser signal consisting of 600 pulse trains per experiment at a pulse repetition frequency of 5 Hz where each train has four pulses of four cycles. The formulation being analyzed is comprised of an SF6 microbubble coated by a DSPC PEG-3000 monolayer nested within a poly-lactic acid (PLA) spherical shell. The effect of varying shell diameters and microbubble concentration on cavitation threshold profile for peak negative pressures ranging from 50 kPa to 2 MPa are presented and discussed in this paper. The nesting shell decreases inertial cavitation events from 97.96% for an un-nested microbubble to 19.09% for the same microbubbles nested within a 2.53 μm shell. As shell diameter decreases, the percentage of inertially cavitating microbubbles also decreases. For nesting formulations with average outer capsule diameters of 20.52, 14.95, 9.95, 5.55, 2.53, and 1.95 μm, the percentage of sample destroyed at 1 MPa was 51.02, 38.94, 33.25, 25.27, 19.09, and 5.37% respectively. Copyright © 2015 Elsevier B.V. All rights reserved.

Magnetic Responsive Hydrogel Material Delivery System II

DTIC Science & Technology

2010-08-29

phase. MNPs have found very useful applications in bioseparation, drug delivery system, hyperthermia for cancer therapy, and magnetic resonance...and the poly(N-isoproplyacrylamide) (poly(NIPAAm) shell in aqueous medium. Magnetic nanoparticles (MNPs) were coated with first oleic acid (OA) and...potentially important in target delivery of therapeutic agent in vivo, hyperthermic treatment of tumors, magnetic resonance imaging (MRI) as contrasting

Study on surface-enhanced Raman scattering efficiency of Ag core-Au shell bimetallic nanoparticles

NASA Astrophysics Data System (ADS)

Dong, Xiao; Gu, Huaimin; Kang, Jian; Yuan, Xiaojuan

2009-08-01

In this article, the relationship between the states of Ag core-Au shell (core-shell) nanoparticles (NP) and the intensity of Raman scattering of analytes dissolved in the water and adsorbed on the NP was studied. The core-shell NP were synthesised by coating Au layers over Ag seeds by the method of "seed-growth". To highlight the advantage of the core-shell NP, Ag colloid and Au colloid were chosen for contrasting. The analyte that were chosen for this testing were methylene blue (MB) for the reason that MB has very strong signal in surface-enhanced Raman scattering (SERS). The SERS activity of optimalizing states of Ag and Au colloids were compared with that of core-shell NP when MB was used as analyte. In this study, sodium chloride, sodium sulfate and sodium nitrate were used as aggregating agents for Ag, Au colloids and core-shell NP, because anions have a strong influence on the SERS efficiency and the stability of colloids. The results indicate that core-shell NP can obviously enhance the SERS of MB. The aim of this study is to prove that compared with the metal colloid, the core-shell NP is a high efficiency SERS active substrate.

Post-buckling of a pressured biopolymer spherical shell with the mode interaction

NASA Astrophysics Data System (ADS)

Zhang, Lei; Ru, C. Q.

2018-03-01

Imperfection sensitivity is essential for mechanical behaviour of biopolymer shells characterized by high geometric heterogeneity. The present work studies initial post-buckling and imperfection sensitivity of a pressured biopolymer spherical shell based on non-axisymmetric buckling modes and associated mode interaction. Our results indicate that for biopolymer spherical shells with moderate radius-to-thickness ratio (say, less than 30) and smaller effective bending thickness (say, less than 0.2 times average shell thickness), the imperfection sensitivity predicted based on the axisymmetric mode without the mode interaction is close to the present results based on non-axisymmetric modes with the mode interaction with a small (typically, less than 10%) relative errors. However, for biopolymer spherical shells with larger effective bending thickness, the maximum load an imperfect shell can sustain predicted by the present non-axisymmetric analysis can be significantly (typically, around 30%) lower than those predicted based on the axisymmetric mode without the mode interaction. In such cases, a more accurate non-axisymmetric analysis with the mode interaction, as given in the present work, is required for imperfection sensitivity of pressured buckling of biopolymer spherical shells. Finally, the implications of the present study to two specific types of biopolymer spherical shells (viral capsids and ultrasound contrast agents) are discussed.

Self-Assembled Nanomicelles as MRI Blood-Pool Contrast Agent.

PubMed

Babič, Andrej; Vorobiev, Vassily; Xayaphoummine, Céline; Lapicorey, Gaëlle; Chauvin, Anne-Sophie; Helm, Lothar; Allémann, Eric

2018-01-26

Gadolinium-loaded nanomicelles show promise as future magnetic resonance imaging (MRI) contrast agents (CAs). Their increased size and high gadolinium (Gd) loading gives them an edge in proton relaxivity over smaller molecular Gd-complexes. Their size and stealth properties are fundamental for their long blood residence time, opening the possibility for use as blood-pool contrast agents. Using l-tyrosine as a three-functional scaffold we synthesized a nanostructure building block 8. The double C18 aliphatic chain on one side, Gd-1,4,7,10-tetraazacyclododecane-1-4-7-triacetic acid (Gd-DO3A) with access to bulk water in the center and 2 kDa PEG on the hydrophilic side gave the amphiphilic properties required for the core-shell nanomicellar architecture. The self-assembly into Gd-loaded monodispersed 10-20 nm nanomicelles occurred spontaneously in water. These nanomicelles (Tyr-MRI) display very high relaxivity at 29 mm -1  s -1 at low field strength and low cytotoxicity. Good contrast enhancement of the blood vessels and the heart together with prolonged circulation time in vivo, makes Tyr-MRI an excellent candidate for a new supramolecular blood-pool MRI CA. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Modeling complicated rheological behaviors in encapsulating shells of lipid-coated microbubbles accounting for nonlinear changes of both shell viscosity and elasticity

NASA Astrophysics Data System (ADS)

Li, Qian; Matula, Thomas J.; Tu, Juan; Guo, Xiasheng; Zhang, Dong

2013-02-01

It has been accepted that the dynamic responses of ultrasound contrast agent (UCA) microbubbles will be significantly affected by the encapsulating shell properties (e.g., shell elasticity and viscosity). In this work, a new model is proposed to describe the complicated rheological behaviors in an encapsulating shell of UCA microbubbles by applying the nonlinear ‘Cross law’ to the shell viscous term in the Marmottant model. The proposed new model was verified by fitting the dynamic responses of UCAs measured with either a high-speed optical imaging system or a light scattering system. The comparison results between the measured radius-time curves and the numerical simulations demonstrate that the ‘compression-only’ behavior of UCAs can be successfully simulated with the new model. Then, the shell elastic and viscous coefficients of SonoVue microbubbles were evaluated based on the new model simulations, and compared to the results obtained from some existing UCA models. The results confirm the capability of the current model for reducing the dependence of bubble shell parameters on the initial bubble radius, which indicates that the current model might be more comprehensive to describe the complex rheological nature (e.g., ‘shear-thinning’ and ‘strain-softening’) in encapsulating shells of UCA microbubbles by taking into account the nonlinear changes of both shell elasticity and shell viscosity.

Modeling complicated rheological behaviors in encapsulating shells of lipid-coated microbubbles accounting for nonlinear changes of both shell viscosity and elasticity.

PubMed

Li, Qian; Matula, Thomas J; Tu, Juan; Guo, Xiasheng; Zhang, Dong

2013-02-21

It has been accepted that the dynamic responses of ultrasound contrast agent (UCA) microbubbles will be significantly affected by the encapsulating shell properties (e.g., shell elasticity and viscosity). In this work, a new model is proposed to describe the complicated rheological behaviors in an encapsulating shell of UCA microbubbles by applying the nonlinear 'Cross law' to the shell viscous term in the Marmottant model. The proposed new model was verified by fitting the dynamic responses of UCAs measured with either a high-speed optical imaging system or a light scattering system. The comparison results between the measured radius-time curves and the numerical simulations demonstrate that the 'compression-only' behavior of UCAs can be successfully simulated with the new model. Then, the shell elastic and viscous coefficients of SonoVue microbubbles were evaluated based on the new model simulations, and compared to the results obtained from some existing UCA models. The results confirm the capability of the current model for reducing the dependence of bubble shell parameters on the initial bubble radius, which indicates that the current model might be more comprehensive to describe the complex rheological nature (e.g., 'shear-thinning' and 'strain-softening') in encapsulating shells of UCA microbubbles by taking into account the nonlinear changes of both shell elasticity and shell viscosity.

WE-D-210-04: Radiation-Induced Polymerization of Ultrasound Contrast Agents in View of Non-Invasive Dosimetry in External Beam Radiation Therapy

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

Callens, M; Verboven, E; Van Den Abeele, K

2015-06-15

Purpose: Ultrasound contrast agents (UCA’s) based on gas-filled microbubbles encapsulated by an amphiphilic shell are well established as safe and effective echo-enhancers in diagnostic imaging. In view of an alternative application of UCA’s, we investigated the use of targeted microbubbles as radiation sensors for external beam radiation therapy. As radiation induces permanent changes in the microbubble’s physico-chemical properties, a robust measure of these changes can provide a direct or indirect estimate of the applied radiation dose. For instance, by analyzing the ultrasonic dispersion characteristics of microbubble distributions before and after radiation treatment, an estimate of the radiation dose at themore » location of the irradiated volume can be made. To increase the radiation sensitivity of microbubbles, polymerizable diacetylene molecules can be incorporated into the shell. This study focuses on characterizing the acoustic response and quantifying the chemical modifications as a function of radiation dose. Methods: Lipid/diacetylene microbubbles were irradiated with a 6 MV photon beam using dose levels in the range of 0–150 Gy. The acoustic response of the microbubbles was monitored by ultrasonic through-transmission measurements in the range of 500 kHz to 20 MHz, thereby providing the dispersion relations of the phase velocity, attenuation and nonlinear coefficient. In addition, the radiation-induced chemical modifications were quantified using UV-VIS spectroscopy. Results: UV-VIS spectroscopy measurements indicate that ionizing radiation induces the polymerization of diacetylenes incorporated in the microbubble shell. The polymer yield strongly depends on the shell composition and the radiation-dose. The acoustic response is inherently related to the visco-elastic properties of the shell and is strongly influenced by the shell composition and the physico-chemical changes in the environment. Conclusion: Diacetylene-containing microbubbles are polymerizable under influence of ionizing radiation and are a promising design concept within the development of a novel non-invasive in-vivo radiation dosimeter for external beam radiation therapy. This work was funded by the Research Foundation - Flanders (FWO)« less

Imperfection sensitivity of pressured buckling of biopolymer spherical shells

NASA Astrophysics Data System (ADS)

Zhang, Lei; Ru, C. Q.

2016-06-01

Imperfection sensitivity is essential for mechanical behavior of biopolymer shells [such as ultrasound contrast agents (UCAs) and spherical viruses] characterized by high geometric heterogeneity. In this work, an imperfection sensitivity analysis is conducted based on a refined shell model recently developed for spherical biopolymer shells of high structural heterogeneity and thickness nonuniformity. The influence of related parameters (including the ratio of radius to average shell thickness, the ratio of transverse shear modulus to in-plane shear modulus, and the ratio of effective bending thickness to average shell thickness) on imperfection sensitivity is examined for pressured buckling. Our results show that the ratio of effective bending thickness to average shell thickness has a major effect on the imperfection sensitivity, while the effect of the ratio of transverse shear modulus to in-plane shear modulus is usually negligible. For example, with physically realistic parameters for typical imperfect spherical biopolymer shells, the present model predicts that actual maximum external pressure could be reduced to as low as 60% of that of a perfect UCA spherical shell or 55%-65% of that of a perfect spherical virus shell, respectively. The moderate imperfection sensitivity of spherical biopolymer shells with physically realistic imperfection is largely attributed to the fact that biopolymer shells are relatively thicker (defined by smaller radius-to-thickness ratio) and therefore practically realistic imperfection amplitude normalized by thickness is very small as compared to that of classical elastic thin shells which have much larger radius-to-thickness ratio.

Ferrimagnetic ferritin cage nanoparticles used as MRI contrast agent

NASA Astrophysics Data System (ADS)

Cai, Y.; Cao, C.; Zhang, T.; Xu, H.; Pan, Y.

2017-12-01

The nano-sized ferrimagnetic ferritin cage nanoparticles are ideal materials for understanding of superparamagnetism, biomimetic synthesis of ultrafine magnetic particles and their application in biomedicine. Ferrimagnetic M-HFn nanoparticles with size of magnetite cores in a mean size ranges from 2.7 nm to 5.3 nm were synthesized through loading different amount of iron into recombinant human H chain ferritin (HFn) shells. Both the saturation magnetization (Ms) and blocking temperature (Tb) were increased with the size of ferrimagnetic cores. In essence, magnetic resonance imaging (MRI) analysis showed that the synthesized M-HFn nanoparticles (5.3 nm magnetite core) has extremely high transverse relaxivity (r2) values up to 320.9 mM-1S-1, which indicate that M-HFn nanoparticles are promising negative contrast agent in early detection of tumors. In addition, the longitudinal relaxivity (r1) (10.4 mM-1S-1) and r2/r1 ratio ( 2.2) of M-HFn nanoparticles ( 2.7 nm magnetite core in diameter) will make it a considerable potential as a positive contrast agent in MRI. This means the M-HFn nanoparticles can be used as dual functional MR contrast agent. Acute toxicity study of M-HFn in rats showed that a dosage of 20 mg Fe/kg makes no abnormalities by serum biochemical and hematological analysis as well as histopathological examination. Compared with a similar commercial contrast agent, combidex (with a clinical dosage of 2.7 mg Fe/kg), it indicates that M-HFn nanoparticle is of a relative safe ferrimagnetic nanoparticle when used in vivo.

Development of Targeted Nanobubbles for Ultrasound Imaging and Ablation of Metastatic Prostate Cancer Lesions

DTIC Science & Technology

2013-08-01

AD_________________ Award Number: W81XWH-12-1-0284 TITLE: Development of Targeted Nanobubbles for...REPORT TYPE Annual 3. DATES COVERED 15 July 2012 - 14 July 2013 4. TITLE AND SUBTITLE Development of Targeted Nanobubbles for Ultrasound...be able to formulate nanodroplets contrast agents with tunable size, PFP content, and shell flexibility to obtain stable and echogenic nanobubbles

Determining the size of nanoparticles in the example of magnetic iron oxide core-shell systems

NASA Astrophysics Data System (ADS)

Jarzębski, Maciej; Kościński, Mikołaj; Białopiotrowicz, Tomasz

2017-08-01

The size of nanoparticles is one of the most important factors for their possible applications. Various techniques for the nanoparticle size characterization are available. In this paper selected techniques will be considered base on the prepared core-shell magnetite nanoparticles. Magnetite is one of the most investigated and developed magnetic material. It shows interesting magnetic properties which can be used for biomedical applications, such as drug delivery, hypothermia and also as a contrast agent. To reduce the toxic effects of Fe3O4, magnetic core was covered by dextran and gelatin. Moreover, the shell was doped by fluorescent dye for confocal microscopy investigation. The main investigation focused on the methods for particles size determination of modified magnetite nanoparticles prepared with different techniques. The size distribution were obtained by nanoparticle tracking analysis, dynamic light scattering and transmission electron microscopy. Furthermore, fluorescent correlation spectroscopy (FCS) and confocal microscopy were used to compare the results for particle size determination of core-shell systems.

Development of Gd3N@C80 encapsulated redox nanoparticles for high-performance magnetic resonance imaging.

PubMed

Gao, Zhenyu; Nakanishi, Yusuke; Noda, Shoko; Omachi, Haruka; Shinohara, Hisanori; Kimura, Hiroyuki; Nagasaki, Yukio

As novel magnetic resonance imaging (MRI) contrast agent, gadofullerene encapsulated redox nanoparticles (Gd 3 NPs) were prepared by encapsulation of Gd 3 N@C 80 in the core of core-shell-type polymer micelles composed of original polyamine with a reactive oxygen species (ROS)-scavenging ability. Because Gd 3 NPs possess biocompatible PEG shell with a smaller size (ca. 50 nm), they had high colloidal stability in a physiological environment, and showed low cytotoxicity. Specific accumulation of Gd 3 NPs in a tumor was confirmed in tumor-bearing mice after systemic administration. The tumor/muscle (T/M) ratio of the Gd ion reached five at 7.5 h after the administration. T 1 -weighted MRI signal enhancement of the T/M ratio increased by 8% at 6 h postinjection of Gd 3 NPs (Gd dose:14.35 μmol/kg). Although Gd 3 NPs showed a tendency for extended blood circulation, they did not have severe adverse effects, probably due to the confinement of Gd in a hydrophobic fullerene in addition to the ROS-scavenging capacity of these nanoparticles. In sharp contrast, systemic administration of Gd-chelate nanoparticles (GdCNPs) to mice disrupts liver function, increases leukocyte counts, and destroys spleen and skin tissues. Leaking of Gd ions from GdCNPs may cause such adverse effects. Based on these results, we expect that Gd 3 NPs is high-performance MRI contrast agents for tumor diagnosis.

Improving performance of nanoscale ultrasound contrast agents using N,N-diethylacrylamide stabilization.

PubMed

Perera, Reshani H; Wu, Hanping; Peiris, Pubudu; Hernandez, Christopher; Burke, Alan; Zhang, Helen; Exner, Agata A

2017-01-01

The design of nanoscale yet highly echogenic agents for imaging outside of the vasculature and for ultrasound-mediated drug delivery remains a formidable challenge. We have previously reported on formulation of echogenic perfluoropropane gas nanobubbles stabilized by a lipid-pluronic surfactant shell. In the current work we describe the development of a new generation of these nanoparticles which consist of perfluoropropane gas stabilized by a surfactant and lipid membrane and a crosslinked network of N,N-diethylacrylamide. The resulting crosslinked nanobubbles (CL-PEG-NB) were 95.2±25.2nm in diameter and showed significant improvement in stability and retention of echogenic signal over 24h. In vivo analysis via ultrasound and fluorescence mediated tomography showed greater tumor extravasation and accumulation with CL-PEG-NB compared to microbubbles. Together these results demonstrate the capabilities and advantages of a new, more stable, nanometer-scale ultrasound contrast agent that can be utilized in future work for diagnostic scans and molecular imaging. Copyright © 2016 Elsevier Inc. All rights reserved.

Polypyrrole coated phase-change contrast agents for sono-photoacoustic imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Li, David S.; Yoon, Soon Joon; Matula, Thomas J.; O'Donnell, Matthew; Pozzo, Lilo D.

2017-03-01

A new light and sound sensitive nanoemulsion contrast agent is presented. The agents feature a low boiling point liquid perfluorocarbon core and a broad light spectrum absorbing polypyrrole (PPy) polymer shell. The PPy coated nanoemulsions can reversibly convert from liquid to gas phase upon cavitation of the liquid perfluorocarbon core. Cavitation can be initiated using a sufficiently high intensity acoustic pulse or from heat generation due to light absorption from a laser pulse. The emulsions can be made between 150 and 350 nm in diameter and PPy has a broad optical absorption covering both the visible spectrum and extending into the near-infrared spectrum (peak absorption 1053 nm). The size, structure, and optical absorption properties of the PPy coated nanoemulsions were characterized and compared to PPy nanoparticles (no liquid core) using dynamic light scattering, ultraviolet-visible spectrophotometry, transmission electron microscopy, and small angle X-ray scattering. The cavitation threshold and signal intensity were measured as a function of both acoustic pressure and laser fluence. Overlapping simultaneous transmission of an acoustic and laser pulse can significantly reduce the activation energy of the contrast agents to levels lower than optical or acoustic activation alone. We also demonstrate that simultaneous light and sound cavitation of the agents can be used in a new sono-photoacoustic imaging method, which enables greater sensitivity than traditional photoacoustic imaging.

Mapping microbubble viscosity using fluorescence lifetime imaging of molecular rotors

PubMed Central

Hosny, Neveen A.; Mohamedi, Graciela; Rademeyer, Paul; Owen, Joshua; Wu, Yilei; Tang, Meng-Xing; Eckersley, Robert J.; Stride, Eleanor; Kuimova, Marina K.

2013-01-01

Encapsulated microbubbles are well established as highly effective contrast agents for ultrasound imaging. There remain, however, some significant challenges to fully realize the potential of microbubbles in advanced applications such as perfusion mapping, targeted drug delivery, and gene therapy. A key requirement is accurate characterization of the viscoelastic surface properties of the microbubbles, but methods for independent, nondestructive quantification and mapping of these properties are currently lacking. We present here a strategy for performing these measurements that uses a small fluorophore termed a “molecular rotor” embedded in the microbubble surface, whose fluorescence lifetime is directly related to the viscosity of its surroundings. We apply fluorescence lifetime imaging to show that shell viscosities vary widely across the population of the microbubbles and are influenced by the shell composition and the manufacturing process. We also demonstrate that heterogeneous viscosity distributions exist within individual microbubble shells even with a single surfactant component. PMID:23690599

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

Chen, Kuangcai; Lin, Chia -Cheng; Vela, Javier

In this study, three-layer core–shell plasmonic nanorods (Au/Ag/SiO 2–NRs), consisting of a gold nanorod core, a thin silver shell, and a thin silica layer, were synthesized and used as optical imaging probes under a differential interference contrast microscope for single particle orientation and rotational tracking. The localized surface plasmon resonance modes were enhanced upon the addition of the silver shell, and the anisotropic optical properties of gold nanorods were maintained. The silica coating enables surface functionalization with silane coupling agents and provides enhanced stability and biocompatibility. Taking advantage of the longitudinal LSPR enhancement, the orientation and rotational information of themore » hybrid nanorods on synthetic lipid bilayers and on live cell membranes were obtained with millisecond temporal resolution using a scientific complementary metal-oxide-semiconductor camera. The results demonstrate that the as-synthesized hybrid nanorods are promising imaging probes with improved sensitivity and good biocompatibility for single plasmonic particle tracking experiments in biological systems.« less

Lipid-based nanoparticles for contrast-enhanced MRI and molecular imaging.

PubMed

Mulder, Willem J M; Strijkers, Gustav J; van Tilborg, Geralda A F; Griffioen, Arjan W; Nicolay, Klaas

2006-02-01

In the field of MR imaging and especially in the emerging field of cellular and molecular MR imaging, flexible strategies to synthesize contrast agents that can be manipulated in terms of size and composition and that can be easily conjugated with targeting ligands are required. Furthermore, the relaxivity of the contrast agents, especially for molecular imaging applications, should be very high to deal with the low sensitivity of MRI. Lipid-based nanoparticles, such as liposomes or micelles, have been used extensively in recent decades as drug carrier vehicles. A relatively new and promising application of lipidic nanoparticles is their use as multimodal MR contrast agents. Lipids are amphiphilic molecules with both a hydrophobic and a hydrophilic part, which spontaneously assemble into aggregates in an aqueous environment. In these aggregates, the amphiphiles are arranged such that the hydrophobic parts cluster together and the hydrophilic parts face the water. In the low concentration regime, a wide variety of structures can be formed, ranging from spherical micelles to disks or liposomes. Furthermore, a monolayer of lipids can serve as a shell to enclose a hydrophobic core. Hydrophobic iron oxide particles, quantum dots or perfluorocarbon emulsions can be solubilized using this approach. MR-detectable and fluorescent amphiphilic molecules can easily be incorporated in lipidic nanoparticles. Furthermore, targeting ligands can be conjugated to lipidic particles by incorporating lipids with a functional moiety to allow a specific interaction with molecular markers and to achieve accumulation of the particles at disease sites. In this review, an overview of different lipidic nanoparticles for use in MRI is given, with the main emphasis on Gd-based contrast agents. The mechanisms of particle formation, conjugation strategies and applications in the field of contrast-enhanced, cellular and molecular MRI are discussed. 2006 John Wiley & Sons, Ltd.

Development of magneto-plasmonic nanoparticles for multimodal image-guided therapy to the brain.

PubMed

Tomitaka, Asahi; Arami, Hamed; Raymond, Andrea; Yndart, Adriana; Kaushik, Ajeet; Jayant, Rahul Dev; Takemura, Yasushi; Cai, Yong; Toborek, Michal; Nair, Madhavan

2017-01-05

Magneto-plasmonic nanoparticles are one of the emerging multi-functional materials in the field of nanomedicine. Their potential for targeting and multi-modal imaging is highly attractive. In this study, magnetic core/gold shell (MNP@Au) magneto-plasmonic nanoparticles were synthesized by citrate reduction of Au ions on magnetic nanoparticle seeds. Hydrodynamic size and optical properties of magneto-plasmonic nanoparticles synthesized with the variation of Au ions and reducing agent concentrations were evaluated. The synthesized magneto-plasmonic nanoparticles exhibited superparamagnetic properties, and their magnetic properties contributed to the concentration-dependent contrast in magnetic resonance imaging (MRI). The imaging contrast from the gold shell part of the magneto-plasmonic nanoparticles was also confirmed by X-ray computed tomography (CT). The transmigration study of the magneto-plasmonic nanoparticles using an in vitro blood-brain barrier (BBB) model proved enhanced transmigration efficiency without disrupting the integrity of the BBB, and showed potential to be used for brain diseases and neurological disorders.

Comparison between maximum radial expansion of ultrasound contrast agents and experimental postexcitation signal results.

PubMed

King, Daniel A; O'Brien, William D

2011-01-01

Experimental postexcitation signal data of collapsing Definity microbubbles are compared with the Marmottant theoretical model for large amplitude oscillations of ultrasound contrast agents (UCAs). After taking into account the insonifying pulse characteristics and size distribution of the population of UCAs, a good comparison between simulated results and previously measured experimental data is obtained by determining a threshold maximum radial expansion (Rmax) to indicate the onset of postexcitation. This threshold Rmax is found to range from 3.4 to 8.0 times the initial bubble radius, R0, depending on insonification frequency. These values are well above the typical free bubble inertial cavitation threshold commonly chosen at 2R0. The close agreement between the experiment and models suggests that lipid-shelled UCAs behave as unshelled bubbles during most of a large amplitude cavitation cycle, as proposed in the Marmottant equation.

Multifunctional gold coated iron oxide core-shell nanoparticles stabilized using thiolated sodium alginate for biomedical applications.

PubMed

Sood, Ankur; Arora, Varun; Shah, Jyoti; Kotnala, R K; Jain, Tapan K

2017-11-01

In this paper we report synthesis of aqueous based gold coated iron oxide nanoparticles to integrate the localized surface plasma resonance (SPR) properties of gold and magnetic properties of iron oxide in a single system. Iron oxide-gold core shell nanoparticles were stabilized by attachment of thiolated sodium alginate to the surface of nanoparticles. Transmission electron microscope (TEM) micrograph presents an average elementary particle size of 8.1±2.1nm. High resolution TEM (HR-TEM) and X-ray photon spectroscopy further confirms the presence of gold shell around iron oxide core. Gold coating is responsible for reducing saturation magnetization (M s ) value from ~41emu/g to ~24emu/g - in thiolated sodium alginate stabilized gold coated iron oxide core-shell nanoparticles. The drug (curcumin) loading efficiency for the prepared nanocomposites was estimated to be around 7.2wt% (72μgdrug/mg nanoparticles) with encapsulation efficiency of 72.8%. Gold-coated iron oxide core-shell nanoparticles could be of immense importance in the field of targeted drug delivery along with capability to be used as contrast agent for MRI & CT. Copyright © 2017 Elsevier B.V. All rights reserved.

TOPICAL REVIEW: Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

NASA Astrophysics Data System (ADS)

Qin, Shengping; Caskey, Charles F.; Ferrara, Katherine W.

2009-03-01

Microbubble contrast agents and the associated imaging systems have developed over the past 25 years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium.

Ultrasound contrast microbubbles in imaging and therapy: physical principles and engineering

PubMed Central

Qin, Shengping; Caskey, Charles F; Ferrara, Katherine W

2010-01-01

Microbubble contrast agents and the associated imaging systems have developed over the past twenty-five years, originating with manually-agitated fluids introduced for intra-coronary injection. Over this period, stabilizing shells and low diffusivity gas materials have been incorporated in microbubbles, extending stability in vitro and in vivo. Simultaneously, the interaction of these small gas bubbles with ultrasonic waves has been extensively studied, resulting in models for oscillation and increasingly sophisticated imaging strategies. Early studies recognized that echoes from microbubbles contained frequencies that are multiples of the microbubble resonance frequency. Although individual microbubble contrast agents cannot be resolved—given that their diameter is on the order of microns—nonlinear echoes from these agents are used to map regions of perfused tissue and to estimate the local microvascular flow rate. Such strategies overcome a fundamental limitation of previous ultrasound blood flow strategies; the previous Doppler-based strategies are insensitive to capillary flow. Further, the insonation of resonant bubbles results in interesting physical phenomena that have been widely studied for use in drug and gene delivery. Ultrasound pressure can enhance gas diffusion, rapidly fragment the agent into a set of smaller bubbles or displace the microbubble to a blood vessel wall. Insonation of a microbubble can also produce liquid jets and local shear stress that alter biological membranes and facilitate transport. In this review, we focus on the physical aspects of these agents, exploring microbubble imaging modes, models for microbubble oscillation and the interaction of the microbubble with the endothelium. PMID:19229096

In Vitro Evaluation of Gd(3+)-Anionic Linear Globular Dendrimer-Monoclonal Antibody: Potential Magnetic Resonance Imaging Contrast Agents for Prostate Cancer Cell Imaging.

PubMed

Mirzaei, Mehdi; Mehravi, Bita; Ardestani, Mehdi Shafiee; Ziaee, Seyed Amir Mohsen; Pourghasem, Peyman

2015-12-01

Early stage prostate cancer diagnosis is of high global interest. Magnetic resonance imaging (MRI) is a non-invasive modality for early cancer diagnosis, in particular for prostate cancer detection. The research aim is to synthesize a nanodendrimer and its conjugate with C595 monoclonal antibody (mAb C595), against prostate cancer, followed by its chelating with Gd(3+). Anti-MUC-1 mAb C595 was conjugated to an anionic linear globular dendrimer (ALGDG2). The polyethylene glycol core and citric acid shell were synthesized followed by loading with Gd(3+) to make novel contrast agents for functional MRI. The in vitro behavior and MRI parameters of the nanoconjugate were investigated performing several studies such as cell toxicity and TNF-alpha evaluations. The investigation of magnetic resonance imaging parameters indicated how well nanoconjugate performs in (1)H-NMR and (17)O-NMR in vitro. Results showed a potential specific MRI activity by improving the swelling responses cell binding. The MTT (2-(4,5-dimethyl-2-thiazolyl)-3,5-diphenyl-2H-tetrazolium bromide) assay demonstrated that this contrast agent had significant cytotoxicity on prostate cancer cells. These results showed that Gd(3+)-ALGDG2-C595 is a potential prostate molecular imaging agent and could be considered as an ideal functional nanoprobe. Additionally, further investigations by clinical trials are in the pipeline.

Rare earth elements in the aragonitic shell of freshwater mussel Corbicula fluminea and the bioavailability of anthropogenic lanthanum, samarium and gadolinium in river water.

PubMed

Merschel, Gila; Bau, Michael

2015-11-15

High-technology metals - such as the rare earth elements (REE) - have become emerging contaminants in the hydrosphere, yet little is known about their bioavailability. The Rhine River and the Weser River in Germany are two prime examples of rivers that are subjected to anthropogenic REE input. While both rivers carry significant loads of anthropogenic Gd, originating from contrast agents used for magnetic resonance imaging, the Rhine River also carries large amounts of anthropogenic La and lately Sm which are discharged into the river from an industrial point source. Here, we assess the bioavailability of these anthropogenic microcontaminants in these rivers by analyzing the aragonitic shells of the freshwater bivalve Corbicula fluminea. Concentrations of purely geogenic REE in shells of comparable size cover a wide range of about one order of magnitude between different sampling sites. At a given sampling site, geogenic REE concentrations depend on shell size, i.e. mussel age. Although both rivers show large positive Gd anomalies in their dissolved loads, no anomalous enrichment of Gd relative to the geogenic REE can be observed in any of the analyzed shells. This indicates that the speciations of geogenic and anthropogenic Gd in the river water differ from each other and that the geogenic, but not the anthropogenic Gd is incorporated into the shells. In contrast, all shells sampled at sites downstream of the industrial point source of anthropogenic La and Sm in the Rhine River show positive La and Sm anomalies, revealing that these anthropogenic REE are bioavailable. Only little is known about the effects of long-term exposure to dissolved REE and their general ecotoxicity, but considering that anthropogenic Gd and even La have already been identified in German tap water and that anthropogenic La and Sm are bioavailable, this should be monitored and investigated further. Copyright © 2015 Elsevier B.V. All rights reserved.

Collapse dynamics of ultrasound contrast agent microbubbles

NASA Astrophysics Data System (ADS)

King, Daniel Alan

Ultrasound contrast agents (UCAs) are micron-sized gas bubbles encapsulated with thin shells on the order of nanometers thick. The damping effects of these viscoelastic coatings are widely known to significantly alter the bubble dynamics for linear and low-amplitude behavior; however, their effects on strongly nonlinear and destruction responses are much less studied. This dissertation examines the behaviors of single collapsing shelled microbubbles using experimental and theoretical methods. The study of their dynamics is particularly relevant for emerging experimental uses of UCAs which seek to leverage localized mechanical forces to create or avoid specialized biomedical effects. The central component in this work is the study of postexcitation rebound and collapse, observed acoustically to identify shell rupture and transient inertial cavitation of single UCA microbubbles. This time-domain analysis of the acoustic response provides a unique method for characterization of UCA destruction dynamics. The research contains a systematic documentation of single bubble postexcitation collapse through experimental measurement with the double passive cavitation detection (PCD) system at frequencies ranging from 0.9 to 7.1 MHz and peak rarefactional pressure amplitudes (PRPA) ranging from 230 kPa to 6.37 MPa. The double PCD setup is shown to improve the quality of collected data over previous setups by allowing symmetric responses from a localized confocal region to be identified. Postexcitation signal percentages are shown to generally follow trends consistent with other similar cavitation metrics such as inertial cavitation, with greater destruction observed at both increased PRPA and lower frequency over the tested ranges. Two different types of commercially available UCAs are characterized and found to have very different collapse thresholds; lipid-shelled Definity exhibits greater postexcitation at lower PRPAs than albumin-shelled Optison. Furthermore, by altering the size distributions of these UCAs, it is shown that the shell material has a large influence on the occurrence of postexcitation rebound at all tested frequencies while moderate alteration of the size distribution may only play a significant role within certain frequency ranges. Finally, the conditions which generate the experimental postexcitation signal are examined theoretically using several forms of single bubble models. Evidence is provided for the usefulness of modeling this large amplitude UCA behavior with a size-varying surface tension as described in the Marmottant model; better agreement for lipid-shelled Definity UCAs is obtained by considering the dynamic response with a rupturing shell rather than either a non-rupturing or nonexistent shell. Moreover, the modeling indicates that maximum radial expansion from the initial UCA size is a suitable metric to predict postexcitation collapse, and that both shell rupture and inertial cavitation are necessary conditions to generate this behavior. Postexcitation analysis is found to be a beneficial characterization metric for studying the destruction behaviors of single UCAs when measured with the double PCD setup. This work provides quantitative documentation of UCA collapse, exploration into UCA material properties which affect this collapse, and comparison of existing single bubble models with experimentally measured postexcitation signals.

Lysosomal degradation of the carboxydextran shell of coated superparamagnetic iron oxide nanoparticles and the fate of professional phagocytes.

PubMed

Lunov, Oleg; Syrovets, Tatiana; Röcker, Carlheinz; Tron, Kyrylo; Nienhaus, G Ulrich; Rasche, Volker; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

2010-12-01

Contrast agents based on dextran-coated superparamagnetic iron oxide nanoparticles (SPIO) are internalized by professional phagocytes such as hepatic Kupffer cells, yet their role in phagocyte biology remains largely unknown. Here we investigated the effects of the SPIO ferucarbotran on murine Kupffer cells and human macrophages. Intravenous injection of ferucarbotran into mice led to rapid accumulation of the particles in phagocytes and to long-lasting increased iron deposition in liver and kidneys. Macrophages incorporate ferucarbotran in lysosomal vesicles containing α-glucosidase, which is capable of degrading the carboxydextran shell of the ferucarbotran particles. Intravenous injection of ferucarbotran into mice followed by incorporation of the nanoparticles into Kupffer cells triggered apoptosis and the subsequent depletion of Kupffer cells. In macrophages, the proinflammatory cytokine TNF-α increased the apoptosis rate, the reactive oxygen species production and the activation of c-Jun N-terminal kinase elicited by ferucarbotran, which might be mediated by the induction of cytoplasmic phospholipase A2 by TNF-α. Notably, the nanoparticle-induced apoptosis of murine Kupffer cells could be prevented by treatment of the mice with the radical scavenger edaravone. Thus, nanosized carboxydextran-coated SPIO-based contrast agents are retained for extended time periods by liver macrophages, where they elicit delayed cell death, which can be antagonized by a therapeutic radical scavenger. Copyright © 2010 Elsevier Ltd. All rights reserved.

Nanomechanics of biocompatible hollow thin-shell polymer microspheres.

PubMed

Glynos, Emmanouil; Koutsos, Vasileios; McDicken, W Norman; Moran, Carmel M; Pye, Stephen D; Ross, James A; Sboros, Vassilis

2009-07-07

The nanomechanical properties of biocompatible thin-shell hollow polymer microspheres with approximately constant ratio of shell thickness to microsphere diameter were measured by nanocompression tests in aqueous conditions. These microspheres encapsulate an inert gas and are used as ultrasound contrast agents by releasing free microbubbles in the presence of an ultrasound field as a result of free gas leakage from the shell. The tests were performed using an atomic force microscope (AFM) employing the force-distance curve technique. An optical microscope, on which the AFM was mounted, was used to guide the positioning of tipless cantilevers on top of individual microspheres. We performed a systematic study using several cantilevers with spring constants varying from 0.08 to 2.3 N/m on a population of microspheres with diameters from about 2 to 6 microm. The use of several cantilevers with various spring constants allowed a systematic study of the mechanical properties of the microsphere thin shell at different regimes of force and deformation. Using thin-shell mechanics theory for small deformations, the Young's modulus of the thin wall material was estimated and was shown to exhibit a strong size effect: it increased as the shell became thinner. The Young's modulus of thicker microsphere shells converged to the expected value for the macroscopic bulk material. For high applied forces, the force-deformation profiles showed a reversible and/or irreversible nonlinear behavior including "steps" and "jumps" which were attributed to mechanical instabilities such as buckling events.

Impulse response method for characterization of echogenic liposomes.

PubMed

Raymond, Jason L; Luan, Ying; van Rooij, Tom; Kooiman, Klazina; Huang, Shao-Ling; McPherson, David D; Versluis, Michel; de Jong, Nico; Holland, Christy K

2015-04-01

An optical characterization method is presented based on the use of the impulse response to characterize the damping imparted by the shell of an air-filled ultrasound contrast agent (UCA). The interfacial shell viscosity was estimated based on the unforced decaying response of individual echogenic liposomes (ELIP) exposed to a broadband acoustic impulse excitation. Radius versus time response was measured optically based on recordings acquired using an ultra-high-speed camera. The method provided an efficient approach that enabled statistical measurements on 106 individual ELIP. A decrease in shell viscosity, from 2.1 × 10(-8) to 2.5 × 10(-9) kg/s, was observed with increasing dilatation rate, from 0.5 × 10(6) to 1 × 10(7) s(-1). This nonlinear behavior has been reported in other studies of lipid-shelled UCAs and is consistent with rheological shear-thinning. The measured shell viscosity for the ELIP formulation used in this study [κs = (2.1 ± 1.0) × 10(-8) kg/s] was in quantitative agreement with previously reported values on a population of ELIP and is consistent with other lipid-shelled UCAs. The acoustic response of ELIP therefore is similar to other lipid-shelled UCAs despite loading with air instead of perfluorocarbon gas. The methods described here can provide an accurate estimate of the shell viscosity and damping for individual UCA microbubbles.

Hydrothermally synthesized PEGylated calcium phosphate nanoparticles incorporating Gd-DTPA for contrast enhanced MRI diagnosis of solid tumors.

PubMed

Mi, Peng; Kokuryo, Daisuke; Cabral, Horacio; Kumagai, Michiaki; Nomoto, Takahiro; Aoki, Ichio; Terada, Yasuko; Kishimura, Akihiro; Nishiyama, Nobuhiro; Kataoka, Kazunori

2014-01-28

Organic-inorganic hybrid nanoparticles with calcium phosphate (CaP) core and PEGylated shell were developed to incorporate magnetic resonance imaging (MRI) contrast agent diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) for noninvasive diagnosis of solid tumors. A two-step preparation method was applied to elaborate hybrid nanoparticles with a z-average hydrodynamic diameter about 80nm, neutral surface ξ-potential and high colloidal stability in physiological environments by self-assembly of poly(ethylene glycol)-b-poly(aspartic acid) block copolymer, Gd-DTPA, and CaP in aqueous solution, followed with hydrothermal treatment. Incorporation into the hybrid nanoparticles allowed Gd-DTPA to show significant enhanced retention ratio in blood circulation, leading to high accumulation in tumor positions due to enhanced permeability and retention (EPR) effect. Moreover, Gd-DTPA revealed above 6 times increase of relaxivity in the nanoparticle system compared to free form, and eventually, selective and elevated contrast enhancements in the tumor positions were observed. These results indicate the high potential of Gd-DTPA-loaded PEGylated CaP nanoparticles as a novel contrast agent for noninvasive cancer diagnosis. Copyright © 2013 Elsevier B.V. All rights reserved.

Contrast-enhanced and targeted ultrasound.

PubMed

Postema, Michiel; Gilja, Odd Helge

2011-01-07

Ultrasonic imaging is becoming the most popular medical imaging modality, owing to the low price per examination and its safety. However, blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies. For perfusion imaging, markers have been designed to enhance the contrast in B-mode imaging. These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells. In this review, the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described. Furthermore, an outline of clinical imaging applications of contrast-enhanced ultrasound is given. It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition, and how these phenomena may be utilized in ultrasonic imaging. Aided by high-speed photography, our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques. More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves, and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs. These are beginning to be accepted into clinical practice. In the long term, targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested.

Contrast-enhanced and targeted ultrasound

PubMed Central

Postema, Michiel; Gilja, Odd Helge

2011-01-01

Ultrasonic imaging is becoming the most popular medical imaging modality, owing to the low price per examination and its safety. However, blood is a poor scatterer of ultrasound waves at clinical diagnostic transmit frequencies. For perfusion imaging, markers have been designed to enhance the contrast in B-mode imaging. These so-called ultrasound contrast agents consist of microscopically small gas bubbles encapsulated in biodegradable shells. In this review, the physical principles of ultrasound contrast agent microbubble behavior and their adjustment for drug delivery including sonoporation are described. Furthermore, an outline of clinical imaging applications of contrast-enhanced ultrasound is given. It is a challenging task to quantify and predict which bubble phenomenon occurs under which acoustic condition, and how these phenomena may be utilized in ultrasonic imaging. Aided by high-speed photography, our improved understanding of encapsulated microbubble behavior will lead to more sophisticated detection and delivery techniques. More sophisticated methods use quantitative approaches to measure the amount and the time course of bolus or reperfusion curves, and have shown great promise in revealing effective tumor responses to anti-angiogenic drugs in humans before tumor shrinkage occurs. These are beginning to be accepted into clinical practice. In the long term, targeted microbubbles for molecular imaging and eventually for directed anti-tumor therapy are expected to be tested. PMID:21218081

Manganese-containing Prussian blue nanoparticles for imaging of pediatric brain tumors

PubMed Central

Dumont, Matthieu F; Yadavilli, Sridevi; Sze, Raymond W; Nazarian, Javad; Fernandes, Rohan

2014-01-01

Pediatric brain tumors (PBTs) are a leading cause of death in children. For an improved prognosis in patients with PBTs, there is a critical need to develop molecularly-specific imaging agents to monitor disease progression and response to treatment. In this paper, we describe manganese-containing Prussian blue nanoparticles as agents for molecular magnetic resonance imaging (MRI) and fluorescence-based imaging of PBTs. Our core-shell nanoparticles consist of a core lattice structure that incorporates and retains paramagnetic Mn2+ ions, and generates MRI contrast (both negative and positive). The biofunctionalized shell is comprised of fluorescent avidin, which serves the dual purpose of enabling fluorescence imaging and functioning as a platform for the attachment of biotinylated ligands that target PBTs. The surfaces of our nanoparticles are modified with biotinylated antibodies targeting neuron-glial antigen 2 or biotinylated transferrin. Both neuron-glial antigen 2 and the transferrin receptor are protein markers overexpressed in PBTs. We describe the synthesis, biofunctionalization, and characterization of these multimodal nanoparticles. Further, we demonstrate the MRI and fluorescence imaging capabilities of manganese-containing Prussian blue nanoparticles in vitro. Finally, we demonstrate the potential of these nanoparticles as PBT imaging agents by measuring their organ and brain biodistribution in an orthotopic mouse model of PBTs using ex vivo fluorescence imaging. PMID:24920896

PLGA/PFC particles loaded with gold nanoparticles as dual contrast agents for photoacoustic and ultrasound imaging

NASA Astrophysics Data System (ADS)

Wang, Yan J.; Strohm, Eric M.; Sun, Yang; Niu, Chengcheng; Zheng, Yuanyi; Wang, Zhigang; Kolios, Michael C.

2014-03-01

Phase-change contrast agents consisting of a perfluorocarbon (PFC) liquid core stabilized by a lipid, protein, or polymer shell have been proposed for a variety of clinical applications. Previous work has demonstrated that vaporization can be induced by laser irradiation through optical absorbers incorporated inside the droplet. In this study, Poly-lactide-coglycolic acid (PLGA) particles loaded with PFC liquid and silica-coated gold nanoparticles (GNPs) were developed and characterized using photoacoustic (PA) methods. Microsized PLGA particles were loaded with PFC liquid and GNPs (14, 35, 55nm each with a 20nm silica shell) using a double emulsion method. The PA signal intensity and optical vaporization threshold were investigated using a 375 MHz transducer and a focused 532-nm laser (up to 450-nJ per pulse). The laser-induced vaporization threshold energy decreased with increasing GNP size. The vaporization threshold was 850, 690 and 420 mJ/cm2 for 5μm-sized PLGA particles loaded with 14, 35 and 55 nm GNPs, respectively. The PA signal intensity increased as the laser fluence increased prior to the vaporization event. This trend was observed for all particles sizes. PLGA particles were then incubated with MDA-MB-231 breast cancer cells for 6 hours to investigate passive targeting, and the vaporization of the PLGA particles that were internalized within cells. The PLGA particles passively internalized by MDA cells were visualized via confocal fluorescence imaging. Upon PLGA particle vaporization, bubbles formed inside the cells resulting in cell destruction. This work demonstrates that GNPs-loaded PLGA/PFC particles have potential as PA theranostic agents in PA imaging and optically-triggered drug delivery systems.

Synthesis route and three different core-shell impacts on magnetic characterization of gadolinium oxide-based nanoparticles as new contrast agents for molecular magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Moghimi, Hamid Reza; Zohdiaghdam, Reza; Rafiei, Behrooz; Gorji, Ensieh

2012-10-01

Despite its good resolution, magnetic resonance imaging intrinsically has low sensitivity. Recently, contrast agent nanoparticles have been used as sensitivity and contrast enhancer. The aim of this study was to investigate a new controlled synthesis method for gadolinium oxide-based nanoparticle preparation. For this purpose, diethyleneglycol coating of gadolinium oxide (Gd2O3-DEG) was performed using new supervised polyol route, and small particulate gadolinium oxide (SPGO) PEGylation was obtained with methoxy-polyethylene-glycol-silane (550 and 2,000 Da) coatings as SPGO-mPEG-silane550 and 2,000, respectively. Physicochemical characterization and magnetic properties of these three contrast agents in comparison with conventional Gd-DTPA were verified by dynamic light scattering transmission electron microscopy, Fourier transform infrared spectroscopy, inductively coupled plasma, X-ray diffraction, vibrating sample magnetometer, and the signal intensity and relaxivity measurements were performed using 1.5-T MRI scanner. As a result, the nanoparticle sizes of Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000 could be reached to 5.9, 51.3, 194.2 nm, respectively. The image signal intensity and longitudinal ( r 1) and transverse relaxivity ( r 2) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r 2/ r 1 ratios of 1.13, 0.89, 33.34, and 33.72 for Gd-DTPA, Gd2O3-DEG, SPGO-mPEG-silane550, and SPGO-mPEG-silane2000, respectively. The achievement of new synthesis route of Gd2O3-DEG resulted in lower r 2/ r 1 ratio for Gd2O3-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r 2/ r 1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r 2/ r 1 ratio of previous PEGylation ( r 2/ r 1 = 81.9 for mPEG-silane 6,000 MW) showed that these new three introduced contrast agents could potentially be proper contrast enhancers for cellular and molecular MR imaging.

Effect of Temperature on the Size Distribution, Shell Properties, and Stability of Definity®.

PubMed

Shekhar, Himanshu; Smith, Nathaniel J; Raymond, Jason L; Holland, Christy K

2018-02-01

Physical characterization of an ultrasound contrast agent (UCA) aids in its safe and effective use in diagnostic and therapeutic applications. The goal of this study was to investigate the impact of temperature on the size distribution, shell properties, and stability of Definity ® , a U.S. Food and Drug Administration-approved UCA used for left ventricular opacification. A Coulter counter was modified to enable particle size measurements at physiologic temperatures. The broadband acoustic attenuation spectrum and size distribution of Definity ® were measured at room temperature (25 °C) and physiologic temperature (37 °C) and were used to estimate the viscoelastic shell properties of the agent at both temperatures. Attenuation and size distribution was measured over time to assess the effect of temperature on the temporal stability of Definity ® . The attenuation coefficient of Definity ® at 37 °C was as much as 5 dB higher than the attenuation coefficient measured at 25 °C. However, the size distributions of Definity ® at 25 °C and 37 °C were similar. The estimated shell stiffness and viscosity decreased from 1.76 ± 0.18 N/m and 0.21 × 10 -6  ± 0.07 × 10 -6 kg/s at 25 °C to 1.01 ± 0.07 N/m and 0.04 × 10 -6  ± 0.04 × 10 -6 kg/s at 37 °C, respectively. Size-dependent differences in dissolution rates were observed within the UCA population at both 25 °C and 37 °C. Additionally, cooling the diluted UCA suspension from 37 °C to 25 °C accelerated the dissolution rate. These results indicate that although temperature affects the shell properties of Definity ® and can influence the stability of Definity ® , the size distribution of this agent is not affected by a temperature increase from 25 °C to 37 °C. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.

Unique pumping-out fracturing mechanism of a polymer-shelled contrast agent: an acoustic characterization and optical visualization.

PubMed

Kothapalli, Satya V V N; Daeichin, Verya; Mastik, Frits; Brodin, Lars Åke; Janerot-Sjoberg, Birgitta; Paradossi, Gaio; de Jong, Nico; Grishenkov, Dmitry

2015-03-01

This work describes the fracturing mechanism of air-filled microbubbles (MBs) encapsulated by a cross-linked poly(vinyl alcohol) (PVA) shell. The radial oscillation and fracturing events following the ultrasound exposure were visualized with an ultrahigh-speed camera, and backscattered timedomain signals were acquired with the acoustic setup specific for harmonic detection. No evidence of gas emerging from defects in the shell with the arrival of the first insonation burst was found. In optical recordings, more than one shell defect was noted, and the gas core was drained without any sign of air extrusion when several consecutive bursts of 1 MPa amplitude were applied. In acoustic tests, the backscattered peak-to-peak voltage gradually reached its maximum and exponentially decreased when the PVA-based MB suspension was exposed to approximately 20 consecutive bursts arriving at pulse repetition frequencies of 100 and 500 Hz. Taking into account that the PVA shell is porous and possibly contains large air pockets between the cross-linked PVA chains, the aforementioned acoustic behavior might be attributed to pumping gas from these pockets in combination with gas release from the core through shell defects. We refer to this fracturing mechanism as pumping-out behavior, and this behavior could have potential use for the local delivery of therapeutic gases, such as nitric oxide.

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast.

PubMed

Farashishiko, Annah; Slack, Jacqueline R; Botta, Mauro; Woods, Mark

2018-01-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM 3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

ParaCEST Agents Encapsulated in Reverse Nano-Assembled Capsules (RACs): How Slow Molecular Tumbling Can Quench CEST Contrast

PubMed Central

Farashishiko, Annah; Slack, Jacqueline R.; Botta, Mauro; Woods, Mark

2018-01-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid (PAA) after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride (PAH) followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. The quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST. PMID:29682499

Dynamics of Ultrasound Contrast Agents and Nonlinear Acoustic Waves: Experiments, Modeling, and Theories

NASA Astrophysics Data System (ADS)

Xia, Lang

Bubbles occur in many natural and biological flows as well as in numerous industrial phenomena, such as pumps, propellers, turbines, and chemical processing plants. They have been widely studied in the past leading to a large body of literature. However, bubbles appearing in different situations differ significantly in their physical characteristics and behaviors. Recently, bubbles of diameter less than 10 micrometers have found applications in diagnostic ultrasound imaging. These microbubble-based ultrasound contrast agents (UCA) are intravenously administered in patients before ultrasound imaging. Due to the compressive gas core, they generate substantial ultrasound echoes leading to significant enhancement of image quality and contrast. Free bubbles of a micrometer diameter experience a large surface tension induced Laplace pressure leading to their quick dissolution in milliseconds. UCAs are stabilized by coating them with a shell of lipids, polymers, proteins, and other surface-active materials and changing the gas content from air to a high molecular weight low solubility gas such as perfluorocarbon. The past literature of bubble dynamics are mostly restricted to free bubbles. The stabilizing shell of UCAs, however, critically affects their dynamics. In this thesis, we performed acoustic characterization of several UCAs coated with polymer and lipids. We experimentally measured their acoustic attenuation and scattering, of which the data were used in mathematical models to determine shell properties and nonlinear dynamics. Several different interfacial rheological models were employed. Experimental acoustic characterization was also extended to a novel type of nanoparticle suspension--polymersomes, vesicles encapsulated by amphiphilic polymers. The later part of the thesis is devoted to modeling the effects of the presence of coated microbubbles to the overall effective bulk properties of bubbly liquids. Introduction of microbubbles in the liquids does not only modify the bulk properties of the medium (bubbly liquids) but also significantly changes the natures of the propagating waves (e.g., the sound velocity in bubble suspension was found to be as low as 20 m/s). We investigate the nonlinear nature of the acoustic wave in bubbly liquids. Specifically, we theoretically show that microbubbles could change the nonlinearity of the medium, characterized by quantity B/A.

31 CFR 1020.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2011 CFR

2011-07-01

... 31 Money and Finance:Treasury 3 2011-07-01 2011-07-01 false Prohibition on correspondent accounts for foreign shell banks; records concerning owners of foreign banks and agents for service of legal... foreign shell banks; records concerning owners of foreign banks and agents for service of legal process...

ZnO@Gd2O3 core/shell nanoparticles for biomedical applications: Physicochemical, in vitro and in vivo characterization.

PubMed

Woźniak, Anna; Grześkowiak, Bartosz F; Babayevska, Nataliya; Zalewski, Tomasz; Drobna, Monika; Woźniak-Budych, Marta; Wiweger, Małgorzata; Słomski, Ryszard; Jurga, Stefan

2017-11-01

The chemical composition of nanoparticles (NPs) may be so designed as to provide measurability for numerous imaging techniques in order to achieve synergistic advantages. Innovative and unique structure of the core/shell ZnO@Gd 2 O 3 NPs possesses luminescent and magnetic properties, and is expected that they will become a new generation of contrast agents for Magnetic Resonance Imaging (MRI) and nanocarriers for theranostics. Thus, by surface biofunctionalization, it is possible to indicate particular nanoparticle compositions which provide efficient imaging, targeted drug delivery, and biocompatibility. Novel ZnO@Gd 2 O 3 NPs were synthesized and biofunctionalized by folic acid (FA) and doxorubicin (Doxo) to provide target and anticancer functions. Physicochemical analyses of the nanoparticles were performed. The biological study included a cytotoxicity in vitro, cellular distribution evaluation, as well as toxicity analyses, performed for the first time, on the in vivo zebrafish (Danio rerio) model. Nanoparticles were found to be effective double-function biomarkers (MRI T 2 contrast agents, fluorescent imaging). The biological study showed that ZnO@Gd 2 O 3 and ZnO@Gd 2 O 3 @OA-polySi@FA NPs are biocompatible in a particular concentration ranges. Conjugation with folic acid and/or doxorubicin resulted in effective drug delivery targeting. The in vivo results described the toxicology profile toward the zebrafish embryo/larvae, including new data concerning the survival, hatching ratio, and developmental malformations. Copyright © 2017 Elsevier B.V. All rights reserved.

Controllable synthesis of a novel magnetic core-shell nanoparticle for dual-modal imaging and pH-responsive drug delivery

NASA Astrophysics Data System (ADS)

Xu, Chen; Zhang, Cheng; Wang, Yingxi; Li, Liu; Li, Ling; Whittaker, Andrew K.

2017-12-01

In this study, novel magnetic core-shell nanoparticles Fe3O4@La-BTC/GO have been synthesized by the layer-by-layer self-assembly (LBL) method and further modified by attachment of amino-modified PEG chains. The nanoparticles were thoroughly characterized by x-ray diffraction, FTIR, scanning electron microscopy and transmission electron microscopy. The core-shell structure was shown to be controlled by the LBL method. The drug loading of doxorubicin (DOX) within the Fe3O4@La-BTC/GO-PEG nanoparticles with different numbers of deposited layers was investigated. It was found that DOX loading increased with increasing number of metal organic framework coating layers, indicating that the drug loading can be controlled through the controllable LBL method. Cytotoxicity assays indicated that the Fe3O4@La-BTC/GO-PEG nanoparticles were biocompatible. The DOX was released rapidly at pH 3.8 and pH 5.8, but at pH 7.4 the rate and extent of release was greatly attenuated. The nanoparticles therefore demonstrate an excellent pH-triggered drug release. In addition, the particles could be tracked by magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI). A clear dose-dependent contrast enhancement in T 2-weighted MR images and fluorescence images indicate the potential of these nanoparticles as dual-mode MRI/FOI contrast agents.

Fluorescence-tagged amphiphilic brush copolymer encapsulated Gd2O3 core-shell nanostructures for enhanced T 1 contrast effect and fluorescent imaging

NASA Astrophysics Data System (ADS)

Wang, Fenghe; Peng, Erwin; Liu, Feng; Li, Pingjing; Fong Yau Li, Sam; Xue, Jun Min

2016-10-01

To obtain suitable T 1 contrast agents for magnetic resonance imaging (MRI) application, aqueous Gd2O3 nanoparticles (NPs) with high longitudinal relativity (r 1) are demanded. High quality Gd2O3 NPs are usually synthesized through a non-hydrolytic route which requires post-synthetic modification to render the NPs water soluble. The current challenge is to obtain aqueous Gd2O3 NPs with high colloidal stability and enhanced r 1 relaxivity. To overcome this challenge, fluorescence-tagged amphiphilic brush copolymer (AFCP) encapsulated Gd2O3 NPs were proposed as suitable T 1 contrast agents. Such a coating layer provided (i) superior aqueous stability, (ii) biocompatibility, as well as (iii) multi-modality (conjugation with fluorescence dye). The polymeric coating layer thickness was simply adjusted by varying the phase-transfer parameters. By reducing the coating thickness, i.e. the distance between the paramagnetic centre and surrounding water protons, the r 1 relaxivity could be enhanced. In contrast, a thicker polymeric layer coating prevents Gd3+ ions leakage, thus improving its biocompatibility. Therefore, it is important to strike a balance between the biocompatibility and the r 1 relaxivity behaviour. Lastly, by conjugating fluorescence moiety, an additional imaging modality was enabled, as demonstrated from the cell-labelling experiment.

Nonspherical dynamics and shape mode stability of ultrasound contrast agent microbubbles

NASA Astrophysics Data System (ADS)

Calvisi, Michael

2016-11-01

Ultrasound contrast agents (UCAs) are shell encapsulated microbubbles developed originally for ultrasound imaging enhancement. UCAs are more recently being exploited for therapeutic applications, such as for drug delivery, gene therapy, and tissue ablation. Ultrasound transducer pulses can induce spherical (radial) UCA oscillations, translation, and nonspherical shape oscillations, the dynamics of which are highly coupled. If driven sufficiently strongly, the ultrasound can induce breakup of UCAs, which can facilitate drug or gene delivery but should be minimized for imaging purposes to increase residence time and maximize diagnostic effect. Therefore, an understanding of the interplay between the acoustic driving and nonspherical shape mode stability of UCAs is essential for both diagnostic and therapeutic applications. In this work, we use both analytical and numerical methods to analyze shape mode stability for cases of small and large nonspherical oscillations, respectively. To analyze shape mode stability in the limit of small nonspherical perturbations, we couple a radial model of a lipid-coated microbubble with a model for bubble translation and nonspherical shape oscillation. This hybrid model is used to predict shape mode stability for ultrasound driving frequencies and pressure amplitudes of clinical interest. In addition, calculations of the stability of individual shape modes, residence time, maximum radius, and translation are provided with respect to acoustic driving parameters and compared to an unshelled bubble. The effects of shell elasticity, shell viscosity, and initial radius on stability are investigated. Furthermore, the well-established boundary element method (BEM) is used to investigate the dynamics and shape stability of large amplitude nonspherical oscillations of an ultrasonically-forced, polymer-coated microbubble near a rigid boundary. Different instability modes are identified based on the degree of jetting and proximity to the boundary. This insight is used to develop diagrams that delineate regions of stability from instability based on the breakup mechanism, in parameter ranges of ultrasound frequency and amplitude relevant to medical applications.

Multishell Au/Ag/SiO 2 nanorods with tunable optical properties as single particle orientation and rotational tracking probes

DOE PAGES

Chen, Kuangcai; Lin, Chia -Cheng; Vela, Javier; ...

2015-04-07

In this study, three-layer core–shell plasmonic nanorods (Au/Ag/SiO 2–NRs), consisting of a gold nanorod core, a thin silver shell, and a thin silica layer, were synthesized and used as optical imaging probes under a differential interference contrast microscope for single particle orientation and rotational tracking. The localized surface plasmon resonance modes were enhanced upon the addition of the silver shell, and the anisotropic optical properties of gold nanorods were maintained. The silica coating enables surface functionalization with silane coupling agents and provides enhanced stability and biocompatibility. Taking advantage of the longitudinal LSPR enhancement, the orientation and rotational information of themore » hybrid nanorods on synthetic lipid bilayers and on live cell membranes were obtained with millisecond temporal resolution using a scientific complementary metal-oxide-semiconductor camera. The results demonstrate that the as-synthesized hybrid nanorods are promising imaging probes with improved sensitivity and good biocompatibility for single plasmonic particle tracking experiments in biological systems.« less

Pushing indium phosphide quantum dot emission deeper into the near infrared

NASA Astrophysics Data System (ADS)

Saeboe, A. M.; Kays, J.; Mahler, A. H.; Dennis, A. M.

2018-02-01

Cadmium-free near infrared (NIR) emitting quantum dots (QDs) have significant potential for multiplexed tissue-depth imaging applications in the first optical tissue window (i.e., 650 - 900 nm). Indium phosphide (InP) chemistry provides one of the more promising cadmium-free options for biomedical imaging, but the full tunability of this material has not yet been achieved. Specifically, InP QD emission has been tuned from 480 - 730 nm in previous literature reports, but examples of samples emitting from 730 nm to the InP bulk bandgap limit of 925 nm are lacking. We hypothesize that by generating inverted structures comprising ZnSe/InP/ZnS in a core/shell/shell heterostructure, optical emission from the InP shell can be tuned by changing the InP shell thickness, including pushing deeper into the NIR than current InP QDs. Colloidal synthesis methods including hot injection precipitation of the ZnSe core and a modified successive ion layer adsorption and reaction (SILAR) method for stepwise shell deposition were used to promote growth of core/shell/shell materials with varying thicknesses of the InP shell. By controlling the number of injections of indium and phosphorous precursor material, the emission peak was tuned from 515 nm to 845 nm (2.41 - 1.47 eV) with consistent full width half maximum (FWHM) values of the emission peak 0.32 eV. To confer water solubility, the nanoparticles were encapsulated in PEGylated phospholipid micelles, and multiplexing of NIR-emitting InP QDs was demonstrated using an IVIS imaging system. These materials show potential for multiplexed imaging of targeted QD contrast agents in the first optical tissue window.

Lanthanum fluoride upconverting nanoparticles for photo-biomodulation of cell function

NASA Astrophysics Data System (ADS)

Tek, Sumeyra; Vincent, Brandy K.; Mimun, L. Christopher; Tran, Ashley N.; Shrestha, Binita; Tang, Liang; Nash, Kelly L.

2017-02-01

Inorganic fluorescent nanoprobes have been widely used as passive agents for intracellular imaging for decades. An emerging field of research is the development of these contrast agents and using them actively in a way that they respond to external stimulation by inducing photo-chemical, thermal or mechanical actions that enable control and modulation over cell function. To achieve such control, methods which are remote, non-invasive and with low-thermal means of stimulation is preferable. Among a large variety of candidates, lanthanide doped upconverting nanoparticles (UCNPs) are one of the most interesting class of fluorescent materials. Non-scattering, low energy near infrared (NIR) light can be used for excitation of UCNPs as on-demand light sources resulting in emission peaks throughout the near-UV and visible wavelengths. Towards this goal, we developed nano-size, hydrophilic, non-toxic and biocompatible core-shell nanoparticles with enhanced upconversion intensity for photo-biomodulation studies. Under this approach, un-doped LaF3 (inert) shell and Yb3+ doped LaF3 (active) shell are grown on core LaF3:20% Yb, 2% Tm upconverting nanoparticles for enhanced luminescence for the first time with rapid microwave-assisted synthesis method that employs Polyvinylpyrrolidone (PVP) as biocompatible surfactant. The as-synthesized high efficiency UCNPs are analyzed through XRD, TEM, HRTEM, and Photoluminescence spectrum that is acquired under 980 nm laser excitation. Confocal microscopy is used to visualize nanoparticles in cells. The cellular response to NIR irradiation and upconverted light are visualized by luminescence microscopy.

Engineered core-shell magnetic nanoparticle for MR dual-modal tracking and safe magnetic manipulation of ependymal cells in live rodents

NASA Astrophysics Data System (ADS)

Peng, Yung-Kang; Lui, Cathy N. P.; Chen, Yu-Wei; Chou, Shang-Wei; Chou, Pi-Tai; Yung, Ken K. L.; Edman Tsang, S. C.

2018-01-01

Tagging recognition group(s) on superparamagnetic iron oxide is known to aid localisation (imaging), stimulation and separation of biological entities using magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS) techniques. Despite the wide applicability of iron oxide nanoparticles in T 2-weighted MRI and MAS, the quality of the images and safe manipulation of the exceptionally delicate neural cells in a live brain are currently the key challenges. Here, we demonstrate the engineered manganese oxide clusters-iron oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem cells (NSCs) imaging and magnetic manipulation in live rodents. As a result, using this engineered nanoparticle and associated technologies, identification, stimulation and transportation of labelled potentially multipotent NSCs from a specific location of a live brain to another by magnetic means for self-healing therapy can therefore be made possible.

Controllable Fabrication of Au Nanocups by Confined-Space Thermal Dewetting for OCT Imaging.

