Science.gov

Sample records for agents including gadolinium

  1. 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.

  2. Tumor growth suppression by gadolinium-neutron capture therapy using gadolinium-entrapped liposome as gadolinium delivery agent.

    PubMed

    Dewi, Novriana; Yanagie, Hironobu; Zhu, Haito; Demachi, Kazuyuki; Shinohara, Atsuko; Yokoyama, Kazuhito; Sekino, Masaki; Sakurai, Yuriko; Morishita, Yasuyuki; Iyomoto, Naoko; Nagasaki, Takeshi; Horiguchi, Yukichi; Nagasaki, Yukio; Nakajima, Jun; Ono, Minoru; Kakimi, Kazuhiro; Takahashi, Hiroyuki

    2013-07-01

    Neutron capture therapy (NCT) is a promising non-invasive cancer therapy approach and some recent NCT research has focused on using compounds containing gadolinium as an alternative to currently used boron-10 considering several advantages that gadolinium offers compared to those of boron. In this study, we evaluated gadolinium-entrapped liposome compound as neutron capture therapy agent by in vivo experiment on colon-26 tumor-bearing mice. Gadolinium compound were injected intravenously via tail vein and allowed to accumulate into tumor site. Tumor samples were taken for quantitative analysis by ICP-MS at 2, 12, and 24 h after gadolinium compound injection. Highest gadolinium concentration was observed at about 2 h after gadolinium compound injection with an average of 40.3 μg/g of wet tumor tissue. We performed neutron irradiation at JRR-4 reactor facility of Japan Atomic Energy Research Institute in Tokaimura with average neutron fluence of 2×10¹² n/cm². The experimental results showed that the tumor growth suppression of gadolinium-injected irradiated group was revealed until about four times higher compared to the control group, and no significant weight loss were observed after treatment suggesting low systemic toxicity of this compound. The gadolinium-entrapped liposome will become one of the candidates for Gd delivery system on NCT.

  3. Magnetic resonance imaging using gadolinium-based contrast agents.

    PubMed

    Mitsumori, Lee M; Bhargava, Puneet; Essig, Marco; Maki, Jeffrey H

    2014-02-01

    The purpose of this article was to review the basic properties of available gadolinium-based magnetic resonance contrast agents, discuss their fundamental differences, and explore common and evolving applications of gadolinium-based magnetic resonance contrast throughout the body excluding the central nervous system. A more specific aim of this article was to explore novel uses of these gadolinium-based contrast agents and applications where a particular agent has been demonstrated to behave differently or be better suited for certain applications than the other contrast agents in this class.

  4. Subcellular SIMS imaging of gadolinium isotopes in human glioblastoma cells treated with a gadolinium containing MRI agent

    NASA Astrophysics Data System (ADS)

    Smith, Duane R.; Lorey, Daniel R.; Chandra, Subhash

    2004-06-01

    Neutron capture therapy is an experimental binary radiotherapeutic modality for the treatment of brain tumors such as glioblastoma multiforme. Recently, neutron capture therapy with gadolinium-157 has gained attention, and techniques for studying the subcellular distribution of gadolinium-157 are needed. In this preliminary study, we have been able to image the subcellular distribution of gadolinium-157, as well as the other six naturally abundant isotopes of gadolinium, with SIMS ion microscopy. T98G human glioblastoma cells were treated for 24 h with 25 mg/ml of the metal ion complex diethylenetriaminepentaacetic acid Gd(III) dihydrogen salt hydrate (Gd-DTPA). Gd-DTPA is a contrast enhancing agent used for MRI of brain tumors, blood-brain barrier impairment, diseases of the central nervous system, etc. A highly heterogeneous subcellular distribution was observed for gadolinium-157. The nuclei in each cell were distinctly lower in gadolinium-157 than in the cytoplasm. Even within the cytoplasm the gadolinium-157 was heterogeneously distributed. The other six naturally abundant isotopes of gadolinium were imaged from the same cells and exhibited a subcellular distribution consistent with that observed for gadolinium-157. These observations indicate that SIMS ion microscopy may be a viable approach for subcellular studies of gadolinium containing neutron capture therapy drugs and may even play a major role in the development and validation of new gadolinium contrast enhancing agents for diagnostic MRI applications.

  5. Linear Gadolinium-Based Contrast Agents Are Associated With Brain Gadolinium Retention in Healthy Rats

    PubMed Central

    Robert, Philippe; Violas, Xavier; Grand, Sylvie; Lehericy, Stéphane; Idée, Jean-Marc; Ballet, Sébastien; Corot, Claire

    2016-01-01

    Objectives The aim of this study was to evaluate Gd retention in the deep cerebellar nuclei (DCN) of linear gadolinium-based contrast agents (GBCAs) compared with a macrocyclic contrast agent. Materials and Methods The brain tissue retention of Gd of 3 linear GBCAs (gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide) and a macrocyclic GBCA (gadoterate meglumine) was compared in healthy rats (n = 8 per group) that received 20 intravenous injections of 0.6 mmol Gd/kg (4 injections per week for 5 weeks). An additional control group with saline was included. T1-weighted magnetic resonance imaging was performed before injection and once a week during the 5 weeks of injections and for another 4 additional weeks after contrast period. Total gadolinium concentration was measured with inductively coupled plasma mass spectrometry. Blinded qualitative and quantitative evaluations of the T1 signal intensity in DCN were performed, as well as a statistical analysis on quantitative data. Results At completion of the injection period, all the linear contrast agents (gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide) induced a significant increase in signal intensity in DCN, unlike the macrocyclic GBCA (gadoterate meglumine) or saline. The T1 hypersignal enhancement kinetic was fast for gadodiamide. Total Gd concentrations for the 3 linear GBCAs groups at week 10 were significantly higher in the cerebellum (1.21 ± 0.48, 1.67 ± 0.17, and 3.75 ± 0.18 nmol/g for gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide, respectively) than with the gadoterate meglumine (0.27 ± 0.16 nmol/g, P < 0.05) and saline (0.09 ± 0.12 nmol/g, P < 0.05). No significant difference was observed between the macrocyclic agent and saline. Conclusions Repeated administrations of the linear GBCAs gadodiamide, gadobenate dimeglumine, and gadopentetate dimeglumine to healthy rats were associated with progressive and significant T1 signal hyperintensity in the

  6. Gadolinium as a Neutron Capture Therapy Agent

    NASA Astrophysics Data System (ADS)

    Shih, Jing-Luen Allen

    The clinical results of treating brain tumors with boron neutron capture therapy are very encouraging and researchers around the world are once again making efforts to develop this therapeutic modality. Boron-10 is the agent receiving the most attention for neutron capture therapy but ^{157}Gd is a nuclide that also holds interesting properties of being a neutron capture therapy agent. The objective of this study is to evaluate ^{157}Gd as a neutron capture therapy agent. In this study it is determined that tumor concentrations of about 300 mug ^{157}Gd/g tumor can be achieved in brain tumors with some FDA approved MRI contrast agents such as Gd-DTPA and Gd-DOTA, and up to 628 mug ^{157 }Gd/g tumor can be established in bone tumors with Gd-EDTMP. Monte Carlo calculations show that with only 250 ppm of ^{157}Gd in tumor, neutron capture therapy can deliver 2,000 cGy to a tumor of 2 cm diameter or larger with 5 times 10^{12} n/cm ^2 fluence at the tumor. Dose measurements which were made with films and TLD's in phantoms verified these calculations. More extended Monte Carlo calculations demonstrate that neutron capture therapy with Gd possesses comparable dose distribution to B neutron capture therapy. With 5 times 10^{12 } n/cm^2 thermal neutrons at the tumor, Auger electrons from the Gd produced an optical density enhancement on the films that is similar to the effect caused by about 300 cGy of Gd prompt gamma dose which will further enhance the therapeutic effects. A technique that combines brachytherapy with Gd neutron capture therapy has been evaluated. Monte Carlo calculations show that 5,000 cGy of prompt gamma dose can be delivered to a treatment volume of 40 cm^3 with a 3-plane implant of a total of 9 Gd needles. The tumor to normal tissue advantage of this method is as good as ^{60} Co brachytherapy. Measurements of prompt gamma dose with films and TLD-700's in a lucite phantom verify the Monte Carlo evaluation. A technique which displays the Gd

  7. Hepatobiliary MR Imaging with Gadolinium Based Contrast Agents

    PubMed Central

    Frydrychowicz, Alex; Lubner, Meghan G.; Brown, Jeffrey J.; Merkle, Elmar M.; Nagle, Scott K.; Rofsky, Neil M.; Reeder, Scott B.

    2011-01-01

    The advent of gadolinium-based “hepatobiliary” contrast agents offers new opportunities for diagnostic MRI and has triggered a great interest for innovative imaging approaches to the liver and bile ducts. In this review article we will discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the USA, gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We will review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared towards optimizing workflow and imaging quality will also be discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents, and will stimulate the reader‘s pursuit of new applications for future benefit. PMID:22334493

  8. Gadolinium oxide nanoparticles as potential multimodal imaging and therapeutic agents.

    PubMed

    Kim, Tae Jeong; Chae, Kwon Seok; Chang, Yongmin; Lee, Gang Ho

    2013-01-01

    Potentials of hydrophilic and biocompatible ligand coated gadolinium oxide nanoparticles as multimodal imaging agents, drug carriers, and therapeutic agents are reviewed. First of all, they can be used as advanced T1 magnetic resonance imaging (MRI) contrast agents because they have r1 larger than those of Gd(III)-chelates due to a high density of Gd(III) per nanoparticle. They can be further functionalized by conjugating other imaging agents such as fluorescent imaging (FI), X-ray computed tomography (CT), positron emission tomography (PET), and single photon emission tomography (SPECT) agents. They can be also useful for drug carriers through morphology modifications. They themselves are also potential CT and ultrasound imaging (USI) contrast and thermal neutron capture therapeutic (NCT) agents, which are superior to commercial iodine compounds, air-filled albumin microspheres, and boron ((10)B) compounds, respectively. They, when conjugated with targeting agents such as antibodies and peptides, will provide enhanced images and be also very useful for diagnosis and therapy of diseases (so called theragnosis).

  9. Gadolinium nanoparticles and contrast agent as radiation sensitizers

    NASA Astrophysics Data System (ADS)

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F.; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist® in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL-1), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly ‘energy dependent’ for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  10. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    PubMed

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs. PMID:25988839

  11. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    PubMed

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  12. A cationic gadolinium contrast agent for magnetic resonance imaging of cartilage.

    PubMed

    Freedman, Jonathan D; Lusic, Hrvoje; Wiewiorski, Martin; Farley, Michelle; Snyder, Brian D; Grinstaff, Mark W

    2015-06-30

    A new cationic gadolinium contrast agent is reported for delayed gadolinium enhanced magnetic resonance imaging of cartilage (dGEMRIC). The agent partitions into the glycosaminoglycan rich matrix of articular cartilage, based on Donnan equilibrium theory, and its use enables imaging of the human cadaveric metacarpal phalangeal joint.

  13. Gadolinium contrast agent-induced CD163+ ferroportin+ osteogenic cells in nephrogenic systemic fibrosis.

    PubMed

    Swaminathan, Sundararaman; Bose, Chhanda; Shah, Sudhir V; Hall, Kimberly A; Hiatt, Kim M

    2013-09-01

    Gadolinium-based contrast agents are linked to nephrogenic systemic fibrosis in patients with renal insufficiency. The pathology of nephrogenic systemic fibrosis is characterized by abnormal tissue repair: fibrosis and ectopic ossification. The mechanisms by which gadolinium could induce fibrosis and ossification are not known. We examined in vitro the effect of a gadolinium-based contrast agent on human peripheral blood mononuclear cells for phenotype and function relevant to the pathology of nephrogenic systemic fibrosis using immunofluorescence, flow cytometry, real-time PCR, and osteogenic assays. We also examined tissues from patients with nephrogenic systemic fibrosis, using IHC to identify the presence of cells with phenotype induced by gadolinium. Gadolinium contrast induced differentiation of human peripheral blood mononuclear cells into a unique cellular phenotype--CD163(+) cells expressing proteins involved in fibrosis and bone formation. These cells express fibroblast growth factor (FGF)23, osteoblast transcription factors Runt-related transcription factor 2, and osterix, and show an osteogenic phenotype in in vitro assays. We show in vivo the presence of CD163(+)/procollagen-1(+)/osteocalcin(+) cells in the fibrotic and calcified tissues of nephrogenic systemic fibrosis patients. Gadolinium contrast-induced CD163(+)/ferroportin(+)/FGF23(+) cells with osteogenic potential may play a role in systemic fibrosis and ectopic ossification in nephrogenic systemic fibrosis.

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

    PubMed

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

    2016-05-19

    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. PMID:27159645

  15. 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.

  16. Thermal Excitation of Gadolinium-Based Contrast Agents Using Spin Resonance

    PubMed Central

    Fridjhon, Peter; Rubin, David M.

    2016-01-01

    Theoretical and experimental investigations into the thermal excitation of liquid paramagnetic contrast agents using the spin resonance relaxation mechanism are presented. The electronic spin-lattice relaxation time τ1e of gadolinium-based contrast agents, which is estimated at 0.1 ns, is ten orders of magnitude faster than the relaxation time of protons in water. The shorter relaxation time is found to significantly increase the rate of thermal energy deposition. To the authors’ knowledge this is the first study of gadolinium based contrast agents in a liquid state used as thermal agents. Analysis shows that when τ1e and other experimental parameters are optimally selected, a maximum theoretical heating rate of 29.4 °C.s−1 could be achieved which would suffice for clinical thermal ablation of neoplasms. The experimental results show a statistically significant thermal response for two out of the four contrast agents tested. The results are compared to the simulated estimates via analysis of a detailed model of the system. While these experimentally determined temperature rises are small and thus of no clinical utility, their presence supports the theoretical analysis and strongly suggests that the chemical structure of the selected compounds plays an important role in this mechanism of heat deposition. There exists an opportunity for the development of alternative gadolinium-based compounds with an order of magnitude longer τ1e in a diluted form to be used as an efficient hyperthermia agent for clinical use. PMID:27341338

  17. Thermal Excitation of Gadolinium-Based Contrast Agents Using Spin Resonance.

    PubMed

    Dinger, Steven C; Fridjhon, Peter; Rubin, David M

    2016-01-01

    Theoretical and experimental investigations into the thermal excitation of liquid paramagnetic contrast agents using the spin resonance relaxation mechanism are presented. The electronic spin-lattice relaxation time τ1e of gadolinium-based contrast agents, which is estimated at 0.1 ns, is ten orders of magnitude faster than the relaxation time of protons in water. The shorter relaxation time is found to significantly increase the rate of thermal energy deposition. To the authors' knowledge this is the first study of gadolinium based contrast agents in a liquid state used as thermal agents. Analysis shows that when τ1e and other experimental parameters are optimally selected, a maximum theoretical heating rate of 29.4 °C.s-1 could be achieved which would suffice for clinical thermal ablation of neoplasms. The experimental results show a statistically significant thermal response for two out of the four contrast agents tested. The results are compared to the simulated estimates via analysis of a detailed model of the system. While these experimentally determined temperature rises are small and thus of no clinical utility, their presence supports the theoretical analysis and strongly suggests that the chemical structure of the selected compounds plays an important role in this mechanism of heat deposition. There exists an opportunity for the development of alternative gadolinium-based compounds with an order of magnitude longer τ1e in a diluted form to be used as an efficient hyperthermia agent for clinical use. PMID:27341338

  18. Field strength and dose dependence of contrast enhancement by gadolinium-based MR contrast agents.

    PubMed

    Rinck, P A; Muller, R N

    1999-01-01

    The relaxivities r1 and r2 of magnetic resonance contrast agents and the T1 relaxation time values of tissues are strongly field dependent. We present quantitative data and simulations of different gadolinium-based extracellular fluid contrast agents and the modulation of their contrast enhancement by the magnetic field to be able to answer the following questions: How are the dose and field dependences of their contrast enhancement? Is there an interrelationship between dose and field dependence? Should one increase or decrease doses at specific fields? Nuclear magnetic relaxation dispersion data were acquired for the following contrast agents: gadopentetate dimeglumine, gadoterate meglumine, gadodiamide injection, and gadoteridol injection, as well as for several normal and pathological human tissue samples. The magnetic field range stretched from 0.0002 to 4.7 T, including the entire clinical imaging range. The data acquired were then fitted with the appropriate theoretical models. The combination of the diamagnetic relaxation rates (R1 = 1/T1 and R2 = 1/T2) of tissues with the respective paramagnetic contributions of the contrast agents allowed the prediction of image contrast at any magnetic field. The results revealed a nearly identical field and dose-dependent increase of contrast enhancement induced by these contrast agents within a certain dose range. The target tissue concentration (TTC) was an important though nonlinear factor for enhancement. The currently recommended dose of 0.1 mmol/kg body weight seems to be a compromise close to the lower limits of diagnostically sufficient contrast enhancement for clinical imaging at all field strengths. At low field contrast enhancement might be insufficient. Adjustment of dose or concentration, or a new class of contrast agents with optimized relaxivity, would be a valuable contribution to a better diagnostic yield of contrast enhancement at all fields.

  19. A new biodegradable and biocompatible gadolinium (III) -polymer for liver magnetic resonance imaging contrast agent.

    PubMed

    Xiao, Yan; Xue, Rong; You, Tianyan; Li, Xiaojing; Pei, Fengkui

    2015-07-01

    A new biodegradable and biocompatible gadolinium (III) -copolymer (ACL-A2-DOTA-Gd) has been developed as a potential liver magnetic resonance imaging (MRI) contrast agent. ACL-A2-DOTA-Gd consisted of a poly (aspartic acid-co-leucine) unit bound with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (Gd-DOTA) via the linkage of ethylenediamine. In vitro, the biodegradable experiment and cytotoxicity assay showed the biodegradability and biocompatibility of this gadolinium-polymer. ACL-A2-DOTA-Gd presented an increase in relaxivity of 2.4 times than the clinical Gd-DOTA. In vivo, gadolinium (III)-copolymer was mainly accumulated in the liver, and it could be excreted via the renal and hepatobiliary mechanism. The average enhancement of ACL-A2-DOTA-Gd (60.71±5.93%, 50-80 min) in liver was 2.62-fold greater than that of Gd-DOTA (23.16±3.55%, 10-30 min). ACL-A2-DOTA-Gd could be as a potential liver MRI contrast agent with a long time-window.

  20. Biocompatible Polyhydroxyethylaspartamide-based Micelles with Gadolinium for MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Jeong, Sang Young; Kim, Hyo Jeong; Kwak, Byung-Kook; Lee, Ha-Young; Seong, Hasoo; Shin, Byung Cheol; Yuk, Soon Hong; Hwang, Sung-Joo; Cho, Sun Hang

    2010-12-01

    Biocompatible poly-[ N-(2-hydroxyethyl)- d, l-aspartamide]-methoxypoly(ethyleneglycol)-hexadecylamine (PHEA-mPEG-C16) conjugated with 1,4,7,10-tetraazacyclododecan-1,4,7,10-tetraacetic acid-gadolinium (DOTA-Gd) via ethylenediamine (ED) was synthesized as a magnetic resonance imaging (MRI) contrast agent. Amphiphilic PHEA-mPEG-C16-ED-DOTA-Gd forms micelle in aqueous solution. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Micelle size and shape were examined by dynamic light scattering (DLS) and atomic force microscopy (AFM). Micelles with PHEA-mPEG-C16-ED-DOTA-Gd showed higher relaxivities than the commercially available gadolinium contrast agent. Moreover, the signal intensity of a rabbit liver was effectively increased after intravenous injection of PHEA-mPEG-C16-ED-DOTA-Gd.

  1. [Physico-chemical and toxicological profile of gadolinium chelates as contrast agents for magnetic resonance imaging].

    PubMed

    Idée, J-M; Fretellier, N; Thurnher, M M; Bonnemain, B; Corot, C

    2015-07-01

    Gadolinium chelates (GC) are contrast agents widely used to facilitate or to enable diagnosis using magnetic resonance imaging (MRI). From a regulatory viewpoint, GC are drugs. GC have largely contributed to the success of MRI, which has become a major component of clinician's diagnostic armamentarium. GC are not metabolised and are excreted by the kidneys. They distribute into the extracellular compartment. Because of its high intrinsic toxicity, gadolinium must be administered as a chelate. GC can be classified according to two key molecular features: (a) nature of the chelating moiety: either macrocyclic molecules in which gadolinium is caged in the pre-organized cavity of the ligand, or linear, open-chain molecules, (b) ionicity: Gd chelates can be ionic (meglumine or sodium salts) or non-ionic. The thermodynamic and kinetic stabilities of the various GCs differ according to these structural characteristics. The kinetic stability of macrocyclic GCs is much higher than that of linear GCs and the thermodynamic stability of ionic GCs is generally higher than that of non-ionic GC, thus leading to a lower risk of gadolinium dissociation. This class of drugs has enjoyed an excellent reputation in terms of safety for a long time, until a causal link with a recently-described serious disease, nephrogenic systemic fibrosis (NSF), was evidenced. It is acknowledged that the vast majority of NSF cases are related to the administration of some linear CG in renally-impaired patients. Health authorities, worldwide, released recommendations which drastically reduced the occurrence of new cases. PMID:25731664

  2. Gadolinium-complexed Aβ-binding contrast agents for MRI diagnosis of Alzheimer's Disease.

    PubMed

    Matharu, Balpreet; Spencer, Nick; Howe, Franklyn; Austen, Brian

    2015-10-01

    MRI contrast agents, containing peptide sequences that bind β-amyloid and gadolinium ions ligated to DOTA have been synthesized for evaluation in early diagnosis of Alzheimer's Disease in transgenic mice models. A number of brain penetration modifications were incorporated and sufficient amounts of contrast agent in the brain were achieved only by addition of a cationic cell penetration sequence along with the use of microparticle assisted ultrasound activation. In the T1 mode of a MRI scan, the peptide (R2) illuminated areas of brain rich in amyloid plaques.

  3. Tracing gadolinium-based contrast agents from surface water to drinking water by means of speciation analysis.

    PubMed

    Birka, Marvin; Wehe, Christoph A; Hachmöller, Oliver; Sperling, Michael; Karst, Uwe

    2016-04-01

    In recent decades, a significant amount of anthropogenic gadolinium has been released into the environment as a result of the broad application of contrast agents for magnetic resonance imaging (MRI). Since this anthropogenic gadolinium anomaly has also been detected in drinking water, it has become necessary to investigate the possible effect of drinking water purification on these highly polar microcontaminats. Therefore, a novel highly sensitive method for speciation analysis of gadolinium is presented. For that purpose, the hyphenation of hydrophilic interaction liquid chromatography (HILIC) and inductively coupled plasma-mass spectrometry (ICP-MS) was employed. In order to enhance the detection power, sample introduction was carried out by ultrasonic nebulization. In combination with a novel HILIC method using a diol-based stationary phase, it was possible to achieve superior limits of detection for frequently applied gadolinium-based contrast agents below 20pmol/L. With this method, the contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A were determined in concentrations up to 159pmol/L in samples from several waterworks in a densely populated region of Germany alongside the river Ruhr as well as from a waterworks near a catchment lake. Thereby, the direct impact of anthropogenic gadolinium species being present in the surface water on the amount of anthropogenic gadolinium in drinking water was shown. There was no evidence for the degradation of contrast agents, the release of Gd(3+) or the presence of further Gd species. PMID:26931429

  4. Tracing gadolinium-based contrast agents from surface water to drinking water by means of speciation analysis.

    PubMed

    Birka, Marvin; Wehe, Christoph A; Hachmöller, Oliver; Sperling, Michael; Karst, Uwe

    2016-04-01

    In recent decades, a significant amount of anthropogenic gadolinium has been released into the environment as a result of the broad application of contrast agents for magnetic resonance imaging (MRI). Since this anthropogenic gadolinium anomaly has also been detected in drinking water, it has become necessary to investigate the possible effect of drinking water purification on these highly polar microcontaminats. Therefore, a novel highly sensitive method for speciation analysis of gadolinium is presented. For that purpose, the hyphenation of hydrophilic interaction liquid chromatography (HILIC) and inductively coupled plasma-mass spectrometry (ICP-MS) was employed. In order to enhance the detection power, sample introduction was carried out by ultrasonic nebulization. In combination with a novel HILIC method using a diol-based stationary phase, it was possible to achieve superior limits of detection for frequently applied gadolinium-based contrast agents below 20pmol/L. With this method, the contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A were determined in concentrations up to 159pmol/L in samples from several waterworks in a densely populated region of Germany alongside the river Ruhr as well as from a waterworks near a catchment lake. Thereby, the direct impact of anthropogenic gadolinium species being present in the surface water on the amount of anthropogenic gadolinium in drinking water was shown. There was no evidence for the degradation of contrast agents, the release of Gd(3+) or the presence of further Gd species.

  5. Gadolinium contrast agent selection and optimal use for body MR imaging.

    PubMed

    Guglielmo, Flavius F; Mitchell, Donald G; Gupta, Shiva

    2014-07-01

    Proper selection of a gadolinium-based contrast agent (GBCA) for body magnetic resonance imaging (MRI) cases requires understanding the indication for the MRI exam, the key features of the different GBCAs, and the effect that the GBCA has on the selected imaging protocol. The different categories of GBCAs require timing optimization on postcontrast sequences and adjusting imaging parameters to obtain the highest T1 contrast. Gadoxetate disodium has many advantages when evaluating liver lesions, although there are caveats and limitations that need to be understood. Gadobenate dimeglumine, a high-relaxivity GBCA, can be used for indications when stronger T1 relaxivity is needed.

  6. Protein-targeted gadolinium-based magnetic resonance imaging (MRI) contrast agents: design and mechanism of action.

    PubMed

    Caravan, Peter

    2009-07-21

    Magnetic resonance imaging (MRI) is a powerful medical diagnostic technique: it can penetrate deep into tissue, provide excellent soft tissue contrast with sub-millimeter resolution, and does not employ ionizing radiation. Targeted contrast agents provide an additional layer of molecular specificity to the wealth of anatomical and functional information already attainable by MRI. However, the major challenge for molecular MR imaging is sensitivity: micromolar concentrations of Gd(III) are required to cause a detectable signal change, which makes detecting proteins by MRI a challenge. Protein-targeted MRI contrast agents are bifunctional molecules comprising a protein-targeting moiety and typically one or more gadolinium chelates for detection by MRI. The ability of the contrast agent to enhance the MR image is termed relaxivity, and it depends upon many molecular factors, including protein binding itself. As in other imaging modalities, protein binding provides the pharmacokinetic effect of concentrating the agent at the region of interest. Unique to MRI, protein binding provides the pharmacodynamic effect of increasing the relaxivity of the contrast agent, thereby increasing the MR signal. In designing new agents, optimization of both the targeting function and the relaxivity is critical. In this Account, we focus on optimization of the relaxivity of targeted agents. Relaxivity depends upon speciation, chemical structure, and dynamic processes, such as water exchange kinetics and rotational tumbling rates. We describe mechanistic studies that relate these factors to the observed relaxivities and use these findings as the basis of rational design of improved agents. In addition to traditional biochemical methods to characterize ligand-protein interactions, the presence of the metal ion enables more obscure biophysical techniques, such as relaxometry and electron nuclear double resonance, to be used to elucidate the mechanism of relaxivity differences. As a case

  7. High Relaxivity Gadolinium Hydroxypyridonate-Viral Capsid Conjugates: Nano-sized MRI Contrast Agents

    SciTech Connect

    Meux, Susan C.; Datta, Ankona; Hooker, Jacob M.; Botta, Mauro; Francis, Matthew B.; Aime, Silvio; Raymond, Kenneth N.