PubMed

Gao, Aiqin; Xu, Wenjing; Ponce de León, Yenisey; Bai, Yaocai; Gong, Mingfu; Xie, Kongliang; Park, Boris Hyle; Yin, Yadong

2017-07-01

Here, this study reports a novel confined-space thermal dewetting strategy for the fabrication of Au nanocups with tunable diameter, height, and size of cup opening. The nanocup morphology is defined by the cup-shaped void space created by a yolk-shell silica template that spontaneously takes an eccentric configuration during annealing. Thermal dewetting of Au, which is sandwiched between the yolk and shell, leads to the desired nanocup morphology. With strong scattering in near infrared, the Au nanocups exhibit superior efficiency as contrast agents for spectral-domain optical coherence tomography imaging. This confined-space thermal dewetting strategy is scalable and general, and can be potentially extended to the synthesis of novel anisotropic nanostructures of various compositions that are difficult to produce by conventional wet chemical or physical methods, thus opening up opportunities for many new applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Towards hybrid biocompatible magnetic rHuman serum albumin-based nanoparticles: use of ultra-small (CeLn)3/4+ cation-doped maghemite nanoparticles as functional shell

NASA Astrophysics Data System (ADS)

Israel, Liron L.; Kovalenko, Elena I.; Boyko, Anna A.; Sapozhnikov, Alexander M.; Rosenberger, Ina; Kreuter, Jörg; Passoni, Lorena; Lellouche, Jean-Paul

2015-01-01

Human serum albumin (HSA) is a protein found in human blood. Over the last decade, HSA has been evaluated as a promising drug carrier. However, not being magnetic, HSA cannot be used for biomedical applications such as magnetic resonance imaging (MRI) and magnetic drug targeting. Therefore, subsequent composites building on iron oxide nanoparticles that are already used clinically as MRI contrast agents are extensively studied. Recently and in this context, innovative fully hydrophilic ultra-small CAN-stabilized maghemite ((CeLn)3/4+-γ-Fe2O3) nanoparticles have been readily fabricated. The present study discusses the design, fabrication, and characterization of a dual phase hybrid core (rHSA)-shell ((CeLn)3/4+-γ-Fe2O3 NPs) nanosystem. Quite importantly and in contrast to widely used encapsulation strategies, rHSA NP surface-attached (CeLn)3/4+-γ-Fe2O3 NPs enabled to exploit both rHSA (protein functionalities) and (CeLn)3/4+-γ-Fe2O3 NP surface functionalities (COOH and ligand L coordinative exchange) in addition to very effective MRI contrast capability due to optimal accessibility of H2O molecules with the outer magnetic phase. Resulting hybrid nanoparticles might be used as a platform modular system for therapeutic (drug delivery system) and MR diagnostic purposes.

Fabrication of core-shell micro/nanoparticles for programmable dual drug release by emulsion electrospraying

NASA Astrophysics Data System (ADS)

Wang, Yazhou; Zhang, Yiqiong; Wang, Bochu; Cao, Yang; Yu, Qingsong; Yin, Tieying

2013-06-01

The study aimed at constructing a novel drug delivery system for programmable multiple drug release controlled with core-shell structure. The core-shell structure consisted of chitosan nanoparticles as core and polyvinylpyrrolidone micro/nanocoating as shell to form core-shell micro/nanoparticles, which was fabricated by ionic gelation and emulsion electrospray methods. As model drug agents, Naproxen and rhodamine B were encapsulated in the core and shell regions, respectively. The core-shell micro/nanoparticles thus fabricated were characterized and confirmed by scanning electron microscope, transmission electron microscope, and fluorescence optical microscope. The core-shell micro/nanoparticles showed good release controllability through drug release experiment in vitro. It was noted that a programmable release pattern for dual drug agents was also achieved by adjusting their loading regions in the core-shell structures. The results indicate that emulsion electrospraying technology is a promising approach in fabrication of core-shell micro/nanoparticles for programmable dual drug release. Such a novel multi-drug delivery system has a potential application for the clinical treatment of cancer, tuberculosis, and tissue engineering.

Core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual modal MRI contrast agents

NASA Astrophysics Data System (ADS)

Li, Fenfen; Zhi, Debo; Luo, Yufeng; Zhang, Jiqian; Nan, Xiang; Zhang, Yunjiao; Zhou, Wei; Qiu, Bensheng; Wen, Longping; Liang, Gaolin

2016-06-01

T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future.T1-T2 dual modal magnetic resonance imaging (MRI) has attracted considerable interest because it offers complementary diagnostic information, leading to more precise diagnosis. To date, a number of nanostructures have been reported as T1-T2 dual modal MR contrast agents (CAs). However, hybrids of nanocubes with both iron and gadolinium (Gd) elements as T1-T2 dual modal CAs have not been reported. Herein, we report the synthesis of novel core/shell Fe3O4/Gd2O3 nanocubes as T1-T2 dual-modal CAs and their application for enhanced T1-T2 MR imaging of rat livers. A relaxivity study at 1.5 T indicated that our Fe3O4/Gd2O3 nanocubes have an r1 value of 45.24 mM-1 s-1 and an r2 value of 186.51 mM-1 s-1, which were about two folds of those of Gd2O3 nanoparticles and Fe3O4 nanocubes, respectively. In vivo MR imaging of rats showed both T1-positive and T2-negative contrast enhancements in the livers. We envision that our Fe3O4/Gd2O3 nanocubes could be applied as T1-T2 dual modal MR CAs for a wide range of theranostic applications in the near future. Electronic supplementary information (ESI) available: Scheme S1, Fig. S1-S8, and Tables S1, S2. See DOI: 10.1039/c6nr02620f

Nonlinear response of lipid-shelled microbubbles to coded excitation: implications for noninvasive atherosclerosis imaging

NASA Astrophysics Data System (ADS)

Shekhar, Himanshu; Doyley, Marvin M.

2013-03-01

Nonlinear (subharmonic/harmonic) imaging with ultrasound contrast agents (UCA) could characterize the vasa vasorum, which could help assess the risk associated with atherosclerosis. However, the sensitivity and specificity of high-frequency nonlinear imaging must be improved to enable its clinical translation. The current excitation scheme employs sine-bursts — a strategy that requires high-peak pressures to produce strong nonlinear response from UCA. In this paper, chirp-coded excitation was evaluated to assess its ability to enhance the subharmonic and harmonic response of UCA. Acoustic measurements were conducted with a pair of single-element transducers at 10-MHz transmit frequencies to evaluate the subharmonic and harmonic response of Targestar-P® (Targeson Inc., San Diego, CA, USA), a commercially available phospholipid-encapsulated contrast agent. The results of this study demonstrated a 2 - 3 fold reduction in the subharmonic threshold, and a 4 - 14 dB increase in nonlinear signal-to-noise ratio, with chirp-coded excitation. Therefore, chirp-coded excitation could be well suited for improving the imaging performance of high-frequency harmonic and subharmonic imaging.

Magnetoferritin nanoparticles for targeting and visualizing tumour tissues

NASA Astrophysics Data System (ADS)

Fan, Kelong; Cao, Changqian; Pan, Yongxin; Lu, Di; Yang, Dongling; Feng, Jing; Song, Lina; Liang, Minmin; Yan, Xiyun

2012-07-01

Engineered nanoparticles have been used to provide diagnostic, therapeutic and prognostic information about the status of disease. Nanoparticles developed for these purposes are typically modified with targeting ligands (such as antibodies, peptides or small molecules) or contrast agents using complicated processes and expensive reagents. Moreover, this approach can lead to an excess of ligands on the nanoparticle surface, and this causes non-specific binding and aggregation of nanoparticles, which decreases detection sensitivity. Here, we show that magnetoferritin nanoparticles (M-HFn) can be used to target and visualize tumour tissues without the use of any targeting ligands or contrast agents. Iron oxide nanoparticles are encapsulated inside a recombinant human heavy-chain ferritin (HFn) protein shell, which binds to tumour cells that overexpress transferrin receptor 1 (TfR1). The iron oxide core catalyses the oxidation of peroxidase substrates in the presence of hydrogen peroxide to produce a colour reaction that is used to visualize tumour tissues. We examined 474 clinical specimens from patients with nine types of cancer and verified that these nanoparticles can distinguish cancerous cells from normal cells with a sensitivity of 98% and specificity of 95%.

Hollow spherical shell manufacture

DOEpatents

O'Holleran, T.P.

1991-11-26

A process is disclosed for making a hollow spherical shell of silicate glass composition in which an aqueous suspension of silicate glass particles and an immiscible liquid blowing agent is placed within the hollow spherical cavity of a porous mold. The mold is spun to reduce effective gravity to zero and to center the blowing agent, while being heated so as to vaporize the immiscible liquid and urge the water carrier of the aqueous suspension to migrate into the body of the mold, leaving a green shell compact deposited around the mold cavity. The green shell compact is then removed from the cavity, and is sintered for a time and a temperature sufficient to form a silicate glass shell of substantially homogeneous composition and uniform geometry. 3 figures.

Hollow spherical shell manufacture

DOEpatents

O'Holleran, Thomas P.

1991-01-01

A process for making a hollow spherical shell of silicate glass composition in which an aqueous suspension of silicate glass particles and an immiscible liquid blowing agent is placed within the hollow spherical cavity of a porous mold. The mold is spun to reduce effective gravity to zero and to center the blowing agent, while being heated so as to vaporize the immiscible liquid and urge the water carrier of the aqueous suspension to migrate into the body of the mold, leaving a green shell compact deposited around the mold cavity. The green shell compact is then removed from the cavity, and is sintered for a time and a temperature sufficient to form a silicate glass shell of substantially homogeneous composition and uniform geometry.

Influence of Shell Properties on High-Frequency Ultrasound Imaging and Drug Delivery Using Polymer-Shelled Microbubbles

PubMed Central

Chitnis, Parag V.; Koppolu, Sujeethraj; Mamou, Jonathan; Chlon, Ceciel; Ketterling, Jeffrey A.

2013-01-01

This two-part study investigated shell rupture of ultrasound contrast agents (UCAs) under static overpressure conditions and the subharmonic component from UCAs subjected to 20-MHz tonebursts. Five different polylactide-shelled UCAs with shell-thickness-to-radius ratios (STRRs) of 7.5, 30, 40, 65, and 100 nm/μm were subjected to static overpressure in a glycerol-filled test chamber. A video microscope imaged the UCAs as pressure varied from 2 to 330 kPa over 90 min. Images were postprocessed to obtain the pressure threshold for rupture and the diameter of individual microbubbles. Backscatter from individual UCAs was investigated by flowing a dilute UCA solution through a wall-less flow phantom placed at the geometric focus of a 20-MHz transducer. UCAs were subjected to 10- and 20-cycle tonebursts of acoustic pressures ranging from 0.3 to 2.3 MPa. A method based on singular-value decomposition (SVD) was employed to obtain a cumulative subharmonic score (SHS). Different UCA types exhibited distinctly different rupture thresholds that were linearly related to their STRR, but uncorrelated with UCA size. The rupture threshold for the UCAs with an STRR = 100 nm/μm was more than 4 times greater than the UCAs with an STRR = 7.5 nm/μm. The polymer-shelled UCAs produced substantial subharmonic response but the subharmonic response to 20-MHz excitation did not correlate with STRRs or UCA-rupture pressures. The 20-cycle excitation resulted in an SHS that was 2 to 3 times that of UCAs excited with 10-cycle tonebursts. PMID:23287913

Gd-DTPA-loaded polymer-metal complex micelles with high relaxivity for MR cancer imaging.

PubMed

Mi, Peng; Cabral, Horacio; Kokuryo, Daisuke; Rafi, Mohammad; Terada, Yasuko; Aoki, Ichio; Saga, Tsuneo; Takehiko, Ishii; Nishiyama, Nobuhiro; Kataoka, Kazunori

2013-01-01

Nanodevices for magnetic resonance imaging of cancer were self-assembled to core-shell micellar structures by metal complex formation of K(2)PtCl(6) with diethylenetriaminepentaacetic acid gadolinium (III) dihydrogen (Gd-DTPA), a T(1)-contrast agent, and poly(ethylene glycol)-b-poly{N-[N'-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-PAsp(DET)) copolymer in aqueous solution. Gd-DTPA-loaded polymeric micelles (Gd-DTPA/m) showed a hydrodynamic diameter of 45 nm and a core size of 22 nm. Confining Gd-DTPA inside the core of the micelles increased the relaxivity of Gd-DTPA more than 13 times (48 mM(-1) s(-1)). In physiological conditions Gd-DTPA/m sustainedly released Gd-DTPA, while the Pt(IV) complexes remain bound to the polymer. Gd-DTPA/m extended the circulation time in plasma and augmented the tumor accumulation of Gd-DTPA leading to successful contrast enhancement of solid tumors. μ-Synchrotron radiation-X-ray fluorescence results confirmed that Gd-DTPA was delivered to the tumor site by the micelles. Our study provides a facile strategy for incorporating contrast agents, dyes and bioactive molecules into nanodevices for developing safe and efficient drug carriers for clinical application. Copyright © 2012 Elsevier Ltd. All rights reserved.

Shell shape variation of queen conch Strombus gigas (Mesograstropoda: Strombidae) from Southwest Caribbean.

PubMed

Márquez, Edna Judith; Restrepo-Escobar, Natalia; Montoya-Herrera, Francisco Luis

2016-12-01

The endangered species Strombus gigas is a marine gastropod of significant economic importance through the Greater Caribbean region. In contrast to phenotypic plasticity, the role of genetics on shell variations in S. gigas has not been addressed so far, despite its importance in evolution, management and conservation of this species. This work used geometric morphometrics to investigate the phenotypic variation of 219 shells of S. gigas from eight sites of the Colombian Southwest Caribbean. Differences in mean size between sexes and among sites were contrasted by analysis of variance. Allometry was tested by multivariate regression and the hypothesis of common slope was contrasted by covariance multivariate analysis. Differences in the shell shape among sites were analyzed by principal component analysis. Sexual size dimorphism was not significant, whereas sexual shape dimorphism was significant and variable across sites. Differences in the shell shape among sites were concordant with genetic differences based on microsatellite data, supporting its genetic background. Besides, differences in the shell shape between populations genetically similar suggest a role of phenotypic plasticity in the morphometric variation of the shell shape. These outcomes evidence the role of genetic background and phenotypic plasticity in the shell shape of S. gigas. Thus, geometric morphometrics of shell shape may constitute a complementary tool to explore the genetic diversity of this species.

Reflexive reasoning for distributed real-time systems

NASA Technical Reports Server (NTRS)

Goldstein, David

1994-01-01

This paper discusses the implementation and use of reflexive reasoning in real-time, distributed knowledge-based applications. Recently there has been a great deal of interest in agent-oriented systems. Implementing such systems implies a mechanism for sharing knowledge, goals and other state information among the agents. Our techniques facilitate an agent examining both state information about other agents and the parameters of the knowledge-based system shell implementing its reasoning algorithms. The shell implementing the reasoning is the Distributed Artificial Intelligence Toolkit, which is a derivative of CLIPS.

Constraints on the design of core-shell resonators of locally resonant acoustic metamaterials

NASA Astrophysics Data System (ADS)

Bos, Lionel; Lukyanova, Lyubov; Wunenburger, Régis

2012-11-01

We perform a parametric study of the analytic model of Liu [Z. Liu , Phys. Rev. B10.1103/PhysRevB.71.014103 71, 014103 (2005)] describing the mechanical response of a core-shell particle to an acoustic excitation in order to help in selecting the constitutive materials and in designing innovative processes of fabrication of downsized core-shell resonators, which are key constituents of locally resonant acoustic metamaterials. We show that the value of the first Lamé coefficient of the material constituting the shell has no marked influence on the value of the resonance frequency of the core-shell resonator, that is, it does not necessarily need to be small for satisfying the condition of subwavelength resonator dimension at resonance. Moreover, we show that the larger the density contrast between the core and the shell and the thinner the shell, the broader is the frequency band over which the effective density of the resonator suspension is negative, but that it is practically useless to decrease the dimensionless shell thickness below 0.6. Finally, we show that the dissipation is also less perceptible the thinner is the shell and the larger is the density contrast. The effect of the density contrast between the core and the shell and of the dissipation on the resonance width are explained by comparing with the harmonic oscillator and the mass-in-mass 1D lattice.

Polydopamine-Coated Magnetic Composite Particles with an Enhanced Photothermal Effect.

PubMed

Zheng, Rui; Wang, Sheng; Tian, Ye; Jiang, Xinguo; Fu, Deliang; Shen, Shun; Yang, Wuli

2015-07-29

Recently, photothermal therapy (PTT) that utilizes photothermal conversion (PTC) agents to ablate cancer under near-infrared (NIR) irradiation has attracted a growing amount of attention because of its excellent therapeutic efficacy and improved target selectivity. Therefore, exploring novel PTC agents with an outstanding photothermal effect is a current research focus. Herein, we reported a polydopamine-coated magnetic composite particle with an enhanced PTC effect, which was synthesized simply through coating polydopamine (PDA) on the surface of magnetic Fe3O4 particles. Compared with magnetic Fe3O4 particles and PDA nanospheres, the core-shell nanomaterials exhibited an increased NIR absorption, and thus, an enhanced photothermal effect was obtained. We demonstrated the in vitro and in vivo effects of the photothermal therapy using our composite particles and their ability as a contrast agent in the T2-weighted magnetic resonance imaging. These results indicated that the multifunctional composite particles with enhanced photothermal effect are superior to magnetic Fe3O4 particles and PDA nanospheres alone.

Nanomechanical properties of phospholipid microbubbles.

PubMed

Buchner Santos, Evelyn; Morris, Julia K; Glynos, Emmanouil; Sboros, Vassilis; Koutsos, Vasileios

2012-04-03

This study uses atomic force microscopy (AFM) force-deformation (F-Δ) curves to investigate for the first time the Young's modulus of a phospholipid microbubble (MB) ultrasound contrast agent. The stiffness of the MBs was calculated from the gradient of the F-Δ curves, and the Young's modulus of the MB shell was calculated by employing two different mechanical models based on the Reissner and elastic membrane theories. We found that the relatively soft phospholipid-based MBs behave inherently differently to stiffer, polymer-based MBs [Glynos, E.; Koutsos, V.; McDicken, W. N.; Moran, C. M.; Pye, S. D.; Ross, J. A.; Sboros, V. Langmuir2009, 25 (13), 7514-7522] and that elastic membrane theory is the most appropriate of the models tested for evaluating the Young's modulus of the phospholipid shell, agreeing with values available for living cell membranes, supported lipid bilayers, and synthetic phospholipid vesicles. Furthermore, we show that AFM F-Δ curves in combination with a suitable mechanical model can assess the shell properties of phospholipid MBs. The "effective" Young's modulus of the whole bubble was also calculated by analysis using Hertz theory. This analysis yielded values which are in agreement with results from studies which used Hertz theory to analyze similar systems such as cells.

Feasibility study of Fe3O4/TaO x nanoparticles as a radiosensitizer for proton therapy

NASA Astrophysics Data System (ADS)

Ahn, Sang Hee; Lee, Nohyun; Choi, Changhoon; Shin, Sung Won; Han, Youngyih; Park, Hee Chul

2018-06-01

We investigated the feasibility of using multifunctional Fe3O4/TaO x (core/shell) nanoparticles, developed for use in contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), as dose-enhancing radiosensitizers. First, to verify the detectability of Fe3O4/TaO x nanoparticles in imaging, in vivo tests were conducted. Approximately 600 mg kg‑1 of 19 nm-diameter Fe3O4/TaO x nanoparticles dispersed in phosphate-buffered saline was injected into the tail vein of six Balb/c mice used as tumour (4T1 mammary carcinoma cell) models. Three mice underwent MRI (BioSpec 70/20 USR, Bruker, Billerica, MA, USA) and micro-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) before and after the injection. The difference between the pre- and post-injection images was quantified by finding the correlation coefficient. The aorta, blood vessel, and liver were clearly seen in the MRI and micro-CT images 60 min after intravenous injection of Fe3O4/TaO x nanoparticles, but the tumour region was not visible in the CT images until after 24 h. There were large differences between the pre- and post-injection images. Second, the therapeutic enhancement dose of nanomaterials was computed via Monte Carlo simulation. Monoenergetic 70- and 150 MeV proton beams irradiated x-ray contrast agent (iodine, BaSO4), MRI contrast agent (gadolinium, Fe3O4), Au, Fe3O4/TaO x (core/shell) nanoparticles and water located at the centre of a 4  ×  4  ×  4 µm3 water phantom, upon which the dose enhancement ratio (DER) (dose with/without nanoparticles) was computed. When 70 MeV protons irradiated the Au, gadolinium, Fe3O4/TaO x , Fe3O4, iodine, and BaSO4 nanoparticles, the DERs at 1 nm were 15.76, 7.68, 7.82, 6.17, 4.85, and 5.51, respectively. Fe3O4/TaO x nanoparticles have the potential to be used as a multifunctional agent that enhances tumour detection and increases the dose. Dose enhancement with Fe3O4/TaO x was half that with Au. However, Fe3O4/TaO x is much cheaper than Au, and it is expected that tumour targeting combined with magnetic field could overcome the low DER.

Feasibility study of Fe₃O₄/TaO_x nanoparticles as a radiosensitizer for proton therapy.

PubMed

Ahn, Sang Hee; Lee, Nohyun; Choi, Changhoon; Shin, Sung Won; Han, Youngyih; Park, Hee Chul

2018-05-04

We investigated the feasibility of using multifunctional Fe3O4/TaOx (core/shell) nanoparticles, developed for use in contrast agents for computed tomography (CT) and magnetic resonance imaging (MRI), as dose-enhancing radiosensitizers. First, to verify the detectability of Fe3O4/TaOx nanoparticles in imaging, in vivo tests were conducted. Approximately 600 mg/kg of 19-nm-diameter Fe3O4/TaOx nanoparticles dispersed in phosphate-buffered saline was injected into the tail vein of six Balb/c mice used as tumour (4T1 mammary carcinoma cell) models. Three mice underwent MRI (BioSpec 70/20 USR, Bruker, Billerica, MA, USA) and micro-CT (Inveon, Siemens Preclinical, Knoxville, TN, USA) before and after the injection. The difference between the pre- and post-injection images was quantified by finding the correlation coefficient. The aorta, blood vessel, and liver were clearly seen in the MRI and micro-CT images 60 min after intravenous injection of Fe3O4/TaOx nanoparticles, but the tumour region was not visible in the CT images until after 24 h. There were large differences between the pre- and post-injection images. Second, the therapeutic enhancement dose of nanomaterials was computed via Monte Carlo simulation. Monoenergetic 70- and 150-MeV proton beams irradiated X-ray contrast agent (iodine, BaSO4) , MRI contrast agent (gadolinium, Fe3O4), Au, Fe3O4/TaOx (core/shell) nanoparticles and water located at the centre of a 4  4  4-μm3 water phantom, upon which the dose enhancement ratio (DER) (dose with/without nanoparticles) was computed. When 70-MeV protons irradiated the Au, gadolinium, Fe3O4/TaOx, Fe3O4, iodine, and BaSO4 nanoparticles, the DERs at 1 nm were 15.76, 7.68, 7.82, 6.17, 4.85, and 5.51, respectively. Fe3O4/TaOx nanoparticles have the potential to be used a multifunctional agent that enhances tumour detection and increases the dose. Dose enhancement with Fe3O4/TaOx was half that with Au. However, Fe3O4/TaOx is much cheaper than Au, and it is expected that tumour targeting combined with magnetic field could overcome the low DER. © 2018 Institute of Physics and Engineering in Medicine.

Contrast Ultrasound Targeted Treatment of Gliomas in Mice via Drug-Bearing Nanoparticle Delivery and Microvascular Ablation

PubMed Central

Burke, Caitlin W.; Price, Richard J.

2010-01-01

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas. PMID:21206463

Contrast ultrasound targeted treatment of gliomas in mice via drug-bearing nanoparticle delivery and microvascular ablation.

PubMed

Burke, Caitlin W; Price, Richard J

2010-12-15

We are developing minimally-invasive contrast agent microbubble based therapeutic approaches in which the permeabilization and/or ablation of the microvasculature are controlled by varying ultrasound pulsing parameters. Specifically, we are testing whether such approaches may be used to treat malignant brain tumors through drug delivery and microvascular ablation. Preliminary studies have been performed to determine whether targeted drug-bearing nanoparticle delivery can be facilitated by the ultrasound mediated destruction of "composite" delivery agents comprised of 100nm poly(lactide-co-glycolide) (PLAGA) nanoparticles that are adhered to albumin shelled microbubbles. We denote these agents as microbubble-nanoparticle composite agents (MNCAs). When targeted to subcutaneous C6 gliomas with ultrasound, we observed an immediate 4.6-fold increase in nanoparticle delivery in MNCA treated tumors over tumors treated with microbubbles co-administered with nanoparticles and a 8.5 fold increase over non-treated tumors. Furthermore, in many cancer applications, we believe it may be desirable to perform targeted drug delivery in conjunction with ablation of the tumor microcirculation, which will lead to tumor hypoxia and apoptosis. To this end, we have tested the efficacy of non-theramal cavitation-induced microvascular ablation, showing that this approach elicits tumor perfusion reduction, apoptosis, significant growth inhibition, and necrosis. Taken together, these results indicate that our ultrasound-targeted approach has the potential to increase therapeutic efficiency by creating tumor necrosis through microvascular ablation and/or simultaneously enhancing the drug payload in gliomas.

Core-shell monodisperse spherical mSiO2/Gd2O3:Eu3+@mSiO2 particles as potential multifunctional theranostic agents

NASA Astrophysics Data System (ADS)

Eurov, Daniil A.; Kurdyukov, Dmitry A.; Kirilenko, Demid A.; Kukushkina, Julia A.; Nashchekin, Alexei V.; Smirnov, Alexander N.; Golubev, Valery G.

2015-02-01

Core-shell nanoparticles with diameters in the range 100-500 nm have been synthesized as monodisperse spherical mesoporous (pore diameter 3 nm) silica particles with size deviation of less than 4 %, filled with gadolinium and europium oxides and coated with a mesoporous silica shell. It is shown that the melt technique developed for filling with gadolinium and europium oxides provides a nearly maximum filling of mesopores in a single-run impregnation, with gadolinium and europium uniformly distributed within the particles and forming no bulk oxides on their surface. The coating with a shell does not impair the monodispersity and causes no coagulation. The coating technique enables controlled variation of the shell thickness within the range 5-100 % relative to the core diameter. The thus produced nanoparticles are easily dispersed in water, have large specific surface area (300 m2 g-1) and pore volume (0.3 cm3 g-1), and are bright solid phosphor with superior stability in aqueous media. The core-shell structured particles can be potentially used for cancer treatment as a therapeutic agent (gadolinium neutron-capture therapy and drug delivery system) and, simultaneously, as a multimodal diagnostic tool (fluorescence and magnetic resonance imaging), thereby serving as a multifunctional theranostic agent.

Stabilization and functionalization of iron oxide nanoparticles for biomedical applications

NASA Astrophysics Data System (ADS)

Amstad, Esther; Textor, Marcus; Reimhult, Erik

2011-07-01

Superparamagnetic iron oxide nanoparticles (NPs) are used in a rapidly expanding number of research and practical applications in the biomedical field, including magnetic cell labeling separation and tracking, for therapeutic purposes in hyperthermia and drug delivery, and for diagnostic purposes, e.g., as contrast agents for magnetic resonance imaging. These applications require good NP stability at physiological conditions, close control over NP size and controlled surface presentation of functionalities. This review is focused on different aspects of the stability of superparamagnetic iron oxide NPs, from its practical definition to its implementation by molecular design of the dispersant shell around the iron oxide core and further on to its influence on the magnetic properties of the superparamagnetic iron oxide NPs. Special attention is given to the selection of molecular anchors for the dispersant shell, because of their importance to ensure colloidal and functional stability of sterically stabilized superparamagnetic iron oxide NPs. We further detail how dispersants have been optimized to gain close control over iron oxide NP stability, size and functionalities by independently considering the influences of anchors and the attached sterically repulsive polymer brushes. A critical evaluation of different strategies to stabilize and functionalize core-shell superparamagnetic iron oxide NPs as well as a brief introduction to characterization methods to compare those strategies is given.Superparamagnetic iron oxide nanoparticles (NPs) are used in a rapidly expanding number of research and practical applications in the biomedical field, including magnetic cell labeling separation and tracking, for therapeutic purposes in hyperthermia and drug delivery, and for diagnostic purposes, e.g., as contrast agents for magnetic resonance imaging. These applications require good NP stability at physiological conditions, close control over NP size and controlled surface presentation of functionalities. This review is focused on different aspects of the stability of superparamagnetic iron oxide NPs, from its practical definition to its implementation by molecular design of the dispersant shell around the iron oxide core and further on to its influence on the magnetic properties of the superparamagnetic iron oxide NPs. Special attention is given to the selection of molecular anchors for the dispersant shell, because of their importance to ensure colloidal and functional stability of sterically stabilized superparamagnetic iron oxide NPs. We further detail how dispersants have been optimized to gain close control over iron oxide NP stability, size and functionalities by independently considering the influences of anchors and the attached sterically repulsive polymer brushes. A critical evaluation of different strategies to stabilize and functionalize core-shell superparamagnetic iron oxide NPs as well as a brief introduction to characterization methods to compare those strategies is given. This article was submitted as part of a collection of articles on surface nanotechnology for biological applications. Other papers on this topic can be found in issue 2 of vol. 3 (2011). This issue can be found from the Nanoscale homepage [http://www.rsc.org/nanoscale].

Synthesis, Characterization, and In Vivo Efficacy of Shell Cross-Linked Nanoparticle Formulations Carrying Silver Antimicrobials as Aerosolized Therapeutics

PubMed Central

2014-01-01

The use of nebulizable, nanoparticle-based antimicrobial delivery systems can improve efficacy and reduce toxicity for treatment of multi-drug-resistant bacteria in the chronically infected lungs of cystic fibrosis patients. Nanoparticle vehicles are particularly useful for applying broad-spectrum silver-based antimicrobials, for instance, to improve the residence time of small-molecule silver carbene complexes (SCCs) within the lung. Therefore, we have synthesized multifunctional, shell cross-linked knedel-like polymeric nanoparticles (SCK NPs) and capitalized on the ability to independently load the shell and core with silver-based antimicrobial agents. We formulated three silver-loaded variants of SCK NPs: shell-loaded with silver cations, core-loaded with SCC10, and combined loading of shell silver cations and core SCC10. All three formulations provided a sustained delivery of silver over the course of at least 2–4 days. The two SCK NP formulations with SCC10 loaded in the core each exhibited excellent antimicrobial activity and efficacy in vivo in a mouse model of Pseudomonas aeruginosa pneumonia. SCK NPs with shell silver cation-load only, while efficacious in vitro, failed to demonstrate efficacy in vivo. However, a single dose of core SCC10-loaded SCK NPs (0.74 ± 0.16 mg Ag) provided a 28% survival advantage over sham treatment, and administration of two doses (0.88 mg Ag) improved survival to 60%. In contrast, a total of 14.5 mg of Ag+ delivered over 5 doses at 12 h intervals was necessary to achieve a 60% survival advantage with a free-drug (SCC1) formulation. Thus, SCK NPs show promise for clinical impact by greatly reducing antimicrobial dosage and dosing frequency, which could minimize toxicity and improve patient adherence. PMID:23718195

Vascular applications of contrast-enhanced ultrasound imaging.

PubMed

Mehta, Kunal S; Lee, Jake J; Taha, Ashraf G; Avgerinos, Efthymios; Chaer, Rabih A

2017-07-01

Contrast-enhanced ultrasound (CEUS) imaging is a powerful noninvasive modality offering numerous potential diagnostic and therapeutic applications in vascular medicine. CEUS imaging uses microbubble contrast agents composed of an encapsulating shell surrounding a gaseous core. These microbubbles act as nearly perfect intravascular reflectors of ultrasound energy and may be used to enhance the overall contrast and quality of ultrasound images. The purpose of this narrative review is to survey the current literature regarding CEUS imaging and discuss its diagnostic and therapeutic roles in current vascular and selected nonvascular applications. The PubMed, MEDLINE, and Embase databases were searched until July 2016 using the PubMed and Ovid Web-based search engines. The search terms used included contrast-enhanced, microbubble, ultrasound, carotid, aneurysm, and arterial. The diagnostic and therapeutic utility of CEUS imaging has grown exponentially, particularly in the realms of extracranial carotid arterial disease, aortic disease, and peripheral arterial disease. Studies have demonstrated that CEUS imaging is diagnostically superior to conventional ultrasound imaging in identifying vessel irregularities and measuring neovascularization to assess plaque vulnerability and end-muscle perfusion. Groups have begun to use microbubbles as agents in therapeutic applications for targeted drug and gene therapy delivery as well as for the enhancement of sonothrombolysis. The emerging technology of microbubbles and CEUS imaging holds considerable promise for cardiovascular medicine and cancer therapy given its diagnostic and therapeutic utility. Overall, with proper training and credentialing of technicians, the clinical implications are innumerable as microbubble technology is rapidly bursting onto the scene of cardiovascular medicine. Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Highly flexible transparent self-healing composite based on electrospun core-shell nanofibers produced by coaxial electrospinning for anti-corrosion and electrical insulation

NASA Astrophysics Data System (ADS)

An, Seongpil; Liou, Minho; Song, Kyo Yong; Jo, Hong Seok; Lee, Min Wook; Al-Deyab, Salem S.; Yarin, Alexander L.; Yoon, Sam S.

2015-10-01

Coaxial electrospinning was used to fabricate two types of core-shell fibers: the first type with liquid resin monomer in the core and polyacrylonitrile in the shell, and the second type with liquid curing agent in the core and polyacrylonitrile in the shell. These two types of core-shell fibers were mutually entangled and embedded into two flexible transparent matrices thus forming transparent flexible self-healing composite materials. Such materials could be formed before only using emulsion electrospinning, rather than coaxial electrospinning. The self-healing properties of such materials are associated with release of healing agents (resin monomer and cure) from nanofiber cores in damaged locations with the subsequent polymerization reaction filing the micro-crack with polydimethylsiloxane. Transparency of these materials is measured and the anti-corrosive protection provided by them is demonstrated in electrochemical experiments.

Dependence of the subharmonic signal from contrast agent microbubbles on ambient pressure: A theoretical analysis.

PubMed

Jiménez-Fernández, J

2018-01-01

This paper investigates the dependence of the subharmonic response in a signal scattered by contrast agent microbubbles on ambient pressure to provide quantitative estimations of local blood pressure. The problem is formulated by assuming a gas bubble encapsulated by a shell of finite thickness with dynamic behavior modeled by a nonlinear viscoelastic constitutive equation. For ambient overpressure compatible with the clinical range, the acoustic pressure intervals where the subharmonic signal may be detected (above the threshold for the onset and below the limit value for the first chaotic transition) are determined. The analysis shows that as the overpressure is increased, all harmonic components are displaced to higher frequencies. This displacement is significant for the subharmonic of order 1/2 and explains the increase or decrease in the subharmonic amplitude with ambient pressure described in previous works. Thus, some questions related to the monotonic dependence of the subharmonic amplitude on ambient pressure are clarified. For different acoustic pressures, quantitative conditions for determining the intervals where the subharmonic amplitude is a monotonic or non-monotonic function of the ambient pressure are provided. Finally, the influence of the ambient pressure on the subharmonic resonance frequency is analyzed.

Tailor-made polyfluoroacrylate and its block copolymer by RAFT polymerization in miniemulsion; improved hydrophobicity in the core-shell block copolymer.

PubMed

Chakrabarty, Arindam; Singha, Nikhil K

2013-10-15

Controlled/living radical polymerization (CRP) of a fluoroacrylate was successfully carried out in miniemulsion by Reversible Addition Fragmentation chain Transfer (RAFT) process. In this case, 2,2,3,3,4,4,4-heptafluorobutyl acrylate (HFBA) was polymerized using 2-cyanopropyl dodecyl trithiocarbonate (CPDTC) as RAFT agent, Triton X-405 and sodium dodecyl sulfonate (SDS) as surfactant, and potassium persulphate (KPS) or 2,2'-azobis isobutyronitrile (AIBN) as initiator. Being compatible with hydrophobic fluoroacrylate, this RAFT agent offered very high conversion and good control over the molecular weight of the polymer. The miniemulsion was stable without any costabilizer. The long chain dodecyl group (-C12H25) (Z-group in the RAFT agent) had beneficial effect in stabilizing the miniemulsion. When 2-cyano 2-propyl benzodithioate (CPBD) (Z=-C6H5) was used as RAFT agent, the conversion was less and particle size distribution was very broad. Block copolymerization with butyl acrylate (BA) using PHFBA as macro-RAFT agent showed core-shell morphology with the aggregation of PHFBA segment in the shell. GPC as well as DSC analysis confirmed the formation of block copolymer. The core-shell morphology was confirmed by TEM analysis. The block copolymers (PHFBA-b-PBA) showed significantly higher water contact angle (WCA) showing much better hydrophobicity compared to PHFBA alone. Copyright © 2013 Elsevier Inc. All rights reserved.

Polypropylenes foam consisting of thermally expandable microcapsule as blowing agent

NASA Astrophysics Data System (ADS)

Jeoung, Sun Kyung; Hwang, Ye Jin; Lee, Hyun Wook; Kwak, Sung Bok; Han, In-Soo; Ha, Jin Uk

2016-03-01

The structure of thermally expandable microcapsule (TEMs) is consisted of a thermoplastic shell which is filled with liquid hydrocarbon at core. The shell of TEMs becomes soft when the temperature is higher than boiling temperature of liquid hydrocarbon. The shell of TEMs is expanded under the high temperature because the inner pressure of TEMs is increased by vaporization of hydrocarbon core. Therefore, the TEMs are applicable for blowing agents and light weight fillers. In this research, we fabricated the polypropylene (PP) foam by using the TEMs and chemical blowing agents and compared to their physical properties. The density of the specimen was decreased when the contents of chemical blowing agents and TEMs were increased. In addition, the mechanical properties (i.e. tensile strength and impact strength) of specimens were deteriorated with increasing amount of chemical blowing agents and TEMs. However, PP foam produced with TEMs showed higher impact strength than the one with the chemical blowing agent. In order to clarify the dependence of impact strength of PP foam as the blowing agent, the morphology difference of the PP foams was investigated. Expanding properties of PP foams produced with TEMs was changed with TEMs content of PP foams. Processing conditions also influenced the mechanical properties of PP foam containing TEMs.

PEG-phospholipid-encapsulated bismuth sulfide and CdSe/ZnS quantum dot core-shell nanoparticle and its computed tomography/fluorescence performance

NASA Astrophysics Data System (ADS)

Chen, Jun; Yang, Xiao-Quan; Qin, Meng-Yao; Zhang, Xiao-Shuai; Xuan, Yang; Zhao, Yuan-Di

2015-11-01

In this paper, polyethylene glycol-phospholipid structure is used to synthesize hybrid cluster of 40-50 nm diameter that contains hydrophobic bismuth sulfide nanoparticles and CdSe/ZnS quantum dots. The composite probe's toxicity, CT imaging, and fluorescence imaging performance are also studied. Experimental results show that the nanocomposite hybrid cluster has obvious CT contrast enhancement and fluorescence imaging capability in vitro even after cellular uptake. It gives a CT number of 700 (Hounsfield units) at 15 mg/mL, higher than that of the current iobitridol CT contrast agent. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide experiment reveals that it has low cytotoxicity at concentration up to of 3.14 mg/mL of Bi, indicating the composite probe has potential ability for CT and fluorescence bimodal imaging.

Hybrid Core-Shell (HyCoS) Nanoparticles produced by Complex Coacervation for Multimodal Applications

NASA Astrophysics Data System (ADS)

Vecchione, D.; Grimaldi, A. M.; Forte, E.; Bevilacqua, Paolo; Netti, P. A.; Torino, E.

2017-03-01

Multimodal imaging probes can provide diagnostic information combining different imaging modalities. Nanoparticles (NPs) can contain two or more imaging tracers that allow several diagnostic techniques to be used simultaneously. In this work, a complex coacervation process to produce core-shell completely biocompatible polymeric nanoparticles (HyCoS) for multimodal imaging applications is described. Innovations on the traditional coacervation process are found in the control of the reaction temperature, allowing a speeding up of the reaction itself, and the production of a double-crosslinked system to improve the stability of the nanostructures in the presence of a clinically relevant contrast agent for MRI (Gd-DTPA). Through the control of the crosslinking behavior, an increase up to 6 times of the relaxometric properties of the Gd-DTPA is achieved. Furthermore, HyCoS can be loaded with a high amount of dye such as ATTO 633 or conjugated with a model dye such as FITC for in vivo optical imaging. The results show stable core-shell polymeric nanoparticles that can be used both for MRI and for optical applications allowing detection free from harmful radiation. Additionally, preliminary results about the possibility to trigger the release of a drug through a pH effect are reported.

Next generation ultrasound platforms for theranostics.

PubMed

Oddo, Letizia; Cerroni, Barbara; Domenici, Fabio; Bedini, Angelico; Bordi, Federico; Chiessi, Ester; Gerbes, Stefan; Paradossi, Gaio

2017-04-01

Microbubbles are a well-established contrast agent which improves diagnostic ultrasound imaging. During the last decade research has focused on expanding their use to include molecular imaging, targeted therapy and imaging modalities other than ultrasound. However, bioadhesion of targeted microbubbles under physiological flow conditions is still difficult to achieve, the main challenge being connected to the poor stability of lipid microbubbles in the body's circulation system. In this article, we investigate the use of polymeric microbubbles based on a poly (vinyl alcohol) shell as an alternative to lipid microbubbles. In particular, we report on the development of microbubble shell modification, using mild reaction conditions, with the aim of designing a multifunctional platform to enable diagnosis and therapy. Superparamagnetic iron oxide nanoparticles and a near infrared fluorescent probe, indocyanine green, are coupled to the bubbles surface in order to support magnetic resonance and fluorescence imaging. Furthermore, anchoring cyclic arginyl-glycyl-aspartic acid (RGD) peptide, and cyclodextrin molecules, allows targeting and drug loading, respectively. Last but not least, shell topography is provided by atomic force microscopy. These applications and features, together with the high echogenicity of poly (vinyl alcohol) microbubbles, may offer a more stable alternative to lipid microbubbles for the development of a multimodal theranostic platform. Copyright © 2016 Elsevier Inc. All rights reserved.

Experimental characterization of a direct conversion amorphous selenium detector with thicker conversion layer for dual-energy contrast-enhanced breast imaging.

PubMed

Scaduto, David A; Tousignant, Olivier; Zhao, Wei

2017-08-01

Dual-energy contrast-enhanced imaging is being investigated as a tool to identify and localize angiogenesis in the breast, a possible indicator of malignant tumors. This imaging technique requires that x-ray images are acquired at energies above the k-shell binding energy of an appropriate radiocontrast agent. Iodinated contrast agents are commonly used for vascular imaging, and require x-ray energies greater than 33 keV. Conventional direct conversion amorphous selenium (a-Se) flat-panel imagers for digital mammography show suboptimal absorption efficiencies at these higher energies. We use spatial-frequency domain image quality metrics to evaluate the performance of a prototype direct conversion flat-panel imager with a thicker a-Se layer, specifically fabricated for dual-energy contrast-enhanced breast imaging. Imaging performance was evaluated in a prototype digital breast tomosynthesis (DBT) system. The spatial resolution, noise characteristics, detective quantum efficiency, and temporal performance of the detector were evaluated for dual-energy imaging for both conventional full-field digital mammography (FFDM) and DBT. The zero-frequency detective quantum efficiency of the prototype detector is improved by approximately 20% over the conventional detector for higher energy beams required for imaging with iodinated contrast agents. The effect of oblique entry of x-rays on spatial resolution does increase with increasing photoconductor thickness, specifically for the most oblique views of a DBT scan. Degradation of spatial resolution due to focal spot motion was also observed. Temporal performance was found to be comparable to conventional mammographic detectors. Increasing the a-Se thickness in direct conversion flat-panel imagers results in better performance for dual-energy contrast-enhanced breast imaging. The reduction in spatial resolution due to oblique entry of x-rays is appreciable in the most extreme clinically relevant cases, but may not profoundly affect reconstructed images due to the algorithms and filters employed. Degradation to projection domain spatial resolution is thus outweighed by the improvement in detective quantum efficiency for high-energy x-rays. © 2017 American Association of Physicists in Medicine.

Multilayer nanoparticles with a magnetite core and a polycation inner shell as pH-responsive carriers for drug delivery

NASA Astrophysics Data System (ADS)

Guo, Miao; Yan, Yu; Liu, Xiaozhou; Yan, Husheng; Liu, Keliang; Zhang, Hongkai; Cao, Youjia

2010-03-01

Nanocarriers with multilayer core-shell architecture were prepared by coating a superparamagnetic Fe3O4 core with a triblock copolymer. The first block of the copolymer formed the biocompatible outermost shell of the nanocarrier. The second block that contains amino groups and hydrophobic moiety formed the inner shell. The third block bound tightly onto the Fe3O4 core. Chlorambucil (an anticancer agent) and indomethacin (an anti-inflammation agent), each containing a carboxyl group and a hydrophobic moiety, were loaded into the amino-group-containing inner shell by a combination of ionic and hydrophobic interactions. The release rate of the loaded drugs was slow at pH 7.4, mimicking the blood environment, whereas the release rate increased significantly at acidic pH, mimicking the intracellular conditions in the endosome/lysosome. This can be attributed to the disruption of the ionic bond caused by protonation of the carboxylate anion of the drugs and the swelling of the inner shell caused by protonation of the amino groups.

Versatile utilization of real-time intraoperative contrast-enhanced ultrasound in cranial neurosurgery: technical note and retrospective case series.

PubMed

Lekht, Ilya; Brauner, Noah; Bakhsheshian, Joshua; Chang, Ki-Eun; Gulati, Mittul; Shiroishi, Mark S; Grant, Edward G; Christian, Eisha; Zada, Gabriel

2016-03-01

Intraoperative contrast-enhanced ultrasound (iCEUS) offers dynamic imaging and provides functional data in real time. However, no standardized protocols or validated quantitative data exist to guide its routine use in neurosurgery. The authors aimed to provide further clinical data on the versatile application of iCEUS through a technical note and illustrative case series. Five patients undergoing craniotomies for suspected tumors were included. iCEUS was performed using a contrast agent composed of lipid shell microspheres enclosing perflutren (octafluoropropane) gas. Perfusion data were acquired through a time-intensity curve analysis protocol obtained using iCEUS prior to biopsy and/or resection of all lesions. Three primary tumors (gemistocytic astrocytoma, glioblastoma multiforme, and meningioma), 1 metastatic lesion (melanoma), and 1 tumefactive demyelinating lesion (multiple sclerosis) were assessed using real-time iCEUS. No intraoperative complications occurred following multiple administrations of contrast agent in all cases. In all neoplastic cases, iCEUS replicated enhancement patterns observed on preoperative Gd-enhanced MRI, facilitated safe tumor debulking by differentiating neoplastic tissue from normal brain parenchyma, and helped identify arterial feeders and draining veins in and around the surgical cavity. Intraoperative CEUS was also useful in guiding a successful intraoperative needle biopsy of a cerebellar tumefactive demyelinating lesion obtained during real-time perfusion analysis. Intraoperative CEUS has potential for safe, real-time, dynamic contrast-based imaging for routine use in neurooncological surgery and image-guided biopsy. Intraoperative CEUS eliminates the effect of anatomical distortions associated with standard neuronavigation and provides quantitative perfusion data in real time, which may hold major implications for intraoperative diagnosis, tissue differentiation, and quantification of extent of resection. Further prospective studies will help standardize the role of iCEUS in neurosurgery.

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging

PubMed Central

Luo, Binhua; Liang, Huageng; Zhang, Shengwei; Qin, Xiaojuan; Liu, Xuhan; Liu, Wei; Zeng, Fuqing; Wu, Yun; Yang, Xiangliang

2015-01-01

In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of −12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0–20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue® microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging. PMID:26396514

Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging.

PubMed

Luo, Binhua; Liang, Huageng; Zhang, Shengwei; Qin, Xiaojuan; Liu, Xuhan; Liu, Wei; Zeng, Fuqing; Wu, Yun; Yang, Xiangliang

2015-01-01

In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of -12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0-20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue(®) microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

Upconverting rare-earth nanoparticles with a paramagnetic lanthanide complex shell for upconversion fluorescent and magnetic resonance dual-modality imaging

NASA Astrophysics Data System (ADS)

Wang, Yan; Ji, Lei; Zhang, Bingbo; Yin, Peihao; Qiu, Yanyan; Song, Daqian; Zhou, Juying; Li, Qi

2013-05-01

Multi-modal imaging based on multifunctional nanoparticles is a promising alternative approach to improve the sensitivity of early cancer diagnosis. In this study, highly upconverting fluorescence and strong relaxivity rare-earth nanoparticles coated with paramagnetic lanthanide complex shells and polyethylene glycol (PEGylated UCNPs@DTPA-Gd3+) are synthesized as dual-modality imaging contrast agents (CAs) for upconverting fluorescent and magnetic resonance dual-modality imaging. PEGylated UCNPs@DTPA-Gd3+ with sizes in the range of 32-86 nm are colloidally stable. They exhibit higher longitudinal relaxivity and transverse relaxivity in water (r1 and r2 values are 7.4 and 27.8 s-1 per mM Gd3+, respectively) than does commercial Gd-DTPA (r1 and r2 values of 3.7 and 4.6 s-1 per mM Gd3+, respectively). They are found to be biocompatible. In vitro cancer cell imaging shows good imaging contrast of PEGylated UCNPs@DTPA-Gd3+. In vivo upconversion fluorescent imaging and T1-weighted MRI show excellent enhancement of both fluorescent and MR signals in the livers of mice administered PEGylated UCNPs@DTPA-Gd3+. All the experimental results indicate that the synthesized PEGylated UCNPs@DTPA-Gd3+ present great potential for biomedical upconversion of fluorescent and magnetic resonance dual-modality imaging applications.

Functional magnetic porous silica for T 1-T 2 dual-modal magnetic resonance imaging and pH-responsive drug delivery of basic drugs

NASA Astrophysics Data System (ADS)

Li, Ling; Zhang, Run; Guo, Yi; Zhang, Cheng; Zhao, Wei; Xu, Zhiping; Whittaker, Andrew K.

2016-12-01

A smart magnetic-targeting drug carrier γ-Fe2O3@p-silica comprising a γ-Fe2O3 core and porous shell has been prepared and characterized. The particles have a uniform size of about 60 nm, and a porous shell of thickness 3 nm. Abundant hydroxyl groups and a large surface area enabled the γ-Fe2O3@p-silica to be readily loaded with a large payload of the basic model drug rhodamine B (RB) (up to 73 mg g-1). Cytotoxicity assays of the γ-Fe2O3@p-silica particles indicated that the particles were biocompatible and suitable for carrying drugs. It was found that the RB was released rapidly at pH 5.5 but at pH 7.4 the rate and extent of release was greatly attenuated. The particles therefore demonstrate an excellent pH-triggered drug release. In addition, the γ-Fe2O3@p-silica particles could be tracked by magnetic resonance imaging (MRI). A clear dose-dependent contrast enhancement in both T 1-weighted and T 2-weighted MR images indicated the potential of the γ-Fe2O3@p-silica particles to act as dual-mode T 1 and T 2 MRI contrast agents.

Diblock-copolymer-mediated self-assembly of protein-stabilized iron oxide nanoparticle clusters for magnetic resonance imaging.

PubMed

Tähkä, Sari; Laiho, Ari; Kostiainen, Mauri A

2014-03-03

Superparamagnetic iron oxide nanoparticles (SPIONs) can be used as efficient transverse relaxivity (T2 ) contrast agents in magnetic resonance imaging (MRI). Organizing small (D<10 nm) SPIONs into large assemblies can considerably enhance their relaxivity. However, this assembly process is difficult to control and can easily result in unwanted aggregation and precipitation, which might further lead to lower contrast agent performance. Herein, we present highly stable protein-polymer double-stabilized SPIONs for improving contrast in MRI. We used a cationic-neutral double hydrophilic poly(N-methyl-2-vinyl pyridinium iodide-block-poly(ethylene oxide) diblock copolymer (P2QVP-b-PEO) to mediate the self-assembly of protein-cage-encapsulated iron oxide (γ-Fe2 O3 ) nanoparticles (magnetoferritin) into stable PEO-coated clusters. This approach relies on electrostatic interactions between the cationic N-methyl-2-vinylpyridinium iodide block and magnetoferritin protein cage surface (pI≈4.5) to form a dense core, whereas the neutral ethylene oxide block provides a stabilizing biocompatible shell. Formation of the complexes was studied in aqueous solvent medium with dynamic light scattering (DLS) and cryogenic transmission electron microcopy (cryo-TEM). DLS results indicated that the hydrodynamic diameter (Dh ) of the clusters is approximately 200 nm, and cryo-TEM showed that the clusters have an anisotropic stringlike morphology. MRI studies showed that in the clusters the longitudinal relaxivity (r1 ) is decreased and the transverse relaxivity (r2 ) is increased relative to free magnetoferritin (MF), thus indicating that clusters can provide considerable contrast enhancement. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Facile deposition of gold nanoparticles on core-shell Fe3O4@polydopamine as recyclable nanocatalyst

NASA Astrophysics Data System (ADS)

Zhao, Yan; Yeh, Yaowen; Liu, Rui; You, Jinmao; Qu, Fengli

2015-07-01

A simple and green method for the controllable synthesis of core-shell Fe3O4 polydopamine nanoparticles (Fe3O4@PDA NPs) with tunable shell thickness and their application as a recyclable nanocatalyst support is presented. Magnetite Fe3O4 NPs formed in a one-pot process by the hydrothermal approach with a diameter of ˜240 nm were coated with a polydopamine shell layer with a tunable thickness of 15-45 nm. The facile deposition of Au NPs atop Fe3O4@PDA NPs was achieved by utilizing PDA as both the reducing agent and the coupling agent. The satellite nanocatalysts exhibited high catalytic performance for the reduction of p-nitrophenol. Furthermore, the recovery and reuse of the catalyst was demonstrated 8 times without detectible loss in activity. The synergistic combination of unique features of PDA and magnetic nanoparticles establishes these core-shell NPs as a versatile platform for potential applications.

DNA double strand break (DSB) induction and cell survival in iodine-enhanced computed tomography (CT)

NASA Astrophysics Data System (ADS)

Streitmatter, Seth W.; Stewart, Robert D.; Jenkins, Peter A.; Jevremovic, Tatjana

2017-08-01

A multi-scale Monte Carlo model is proposed to assess the dosimetric and biological impact of iodine-based contrast agents commonly used in computed tomography. As presented, the model integrates the general purpose MCNP6 code system for larger-scale radiation transport and dose assessment with the Monte Carlo damage simulation to determine the sub-cellular characteristics and spatial distribution of initial DNA damage. The repair-misrepair-fixation model is then used to relate DNA double strand break (DSB) induction to reproductive cell death. Comparisons of measured and modeled changes in reproductive cell survival for ultrasoft characteristic k-shell x-rays (0.25-4.55 keV) up to orthovoltage (200-500 kVp) x-rays indicate that the relative biological effectiveness (RBE) for DSB induction is within a few percent of the RBE for cell survival. Because of the very short range of secondary electrons produced by low energy x-ray interactions with contrast agents, the concentration and subcellular distribution of iodine within and near cellular targets have a significant impact on the estimated absorbed dose and number of DSB produced in the cell nucleus. For some plausible models of the cell-level distribution of contrast agent, the model predicts an increase in RBE-weighted dose (RWD) for the endpoint of DSB induction of 1.22-1.40 for a 5-10 mg ml-1 iodine concentration in blood compared to an RWD increase of 1.07  ±  0.19 from a recent clinical trial. The modeled RWD of 2.58  ±  0.03 is also in good agreement with the measured RWD of 2.3  ±  0.5 for an iodine concentration of 50 mg ml-1 relative to no iodine. The good agreement between modeled and measured DSB and cell survival estimates provides some confidence that the presented model can be used to accurately assess biological dose for other concentrations of the same or different contrast agents.

Microbubble Compositions, Properties and Biomedical Applications

PubMed Central

Sirsi, Shashank

2010-01-01

Over the last decade, there has been significant progress towards the development of microbubbles as theranostics for a wide variety of biomedical applications. The unique ability of microbubbles to respond to ultrasound makes them useful agents for contrast ultrasound imaging, molecular imaging, and targeted drug and gene delivery. The general composition of a microbubble is a gas core stabilized by a shell comprised of proteins, lipids or polymers. Each type of microbubble has its own unique advantages and can be tailored for specialized functions. In this review, different microbubbles compositions and physiochemical properties are discussed in the context of current progress towards developing novel constructs for biomedical applications, with specific emphasis on molecular imaging and targeted drug/gene delivery. PMID:20574549

Influence of temperature, needle gauge and injection rate on the size distribution, concentration and acoustic responses of ultrasound contrast agents at high frequency.

PubMed

Sun, Chao; Panagakou, Ioanna; Sboros, Vassilis; Butler, Mairead B; Kenwright, David; Thomson, Adrian J W; Moran, Carmel M

2016-08-01

This paper investigated the influence of needle gauge (19G and 27G), injection rate (0.85ml·min(-1), 3ml·min(-1)) and temperature (room temperature (RT) and body temperature (BT)) on the mean diameter, concentration, acoustic attenuation, contrast to tissue ratio (CTR) and normalised subharmonic intensity (NSI) of three ultrasound contrast agents (UCAs): Definity, SonoVue and MicroMarker (untargeted). A broadband substitution technique was used to acquire the acoustic properties over the frequency range 17-31MHz with a preclinical ultrasound scanner Vevo770 (Visualsonics, Canada). Significant differences (P<0.001-P<0.05) between typical in vitro setting (19G needle, 3ml·min(-1) at RT) and typical in vivo setting (27G needle, 0.85ml·min(-1) at BT) were found for SonoVue and MicroMarker. Moreover we found that the mean volume-based diameter and concentration of both SonoVue and Definity reduced significantly when changing from typical in vitro to in vivo experimental set-ups, while those for MicroMarker did not significantly change. From our limited measurements of Definity, we found no significant change in attenuation, CTR and NSI with needle gauge. For SonoVue, all the measured acoustic properties (attenuation, CTR and NSI) reduced significantly when changing from typical in vitro to in vivo experimental conditions, while for MicroMarker, only the NSI reduced, with attenuation and CTR increasing significantly. These differences suggest that changes in physical compression and temperature are likely to alter the shell structure of the UCAs resulting in measureable and significant changes in the physical and high frequency acoustical properties of the contrast agents under typical in vitro and preclinical in vivo experimental conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Preparation and characterization of a novel silicon-modified nanobubble

PubMed Central

Li, Maotong; Zhou, Meijun; Li, Fei; Huang, Xiuxian; Pan, Min; Xue, Li

2017-01-01

Nanobubbles (NBs) opened a new field of ultrasound imaging. There is still no practical method to control the diameter of bubbles. In this study, we developed a new method to control the size by incorporating of silicon hybrid lipids into the bubble membrane. The range of particle size of resulting NBs is between 523.02 ± 46.45 to 857.18 ± 82.90, smaller than the conventional microbubbles. The size of resulting NBs increased with the decrease in amount of silicon hybrid lipids, indicating the diameter of NBs can be regulated through modulating the ratio of silicon hybrid lipids in the bubble shell. Typical harmonic signals could be detected. The in vitro and in vivo ultrasound imaging experiments demonstrated these silicon-modified NBs had significantly improved ultrasound contrast enhancement abilities. Cytotoxicity assays revealed that these NBs had no obvious cytotoxicity to the 293 cell line at the tested bubble concentration. Our results showed that the novel NBs could use as nanoscale ultrasound contrast agents, providing the foundation for NBs in future applications including contrast-enhanced imaging and drug/gene delivery. PMID:28557995

Thermochromic microcapsules with highly transparent shells obtained through in-situ polymerization of urea formaldehyde around thermochromic cores for smart wood coatings.

PubMed

Zhu, Xiaodong; Liu, Yu; Li, Zhao; Wang, Weicong

2018-03-05

In this paper, thermochromic microcapsules were synthesized in situ polymerization with urea formaldehyde as shell material and thermochromic compounds as core material. The effects of emulsifying agent and conditions on surface morphology and particle size of microcapsules were studied. It was found that the size and surface morphology of microcapsules were strongly depending on stirring rate and the ratio of core to shell. The stable and small size spherical microcapsules with excellent transparency can be obtained at an emulsifying agent to core to shell ratio as 1:5:7.5 under mechanical stirring at 12 krpm for 15 min. Finally, the thermochromic property was discussed by loading microcapsules in wood and wood coatings. Results indicate that microcapsules can realize the thermochromic property while incorporated with wood and coatings, and could have high potential in smart material fabrication.

Optimization of multicore-shell Fe3O4-SiO2 magnetic nanocomposites synthesis and retention in cellulose pulp

NASA Astrophysics Data System (ADS)

Buteica, Dan; Borbath, Istvan; Nicolae, Ionel Valentin; Turcu, Rodica; Marinica, Oana; Socoliuc, Vlad

2017-12-01

The use of magnetite nanoparticles to produce magnetic paper has a severe effect on the color of the paper, which is worth searching means to alleviate. Multicore-shell Fe3O4-SiO2 magnetic nanocomposites were synthesized. The nanocomposite powder was dispersed in cellulose pulp and paper was produced by dehydration on a Rapid Kothen machine. The nanocomposite retention efficiency was investigated in correlation with nanocomposite shell thickness, the resinous vs. deciduous fiber content of the cellulose pulp, the long and short fibers' grinding degree, the cationic starch and polymeric retention agent content of the pulp. The whiteness and magnetization was measured for all paper samples. It was proved that the use of multi-core shell magnetic nanocomposites leads to weaker paper coloring. This effect is enhanced by increasing the polymeric retention agent content of the pulp, in spite of higher composite content.

Preparation and characterization of chain-like and peanut-like Fe3O4@SiO2 core-shell structure.

PubMed

Shi, Haowei; Huang, Yan; Cheng, Chao; Ji, Guoyuan; Yang, Yuxiang; Yuan, Hongming

2013-10-01

The size- and shape-controlled Fe3O4@SiO2 nanocomposites were successfully synthesized via the sol-gel method. The results showed that the size, shape, and property of the products were directly influenced by the amount of TEOS, and the concentration of water-based magnetic fluid in the coating process. The morphology and properties of the products were characterized by TEM, SEM, X-ray powder diffraction, IR and EDS. The Fe3O4@SiO2 composites with easily-controlled size arranged from 58 to 835 nm could be synthesized by adjusting the experimental parameters. When TEOS amount is 1 mL and the concentration of magnetic fluid were 30.0 and 10.0 mg/mL respectively, chain-like and peanuts-like well-dispersed Fe3O4@SiO2 particles with clear core-shell structure were obtained. These size- and shape-controlled Fe3O4@SiO2 composites may have potential application in the field of targeted drug delivery and MRI contrast agent.

Prussian blue coated gold nanoparticles for simultaneous photoacoustic/CT bimodal imaging and photothermal ablation of cancer.

PubMed

Jing, Lijia; Liang, Xiaolong; Deng, Zijian; Feng, Shanshan; Li, Xiaoda; Huang, Maomao; Li, Changhui; Dai, Zhifei

2014-07-01

The combination of CT imaging and photoacoustic (PA) imaging represents not only high resolution and ease of forming 3D visual image for locating tissues of interest, but also good soft tissue contrast and excellent high sensitivity, which is very beneficial to the precise guidance for photothermal therapy (PTT). The near infrared (NIR) absorbing Au nanostructures take advantages to operate as a CT contrast agent due to high absorption coefficient of X-ray and outstanding biocompatibility, but show obvious deficiency for PA imaging and PTT because of low photostability. Attacking this problem head on, the Au nanoparticles (NPs) were coated with Prussian blue (PB) which is a typical FDA-approved drug in clinic for safe and effective treatment of radioactive exposure. The obtained core/shell NPs of Au@PB NPs of 17.8 ± 2.3 nm were found to be an excellent photoabsorbing agent for both PTT and PA imaging due to high photostability and high molar extinction coefficient in NIR region. Their gold core of 9.1 ± 0.64 nm ensured a remarkable contrast enhancement for CT imaging. Through a one-time treatment of NIR laser irradiation after intravenous injection of Au@PB NPs, 100 mm(3) sized tumors in nude mice could be completely ablated without recurrence. Such versatile nanoparticles integrating effective cancer diagnosis with noninvasive therapy might bring opportunities to future cancer therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Preparation and preliminary evaluation of KGDS-targeted ultrasound contrast agent].

PubMed

Gao, Feng; Ding, Yanfei; Sheng, Xiaoxi; Wang, Wei; Liang, Qi; Luo, Zhuoqiong; Zhou, Ping; Li, Hui

2009-12-01

To prepare a thrombus-targeted ultrasonic contrast agent and to investigate its targeted ability to fresh blood clots. We first synthesized FITC-KGDS-Palm compound, and then prepared thrombus-targeted microbubbles using "ultrasound & high speed shearing method". Fluorescence labeling thrombus-specific peptides and KGDS, directed at the activated glycoprotein(GP)IIb/IIIa receptor of platelets were attached to the surface of lipid microbubbles. The concentration and size of TUCA were measured by Malvern Zeta Sizer Nano-ZS590 and Coulter counter. Immunofluorescence was applied to confirm the conjugation. The conjunct ratio was assessed by flow cytometer (FCM). The KGDS-TUCA was straw yellow turbid liquor, and the concentration was 1.5 x 10(9)/mL, and the average size was 1.5 microm. The targeted microbubbles conjugated with the thrombus-specific peptides showed bright green rings by fluorescence microscope. FCM demonstrated that the wavelength of shell of KGDS-TUCA changed greatly, and the conjunct ratio was 90.04%. In vitro study showed KGDS-TUCA remained stable for 48 h at 4 degree C and target-attached to blood clots and showed good stability. The ultrasound & high speed shearing method to prepare TUCA is easy and in favor of purification. KGDS-TUCA has high specific biological activity. The conjunct ratio and stability of KGDS-TUCA are excellent.

Atomic level characterization of cadmium selenide nanocrystal systems using atomic number contrast scanning transmission electron microscopy and Rutherford backscattering spectroscopy

NASA Astrophysics Data System (ADS)

McBride, James R.

This project involved the characterization of CdSe nanocrystals. Through the use of Atomic Number Contrast Scanning Transmission Electron Microscopy (Z-STEM) and Rutherford Backscattering Spectroscopy (RBS), atomic level structure and chemical information was obtained. Specifically, CdSe nanocrystals produced using a mixture of hexadecylamine (HDA) and trioctylphosphine oxide (TOPO) were determined to be spherical compared to nanocrystals produced in TOPO only, which had elongated (101) facets. Additionally, the first Z-STEM images of CdSe/ZnS core/shell nanocrystals were obtained. From these images, the growth mechanism of the ZnS shell was determined and the existence of non-fluorescent ZnS particles was confirmed. Through collaboration with Quantum Dot Corp., core/shell nanocrystals with near unity quantum yield were developed. These core/shell nanocrystals included a US intermediate layer to improve shell coverage.

Method of fabricating nested shells and resulting product

DOEpatents

Henderson, Timothy M.; Kool, Lawrence B.

1982-01-01

A multiple shell structure and a method of manufacturing such structure wherein a hollow glass microsphere is surface treated in an organosilane solution so as to render the shell outer surface hydrophobic. The surface treated glass shell is then suspended in the oil phase of an oil-aqueous phase dispersion. The oil phase includes an organic film-forming monomer, a polymerization initiator and a blowing agent. A polymeric film forms at each phase boundary of the dispersion and is then expanded in a blowing operation so as to form an outer homogeneously integral monocellular substantially spherical thermoplastic shell encapsulating an inner glass shell of lesser diameter.

Ligand conjugation to bimodal poly(ethylene glycol) brush layers on microbubbles.

PubMed

Chen, Cherry C; Borden, Mark A

2010-08-17

Using microbubbles as model systems, we examined molecular diffusion and binding to colloidal surfaces in bimodal poly(ethylene glycol) (PEG) brush layers. A microbubble is a gaseous colloidal particle with a diameter of less than 10 mum, of which the surface comprises amphiphilic phospholipids self-assembled to form a lipid monolayer shell. Due to the compressible gas core, microbubbles provide a sensitive acoustic response and are currently used as ultrasound contrast agents. Similar to the design of long circulating liposomes, PEG chains are typically incorporated into the shell of microbubbles to form a steric barrier against coalescence and adsorption of macromolecules to the microbubble surface. We introduced a buried-ligand architecture (BLA) design where the microbubble surface was coated with a bimodal PEG brush. After microbubbles were generated, fluorescent ligands with different molecular weights were conjugated to the tethered functional groups on the shorter PEG chains, while the longer PEG chains served as a shield to protect these ligands from exposure to the surrounding environment. BLA microbubbles reduced the binding of macromolecules (>10 kDa) to the tethers due to the steric hindrance of the PEG overbrush while allowing the uninhibited attachment of small molecules (<1 kDa). Roughly 40% less fluorescein-conjugated streptavidin (SA-FITC) bound to BLA microbubbles compared to exposed-ligand architecture (ELA) microbubbles. The binding of SA-FITC to BLA microbubbles suggested a possible phase separation between the lipid species on the surface leading to populations of revealed and concealed ligands. Ligand conjugation kinetics was independent of microbubble size, regardless of ligand size or microbubble architecture. We observed, for the first time, streptavidin-induced surface structure formation for ELA microbubbles and proposed that this phenomenon may be correlated to flow cytometry scattering measurements. We therefore demonstrated the feasibility of postlabeling for small-molecule ligands to BLA microbubbles to generate stealth targeted ultrasound contrast agents.

Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

PubMed

Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

2013-12-28

Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

Toxic-Waste Disposal by Combustion in Containers

NASA Technical Reports Server (NTRS)

Houseman, J.; Stephens, J. B.; Moynihan, P. I.; Compton, L. E.; Kalvinskas, J. J.

1986-01-01

Chemical wastes burned with minimal handling in storage containers. Technique for disposing of chemical munitions by burning them inside shells applies to disposal of toxic materials stored in drums. Fast, economical procedure overcomes heat-transfer limitations of conventional furnace designs by providing direct contact of oxygenrich combustion gases with toxic agent. No need to handle waste material, and container also decontaminated in process. Oxygen-rich torch flame cuts burster well and causes vaporization and combustion of toxic agent contained in shell.

Use of positive oral contrast agents in abdominopelvic computed tomography for blunt abdominal injury: meta-analysis and systematic review.

PubMed

Lee, Chau Hung; Haaland, Benjamin; Earnest, Arul; Tan, Cher Heng

2013-09-01

To determine whether positive oral contrast agents improve accuracy of abdominopelvic CT compared with no, neutral or negative oral contrast agent. Literature was searched for studies evaluating the diagnostic performance of abdominopelvic CT with positive oral contrast agents against imaging with no, neutral or negative oral contrast agent. Meta-analysis reviewed studies correlating CT findings of blunt abdominal injury with positive and without oral contrast agents against surgical, autopsy or clinical outcome allowing derivation of pooled sensitivity and specificity. Systematic review was performed on studies with common design and reference standard. Thirty-two studies were divided into two groups. Group 1 comprised 15 studies comparing CT with positive and without oral contrast agents. Meta-analysis of five studies from group 1 provided no difference in sensitivity or specificity between CT with positive or without oral contrast agents. Group 2 comprised 17 studies comparing CT with positive and neutral or negative oral contrast agents. Systematic review of 12 studies from group 2 indicated that neutral or negative oral contrasts were as effective as positive oral contrast agents for bowel visualisation. There is no difference in accuracy between CT performed with positive oral contrast agents or with no, neutral or negative oral contrast agent. • There is no difference in the accuracy of CT with or without oral contrast agent. • There is no difference in the accuracy of CT with Gastrografin or water. • Omission of oral contrast, utilising neutral or negative oral contrast agent saves time, costs and decreases risk of aspiration.

Method and apparatus to characterize ultrasonically reflective contrast agents

NASA Technical Reports Server (NTRS)

Pretlow, Robert A., III (Inventor)

1993-01-01

A method and apparatus for characterizing the time and frequency response of an ultrasonically reflective contrast agent is disclosed. An ultrasonically reflective contrast agent is injected, under constant pressure, into a fluid flowing through a pump flow circuit. The fluid and the ultrasonically reflective contrast agent are uniformly mixed in a mixing chamber, and the uniform mixture is passed through a contrast agent chamber. The contrast agent chamber is acoustically and axially interposed between an ultrasonic transducer chamber and an acoustic isolation chamber. A pulse of ultrasonic energy is transmitted into the contrast agent chamber from the ultrasonic transducer chamber. An echo waveform is received from the ultrasonically reflective contrast agent, and it is analyzed to determine the time and frequency response of the ultrasonically reflective contrast agent.

Designed synthesis of multi-functional PEGylated Yb2O3:Gd@SiO2@CeO2 islands core@shell nanostructure.

PubMed

Li, Junqi; Yao, Shuang; Song, Shuyan; Wang, Xiao; Wang, Yinghui; Ding, Xing; Wang, Fan; Zhang, Hongjie

2016-07-28

Nanomaterials that can restrain or reduce the production of excessive reactive oxygen species such as H2O2 to defend and treat against Alzheimer's disease (AD) have attracted much attention. In this paper, we adopt the strategy of layer-by-layer deposition; namely, first synthesizing available gadolinium-doped ytterbia nanoparticles (Yb2O3:Gd NPs) as cores, and then coating them with silica via the classical Stöber method to prevent leakage and act as a carrier for subsequent ceria deposition and PEGylation, and finally obtain the expected core@shell-structured nanocomposite of PEGylated Yb2O3:Gd@SiO2@CeO2 islands. The nanomaterial has proved not only to be a high-performance dual-modal contrast agent for use in MRI and CT, but also to exhibit excellent catalase mimetic activity, which may help the prognosis, diagnosis and treatment of AD in the future. In addition, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR) spectroscopy characterization have revealed the successful design and synthesis of the cores with remarkable size uniformity, with well-distributed CeO2 islands decorated on the surface of SiO2 shells, and tightly immobilized PEG.

Structural Basis for Near Unity Quantum Yield Core/Shell Nanostructures

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

McBride, James; Treadway, Joe; Pennycook, Stephen J

2006-01-01

Aberration-corrected Z-contrast scanning transmission electron microscopy of core/shell nanocrystals shows clear correlations between structure and quantum efficiency. Uniform shell coverage is obtained only for a graded CdS/ZnS shell material and is found to be critical to achieving near 100% quantum yield. The sublattice sensitivity of the images confirms that preferential growth takes place on the anion-terminated surfaces. This explains the three-dimensional "nanobullet" shape observed in the case of core/shell nanorods.

Coaxial electrospinning for encapsulation and controlled release of fragile water-soluble bioactive agents.

PubMed

Jiang, Hongliang; Wang, Liqun; Zhu, Kangjie

2014-11-10

Coaxial electrospinning is a robust technique for one-step encapsulation of fragile, water-soluble bioactive agents, including growth factors, DNA and even living organisms, into core-shell nanofibers. The coaxial electrospinning process eliminates the damaging effects due to direct contact of the agents with organic solvents or harsh conditions during emulsification. The shell layer serves as a barrier to prevent the premature release of the water-soluble core contents. By varying the structure and composition of the nanofibers, it is possible to precisely modulate the release of the encapsulated agents. Promising work has been done with coaxially electrospun non-woven mats integrated with bioactive agents for use in tissue engineering, in local delivery and in wound healing, etc. This paper reviews the origins of the coaxial electrospinning method, its updated status and potential future developments for controlled release of the class of fragile, water-soluble bioactive agents. Copyright © 2014 Elsevier B.V. All rights reserved.

In vitro and in vivo MRI visualization of nanocomposite biodegradable microcapsules with tunable contrast.

PubMed

German, Sergey V; Bratashov, Daniil N; Navolokin, Nikita A; Kozlova, Anastasia A; Lomova, Maria V; Novoselova, Marina V; Burilova, Evgeniya A; Zyev, Victor V; Khlebtsov, Boris N; Bucharskaya, Alla B; Terentyuk, Georgy S; Amirov, Rustem R; Maslyakova, Galina N; Sukhorukov, Gleb B; Gorin, Dmitry A

2016-11-30

Microcapsules, made of biodegradable polymers, containing magnetite nanoparticles with tunable contrast in both the T1 and T2 MRI modes, were successfully prepared using a layer-by-layer approach. The MRI contrast of the microcapsules was shown to depend on the distance between magnetite nanoparticles in the polymeric layers, which is controlled by their concentration in the microcapsule shell. A fivefold increase in the average distance between the nanoparticles in the microcapsule shell led to a change in the intensity of the MR signal of 100% for both the T1 and T2 modes. Enzyme treatment of biodegradable shells resulted in a change of the microcapsules' MRI contrast. In vivo degradation of nanocomposite microcapsules concentrated in the liver after intravenous injection was demonstrated by MRI. This method can be used for the creation of a new generation of drug delivery systems, including drug depot, with combined navigation, visualization and remote activated release of bioactive substances in vivo.

Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

PubMed Central

Sinharay, Sanhita; Pagel, Mark D.

2016-01-01

Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

Iodinated contrast media and contrast-induced nephropathy: is there a preferred cost-effective agent?

PubMed

Sharma, Samin K

2008-05-01

Over 20 years have passed since the introduction of the tri-iodinated low-osmolar nonionic contrast agents such as iopamidol, iohexol, ioversol and iopromide. During this time, most cardiology practices have switched to these nonionic agents to avoid the nuisance side effects and cardiac adverse events associated with the older ionic contrast agents. Although the improved tolerability of the nonionic agents is generally attributed to their decreased osmolality (approximately half that of the older ionic contrast agents), in fact, these contrast agents also differ from the older agents in their ionicity, viscosity and direct chemotoxicity. The impact of these properties on safety, together with cost differences, should be considered when selecting a contrast agent.

Soft shell clams Mya arenaria with disseminated neoplasia demonstrate reverse transcriptase activity

USGS Publications Warehouse

House, M.L.; Kim, C.H.; Reno, P.W.

1998-01-01

Disseminated neoplasia (DN), a proliferative cell disorder of the circulatory system of bivalves, was first reported in oysters in 1969. Since that time, the disease has been determined to be transmissible through water-borne exposure, but the etiological agent has not been unequivocally identified. In order to determine if a viral agent, possibly a retrovirus, could be the causative agent of DN, transmission experiments were performed, using both a cell-free filtrate and a sucrose gradient-purified preparation of a cell-free filtrate of DN positive materials. Additionally, a PCR-enhanced reverse transcriptase assay was used to determine if reverse transcriptase was present in tissues or hemolymph from DN positive soft shell clams Mya arenaria. DN was transmitted to healthy clams by injection with whole DN cells, but not with cell-free flitrates prepared from either tissues from DN positive clams, or DN cells. The cell-free preparations from DN-positive tissues and hemolymph having high levels of DN cells in circulation exhibited positive reactions in the PCR-enhanced reverse transcriptase assay. Cell-free preparations of hemolymph from clams having low levels of DN (<0.1% of cells abnormal), hemocytes from normal soft shell clams, and normal soft shell clam tissues did not produce a positive reaction in the PCR enhanced reverse transcriptase assay.

[Utilization of polymeric micelle magnetic resonance imaging (MRI) contrast agent for theranostic system].

PubMed

Shiraishi, Kouichi

2013-01-01

We applied a polymeric micelle carrier system for the targeting of a magnetic resonance imaging (MRI) contrast agent. Prepared polymeric micelle MRI contrast agent exhibited a long circulation characteristic in blood, and considerable amount of the contrast agent was found to accumulate in colon 26 solid tumor by the EPR effect. The signal intensities of tumor area showed 2-folds increase in T1-weighted images at 24 h after i.v. injection. To observe enhancement of the EPR effect by Cderiv pretreatment on tumor targeting, we used the contrast agent for the evaluation by means of MRI. Cderiv pretreatment significantly enhanced tumor accumulation of the contrast agent. Interestingly, very high signal intensity in tumor region was found at 24 h after the contrast agent injection in Cderiv pretreated mice. The contrast agent visualized a microenvironmental change in tumor. These results indicate that the contrast agent exhibits potential use for tumor diagnostic agent. To combine with a polymeric micelle carrier system for therapeutic agent, the usage of the combination makes a new concept of "theranostic" for a better cancer treatment.

ParaCEST agents encapsulated in Reverse nano-Assembled Capsules (RACs): How slow molecular tumbling can quench CEST

NASA Astrophysics Data System (ADS)

Farashishiko, Annah; Slack, Jacqueline R.; Botta, Mauro; Woods, Mark

2018-04-01

Although paraCEST is a method with immense scope for generating image contrast in MRI, it suffers from the series the serious drawback of high detection limits. For a typical discrete paraCEST agent the detection limit is roughly an order of magnitude higher than that of a clinically used relaxation agent. One solution to this problem may be the incorporation of a large payload of paraCEST agents into a single macromolecular agent. Here we report a new synthetic method for accomplishing this goal: incorporating a large payload of the paraCEST agent DyDOTAM3+ into a Reverse Assembled nano-Capsule. An aggregate can be generated between this chelate and polyacrylic acid after the addition of ethylene diamine. Subsequent addition of polyallylamine hydrochloride followed by silica nanoparticles generated a robust encapsulating shell and afforded capsule with a mean hydrodynamic diameter of 650 ± 250 nm. Unfortunately this encapsulation did not have the effect of amplifying the CEST effect per agent, but quenched the CEST altogether. A significant proportion of the quenching effect of encapsulation could be attributed to the effect of slowing molecular tumbling, which is inevitable when the chelate is incorporated into a nano-scale material. This increases the transverse relaxation rate of chelate protons and a theoretical examination using Solomon Bloembergen Morgan theory and the Bloch equations shows that the increase in the transverse relaxation rate constant for the amide protons, in even modestly sized nano-materials, is sufficient to significantly quench CEST.

Inhibitive effect of Pt on Pd-hydride formation of Pd@Pt core-shell electrocatalysts: An in situ EXAFS and XRD study

DOE PAGES

Wise, Anna M.; Richardson, Peter W.; Price, Stephen W. T.; ...

2017-12-27

In situ EXAFS and XRD have been used to study the electrochemical formation of hydride phases, H abs, in 0.5 M H 2SO 4 for a Pd/C catalyst and a series of Pd@Pt core-shell catalysts with varying Pt shell thickness, from 0.5 to 4 monolayers. Based on the XRD data a 3% lattice expansion is observed for the Pd/C core catalyst upon hydride formation at 0.0 V. In contrast, the expansion was ≤0.6% for all of the core-shell catalysts. The limited extent of the lattice expansion observed suggests that hydride formation, which may occur during periodic active surface area measurementsmore » conducting during accelerated aging tests or driven by H 2 crossover in PEM fuel cells, is unlikely to contribute significantly to the degradation of Pd@Pt core-shell electrocatalysts in contrast to the effects of oxide formation.« less

Inhibitive effect of Pt on Pd-hydride formation of Pd@Pt core-shell electrocatalysts: An in situ EXAFS and XRD study

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

Wise, Anna M.; Richardson, Peter W.; Price, Stephen W. T.

In situ EXAFS and XRD have been used to study the electrochemical formation of hydride phases, H abs, in 0.5 M H 2SO 4 for a Pd/C catalyst and a series of Pd@Pt core-shell catalysts with varying Pt shell thickness, from 0.5 to 4 monolayers. Based on the XRD data a 3% lattice expansion is observed for the Pd/C core catalyst upon hydride formation at 0.0 V. In contrast, the expansion was ≤0.6% for all of the core-shell catalysts. The limited extent of the lattice expansion observed suggests that hydride formation, which may occur during periodic active surface area measurementsmore » conducting during accelerated aging tests or driven by H 2 crossover in PEM fuel cells, is unlikely to contribute significantly to the degradation of Pd@Pt core-shell electrocatalysts in contrast to the effects of oxide formation.« less

Synthesis of internally functionalized silica nanoparticles for theranostic applications

NASA Astrophysics Data System (ADS)

Walton, Nathan Isaac

This thesis addresses the synthesis and characterization of novel inorganic silica nanoparticle hybrids. It focuses in large part on their potential applications in the medical field. Silica acts as a useful carrier for a variety of compounds and this thesis silica will demonstrate its use as a carrier for boron or gadolinium. Boron-10 and gadolinium-157 have been suggested for the radiological treatment of tumor cells through the process called neutron capture therapy (NCT). Gadolinium is also commonly used as a Magnetic Resonance Imaging (MRI) contrast agent. Particles that carry it have potential theranostic applications of both imaging and treating tumors. Chapter 1 presents a background on synthetic strategies and usages of silica nanoparticles, and NCT theory. Chapter 2 describes a procedure to create mesoporous metal chelating silica nanoparticles, mDTTA. This is achieved via a co-condensation of tetraethoxysilane (TEOS) and 3-trimethoxysilyl-propyl diethylenetriamine (SiDETA) followed by a post-synthesis modification step with bromoacetic acid (BrAA). These particles have a large surface area and well-defined pores of ~2 nm. The mDTTA nanoparticles were used to chelate the copper(II), cobalt(II) and gadolinium(III). The chelating of gadolinium is the most interesting since it can be used as a MRI contrast agent and a neutron capture therapeutic. The synthetic procedure developed also allows for the attachment of a fluorophore that gives the gadolinium chelating mDTTA nanoparticles a dual imaging modality. Chapter 3 presents the synthetic method used to produce two classes of large surface area organically modified silica (ORMOSIL) nanoparticles. Condensating the organosilane vinyltrimethoxysilane in a micellar solution results in nanoparticles that are either surface rough (raspberry-like) or mesoporous nanoparticles, which prior to this thesis has not been demonstrated in ORMOSIL chemistry. Furthermore, the vinyl functionalities are modified, using hydroboration, to make the nanoparticles into water-dispersible boron carriers that also have potential boron neutron capture therapy (BNCT) applications. Lastly, Chapter 4 provides a general description of NCT, specifically that involving boron-10 and gadolinium-157. It further describes the synthetic methodology used in producing fatty acid coated boron nanoparticles (BNPs). The BNPs are encapsulated with silica to add a hydrophilic shell so that they can potentially be used in biological systems as BNCT agents. The silica shell is also modified with a fluorophore, dansyl chloride, so that the particle hybrid could be imaged during cell studies.

Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF): A Platform for Simultaneous Quantification of Multiple MRI Contrast Agents.

PubMed

Anderson, Christian E; Donnola, Shannon B; Jiang, Yun; Batesole, Joshua; Darrah, Rebecca; Drumm, Mitchell L; Brady-Kalnay, Susann M; Steinmetz, Nicole F; Yu, Xin; Griswold, Mark A; Flask, Chris A

2017-08-16

Injectable Magnetic Resonance Imaging (MRI) contrast agents have been widely used to provide critical assessments of disease for both clinical and basic science imaging research studies. The scope of available MRI contrast agents has expanded over the years with the emergence of molecular imaging contrast agents specifically targeted to biological markers. Unfortunately, synergistic application of more than a single molecular contrast agent has been limited by MRI's ability to only dynamically measure a single agent at a time. In this study, a new Dual Contrast - Magnetic Resonance Fingerprinting (DC - MRF) methodology is described that can detect and independently quantify the local concentration of multiple MRI contrast agents following simultaneous administration. This "multi-color" MRI methodology provides the opportunity to monitor multiple molecular species simultaneously and provides a practical, quantitative imaging framework for the eventual clinical translation of molecular imaging contrast agents.

Botanical pesticides effect from shells of bean’s cashew nut on biological agents of trichoderma sp. and gliocladium sp.

NASA Astrophysics Data System (ADS)

Bande, L. O. S.; Mariadi; Gusnawaty, HS; Nuriadi; Trisulpa, L.; Rahmania

2018-02-01

A shell of cashew nut (Anacardium occidentanle) has contained Cashew Nut Shell Liquid (CNSL) that is used as botanical pesticides. CNSL oil consists of active substance such as anacardat acid, cardol and cardanol. Utilization of the pesticides from shells of cashew nut to control pests and diseases of plants would be affected on biological agents. The objective of this research was to investigate pesticides inhibition on the increase of mycelium Trichoderma sp. and Gliocladium sp. by in vitro method. The tested concentration sample consisted of 0.0% (control), 2.5%, 7.5% and 10.0% in PDA media. The results of this research showed that 2.5% botanical pesticides concentration could minimize mycelium of Trichoderma sp. and Gliocladium sp. 22.73% and 21.04% respectively and also the increase shells of cashew extract could be affected the increase of mycelium inhibition. The extract with 2.5% concentration was the recommended concentration to control of fruit rot diseases and if concentration was 10.0% then its inhibition become 54.98% and 49.35%, respectively. The results proved that uncontrolled utilization of the pesticides could be affected on decrease of Trichoderma sp. and Gliocladium sp. growth.

Phase Transition of Poly(acrylic acid-co-N-isopropylacrylamide) Core-shell Nanogels

NASA Astrophysics Data System (ADS)

Liu, Xiao-bing; Zhou, Jian-feng; Ye, Xiao-dong

2012-08-01

A series of poly(acrylic acid) macromolecular chain transfer agents with different molecular weights were synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and characterized by 1H NMR and gel permeation chromatography. Multiresponsive core-shell nanogels were prepared by dispersion polymerization of N-isopropylacrylamide in water using these poly(potassium acrylate) macro-RAFT agents as the electrosteric stabilizer. The size of the nanogels decreases with the amount of the macro-RAFT agent, indicating that the surface area occupied by per polyelectrolyte group is a critical parameter for stabilizing the nanogels. The volume phase transition and the zeta potentials of the nanogels in aqueous solutions were studied by dynamic light scattering and zetasizer analyzer, respectively.

Multi-Shell Hollow Nanogels with Responsive Shell Permeability

PubMed Central

Schmid, Andreas J.; Dubbert, Janine; Rudov, Andrey A.; Pedersen, Jan Skov; Lindner, Peter; Karg, Matthias; Potemkin, Igor I.; Richtering, Walter

2016-01-01

We report on hollow shell-shell nanogels with two polymer shells that have different volume phase transition temperatures. By means of small angle neutron scattering (SANS) employing contrast variation and molecular dynamics (MD) simulations we show that hollow shell-shell nanocontainers are ideal systems for controlled drug delivery: The temperature responsive swelling of the inner shell controls the uptake and release, while the thermoresponsive swelling of the outer shell controls the size of the void and the colloidal stability. At temperatures between 32 °C < T < 42 °C, the hollow nanocontainers provide a significant void, which is even larger than the initial core size of the template, and they possess a high colloidal stability due to the steric stabilization of the swollen outer shell. Computer simulations showed, that temperature induced switching of the permeability of the inner shell allows for the encapsulation in and release of molecules from the cavity. PMID:26984478

Monitoring Agents for Assisting NASA Engineers with Shuttle Ground Processing

NASA Technical Reports Server (NTRS)

Semmel, Glenn S.; Davis, Steven R.; Leucht, Kurt W.; Rowe, Danil A.; Smith, Kevin E.; Boeloeni, Ladislau

2005-01-01

The Spaceport Processing Systems Branch at NASA Kennedy Space Center has designed, developed, and deployed a rule-based agent to monitor the Space Shuttle's ground processing telemetry stream. The NASA Engineering Shuttle Telemetry Agent increases situational awareness for system and hardware engineers during ground processing of the Shuttle's subsystems. The agent provides autonomous monitoring of the telemetry stream and automatically alerts system engineers when user defined conditions are satisfied. Efficiency and safety are improved through increased automation. Sandia National Labs' Java Expert System Shell is employed as the agent's rule engine. The shell's predicate logic lends itself well to capturing the heuristics and specifying the engineering rules within this domain. The declarative paradigm of the rule-based agent yields a highly modular and scalable design spanning multiple subsystems of the Shuttle. Several hundred monitoring rules have been written thus far with corresponding notifications sent to Shuttle engineers. This chapter discusses the rule-based telemetry agent used for Space Shuttle ground processing. We present the problem domain along with design and development considerations such as information modeling, knowledge capture, and the deployment of the product. We also present ongoing work with other condition monitoring agents.

Prevalence and Antimicrobial Resistance of Enterobacteriaceae in Shell Eggs from Small-Scale Poultry Farms and Farmers' Markets.

PubMed

Kilonzo-Nthenge, A; Nahashon, S N; Godwin, S; Liu, S; Long, D

2016-12-01

Public health concerns over the emergence of antimicrobial resistant bacteria have increased recently. The purpose of this study was to investigate the prevalence of antimicrobial resistant Enterobacteriaceae in shell eggs purchased from small poultry farms and farmers' markets. A total of 504 eggs were pooled to make 252 composite samples, consisting of 2 eggs per composite. The microbial quality of shell eggs was determined by standard quantitative, biochemical, and PCR techniques. Susceptibility to 13 antimicrobial agents was determined by the Kirby-Bauer disk diffusion technique, and results were interpreted based on Clinical and Laboratory Standards Institute values. Shell eggs and egg contents were positive for Escherichia coli (11.9 and 5.2%, respectively), Enterobacter (9.1 and 7.9%), and Serratia (11.5 and 4.8%). Salmonella was isolated from 3.6% of egg shells but not from egg contents. Mean (±SD) Enterobacteriaceae levels (4.4 ± 2.0 log CFU per eggshell) on shell eggs from poultry farms was significantly higher (P ≤ 0.05) than that on shell eggs from farmers' markets (2.1 ± 1.3 log CFU per eggshell). Of the 134 isolates recovered, resistance among isolates from farm and market shell eggs to erythromycin was most common (48.5 and 32.8%, respectively) followed by ampicillin (44.8 and 17.2%), and tetracycline (29.9 and 17.2%). The multiple antibiotic resistance index value for E. coli and Pantoea was 0.62, and that for Salmonella and Klebsiella terrigena was 0.08, indicating that Enterobacteriaceae in shell eggs can be resistant to multiple antimicrobial agents. These data reveal that shell eggs from small poultry farms and farmers' markets can harbor antimicrobial resistant pathogenic and commensal bacteria. Thus, failure to properly handle shell eggs poses a potential health hazard to consumers.

Comparison of in vitro and in vivo acoustic response of a novel 50:50 PLGA contrast agent.

PubMed

Wheatley, Margaret A; Forsberg, Flemming; Oum, Kelleny; Ro, Raymond; El-Sherif, Dalia

2006-11-01

A comparison between in vitro and in vivo experiments conducted to investigate the acoustic properties of a novel, 1.2 microm diameter poly(lactic-co-glycolic acid) (50:50) (PLGA) ultrasound contrast agent, the development of which was described previously by us, is presented. A pulse-echo setup was used to determine enhancement in vitro. Additional in vitro studies further characterized the hollow microcapsules, including resonance frequency from attenuation measurements (from 2.25 to 15 MHz) and temperature effects (25 degrees C vs. 37 degrees C). In vivo, four rabbits received intravenous injections of the agent (dose range: 0.005-0.13 ml/kg). Quantitative in vivo dose-responses were calculated off-line using spectral power analysis of audio Doppler signals acquired from a custom-made 10 MHz cuff transducer placed around the surgically exposed distal aorta. This frequency was chosen since the very shallow scanning depths encountered in rabbits, in particular for the cuff transducer placed directly around the vessel, necessitates the use of high frequency imaging devices with sufficient spatial resolution to enable meaningful measurements. For qualitative assessments, two rabbits were imaged pre- and post-contrast administration (dose: 0.1 ml/kg) in power Doppler mode. Significant acoustic enhancements (up to 24 dB) were reported both in vitro and in vivo. Moreover, the rabbits did not show any adverse side effects from multiple injections (>20) of the agent. Measured in vitro resonance frequency between 3.09 and 3.49 MHz was lower than predicted for a similar sized free bubble, potentially due to capsule wall structure. Minimal loss of signal (approximately 4 dB) was observed at 25 degrees C over 20 min of insonation at 5 MHz but at 37 degrees C the signal dropped close to base line within the first 5 min. This temperature sensitivity could be due to loss of capsule integrity (and hence loss of gas). Potential causes include increased hydrolysis or polymer softening and increased water uptake by the shell at temperatures closer to the glass transition temperature (T(g)).

Do I stand out or blend in? Conspicuousness awareness and consistent behavioural differences in hermit crabs

PubMed Central

Briffa, Mark; Twyman, Claire

2011-01-01

Animals titrate their behaviour against the level of risk and an individual's conspicuousness should influence decisions such as when to flee and for how long to hide. Conspicuousness will vary with variation in substrate colour. Since hermit crabs frequently change the shells they occupy, shell colour will also influence conspicuousness and to be aware of their conspicuousness would require information on both of these factors to be integrated. Reduced boldness in high-contrast shell and substrate combinations compared with situations of low contrast indicates that hermit crabs are aware of current conspicuousness. Differences between individuals remained consistent across conspicuousness levels indicating the presence of animal personalities. PMID:20980296

Do I stand out or blend in? Conspicuousness awareness and consistent behavioural differences in hermit crabs.

PubMed

Briffa, Mark; Twyman, Claire

2011-06-23

Animals titrate their behaviour against the level of risk and an individual's conspicuousness should influence decisions such as when to flee and for how long to hide. Conspicuousness will vary with variation in substrate colour. Since hermit crabs frequently change the shells they occupy, shell colour will also influence conspicuousness and to be aware of their conspicuousness would require information on both of these factors to be integrated. Reduced boldness in high-contrast shell and substrate combinations compared with situations of low contrast indicates that hermit crabs are aware of current conspicuousness. Differences between individuals remained consistent across conspicuousness levels indicating the presence of animal personalities.

Stability of echogenic liposomes as a blood pool ultrasound contrast agent in a physiologic flow phantom

PubMed Central

Radhakrishnan, Kirthi; Haworth, Kevin J.; Huang, Shao-Ling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

2016-01-01

Echogenic liposomes (ELIP) are multifunctional ultrasound contrast agents (UCAs) with a lipid shell encapsulating both air and an aqueous core. ELIP are being developed for molecular imaging and image-guided therapeutic delivery. Stability of the echogenicity of ELIP in physiologic conditions is crucial to their successful translation to clinical use. In this study we determined the effects of the surrounding media’s dissolved air concentration, temperature transition and hydrodynamic pressure on the echogenicity of a chemically modified formulation of ELIP to promote stability and echogenicity. ELIP samples were diluted in porcine plasma or whole blood and pumped through a pulsatile flow system with adjustable hydrodynamic pressures and temperature. B-mode images were acquired using a clinical diagnostic scanner every 5 s for a total duration of 75 s. Echogenicity in porcine plasma was assessed as a function of total dissolved gas saturation. ELIP were added to plasma at room temperature (22 °C) or body temperature (37 °C) and pumped through a system maintained at 22 °C or 37 °C to study the effect of temperature transitions on ELIP echogenicity. Echogenicity at normotensive (120/80 mmHg) and hypertensive pressures (145/90 mmHg) was measured. ELIP were echogenic in plasma and whole blood at body temperature under normotensive to hypertensive pressures. Warming of samples from room temperature to body temperature did not alter echogenicity. However, in plasma cooled rapidly from body temperature to room temperature or in degassed plasma, ELIP lost echogenicity within 20 s at 120/80 mmHg. The stability of echogenicity of a modified ELIP formulation was determined in vitro at body temperature, physiologic gas concentration and throughout the physiologic pressure range. However, proper care should be taken to ensure that ELIP are not cooled rapidly from body temperature to room temperature as they will lose their acoustic properties. Further in vivo investigations will be needed to evaluate the optimal usage of ELIP as blood pool contrast agents. PMID:22929652

Near-Infrared-Light-Responsive Magnetic DNA Microgels for Photon- and Magneto-Manipulated Cancer Therapy.

PubMed

Wang, Yitong; Wang, Ling; Yan, Miaomiao; Dong, Shuli; Hao, Jingcheng

2017-08-30

Functional DNA molecules have been introduced into polymer-based nanocarrier systems to incorporate chemotherapy drugs for cancer therapy. Here is the first report of dual-responsive microgels composed of a core of Au nanorods and a shell of magnetic ionic liquid and DNA moieties in the cross-linking network simultaneously, as effective drug delivery vectors. TEM images indicated a magnetic polymer shell has an analogous "doughnut" shape which loosely surround the AuNRs core. When irradiated with a near-infrared-light (near-IR) laser, Au nanorods are the motors which convert the light to heat, leading to the release of the encapsulated payloads with high controllability. DNA acts not only as a cross-linker agent, but also as a gatekeeper to regulate the release of drugs. The internalization study and MTT assay confirm that these core-shell DNA microgels are excellent candidates which can enhance the cytotoxicity of cancer cells controlled by near-IR laser and shield the high toxicity of chemotherapeutic agents to improve the killing efficacy of chemotherapeutic agents efficiently in due course.

High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

PubMed Central

Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

2017-01-01

Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging. PMID:28091590

High performance magneto-fluorescent nanoparticles assembled from terbium and gadolinium 1,3-diketones

NASA Astrophysics Data System (ADS)

Zairov, Rustem; Mustafina, Asiya; Shamsutdinova, Nataliya; Nizameev, Irek; Moreira, Beatriz; Sudakova, Svetlana; Podyachev, Sergey; Fattakhova, Alfia; Safina, Gulnara; Lundstrom, Ingemar; Gubaidullin, Aidar; Vomiero, Alberto

2017-01-01

Polyelectrolyte-coated nanoparticles consisting of terbium and gadolinium complexes with calix[4]arene tetra-diketone ligand were first synthesized. The antenna effect of the ligand on Tb(III) green luminescence and the presence of water molecules in the coordination sphere of Gd(III) bring strong luminescent and magnetic performance to the core-shell nanoparticles. The size and the core-shell morphology of the colloids were studied using transmission electron microscopy and dynamic light scattering. The correlation between photophysical and magnetic properties of the nanoparticles and their core composition was highlighted. The core composition was optimized for the longitudinal relaxivity to be greater than that of the commercial magnetic resonance imaging (MRI) contrast agents together with high level of Tb(III)-centered luminescence. The tuning of both magnetic and luminescent output of nanoparticles is obtained via the simple variation of lanthanide chelates concentrations in the initial synthetic solution. The exposure of the pheochromocytoma 12 (PC 12) tumor cells and periphery human blood lymphocytes to nanoparticles results in negligible effect on cell viability, decreased platelet aggregation and bright coloring, indicating the nanoparticles as promising candidates for dual magneto-fluorescent bioimaging.

Gadolinium-Based Contrast Agents for MR Cancer Imaging

PubMed Central

Zhou, Zhuxian; Lu, Zheng-Rong

2013-01-01

Magnetic resonance imaging (MRI) is a clinical imaging modality effective for anatomical and functional imaging of diseased soft tissues, including solid tumors. MRI contrast agents have been routinely used for detecting tumor at an early stage. Gadolinium based contrast agents are the most commonly used contrast agents in clinical MRI. There have been significant efforts to design and develop novel Gd(III) contrast agents with high relaxivity, low toxicity and specific tumor binding. The relaxivity of the Gd(III) contrast agents can be increased by proper chemical modification. The toxicity of Gd(III) contrast agents can be reduced by increasing the agents’ thermodynamic and kinetic stability, as well as optimizing their pharmacokinetic properties. The increasing knowledge in the field of cancer genomics and biology provides an opportunity for designing tumor-specific contrast agents. Various new Gd(III) chelates have been designed and evaluated in animal models for more effective cancer MRI. This review outlines the design and development, physicochemical properties, and in vivo properties of several classes of Gd(III)-based MR contrast agents for tumor imaging. PMID:23047730

Microcapsules: Reverse Sonoporation and Long-lasting, Safe Contrast

NASA Astrophysics Data System (ADS)

Wrenn, Steven; Dicker, Stephen; Small, Eleanor; Maghnouj, Abdelouahid; Hahn, Stephan A.; Mleczko, Michał; Hensel, Karin; Schmitz, Georg

We present a novel vehicle designed to serve the dual roles of enhanced ultrasound contrast and ultrasound-triggered drug delivery. The vehicle is comprised of a microcapsule that is filled with water in whose aqueous core a population of freely floating, phospholipid-coated microbubbles is suspended. At ultrasound intensities below the inertial cavitation threshold of the microbubbles, the microbubbles provide enhanced ultrasound contrast. The measured contrast is comparable in strength with SonoVue®. Encapsulation of microbubbles within microcapsules putatively eliminates - or at least significantly slows - dissolution of gas in the bulk aqueous medium, thereby avoiding disappearance of microbubbles that would otherwise occur due to pressure-induced gas diffusion across the surfactant monolayer coating the microbubble-water interface. Results suggest that our vehicle might provide longer lasting contrast in a clinical setting. We demonstrate that encapsulation of the microbubbles within microcapsules causes at least a doubling of the ultrasound intensity necessary to induce inertial cavitation. Moreover, no cell death was observed when cells were insonified in the presence of microbubble-containing microcapsules, whereas appreciable cell death occurs with unencapsulated microbubbles. These results point toward a potential safety benefit during ultrasound contrast imaging by using encapsulated microbubbles. Studies are underway to investigate the feasibility of ultrasound-triggered release of drug from the microcapsules, owing to inertial- or stable-cavitation, or both. Whereas leakage from polymeric microcapsule shells, such as poly(lactic acid), seemingly requires shell rupture and is exceedingly difficult to achieve, leakage across a lipid bilayer microcapsule shells appears feasible. Leakage across a bilayer shell has the additional benefit that the leakage mechanism can be tuned via phase behavior (liquid-ordered versus liquid-disordered) and cavitation mechanism (stable versus inertial).

Hydrophobic-Core Microcapsules and Their Formation

NASA Technical Reports Server (NTRS)

Buhrow, Jerry W. (Inventor); Li, Wenyan (Inventor); Jolley, Scott T. (Inventor); Calle, Luz M. (Inventor)

2016-01-01

Hydrophobic-core microcapsules and methods of their formation are provided. A hydrophobic-core microcapsule may include a shell that encapsulates a hydrophobic substance with a core substance, such as dye, corrosion indicator, corrosion inhibitor, and/or healing agent, dissolved or dispersed therein. The hydrophobic-core microcapsules may be formed from an emulsion having hydrophobic-phase droplets, e.g., containing the core substance and shell-forming compound, dispersed in a hydrophilic phase. The shells of the microcapsules may be capable of being broken down in response to being contacted by an alkali, e.g., produced during corrosion, contacting the shell.

Integrin Targeted MR Imaging

PubMed Central

Tan, Mingqian; Lu, Zheng-Rong

2011-01-01

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 T1, T2, 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. PMID:21547154

Development of Lipid-Based Nanoparticles for In Vivo Targeted Delivery of Imaging Agents into Breast Cancer Cells

DTIC Science & Technology

2009-10-01

nanoparticles size of 8 nm; found out that shell loaded image is much more effective than core loaded one. We have prepared a number of lipid nanoparticles ...strategies: lipid - conjugated fluorochrome was introduced into either core or shell lipids of the nanoparticles . Pyro- CE-OA that contains cholesterol... lipids either in the core or in the shell . We have conjugated the nanoparticles with the integrin ligands. We have showed

Intravascular forward-looking ultrasound transducers for microbubble-mediated sonothrombolysis.

PubMed

Kim, Jinwook; Lindsey, Brooks D; Chang, Wei-Yi; Dai, Xuming; Stavas, Joseph M; Dayton, Paul A; Jiang, Xiaoning

2017-06-14

Effective removal or dissolution of large blood clots remains a challenge in clinical treatment of acute thrombo-occlusive diseases. Here we report the development of an intravascular microbubble-mediated sonothrombolysis device for improving thrombolytic rate and thus minimizing the required dose of thrombolytic drugs. We hypothesize that a sub-megahertz, forward-looking ultrasound transducer with an integrated microbubble injection tube is more advantageous for efficient thrombolysis by enhancing cavitation-induced microstreaming than the conventional high-frequency, side-looking, catheter-mounted transducers. We developed custom miniaturized transducers and demonstrated that these transducers are able to generate sufficient pressure to induce cavitation of lipid-shelled microbubble contrast agents. Our technology demonstrates a thrombolysis rate of 0.7 ± 0.15 percent mass loss/min in vitro without any use of thrombolytic drugs.

Direct Observation of the Growth of Au-Pd Core-Shell Nanoparticles Using in situ Low-Dose Liquid Cell STEM imaging

DOE PAGES

Bhattarai, Nabraj; Prozorov, Tanya

2016-07-25

Bimetallic core-shell nanoparticles are widely used as catalysts in several industrial reactions, with core-shell structures permitting facile surface modification and allowing increased stability and durability, and cost-effectiveness of the catalysts. We report, for the first time, on observing the early stages of the formation of Au-Pd core-shell bimetallic nanoparticles via the seed-mediated growth in the presence of reducing agent, while employing the low-dose scanning transmission electron microscopy imaging with the fluid cell in situ. Use of the continuous flow in situ fluid cell platform allows for delivery of reagent solutions and generation of near-native reaction environment in the reaction chamber,more » and permits direct visualization of the early stages of formation of Au-Pd core-shell structures at low dose rate (0.1 e -/(Å 2s)) in the presence of ascorbic acid. No core-shell structures were detected in the absence of reducing agent at the electron dose of 32.6 e -/Å 2. While the core-shell structures formed in situ under the low-dose imaging closely resemble those obtained in solution synthesis, the reaction kinetics in the fluid cell is affected by the radiolysis of liquid reagents induced by electron beam, altering the rate-determining reaction steps. The enhanced reduction of Pd ions leads to initial rapid growth of the nascent Pd shell along the <111> direction at the Au interface, followed by a slower rearrangement of the outer Pd layer. The latter becomes the rate-determining step in the in situ reaction and appears to follow the oriented attachment-like movement to yield a remodeled, compact and stable Au-Pd core-shell nanostructure. Our findings highlight the differences between the two reaction pathways and aid in understanding the mechanism of formation of the core-shell nanostructure in situ.« less

Nanodiamond-Manganese dual mode MRI contrast agents for enhanced liver tumor detection.

PubMed

Hou, Weixin; Toh, Tan Boon; Abdullah, Lissa Nurrul; Yvonne, Tay Wei Zheng; Lee, Kuan J; Guenther, Ilonka; Chow, Edward Kai-Hua

2017-04-01

Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl 2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn 2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging

NASA Astrophysics Data System (ADS)

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-01

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×109 MBs ml-1 using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C3F8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd3+ ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T1-weighted turbo-spin-echo sequence MR imaging. Heavy T2*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2- and T2*-weighted MR images. The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35 s-1mM-1, respectively, indicating that the MBs represent a positive contrast agent in T1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from ICH, and can monitor the focused ultrasound brain drug delivery process.

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood-brain barrier opening and concurrent MR and ultrasound imaging.

PubMed

Liao, Ai-Ho; Liu, Hao-Li; Su, Chia-Hao; Hua, Mu-Yi; Yang, Hung-Wei; Weng, Yu-Ting; Hsu, Po-Hung; Huang, Sheng-Min; Wu, Shih-Yen; Wang, Hsin-Ell; Yen, Tzu-Chen; Li, Pai-Chi

2012-05-07

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from ICH, and can monitor the focused ultrasound brain drug delivery process.

Contrast enhanced spectroscopic optical coherence tomography

NASA Technical Reports Server (NTRS)

Xu, Chenyang (Inventor); Boppart, Stephen A. (Inventor)

2010-01-01

A method of forming an image of a sample includes performing SOCT on a sample. The sample may include a contrast agent, which may include an absorbing agent and/or a scattering agent. A method of forming an image of tissue may include selecting a contrast agent, delivering the contrast agent to the tissue, acquiring SOCT data from the tissue, and converting the SOCT data into an image. The contributions to the SOCT data of an absorbing agent and a scattering agent in a sample may be quantified separately.

First application of core-shell Ag@Ni magnetic nanocatalyst for transfer hydrogenation reactions of aromatic nitro and carbonyl compounds

EPA Science Inventory

A magnetic separable core-shell Ag@Ni nanocatalyst was prepared by a simple one-pot synthetic route using oleylamine both as solvent and reducing agent and triphenylphosphine as surfactant. The synthesized nanoparticles were characterized by several techniques such as X-ray diffr...

31 CFR 1020.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2012 CFR

2012-07-01

... process. 1020.630 Section 1020.630 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULE FOR BANKS Special Standards... foreign shell banks; records concerning owners of foreign banks and agents for service of legal process...

31 CFR 1020.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2014 CFR

2014-07-01

... process. 1020.630 Section 1020.630 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULE FOR BANKS Special Standards... foreign shell banks; records concerning owners of foreign banks and agents for service of legal process...

31 CFR 1020.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2013 CFR

2013-07-01

... process. 1020.630 Section 1020.630 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULE FOR BANKS Special Standards... foreign shell banks; records concerning owners of foreign banks and agents for service of legal process...

Selection of pecan shell based activated carbons for removal of organic and inorganic impurities from simulated well-water

USDA-ARS?s Scientific Manuscript database

Activated carbons are a byproduct from pyrolysis and have value as a purifying agent. The effectiveness of activated carbons is dependent on feedstock selection and pyrolysis conditions that modify its surface properties. Therefore, pecan shell-based activated carbons (PSACs) were prepared by soakin...

31 CFR 1021.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2014 CFR

2014-07-01

... for foreign shell banks; records concerning owners of foreign banks and agents for service of legal... (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR CASINOS AND CARD CLUBS Special Standards of Diligence; Prohibitions; and Special Measures for Casinos and Card Clubs § 1021.630...

31 CFR 1021.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2013 CFR

2013-07-01

... for foreign shell banks; records concerning owners of foreign banks and agents for service of legal... (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR CASINOS AND CARD CLUBS Special Standards of Diligence; Prohibitions; and Special Measures for Casinos and Card Clubs § 1021.630...

31 CFR 1021.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2011 CFR

2011-07-01

... for foreign shell banks; records concerning owners of foreign banks and agents for service of legal... (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR CASINOS AND CARD CLUBS Special Standards of Diligence; Prohibitions; and Special Measures for Casinos and Card Clubs § 1021.630...

31 CFR 1021.630 - Prohibition on correspondent accounts for foreign shell banks; records concerning owners of...

Code of Federal Regulations, 2012 CFR

2012-07-01

... for foreign shell banks; records concerning owners of foreign banks and agents for service of legal... (Continued) FINANCIAL CRIMES ENFORCEMENT NETWORK, DEPARTMENT OF THE TREASURY RULES FOR CASINOS AND CARD CLUBS Special Standards of Diligence; Prohibitions; and Special Measures for Casinos and Card Clubs § 1021.630...

Fabrication and characterization of optical sensors using metallic core-shell thin film nanoislands for ozone detection

NASA Astrophysics Data System (ADS)

Addanki, Satish; Nedumaran, D.

2017-07-01

Core-Shell nanostructures play a vital role in the sensor field owing to their performance improvements in sensing characteristics and well-established synthesis procedures. These nanostructures can be ingeniously tuned to achieve tailored properties for a particular application of interest. In this work, an Ag-Au core-shell thin film nanoislands with APTMS (3-Aminopropyl trimethoxysilane) and PVA (Polyvinyl alcohol) binding agents was modeled, synthesized and characterized. The simulation results were used to fabricate the sensor through chemical route. The results of this study confirmed that the APTMS based Ag-Au core-shell thin film nanoislands offered a better performance over the PVA based Ag-Au core-shell thin film nanoislands. Also, the APTMS based Ag-Au core-shell thin film nanoislands exhibited better sensitivity towards ozone sensing over the other types, viz., APTMS/PVA based Au-Ag core-shell and standalone Au/Ag thin film nanoislands.

Blood-pool contrast agent for pre-clinical computed tomography

NASA Astrophysics Data System (ADS)

Cruje, Charmainne; Tse, Justin J.; Holdsworth, David W.; Gillies, Elizabeth R.; Drangova, Maria

2017-03-01

Advances in nanotechnology have led to the development of blood-pool contrast agents for micro-computed tomography (micro-CT). Although long-circulating nanoparticle-based agents exist for micro-CT, they are predominantly based on iodine, which has a low atomic number. Micro-CT contrast increases when using elements with higher atomic numbers (i.e. lanthanides), particularly at higher energies. The purpose of our work was to develop and evaluate a lanthanide-based blood-pool contrast agent that is suitable for in vivo micro-CT. We synthesized a contrast agent in the form of polymer-encapsulated Gd nanoparticles and evaluated its stability in vitro. The synthesized nanoparticles were shown to have an average diameter of 127 +/- 6 nm, with good size dispersity. Particle size distribution - evaluated by dynamic light scattering over the period of two days - demonstrated no change in size of the contrast agent in water and saline. Additionally, our contrast agent was stable in a mouse serum mimic for up to 30 minutes. CT images of the synthesized contrast agent (containing 27 mg/mL of Gd) demonstrated an attenuation of over 1000 Hounsfield Units. This approach to synthesizing a Gd-based blood-pool contrast agent promises to enhance the capabilities of micro-CT imaging.

Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

PubMed Central

Cormode, David P.; Naha, Pratap C.; Fayad, Zahi A.

2014-01-01

Computed tomography (CT) is an X-ray based whole body imaging technique that is widely used in medicine. Clinically approved contrast agents for CT are iodinated small molecules or barium suspensions. Over the past seven years there has been a great increase in the development of nanoparticles as CT contrast agents. Nanoparticles have several advantages over small molecule CT contrast agents, such as long blood-pool residence times, and the potential for cell tracking and targeted imaging applications. Furthermore, there is a need for novel CT contrast agents, due to the growing population of renally impaired patients and patients hypersensitive to iodinated contrast. Micelles and lipoproteins, a micelle-related class of nanoparticle, have notably been adapted as CT contrast agents. In this review we discuss the principles of CT image formation and the generation of CT contrast. We discuss the progress in developing non-targeted, targeted and cell tracking nanoparticle CT contrast agents. We feature agents based on micelles and used in conjunction with spectral CT. The large contrast agent doses needed will necessitate careful toxicology studies prior to clinical translation. However, the field has seen tremendous advances in the past decade and we expect many more advances to come in the next decade. PMID:24470293

Biocompatible KMnF3 nanoparticular contrast agent with proper plasma retention time for in vivo magnetic resonance imaging.

PubMed

Liu, Zhi-jun; Song, Xiao-xia; Xu, Xian-zhu; Tang, Qun

2014-04-18

Nanoparticular MRI contrast agents are rapidly becoming suitable for use in clinical diagnosis. An ideal nanoparticular contrast agent should be endowed with high relaxivity, biocompatibility, proper plasma retention time, and tissue-specific or tumor-targeting imaging. Herein we introduce PEGylated KMnF3 nanoparticles as a new type of T1 contrast agent. Studies showed that the nanoparticular contrast agent revealed high bio-stability with bovine serum albumin in PBS buffer solution, and presented excellent biocompatibility (low cytotoxicity, undetectable hemolysis and hemagglutination). Meanwhile the new contrast agent possessed proper plasma retention time (circulation half-life t1/2 is approximately 2 h) in the body of the administrated mice. It can be delivered into brain vessels and maintained there for hours, and is mostly cleared from the body within 48 h, as demonstrated by time-resolved MRI and Mn-biodistribution analysis. Those distinguishing features make it suitable to obtain contrast-enhanced brain magnetic resonance angiography. Moreover, through the process of passive targeting delivery, the T1 contrast agent clearly illuminates a brain tumor (glioma) with high contrast image and defined shape. This study demonstrates that PEGylated KMnF3 nanoparticles represent a promising biocompatible vascular contrast agent for magnetic resonance angiography and can potentially be further developed into an active targeted tumor MRI contrast agent.

Influence of capsule shell composition on the performance indicators of hypromellose capsule in comparison to hard gelatin capsules.

PubMed

Al-Tabakha, Moawia M; Arida, Adi Issam; Fahelelbom, Khairi M S; Sadek, Bassem; Saeed, Dima Ahmed; Abu Jarad, Rami A; Jawadi, Jeevani

2015-01-01

The purpose of this study was to assess the in vitro performances of "vegetable" capsules in comparison to hard gelatin capsules in terms of shell weight variation, reaction to different humidity conditions, resistance to stress in the absence of moisture, powder leakage, disintegration and dissolution. Two types of capsules made of HPMC produced with (Capsule 2) or without (Capsule 3) a gelling agent and hard gelatin capsules (Capsule 1) were assessed. Shell weight variability was relatively low for all tested capsules shells. Although Capsule 1 had the highest moisture content under different humidity conditions, all capsule types were unable to protect the encapsulated hygroscopic polyvinylpyrrolidone (PVP) powder from surrounding humidity. The initial disintegration for all Capsule 1 occurred within 3 min, but for other types of capsules within 6 min (n = 18). Dissolution of acetaminophen was better when the deionized water (DIW) temperature increased from 32 to 42 °C in case of Capsule 1, but the effect of temperature was not significant for the other types of capsules. Acetaminphen dissolution from Capsule 1 was the fastest (i.e. >90% in 10 min) and independent of the media pH or contents unlike Capsule 2 which was influenced by the pH and dissolution medium contents. It is feasible to use hypromellose capsules shells with or without gelling agent for new lines of pharmaceutical products, however, there is a window for capsule shells manufacturing companies to improve the dissolution of their hypromellose capsules to match the conventional gelatin capsule shells and eventually replace them.

Functionalized magnetic iron oxide/alginate core-shell nanoparticles for targeting hyperthermia

PubMed Central

Liao, Shih-Hsiang; Liu, Chia-Hung; Bastakoti, Bishnu Prasad; Suzuki, Norihiro; Chang, Yung; Yamauchi, Yusuke; Lin, Feng-Huei; Wu, Kevin C-W

2015-01-01

Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe3O4) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe3O4@Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe3O4@Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems. PMID:26005343

An inorganic capping strategy for the seeded growth of versatile bimetallic nanostructures

DOE PAGES

Pei, Yuchen; Maligal-Ganesh, Raghu V.; Xiao, Chaoxian; ...

2015-09-11

Metal nanostructures have attracted great attention in various fields due to their tunable properties through precisely tailored sizes, compositions and structures. Using mesoporous silica (mSiO 2) as the inorganic capping agent and encapsulated Pt nanoparticles as the seeds, we developed a robust seeded growth method to prepare uniform bimetallic nanoparticles encapsulated in mesoporous silica shells (PtM@mSiO 2, M = Pd, Rh, Ni and Cu). Unexpectedly, we found that the inorganic silica shell is able to accommodate an eight-fold volume increase in the metallic core by reducing its thickness. The bimetallic nanoparticles encapsulated in mesoporous silica shells showed enhanced catalytic propertiesmore » and thermal stabilities compared with those prepared with organic capping agents. As a result, this inorganic capping strategy could find a broad application in the synthesis of versatile bimetallic nanostructures with exceptional structural control and enhanced catalytic properties.« less

Functionalized magnetic iron oxide/alginate core-shell nanoparticles for targeting hyperthermia.

PubMed

Liao, Shih-Hsiang; Liu, Chia-Hung; Bastakoti, Bishnu Prasad; Suzuki, Norihiro; Chang, Yung; Yamauchi, Yusuke; Lin, Feng-Huei; Wu, Kevin C-W

2015-01-01

Hyperthermia is one of the promising treatments for cancer therapy. However, the development of a magnetic fluid agent that can selectively target a tumor and efficiently elevate temperature while exhibiting excellent biocompatibility still remains challenging. Here a new core-shell nanostructure consisting of inorganic iron oxide (Fe3O4) nanoparticles as the core, organic alginate as the shell, and cell-targeting ligands (ie, D-galactosamine) decorated on the outer surface (denoted as Fe3O4@Alg-GA nanoparticles) was prepared using a combination of a pre-gel method and coprecipitation in aqueous solution. After treatment with an AC magnetic field, the results indicate that Fe3O4@Alg-GA nanoparticles had excellent hyperthermic efficacy in a human hepatocellular carcinoma cell line (HepG2) owing to enhanced cellular uptake, and show great potential as therapeutic agents for future in vivo drug delivery systems.

Synthesis and characterization of silver-copper core-shell nanoparticles using polyol method for antimicrobial agent

NASA Astrophysics Data System (ADS)

Hikmah, N.; Idrus, N. F.; Jai, J.; Hadi, A.

2016-06-01

Silver and copper nanoparticles are well-known as the good antimicrobial agent. The nano-size of particles influences in enhancing the antimicrobial activity. This paper discusses the effect of molarity on the microstructure and morphology of silver-copper core-shell nanoparticles prepared by a polyol method. In this study, silver-copper nanoparticles are synthesized through the green approach of polyol method using ethylene glycol (EG) as green solvent and reductant, and polyoxyethylene-(80)-sorbitan monooleate (Tween 80) as a nontoxic stabilizer. The phase and morphology of silver-copper nanoparticles are characterized by X-ray diffraction (XRD) and Field emission scanning electron microscope (FESEM) and Transmission electron microscope (TEM). The results XRD confirm the pure crystalline of silver and copper nanoparticles with face-centered cubic (FCC) structure. FESEM and TEM analysis confirm the existence of Ag and Cu nanoparticles in core-shell shape.

Designing Mixed Detergent Micelles for Uniform Neutron Contrast

DOE PAGES

Oliver, Ryan C.; Pingali, Sai Venkatesh; Urban, Volker S.

2017-09-29

Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural datamore » of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.« less

Designing Mixed Detergent Micelles for Uniform Neutron Contrast

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

Oliver, Ryan C.; Pingali, Sai Venkatesh; Urban, Volker S.

Micelle-forming detergents provide an amphipathic environment that mimics lipid bilayers and are important tools used to solubilize and stabilize membrane proteins in solution for in vitro structural investigations. Small-angle neutron scattering (SANS) performed at the neutron contrast match point of detergent molecules allows observing the scattering signal from membrane proteins unobstructed by contributions from the detergent. However, we show here that even for a perfectly average-contrast matched detergent there arises significant core-shell scattering from the contrast difference between aliphatic detergent tails and hydrophilic head groups. This residual signal at the average detergent contrast match point interferes with interpreting structural datamore » of membrane proteins. This complication is often made worse by the presence of excess empty (protein-free) micelles. Here, we present an approach for the rational design of mixed micelles containing a deuterated detergent analog, which eliminates neutron contrast between core and shell, and allows the micelle scattering to be fully contrast matched to unambiguously resolve membrane protein structure using solution SANS.« less

Microcapsule and methods of making and using microcapsules

DOEpatents

Okawa, David C.; Pastine, Stefan J.; Zettl, Alexander K.; Frechet, Jean M.J.

2014-09-02

An embodiment of a microcapsule includes a shell surrounding a space, a liquid within the shell, and a light absorbing material within the liquid. An embodiment of a method of making microcapsules includes forming a mixture of a light absorbing material and an organic solution. An emulsion of the mixture and an aqueous solution is then formed. A polymerization agent is added to the emulsion, which causes microcapsules to be formed. Each microcapsule includes a shell surrounding a space, a liquid within the shell, and light absorbing material within the liquid. An embodiment of a method of using microcapsules includes providing phototriggerable microcapsules within a bulk material. Each of the phototriggerable microcapsules includes a shell surrounding a space, a chemically reactive material within the shell, and a light absorbing material within the shell. At least some of the phototriggerable microcapsules are exposed to light, which causes the chemically reactive material to release from the shell and to come into contact with bulk material.

Assessment of MRI Contrast Agent Kinetics via Retro-Orbital Injection in Mice: Comparison with Tail Vein Injection.

PubMed

Wang, Fang; Nojima, Masanori; Inoue, Yusuke; Ohtomo, Kuni; Kiryu, Shigeru

2015-01-01

It is not known whether administration of contrast agent via retro-orbital injection or the tail vein route affects the efficiency of dynamic contrast-enhanced magnetic resonance imaging (MRI). Therefore, we compared the effects of retro-orbital and tail vein injection on the kinetics of the contrast agent used for MRI in mice. The same group of nine healthy female mice received contrast agent via either route. An extracellular contrast agent was infused via the tail vein and retro-orbital vein, in random order. Dynamic contrast-enhanced MRI was performed before and after administering the contrast agent. The contrast effects in the liver, kidney, lung, and myocardium were assessed. The average total times of venous puncture and mounting of the injection system were about 10 and 4 min for the tail vein and retro-orbital route, respectively. For all organs assessed, the maximum contrast ratio occurred 30 s after administration and the time course of the contrast ratio was similar with either routes. For each organ, the contrast ratios correlated strongly; the contrast ratios were similar. The retro-orbital and tail vein routes afforded similar results in terms of the kinetics of the contrast agent. The retro-orbital route can be used as a simple efficient alternative to tail vein injection for dynamic contrast-enhanced MRI of mice.

Eco-friendly microwave-assisted green and rapid synthesis of well-stabilized gold and core-shell silver-gold nanoparticles.

PubMed

El-Naggar, Mehrez E; Shaheen, Tharwat I; Fouda, Moustafa M G; Hebeish, Ali A

2016-01-20

Herein, we present a new approach for the synthesis of gold nanoparticles (AuNPs) individually and as bimetallic core-shell nanoparticles (AgNPs-AuNPs). The novelty of the approach is further maximized by using curdlan (CRD) biopolymer to perform the dual role of reducing and capping agents and microwave-aided technology for affecting the said nanoparticles with varying concentrations in addition to those affected by precursor concentrations. Thus, for preparation of AuNPs, curdlan was solubilized in alkali solution followed by an addition of tetrachloroauric acid (HAuCl4). The curdlan solution containing HAuCl4 was then subjected to microwave radiation for up to 10 min. The optimum conditions obtained with the synthesis of AuNPs were employed for preparation of core-shell silver-gold nanoparticles by replacing definite portion of HAuCl4 with an equivalent portion of silver nitrate (AgNO3). The portion of AgNO3 was added initially and allowed to be reduced by virtue of the dual role of curdlan under microwave radiation. The corresponding portion of HAuCl4 was then added and allowed to complete the reaction. Characterization of AuNPs and AgNPs-AuNPs core-shell were made using UV-vis spectra, TEM, FTIR, XRD, zeta potential, and AFM analysis. Accordingly, strong peaks of the colloidal particles show surface plasmon resonance (SPR) at maximum wavelength of 540 nm, proving the formation of well-stabilized gold nanoparticles. TEM investigations reveal that the major size of AuNPs formed at different Au(+3)concentration lie below 20 nm with narrow size distribution. Whilst, the SPR bands of AgNPs-AuNPs core-shell differ than those obtained from original AgNPs (420 nm) and AuNPs (540 nm). Such shifting due to SPR of Au nanoshell deposited onto AgNPs core was significantly affected by the variation of bimetallic ratios applied. TEM micrographs show variation in contrast between dark silver core and the lighter gold shell. Increasing the ratio of silver ions leads to significant decrease in zeta potential of the formed bimetallic core-shell. FT-IR discloses the interaction between CRD and metal nanoparticles, which could be the question of reducing and stabilizing metal and bimetallic nanoparticles. XRD patterns assume insufficient difference for the AuNPs and AgNPs-AuNPs core-shell samples due to close lattice constants of Ag and Au. Based on AFM, AuNPs and AgNPs-AuNPs core-shell exhibited good monodispersity with spherical particles possessing different sizes in the studied samples. The average sizes of both metal and bimetallic core-shell were found to be 52 and 45 nm, respectively. Copyright © 2015 Elsevier Ltd. All rights reserved.

Micro- and nanobubbles: a versatile non-viral platform for gene delivery.

PubMed

Cavalli, Roberta; Bisazza, Agnese; Lembo, David

2013-11-18

Micro- and nanobubbles provide a promising non-viral strategy for ultrasound mediated gene delivery. Microbubbles are spherical gas-filled structures with a mean diameter of 1-8 μm, characterised by their core-shell composition and their ability to circulate in the bloodstream following intravenous injection. They undergo volumetric oscillations or acoustic cavitation when insonified by ultrasound and, most importantly, they are able to resonate at diagnostic frequencies. It is due to this behaviour that microbubbles are currently being used as ultrasound contrast agents, but their use in therapeutics is still under investigation. For example, microbubbles could play a role in enhancing gene delivery to cells: when combined with clinical ultrasound exposure, microbubbles are able to favour gene entry into cells by cavitation. Two different delivery strategies have been used to date: DNA can be co-administered with the microbubbles (i.e. the contrast agent) or 'loaded' in purposed-built bubble systems - indeed a number of different technological approaches have been proposed to associate genes within microbubble structures. Nanobubbles, bubbles with sizes in the nanometre order of magnitude, have also been developed with the aim of obtaining more efficient gene delivery systems. Their small sizes allow the possibility of extravasation from blood vessels into the surrounding tissues and ultrasound-targeted site-specific release with minimal invasiveness. In contrast, microbubbles, due to their larger sizes, are unable to extravasate, thus and their targeting capacity is limited to specific antigens present within the vascular lumen. This review provides an overview of the use of microbubbles as gene delivery systems, with a specific focus on recent research into the development of nanosystems. In particular, ultrasound delivery mechanisms, formulation parameters, gene-loading approaches and the advantages of nanometric systems will be described. Copyright © 2013 Elsevier B.V. All rights reserved.

Green synthesis of Pd nanoparticles at Apricot kernel shell substrate using Salvia hydrangea extract: Catalytic activity for reduction of organic dyes.

PubMed

Khodadadi, Bahar; Bordbar, Maryam; Nasrollahzadeh, Mahmoud

2017-03-15

For the first time the extract of the plant of Salvia hydrangea was used to green synthesis of Pd nanoparticles (NPs) supported on Apricot kernel shell as an environmentally benign support. The Pd NPs/Apricot kernel shell as an effective catalyst was prepared through reduction of Pd 2+ ions using Salvia hydrangea extract as the reducing and capping agent and Pd NPs immobilization on Apricot kernel shell surface in the absence of any stabilizer or surfactant. According to FT-IR analysis, the hydroxyl groups of phenolics in Salvia hydrangea extract as bioreductant agents are directly responsible for the reduction of Pd 2+ ions and formation of Pd NPs. The as-prepared catalyst was characterized by Fourier transform infrared (FT-IR) and UV-Vis spectroscopy, field emission scanning electron microscopy (FESEM) equipped with an energy dispersive X-ray spectroscopy (EDS), Elemental mapping, X-ray diffraction analysis (XRD) and transmittance electron microscopy (TEM). The synthesized catalyst was used in the reduction of 4-nitrophenol (4-NP), Methyl Orange (MO), Methylene Blue (MB), Rhodamine B (RhB), and Congo Red (CR) at room temperature. The Pd NPs/Apricot kernel shell showed excellent catalytic activity in the reduction of these organic dyes. In addition, it was found that Pd NPs/Apricot kernel shell can be recovered and reused several times without significant loss of catalytic activity. Copyright © 2016 Elsevier Inc. All rights reserved.

Ferrimagnetic susceptibility contrast agents.

PubMed

Bach-Gansmo, T

1993-01-01

Contrast agents based on superparamagnetic particles have been in clinical development for more than 5 years, and the complexity of their effects is still not elucidated. The relaxivities are frequently used to give an idea of their efficacy, but these parameters can only be used if they are concentration independent. For large superparamagnetic systems, the evolution of the transverse magnetization is biexponential, after an initial loss of magnetization. Both these characteristics of large superparamagnetic systems should lead to prudence in using the relaxivities as indicators of contrast medium efficacy. Susceptibility induced artefacts have been associated with the use of superparamagnetic contrast agents since the first imaging evaluation took place. The range of concentrations where good contrast effect was achieved without inducing artefacts, as well as blurring and metal artefacts were evaluated. The influence of motion on the induction of artefacts was studied, and compared to the artefacts induced by a paramagnetic agent subject to motion. With a suitable concentration of a negative contrast agent, a signal void could be achieved in the region prone to motion, and no artefacts were induced. If the concentration was too high, a displacement of the region close to the contrast agent was observed. The artefacts occurred in a volume surrounding the contrast agent, i.e., also outside the imaging plane. In comparison a positive, paramagnetic contrast agent induced heavy artefacts in the phase encoding direction, appearing as both high intensity regions and black holes, in a mosaic pattern. Clinical trials of the oral contrast agent OMP for abdominal MR imaging showed this agent to be safe and efficacious. OMP increased the diagnostic efficacy of abdominal MR imaging in 2 of 3 cases examined, with a significant decrease in motion artefacts. Susceptibility contrast agents may also be of use in the evaluation of small lesions in the liver. Particulate material injected i.v. will be targeted to the liver and spleen by way of the mononuclear phagocyte system (MPS). Small particles, without specific receptor affinities were targeted to the hepatocytes and the MPS. The distribution correlated with a high efficiency as a contrast agent, whereas no correlation to in vitro relaxation rates and relaxivities could be found. Superparamagnetic particles have important possibilities as contrast agents. The identification of in vitro properties of these agents may help the comparison of various agents before in vivo imaging.