    2007-08-29

    High relaxivity macromolecular contrast agents based on the conjugation of gadolinium chelates to the interior and exterior surfaces of MS2 viral capsids are assessed. The proton nuclear magnetic relaxation dispersion (NMRD) profiles of the conjugates show up to a five-fold increase in relaxivity, leading to a peak relaxivity (per Gd{sup 3+} ion) of 41.6 mM{sup -1}s{sup -1} at 30 MHz for the internally modified capsids. Modification of the exterior was achieved through conjugation to flexible lysines, while internal modification was accomplished by conjugation to relatively rigid tyrosines. Higher relaxivities were obtained for the internally modified capsids, showing that (1) there is facile diffusion of water to the interior of capsids and (2) the rigidity of the linker attaching the complex to the macromolecule is important for obtaining high relaxivity enhancements. The viral capsid conjugated gadolinium hydroxypyridonate complexes appear to possess two inner-sphere water molecules (q = 2) and the NMRD fittings highlight the differences in the local motion for the internal ({tau}{sub RI} = 440 ps) and external ({tau}{sub RI} = 310 ps) conjugates. These results indicate that there are significant advantages of using the internal surface of the capsids for contrast agent attachment, leaving the exterior surface available for the installation of tissue targeting groups.

  8. Characteristics of Gadolinium Oxide Nanoparticles as Contrast Agents for Terahertz Imaging

    NASA Astrophysics Data System (ADS)

    Lee, Dong-Kyu; Kim, Hyeongmun; Kim, Taekhoon; Cho, Byungkyu; Lee, Kwangyeol; Son, Joo-Hiuk

    2011-04-01

    For the application of gadolinium oxide (Gd2O3) nanoparticles as terahertz contrast agents, their optical properties in a solvent were studied using terahertz time-domain spectroscopy. The power absorption and refractive index of the samples were measured with various concentrations of nanoparticles. The power absorption was extremely large, as much as three orders of magnitude higher than that of water, so that a few ppms of Gd2O3 nanoparticles were distinguished in terms of their power absorption capacity. The results show that the interaction between the terahertz electromagnetic waves and the Gd2O3 nanoparticles is strong enough to allow their exploitation as contrast agents for terahertz medical imaging.

  9. Comparison of gadolinium Cy{sub 2}DOTA, a new hepatobiliary agent, and gadolinium HP-DO3A, an extracellular agent, in healthy liver and metastatic disease

    SciTech Connect

    Runge, V.M.; Wells, J.W.; Williams, N.M.

    1995-02-01

    A new gadolinium (Gd) chelate with preferential hepatobiliary uptake, Gd Cy{sub 2}DOTA, was compared in two animal species with Gd HP-DO3A (gadoteridol), a clinically approved contrast agent with extracellular distribution. Liver enhancement was evaluated for these two contrast agents using magnetic resonance imaging, whereas an experimental model of metastatic disease was used to evaluate the agents` efficacy for liver-lesion delineation. The two agents were compared in four healthy Rhesus monkeys (eight studies) and five New Zealand White rabbits with implanted VX-2 liver tumors (ten studies). The contrast dose was 0.1 mmol/kg, with the agents given in random order and at least 72 hours between contrast injections. Breathhold T1-weighted spin echo scans were obtained at 1.5 tesla (T) before and after contrast was administered. Postcontrast scans were obtained 1 to 90 minutes after injection in the monkeys and 1 to 240 minutes after injection in the rabbits. Prolonged hepatic enhancement, superior in degree to that with Gd HP-DO3A, was noted to both monkeys and rabbits after injection of Gd Cy{sub 2}DOTA. Two minutes after contrast, liver SI was 1.94 {+-} 0.05 with Gd Cy{sub 2}DOTA compared with 1.5 {+-} 0.05 with Gd HP-DO3A in monkeys. Sixty minutes after contrast, liver SI was 1.60 {+-} 0.09 compared with 1.20 {+-} 0.02. The difference between agents was significant at all times from 2 to 60 minutes after contrast injection (P < 0.01). Excretion of contrast into the gall bladder was observed in both animal species with Gd Cy{sub 2}DOTA but not with Gd HP-DO3A. The maximum improvement in lesion conspicuity (rabbit) occurred 45 minutes after injection of Gd Cy{sub 2}DOTA and 5 minutes after injection of Gd HP-DO3A. 22 refs., 12 figs.

  10. 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.

  11. Evaluation of a novel gadolinium-based contrast agent for intraoperative magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Madsen, Steen J.; Wu, Genevieve N.; Chow, Rayland; Kim, Sung-Yop; Hirschberg, Henry

    2008-02-01

    The aim of this experimental study was to determine whether Motexafin Gadolinium (MGd) could serve as an efficient intraoperative contrast agent avoiding problems that arise with surgically-induced intracranial enhancement. F98 orthotopic brain tumors or surgical lesions were induced in Fisher rats. T1-weighted MRI studies were performed with either a single or multiple daily doses of MGd. The last contrast dose was administered either 7 or 24 h prior to scanning in both tumor-bearing and surgically treated animals. Animals receiving either 30 or 60 mg/kg MGd i.v. developed clinical signs of impaired motor activity, and increasing lethargy. MGd given i.p. was tolerated up to a dose of 140 mg/kg. Despite multiple dosages, and several administration modes (i.p. and i.v.), no significant enhancement was observed if the scans were performed 7 or 24 h following the last MGd dose. Clear enhancement was observed if the scans were performed 30 min. following MGd administration. Scans of necrotic lesions were positive 7 h post MGd injection. MGd scans showed no significant enhancement following surgically-induced lesions while scans with conventional contrast agents showed both meningeal and intraparenchymal enhancement. This study suggests that MGd is not sequestered in viable tumor for the necessary time interval required to allow delayed imaging in this model. The agent does seem to remain in necrotic tissue for longer time intervals. MGd therefore would not be suitable as a contrast agent in iMRI for the detection of residual tumor tissue during surgery.

  12. Efficient labeling in vitro with non-ionic gadolinium magnetic resonance imaging contrast agent and fluorescent transfection agent in bone marrow stromal cells of neonatal rats.

    PubMed

    Li, Ying-Qin; Tang, Ying; Fu, Rao; Meng, Qiu-Hua; Zhou, Xue; Ling, Ze-Min; Cheng, Xiao; Tian, Su-Wei; Wang, Guo-Jie; Liu, Xue-Guo; Zhou, Li-Hua

    2015-07-01

    Although studies have been undertaken on gadolinium labeling-based molecular imaging in magnetic resonance imaging (MRI), the use of non-ionic gadolinium in the tracking of stem cells remains uncommon. To investigate the efficiency in tracking of stem cells with non-ionic gadolinium as an MRI contrast agent, a rhodamine-conjugated fluorescent reagent was used to label bone marrow stromal cells (BMSCs) of neonatal rats in vitro, and MRI scanning was undertaken. The fluorescent-conjugated cell uptake reagents were able to deliver gadodiamide into BMSCs, and cell uptake was verified using flow cytometry. In addition, the labeled stem cells with paramagnetic contrast medium remained detectable by an MRI monitor for a minimum of 28 days. The present study suggested that this method can be applied efficiently and safely for the labeling and tracking of bone marrow stromal cells in neonatal rats.

  13. Gadolinium(III) Complexes with N-Alkyl-N-methylglucamine Surfactants Incorporated into Liposomes as Potential MRI Contrast Agents

    PubMed Central

    Silva, Simone Rodrigues; Duarte, Érica Correia; Ramos, Guilherme Santos; Kock, Flávio Vinícius Crizóstomo; Andrade, Fabiana Diuk; Frézard, Frédéric; Colnago, Luiz Alberto; Demicheli, Cynthia

    2015-01-01

    Complexes of gadolinium(III) with N-octanoyl-N-methylglucamine (L8) and N-decanoyl-N-methylglucamine (L10) with 1 : 2 stoichiometry were synthesized and characterized by elemental analysis, electrospray ionization-tandem mass spectrometry (ESI-MS), infrared (IR) spectroscopy, and molar conductivity measurements. The transverse (r2) and longitudinal (r1) relaxivity protons were measured at 20 MHz and compared with those of the commercial contrasts. These complexes were incorporated in liposomes, resulting in the increase of the vesicle zeta potential. Both the free and liposome-incorporated gadolinium complexes showed high relaxation effectiveness, compared to commercial contrast agent gadopentetate dimeglumine (Magnevist). The high relaxivity of these complexes was attributed to the molecular rotation that occurs more slowly, because of the elevated molecular weight and incorporation in liposomes. The results establish that these paramagnetic complexes are highly potent contrast agents, making them excellent candidates for various applications in molecular MR imaging. PMID:26347596

  14. Investigating the stability of gadolinium based contrast agents towards UV radiation.

    PubMed

    Birka, Marvin; Roscher, Jörg; Holtkamp, Michael; Sperling, Michael; Karst, Uwe

    2016-03-15

    Since the 1980s, the broad application of gadolinium(Gd)-based contrast agents for magnetic resonance imaging (MRI) has led to significantly increased concentrations of Gd in the aqueous environment. Little is known about the stability of these highly polar xenobiotics under environmental conditions, in wastewater and in drinking water treatment. Therefore, the stability of frequently applied Gd-based MRI contrast agents towards UV radiation was investigated. The hyphenation of hydrophilic interaction liquid chromatography (HILIC) with inductively coupled plasma mass spectrometry (ICP-MS) and of HILIC with electrospray ionization mass spectrometry (ESI-MS) provided quantitative elemental information as well as structural information. The contrast agents Gd-DTPA, Gd-DOTA and Gd-BT-DO3A showed a high stability in irradiation experiments applying a wavelength range from 220 nm to 500 nm. Nevertheless, the degradation of Gd-BOPTA as well as the formation of Gd-containing transformation products was observed by means of HILIC-ICP-MS. Matrix-dependent irradiation experiments showed a degradation of Gd-BOPTA down to 3% of the initial amount in purified water after 300 min, whereas the degradation was slowed down in drinking water and surface water. Furthermore, it was observed that the sum of species continuously decreased with proceeding irradiation in all matrices. After irradiation in purified water for 300 min only 16% of the sum of species was left. This indicates a release of Gd(III) ions from the complex in course of irradiation. HILIC-ESI-MS measurements revealed that the transformation products mostly resulted from O-dealkylation and N-dealkylation reactions. In good correlation with retention times, the majority of transformation products were found to be more polar than Gd-BOPTA itself. Based on accurate masses, sum formulas were obtained and structures could be proposed.

  15. Comparative study of the physicochemical properties of six clinical low molecular weight gadolinium contrast agents.

    PubMed

    Laurent, Sophie; Elst, Luce Vander; Muller, Robert N

    2006-01-01

    This paper compares the physicochemical properties of six low molecular weight clinical complexes of gadolinium studied under identical experimental conditions. Magnevist, Dotarem, Omniscan, ProHance, MultiHance and Gadovist were investigated by oxygen-17 relaxometry at different temperatures and by proton relaxometry at various magnetic fields, temperatures and media [pure water, zinc(II)-containing aqueous solutions and HSA-containing solutions]. Osmolality, viscosity and stability versus transmetallation by zinc(II) ions were added for a more comprehensive description. The relaxivities of the clinical formulations as measured in water are similar in the imaging magnetic field region, with a slightly better performance for MultiHance. This can be explained by a shorter distance between the hydrogen nuclei of the water molecule bound to the Gd(3+) ion and this paramagnetic centre. In contrast to the open-chain complexes, all macrocyclic systems (Dotarem, ProHance and Gadovist) are insensitive to transmetallation by zinc ions. The stability of the open-chain complexes with respect to transmetallation depends on the chemical structure of the ligand, with a better stability for MultiHance. The presence of human serum albumin has no significant effect on the proton relaxivity of Magnevist, Dotarem, Omniscan, ProHance and Gadovist but markedly increases the relaxivity of MultiHance because of a non-covalent interaction with the protein. As a result, the relaxivity of MultiHance in HSA-containing media of fixed concentration decreases with increasing concentration of the contrast agent.

  16. Regulation of Collagen Turnover in Human Skin Fibroblasts Exposed to a Gadolinium-Based Contrast Agent

    PubMed Central

    Bhagavathula, Narasimharao; DaSilva, Marissa; Aslam, Muhammad N.; Dame, Michael K.; Warner, Roscoe L.; Xu, Yiru; Fisher, Gary J.; Johnson, Kent J.; Swartz, Richard; Varani, James

    2010-01-01

    Objective Nephrogenic systemic fibrosis (NSF) is a clinical syndrome linked with exposure in renal failure patients to gadolinium-based contrast agents (GBCAs) during magnetic resonance imaging. Recently, we demonstrated that GBCA exposure led to increased matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in human skin fibroblasts. The goals of the present work were to assess the relationship between altered MMP-1 / TIMP-1 expression and collagen production / deposition, and the intracellular signaling events that lead from GBCA stimulation to altered MMP-1 and TIMP-1 production. Materials and Methods Human dermal fibroblasts were treated with one of the currently used GBCAs (Omniscan). Proliferation was quantified as were levels of MMP-1, TIMP-1, procollagen type I and collagen type I. Signaling events were concomitantly assessed, and signaling inhibitors were used. Results Fibroblasts exposed to Omniscan had increases in both MMP-1 and TIMP-1 levels. Omniscan treatment interfered with collagen turnover, leading to increased type I collagen deposition without an increase in type I procollagen production. U0126, an inhibitor of mitogen-activated protein kinase signaling, and LY294002, a phosphatidylinositol-3 kinase inhibitor, reduced MMP-1 levels. U0126 also reduced TIMP-1 levels, but LY294002 increased TIMP-1. Conclusion These data provide evidence for complex regulation of collagen deposition in Omniscan-treated skin. They suggest that the major effect of Omniscan exposure is on an enzyme / inhibitor system that regulates collagen breakdown rather than on collagen production, per se. PMID:19561517

  17. 13 CFR 107.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including... Assistance SMALL BUSINESS ADMINISTRATION SMALL BUSINESS INVESTMENT COMPANIES SBA Financial Assistance for... Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. (a) Agents....

  18. Native T1-mapping detects the location, extent and patterns of acute myocarditis without the need for gadolinium contrast agents

    PubMed Central

    2014-01-01

    Background Acute myocarditis can be diagnosed on cardiovascular magnetic resonance (CMR) using multiple techniques, including late gadolinium enhancement (LGE) imaging, which requires contrast administration. Native T1-mapping is significantly more sensitive than LGE and conventional T2-weighted (T2W) imaging in detecting myocarditis. The aims of this study were to demonstrate how to display the non-ischemic patterns of injury and to quantify myocardial involvement in acute myocarditis without the need for contrast agents, using topographic T1-maps and incremental T1 thresholds. Methods We studied 60 patients with suspected acute myocarditis (median 3 days from presentation) and 50 controls using CMR (1.5 T), including: (1) dark-blood T2W imaging; >(2) native T1-mapping (ShMOLLI); (3) LGE. Analysis included: (1) global myocardial T2 signal intensity (SI) ratio compared to skeletal muscle; (2) myocardial T1 times; (3) areas of injury by T2W, T1-mapping and LGE. Results Compared to controls, patients had more edema (global myocardial T2 SI ratio 1.71 ± 0.27 vs.1.56 ± 0.15), higher mean myocardial T1 (1011 ± 64 ms vs. 946 ± 23 ms) and more areas of injury as detected by T2W (median 5% vs. 0%), T1 (median 32% vs. 0.7%) and LGE (median 11% vs. 0%); all p < 0.001. A threshold of T1 > 990 ms (sensitivity 90%, specificity 88%) detected significantly larger areas of involvement than T2W and LGE imaging in patients, and additional areas of injury when T2W and LGE were negative. T1-mapping significantly improved the diagnostic confidence in an additional 30% of cases when at least one of the conventional methods (T2W, LGE) failed to identify any areas of abnormality. Using incremental thresholds, T1-mapping can display the non-ischemic patterns of injury typical of myocarditis. Conclusion Native T1-mapping can display the typical non-ischemic patterns in acute myocarditis, similar to LGE imaging but without the need for contrast agents. In

  19. Application of extracellular gadolinium-based MRI contrast agents and the risk of nephrogenic systemic fibrosis.

    PubMed

    Heverhagen, J T; Krombach, G A; Gizewski, E

    2014-07-01

    Nephrogenic systemic fibrosis (NSF) is a serious, sometimes fatal disease. Findings in recent years have shown that a causal association between gadolinium containing contrast media and NSF is most likely. Therefore, the regulatory authorities have issued guidelines on the use of gadolinium-containing contrast media which have reduced the number of new cases of NSF to almost zero. However, it is for precisely this reason that the greatest care must still be taken to ensure that these guidelines are complied with. The most important factors are renal function, the quantity of gadolinium administered and coexisting diseases such as inflammation. All of these factors crucially influence the quantity of gadolinium released from the chelat in the body. This free gadolinium is thought to be the trigger for NSF. Other important factors are the stability of the gadolinium complex and furthermore the route of its elimination from the body. Partial elimination via the liver might be an additional protective mechanism. In conclusion, despite the NSF risk, contrast-enhanced MRI is a safe diagnostic procedure which can be used reliably and safely even in patients with severe renal failure, and does not necessarily have to be replaced by other methods.

  20. 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

  1. Spatially resolved quantification of gadolinium(III)-based magnetic resonance agents in tissue by MALDI imaging mass spectrometry after in vivo MRI.

    PubMed

    Aichler, Michaela; Huber, Katharina; Schilling, Franz; Lohöfer, Fabian; Kosanke, Katja; Meier, Reinhard; Rummeny, Ernst J; Walch, Axel; Wildgruber, Moritz

    2015-03-27

    Gadolinium(III)-based contrast agents improve the sensitivity and specificity of magnetic resonance imaging (MRI), especially when targeted contrast agents are applied. Because of nonlinear correlation between the contrast agent concentration in tissue and the MRI signal obtained in vivo, quantification of certain biological or pathophysiological processes by MRI remains a challenge. Up to now, no technology has been able to provide a spatially resolved quantification of MRI agents directly within the tissue, which would allow a more precise verification of in vivo imaging results. MALDI imaging mass spectrometry for spatially resolved in situ quantification of gadolinium(III) agents, in correlation to in vivo MRI, were evaluated. Enhanced kinetics of Gadofluorine M were determined dynamically over time in a mouse model of myocardial infarction. MALDI imaging was able to corroborate the in vivo imaging MRI signals and enabled in situ quantification of the gadolinium probe with high spatial resolution.

  2. Changes in Urinary and Serum Levels of Novel Biomarkers after Administration of Gadolinium-based Contrast Agents

    PubMed Central

    Mawad, Habib; Laurin, Louis-Philippe; Naud, Jean-François; Leblond, François A.; Henley, Nathalie; Vallée, Michel; Pichette, Vincent; Leblanc, Martine

    2016-01-01

    OBJECTIVE The aim of our study is to describe the changes in urinary and serum levels of novel biomarkers after gadolinium contrast administration in patients with normal renal function. METHODS We measured four biomarkers in 28 volunteers: interleukin-18 (IL-18), N-acetyl-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin, and cystatin C. Urinary and serum samples were collected at 0, 3, and 24 hours following gadolinium administration. RESULTS Baseline serum creatinine was 57.8 ± 34.5 µmol/L and remained stable. Urinary IL-18 levels increased significantly at three hours (10.7 vs. 7.3 ng/mg creatinine; P < 0.05). Similarly, urinary NAG levels increased significantly at three hours (3.9 vs. 2.2 IU/mg creatinine; P < 0.001). For both these markers, the difference was no longer significant at 24 hours. No statistically significant differences were observed for urinary and serum neutrophil gelatinase-associated lipocalin levels and for serum cystatin C levels. CONCLUSIONS Urinary IL-18 and NAG levels increased transiently after administration of gadolinium-based contrast agents in patients with normal renal function. PMID:27398022

  3. Biodistribution of ultra small gadolinium-based nanoparticles as theranostic agent: application to brain tumors.

    PubMed

    Miladi, Imen; Duc, Géraldine Le; Kryza, David; Berniard, Aurélie; Mowat, Pierre; Roux, Stéphane; Taleb, Jacqueline; Bonazza, Pauline; Perriat, Pascal; Lux, François; Tillement, Olivier; Billotey, Claire; Janier, Marc

    2013-09-01

    Gadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood-brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors.

  4. Colloids containing gadolinium-capped gold nanoparticles as high relaxivity dual-modality contrast agents for CT and MRI.

    PubMed

    Zeng, ChengCai; Shi, XiaoNi; Wu, Bo; Zhang, Dong; Zhang, WeiLu

    2014-11-01

    A type of novel macromolecular colloid was prepared from gadolinium-based poly(l-succinimide) and gold nanoparticles (GNPs) with Au-S covalent bonds. The colloid displayed improved stability in aqueous media and regular arrays in partial region. Moreover, these materials enhanced the contrast 9 times more than that of the corresponding uncoated Au compound when the Au mass content was only 0.15%. Therefore, these materials might have potential as dual-modality contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT).

  5. Vibrational dynamics of zero-field-splitting hamiltonian in gadolinium-based MRI contrast agents from ab initio molecular dynamics

    SciTech Connect

    Lasoroski, Aurélie; Vuilleumier, Rodolphe; Pollet, Rodolphe

    2014-07-07

    The electronic relaxation of gadolinium complexes used as MRI contrast agents was studied theoretically by following the short time evolution of zero-field-splitting parameters. The statistical analysis of ab initio molecular dynamics trajectories provided a clear separation between static and transient contributions to the zero-field-splitting. For the latter, the correlation time was estimated at approximately 0.1 ps. The influence of the ligand was also probed by replacing one pendant arm of our reference macrocyclic complex by a bulkier phosphonate arm. In contrast to the transient contribution, the static zero-field-splitting was significantly influenced by this substitution.

  6. Gadolinium-Induced Fibrosis.

    PubMed

    Todd, Derrick J; Kay, Jonathan

    2016-01-01

    Gadolinium-based contrast agents (GBCAs), once believed to be safe for patients with renal disease, have been strongly associated with nephrogenic systemic fibrosis (NSF), a severe systemic fibrosing disorder that predominantly afflicts individuals with advanced renal dysfunction. We provide a historical perspective on the appearance and disappearance of NSF, including its initial recognition as a discrete clinical entity, its association with GBCA exposure, and the data supporting a causative relationship between GBCA exposure and NSF. On the basis of this body of evidence, we propose that the name gadolinium-induced fibrosis (GIF) more accurately reflects the totality of knowledge regarding this disease. Use of high-risk GBCAs, such as formulated gadodiamide, should be avoided in patients with renal disease. Restriction of GBCA use in this population has almost completely eradicated new cases of this debilitating condition. Emerging antifibrotic therapies may be useful for patients who suffer from GIF.

  7. 13 CFR 108.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent. 108.1620 Section 108.1620 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION NEW MARKETS VENTURE CAPITAL (âNMVCâ) PROGRAM SBA...

  8. Folate-targeted gadolinium-lipid-based nanoparticles as a bimodal contrast agent for tumor fluorescent and magnetic resonance imaging.

    PubMed

    Nakamura, Taro; Kawano, Kumi; Shiraishi, Kouichi; Yokoyama, Masayuki; Maitani, Yoshie

    2014-01-01

    To enhance tumor magnetic resonance imaging (MRI) signals via the selective accumulation of contrast agents, we prepared folate-modified gadolinium-lipid-based nanoparticles as MRI contrast agents. Folate-modified nanoparticles were comprised of polyethylene glycol (PEG)-lipid, gadolinium diethylenetriamine pentaacetic acid lipid, cationic cholesterol derivatives, folate-conjugated PEG-lipid, and Cy7-PEG-lipid. Folate receptor-mediated cellular nanoparticle association was examined in KB cells, which overexpress the folate receptor. The biodistribution of nanoparticles after their intravenous injection into KB tumor-bearing mice was measured. Mice were imaged through in vivo fluorescence imaging and MRI 24 h after nanoparticle injection, and the intensity enhancement of the tumor MRI signal was evaluated. Increased cellular association of folate-modified nanoparticles was inhibited by excess free folic acid, indicating that nanoparticle association was folate receptor-mediated. Irrespective of folate modification, the amount of nanoparticles in blood 24 h after injection was ca. 10% of the injected dose. Compared with non-modified nanoparticles, folate-modified nanoparticles exhibited significant accumulation in tumor tissues without altering other biodistribution, as well as enhanced tumor fluorescence and MRI signal intensity. The results support the feasibility of MRI- and in vivo fluorescence imaging-based tumor visualization using folate-modified nanoparticles and provide opportunities to develop folate targeting-based imaging applications.

  9. Parallel Comparative Studies on Mouse Toxicity of Oxide Nanoparticle- and Gadolinium-Based T1 MRI Contrast Agents.

    PubMed

    Chen, Rui; Ling, Daishun; Zhao, Lin; Wang, Shuaifei; Liu, Ying; Bai, Ru; Baik, Seungmin; Zhao, Yuliang; Chen, Chunying; Hyeon, Taeghwan

    2015-12-22

    Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.

  10. Nephrogenic systemic fibrosis and class labeling of gadolinium-based contrast agents by the Food and Drug Administration.

    PubMed

    Yang, Lucie; Krefting, Ira; Gorovets, Alex; Marzella, Louis; Kaiser, James; Boucher, Robert; Rieves, Dwaine

    2012-10-01

    In 2007, the Food and Drug Administration requested that manufacturers of all approved gadolinium-based contrast agents (GBCAs), drugs widely used in magnetic resonance imaging, use nearly identical text in their product labeling to describe the risk of nephrogenic systemic fibrosis (NSF). Accumulating information about NSF risks led to revision of the labeling text for all of these drugs in 2010. The present report summarizes the basis and purpose of this class-labeling approach and describes some of the related challenges, given the evolutionary nature of the NSF risk evidence. The class-labeling approach for presentation of product risk is designed to decrease the occurrence of NSF and to enhance the safe use of GBCAs in radiologic practice.