Buckling and Failure of Compression-Loaded Composite Laminated Shells With Cutouts

NASA Technical Reports Server (NTRS)

Hilburger, Mark W.

2007-01-01

Results from a numerical and experimental study that illustrate the effects of laminate orthotropy on the buckling and failure response of compression-loaded composite cylindrical shells with a cutout are presented. The effects of orthotropy on the overall response of compression-loaded shells is described. In general, preliminary numerical results appear to accurately predict the buckling and failure characteristics of the shell considered herein. In particular, some of the shells exhibit stable post-local-buckling behavior accompanied by interlaminar material failures near the free edges of the cutout. In contrast another shell with a different laminate stacking sequence appears to exhibit catastrophic interlaminar material failure at the onset of local buckling near the cutout and this behavior correlates well with corresponding experimental results.

Functional Nanoparticles for Magnetic Resonance Imaging

PubMed Central

Mao, Xinpei; Xu, Jiadi; Cui, Honggang

2016-01-01

Nanoparticle-based magnetic resonance imaging (MRI) contrast agents have received much attention over the past decade. By virtue of a high payload of magnetic moieties, enhanced accumulation at disease sites, and a large surface area for additional modification with targeting ligands, nanoparticle-based contrast agents offer promising new platforms to further enhance the high resolution and sensitivity of MRI for various biomedical applications. T2* superparamagnetic iron oxide nanoparticles (SPIONs) first demonstrated superior improvement on MRI sensitivity. The prevailing SPION attracted growing interest in the development of refined nanoscale versions of MRI contrast agents. Afterwards, T1-based contrast agents were developed, and became the most studied subject in MRI due to the positive contrast they provide that avoids the susceptibility associated with MRI signal reduction. Recently, chemical exchange saturation transfer (CEST) contrast agents have emerged and rapidly gained popularity. The unique aspect of CEST contrast agents is that their contrast can be selectively turned “on” and “off” by radiofrequency (RF) saturation. Their performance can be further enhanced by incorporating a large number of exchangeable protons into well-defined nanostructure. Besides activatable CEST contrast agents, there is growing interest in developing nanoparticle-based activatable MRI contrast agents responsive to stimuli (pH, enzyme, etc.), which improves sensitivity and specificity. In this review, we summarize the recent development of various types of nanoparticle-based MRI contrast agents, and have focused our discussions on the key advantages of introducing nanoparticles in MRI. PMID:27040463

Size-Tunable and Functional Core-Shell Structured Silica Nanoparticles for Drug Release

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

Chi, Fangli; Guo, Ya Nan; Liu, Jun

2010-02-18

Size-tunable silica cross-linked micellar core-shell nanoparticles (SCMCSNs) were successfully synthesized from a Pluronic nonionic surfactant (F127) template system with organic swelling agents such as 1,3,5-trimethylbenzene (TMB) and octanoic acid at room temperature. The size and morphology of SCMCSNs were directly evidenced by TEM imaging and DLS measurements (up to ~90 nm). Pyrene and coumarin 153 (C153) were used as fluorescent probe molecules to investigate the effect and location of swelling agent molecules. Papaverine as a model drug was used to measure the loading capacity and release property of nanoparticles. The swelling agents can enlarge the nanoparticle size and improve themore » drug loading capacity of nanoparticles. Moreover, the carboxylic acid group of fatty acid can adjust the release behavior of the nanoparticles.« less

Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

NASA Astrophysics Data System (ADS)

Ma, J.; Chen, K.

2016-04-01

Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol-1 L s-1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

Graphitic carbon nitride nanosheet@metal-organic framework core-shell nanoparticles for photo-chemo combination therapy

NASA Astrophysics Data System (ADS)

Chen, Rui; Zhang, Jinfeng; Wang, Yu; Chen, Xianfeng; Zapien, J. Antonio; Lee, Chun-Sing

2015-10-01

Recently, nanoscale metal-organic frameworks (NMOFs) have started to be developed as a promising platform for bioimaging and drug delivery. On the other hand, combination therapies using multiple approaches are demonstrated to achieve much enhanced efficacy. Herein, we report, for the first time, core-shell nanoparticles consisting of a photodynamic therapeutic (PDT) agent and a MOF shell while simultaneously carrying a chemotherapeutic drug for effective combination therapy. In this work, core-shell nanoparticles of zeolitic-imadazolate framework-8 (ZIF-8) as shell embedded with graphitic carbon nitride (g-C3N4) nanosheets as core are fabricated by growing ZIF-8 in the presence of g-C3N4 nanosheets. Doxorubicin hydrochloride (DOX) is then loaded into the ZIF-8 shell of the core-shell nanoparticles. The combination of the chemotherapeutic effects of DOX and the PDT effect of g-C3N4 nanosheets can lead to considerably enhanced efficacy. Furthermore, the red fluorescence of DOX and the blue fluorescence of g-C3N4 nanosheets provide the additional function of dual-color imaging for monitoring the drug release process.Recently, nanoscale metal-organic frameworks (NMOFs) have started to be developed as a promising platform for bioimaging and drug delivery. On the other hand, combination therapies using multiple approaches are demonstrated to achieve much enhanced efficacy. Herein, we report, for the first time, core-shell nanoparticles consisting of a photodynamic therapeutic (PDT) agent and a MOF shell while simultaneously carrying a chemotherapeutic drug for effective combination therapy. In this work, core-shell nanoparticles of zeolitic-imadazolate framework-8 (ZIF-8) as shell embedded with graphitic carbon nitride (g-C3N4) nanosheets as core are fabricated by growing ZIF-8 in the presence of g-C3N4 nanosheets. Doxorubicin hydrochloride (DOX) is then loaded into the ZIF-8 shell of the core-shell nanoparticles. The combination of the chemotherapeutic effects of DOX and the PDT effect of g-C3N4 nanosheets can lead to considerably enhanced efficacy. Furthermore, the red fluorescence of DOX and the blue fluorescence of g-C3N4 nanosheets provide the additional function of dual-color imaging for monitoring the drug release process. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04436g

Gadolinium-enhanced MR images of the growing piglet skeleton: ionic versus nonionic contrast agent.

PubMed

Menezes, Nina M; Olear, Elizabeth A; Li, Xiaoming; Connolly, Susan A; Zurakowski, David; Foley, Mary; Shapiro, Frederic; Jaramillo, Diego

2006-05-01

To determine whether there are differences in the distribution of ionic and nonionic gadolinium-based contrast agents by evaluating contrast enhancement of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis in the knees of normal piglets. Following approval from the Subcommittee on Research Animal Care, knees of 12 3-week-old piglets were imaged at 3-T magnetic resonance (MR) imaging after intravenous injection of gadoteridol (nonionic contrast agent; n = 6) or gadopentetate dimeglumine (ionic contrast agent; n = 6). Early enhancement evaluation with gradient-echo MR imaging was quantified and compared (Student t test) by means of enhancement ratios. Distribution of contrast material was assessed and compared (Student t test) by means of T1 measurements obtained before and at three 15-minute intervals after contrast agent administration. The relative visibility of the physis, epiphyseal cartilage, secondary ossification center, and metaphysis was qualitatively assessed by two observers and compared (Wilcoxon signed rank test). Differences in matrix content and cellularity that might explain the imaging findings were studied at histologic evaluation. Enhancement ratios were significantly higher for gadoteridol than for gadopentetate dimeglumine in the physis, epiphyseal cartilage, and secondary ossification center (P < .05). After contrast agent administration, T1 values decreased sharply for both agents-but more so for gadoteridol. Additionally, there was less variability in T1 values across structures with this contrast agent. Gadoteridol resulted in greater visibility of the physis, while gadopentetate dimeglumine resulted in greater contrast between the physis and metaphysis (P < .05). The results suggest different roles for the two gadolinium-based contrast agents: The nonionic contrast medium is better suited for evaluating perfusion and anatomic definition in the immature skeleton, while the ionic contrast medium is better for evaluating cartilage fixed-charge density. (c) RSNA, 2006.

Inorganic nanoparticle-based T1 and T1/T2 magnetic resonance contrast probes

NASA Astrophysics Data System (ADS)

Hu, Fengqin; Zhao, Yong Sheng

2012-09-01

Magnetic resonance imaging (MRI) yields high spatially resolved contrast with anatomical details for diagnosis, deeper penetration depth and rapid 3D scanning. To improve imaging sensitivity, adding contrast agents accelerates the relaxation rate of water molecules, thereby greatly increasing the contrast between specific issues or organs of interest. Currently, the majority of T1 contrast agents are paramagnetic molecular complexes, typically Gd(iii) chelates. Various nanoparticulate T1 and T1/T2 contrast agents have recently been investigated as novel agents possessing the advantages of both the T1 contrast effect and nanostructural characteristics. In this minireview, we describe the recent progress of these inorganic nanoparticle-based MRI contrast agents. Specifically, we mainly report on Gd and Mn-based inorganic nanoparticles and ultrasmall iron oxide/ferrite nanoparticles.

K-edge ratio method for identification of multiple nanoparticulate contrast agents by spectral CT imaging

PubMed Central

Ghadiri, H; Ay, M R; Shiran, M B; Soltanian-Zadeh, H

2013-01-01

Objective: Recently introduced energy-sensitive X-ray CT makes it feasible to discriminate different nanoparticulate contrast materials. The purpose of this work is to present a K-edge ratio method for differentiating multiple simultaneous contrast agents using spectral CT. Methods: The ratio of two images relevant to energy bins straddling the K-edge of the materials is calculated using an analytic CT simulator. In the resulting parametric map, the selected contrast agent regions can be identified using a thresholding algorithm. The K-edge ratio algorithm is applied to spectral images of simulated phantoms to identify and differentiate up to four simultaneous and targeted CT contrast agents. Results: We show that different combinations of simultaneous CT contrast agents can be identified by the proposed K-edge ratio method when energy-sensitive CT is used. In the K-edge parametric maps, the pixel values for biological tissues and contrast agents reach a maximum of 0.95, whereas for the selected contrast agents, the pixel values are larger than 1.10. The number of contrast agents that can be discriminated is limited owing to photon starvation. For reliable material discrimination, minimum photon counts corresponding to 140 kVp, 100 mAs and 5-mm slice thickness must be used. Conclusion: The proposed K-edge ratio method is a straightforward and fast method for identification and discrimination of multiple simultaneous CT contrast agents. Advances in knowledge: A new spectral CT-based algorithm is proposed which provides a new concept of molecular CT imaging by non-iteratively identifying multiple contrast agents when they are simultaneously targeting different organs. PMID:23934964

Synthesis of hollow silica spheres with hierarchical shell structure by the dual action of liquid indium microbeads in vapor-liquid-solid growth.

PubMed

Wang, Jian-Tao; Wang, Hui; Ou, Xue-Mei; Lee, Chun-Sing; Zhang, Xiao-Hong

2011-07-05

Geometry-based adhesion arising from hierarchical surface structure enables microspheres to adhere to cells strongly, which is essential for inorganic microcapsules that function as drug delivery or diagnostic imaging agents. However, constructing a hierarchical structure on the outer shell of the products via the current microcapsule synthesis method is difficult. This work presents a novel approach to fabricating hollow microspheres with a hierarchical shell structure through the vapor-liquid-solid (VLS) process in which liquid indium droplets act as both templates for the formation of silica capsules and catalysts for the growth of hierarchical shell structure. This hierarchical shell structure offers the hollow microsphere an enhanced geometry-based adhesion. The results provide a facile method for fabricating hollow spheres and enriching their function through tailoring the geometry of their outer shells. © 2011 American Chemical Society

Gadolinium chloride as a contrast agent for imaging wood composite components by magnetic resonance

Treesearch

Thomas L. Eberhardt; Chi-Leung So; Andrea Protti; Po-Wah So

2009-01-01

Although paramagnetic contrast agents have an established track record in medical uses of magnetic resonance imaging (MRI), only recently has a contrast agent been used for enhancing MRI images of solid wood specimens. Expanding on this concept, wood veneers were treated with a gadolinium-based contrast agent and used in a model system comprising three-ply plywood...

Porphyrin synthesized from cashew nut shell liquid as part of a novel superparamagnetic fluorescence nanosystem

NASA Astrophysics Data System (ADS)

Clemente, C. S.; Ribeiro, V. G. P.; Sousa, J. E. A.; Maia, F. J. N.; Barreto, A. C. H.; Andrade, N. F.; Denardin, J. C.; Mele, G.; Carbone, L.; Mazzetto, S. E.; Fechine, P. B. A.

2013-06-01

Magnetic Fe3O4 nanoparticles with average size approximately 11 nm were first oleic acid coated to interact with the meso-porphyrin derivative from CNSL. This procedure produced a novel superparamagnetic fluorescent nanosystem (SFN) linked by van der Waals interactions. This system was characterized by transmission electron microscope, infrared spectroscopy, thermogravimetric analysis, magnetic measurements, UV-Vis absorption, and fluorescence emission measurements. These results showed that SFN has good thermal stability, excellent magnetization, and nanosized dimensions ( 13 nm). It exhibited emission peaks at 668 and 725 nm with a maximum emission at 467 nm of excitation wavelength. The type of interaction between porphyrin and magnetic nanoparticles allowed to obtain a material with interesting optical properties which might be used as an imaging agent for contrast in cells as well as heterogeneous photocatalysis.

Synthetic lipid nanoparticles targeting steroid organs.

PubMed

Mérian, Juliette; Boisgard, Raphaël; Decleves, Xavier; Thezé, Benoît; Texier, Isabelle; Tavitian, Bertrand

2013-11-01

Lipidots are original nanoparticulate lipid delivery vectors for drugs and contrast agents made from materials generally regarded as safe. Here, we characterized the in vivo stability, biodistribution, and pharmacokinetics of lipidots. Lipidots 55 nm in diameter and coated with a phospholipid/poly(ethyleneglycol) surfactant shell were triply labeled with (3)H-cholesteryl-hexadecyl-ether, cholesteryl-(14)C-oleate, and the 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine infrared fluorescent dye and injected intravenously into immunocompetent Friend virus B-type mice. The pharmacokinetics and biodistribution of lipidots were analyzed quantitatively in serial samples of blood and tissue and with in vivo optical imaging and were refined by microscopic examination of selected target tissues. The plasmatic half-life of lipidots was approximately 30 min. Radioactive and fluorescent tracers displayed a similar nanoparticle-driven biodistribution, indicative of the lipidots' integrity during the first hours after injection. Lipidots distributed in the liver and, surprisingly, in the steroid-rich organs adrenals and ovaries, but not in the spleen. This tropism was confirmed at the microscopic level by histologic detection of 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine. Nanoparticle loading with cholesterol derivatives increased accumulation in ovaries in a dose-dependent manner. This previously unreported distribution pattern is specific to lipidots and attributed to their nanometric size and composition, conferring on them a lipoproteinlike behavior. The affinity of lipidots for steroid hormone-rich areas is of interest to address drugs and contrast agents to lipoprotein-receptor-overexpressing cancer cells found in hormone-dependent tumors.

Porous Fe3O4-SiO2 core-shell nanorods as high-performance MRI contrast agent and drug delivery vehicle

NASA Astrophysics Data System (ADS)

Beg, Muhammad Shahbaz; Mohapatra, Jeotikanta; Pradhan, Lina; Patkar, D.; Bahadur, D.

2017-04-01

A high-performance MRI contrast agent and a drug nanocarrier have been realized in porous Fe3O4@SiO2 nanorods (NRs). The Fe3O4@SiO2 NRs of length 520 nm and diameter 180 nm are synthesized by annealing FeOOH@SiO2 nanorods at a temperature of 300 ℃ under continuous flow of forming gas. The magnetic measurement confirms that the Fe3O4@SiO2 NRs is ferrimagnetic in nature with magnetization of 20 emu/g and coercivity HC 450 Oe. The aqueous suspension of the NRs is stable over a time frame of one month and exhibits a high R2 relaxivity value of 192 mM-1 s-1. The R2 darkening effect is also observed in HeLa cells incubated with NRs in comparison to untreated control cells. The porous Fe3O4@SiO2 NRs further work as an excellent carrier for doxorubicin (DOX) drug with loading efficiency of 65%. The drug release study shows a pH-dependent behavior and is higher in acidic pH (4.3) as compared to the physiological pH (7.4). After 72 h, the cumulative DOX release is found to be 58% at pH 4.3 and 17% at pH 7.4. The induction heating studies of the NRs exhibit a sharp increasing trend of SAR value with the increase of magnetic field.

Holistic assessment of covalently-labelled core-shell polymeric nanoparticles with fluorescent contrast agents towards theranostic applications

PubMed Central

Gustafson, Tiffany P.; Lim, Young H.; Flores, Jeniree A.; Heo, Gyu Seong; Zhang, Fuwu; Zhang, Shiyi; Samarajeewa, Sandani; Raymond, Jeffery E.; Wooley, Karen L.

2014-01-01

The successful development of degradable polymeric nanostructures as optical probes for use in nanotheranostic applications requires the intelligent design of materials such that their surface response, degradation, drug delivery and imaging properties are all optimized. In the case of imaging, optimization must result in materials that allow differentiation between unbound optical contrast agents and labeled polymeric materials as they undergo degradation. In this study, we have shown that use of traditional electrophoretic gel-plate assays for determination of the purity of dye-conjugated degradable nanoparticles is limited, due to polymer degradation characteristics. To overcome these limitations, we have outlined a holistic approach to evaluating dye-and peptide-polymer nanoparticle conjugation by utilizing steady-state fluorescence, anisotropy, and emission and anisotropy life-time decay profiles, through which nanoparticle-dye binding can be assessed independent of perturbations, such as those presented during the execution of electrolyte gel-based assays. This approach has been demonstrated to provide an overall understanding of the spectral signature-structure-function relationship, ascertaining key information on interactions between the fluorophore, polymer and solvent components that have a direct and measurable impact on the emissive properties of the optical probe. The use of these powerful techniques provides feedback that can be utilized to improve nanotheranostics by evaluating dye emissivity in degradable nanotheranostic systems, which has become increasingly important as modern platforms transition to architectures intentionally reliant on degradation and built-in environmental responses. PMID:24392760

Silica-Coated Nonstoichiometric Nano Zn-Ferrites for Magnetic Resonance Imaging and Hyperthermia Treatment.

PubMed

Starsich, Fabian H L; Sotiriou, Georgios A; Wurnig, Moritz C; Eberhardt, Christian; Hirt, Ann M; Boss, Andreas; Pratsinis, Sotiris E

2016-10-01

Large-scale and reproducible synthesis of nanomaterials is highly sought out for successful translation into clinics. Flame aerosol technology with its proven capacity to manufacture high purity materials (e.g., light guides) up to kg h -1 is explored here for the preparation of highly magnetic, nonstoichiometric Zn-ferrite (Zn 0.4 Fe 2.6 O 4 ) nanoparticles coated in situ with a nanothin SiO 2 layer. The focus is on their suitability as magnetic multifunctional theranostic agents analyzing their T2 contrast enhancing capability for magnetic resonance imaging (MRI) and their magnetic hyperthermia performance. The primary particle size is closely controlled from 5 to 35 nm evaluating its impact on magnetic properties, MRI relaxivity, and magnetic heating performance. Most importantly, the addition of Zn in the flame precursor solution facilitates the growth of spinel Zn-ferrite crystals that exhibit superior magnetic properties over iron oxides typically made in flames. These properties result in strong MRI T2 contrast agents as shown on a 4.7 T small animal MRI scanner and lead to a more efficient heating with alternating magnetic fields. Also, by injecting Zn 0.4 Fe 2.6 O 4 nanoparticle suspensions into pork tissue, MR-images are acquired at clinically relevant concentrations. Furthermore, the nanothin SiO 2 shell facilitates functionalization with polymers, which improves the biocompatibility of the theranostic system. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

High throughput chemical munitions treatment system

DOEpatents

Haroldsen, Brent L [Manteca, CA; Stofleth, Jerome H [Albuquerque, NM; Didlake, Jr., John E.; Wu, Benjamin C-P [San Ramon, CA

2011-11-01

A new High-Throughput Explosive Destruction System is disclosed. The new system is comprised of two side-by-side detonation containment vessels each comprising first and second halves that feed into a single agent treatment vessel. Both detonation containment vessels further comprise a surrounding ventilation facility. Moreover, the detonation containment vessels are designed to separate into two half-shells, wherein one shell can be moved axially away from the fixed, second half for ease of access and loading. The vessels are closed by means of a surrounding, clam-shell type locking seal mechanisms.

A mineralogical record of ocean change: Decadal and centennial patterns in the California mussel.

PubMed

McCoy, Sophie J; Kamenos, Nicholas A; Chung, Peter; Wootton, Timothy J; Pfister, Catherine A

2018-06-01

Ocean acidification, a product of increasing atmospheric carbon dioxide, may already have affected calcified organisms in the coastal zone, such as bivalves and other shellfish. Understanding species' responses to climate change requires the context of long-term dynamics. This can be particularly difficult given the longevity of many important species in contrast with the relatively rapid onset of environmental changes. Here, we present a unique archival dataset of mussel shells from a locale with recent environmental monitoring and historical climate reconstructions. We compare shell structure and composition in modern mussels, mussels from the 1970s, and mussel shells dating back to 1000-2420 years BP. Shell mineralogy has changed dramatically over the past 15 years, despite evidence for consistent mineral structure in the California mussel, Mytilus californianus, over the prior 2500 years. We present evidence for increased disorder in the calcium carbonate shells of mussels and greater variability between individuals. These changes in the last decade contrast markedly from a background of consistent shell mineralogy for centuries. Our results use an archival record of natural specimens to provide centennial-scale context for altered minerology and variability in shell features as a response to acidification stress and illustrate the utility of long-term studies and archival records in global change ecology. Increased variability between individuals is an emerging pattern in climate change responses, which may equally expose the vulnerability of organisms and the potential of populations for resilience. © 2017 John Wiley & Sons Ltd.

Contrast-enhanced voiding urosonography: in vitro evaluation of a second-generation ultrasound contrast agent for in vivo optimization.

PubMed

Back, Susan J; Edgar, J Christopher; Canning, Douglas A; Darge, Kassa

2015-09-01

Pediatric contrast-enhanced ultrasound (CEUS) is primarily performed outside the United States where a track record for safety in intravenous and intravesical applications has been established. Contrast-enhanced voiding urosonography (ceVUS) has also been shown to have a much higher rate of vesicoureteral reflux detection compared to voiding cystourethrography. US contrast agents available in the United States differ from those abroad. Optison® (GE Healthcare, Princeton, NJ) is such an US contrast agent. While Optison® has similar characteristics to other second-generation agents, it has never been used for ceVUS. In vitro optimization of dose and imaging parameters as well as assessment of contrast visualization when delivered in conditions similar to ceVUS are necessary starting points prior to in vivo applications. To optimize the intravesical use of Optison® in vitro for ceVUS before its use in pediatric studies. The experimental design simulated intravesical use. Using 9- and 12-MHz linear transducers, we scanned 20-mL syringes varying mechanical index, US contrast agent concentration (0.25%, 0.5%, 1.0%), solvent (saline, urine, radiographic contrast agent) and time out of refrigeration. We evaluated mechanical index settings and contrast duration, optimized the contrast dose, measured the effect of urine and radiographic contrast agent, and the impact of length of time of contrast outside of the refrigerator on US contrast appearance. We scanned 50-ml saline bags to assess the appearance and duration of US contrast with different delivery systems (injection vs. infusion). Consistent contrast visualization was achieved at a mechanical index of 0.06-0.17 and 0.11-0.48 for the L9 and L12 MHz transducers (P < 0.01), respectively. Thus, it was necessary to increase the mechanical index for better contrast visualization of the microbubbles with a higher transducer frequency. The lowest mechanical index for earliest visible microbubble destruction was 0.21 for the 9 MHz and 0.39 for the 12 MHz (P < 0.01) transducers. The 0.5% US contrast agent volume to bladder filling was the most optimal. At this concentration, the mean time to visualize homogenous contrast was 2 min and destruction of approximately half of the microbubbles in the field of view occurred in 7.8 min using the 9-MHz transducer. During contrast infusion, the contrast dose needed to be reduced to 0.12% for maintenance of optimal visualization of microbubbles. There was no deleterious effect on the visualization of contrast in the presence of urine or radiographic contrast agent. Infusion of the US contrast agent speeded visualization of homogeneous enhancement compared with injection. Time outside refrigeration did not affect contrast performance. Transducer mechanical index settings need to be optimized. A very low dose of the US contrast agent Optison® will suffice for intravesical application, i.e. 0.12% to 0.50% of the bladder filling volume. The presence of urine or radiographic contrast agent did not compromise contrast visualization. The best mode of administration is the infusion method due to fast homogenous distribution at the lowest dose of 0.12%. Leaving the US contrast agent outside the refrigerator for an hour does not affect the microbubbles.

Achillea millefolium L. extract mediated green synthesis of waste peach kernel shell supported silver nanoparticles: Application of the nanoparticles for catalytic reduction of a variety of dyes in water.

PubMed

Khodadadi, Bahar; Bordbar, Maryam; Nasrollahzadeh, Mahmoud

2017-05-01

In this paper, silver nanoparticles (Ag NPs) are synthesized using Achillea millefolium L. extract as reducing and stabilizing agents and peach kernel shell as an environmentally benign support. FT-IR spectroscopy, UV-Vis spectroscopy, X-ray Diffraction (XRD), Field emission scanning electron microscopy (FESEM), Energy Dispersive X-ray Spectroscopy (EDS), Thermo gravimetric-differential thermal analysis (TG-DTA) and Transmission Electron Microscopy (TEM) were used to characterize peach kernel shell, Ag NPs, and Ag NPs/peach kernel shell. The catalytic activity of the Ag NPs/peach kernel shell was investigated for the reduction of 4-nitrophenol (4-NP), Methyl Orange (MO), and Methylene Blue (MB) at room temperature. Ag NPs/peach kernel shell was found to be a highly active catalyst. In addition, Ag NPs/peach kernel shell can be recovered and reused several times with no significant loss of its catalytic activity. Copyright © 2017 Elsevier Inc. All rights reserved.

Model and reconstruction of a K-edge contrast agent distribution with an X-ray photon-counting detector

PubMed Central

Meng, Bo; Cong, Wenxiang; Xi, Yan; De Man, Bruno; Yang, Jian; Wang, Ge

2017-01-01

Contrast-enhanced computed tomography (CECT) helps enhance the visibility for tumor imaging. When a high-Z contrast agent interacts with X-rays across its K-edge, X-ray photoelectric absorption would experience a sudden increment, resulting in a significant difference of the X-ray transmission intensity between the left and right energy windows of the K-edge. Using photon-counting detectors, the X-ray intensity data in the left and right windows of the K-edge can be measured simultaneously. The differential information of the two kinds of intensity data reflects the contrast-agent concentration distribution. K-edge differences between various matters allow opportunities for the identification of contrast agents in biomedical applications. In this paper, a general radon transform is established to link the contrast-agent concentration to X-ray intensity measurement data. An iterative algorithm is proposed to reconstruct a contrast-agent distribution and tissue attenuation background simultaneously. Comprehensive numerical simulations are performed to demonstrate the merits of the proposed method over the existing K-edge imaging methods. Our results show that the proposed method accurately quantifies a distribution of a contrast agent, optimizing the contrast-to-noise ratio at a high dose efficiency. PMID:28437900

Section 6—Mechanical Bioeffects in the Presence of Gas-Carrier Ultrasound Contrast Agents

PubMed Central

2007-01-01

This review addresses the issue of mechanical ultrasound-induced bioeffects in the presence of gas carrier contrast agents (GCAs). Here, the term “contrast agent” refers to those agents that provide ultrasound contrast by being composed of microbubbles, encapsulated or not, containing one or more gases. Provided in this section are summaries on how contrast agents work, some of their current uses, and the potential for bio-effects associated with their presence in an ultrasonic field. PMID:10680618

Basic MR relaxation mechanisms and contrast agent design.

PubMed

De León-Rodríguez, Luis M; Martins, André F; Pinho, Marco C; Rofsky, Neil M; Sherry, A Dean

2015-09-01

The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. © 2015 Wiley Periodicals, Inc.

"Basic MR Relaxation Mechanisms & Contrast Agent Design"

PubMed Central

De León-Rodríguez, Luis M.; Martins, André F.; Pinho, Marco; Rofsky, Neil; Sherry, A. Dean

2015-01-01

The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we will detail the many important considerations when pursuing the design and use of MR contrast media. We will offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand based contrast agents. We will discuss the mechanisms involved in magnetic resonance relaxation in the context of probe design strategies. A brief description of currently available contrast agents will be accompanied by an in-depth discussion that highlights promising MRI contrast agents in development for future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. PMID:25975847

Strategies for Optimizing Water-Exchange Rates of Lanthanide-Based Contrast Agents for Magnetic Resonance Imaging

PubMed Central

Siriwardena-Mahanama, Buddhima N.; Allen, Matthew J.

2013-01-01

This review describes recent advances in strategies for tuning the water-exchange rates of contrast agents for magnetic resonance imaging (MRI). Water-exchange rates play a critical role in determining the efficiency of contrast agents; consequently, optimization of water-exchange rates, among other parameters, is necessary to achieve high efficiencies. This need has resulted in extensive research efforts to modulate water-exchange rates by chemically altering the coordination environments of the metal complexes that function as contrast agents. The focus of this review is coordination-chemistry-based strategies used to tune the water-exchange rates of lanthanide(III)-based contrast agents for MRI. Emphasis will be given to results published in the 21st century, as well as implications of these strategies on the design of contrast agents. PMID:23921796

Tidal dissipation in the subsurface ocean of Enceladus

NASA Astrophysics Data System (ADS)

Matsuyama, I.; Hay, H.; Nimmo, F.; Kamata, S.

2017-12-01

Icy satellites of the outer solar system have emerged as potential habitable worlds due to the presence of subsurface oceans. As a long-term energy source, tidal heating in these oceans can influence the survivability of subsurface oceans, and the thermal, rotational, and orbital evolution of these satellites. Additionally, the spatial and temporal variation of tidal heating has implications for the interior structure and spacecraft observations. Previous models for dissipation in thin oceans are not generally applicable to icy satellites because either they ignore the presence of an overlying solid shell or use a thin shell membrane approximation. We present a new theoretical treatment for tidal dissipation in thin oceans with overlying shells of arbitrary thickness and apply it to Enceladus. The shell's resistance to ocean tides increases with shell thickness, reducing tidal dissipation as expected. Both the magnitude of energy dissipation and the resonant ocean thicknesses decrease as the overlying shell thickness increases, as previously shown using a membrane approximation. In contrast to previous work based on the traditional definition of the tidal quality factor, Q, our new definition is consistent with higher energy dissipation for smaller Q, and introduces a lower limit on Q. The dissipated power and tides are not in phase with the forcing tidal potential due to the delayed ocean response. The phase lag depends on the Rayleigh friction coefficient and ocean and shell thicknesses, which implies that phase lag observations can be used to constrain these parameters. Eccentricity heating produces higher dissipation near the poles, while obliquity heating produces higher dissipation near the equator, in contrast to the dissipation patterns in the shell. The time-averaged surface distribution of tidal heating can generate lateral shell thickness variations, providing an additional constraint on the Rayleigh friction coefficient. Explaining the endogenic power radiated from the south polar terrain requires shell thicknesses smaller than about 1 km, a value that is not consistent with recent libration, gravity and topography constraints.

The R-Shell approach - Using scheduling agents in complex distributed real-time systems

NASA Technical Reports Server (NTRS)

Natarajan, Swaminathan; Zhao, Wei; Goforth, Andre

1993-01-01

Large, complex real-time systems such as space and avionics systems are extremely demanding in their scheduling requirements. The current OS design approaches are quite limited in the capabilities they provide for task scheduling. Typically, they simply implement a particular uniprocessor scheduling strategy and do not provide any special support for network scheduling, overload handling, fault tolerance, distributed processing, etc. Our design of the R-Shell real-time environment fcilitates the implementation of a variety of sophisticated but efficient scheduling strategies, including incorporation of all these capabilities. This is accomplished by the use of scheduling agents which reside in the application run-time environment and are responsible for coordinating the scheduling of the application.

Extraction of chitosan from shrimp shells waste and application in antibacterial finishing of bamboo rayon.

PubMed

Teli, M D; Sheikh, Javed

2012-06-01

Chitosan can be best utilized as safe antibacterial agent for textiles but there is always a limitation of its durability. The chitin containing shellfish waste is available in huge quantities, but very low quantities are utilized for extraction of high value products like chitosan. In the current work chitosan was extracted from shrimp shells and then used as antibacterial exhaust finishing agent for grafted bamboo rayon. Chitosan bound bamboo rayon was then evaluated for antibacterial activity against both gram positive and gram negative bacteria. The product showed antibacterial activity against both types of bacterias which was durable till 30 washes. Copyright © 2012 Elsevier B.V. All rights reserved.

Ultrasonic Analysis of Peptide- and Antibody-Targeted Microbubble Contrast Agents for Molecular Imaging of αvβ3-Expressing Cells

PubMed Central

Dayton, Paul A.; Pearson, David; Clark, Jarrod; Simon, Scott; Schumann, Patricia A.; Zutshi, Reena; Matsunaga, Terry O.; Ferrara, Katherine W.

2008-01-01

The goal of targeted ultrasound contrast agents is to significantly and selectively enhance the detection of a targeted vascular site. In this manuscript, three distinct contrast agents targeted to the αvβ3 integrin are examined. The αvβ3 integrin has been shown to be highly expressed on metastatic tumors and endothelial cells during neovascularization, and its expression has been shown to correlate with tumor grade. Specific adhesion of these contrast agents to αvβ3-expressing cell monolayers is demonstrated in vitro, and compared with that of nontargeted agents. Acoustic studies illustrate a backscatter amplitude increase from monolayers exposed to the targeted contrast agents of up to 13-fold (22 dB) relative to enhancement due to control bubbles. A linear dependence between the echo amplitude and bubble concentration was observed for bound agents. The decorrelation of the echo from adherent targeted agents is observed over successive pulses as a function of acoustic pressure and bubble density. Frequency–domain analysis demonstrates that adherent targeted bubbles exhibit high-amplitude narrowband echo components, in contrast to the primarily wideband response from free microbubbles. Results suggest that adherent targeted contrast agents are differentiable from free-floating microbubbles, that targeted contrast agents provide higher sensitivity in the detection of angiogenesis, and that conventional ultrasound imaging techniques such as signal subtraction or decorrelation detection can be used to detect integrin-expressing vasculature with sufficient signal-to-noise. PMID:15296677

High-value utilization of egg shell to synthesize Silver and Gold-Silver core shell nanoparticles and their application for the degradation of hazardous dyes from aqueous phase-A green approach.

PubMed

Sinha, Tanur; Ahmaruzzaman, M

2015-09-01

The common household material, egg shell of Anas platyrhynchos is utilized for the synthesis of Silver and Gold-Silver core shell nanoparticles using greener, environment friendly and economic way. The egg shell extracts were acting as a stabilizing and reducing agents. This method avoids the use of external reducing and stabilizing agents, templates and solvents. The effects of various reaction parameters, such as reaction temperature, concentration in the formation of nanoparticles have also been investigated. The compositional abundance of gelatin may be envisaged for the effective reductive as well as stabilizing potency. The mechanisms for the formation of NPs have also been presented. The synthesized Ag NPs formed were predominantly spherical in nature with an average size of particles in the range of 6-26 nm. While, Au-Ag core shell nanoparticles formed were spherical and oval shaped, within a narrow size spectrum of 9-18 nm. Both the Ag NPs Au-and Ag core shell nanoparticles showed characteristic Bragg's reflection planes of fcc structure and surface plasmon resonance at 430 nm and 365 nm, respectively. The NPs were utilized for the removal of toxic and hazardous dyes, such as Rose Bengal, Methyl Violet 6 B and Methylene Blue from aqueous phase. Approximately 98.2%, 98.4% and 97% degradations of Rose Bengal, Methyl Violet 6 B, and Methylene Blue were observed with Ag NPs, while the percentage degradation of these dyes was 97.3%, 97.6% and 96% with Au-Ag NPs, respectively. Therefore, the present study has opened up an innovative way for synthesizing Ag NPs and Au-Ag bimetallic nanostructures of different morphologies and sizes involving the utilization of egg shell extract. The high efficiency of the NPs as photocatalysts has opened a promising application for the removal of hazardous dyes from the industrial effluents. Copyright © 2015 Elsevier Inc. All rights reserved.

Contrast echocardiography: new agents.

PubMed

Miller, Andrew P; Nanda, Navin C

2004-04-01

In this report, we review the history, rationale, current status and future directions of contrast agents in echocardiography. First, we discuss the historic development of contrast agents through a review of important physical principles of microbubbles in ultrasonography. Second, we identify attributes of an ideal contrast agent and review those that are currently available or in the "pipeline" for clinical use. Third, we review indications for contrast echocardiography, including endocardial border detection, perfusion quantification and reperfusion assessment, and validate these observations by comparisons with other imaging modalities. Then, we briefly review different methodologies of performing a contrast study, including interrupted, real-time and a hybrid modality. Finally, we identify novel future applications of the newest contrast agents. These newer concepts in contrast echocardiography should form a foundation for nearly limitless application of echocardiography in improved anatomical assessment, perfusion imaging and even special applications, such as detection of vascular inflammation and site-specific drug delivery.

Biogenic Growth of Alloys and Core-Shell Nanostructures Using Urease as a Nanoreactor at Ambient Conditions

PubMed Central

Sharma, Bhagwati; Mandani, Sonam; Sarma, Tridib K.

2013-01-01

Biomineralization is an extremely efficient biologically guided process towards the advancement of nano-bio integrated materials. As a prime module of the natural world, enzymes are expected to play a major role in biogenic growth of inorganic nanostructures. Although there have been developments in designing enzyme-responsive nanoparticle systems or generation of inorganic nanostructures in an enzyme-stimulated environment, reports regarding action of enzymes as reducing agents themselves for the growth of inorganic nanoparticles still remains elusive. Here we present a mechanistic investigation towards the synthesis of metal and metallic alloy nanoparticles using a commonly investigated enzyme, Jack bean urease (JBU), as a reducing as well as stabilizing agent under physiological conditions. The catalytic functionality of urease was taken advantage of towards the development of metal-ZnO core-shell nanocomposites, making urease an ideal bionanoreactor for synthesizing higher order nanostructures such as alloys and core- shell under ambient conditions. PMID:24018831

Fabrication of Cu-Ag core-shell bimetallic superfine powders by eco-friendly reagents and structures characterization

NASA Astrophysics Data System (ADS)

Zhao, Jun; Zhang, Dongming; Zhao, Jie

2011-09-01

Superfine bimetallic Cu-Ag core-shell powders were synthesized by reduction of copper sulfate pentahydrate and silver nitrate with eco-friendly ascorbic acid as a reducing agent and cyclodextrins as a protective agent in an aqueous system. The influence of Ag/Cu ratio on coatings was investigated. Ag was homogeneously distributed on the surface of Cu particles at a mole ratio of Ag/Cu=1. FE-SEM showed an uniformity of Ag coatings on Cu particles. Antioxidation of Cu particles was improved by increasing Ag/Cu ratio. TEM-EDX and UV-vis spectra also revealed that Cu cores were covered by Ag nanoshells on the whole. The surface composition analysis by XPS indicated that only small parts of Cu atoms in the surface were oxidized. It was noted that the hindrance of cyclodextrins chemisorbed on particles plays an important role in forming high quality and good dispersity Cu-Ag (Cu@Ag) core-shell powders.

Plasma-Based Synthesis of Nanostructured Materials and their Characterization

NASA Astrophysics Data System (ADS)

Chaudhary, Rakesh P.

The aim of this thesis is to explore the novel cost-effective synthesis technique to develop nanostructured materials and investigate their structural and magnetic properties. Nanomaterials were synthesized by a plasma discharge between desired metal electrodes in the cavitation field of an organic solvent. Multifunctional core-shell magnetic nanoparticles of 3d transition elements (Fe, Ni) and bimetallic (FeNi) were synthesized by varying experimental conditions. The phase, crystallinity and the magnetic properties of the materials synthesized were found to be dependent on experimental reaction parameters such as different solvents, electrodes, the spacing between electrodes, applied voltage, experiment time and high-temperature annealing. Fe and Gd-based nanoparticles were developed for high-performance magnetic resonance imaging (MRI) contrast enhancement. Biocompatible hybrid composite of Fe core - C shell nanoparticles evaluated as negative MRI contrast agents display remarkably high transverse relaxivity (r2) of 70 mM-1S-1 at 7T. In addition to 3d transition magnetic materials, magnetism of multilayer graphene nanosheets with only s and p electrons was investigated to understand and explain the intrinsic origin of ferromagnetism in carbon-based material. Apart from magnetic materials, noble metal Pd nanoparticles were developed using one-step process for hydrogen storage. The role of hydrogen on the dilation of Pd lattice was investigated using the experiment and density functional theory (DFT) studies. This method demonstrates that plasma discharge method using appropriate electrodes and solvents can be used to synthesize desired nanoparticles. This potential emphasizes the importance of adopting this methodology, which offers advantages that include a rapid reaction rate and ability to form very small nanoparticles with narrow size distribution.

Application of gold nanoparticles as contrast agents in confocal laser scanning microscopy

NASA Astrophysics Data System (ADS)

Lemelle, A.; Veksler, B.; Kozhevnikov, I. S.; Akchurin, G. G.; Piletsky, S. A.; Meglinski, I.

2009-01-01

Confocal laser scanning microscopy (CLSM) is a modern high-resolution optical technique providing detailed image of tissue structure with high (down to microns) spatial resolution. Aiming at a concurrent improvement of imaging depth and image quality the CLSM requires the use of contrast agents. Commonly employed fluorescent contrast agents, such as fluorescent dyes and proteins, suffer from toxicity, photo-bleaching and overlapping with the tissues autofluorescence. Gold nanoparticles are potentially highly attractive to be applied as a contrast agent since they are not subject to photo-bleaching and can target biochemical cells markers associated with the specific diseases. In current report we consider the applicability of gold nano-spheres as a contrast agent to enhance quality of CLSM images of skin tissues in vitro versus the application of optical clearing agent, such as glycerol. The enhancement of CLSM image contrast was observed with an application of gold nano-spheres diffused within the skin tissues. We show that optical clearing agents such as a glycerol provide better CLSM image contrast than gold nano-spheres.

Multifunctional compact hybrid Au nanoshells: a new generation of nanoplasmonic probes for biosensing, imaging, and controlled release.

PubMed

Jin, Yongdong

2014-01-21

Gold nanoshells (AuNSs) with tunable localized surface plasmon resonance (LSPR) peaks in the near-infrared (NIR) region possess unique optical properties-particularly that soft tissues are "transparent" at these wavelengths-making them of great interest in cancer diagnosis and treatment. Since 1998 when Halas and co-workers invented the first generation of AuNS, with a silica core and Au shell, researchers have studied and designed AuNSs for theranostic-individualized, combination diagnosis and therapy-nanomedicine. As demand has increased for more powerful and practical theranostic applications, so has demand for the next generation of AuNSs-compact yet complex multifunctional AuNSs with finely integrated plasmonic and nonplasmonic inorganic components. For in vivo biomedical applications, such a hybrid AuNS offers the desirable optical properties of NIR LSPR. Size, however, has proved a more challenging parameter to control in hybrid AuNSs. The ideal size of therapeutic NPs is 10-100 nm. Larger particles have limited diffusion in the extracellular space, while particles less than 5 nm are rapidly cleared from the circulation through extravasation or renal clearance. Conventional methods of preparing AuNS have failed to obtain small-sized hybrid AuNSs with NIR LSPR responses. In this Account, we present a new class of multifunctional hybrid AuNSs with ultrathin AuNSs and varied, functional (nonplasmonic) core components ranging from "hard" semiconductor quantum dots (QDs), to superparamagnetic NPs, to "soft" liposomes made using poly-l-histidine as a template to direct Au deposition. The resultant hybrid AuNSs are uniform and compact (typically 15-60 nm) but also preserve the optical properties and shell-type NIR response necessary for biomedical use. We also demonstrate these particles' innovative plasmonic applications in biosensing, multimodal imaging and controlled release. More importantly, the magnetic-plasmonic Fe3O4/Au core-shell NP enables a new biological imaging method-magnetomotive photoacoustic (mmPA) imaging, which suppresses the nonmagnetomotive background and therefore offers remarkable contrast enhancement and improved specificity compared with photoacoustic images using conventional NP contrast agents. The advantages of our AuNSs are obvious: they are monodisperse, small (<100 nm), highly integrated, and have tunable visible-NIR plasmonic responses. All of these properties are crucial for in vitro or in vivo biological/biomedical studies and many applications, especially for studies of single cells or molecules which require particle monodispersity and tight size control. The plasmonic fluorescent QD/Au and the magnetic plasmonic Fe3O4/Au core-shell NPs may also reveal new physical phenomena that may lead to useful applications, owing to their well-defined core-shell nanoarchitectures and underlying nanoscale physical interactions.

Nitroxide-Based Macromolecular Contrast Agents with Unprecedented Transverse Relaxivity and Stability for Magnetic Resonance Imaging of Tumors

PubMed Central

2017-01-01

Metal-free magnetic resonance imaging (MRI) agents could overcome the established toxicity associated with metal-based agents in some patient populations and enable new modes of functional MRI in vivo. Herein, we report nitroxide-functionalized brush-arm star polymer organic radical contrast agents (BASP-ORCAs) that overcome the low contrast and poor in vivo stability associated with nitroxide-based MRI contrast agents. As a consequence of their unique nanoarchitectures, BASP-ORCAs possess per-nitroxide transverse relaxivities up to ∼44-fold greater than common nitroxides, exceptional stability in highly reducing environments, and low toxicity. These features combine to provide for accumulation of a sufficient concentration of BASP-ORCA in murine subcutaneous tumors up to 20 h following systemic administration such that MRI contrast on par with metal-based agents is observed. BASP-ORCAs are, to our knowledge, the first nitroxide MRI contrast agents capable of tumor imaging over long time periods using clinical high-field 1H MRI techniques. PMID:28776023

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging

PubMed Central

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-01-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane–modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. PMID:26874280

Submicron polycaprolactone particles as a carrier for imaging contrast agent for in vitro applications.

PubMed

Iqbal, Muhammad; Robin, Sophie; Humbert, Philippe; Viennet, Céline; Agusti, Geraldine; Fessi, Hatem; Elaissari, Abdelhamid

2015-12-01

Fluorescent materials have recently attracted considerable attention due to their unique properties and high performance as imaging agent in biomedical fields. Different imaging agents have been encapsulated in order to restrict its delivery to a specific area. In this study, a fluorescent contrast agent was encapsulated for in vitro application by polycaprolactone (PCL) polymer. The encapsulation was performed using modified double emulsion solvent evaporation technique with sonication. Fluorescent nanoparticles (20 nm) were incorporated in the inner aqueous phase of double emulsion. A number of samples were fabricated using different concentrations of fluorescent contrast agent. The contrast agent-containing submicron particle was characterized by a zetasizer for average particle size, SEM and TEM for morphology observations and fluorescence spectrophotometer for encapsulation efficiency. Moreover, contrast agent distribution in the PCL matrix was determined by confocal microscopy. The incorporation of contrast agent in different concentrations did not affect the physicochemical properties of PCL particles and the average size of encapsulated particles was found to be in the submicron range. Copyright © 2015 Elsevier B.V. All rights reserved.

Polydisulfide Manganese(II) Complexes as Non-Gadolinium Biodegradable Macromolecular MRI Contrast Agents

PubMed Central

Ye, Zhen; Jeong, Eun-Kee; Wu, Xueming; Tan, Mingqian; Yin, Shouyu; Lu, Zheng-Rong

2011-01-01

Purpose To develop safe and effective manganese(II) based biodegradable macromolecular MRI contrast agents. Materials and Methods In this study, we synthesized and characterized two polydisulfide manganese(II) complexes, Mn-DTPA cystamine copolymers and Mn-EDTA cystamine copolymers, as new biodegradable macromolecular MRI contrast agents. The contrast enhancement of the two manganese based contrast agents were evaluated in mice bearing MDA-MB-231 human breast carcinoma xenografts, in comparison with MnCl2. Results The T1 and T2 relaxivities were 4.74 and 10.38 mM−1s−1 per manganese at 3T for Mn-DTPA cystamine copolymers (Mn=30.50 kDa) and 6.41 and 9.72 mM−1s−1 for Mn-EDTA cystamine copolymers (Mn= 61.80 kDa). Both polydisulfide Mn(II) complexes showed significant liver, myocardium and tumor enhancement. Conclusion The manganese based polydisulfide contrast agents have a potential to be developed as alternative non-gadolinium contrast agents for MR cancer and myocardium imaging. PMID:22031457

The use of innovative gadolinium-based contrast agent for MR-diagnosis of cancer in the experiment

NASA Astrophysics Data System (ADS)

Chernov, V.; Medvedeva, A.; Sinilkin, I.; Zelchan, R.; Grigorev, E.; Frolova, I.; Nam, I.

2016-02-01

The present study of the functional suitability and specific activity of the contrast agent gadolinium-based for magnetic resonance imaging demonstrated that the investigated contrast agent intensively accumulates in organs and anatomical structures of the experimental animals. In the model of tumor lesions in animals, study have shown that investigational contrast agent accumulates in the tumor tissue and retained there in for a long enough time.

Double walled POE/PLGA microspheres: encapsulation of water-soluble and water-insoluble proteins and their release properties.

PubMed

Shi, Meng; Yang, Yi-Yan; Chaw, Cheng-Shu; Goh, Suat-Hong; Moochhala, Shabbir M; Ng, Steve; Heller, Jorge

2003-04-29

The poly(orthoester) (POE)-poly(D,L-lactide-co-glycolide) (50:50) (PLGA) double-walled microspheres with 50% POE in weight were loaded with hydrophilic bovine serum albumin (BSA) and hydrophobic cyclosporin A (CyA). Most of the BSA and CyA was entrapped within the shell and core, respectively, because of the difference in their hydrophilicity. The morphologies and release mechanisms of proteins-loaded double-walled POE/PLGA microspheres were investigated. Scanning electron microscope studies revealed that the CyA-BSA-loaded double-walled POE/PLGA microspheres yielded a more porous surface and PLGA shell than those without BSA. The neat POE and PLGA yielded slow and incomplete CyA and BSA release. In contrast, nearly complete BSA and more than 95% CyA were released in a sustained manner from the double-walled POE/PLGA microspheres. Both the BSA- and CyA-BSA-loaded POE/PLGA microspheres yielded a sustained BSA release over 5 days. The CyA release pattern of the CyA-loaded double-walled POE/PLGA microspheres was biphasic, characterized by a slow release over 15 days followed by a sustained release over 27 days. However, the CyA-BSA-loaded double-walled POE/PLGA microspheres provided a more constant and faster CyA release due to their more porous shell. In the CyA-BSA-loaded double-walled POE/PLGA microspheres system, the PLGA layer acted as a carrier for BSA and mild reservoir for CyA. During the first 5 days, most BSA was released from the shell but only 14% CyA was left from the microspheres. Subsequently, more than 80% CyA were released in the next 25 days. The distinct structure of double-walled POE/PLGA microspheres would make an interesting device for controlled delivery of therapeutic agents.

Development of Modified Titanium Nitride Nanoparticles as Potential Contrast Material for Photoacoustic Imaging

DTIC Science & Technology

2014-05-10

based on modified fullerenes , carbon nanotubes and gold nanoparticles (including nanocages and nanorods) were very recently reported.4 Nevertheless, this...ratios of 1:1.6 and 1:16, in order to form an onion- like core-shell structure, containing TiN core and shells of TPP (inner shell) and chitosan (outer...These results nicely correlate with the cells viability results and the formation of the ROS is most likely the cause of the cells death (Figure 24

Effect of energy transfer from atomic electron shell to an α particle emitted by decaying nucleus

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

Igashov, S. Yu., E-mail: igashov@theor.mephi.ru; Tchuvil’sky, Yu. M.

2016-12-15

The process of energy transfer from the electron shell of an atom to an α particle propagating through the shell is formulated mathematically. Using the decay of the {sup 226}Ra nucleus as an example, it is demonstrated that this phenomenon increases the α-decay intensity in contrast with other known effects of similar type. Moreover, the α decay of the nucleus is more strongly affected by the energy transfer than by all other effects taken together.

Stress concentration in a cylindrical shell containing a circular hole.

NASA Technical Reports Server (NTRS)

Adams, N. J. I.

1971-01-01

The state of stress in a cylindrical shell containing a circular cutout was determined for axial tension, torsion, and internal pressure loading. The solution was obtained for the shallow shell equations by a variational method. The results were expressed in terms of a nondimensional curvature parameter which was a function of shell radius, shell thickness, and hole radius. The function chosen for the solution was such that when the radius of the cylindrical shell approaches infinity, the flat-plate solution was obtained. The results are compared with solutions obtained by more rigorous analytical methods, and with some experimental results. For small values of the curvature parameter, the agreement is good. For higher values of the curvature parameter, the present solutions indicate a limiting value of stress concentration, which is in contrast to previous results.

Stability of echogenic liposomes as a blood pool ultrasound contrast agent in a physiologic flow phantom.

PubMed

Radhakrishnan, Kirthi; Haworth, Kevin J; Huang, Shao-Ling; Klegerman, Melvin E; McPherson, David D; Holland, Christy K

2012-11-01

Echogenic liposomes (ELIP) are multifunctional ultrasound contrast agents (UCAs) with a lipid shell encapsulating both air and an aqueous core. ELIP are being developed for molecular imaging and image-guided therapeutic delivery. Stability of the echogenicity of ELIP in physiologic conditions is crucial to their successful translation to clinical use. In this study, we determined the effects of the surrounding media's dissolved air concentration, temperature transition and hydrodynamic pressure on the echogenicity of a chemically modified formulation of ELIP to promote stability and echogenicity. ELIP samples were diluted in porcine plasma or whole blood and pumped through a pulsatile flow system with adjustable hydrodynamic pressures and temperature. B-mode images were acquired using a clinical diagnostic scanner every 5 s for a total duration of 75 s. Echogenicity in porcine plasma was assessed as a function of total dissolved gas saturation. ELIP were added to plasma at room temperature (22 °C) or body temperature (37 °C) and pumped through a system maintained at 22 °C or 37 °C to study the effect of temperature transitions on ELIP echogenicity. Echogenicity at normotensive (120/80 mmHg) and hypertensive pressures (145/90 mmHg) was measured. ELIP were echogenic in plasma and whole blood at body temperature under normotensive to hypertensive pressures. Warming of samples from room temperature to body temperature did not alter echogenicity. However, in plasma cooled rapidly from body temperature to room temperature or in degassed plasma, ELIP lost echogenicity within 20 s at 120/80 mmHg. The stability of echogenicity of a modified ELIP formulation was determined in vitro at body temperature, physiologic gas concentration and throughout the physiologic pressure range. However, proper care should be taken to ensure that ELIP are not cooled rapidly from body temperature to room temperature as they will lose their echogenic properties. Further in vivo investigations will be needed to evaluate the optimal usage of ELIP as blood pool contrast agents. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Effects of iodinated contrast agent, xylocaine and gadolinium concentration on the signal emitted in magnetic resonance arthrography: a samples study*

PubMed Central

da Silva, Yvana Lopes Pinheiro; Costa, Rita Zanlorensi Visneck; Pinho, Kátia Elisa Prus; Ferreira, Ricardo Rabello; Schuindt, Sueliton Miyamoto

2015-01-01

Objective To investigate the effects of dilution of paramagnetic contrast agent with iodinated contrast and xylocaine on the signal intensity during magnetic resonance arthrography, and to improve the paramagnetic contrast agent concentration utilized in this imaging modality. Materials and Methods Samples specially prepared for the study with three different concentrations of paramagnetic contrast agent diluted in saline, iodinated contrast agent and xylocaine were imaged with fast spin echo T1-weighted sequences with fat saturation. The samples were placed into flasks and graphical analysis of the signal intensity was performed as a function of the paramagnetic contrast concentration. Results As compared with samples of equal concentrations diluted only with saline, the authors have observed an average signal intensity decrease of 20.67% for iodinated contrast agent, and of 28.34% for xylocaine. However, the increased gadolinium concentration in the samples caused decrease in signal intensity with all the dilutions. Conclusion Minimizing the use of iodinated contrast media and xylocaine and/or the use of a gadolinium concentration of 2.5 mmol/L diluted in saline will improve the sensitivity of magnetic resonance arthrography. PMID:25987746

One-Pot Synthesis of Fe3O4@PS@P(AEMH-FITC) Magnetic Fluorescent Nanocomposites for Bimodal Imaging.

PubMed

Wang, Xuandong; Liu, Huiyu; Jun, Ren; Fu, Changhui; Li, Linlin; Li, Tianlong; Tang, Fangqiong; Meng, Xianwei

2016-03-01

Magnetic fluorescent nanocomposites have attracted much attention because of their merging magnetic and fluorescent properties for biomedical application. However, the procedure of synthesis of magnetic fluorescent nanocomposites is always complicated. In addition, the properties of fluorescent component could be easily influenced by magnetic component, retaining both of the magnetic and fluorescent properties into one single nanoparticle considered to be a significant challenge. Herein, we report one-pot method to synthesize multifunctional magnetic fluorescent Fe3O4@PS@P(AEMH-FITC) nanocomposites for bimodal imaging. The asprepared Fe3O4@PS@P(AEMH-FITC) nanocomposites with well-define spherical core/shell structure were stable properties. Moreover, the Fe3O4@PS@P(AEMH-FITC) nanocomposites displayed efficient fluorescent and magnetic properties, respectively. Meanwhile, the magnetic resonance imaging (MRI) and HePG2 cancer cell fluorescent images experiment results suggested that Fe3O4@PS@P(AEMH-FITC) nanocomposites could be used as MRI contrast agents and Fluorescence Imaging (FLI) agents for bioimaging application. Our investigation paves a facile avenue for synthesized magnetic fluorescent nanostructures with well biocompatibility for potential bioimaging application in MRI and FLI.

CHANGES IN LIPID-ENCAPSULATED MICROBUBBLE POPULATION DURING CONTINUOUS INFUSION AND METHODS TO MAINTAIN CONSISTENCY

PubMed Central

KAYA, MEHMET; GREGORY, THOMAS S.; DAYTON, PAUL A.

2009-01-01

Stabilized microbubbles are utilized as ultrasound contrast agents. These micron-sized gas capsules are injected into the bloodstream to provide contrast enhancement during ultrasound imaging. Some contrast imaging strategies, such as destruction-reperfusion, require a continuous injection of microbubbles over several minutes. Most quantitative imaging strategies rely on the ability to administer a consistent dose of contrast agent. Because of the buoyancy of these gas-filled agents, their spatial distribution within a syringe changes over time. The population of microbubbles that is pumped from a horizontal syringe outlet differs from initial population as the microbubbles float to the syringe top. In this manuscript, we study the changes in the population of a contrast agent that is pumped from a syringe due to microbubble floatation. Results are presented in terms of change in concentration and change in mean diameter, as a function of time, suspension medium, and syringe diameter. Data illustrate that the distribution of contrast agents injected from a syringe changes in both concentration and mean diameter over several minutes without mixing. We discuss the application of a mixing system and viscosity agents to keep the contrast solution more evenly distributed in a syringe. These results are significant for researchers utilizing microbubble contrast agents in continuous-infusion applications where it is important to maintain consistent contrast agent delivery rate, or in situations where the injection syringe cannot be mixed immediately prior to administration. PMID:19632760

Contrast agent enhanced pQCT of articular cartilage

NASA Astrophysics Data System (ADS)

Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

2007-02-01

The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded articular cartilage in vitro. As high resolution imaging of e.g. the knee joint is possible with pQCT, the present technique may be further developed for in vivo quantification of PG depletion in osteoarthritic cartilage. However, careful in vitro and in vivo characterization of diffusion mechanics and optimal contrast agent concentrations are needed before diagnostic applications are feasible.

Safe Use of Contrast Media: What the Radiologist Needs to Know.

PubMed

Beckett, Katrina R; Moriarity, Andrew K; Langer, Jessica M

2015-10-01

Iodinated and gadolinium-based contrast media are used on a daily basis in most radiology practices. These agents often are essential to providing accurate diagnoses, and are nearly always safe and effective when administered correctly. However, reactions to contrast media do occur and can be life threatening. Therefore, it is critical for faculty and staff to know how reactions to contrast agents manifest and how to treat them promptly. The decline in renal function seen occasionally after intravenous administration of iodinated contrast agents is poorly understood and likely multifactorial, and its association with the contrast medium may be overemphasized. However, it is important that radiologists be aware of current understanding and strategies to decrease the incidence of renal dysfunction. Nephrogenic systemic fibrosis, a skin disease, is an adverse reaction related to use of some gadolinium-based contrast agents in patients with chronic renal failure. The types of gadolinium most often associated with this condition and the indications for withholding gadolinium are important and are discussed in this article. The use of enteric contrast agents and contrast agents during pregnancy and nursing are reviewed briefly. Current knowledge for safe use of contrast media and key concepts that all radiologists should know are summarized in this review. © RSNA, 2015.

Fabrication of Fe3O4@CuO core-shell from MOF based materials and its antibacterial activity

NASA Astrophysics Data System (ADS)

Rajabi, S. K.; Sohrabnezhad, Sh.; Ghafourian, S.

2016-12-01

Magnetic Fe3O4@CuO nanocomposite with a core/shell structure was successfully synthesized via direct calcinations of magnetic Fe3O4@HKUST-1 in air atmosphere. The morphology, structure, magnetic and porous properties of the as-synthesized nano composites were characterized by using scanning electron microscope (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and vibration sample magnetometer (VSM). The results showed that the nanocomposite material included a Fe3O4 core and a CuO shell. The Fe3O4@CuO core-shell can be separated easily from the medium by a small magnet. The antibacterial activity of Fe3O4-CuO core-shell was investigated against gram-positive and gram-negative bacteria. A new mechanism was proposed for inactivation of bacteria over the prepared sample. It was demonstrated that the core-shell exhibit recyclable antibacterial activity, acting as an ideal long-acting antibacterial agent.

Development of contrast agents targeted to macrophage scavenger receptors for MRI of vascular inflammation

PubMed Central

Gustafsson, Björn; Youens, Susan; Louie, Angelique Y.

2008-01-01

Atherosclerosis is a leading cause of death in the U.S. Because there is a potential to prevent coronary and arterial diseases through early diagnosis, there is a need for methods to image arteries in the sub-clinical stage as well as clinical stage using various non-invasive techniques, including Magnetic Resonance Imaging (MRI). We describe a development of a novel MRI contrast agent targeted to plaques that will allow imaging of lesion formation. The contrast agent is directed to macrophages, one of the earliest components of developing plaques. Macrophages are labeled through the macrophage scavenger receptor A, a macrophage specific cell surface protein, using an MRI contrast agent derived from scavenger receptor ligands. We have synthesized and characterized these contrast agents with a range of relaxivities. In vitro studies show that the targeted contrast agent accumulates in macrophages and solution studies indicate that micromolar concentrations are sufficient to produce contrast in an MR image. Cell toxicity and initial biodistribution studies indicate low toxicity, no detectable retention in normal blood vessels, and rapid clearance from blood. The promising performance of this contrast agent targeted towards vascular inflammation opens doors to tracking of other inflammatory diseases such as tumor immunotherapy and transplant acceptance using MRI. PMID:16536488

Contrast-enhanced peripheral MRA: technique and contrast agents.

PubMed

Nielsen, Yousef W; Thomsen, Henrik S

2012-09-01

In the last decade contrast-enhanced magnetic resonance angiography (CE-MRA) has gained wide acceptance as a valuable tool in the diagnostic work-up of patients with peripheral arterial disease. This review presents current concepts in peripheral CE-MRA with emphasis on MRI technique and contrast agents. Peripheral CE-MRA is defined as an MR angiogram of the arteries from the aortic bifurcation to the feet. Advantages of CE-MRA include minimal invasiveness and lack of ionizing radiation. The basic technique employed for peripheral CE-MRA is the bolus-chase method. With this method a paramagnetic MRI contrast agent is injected intravenously and T1-weighted images are acquired in the subsequent arterial first-pass phase. In order to achieve high quality MR angiograms without interfering venous contamination or artifacts, a number of factors need to be taken into account. This includes magnetic field strength of the MRI system, receiver coil configuration, use of parallel imaging, contrast bolus timing technique, and k-space filling strategies. Furthermore, it is possible to optimize peripheral CE-MRA using venous compression techniques, hybrid scan protocols, time-resolved imaging, and steady-state MRA. Gadolinium(Gd)-based contrast agents are used for CE-MRA of the peripheral arteries. Extracellular Gd agents have a pharmacokinetic profile similar to iodinated contrast media. Accordingly, these agents are employed for first-pass MRA. Blood-pool Gd-based agents are characterized by prolonged intravascular stay, due to macromolecular structure or protein binding. These agents can be used for first-pass, as well as steady-state MRA. Some Gd-based contrast agents with low thermodynamic stability have been linked to development of nephrogenic systemic fibrosis in patients with severe renal insufficiency. Using optimized technique and a stable MRI contrast agent, peripheral CE-MRA is a safe procedure with diagnostic accuracy close to that of conventional catheter X-ray angiography.

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging.

PubMed

Daryaei, Iman; Pagel, Mark D

2015-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a "double-agent" approach to molecular imaging. Exogenous T 2 -exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T 1 and T 2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as "secret agents" in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging.

MRI-guided targeting delivery of doxorubicin with reduction-responsive lipid-polymer hybrid nanoparticles.

PubMed

Wu, Bo; Lu, Shu-Ting; Deng, Kai; Yu, Hui; Cui, Can; Zhang, Yang; Wu, Ming; Zhuo, Ren-Xi; Xu, Hai-Bo; Huang, Shi-Wen

2017-01-01

In recent years, there has been increasing interest in developing a multifunctional nanoscale platform for cancer monitoring and chemotherapy. However, there is still a big challenge for current clinic contrast agents to improve their poor tumor selectivity and response. Herein, we report a new kind of Gd complex and folate-coated redox-sensitive lipid-polymer hybrid nanoparticle (Gd-FLPNP) for tumor-targeted magnetic resonance imaging and therapy. Gd-FLPNPs can simultaneously accomplish diagnostic imaging, and specific targeting and controlled release of doxorubicin (DOX). They exhibit good monodispersity, excellent size stability, and a well-defined core-shell structure. Paramagnetic nanoparticles based on gadolinium-diethylenetriaminepentaacetic acid-bis-cetylamine have paramagnetic properties with an approximately two-fold enhancement in the longitudinal relaxivity compared to clinical used Magnevist. For targeted and reduction-sensitive drug delivery, Gd-FLPNPs released DOX faster and enhanced cell uptake in vitro, and exhibited better antitumor effect both in vitro and in vivo.

Coordinated scheduling for dynamic real-time systems

NASA Technical Reports Server (NTRS)

Natarajan, Swaminathan; Zhao, Wei

1994-01-01

In this project, we addressed issues in coordinated scheduling for dynamic real-time systems. In particular, we concentrated on design and implementation of a new distributed real-time system called R-Shell. The design objective of R-Shell is to provide computing support for space programs that have large, complex, fault-tolerant distributed real-time applications. In R-shell, the approach is based on the concept of scheduling agents, which reside in the application run-time environment, and are customized to provide just those resource management functions which are needed by the specific application. With this approach, we avoid the need for a sophisticated OS which provides a variety of generalized functionality, while still not burdening application programmers with heavy responsibility for resource management. In this report, we discuss the R-Shell approach, summarize the achievement of the project, and describe a preliminary prototype of R-Shell system.

One-pot synthesis of monodisperse CoFe2O4@Ag core-shell nanoparticles and their characterization.

PubMed

Hara, Shuta; Aisu, Jumpei; Kato, Masahiro; Aono, Takashige; Sugawa, Kosuke; Takase, Kouichi; Otsuki, Joe; Shimizu, Shigeru; Ikake, Hiroki

2018-06-08

In recent years, monodispersed magnetic nanoparticles with a core/shell structure are expected for their wide applications including magnetic fluid, recoverable catalysts, and biological analysis. However, their synthesis method needs numerous processes such as solvent substitution, exchange of protective agents, and centrifugation. A simple and rapid method for the synthesis of monodispersed core-shell nanoparticles makes it possible to accelerate their further applications. This paper describes a simple and rapid one-pot synthesis of core (CoFe 2 O 4 )-shell (Ag) nanoparticles with high monodispersity. The synthesized nanoparticles showed plasmonic light absorption owing to the Ag shell. Moreover, the magnetic property of the nanoparticles had a soft magnetic behavior at room temperature and a hard magnetic behavior at 5 K. In addition, the nanoparticles showed high monodispersity with a low polydispersity index (PDI) value of 0.083 in hexane.

One-pot synthesis of monodisperse CoFe2O4@Ag core-shell nanoparticles and their characterization

NASA Astrophysics Data System (ADS)

Hara, Shuta; Aisu, Jumpei; Kato, Masahiro; Aono, Takashige; Sugawa, Kosuke; Takase, Kouichi; Otsuki, Joe; Shimizu, Shigeru; Ikake, Hiroki

2018-06-01

In recent years, monodispersed magnetic nanoparticles with a core/shell structure are expected for their wide applications including magnetic fluid, recoverable catalysts, and biological analysis. However, their synthesis method needs numerous processes such as solvent substitution, exchange of protective agents, and centrifugation. A simple and rapid method for the synthesis of monodispersed core-shell nanoparticles makes it possible to accelerate their further applications. This paper describes a simple and rapid one-pot synthesis of core (CoFe2O4)-shell (Ag) nanoparticles with high monodispersity. The synthesized nanoparticles showed plasmonic light absorption owing to the Ag shell. Moreover, the magnetic property of the nanoparticles had a soft magnetic behavior at room temperature and a hard magnetic behavior at 5 K. In addition, the nanoparticles showed high monodispersity with a low polydispersity index (PDI) value of 0.083 in hexane.

Protein coated gold nanoparticles as template for the directed synthesis of highly fluorescent gold nanoclusters

NASA Astrophysics Data System (ADS)

Zhang, Lingyan; Han, Fei

2018-04-01

Bovine serum albumin (BSA) modified gold nanoparticles (AuNPs) was selected as template for the synthesis of AuNPs@gold nanoclusters (AuNCs) core/shell nanoparticles, in which BSA not only acted as dual functions agent for both anchoring and reducing Au3+ ions, but also was employed as a bridge between the AuNPs and AuNCs. Optical properties of AuNPs@AuNCs core/shell nanoparticles were studied using UV-visible and fluorescence spectroscopy. The prepared AuNPs@AuNCs core/shell nanoparticles exhibited sphere size uniformity with improved monodispersity, excellent fluorescence and fluorescent stability. Compared with AuNCs, AuNPs@AuNCs core/shell nanoparticles possessed large size and strong fluorescence intensity due to the effect of AuNPs as core. Moreover, the mechanism of the AuNPs induced fluorescence changes of the core/shell nanoparticles was first explored.

Nuclear magnetic resonance contrast agents

DOEpatents

Smith, P.H.; Brainard, J.R.; Jarvinen, G.D.; Ryan, R.R.

1997-12-30

A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC{sub 16}H{sub 14}N{sub 6}. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques. 10 figs.

Nuclear magnetic resonance contrast agents

DOEpatents

Smith, Paul H.; Brainard, James R.; Jarvinen, Gordon D.; Ryan, Robert R.

1997-01-01

A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC.sub.16 H.sub.14 N.sub.6. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques.

Comparison of contrast media for visualization of the colon of healthy dogs during computed tomography and ultrasonography.

PubMed

Cheon, Byunggyu; Moon, Sohyeon; Park, Seungjo; Lee, Sang-Kwon; Hong, Sunghwa; Cho, Hyun; Choi, Jihye

2016-11-01

OBJECTIVE To evaluate contrast agents for their ability to improve visualization of the colon wall and lumen during CT and ultrasonography. ANIMALS 10 healthy adult Beagles. PROCEDURES Food was withheld from dogs for 36 hours, after which dogs consumed 250 mL of polyethylene glycol solution. Dogs were then anesthetized, a contrast agent (tap water, diluted barium, or air; order randomly assigned) was administered rectally, iodine contrast medium (880 mg of I/kg) was administered IV, and CT and ultrasonography of the colon were performed. After a 1-week washout period, this process was repeated with a different contrast agent until all agents had been evaluated. Two investigators reviewed the CT and ultrasonographic images for colon wall thickness, conspicuity, artifacts, wall layering, and degree of lumen dilation at 4 sites. RESULTS Thickness of the colon wall was greatest in CT and ultrasonographic images with water used as contrast agent, followed by barium and then air. The CT images obtained after water administration had a smooth appearance that outlined the colonic mucosa and had the highest score of the 3 contrast agents for wall conspicuity. Although no substantial artifacts related to any of the contrast agents were identified on CT images, barium- and gas-induced shadowing and reverberation artifacts hindered wall evaluation during ultrasonography. For ultrasonography, the degree of conspicuity was highest with barium in the near-field wall and with water in the far-field wall. In contrast to CT, ultrasonography could be used to distinguish wall layering, and the mucosal and muscular layers were distinct with all contrast agents. CONCLUSIONS AND CLINICAL RELEVANCE Use of water as a contrast agent for both CT and ultrasonography of the colon in dogs compensated for each imaging modality's disadvantages and could be beneficial in the diagnosis of colon disease.

A targeted nanoglobular contrast agent from host-guest self-assembly for MR cancer molecular imaging.

PubMed

Zhou, Zhuxian; Han, Zhen; Lu, Zheng-Rong

2016-04-01

The clinical application of nanoparticular Gd(III) based contrast agents for tumor molecular MRI has been hindered by safety concerns associated with prolonged tissue retention, although they can produce strong tumor enhancement. In this study, a targeted well-defined cyclodextrin-based nanoglobular contrast agent was developed through self-assembly driven by host-guest interactions for safe and effective cancer molecular MRI. Multiple β-cyclodextrins attached POSS (polyhedral oligomeric silsesquioxane) nanoglobule was used as host molecule. Adamantane-modified macrocyclic Gd(III) contrast agent, cRGD (cyclic RGDfK peptide) targeting ligand and fluorescent probe was used as guest molecules. The targeted host-guest nanoglobular contrast agent cRGD-POSS-βCD-(DOTA-Gd) specifically bond to αvβ3 integrin in malignant 4T1 breast tumor and provided greater contrast enhancement than the corresponding non-targeted agent. The agent also provided significant fluorescence signal in tumor tissue. The histological analysis of the tumor tissue confirmed its specific and effective targeting to αvβ3 integrin. The targeted imaging agent has a potential for specific cancer molecular MR and fluorescent imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Green synthesis and characterization of Au@Pt core-shell bimetallic nanoparticles using gallic acid

NASA Astrophysics Data System (ADS)

Zhang, Guojun; Zheng, Hongmei; Shen, Ming; Wang, Lei; Wang, Xiaosan

2015-06-01

In this study, we developed a facile and benign green synthesis approach for the successful fabrication of well-dispersed urchin-like Au@Pt core-shell nanoparticles (NPs) using gallic acid (GA) as both a reducing and protecting agent. The proposed one-step synthesis exploits the differences in the reduction potentials of AuCl4- and PtCl62-, where the AuCl4- ions are preferentially reduced to Au cores and the PtCl62- ions are then deposited continuously onto the Au core surface as a Pt shell. The as-prepared Au@Pt NPs were characterized by transmission electron microscope (TEM); high-resolution transmission electron microscope (HR-TEM); scanning electron microscope (SEM); UV-vis absorption spectra (UV-vis); X-ray diffraction (XRD); Fourier transmission infrared spectra (FT-IR). We systematically investigated the effects of some experimental parameters on the formation of the Au@Pt NPs, i.e., the reaction temperature, the molar ratios of HAuCl4/H2PtCl6, and the amount of GA. When polyvinylpyrrolidone K-30 (PVP) was used as a protecting agent, the Au@Pt core-shell NPs obtained using this green synthesis method were better dispersed and smaller in size. The as-prepared Au@Pt NPs exhibited better catalytic activity in the reaction where NaBH4 reduced p-nitrophenol to p-aminophenol. However, the results showed that the Au@Pt bimetallic NPs had a lower catalytic activity than the pure Au NPs obtained by the same method, which confirmed the formation of Au@Pt core-shell nanostructures because the active sites on the surfaces of the Au NPs were covered with a Pt shell.

Study of the effect of varying core diameter, shell thickness and strain velocity on the tensile properties of single crystals of Cu-Ag core-shell nanowire using molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Sarkar, Jit; Das, D. K.

2018-01-01

Core-shell type nanostructures show exceptional properties due to their unique structure having a central solid core of one type and an outer thin shell of another type which draw immense attention among researchers. In this study, molecular dynamics simulations are carried out on single crystals of copper-silver core-shell nanowires having wire diameter ranging from 9 to 30 nm with varying core diameter, shell thickness, and strain velocity. The tensile properties like yield strength, ultimate tensile strength, and Young's modulus are studied and correlated by varying one parameter at a time and keeping the other two parameters constant. The results obtained for a fixed wire size and different strain velocities were extrapolated to calculate the tensile properties like yield strength and Young's modulus at standard strain rate of 1 mm/min. The results show ultra-high tensile properties of copper-silver core-shell nanowires, several times than that of bulk copper and silver. These copper-silver core-shell nanowires can be used as a reinforcing agent in bulk metal matrix for developing ultra-high strength nanocomposites.

Glass shell manufacturing in space. [residual gases in spherical shells made from metal-organic gels

NASA Technical Reports Server (NTRS)

Nolen, R. J.; Ebner, M. A.; Downs, R. L.

1980-01-01

Residual gases always found in glass shells are CO2, O2 and N2. In those cases where high water vapor pressure is maintained in the furnace, water is also found in the shells. Other evidence for the existence of water in shells is the presence of water-induced surface weathering of the interior shell surface. Water and CO2 are the predominant volatiles generated by the pyrolysis of both inorganic and hydrolyzed metal-organic gels. The pyrolysates of unhydrolyzed metal-organic gels also contain, in addition to water and CO2, significant levels of organic volatiles, such as ethanol and some hydrocarbons; on complete oxidation, these produce CO2 and water as well. Water is most likely the initial blowing agent, it is produced copiously during the initial stages of heating. In the later stages, CO2 becomes the dominant gas as H2O is lost at increasing rates. Water in the shell arises mainly from gel dehydration, CO2 by sodium bicarbonate/carbonate decomposition and carbon oxidation, and O2 and N2 by permeation of the ambient furnace air through the molten shell wall.

Contrast agents in dynamic contrast-enhanced magnetic resonance imaging

PubMed Central

Yan, Yuling; Sun, Xilin; Shen, Baozhong

2017-01-01

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a noninvasive method to assess angiogenesis, which is widely used in clinical applications including diagnosis, monitoring therapy response and prognosis estimation in cancer patients. Contrast agents play a crucial role in DCE-MRI and should be carefully selected in order to improve accuracy in DCE-MRI examination. Over the past decades, there was much progress in the development of optimal contrast agents in DCE-MRI. In this review, we describe the recent research advances in this field and discuss properties of contrast agents, as well as their advantages and disadvantages. Finally, we discuss the research perspectives for improving this promising imaging method. PMID:28415647

The evolution of gadolinium based contrast agents: from single-modality to multi-modality

NASA Astrophysics Data System (ADS)

Zhang, Li; Liu, Ruiqing; Peng, Hui; Li, Penghui; Xu, Zushun; Whittaker, Andrew K.

2016-05-01

Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications.

Imaging-related medications: a class overview

PubMed Central

2007-01-01

Imaging-related medications (contrast agents) are commonly utilized to improve visualization of radiographic, computed tomography (CT), and magnetic resonance (MR) images. While traditional medications are used specifically for their pharmacological actions, the ideal imaging agent provides enhanced contrast with little biological interaction. The radiopaque agents, barium sulfate and iodinated contrast agents, confer “contrast” to x-ray films by their physical ability to directly absorb x-rays. Gadolinium-based MR agents enhance visualization of tissues when exposed to a magnetic field. Ferrous-ferric oxide–based paramagnetic agents provide negative contrast for MR liver studies. This article provides an overview of clinically relevant information for the imaging-related medications commonly in use. It reviews the safety improvements in new generations of drugs; risk factors and precautions for the reduction of severe adverse reactions (i.e., extravasation, contrast-induced nephropathy, metformin-induced lactic acidosis, and nephrogenic fibrosing dermopathy/nephrogenic systemic fibrosis); and the significance of diligent patient screening before contrast exposure and appropriate monitoring after exposure. PMID:17948119

A Pictorial Review of Hepatobiliary Magnetic Resonance Imaging With Hepatocyte-Specific Contrast Agents: Uses, Findings, and Pitfalls of Gadoxetate Disodium and Gadobenate Dimeglumine.

PubMed

Scali, Elena P; Walshe, Triona; Tiwari, Hina Arif; Harris, Alison C; Chang, Silvia D

2017-08-01

Magnetic resonance imaging (MRI) has a well-established role as a highly specific and accurate modality for characterizing benign and malignant focal liver lesions. In particular, contrast-enhanced MRI using hepatocyte-specific contrast agents (HSCAs) improves lesion detection and characterization compared to other imaging modalities and MRI techniques. In this pictorial review, the mechanism of action of gadolinium-based MRI contrast agents, with a focus on HSCAs, is described. The clinical indications, protocols, and emerging uses of the 2 commercially available combined contrast agents available in the United States, gadoxetate disodium and gadobenate dimeglumine, are discussed. The MRI features of these agents are compared with examples of focal hepatic masses, many of which have been obtained within the same patient therefore allowing direct lesion comparison. Finally, the pitfalls in the use of combined contrast agents in liver MRI are highlighted. Copyright © 2016 Canadian Association of Radiologists. Published by Elsevier Inc. All rights reserved.

Double agents and secret agents: the emerging fields of exogenous chemical exchange saturation transfer and T2-exchange magnetic resonance imaging contrast agents for molecular imaging

PubMed Central

Daryaei, Iman; Pagel, Mark D

2016-01-01

Two relatively new types of exogenous magnetic resonance imaging contrast agents may provide greater impact for molecular imaging by providing greater specificity for detecting molecular imaging biomarkers. Exogenous chemical exchange saturation transfer (CEST) agents rely on the selective saturation of the magnetization of a proton on an agent, followed by chemical exchange of a proton from the agent to water. The selective detection of a biomarker-responsive CEST signal and an unresponsive CEST signal, followed by the ratiometric comparison of these signals, can improve biomarker specificity. We refer to this improvement as a “double-agent” approach to molecular imaging. Exogenous T2-exchange agents also rely on chemical exchange of protons between the agent and water, especially with an intermediate rate that lies between the slow exchange rates of CEST agents and the fast exchange rates of traditional T1 and T2 agents. Because of this intermediate exchange rate, these agents have been relatively unknown and have acted as “secret agents” in the contrast agent research field. This review exposes these secret agents and describes the merits of double agents through examples of exogenous agents that detect enzyme activity, nucleic acids and gene expression, metabolites, ions, redox state, temperature, and pH. Future directions are also provided for improving both types of contrast agents for improved molecular imaging and clinical translation. Therefore, this review provides an overview of two new types of exogenous contrast agents that are becoming useful tools within the armamentarium of molecular imaging. PMID:27747191

Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

PubMed Central

Estelrich, Joan; Sánchez-Martín, María Jesús; Busquets, Maria Antònia

2015-01-01

Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents. PMID:25834422

A systems approach to hemostasis: 4. How hemostatic thrombi limit the loss of plasma-borne molecules from the microvasculature

PubMed Central

Welsh, John D.; Muthard, Ryan W.; Stalker, Timothy J.; Taliaferro, Joshua P.; Diamond, Scott L.

2016-01-01

Previous studies have shown that hemostatic thrombi formed in response to penetrating injuries have a core of densely packed, fibrin-associated platelets overlaid by a shell of less-activated, loosely packed platelets. Here we asked, first, how the diverse elements of this structure combine to stem the loss of plasma-borne molecules and, second, whether antiplatelet agents and anticoagulants that perturb thrombus structure affect the re-establishment of a tight vascular seal. The studies combined high-resolution intravital microscopy with a photo-activatable fluorescent albumin marker to simultaneously track thrombus formation and protein transport following injuries to mouse cremaster muscle venules. The results show that protein loss persists after red cell loss has ceased. Blocking platelet deposition with an αIIbβ3 antagonist delays vessel sealing and increases extravascular protein accumulation, as does either inhibiting adenosine 5′-diphosphate (ADP) P2Y12 receptors or reducing integrin-dependent signaling and retraction. In contrast, sealing was unaffected by introducing hirudin to block fibrin accumulation or a Gi2α gain-of-function mutation to expand the thrombus shell. Collectively, these observations describe a novel approach for studying vessel sealing after injury in real time in vivo and show that (1) the core/shell architecture previously observed in arterioles also occurs in venules, (2) plasma leakage persists well beyond red cell escape and mature thrombus formation, (3) the most critical events for limiting plasma extravasation are the stable accumulation of platelets, ADP-dependent signaling, and the emergence of a densely packed core, not the accumulation of fibrin, and (4) drugs that affect platelet accumulation and packing can delay vessel sealing, permitting protein escape to continue. PMID:26738537

Dual Contrast CT Method Enables Diagnostics of Cartilage Injuries and Degeneration Using a Single CT Image.

PubMed

Saukko, Annina E A; Honkanen, Juuso T J; Xu, Wujun; Väänänen, Sami P; Jurvelin, Jukka S; Lehto, Vesa-Pekka; Töyräs, Juha

2017-12-01

Cartilage injuries may be detected using contrast-enhanced computed tomography (CECT) by observing variations in distribution of anionic contrast agent within cartilage. Currently, clinical CECT enables detection of injuries and related post-traumatic degeneration based on two subsequent CT scans. The first scan allows segmentation of articular surfaces and lesions while the latter scan allows evaluation of tissue properties. Segmentation of articular surfaces from the latter scan is difficult since the contrast agent diffusion diminishes the image contrast at surfaces. We hypothesize that this can be overcome by mixing anionic contrast agent (ioxaglate) with bismuth oxide nanoparticles (BINPs) too large to diffuse into cartilage, inducing a high contrast at the surfaces. Here, a dual contrast method employing this mixture is evaluated by determining the depth-wise X-ray attenuation profiles in intact, enzymatically degraded, and mechanically injured osteochondral samples (n = 3 × 10) using a microCT immediately and at 45 min after immersion in contrast agent. BiNPs were unable to diffuse into cartilage, producing high contrast at articular surfaces. Ioxaglate enabled the detection of enzymatic and mechanical degeneration. In conclusion, the dual contrast method allowed detection of injuries and degeneration simultaneously with accurate cartilage segmentation using a single scan conducted at 45 min after contrast agent administration.

Active extravasation of gadolinium-based contrast agent into the subdural space following lumbar puncture.

PubMed

Kothari, Pranay D; Hanser, Evelyn M; Wang, Harrison; Farid, Nikdokht

2016-01-01

A 38year-old male presented with cauda equina syndrome following multiple lumbar puncture attempts. Lumbar spine magnetic resonance imaging (MRI) showed a subdural hematoma and an area of apparent contrast enhancement in the spinal canal on sagittal post-contrast images. Axial post-contrast images obtained seven minutes later demonstrated an increase in size and change in shape of the region of apparent contrast enhancement, indicating active extravasation of the contrast agent. This is the first reported case of active extravasation of gadolinium-based contrast agent in the spine. Copyright © 2016 Elsevier Inc. All rights reserved.

A Coulomb-Like Off-Shell T-Matrix with the Correct Coulomb Phase Shift

NASA Astrophysics Data System (ADS)

Oryu, Shinsho; Watanabe, Takashi; Hiratsuka, Yasuhisa; Togawa, Yoshio

2017-03-01

We confirm the reliability of the well-known Coulomb renormalization method (CRM). It is found that the CRM is only available for a very-long-range screened Coulomb potential (SCP). However, such an SCP calculation in momentum space is considerably difficult because of the cancelation of significant digits. In contrast to the CRM, we propose a new method by using an on-shell equivalent SCP and the rest term. The two-potential theory with r-space is introduced, which defines fully the off-shell Coulomb amplitude.

The Effect of Ligands on FePt–Fe 3O 4 Core–Shell Magnetic Nanoparticles

DOE PAGES

Kim, Dong-Hyun; Tamada, Yoshinori; Ono, Teruo; ...

2014-03-01

FePt–Fe 3O 4 core–shell nanoparticles functionalized with 3,4-dihydroxyphenylacetic acid (DOPAC) and dimercaptosuccinic acid (DMSA) ligands were synthesized and characterized. We also found that the DOPAC ligand enhances the magnetic properties of the FePt–Fe 3O 4 particles, in comparison with the DMSA ligand, which induces the oxidation of the shell layer that causes a significant reduction of the saturation magnetization. We evaluated the synthesized magnetic nanoparticles for applications in magnetic hyperthermia and magnetic resonance imaging contrast enhancement.

X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents

PubMed Central

Rand, Danielle; Uchida, Masaki; Douglas, Trevor; Rose-Petruck, Christoph

2014-01-01

Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based “nanobubble” contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

Homoepitaxial n-core: p-shell gallium nitride nanowires: HVPE overgrowth on MBE nanowires.

PubMed

Sanders, Aric; Blanchard, Paul; Bertness, Kris; Brubaker, Matthew; Dodson, Christopher; Harvey, Todd; Herrero, Andrew; Rourke, Devin; Schlager, John; Sanford, Norman; Chiaramonti, Ann N; Davydov, Albert; Motayed, Abhishek; Tsvetkov, Denis

2011-11-18

We present the homoepitaxial growth of p-type, magnesium doped gallium nitride shells by use of halide vapor phase epitaxy (HVPE) on n-type gallium nitride nanowires grown by plasma-assisted molecular beam epitaxy (MBE). Scanning electron microscopy shows clear dopant contrast between the core and shell of the nanowire. The growth of magnesium doped nanowire shells shows little or no effect on the lattice parameters of the underlying nanowires, as measured by x-ray diffraction (XRD). Photoluminescence measurements of the nanowires show the appearance of sub-bandgap features in the blue and the ultraviolet, indicating the presence of acceptors. Finally, electrical measurements confirm the presence of electrically active holes in the nanowires.

Exogenous contrast agents for thermoacoustic imaging: An investigation into the underlying sources of contrast

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

Ogunlade, Olumide, E-mail: o.ogunlade@ucl.ac.uk; Beard, Paul

2015-01-15

Purpose: Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the underlying sources of contrast. To address this, measurements of the complex permittivity, complex permeability, DC conductivity, and Grüneisen parameter have been made. These measurements allowed the origins of the contrast provided by each substancemore » to be identified. Methods: The electric and magnetic properties of the contrast agents were characterized at 3 GHz using two rectangular waveguide cavities. The DC conductivity was measured separately using a conductivity meter. Thermoacoustic signals were then acquired and compared to those generated in water. Finally, 3D electromagnetic simulations were used to decouple the different contributions to the absorbed power density. Results: It was found that the gadolinium compounds provided appreciable electric contrast but not originating from the gadolinium itself. The contrast was either due to dissociation of the gadolinium salt which increased ionic conductivity or its nondissociated polar fraction which increased dielectric polarization loss or a combination of both. In addition, very high concentrations were required to achieve appreciable contrast, to the extent that the Grüneisen parameter increased significantly and became a source of contrast. Iron oxide particles were found to produce low but measurable dielectric contrast due to dielectric polarization loss, but this is attributed to the coating of the particles not the iron oxide. Single wall carbon nanotubes did not provide measurable contrast of any type. Conclusions: It is concluded that gadolinium based contrast agents, iron oxide particles, and single walled carbon nanotubes have little intrinsic merit as thermoacoustic contrast agents. Simple electrolytes such as saline which yield high contrast based on ionic conductivity provide much higher dielectric contrast per unit solute concentration and are likely to be significantly more effective as contrast agents.« less

Solute Transport of Negatively Charged Contrast Agents Across Articular Surface of Injured Cartilage.

PubMed

Kokkonen, H T; Chin, H C; Töyräs, J; Jurvelin, J S; Quinn, T M

2017-04-01

Solute transport through the extracellular matrix (ECM) is crucial to chondrocyte metabolism. Cartilage injury affects solute transport in cartilage due to alterations in ECM structure and solute-matrix interactions. Therefore, cartilage injury may be detected by using contrast agent-based clinical imaging. In the present study, effects of mechanical injury on transport of negatively charged contrast agents in cartilage were characterized. Using cartilage plugs injured by mechanical compression protocol, effective partition coefficients and diffusion fluxes of iodine- and gadolinium-based contrast agents were measured using high resolution microCT imaging. For all contrast agents studied, effective diffusion fluxes increased significantly, particularly at early times during the diffusion process (38 and 33% increase after 4 min, P < 0.05 for iodine and Gd-DTPA; and 76% increase after 10 min for diatrizoate, P < 0.05). Effective partition coefficients were unaffected in mechanically injured cartilage. Mechanical injury reduced PG content and collagen integrity in cartilage superficial zone. This study suggests that alterations in contrast agent diffusion flux, a non-equilibrium transport parameter, provides a more sensitive indicator for assessment of cartilage matrix integrity than partition coefficient and the equilibrium distribution of solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

Pediatric Patients Demonstrate Progressive T1-Weighted Hyperintensity in the Dentate Nucleus following Multiple Doses of Gadolinium-Based Contrast Agent.

PubMed

Roberts, D R; Chatterjee, A R; Yazdani, M; Marebwa, B; Brown, T; Collins, H; Bolles, G; Jenrette, J M; Nietert, P J; Zhu, X

2016-12-01

While there have been recent reports of brain retention of gadolinium following gadolinium-based contrast agent administration in adults, a retrospective series of pediatric patients has not previously been reported, to our knowledge. We investigated the relationship between the number of prior gadolinium-based contrast agent doses and increasing T1 signal in the dentate nucleus on unenhanced T1-weighted MR imaging. We hypothesized that despite differences in pediatric physiology and the smaller gadolinium-based contrast agent doses that pediatric patients are typically administered based on weighted-adjusted dosing, the pediatric brain would also demonstrate dose-dependent increasing T1 signal in the dentate nucleus. We included children with multiple gadolinium-based contrast agent administrations at our institution. A blinded reader placed ROIs within the dentate nucleus and adjacent cerebellar white matter. To eliminate reader bias, we also performed automated ROI delineation of the dentate nucleus, cerebellar white matter, and pons. Dentate-to-cerebellar white matter and dentate-to pons ratios were compared with the number of gadolinium-based contrast agent administrations. During 20 years at our institution, 280 patients received at least 5 gadolinium-based contrast agent doses, with 1 patient receiving 38 doses. Sixteen patients met the inclusion/exclusion criteria for ROI analysis. Blinded reader dentate-to-cerebellar white matter ratios were significantly associated with gadolinium-based contrast agent doses (r s = 0.77, P = .001). The dentate-to-pons ratio and dentate-to-cerebellar white matter ratios based on automated ROI placement were also significantly correlated with gadolinium-based contrast agent doses (t = 4.98, P < .0001 and t = 2.73, P < .02, respectively). In pediatric patients, the number of prior gadolinium-based contrast agent doses is significantly correlated with progressive T1-weighted dentate hyperintensity. Definitive confirmation of gadolinium deposition requires tissue analysis. Any potential clinical sequelae of gadolinium retention in the developing brain are unknown. Given this uncertainty, we suggest taking a cautious stance, including the use, in pediatric patients, of higher stability, macrocyclic agents, which in both human and animal studies have been shown to be associated with lower levels of gadolinium deposition, and detailed documentation of dosing. Most important, a patient should not be deprived of a well-indicated contrasted MR examination. © 2016 by American Journal of Neuroradiology.

Molecular Contrast Optical Coherence Tomography: A Review¶

PubMed Central

Yang, Changhuei

2005-01-01

This article reviews the current state of research on the use of molecular contrast agents in optical coherence tomography (OCT) imaging techniques. After a brief discussion of the basic principle of OCT and the importance of incorporating molecular contrast agent usage into this imaging modality, we shall present an overview of the different molecular contrast OCT (MCOCT) methods that have been developed thus far. We will then discuss several important practical issues that define the possible range of contrast agent choice, the design criteria for engineered molecular contrast agent and the implementability of a given MCOCT method for clinical or biological applications. We will conclude by outlining a few areas of pursuit that deserve a greater degree of research and development. PMID:15588122

Preparation and Characterization of WS2@SiO2 and WS2@PANI Core-Shell Nanocomposites

PubMed Central

Sade, Hagit

2018-01-01

Two tungsten disulfide (WS2)-based core-shell nanocomposites were fabricated using readily available reagents and simple procedures. The surface was pre-treated with a surfactant couple in a layer-by-layer approach, enabling good dispersion of the WS2 nanostructures in aqueous media and providing a template for the polymerization of a silica (SiO2) shell. After a Stöber-like reaction, a conformal silica coating was achieved. Inspired by the resulting nanocomposite, a second one was prepared by reacting the surfactant-modified WS2 nanostructures with aniline and an oxidizing agent in an aqueous medium. Here too, a conformal coating of polyaniline (PANI) was obtained, giving a WS2@PANI nanocomposite. Both nanocomposites were analyzed by electron microscopy, energy dispersive X-ray spectroscopy (EDS) and FTIR, verifying the core-shell structure and the character of shells. The silica shell was amorphous and mesoporous and the surface area of the composite increases with shell thickness. Polyaniline shells slightly differ in their morphologies dependent on the acid used in the polymerization process and are amorphous like the silica shell. Electron paramagnetic resonance (EPR) spectroscopy of the WS2@PANI nanocomposite showed variation between bulk PANI and the PANI shell. These two nanocomposites have great potential to expand the use of transition metals dichalcogenides (TMDCs) for new applications in different fields. PMID:29534426

Engineering biofunctional magnetic nanoparticles for biotechnological applications

NASA Astrophysics Data System (ADS)

Moros, Maria; Pelaz, Beatriz; López-Larrubia, Pilar; García-Martin, Maria L.; Grazú, Valeria; de La Fuente, Jesus M.

2010-09-01

Synthesis and characterization of magnetic nanoparticles with excellent size control are showed here. Their functionalization using an amphiphilic polymer is also described. This strategy allows the stabilization of magnetic nanoparticles in aqueous solvents and in addition, the polymer shell serves as a platform to incorporate relevant biomolecules, such as poly(ethylene glycol) and a number of carbohydrates. Nanoparticles functionalized with carbohydrates show the ability to avoid unspecific interactions between proteins present in the working medium and the nanoparticles, so can be used as an alternative to poly(ethylene glycol) molecules. Results confirm these nanoparticles as excellent contrast agents for magnetic resonance imaging. Changes in the spin-spin transversal relaxation times of the surrounding water protons due to nanoparticle aggregation demonstrates the bioactivity of these nanoparticles functionalized with carbohydrates. To finish with, nanoparticle toxicity is evaluated by means of MTT assay. The obtained results clearly indicate that these nanoparticles are excellent candidates for their further application in nanomedicine or nanobiotechnology.Synthesis and characterization of magnetic nanoparticles with excellent size control are showed here. Their functionalization using an amphiphilic polymer is also described. This strategy allows the stabilization of magnetic nanoparticles in aqueous solvents and in addition, the polymer shell serves as a platform to incorporate relevant biomolecules, such as poly(ethylene glycol) and a number of carbohydrates. Nanoparticles functionalized with carbohydrates show the ability to avoid unspecific interactions between proteins present in the working medium and the nanoparticles, so can be used as an alternative to poly(ethylene glycol) molecules. Results confirm these nanoparticles as excellent contrast agents for magnetic resonance imaging. Changes in the spin-spin transversal relaxation times of the surrounding water protons due to nanoparticle aggregation demonstrates the bioactivity of these nanoparticles functionalized with carbohydrates. To finish with, nanoparticle toxicity is evaluated by means of MTT assay. The obtained results clearly indicate that these nanoparticles are excellent candidates for their further application in nanomedicine or nanobiotechnology. Electronic supplementary information (ESI) available: Chemical, physical and magnetic characterization; R2 maps; stability of NPs at different conditions; size of glucose NPs in the presence of Concanavalin A; MTT assays of the samples are shown in figures S1-S10. Table S1 represents the hydrodynamic size of PMAO NPs after being washed with different solvents. See DOI: 10.1039/c0nr00104j

Preparation of Activated Carbon from Palm Shells Using KOH and ZnCl2 as the Activating Agent

NASA Astrophysics Data System (ADS)

Yuliusman; Nasruddin; Afdhol, M. K.; Amiliana, R. A.; Hanafi, A.

2017-07-01

Palm shell is a potential source of raw materials for the produce of activated carbon as biosorbent for quite large numbers. The purpose of this study is to produce activated carbon qualified Indonesian Industrial Standard (SNI), which will be used as biosorbent to purify the impurities in the off gas petroleum refinery products. Stages of manufacture of activated carbon include carbonization, activation of chemistry and physics. Carbonization of activated carbon is done at a temperature of 400°C followed by chemical activation with active agent KOH and ZnCl2. Then the physical activation is done by flowing N2 gas for 1 hour at 850°C and followed by gas flow through the CO2 for 1 hour at 850°C. Research results indicate that activation of the active agent KOH produce activated carbon is better than using the active agent ZnCl2. The use of KOH as an active agent to produce activated carbon with a water content of 13.6%, ash content of 9.4%, iodine number of 884 mg/g and a surface area of 1115 m2/g. While the use of ZnCl2 as the active agent to produce activated carbon with a water content of 14.5%, total ash content of 9.0%, iodine number 648 mg/g and a surface area of 743 m2/g.

Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

NASA Astrophysics Data System (ADS)

Shan, Liang; Gu, Xinbin; Wang, Paul

2013-09-01

Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

Fabrication of a transparent ultraviolet detector by using n-type Ga2O3 and p-type Ga-doped SnO2 core-shell nanowires.

PubMed

Hsu, Cheng-Liang; Lu, Ying-Ching

2012-09-21

This study investigates the feasibility of synthesizing high-density transparent Ga(2)O(3)/SnO(2):Ga core-shell nanowires on a sapphire substrate at 1000 °C by VLS. The doping Ga concentrations are 0.46, 1.07, 2.30 and 17.53 atomic%. The XRD spectrum and HR-TEM reveal Ga(2)O(3) and SnO(2) as having monoclinic and tetragonal rutile structures, respectively. Experimental results indicate that the XRD peak shift of SnO(2) to a larger angle increases with the increasing amount of Ga doping. According to the CL spectrum, SnO(2) and Ga(2)O(3) peak at approximately 528-568 nm and 422-424 nm, respectively. The maximum quantum efficiency of Ga(2)O(3)/SnO(2):Ga core-shell nanowires is around 0.362%. The UV light on-off current contrast ratio of Ga(2)O(3)/SnO(2):Ga core-shell nanowires is around 1066.7 at a bias of 5 V. Moreover, the dynamic response of Ga(2)O(3)/SnO(2):Ga core-shell nanowires has an on-off current contrast ratio of around 16. Furthermore, the Ga(2)O(3) region functions similar to a capacitor and continues to accumulate SnO(2):Ga excited electrons under UV light exposure.

Technical aspects of contrast-enhanced ultrasound (CEUS) examinations: tips and tricks.

PubMed

Greis, C

2014-01-01

Ultrasound contrast agents have substantially extended the clinical value of ultrasound, allowing the assessment of blood flow and distribution in real-time down to microcapillary level. Selective imaging of contrast agent signals requires a contrast-specific imaging mode on the ultrasound scanner, allowing real-time separation of tissue and contrast agent signals. The creation of a contrast image requires a specific interaction between the insonated ultrasound wave and the contrast agent microbubbles, leading to persistent oscillation of the bubbles. Several technical and procedural parameters have a significant influence on the quality of CEUS images and should be controlled carefully to obtain good image quality and a reliable diagnosis. Achieving the proper balance between the respective parameters is a matter of technical knowledge and experience. Appropriate training and education should be mandatory for every investigator performing CEUS examinations.

Pre-clinical evaluation of a nanoparticle-based blood-pool contrast agent for MR imaging of the placenta.

PubMed

Ghaghada, Ketan B; Starosolski, Zbigniew A; Bhayana, Saakshi; Stupin, Igor; Patel, Chandreshkumar V; Bhavane, Rohan C; Gao, Haijun; Bednov, Andrey; Yallampalli, Chandrasekhar; Belfort, Michael; George, Verghese; Annapragada, Ananth V

2017-09-01

Non-invasive 3D imaging that enables clear visualization of placental margins is of interest in the accurate diagnosis of placental pathologies. This study investigated if contrast-enhanced MRI performed using a liposomal gadolinium blood-pool contrast agent (liposomal-Gd) enables clear visualization of the placental margins and the placental-myometrial interface (retroplacental space). Non-contrast MRI and contrast-enhanced MRI using a clinically approved conventional contrast agent were used as comparators. Studies were performed in pregnant rats under an approved protocol. MRI was performed at 1T using a permanent magnet small animal scanner. Pre-contrast and post-liposomal-Gd contrast images were acquired using T1-weighted and T2-weighted sequences. Dynamic Contrast enhanced MRI (DCE-MRI) was performed using gadoterate meglumine (Gd-DOTA, Dotarem ® ). Visualization of the retroplacental clear space, a marker of normal placentation, was judged by a trained radiologist. Signal-to-noise (SNR) and contrast-to-noise (CNR) ratios were calculated for both single and averaged acquisitions. Images were reviewed by a radiologist and scored for the visualization of placental features. Contrast-enhanced CT (CE-CT) imaging using a liposomal CT agent was performed for confirmation of the MR findings. Transplacental transport of liposomal-Gd was evaluated by post-mortem elemental analysis of tissues. Ex-vivo studies in perfused human placentae from normal, GDM, and IUGR pregnancies evaluated the transport of liposomal agent across the human placental barrier. Post-contrast T1w images acquired with liposomal-Gd demonstrated significantly higher SNR (p = 0.0002) in the placenta compared to pre-contrast images (28.0 ± 4.7 vs. 6.9 ± 1.8). No significant differences (p = 0.39) were noted between SNR in pre-contrast and post-contrast liposomal-Gd images of the amniotic fluid, indicating absence of transplacental passage of the agent. The placental margins were significantly (p < 0.001) better visualized on post-contrast liposomal-Gd images. DCE-MRI with the conventional Gd agent demonstrated retrograde opacification of the placenta from fetal edge to the myometrium, consistent with the anatomy of the rat placenta. However, no consistent and reproducible visualization of the retroplacental space was demonstrated on the conventional Gd-enhanced images. The retroplacental space was only visualized on post-contrast T1w images acquired using the liposomal agent (SNR = 15.5 ± 3.4) as a sharply defined, hypo-enhanced interface. The retroplacental space was also visible as a similar hypo-enhancing interface on CE-CT images acquired using a liposomal CT contrast agent. Tissue analysis demonstrated undetectably low transplacental permeation of liposomal-Gd, and was confirmed by lack of permeation through a perfused human placental model. Contrast-enhanced T1w-MRI performed using liposomal-Gd enabled clear visualization of placental margins and delineation of the retroplacental space from the rest of the placenta; the space is undetectable on non-contrast imaging and on post-contrast T1w images acquired using a conventional, clinically approved Gd chelate contrast agent. Copyright © 2017 Elsevier Ltd. All rights reserved.

Investigation of star polymer nanoshells for use in diagnostic imaging and photothermal cancer therapy applications

NASA Astrophysics Data System (ADS)

Gomez, Lizabeth

Gold nanoshells can be designed to possess high light scattering and strong absorption of near-infrared light. Thus, they have the potential to be used in biological applications as contrast agents for diagnostic imaging as well as for thermal ablation of tumor cells in future cancer treatments. In this study, gold nanoshells with dye-loaded star polymer cores were investigated. Uniform near-infrared gold nanoshells with 100 nm diameters were successfully generated using different batches of star polymer templates and were characterized by UV-visible spectroscopy and scanning electron microscopy. The star polymers used were block copolymer structures with a hydrophobic polystyrene (PS) core and a hydrophilic poly(N,N-dimethylaminoethylmethracrylate) (DMAEMA) outer shell. Within this work, a general procedure was established in order to achieve a desired gold nanoshell size regardless of the star polymer batch used, since the synthesis process conditions can cause star polymers to vary in size as well in the number and length of amino-functionalized arms. Control of the gold nanoshell diameter was optimized after an in-depth analysis of the synthesis parameters that affected the formation and final size of the dye-loaded star polymer gold nanoshells. The main parameters examined were pH of the gold seeds used to nucleate the templates and the ratio of star polymer to gold hydroxide used during the growth of the outer gold shell.

Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T1 contrast ability

NASA Astrophysics Data System (ADS)

Ni, Kaiyuan; Zhao, Zhenghuan; Zhang, Zongjun; Zhou, Zijian; Yang, Li; Wang, Lirong; Ai, Hua; Gao, Jinhao

2016-02-01

High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM-1 s-1. Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis. Electronic supplementary information (ESI) available: Supplementary Fig. S1-S6. See DOI: 10.1039/c5nr08402d

Biophysical characterization of hydrogel-core, lipid-shell nanoparticles (nanolipogels) for HIV chemoprophylaxis

NASA Astrophysics Data System (ADS)

Mahadevan, Reena

Nanoparticles are emerging as versatile vehicles for drug delivery, providing targeting, protection, and controlled-release capabilities to encapsulated cargo. Polymeric nanoparticles made from poly(lactide-co-glycolide) (PLGA) are biodegradable, exhibit tunable drug release, and have encapsulated a wide variety of biological agents. However, PLGA nanoparticles are relatively inefficient at encapsulating small-molecule hydrophilic drugs. Liposomes encapsulate greater amounts of hydrophilic agents and demonstrate good cellular affinity; however, they lack controlled-release functionality. Hydrogel-core lipid-shell nanoparticles, or nanolipogels, combine the controlled-release capability of polymeric nanocarriers with the hydrophilic and cellular affinity of liposomes into a single drug delivery vehicle. This study establishes a facile, reproducible synthetic protocol for nanolipogels and evaluates hydrogel swelling as a mechanism for release of the small hydrophilic antiretroviral azidothymidine from nanolipogels.

Gadolinium-based magnetic resonance imaging contrast agents in interventional radiology.

PubMed

Atar, Eli

2004-07-01

Gadolinium-based agents are widely used in magnetic resonance imaging as contrast agents. These agents are radio-opaque enough for diagnostic imaging of the vascular tree by using digitally subtracted images as well as for imaging of the biliary system and the urinary tract. The recommended doses for gadolinium do not impair renal function or cause adverse reactions in patients with iodine sensitivity; thus patients with such conditions can safely undergo diagnostic angiography, either by MRI angiography or by catheterization using gadolinium as contrast agent, for diagnostic and therapeutic purposes.

High potential of Mn-doped ZnS nanoparticles with different dopant concentrations as novel MRI contrast agents: synthesis and in vitro relaxivity studies

NASA Astrophysics Data System (ADS)

Jahanbin, Tania; Gaceur, Meriem; Gros-Dagnac, Hélène; Benderbous, Soraya; Merah, Souad Ammar

2015-06-01

Over several decades, metal-doped quantum dots (QDs) with core-shell structure have been studied as dual probes: fluorescence and magnetic resonance imaging (MRI) probes (Dixit et al., Mater Lett 63(30):2669-2671, 2009). However, metal-doped nanoparticles, in which the majority of metal ions are close to the surface, can affect their efficacy as MRI contrast agents (CAs). In this context, herein the high potential of synthesized Mn-doped ZnS QDs via polyol method as imaging probe is demonstrated. The mean diameters of QDs were measured via transmission electron microscopy (TEM) and X-ray diffraction (XRD). Optical and magnetic properties of MnZnS nanoparticles were characterized using fluorescence spectroscopy and super quanducting interference devices magnetometer and electron paramagnetic resonance system, respectively. T1- and T2-weighted images of nanoparticles in aqueous solution were acquired from spin-echo sequences at 3 T. From TEM images and XRD spectra of the prepared nanoparticles, it is observed that the average diameter of particles does not significantly change with Mn dopant content ( 1.6-1.9 nm). All three samples exhibit broad blue emission under UV light excitation. According to the MRI studies, MnZnS nanoparticles generate strong T1 contrast enhancement (bright T1-weighted images) at the low concentration (<0.1 mM). The MnZnS nanoparticles exhibit the high longitudinal ( r 1) relaxivity that increases from 20.34 to 75.5 mM-1 s-1 with the Mn dopant contents varying between 10 and 30 %. Strong signal intensity on T1-weighted images and high r 1 with {r2 }/{r_{1 }} ≈ 1 can demonstrate the high potential of the synthesized Mn:ZnS nanoparticles, which can serve as an effective T1 CA.

Iron Oxide as an MRI Contrast Agent for Cell Tracking

PubMed Central

Korchinski, Daniel J.; Taha, May; Yang, Runze; Nathoo, Nabeela; Dunn, Jeff F.

2015-01-01

Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation. PMID:26483609

Thermal Expansion Measurements of Polymer Matrix Composites and Syntactics

DTIC Science & Technology

1992-04-01

828 (Shell Chemical) epoxy combined with 50.0 PBW EPON® V-40 polyamide curing agent (Shell Chemical) and Owens Corning (E-780) polyester combined 1...with 24 oz. woven roving with an Owens Corning 463 finish. " A 3 x 1, S-2 glass with 27 oz. woven roving with an Owens Corning 933 finish, nominally...wet polyester resin ( Owens Corning E-780) and subsequently processing the composites using the standard vacuum bag cure cycle for this polyester

Counter-propagating wave interaction for contrast-enhanced ultrasound imaging

NASA Astrophysics Data System (ADS)

Renaud, G.; Bosch, J. G.; ten Kate, G. L.; Shamdasani, V.; Entrekin, R.; de Jong, N.; van der Steen, A. F. W.

2012-11-01

Most techniques for contrast-enhanced ultrasound imaging require linear propagation to detect nonlinear scattering of contrast agent microbubbles. Waveform distortion due to nonlinear propagation impairs their ability to distinguish microbubbles from tissue. As a result, tissue can be misclassified as microbubbles, and contrast agent concentration can be overestimated; therefore, these artifacts can significantly impair the quality of medical diagnoses. Contrary to biological tissue, lipid-coated gas microbubbles used as a contrast agent allow the interaction of two acoustic waves propagating in opposite directions (counter-propagation). Based on that principle, we describe a strategy to detect microbubbles that is free from nonlinear propagation artifacts. In vitro images were acquired with an ultrasound scanner in a phantom of tissue-mimicking material with a cavity containing a contrast agent. Unlike the default mode of the scanner using amplitude modulation to detect microbubbles, the pulse sequence exploiting counter-propagating wave interaction creates no pseudoenhancement behind the cavity in the contrast image.

Development of a platform for co-registered ultrasound and MR contrast imaging in vivo

NASA Astrophysics Data System (ADS)

Chandrana, Chaitanya; Bevan, Peter; Hudson, John; Pang, Ian; Burns, Peter; Plewes, Donald; Chopra, Rajiv

2011-02-01

Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.

High-Accuracy Ultrasound Contrast Agent Detection Method for Diagnostic Ultrasound Imaging Systems.

PubMed

Ito, Koichi; Noro, Kazumasa; Yanagisawa, Yukari; Sakamoto, Maya; Mori, Shiro; Shiga, Kiyoto; Kodama, Tetsuya; Aoki, Takafumi

2015-12-01

An accurate method for detecting contrast agents using diagnostic ultrasound imaging systems is proposed. Contrast agents, such as microbubbles, passing through a blood vessel during ultrasound imaging are detected as blinking signals in the temporal axis, because their intensity value is constantly in motion. Ultrasound contrast agents are detected by evaluating the intensity variation of a pixel in the temporal axis. Conventional methods are based on simple subtraction of ultrasound images to detect ultrasound contrast agents. Even if the subject moves only slightly, a conventional detection method will introduce significant error. In contrast, the proposed technique employs spatiotemporal analysis of the pixel intensity variation over several frames. Experiments visualizing blood vessels in the mouse tail illustrated that the proposed method performs efficiently compared with conventional approaches. We also report that the new technique is useful for observing temporal changes in microvessel density in subiliac lymph nodes containing tumors. The results are compared with those of contrast-enhanced computed tomography. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Quantitative Differences Between the First and Second Injection of Contrast Agent in Contrast-Enhanced Ultrasonography of Feline Kidneys and Spleen.

PubMed

Stock, Emmelie; Vanderperren, Katrien; Haers, Hendrik; Duchateau, Luc; Hesta, Myriam; Saunders, Jimmy H

2017-02-01

Contrast-enhanced ultrasound is a valuable and safe technique for the evaluation of organ perfusion. Repeated injections of ultrasound contrast agent are often administered during the same imaging session. However, it remains unclear if quantitative differences are present between the consecutive microbubble injections. Therefore, the first and second injection of contrast agent for the left renal cortex, renal medulla and the splenic parenchyma in healthy cats were compared. A lower peak intensity and area under the curve were observed for the first injection of contrast agent in the feline kidney, both for the renal cortex and medulla, and spleen. Moreover, for the renal cortex, the time-intensity curve was steeper after the second injection. Findings from the present study demonstrate that a second injection of contrast agent provides stronger enhancement. The exact mechanism behind our findings remains unclear; however, saturation of the lung macrophages is believed to play an important role. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

The use of iohexol as oral contrast for computed tomography of the abdomen and pelvis.

PubMed

Horton, Karen M; Fishman, Elliot K; Gayler, Bob

2008-01-01

Positive oral contrast agents (high-osmolar iodinated solutions [high-osmolar contrast medium] or barium sulfate suspensions) are used routinely for abdominal computed tomography. However, these agents are not ideal. Patients complain about the taste and, sometimes, refuse to drink the required quantity. Nausea, vomiting, and diarrhea are frequent. In certain clinical indications, either barium suspensions or high-osmolar contrast mediums may be contraindicated. This technical note describes the potential advantages of using low-osmolar iodinated solutions as an oral contrast agent for computed tomography.

Gadolinium-based magnetic resonance contrast agents at 7 Tesla: in vitro T1 relaxivities in human blood plasma.

PubMed

Noebauer-Huhmann, Iris M; Szomolanyi, Pavol; Juras, Vladimír; Kraff, Oliver; Ladd, Mark E; Trattnig, Siegfried

2010-09-01

PURPOSE/INTRODUCTION: The aim of this study was to determine the T1 relaxivities (r1) of 8 gadolinium (Gd)-based MR contrast agents in human blood plasma at 7 Tesla, compared with 3 Tesla. Eight commercially available Gd-based MR contrast agents were diluted in human blood plasma to concentrations of 0, 0.25, 0.5, 1, and 2 mmol/L. In vitro measurements were performed at 37 degrees C, on a 7 Tesla and on a 3 Tesla whole-body magnetic resonance imaging scanner. For the determination of T1 relaxation times, Inversion Recovery Sequences with inversion times from 0 to 3500 ms were used. The relaxivities were calculated. The r1 relaxivities of all agents, diluted in human blood plasma at body temperature, were lower at 7 Tesla than at 3 Tesla. The values at 3 Tesla were comparable to those published earlier. Notably, in some agents, a minor negative correlation of r1 with a concentration of up to 2 mmol/L could be observed. This was most pronounced in the agents with the highest protein-binding capacity. At 7 Tesla, the in vitro r1 relaxivities of Gd-based contrast agents in human blood plasma are lower than those at 3 Tesla. This work may serve as a basis for the application of Gd-based MR contrast agents at 7 Tesla. Further studies are required to optimize the contrast agent dose in vivo.

Superparamagnetic And Paramagnetic MRI Contrast Agents: Application Of Rapid Magnetic Resonance Imaging To Assess Renal Function

NASA Astrophysics Data System (ADS)

Carvlin, Mark J.; Renshaw, Perry F.; Arger, Peter; Kundel, Harold L.; Dougherty, Larry; Axel, Leon; Kassab, Eleanor; Moore, Bethanne

1988-06-01

The paramagnetic chelate complex, gadolinium-diethylene-triamine-pentaacetic acid, Gd-DTPA, and superparamagnetic particles, such as those composed of dextran coated magnetite, function as magnetic resonance contrast agents by changing the relaxation rates, 1/T1 and 1/T2. The effects that these agents have upon MR signal intensity are determined by: the inherent biophysical properties of the tissue being imaged, the concentration of the contrast agent and the data acquisition scheme (pulse sequence parameters) employed. Following the time course of MR signal change in the first minutes after the injection of contrast agent(s) allows a dynamic assessment of organ functions in a manner analogous to certain nuclear medicine studies. In order to study renal function, sequential MR fast scan images, gradient echo (TR=35/TE=7 msec, flip angle=25 degrees), were acquired, one every 12 seconds, after intravenous injection of Gd-DTPA and/or dextran-magnetite. Gd-DTPA, which is freely filtered at the glomerulus and is neither secreted nor reabsorbed, provides information concerning renal perfusion, glomerular filtration and tubular concentrating ability. Dextran-magnetite (200 A diameter), which is primarily contained within the intravascular space shortly after injection, provides information on blood flow to and distribution within the kidney. The MR signal change observed after administration of contrast agents varied dramatically depending upon the agents injected and the imaging parameters used. Hence a broad range of physiolgic processes may be described using these techniques, i.e. contrast agent enhanced functional MR examinations.

Fabrication of Fe3O4@mSiO2 Core-Shell Composite Nanoparticles for Drug Delivery Applications

NASA Astrophysics Data System (ADS)

Uribe Madrid, Sergio I.; Pal, Umapada; Kang, Young Soo; Kim, Junghoon; Kwon, Hyungjin; Kim, Jungho

2015-05-01

We report the synthesis of Fe3O4@mSiO2 nanostructures of different meso-silica (mSiO2) shell thickness, their biocompatibility and behaviors for loading and release of a model drug ibuprofen. The composite nanostructures have superparamagnetic magnetite cores of 208 nm average size and meso-silica shells of 15 to 40 nm thickness. A modified Stöber method was used to grow the meso-silica shells over the hydrothermally grown monodispersed magnetite particles. The composite nanoparticles show very promising drug holding and releasing behaviors, which depend on the thickness of meso-silica shell. The biocompatibility of the meso-silica-coated and uncoated magnetite nanoparticles was tested through cytotoxicity assay on breast cancer (MCF-7), ovarian cancer (SKOV3), normal human lung fibroblasts MRC-5, and IMR-90 cells. The high drug holding capacity and reasonable biocompatibility of the nanostructures make them ideal agents for targeted drug delivery applications in human body.

Luminescence study of Eu3+ doped GdVO4 nanoparticles: Concentration, particle size, and core/shell effects

NASA Astrophysics Data System (ADS)

Singh, N. Shanta; Ningthoujam, R. S.; Devi, L. Romila; Yaiphaba, N.; Sudarsan, V.; Singh, S. Dorendrajit; Vatsa, R. K.; Tewari, R.

2008-11-01

Nanoparticles of GdVO4 doped with Eu3+ and core/shell of GdVO4:Eu3+/GdVO4 are prepared by urea hydrolysis method using ethylene glycol as capping agent as well as reaction medium at 130 °C. Unit cell volume increases when GdVO4 is doped with Eu3+ indicating the substitution of Gd3+ lattice sites by Eu3+. From luminescence study, it is confirmed that there is no particle size effect on emission positions of Eu3+. Optimum luminescence intensity is found to be in 5-10 at. % Eu3+. Above these concentrations, luminescence intensity decreases due to concentration quenching effect. There is an enhancement in luminescence intensity of core/shell nanoparticles. This has been attributed to the reduction in surface inhomogenities of Eu3+ surroundings by bonding to GdVO4 shell. The lifetime for D50 level increases with annealing and core/shell formation.

Toward “Green” Hybrid Materials: Core–Shell Particles with Enhanced Impact Energy Absorbing Ability

PubMed Central

2016-01-01

Restrained properties of “green” degradable products drive the creation of materials with innovative structures and retained eco-attributes. Herein, we introduce the creation of impact modifiers in the form of core–shell (CS) particles toward the creation of “green” composite materials. Particles with CS structure constituted of PLA stereocomplex (PLASC) and a rubbery phase of poly(ε-caprolactone-co-d,l-lactide) (P[CL-co-LA]) were successfully achieved by spray droplet atomization. A synergistic association of the soft P[CL-co-LA] and hard PLASC domains in the core–shell structure induced unique thermo-mechanical effects on the PLA-based composites. The core–shell particles enhanced the crystallization of PLA matrices by acting as nucleating agents. The core–shell particles functioned efficiently as impact modifiers with minimal effect on the composites stiffness and strength. These findings provide a new platform for scalable design of polymeric-based structures to be used in the creation of advanced degradable materials. PMID:29503773

Highly luminescent core-shell InP/ZnX (X = S, Se) quantum dots prepared via a phosphine synthetic route.

PubMed

Mordvinova, Natalia; Vinokurov, Alexander; Kuznetsova, Tatiana; Lebedev, Oleg I; Dorofeev, Sergey

2017-01-24

Here we report a simple method for the creation of highly luminescent core-shell InP/ZnX (X = S, Se) quantum dots (QDs) on the basis of a phosphine synthetic route. In this method a Zn precursor was added to the reaction mixture at the beginning of the synthesis to form an In(Zn)P alloy structure, which promoted the formation of a ZnX shell. Core-shell InP/ZnX QDs exhibit highly intensive emission with a quantum yield over 50%. The proposed method is primarily important for practical applications. Advantages of this method compared to the widely used SILAR technique are discussed. We further demonstrate that the SILAR approach consisting of consequent addition of Zn and chalcogen precursors to pre-prepared non-doped InP colloidal nanoparticles is not quite suitable for shell growth without the addition of special activator agents or the use of very reactive precursors.

The Study of Blocking Agent on Lengkeng (Euphoria Logan Lour) Fruit Shell and Seed for Adsorption of Pb (II) from Aqueous Solution

NASA Astrophysics Data System (ADS)

Kurniawati, D.; Zein, R.; Chaidir, Z.; Aziz, H.

2018-04-01

The study focuses on the roles played by mayor functional groups(carboxyl) in the lengkeng shell for sorption of Pb (II). The biosorbent was characterized by FTIR and elemental analyses. The parameters such as pH, initial concentration, particle sizes, adsorbent dose and flow rate were also studied. The results showed that the optimum condition was at pH = 3, concentration 400 mg/l, 250 μm particle sizes, adsorbent dose 0,5 g and 2 ml/min flow rate with adsorption capacity 4,8933 mg/g(shell) and 5,2720 mg/g(seed). It is show that ion exchange play as a more important role in the sorption of Pb (II) on lengkeng shell and seed. Blocking of COOH groups by chemical esterification resulted in Pb important reduction in metal binding.The result showed that adsorption capacity of lengkeng shell uncreases until 63.67 % and lengkeng seed uncreases 98.70%.

Rigid shells enhance survival of gekkotan eggs.

PubMed

Andrews, Robin M

2015-11-01

The majority of lizards and snakes produce permeable parchment-shelled eggs that require high moisture conditions for successful embryonic development. One clade of gekkotan lizards is an exception; females produce relatively impermeable rigid-shelled eggs that normally incubate successfully under low moisture conditions. I tested the hypothesis that the rigid-shell increases egg survival during incubation, but only under low moisture conditions. To test this hypothesis, I incubated rigid-shelled eggs of Chondrodactylus turneri under low and under high moisture conditions. Eggs were incubated with parchment-shelled eggs of Eublepharis macularius to insure that incubation conditions were suitable for parchment-shelled eggs. Chondrodactylus turneri eggs had very high survival (>90%) when they were incubated under low moisture conditions. In contrast, eggs incubated under high moisture conditions had low survival overall, and lower survival than those of the parchment-shelled eggs of E. macularius. Mortality of C. turneri and E. macularius eggs incubated under high moisture conditions was the result of fungal infection, a common source of egg mortality for squamates under laboratory and field conditions. These observations document high survival of rigid-shelled eggs under low moisture conditions because eggs escape from fungal infection. Highly mineralized rigid shells also make egg survival independent of moisture availability and may also provide protection from small invertebrates in nature. Enhanced egg survival could thus compensate for the low reproductive output of gekkotans that produce rigid-shelled eggs. © 2015 Wiley Periodicals, Inc.

Impacts of Near-Future Ocean Acidification and Warming on the Shell Mechanical and Geochemical Properties of Gastropods from Intertidal to Subtidal Zones.

PubMed

Leung, Jonathan Y S; Connell, Sean D; Nagelkerken, Ivan; Russell, Bayden D

2017-11-07

Many marine organisms produce calcareous shells as the key structure for defense, but the functionality of shells may be compromised by ocean acidification and warming. Nevertheless, calcifying organisms may adaptively modify their shell properties in response to these impacts. Here, we examined how reduced pH and elevated temperature affect shell mechanical and geochemical properties of common grazing gastropods from intertidal to subtidal zones. Given the greater environmental fluctuations in the intertidal zone, we hypothesized that intertidal gastropods would exhibit more plastic responses in shell properties than subtidal gastropods. Overall, three out of five subtidal gastropods produced softer shells at elevated temperature, while intertidal gastropods maintained their shell hardness at both elevated pCO 2 (i.e., reduced pH) and temperature. Regardless of pH and temperature, degree of crystallization was maintained (except one subtidal gastropod) and carbonate polymorph remained unchanged in all tested species. One intertidal gastropod produced less soluble shells (e.g., higher calcite/aragonite) in response to reduced pH. In contrast, subtidal gastropods produced only aragonite which has higher solubility than calcite. Overall, subtidal gastropods are expected to be more susceptible than intertidal gastropods to shell dissolution and physical damage under future seawater conditions. The increased vulnerability to shell dissolution and predation could have serious repercussions for their survival and ecological contributions in the future subtidal environment.

Shell crosslinked nanoparticles carrying silver antimicrobials as therapeutics†

PubMed Central

Li, Yali; Hindi, Khadijah; Watts, Kristin M.; Taylor, Jane B.; Zhang, Ke; Li, Zicheng

2010-01-01

Amphiphilic polymer nanoparticles loaded with silver cations or/and N-heterocyclic carbene–silver complexes were assessed as antimicrobial agents against Gram-negative pathogens Escherichia coli and Pseudomonas aeruginosa. PMID:20024313

Biodegradable polymer based theranostic agents for photoacoustic imaging and cancer therapy

NASA Astrophysics Data System (ADS)

Wang, Yan J.; Strohm, Eric M.; Kolios, Michael C.

2016-03-01

In this study, multifunctional theranostic agents for photoacoustic (PA), ultrasound (US), fluorescent imaging, and for therapeutic drug delivery were developed and tested. These agents consisted of a shell made from a biodegradable Poly(lactide-co-glycolic acid) (PLGA) polymer, loaded with perfluorohexane (PFH) liquid and gold nanoparticles (GNPs) in the core, and lipophilic carbocyanines fluorescent dye DiD and therapeutic drug Paclitaxel (PAC) in the shell. Their multifunctional capacity was investigated in an in vitro study. The PLGA/PFH/DiD-GNPs particles were synthesized by a double emulsion technique. The average PLGA particle diameter was 560 nm, with 50 nm diameter silica-coated gold nano-spheres in the shell. MCF7 human breast cancer cells were incubated with PLGA/PFH/DiDGNPs for 24 hours. Fluorescent and PA images were recorded using a fluorescent/PA microscope using a 1000 MHz transducer and a 532 nm pulsed laser. For the particle vaporization and drug delivery test, MCF7 cells were incubated with the PLGA/PFH-GNPs-PAC or PLGA/PFH-GNPs particles for 6, 12 and 24 hours. The effects of particle vaporization and drug delivery inside the cells were examined by irradiating the cells with a laser fluence of 100 mJ/cm2, and cell viability quantified using the MTT assay. The PA images of MCF7 cells containing PLGA/PFH/DiD-GNPs were spatially coincident with the fluorescent images, and confirmed particle uptake. After exposure to the PLGA/PFHGNP- PAC for 6, 12 and 24 hours, the cell survival rate was 43%, 38%, and 36% respectively compared with the control group, confirming drug delivery and release inside the cells. Upon vaporization, cell viability decreased to 20%. The particles show potential as imaging agents and drug delivery vehicles.

Element-specific spectral imaging of multiple contrast agents: a phantom study

NASA Astrophysics Data System (ADS)

Panta, R. K.; Bell, S. T.; Healy, J. L.; Aamir, R.; Bateman, C. J.; Moghiseh, M.; Butler, A. P. H.; Anderson, N. G.

2018-02-01

This work demonstrates the feasibility of simultaneous discrimination of multiple contrast agents based on their element-specific and energy-dependent X-ray attenuation properties using a pre-clinical photon-counting spectral CT. We used a photon-counting based pre-clinical spectral CT scanner with four energy thresholds to measure the X-ray attenuation properties of various concentrations of iodine (9, 18 and 36 mg/ml), gadolinium (2, 4 and 8 mg/ml) and gold (2, 4 and 8 mg/ml) based contrast agents, calcium chloride (140 and 280 mg/ml) and water. We evaluated the spectral imaging performances of different energy threshold schemes between 25 to 82 keV at 118 kVp, based on K-factor and signal-to-noise ratio and ranked them. K-factor was defined as the X-ray attenuation in the K-edge containing energy range divided by the X-ray attenuation in the preceding energy range, expressed as a percentage. We evaluated the effectiveness of the optimised energy selection to discriminate all three contrast agents in a phantom of 33 mm diameter. A photon-counting spectral CT using four energy thresholds of 27, 33, 49 and 81 keV at 118 kVp simultaneously discriminated three contrast agents based on iodine, gadolinium and gold at various concentrations using their K-edge and energy-dependent X-ray attenuation features in a single scan. A ranking method to evaluate spectral imaging performance enabled energy thresholds to be optimised to discriminate iodine, gadolinium and gold contrast agents in a single spectral CT scan. Simultaneous discrimination of multiple contrast agents in a single scan is likely to open up new possibilities of improving the accuracy of disease diagnosis by simultaneously imaging multiple bio-markers each labelled with a nano-contrast agent.

Evolution of king crabs from hermit crab ancestors

NASA Astrophysics Data System (ADS)

Cunningham, C. W.; Blackstone, N. W.; Buss, L. W.

1992-02-01

KING crabs (Family Lithodidae) are among the world's largest arthropods, having a crab-like morphology and a strongly calcified exoskeleton1-6. The hermit crabs, by contrast, have depended on gastropod shells for protection for over 150 million years5,7. Shell-living has constrained the morphological evolution of hermit crabs by requiring a decalcified asymmetrical abdomen capable of coiling into gastropod shells and by preventing crabs from growing past the size of the largest available shells1-6. Whereas reduction in shell-living and acquisition of a crab-like morphology (carcinization) has taken place independently in several hermit crab lineages, and most dramatically in king crabs1-6, the rate at which this process has occurred was entirely unknown2,7. We present molecular evidence that king crabs are not only descended from hermit crabs, but are nested within the hermit crab genus Pagurus. We estimate that loss of the shell-living habit and the complete carcinization of king crabs has taken between 13 and 25 million years.

Strain-Driven Stacking Faults in CdSe/CdS Core/Shell Nanorods.

PubMed

Demortière, Arnaud; Leonard, Donovan N; Petkov, Valeri; Chapman, Karena; Chattopadhyay, Soma; She, Chunxing; Cullen, David A; Shibata, Tomohiro; Pelton, Matthew; Shevchenko, Elena V

2018-04-19

Colloidal semiconductor nanocrystals are commonly grown with a shell of a second semiconductor material to obtain desired physical properties, such as increased photoluminescence quantum yield. However, the growth of a lattice-mismatched shell results in strain within the nanocrystal, and this strain has the potential to produce crystalline defects. Here, we study CdSe/CdS core/shell nanorods as a model system to investigate the influence of core size and shape on the formation of stacking faults in the nanocrystal. Using a combination of high-angle annular dark-field scanning transmission electron microscopy and pair-distribution-function analysis of synchrotron X-ray scattering, we show that growth of the CdS shell on smaller, spherical CdSe cores results in relatively small strain and few stacking faults. By contrast, growth of the shell on larger, prolate spheroidal cores leads to significant strain in the CdS lattice, resulting in a high density of stacking faults.