  11. Non-Specific Zn2+ Ion Sensing Using Ultrasmall Gadolinium Oxide Nanoparticle as a Magnetic Resonance Imaging Contrast Agent.

    PubMed

    Bony, Badrul Alam; Baeck, Jong Su; Chang, Yongmin; Lee, Gang Ho

    2016-03-01

    The gadolinium oxide (Gd2O3) nanoparticles are well-known potential candidates for a positive magnetic resonance imaging (MRI) contrast agent owing to their large longitudinal water proton relaxivity (r1) value with r2/r1 ratio close to one (r2 = transverse water proton relaxivity). In addition they may be used to sense metal ions because their r1 and r2 values can be altered in the presence of metal ions. This may allow us to study metabolic processes involving metal ions and to diagnose disease related to abnormal concentrations of metal ions in the body in a non-invasive way. In this study ultrasmall Gd2O3 nanoparticles were for the first time applied to non-specifically sense Zn2+ ions in aqueous solution. We explored this by measuring r1 and r2 values in the presence of Zn2+ ions in solution.

  12. [Gadolinium as an alternative radiocontrast agent in patients with allergy to iodine-based contrast provide for useful diagnostic imagings and safely treatment of biliary tract diseases].

    PubMed

    Natsume, Makoto; Sano, Hitoshi; Fukusada, Shigeki; Kachi, Kenta; Inoue, Tadahisa; Anbe, Kaiki; Nishie, Hirotada; Nishi, Yuji; Yoshimura, Norihiro; Mizushima, Takashi; Okumura, Fumihiro; Miyabe, Katsuyuki; Naitoh, Itaru; Hayashi, Kazuki; Nakazawa, Takahiro

    2013-05-01

    Diagnosis and treatment of biliary tract disease requires an intraductal radiocontrast agent. Although iodine-based contrast medium is commonly used, some patients show severe allergy to iodinated contrast agent. We have retrospectively reviewed the usefulness and safety of gadolinium as an alternative radiocontrast agent in 3 patients with allergy to iodine-based contrast medium in the diagnosis and treatment of biliary tract diseases. In case 1, percutaneous transhepatic biliary drainage and cholangiography were performed successfully and it was possible to visualize an intrahepatic bile duct stone. Percutaneous transhepatic cholangioscopic lithotomy was performed and the intrahepatic bile duct stone was removed. In case 2, endoscopic biliary lithotripsy was performed. In case 3, percutaneous transhepatic cholangiography and cholangioscopy provided a diagnosis of moderately differentiated carcinoma. He underwent pancreatoduodenectomy. Postoperative cholangiograms were also obtained successfully. Gadolinium contrast agent is an alternative to iodine-based cholangiography for the patients with allergy to iodine.

  13. In vivo selective cancer-tracking gadolinium eradicator as new-generation photodynamic therapy agent

    PubMed Central

    Zhang, Tao; Lan, Rongfeng; Chan, Chi-Fai; Law, Ga-Lai; Wong, Wai-Kwok; Wong, Ka-Leung

    2014-01-01

    In this work, we demonstrate a modality of photodynamic therapy (PDT) through the design of our truly dual-functional—PDT and imaging—gadolinium complex (Gd-N), which can target cancer cells specifically. In the light of our design, the PDT drug can specifically localize on the anionic cell membrane of cancer cells in which its laser-excited photoemission signal can be monitored without triggering the phototoxic generation of reactive oxygen species—singlet oxygen—before due excitation. Comprehensive in vitro and in vivo studies had been conducted for the substantiation of the effectiveness of Gd-N as such a tumor-selective PDT photosensitizer. This treatment modality does initiate a new direction in the development of “precision medicine” in line with stem cell and gene therapies as tools in cancer therapy. PMID:25453097

  14. 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.

  15. Late gadolinium enhancement magnetic resonance imaging for the assessment of myocardial infarction: comparison of image quality between single and double doses of contrast agents.

    PubMed

    Kim, Yeo Koon; Park, Eun-Ah; Lee, Whal; Kim, Sang Yoon; Chung, Jin Wook

    2014-12-01

    To compare the image quality of late gadolinium enhancement (LGE) cardiac magnetic resonance imaging (CMR) using a single dose of gadolinium contrast agent versus the conventional double dose for assessing myocardial infarction. This retrospective study examined 37 patients with chronic myocardial infarction who underwent LGE CMR using both inversion recovery (IR)-turbo fast low-angle shot magnitude-reconstructed and phase-sensitive images with two different dosages of gadolinium contrast agent: a single dose of 0.1 mmol/kg gadolinium-DTPA in 17 patients and a double dose of 0.2 mmol/kg in 20 patients. The contrast-to-noise ratio (CNR) and visual conspicuity between infarct and normal myocardium (CNRinfarct-normal, conspicuityinfarct-normal) and between infarct and left ventricular cavity (CNRinfarct-LVC, conspicuityinfarct-LVC) were compared. Interobserver agreement for the maximal transmural extent of infarction was also evaluated. CNRinfarct-normal was significantly higher with double-dose gadolinium contrast agent (15.5 ± 20.7 vs. 40.4 ± 16.1 in magnitude images and 9.5 ± 2.8 vs. 11.2 ± 2.7 in phase-sensitive images, P < 0.001) while conspicuityinfarct-normal showed no significant difference between the two groups (P > 0.05). Both CNRinfarct-LVC (7.7 ± 10.7 vs. -6.6 ± 19.0 in magnitude images and 4.1 ± 2.3 vs. -0.4 ± 4.1 in phase-sensitive images, P < 0.05) and conspicuityinfarct-LVC were significantly better with single-dose gadolinium contrast. Interobserver agreement for assessing the transmural extent of infarction was moderate in both groups: 0.591 for single-dose and 0.472 for double-dose. LGE CMR using a single dose of gadolinium contrast agent showed significantly better contrast between infarcted myocardium and left ventricular cavity lumen without a significant decrease in visual contrast between infarcted myocardium and normal myocardium, compared to a double dose.

  16. Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

    NASA Astrophysics Data System (ADS)

    Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

    2004-10-01

    Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

  17. Gadolinium-Encapsulating Iron Oxide Nanoprobe as Activatable NMR/MRI Contrast Agent

    PubMed Central

    Santra, Santimukul; Jativa, Samuel D.; Kaittanis, Charalambos; Normand, Guillaume; Grimm, Jan; Perez, J. Manuel

    2012-01-01

    Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the polyacrylic acid (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA) yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T1). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T1 relaxation rate (1/T1) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T1-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T1 signal was observed. This result suggests that upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH = 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T1 activation. No change in T1 was observed when the Gd-DTPA complex was chemically conjugated on the surface of the nanoparticle's polymeric coating or when encapsulated in the polymeric coating of a non-magnetic nanoparticle. These results confirmed that the observed (T1) quenching of the composite magnetic nanoprobe is due to the encapsulation and close proximity of the Gd ion to the nanoparticles superparamagnetic iron oxide (IO) core. In addition, when an anticancer drug (Taxol) was co-encapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T1 activation of the probe coincide with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T1 nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI. PMID:22809405

  18. Gadolinium-encapsulating iron oxide nanoprobe as activatable NMR/MRI contrast agent.

    PubMed

    Santra, Santimukul; Jativa, Samuel D; Kaittanis, Charalambos; Normand, Guillaume; Grimm, Jan; Perez, J Manuel

    2012-08-28

    Herein we report a novel gadolinium-encapsulating iron oxide nanoparticle-based activatable NMR/MRI nanoprobe. In our design, Gd-DTPA is encapsulated within the poly(acrylic acid) (PAA) polymer coating of a superparamagnetic iron oxide nanoparticle (IO-PAA), yielding a composite magnetic nanoprobe (IO-PAA-Gd-DTPA) with quenched longitudinal spin-lattice magnetic relaxation (T(1)). Upon release of the Gd-DTPA complex from the nanoprobe's polymeric coating in acidic media, an increase in the T(1) relaxation rate (1/T(1)) of the composite magnetic nanoprobe was observed, indicating a dequenching of the nanoprobe with a corresponding increase in the T(1)-weighted MRI signal. When a folate-conjugated nanoprobe was incubated in HeLa cells, a cancer cell line overexpressing folate receptors, an increase in the 1/T(1) signal was observed. This result suggests that, upon receptor-mediated internalization, the composite magnetic nanoprobe degraded within the cell's lysosome acidic (pH 5.0) environment, resulting in an intracellular release of Gd-DTPA complex with subsequent T(1) activation. In addition, when an anticancer drug (Taxol) was coencapsulated with the Gd-DTPA within the folate receptor targeting composite magnetic nanoprobe, the T(1) activation of the probe coincided with the rate of drug release and corresponding cytotoxic effect in cell culture studies. Taken together, these results suggest that our activatable T(1) nanoagent could be of great importance for the detection of acidic tumors and assessment of drug targeting and release by MRI.

  19. Gd(DOTAlaP): Exploring the Boundaries of Fast Water Exchange in Gadolinium-Based Magnetic Resonance Imaging Contrast Agents

    PubMed Central

    2015-01-01

    Here, we describe the synthesis of the single amino acid chelator DOTAlaP and four of its derivatives. The corresponding gadolinium(III) complexes were investigated for their kinetic inertness, relaxometric properties at a range of fields and temperatures, water exchange rate, and interaction with human serum albumin (HSA). Derivatives with one inner-sphere water (q = 1) were determined to have a mean water residency time between 8 and 6 ns in phoshate-buffered saline at 37 °C. The corresponding europium complexes were also formed and used to obtain information on the hydration number of the corresponding coordination complexes. Two complexes capable of binding HSA were also synthesized, of which one, Gd(5b), contains no inner-sphere water, while the other derivative, Gd(4b), is a mixture of ca. 15% q =1 and 85% q = 0. In the presence of HSA, the latter displayed a very short mean water residency time (τM310 = 2.4 ns) and enhanced relaxivity at intermediate and high fields. The kinetic inertness of Gd(4b) with respect to complex dissociation was decreased compared to its DOTAla analogue but still 100-fold more inert than [Gd(BOPTA)(H2O)]2–. Magnetic resonance imaging in mice showed that Gd(4b) was able to provide 38% better vessel to muscle contrast compared to the clinically used HSA binding agent MS-325. PMID:24922178

  20. Biodistribution study of nanometric hybrid gadolinium oxide particles as a multimodal SPECT/MR/optical imaging and theragnostic agent.

    PubMed

    Kryza, David; Taleb, Jacqueline; Janier, Marc; Marmuse, Laurence; Miladi, Imen; Bonazza, Pauline; Louis, Cédric; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier; Billotey, Claire

    2011-06-15

    Nanometric hybrid gadolinium oxide particles (Gado-6Si-NP) for diagnostic and therapeutic applications (mean diameter 3-4 nm) were obtained by encapsulating Gd(2)O(3) cores within a polysiloxane shell, which carries organic fluorophore (Cy 5) and is derivatized by a hydrophilic carboxylic layer. As residency time in the living body and methods of waste elimination are crucial to defining a good nanoparticle candidate and moving forward with steps for validation, this study was aimed at evaluating the biodistribution of these multimodal Gado-6Si-NP in rodents. Gado-6Si-NP were imaged following intravenous injection in control Wistar rats and mice using MRI (7 T), optical fluorescent imaging, and SPECT. A clear correlation was observed among MRI, optical imaging, and SPECT regarding the renal elimination. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles circulated freely in the blood pool and were rapidly cleared by renal excretion without accumulation in liver and RES uptake. These results demonstrate that Gado-6Si-NP display optimal biodistribution properties, enabling them to be developed as multimodal agents for in vivo imaging and theragnostics, especially in oncological applications.

  1. Highly stabilized gadolinium chelates functionalized on metal nanoparticles as magnetic resonance imaging contrast agent

    NASA Astrophysics Data System (ADS)

    Siddiqui, Talha S.

    Magnetic resonance imaging (MRI) is a non-invasive method for imaging and diagnosing tissue damage, organ function and the vascular system. Magnevist(TM) a complex of diethylenetriaminepentaacetic acid (DTPA) and Gd3+ is a clinically approved contrast agent for MRI. A derivative of DTPA was formed by the addition of two cysteine groups (DTPA-L-Cys) through amide linkage. The Gd complex of this ligand bonds with the silver surfaces through the cysteine thiols. GdDTPA-L-Cys was bound to ˜10nm diameter Ag nanoparticles for use as a multifunctional MRI contrast agent. The ligand and complex were characterized by 1H and 13C NMR, ESI-MS and IR spectroscopy. The silver construct was characterized by TEM, TGA and UV-Vis absorption spectra. The per metal complex r1 relaxivity of GdDTPA-L-Cys{Ag} greater than that of Magnavist(TM) with the same molarity for both compounds. The synthesis of a DTPA derivative is described that allows it to bind to silver or gold nanoparticles through a single thiol linkage (DTPASH). The resulting Gd complex, GdDTPASH, was bound to Ag nanoparticles to create a single monolayer on the surface. The construct was further stabilized in buffered solution with the addition of a thiolated PEG chain. The highly stabilized nanoparticle construct delivers a high payload of Gd compelex and is an effective T1 brightening agent. The production of this type of construct opens the way for engineered multimodal MRI contrast agents.

  2. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    NASA Astrophysics Data System (ADS)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  3. Hybrid gadolinium oxide nanoparticles: multimodal contrast agents for in vivo imaging.

    PubMed

    Bridot, Jean-Luc; Faure, Anne-Charlotte; Laurent, Sophie; Rivière, Charlotte; Billotey, Claire; Hiba, Bassem; Janier, Marc; Josserand, Véronique; Coll, Jean-Luc; Elst, Luce Vander; Muller, Robert; Roux, Stéphane; Perriat, Pascal; Tillement, Olivier

    2007-04-25

    Luminescent hybrid nanoparticles with a paramagnetic Gd2O3 core were applied as contrast agents for both in vivo fluorescence and magnetic resonance imaging. These hybrid particles were obtained by encapsulating Gd2O3 cores within a polysiloxane shell which carries organic fluorophores and carboxylated PEG covalently tethered to the inorganic network. Longitudinal proton relaxivities of these particles are higher than the positive contrast agents like Gd-DOTA which are commonly used for clinical magnetic resonance imaging. Moreover these particles can be followed up by fluorescence imaging. This study revealed that these particles suited for dual modality imaging freely circulate in the blood vessels without undesirable accumulation in lungs and liver.

  4. Gadolinium-based hybrid nanoparticles as a positive MR contrast agent.

    PubMed

    Hifumi, Hiroki; Yamaoka, Seiichi; Tanimoto, Akihiro; Citterio, Daniel; Suzuki, Koji

    2006-11-29

    A new nanoparticulate inorganic-organic hybrid-type positive contrast agent (CA), PGP/dextran-K01, was synthesized based on a GdPO4 inorganic core as a relaxation-time-shortening moiety and a dextran-coating, which generates monodispersibility in water, a high relaxation-time-shortening effect by retaining a large number of water molecules in proximity of the core and toxicity reduction in in-vivo studies. This PGP/dextran-K01 nanoparticle has high r1 and r2 values and a significantly low r2/r1 value, 1.1, which is unprecedented and which is the lowest value among existing nanoparticulate CAs indicating that PGP/dextran-K01 is a positive contrast agent. Because of this low r2/r1 value and the nanoparticulate shape, PGP/dextran-K01 will be a useful clinical substitute for negative CAs based on iron oxides.

  5. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Functions of agents, including Central Registration..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of...

  6. Synthesis and biological evaluation of a class of mitochondrially-targeted gadolinium(III) agents.

    PubMed

    Morrison, Daniel E; Aitken, Jade B; de Jonge, Martin D; Issa, Fatiah; Harris, Hugh H; Rendina, Louis M

    2014-12-01

    A structure-activity relationship study of a library of novel bifunctional Gd(III) complexes covalently linked to arylphosphonium cations is reported. Such complexes have been designed for potential application in binary cancer therapies such as neutron capture therapy and photon activation therapy. A positive correlation was found between lipophilicity and cytotoxicity of the complexes. Mitochondria uptake was determined by means of inductively coupled plasma mass spectrometry (ICP-MS), and Gd uptake was determined by means of quantification using synchrotron X-ray fluorescence (XRF) imaging. A negative correlation between lipophilicity and tumour selectivity of the Gd(III) complexes was demonstrated. This study highlights the delicate balance required to minimise in vitro cytotoxicity and optimise in vitro tumour selectivity and mitochondrial localisation for this new class of mitochondrially-targeted binary therapy agents. We also report the highest in vitro tumour selectivity for any Gd agent reported to date, with a T/N (tumour/normal cell) ratio of up to 23.5±6.6.

  7. MRI-Monitored Intra-Shunt Local Agent Delivery of Motexafin Gadolinium: Towards Improving Long-Term Patency of TIPS

    PubMed Central

    Meng, Yanfeng; Zhang, Tong; Willis, Patrick; Le, Thomas; Soriano, Stephanie; Ray, Erik; Valji, Karim; Zhang, Guixiang; Yang, Xiaoming

    2013-01-01

    Background Transjugular intrahepatic portosystemic shunt (TIPS) has become an important and effective interventional procedure in treatment of the complications related to portal hypertension. Although the primary patency of TIPS has been greatly improved due to the clinical application of cover stent-grafts, the long-term patency is still suboptimal. This study was to investigate the feasibility of using magnetic resonance imaging (MRI)-monitored intra-shunt local agent delivery of motexafin gadolinium (MGd) into shunt-vein walls of TIPS. This new technique aimed to ultimately inhibit shuntstenosis of TIPS. Methodology Human umbilical vein smooth muscle cells (SMCs) were incubated with various concentrations of MGd, and then examed by confocal microscopy and T1-map MRI. In addition, the proliferation of MGd-treated cells was evaluated. For in vivo validation, seventeen pigs underwent TIPS. Before placement of the stent, an MGd/trypan-blue mixture was locally delivered, via a microporous balloon, into eleven shunt-hepatic vein walls under dynamic MRI monitoring, while trypan-blue only was locally delivered into six shunt-hepatic vein walls as serve as controls. T1-weighted MRI of the shunt-vein walls was achieved before- and at different time points after agent injections. Contrast-to-noise ratio (CNR) of the shunt-vein wall at each time-point was measured. Shunts were harvested for subsequent histology confirmation. Principal Findings In vitro studies confirmed the capability of SMCs in uptaking MGds in a concentration-dependent fashion, and demonstrated the suppression of cell proliferation by MGds as well. Dynamic MRI displayed MGd/blue penetration into the shunt-vein walls, showing significantly higher CNR of shunt-vein walls on post-delivery images than on pre-delivery images (49.5±9.4 vs 11.2±1.6, P<0.01), which was confirmed by histology. Conclusion Results of this study indicate that MRI-monitored intra-shunt local MGd delivery is feasible and MGd

  8. Gadolinium-labeled dendronized gold nanoparticles as new targeted MRI contrast agent

    NASA Astrophysics Data System (ADS)

    Pan, Hongmu; Daniel, Marie-Christine

    2010-04-01

    Early diagnosis is critical for positive outcome of cancer treatments. In many cases, lives would be saved if the tumor could be detected at a very early stage. Nanoparticles have the property of passively targeting tumor sites due to their enhanced permeation and retention (EPR) effect. Thus they can play a critical role in improving the ability to find cancer in its earliest and most treatable stages. Furthermore magnetic resonance imaging is one of the most precise techniques for cancer screening since it can show 3D images of the tumors. For a better enhancement of the sensitivity of this method, MRI contrast agent (DOTA)Gd was attached to poly(propylene imine) dendrons of third generation and the obtained dendrons were used for modification of gold nanoparticles.

  9. Gadolinium Nanoparticles Conjugated with Therapeutic Bifunctional Chelate as a Potential T1 Theranostic Magnetic Resonance Imaging Agent.

    PubMed

    Kang, Min-Kyoung; Lee, Gang Ho; Jung, Ki-Hye; Jung, Jae-Chang; Kim, Hee-Kyung; Kim, Yeon-Hee; Lee, Jongmin; Ryeom, Hun-Kyu; Kim, Tae-Jeong; Chang, Yongmin

    2016-05-01

    This work is directed toward the synthesis of two types of gadolinium oxide nanoparticles (Gd-oxide NPs), abbreviated as Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA, with diameters of 50-60 nm. The synthesis involves sequential coating of Gd-oxide NPs with tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES), followed by functionalization of the aminopropylsilane group with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid conjugates of benzothiazoles (DO3A-BTA). Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA exhibit high water solubility and colloidal stability. The r1 relaxivities of both Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA are higher than those of the corresponding low-molecular-weight magnetic resonance imaging contrast agents (MRI CAs), and their r2/r1 ratios are close to 1, indicating that both can be used as potential T1 MRI CAs. Biodistribution studies demonstrated that Gd@SiO2-DO2A-BTA was excreted via both hepatobiliary and renal pathways. Gd@SiO2-DO2A-BTA exhibits a strong intracellular uptake property in a series of tumor cell lines, and has significant anticancer characteristics against cell lines such as SK-HEP-1, MDA-MB-231, HeLa, and Hep-3B.

  10. Gadolinium Nanoparticles Conjugated with Therapeutic Bifunctional Chelate as a Potential T1 Theranostic Magnetic Resonance Imaging Agent.

    PubMed

    Kang, Min-Kyoung; Lee, Gang Ho; Jung, Ki-Hye; Jung, Jae-Chang; Kim, Hee-Kyung; Kim, Yeon-Hee; Lee, Jongmin; Ryeom, Hun-Kyu; Kim, Tae-Jeong; Chang, Yongmin

    2016-05-01

    This work is directed toward the synthesis of two types of gadolinium oxide nanoparticles (Gd-oxide NPs), abbreviated as Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA, with diameters of 50-60 nm. The synthesis involves sequential coating of Gd-oxide NPs with tetraethyl orthosilicate (TEOS) and (3-aminopropyl) triethoxysilane (APTES), followed by functionalization of the aminopropylsilane group with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) or 1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid conjugates of benzothiazoles (DO3A-BTA). Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA exhibit high water solubility and colloidal stability. The r1 relaxivities of both Gd@SiO2-DO3A and Gd@SiO2-DO2A-BTA are higher than those of the corresponding low-molecular-weight magnetic resonance imaging contrast agents (MRI CAs), and their r2/r1 ratios are close to 1, indicating that both can be used as potential T1 MRI CAs. Biodistribution studies demonstrated that Gd@SiO2-DO2A-BTA was excreted via both hepatobiliary and renal pathways. Gd@SiO2-DO2A-BTA exhibits a strong intracellular uptake property in a series of tumor cell lines, and has significant anticancer characteristics against cell lines such as SK-HEP-1, MDA-MB-231, HeLa, and Hep-3B. PMID:27305813

  11. Effect of hepatocyte-specific gadolinium-based contrast agents on hepatic fat-fraction and R2(⁎).

    PubMed

    Hernando, Diego; Wells, Shane A; Vigen, Karl K; Reeder, Scott B

    2015-01-01

    The purpose of this work was to investigate the effect of a hepatocyte-specific gadolinium based contrast agent (GBCA) on quantitative hepatic fat-fraction (FF) and R2* measurements. Fifty patients were imaged at 1.5T, using chemical-shift encoded water-fat MRI with low (5°) and high (15°) flip angles (FA), both before and after administration of a hepatocyte-specific GBCA (gadoxetic acid). Low and high FA, pre- and post-contrast FF and R2* values were measured for each subject. Available serum laboratory studies related to liver disease were also recorded. Linear regression and Bland-Altman analysis were performed to compare measurements. Hepatic FF was unaffected by GBCA at low FA (slope=1.02±0.02, p=0.32). FF was overestimated at high FA pre-contrast (slope=1.33±0.03, p<10(-10)), but underestimated post-contrast (slope=0.81±0.02, p<10(-10)). Hepatic R2* was unaffected by FA (mean difference±95% CI pre-contrast:2.2±4.9s(-1), post-contrast:2.8±3.6s(-1)), but increased post-contrast in patients with total bilirubin <2.5mg/dL (ΔR2*=13.4±12.7s(-1)). Regression analysis of serum values demonstrated a correlation of post-contrast change in R2* with total bilirubin (p<0.01) and model for end-stage liver disease (MELD) score (p≈0.01). In conclusion, GBCA has no effect on hepatic FF at low FA due to a lack of T1-weighting, potentially allowing flexibility for FF imaging with hepatobiliary imaging protocols. Hepatic R2* increased significantly after GBCA administration, particularly in the biliary tree. Therefore, R2* maps should be obtained prior to contrast administration.

  12. Collagenolytic Activity is Suppressed in Organ-Cultured Human Skin Exposed to a Gadolinium-Based MRI Contrast Agent

    PubMed Central

    Perone, Patricia A.; Weber, Stephanie L.; DaSilva, Marissa; Paruchuri, Tejaswi; Bhagavathula, Narasimharao; Aslam, Muhammad N.; Dame, Michael K.; Johnson, Kent J.; Swartz, Richard D.; Varani, James

    2010-01-01

    Objective Human skin produces increased amounts of matrix metalloproteinase-1 (MMP-1) when exposed in organ culture to Omniscan, one of the gadolinium-based MRI contrast agents (GBCA). MMP-1, by virtue of its ability to degrade structural collagen, contributes to collagen turnover in the skin. The objective of the present study was to determine if collagenolytic activity was concomitantly upregulated with increased enzyme. Materials and Methods Skin biopsies from normal volunteers were exposed in organ culture to Omniscan. Organ culture fluids obtained from control and treated skin were examined for ability to degrade type I collagen. The same culture fluids were examined for levels of MMP-1, tissue inhibitor of metalloproteinases-1 (TIMP-1), and complexes of MMP-1 and TIMP-1. Results Although MMP-1 was increased in culture fluid from Omniscan-treated skin, there was no increase in collagenolytic activity. In fact, collagenolytic activity declined. Increased production of TIMP-1 was also observed in Omniscan-treated skin, and the absolute amount of TIMP-1 was greater than the amount of MMP-1. Virtually all of the MMP-1 was present in MMP-1–TIMP-1 complexes, but the majority of TIMP-1 was not associated with MMP-1. When human dermal fibroblasts were exposed to TIMP-1 (up to 250 ng/ml), no increase in proliferation was observed, but an increase in collagen deposition into the cell layer was seen. Conclusion GBCA exposure has recently been linked to a fibrotic skin condition in patients with impaired kidney function. The mechanism is unknown. The increase in TIMP-1 production and concomitant reduction in collagenolytic activity demonstrated here could result in decreased collagen turnover and increased deposition of collagen in lesional skin. PMID:19996758

  13. Induction of a type I interferon signature in normal human monocytes by gadolinium-based contrast agents: comparison of linear and macrocyclic agents.