Threefold rotational symmetry in hexagonally shaped core-shell (In,Ga)As/GaAs nanowires revealed by coherent X-ray diffraction imaging.

PubMed

Davtyan, Arman; Krause, Thilo; Kriegner, Dominik; Al-Hassan, Ali; Bahrami, Danial; Mostafavi Kashani, Seyed Mohammad; Lewis, Ryan B; Küpers, Hanno; Tahraoui, Abbes; Geelhaar, Lutz; Hanke, Michael; Leake, Steven John; Loffeld, Otmar; Pietsch, Ullrich

2017-06-01

Coherent X-ray diffraction imaging at symmetric hhh Bragg reflections was used to resolve the structure of GaAs/In 0.15 Ga 0.85 As/GaAs core-shell-shell nanowires grown on a silicon (111) substrate. Diffraction amplitudes in the vicinity of GaAs 111 and GaAs 333 reflections were used to reconstruct the lost phase information. It is demonstrated that the structure of the core-shell-shell nanowire can be identified by means of phase contrast. Interestingly, it is found that both scattered intensity in the (111) plane and the reconstructed scattering phase show an additional threefold symmetry superimposed with the shape function of the investigated hexagonal nanowires. In order to find the origin of this threefold symmetry, elasticity calculations were performed using the finite element method and subsequent kinematic diffraction simulations. These suggest that a non-hexagonal (In,Ga)As shell covering the hexagonal GaAs core might be responsible for the observation.

Seasonality in the Western Mediterranean During the Last Glacial From Paired Oxygen Isotopes and Mg/Ca in Limpet Shells

NASA Astrophysics Data System (ADS)

Ferguson, J. E.; Henderson, G. M.; Fa, D.; Finlayson, C.

2008-12-01

Molluscs have shown great potential to act as seasonal-resolution archives of sea-surface temperatures (SST) at mid to high latitudes, outside the range of tropical surface corals. Seasonal resolution climate records from higher latitudes are important to allow investigation of the role of seasonality in controlling mean climate on diverse timescales, and of the evolution of climate systems such as the North Atlantic Oscillation. Long sequences of intertidal mollusc shells are difficult to find due to sea level fluctuations over glacial- interglacial periods. This study makes use of Patella shells collected by Neanderthals and humans and transported inland to caves on Gibraltar over at least the last 120 kyrs. Some 30 fossil Patella shells were selected from several hundred excavated from Gorham's and Vanguard Caves at Gibraltar. Oxygen isotope analysis of micromilled samples of modern Patella shells from the Gibraltar coastline demonstrate that the shells accurately record absolute SSTs and capture more than 80% of the full seasonal range. Analysis of fossil Patella shells, dated using 14C, provides records of the change in absolute SST and seasonality during the last glacial. Paired Mg/Ca ratios of micromilled samples in modern Patella shells follow a consistent positive relationship with SST providing an independent paleothermometer, analogous with coral Sr/Ca. Applying this Mg/Ca-SST relationship to fossil Patella shells allows the independent reconstruction of the absolute values and range of SSTs and the reconstruction of seawater δ18O for the western Mediterranean. Results show a cooling of glacial summer SSTs from 36 kyr BP to the LGM with maximum cooling of glacial summer SSTs of 7.5 °C relative to modern. In contrast, winter SSTs show greater variability on millennial timescales with a maximum cooling of up to 10 °C. SST seasonality is therefore extended due to greater winter cooling but SST seasonality is highly variable as a result of large fluctuation in the extent of winter cooling. These results contrast with GCM model estimates of SST values and seasonality during the glacial.

Facile consecutive solvothermal growth of highly fluorescent InP/ZnS core/shell quantum dots using a safer phosphorus source.

PubMed

Byun, Ho-June; Song, Woo-Seuk; Yang, Heesun

2011-06-10

The work presents a facile, stepwise synthetic approach for the production of highly fluorescent InP/ZnS core/shell quantum dots (QDs) by using a safer phosphorus (P) precursor. First, InP quantum dots (QDs) were solvothermally prepared at 180 °C for 24 h by using a P source of P(N(CH(3))(2))(3). The as-grown InP QDs were consecutively placed in another solvothermal condition for ZnS shell overcoating. In contrast to the almost non-fluorescent InP QDs, due to their highly defective surface states, the ZnS-coated InP QDs were highly fluorescent as a result of effective surface passivation. After the shell growth, the resulting InP/ZnS core/shell QDs were subjected to a size-sorting processing, by which red- to green-emitting QDs with quantum yields (QYs) of 24-60% were produced. Solvothermal shell growth parameters such as the reaction time and Zn/In solution concentration ratio were varied and optimized toward the highest QYs of core/shell QDs.

Facile consecutive solvothermal growth of highly fluorescent InP/ZnS core/shell quantum dots using a safer phosphorus source

NASA Astrophysics Data System (ADS)

Byun, Ho-June; Song, Woo-Seuk; Yang, Heesun

2011-06-01

The work presents a facile, stepwise synthetic approach for the production of highly fluorescent InP/ZnS core/shell quantum dots (QDs) by using a safer phosphorus (P) precursor. First, InP quantum dots (QDs) were solvothermally prepared at 180 °C for 24 h by using a P source of P(N(CH3)2)3. The as-grown InP QDs were consecutively placed in another solvothermal condition for ZnS shell overcoating. In contrast to the almost non-fluorescent InP QDs, due to their highly defective surface states, the ZnS-coated InP QDs were highly fluorescent as a result of effective surface passivation. After the shell growth, the resulting InP/ZnS core/shell QDs were subjected to a size-sorting processing, by which red- to green-emitting QDs with quantum yields (QYs) of 24-60% were produced. Solvothermal shell growth parameters such as the reaction time and Zn/In solution concentration ratio were varied and optimized toward the highest QYs of core/shell QDs.

Tumor environment changed by combretastatin derivative (Cderiv) pretreatment that leads to effective tumor targeting, MRI studies, and antitumor activity of polymeric micelle carrier systems.

PubMed

Shiraishi, Kouichi; Harada, Yoshiko; Kawano, Kumi; Maitani, Yoshie; Hori, Katsuyoshi; Yanagihara, Kazuyoshi; Takigahira, Misato; Yokoyama, Masayuki

2012-01-01

To evaluate effect of a vascular disrupting agent, a combretastatin derivative (Cderiv), on tumor targeting for polymeric micelle carrier systems, containing either a diagnostic MRI contrast agent or a therapeutic anticancer drug. Cderiv was pre-administered 72 h before polymeric micelle MRI contrast agent injection. Accumulation of the MRI contrast agent in colon 26 murine tumor was evaluated with or without pretreatment of Cderiv by ICP and MRI. Significantly higher accumulation of the MRI contrast agent was found in tumor tissues when Cderiv was administered at 72 h before MRI contrast agent injection. T(1)-weighted images of the tumor exhibited substantial signal enhancement in tumor area at 24 h after the contrast agent injection. In T(1)-weighted images, remarkable T(1)-signal enhancements were observed in part of tumor, not in whole tumor. These results indicate that Cderiv pretreatment considerably enhanced the permeability of the tumor blood vessels. Antitumor activity of adriamycin encapsulated polymeric micelles with the Cderiv pretreatment suppressed tumor growth in 44As3 human gastric scirrhous carcinoma-bearing nude mice. Pretreatment of Cderiv enhanced tumor permeability, resulting in higher accumulation of polymeric micelle carrier systems in solid tumors.

Novel fluorescence nanobubbles for contrast-enhanced ultrasound imaging in rabbit VX2 hepatocellular carcinoma model

NASA Astrophysics Data System (ADS)

Yu, Houqiang; Wang, Wei; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

2017-03-01

Ultrasound contrast agents (UCAs) such as SonoVue or Optison have been used widely in clinic for contrast-enhanced vascular imaging. However, microbubbles UCAs display limitations in tumor-targeted imaging due to the large sizes, nanoscaled UCAs has consequently attracted increasing attentions. In this work, we synthesized nanobubbles (NBs) by ultrasonic cavitation method, then a fluorescent marker of Alexa Fluor 680 was conjugated to the shell in order to observe the localization of NBs in tumor tissue. Measurement of fundamental characteristics showed that the NBs had homogeneous distribution of mean diameter of 267.9 +/- 19.2 nm and polydispersity index of 0.410 +/- 0.056. To assess in vivo tumor-selectivity of NBs, we established the rabbits VX2 hepatocellular carcinoma model though surgical implantation method. After the rabbits were intravenous administered of NBs, contrast-enhanced sonograms was observed in the surrounding of VX2 tumor, which showed there are rich capillaries in the tumor periphery. We additionally investigated the toxic of the NBs by hematoxylin-eosin staining. The results indicated that the NBs is a biocompatible non-toxic lipid system. Furthermore, the VX2 tumors and major organs were analyzed using ex vivo fluorescence imaging to confirm the targeted selectivity of NBs, and the results verified that the NBs were capable of targeting VX2 tumor. Confocal laser scanning microscopy examination showed that the NBs can traverse the VX2 tumor capillaries and target to the hepatocellular carcinoma tumor cells. All these results suggested that the newly prepared NBs have a potential application in molecular imaging and tumor-targeting therapy.

GADOLINIUM(Gd)-BASED and Ion Oxide Nanoparticle Contrast Agents for Pre-Clinical and Clinical Magnetic Resonance Imaging (mri) Research

NASA Astrophysics Data System (ADS)

Ng, Thian C.

2012-06-01

It is known that one strength of MRI is its excellent soft tissue discrimination. It naturally provides sufficient contrast between the structural differences of normal and pathological tissues, their spatial extent and progression. However, to further extend its applications and enhance even more contrast for clinical studies, various Gadolinium (Gd)-based contrast agents have been developed for different organs (brain strokes, cancer, cardio-MRI, etc). These Gd-based contrast agents are paramagnetic compounds that have strong T1-effect for enhancing the contrast between tissue types. Gd-contrast can also enhance magnetic resonance angiography (CE-MRA) for studying stenosis and for measuring perfusion, vascular susceptibility, interstitial space, etc. Another class of contrast agents makes use of ferrite iron oxide nanoparticles (including Superparamagnetic Ion Oxide (SPIO) and Ultrasmall Superparamagnetic Iron Oxide (USPIO)). These nanoparticles have superior magnetic susceptibility effect and produce a drop in signal, namely in T2*-weighted images, useful for the determination of lymph nodes metastases, angiogenesis and arteriosclerosis plaques.

Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

PubMed Central

Nie, Liming

2015-01-01

Photoacoustic tomography (PAT) can offer structural, functional and molecular contrasts at scalable observation level. By ultrasonically overcoming the strong optical scattering, this imaging technology can reach centimeters penetration depth while retaining high spatial resolution in biological tissue. Recent extensive research has been focused on developing new contrast agents to improve the imaging sensitivity, specificity and efficiency. These emerging materials have substantially accelerated PAT applications in signal sensing, functional imaging, biomarker labeling and therapy monitoring etc. Here, the potentials of different optical probes as PAT contrast agents were elucidated. We first describe the instrumental embodiments and the measured functional parameters, then focus on emerging contrast agent-based PAT applications, and finally discuss the challenges and prospects. PMID:24967718

Biocompatible and high-performance amino acids-capped MnWO4 nanocasting as a novel non-lanthanide contrast agent for X-ray computed tomography and T1-weighted magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Dong, Kai; Liu, Zhen; Liu, Jianhua; Huang, Sa; Li, Zhenhua; Yuan, Qinghai; Ren, Jinsong; Qu, Xiaogang

2014-01-01

In the present work, a novel non-lanthanide dual-modality contrast agent, manganese tungstate (MnWO4), has been successfully constructed by a facile and versatile hydrothermal route. With the merits of a high atomic number and a well-positioned K-edge energy of tungsten, our well-prepared non-lanthanide nanoprobes provide a higher contrast efficacy than routine iodine-based agents in clinics. Additionally, the presence of Mn in these nanoparticles endow them with excellent T1-weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents.In the present work, a novel non-lanthanide dual-modality contrast agent, manganese tungstate (MnWO4), has been successfully constructed by a facile and versatile hydrothermal route. With the merits of a high atomic number and a well-positioned K-edge energy of tungsten, our well-prepared non-lanthanide nanoprobes provide a higher contrast efficacy than routine iodine-based agents in clinics. Additionally, the presence of Mn in these nanoparticles endow them with excellent T1-weighted MR imaging capabilities. As an alternative to T2-weighted MRI and CT dual-modality contrast agents, the nanoprobes can provide a positive contrast signal, which prevents confusion with the dark signals from hemorrhage and blood clots. To the best of our knowledge, this is the first report that a non-lanthanide imaging nanoprobe is applied for CT and T1-weighted MRI simultaneously. Moreover, comparing with gadolinium-based T1-weighted MRI and CT dual-modality contrast agents that were associated with nephrogenic systemic fibrosis (NSF), our contrast agents have superior biocompatibility, which is proved by a detailed study of the pharmacokinetics, biodistribution, and in vivo toxicology. Together with excellent dispersibility, high biocompatibility and superior contrast efficacy, these nanoprobes provide detailed and complementary information from dual-modality imaging over traditional single-mode imaging and bring more opportunities to the new generation of non-lanthanide nanoparticulate-based contrast agents. Electronic supplementary information (ESI) available: TEM images of MnWO4 nanoparticles synthesized at pH = 7, 180 °C pH = 9, 180 °C pH = 6, 200 °C with various amino acid molecules as capped agents, survey XPS spectra, FTIR spectrum of glycine capped MnWO4 nanorods, photos of glycine capped MnWO4 nanorods in various solutions including PBS, DMEM cell medium, and FBS, in vivo coronal view CT images of a rat before and after intravenous injection of iobitridol at different timed intervals, in vivo CT imaging of the rat one month after intravenous injection of MnWO4 nanorods, CT values of the heart, liver, spleen and kidney of a rat before and after intravenous administration of MnWO4 nanorods and iobitridol at different time intervals, hematology analysis and blood biochemical assay. See DOI: 10.1039/c3nr05455a

A proposed CT contrast agent using carboxybetaine zwitterionic tantalum oxide nanoparticles: Imaging, biological, and physicochemical performance

PubMed Central

FitzGerald, Paul F.; Butts, Matthew D.; Roberts, Jeannette C.; Colborn, Robert E.; Torres, Andrew S.; Lee, Brian D.; Yeh, Benjamin M.; Bonitatibus, Peter J.

2016-01-01

Objectives To produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ) coated soluble tantalum oxide nanoparticles (CZ-TaO NPs). We chose tantalum to provide superior imaging performance compared to current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. The aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared to clinically-used iodinated agents. Materials and Methods We evaluated CT imaging performance of our CZ-TaO NPs compared to an iodinated agent in live rats, imaged centrally-located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats’ great vessels at high temporal resolution during and following contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. CZ-TaO NPs were synthesized and analyzed in detail. We used multi-dimensional nuclear magnetic resonance (NMR) to determine surface functionality of the nanoparticles. We measured nanoparticle size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Results CT imaging studies demonstrated image contrast improvement of approximately 40–50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects following injection in healthy naïve rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week following injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin (NGAL) biomarker was measured at 24 and 48 hours. Compared to other tantalum oxide nanoparticles reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations >200 mg Ta/mL, and were similar in these physical properties to dimeric iodine-based contrast agents. Conclusions We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically-viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared to current iodinated agents. PMID:27115702

A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.

PubMed

FitzGerald, Paul F; Butts, Matthew D; Roberts, Jeannette C; Colborn, Robert E; Torres, Andrew S; Lee, Brian D; Yeh, Benjamin M; Bonitatibus, Peter J

2016-12-01

The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations, including the high concentrations required for standard clinical CT imaging. Computed tomography imaging studies demonstrated image contrast improvement of approximately 40% to 50% using CZ-TaO NPs compared with an iodinated agent injected at the same mass concentration. Blood and organ analyses showed no adverse effects after injection in healthy naive rats at 3 times the ACD. Retention of tantalum at 48 hours after injection was less than 2% of the injected dose in the whole carcass, which very closely matched the reported retention of existing commercial iodine-based contrast agents. Urine analysis of sensitive markers for acute kidney injury showed no responses at 1 week after injection at 3 times the ACD; however, a moderate response in the neutrophil gelatinase-associated lipocalin biomarker was measured at 24 and 48 hours. Compared with other TaO NPs reported in the literature, CZ-TaO NPs had relatively low osmolality and viscosity at concentrations greater than 200 mg Ta/mL and were similar in these physical properties to dimeric iodine-based contrast agents. We found that a CZ-TaO NP-based contrast agent is potentially viable for general-purpose clinical CT imaging. Our results suggest that such an agent can be formulated with clinically viable physicochemical properties, can be biologically safe and cleared rapidly in urine, and can provide substantially improved image contrast at CT compared with current iodinated agents.

Cationic Contrast Agent Diffusion Differs Between Cartilage and Meniscus.

PubMed

Honkanen, Juuso T J; Turunen, Mikael J; Freedman, Jonathan D; Saarakkala, Simo; Grinstaff, Mark W; Ylärinne, Janne H; Jurvelin, Jukka S; Töyräs, Juha

2016-10-01

Contrast enhanced computed tomography (CECT) is a non-destructive imaging technique used for the assessment of composition and structure of articular cartilage and meniscus. Due to structural and compositional differences between these tissues, diffusion and distribution of contrast agents may differ in cartilage and meniscus. The aim of this study is to determine the diffusion kinematics of a novel iodine based cationic contrast agent (CA(2+)) in cartilage and meniscus. Cylindrical cartilage and meniscus samples (d = 6 mm, h ≈ 2 mm) were harvested from healthy bovine knee joints (n = 10), immersed in isotonic cationic contrast agent (20 mgI/mL), and imaged using a micro-CT scanner at 26 time points up to 48 h. Subsequently, normalized X-ray attenuation and contrast agent diffusion flux, as well as water, collagen and proteoglycan (PG) contents in the tissues were determined. The contrast agent distributions within cartilage and meniscus were different. In addition, the normalized attenuation and diffusion flux were higher (p < 0.05) in cartilage. Based on these results, diffusion kinematics vary between cartilage and meniscus. These tissue specific variations can affect the interpretation of CECT images and should be considered when cartilage and meniscus are assessed simultaneously.

Chemical insights into the roles of nanowire cores on the growth and supercapacitor performances of Ni-Co-O/Ni(OH)2 core/shell electrodes

PubMed Central

Yin, Xuesong; Tang, Chunhua; Zhang, Liuyang; Yu, Zhi Gen; Gong, Hao

2016-01-01

Nanostructured core/shell electrodes have been experimentally demonstrated promising for high-performance electrochemical energy storage devices. However, chemical insights into the significant roles of nanowire cores on the growth of shells and their supercapacitor behaviors still remain as a research shortfall. In this work, by substituting 1/3 cobalt in the Co3O4 nanowire core with nickel, a 61% enhancement of the specific mass-loading of the Ni(OH)2 shell, a tremendous 93% increase of the volumetric capacitance and a superior cyclability were achieved in a novel NiCo2O4/Ni(OH)2 core/shell electrode in contrast to a Co3O4/Ni(OH)2 one. A comparative study suggested that not only the growth of Ni(OH)2 shells but also the contribution of cores were attributed to the overall performances. Importantly, their chemical origins were revealed through a theoretical simulation of the core/shell interfacial energy changes. Besides, asymmetric supercapacitor devices and applications were also explored. The scientific clues and practical potentials obtained in this work are helpful for the design and analysis of alternative core/shell electrode materials. PMID:26857606

Large-area super-resolution optical imaging by using core-shell microfibers

NASA Astrophysics Data System (ADS)

Liu, Cheng-Yang; Lo, Wei-Chieh

2017-09-01

We first numerically and experimentally report large-area super-resolution optical imaging achieved by using core-shell microfibers. The particular spatial electromagnetic waves for different core-shell microfibers are studied by using finite-difference time-domain and ray tracing calculations. The focusing properties of photonic nanojets are evaluated in terms of intensity profile and full width at half-maximum along propagation and transversal directions. In experiment, the general optical fiber is chemically etched down to 6 μm diameter and coated with different metallic thin films by using glancing angle deposition. The direct imaging of photonic nanojets for different core-shell microfibers is performed with a scanning optical microscope system. We show that the intensity distribution of a photonic nanojet is highly related to the metallic shell due to the surface plasmon polaritons. Furthermore, large-area super-resolution optical imaging is performed by using different core-shell microfibers placed over the nano-scale grating with 150 nm line width. The core-shell microfiber-assisted imaging is achieved with super-resolution and hundreds of times the field-of-view in contrast to microspheres. The possible applications of these core-shell optical microfibers include real-time large-area micro-fluidics and nano-structure inspections.

Chemical insights into the roles of nanowire cores on the growth and supercapacitor performances of Ni-Co-O/Ni(OH)₂ core/shell electrodes.

PubMed

Yin, Xuesong; Tang, Chunhua; Zhang, Liuyang; Yu, Zhi Gen; Gong, Hao

2016-02-09

Nanostructured core/shell electrodes have been experimentally demonstrated promising for high-performance electrochemical energy storage devices. However, chemical insights into the significant roles of nanowire cores on the growth of shells and their supercapacitor behaviors still remain as a research shortfall. In this work, by substituting 1/3 cobalt in the Co3O4 nanowire core with nickel, a 61% enhancement of the specific mass-loading of the Ni(OH)2 shell, a tremendous 93% increase of the volumetric capacitance and a superior cyclability were achieved in a novel NiCo2O4/Ni(OH)2 core/shell electrode in contrast to a Co3O4/Ni(OH)2 one. A comparative study suggested that not only the growth of Ni(OH)2 shells but also the contribution of cores were attributed to the overall performances. Importantly, their chemical origins were revealed through a theoretical simulation of the core/shell interfacial energy changes. Besides, asymmetric supercapacitor devices and applications were also explored. The scientific clues and practical potentials obtained in this work are helpful for the design and analysis of alternative core/shell electrode materials.

Ni3Si(Al)/a-SiOx core shell nanoparticles: characterization, shell formation, and stability

NASA Astrophysics Data System (ADS)

Pigozzi, G.; Mukherji, D.; Gilles, R.; Barbier, B.; Kostorz, G.

2006-08-01

We have used an electrochemical selective phase dissolution method to extract nanoprecipitates of the Ni3Si-type intermetallic phase from two-phase Ni-Si and Ni-Si-Al alloys by dissolving the matrix phase. The extracted nanoparticles are characterized by transmission electron microscopy, energy-dispersive x-ray spectrometry, x-ray powder diffraction, and electron powder diffraction. It is found that the Ni3Si-type nanoparticles have a core-shell structure. The core maintains the size, the shape, and the crystal structure of the precipitates that existed in the bulk alloys, while the shell is an amorphous phase, containing only Si and O (SiOx). The shell forms around the precipitates during the extraction process. After annealing the nanoparticles in nitrogen at 700 °C, the tridymite phase recrystallizes within the shell, which remains partially amorphous. In contrast, on annealing in air at 1000 °C, no changes in the composition or the structure of the nanoparticles occur. It is suggested that the shell forms after dealloying of the matrix phase, where Si atoms, the main constituents of the shell, migrate to the surface of the precipitates.

Ni(3)Si(Al)/a-SiO(x) core-shell nanoparticles: characterization, shell formation, and stability.

PubMed

Pigozzi, G; Mukherji, D; Gilles, R; Barbier, B; Kostorz, G

2006-08-28

We have used an electrochemical selective phase dissolution method to extract nanoprecipitates of the Ni(3)Si-type intermetallic phase from two-phase Ni-Si and Ni-Si-Al alloys by dissolving the matrix phase. The extracted nanoparticles are characterized by transmission electron microscopy, energy-dispersive x-ray spectrometry, x-ray powder diffraction, and electron powder diffraction. It is found that the Ni(3)Si-type nanoparticles have a core-shell structure. The core maintains the size, the shape, and the crystal structure of the precipitates that existed in the bulk alloys, while the shell is an amorphous phase, containing only Si and O (SiO(x)). The shell forms around the precipitates during the extraction process. After annealing the nanoparticles in nitrogen at 700 °C, the tridymite phase recrystallizes within the shell, which remains partially amorphous. In contrast, on annealing in air at 1000 °C, no changes in the composition or the structure of the nanoparticles occur. It is suggested that the shell forms after dealloying of the matrix phase, where Si atoms, the main constituents of the shell, migrate to the surface of the precipitates.

Renal contrast-enhanced MR angiography: timing errors and accurate depiction of renal artery origins.

PubMed

Schmidt, Maria A; Morgan, Robert

2008-10-01

To investigate bolus timing artifacts that impair depiction of renal arteries at contrast material-enhanced magnetic resonance (MR) angiography and to determine the effect of contrast agent infusion rates on artifact generation. Renal contrast-enhanced MR angiography was simulated for a variety of infusion schemes, assuming both correct and incorrect timing between data acquisition and contrast agent injection. In addition, the ethics committee approved the retrospective evaluation of clinical breath-hold renal contrast-enhanced MR angiographic studies obtained with automated detection of contrast agent arrival. Twenty-two studies were evaluated for their ability to depict the origin of renal arteries in patent vessels and for any signs of timing errors. Simulations showed that a completely artifactual stenosis or an artifactual overestimation of an existing stenosis at the renal artery origin can be caused by timing errors of the order of 5 seconds in examinations performed with contrast agent infusion rates compatible with or higher than those of hand injections. Lower infusion rates make the studies more likely to accurately depict the origin of the renal arteries. In approximately one-third of all clinical examinations, different contrast agent uptake rates were detected on the left and right sides of the body, and thus allowed us to confirm that it is often impossible to optimize depiction of both renal arteries. In three renal arteries, a signal void was found at the origin in a patent vessel, and delayed contrast agent arrival was confirmed. Computer simulations and clinical examinations showed that timing errors impair the accurate depiction of renal artery origins. (c) RSNA, 2008.

[Adult transient intestinal intussusception: can abdominal CT guide resolution?].

PubMed

Stabile Ianora, Amato Antonio; Telegrafo, Michele; Lorusso, Valentina; Rella, Leonarda; Niccoli Asabella, Artor; La Porta, Michele; Moschetta, Marco

2013-01-01

The purpose of this study was to evaluate the adult transient intestinal intussusceptions on CT before and after the administration of gastrointestinal contrast material. We evaluated two different gastrointestinal contrast materials: hyperdense and hypodense. In all cases the gastrointestinal contrast agent solved the invaginations. In the group of patients treated with hypodense contrast medium relapses occurred in the short and long term; no recurrence was observed in the other group. CT is useful in the recognition of intestinal intussusception. The gastrointestinal contrast agent could define the real transience of intussusceptions and hyperdense contrast agent could be more effective in short and long term resolution.

Biological and Clinical Aspects of Lanthanide Coordination Compounds

PubMed Central

Misra, Sudhindra N.; M., Indira Devi; Shukla, Ram S.

2004-01-01

The coordinating chemistry of lanthanides, relevant to the biological, biochemical and medical aspects, makes a significant contribution to understanding the basis of application of lanthanides, particularly in biological and medical systems. The importance of the applications of lanthanides, as an excellent diagnostic and prognostic probe in clinical diagnostics, and an anticancer material, is remarkably increasing. Lanthanide complexes based X-ray contrast imaging and lanthanide chelates based contrast enhancing agents for magnetic resonance imaging (MRI) are being excessively used in radiological analysis in our body systems. The most important property of the chelating agents, in lanthanide chelate complex, is its ability to alter the behaviour of lanthanide ion with which it binds in biological systems, and the chelation markedly modifies the biodistribution and excretion profile of the lanthanide ions. The chelating agents, especially aminopoly carboxylic acids, being hydrophilic, increase the proportion of their complex excreted from complexed lanthanide ion form biological systems. Lanthanide polyamino carboxylate-chelate complexes are used as contrast enhancing agents for Magnetic Resonance Imaging. Conjugation of antibodies and other tissue specific molecules to lanthanide chelates has led to a new type of specific MRI contrast agents and their conjugated MRI contrast agents with improved relaxivity, functioning in the body similar to drugs. Many specific features of contrast agent assisted MRI make it particularly effective for musculoskeletal and cerebrospinal imaging. Lanthanide-chelate contrast agents are effectively used in clinical diagnostic investigations involving cerebrospinal diseases and in evaluation of central nervous system. Chelated lanthanide complexes shift reagent aided 23Na NMR spectroscopic analysis is used in cellular, tissue and whole organ systems. PMID:18365075

Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

NASA Astrophysics Data System (ADS)

Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

2017-09-01

Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

Anti-EpCAM scFv gadolinium chelate: a novel targeted MRI contrast agent for imaging of colorectal cancer.

PubMed

Khantasup, Kannika; Saiviroonporn, Pairash; Jarussophon, Suwatchai; Chantima, Warangkana; Dharakul, Tararaj

2018-05-08

The development of targeted contrast agents for magnetic resonance imaging (MRI) facilitates enhanced cancer imaging and more accurate diagnosis. In the present study, a novel contrast agent was developed by conjugating anti-EpCAM humanized scFv with gadolinium chelate to achieve target specificity. The material design strategy involved site-specific conjugation of the chelating agent to scFv. The scFv monomer was linked to maleimide-DTPA via unpaired cysteine at the scFv C-terminus, followed by chelation with gadolinium (Gd). Successful scFv-DTPA conjugation was achieved at 1:10 molar ratio of scFv to maleimide-DTPA at pH 6.5. The developed anti-EpCAM-Gd-DTPA MRI contrast agent was evaluated for cell targeting ability, in vitro serum stability, cell cytotoxicity, relaxivity, and MR contrast enhancement. A high level of targeting efficacy of anti-EpCAM-Gd-DTPA to an EpCAM-overexpressing HT29 colorectal cell was demonstrated by confocal microscopy. Good stability of the contrast agent was obtained and no cytotoxicity was observed in HT29 cells after 48 h incubation with 25-100 µM of Gd. Favorable imaging was obtained using anti-EpCAM-Gd-DTPA, including 1.8-fold enhanced relaxivity compared with Gd-DTPA, and MR contrast enhancement observed after binding to HT29. The potential benefit of this contrast agent for in vivo MR imaging of colorectal cancer, as well as other EpCAM positive cancers, is suggested and warrants further investigation.

Effect of iodinated low-osmolar contrast media on the hemostatic system after intraarterial and intravenous contrast administration.

PubMed

Lukasiewicz, A; Lebkowska, U; Galar, M

2012-01-01

Some of the adverse clinical effects of intravascular radiological contrast agents include the interference of these contrast media with normal hemostatic processes. The aim of this report was to investigate in vivo whether a non-ionic iodinated contrast agent possess prothrombotic or anticoagulant properties. Hemostatic parameters: vWF (von Willebrand factor), F1+2 (prothrombin fragments 1+2), TAT (thrombin-antithrombin complexes), D-Dimer, β-TG (beta-thromboglobulin) were measured in a group of 35 patients. Blood samples for laboratory investigations were collected before and 30 min after the administration of a iodine contrast agent. There was observed statistically highly significant contrast-induced increase in TAT and F1+2 (p = 0.005 and p = 0.008, respectively). D-Dimer increase and decrease of β-TG and vWF after contrast medium administration were non significant. The volume of contrast medium has no influence on the assessed hemostatic parameters, while the type of contrast medium and/or the route of the contrast administration may significantly affect hemostatic parameters. We found significant effects of non-ionic agents on hemostatic activation. These effects may be important for adverse reactions and for thromboembolic complications.

Convection-enhanced delivery and in vivo imaging of polymeric nanoparticles for the treatment of malignant glioma.

PubMed

Bernal, Giovanna M; LaRiviere, Michael J; Mansour, Nassir; Pytel, Peter; Cahill, Kirk E; Voce, David J; Kang, Shijun; Spretz, Ruben; Welp, Ulrich; Noriega, Sandra E; Nunez, Luis; Larsen, Gustavo F; Weichselbaum, Ralph R; Yamini, Bakhtiar

2014-01-01

A major obstacle to the management of malignant glioma is the inability to effectively deliver therapeutic agent to the tumor. In this study, we describe a polymeric nanoparticle vector that not only delivers viable therapeutic, but can also be tracked in vivo using MRI. Nanoparticles, produced by a non-emulsion technique, were fabricated to carry iron oxide within the shell and the chemotherapeutic agent, temozolomide (TMZ), as the payload. Nanoparticle properties were characterized and subsequently their endocytosis-mediated uptake by glioma cells was demonstrated. Convection-enhanced delivery (CED) can disperse nanoparticles through the rodent brain and their distribution is accurately visualized by MRI. Infusion of nanoparticles does not result in observable animal toxicity relative to control. CED of TMZ-bearing nanoparticles prolongs the survival of animals with intracranial xenografts compared to control. In conclusion, the described nanoparticle vector represents a unique multifunctional platform that can be used for image-guided treatment of malignant glioma. GBM remains one of the most notoriously treatment-unresponsive cancer types. In this study, a multifunctional nanoparticle-based temozolomide delivery system was demonstrated to possess enhanced treatment efficacy in a rodent xenograft GBM model, with the added benefit of MRI-based tracking via the incorporation of iron oxide as a T2* contrast material in the nanoparticles. © 2014.

[Complications due to contrast agent administration: what has been confirmed in prevention?].

PubMed

Schönenberger, E; Mühler, M; Dewey, M

2010-12-01

Computed tomography (CT) and magnetic resonance imaging (MRI) have been evaluated by internists to be the most important medical innovations. Often, intravenous contrast agent administration is required for answering the clinical questions to CT and MRI. In this review we present an overview of the most common and most important aspects that need to be considered prior to intravenous contrast agent administration. We discuss aspects of renal impairment (contrast-induced nephropathy, nephrogenic systemic fibrosis), allergy-like reactions, hyperthyroidism, and pregnancy and breast-feeding.

Image reconstruction for x-ray K-edge imaging with a photon counting detector

NASA Astrophysics Data System (ADS)

Meng, Bo; Cong, Wenxiang; Xi, Yan; Wang, Ge

2014-09-01

Contrast agents with high-Z elements have K-absorption edges which significantly change X-ray attenuation coefficients. The K-edge characteristics is different for various kinds of contrast agents, which offers opportunities for material decomposition in biomedical applications. In this paper, we propose a new K-edge imaging method, which not only quantifies a distribution of a contrast agent but also provides an optimized contrast ratio. Our numerical simulation tests demonstrate the feasibility and merits of the proposed methodology.

Optical trapping of core-shell magnetic microparticles by cylindrical vector beams

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

Zhong, Min-Cheng; Gong, Lei; Li, Di

2014-11-03

Optical trapping of core-shell magnetic microparticles is experimentally demonstrated by using cylindrical vector beams. Second, we investigate the optical trapping efficiencies. The results show that radially and azimuthally polarized beams exhibit higher axial trapping efficiencies than the Gaussian beam. Finally, a trapped particle is manipulated to kill a cancer cell. The results make possible utilizing magnetic particles for optical manipulation, which is an important advantage for magnetic particles as labeling agent in targeted medicine and biological analysis.

Contrast-enhanced CT with a High-Affinity Cationic Contrast Agent for Imaging ex Vivo Bovine, Intact ex Vivo Rabbit, and in Vivo Rabbit Cartilage

PubMed Central

Stewart, Rachel C.; Bansal, Prashant N.; Entezari, Vahid; Lusic, Hrvoje; Nazarian, Rosalynn M.; Snyder, Brian D.

2013-01-01

Purpose: To quantify the affinity of a cationic computed tomography (CT) contrast agent (CA4+) and that of an anionic contrast agent (ioxaglate) to glycosaminoglycans (GAGs) in ex vivo cartilage tissue explants and to characterize the in vivo diffusion kinetics of CA4+ and ioxaglate in a rabbit model. Materials and Methods: All in vivo procedures were approved by the institutional animal care and use committee. The affinities of ioxaglate and CA4+ to GAGs in cartilage (six bovine osteochondral plugs) were quantified by means of a modified binding assay using micro-CT after plug equilibration in serial dilutions of each agent. The contrast agents were administered intraarticularly to the knee joints of five New Zealand white rabbits to determine the in vivo diffusion kinetics and cartilage tissue imaging capabilities. Kinetics of diffusion into the femoral groove cartilage and relative contrast agent uptake into bovine plugs were characterized by means of nonlinear mixed-effects models. Diffusion time constants (τ) were compared by using a Student t test. Results: The uptake of CA4+ in cartilage was consistently over 100% of the reservoir concentration, whereas it was only 59% for ioxaglate. In vivo, the contrast material–enhanced cartilage reached a steady CT attenuation for both CA4+ and ioxaglate, with τ values of 13.8 and 6.5 minutes, respectively (P = .04). The cartilage was easily distinguishable from the surrounding tissues for CA4+ (12 mg of iodine per milliliter); comparatively, the anionic contrast agent provided less favorable imaging results, even when a higher concentration was used (80 mg of iodine per milliliter). Conclusion: The affinity of the cationic contrast agent CA4+ to GAGs enables high-quality imaging and segmentation of ex vivo bovine and rabbit cartilage, as well as in vivo rabbit cartilage. © RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.12112246/-/DC1 PMID:23192774

Preclinical evaluation of Gd-DTPA and gadomelitol as contrast agents in DCE-MRI of cervical carcinoma interstitial fluid pressure.

PubMed

Hompland, Tord; Ellingsen, Christine; Rofstad, Einar K

2012-11-22

High interstitial fluid pressure (IFP) in the primary tumor is associated with poor disease-free survival in locally advanced cervical carcinoma. A noninvasive assay is needed to identify cervical cancer patients with highly elevated tumor IFP because these patients may benefit from particularly aggressive treatment. It has been suggested that dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with gadolinium diethylene-triamine penta-acetic acid (Gd-DTPA) as contrast agent may provide useful information on the IFP of cervical carcinomas. In this preclinical study, we investigated whether DCE-MRI with contrast agents with higher molecular weights (MW) than Gd-DTPA would be superior to Gd-DTPA-based DCE-MRI. CK-160 human cervical carcinoma xenografts were subjected to DCE-MRI with Gd-DTPA (MW of 0.55 kDa) or gadomelitol (MW of 6.5 kDa) as contrast agent before tumor IFP was measured invasively with a Millar SPC 320 catheter. The DCE-MRI was carried out at a spatial resolution of 0.23 × 0.23 × 2.0 mm³ and a time resolution of 14 s by using a 1.5-T whole-body scanner and a slotted tube resonator transceiver coil constructed for mice. Parametric images were derived from the DCE-MRI recordings by using the Tofts iso-directional transport model and the Patlak uni-directional transport model. When gadomelitol was used as contrast agent, significant positive correlations were found between the parameters of both pharmacokinetic models and tumor IFP. On the other hand, significant correlations between DCE-MRI-derived parameters and IFP could not be detected with Gd-DTPA as contrast agent. Gadomelitol is a superior contrast agent to Gd-DTPA in DCE-MRI of the IFP of CK-160 cervical carcinoma xenografts. Clinical studies attempting to develop DCE-MRI-based assays of the IFP of cervical carcinomas should involve contrast agents with higher MW than Gd-DTPA.

Aptamer-Targeted Gold Nanoparticles As Molecular-Specific Contrast Agents for Reflectance Imaging

PubMed Central

2008-01-01

Targeted metallic nanoparticles have shown potential as a platform for development of molecular-specific contrast agents. Aptamers have recently been demonstrated as ideal candidates for molecular targeting applications. In this study, we investigated the development of aptamer-based gold nanoparticles as contrast agents, using aptamers as targeting agents and gold nanoparticles as imaging agents. We devised a novel conjugation approach using an extended aptamer design where the extension is complementary to an oligonucleotide sequence attached to the surface of the gold nanoparticles. The chemical and optical properties of the aptamer−gold conjugates were characterized using size measurements and oligonucleotide quantitation assays. We demonstrate this conjugation approach to create a contrast agent designed for detection of prostate-specific membrane antigen (PSMA), obtaining reflectance images of PSMA(+) and PSMA(−) cell lines treated with the anti-PSMA aptamer−gold conjugates. This design strategy can easily be modified to incorporate multifunctional agents as part of a multimodal platform for reflectance imaging applications. PMID:18512972

Thick-shelled, grazer-protected diatoms decouple ocean carbon and silicon cycles in the iron-limited Antarctic Circumpolar Current

PubMed Central

Assmy, Philipp; Smetacek, Victor; Montresor, Marina; Klaas, Christine; Henjes, Joachim; Strass, Volker H.; Arrieta, Jesús M.; Bathmann, Ulrich; Berg, Gry M.; Breitbarth, Eike; Cisewski, Boris; Friedrichs, Lars; Fuchs, Nike; Herndl, Gerhard J.; Jansen, Sandra; Krägefsky, Sören; Latasa, Mikel; Peeken, Ilka; Röttgers, Rüdiger; Scharek, Renate; Schüller, Susanne E.; Steigenberger, Sebastian; Webb, Adrian; Wolf-Gladrow, Dieter

2013-01-01

Diatoms of the iron-replete continental margins and North Atlantic are key exporters of organic carbon. In contrast, diatoms of the iron-limited Antarctic Circumpolar Current sequester silicon, but comparatively little carbon, in the underlying deep ocean and sediments. Because the Southern Ocean is the major hub of oceanic nutrient distribution, selective silicon sequestration there limits diatom blooms elsewhere and consequently the biotic carbon sequestration potential of the entire ocean. We investigated this paradox in an in situ iron fertilization experiment by comparing accumulation and sinking of diatom populations inside and outside the iron-fertilized patch over 5 wk. A bloom comprising various thin- and thick-shelled diatom species developed inside the patch despite the presence of large grazer populations. After the third week, most of the thinner-shelled diatom species underwent mass mortality, formed large, mucous aggregates, and sank out en masse (carbon sinkers). In contrast, thicker-shelled species, in particular Fragilariopsis kerguelensis, persisted in the surface layers, sank mainly empty shells continuously, and reduced silicate concentrations to similar levels both inside and outside the patch (silica sinkers). These patterns imply that thick-shelled, hence grazer-protected, diatom species evolved in response to heavy copepod grazing pressure in the presence of an abundant silicate supply. The ecology of these silica-sinking species decouples silicon and carbon cycles in the iron-limited Southern Ocean, whereas carbon-sinking species, when stimulated by iron fertilization, export more carbon per silicon. Our results suggest that large-scale iron fertilization of the silicate-rich Southern Ocean will not change silicon sequestration but will add carbon to the sinking silica flux. PMID:24248337

A Brief Account of Nanoparticle Contrast Agents for Photoacoustic Imaging

PubMed Central

Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V.; Lanza, Gregory M

2014-01-01

Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds. PMID:23983210

Structural heterogeneity of milk casein micelles: a SANS contrast variation study.

PubMed

Bouchoux, Antoine; Ventureira, Jorge; Gésan-Guiziou, Geneviève; Garnier-Lambrouin, Fabienne; Qu, Peng; Pasquier, Coralie; Pézennec, Stéphane; Schweins, Ralf; Cabane, Bernard

2015-01-14

We examine the internal structure of milk casein micelles using the contrast variation method in Small-Angle Neutron Scattering (SANS). Experiments were performed with casein dispersions of different origins (i.e., milk powder or fresh milk) and extended to very low q-values (∼9 × 10(-4) Å(-1)), thus making it possible to precisely determine the apparent gyration radius Rg at each contrast. From the variation of I(q → 0) with contrast, we determine the distribution of composition of all the particles in the dispersions. As expected, most of these particles are micelles, made of casein and calcium phosphate, with a narrow distribution in compositions. These micelles always coexist with a very small fraction of fat droplets, with sizes in the range of 20-400 nm. For the dispersions prepared from fresh milk, which were purified under particularly stringent conditions, the number ratio of fat droplets to casein micelles is as low as 1 to 10(6). In that case, we are able to subtract from the total intensity the contribution of the fat droplets and in this way obtain the contribution of the micelles only. We then analyze the variation of this contribution with contrast using the approach pioneered by H. B. Stuhrmann. We model the casein micelle as a core-shell spherical object, in which the local scattering length density is determined by the ratio of calcium phosphate nanoclusters to proteins. We find that models in which the shell has a lower concentration of calcium phosphate than the core give a better agreement than models in which the shell has a higher density than the core.

Radioprotection and contrast agent use in pediatrics: what, how, and when.

PubMed

Lancharro Zapata, Á M; Rodríguez, C Marín

2016-05-01

It is essential to minimize exposure to ionizing radiation in children for various reasons. The risk of developing a tumor from exposure to a given dose of radiation is greater in childhood. Various strategies can be used to reduce exposure to ionizing radiation. It is fundamental to avoid unnecessary tests and tests that are not indicated, to choose an alternative test that does not use ionizing radiation, and/or to take a series of measures that minimize the dose of radiation that the patient receives, such as avoiding having to repeat tests, using the appropriate projections, using shields, adjusting the protocol (mAs, Kv, or pitch) to the patient's body volume, etc… When contrast agents are necessary, intracavitary ultrasound agents can be used, although the use of ultrasound agents is also being extended to include intravenous administration. In fluoroscopy, contrast agents with low osmolarity must be used, as in CT where we must adjust the dose and speed of injection to the patient's weight and to the caliber of the peripheral line, respectively. In MRI, only three types of contrast agents have been approved for pediatric use. It is sometimes necessary to use double doses or organ-specific contrast agents in certain clinical situations; the safety of contrast agents for these indications has not been proven, so they must be used off label. Copyright © 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

Advantages of paramagnetic CEST complexes having slow-to-intermediate water exchange properties as responsive MRI agents

PubMed Central

Soesbe, Todd C.; Wu, Yunkou; Sherry, A. Dean

2012-01-01

Paramagnetic saturation transfer chemical exchange (PARACEST) complexes are exogenous contrast agents that have great potential to further extend the functional and molecular imaging capabilities of magnetic resonance. Due to the presence of a central paramagnetic lanthanide ion (Ln3+ ≠ La3+, Gd3+, Lu3+) within the chelate, the resonance frequencies of protons and water molecules bound to the PARACEST agent are shifted far away from the bulk water frequency. This large chemical shift combined with an extreme sensitivity to the chemical exchange rate make PARACEST agents ideally suited for reporting significant biological metrics such as temperature, pH, and the presence of metabolites. Also, the ability to turn PARACEST agents “off” and “on” using a frequency selective saturation pulse gives them a distinct advantage over Gd3+-based contrast agents. A current challenge for PARACEST research is translating the promising in vitro results into in vivo systems. This short review article first describes the basic theory behind PARACEST contrast agents, their benefits over other contrast agents, and their applications to magnetic resonance imaging. It then describes some of the recent PARACEST research results. Specifically, pH measurements using water molecule exchange rate modulation, T2-exchange contrast due to water molecule exchange, the use of ultra-short echo times (TE<10 μs) to overcome T2-exchange line-broadening, and the potential application of T2-exchange as a new contrast mechanism for magnetic resonance imaging. PMID:23055299

Deposition of hermetic silver shells onto copper flakes.

PubMed

Njagi, John I; Netzband, Christopher M; Goia, Dan V

2017-02-15

Continuous silver shells were deposited on copper flakes using a two-stage precipitation process. A tightly packed layer of silver nanoparticles was first formed on the surface of the base metal by galvanic displacement. The size of the noble metal particles and their distribution on the substrate were controlled using complexing agents and dispersants. A continuous Ag deposit was subsequently grown by reducing slowly [Ag(NH 3 ) 2 ] + ions with glucose. The final shell thickness was controlled by varying the amount of metal deposited in the second step. The electrical properties of resulting silver coated copper flakes are comparable to those measured for silver flakes of similar size and aspect ratio. By preventing the oxidation of copper cores up to 400°C, the hermetic noble metal shell dramatically extends the temperature range in which Ag/Cu flakes can successfully replace pure silver. Copyright © 2016 Elsevier Inc. All rights reserved.

Ln(3+)-doped nanoparticles for upconversion and magnetic resonance imaging: some critical notes on recent progress and some aspects to be considered.

PubMed

van Veggel, Frank C J M; Dong, Cunhai; Johnson, Noah J J; Pichaandi, Jothirmayanantham

2012-12-07

In this feature article we will critically discuss the synthesis and characterisation aspects of Ln(3+)-doped nanoparticles (NPs) that show upconversion, upon 980 nm excitation. Upconversion is a non-linear process that converts two or more low-energy photons, often near-infrared photons, into one of higher energy, e.g. blue and 800 nm from Tm(3+) and green and red from Er(3+) or Ho(3+). Nearly all researchers use the absorption of 980 nm light by Yb(3+) as the sensitiser for the co-doped emissive Ln(3+) ions. The focus will be on LnF(3) and MLnF(4) (M = alkali metal) as the host matrix, because most progress has been made with these. In particular we will argue that a detailed understanding of how the dopant ions and the host Ln(3+) ions are distributed (in the core) and how (doped) shell growth occurs is not well understood. Moreover, their use as optical and magnetic resonance imaging contrast agents will be discussed. We will argue that deep-tissue imaging beyond 600 μm with retention of optical resolution, i.e. to see fine structure such as blood capillaries in brain tissues, has not yet been achieved. Three key parameters have been identified as impediments: (i) the low absorption efficiency of the Yb(3+) sensitiser, (ii) the low quantum yield of upconversion, and (iii) the long-lived excited states. On the other hand, there are very encouraging results that suggest that these nanoparticles could be developed into very potent magnetic resonance imaging (MRI) contrast agents.

Acoustic behavior of Halobacterium salinarum gas vesicles in the high frequency range: experiments and modeling

PubMed Central

Cherin, Emmanuel; Melis, Johan M.; Bourdeau, Raymond W.; Yin, Melissa; Kochmann, Dennis M.; Foster, F. Stuart; Shapiro, Mikhail G.

2017-01-01

Gas vesicles are a new and unique class of biologically derived ultrasound contrast agents with sub-micron size whose acoustic properties have not been fully elucidated. In this study, we investigated the acoustic collapse pressure and behavior of Halobacterium salinarum gas vesicles at transmit center frequencies ranging from 12.5 to 27.5 MHz. The acoustic collapse pressure was found to be above 550 kPa at all frequencies, 9 fold higher than the critical pressure observed in hydrostatic conditions. We show that gas vesicles behave non-linearly when exposed to ultrasound at incident pressure ranging from 160 kPa to the collapse pressure, and generate second harmonic amplitudes of −2 to −6 dB below the fundamental in media with viscosities ranging from 0.89 to 8 mPa.s. Simulations performed using a Rayleigh-Plesset type model accounting for buckling, and a dynamic finite element analysis, suggest that buckling is the mechanism behind the generation of harmonics. We found good agreement between the level of second harmonic relative to the fundamental measured at 20 MHz and the Rayleigh-Plesset model predictions. Finite element simulations extended these findings to a non-spherical geometry, confirmed that the acoustic buckling pressure corresponds to the critical pressure in hydrostatic conditions, and support the hypothesis of limited gas flow across the GV shell during the compression phase in the frequency range investigated. From simulations, estimates of GV bandwidth-limited scattering indicate that a single GV has a scattering cross-section comparable to that of a red blood cell. These findings will inform the development of GV-based contrast agents and pulse sequences to optimize their detection with ultrasound. PMID:28258771

Ln3+-doped nanoparticles for upconversion and magnetic resonance imaging: some critical notes on recent progress and some aspects to be considered

NASA Astrophysics Data System (ADS)

van Veggel, Frank C. J. M.; Dong, Cunhai; Johnson, Noah J. J.; Pichaandi, Jothirmayanantham

2012-11-01

In this feature article we will critically discuss the synthesis and characterisation aspects of Ln3+-doped nanoparticles (NPs) that show upconversion, upon 980 nm excitation. Upconversion is a non-linear process that converts two or more low-energy photons, often near-infrared photons, into one of higher energy, e.g. blue and 800 nm from Tm3+ and green and red from Er3+ or Ho3+. Nearly all researchers use the absorption of 980 nm light by Yb3+ as the sensitiser for the co-doped emissive Ln3+ ions. The focus will be on LnF3 and MLnF4 (M = alkali metal) as the host matrix, because most progress has been made with these. In particular we will argue that a detailed understanding of how the dopant ions and the host Ln3+ ions are distributed (in the core) and how (doped) shell growth occurs is not well understood. Moreover, their use as optical and magnetic resonance imaging contrast agents will be discussed. We will argue that deep-tissue imaging beyond 600 μm with retention of optical resolution, i.e. to see fine structure such as blood capillaries in brain tissues, has not yet been achieved. Three key parameters have been identified as impediments: (i) the low absorption efficiency of the Yb3+ sensitiser, (ii) the low quantum yield of upconversion, and (iii) the long-lived excited states. On the other hand, there are very encouraging results that suggest that these nanoparticles could be developed into very potent magnetic resonance imaging (MRI) contrast agents.

The Dependence of the Ultrasound-Induced Blood-Brain Barrier Opening Characteristics on Microbubble Size In Vivo

NASA Astrophysics Data System (ADS)

Choi, James J.; Feshitan, Jameel A.; Wang, Shougang; Tung, Yao-Sheng; Baseri, Babak; Borden, Mark A.; Konofagou, Elisa E.

2009-04-01

Recent neuropharmaceutical developments have led to potent disease-modifying drugs. In spite of these advancements, most agents cannot traverse the blood-brain barrier (BBB) and deposit in the brain. Focused ultrasound (FUS) with microbubbles has been shown to induce noninvasive, localized, and transient BBB opening. Although promising, safety and efficacy concerns still remain. Previously reported experiments used conventional imaging contrast agents that have a wide size distribution. In this study, we hypothesize that BBB opening characteristics are dependent on bubble diameter. A 25 μl bolus of in-house manufactured, lipid-shelled bubbles with either 1-2 or 4-5 μm diameter ranges was injected intravenously. Pulsed FUS (frequency: 1.5 MHz, peak-negative pressure: 146-607 kPa, duty cycle: 20%, duration: 1-min) was then applied to the left hippocampus of mice (n = 16) in vivo through the intact skin and skull. MRI or fluorescence microscopy was used to determine BBB opening. Contrast-enhanced (Omniscan™; 0.75 mL; molecular weight: 574 Da) MRI (9.4-T) was acquired on multiple days after sonication to determine BBB opening and closing. Fluorescence microscopy was also used to determine the feasibility of delivering large, 3 kDa dextran compounds through the BBB. The BBB opening acoustic pressure threshold for the 4-5μm bubbles was in the 146-304 kPa range while the threshold for the 1-2μm bubbles was higher. In conclusion, FUS-induced BBB opening and closing was shown to be dependent on the bubble diameter indicating the possibility of specifically designing bubbles to enhance this therapeutic application.

Monolithic photonic crystals created by partial coalescence of core-shell particles.

PubMed

Lee, Joon-Seok; Lim, Che Ho; Yang, Seung-Man; Kim, Shin-Hyun

2014-03-11

Colloidal crystals and their derivatives have been intensively studied and developed during the past two decades due to their unique photonic band gap properties. However, complex fabrication procedures and low mechanical stability severely limit their practical uses. Here, we report stable photonic structures created by using colloidal building blocks composed of an inorganic core and an organic shell. The core-shell particles are convectively assembled into an opal structure, which is then subjected to thermal annealing. During the heat treatment, the inorganic cores, which are insensitive to heat, retain their regular arrangement in a face-centered cubic lattice, while the organic shells are partially fused with their neighbors; this forms a monolithic structure with high mechanical stability. The interparticle distance and therefore stop band position are precisely controlled by the annealing time; the distance decreases and the stop band blue shifts during the annealing. The composite films can be further treated to give a high contrast in the refractive index. The inorganic cores are selectively removed from the composite by wet etching, thereby providing an organic film containing regular arrays of air cavities. The high refractive index contrast of the porous structure gives rise to pronounced structural colors and high reflectivity at the stop band position.

Variation in Orthologous Shell-Forming Proteins Contribute to Molluscan Shell Diversity

PubMed Central

Jackson, Daniel J.; Reim, Laurin; Randow, Clemens; Cerveau, Nicolas; Degnan, Bernard M.; Fleck, Claudia

2017-01-01

Abstract Despite the evolutionary success and ancient heritage of the molluscan shell, little is known about the molecular details of its formation, evolutionary origins, or the interactions between the material properties of the shell and its organic constituents. In contrast to this dearth of information, a growing collection of molluscan shell-forming proteomes and transcriptomes suggest they are comprised of both deeply conserved, and lineage specific elements. Analyses of these sequence data sets have suggested that mechanisms such as exon shuffling, gene co-option, and gene family expansion facilitated the rapid evolution of shell-forming proteomes and supported the diversification of this phylum specific structure. In order to further investigate and test these ideas we have examined the molecular features and spatial expression patterns of two shell-forming genes (Lustrin and ML1A2) and coupled these observations with materials properties measurements of shells from a group of closely related gastropods (abalone). We find that the prominent “GS” domain of Lustrin, a domain believed to confer elastomeric properties to the shell, varies significantly in length between the species we investigated. Furthermore, the spatial expression patterns of Lustrin and ML1A2 also vary significantly between species, suggesting that both protein architecture, and the regulation of spatial gene expression patterns, are important drivers of molluscan shell evolution. Variation in these molecular features might relate to certain materials properties of the shells of these species. These insights reveal an important and underappreciated source of variation within shell-forming proteomes that must contribute to the diversity of molluscan shell phenotypes. PMID:28961798

Contrast agent choice for intravenous coronary angiography

NASA Astrophysics Data System (ADS)

Zeman, H. D.; Siddons, D. P.

1990-05-01

The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. Gd-DTPA is already approved for use as a contrast agent for magnetic resonance imaging. Experiments have already been performed with Yb-DTPA in animals, and it appears to have a lower toxicity than that of Gd-DTPA. Reported animal experiments with Gd-DOTA contrast agent show no toxicity at all.

Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

NASA Astrophysics Data System (ADS)

Feng, Yi

Macromolecular contrast agents have been shown to be superior to small molecular weight contrast agents for MRI in blood pool imaging, tumor diagnosis and grading. However, none has been approved by the FDA because they circulate in the bloodstream much longer than small molecular weight contrast agents and result in high tissue accumulation of toxic Gd(III) ions. Biodegradable macromolecular contrast agents (BMCA) were invented to alleviate the toxic accumulation. They have a cleavable disulfide bond based backbone that can be degraded in vivo and excreted out of the body via renal filtration. Furthermore, the side chain of the backbone can be modified to achieve various degradation rates. Three BMCA, (Gd-DTPA)-cystamine copolymers (GDCC), Gd-DTPA cystine copolymers (GDCP), and Gd-DTPA cystine diethyl ester copolymers (GDCEP), were evaluated as blood pool contrast agents in a rat model. They have excellent blood pool enhancement, preferred pharmacokinetics, and only minimal long-term tissue retention of toxic Gd(III) ions. GDCC and GDCP, the lead agents with desired degradation rates, with molecular weights of 20 KDa and 70 KDa, were chosen for dynamic contrast enhanced MRI (DCE-MRI) to differentiate human prostate tumor models of different malignancy and growth rates. GDCC and GDCP could differentiate these tumor models, providing more accurate estimations of plasma volume, flow leakage rate, and permeability surface area product than a small molecular weight contrast agent Gd-DTPA-BMA when compared to the prototype macromolecular contrast agent albumin-Gd-DTPA. GDCC was favored for its neutral charge side chain and reasonable uptake rate by the tumors. GDCC with a molecular weight of 40 KDa (GDCC-40, above the renal filtration cutoff size) was used to assess the efficacy of two photothermal therapies (interstitial and indocyanine green enhanced). GDCC-40 provided excellent tumor enhancement shortly after its injection. Acute tumor response (4 hr) after therapies was revealed by DCE-MRI using GDCC-40. The region of the tumor with suspicious uptake of GDCC-40 could be correlated to the residual tumor. With only minimum tissue accumulation, BMCA have applications in blood pool imaging, cancer diagnosis, and efficacy assessment of anticancer treatment. Therefore, BMCA are promising for clinical applications.

Enhanced Positive-Contrast Visualization of Paramagnetic Contrast Agents Using Phase Images

PubMed Central

Mills, Parker H.; Ahrens, Eric T.

2009-01-01

Iron oxide–based MRI contrast agents are increasingly being used to noninvasively track cells, target molecular epitopes, and monitor gene expression in vivo. Detecting regions of contrast agent accumulation can be challenging if resulting contrast is subtle relative to endogenous tissue hypointensities. A postprocessing method is presented that yields enhanced positive-contrast images from the phase map associated with T2*-weighted MRI data. As examples, the method was applied to an agarose gel phantom doped with superparamagnetic iron-oxide nanoparticles and in vivo and ex vivo mouse brains inoculated with recombinant viruses delivering transgenes that induce overexpression of paramagnetic ferritin. Overall, this approach generates images that exhibit a 1- to 8-fold improvement in contrast-to-noise ratio in regions where paramagnetic agents are present compared to conventional magnitude images. This approach can be used in conjunction with conventional T2* pulse sequences, requires no prescans or increased scan time, and can be applied retrospectively to previously acquired data. PMID:19780169

Magnetic nanoparticles in magnetic resonance imaging and diagnostics.

PubMed

Rümenapp, Christine; Gleich, Bernhard; Haase, Axel

2012-05-01

Magnetic nanoparticles are useful as contrast agents for magnetic resonance imaging (MRI). Paramagnetic contrast agents have been used for a long time, but more recently superparamagnetic iron oxide nanoparticles (SPIOs) have been discovered to influence MRI contrast as well. In contrast to paramagnetic contrast agents, SPIOs can be functionalized and size-tailored in order to adapt to various kinds of soft tissues. Although both types of contrast agents have a inducible magnetization, their mechanisms of influence on spin-spin and spin-lattice relaxation of protons are different. A special emphasis on the basic magnetism of nanoparticles and their structures as well as on the principle of nuclear magnetic resonance is made. Examples of different contrast-enhanced magnetic resonance images are given. The potential use of magnetic nanoparticles as diagnostic tracers is explored. Additionally, SPIOs can be used in diagnostic magnetic resonance, since the spin relaxation time of water protons differs, whether magnetic nanoparticles are bound to a target or not.

Surface impact on nanoparticle-based magnetic resonance imaging contrast agents

PubMed Central

Zhang, Weizhong; Liu, Lin; Chen, Hongmin; Hu, Kai; Delahunty, Ian; Gao, Shi; Xie, Jin

2018-01-01

Magnetic resonance imaging (MRI) is one of the most widely used diagnostic tools in the clinic. To improve imaging quality, MRI contrast agents, which can modulate local T1 and T2 relaxation times, are often injected prior to or during MRI scans. However, clinically used contrast agents, including Gd3+-based chelates and iron oxide nanoparticles (IONPs), afford mediocre contrast abilities. To address this issue, there has been extensive research on developing alternative MRI contrast agents with superior r1 and r2 relaxivities. These efforts are facilitated by the fast progress in nanotechnology, which allows for preparation of magnetic nanoparticles (NPs) with varied size, shape, crystallinity, and composition. Studies suggest that surface coatings can also largely affect T1 and T2 relaxations and can be tailored in favor of a high r1 or r2. However, the surface impact of NPs has been less emphasized. Herein, we review recent progress on developing NP-based T1 and T2 contrast agents, with a focus on the surface impact. PMID:29721097

Gold nanoshells-mediated bimodal photodynamic and photothermal cancer treatment using ultra-low doses of near infra-red light.

PubMed

Vankayala, Raviraj; Lin, Chun-Chih; Kalluru, Poliraju; Chiang, Chi-Shiun; Hwang, Kuo Chu

2014-07-01

Previously, gold nanoshells were shown to be able to effectively convert photon energy to heat, leading to hyperthermia and suppression of tumor growths in mice. Herein, we show that in addition to the nanomaterial-mediated photothermal effects (NmPTT), gold nanoshells (including, nanocages, nanorod-in-shell and nanoparticle-in-shell) not only are able to absorb NIR light, but can also emit fluorescence, sensitize formation of singlet oxygen and exert nanomaterial-mediated photodynamic therapeutic (NmPDT) complete destruction of solid tumors in mice. The modes of NmPDT and NmPTT can be controlled and switched from one to the other by changing the excitation wavelength. In the in vitro experiments, gold nanocages and nanorod-in-shell show larger percentage of cellular deaths originating from NmPDT along with the minor fraction of NmPTT effects. In contrast, nanoparticle-in-shell exhibits larger fraction of NmPTT-induced cellular deaths together with minor fraction of NmPDT-induced apoptosis. Fluorescence emission spectra and DPBF quenching studies confirm the generation of singlet O2 upon NIR photoirradiation. Both NmPDT and NmPTT effects were confirmed by measurements of reactive oxygen species (ROS) and subsequent sodium azide quenching, heat shock protein expression (HSP 70), singlet oxygen sensor green (SOSG) sensing, changes in mitochondria membrane potential and apoptosis in the cellular experiments. In vivo experiments further demonstrate that upon irradiation at 980 nm under ultra-low doses (∼150 mW/cm(2)), gold nanocages mostly exert NmPDT effect to effectively suppress the B16F0 melanoma tumor growth. The combination of NmPDT and NmPTT effects on destruction of solid tumors is far better than pure NmPTT effect by 808 nm irradiation and also doxorubicin. Overall, our study demonstrates that gold nanoshells can serve as excellent multi-functional theranostic agents (fluorescence imaging + NmPDT + NmPTT) upon single photon NIR light excitation under ultra-low laser doses. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimizing radiologist e-prescribing of CT oral contrast agent using a protocoling portal.

PubMed

Wasser, Elliot J; Galante, Nicholas J; Andriole, Katherine P; Farkas, Cameron; Khorasani, Ramin

2013-12-01

The purpose of this study is to quantify the time expenditure associated with radiologist ordering of CT oral contrast media when using an integrated protocoling portal and to determine radiologists' perceptions of the ordering process. This prospective study was performed at a large academic tertiary care facility. Detailed timing information for CT inpatient oral contrast orders placed via the computerized physician order entry (CPOE) system was gathered over a 14-day period. Analyses evaluated the amount of physician time required for each component of the ordering process. Radiologists' perceptions of the ordering process were assessed by survey. Descriptive statistics and chi-square analysis were performed. A total of 96 oral contrast agent orders were placed by 13 radiologists during the study period. The average time necessary to create a protocol for each case was 40.4 seconds (average range by subject, 20.0-130.0 seconds; SD, 37.1 seconds), and the average total time to create and sign each contrast agent order was 27.2 seconds (range, 10.0-50.0 seconds; SD, 22.4 seconds). Overall, 52.5% (21/40) of survey respondents indicated that radiologist entry of oral contrast agent orders improved patient safety. A minority of respondents (15% [6/40]) indicated that contrast agent order entry was either very or extremely disruptive to workflow. Radiologist e-prescribing of CT oral contrast agents using CPOE can be embedded in a protocol workflow. Integration of health IT tools can help to optimize user acceptance and adoption.

Adverse reactions of low osmolar non-ionic and ionic contrast media when used together or separately during percutaneous coronary intervention.