    PubMed

    Wermuth, P J; Jimenez, S A

    2014-01-01

    The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between the magnitude of the measured response and the Gd chelate used. To explore the mechanisms responsible for GdBCA induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal human dermal fibroblasts were incubated with GdBCA-treated monocyte culture supernatants and the effects on profibrotic gene expression were examined. Supernatants from monocytes exposed to all GdBCA stimulated types I and III collagen, fibronectin and α-smooth muscle actin (α-SMA) expression in normal dermal fibroblasts. The results indicate that the monocyte activation induced by GdBCA may be the initial step in the development of GdBCA associated fibrosis in NSF.

  14. Induction of a type I interferon signature in normal human monocytes by gadolinium-based contrast agents: comparison of linear and macrocyclic agents

    PubMed Central

    Wermuth, P J; Jimenez, S A

    2014-01-01

    The gadolinium-based contrast agent (GdBCA) Omniscan activates human macrophages through Toll-like receptor (TLR)-4 and TLR-7 signalling. To explore the mechanisms responsible we compared the ability of linear and macrocyclic GdBCA to induce a type I interferon signature and a proinflammatory/profibrotic phenotype in normal human monocytes in vitro. Expression of genes associated with type I interferon signalling and inflammation and production of their corresponding proteins were determined. Both linear and macrocyclic GdBCA stimulated expression of multiple type I interferon-regulated genes and the expression of numerous chemokines, cytokines and growth factors in normal human peripheral blood monocytes. There was no correlation between the magnitude of the measured response and the Gd chelate used. To explore the mechanisms responsible for GdBCA induction of fibrosis in nephrogenic systemic fibrosis (NSF) in vitro, normal human dermal fibroblasts were incubated with GdBCA-treated monocyte culture supernatants and the effects on profibrotic gene expression were examined. Supernatants from monocytes exposed to all GdBCA stimulated types I and III collagen, fibronectin and α-smooth muscle actin (α-SMA) expression in normal dermal fibroblasts. The results indicate that the monocyte activation induced by GdBCA may be the initial step in the development of GdBCA associated fibrosis in NSF. PMID:24111526

  15. T1-T2 Dual-modal MRI contrast agents based on superparamagnetic iron oxide nanoparticles with surface attached gadolinium complexes.

    PubMed

    Szpak, Agnieszka; Fiejdasz, Sylwia; Prendota, Witold; Strączek, Tomasz; Kapusta, Czesław; Szmyd, Janusz; Nowakowska, Maria; Zapotoczny, Szczepan

    2014-01-01

    Dual-mode MRI contrast agents consisting of superparamagnetic iron oxide nanoparticle (SPION) cores and gadolinium ions associated with the ionic chitosan protecting layer were synthesized and studied. Gadolinium ions were introduced into the coating layer via direct complex formation on the nanoparticles surface, covalent attachment or electrostatically driven deposition of the preformed Gd complex. The modified SPIONs having hydrodynamic diameters ca. 100 nm form stable, well-defined dispersions in water and have excellent magnetic properties. Physiochemical properties of those new materials were characterized using e.g., FTIR spectroscopy, dynamic light scattering, X-ray fluorescence, TEM, and vibrating sample magnetometry. They behave as superparamagnetics and shorten both T1 and T2 proton relaxation times, thus influencing both r1 and r2 relaxivity values that reach 53.7 and 375.5 mM(-1) s(-1), respectively, at 15 MHz. The obtained materials can be considered as highly effective contrast agents for low-field MRI, particularly useful at permanent magnet-based scanners.

  16. Terbium-doped gadolinium oxide nanoparticles prepared by laser ablation in liquid for use as a fluorescence and magnetic resonance imaging dual-modal contrast agent.

    PubMed

    Chen, Fei; Chen, Min; Yang, Chuan; Liu, Jun; Luo, Ningqi; Yang, Guowei; Chen, Dihu; Li, Li

    2015-01-14

    Dual-modal lanthanide-doped gadolinium nanoparticles (NPs), which exhibit an excellent magnetic resonance imaging (MRI) spatial resolution and high fluorescence imaging (FI) sensitivity, have attracted tremendous attention in biotechnology and nanomedicine applications. In this paper, terbium (Tb) ion doped gadolinium oxide (Gd2O3:Tb) NPs with varied Tb concentrations were synthesized by a laser ablation in liquid (LAL) method. The characterization of the structure, morphology, and composition shows that these NPs are spherical with excellent crystallinity. The effects of Tb ion concentration on the visible green fluorescence and longitudinal relaxivity were investigated, indicating that the fluorescence properties were significantly influenced by the Tb ion concentration, but all samples were still efficient T1-weighted contrast agents. Furthermore, the optimum Tb doping concentration was determined to be 1%. The cell viability, cellular fluorescence imaging and in vivo MRI of this dual-modal nano-probe were studied, with the results revealing that the Gd2O3:Tb NPs did not have a significant cytotoxic effect, making them good candidates for use as a dual-modal contrast agent for MRI and fluorescence imaging.

  17. Effect of ionic interaction between a hyperpolarized magnetic resonance chemical probe and a gadolinium contrast agent for the hyperpolarized lifetime after dissolution

    NASA Astrophysics Data System (ADS)

    Takakusagi, Yoichi; Inoue, Kaori; Naganuma, Tatsuya; Hyodo, Fuminori; Ichikawa, Kazuhiro

    2016-09-01

    In hyperpolarization of 13C-enriched magnetic resonance chemical probes in the solid-state, a trace amount of gadolinium (Gd) contrast agent can be used to maximize polarization of the 13C nuclear spins. Here, we report systematic measurement of the spin-lattice relaxation time (T1) and enhancement level of 13C-enriched chemical probes in the presence of various Gd contrast agents in the liquid-state after dissolution. Using two different 13C probes having opposite electric charges at neutral pH, we clearly show the T1 of hyperpolarized 13C was barely affected by the use of a Gd complex that displays repulsive interaction with the 13C probe in solution, whilst T1 was drastically shortened when there was ionic attraction between probe and complex.

  18. 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

    PubMed Central

    2012-01-01

    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 (r1) and transverse relaxivity (r2) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r2/r1 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 r2/r1 ratio for Gd2O3-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r2/r1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r2/r1 ratio of previous PEGylation (r2/r1 = 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. PMID:23033866

  19. 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.

  20. 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.

    PubMed

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

    2012-10-03

    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 (r1) and transverse relaxivity (r2) measurements in different concentrations (0.3 to approximately 2.5 mM), revealed the r2/r1 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 r2/r1 ratio for Gd2O3-DEG than Gd-DTPA and other previous synthesized methods by this and other groups. The smaller r2/r1 ratios of two PEGylated-SPGO contrast agents in our study in comparison with r2/r1 ratio of previous PEGylation (r2/r1 = 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.

  1. Paramagnetic ultrasmall gadolinium oxide nanoparticles as advanced T1 MRI contrast agent: account for large longitudinal relaxivity, optimal particle diameter, and in vivo T1 MR images.

    PubMed

    Park, Ja Young; Baek, Myung Ju; Choi, Eun Sook; Woo, Seungtae; Kim, Joo Hyun; Kim, Tae Jeong; Jung, Jae Chang; Chae, Kwon Seok; Chang, Yongmin; Lee, Gang Ho

    2009-11-24

    Paramagnetic ultrasmall gadolinium oxide (Gd(2)O(3)) nanoparticles with particle diameters (d) of approximately 1 nm were synthesized by using three kinds of Gd(III) ion precursors and by refluxing each of them in tripropylene glycol under an O(2) flow. A large longitudinal relaxivity (r(1)) of water proton of 9.9 s(-1) mM(-1) was estimated. As a result, high contrast in vivo T(1) MR images of the brain tumor of a rat were observed. This large r(1) is discussed in terms of the huge surface to volume ratio (S/V) of the ultrasmall gadolinium oxide nanoparticles coupled with the cooperative induction of surface Gd(III) ions for the longitudinal relaxation of a water proton. It is found from the d dependence of r(1) that the optimal range of d for the maximal r(1), which may be used as an advanced T(1) MRI contrast agent, is 1-2.5 nm.

  2. Gadolinium- and manganite-based contrast agents with fluorescent probes for both magnetic resonance and fluorescence imaging of pancreatic islets: a comparative study.

    PubMed

    Berkova, Zuzana; Jirak, Daniel; Zacharovova, Klara; Lukes, Ivan; Kotkova, Zuzana; Kotek, Jan; Kacenka, Michal; Kaman, Ondrej; Rehor, Ivan; Hajek, Milan; Saudek, Frantisek

    2013-04-01

    Three magnetic resonance (MR)/fluorescence imaging probes were tested for visualization, cellular distribution, and survival of labeled pancreatic islets in vitro and following transplantation. As T(1) contrast agents (CAs), gadolinium(III) complexes linked to β-cyclodextrin (Gd-F-βCD) or bound to titanium dioxide (TiO2 @RhdGd) were tested. As a T(2) CA, perovskite manganite nanoparticles (LSMO@siF@si) were examined. Fluorescein or rhodamine was incorporated as a fluorescent marker in all probes. Islets labeled with gadolinium(III) CAs were visible as hyperintense spots on MR in vitro, but detection in vivo was inconclusive. Islets labeled with LSMO@siF@si CA were clearly visible as hypointense spots or areas on MR scans in vitro as well as in vivo. All CAs were detected inside the islet cells by fluorescence. Although the vitality and function of the labeled islets was not impaired by any of the tested CAs, results indicate that LSMO@siF@si CA is a superior marker for islet labeling, as it provides better contrast enhancement within a shorter scan time. PMID:23316021

  3. Evaluation of absorbed dose in Gadolinium neutron capture therapy

    NASA Astrophysics Data System (ADS)

    Abdullaeva, Gayane; Djuraeva, Gulnara; Kim, Andrey; Koblik, Yuriy; Kulabdullaev, Gairatulla; Rakhmonov, Turdimukhammad; Saytjanov, Shavkat

    2015-02-01

    Gadolinium neutron capture therapy (GdNCT) is used for treatment of radioresistant malignant tumors. The absorbed dose in GdNCT can be divided into four primary dose components: thermal neutron, fast neutron, photon and natural gadolinium doses. The most significant is the dose created by natural gadolinium. The amount of gadolinium at the irradiated region is changeable and depends on the gadolinium delivery agent and on the structure of the location where the agent is injected. To de- fine the time dependence of the gadolinium concentration ρ(t) in the irradiated region the pharmacokinetics of gadolinium delivery agent (Magnevist) was studied at intratumoral injection in mice and intramuscular injection in rats. A polynomial approximation was applied to the experimental data and the influence of ρ(t) on the relative change of the absorbed dose of gadolinium was studied.

  4. 7 CFR 4290.1620 - Functions of agents, including Central Registration Agent, Selling Agent and Fiscal Agent.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., DEPARTMENT OF AGRICULTURE RURAL BUSINESS INVESTMENT COMPANY (âRBICâ) PROGRAM Financial Assistance for RBICs (Leverage) Funding Leverage by Use of Guaranteed Trust Certificates (âtcsâ) § 4290.1620 Functions of agents... to: (i) Establish performance criteria for Poolers. (ii) Monitor and evaluate the financial...

  5. Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging

    PubMed Central

    Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G.

    2015-01-01

    Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early-stage cancer diagnosis. Gadolinium (Gd) (III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high x-ray attenuation coefficient, is an ideal contrast agent candidate for x-ray based CT imaging. Gd metal organic framework (MOF) nanoparticles with tunable size, high Gd (III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multi-modal imaging probes. PMID:26147906

  6. Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application

    NASA Astrophysics Data System (ADS)

    Tegafaw, Tirusew; Xu, Wenlong; Wasi Ahmad, Md; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Lee, Gang Ho

    2015-09-01

    A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd3+ (8S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy3+ (6H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd3+ and Dy3+ and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.

  7. Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application.

    PubMed

    Tegafaw, Tirusew; Xu, Wenlong; Ahmad, Md Wasi; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Lee, Gang Ho

    2015-09-11

    A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd(3+) ((8)S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy(3+) ((6)H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd(3+) and Dy(3+) and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images.

  8. Dual-mode T1 and T2 magnetic resonance imaging contrast agent based on ultrasmall mixed gadolinium-dysprosium oxide nanoparticles: synthesis, characterization, and in vivo application.

    PubMed

    Tegafaw, Tirusew; Xu, Wenlong; Ahmad, Md Wasi; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Lee, Gang Ho

    2015-09-11

    A new type of dual-mode T1 and T2 magnetic resonance imaging (MRI) contrast agent based on mixed lanthanide oxide nanoparticles was synthesized. Gd(3+) ((8)S7/2) plays an important role in T1 MRI contrast agents because of its large electron spin magnetic moment resulting from its seven unpaired 4f-electrons, and Dy(3+) ((6)H15/2) has the potential to be used in T2 MRI contrast agents because of its very large total electron magnetic moment: among lanthanide oxide nanoparticles, Dy2O3 nanoparticles have the largest magnetic moments at room temperature. Using these properties of Gd(3+) and Dy(3+) and their oxide nanoparticles, ultrasmall mixed gadolinium-dysprosium oxide (GDO) nanoparticles were synthesized and their potential to act as a dual-mode T1 and T2 MRI contrast agent was investigated in vitro and in vivo. The D-glucuronic acid coated GDO nanoparticles (davg = 1.0 nm) showed large r1 and r2 values (r2/r1 ≈ 6.6) and as a result clear dose-dependent contrast enhancements in R1 and R2 map images. Finally, the dual-mode imaging capability of the nanoparticles was confirmed by obtaining in vivo T1 and T2 MR images. PMID:26291827

  9. Poly(acrylic acid) Bridged Gadolinium Metal-Organic Framework-Gold Nanoparticle Composites as Contrast Agents for Computed Tomography and Magnetic Resonance Bimodal Imaging.

    PubMed

    Tian, Chixia; Zhu, Liping; Lin, Feng; Boyes, Stephen G

    2015-08-19

    Imaging contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT) have received significant attention in the development of techniques for early stage cancer diagnosis. Gadolinium (Gd)(III), which has seven unpaired electrons and a large magnetic moment, can dramatically influence the water proton relaxation and hence exhibits excellent MRI contrast. On the other hand, gold (Au), which has a high atomic number and high X-ray attenuation coefficient, is an ideal contrast agent candidate for X-ray-based CT imaging. Gd metal-organic framework (MOF) nanoparticles with tunable size, high Gd(III) loading and multivalency can potentially overcome the limitations of clinically utilized Gd chelate contrast agents. In this work, we report for the first time the integration of GdMOF nanoparticles with gold nanoparticles (AuNPs) for the preparation of a MRI/CT bimodal imaging agent. Highly stable hybrid GdMOF/AuNPs composites have been prepared by using poly(acrylic acid) as a bridge between the GdMOF nanoparticles and AuNPs. The hybrid nanocomposites were then evaluated in MRI and CT imaging. The results revealed high longitudinal relaxivity in MRI and excellent CT imaging performance. Therefore, these GdMOF/AuNPs hybrid nanocomposites potentially provide a new platform for the development of multimodal imaging probes.

  10. Gadolinium and nephrogenic systemic fibrosis: an update.

    PubMed

    Weller, Alex; Barber, Joy L; Olsen, Oystein E

    2014-10-01

    Nephrogenic systemic fibrosis (NSF) is a multisystem disease seen exclusively in patients with renal impairment. It can be severely debilitating and sometimes fatal. There is a strong association with gadolinium-based contrast agents used in magnetic resonance imaging (MRI). Risk factors include renal impairment and proinflammatory conditions, e.g. major surgery and vascular events. Although there is no single effective treatment for NSF, the most successful outcomes are seen following restoration of renal function, either following recovery from acute kidney injury or following renal transplantation. There have been ten biopsy-proved pediatric cases of NSF, with no convincing evidence that children have a significantly altered risk compared with the adult population. After implementation of guidelines restricting the use of gadolinium-based contrast agents in at-risk patients, there has been a sharp reduction in new cases and no new reports in children. Continued vigilance is recommended: screening for renal impairment, use of more stable gadolinium chelates, consideration of non-contrast-enhanced MRI or alternative imaging modalities where appropriate.

  11. Gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid conjugate of arabinogalactan as a potential liver-targeting magnetic resonance imaging contrast agent.

    PubMed

    Xiao, Yan; Xue, Rong; You, Tianyan; Li, Xiaojing; Pei, Fengkui; Wang, Xuxia; Lei, Hao

    2014-08-18

    A novel biocompatible macromolecule (AG-CM-EDA-DOTA-Gd) was synthesized as a liver magnetic resonance imaging (MRI) contrast agent. AG-CM-EDA-DOTA-Gd consisted of a carboxymethyl-arabinogalactan unit conjugated with gadolinium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (Gd-DOTA) via ethylenediamine, and was specifically designed to bind to hepatocyte asialoglycoprotein in vivo, in an effort to develop a potential new tool for the diagnosis of liver diseases. The T1-relaxivity (8.87mmol(-1)Ls(-1)) of AG-CM-EDA-DOTA-Gd was 1.86 times than that of Gd-DOTA (4.76mmol(-1)Ls(-1)) in D2O at 9.4 T and 25°C. MRI experiments showed significant enhancement in rat liver following the intravenous administration of AG-CM-EDA-DOTA-Gd (0.094mmol Gd(3+)/kg body weight), which persisted for longer than Gd-DOTA (0.098mmol Gd(3+)/kg body weight). The mean percentage enhancements in the liver parenchyma were 85.2±6.5% and 19.3±3.3% for AG-CM-EDA-DOTA-Gd and Gd-DOTA, respectively. The results of this study therefore indicate that AG-CM-EDA-DOTA-Gd could be used as a potential liver-targeting contrast agent for MRI.

  12. Adenosine Stress and Rest T1 Mapping Can Differentiate Between Ischemic, Infarcted, Remote, and Normal Myocardium Without the Need for Gadolinium Contrast Agents

    PubMed Central

    Liu, Alexander; Wijesurendra, Rohan S.; Francis, Jane M.; Robson, Matthew D.; Neubauer, Stefan; Piechnik, Stefan K.; Ferreira, Vanessa M.

    2016-01-01

    Objectives The aim of this study was to evaluate the potential of T1 mapping at rest and during adenosine stress as a novel method for ischemia detection without the use of gadolinium contrast. Background In chronic coronary artery disease (CAD), accurate detection of ischemia is important because targeted revascularization improves clinical outcomes. Myocardial blood volume (MBV) may be a more comprehensive marker of ischemia than myocardial blood flow. T1 mapping using cardiac magnetic resonance (CMR) is highly sensitive to changes in myocardial water content, including MBV. We propose that T1 mapping at rest and during adenosine vasodilatory stress can detect MBV changes in normal and diseased myocardium in CAD. Methods Twenty normal controls (10 at 1.5-T; 10 at 3.0-T) and 10 CAD patients (1.5-T) underwent conventional CMR to assess for left ventricular function (cine), infarction (late gadolinium enhancement [LGE]) and ischemia (myocardial perfusion reserve index [MPRI] on first-pass perfusion imaging during adenosine stress). These were compared to novel pre-contrast stress/rest T1 mapping using the Shortened Modified Look-Locker Inversion recovery technique, which is heart rate independent. T1 values were derived for normal myocardium in controls and for infarcted, ischemic, and remote myocardium in CAD patients. Results Normal myocardium in controls (normal wall motion, MPRI, no LGE) showed normal resting T1 (954 ± 19 ms at 1.5-T; 1,189 ± 34 ms at 3.0-T) and significant positive T1 reactivity during adenosine stress compared to baseline (6.2 ± 0.5% at 1.5-T; 6.3 ± 1.1% at 3.0-T; all p < 0.0001). Infarcted myocardium showed the highest resting T1 of all tissue classes (1,442 ± 84 ms), without significant T1 reactivity (0.2 ± 1.5%). Ischemic myocardium showed elevated resting T1 compared to normal (987 ± 17 ms; p < 0.001) without significant T1 reactivity (0.2 ± 0.8%). Remote myocardium, although having comparable resting T1 to normal (955 ± 17 ms

  13. A Theranostic Agent Combining a Two-Photon-Absorbing Photosensitizer for Photodynamic Therapy and a Gadolinium(III) Complex for MRI Detection.

    PubMed

    Schmitt, Julie; Heitz, Valérie; Sour, Angélique; Bolze, Frédéric; Kessler, Pascal; Flamigni, Lucia; Ventura, Barbara; Bonnet, Célia S; Tóth, Éva

    2016-02-18

    The convergent synthesis and characterization of a potential theranostic agent, [DPP-ZnP-GdDOTA](-), which combines a diketopyrrolopyrrole-porphyrin component DPP-ZnP as a two-photon photosensitizer for photodynamic therapy (PDT) with a gadolinium(III) DOTA complex as a magnetic resonance imaging probe, is presented. [DPP-ZnP-GdDOTA](-) has a remarkably high longitudinal water proton relaxivity (19.94 mm(-1)  s(-1) at 20 MHz and 25 °C) for a monohydrated molecular system of this size. The Nuclear Magnetic Relaxation Dispersion (NMRD) profile is characteristic of slow rotation, related to the extended and rigid aromatic units integrated in the molecule and to self-aggregation occurring in aqueous solution. The two-photon properties were examined and large two-photon absorption cross-sections around 1000 GM were determined between 910 and 940 nm in DCM with 1 % pyridine and in DMSO. Furthermore, the new conjugate was able to generate singlet oxygen, with quantum yield of 0.42 and 0.68 in DCM with 1 % pyridine and DMSO, respectively. Cellular studies were also performed. The [DPP-ZnP-GdDOTA](-) conjugate demonstrated low dark toxicity and was able to induce high one-photon and moderate two-photon phototoxicity on cancer cells.

  14. Toward single-walled carbon nanotube–gadolinium complex as advanced MRI contrast agents: pharmacodynamics and global genomic response in small animals

    PubMed Central

    Avti, Pramod K.; Talukdar, Yahfi; Sirotkin, Matvey V.; Shroyer, Kenneth R.; Sitharaman, Balaji

    2013-01-01

    Gadolinium nanoparticle-catalyzed single-walled carbon nanotubes (Gd-SWCNTs) have recently shown potential in vitro as high-performance T1 magnetic resonance imaging (MRI) contrast agents (CAs). Their preclinical safety assessment at nontoxic dosages is essential for MRI applications. Herein, the in vivo (in rats) pharmacodynamics of Gd-SWCNTs (water solubilized with the amphiphilic polymer PEG-DSPE) at the organ, tissue, molecular, and genetic level is reported. Gd-SWCNT, commercially available iron catalyzed SWCNTs (Fe-SWCNTs, control 1) and PEG-DSPE (control 2) solutions were intravenously injected at a potential nontoxic therapeutic dose (0.5 mg/kg body weight, single bolus). Post-injection, bright-field optical microscopy showed their macroscale distribution in lung, liver, kidney, brain, and spleen up to 5 days. Raman and transmission electron microscopy (TEM) showed their presence at the nanoscale within hepatocytes. Their effects on the host organ tissue, molecular, and genetic level were analyzed after 1, 5, 10, 20, and 30 days by histology, biomolecular [lipid peroxidation, plasma tumor necrosis factor TNF-α assay, microarrays] assays. The results indicate that Gd-SWCNTs neither cause any inflammation, nor damage to the above organs, nor any significant change in the lipid peroxidation or plasma proinflammatory cytokine (TNF-α) levels for all the groups at all time points. Global gene expression profile of liver (main organ for the metabolism) after day 1 treatment with Gd-SWCNTs shows that the gene regulation is directed toward maintaining normal homeostasis. The results taken together indicate that PEG-DSPE water-solubilized Gd-SWCNTs at potentially nontoxic dosages have pharmacodynamics similar to other commercially available Fe-SWCNTs and are suitable for future preclinical development as in vivo MRI CAs. PMID:23559429

  15. Approaching the Kinetic Inertness of Macrocyclic Gadolinium(III)-Based MRI Contrast Agents with Highly Rigid Open-Chain Derivatives.

    PubMed

    Tircsó, Gyula; Regueiro-Figueroa, Martín; Nagy, Viktória; Garda, Zoltán; Garai, Tamás; Kálmán, Ferenc Krisztián; Esteban-Gómez, David; Tóth, Éva; Platas-Iglesias, Carlos

    2016-01-18

    A highly rigid open-chain octadentate ligand (H4 cddadpa) containing a diaminocylohexane unit to replace the ethylenediamine bridge of 6,6'-[(ethane-1,2 diylbis{(carboxymethyl)azanediyl})bis(methylene)]dipicolinic acid (H4 octapa) was synthesized. This structural modification improves the thermodynamic stability of the Gd(3+) complex slightly (log KGdL =20.68 vs. 20.23 for [Gd(octapa)](-) ) while other MRI-relevant parameters remain unaffected (one coordinated water molecule; relaxivity r1 =5.73 mm(-1)  s(-1) at 20 MHz and 295 K). Kinetic inertness is improved by the rigidifying effect of the diaminocylohexane unit in the ligand skeleton (half-life of dissociation for physiological conditions is 6 orders of magnitude higher for [Gd(cddadpa)](-) (t1/2 =1.49×10(5)  h) than for [Gd(octapa)](-) . The kinetic inertness of this novel chelate is superior by 2-3 orders of magnitude compared to non-macrocyclic MRI contrast agents approved for clinical use. PMID:26583317

  16. Four-dimensional MR microscopy of the mouse heart using radial acquisition and liposomal gadolinium contrast agent

    PubMed Central

    Bucholz, Elizabeth; Ghaghada, Ketan; Qi, Yi; Mukundan, Srinivasan; Johnson, G. Allan

    2009-01-01

    Magnetic resonance (MR) microscopy has become an important tool for small animal cardiac imaging. In relation to competing technologies (microCT and ultrasound), MR is limited by spatial resolution, temporal resolution, and acquisition time. All three of these limitations have been addressed by developing a 4D (3D plus time) radial acquisition sequence. The signal-to-noise has been optimized by minimizing the echo time (300 μs). The temporal resolution and throughput have been improved by center-out trajectories resulting in TR < 2.5 ms. The contrast has been enhanced through the use of a liposomal blood pool agent that reduces T1 of the blood to < 400 ms. We have developed protocols for three specific applications: a) high-throughput with spatial resolution of 87×87×352 μm3 (voxel volume=2.7 nL) and acquisition time of 16 minutes; b) high-temporal resolution with spatial resolution of 87×87×352 μm3 (voxel volume=2.7 nL); temporal resolution at 4.8 ms and acquisition time of 32 minutes; and c) high-resolution isotropic imaging at 87×87×87 μm3 (voxel volume=0.68 nL), and acquisition time of 31 minutes. The 4D image arrays allow direct measure of cardiac functional parameters dependent on chamber volumes, e.g. ejection fraction, end diastolic volume, and end systolic volume. PMID:18581419

  17. GADOLINIUM SOLUBILITY AND VOLATILITY DURING DWPF PROCESSING

    SciTech Connect

    Reboul, S

    2008-01-30

    Understanding of gadolinium behavior, as it relates to potential neutron poisoning applications at the DWPF, has increased over the past several years as process specific data have been generated. Of primary importance are phenomena related to gadolinium solubility and volatility, which introduce the potential for gadolinium to be separated from fissile materials during Chemical Process Cell (CPC) and Melter operations. Existing data indicate that gadolinium solubilities under moderately low pH conditions can vary over several orders of magnitude, depending on the quantities of other constituents that are present. With respect to sludge batching processes, the gadolinium solubility appears to be highly affected by iron. In cases where the mass ratio of Fe:Gd is 300 or more, the gadolinium solubility has been observed to be low, one milligram per liter or less. In contrast, when the ratio of Fe:Gd is 20 or less, the gadolinium solubility has been found to be relatively high, several thousands of milligrams per liter. For gadolinium to serve as an effective neutron poison in CPC operations, the solubility needs to be limited to approximately 100 mg/L. Unfortunately, the Fe:Gd ratio that corresponds to this solubility limit has not been identified. Existing data suggest gadolinium and plutonium are not volatile during melter operations. However, the data are subject to inherent uncertainties preventing definitive conclusions on this matter. In order to determine if gadolinium offers a practical means of poisoning waste in DWPF operations, generation of additional data is recommended. This includes: Gd solubility testing under conditions where the Fe:Gd ratio varies from 50 to 150; and Gd and Pu volatility studies tailored to quantifying high temperature partitioning. Additional tests focusing on crystal aging of Gd/Pu precipitates should be pursued if receipt of gadolinium-poisoned waste into the Tank Farm becomes routine.

  18. Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy (abstract)

    NASA Astrophysics Data System (ADS)

    Lee, Dongkyu; Maeng, Inhee; Oh, Seung Jae; Kim, Taekhoon; Cho, Byung Kyu; Lee, Kwangyeol; Son, Joo-Hiuk

    2009-04-01

    The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRI technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd2O3) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.

  19. Characteristics of Gadolinium Oxide Nanoparticles Using Terahertz Spectroscopy

    SciTech Connect

    Lee, Dongkyu; Maeng, Inhee; Son, Joo-Hiuk; Oh, Seung Jae; Kim, Taekhoon; Cho, Byung Kyu; Lee, Kwangyeol

    2009-04-19

    The penetration property of the terahertz electromagnetic (THz) wave is relevant to its use. We used the THz wave spectroscopy system which easily penetrates some materials that do not contain water, e.g., plastic and ceramics. The system has been developed for several purposes, including measuring the properties of semiconductors and bio-materials, and detecting plastic bombs and ceramic knives at airports. It is also used for medical imaging systems, such as magnetic resonance imaging (MRI), at some research institutes. It can show not only the difference in amplitude, but also the difference of the phase of each point of sample. MRI technology usually uses contrast agents to enhance the quality of the image. Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), made with a heavy metal ion, is commonly used as a clinical MRI contrast agent. Gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticle is a new contrast agent. It serves to equip the core of each particle with antibodies or ligands. It can freely circulate in blood vessels without amassing in the liver or lungs. This study shows the characteristics of gadolinium oxide nanoparticles to further advance terahertz medical imaging.

  20. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 28 Judicial Administration 2 2013-07-01 2013-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  1. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 28 Judicial Administration 2 2014-07-01 2014-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  2. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 28 Judicial Administration 2 2012-07-01 2012-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  3. 28 CFR 552.25 - Use of less-than-lethal weapons, including chemical agents.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 28 Judicial Administration 2 2011-07-01 2011-07-01 false Use of less-than-lethal weapons... Use of less-than-lethal weapons, including chemical agents. (a) The Warden may authorize the use of less-than-lethal weapons, including those containing chemical agents, only when the situation is...

  4. Effects of Gadolinium-Based Contrast Agents on Thyroid Hormone Receptor Action and Thyroid Hormone-Induced Cerebellar Purkinje Cell Morphogenesis

    PubMed Central

    Ariyani, Winda; Iwasaki, Toshiharu; Miyazaki, Wataru; Khongorzul, Erdene; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito; Koibuchi, Noriyuki

    2016-01-01

    Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical for the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and TH-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells. By contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10−8 to 10−6M) augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10−5 to 10−4M), with decreased β-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in β-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10−9M T4 was augmented by low-dose Gd-DTPA-BMA (10−7M) but was suppressed by higher dose (10−5M). Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10−9M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10−5M) as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization was much weaker

  5. Effects of Gadolinium-Based Contrast Agents on Thyroid Hormone Receptor Action and Thyroid Hormone-Induced Cerebellar Purkinje Cell Morphogenesis

    PubMed Central

    Ariyani, Winda; Iwasaki, Toshiharu; Miyazaki, Wataru; Khongorzul, Erdene; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito; Koibuchi, Noriyuki

    2016-01-01

    Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical for the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and TH-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells. By contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10−8 to 10−6M) augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10−5 to 10−4M), with decreased β-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in β-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10−9M T4 was augmented by low-dose Gd-DTPA-BMA (10−7M) but was suppressed by higher dose (10−5M). Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10−9M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10−5M) as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization was much weaker

  6. Effects of Gadolinium-Based Contrast Agents on Thyroid Hormone Receptor Action and Thyroid Hormone-Induced Cerebellar Purkinje Cell Morphogenesis.

    PubMed

    Ariyani, Winda; Iwasaki, Toshiharu; Miyazaki, Wataru; Khongorzul, Erdene; Nakajima, Takahito; Kameo, Satomi; Koyama, Hiroshi; Tsushima, Yoshito; Koibuchi, Noriyuki

    2016-01-01

    Gadolinium (Gd)-based contrast agents (GBCAs) are used in diagnostic imaging to enhance the quality of magnetic resonance imaging or angiography. After intravenous injection, GBCAs can accumulate in the brain. Thyroid hormones (THs) are critical for the development and functional maintenance of the central nervous system. TH actions in brain are mainly exerted through nuclear TH receptors (TRs). We examined the effects of GBCAs on TR-mediated transcription in CV-1 cells using transient transfection-based reporter assay and TH-mediated cerebellar Purkinje cell morphogenesis in primary culture. We also measured the cellular accumulation and viability of Gd after representative GBCA treatments in cultured CV-1 cells. Both linear (Gd-diethylene triamine pentaacetic acid-bis methyl acid, Gd-DTPA-BMA) and macrocyclic (Gd-tetraazacyclododecane tetraacetic acid, Gd-DOTA) GBCAs were accumulated without inducing cell death in CV-1 cells. By contrast, Gd chloride (GdCl3) treatment induced approximately 100 times higher Gd accumulation and significantly reduced the number of cells. Low doses of Gd-DTPA-BMA (10(-8) to 10(-6)M) augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10(-5) to 10(-4)M), with decreased β-galactosidase activity indicating cellular toxicity. TR-mediated transcription was not altered by Gd-DOTA or GdCl3, but the latter induced a significant reduction in β-galactosidase activity at high doses, indicating cellular toxicity. In cerebellar cultures, the dendrite arborization of Purkinje cells induced by 10(-9)M T4 was augmented by low-dose Gd-DTPA-BMA (10(-7)M) but was suppressed by higher dose (10(-5)M). Such augmentation by low-dose Gd-DTPA-BMA was not observed with 10(-9)M T3, probably because of the greater dendrite arborization by T3; however, the arborization by T3 was suppressed by a higher dose of Gd-DTPA-BMA (10(-5)M) as seen in T4 treatment. The effect of Gd-DOTA on dendrite arborization was much weaker

  7. Emerging concepts for myocardial late gadolinium enhancement MRI.

    PubMed

    Doltra, Adelina; Amundsen, Brage Hoyem; Gebker, Rolf; Fleck, Eckart; Kelle, Sebastian

    2013-08-01

    Late gadolinium enhancement is a useful tool for scar detection, based on differences in the volume of distribution of gadolinium, an extracellular agent. The presence of fibrosis in the myocardium amenable to be detected with late gadolinium enhancement MRI is found not only in ischemic cardiomyopathy, in which it offers information regarding viability and prognosis, but also in a wide variety of non-ischemic cardiomyopathies. In the following review we will discuss the methodological aspects of gadolinium-based imaging, as well as its applications and anticipated future developments.

  8. Toxicity of Gadolinium to Some Aquatic Microbes

    SciTech Connect

    Wilde, E.W.

    2001-01-24

    The toxicity of gadolinium to algae and bacteria was determined as part of an effort to develop a biological process to purify drums containing spent nuclear reactor heavy water moderator (D2O). This water was contaminated with high concentrations of gadolinium nitrate, a chemical used as a neutron poison during former nuclear reactor operations at the Savannah River Site (SRS) near Aiken, SC. Nuclear reactors were operated for approximately 30 years at the SRS to produce nuclear weapons materials for national defense. Throughout this period, a heavy water solution of gadolinium nitrate was utilized in a standby emergency shutdown system that could inject this chemical into the reactor moderator coolant water. The chemical was used for this purpose because the high neutron absorption cross sections of some gadolinium isotopes make gadolinium salts such as GdNO3 effective in controlling nuclear activity in aqueous systems (Gilbert et al. 1985; Rodenas et al. 1990). The use of this practice resulted in a large inventory of this degraded heavy water containing gadolinium nitrate. Microbiological and chemical studies were initiated to evaluate the potential use of bacteria and algae for water purification of the drums. Since metals are often toxic to microbes when present at concentrations substantially higher than natural environmental levels, it was hypothesized that Gd may be toxic to selected microorganisms (algae and bacteria) at the very high concentrations (average 80,000 mg/L, maximum 259,000 mg/L) present in most of the drums. Two principal components of the study included: (1) chemical and microbiological characterization of representative drums, and (2) an evaluation of the toxicity of gadolinium to selected species of algae. In addition to wastewater from nuclear production reactor operations, gadolinium waste is also generated from medical applications, especially MRI, and various electronic components including CD disks. Despite growing and widespread

  9. Signal Increase on Unenhanced T1-Weighted Images in the Rat Brain After Repeated, Extended Doses of Gadolinium-Based Contrast Agents

    PubMed Central

    Jost, Gregor; Lenhard, Diana Constanze; Sieber, Martin Andrew; Lohrke, Jessica; Frenzel, Thomas; Pietsch, Hubertus

    2016-01-01

    Objectives In this prospective preclinical study, we evaluated T1-weighted signal intensity in the deep cerebellar nuclei (CN) and globus pallidus (GP) up to 24 days after repeated administration of linear and macrocyclic gadolinium-based contrast agents (GBCAs) using homologous imaging and evaluation methods as in the recently published retrospective clinical studies. In a second part of the study, cerebrospinal fluid (CSF) spaces were evaluated for contrast enhancement by fluid-attenuated magnetic resonance imaging (MRI). Materials and Methods Sixty adult male Wistar-Han rats were randomly divided into a control and 5 GBCA groups (n = 10 per group). The administered GBCAs were gadodiamide, gadopentetate dimeglumine, and gadobenate dimeglumine (linear GBCAs) as well as gadobutrol and gadoterate meglumine (macrocyclic GBCAs) and saline (control). Over a period of 2 weeks, the animals received 10 intravenous injections at a dose of 2.5 mmol Gd/kg body weight, each on 5 consecutive days per week. Before GBCA administration, as well as 3 and 24 days after the last injection, a whole-brain MRI was performed using a standard T1-weighted 3-dimensional turbo spin echo sequence on a clinical 1.5 T scanner. The ratios of signal intensities in deep CN to pons (CN/Po) and GP to thalamus (GP/Th) were determined. For the evaluation of the CSF spaces, 18 additional rats were randomly divided into 6 groups (n = 3 per group) that received the same GBCAs as in the first part of the study. After MR cisternography for anatomical reference, a fluid-attenuated inversion recovery sequence was performed before and 1 minute after intravenous injection of a dose of 1 mmol Gd/kg body weight GBCA or saline. Results A significantly increased signal intensity ratio of CN/Po was observed 3 and 24 days after the last injection of gadodiamide and gadobenate dimeglumine. No significant changes were observed between the 2 time points. Gadopentetate dimeglumine injection led to a moderately elevated

  10. Mass spectrometry in identification of ecotoxicants including chemical and biological warfare agents.

    PubMed

    Lebedev, Albert T

    2005-09-01

    Mass spectrometry is a unique tool to detect and identify trace levels of organic and bioorganic compounds as well as microorganisms in the environment. The range of potential chemical warfare (CW) and biological warfare (BW) agents is very broad. An important advantage of mass spectrometry over other techniques involves potential for full spectrum detection of chemical and biological agents including mid-spectrum materials (i.e. bioactive peptides, toxins, etc.) for which biological approaches are inadequate. Being very fast (seconds and minutes), extremely sensitive (zeptomoles 10(-21)), and informative (detailed qualitative and quantitative composition of mixtures containing hundreds of chemicals), mass spectrometry is a principal analytical tool at the sites of destruction of CW. Due to its unique features, mass spectrometry is applied not only for the detection of CW agents, but for the analysis of products of metabolism and degradation of these agents in organisms or environment as well. The present paper deals with some examples of successful application of mass spectrometry for the analyses of ecotoxicants, chemical warfare agents, explosives, and microorganisms including biology warfare agents.

  11. Mass spectrometry in identification of ecotoxicants including chemical and biological warfare agents

    SciTech Connect

    Lebedev, Albert T. . E-mail: lebedev@org.chem.msu.ru

    2005-09-01

    Mass spectrometry is a unique tool to detect and identify trace levels of organic and bioorganic compounds as well as microorganisms in the environment. The range of potential chemical warfare (CW) and biological warfare (BW) agents is very broad. An important advantage of mass spectrometry over other techniques involves potential for full spectrum detection of chemical and biological agents including mid-spectrum materials (i.e. bioactive peptides, toxins, etc.) for which biological approaches are inadequate. Being very fast (seconds and minutes), extremely sensitive (zeptomoles 10{sup -21}), and informative (detailed qualitative and quantitative composition of mixtures containing hundreds of chemicals), mass spectrometry is a principal analytical tool at the sites of destruction of CW. Due to its unique features, mass spectrometry is applied not only for the detection of CW agents, but for the analysis of products of metabolism and degradation of these agents in organisms or environment as well. The present paper deals with some examples of successful application of mass spectrometry for the analyses of ecotoxicants, chemical warfare agents, explosives, and microorganisms including biology warfare agents.

  12. Gadolinium photoionization process

    DOEpatents

    Paisner, J.A.; Comaskey, B.J.; Haynam, C.A.; Eggert, J.H.

    1993-04-13

    A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

  13. Gadolinium photoionization process

    DOEpatents

    Paisner, Jeffrey A.; Comaskey, Brian J.; Haynam, Christopher A.; Eggert, Jon H.

    1993-01-01

    A method is provided for selective photoionization of the odd-numbered atomic mass gadolinium isotopes 155 and 157. The selective photoionization is accomplished by circular or linear parallel polarized laser beam energy effecting a three-step photoionization pathway.

  14. Is the Transport of a Gadolinium-Based Contrast Agent Decreased in a Degenerated or Aged Disc? A Post Contrast MRI Study

    PubMed Central

    Tibiletti, Marta; Galbusera, Fabio; Ciavarro, Cristina; Brayda-Bruno, Marco

    2013-01-01

    A post contrast magnetic resonance imaging study has been performed in a wide population of low back pain patients to investigate which radiological and phenotypic characteristics influence the penetration of the contrast agent in lumbar discs in vivo. 37 patients affected by different pathologies (disc herniation, spondylolisthesis, foraminal stenosis, central canal stenosis) were enrolled in the study. The selected population included 26 male and 11 female subjects, with a mean age of 42.4±9.3 years (range 18–60). Magnetic resonance images of the lumbar spine were obtained with a 1.5 T scanner (Avanto, Siemens, Erlangen, Germany) with a phased-array back coil. A paramagnetic non–ionic contrast agent was injected with a dose of 0.4 ml/kg. T1-weighted magnetic resonance images were subsequently acquired at 5 time points, 5 and 10 minutes, 2, 4 and 6 hours after injection. Endplates presented clear enhancement already 5 minutes after injection, and showed an increase in the next 2 hours followed by a decrease. At 5 and 10 minutes, virtually no contrast medium was present inside the intervertebral disc; afterwards, enhancement significantly increased. Highly degenerated discs showed higher enhancement in comparison with low and medium degenerated discs. Discs classified as Pfirrmann 5 showed a statistically significant higher enhancement than Pfirrmann 1, 2 and 3 at all time points but the first one, possibly due to vascularization. Disc height collapse and Modic changes significantly increased enhancement. Presence of endplate defects did not show any significant influence on post contrast enhancement, but the lack of a clear classification of endplate defects as seen on magnetic resonance scans may be shadowing some effects. In conclusion, disc height, high level of degeneration and presence of Modic changes are factors which increase post contrast enhancement in the intervertebral disc. The effect of age could not be demonstrated. PMID:24146913

  15. Gain of a 500-fold sensitivity on an intravital MR Contrast Agent based on an endohedral Gadolinium-Cluster-Fullerene-Conjugate: A new chance in cancer diagnostics

    PubMed Central

    Braun, Klaus; Dunsch, Lothar; Pipkorn, Ruediger; Bock, Michael; Baeuerle, Tobias; Yang, Shangfeng; Waldeck, Waldemar; Wiessler, Manfred

    2010-01-01

    Among the applications of fullerene technology in health sciences the expanding field of magnetic resonance imaging (MRI) of molecular processes is most challenging. Here we present the synthesis and application of a GdxSc3-xN@C80-BioShuttle-conjugate referred to as Gd-cluster@-BioShuttle, which features high proton relaxation and, in comparison to the commonly used contrast agents, high signal enhancement at very low Gd concentrations. This modularly designed contrast agent represents a new tool for improved monitoring and evaluation of interventions at the gene transcription level. Also, a widespread monitoring to track individual cells is possible, as well as sensing of microenvironments. Furthermore, BioShuttle can also deliver constructs for transfection or active pharmaceutical ingredients, and scaffolding for incorporation with the host's body. Using the Gd-cluster@-BioShuttle as MRI contrast agent allows an improved evaluation of radio- or chemotherapy treated tissues. PMID:20567614

  16. Histological validation of iron-oxide and gadolinium based MRI contrast agents in experimental atherosclerosis: the do's and don't's.

    PubMed

    den Adel, Brigit; Bovens, Sandra M; te Boekhorst, Bernard; Strijkers, Gustav J; Poelmann, Robert E; van der Weerd, Louise; Pasterkamp, Gerard

    2012-12-01

    MRI using targeted contrast agents (CA) has emerged as a promising technique to study atherothrombotic disease in vivo. Particularly, the use of targeted Gd and lipid-based nanoparticles has enabled detailed in vivo imaging of various molecular markers of atherosclerotic plaque pathophysiology. For validation purposes, it is crucial that nanoparticle accumulation in the plaque, cellular association and localization can be assessed by ex vivo immuno-histology or fluorescence microscopy of tissue sections. In this review we discuss the various methods that are available for histological evaluation of targeted MRI contrast agents such as lipid-based nanoparticles and iron oxide particles. We discuss the detection of these contrast agents in paraffin-embedded and in cryopreserved tissue sections of atherosclerotic plaques. During the embedding procedure in paraffin, most components of targeted lipid-based nanoparticles are generally washed out, though the actual targeting moieties may be retained in the embedded sections. Therefore staining of the antibody-antigen complex provides a suitable way to visualize the presence of the nanoparticle in the plaque. In cryosections, the localization of nanoparticles can be assessed directly by measuring the fluorescence of an incorporated fluorophore or by secondary stainings of the Gd-containing DTPA lipids or the iron oxide particles. With certain secondary stainings, be it for the contrast agent or for co-localization with the target, the contrast agent itself may interfere with standard histological protocols, yielding false positive results. The here presented techniques enable proper visualization of MR contrast agent accumulation and localization in atherosclerotic plaque, which will provide the validation necessary to advance these lipid-based nanoparticles to the clinic.

  17. Genome Sequencing of Four Strains of Rickettsia prowazekii, the Causative Agent of Epidemic Typhus, Including One Flying Squirrel Isolate.

    PubMed

    Bishop-Lilly, Kimberly A; Ge, Hong; Butani, Amy; Osborne, Brian; Verratti, Kathleen; Mokashi, Vishwesh; Nagarajan, Niranjan; Pop, Mihai; Read, Timothy D; Richards, Allen L

    2013-01-01

    Rickettsia prowazekii is a notable intracellular pathogen, the agent of epidemic typhus, and a potential biothreat agent. We present here whole-genome sequence data for four strains of R. prowazekii, including one from a flying squirrel. PMID:23814035

  18. Novel sorbents for removal of gadolinium-based contrast agents in sorbent dialysis and hemoperfusion: preventive approaches to nephrogenic systemic fibrosis

    SciTech Connect

    Yantasee, Wassana; Fryxell, Glen E.; Porter, George A.; Pattamakomsan, Kanda; Sukwarotwat, Vichaya; Chouyyok, Wilaiwan; Koonsiripaiboon, View; Xu, Jide; Raymond, Kenneth N.

    2010-02-01

    Gd based contrast agents in many forms of organocomplex have recently been linked to a debilitating and a potentially fatal skin disease called Nephrogenic Systemic Fibrosis (NSF) in patients with renal failures. Free Gd released from the complexes by transmetallation is believed to be the most important trigger for NSF. Removal of Gd complex from the patients immediately after the contrast study would prevent the dissociation of Gd and should eliminate NSF as a complication. Although removal of Gd based contrast agents may be accomplished with conventional hemodialysis, it requires three hemodialysis sessions at 3 hours each to remove 98% of the contrast agents. In this work, mesoporous silica material that are functionalized with 1-hydroxy-2-pyridinone (1,2-HOPO-SAMMS®) has been evaluated for effective removal of both free and chelated Gd (Magnevist, a brand of gadopentetate dimeglumine) from the dialysate and sodium chloride solution. The material has high affinity, rapid removal rate, and large sorption capacity for both free and chelated Gd, the properties that are far superior to those of activated carbon and zirconium phosphate currently used in the state-of-the-art sorbent dialysis systems. 99% of both free and chelated Gd would be removed in a single pass thru the sorbent bed of 1,2-HOPO-SAMMS®. The sorbent provides an effective and predicable strategy for removing Gd from patients with impaired renal function, thus it would allow for the continued use of contrast MRI while removing the risk of NSF and would represent a safe alternative to traditional contrast studies in the patient population.

  19. Advancing pharmacovigilance through academic–legal collaboration: the case of gadolinium-based contrast agents and nephrogenic systemic fibrosis—a research on adverse drug events and reports (RADAR) report

    PubMed Central

    Edwards, B J; Laumann, A E; Nardone, B; Miller, F H; Restaino, J; Raisch, D W; McKoy, J M; Hammel, J A; Bhatt, K; Bauer, K; Samaras, A T; Fisher, M J; Bull, C; Saddleton, E; Belknap, S M; Thomsen, H S; Kanal, E; Cowper, S E; Abu Alfa, A K

    2014-01-01

    Objective: To compare and contrast three databases, that is, The International Centre for Nephrogenic Systemic Fibrosis Registry (ICNSFR), the Food and Drug Administration Adverse Event Reporting System (FAERS) and a legal data set, through pharmacovigilance and to evaluate international nephrogenic systemic fibrosis (NSF) safety efforts. Methods: The Research on Adverse Drug events And Reports methodology was used for assessment—the FAERS (through June 2009), ICNSFR and the legal data set (January 2002 to December 2010). Safety information was obtained from the European Medicines Agency, the Danish Medicine Agency and the Food and Drug Administration. Results: The FAERS encompassed the largest number (n = 1395) of NSF reports. The ICNSFR contained the most complete (n = 335, 100%) histopathological data. A total of 382 individual biopsy-proven, product-specific NSF cases were analysed from the legal data set. 76.2% (291/382) identified exposure to gadodiamide, of which 67.7% (197/291) were unconfounded. Additionally, 40.1% (153/382) of cases involved gadopentetate dimeglumine, of which 48.4% (74/153) were unconfounded, while gadoversetamide was identified in 7.3% (28/382) of which 28.6% (8/28) were unconfounded. Some cases involved gadobenate dimeglumine or gadoteridol, 5.8% (22/382), all of which were confounded. The mean number of exposures to gadolinium-based contrast agents (GBCAs) was gadodiamide (3), gadopentetate dimeglumine (5) and gadoversetamide (2). Of the 279 unconfounded cases, all involved a linear-structured GBCA. 205 (73.5%) were a non-ionic GBCA while 74 (26.5%) were an ionic GBCA. Conclusion: Clinical and legal databases exhibit unique characteristics that prove complementary in safety evaluations. Use of the legal data set allowed the identification of the most commonly implicated GBCA. Advances in knowledge: This article is the first to demonstrate explicitly the utility of a legal data set to pharmacovigilance research. PMID:25230161

  20. SIMS imaging of gadolinium isotopes in tissue from Nephrogenic Systemic Fibrosis patients: Release of free Gd from magnetic resonance imaging (MRI) contrast agents

    NASA Astrophysics Data System (ADS)

    Abraham, Jerrold L.; Chandra, Subhash; Thakral, Charu; Abraham, Joshua M.

    2008-12-01

    Recently, Gd-based magnetic resonance imaging (MRI) contrast agents (GBMCA) have been linked to a new disease, Nephrogenic Systemic Fibrosis (NSF), with skin and systemic toxicity and death in certain patients with renal failure. Due to widespread use of GBMCA in diagnostic MRI, it is essential to study their excretion, metabolism, and target sites in cells and tissues. A CAMECA IMS-3f SIMS ion microscope and scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS) were used for imaging Gd isotopes in relation to calcium distributions in histologic sections of human tissues. SIMS imaging revealed two types of Gd localization in skin biopsies of patients who received GBMCA. The Gd was present in micrometer size deposits in association with calcium, and in detectable amounts in a more diffuse cellular distribution. Only the Gd-containing deposits associated with Ca and P were detectable using SEM/EDS. As only insoluble deposits remain in the biopsy tissues after aqueous and organic solvent processing of the tissue, our observations support release of free Gd from the GBMCA and selective localization of insoluble Gd in the target tissue from patients with NSF. This study opens new novel applications of SIMS for characterization of the safety of GBMCA.

  1. 21 CFR 700.13 - Use of mercury compounds in cosmetics including use as skinbleaching agents in cosmetic...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Use of mercury compounds in cosmetics including...) COSMETICS GENERAL Requirements for Specific Cosmetic Products § 700.13 Use of mercury compounds in cosmetics including use as skinbleaching agents in cosmetic preparations also regarded as drugs. (a)...

  2. Importance of outer-sphere and aggregation phenomena in the relaxation properties of phosphonated gadolinium complexes with potential applications as MRI contrast agents.