PubMed

Juergens, Craig P; Khaing, Aye Mi; McIntyre, Geraldine J; Leung, Dominic Y C; Lo, Sidney T H; Fernandes, Clyne; Hopkins, Andrew P

2005-09-01

Due to perceived advantages in the use of non-ionic contrast agents for diagnostic angiography and ionic agents for percutaneous coronary intervention (PCI), patients often receive various combinations of both types of agents. To assess potential adverse effects of non-ionic and ionic contrast media when used together or separately during percutaneous coronary intervention. We retrospectively evaluated the outcomes of 532 patients undergoing percutaneous coronary intervention in our institution. Patients were divided into two groups: those that underwent diagnostic angiography and "follow on" PCI; and those that underwent "planned" PCI. The groups were subdivided on the basis of the use of the ionic agent ioxaglate or the non-ionic agent iopromide during PCI. The frequency of allergic reactions and major adverse cardiac events (MACE) were noted. With respect to the "follow on" group, allergic reactions occurred in 9 of 150 patients (6.0%) who received the combination of ioxaglate and iopromide versus 1 of 93 (1.1%) who only received iopromide (p=0.094). There was no difference with respect to MACE [6 (4.0%) ioxaglate and iopromide versus 4 (4.3%) iopromide alone, p=1.00]. In the "planned" group, 7 of 165 patients (4.2%) receiving ioxaglate had an allergic reaction as opposed 0.0% (0 of 124 patients) in the iopromide group (p=0.021). All contrast reactions were mild. The incidence of a MACE was similar in both groups [1 (0.6%) ioxaglate versus 2 (1.6%) iopromide, p=0.579]. The incidence of allergic reactions was similar if ioxaglate was used alone or in combination with iopromide (p=0.478). Whilst combining ionic and non-ionic contrast agents in the same procedure was not associated with any more adverse reactions than using an ionic contrast agent alone, the ionic contrast agent ioxaglate was associated with the majority of allergic reactions. With respect to choice of contrast agent, using the non-ionic agent iopromide alone for coronary intervention is associated with the lowest risk of an adverse event.

Interleukin 16- (IL-16-) Targeted Ultrasound Imaging Agent Improves Detection of Ovarian Tumors in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Adur, Malavika K; Utterback, Chet W; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-01-01

Limited resolution of transvaginal ultrasound (TVUS) scanning is a significant barrier to early detection of ovarian cancer (OVCA). Contrast agents have been suggested to improve the resolution of TVUS scanning. Emerging evidence suggests that expression of interleukin 16 (IL-16) by the tumor epithelium and microvessels increases in association with OVCA development and offers a potential target for early OVCA detection. The goal of this study was to examine the feasibility of IL-16-targeted contrast agents in enhancing the intensity of ultrasound imaging from ovarian tumors in hens, a model of spontaneous OVCA. Contrast agents were developed by conjugating biotinylated anti-IL-16 antibodies with streptavidin coated microbubbles. Enhancement of ultrasound signal intensity was determined before and after injection of contrast agents. Following scanning, ovarian tissues were processed for the detection of IL-16 expressing cells and microvessels. Compared with precontrast, contrast imaging enhanced ultrasound signal intensity significantly in OVCA hens at early (P < 0.05) and late stages (P < 0.001). Higher intensities of ultrasound signals in OVCA hens were associated with increased frequencies of IL-16 expressing cells and microvessels. These results suggest that IL-16-targeted contrast agents improve the visualization of ovarian tumors. The laying hen may be a suitable model to test new imaging agents and develop targeted anti-OVCA therapeutics.

Hierarchical Mesoporous Organosilica-Silica Core-Shell Nanoparticles Capable of Controlled Fungicide Release.

PubMed

Luo, Leilei; Liang, Yucang; Erichsen, Egil Severin; Anwander, Reiner

2018-05-17

A new class of hierarchically structured mesoporous silica core-shell nanoparticles (HSMSCSNs) with a periodic mesoporous organosilica (PMO) core and a mesoporous silica (MS) shell is reported. The applied one-pot, two-step strategy allows rational control over the core/shell chemical composition, topology, and pore/particle size, simply by adjusting the reaction conditions in the presence of cetyltrimethylammonium bromide (CTAB) as structure-directing agent under basic conditions. The spherical, ethylene- or methylene-bridged PMO cores feature hexagonal (p6mm) or cage-like cubic symmetry (Pm3‾ n) depending on the organosilica precursor. The hexagonal MS shell was obtained by n-hexane-induced controlled hydrolysis of TEOS followed by directional co-assembly/condensation of silicate/CTAB composites at the PMO cores. The HSMSCSNs feature a hierarchical pore structure with pore diameters of about 2.7 and 5.6 nm in the core and shell domains, respectively. The core sizes and shell thicknesses are adjustable in the ranges of 90-275 and 15-50 nm, respectively, and the surface areas (max. 1300 m 2  g -1 ) and pore volumes (max. 1.83 cm 3  g -1 ) are among the highest reported for core-shell nanoparticles. The adsorption and controlled release of the fungicide propiconazole by the HSMSCSNs showed a three-stage release profile. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhancing the methanol tolerance of platinum nanoparticles for the cathode reaction of direct methanol fuel cells through a geometric design.

PubMed

Feng, Yan; Ye, Feng; Liu, Hui; Yang, Jun

2015-11-18

Mastery over the structure of nanoparticles might be an effective way to enhance their performance for a given application. Herein we demonstrate the design of cage-bell nanostructures to enhance the methanol tolerance of platinum (Pt) nanoparticles while remaining their catalytic activity for oxygen reduction reaction. This strategy starts with the synthesis of core-shell-shell nanoparticles with Pt and silver (Ag) residing respectively in the core and inner shell regions, which are then agitated with saturated sodium chloride (NaCl) solution to eliminate the Ag component from the inner shell region, leading to the formation of bimetallic nanoparticles with a cage-bell structure, defined as a movable Pt core enclosed by a metal shell with nano-channels, which exhibit superior methanol-tolerant property in catalyzing oxygen reduction reaction due to the different diffusion behaviour of methanol and oxygen in the porous metal shell of cage-bell structured nanoparticles. In particular, the use of remarkably inexpensive chemical agent (NaCl) to promote the formation of cage-bell structured particles containing a wide spectrum of metal shells highlights its engineering merit to produce highly selective electrocatalysts on a large scale for the cathode reaction of direct methanol fuel cells.

Facile method for preparing organic/inorganic hybrid capsules using amino-functional silane coupling agent in aqueous media.

PubMed

Kurayama, Fumio; Suzuki, Satoru; Oyamada, Tetsuro; Furusawa, Takeshi; Sato, Masahide; Suzuki, Noboru

2010-09-01

A new and facile method for preparing microcapsules with 3-aminopropyltriethoxysilane (APTES)/alginate hybrid shell (AP-capsule) is proposed based on gelling and sol-gel processes. In this method, conventional capsules with alginate shells (Alg-capsule) are produced by dripping carboxymethyl cellulose solution containing calcium chloride into a sodium alginate solution. Subsequently, addition of the Alg-capsules to an aqueous APTES solution induces the formation of APTES/alginate hybrid shells. The optical observation shows that the texture of AP-capsules is more glossy and transparent than that of Alg-capsules. The surface morphology and elemental composition of microcapsules were characterized by Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FT-IR) and X-ray Photoelectron Spectroscopy (XPS). The results suggest that APTES molecules are incorporated to the framework of the alginate shells via electrostatic interaction between amino groups of APTES and carboxyl groups of alginate and the hybrid shells have a dense and homogeneous structure. In the formation reaction, the shrinking of the capsule shells occurs and the accumulation of APTES in the capsule shells proceeds with pseudo first-order kinetics. Moreover, these behaviors are greatly influenced by pH of the reaction solution, especially promoted under acidic and alkaline conditions. Copyright 2010 Elsevier Inc. All rights reserved.

Direct visualization of gastrointestinal tract with lanthanide-doped BaYbF5 upconversion nanoprobes.

PubMed

Liu, Zhen; Ju, Enguo; Liu, Jianhua; Du, Yingda; Li, Zhengqiang; Yuan, Qinghai; Ren, Jinsong; Qu, Xiaogang

2013-10-01

Nanoparticulate contrast agents have attracted a great deal of attention along with the rapid development of modern medicine. Here, a binary contrast agent based on PAA modified BaYbF5:Tm nanoparticles for direct visualization of gastrointestinal (GI) tract has been designed and developed via a one-pot solvothermal route. By taking advantages of excellent colloidal stability, low cytotoxicity, and neglectable hemolysis of these well-designed nanoparticles, their feasibility as a multi-modal contrast agent for GI tract was intensively investigated. Significant enhancement of contrast efficacy relative to clinical barium meal and iodine-based contrast agent was evaluated via X-ray imaging and CT imaging in vivo. By doping Tm(3+) ions into these nanoprobes, in vivo NIR-NIR imaging was then demonstrated. Unlike some invasive imaging modalities, non-invasive imaging strategy including X-ray imaging, CT imaging, and UCL imaging for GI tract could extremely reduce the painlessness to patients, effectively facilitate imaging procedure, as well as rationality economize diagnostic time. Critical to clinical applications, long-term toxicity of our contrast agent was additionally investigated in detail, indicating their overall safety. Based on our results, PAA-BaYbF5:Tm nanoparticles were the excellent multi-modal contrast agent to integrate X-ray imaging, CT imaging, and UCL imaging for direct visualization of GI tract with low systemic toxicity. Copyright © 2013 Elsevier Ltd. All rights reserved.

A functional form for injected MRI Gd-chelate contrast agent concentration incorporating recirculation, extravasation and excretion

NASA Astrophysics Data System (ADS)

Horsfield, Mark A.; Thornton, John S.; Gill, Andrew; Jager, H. Rolf; Priest, Andrew N.; Morgan, Bruno

2009-05-01

A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T1-weighted data from the descending aorta and hepatic portal vein, and on T*2-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

PubMed

Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

2016-01-01

Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

Biofilm imaging in porous media by laboratory X-Ray tomography: Combining a non-destructive contrast agent with propagation-based phase-contrast imaging tools.

PubMed

Carrel, Maxence; Beltran, Mario A; Morales, Verónica L; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

2017-01-01

X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent-biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development and bioclogging mechanisms in porous materials and the obtained biofilm morphology could be an ideal basis for 3D numerical calculations of hydrodynamic conditions to investigate biofilm-flow coupling.

75 FR 875 - Guidance for Industry on New Contrast Imaging Indication Considerations for Devices and Approved...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-06

... imaging devices for use with imaging contrast agents or radiopharmaceuticals. FDA intends this guidance to..., for medical imaging devices for use with imaging contrast agents or radiopharmaceuticals. Further, the...] Guidance for Industry on New Contrast Imaging Indication Considerations for Devices and Approved Drug and...

Investigation of X-ray permeability of surgical gloves coated with different contrast agents

PubMed Central

Kayan, Mustafa; Yaşar, Selçuk; Saygın, Mustafa; Yılmaz, Ömer; Aktaş, Aykut Recep; Kayan, Fatmanur; Türker, Yasin; Çetinkaya, Gürsel

2016-01-01

Objective: We aimed to investigate the effectiveness and radiation protection capability of latex gloves coated with various contrast agents as an alternative to lead gloves. Methods: The following six groups were created to evaluate the permeability of X-ray in this experimental study: lead gloves, two different non-ionic contrast media (iopromide 370/100 mg I/mL and iomeprol 400/100 mg I/mL), 10% povidone–iodine (PV–I), 240/240 g/mL barium sulphate and a mixture of equal amounts of all contrast agents. A radiation dose detector was placed in coated latex gloves for each one. The absorption values of radiation from latex gloves coated with various contrast agents were measured and compared with the absorption of radiation from lead gloves. This study was designed as an ‘experimental study’. Results: The mean absorption value of X-ray from lead gloves was 3.0±0.08 µG/s. The mean absorption values of X-ray from latex gloves coated with various contrast agents were 3.7±0.09 µG/s (iopromide 370/100 mg I/mL), 3.6±0.09 µG/s (iomeprol 400/100 mg I/mL), 3.7±0.04 µG/s (PV–I), 3.1±0.07 µG/s (barium sulphate) and 3.8±0.05 µG/s (mixture of all contrast agents). Latex gloves coated with barium sulphate provided the best radiation absorption compared with latex gloves coated with other radiodense contrast agents. Conclusion: Latex gloves coated with barium sulphate may provide protection equivalent to lead gloves. PMID:26680548

VEGFR2-Targeted Ultrasound Imaging Agent Enhances the Detection of Ovarian Tumors at Early Stage in Laying Hens, a Preclinical Model of Spontaneous Ovarian Cancer.

PubMed

Barua, Animesh; Yellapa, Aparna; Bahr, Janice M; Machado, Sergio A; Bitterman, Pincas; Basu, Sanjib; Sharma, Sameer; Abramowicz, Jacques S

2015-07-01

Tumor-associated neoangiogenesis (TAN) is an early event in ovarian cancer (OVCA) development. Increased expression of vascular endothelial growth factor receptor 2 (VEGFR2) by TAN vessels presents a potential target for early detection by ultrasound imaging. The goal of this study was to examine the suitability of VEGFR2-targeted ultrasound contrast agents in detecting spontaneous OVCA in laying hens. Effects of VEGFR2-targeted contrast agents in enhancing the intensity of ultrasound imaging from spontaneous ovarian tumors in hens were examined in a cross-sectional study. Enhancement in the intensity of ultrasound imaging was determined before and after injection of VEGFR2-targeted contrast agents. All ultrasound images were digitally stored and analyzed off-line. Following scanning, ovarian tissues were collected and processed for histology and detection of VEGFR2-expressing microvessels. Enhancement in visualization of ovarian morphology was detected by gray-scale imaging following injection of VEGFR2-targeted contrast agents. Compared with pre-contrast, contrast imaging enhanced the intensities of ultrasound imaging significantly (p < 0.0001) irrespective of the pathological status of ovaries. In contrast to normal hens, the intensity of ultrasound imaging was significantly (p < 0.0001) higher in hens with early stage OVCA and increased further in hens with late stage OVCA. Higher intensities of ultrasound imaging in hens with OVCA were positively correlated with increased (p < 0.0001) frequencies of VEGFR2-expressing microvessels. The results of this study suggest that VEGFR2-targeted contrast agents enhance the visualization of spontaneous ovarian tumors in hens at early and late stages of OVCA. The laying hen may be a suitable model to test new imaging agents and develop targeted therapeutics. © The Author(s) 2014.

Physical property control in core/shell inorganic nanostructures for fluorescence and magnetic targeting applications

NASA Astrophysics Data System (ADS)

Roberts, Stephen K.

Nanomaterials show immense promise for the future in numerous areas of application. Properties that are unique from the bulk material and are tunable allow for innovation in material design. This thesis will focus on controlling the physical properties of core/shell nanostructures to enhance the utility of the materials. The first focus is on the impact of different solvent mixtures during the shell growth phase of SILAR based core/shell quantum dot synthesis is studied. Gaining insight into the mechanism for SILAR growth of core/shell nanoparticles allows improved synthetic yields and precursor binding, providing enhanced control to synthesis of core/shell nanoparticles. The second focus of this thesis is exploring the use of magnetic nanoparticles for magnetic drug targeting for cardiovascular conditions. Magnetic targeting for drug delivery enables increased local drug concentration, while minimizing non-specific interactions. In order to be effective for magnetic targeting, it must be shown that low magnetic strength is sufficient to capture flowing nanoparticles. By demonstrating the binding of a therapeutic agent to the surface at medicinal levels, the viability for use as a nanoparticle drug delivery system is improved.

The multifunctional wound dressing with core-shell structured fibers prepared by coaxial electrospinning

NASA Astrophysics Data System (ADS)

Wei, Qilin; Xu, Feiyang; Xu, Xingjian; Geng, Xue; Ye, Lin; Zhang, Aiying; Feng, Zengguo

2016-06-01

The non-woven wound dressing with core-shell structured fibers was prepared by coaxial electrospinning. The polycaprolactone (PCL) was electrospun as the fiber's core to provide mechanical strength whereas collagen was fabricated into the shell in order to utilize its good biocompatibility. Simultaneously, the silver nanoparticles (Ag-NPs) as anti-bacterial agent were loaded in the shell whereas the vitamin A palmitate (VA) as healing-promoting drug was encapsulated in the core. Resulting from the fiber's core-shell structure, the VA released from the core and Ag-NPs present in the shell can endow the dressing both heal-promoting and anti-bacteria ability simultaneously, which can greatly enhance the dressing's clinical therapeutic effect. The dressing can maintain high swelling ratio of 190% for 3 d indicating its potential application as wet dressing. Furthermore, the dressing's anti-bacteria ability against Staphylococcus aureus was proved by in vitro anti-bacteria test. The in vitro drug release test showed the sustainable release of VA within 72 h, while the cell attachment showed L929 cells can well attach on the dressing indicating its good biocompatibility. In conclusion, the fabricated nanofibrous dressing possesses multiple functions to benefit wound healing and shows promising potential for clinical application.

Synthesis and characterization of a smart contrast agent sensitive to calcium.

PubMed

Dhingra, Kirti; Maier, Martin E; Beyerlein, Michael; Angelovski, Goran; Logothetis, Nikos K

2008-08-07

A novel first-generation Ca2+ sensitive contrast agent, Gd-DOPTRA has been synthesized and characterized. The agent shows approximately 100% relaxivity enhancement upon addition of Ca2+. The agent is selective and sensitive to Ca2+ also in the presence of Mg2+ and Zn2+. The relaxivity studies carried out in physiological fluids prove the prospects of the agent for in vivo measurements.

Magnetic resonance properties of Gd(III)-bound lipid-coated microbubbles and their cavitation fragments.

PubMed

Feshitan, Jameel A; Boss, Michael A; Borden, Mark A

2012-10-30

Gas-filled microbubbles are potentially useful theranostic agents for magnetic resonance imaging-guided focused ultrasound surgery (MRIgFUS). Previously, MRI at 9.4 T was used to measure the contrast properties of lipid-coated microbubbles with gadolinium (Gd(III)) bound to lipid headgroups, which revealed that the longitudinal molar relaxivity (r(1)) increased after microbubble fragmentation. This behavior was attributed to an increase in water proton exchange with the Gd(III)-bound lipid fragments caused by an increase in the lipid headgroup area that accompanied the lipid shell monolayer-to-bilayer transition. In this article, we explore this mechanism by comparing the changes in r(1) and its transverse counterpart, r(2)*, after the fragmentation of microbubbles consisting of Gd(III) bound to two different locations on the lipid monolayer shell: the phosphatidylethanolamine (PE) lipid headgroup region or the distal region of the poly(ethylene glycol) (PEG) brush. Nuclear magnetic resonance (NMR) at 1.5 T was used to measure the contrast properties of the various microbubble constructs because this is the most common field strength used in clinical MRI. Results for the lipid-headgroup-labeled Gd(III) microbubbles revealed that r(1) increased after microbubble fragmentation, whereas r(2)* was unchanged. An analysis of PEG-labeled Gd(III) microbubbles revealed that both r(1) and r(2)* decreased after microbubble fragmentation. Further analysis revealed that the microbubble gas core enhanced the transverse MR signal (T(2)*) in a concentration-dependent manner but minimally affected the longitudinal (T(1)) signal. These results illustrate a new method for the use of NMR to measure the biomembrane packing structure and suggest that two mechanisms, proton-exchange enhancement by lipid membrane relaxation and magnetic field inhomogeneity imposed by the gas/liquid interface, may be used to detect and differentiate Gd(III)-labeled microbubbles and their cavitation fragments with MRI.

Controlled fabrication of photoactive copper oxide-cobalt oxide nanowire heterostructures for efficient phenol photodegradation.

PubMed

Shi, Wenwu; Chopra, Nitin

2012-10-24

Fabrication of oxide nanowire heterostructures with controlled morphology, interface, and phase purity is critical for high-efficiency and low-cost photocatalysis. Here, we have studied the formation of copper oxide-cobalt nanowire heterostructures by sputtering and subsequent air annealing to result in cobalt oxide (Co(3)O(4))-coated CuO nanowires. This approach allowed fabrication of standing nanowire heterostructures with tunable compositions and morphologies. The vertically standing CuO nanowires were synthesized in a thermal growth method. The shell growth kinetics of Co and Co(3)O(4) on CuO nanowires, morphological evolution of the shell, and nanowire self-shadowing effects were found to be strongly dependent on sputtering duration, air-annealing conditions, and alignment of CuO nanowires. Finite element method (FEM) analysis indicated that alignment and stiffness of CuO-Co nanowire heterostructures greatly influenced the nanomechanical aspects such as von Mises equivalent stress distribution and bending of nanowire heterostructures during the Co deposition process. This fundamental knowledge was critical for the morphological control of Co and Co(3)O(4) on CuO nanowires with desired interfaces and a uniform coating. Band gap energies and phenol photodegradation capability of CuO-Co(3)O(4) nanowire heterostructures were studied as a function of Co(3)O(4) morphology. Multiple absorption edges and band gap tailings were observed for these heterostructures, indicating photoactivity from visible to UV range. A polycrystalline Co(3)O(4) shell on CuO nanowires showed the best photodegradation performance (efficiency ~50-90%) in a low-powered UV or visible light illumination with a sacrificial agent (H(2)O(2)). An anomalously high efficiency (~67.5%) observed under visible light without sacrificial agent for CuO nanowires coated with thin (∼5.6 nm) Co(3)O(4) shell and nanoparticles was especially interesting. Such photoactive heterostructures demonstrate unique sacrificial agent-free, robust, and efficient photocatalysts promising for organic decontamination and environmental remediation.

Targeted Gold Nanoparticle Contrast Agent for Digital Breast Tomosynthesis and Computed Tomography

DTIC Science & Technology

2011-03-01

injection series was repeated with an iodinated contrast agent, Omnipaque 320 (320 mg I/mL). Iodine enhancement was observed immediately post-injection...shape, size, growth rate, and expression level of cell-surface markers. Today, the most commonly used x-ray contrast agents are iodine-based...structural and radiographic properties of the AuNP. (iii) Evaluate the in vivo effect of the nanoparticles: tumor- enhancement , biodistribution, and

Synthesis of sharply thermo and PH responsive PMA-b-PNIPAM-b-PEG-b-PNIPAM-b-PMA by RAFT radical polymerization and its schizophrenic micellization in aqueous solutions.

PubMed

Ahmadkhani, Lida; Abbasian, Mojtaba; Akbarzadeh, Abolfazl

2017-01-01

Sharply thermo- and pH-responsive pentablock terpolymer with a core-shell-corona structure was prepared by RAFT polymerization of N-isopropylacrylamide and methacrylic acid monomers using PEG-based benzoate-type of RAFT agent. The PEG-based RAFT agent could be easily synthesized by dihydroxyl-capped PEG with 4-cyano-4-(thiobenzoyl) sulfanylpentanoic acids, using esterification reaction. This pentablock terpolymer was characterized by 1 H NMR, FT-IR, and GPC. The PDI was obtained by GPC, indicating that the molecular weight distribution was narrow and the polymerization was well controlled. The thermo- and pH-responsive micellization of the pentablock terpolymer in aqueous solution was investigated using fluorescence spectroscopy technique, UV-vis transmittance, and TEM. The LCST of pentablock terpolymer increased (over 50 °C) compared to the NIPAM homopolymer (~32 °C), due to the incorporation of the hydrophilic PEG and PMA blocks in pentablock terpolymer (PNIPAM block as the core, PEG the block and the hydrophilic PMA block as the shell and the corona). Also, pH-dependent phase transition behavior shows at a pH value of about ~5.8, according to pKa of MAA. Thus, in acidic solution at room temperature, the pentablock terpolymer self-assembled to form core-shell-corona micelles, with the hydrophobic PMA block as the core, the PNIPAM block and the hydrophilic PEG block as the shell and the corona, respectively.

Benchmark Intelligent Agent Systems for Distributed Battle Tracking

DTIC Science & Technology

2008-06-20

services in the military and other domains, each entity in the benchmark system exposes a standard set of Web services. Jess ( Java Expert Shell...System) is a rule engine for the Java platform and is an interpreter for the Jess rule language. It is used here to implement policies that maintain...battle tracking system (DBTS), maintaining distributed situation awareness. The Java Agent DEvelopment (JADE) framework is a software framework

Hierarchically assembled theranostic nanostructures for siRNA delivery and imaging applications.

PubMed

Shrestha, Ritu; Elsabahy, Mahmoud; Luehmann, Hannah; Samarajeewa, Sandani; Florez-Malaver, Stephanie; Lee, Nam S; Welch, Michael J; Liu, Yongjian; Wooley, Karen L

2012-10-24

Dual functional hierarchically assembled nanostructures, with two unique functions of carrying therapeutic cargo electrostatically and maintaining radiolabeled imaging agents covalently within separate component building blocks, have been developed via the supramolecular assembly of several spherical cationic shell cross-linked nanoparticles clustered around a central anionic shell cross-linked cylinder. The shells of the cationic nanoparticles and the hydrophobic core domain of the anionic central cylindrical nanostructure of the assemblies were utilized to complex negatively charged nucleic acids (siRNA) and to undergo radiolabeling, respectively, for potential theranostic applications. The assemblies exhibited exceptional cell transfection and radiolabeling efficiencies, providing an overall advantage over the individual components, which could each facilitate only one or the other of the functions.

Penetrating Colorectal Injuries: Diagnostic Performance of Multidetector CT with Trajectography.

PubMed

Dreizin, David; Boscak, Alexis R; Anstadt, Michael J; Tirada, Nikki; Chiu, William C; Munera, Felipe; Bodanapally, Uttam K; Hornick, Michael; Stein, Deborah M

2016-12-01

Purpose To determine the diagnostic performance of multidetector computed tomography (CT) with trajectography for penetrating colorectal injuries. Materials and Methods This institutional review board-approved and HIPAA-compliant study was a 6-year blinded retrospective review by two independent readers of 182 consecutive patients who preoperatively underwent 40- or 64-row multidetector CT for penetrating torso trauma below the diaphragm and had surgically confirmed findings. Colorectal perforation was present in 42 patients. Trajectory analysis with postprocessing software was used for all studies. Additional signs evaluated were rectal contrast agent leak, collections of extruded fecal material, mural defect, wall thickening, abnormal enhancement, free fluid or stranding, and free air. The quality of the colorectal contrast agent administration was recorded. Sensitivity, specificity, predictive values, areas under the receiver operating characteristic curves (AUCs), and Cohen κ were determined. Results In patients with rectal contrast agent administration (n = 151), AUCs were 0.90-0.91, which indicated excellent accuracy. Trajectory was sensitive (88%-91%). For single wounds (n = 104), sensitivity of trajectory was 96% for both readers, but was only 80% for multiple wounds (n = 47). Contrast agent leak was highly specific (96%-98%), but insensitive (42%-46%). Improved diagnostic performance was observed in patients with poor colonic distension or opacification. Accuracy remained high (AUC, 0.86-0.99) in the group without rectal contrast agent administration (n = 31). Conclusion Trajectory had excellent sensitivity, while rectal contrast agent leak was specific but insensitive. Sensitivity of trajectory was lower for multiple wounds. Accuracy remained high in patients without rectal contrast agent administration. © RSNA, 2016.

Combined optical sizing and acoustical characterization of single freely-floating microbubbles

NASA Astrophysics Data System (ADS)

Luan, Ying; Renaud, Guillaume; Raymond, Jason L.; Segers, Tim; Lajoinie, Guillaume; Beurskens, Robert; Mastik, Frits; Kokhuis, Tom J. A.; van der Steen, Antonius F. W.; Versluis, Michel; de Jong, Nico

2016-12-01

In this study we present a combined optical sizing and acoustical characterization technique for the study of the dynamics of single freely-floating ultrasound contrast agent microbubbles exposed to long burst ultrasound excitations up to the milliseconds range. A co-axial flow device was used to position individual microbubbles on a streamline within the confocal region of three ultrasound transducers and a high-resolution microscope objective. Bright-field images of microbubbles passing through the confocal region were captured using a high-speed camera synchronized to the acoustical data acquisition to assess the microbubble response to a 1-MHz ultrasound burst. Nonlinear bubble vibrations were identified at a driving pressure as low as 50 kPa. The results demonstrate good agreement with numerical simulations based on the shell-buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. The system demonstrates the potential for a high-throughput in vitro characterization of individual microbubbles.

Mie scattering off coated microbubbles

NASA Astrophysics Data System (ADS)

Nelissen, Radboud; Koene, Elmer; Hilgenfeldt, Sascha; Versluis, Michel

2002-11-01

The acoustic behavior of coated microbubbles depends on parameters of the shell coating, which are in turn dependent on bubble size. More intimate knowledge of this size dependence is required for an improved modeling of a distribution of coated microbubbles such as found in ultrasound contrast agents (UCA). Here a setup is designed to simultaneously measure the optical and acoustic response of an ultrasound-driven single bubble contained in a capillary or levitated by the pressure field of a focused transducer. Optical detection is done by Mie scattering through an inverted microscope. Acoustical detection of the single bubble by a receiving transducer is made possible because of the large working distance of the microscope. For Mie scattering investigation of excited bubbles, two regimes can be distinguished, which require different detection techniques: Conventional wide-angle detection through the microscope objective is sufficient for bubbles of radius exceeding 10 mum. For smaller bubbles, two narrow-aperture detectors are used to reconstruct the bubble dynamics from the complex angle-dependence of the scattered light.

Marriage of scintillator and semiconductor for synchronous radiotherapy and deep photodynamic therapy with diminished oxygen dependence.

PubMed

Zhang, Chen; Zhao, Kuaile; Bu, Wenbo; Ni, Dalong; Liu, Yanyan; Feng, Jingwei; Shi, Jianlin

2015-02-02

Strong oxygen dependence and limited penetration depth are the two major challenges facing the clinical application of photodynamic therapy (PDT). In contrast, ionizing radiation is too penetrative and often leads to inefficient radiotherapy (RT) in the clinic because of the lack of effective energy accumulation in the tumor region. Inspired by the complementary advantages of PDT and RT, we present herein the integration of a scintillator and a semiconductor as an ionizing-radiation-induced PDT agent, achieving synchronous radiotherapy and depth-insensitive PDT with diminished oxygen dependence. In the core-shell Ce(III)-doped LiYF4@SiO2@ZnO structure, the downconverted ultraviolet fluorescence from the Ce(III)-doped LiYF4 nanoscintillator under ionizing irradiation enables the generation of electron-hole (e(-)-h(+)) pairs in ZnO nanoparticles, giving rise to the formation of biotoxic hydroxyl radicals. This process is analogous to a type I PDT process for enhanced antitumor therapeutic efficacy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Viruslike Nanoparticles with Maghemite Cores Allow for Enhanced MRI Contrast Agents

DOE PAGES

Malyutin, Andrey G.; Easterday, Rosemary; Lozovyy, Yaroslav; ...

2014-12-15

Here, for the first time, we demonstrate formation of virus-like nanoparticles (VNPs) utilizing gold-coated iron oxide nanoparticles as cores and capsidprotein of brome mosaic virus (BMV) or hepatitis B virus (HBV) as shells. Further, utilizing cryo-electron microscopy and single particle methods, we are able to show that the BMV coat on VNPs assembles into a structure very close to that of a native virion. This is a consequence of an optimal iron oxide NP size (~11 nm) fitting the virus cavity and an ultrathin gold layer on the maghemite cores, which allows for utilization of SH-(CH 2) 11-(CH 2-CH 2-O)more » 4-OCH 2-COOH as capping molecules to provide sufficient stability, charge density, and small form factor. MRI studies show unique relaxivity ratios that diminish only slightly with gold coating. In conclusion, a virus protein coating of a magnetic core mimicking the wild-type virus makes these VNPs a versatile platform for biomedical applications.« less

Double-scattering/reflection in a Single Nanoparticle for Intensified Ultrasound Imaging

PubMed Central

Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

2015-01-01

Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled). PMID:25739832

Nanoparticles of adaptive supramolecular networks self-assembled from nucleotides and lanthanide ions.

PubMed

Nishiyabu, Ryuhei; Hashimoto, Nozomi; Cho, Ten; Watanabe, Kazuto; Yasunaga, Takefumi; Endo, Ayataka; Kaneko, Kenji; Niidome, Takuro; Murata, Masaharu; Adachi, Chihaya; Katayama, Yoshiki; Hashizume, Makoto; Kimizuka, Nobuo

2009-02-18

Amorphous nanoparticles of supramolecular coordination polymer networks are spontaneously self-assembled from nucleotides and lanthanide ions in water. They show intrinsic functions such as energy transfer from nucleobase to lanthanide ions and excellent performance as contrast enhancing agents for magnetic resonance imaging (MRI). Furthermore, adaptive inclusion properties are observed in the self-assembly process: functional materials such as fluorescent dyes, metal nanoparticles, and proteins are facilely encapsulated. Dyes in these nanoparticles fluoresce in high quantum yields with a single exponential decay, indicating that guest molecules are monomerically wrapped in the network. Gold nanoparticles and ferritin were also wrapped by the supramolecular shells. In addition, these nucleotide/lanthanide nanoparticles also serve as scaffolds for immobilizing enzymes. The adaptive nature of present supramolecular nanoparticles provides a versatile platform that can be utilized in a variety of applications ranging from material to biomedical sciences. As examples, biocompatibility and liver-directing characteristics in in vivo tissue localization experiments are demonstrated.

Double-scattering/reflection in a single nanoparticle for intensified ultrasound imaging.

PubMed

Zhang, Kun; Chen, Hangrong; Guo, Xiasheng; Zhang, Dong; Zheng, Yuanyi; Zheng, Hairong; Shi, Jianlin

2015-03-05

Ultrasound contrast agents (UCAs) designed by the conventional composition-based strategy, often suffer from relatively low ultrasound utilization efficiency. In this report, a structure-based design concept of double-scattering/reflection in a single nanoparticle for enhancing ultrasound imaging has been proposed. To exemplify this concept, a rattle-type mesoporous silica nanostructure (MSN) with two contributing interfaces has been employed as the ideal model. Contributed by double-scattering/reflection interfaces, the rattle-type MSN, as expected, performs much better in in vitro and in vivo ultrasound imaging than the other two nanostructures (solid and hollow) containing only one scattering/reflection interface. More convincingly, related acoustic measurements and simulation calculations also confirm this design concept. Noticeably, the rattle-type MSN has also been demonstrated capable of improving intracellular ultrasound molecular imaging. As a universal method, the structure-design concept can extend to guide the design of new generation UCAs with many other compositions and similar structures (e.g., heterogeneous rattle-type, double-shelled).

Introduction to the ultrasound targeted microbubble destruction technique.

PubMed

Walton, Chad B; Anderson, Cynthia D; Boulay, Rachel; Shohet, Ralph V

2011-06-12

In UTMD, bioactive molecules, such as negatively charged plasmid DNA vectors encoding a gene of interest, are added to the cationic shells of lipid microbubble contrast agents. In mice these vector-carrying microbubbles can be administered intravenously or directly to the left ventricle of the heart. In larger animals they can also be infused through an intracoronary catheter. The subsequent delivery from the circulation to a target organ occurs by acoustic cavitation at a resonant frequency of the microbubbles. It seems likely that the mechanical energy generated by the microbubble destruction results in transient pore formation in or between the endothelial cells of the microvasculature of the targeted region. As a result of this sonoporation effect, the transfection efficiency into and across the endothelial cells is enhanced, and transgene-encoding vectors are deposited into the surrounding tissue. Plasmid DNA remaining in the circulation is rapidly degraded by nucleases in the blood, which further reduces the likelihood of delivery to non-sonicated tissues and leads to highly specific target-organ transfection.

Fabrication of Fe{sub 3}O{sub 4}@CuO core-shell from MOF based materials and its antibacterial activity

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

Rajabi, S.K.; Sohrabnezhad, Sh., E-mail: sohrabnezhad@guilan.ac.ir; Ghafourian, S.

Magnetic Fe{sub 3}O{sub 4}@CuO nanocomposite with a core/shell structure was successfully synthesized via direct calcinations of magnetic Fe{sub 3}O{sub 4}@HKUST-1 in air atmosphere. The morphology, structure, magnetic and porous properties of the as-synthesized nano composites were characterized by using scanning electron microscope (SEM), transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), and vibration sample magnetometer (VSM). The results showed that the nanocomposite material included a Fe{sub 3}O{sub 4} core and a CuO shell. The Fe{sub 3}O{sub 4}@CuO core-shell can be separated easily from the medium by a small magnet. The antibacterial activity of Fe{sub 3}O{sub 4}-CuO core-shell was investigated againstmore » gram-positive and gram-negative bacteria. A new mechanism was proposed for inactivation of bacteria over the prepared sample. It was demonstrated that the core-shell exhibit recyclable antibacterial activity, acting as an ideal long-acting antibacterial agent. - Graphical abstract: Fe{sub 3}O{sub 4}@CuO core-shell release of copper ions. These Cu{sup 2+} ions were responsible for the exhibited antibacterial activity. - Highlights: • The Fe{sub 3}O{sub 4}@CuO core-shell was prepared by MOF method. • This is the first study of antibacterial activity of core-shell consist of CuO and Fe{sub 3}O{sub 4}. • The core-shell can be reused effectively. • Core-shell was separated from the reaction solution by external magnetic field.« less

Preliminary evaluation of physical and chemical characterization of waste palm oil shell as cool material replaced in asphaltic concrete as fine aggregate

NASA Astrophysics Data System (ADS)

Anuar, M. A. M.; Anting, N.; Shahidan, S.; Lee, Y. Y.; Din, M. F. Md; Khalid, F. S.; Nazri, W. M. H. W.

2017-11-01

Malaysia is one of the biggest producer of palm oil product and currently as main source of economy for the country. During the production of crude palm oil, a large amount of waste material is generated, such as palm oil fibres, palm oil shells and empty fruit bunches. Palm oil shell aggregate (POSA) is identified as a material that shows good potential to be used as a fine aggregate replacement in asphaltic concrete. On other hand, the chemical compound that exist in the Palm Oil Shell (POS) have shown a good potential as reflective component in cool-material. The purpose of this study is to obtain the physical and chemical properties of palm oil shell. The result shows the apparent particle density of Palm Oil Shell is 1.6 mg/m3. The specific gravity of palm oil shell was obtained with the value 1.6 and the water absorption amount of palm oil shell recorded from this study was 25.1%. The X-Ray Fluorescence study shows that palm oil shell contains the highest amount of SiO2 (46.412 wt%) and the second highest amount of Fe2O3 (34.016 wt%), both is the main output of relectivity compound. As a conclusion, waste palm oil shell has a potential to be used as alternative material for fine aggregate replacement. Besides that, the amount of chemical element that consist in palm oil shell which high in SiO2 and Fe2O3, promising the benefit to mitigate urban heat island as a cooling material agent.

Gastropod shell size and architecture influence the applicability of methods used to estimate internal volume.

PubMed

Ragagnin, Marilia Nagata; Gorman, Daniel; McCarthy, Ian Donald; Sant'Anna, Bruno Sampaio; de Castro, Cláudio Campi; Turra, Alexander

2018-01-11

Obtaining accurate and reproducible estimates of internal shell volume is a vital requirement for studies into the ecology of a range of shell-occupying organisms, including hermit crabs. Shell internal volume is usually estimated by filling the shell cavity with water or sand, however, there has been no systematic assessment of the reliability of these methods and moreover no comparison with modern alternatives, e.g., computed tomography (CT). This study undertakes the first assessment of the measurement reproducibility of three contrasting approaches across a spectrum of shell architectures and sizes. While our results suggested a certain level of variability inherent for all methods, we conclude that a single measure using sand/water is likely to be sufficient for the majority of studies. However, care must be taken as precision may decline with increasing shell size and structural complexity. CT provided less variation between repeat measures but volume estimates were consistently lower compared to sand/water and will need methodological improvements before it can be used as an alternative. CT indicated volume may be also underestimated using sand/water due to the presence of air spaces visible in filled shells scanned by CT. Lastly, we encourage authors to clearly describe how volume estimates were obtained.

Core-shell structure of Miglyol/poly(D,L-lactide)/Poloxamer nanocapsules studied by small-angle neutron scattering.

PubMed

Rübe, Andrea; Hause, Gerd; Mäder, Karsten; Kohlbrecher, Joachim

2005-10-03

The contrast variation technique in small angle neutron scattering (SANS) was used to investigate the inner structure of nanocapsules on the example of poly(D,L-lactide) (PLA) nanocapsules. The determination of the PLA and Poloxamer shell thickness was the focus of this study. Highest sensitivity on the inner structure of the nanocapsules was obtained when the scattering length density of the solvent was varied between the one of the Miglyol core and the PLA shell. According to the fit data the PLA shell thickness was 9.8 nm. The z-averaged radius determined by SANS experiments correlated well with dynamic light scattering (DLS) results, although DLS values were systematically slightly higher than the ones measured by SANS. This could be explained by taking into account the influence of Poloxamer attached to the nanocapsules surface. For a refined fit model with a second shell consisting of Poloxamer, SANS values and DLS values fitted well with each other. The characterization method presented here is significant because detailed insights into the nanocapsule and the Poloxamer shell were gained for the first time. This method could be used to develop strategies for the optimization of the shell properties concerning controlled release and to study changes in the shell structure during degradation processes.

Advantages of paramagnetic chemical exchange saturation transfer (CEST) complexes having slow to intermediate water exchange properties as responsive MRI agents.

PubMed

Soesbe, Todd C; Wu, Yunkou; Dean Sherry, A

2013-07-01

Paramagnetic chemical exchange saturation transfer (PARACEST) complexes are exogenous contrast agents that have great potential to further extend the functional and molecular imaging capabilities of magnetic resonance. As a result of the presence of a central paramagnetic lanthanide ion (Ln(3+) ≠ La(3+) , Gd(3+) , Lu(3+) ) within the chelate, the resonance frequencies of exchangeable protons bound to the PARACEST agent are shifted far away from the bulk water frequency. This large chemical shift, combined with an extreme sensitivity to the chemical exchange rate, make PARACEST agents ideally suited for the reporting of significant biological metrics, such as temperature, pH and the presence of metabolites. In addition, the ability to turn PARACEST agents 'off' and 'on' using a frequency-selective saturation pulse gives them a distinct advantage over Gd(3+) -based contrast agents. A current challenge for PARACEST research is the translation of the promising in vitro results into in vivo systems. This short review article first describes the basic theory behind PARACEST contrast agents, their benefits over other contrast agents and their applications to MRI. It then describes some of the recent PARACEST research results: specifically, pH measurements using water molecule exchange rate modulation, T2 exchange contrast caused by water molecule exchange, the use of ultrashort TEs (TE < 10 µs) to overcome T2 exchange line broadening and the potential application of T2 exchange as a new contrast mechanism for MRI. Copyright © 2012 John Wiley & Sons, Ltd.

Bubble template synthesis of hollow gold nanoparticles and their applications as theranostic agents

NASA Astrophysics Data System (ADS)

Huang, Chienwen

Hollow gold nanoparticle with a sub-30nm polycrystalline shell and a 50 nm hollow core has been successfully synthesized through the reduction of sodium gold sulfite by electrochemically evolved hydrogen. Such hollow gold nanoparticles exhibit unique plasmonic properties. They strongly scatter and absorb near infrared light. In this thesis we seek to understand the formation mechanism of hollow gold nanoparticles in this new synthesis process and their plasmonic properties. Also, we explore their biomedical applications as theranostic agents (therapeutic and diagnostic imaging). A lithographically patterned electrode consisting of Ag stripes on a glass substrate was used to investigate the formation process of hollow gold nanoparticles. Ag stripes served as working electrode for electrochemically evolution of hydrogen, and adjacent glass areas provided supporting surface for hydrogen nanobubbles nucleation and growth. Hydrogen nanobubbles served as both templates and reducing agents to trigger the autocatalytic disproportionation reaction of sodium gold sulfite. The effects of applied potential and the additives in the electrolyte have been studied. It has been found that the size and size distribution of hollow gold nanoparticle are directly relative to the applied potential, i.e. the hydrogen evolution rate. It has also been found the addition of Ni2+ ions can greatly improve the size distribution of hollow gold nanoparticles that can be contributed to that the newly electrodeposited nickel metal can enhance the hydrogen evolution efficiency. Another additive, ethylenediamine (EDA) can suppress the autocatalytic reaction of gold sulfite to increase the stability of sodium gold sulfite electrolyte. To capture such electrochemically evolved hydrogen nanobubbles, and subsequently to generate hollow gold nanoparticles in large numbers, alumina membranes were placed on the top of the working electrode. Anodic alumina membrane consists of ~200 nm pores, which provides a large surface area for the formation of hydrogen nanobubbles. By this approach, the electroless reaction can be easily separated from the electrodeposition process, and hollow gold nanoparticles can be easily collected. Synthesized hollow gold nanoparticles exhibit unique plasmonic properties; the surface plasmon resonance (SPR) lies in the near infrared region (NIR). This is very different from the solid spherical gold nanoparticles. Three-dimensional finite difference time domain (FDTD) simulation was employed to study the plasmonic properties of hollow gold nanoparticles. It has been found that the red-shifts of SPR peaks are mainly caused by their surface roughness, and the hollow nature of these particles only plays a minor role. The surface roughness of hollow gold nanoparticles can be tuned by adjusting the pH of the electrolyte (from 6.0 to 7.0) by adding sodium sulfite. Different surface roughness (from smooth to very rough) can be readily obtained, and correspondingly, surface plasmon resonance (SPR) peaks red-shift from ~600 nm to ~750 nm. Using hollow gold nanoparticles as multifunctional agents for biomedical applications have been explored. Two kinds of agents have been constructed. It has been demonstrated that pegylated Raman dye encoded hollow gold nanoparticles, terms as Raman nanotags, can serve as both diagnostic imaging agents and photothermal therapy agents. When illuminated by near infrared light, the enhanced Raman signal makes the hollow gold nanoparticles to become optically detectable for biomedical imaging, and absorbed light rapidly heat up the hollow gold nanoparticles which can be used to photothermal ablation therapy. The cytotoxicity evaluation using [3H] thymidine incorporation method has shown non-toxicity of the Raman nanotags. The photothermal effects of hollow gold nanoparticles have been examined by two methods: (1) by embedding hollow gold nanoparticles in tissue-like phantom environment; (2) by recording infrared images as temperature increase. The results show that hollow gold nanoparticles are capable to generate sufficiency heat for photothermal therapy. To fully take advantage of the unique hollow core space of hollow gold nanoparticles, a facile route has been develop to trap Fe3O4 nanoparticles into the hollow gold nanoparticles to form Fe3O4/Au core/shell nanoparticles. Fe3O4/Au core/shell nanoparticles possess the desirable magnetic and plasmonic properties that can be used as magnetic resonance contrast (MRI) agents and photothermal therapy agents.

Diffusion properties of conventional and calcium-sensitive MRI contrast agents in the rat cerebral cortex.

PubMed

Hagberg, Gisela E; Mamedov, Ilgar; Power, Anthony; Beyerlein, Michael; Merkle, Hellmut; Kiselev, Valerij G; Dhingra, Kirti; Kubìček, Vojtĕch; Angelovski, Goran; Logothetis, Nikos K

2014-01-01

Calcium-sensitive MRI contrast agents can only yield quantitative results if the agent concentration in the tissue is known. The agent concentration could be determined by diffusion modeling, if relevant parameters were available. We have established an MRI-based method capable of determining diffusion properties of conventional and calcium-sensitive agents. Simulations and experiments demonstrate that the method is applicable both for conventional contrast agents with a fixed relaxivity value and for calcium-sensitive contrast agents. The full pharmacokinetic time-course of gadolinium concentration estimates was observed by MRI before, during and after intracerebral administration of the agent, and the effective diffusion coefficient D* was determined by voxel-wise fitting of the solution to the diffusion equation. The method yielded whole brain coverage with a high spatial and temporal sampling. The use of two types of MRI sequences for sampling of the diffusion time courses was investigated: Look-Locker-based quantitative T(1) mapping, and T(1) -weighted MRI. The observation times of the proposed MRI method is long (up to 20 h) and consequently the diffusion distances covered are also long (2-4 mm). Despite this difference, the D* values in vivo were in agreement with previous findings using optical measurement techniques, based on observation times of a few minutes. The effective diffusion coefficient determined for the calcium-sensitive contrast agents may be used to determine local tissue concentrations and to design infusion protocols that maintain the agent concentration at a steady state, thereby enabling quantitative sensing of the local calcium concentration. Copyright © 2014 John Wiley & Sons, Ltd.

Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage.

PubMed

Stewart, Rachel C; Patwa, Amit N; Lusic, Hrvoje; Freedman, Jonathan D; Wathier, Michel; Snyder, Brian D; Guermazi, Ali; Grinstaff, Mark W

2017-07-13

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

Magnetic and Plasmonic Contrast Agents in Optical Coherence Tomography

PubMed Central

Oldenburg, Amy L.; Blackmon, Richard L.; Sierchio, Justin M.

2016-01-01

Optical coherence tomography (OCT) has gained widespread application for many biomedical applications, yet the traditional array of contrast agents used in incoherent imaging modalities do not provide contrast in OCT. Owing to the high biocompatibility of iron oxides and noble metals, magnetic and plasmonic nanoparticles, respectively, have been developed as OCT contrast agents to enable a range of biological and pre-clinical studies. Here we provide a review of these developments within the past decade, including an overview of the physical contrast mechanisms and classes of OCT system hardware addons needed for magnetic and plasmonic nanoparticle contrast. A comparison of the wide variety of nanoparticle systems is also presented, where the figures of merit depend strongly upon the choice of biological application. PMID:27429543

Iodinated contrast media and the role of renal replacement therapy.

PubMed

Weisbord, Steven D; Palevsky, Paul M

2011-05-01

Iodinated contrast media are among the most commonly used pharmacologic agents in medicine. Although generally highly safe, iodinated contrast media are associated with several adverse effects, most significantly the risk of acute kidney injury, particularly in patients with underlying renal dysfunction. By virtue of their pharmacokinetic characteristics, these contrast agents are efficiently cleared by hemodialysis and to a lesser extent, hemofiltration. This has led to research into the capacity for renal replacement therapies to prevent certain adverse effects of iodinated contrast. This review examines the molecular and pharmacokinetic characteristics of iodinated contrast media and critically analyzes data from past studies on the role of renal replacement therapy to prevent adverse effects of these diagnostic agents. Published by Elsevier Inc.

Problems in understanding the structure and assembly of viruses

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

King, J.

1997-12-01

Though viruses infect the cells of all groups of animals, plants, and microorganisms, their structures follow a limited number of general themes; spherical or cylindrical shells built of hundreds of repeated protein subunits enclosing a nucleic acid - DNA or RNA - genome. Since the 1960s it has been known that the protein shells of spherical viruses in fact conform to icosahedral symmetry or to subtle deviations from icosahedral symmetry. The construction of the shell lattices and the transformations they go through in the different stages of the viral life cycle are not fully understood. The shells contain the nucleicmore » in a highly condensed state, of unknown coiling/organization. Features of the well studied bacterial viruses will be reviewed, with examples from adenoviruses, herpesviruses, poliovirus, and HIV. The emergence of new viral disease has led to increased interest in the development of agents which interfere with virus reproduction at the level of the assembly or function of the organized particle. Recently computational approaches to the problem of virus assembly have made important contributions to clarifying shell assembly processes. 1 ref.« less

A Study on the Plasmonic Properties of Silver Core Gold Shell Nanoparticles: Optical Assessment of the Particle Structure

NASA Astrophysics Data System (ADS)

Mott, Derrick; Lee, JaeDong; Thi Bich Thuy, Nguyen; Aoki, Yoshiya; Singh, Prerna; Maenosono, Shinya

2011-06-01

This paper reports a qualitative comparison between the optical properties of a set of silver core, gold shell nanoparticles with varying composition and structure to those calculated using the Mie solution. To achieve this, silver nanoparticles were synthesized in aqueous phase from a silver hydroxide precursor with sodium acrylate as dual reducing-capping agent. The particles were then coated with a layer of gold with controllable thickness through a reduction-deposition process. The resulting nanoparticles reveal well defined optical properties that make them suitable for comparison to ideal calculated results using the Mie solution. The discussion focuses on the correlation between the synthesized core shell nanoparticles with varying Au shell thickness and the Mie solution results in terms of the optical properties. The results give insight in how to design and synthesize silver core, gold shell nanoparticles with controllable optical properties (e.g., SPR band in terms of intensity and position), and has implications in creating nanoparticle materials to be used as biological probes and sensing elements.

Characterization and hypoglycemic activity of a β-pyran polysaccharides from bamboo shoot (Leleba oldhami Nakal) shells.

PubMed

Zheng, Yafeng; Zhang, Shuai; Wang, Qi; Lu, Xu; Lin, Liangmei; Tian, Yuting; Xiao, Jianbo; Zheng, Baodong

2016-06-25

The bamboo shoot (Leleba oldhami Nakal) shell is a by-product during bamboo shoot processing. It is a cheap and available resource for dietary polysaccharides. Herein, a novel polysaccharide BSSP2a was isolated and characterized from the bamboo shoot shell polysaccharides, and it was identified as a homogeneous highly-branched beta type pyran polysaccharide with a molecular weight of 1.63×10(4)kDa, which consisted of arabinose, xylose, mannose, glucose and galactose at a molar ratio of 20.4:4.9:1:3.4:20.6. The crude polysaccharides (BSSP) from the bamboo shoots shell showed hypoglycemic activity on the high fat diet and streptozotocin induced diabetic mice in a dose-dependent manner. The administration of high dose BSSP (400mg/kg) improved body weight loss and serum insulin loss, and significantly decreased the blood glucose level, serum triglycerides as well as total cholesterol levels by 48.7%, 34.8% and 26.5%, respectively. The results highlight the potential of the bamboo shoot shell polysaccharides as a natural anti-diabetic agent. Copyright © 2016 Elsevier Ltd. All rights reserved.

Contrast-Enhanced Sonography Depicts Spontaneous Ovarian Cancer at Early Stages in a Preclinical Animal Model

PubMed Central

Barua, Animesh; Bitterman, Pincas; Bahr, Janice M.; Basu, Sanjib; Sheiner, Eyal; Bradaric, Michael J.; Hales, Dale B.; Luborsky, Judith L.; Abramowicz, Jacques S.

2011-01-01

Objective Our goal was to examine the feasibility of using laying hens, a preclinical model of human spontaneous ovarian cancer, in determining the kinetics of an ultrasound contrast agent indicative of ovarian tumor-associated neoangiogenesis in early-stage ovarian cancer. Methods Three-year-old White Leghorn laying hens with decreased ovarian function were scanned before and after intravenous injection of a human serum albumin–perflutren contrast agent at a dose of 5 µL/kg body weight. Gray scale morphologic characteristics, Doppler indices, the arrival time, peak intensity, and wash-out of the contrast agent were recorded and archived on still images and video clips. Hens were euthanized thereafter; sonographic predictions were compared at gross examination; and ovarian tissues were collected. Archived clips were analyzed to determine contrast parameters and Doppler intensities of vessels. A time-intensity curve per hen was drawn, and the area under the curve was derived. Tumor types and the density of ovarian microvessels were determined by histologic examination and immunohistochemistry and compared to sonographic predictions. Results The contrast agent significantly (P < .05) enhanced the visualization of microvessels, which was confirmed by immunohistochemistry. Contrast parameters, including the time of wash-out and area under the curve, were significantly different (P < .05) between ovaries of normal hens and hens with ovarian cancer and correctly detected cancer at earlier stages than the time of peak intensity. Conclusions The laying hen may be a useful animal model for determining ovarian tumor-associated vascular kinetics diagnostic of early-stage ovarian cancer using a contrast agent. This model may also be useful for testing the efficacy of different contrast agents in a preclinical setting. PMID:21357555

Immediate reactions following iodinated contrast media injection: a study of 38 cases.

PubMed

Dewachter, Pascale; Laroche, Dominique; Mouton-Faivre, Claudie; Bloch-Morot, Evelyne; Cercueil, Jean-Pierre; Metge, Liliane; Carette, Marie-France; Vergnaud, Marie-Claude; Clément, Olivier

2011-03-01

To investigate the pathomechanisms involved in cases of immediate hypersensitivity reactions occurring after the administration of iodinated contrast media. Patients having presented clinical signs of immediate hypersensitivity suggesting allergy after iodinated contrast medium were investigated. Histamine and tryptase concentrations were measured, and/or skin tests were performed. Patients with positive skin tests to the culprit contrast agent were classified as IgE-mediated allergic hypersensitivity (Group I) and patients with negative skin tests as non-allergic hypersensitivity (Group II). 38 patients were included. Most reactions appeared after non-ionic (n = 32). Reactions were more frequently severe following ionic than non-ionic (p = 0.014). Skin testing was not performed in 11 patients. Skin tests with the culprit contrast agent were negative in 26% of the patients (Group II, n = 7) whereas they were found positive with the contrast agent in 73% of the patients (Group I, n = 19). Latex-induced reaction was diagnosed in one patient, and was consequently excluded from the cohort. In Group I, the frequency of cross-reactivity with the other commercialized iodinated contrast media was low (7%). Cardiovascular signs were present in Group I (52.6%, n = 10), and absent in Group II (p = 0.023). Histamine and tryptase concentrations were higher in patients who had cardiovascular signs (p < 0.02). Immediate reactions with clinical signs suggesting allergy along with positive skin tests with the administered contrast agent confirm immediate allergic hypersensitivity (anaphylaxis) to this agent. Consequently, the culprit contrast agent should be definitely avoided as well as cross-reactive ICM in order to prevent further recurrences. Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.

Porous metal oxide particles and their methods of synthesis

DOEpatents

Chen, Fanglin; Liu, Qiang

2013-03-12

Methods are generally disclosed for synthesis of porous particles from a solution formed from a leaving agent, a surfactant, and a soluble metal salt in a solvent. The surfactant congregates to form a nanoparticle core such that the metal salt forms about the nanoparticle core to form a plurality of nanoparticles. The solution is heated such that the leaving agent forms gas bubbles in the solution, and the plurality of nanoparticles congregate about the gas bubbles to form a porous particle. The porous particles are also generally disclosed and can include a particle shell formed about a core to define an average diameter from about 0.5 .mu.m to about 50 .mu.m. The particle shell can be formed from a plurality of nanoparticles having an average diameter of from about 1 nm to about 50 nm and defined by a metal salt formed about a surfactant core.

Variation in Orthologous Shell-Forming Proteins Contribute to Molluscan Shell Diversity.

PubMed

Jackson, Daniel J; Reim, Laurin; Randow, Clemens; Cerveau, Nicolas; Degnan, Bernard M; Fleck, Claudia

2017-11-01

Despite the evolutionary success and ancient heritage of the molluscan shell, little is known about the molecular details of its formation, evolutionary origins, or the interactions between the material properties of the shell and its organic constituents. In contrast to this dearth of information, a growing collection of molluscan shell-forming proteomes and transcriptomes suggest they are comprised of both deeply conserved, and lineage specific elements. Analyses of these sequence data sets have suggested that mechanisms such as exon shuffling, gene co-option, and gene family expansion facilitated the rapid evolution of shell-forming proteomes and supported the diversification of this phylum specific structure. In order to further investigate and test these ideas we have examined the molecular features and spatial expression patterns of two shell-forming genes (Lustrin and ML1A2) and coupled these observations with materials properties measurements of shells from a group of closely related gastropods (abalone). We find that the prominent "GS" domain of Lustrin, a domain believed to confer elastomeric properties to the shell, varies significantly in length between the species we investigated. Furthermore, the spatial expression patterns of Lustrin and ML1A2 also vary significantly between species, suggesting that both protein architecture, and the regulation of spatial gene expression patterns, are important drivers of molluscan shell evolution. Variation in these molecular features might relate to certain materials properties of the shells of these species. These insights reveal an important and underappreciated source of variation within shell-forming proteomes that must contribute to the diversity of molluscan shell phenotypes. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Lightweight and efficient microwave absorbing materials based on walnut shell-derived nano-porous carbon.

PubMed

Qiu, Xu; Wang, Lixi; Zhu, Hongli; Guan, Yongkang; Zhang, Qitu

2017-06-08

Lightweight microwave absorbing materials have drawn tremendous attention. Herein, nano-porous biomass carbon materials have been prepared by carbonization with a subsequent potassium hydroxide activation of walnut shells and the microwave absorption properties have also been investigated. The obtained samples have large specific surface areas with numerous micropores and nanopores. The sample activated at 600 °C with a specific surface area of 736.2 m 2 g -1 exhibits the most enhanced microwave absorption performance. It has the maximum reflection loss of -42.4 dB at 8.88 GHz and the effective absorption bandwidth (reflection loss below -10 dB) is 1.76 GHz (from 8.08 GHz to 9.84 GHz), corresponding to a thickness of 2 mm. Additionally, the effective absorption bandwidth can reach 2.24 GHz (from 10.48 GHz to 12.72 GHz) when the absorber thickness is 1.5 mm. Three-dimensional porous architecture, interfacial polarization relaxation loss, and the dipolar relaxation loss make a great contribution to the excellent microwave absorption performance. In contrast, the non-activated sample with lower specific surface area (435.3 m 2 g -1 ) has poor microwave absorption performance due to a poor dielectric loss capacity. This comparison highlights the role of micropores and nanopores in improving the dielectric loss property of porous carbon materials. To sum up, porous biomass carbon has great potential to become lightweight microwave absorbers. Moreover, KOH is an efficient activation agent in the fabrication of carbonaceous materials.

Ultra-small nanocluster mediated synthesis of Nd3+-doped core-shell nanocrystals with emission in the second near-infrared window for multimodal imaging of tumor vasculature.

PubMed

Ren, Feng; Ding, Lihua; Liu, Hanghang; Huang, Qian; Zhang, Hao; Zhang, Lijuan; Zeng, Jianfeng; Sun, Qiao; Li, Zhen; Gao, Mingyuan

2018-08-01

In-vivo intravital short wavelength infrared (SWIR, 1000-2300 nm) fluorescence imaging has attracted considerable attention in the imaging of tumor vasculature due to its low background, high sensitivity, and deep penetration. It can noninvasively provide dynamic feedback on the tumorigenesis, growth, necrosis and metastasis. Herein, monodisperse Nd 3+ -doped core-shell downconversion luminescent nanocrystals with strong emission in the second near-infrared (NIR II) window, strong temperature-dependent paramagnetism and fast attenuation to X-rays were prepared from ultra-small nanoclusters. The use of nanoclusters resulted in very uniform bright nanocrystals with a relative quantum yield comparable to the standard dye IR-26. These bright NIR nanocrystals were modified with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] to endow with excellent water-solubility, biocompatibility and a blood circulation half-life of 5.9 h. They were then successfully used to demonstrate the variation of tumor vasculature with tumor progression from tumorigenesis, growth, to necrosis in the subcutaneous breast tumor through the NIR II fluorescence imaging. They were also used as contrast agent of magnetic resonance imaging (MRI) and X-ray computed tomography (CT) imaging of tumor to provide complementary anatomic structure. Their great potential in NIR II imaging of tumor was further demonstrated with an orthotopic breast tumor. Their in-vivo biosafety was also investigated by hemanalysis and histological analyses. Copyright © 2018 Elsevier Ltd. All rights reserved.

Near infrared spectral polarization imaging of prostate cancer tissues using Cybesin: a receptor-targeted contrast agent

NASA Astrophysics Data System (ADS)

Pu, Yang; Wang, W. B.; Tang, G. C.; Liang, Kexian; Achilefu, S.; Alfano, R. R.

2013-03-01

Cybesin, a smart contrast agent to target cancer cells, was investigated using a near infrared (NIR) spectral polarization imaging technique for prostate cancer detection. The approach relies on applying a contrast agent that can target cancer cells. Cybesin, as a small ICG-derivative dye-peptide, emit fluorescence between 750 nm and 900 nm, which is in the "tissue optical window". Cybesin was reported targeting the over-expressed bombesin receptors in cancer cells in animal model and the human prostate cancers over-expressing bombesin receptors. The NIR spectral polarization imaging study reported here demonstrated that Cybesin can be used as a smart optical biomarker and as a prostate cancer receptor targeted contrast agent.

[Gadolinium-based contrast agents for magnetic resonance imaging].

PubMed

Carrasco Muñoz, S; Calles Blanco, C; Marcin, Javier; Fernández Álvarez, C; Lafuente Martínez, J

2014-06-01

Gadolinium-based contrast agents are increasingly being used in magnetic resonance imaging. These agents can improve the contrast in images and provide information about function and metabolism, increasing both sensitivity and specificity. We describe the gadolinium-based contrast agents that have been approved for clinical use, detailing their main characteristics based on their chemical structure, stability, and safety. In general terms, these compounds are safe. Nevertheless, adverse reactions, the possibility of nephrotoxicity from these compounds, and the possibility of developing nephrogenic systemic fibrosis will be covered in this article. Lastly, the article will discuss the current guidelines, recommendations, and contraindications for their clinical use, including the management of pregnant and breast-feeding patients. Copyright © 2014 SERAM. Published by Elsevier Espana. All rights reserved.

A review of responsive MRI contrast agents: 2005–2014

PubMed Central

Hingorani, Dina V.; Bernstein, Adam S.; Pagel, Mark D.

2014-01-01

This review focuses on MRI contrast agents that are responsive to a change in a physiological biomarker. The response mechanisms are dependent on six physicochemical characteristics, including the accessibility of water to the agent, tumbling time, proton exchange rate, electron spin state, MR frequency, or superparamagnetism of the agent. These characteristics can be affected by changes in concentrations or activities of enzymes, proteins, nucleic acids, metabolites, or metal ions, or changes in redox state, pH, temperature, or light. A total of 117 examples are presented, including examples that employ nuclei other than 1H, which attests to the creativity of multidisciplinary research efforts to develop responsive MRI contrast agents. PMID:25355685

In vivo tumor characterization using both MR and optical contrast agents with a hybrid MRI-DOT system

NASA Astrophysics Data System (ADS)

Lin, Yuting; Ghijsen, Michael; Thayer, David; Nalcioglu, Orhan; Gulsen, Gultekin

2011-03-01

Dynamic contrast enhanced MRI (DCE-MRI) has been proven to be the most sensitive modality in detecting breast lesions. Currently available MR contrast agent, Gd-DTPA, is a low molecular weight extracellular agent and can diffuse freely from the vascular space into interstitial space. Due to this reason, DCE-MRI has low sensitivity in differentiating benign and malignant tumors. Meanwhile, diffuse optical tomography (DOT) can be used to provide enhancement kinetics of an FDA approved optical contrast agent, ICG, which behaves like a large molecular weight optical agent due to its binding to albumin. The enhancement kinetics of ICG may have a potential to distinguish between the malignant and benign tumors and hence improve the specificity. Our group has developed a high speed hybrid MRI-DOT system. The DOT is a fully automated, MR-compatible, multi-frequency and multi-spectral imaging system. Fischer-344 rats bearing subcutaneous R3230 tumor are injected simultaneously with Gd-DTPA (0.1nmol/kg) and IC-Green (2.5mg/kg). The enhancement kinetics of both contrast agents are recorded simultaneously with this hybrid MRI-DOT system and evaluated for different tumors.

Gadolinium Endohedral Metallofullerene-Based MRI Contrast Agents

NASA Astrophysics Data System (ADS)

Bolskar, Robert D.

With the ability to encapsulate and carry the highly paramagnetic Gd3+ ion, gadolinium endohedral metallofullerenes or "gadofullerenes" are being explored as alternatives to the chelate complexes that are currently used for contrast-enhanced magnetic resonance imaging (MRI). Reviewed here are the various water-soluble derivatives of the gadofullerenes Gd@C82, Gd@C60, and Gd3N@C80 that have been investigated as MRI contrast agents. The water proton r1 relaxivities of gadofullerenes can be more than an order of magnitude higher than those of clinically used chelate agents. Gadofullerene relaxivity mechanisms have been studied, and multiple factors are found to contribute to their high relaxivities. In vitro and in vivoT1-weighted MRI tests of gadofullerene derivatives have shown their utility as bright image-enhancing agents. The gadofullerene MRI contrast agents are a promising new and unique style of gadolinium carrier for advanced imaging applications, including cellular and molecular imaging.

Nephrogenic systemic fibrosis (NSF): a late adverse reaction to some of the gadolinium based contrast agents

PubMed Central

Marckmann, Peter; Logager, Vibeke B.

2007-01-01

Abstract Until recently it was believed that extracellular gadolinium based contrast agents were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some gadolinium based contrast agents may trigger the development of nephrogenic systemic fibrosis, a generalised fibrotic disorder, in renal failure patients. Accordingly, the use of gadodiamide and gadopentate dimeglumine for renal failure patients was banned in Europe in spring 2007. The same two compounds should only be used cautiously in patients with moderate renal dysfunction. The current paper reviews the situation (July 2007) regarding gadolinium based contrast agent and the severe delayed reaction to some of these agents. The fear of nephrogenic systemic fibrosis should not lead to a denial of a well indicated enhanced magnetic resonance imaging examination. PMID:17905680

Characterization of image heterogeneity using 2D Minkowski functionals increases the sensitivity of detection of a targeted MRI contrast agent.