    PubMed

    Elhabiri, Mourad; Abada, Sabah; Sy, Mohamadou; Nonat, Aline; Choquet, Philippe; Esteban-Gómez, David; Cassino, Claudio; Platas-Iglesias, Carlos; Botta, Mauro; Charbonnière, Loïc J

    2015-04-20

    A series composed of a tetra-, a tris- and a bisphosphonated ligand based on a pyridine scaffold (L(4) , L(3) and L(2) , respectively) was studied within the frame of lanthanide (Ln) coordination. The stability constants of the complexes formed with lanthanide cations (Ln=La, Nd, Eu, Gd, Tb, Er and Lu) were determined by potentiometry in aqueous solutions (25.0 °C, 0.1 M NaClO4 ), showing that the tetraphosphonated complexes are among the most stable Ln(III) complexes reported in the literature. The complexation of L(4) was further studied by different titration experiments using mass spectrometry and various spectroscopic techniques including UV/Vis absorption, and steady state and time-resolved luminescence (Ln=Eu and Tb). Titration experiments confirmed the formation of highly stable [LnL(4) ] complexes. (31) P NMR experiments of the LuL(4) complex revealed an intramolecular interconversion process which was studied at different temperatures and was rationalized by DFT modelling. The relaxivity properties of the Gd(III) complexes were studied by recording their (1) H NMRD profiles at various temperatures, by temperature dependent (17) O NMR experiments (GdL(4) ) and by pH dependent relaxivity measurements at 0.47 T (GdL(3) and GdL(2) ). In addition to the high relaxivity values observed for all complexes, the results showed an important second-sphere contribution to relaxivity and pH dependent variations associated with the formation of aggregates for GdL(2) and GdL(3) . Finally, intravenous injection of GdL(4) to a mouse was followed by dynamic MRI imaging at 1.5 T, which showed that the complex can be immediately found in the blood stream and rapidly eliminated through the liver and in large part through the kidneys.

  3. Distribution profile of gadolinium in gadolinium chelate-treated renally-impaired rats: role of pharmaceutical formulation.

    PubMed

    Fretellier, Nathalie; Salhi, Mariem; Schroeder, Josef; Siegmund, Heiko; Chevalier, Thibaut; Bruneval, Patrick; Jestin-Mayer, Gaëlle; Delaloge, Francette; Factor, Cécile; Mayer, Jean-François; Fabicki, Jean-Michel; Robic, Caroline; Bonnemain, Bruno; Idée, Jean-Marc; Corot, Claire

    2015-05-25

    While not acutely toxic, chronic hepatic effect of certain gadolinium chelates (GC), used as contrast agent for magnetic resonance imaging, might represent a risk in renally-impaired patients due to free gadolinium accumulation in the liver. To answer this question, this study investigated the consequences of the presence of small amounts of either a soluble gadolinium salt ("free" Gd) or low-stability chelating impurity in the pharmaceutical solution of gadoteric acid, a macrocyclic GC with high thermodynamic and kinetic stabilities, were investigated in renally-impaired rats. Renal failure was induced by adding 0.75% adenine in the diet for three weeks. The pharmaceutical and commercial solution of gadoteric acid was administered (5 daily intravenous injections of 2.5 mmol Gd/kg) either alone or after being spiked with either "free" gadolinium (i.e., 0.04% w/v) or low-stability impurity (i.e., 0.06 w/v). Another GC, gadodiamide (low thermodynamic and kinetic stabilities) was given as its commercial solution at a similar dose. Non-chelated gadolinium was tested at two doses (0.005 and 0.01 mmol Gd/kg) as acetate salt. Gadodiamide induced systemic toxicity (mortality, severe epidermal and dermal lesions) and substantial tissue Gd retention. The addition of very low amounts of "free", non-chelated gadolinium or low thermodynamic stability impurity to the pharmaceutical solution of the thermodynamically stable GC gadoteric acid resulted in substantial capture of metal by the liver, similar to what was observed in "free" gadolinium salt-treated rats. Relaxometry studies strongly suggested the presence of free and soluble gadolinium in the liver. Electron microscopy examinations revealed the presence of free and insoluble gadolinium deposits in hepatocytes and Kupffer cells of rats treated with gadoteric acid solution spiked with low-stability impurity, free gadolinium and gadodiamide, but not in rats treated with the pharmaceutical solution of gadoteric acid. The

  4. Studies of MRI relaxivities of gadolinium-labeled dendrons

    NASA Astrophysics Data System (ADS)

    Pan, Hongmu; Daniel, Marie-Christine

    2011-05-01

    In cancer detection, imaging techniques have a great importance in early diagnosis. The more sensitive the imaging technique and the earlier the tumor can be detected. Contrast agents have the capability to increase the sensitivity in imaging techniques such as magnetic resonance imaging (MRI). Until now, gadolinium-based contrast agents are mainly used for MRI, and show good enhancement. But improvement is needed for detection of smaller tumors at the earliest stage possible. The dendrons complexed with Gd(DOTA) were synthesized and evaluated as a new MRI contrast agent. The longitudinal and transverse relaxation effects were tested and compared with commercial drug Magnevist, Gd(DTPA).

  5. Toxic effects of mercury, lead and gadolinium on vascular reactivity.

    PubMed

    Vassallo, D V; Simões, M R; Furieri, L B; Fioresi, M; Fiorim, J; Almeida, E A S; Angeli, J K; Wiggers, G A; Peçanha, F M; Salaices, M

    2011-09-01

    Heavy metals have been used in a wide variety of human activities that have significantly increased both professional and environmental exposure. Unfortunately, disasters have highlighted the toxic effects of metals on different organs and systems. Over the last 50 years, the adverse effects of chronic lead, mercury and gadolinium exposure have been underscored. Mercury and lead induce hypertension in humans and animals, affecting endothelial function in addition to their other effects. Increased cardiovascular risk after exposure to metals has been reported, but the underlying mechanisms, mainly for short periods of time and at low concentrations, have not been well explored. The presence of other metals such as gadolinium has raised concerns about contrast-induced nephropathy and, interestingly, despite this negative action, gadolinium has not been defined as a toxic agent. The main actions of these metals, demonstrated in animal and human studies, are an increase of free radical production and oxidative stress and stimulation of angiotensin I-converting enzyme activity, among others. Increased vascular reactivity, highlighted in the present review, resulting from these actions might be an important mechanism underlying increased cardiovascular risk. Finally, the results described in this review suggest that mercury, lead and gadolinium, even at low doses or concentrations, affect vascular reactivity. Acting via the endothelium, by continuous exposure followed by their absorption, they can increase the production of free radicals and of angiotensin II, representing a hazard for cardiovascular function. In addition, the actual reference values, considered to pose no risk, need to be reduced.

  6. Tumor-induced lymph node alterations detected by MRI lymphography using gadolinium nanoparticles.

    PubMed

    Partridge, S C; Kurland, B F; Liu, C-L; Ho, R J Y; Ruddell, A

    2015-10-26

    Contrast-enhanced MRI lymphography shows potential to identify alterations in lymph drainage through lymph nodes (LNs) in cancer and other diseases. MRI studies have typically used low molecular weight gadolinium contrast agents, however larger gadolinium-loaded nanoparticles possess characteristics that could improve the specificity and sensitivity of lymphography. The performance of three gadolinium contrast agents with different sizes and properties was compared by 3T MRI after subcutaneous injection. Mice bearing B16-F10 melanoma footpad tumors were imaged to assess tumor-induced alterations in lymph drainage through tumor-draining popliteal and inguinal LNs versus contralateral uninvolved drainage. Gadolinium lipid nanoparticles were able to identify tumor-induced alterations in contrast agent drainage into the popliteal LN, while lower molecular weight or albumin-binding gadolinium agents were less effective. All of the contrast agents distributed in foci around the cortex and medulla of tumor-draining popliteal LNs, while they were restricted to the cortex of non-draining LNs. Surprisingly, second-tier tumor-draining inguinal LNs exhibited reduced uptake, indicating that tumors can also divert LN drainage. These characteristics of tumor-induced lymph drainage could be useful for diagnosis of LN pathology in cancer and other diseases. The preferential uptake of nanoparticle contrasts into tumor-draining LNs could also allow selective targeting of therapies to tumor-draining LNs.

  7. Structural and chemical analysis of gadolinium halides encapsulated within WS2 nanotubes

    NASA Astrophysics Data System (ADS)

    Anumol, E. A.; Enyashin, Andrey N.; Batra, Nitin M.; Costa, Pedro M. F. J.; Deepak, Francis Leonard

    2016-06-01

    The hollow cavities of nanotubes serve as templates for the growth of size- and shape-confined functional nanostructures, giving rise to novel materials and properties. In this work, considering their potential application as MRI contrast agents, gadolinium halides are encapsulated within the hollow cavities of WS2 nanotubes by capillary filling to obtain GdX3@WS2 nanotubes (where X = Cl, Br or I and @ means encapsulated in). Aberration corrected scanning/transmission electron microscopy (S/TEM) and spectroscopy is employed to understand the morphology and composition of the GdI3@WS2 nanotubes. The three dimensional morphology is studied with STEM tomography but understanding the compositional information is non-trivial due to the presence of multiple high atomic number elements. Therefore, energy dispersive X-ray spectroscopy (EDS) tomography was employed revealing the three dimensional chemical composition. Molecular dynamics simulations of the filling procedure shed light into the mechanics behind the formation of the confined gadolinium halide crystals. The quasi-1D system employed here serves as an example of a TEM-based chemical nanotomography method that could be extended to other materials, including beam-sensitive soft materials.The hollow cavities of nanotubes serve as templates for the growth of size- and shape-confined functional nanostructures, giving rise to novel materials and properties. In this work, considering their potential application as MRI contrast agents, gadolinium halides are encapsulated within the hollow cavities of WS2 nanotubes by capillary filling to obtain GdX3@WS2 nanotubes (where X = Cl, Br or I and @ means encapsulated in). Aberration corrected scanning/transmission electron microscopy (S/TEM) and spectroscopy is employed to understand the morphology and composition of the GdI3@WS2 nanotubes. The three dimensional morphology is studied with STEM tomography but understanding the compositional information is non-trivial due to the

  8. Discovery of samarium, europium, gadolinium, and terbium isotopes

    SciTech Connect

    May, E.; Thoennessen, M.

    2013-01-15

    Currently, thirty-four samarium, thirty-four europium, thirty-one gadolinium, and thirty-one terbium isotopes have been observed and the discovery of these isotopes is described here. For each isotope a brief synopsis of the first refereed publication, including the production and identification method, is presented.

  9. Type of MRI contrast, tissue gadolinium, and fibrosis.

    PubMed

    Do, Catherine; Barnes, Jeffrey L; Tan, Chunyan; Wagner, Brent

    2014-10-01

    It has been presupposed that the thermodynamic stability constant (K(therm)) of gadolinium-based MRI chelates relate to the risk of precipitating nephrogenic systemic fibrosis. The present study compared low-K(therm) gadodiamide with high-K(therm) gadoteridol in cultured fibroblasts and rats with uninephrectomies. Gadolinium content was assessed using scanning electron microscopy equipped with energy-dispersive X-ray spectroscopy in paraffin-embedded tissues. In vitro, fibroblasts demonstrated dose-dependent fibronectin generation, transforming growth factor-β production, and expression of activated myofibroblast stress fiber protein α-smooth muscle actin. There were negligible differences with respect to toxicity or proliferation between the two contrast agents. In the rodent model, gadodiamide treatment led to greater skin fibrosis and dermal cellularity than gadoteridol. In the kidney, both contrast agents led to proximal tubule vacuolization and increased fibronectin accumulation. Despite large detectable gadolinium signals in the spleen, skin, muscle, and liver from the gadodiamide-treated group, contrast-induced fibrosis appeared to be limited to the skin and kidney. These findings support the hypothesis that low-K(therm) chelates have a greater propensity to elicit nephrogenic systemic fibrosis and demonstrate that certain tissues are resistant to these effects.

  10. Growth control in colon epithelial cells: gadolinium enhances calcium-mediated growth regulation.

    PubMed

    Attili, Durga; Jenkins, Brian; Aslam, Muhammad Nadeem; Dame, Michael K; Varani, James

    2012-12-01

    Gadolinium, a member of the lanthanoid family of transition metals, interacts with calcium-binding sites on proteins and other biological molecules. The overall goal of the present investigation was to determine if gadolinium could enhance calcium-induced epithelial cell growth inhibition in the colon. Gadolinium at concentrations as low as 1-5 μM combined with calcium inhibits proliferation of human colonic epithelial cells more effectively than calcium alone. Gadolinium had no detectable effect on calcium-induced differentiation in the same cells based on change in cell morphology, induction of E-cadherin synthesis, and translocation of E-cadherin from the cytosol to the cell surface. When the colon epithelial cells were treated with gadolinium and then exposed to increased calcium concentrations, movement of extracellular calcium into the cell was suppressed. In contrast, gadolinium treatment had no effect on ionomycin-induced release of stored intracellular calcium into the cytoplasm. Whether these in vitro observations can be translated into an approach for reducing abnormal proliferation in the colonic mucosa (including polyp formation) is not known. These results do, however, provide an explanation for our recent findings that a multi-mineral supplement containing all of the naturally occurring lanthanoid metals including gadolinium are more effective than calcium alone in preventing colon polyp formation in mice on a high-fat diet.

  11. [Causal relationship between the use of gadolinium based contrast media and nephrogenic systemic fibrosis].

    PubMed

    Varela, Cristian U; Prieto-Rayo, Juan Carlos

    2014-12-01

    Nephrogenic systemic fibrosis (NSF) is a severe iatrogenic disease that affect patients with impaired renal function exposed to gadolinium-based contrast agents. Clinically, symptoms develop within days or weeks after the exposure and mimic a scleromyxedema. The causal relationship between use of gadolinium-based contrast agents and NSF led to develop clinical guidelines aiming to limit the use of this contrast medium in high risk patients. These guidelines decreased the incidence of NSF in the last years. Unfortunately there is no specific treatment for NSF yet. Thus, strict adherence to current guidelines is key to prevent new cases. Renal dysfunction is increasingly common in our population. Therefore, practicing physicians should be aware of this potential complication of the use of gadolinium based contrast media.

  12. Rural-urban migration including formal and informal workers in the urban sector: an agent-based numerical simulation study

    NASA Astrophysics Data System (ADS)

    Branco, Nilton; Oliveira, Tharnier; Silveira, Jaylson

    2012-02-01

    The goal of this work is to study rural-urban migration in the early stages of industrialization. We use an agent-based model and take into account the existence of informal and formal workers on the urban sector and possible migration movements, dependent on the agents' social and private utilities. Our agents are place on vertices of a square lattice, such that each vertex has only one agent. Rural, urban informal and urban formal workers are represented by different states of a three-state Ising model. At every step, a fraction a of the agents may change sectors or migrate. The total utility of a given agent is then calculated and compared to a random utility, in order to check if this agent turns into an actual migrant or changes sector. The dynamics is carried out until an equilibrium state is reached and equilibrium variables are then calculated and compared to available data. We find that a generalized Harris-Todaro condition is satisfied [1] on these equilibrium regimes, i.e, the ratio between expected wages between any pair of sectors reach a constant value. [4pt] [1] J. J. Silveira, A. L. Esp'indola and T. J. Penna, Physica A, 364, 445 (2006).

  13. Gadolinium Chelate Contrast Material in Pregnancy: Fetal Biodistribution in the Nonhuman Primate

    PubMed Central

    Roberts, Victoria H. J.; Schabel, Matthias C.; Grove, Kevin L.; Woods, Mark; Frias, Antonio E.

    2015-01-01

    Purpose To determine the extent to which gadolinium chelate is found in nonhuman primate fetal tissues and amniotic fluid at 19–45 hours after intravenous injection of a weight-appropriate maternal dose of the contrast agent gadoteridol. Materials and Methods Gravid Japanese macaques (n = 14) were maintained as approved by the institutional animal care and utilization committee. In the 3rd trimester of pregnancy, the macaques were injected with gadoteridol (0.1 mmol per kilogram of maternal weight). Fetuses were delivered by means of cesarean section within 24 hours of maternal injection (range, 19–21 hours; n = 11) or 45 hours after injection (n = 3). Gadolinium chelate levels in the placenta, fetal tissues, and amniotic fluid were obtained by using inductively coupled plasma mass spectrometry. The Wilcoxon rank sum test was used for quantitative comparisons. Results Gadoteridol was present in the fetoplacental circulation at much lower quantities than in the mother. At both time points, the distribution of gadolinium chelate in the fetus was comparable to that expected in an adult. The highest concentration of the injected dose (ID) was found in the fetal kidney (0.0161% ID per gram in the 19–21-hour group). The majority of the in utero gadolinium chelate was found in the amniotic fluid and the placenta (mean, 0.1361% ID per organ ± 0.076 [standard deviation] and 0.0939% ID per organ ± 0.0494, respectively). Data acquired 45 hours after injection showed a significant decrease in the gadolinium chelate concentration in amniotic fluid compared with that in the 19–21-hour group (from 0.0017% to 0.0007% ID per gram; P = .01). Conclusion Amounts of gadolinium chelate in the fetal tissues and amniotic fluid were minimal compared with the maternal ID. This may impact future clinical studies on the safety of gadolinium contrast agent use in pregnancy. © RSNA, 2015 PMID:25763829

  14. 21 CFR 700.13 - Use of mercury compounds in cosmetics including use as skinbleaching agents in cosmetic...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... and lotions; hair shampoos, hair sets and rinses, hair straighteners, hair coloring, and other... containing mercury as a skin-bleaching agent and offered for sale as skin-bleaching, beauty, or...

  15. 21 CFR 700.13 - Use of mercury compounds in cosmetics including use as skinbleaching agents in cosmetic...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... and lotions; hair shampoos, hair sets and rinses, hair straighteners, hair coloring, and other... containing mercury as a skin-bleaching agent and offered for sale as skin-bleaching, beauty, or...

  16. 21 CFR 700.13 - Use of mercury compounds in cosmetics including use as skinbleaching agents in cosmetic...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... and lotions; hair shampoos, hair sets and rinses, hair straighteners, hair coloring, and other... containing mercury as a skin-bleaching agent and offered for sale as skin-bleaching, beauty, or...

  17. 21 CFR 700.13 - Use of mercury compounds in cosmetics including use as skinbleaching agents in cosmetic...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... and lotions; hair shampoos, hair sets and rinses, hair straighteners, hair coloring, and other... containing mercury as a skin-bleaching agent and offered for sale as skin-bleaching, beauty, or...

  18. Removal of gadolinium nitrate from heavy water

    SciTech Connect

    Wilde, E.W.

    2000-03-22

    Work was conducted to develop a cost-effective process to purify 181 55-gallon drums containing spent heavy water moderator (D2O) contaminated with high concentrations of gadolinium nitrate, a chemical used as a neutron poison during former nuclear reactor operations at the Savannah River Site (SRS). These drums also contain low level radioactive contamination, including tritium, which complicates treatment options. Presently, the drums of degraded moderator are being stored on site. It was suggested that a process utilizing biological mechanisms could potentially lower the total cost of heavy water purification by allowing the use of smaller equipment with less product loss and a reduction in the quantity of secondary waste materials produced by the current baseline process (ion exchange).

  19. Gadolinium-based nanoparticles for theranostic MRI-radiosensitization.

    PubMed

    Lux, François; Sancey, Lucie; Bianchi, Andrea; Crémillieux, Yannick; Roux, Stéphane; Tillement, Olivier

    2015-01-01

    A rapid development of gadolinium-based nanoparticles is observed due to their attractive properties as MRI-positive contrast agents. Indeed, they display high relaxivity, adapted biodistribution and passive uptake in the tumor thanks to enhanced permeability and retention effect. In addition to these imaging properties, it has been recently shown that they can act as effective radiosensitizers under different types of irradiation (radiotherapy, neutron therapy or hadron therapy). These new therapeutic modalities pave the way to therapy guided by imaging and to personalized medicine.

  20. Simultaneous determination of four anti-dandruff agents including octopirox in shampoo products by reversed-phase liquid chromatography.

    PubMed

    Chao, L

    2001-06-01

    A method based on reversed-phase liquid chromatography (HPLC) has been developed for the simultaneous identification and quantitative determination of four anti-dandruff agents such as salicylic acid, ketoconazole, climbazole, octopirox in commercial anti-dandruff shampoo products. A symmetry C18 column (5 microm, 250 mm x 4.6 mm i.d.) was used at temperature of 35 degrees C, mobile phase with flow rate of 0.8 mL min(-1) was acetonitrile: water (containing 10 mm potassium dihydrogen phosphate, pH 4.0, adjusted with orthophosphoric acid) = 60 : 40 (V/V) and UV detection at 224 nm and 305 nm. Samples were extracted with mobile phase by stirring and ultrasonic method. The average recoveries of four anti-dandruff agents were 98.0-104.1%. The relative standard deviations for samples were 0.11-0.90%. The method is simple, rapid and reproducible. PMID:18498472

  1. The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors.

    PubMed

    Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2016-01-01

    We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps. PMID:27411781

  2. The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

    NASA Astrophysics Data System (ADS)

    Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2016-07-01

    We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps.

  3. The High Radiosensitizing Efficiency of a Trace of Gadolinium-Based Nanoparticles in Tumors

    PubMed Central

    Dufort, Sandrine; Le Duc, Géraldine; Salomé, Murielle; Bentivegna, Valerie; Sancey, Lucie; Bräuer-Krisch, Elke; Requardt, Herwig; Lux, François; Coll, Jean-Luc; Perriat, Pascal; Roux, Stéphane; Tillement, Olivier

    2016-01-01

    We recently developed the synthesis of ultrasmall gadolinium-based nanoparticles (GBN), (hydrodynamic diameter <5 nm) characterized by a safe behavior after intravenous injection (renal clearance, preferential accumulation in tumors). Owing to the presence of gadolinium ions, GBN can be used as contrast agents for magnetic resonance imaging (MRI) and as radiosensitizers. The attempt to determine the most opportune delay between the intravenous injection of GBN and the irradiation showed that a very low content of radiosensitizing nanoparticles in the tumor area is sufficient (0.1 μg/g of particles, i.e. 15 ppb of gadolinium) for an important increase of the therapeutic effect of irradiation. Such a promising and unexpected result is assigned to a suited distribution of GBN within the tumor, as revealed by the X-ray fluorescence (XRF) maps. PMID:27411781

  4. Mitochondrial dysfunction induced by different concentrations of gadolinium ion.

    PubMed

    Zhao, Jie; Zhou, Zhi-Qiang; Jin, Jian-Cheng; Yuan, Lian; He, Huan; Jiang, Feng-Lei; Yang, Xiao-Gang; Dai, Jie; Liu, Yi

    2014-04-01

    Gadolinium-based compounds are the most widely used paramagnetic contrast agents in magnetic resonance imaging on the world. But the tricationic gadolinium ion (Gd(3+)) could induce cell apoptosis probably because of its effects on mitochondria. Until now, the mechanism about how Gd(3+) interacts with mitochondria is not well elucidated. In this work, mitochondrial swelling, collapsed transmembrane potential and decreased membrane fluidity were observed to be important factors for mitochondrial permeability transition pore (mtPTP) opening induced by Gd(3+). The protection effect of CsA (Cyclosporin A) could confirm high concentration of Gd(3+) (500 μM) would trigger mtPTP opening. Moreover, mitochondrial outer membrane breakdown and volume expansion observed clearly by transmission electron microscopy and the release of Cyt c (Cytochrome c) could explain the mtPTP opening from another aspect. In addition, MBM(+) (monobromobimane(+)) and DTT (dithiothreitol) could protect thiol (-SH) groups from oxidation so that the toxicity of Gd(3+) might be resulted from the chelation of -SH of membrane proteins by free Gd(3+). Gd(3+) could inhibit the initiation of mitochondrial membrane lipid peroxidation, so it might interact with anionic lipids too. These findings will highly contribute to the safe applications of Gd-based agents.

  5. New Pyrrole Derivatives with Potent Tubulin Polymerization Inhibiting Activity As Anticancer Agents Including Hedgehog-Dependent Cancer

    PubMed Central

    La Regina, Giuseppe; Bai, Ruoli; Coluccia, Antonio; Famiglini, Valeria; Pelliccia, Sveva; Passacantilli, Sara; Mazzoccoli, Carmela; Ruggieri, Vitalba; Sisinni, Lorenza; Bolognesi, Alessio; Rensen, Whilelmina Maria; Miele, Andrea; Nalli, Marianna; Alfonsi, Romina; Di Marcotullio, Lucia; Gulino, Alberto; Brancale, Andrea; Novellino, Ettore; Dondio, Giulio; Vultaggio, Stefania; Varasi, Mario; Mercurio, Ciro; Hamel, Ernest; Lavia, Patrizia; Silvestri, Romano

    2014-01-01

    We synthesized 3-aroyl-1-arylpyrrole (ARAP) derivatives as potential anticancer agents having different substituents at the pendant 1-phenyl ring. Both the 1-phenyl ring and 3-(3,4,5-trimethoxyphenyl)carbonyl moieties were mandatory to achieve potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARAP 22 showed strong inhibition of the P-glycoprotein-overexpressing NCI-ADR-RES and Messa/Dx5MDR cell lines. Compounds 22 and 27 suppressed in vitro the Hedgehog signaling pathway, strongly reducing luciferase activity in SAG treated NIH3T3 Shh-Light II cells, and inhibited the growth of medulloblastoma D283 cells at nanomolar concentrations. ARAPs 22 and 27 represent a new potent class of tubulin polymerization and cancer cell growth inhibitors with the potential to inhibit the Hedgehog signaling pathway. PMID:25025991

  6. Mechanism of inhibition of ribonucleotide reductase with motexafin gadolinium (MGd)

    SciTech Connect

    Zahedi Avval, Farnaz; Berndt, Carsten; Pramanik, Aladdin; Holmgren, Arne

    2009-02-13

    Motexafin gadolinium (MGd) is an expanded porphyrin anticancer agent which selectively targets tumor cells and works as a radiation enhancer, with promising results in clinical trials. Its mechanism of action is oxidation of intracellular reducing molecules and acting as a direct inhibitor of mammalian ribonucleotide reductase (RNR). This paper focuses on the mechanism of inhibition of RNR by MGd. Our experimental data present at least two pathways for inhibition of RNR; one precluding subunits oligomerization and the other direct inhibition of the large catalytic subunit of the enzyme. Co-localization of MGd and RNR in the cytoplasm particularly in the S-phase may account for its inhibitory properties. These data can elucidate an important effect of MGd on the cancer cells with overproduction of RNR and its efficacy as an anticancer agent and not only as a general radiosensitizer.

  7. A polymeric fastener can easily functionalize liposome surfaces with gadolinium for enhanced magnetic resonance imaging.

    PubMed

    Smith, Cartney E; Shkumatov, Artem; Withers, Sarah G; Yang, Binxia; Glockner, James F; Misra, Sanjay; Roy, Edward J; Wong, Chun-Ho; Zimmerman, Steven C; Kong, Hyunjoon

    2013-11-26

    Common methods of loading magnetic resonance imaging (MRI) contrast agents into nanoparticles often suffer from challenges related to particle formation, complex chemical modification/purification steps, and reduced contrast efficiency. This study presents a simple, yet advanced process to address these issues by loading gadolinium, an MRI contrast agent, exclusively on a liposome surface using a polymeric fastener. The fastener, so named for its ability to physically link the two functional components together, consisted of chitosan substituted with diethylenetriaminepentaacetic acid (DTPA) to chelate gadolinium, as well as octadecyl chains to stabilize the modified chitosan on the liposome surface. The assembly strategy, mimicking the mechanisms by which viruses and proteins naturally anchor to a cell, provided greater T1 relaxivity than liposomes loaded with gadolinium in both the interior and outer leaflet. Gadolinium-coated liposomes were ultimately evaluated in vivo using murine ischemia models to highlight the diagnostic capability of the system. Taken together, this process decouples particle assembly and functionalization and, therefore, has considerable potential to enhance imaging quality while alleviating many of the difficulties associated with multifunctional particle fabrication.

  8. The use of theranostic gadolinium-based nanoprobes to improve radiotherapy efficacy

    PubMed Central

    Sancey, L; Kotb, S; Roux, S; Dufort, S; Bianchi, A; Crémillieux, Y; Fries, P; Coll, J-L; Rodriguez-Lafrasse, C; Janier, M; Dutreix, M; Barberi-Heyob, M; Boschetti, F; Denat, F; Louis, C; Porcel, E; Lacombe, S; Le Duc, G; Deutsch, E; Perfettini, J-L; Detappe, A; Verry, C; Berbeco, R; Butterworth, K T; McMahon, S J; Prise, K M; Perriat, P; Tillement, O

    2014-01-01

    A new efficient type of gadolinium-based theranostic agent (AGuIX®) has recently been developed for MRI-guided radiotherapy (RT). These new particles consist of a polysiloxane network surrounded by a number of gadolinium chelates, usually 10. Owing to their small size (<5 nm), AGuIX typically exhibit biodistributions that are almost ideal for diagnostic and therapeutic purposes. For example, although a significant proportion of these particles accumulate in tumours, the remainder is rapidly eliminated by the renal route. In addition, in the absence of irradiation, the nanoparticles are well tolerated even at very high dose (10 times more than the dose used for mouse treatment). AGuIX particles have been proven to act as efficient radiosensitizers in a large variety of experimental in vitro scenarios, including different radioresistant cell lines, irradiation energies and radiation sources (sensitizing enhancement ratio ranging from 1.1 to 2.5). Pre-clinical studies have also demonstrated the impact of these particles on different heterotopic and orthotopic tumours, with both intratumoural or intravenous injection routes. A significant therapeutical effect has been observed in all contexts. Furthermore, MRI monitoring was proven to efficiently aid in determining a RT protocol and assessing tumour evolution following treatment. The usual theoretical models, based on energy attenuation and macroscopic dose enhancement, cannot account for all the results that have been obtained. Only theoretical models, which take into account the Auger electron cascades that occur between the different atoms constituting the particle and the related high radical concentrations in the vicinity of the particle, provide an explanation for the complex cell damage and death observed. PMID:24990037

  9. Bioinspired synthesis and characterization of gadolinium-labeled magnetite nanoparticles for dual contrast t1- and T2-weighted magnetic resonance imaging.

    PubMed

    Bae, Ki Hyun; Kim, Young Beom; Lee, Yuhan; Hwang, Jinyoung; Park, Hyunwook; Park, Tae Gwan

    2010-03-17

    Gadolinium-labeled magnetite nanoparticles (GMNPs) were synthesized via a bioinspired manner to use as dual contrast agents for T1- and T2-weighted magnetic resonance imaging. A mussel-derived adhesive moiety, 3,4-dihydroxy-l-phenylalanine (DOPA), was utilized as a robust anchor to form a mixed layer of poly(ethylene glycol) (PEG) chains and dopamine molecules on the surface of iron oxide nanoparticles. Gadolinium ions were subsequently complexed at the distal end of the dopamine molecules that were prefunctionalized with a chelating ligand for gadolinium. The resultant GMNPs exhibited high dispersion stability in aqueous solution. Crystal structure and superparamagnetic properties of magnetite nanocrystals were also maintained after the complexation of gadolinium. The potential of GMNPs as dual contrast agents for T1 and T2-weighted magnetic resonance imaging was demonstrated by conducting in vitro and in vivo imaging and relaxivity measurements.

  10. Studies of narrow autoionizing resonances in gadolinium

    SciTech Connect

    Bushaw, Bruce A.; Nortershauser, W.; Blaum, K.; Wendt, Klaus

    2003-06-30

    The autoionization (AI) spectrum of gadolinium between the first and second limits has been investigated by triple-resonance excitation with high-resolution cw lasers. A large number of narrow AI resonances have been observed and assigned total angular momentum J values. The resonances are further divided into members of AI Rydberg series converging to the second limit or other ''interloping'' levels. Fine structure in the Rydberg series has been identified and interpreted in terms of Jc j coupling. A number of detailed studies have been performed on the interloping resonances: These include lifetime determination by lineshape analysis, isotope shifts, hyperfine structure, and photoionization saturation parameters. The electronic structure of the interloping levels is discussed in terms of these studies. Linewidths generally decrease with increasing total angular momentum and the J = 7 resonances are extremely narrow with Lorentzian widths ranging from < 1 MHz up to 157 MHz. The strongest resonances are found to have cross-sections of {approx}10-12 cm{sup 2} and photoionization can be saturated with powers available from cw diode lasers.

  11. Structural, optical and magnetic properties of gadolinium sesquioxide nanobars synthesized via thermal decomposition of gadolinium oxalate

    SciTech Connect

    Manigandan, R.; Giribabu, K.; Suresh, R.; Vijayalakshmi, L.; Stephen, A.; Narayanan, V.

    2013-10-15

    Graphical abstract: - Highlights: • The cubic Gd{sub 2}O{sub 3} nanobars are synthesized by decomposition of C{sub 6}H{sub 20}Gd{sub 2}O{sub 22}. • The nanoparticles are rectangular bar shape with high porous surface. • The combination of magnetic and optical properties within a single particle. • The Gd{sub 2}O{sub 3} nanobars have tailorable nanostructure, wide bandgap and are paramagnetic. - Abstract: Gadolinium oxide nanobars were obtained by thermal decomposition of gadolinium oxalate, which was synthesized by the chemical precipitation method along with glycerol. The functional group analysis and formation of gadolinium oxide from gadolinium oxalate were characterized by the Fourier transform infrared spectroscopy and thermo gravimetric analyzer. The crystal structure, average crystallite size, and lattice parameter were analyzed by X-ray diffraction technique. Moreover, Raman shifts, elemental composition and morphology of the gadolinium oxide was widely investigated by the laser Raman microscope, X-ray photoelectron spectroscopy, FE-SEM-EDAX and HR-TEM, respectively. Furthermore, the optical properties like band gap, absorbance measurement of the gadolinium oxide were extensively examined. In addition, the paramagnetic property of gadolinium oxide nanobars was explored by the vibrating sample magnetometer.

  12. Enhancement of the electron electric dipole moment in gadolinium garnets

    SciTech Connect

    Mukhamedjanov, T.N.; Dzuba, V.A.; Sushkov, O.P.

    2003-10-01

    Effects caused by the electron electric dipole moment (EDM) in gadolinium garnets are considered. Experimental studies of these effects could improve the current upper limit on the electron EDM by several orders of magnitude. We suggest a consistent theoretical model and perform calculations of observable effects in gadolinium gallium garnet and gadolinium iron garnet. Our calculation accounts for both direct and exchange diagrams.

  13. Gadolinium-modulated 19F signals from Perfluorocarbon Nanoparticles as a New Strategy for Molecular Imaging

    PubMed Central

    Neubauer, Anne M.; Myerson, Jacob; Caruthers, Shelton D.; Hockett, Franklin D.; Winter, Patrick M.; Chen, Junjie; Gaffney, Patrick J.; Robertson, J. David; Lanza, Gregory M.; Wickline, Samuel A.

    2008-01-01

    Recent advances in the design of fluorinated nanoparticles for magnetic resonance molecular imaging have enabled specific detection of 19F nuclei, providing unique and quantifiable spectral signatures. However, a pressing need for signal enhancement exists because the total 19F in imaging voxels is often limited. By directly incorporating a relaxation agent (gadolinium) into the lipid monolayer that surrounds the perfluorocarbon, a marked augmentation of the 19F signal from 200nm nanoparticles was achieved. This design increases the magnetic relaxation rate of the 19F nuclei 4-fold at 1.5 T and effects a 125% increase in signal, an effect which is maintained when they are targeted to human plasma clots. By varying the surface concentration of gadolinium, the relaxation effect can be quantitatively modulated to tailor particle properties. This novel strategy dramatically improves the sensitivity and range of 19F MRI/MRS and forms the basis for designing contrast agents capable of sensing their surface chemistry. PMID:18956457

  14. The alkaline single cell electrophoresis assay with eight mouse organs: results with 22 mono-functional alkylating agents (including 9 dialkyl N-nitrosoamines) and 10 DNA crosslinkers.

    PubMed

    Tsuda, S; Matsusaka, N; Madarame, H; Miyamae, Y; Ishida, K; Satoh, M; Sekihashi, K; Sasaki, Y F

    2000-04-13

    The genotoxicity of 22 mono-functional alkylating agents (including 9 dialkyl N-nitrosoamines) and 10 DNA crosslinkers selected from IARC (International Agency for Research on Cancer) groups 1, 2A, and 2B was evaluated in eight mouse organs with the alkaline single cell gel electrophoresis (SCGE) (comet) assay. Groups of four mice were treated once intraperitoneally at the dose at which micronucleus tests had been conducted, and the stomach, colon, liver, kidney, bladder, lung, brain, and bone marrow were sampled 3, 8, and/or 24 h later. All chemicals were positive in the SCGE assay in at least one organ. Of the 22 mono-functional alkylating agents, over 50% were positive in all organs except the brain and bone marrow. The two subsets of mono-functional alkylating agents differed in their bone marrow genotoxicity: only 1 of the 9 dialkyl N-nitrosoamines was positive in bone marrow as opposed to 8 of the 13 other alkylating agents, reflecting the fact that dialkyl N-nitrosoamines are poor micronucleus inducers in hematopoietic cells. The two groups of mono-functional alkylating agents also differ in hepatic carcinogenicity in spite of the fact that they are similar in hepatic genotoxicity. While dialkyl N-nitrosoamines produce tumors primarily in mouse liver, only one (styrene-7,8-oxide) out of 10 of the other type of mono-functional alkylating agents is a mouse hepatic carcinogen. Taking into consideration our previous results showing high concordance between hepatic genotoxicity and carcinogenicity for aromatic amines and azo compounds, a possible explanation for the discrepancy might be that chemicals that require metabolic activation show high concordance between genotoxicity and carcinogenicity in the liver. A high percent of the 10 DNA crosslinkers were positive in the SCGE assay in the gastrointestinal mucosa, but less than 50% were positive in the liver and lung. In this study, we allowed 10 min alkali-unwinding to obtain low and stable control values

  15. The feasibility of in vivo quantification of bone-gadolinium in humans by prompt gamma neutron activation analysis (PGNAA) following gadolinium-based contrast-enhanced MRI

    NASA Astrophysics Data System (ADS)

    Mostafaei, F.; McNeill, F. E.; Chettle, D. R.; Noseworthy, M. D.; Prestwich, W. V.

    2015-11-01

    The feasibility of using a 238Pu/Be-based in vivo prompt γ-ray neutron activation analysis (IVNAA) system, previously successfully used for measurements of muscle, for the detection of gadolinium (Gd) in bone was presented. Gd is extensively used in contrast agents in MR imaging. We present phantom measurement data for the measurement of Gd in the tibia. Gd has seven naturally occurring isotopes, of which two have extremely large neutron capture cross sections; 155Gd (14.8% natural abundance (NA), σ= 60,900 barns) and 157Gd (15.65% NA, σ= 254,000 barns). Our previous work focused on muscle but this only informs about the short term kinetics of Gd. We studied the possibility of measuring bone, as it may be a long term storage site for Gd. A human simulating bone phantom set was developed. The phantoms were doped with seven concentrations of Gd of concentrations 0.0, 25, 50, 75, 100, 120 and 150 ppm. Additional elements important for neutron activation analysis, Na, Cl and Ca, were also included to create an overall elemental composition consistent with Reference Man. The overall conclusion is that the potential application of this Pu-Be-based prompt in vivo NAA for the monitoring of the storage and retention of Gd in bone is not feasible.

  16. Gadolinium: Central Metal of the Lanthanoids

    ERIC Educational Resources Information Center

    Laing, Michael

    2009-01-01

    The physical and chemical properties of gadolinium are compared with those of the other lanthanoids. Some properties are intermediate between those of lanthanum and lutetium; some between those of barium and hafnium; and others (unexpectedly) between those of ytterbium and lutetium. Both the remarkably high molar heat capacity of the metal and the…

  17. A toxicological study of gadolinium nitrate

    SciTech Connect

    London, J.E.

    1988-05-01

    The sensitization study in the guinea pig did not show gadolinium nitrate to have potential sensitizing properties. Skin application studies in the rabbit demonstrated that it was cutaneously a severe irritant. This material was considered an irritant in the rabbit eye application studies. 3 refs., 1 tab.

  18. Gadolinium-Enhanced Angiography for Diagnosis and Interventional Treatment of Subclavian Artery Stenosis Prior to Fistula Creation

    SciTech Connect

    Termote, Bruno; Maleux, Geert Heye, Sam; Fourneau, Inge; Claes, Kathleen

    2008-07-15

    We report the use of gadolinium-based contrast agent for both diagnostic and interventional subclavian angiography in two azotemic patients, presenting with an asymptomatic, high-grade stenosis of the left subclavian artery, ipsilateral to the site of choice for native fistula creation. Angiographic imaging performed with diluted gadolinium-based contrast material was clear enough to perform successful subclavian artery stenting, resulting in normalization of the arterial blood pressure in the afferent artery of the dialysis fistula. Clinically, no decrease in residual renal function and no other complication were noted immediately or a longer period after the interventional treatment.

  19. Gadolinium Deposition in Nephrogenic Systemic Fibrosis: An Examination of Tissue using Synchrotron X-ray Fluorescence Spectroscopy

    SciTech Connect

    High, W.; Ranville, J; Brown, M; Punshon, T; Lanzirotti, A; Jackson, B

    2010-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder associated with gadolinium (Gd)-based contrast agents dosed during renal insufficiency. In two patients, Gd deposition in tissue affected by nephrogenic systemic fibrosis was quantified using inductively coupled plasma mass spectrometry. The presence of Gd was confirmed and mapped using synchrotron x-ray fluorescence spectroscopy. Affected skin and soft tissue from the lower extremity demonstrated 89 and 209 ppm ({micro}g/g, dry weight, formalin fixed) in cases 1 and 2, respectively. In case 2, the same skin and soft tissue was retested after paraffin embedding, with the fat content removed by xylene washes, and this resulted in a measured value of 189 ppm ({micro}g/g, dry weight, paraffin embedded). Synchrotron x-ray fluorescence spectroscopy confirmed Gd in the affected tissue of both cases, and provided high-sensitivity and high-resolution spatial mapping of Gd deposition. A gradient of Gd deposition in tissue correlated with fibrosis and cellularity. Gd deposited in periadnexal locations within the skin, including hair and eccrine ducts, where it colocalized to areas of high calcium and zinc content. Because of the difficulty in obtaining synchrotron x-ray fluorescence spectroscopy scans, tissue from only two patients were mapped. A single control with kidney disease and gadolinium-based contrast agent exposure did not contain Gd. Gd content on a gravimetric basis was impacted by processing that removed fat and altered the dry weight of the specimens. Gradients of Gd deposition in tissue corresponded to fibrosis and cellularity. Adnexal deposition of Gd correlated with areas of high calcium and zinc content.

  20. Clinical evaluation of a frozen commercially prepared microdilution panel for antifungal susceptibility testing of seven antifungal agents, including the new triazoles posaconazole, ravuconazole, and voriconazole.

    PubMed

    Pfaller, M A; Diekema, D J; Messer, S A; Boyken, L; Huynh, H; Hollis, R J

    2002-05-01

    A commercially prepared frozen broth microdilution panel (Trek Diagnostic Systems, Westlake, Ohio) was compared with a reference microdilution panel for antifungal susceptibility testing of two quality control (QC) strains and 99 clinical isolates of Candida spp. The antifungal agents tested included amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, ravuconazole, and voriconazole. Microdilution testing was performed according to NCCLS recommendations. MIC endpoints were read visually after 48 h of incubation and were assessed independently for each microdilution panel. The MICs for the QC strains were within published limits for both the reference and Trek microdilution panels. Discrepancies among MIC endpoints of no more than 2 dilutions were used to calculate the percent agreement. Acceptable levels of agreement between the Trek and reference panels were observed for all antifungal agents tested against the 99 clinical isolates. The overall agreement for each antifungal agent ranged from 96% for ravuconazole to 100% for amphotericin B. The Trek microdilution panel appears to be a viable alternative to frozen microdilution panels prepared in-house. PMID:11980944

  1. Gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres for gadolinium neutron-capture therapy.

    PubMed

    Saha, Tapan Kumar; Ichikawa, Hideki; Fukumori, Yoshinobu

    2006-12-11

    In order to provide a suitable device that would contain water-soluble drugs, highly water-soluble gadolinium diethylenetriaminopentaacetic acid-loaded chitosan microspheres (CMS-Gd-DTPA) were prepared by the emulsion method using glutaraldehyde as a cross-linker and Span 80 as a surfactant for gadolinium neutron-capture therapy of cancer. The gadolinium content and the mass median diameter of CMS-Gd-DTPA were estimated. The size and morphology of the CMS-Gd-DTPA were strongly influenced by the initial applied weight ratio of Gd-DTPA:chitosan. FTIR spectra showed that the electrostatic interaction between chitosan and Gd-DTPA accelerated the formation of gadolinium-enriched chitosan microspheres. Sufficient amounts of glutaraldehyde and Span 80 were necessary for producing discrete CMS-Gd-DTPA. The CMS-Gd-DTPA having a mass median diameter 11.7microm and 11.6% of gadolinium could be used in Gd-NCT following intratumoral injection. PMID:17045253

  2. 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

  3. Method of separating and purifying gadolinium-153

    DOEpatents

    Bray, Lane A [Richland, WA; Corneillie, Todd M [Davis, CA

    2001-01-01

    The present invention is an improvement to the method of separating and purifying gadolinium from a mixture of gadolinium and europium having the steps of (a) dissolving the mixture in an acid; (b) reducing europium+3 to europium+2; and (c) precipitating the europium+2 with a sulfate ion in a superstoichiometric amount; wherein the improvement is achieved by using one or more of the following: (i) the acid is an anoic acid; (ii) the reducing is with zinc metal in the absence of a second metal or with an amount of the second metal that is ineffective in the reducing; (iii) adding a group IIA element after step (c) for precipitating the excess sulfate prior to repeating step (c); (iv) the sulfate is a sulfate salt with a monovalent cation; (v) adding cold europium+3 prior to repeating step (c).

  4. Progress Towards Laser Cooling and Trapping Gadolinium

    NASA Astrophysics Data System (ADS)

    Adhikari, Upendra; Simien, Clayton

    2016-05-01

    Lanthanide elements are of interest because of their potential for investigating next generation optical clock transitions, novel non-S ground state ultracold collisions, and the physics of quantum degenerate dipolar gases. We present our progress towards laser cooling and trapping atomic Gadolinium (Gd). A magneto-optical trap is the first step towards precision measurements, ultracold collision studies, and for probing dipolar physics of Gd. The design, construction, and performance of the apparatus will be presented.

  5. Gadolinium-based nanoparticles for highly efficient T1-weighted magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Lim, Eun-Kyung; Kang, Byunghoon; Choi, Yuna; Jang, Eunji; Han, Seungmin; Lee, Kwangyeol; Suh, Jin-Suck; Haam, Seungjoo; Huh, Yong-Min

    2014-06-01

    We developed Pyrene-Gadolinium (Py-Gd) nanoparticles as pH-sensitive magnetic resonance imaging (MRI) contrast agents capable of showing a high-Mr signal in cancer-specific environments, such as acidic conditions. Py-Gd nanoparticles were prepared by coating Py-Gd, which is a complex of gadolinium with pyrenyl molecules, with pyrenyl polyethyleneglycol PEG using a nano-emulsion method. These particles show better longitudinal relaxation time (T1) MR signals in acidic conditions than they do in neutral conditions. Furthermore, the particles exhibit biocompatibility and MR contrast effects in both in vitro and in vivo studies. From these results, we confirm that Py-Gd nanoparticles have the potential to be applied for accurate cancer diagnosis and therapy.

  6. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update.

    PubMed

    Idée, Jean-Marc; Fretellier, Nathalie; Robic, Caroline; Corot, Claire

    2014-11-01

    Nephrogenic systemic fibrosis (NSF) is an iatrogenic scleroderma-like fibrosing systemic disorder occurring in patients with severe or end-stage renal disease. It was established as a new clinical entity in the year 2000. A causal role for gadolinium chelates (GC), widely used as contrast agents for magnetic resonance imaging, was suggested six years later. It rapidly appeared that the occurrence of NSF was associated with prior administration of GCs with lower thermodynamic stability, leading to warnings being published by health authorities and learned societies worldwide. Although a role for the chelated form of the less stable GCs has been proposed, the most commonly accepted hypothesis involves the gradual release of dissociated gadolinium in the body, leading to systemic fibrosis. However, the entire chain of events is still not fully understood in a causal way and many uncertainties remain.

  7. Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects.

    PubMed

    Nwe, Kido; Huang, Ching-Hui; Qu, Feini; Warden-Rothman, Robert; Zhang, Clare Y; Mauck, Robert L; Tsourkas, Andrew

    2016-05-01

    The ability to detect meniscus defects by magnetic resonance arthrography (MRA) can be highly variable. To improve the delineation of fine tears, we synthesized a cationic gadolinium complex, (Gd-DOTA-AM4 )(2+) , that can electrostatically interact with Glycosaminoglycans (GAGs). The complex has a longitudinal relaxivity (r1) of 4.2 mM(-1) s(-1) and is highly stable in serum. Its efficacy in highlighting soft tissue tears was evaluated in comparison to a clinically employed contrast agent (Magnevist) using explants obtained from adult bovine menisci. In all cases, Gd-DOTA-AM4 appeared to improve the ability to detect the soft tissue defect by providing increased signal intensity along the length of the tear. Magnevist shows a strong signal near the liquid-meniscus interface, but much less contrast is observed within the defect at greater depths. This provides initial evidence that cationic contrast agents can be used to improve the diagnostic accuracy of MRA. Copyright © 2016 John Wiley & Sons, Ltd.

  8. Cationic gadolinium chelate for magnetic resonance imaging of cartilaginous defects.

    PubMed

    Nwe, Kido; Huang, Ching-Hui; Qu, Feini; Warden-Rothman, Robert; Zhang, Clare Y; Mauck, Robert L; Tsourkas, Andrew

    2016-05-01

    The ability to detect meniscus defects by magnetic resonance arthrography (MRA) can be highly variable. To improve the delineation of fine tears, we synthesized a cationic gadolinium complex, (Gd-DOTA-AM4 )(2+) , that can electrostatically interact with Glycosaminoglycans (GAGs). The complex has a longitudinal relaxivity (r1) of 4.2 mM(-1) s(-1) and is highly stable in serum. Its efficacy in highlighting soft tissue tears was evaluated in comparison to a clinically employed contrast agent (Magnevist) using explants obtained from adult bovine menisci. In all cases, Gd-DOTA-AM4 appeared to improve the ability to detect the soft tissue defect by providing increased signal intensity along the length of the tear. Magnevist shows a strong signal near the liquid-meniscus interface, but much less contrast is observed within the defect at greater depths. This provides initial evidence that cationic contrast agents can be used to improve the diagnostic accuracy of MRA. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26853708

  9. Current state of evidence on 'off-label' therapeutic options for systemic lupus erythematosus, including biological immunosuppressive agents, in Germany, Austria and Switzerland--a consensus report.

    PubMed

    Aringer, M; Burkhardt, H; Burmester, G R; Fischer-Betz, R; Fleck, M; Graninger, W; Hiepe, F; Jacobi, A M; Kötter, I; Lakomek, H J; Lorenz, H M; Manger, B; Schett, G; Schmidt, R E; Schneider, M; Schulze-Koops, H; Smolen, J S; Specker, C; Stoll, T; Strangfeld, A; Tony, H P; Villiger, P M; Voll, R; Witte, T; Dörner, T

    2012-04-01

    Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, chloroquine and hydroxychloroquine, azathioprine, cyclophosphamide and very recently belimumab have been approved for SLE therapy in Germany, Austria and Switzerland. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. Therefore, treatment considerations will include 'off-label' use of medication approved for other indications. In this consensus approach, an effort has been undertaken to delineate the limits of the current evidence on therapeutic options for SLE organ disease, and to agree on common practice. This has been based on the best available evidence obtained by a rigorous literature review and the authors' own experience with available drugs derived under very similar health care conditions. Preparation of this consensus document included an initial meeting to agree upon the core agenda, a systematic literature review with subsequent formulation of a consensus and determination of the evidence level followed by collecting the level of agreement from the panel members. In addition to overarching principles, the panel have focused on the treatment of major SLE organ manifestations (lupus nephritis, arthritis, lung disease, neuropsychiatric and haematological manifestations, antiphospholipid syndrome and serositis). This consensus report is intended to support clinicians involved in the care of patients with difficult courses of SLE not responding to standard therapies by providing up-to-date information on the best available evidence.

  10. Polycatechol Nanoparticle MRI Contrast Agents.

    PubMed

    Li, Yiwen; Huang, Yuran; Wang, Zhao; Carniato, Fabio; Xie, Yijun; Patterson, Joseph P; Thompson, Matthew P; Andolina, Christopher M; Ditri, Treffly B; Millstone, Jill E; Figueroa, Joshua S; Rinehart, Jeffrey D; Scadeng, Miriam; Botta, Mauro; Gianneschi, Nathan C

    2016-02-01

    Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement. PMID:26681255

  11. Extraction-chromatographic affinage in gadolinium-153 preparation production technology

    SciTech Connect

    Melnik, M.I.; Karelin, E.A.; Kuznetsov, R.A.

    1993-12-31

    The gadolinium 153 preparation is used for production of medical gamma-sources which are applicable in bone densimeters for early diagnostics of osteoporosis. This preparation must meet strict requirements with respect to the content of europium radionuclides and specific activity. In The Research Institute of Atomic Reactors (RIAR) the gadolinium 153 is produced by neutron irradiation of Europium 151. This process is described.