PubMed

Canuto, Holly C; McLachlan, Charles; Kettunen, Mikko I; Velic, Marko; Krishnan, Anant S; Neves, Andre' A; de Backer, Maaike; Hu, D-E; Hobson, Michael P; Brindle, Kevin M

2009-05-01

A targeted Gd(3+)-based contrast agent has been developed that detects tumor cell death by binding to the phosphatidylserine (PS) exposed on the plasma membrane of dying cells. Although this agent has been used to detect tumor cell death in vivo, the differences in signal intensity between treated and untreated tumors was relatively small. As cell death is often spatially heterogeneous within tumors, we investigated whether an image analysis technique that parameterizes heterogeneity could be used to increase the sensitivity of detection of this targeted contrast agent. Two-dimensional (2D) Minkowski functionals (MFs) provided an automated and reliable method for parameterization of image heterogeneity, which does not require prior assumptions about the number of regions or features in the image, and were shown to increase the sensitivity of detection of the contrast agent as compared to simple signal intensity analysis. (c) 2009 Wiley-Liss, Inc.

MRI contrast agent concentration and tumor interstitial fluid pressure.

PubMed

Liu, L J; Schlesinger, M

2016-10-07

The present work describes the relationship between tumor interstitial fluid pressure (TIFP) and the concentration of contrast agent for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We predict the spatial distribution of TIFP based on that of contrast agent concentration. We also discuss the cases for estimating tumor interstitial volume fraction (void fraction or porosity of porous medium), ve, and contrast volume transfer constant, K(trans), by measuring the ratio of contrast agent concentration in tissue to that in plasma. A linear fluid velocity distribution may reflect a quadratic function of TIFP distribution and lead to a practical method for TIFP estimation. To calculate TIFP, the parameters or variables should preferably be measured along the direction of the linear fluid velocity (this is in the same direction as the gray value distribution of the image, which is also linear). This method may simplify the calculation for estimating TIFP. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

In vitro and ex vivo evaluation of silica-coated super paramagnetic iron oxide nanoparticles (SPION) as biomedical photoacoustic contrast agent

NASA Astrophysics Data System (ADS)

Alwi, Rudolf; Telenkov, Sergey A.; Mandelis, Andreas; Leshuk, Timothy; Gu, Frank; Oladepo, Sulayman; Michaelian, Kirk; Dickie, Kristopher

2013-03-01

The employment of contrast agents in photoacoustic imaging has gained significant attention within the past few years for their biomedical applications. In this study, the use of silica-coated superparamagnetic iron oxide (Fe3O4) nanoparticles (SPION) was investigated as a contrast agent in biomedical photoacoustic imaging. SPIONs have been widely used as Food-and-Drug-Administration (FDA)-approved contrast agents for magnetic resonance imaging (MRI) and are known to have an excellent safety profile. Using our frequency-domain photoacoustic correlation technique ("the photoacoustic radar") with modulated laser excitation, we examined the effects of nanoparticle size, concentration and biological medium (e.g. serum, sheep blood) on its photoacoustic response in turbid media (intralipid solution). Maximum detection depth and minimum measurable SPION concentration were determined experimentally. The detection was performed using a single element transducer. The nanoparticle-induced optical contrast ex vivo in dense muscular tissues (avian pectus) was evaluated using a phased array photoacoustic probe and the strong potential of silicacoated SPION as a possible photoacoustic contrast agent was demonstrated. This study opens the way for future clinical applications of nanoparticle-enhanced photoacoustic imaging in cancer therapy.

Applying tattoo dye as a third-harmonic generation contrast agent for in vivo optical virtual biopsy of human skin

NASA Astrophysics Data System (ADS)

Tsai, Ming-Rung; Lin, Chen-Yu; Liao, Yi-Hua; Sun, Chi-Kuang

2013-02-01

Third-harmonic generation (THG) microscopy has been reported to provide intrinsic contrast in elastic fibers, cytoplasmic membrane, nucleus, actin filaments, lipid bodies, hemoglobin, and melanin in human skin. For advanced molecular imaging, exogenous contrast agents are developed for a higher structural or molecular specificity. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical biopsy of human skin. Spectroscopy and microscopy experiments were performed on cultured cells with tattoo dyes, in tattooed mouse skin, and in tattooed human skin to demonstrate the THG enhancement effect. Compared with other absorbing dyes or nanoparticles used as exogenous THG contrast agents, tattoo dyes are widely adopted in human skin so that future clinical biocompatibility evaluation is relatively achievable. Combined with the demonstrated THG enhancement effect, tattoo dyes show their promise for future clinical imaging applications.

Comparison of colonic transit between polyethylene glycol and water as oral contrast vehicles in the CT evaluation of acute appendicitis.

PubMed

Hebert, Jeffrey J; Taylor, Andrew J; Winter, Thomas C

2006-11-01

The objective of our study was to assess the efficacy of a new positive oral contrast agent's ability to reach the colon during CT evaluation of acute appendicitis. Eighty adult emergency department patients who underwent abdominal CT to evaluate for appendicitis were studied. Forty patients received the department's standard dose of 1,600 mL of a water-iodinated contrast mixture (ratio of 2 mL of iodinated contrast material to 100 mL of water) with a standard delay time of 2-2.5 hours from the beginning of contrast medium ingestion. Forty patients were given a new oral contrast mixture of 1,000 mL of polyethylene glycol (PEG) mixed with 30 mL of iodinated contrast agent, and the examination was conducted only 1 hour from inception of contrast administration. Examinations were reviewed for the presence of contrast medium in the cecum and the presence of appendicitis or other abdominal abnormality. Thirty-eight of 40 patients in the PEG group had contrast medium in the colon at 1 hour after contrast administration, 20 of whom had surgically confirmed cases of appendicitis. In five other patients in that group, another cause to explain the patient's complaints was identified on imaging. Only 18 of the 40 patients who received the standard oral preparation had contrast material present in the cecum. Eleven patients in that group had confirmed appendicitis, and four others had another abnormal finding detected at CT. There was a significant difference in the success of contrast medium transit to the colon with these two agents (p < 0.0001). The use of an oral contrast agent composed of PEG and iodinated contrast material provided a marked improvement in oral agent transit to the colon even in patients with intraabdominal inflammation.

DYNACLIPS (DYNAmic CLIPS): A dynamic knowledge exchange tool for intelligent agents

NASA Technical Reports Server (NTRS)

Cengeloglu, Yilmaz; Khajenoori, Soheil; Linton, Darrell

1994-01-01

In a dynamic environment, intelligent agents must be responsive to unanticipated conditions. When such conditions occur, an intelligent agent may have to stop a previously planned and scheduled course of actions and replan, reschedule, start new activities and initiate a new problem solving process to successfully respond to the new conditions. Problems occur when an intelligent agent does not have enough knowledge to properly respond to the new situation. DYNACLIPS is an implementation of a framework for dynamic knowledge exchange among intelligent agents. Each intelligent agent is a CLIPS shell and runs a separate process under SunOS operating system. Intelligent agents can exchange facts, rules, and CLIPS commands at run time. Knowledge exchange among intelligent agents at run times does not effect execution of either sender and receiver intelligent agent. Intelligent agents can keep the knowledge temporarily or permanently. In other words, knowledge exchange among intelligent agents would allow for a form of learning to be accomplished.

Poly(iohexol) nanoparticles as contrast agents for in vivo X-ray computed tomography imaging.

PubMed

Yin, Qian; Yap, Felix Y; Yin, Lichen; Ma, Liang; Zhou, Qin; Dobrucki, Lawrence W; Fan, Timothy M; Gaba, Ron C; Cheng, Jianjun

2013-09-18

Biocompatible poly(iohexol) nanoparticles, prepared through cross-linking of iohexol and hexamethylene diisocyanate followed by coprecipitation of the resulting cross-linked polymer with mPEG-polylactide, were utilized as contrast agents for in vivo X-ray computed tomography (CT) imaging. Compared to conventional small-molecule contrast agents, poly(iohexol) nanoparticles exhibited substantially protracted retention within the tumor bed and a 36-fold increase in CT contrast 4 h post injection, which makes it possible to acquire CT images with improved diagnosis accuracy over a broad time frame without multiple administrations.

Copper complexes as a source of redox active MRI contrast agents.

PubMed

Dunbar, Lynsey; Sowden, Rebecca J; Trotter, Katherine D; Taylor, Michelle K; Smith, David; Kennedy, Alan R; Reglinski, John; Spickett, Corinne M

2015-10-01

The study reports an advance in designing copper-based redox sensing MRI contrast agents. Although the data demonstrate that copper(II) complexes are not able to compete with lanthanoids species in terms of contrast, the redox-dependent switch between diamagnetic copper(I) and paramagnetic copper(II) yields a novel redox-sensitive contrast moiety with potential for reversibility.

Subharmonic emissions from microbubbles: effect of the driving pulse shape.

PubMed

Biagi, Elena; Breschi, Luca; Vannacci, Enrico; Masotti, Leonardo

2006-11-01

The aims of this work are to investigate the response of the ultrasonic contrast agents (UCA) insonified by different arbitrary-shaped pulses at different acoustic pressures and concentration of the contrast agent focusing on subharmonic emission. A transmission setup was developed in order to insonify the contrast agent contained in a measurement chamber. The transmitted ultrasonic signals were generated by an arbitrary wave generator connected to a linear power amplifier able to drive a single-element transducer. The transmitted ultrasonic pulses that passed through the contrast agent-filled chamber were received by a second transducer or a hydrophone aligned with the first one. The radio frequency (RF) signals were acquired by fast echographic multiparameters multi-image novel apparatus (FEMMINA), which is an echographic platform able to acquire ultrasonic signals in a real-time modality. Three sets of ultrasonic signals were devised in order to evaluate subharmonic response of the contrast agent respect with sinusoidal burst signals used as reference pulses. A decreasing up to 30 dB in subharmonic response was detected for a Gaussian-shaped pulse; differences in subharmonic emission up to 21 dB were detected for a composite pulse (two-tone burst) for different acoustic pressures and concentrations. Results from this experimentation demonstrated that the transmitted pulse shape strongly affects subharmonic emission in spite of a second harmonic one. In particular, the smoothness of the initial portion of the shaped pulses can inhibit subharmonic generation from the contrast agents respect with a reference sinusoidal burst signal. It also was shown that subharmonic generation is influenced by the amplitude and the concentration of the contrast agent for each set of the shaped pulses. Subharmonic emissions that derive from a nonlinear mechanism involving nonlinear coupling among different oscillation modes are strongly affected by the shape of the ultrasonic driving pulse.

Hyperspectral fluorescence imaging with multi wavelength LED excitation

NASA Astrophysics Data System (ADS)

Luthman, A. Siri; Dumitru, Sebastian; Quirós-Gonzalez, Isabel; Bohndiek, Sarah E.

2016-04-01

Hyperspectral imaging (HSI) can combine morphological and molecular information, yielding potential for real-time and high throughput multiplexed fluorescent contrast agent imaging. Multiplexed readout from targets, such as cell surface receptors overexpressed in cancer cells, could improve both sensitivity and specificity of tumor identification. There remains, however, a need for compact and cost effective implementations of the technology. We have implemented a low-cost wide-field multiplexed fluorescence imaging system, which combines LED excitation at 590, 655 and 740 nm with a compact commercial solid state HSI system operating in the range 600 - 1000 nm. A key challenge for using reflectance-based HSI is the separation of contrast agent fluorescence from the reflectance of the excitation light. Here, we illustrate how it is possible to address this challenge in software, using two offline reflectance removal methods, prior to least-squares spectral unmixing. We made a quantitative comparison of the methods using data acquired from dilutions of contrast agents prepared in well-plates. We then established the capability of our HSI system for non-invasive in vivo fluorescence imaging in small animals using the optimal reflectance removal method. The HSI presented here enables quantitative unmixing of at least four fluorescent contrast agents (Alexa Fluor 610, 647, 700 and 750) simultaneously in living mice. A successful unmixing of the four fluorescent contrast agents was possible both using the pure contrast agents and with mixtures. The system could in principle also be applied to imaging of ex vivo tissue or intraoperative imaging in a clinical setting. These data suggest a promising approach for developing clinical applications of HSI based on multiplexed fluorescence contrast agent imaging.

Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.

PubMed

Huang, Haitao; Yue, Tao; Xu, Ke; Golzarian, Jafar; Yu, Jiahui; Huang, Jin

2015-07-01

Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor. Crown Copyright © 2015. Published by Elsevier B.V. All rights reserved.

Synthesis and characterization of a porphyrazine-Gd(III) MRI contrast agent and in vivo imaging of a breast cancer xenograft model.

PubMed

Trivedi, Evan R; Ma, Zhidong; Waters, Emily A; Macrenaris, Keith W; Subramanian, Rohit; Barrett, Anthony G M; Meade, Thomas J; Hoffman, Brian M

2014-01-01

Porphyrazines (Pz), or tetraazaporphyrins, are being studied for their potential use in detection and treatment of cancer. Here, an amphiphilic Cu-Pz-Gd(III) conjugate has been prepared via azide-alkyne Huisgen cycloaddition or 'click' chemistry between an azide functionalized Pz and alkyne functionalized DOTA-Gd(III) analog for use as an MRI contrast agent. This agent, Cu-Pz-Gd(III), is synthesized in good yield and exhibits solution-phase ionic relaxivity (r1  = 11.5 mM(-1) s(-1)) that is approximately four times higher than that of a clinically used monomeric Gd(III) contrast agent, DOTA-Gd(III). Breast tumor cells (MDA-MB-231) associate with Cu-Pz-Gd(III) in vitro, where significant contrast enhancement (9.336 ± 0.335 contrast-to-noise ratio) is observed in phantom cell pellet MR images. This novel contrast agent was administered in vivo to an orthotopic breast tumor model in athymic nude mice and MR images were collected. The average T1 of tumor regions in mice treated with 50 mg kg(-1) Cu-Pz-Gd(III) decreased relative to saline-treated controls. Furthermore, the decrease in T1 was persistent relative to mice treated with the monomeric Gd(III) contrast agent. An ex vivo biodistribution study confirmed that Cu-Pz-Gd(III) accumulates in the tumors and is rapidly cleared, primarily through the kidneys. Differential accumulation and T1 enhancement by Cu-Pz-Gd(III) in the tumor's core relative to the periphery offer preliminary evidence that this agent would find application in the imaging of necrotic tissue. Copyright © 2014 John Wiley & Sons, Ltd.

Spectral Imaging Technology-Based Evaluation of Radiation Treatment Planning to Remove Contrast Agent Artifacts.

PubMed

Yi-Qun, Xu; Wei, Liu; Xin-Ye, Ni

2016-10-01

This study employs dual-source computed tomography single-spectrum imaging to evaluate the effects of contrast agent artifact removal and the computational accuracy of radiotherapy treatment planning improvement. The phantom, including the contrast agent, was used in all experiments. The amounts of iodine in the contrast agent were 30, 15, 7.5, and 0.75 g/100 mL. Two images with different energy values were scanned and captured using dual-source computed tomography (80 and 140 kV). To obtain a fused image, 2 groups of images were processed using single-energy spectrum imaging technology. The Pinnacle planning system was used to measure the computed tomography values of the contrast agent and the surrounding phantom tissue. The difference between radiotherapy treatment planning based on 80 kV, 140 kV, and energy spectrum image was analyzed. For the image with high iodine concentration, the quality of the energy spectrum-fused image was the highest, followed by that of the 140-kV image. That of the 80-kV image was the worst. The difference in the radiotherapy treatment results among the 3 models was significant. When the concentration of iodine was 30 g/100 mL and the distance from the contrast agent at the dose measurement point was 1 cm, the deviation values (P) were 5.95% and 2.20% when image treatment planning was based on 80 and 140 kV, respectively. When the concentration of iodine was 15 g/100 mL, deviation values (P) were -2.64% and -1.69%. Dual-source computed tomography single-energy spectral imaging technology can remove contrast agent artifacts to improve the calculated dose accuracy in radiotherapy treatment planning. © The Author(s) 2015.

Redox-activated MRI contrast agents based on lanthanide and transition metal ions.

PubMed

Tsitovich, Pavel B; Burns, Patrick J; McKay, Adam M; Morrow, Janet R

2014-04-01

The reduction/oxidation (redox) potential of tissue is tightly regulated in order to maintain normal physiological processes, but is disrupted in disease states. Thus, the development of new tools to map tissue redox potential may be clinically important for the diagnosis of diseases that lead to redox imbalances. One promising area of chemical research is the development of redox-activated probes for mapping tissue through magnetic resonance imaging (MRI). In this review, we summarize several strategies for the design of redox-responsive MRI contrast agents. Our emphasis is on both lanthanide(III) and transition metal(II/III) ion complexes that provide contrast either as T1 relaxivity MRI contrast agents or as paramagnetic chemical exchange saturation transfer (PARACEST) contrast agents. These agents are redox-triggered by a variety of chemical reactions or switches including redox-activated thiol groups, and heterocyclic groups that interact with the metal ion or influence properties of other ancillary ligands. Metal ion centered redox is an approach which is ripe for development by coordination chemists. Redox-triggered metal ion approaches have great potential for creating large differences in magnetic properties that lead to changes in contrast. An attractive feature of these agents is the ease of fine-tuning the metal ion redox potential over a biologically relevant range. Copyright © 2014 Elsevier Inc. All rights reserved.

Gadolinium-Loaded Solid Lipid Nanoparticles as a Tumor-Absorbable Contrast Agent for Early Diagnosis of Colorectal Tumors Using Magnetic Resonance Colonography.

PubMed

Sun, Jihong; Zhang, Shizheng; Jiang, Shaojie; Bai, Weixian; Liu, Fei; Yuan, Hong; Ji, Jiansong; Luo, Jingfeng; Han, Guocan; Chen, Lumin; Jin, Yin; Hu, Peng; Yu, Lei; Yang, Xiaoming

2016-09-01

Magnetic resonance (MR) contrast agents focusing on special functions are required to improve cancer diagnosis, particularly in the early stages. Here, we designed multifunctional solid lipid nanoparticles (SLNs) with simultaneous loading of gadolinium (Gd) diethylenetriaminepentaacetic acid (Gd-DTPA) and octadecylamine fluorescein isothiocyanate (FITC) to obtain Gd-FITC-SLNs as a tumor-absorbable nanoparticle contrast agent for the histological confirmation of MR imaging (MRI) findings. Colorectal tumors were evaluated in vitro and in vivo via direct uptake of this contrast agent, which displayed reasonable T1 relaxivity and no significant cytotoxicity at the experimental concentrations in human colon carcinoma cells (HT29) and mouse colon carcinoma cells (CT26). In vitro cell uptake experiments demonstrated that contrast agent absorption by the two types of cancer cells was concentration-dependent in the safe concentration range. During in vivo MRI, transrectal infusion of Gd-FITC-SLNs showed more significant enhancement at the tumor site compared with the infusion of Gd-DTPA in female C57/BL mice with azoxymethane/dextran sulfate sodium-induced colorectal highgrade intraepithelial neoplasia. Subsequent confocal fluorescence microscopy demonstrated Gd-FITC-SLNs as highly concentrated green fluorescent spots distributed from the tumor capsule into the tumor. This study establishes the "proof-of-principle" of a new MRI technique wherein colorectal tumors are enhanced via direct absorption or uptake of the nanoparticle contrast agent.

Biofilm imaging in porous media by laboratory X-Ray tomography: Combining a non-destructive contrast agent with propagation-based phase-contrast imaging tools

PubMed Central

Beltran, Mario A.; Morales, Verónica L.; Derlon, Nicolas; Morgenroth, Eberhard; Kaufmann, Rolf; Holzner, Markus

2017-01-01

X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011), which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent—biofilm interactions (e.g. biofilm detachment) occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand biofilm development and bioclogging mechanisms in porous materials and the obtained biofilm morphology could be an ideal basis for 3D numerical calculations of hydrodynamic conditions to investigate biofilm-flow coupling. PMID:28732010

One-pot synthesis of BiOCl half-shells using microemulsion droplets as templates with highly photocatalytic performance for the degradation of ciprofloxacin

NASA Astrophysics Data System (ADS)

Mao, Danjun; Yu, Anqing; Ding, Shanshan; Wang, Fei; Yang, Shaogui; Sun, Cheng; He, Huan; Liu, Yazi; Yu, Kai

2016-12-01

Ultrathin BiOCl half-shells have been synthesized via an ionic liquid-in-water (IL/W) microemulsion, applying the liquid-liquid boundary of the emulsion system as a template. Surfactant TX-100 acted as the stabilizer of the IL-microemulsion, which is of critical importance for the formation of BiOCl half-shells. The hollow structures were characterized using X-ray diffraction, scanning and transmission electron microscopy, diffuse reflectance spectroscopy and specific surface area, respectively. Possible formation mechanisms for the BiOCl half-shells were discussed. Moreover, the ultrathin BiOCl half-shells exhibited distinctly enhanced photocatalytic efficiency toward the degradation of colourless ciprofloxacin (CIP, a representative broad-spectrum antibiotic agent) under solar light irradiation as compared to BiOCl nanosheets. The photogenerated reactive species are verified by scavenger experiments, which reveals that rad O2- and h+ were the two major photoactive species toward the photodegradation of CIP over ultrathin BiOCl half-shells under solar-light. The enhanced activities of ultrathin BiOCl half-shells were mainly ascribed to the synergistic effect of the increased light-harvesting, larger BET surface area, faster separation and transfer of electron-hole pairs. It is hoped that the ionic liquid microemulsion-mediated route can be extended to the purposive design and fabrication of other halogen-containing inorganic hollow materials.

Dose Reduction Study in Vaginal Balloon Packing Filled With Contrast for HDR Brachytherapy Treatment;HDR; Uterine cervix cancer; Vaginal balloon packing; Contrast; Monte Carlo

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

Saini, Amarjit S.; Zhang, Geoffrey G., E-mail: geoffrey.zhang@moffitt.org; Finkelstein, Steven E.

2011-07-15

Purpose: Vaginal balloon packing is a means to displace organs at risk during high dose rate brachytherapy of the uterine cervix. We tested the hypothesis that contrast-filled vaginal balloon packing reduces radiation dose to organs at risk, such as the bladder and rectum, in comparison to water- or air-filled balloons. Methods and Materials: In a phantom study, semispherical vaginal packing balloons were filled with air, saline solution, and contrast agents. A high dose rate iridium-192 source was placed on the anterior surface of the balloon, and the diode detector was placed on the posterior surface. Dose ratios were taken withmore » each material in the balloon. Monte Carlo (MC) simulations, by use of the MC computer program DOSXYZnrc, were performed to study dose reduction vs. balloon size and contrast material, including commercially available iodine- and gadolinium-based contrast agents. Results: Measured dose ratios on the phantom with the balloon radius of 3.4 cm were 0.922 {+-} 0.002 for contrast/saline solution and 0.808 {+-} 0.001 for contrast/air. The corresponding ratios by MC simulations were 0.895 {+-} 0.010 and 0.781 {+-} 0.010. The iodine concentration in the contrast was 23.3% by weight. The dose reduction of contrast-filled balloon ranges from 6% to 15% compared with water-filled balloon and 11% to 26% compared with air-filled balloon, with a balloon size range between 1.4 and 3.8 cm, and iodine concentration in contrast of 24.9%. The dose reduction was proportional to the contrast agent concentration. The gadolinium-based contrast agents showed less dose reduction because of much lower concentrations in their solutions. Conclusions: The dose to the posterior wall of the bladder and the anterior wall of the rectum can be reduced if the vaginal balloon is filled with contrast agent in comparison to vaginal balloons filled with saline solution or air.« less

A "win-win" nanoplatform: TiO2:Yb,Ho,F for NIR light-induced synergistic therapy and imaging.

PubMed

Zhou, Jie; Luo, Pei; Sun, Chong; Meng, Lingchang; Ye, Weiran; Chen, Shanshan; Du, Bin

2017-03-23

To avoid the defect of low energy transfer efficiency in core-shell UCNP-TiO 2 NPs, doping rare earth into TiO 2 and improving the photocatalytic activity of TiO 2 itself under Vis-NIR light might be a more direct and efficient strategy for high 1 O 2 production. Here, we designed a TiO 2 :Yb,Ho,F-β-CD@DTX/HA nanoplatform using TiO 2 :Yb,Ho,F as the core, β-CD as the drug carrier, hyaluronic acid (HA) as the capping agent and target, and then applied it for 808 nm induced photodynamic-chemotherapy and 980 nm upconversion fluorescence/MR imaging. The results were as follows: (i) for TiO 2 as a photosensitizer, after doping Yb, Ho, F into TiO 2 , it could directly generate reactive oxygen species under an 808 nm laser; the dopants enhanced the absorption under the UV-Vis-NIR region and increased the electron-hole pair separation. (ii) For TiO 2 as the upconversion host, F and Ho also endowed TiO 2 :Yb,Ho,F with enhanced upconversion fluorescence under a 980 nm laser and T 2 -MRI contrast performance (r 2 = 30.71 mM -1 s -1 ), respectively, thus, facilitating imaging for deep tissues. (iii) The HA shell outside of β-CD prevented the unexpected leaking of DTX, which improved the target abilities and achieved the enzyme-responsive drug release. The in vitro and in vivo studies also demonstrated the nanosystem could efficiently suppress tumor growth by combination therapy and had excellent imaging (UCL/MR) ability. Particularly, our work was the first example that utilized TiO 2 simultaneously as a photosensitizer and upconversion host, which simplified the core-shell UCNP-TiO 2 nanocomposites and reached a "win-win" cooperation in NIR-induced photodynamic therapy and UCL imaging.

Fabrication of quantum dot/silica core-shell particles immobilizing Au nanoparticles and their dual imaging functions

NASA Astrophysics Data System (ADS)

Kobayashi, Yoshio; Matsudo, Hiromu; Li, Ting-ting; Shibuya, Kyosuke; Kubota, Yohsuke; Oikawa, Takahiro; Nakagawa, Tomohiko; Gonda, Kohsuke

2016-03-01

The present work proposes preparation methods for quantum dot/silica (QD/SiO2) core-shell particles that immobilize Au nanoparticles (QD/SiO2/Au). A colloid solution of QD/SiO2 core-shell particles with an average size of 47.0 ± 6.1 nm was prepared by a sol-gel reaction of tetraethyl orthosilicate in the presence of the QDs with an average size of 10.3 ± 2.1 nm. A colloid solution of Au nanoparticles with an average size of 17.9 ± 1.3 nm was prepared by reducing Au3+ ions with sodium citrate in water at 80 °C. Introduction of amino groups to QD/SiO2 particle surfaces was performed using (3-aminopropyl)-triethoxysilane (QD/SiO2-NH2). The QD/SiO2/Au particles were fabricated by mixing the Au particle colloid solution and the QD/SiO2-NH2 particle colloid solution. Values of radiant efficiency and computed tomography for the QD/SiO2/Au particle colloid solution were 2.23 × 107 (p/s/cm2/sr)/(μW/cm2) at a QD concentration of 8 × 10-7 M and 1180 ± 314 Hounsfield units and an Au concentration of 5.4 × 10-2 M. The QD/SiO2/Au particle colloid solution was injected into a mouse chest wall. Fluorescence emitted from the colloid solution could be detected on the skin covering the chest wall. The colloid solution could also be X-ray-imaged in the chest wall. Consequently, the QD/SiO2/Au particle colloid solution was found to have dual functions, i.e., fluorescence emission and X-ray absorption in vivo, which makes the colloid solution suitable to function as a contrast agent for dual imaging processes.

Brain tumor enhancement in magnetic resonance imaging at 3 tesla: intraindividual comparison of two high relaxivity macromolecular contrast media with a standard extracellular gd-chelate in a rat brain tumor model.

PubMed

Fries, Peter; Runge, Val M; Bücker, Arno; Schürholz, Hellmut; Reith, Wolfgang; Robert, Philippe; Jackson, Carney; Lanz, Titus; Schneider, Günther

2009-04-01

The aim of this study was to evaluate lesion enhancement (LE) and contrast-to-noise ratio (CNR) properties of P846, a new intermediate sized, high relaxivity Gd-based contrast agent at 3 Tesla in a rat brain glioma model, and to compare this contrast agent with a high relaxivity, macromolecular compound (P792), and a standard extracellular Gd-chelate (Gd-DOTA). Seven rats with experimental induced brain glioma were evaluated using 3 different contrast agents, with each MR examination separated by at least 24 hours. The time between injections assured sufficient clearance of the agent from the tumor, before the next examination. P792 (Gadomelitol, Guerbet, France) and P846 (a new compound from Guerbet Research) are macromolecular and high relaxivity contrast agents with no protein binding, and were compared with the extracellular agent Gd-DOTA (Dotarem, Guerbet, France). T1w gradient echo sequences (TR/TE 200 milliseconds/7.38 milliseconds, flip angle = 90 degrees , acquisition time: 1:42 minutes:sec, voxel size: 0.2 x 0.2 x 2.0 mm, FOV = 40 mm, acquisition matrix: 256 x 256) were acquired before and at 5 consecutive time points after each intravenous contrast injection in the identical slice orientation, using a dedicated 4-channel head array animal coil. The order of contrast media injection was randomized, with however Gd-DOTA used either as the first or second contrast agent. Contrast agent dose was adjusted to compensate for the different T1 relaxivities of the 3 agents. Signal-to-noise ratio, CNR, and LE were evaluated using region-of-interest analysis. A veterinary histopathologist confirmed the presence of a glioma in each subject, after completion of the imaging study. P792 showed significantly less LE as compared with Gd-DOTA within the first 7 minutes after contrast agent injection (P < 0.05) with, however, reaching comparable LE values at 9 minutes after injection (P = 0.07). However, P792 provided significantly less CNR as compared with Gd-DOTA (P < 0.05) for all examination time points. P846 provided comparable but persistent LE as compared with Gd-DOTA (P < 0.05) and demonstrated significantly greater LE and CNR when compared with P792 (P < 0.05). No statistically significant differences between CNR values for Gd-DOTA and P846 were noted for all examination time points (P < 0.05), with P846 administered at one-fourth the dose as compared with Gd-DOTA. The intravascular contrast medium P792 showed significantly less LE and CNR in comparison to Gd-DOTA and P846, suggesting that it does not show marked extravasation from tumor neocapillaries and does not significantly cross the disrupted blood brain-barrier in this rat glioma model. In distinction, P846 provides comparable enhancement properties at a field strength of 3 Tesla to the extracellular contrast agent Gd-DOTA, using the adjusted dose, suggesting that it crosses the disrupted blood-brain-barrier and tumor capillaries, most likely based on the decreased molecular weight as compared with P792. At the same time, the high relaxivity of this compound allows for decreasing the injected gadolinium dose by a factor of 4 whereas providing comparable enhancement properties when compared with a standard extracellular Gd-chelate (Gd-DOTA) at a dose of 0.1 mmol/kg body weight.

Cystogram

MedlinePlus

... showing the bladder (solid arrow) filling with a contrast agent. The catheter used to fill the bladder also ... taken. This final radiograph will show whether any contrast agent stays in your bladder following urina- tion. Any ...

Evaluation of bowel distension and mural visualisation using neutral oral contrast agents for multidetector-row computed tomography.

PubMed

Lim, Bee Kuan; Bux, Shaik Ismail; Rahmat, Kartini; Lam, Sze Yin; Liew, Yew Wai

2012-11-01

We compared the effectiveness of different types of non-commercial neutral oral contrast agents for bowel distension and mural visualisation in computed tomographic (CT) enterography. 90 consecutive patients from a group of 108 were randomly assigned to receive water (n = 30), 3.8% milk (n = 30) or 0.1% gastrografin (n = 30) as oral contrast agent. The results were independently reviewed by two radiologists who were blinded to the contrast agents used. The degree of bowel distension was qualitatively scored on a four-point scale. The discrimination of bowel loops, mural visualisation and visualisation of mucosal folds were evaluated on a 'yes' or 'no' basis. Side effects of the various agents were also recorded. 3.8% milk was significantly superior to water for bowel distension (jejunum, ileum and terminal ileum), discrimination of bowel loops (jejunum and ileum), mural visualisation and visualisation of mucosal folds (ileum and terminal ileum). It was also significantly superior to 0.1% gastrografin for bowel distension, discrimination of bowel loops, mural visualisation and visualisation of mucosal folds (jejunum, ileum and terminal ileum). However, 10% of patients who received 3.8% milk reported immediate post-test diarrhoea. No side effects were documented for patients who received water and 0.1% gastrografin. 3.8% milk is an effective and superior neutral oral contrast agent for the assessment of the jejunum, ileum and terminal ileum in CT enterography. However, further studies are needed to explore other suitable oral contrast agents for CT enterography in lactose- or cow's milk-intolerant patients.

High Energy Resolution Hyperspectral X-Ray Imaging for Low-Dose Contrast-Enhanced Digital Mammography.

PubMed

Pani, Silvia; Saifuddin, Sarene C; Ferreira, Filipa I M; Henthorn, Nicholas; Seller, Paul; Sellin, Paul J; Stratmann, Philipp; Veale, Matthew C; Wilson, Matthew D; Cernik, Robert J

2017-09-01

Contrast-enhanced digital mammography (CEDM) is an alternative to conventional X-ray mammography for imaging dense breasts. However, conventional approaches to CEDM require a double exposure of the patient, implying higher dose, and risk of incorrect image registration due to motion artifacts. A novel approach is presented, based on hyperspectral imaging, where a detector combining positional and high-resolution spectral information (in this case based on Cadmium Telluride) is used. This allows simultaneous acquisition of the two images required for CEDM. The approach was tested on a custom breast-equivalent phantom containing iodinated contrast agent (Niopam 150®). Two algorithms were used to obtain images of the contrast agent distribution: K-edge subtraction (KES), providing images of the distribution of the contrast agent with the background structures removed, and a dual-energy (DE) algorithm, providing an iodine-equivalent image and a water-equivalent image. The high energy resolution of the detector allowed the selection of two close-by energies, maximising the signal in KES images, and enhancing the visibility of details with the low surface concentration of contrast agent. DE performed consistently better than KES in terms of contrast-to-noise ratio of the details; moreover, it allowed a correct reconstruction of the surface concentration of the contrast agent in the iodine image. Comparison with CEDM with a conventional detector proved the superior performance of hyperspectral CEDM in terms of the image quality/dose tradeoff.

Development of silica-encapsulated silver nanoparticles as contrast agents intended for dual-energy mammography.

PubMed

Karunamuni, Roshan; Naha, Pratap C; Lau, Kristen C; Al-Zaki, Ajlan; Popov, Anatoliy V; Delikatny, Edward J; Tsourkas, Andrew; Cormode, David P; Maidment, Andrew D A

2016-09-01

Dual-energy (DE) mammography has recently entered the clinic. Previous theoretical and phantom studies demonstrated that silver provides greater contrast than iodine for this technique. Our objective was to characterize and evaluate in vivo a prototype silver contrast agent ultimately intended for DE mammography. The prototype silver contrast agent was synthesized using a three-step process: synthesis of a silver core, silica encapsulation and PEG coating. The nanoparticles were then injected into mice to determine their accumulation in various organs, blood half-life and dual-energy contrast. All animal procedures were approved by the institutional animal care and use committee. The final diameter of the nanoparticles was measured to be 102 (±9) nm. The particles were removed from the vascular circulation with a half-life of 15 min, and accumulated in macrophage-rich organs such as the liver, spleen and lymph nodes. Dual-energy subtraction techniques increased the signal difference-to-noise ratio of the particles by as much as a factor of 15.2 compared to the single-energy images. These nanoparticles produced no adverse effects in mice. Silver nanoparticles are an effective contrast agent for dual-energy x-ray imaging. With further design improvements, silver nanoparticles may prove valuable in breast cancer screening and diagnosis. • Silver has potential as a contrast agent for DE mammography. • Silica-coated silver nanoparticles are biocompatible and suited for in vivo use. • Silver nanoparticles produce strong contrast in vivo using DE mammography imaging systems.

Dual PET and Near-Infrared Fluorescence Imaging Probes as Tools for Imaging in Oncology

PubMed Central

An, Fei-Fei; Chan, Mark; Kommidi, Harikrishna; Ting, Richard

2016-01-01

OBJECTIVE The purpose of this article is to summarize advances in PET fluorescence resolution, agent design, and preclinical imaging that make a growing case for clinical PET fluorescence imaging. CONCLUSION Existing SPECT, PET, fluorescence, and MRI contrast imaging techniques are already deeply integrated into the management of cancer, from initial diagnosis to the observation and management of metastases. Combined positron-emitting fluorescent contrast agents can convey new or substantial benefits that improve on these proven clinical contrast agents. PMID:27223168

Core-based lipid nanoparticles as a nanoplatform for delivery of near-infrared fluorescent imaging agents.

PubMed

Anikeeva, Nadia; Sykulev, Yuri; Delikatny, Edward J; Popov, Anatoliy V

2014-01-01

Pyropheophorbide a (Pyro) is a near-infrared (NIR) fluorescent dye and photosensitizer with high quantum yield that makes the dye suitable for tumor treatment both as an imaging and therapy agent. We have designed and synthesized a series of a Pyro-based NIR probes, based on the conjugation of Pyro with lipids. The nature of our probes requires the use of a lipophilic carrier to deliver the probes to cancer cell membranes. To address this, we have utilized lipid-based nanoparticles (LNPs) consisting of PEGylated lipids, which form the nanoparticle shell, and a lipid core. To endow the LNPs with targeting properties, nitrilotriacetic acid (NTA) lipids were included in the composition that enables the non-covalent attachment of His-tag targeting proteins preserving their functional activity. We found that the nature of the core molecules influence the nanoparticle size, shelf-life and stability at physiological temperature. Two different Pyro-lipid conjugates were loaded either into the core or shell of the LNPs. The conjugates revealed differential ability to be accumulated in the cell membrane of the target cells with time. Thus, the modular organization of the core-shell LNPs allows facile adjustment of their composition with goal to fine tuning the nanoparticle properties for in vivo application.

Core-based lipid nanoparticles as a nanoplatform for delivery of near-infrared fluorescent imaging agents

PubMed Central

Anikeeva, Nadia; Sykulev, Yuri; Delikatny, Edward J; Popov, Anatoliy V

2014-01-01

Pyropheophorbide a (Pyro) is a near-infrared (NIR) fluorescent dye and photosensitizer with high quantum yield that makes the dye suitable for tumor treatment both as an imaging and therapy agent. We have designed and synthesized a series of a Pyro-based NIR probes, based on the conjugation of Pyro with lipids. The nature of our probes requires the use of a lipophilic carrier to deliver the probes to cancer cell membranes. To address this, we have utilized lipid-based nanoparticles (LNPs) consisting of PEGylated lipids, which form the nanoparticle shell, and a lipid core. To endow the LNPs with targeting properties, nitrilotriacetic acid (NTA) lipids were included in the composition that enables the non-covalent attachment of His-tag targeting proteins preserving their functional activity. We found that the nature of the core molecules influence the nanoparticle size, shelf-life and stability at physiological temperature. Two different Pyro-lipid conjugates were loaded either into the core or shell of the LNPs. The conjugates revealed differential ability to be accumulated in the cell membrane of the target cells with time. Thus, the modular organization of the core-shell LNPs allows facile adjustment of their composition with goal to fine tuning the nanoparticle properties for in vivo application. PMID:25250201

Microwave pyrolysis using self-generated pyrolysis gas as activating agent: An innovative single-step approach to convert waste palm shell into activated carbon

NASA Astrophysics Data System (ADS)

Yek, Peter Nai Yuh; Keey Liew, Rock; Shahril Osman, Mohammad; Chung Wong, Chee; Lam, Su Shiung

2017-11-01

Waste palm shell (WPS) is a biomass residue largely available from palm oil industries. An innovative microwave pyrolysis method was developed to produce biochar from WPS while the pyrolysis gas generated as another product is simultaneously used as activating agent to transform the biochar into waste palm shell activated carbon (WPSAC), thus allowing carbonization and activation to be performed simultaneously in a single-step approach. The pyrolysis method was investigated over a range of process temperature and feedstock amount with emphasis on the yield and composition of the WPSAC obtained. The WPSAC was tested as dye adsorbent in removing methylene blue. This pyrolysis approach provided a fast heating rate (37.5°/min) and short process time (20 min) in transforming WPS into WPSAC, recording a product yield of 40 wt%. The WPSAC was detected with high BET surface area (≥ 1200 m2/g), low ash content (< 5 wt%), and high pore volume (≥ 0.54 cm3/g), thus recording high adsorption efficiency of 440 mg of dye/g. The desirable process features (fast heating rate, short process time) and the recovery of WPSAC suggest the exceptional promise of the single-step microwave pyrolysis approach to produce high-grade WPSAC from WPS.

Nonaqueous slip casting of high temperature ceramic superconductors using an investment casting technique

NASA Technical Reports Server (NTRS)

Hooker, Matthew W. (Inventor); Taylor, Theodore D. (Inventor); Wise, Stephanie A. (Inventor); Buckley, John D. (Inventor); Vasquez, Peter (Inventor); Buck, Gregory M. (Inventor); Hicks, Lana P. (Inventor)

1993-01-01

A process for slip casting ceramic articles that does not employ parting agents and affords the casting of complete, detailed, precision articles that do not possess parting lines is presented. This process is especially useful for high temperature superconductors and water-sensitive ceramics. A wax pattern for a shell mold is provided, and an aqueous mixture of a calcium sulfate-bonded investment material is applied as a coating to the wax pattern. The coated wax pattern is then dried, followed by curing to vaporize the wax pattern and leave a shell mold of the calcium sulfate-bonded investment material. The shell mold is cooled to room temperature, and a ceramic slip, created by dispersing a ceramic powder in an organic liquid, is poured therein. After a ceramic shell of desired thickness or a solid article has set up in the shell mold, excess ceramic slip is poured out. The shell mold is misted with water and peeled away from the ceramic article, after which the ceramic is fired to provide a complete, detailed, precision, high temperature superconductive ceramic article without parting lines. The casting technique may take place in the presence of a magnetic field to orient the ceramic powders during the casting process.

Glomerular filtration rate in evaluation of the effect of iodinated contrast media on renal function.

PubMed

Becker, Joshua; Babb, James; Serrano, Manuel

2013-04-01

The purpose of this study was to use measured glomerular filtration rate (GFR), the reference standard of renal function, to assess the deleterious effect of iodinated contrast media on renal function. Such an effect has been traditionally defined as a greater than 0.5-mg/dL increase in serum creatinine concentration or a 25% or greater increase 24-72 hours after the injection of iodinated contrast medium. This pilot investigation was focused on the consequences of clinically indicated IV injection of iodinated contrast media; intraarterial injection was excluded. One hundred thirteen patients with normal serum creatinine concentrations were enrolled in an approved protocol. At random, as chosen by one of the investigators, patients underwent imaging with one of three monomeric agents (iopamidol 300, iopromide 300, iohexol 300) and one dimeric agent (iodixanol 320). Measured GFR was determined immediately before CT and approximately 3 and 72 hours after the contrast injection for the CT examination. Iodinated contrast medium, a glomerular filtrate with no tubular excretion or reabsorption, was the GFR marker. Measured GFR was determined by x-ray fluorescence analysis with nonisotopic iodinated contrast media. Monomeric and dimeric contrast agents in diagnostic CT volumes (based on bodyweight and imaging protocol) did not induce a significant change in measured GFR (95% confidence by Wilcoxon test), suggesting that use of the evaluated contrast media will not lead to more than a 12% variation. The three monomeric agents studied and the one dimeric agent were equivalent in terms of lack of a significant effect on measured GFR when administered to patients with a normal GFR.

Noninvasive visualization of in vivo release and intratumoral distribution of surrogate MR contrast agent using the dual MR contrast technique.

PubMed

Onuki, Yoshinori; Jacobs, Igor; Artemov, Dmitri; Kato, Yoshinori

2010-09-01

A direct evaluation of the in vivo release profile of drugs from carriers is a clinical demand in drug delivery systems, because drug release characterized in vitro correlates poorly with in vivo release. The purpose of this study is to demonstrate the in vivo applicability of the dual MR contrast technique as a useful tool for noninvasive monitoring of the stability and the release profile of drug carriers, by visualizing in vivo release of the encapsulated surrogate MR contrast agent from carriers and its subsequent intratumoral distribution profile. The important aspect of this technique is that it incorporates both positive and negative contrast agents within a single carrier. GdDTPA, superparamagnetic iron oxide nanoparticles, and 5-fluorouracil were encapsulated in nano- and microspheres composed of poly(D,L-lactide-co-glycolide), which was used as a model carrier. In vivo studies were performed with orthotopic xenograft of human breast cancer. The MR-based technique demonstrated here has enabled visualization of the delivery of carriers, and release and intratumoral distribution of the encapsulated positive contrast agent. This study demonstrated proof-of-principle results for the noninvasive monitoring of in vivo release and distribution profiles of MR contrast agents, and thus, this technique will make a great contribution to the field. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Anatomy of a Busted Comet

NASA Technical Reports Server (NTRS)

2008-01-01

[figure removed for brevity, see original site] Poster Version (Figure 1)

NASA's Spitzer Space Telescope captured the picture on the left of comet Holmes in March 2008, five months after the comet suddenly erupted and brightened a millionfold overnight. The contrast of the picture has been enhanced on the right to show the anatomy of the comet.

Every six years, comet 17P/Holmes speeds away from Jupiter and heads inward toward the sun, traveling the same route typically without incident. However, twice in the last 116 years, in November 1892 and October 2007, comet Holmes mysteriously exploded as it approached the asteroid belt. Astronomers still do not know the cause of these eruptions.

Spitzer's infrared picture at left hand side of figure 1, reveals fine dust particles that make up the outer shell, or coma, of the comet. The nucleus of the comet is within the bright whitish spot in the center, while the yellow area shows solid particles that were blown from the comet in the explosion. The comet is headed away from the sun, which lies beyond the right-hand side of figure 1.

The contrast-enhanced picture on the right shows the comet's outer shell, and strange filaments, or streamers, of dust. The streamers and shell are a yet another mystery surrounding comet Holmes. Scientists had initially suspected that the streamers were small dust particles ejected from fragments of the nucleus, or from hyerpactive jets on the nucleus, during the October 2007 explosion. If so, both the streamers and the shell should have shifted their orientation as the comet followed its orbit around the sun. Radiation pressure from the sun should have swept the material back and away from it. But pictures of comet Holmes taken by Spitzer over time show the streamers and shell in the same configuration, and not pointing away from the sun. The observations have left astronomers stumped.

The horizontal line seen in the contrast-enhanced picture is a trail of debris that travels along with the comet in its orbit.

The Spitzer picture was taken with the spacecraft's multiband imaging photometer at an infrared wavelength of 24 microns.

Antibiofouling polymer-coated gold nanoparticles as a contrast agent for in vivo X-ray computed tomography imaging.

PubMed

Kim, Dongkyu; Park, Sangjin; Lee, Jae Hyuk; Jeong, Yong Yeon; Jon, Sangyong

2007-06-20

Current computed tomography (CT) contrast agents such as iodine-based compounds have several limitations, including short imaging times due to rapid renal clearance, renal toxicity, and vascular permeation. Here, we describe a new CT contrast agent based on gold nanoparticles (GNPs) that overcomes these limitations. Because gold has a higher atomic number and X-ray absorption coefficient than iodine, we expected that GNPs can be used as CT contrast agents. We prepared uniform GNPs ( approximately 30 nm in diameter) by general reduction of HAuCl4 by boiling with sodium citrate. The resulting GNPs were coated with polyethylene glycol (PEG) to impart antibiofouling properties, which extends their lifetime in the bloodstream. Measurement of the X-ray absorption coefficient in vitro revealed that the attenuation of PEG-coated GNPs is 5.7 times higher than that of the current iodine-based CT contrast agent, Ultravist. Furthermore, when injected intravenously into rats, the PEG-coated GNPs had a much longer blood circulation time (>4 h) than Ultravist (<10 min). Consequently, CT images of rats using PEG-coated GNPs showed a clear delineation of cardiac ventricles and great vessels. On the other hand, relatively high levels of GNPs accumulated in the spleen and liver, which contain phagocytic cells. Intravenous injection of PEG-coated GNPs into hepatoma-bearing rats resulted in a high contrast ( approximately 2-fold) between hepatoma and normal liver tissue on CT images. These results suggest that PEG-coated GNPs can be useful as a CT contrast agent for a blood pool and hepatoma imaging.

Focused ultrasound and microbubbles for enhanced extravasation.

PubMed

Böhmer, M R; Chlon, C H T; Raju, B I; Chin, C T; Shevchenko, T; Klibanov, A L

2010-11-20

The permeability of blood vessels for albumin can be altered by using ultrasound and polymer or lipid-shelled microbubbles. The region in which the microbubbles were destroyed with focused ultrasound was quantified in gel phantoms as a function of pressure, number of cycles and type of microbubble. At 2MPa the destruction took place in a fairly wide area for a lipid-shelled agent, while for polymer-shelled agents at this setting, distinct destruction spots with a radius of only 1mm were obtained. When microbubbles with a thicker shell were used, the pressure above which the bubbles were destroyed shifts to higher values. In vivo both lipid and polymer microbubbles increased the extravasation of the albumin binding dye Evans Blue, especially in muscle leading to about 6-8% of the injected dose to extravasate per gram muscle tissue 30 min after start of the treatment, while no Evans Blue could be detected in muscle in the absence of microbubbles. Variation in the time between ultrasound treatment and Evans Blue injection, demonstrated that the time window for promoting extravasation is at least an hour at the settings used. In MC38 tumors, extravasation already occurred without ultrasound and only a trend towards enhancement with about a factor of 2 could be established with a maximum percentage injected dose per gram of 3%. Ultrasound mediated microbubble destruction especially enhances the extravasation in the highly vascularized outer part of the MC38 tumor and adjacent muscle and would, therefore, be most useful for release of, for instance, anti-angiogenic drugs. Copyright © 2010 Elsevier B.V. All rights reserved.

A Numeric Study of the Dependence of the Surface Temperature of Beta-Layered Regions on Absolute Thickness

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

Ebey, Peter S.; Asaki, Thomas J.; Hoffer, James K.

2000-01-15

Beta-layering of deuterium-tritium (D-T) ice in spherical shell geometries is numerically and analytically considered to investigate the relationship between temperature differences that arise because of inner-surface perturbations and the absolute shell thickness. The calculations use dimensions based on a proposed design of an inertial confinement fusion target for use at the National Ignition Facility. The temperature differences are calculated within D-T ice shells of varying total thicknesses, and the temperature differences calculated in three dimensions are compared both to the one-dimensional results and to the expected limits in three dimensions for long- and short-wavelength surface perturbations. The three-dimensional numeric resultsmore » agree well with both the long- and short-wavelength limits; the region of crossover from short- to long-wavelength behavior is mapped out. Temperature differences due to surface perturbations are proportional to D-T layer thickness in one-dimensional systems but not in three-dimensional spherical shells. In spherical shells, surface perturbations of long wavelength give rise to temperature perturbations that are approximately proportional to the total shell thickness, while for short-wavelength perturbations, the temperature differences are inversely related to total shell thickness. In contrast to the one-dimensional result, we find that in three dimensions there is not a general relationship between shell thickness and surface temperature differences.« less

Self-healing fiber-reinforced composite

NASA Astrophysics Data System (ADS)

Lee, Minwook; Yoon, Sam; Yarin, Alexander

In the present work two parts of the healing agent (commercially available epoxy resin and hardener) are encapsulated in separate polymeric nanofibers. The fibers are generated by a single-step dual coaxial solution blowing. The core-shell fibers with the diameters in the 200-2600 nm range are encased in the PDMS (polydimethyl siloxane) matrix to form a self-healing composite material. Under fatigue conditions, the core-shell fibers inside the composite material are ruptured and the healing agents released into the surrounding matrix. Various fatigue conditions including repeated bending and stretching are used to damage the composites and the degree of self-healing is quantified after that. Also, an incision resembling a crack is pre-notched and crack propagation is studied. It is found that the presence of the self-healing agents in the fibers significantly retards crack propagation due to curing by the epoxy at the ruptured site. The stiffness of the composites is also measured for the samples containing self-healing fibers inside them before and after the fatigue tests. A novel theory of crack propagation is proposed, which explains the observed jump-like growth of sub-critical cracks. This work was supported by the International Collaboration Program funded by the Agency for Defense Development.

Synthesis and characterization of melamine-urea-formaldehyde microcapsules containing ENB-based self-healing agents

NASA Astrophysics Data System (ADS)

Liu, Xing; Sheng, Xia; Lee, Jong Keun; Kessler, Michael R.

2007-07-01

Microcapsules for self-healing applications were produced with a melamine-urea-formaldehyde (MUF) polymer shell containing two different healing agent candidates, ENB (5-ethylidene-2-norbornene) and ENB with 10 wt.% of a norbornene based crosslinking agent (CL), by in-situ polymerization in an oil-in-water emulsion. Relatively neat outer surfaces with minor roughness were observed on the MUF microcapsules under optical and scanning electron microscopy. Shell thickness of the capsules ranged from 700 to 900 nm. Particle size analysis of the microcapsules showed narrow size distributions with a mean diameter of 113 μm for ENB-filled and 122 μm for ENB+CL-filled microcapsules at an agitation rate of 500 rpm. The microcapsules were found to be thermally stable up to 300°C and exhibited a 10 to 15 % weight loss when isothermally held at 150°C for 2 hr from thermogravimetric analysis. Overall, these MUF microcapsules exhibited superior properties compared to the urea-formaldehyde (UF) microcapsules used extensively for self-healing composites to date. In addition, the manufacturing process of MUF microcapsules is much simpler than those made from UF. Additional advantages of MUF microcapsules for self-healing composites are discussed.

Morphological study of polymethyl methacrylate microcapsules filled with self-healing agents

NASA Astrophysics Data System (ADS)

Ahangaran, Fatemeh; Hayaty, Mehran; Navarchian, Amir H.

2017-03-01

Polymethyl methacrylate (PMMA) microcapsules filled with epoxy prepolymer, 3-aminomethyl-3,5,5-trimethylcyclohexylamine, and pentaerythritol tetrakis (3-mercaptopropionate) as healing agents have been prepared separately through internal phase separation method for self-healing purposes. PMMA with two different molecular weights (M bar1 = 36,000 g/mol and M bar2 = 550,000 g/mol) were used with two types of different emulsifiers (ionic and polymeric) to prepare microcapsules. The morphology of healing agent microcapsules was investigated using field emission scanning electron microscopy (FESEM). It was found that PMMA microcapsules separately filled with epoxy and amine had core-shell morphologies with smooth surfaces. The mercaptan/PMMA particles exhibited core-shell and acorn-shape morphologies. The surface morphology of mercaptan microcapsules changed from holed to plain in different emulsion systems. The spreading coefficient (S) of phases in the prepared emulsion systems were calculated from interfacial tension (σ) and contact angle (θ) measurements. The theoretical equilibrium morphology of PMMA microcapsules was predicted according to spreading coefficient values of phases in emulsion systems. It was also found that the surface morphology of PMMA microcapsules depended strongly on the nature of the core, molecular weight of PMMA, type and concentration of emulsifier.

Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children.

PubMed

Ayyala, Rama S; Zurakowski, David; Lee, Edward Y

2015-11-01

Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand administration of IV contrast agent and 30 (65%; 10.2 ± 4.2 years; range 4-18 years) had mechanical administration of IV contrast agent. All 46 abdominal CT angiography studies were of diagnostic quality based on qualitative evaluation (all ≥3). All abdominal CT angiography studies from both groups showed diagnostic quality of contrast enhancement (>150 HU) at both the celiac axis and the inferior mesenteric artery (IMA) levels. The contrast enhancement of the abdominal aorta was not significantly different between the IV contrast administration methods at either the celiac axis level (360 ± 158 vs. 353 ± 116, P = 0.24) or the IMA level (340 ± 140 vs. 351 ± 90, P = 0.27), adjusting for age. Diagnostic-quality abdominal CT angiography can be achieved using hand administration of IV contrast agent in infants and young children (≤5 years).

Prospective randomized trial of iohexol 350 versus meglumine sodium diatrizoate as an oral contrast agent for abdominopelvic computed tomography.

PubMed

Peterson, Christine M; Lin, Michael; Pilgram, Thomas; Heiken, Jay P

2011-01-01

To compare the efficacy and patient tolerance of iohexol and meglumine sodium diatrizoate as oral contrast agents for computed tomography (CT). One hundred patients were randomly assigned to drink 1000 mL of either meglumine sodium diatrizoate or iohexol 350 before their abdominopelvic CT examination. The images were evaluated independently and in a blinded fashion by 2 radiologists who scored the extent and density of bowel opacification. Attenuation value measurements were obtained in representative areas of each gastrointestinal tract segment (stomach, duodenum, jejunum, ileum, and colon) by a research technologist. Patients' tolerance of the oral contrast agent was assessed through a questionnaire administered immediately after the CT and with a follow-up phone call 2 to 3 days later. For most of the bowel, there was no statistically significant difference in the extent or degree of opacification between the 2 contrast agents. Opacification of the ileum was better with iohexol. There was no statistically significant difference between the 2 agents in adverse effects. Patients had a small but statistically significant preference for the taste of iohexol. Iohexol 350 is a satisfactory oral contrast agent for abdominopelvic CT. It opacifies the gastrointestinal tract as well as meglumine sodium diatrizoate does, and patients prefer the taste of iohexol to that of diatrizoate.

Theranostic nanoshells: from probe design to imaging and treatment of cancer.

PubMed

Bardhan, Rizia; Lal, Surbhi; Joshi, Amit; Halas, Naomi J

2011-10-18

Recent advances in nanoscience and biomedicine have expanded our ability to design and construct multifunctional nanoparticles that combine targeting, therapeutic, and diagnostic functions within a single nanoscale complex. The theranostic capabilities of gold nanoshells, spherical nanoparticles with silica cores and gold shells, have attracted tremendous attention over the past decade as nanoshells have emerged as a promising tool for cancer therapy and bioimaging enhancement. This Account examines the design and synthesis of nanoshell-based theranostic agents, their plasmon-derived optical properties, and their corresponding applications. We discuss the design and preparation of nanoshell complexes and their ability to enhance the photoluminescence of fluorophores while maintaining their properties as MR contrast agents. In this Account, we discuss the underlying physical principles that contribute to the photothermal response of nanoshells. We then elucidate the photophysical processes that induce nanoshells to enhance the fluorescence of weak near-infrared fluorophores. Nanoshells illuminated with resonant light are either strong optical absorbers or scatterers, properties that give rise to their unique capabilities. These physical processes have been harnessed to visualize and eliminate cancer cells. We describe the application of nanoshells as a contrast agent for optical coherence tomography of breast carcinoma cells in vivo. Our recent studies examine nanoshells as a multimodal theranostic probe, using these nanoparticles for near-infrared fluorescence and magnetic resonance imaging (MRI) and for the photothermal ablation of cancer cells. Multimodal nanoshells show theranostic potential for imaging subcutaneous breast cancer tumors in animal models and the distribution of tumors in various tissues. Nanoshells also show promise as light-triggered gene therapy vectors, adding temporal control to the spatial control characteristic of nanoparticle-based gene therapy approaches. We describe the fabrication of DNA-conjugated nanoshell complexes and compare the efficiency of light-induced and thermally-induced release of DNA. Double-stranded DNA nanoshells also provide a way to deliver small molecules into cells: we describe the delivery and light-triggered release of DAPI (4',6-diamidino-2-phenylindole), a dye molecule used to stain DNA in the nuclei of cells.

Electrospun Polyurethane-Core and Gelatin-Shell Coaxial Fibre Coatings for Miniature Implantable Biosensors

PubMed Central

Wang, Ning; Burugapalli, Krishna; Wijesuriya, Shavini; Far, Mahshid Yazdi; Song, Wenhui; Moussy, Francis; Zheng, Yudong; Ma, Yanxuan; Wu, Zhentao; Li, Kang

2014-01-01

The aim of this study was to introduce bioactivity to the electrospun coating for implantable glucose biosensors. Coaxial fibre membranes having polyurethane as the core and gelatin as the shell were produced using a range of polyurethane concentrations (2, 4, 6 & 8% wt/v) while keeping gelatin concentration (10% wt/v) constant in 2,2,2-trifluoroethanol. The gelatin shell was stabilized using glutaraldehyde vapour. The formation of core-shell structure was confirmed using TEM, SEM and FTIR. The coaxial fibre membranes showed uniaxial tensile properties intermediate to that of the pure polyurethane and the gelatin fibre membranes. The gelatin shell increased hydrophilicity and glucose transport flux across the coaxial fibre membranes. The coaxial fibre membranes having small fibre diameter (541 nm) and a thick gelatin shell (52%) did not affect the sensor sensitivity, but decreased sensor’s linearity in the long run. In contrast, thicker coaxial fibre membranes (1133 nm) having a thin gelatin shell (34%) maintained both sensitivity and linearity till 84 days of the study period. To conclude, polyurethane-gelatin co-axial fibre membranes, due to their faster permeability to glucose, tailorable mechanical properties and bioactivity are potential candidates for coatings to favourably modify the host responses to extend the reliable in vivo lifetime of implantable glucose biosensors. PMID:24346001

Lipid-shelled vehicles: engineering for ultrasound molecular imaging and drug delivery.

PubMed

Ferrara, Katherine W; Borden, Mark A; Zhang, Hua

2009-07-21

Ultrasound pressure waves can map the location of lipid-stabilized gas micro-bubbles after their intravenous administration in the body, facilitating an estimate of vascular density and microvascular flow rate. Microbubbles are currently approved by the Food and Drug Administration as ultrasound contrast agents for visualizing opacification of the left ventricle in echocardiography. However, the interaction of ultrasound waves with intravenously-injected lipid-shelled particles, including both liposomes and microbubbles, is a far richer field. Particles can be designed for molecular imaging and loaded with drugs or genes; the mechanical and thermal properties of ultrasound can then effect localized drug release. In this Account, we provide an overview of the engineering of lipid-shelled microbubbles (typical diameter 1000-10 000 nm) and liposomes (typical diameter 65-120 nm) for ultrasound-based applications in molecular imaging and drug delivery. The chemistries of the shell and core can be optimized to enhance stability, circulation persistence, drug loading and release, targeting to and fusion with the cell membrane, and therapeutic biological effects. To assess the biodistribution and pharmacokinetics of these particles, we incorporated positron emission tomography (PET) radioisotopes on the shell. The radionuclide (18)F (half-life approximately 2 h) was covalently coupled to a dipalmitoyl lipid, followed by integration of the labeled lipid into the shell, facilitating short-term analysis of particle pharmacokinetics and metabolism of the lipid molecule. Alternately, labeling a formed particle with (64)Cu (half-life 12.7 h), after prior covalent incorporation of a copper-chelating moiety onto the lipid shell, permits pharmacokinetic study of particles over several days. Stability and persistence in circulation of both liposomes and microbubbles are enhanced by long acyl chains and a poly(ethylene glycol) coating. Vascular targeting has been demonstrated with both nano- and microdiameter particles. Targeting affinity of the microbubble can be modulated by burying the ligand within a polymer brush layer; the application of ultrasound then reveals the ligand, enabling specific targeting of only the insonified region. Microbubbles and liposomes require different strategies for both drug loading and release. Microbubble loading is inhibited by the gas core and enhanced by layer-by-layer construction or conjugation of drug-entrapped particles to the surface. Liposome loading is typically internal and is enhanced by drug-specific loading techniques. Drug release from a microbubble results from the oscillation of the gas core diameter produced by the sound wave, whereas that from a liposome is enhanced by heat produced from the local absorption of acoustic energy within the tissue microenvironment. Biological effects induced by ultrasound, such as changes in cell membrane and vascular permeability, can enhance drug delivery. In particular, as microbubbles oscillate near a vessel wall, shock waves or liquid jets enhance drug transport. Mild heating induced by ultrasound, either before or after injection of the drug, facilitates the transport of liposomes from blood vessels to the tissue interstitium, thus increasing drug accumulation in the target region. Lipid-shelled vehicles offer many opportunities for chemists and engineers; ultrasound-based applications beyond the few currently in common use will undoubtedly soon multiply as molecular construction techniques are further refined.

A model for acoustic vaporization dynamics of a bubble/droplet system encapsulated within a hyperelastic shell.

PubMed

Lacour, Thomas; Guédra, Matthieu; Valier-Brasier, Tony; Coulouvrat, François

2018-01-01

Nanodroplets have great, promising medical applications such as contrast imaging, embolotherapy, or targeted drug delivery. Their functions can be mechanically activated by means of focused ultrasound inducing a phase change of the inner liquid known as the acoustic droplet vaporization (ADV) process. In this context, a four-phases (vapor + liquid + shell + surrounding environment) model of ADV is proposed. Attention is especially devoted to the mechanical properties of the encapsulating shell, incorporating the well-known strain-softening behavior of Mooney-Rivlin material adapted to very large deformations of soft, nearly incompressible materials. Various responses to ultrasound excitation are illustrated, depending on linear and nonlinear mechanical shell properties and acoustical excitation parameters. Different classes of ADV outcomes are exhibited, and a relevant threshold ensuring complete vaporization of the inner liquid layer is defined. The dependence of this threshold with acoustical, geometrical, and mechanical parameters is also provided.

Geochemistry of amino acids in shells of the clam Saxidomus

USGS Publications Warehouse

Kvenvolden, K.A.; Blunt, D.J.; McMenamin, M.A.; Straham, S.E.

1980-01-01

Concentrations of amino acids and their corresponding d l enantiomeric ratios have been measured in shells of the bivalve mollusk Saxidomus from eleven localities, ranging in age from modern to probably more than 500,000 yr, along the Pacific coast of North America. Natural logarithms of amino acid concentrations correlate well with d l ratios, and the relationship provides a possible guide to the selection of fossils for use in amino acid dating. The relative order of the extents of racemization of amino acids at any given time appears to change with increasing sample age. Application of the amino acid dating method to shells from Whidbey Island, Washington, yields an age of about 80,000 yr, in contrast to the previously determined radiocarbon age of 36,000 yr which was measured on some shell carbonate and considered a minimum age. The amino acid age is compatible with the geologic record in the area. ?? 1980.

Importance of counteranions on the hydration structure of the curium ion

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

Atta Fynn, Raymond; Bylaska, Eric J.; De Jong, Wibe A.

2013-07-04

Using density functional theory based ab initio molecular dynamics and metadynamics we show that counter ions can trigger noticeable changes in the hydration shell structure of the curium ion. The free energies of curium-water coordination and the solvent hydrogen bond (HB) lifetimes in the absence and presence the counter anions predict that chloride and bromide counter anions strengthen the first shell and consequently the 8-fold coordination state is dominant by at least 98%. In contrast, the perchlorate counter anions are found to weaken the coordination shell and the HB network, with the 9-fold and 8-fold states existing in an 8:1more » ratio, which is in good agreement with reported 9:1 ratio seen in time resolved fluorescence spectroscopy experiments. To our knowledge this is the first time molecular simulations have shown that counter anions can directly affect the first hydration shell structure of a cation.« less

Modeling Encapsulated Microbubble Dynamics at High Pressure Amplitudes

NASA Astrophysics Data System (ADS)

Heyse, Jan F.; Bose, Sanjeeb; Iaccarino, Gianluca

2017-11-01

Encapsulated microbubbles are commonly used in ultrasound contrast imaging and are of growing interest in therapeutic applications where local cavitation creates temporary perforations in cell membranes allowing for enhanced drug delivery. Clinically used microbubbles are encapsulated by a shell commonly consisting of protein, polymer, or phospholipid; the response of these bubbles to externally imposed ultrasound waves is sensitive to the compressibility of the encapsulating shell. Existing models approximate the shell compressibility via an effective surface tension (Marmottant et al. 2005). We present simulations of microbubbles subjected to high amplitude ultrasound waves (on the order of 106 Pa) and compare the results with the experimental measurements of Helfield et al. (2016). Analysis of critical points (corresponding to maximum and minimum expansion) in the governing Rayleigh-Plesset equation is used to make estimates of the parameters used to characterize the effective surface tension of the encapsulating shell. Stanford Graduate Fellowship.