  12. Geometrically confined ultrasmall gadolinium oxide nanoparticles boost the T(1) contrast ability.

    PubMed

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

    2016-02-14

    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.

  13. Resonance parameter measurements and analysis of gadolinium

    SciTech Connect

    Leinweber, G.; Barry, D. P.; Trbovich, M. J.; Burke, J. A.; Drindak, N. J.; Knox, H. D.; Ballad, R. V.; Block, R. C.; Danon, Y.; Severnyak, L. I.

    2006-07-01

    The purpose of the present work is to measure the neutron cross sections of gadolinium accurately. Gd has the highest thermal absorption cross section of any natural element. Therefore it is an important element for thermal reactor applications Neutron capture and transmission measurements were performed by the time-of-flight technique at the Rensselaer Polytechnic Inst. (RPI) LINAC facility using metallic and liquid Gd samples. The liquid samples were isotopically-enriched in either {sup 155}Gd or {sup 157}Gd. The capture measurements were made at the 25-m flight station with a sodium iodide detector, and the transmission measurements were performed at 15- and 25-m flight stations with {sup 6}Li glass scintillation detectors. The multilevel R-matrix Bayesian code SAMMY was used to extract resonance parameters. The results of the thermal region analysis are significant. Resonance parameters for the low energy doublet, at 0.025 and 0.032 eV, are presented. The thermal (2200 m/s) capture cross section of {sup 157}Gd has been measured to be 11% smaller than that calculated from ENDF/B-VI updated through release 8. Thermal capture cross sections and capture resonance integrals for each isotope as well as elemental gadolinium are presented. In the epithermal region, natural metal samples were measured in capture and transmission. Neutron interaction data up to 300 eV have been analyzed. Substantial improvement to the understanding of gadolinium cross sections is presented, particularly above 180 eV where the ENDF resolved region for {sup 155}Gd ends. (authors)

  14. Gadolinium Chloride Inhibits the Spontaneous Resolution of Fibrosis in CCL(4)-Induced Cirrhosis.

    PubMed

    Chávez, Enrique; Alcantar, Lidia K; Moreno, Mario G; Muriel, Pablo

    2006-01-01

    Current evidence indicates that liver fibrosis is dynamic and can be bidirectional, involving phases of progression and regression, and that in addition to increased matrix synthesis, this pathological process involves major changes in the regulation of matrix degradation. There is also evidence that Kupffer cells participate in both fibrogenesis and fibrolysis. Therefore, the aim of the present work was to study the participation of Kupffer cells on the spontaneous resolution of hepatic fibrosis. Cirrhosis was produced by 3 months of chronic CCl(4) intoxication in male Wistar rats, and then CCl(4) was discontinued and two groups were formed: One group received gadolinium chloride (10 mg/kg, IP, daily) and the other received the vehicle (water) only for 2 months. Serum enzyme activities of alkaline phosphatase and alanine aminotransferase and liver lipid peroxidation increased by CCl(4) treatment but returned to normal by discontinuation of CCl(4). GSH, GSH/GSSG, and GSH+GSSG decreased significantly by CCl(4), but withdrawal of CCl(4) restored normal glutathione parameters. Fibrosis increased five-fold and glycogen decreased significantly by CCl(4) treatment, while discontinuation of CCl(4) reversed completely glycogen depletion and partially fibrosis. Gadolinium chloride showed effects only in the content of glycogen and collagen; the former was decreased further and the latter remained elevated despite discontinuation of the toxic agent. Persistent fibrosis induced by gadolinium chloride, a selective inhibitor of Kupffer cells, indicates that these cells play a pivotal role in fibrolysis. PMID:20020993

  15. Ultra-small gadolinium oxide nanoparticles to image brain cancer cells in vivo with MRI.

    PubMed

    Faucher, Luc; Guay-Bégin, Andrée-Anne; Lagueux, Jean; Côté, Marie-France; Petitclerc, Eric; Fortin, Marc-André

    2011-01-01

    The majority of contrast agents used in magnetic resonance imaging (MRI) is based on the rare-earth element gadolinium. Gadolinium-based nanoparticles could find promising applications in pre-clinical diagnostic procedures of certain types of cancer, such as glioblastoma multiforme. This is one of the most malignant, lethal and poorly accessible forms of cancer. Recent advances in colloidal nanocrystal synthesis have led to the development of ultra-small crystals of gadolinium oxide (US-Gd(2)O(3), 2-3 nm diameter). As of today, this is the smallest and the densest of all Gd-containing nanoparticles. Cancer cells labeled with a sufficient quantity of this compound appear bright in T(1)-weighted MRI images. Here we demonstrate that US-Gd(2)O(3) can be used to label GL-261 glioblastoma multiforme cells, followed by localization and visualization in vivo using MRI. Very high amounts of Gd are efficiently internalized and retained in cells, as confirmed with TEM and ICP-MS. Labeled cells were visualized in vivo at 1.5 T using the chicken embryo model. This is one more step toward the development of "positively contrasted" cell tracking procedures with MRI.

  16. Specific lipase-responsive polymer-coated gadolinium nanoparticles for MR imaging of early acute pancreatitis.

    PubMed

    Zhang, Hong-Wu; Wang, Li-Qin; Xiang, Qing-Feng; Zhong, Qian; Chen, Lu-Ming; Xu, Cai-Xia; Xiang, Xian-Hong; Xu, Bo; Meng, Fei; Wan, Yi-Qian; Deng, David Y B

    2014-01-01

    Currently, available methods for diagnosis of acute pancreatitis (AP) are mainly dependent on serum enzyme analysis and imaging techniques that are too low in sensitivity and specificity to accurately and promptly diagnose AP. The lack of early diagnostic tools highlights the need to search for a highly effective and specific diagnostic method. In this study, we synthesized a conditionally activated, gadolinium-containing, nanoparticle-based MRI nanoprobe as a diagnostic tool for the early identification of AP. Gadolinium diethylenetriaminepentaacetic fatty acid (Gd-DTPA-FA) nanoparticles were synthesized by conjugation of DTPA-FA ligand and gadolinium acetate. Gd-DTPA-FA exhibited low cytotoxicity and excellent biocompatibility when characterized in vitro and in vivo studies. L-arginine induced a gradual increase in the intensity of the T1-weighted MRI signal from 1 h to 36 h in AP rat models. The increase in signal intensity was most significant at 1 h, 6 h and 12 h. These results suggest that the Gd-DTPA-FA as an MRI contrast agent is highly efficient and specific to detect early AP.

  17. Substitution of gadolinium ethylenediaminetetraacetate with phosphites: towards gadolinium deposit in nephrogenic systemic fibrosis.

    PubMed

    Gao, Song; Chen, Mao-Long; Zhou, Zhao-Hui

    2014-01-14

    In neutral media, reactions of gadolinium ethylenediaminetetraacetates with phosphorous acid result in the formation of the mixed-ligand polymeric complex K3n[Gd(EDTA)(HPO3)]n·7nH2O () and dimeric complex Na6[Gd2(EDTA)2(HPO3)2]·2.5NaCl·21H2O () (H4EDTA = ethylenediaminetetraacetic acid) in warm solution. Further substitution with citric acid gives the monomeric gadolinium citrate with EDTA (NH4)2Na[Gd(EDTA)(H2cit)]·4H2O (). The compounds were characterized by elemental analysis, single crystal X-ray diffraction, FT-IR, ESI-MS and thermogravimetric analysis. Structural analysis indicates that three coordinated water molecules in the gadolinium ethylenediaminetetraacetate trihydrates are replaced by phosphite ions (HPO3(2-)) in the compounds and . Gadolinium atoms are octa-coordinated by EDTA and the phosphite ion, the latter links adjacent Gd-EDTA units to generate an infinite one-dimensional chain in compound and a dimeric octatomic ring in . In complex , coordinated water molecules were substituted by the α-hydroxy, α-carboxy and β-carboxy groups of citrate. Citrate is favourable for inhibiting the formation of Gd-EDTA phosphite. All the complexes are very easily soluble in water. The solution behavior of the isostructural lanthanum complexes was probed with (13)C and (31)P NMR spectra in D2O for comparison. ESI-MS analysis and recrystallization proved that complexes and dissociate to the monomeric unit of Gd-EDTA and free HPO3(2-) in aqueous solution. Substitutions of gadolinium ethylenediaminetetraacetates to and are attributed to be the cause of nephrogenic systemic fibrosis in some way.

  18. Light deflection in gadolinium molybdate ferroelastic crystals

    NASA Astrophysics Data System (ADS)

    Staniorowski, Piotr; Bornarel, Jean

    2000-02-01

    The deflection of a He-Ne light beam by polydomain gadolinium molybdate (GMO) crystals has been studied with respect to incidence angle icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> i on the sample at room temperature. The A and B deflected beams do not cross each other during the icons/Journals/Common/alpha" ALT="alpha" ALIGN="TOP"/> i variation, in contrast to results and calculations previously published. The model using the Fresnel equation confirms this result. The model presented is more accurate for numerical calculation than that using the Huygens construction.

  19. Towards modeling gadolinium-lead-borate glasses

    SciTech Connect

    Rada, S.; Ristoiu, T.; Rada, M.; Coroiu, I.; Maties, V.; Culea, E.

    2010-01-15

    Infrared spectra of gadolinium-lead-borate glasses of the xGd{sub 2}O{sub 3}.(100 - x)[3B{sub 2}O{sub 3}.PbO] system, where x = 0, 5, 10, 15, 25, 35 and 50 mol.%, have been recorded to explore the role of content of gadolinium ions behaving as glass modifier. The FTIR spectroscopy data for the xGd{sub 2}O{sub 3}.(1 - x)[3B{sub 2}O{sub 3}.PbO] glasses show the structural role of lead ions as a network-formers and of the gadolinium ions network modifiers. Adding of the rare earth ion up to 35 mol.% into the glass matrix, the IR bands characteristic to the studied glasses become sharper and more pronounced. Structural changes, as recognized by analyzing band shapes of IR spectra, revealed that Gd{sub 2}O{sub 3} causes a change from the continuous borate network to the continuous lead-borate network interconnected through Pb-O-B and B-O-B bridges and the transformation of some tetrahedral [BO{sub 4}] units into trigonal [BO{sub 3}] units. Then, gadolinium ions have affinity towards [BO{sub 3}] structural units which contain non-bridging oxygens necessary for the charge compensation because the more electronegative [BO{sub 3}] structural units were implied in the formation of B-O-Gd bonds and the transformation of glass network into a glass ceramic. We propose a possible structural model of building blocks for the formation of continuous random 3B{sub 2}O{sub 3}.PbO network glass used by density functional theory (DFT) calculations. DFT calculations show that lead atoms occupy three different sites in the proposed model. The first is coordinated with six oxygen atoms forming distorted octahedral geometries. The second lead atom has an octahedral oxygen environment and the five longer Pb-O bonds are considered as participating in the metal coordination scheme. The third lead atom has ionic character. In agreement with the results offered by the experimental FTIR data, the theoretical IR data confirm that our proposed structure is highly possible.

  20. In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging

    PubMed Central

    Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

    2015-01-01

    Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N′-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor. PMID:26316749

  1. In vitro study of novel gadolinium-loaded liposomes guided by GBI-10 aptamer for promising tumor targeting and tumor diagnosis by magnetic resonance imaging.

    PubMed

    Gu, Meng-Jie; Li, Kun-Feng; Zhang, Lan-Xin; Wang, Huan; Liu, Li-Si; Zheng, Zhuo-Zhao; Han, Nan-Yin; Yang, Zhen-Jun; Fan, Tian-Yuan

    2015-01-01

    Novel gadolinium-loaded liposomes guided by GBI-10 aptamer were developed and evaluated in vitro to enhance magnetic resonance imaging (MRI) diagnosis of tumor. Nontargeted gadolinium-loaded liposomes were achieved by incorporating amphipathic material, Gd (III) [N,N-bis-stearylamidomethyl-N'-amidomethyl] diethylenetriamine tetraacetic acid, into the liposome membrane using lipid film hydration method. GBI-10, as the targeting ligand, was then conjugated onto the liposome surface to get GBI-10-targeted gadolinium-loaded liposomes (GTLs). Both nontargeted gadolinium-loaded liposomes and GTLs displayed good dispersion stability, optimal size, and zeta potential for tumor targeting, as well as favorable imaging properties with enhanced relaxivity compared with a commercial MRI contrast agent (CA), gadopentetate dimeglumine. The use of GBI-10 aptamer in this liposomal system was intended to result in increased accumulation of gadolinium at the periphery of C6 glioma cells, where the targeting extracellular matrix protein tenascin-C is overexpressed. Increased cellular binding of GTLs to C6 cells was confirmed by confocal microscopy, flow cytometry, and MRI, demonstrating the promise of this novel delivery system as a carrier of MRI contrast agent for the diagnosis of tumor. These studies provide a new strategy furthering the development of nanomedicine for both diagnosis and therapy of tumor.

  2. The Complex Fate in Plasma of Gadolinium Incorporated into High-Density Lipoproteins Used for Magnetic Imaging of Atherosclerotic Plaques

    PubMed Central

    Barazza, Alessandra; Blachford, Courtney; Even-Or, Orli; Joaquin, Victor A.; Briley-Saebo, Karen C.; Chen, Wei; Jiang, Xian-Cheng; Mulder, Willem J. M.; Cormode, David P.; Fayad, Zahi A.; Fisher, Edward A.

    2014-01-01

    We have previously reported enhancing the imaging of atherosclerotic plaques in mice using reconstituted high density lipoproteins (HDL) as nanocarriers for the MRI contrast agent gadolinium (Gd). This study focuses on the underlying mechanisms of Gd delivery to atherosclerotic plaques. HDL, LDL, and VLDL particles containing Gd chelated to phosphatidyl ethanolamine (DTPA-DMPE) and a lipidic fluorophore were used to demonstrate the transfer of Gd-phospholipids among plasma lipoproteins in vitro and in vivo. To determine the basis of this transfer, the roles of phospholipid transfer protein (PLTP) and lipoprotein lipase (LpL) in mediating the migration of Gd-DTPA-DMPE among lipoproteins were investigated. The results indicated that neither was an important factor, suggesting that spontaneous transfer of Gd-DTPA-DMPE was the most probable mechanism. Finally, two independent mouse models were used to quantify the relative contributions of HDL and LDL reconstituted with Gd-DTPA-DMPE to plaque imaging enhancement by MR. Both sets of results suggested that Gd-DTPA-DMPE originally associated with LDL was about twice as effective as that injected in the form of Gd-HDL, and that some of Gd-HDL’s effectiveness in vivo is indirect through transfer of the imaging agent to LDL. In conclusion, the fate of Gd-DTPA-DMPE associated with a particular type of lipoprotein is complex, and includes its transfer to other lipoprotein species that are then cleared from the plasma into tissues. PMID:23617731

  3. Low Temperature Spin Structure of Gadolinium Titanate

    NASA Astrophysics Data System (ADS)

    Javanparast, Behnam; McClarty, Paul; Gingras, Michel

    2012-02-01

    Many rare earth pyrochlore oxides exhibit exotic spin configurations at low temperatures due to frustration. The nearest neighbor coupling between spins on the corner-sharing tetrahedral network generate geometrical magnetic frustration. Among these materials, gadolinium titanate (Gd2Ti2O7) is of particular interest. Its low temperature ordered phases are not yet understood theoretically. Bulk thermal measurements such as specific heat and magnetic susceptibility measurements find two phase transitions in zero external field, in agreement with simple mean field calculations. However, recent neutron scattering experiments suggest a so-called 4-k spin structure for intermediate phase and a so called canted 4-k structure for lower temperature phase that does not agree with either mean-field theory or Monte Carlo simulation which find the 1-k state and Palmer-Chalker state respectively as the lowest free energy configuration for those phases. In our work, we study the 4-k structure in detail and present a new phase diagram for dipolar Heisenberg spins on a pyrochlore lattice, certain portions of which describe gadolinium titanate.

  4. Diagnosis of Vascular Compression at the Thoracic Outlet Using Gadolinium-Enhanced High-Resolution Ultrafast MR Angiography in Abduction and Adduction

    SciTech Connect

    Hagspiel, Klaus D.; Spinosa, David J.; Angle, J. Fritz; Matsumoto, Alan H.

    2000-03-15

    Gadolinium-enhanced magnetic resonance angiography allows rapid evaluation of the vascular structures of the thoracic outlet both in the neutral position and in abduction during one examination within FDA-approved dose limitations for contrast agents. The technique appears to be a good screening one for patients suspected of having vascular thoracic outlet syndrome.

  5. Bioconjugation of luminescent silicon quantum dots to gadolinium ions for bioimaging applications

    NASA Astrophysics Data System (ADS)

    Erogbogbo, Folarin; Chang, Ching-Wen; May, Jasmine L.; Liu, Liwei; Kumar, Rajiv; Law, Wing-Cheung; Ding, Hong; Yong, Ken Tye; Roy, Indrajit; Sheshadri, Mukund; Swihart, Mark T.; Prasad, Paras N.

    2012-08-01

    Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they maintain their optical properties within the intracellular environment. The magnetic resonance relaxivity of the nanoconstruct was 2.4 mM-1 s-1 (in terms of Gd3+ concentration), calculated to be around 6000 mM-1 s-1 per nanoconstruct. These desirable optical and relaxivity properties of the newly developed probe open the door for use of SiQDs in future multimodal applications such as tumour imaging.Luminescent imaging agents and MRI contrast agents are desirable components in the rational design of multifunctional nanoconstructs for biological imaging applications. Luminescent biocompatible silicon quantum dots (SiQDs) and gadolinium chelates can be applied for fluorescence microscopy and MRI, respectively. Here, we report the first synthesis of a nanocomplex incorporating SiQDs and gadolinium ions (Gd3+) for biological applications. The nanoconstruct is composed of a PEGylated micelle, with hydrophobic SiQDs in its core, covalently bound to DOTA-chelated Gd3+. Dynamic light scattering reveals a radius of 85 nm for these nanoconstructs, which is consistent with the electron microscopy results depicting radii ranging from 25 to 60 nm. Cellular uptake of the probes verified that they

  6. A case of delayed onset nephrogenic systemic fibrosis after gadolinium based contrast injection.

    PubMed

    Do, Jong Geol; Kim, Young Bum; Lee, Dae Gu; Hwang, Ji Hye

    2012-12-01

    Nephrogenic systemic fibrosis (NSF) is a rare fibrosing disorder of the skin and joints that occurs in patients with advanced renal insufficiency. This condition is progressive and can be seriously disabling. Gadolinium based contrast agent (GBCA) has been identified as a potential cause of this condition. A 56-years-old man in hemodialysis developed stiffness and contracture of the whole limbs eight years after frequent GBCA exposure for cervical magnetic resonance imaging. For the first time in Korea, we report late-onset nephrogenic systemic fibrosis after GBCA exposure and performed an electrophysiologic study of this condition. PMID:23342325

  7. Ligand-free gadolinium oxide for in vivo T1-weighted magnetic resonance imaging.

    PubMed

    Luo, Ningqi; Tian, Xiumei; Yang, Chuan; Xiao, Jun; Hu, Wenyong; Chen, Dihu; Li, Li

    2013-08-01

    Gadolinium oxide (Gd2O3), which can be used as a T1-weighted magnetic resonance imaging (MRI) contrast agent, has attracted intense attention in recent years. In this paper, ligand-free monoclinic Gd2O3 nanocrystals of 7.1 nm in diameter are synthesized by a simple and green approach, namely microsecond laser ablation of a gadolinium (Gd) target in deionized water. These nanocrystals obtain high r1 relaxivity of 5.53 s(-1) mM(-1), and their low toxicity was demonstrated by the cell viability of S18 cells and apoptosis in RAW264.7 cells. In vitro and in vivo MR images show these particles to be good T1-weighted MRI contrast agents. Base on the experimental results and theoretical analysis, we suggest that the purity of the Gd2O3 contributes to its high r1 relaxivity value, while the low toxicity is due to its good crystallinity. These findings show that laser ablation in liquid (LAL) is a promising strategy to synthesize ligand-free monoclinic Gd2O3 nanocrystals for use as high efficient T1-weighted MRI contrast agents.

  8. Biological Agents

    MedlinePlus

    ... to Z Index Contact Us FAQs What's New Biological Agents This page requires that javascript be enabled ... and Health Topics A-Z Index What's New Biological agents include bacteria, viruses, fungi, other microorganisms and ...

  9. Alkali metal and alkali earth metal gadolinium halide scintillators

    DOEpatents

    Bourret-Courchesne, Edith; Derenzo, Stephen E.; Parms, Shameka; Porter-Chapman, Yetta D.; Wiggins, Latoria K.

    2016-08-02

    The present invention provides for a composition comprising an inorganic scintillator comprising a gadolinium halide, optionally cerium-doped, having the formula A.sub.nGdX.sub.m:Ce; wherein A is nothing, an alkali metal, such as Li or Na, or an alkali earth metal, such as Ba; X is F, Br, Cl, or I; n is an integer from 1 to 2; m is an integer from 4 to 7; and the molar percent of cerium is 0% to 100%. The gadolinium halides or alkali earth metal gadolinium halides are scintillators and produce a bright luminescence upon irradiation by a suitable radiation.

  10. Speciation of gadolinium in surface water samples and plants by hydrophilic interaction chromatography hyphenated with inductively coupled plasma mass spectrometry.

    PubMed

    Lindner, Uwe; Lingott, Jana; Richter, Silke; Jakubowski, Norbert; Panne, Ulrich

    2013-02-01

    Hydrophilic interaction chromatography (HILIC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) was optimized for speciation analysis of gadolinium-based contrast agents in environmental samples, in particular surface river waters and plants. Surface water samples from the Teltow channel, near Berlin, were investigated over a distance of 5 km downstream from the influx of a wastewater treatment plant. The total concentration of gadolinium increased significantly from 50 to 990 ng L(-1) due to the influx of the contrast agents. After complete mixing with the river water, the concentration remained constant over a distance of at least 4 km. Two main substances [Dotarem(®) (Gd-DOTA) and Gadovist(®) (Gd-BT-DO3A)] have been identified in the river water using standards. A gadolinium-based contrast agent, possibly Gd-DOTA (Dotarem(®)), was also detected in water plant samples taken from the Teltow channel. Therefore, uptake of contrast agents [Gadovist(®) (Gd-BTDO3A), Magnevist(®) (Gd-DTPA), Omniscan(®) (Gd-DTPA-BMA), Dotarem(®) (Gd-DOTA), and Multihance(®) (Gd-BOPTA)] by plants was investigated in a model experiment using Lepidium sativum (cress plants). HILIC-ICP-MS was used for identification of different contrast agents, and a first approach for quantification using aqueous standard solutions was tested. For speciation analysis, all investigated contrast agents could be extracted from the plant tissues with a recovery of about 54 % for Multihance(®) (Gd-BOPTA) up to 106 % for Gadovist(®) (Gd-BT-DO3A). These experiments demonstrate that all contrast agents investigated are transported from the roots to the leaves where the highest content was measured.

  11. Comparison of inhibition kinetics of several organophosphates, including some nerve agent surrogates, using human erythrocyte and rat and mouse brain acetylcholinesterase.

    PubMed

    Coban, Alper; Carr, Russell L; Chambers, Howard W; Willeford, Kenneth O; Chambers, Janice E

    2016-04-25

    Because testing of nerve agents is limited to only authorized facilities, our laboratory developed several surrogates that resemble nerve agents because they phosphylate the acetylcholinesterase (AChE) with the same moiety as the actual nerve agents. The inhibition kinetic parameters were determined for AChE by surrogates of cyclosarin (NCMP), sarin (NIMP, PIMP and TIMP) and VX (NEMP and TEMP) and other organophosphorus compounds derived from insecticides. All compounds were tested with rat brain and a subset was tested with mouse brain and purified human erythrocyte AChE. Within the compounds tested on all AChE sources, chlorpyrifos-oxon had the highest molecular rate constant followed by NCMP and NEMP. This was followed by NIMP then paraoxon and DFP with rat and mouse brain AChE but DFP was a more potent inhibitor than NIMP and paraoxon with human AChE. With the additional compounds tested only in rat brain, TEMP was slightly less potent than NEMP but more potent than PIMP which was more potent than NIMP. Methyl paraoxon was slightly less potent than paraoxon but more potent than TIMP which was more potent than DFP. Overall, this study validates that the pattern of inhibitory potencies of our surrogates is comparable to the pattern of inhibitory potencies of actual nerve agents (i.e., cyclosarin>VX>sarin), and that these are more potent than insecticidal organophosphates.

  12. Optical properties of gadolinium gallium garnet.

    PubMed

    Wood, D L; Nassau, K

    1990-09-01

    The refractive index, the temperature coefficient of the refractive index, and the optical transparency of gadolinium gallium garnet are reported as a function of wavelength from the near UV to the middle IR. The materialis transparent enough for good optical components between 0.36 and 6.0 microm, and the refractive index ranges from 2.0 at the UV end to 1.8 at the IR end of the spectrum. The wavelength dependence of index is expressed as a three-term Sellmeier formula with agreement better than two parts in the fourth decimal between calculated and experimental values. Variations in composition depending on growth from various melts (e.g., stoichiometric vs congruent) have no effect on the optical parameters at this level of precision.

  13. Regression of gadolinium-enhanced lesions in patients affected by neurofibromatosis type 1.

    PubMed

    Lucchetta, Marta; Manara, Renzo; Perilongo, Giorgio; Clementi, Maurizio; Trevisson, Eva

    2016-03-01

    Neurofibromatosis type I is a genetic condition with an autosomal dominant transmission characterized by neurocutaneous involvement and a predisposition to tumor development. Central nervous system manifestations include benign areas of dysmyelination and possibly hazardous glial tumors whose clinical management may result challenging. Here, we report on three patients diagnosed with Neurofibromatosis type I whose brain MRI follow-up showed the presence of gadolinium-enhancing lesions which spontaneously regressed. In none of the three cases, the lesions showed any clinical correlate and eventually presented a striking reduction in size while gadolinium enhancement disappeared despite no specific therapy administration during the follow-up. Although their nature remains undetermined, these lesions presented a benign evolution. However, they might be misdiagnosed as potentially life-threatening tumors. Hitherto, a similar behavior has been described only in scattered cases and we believe these findings may be of particular interest for the clinical management of patients affected by neurofibromatosis type I.

  14. Synthesis of gadolinium oxide magnetoliposomes for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Roberts, Danielle; Zhu, Weibe L.; Frommen, Christoph M.; Rosenzweig, Zeev

    2000-05-01

    A method for the synthesis of gadolinium oxide magnetoliposomes, i.e., nanosized gadolinium oxide magnetic particles coated by a phospholipid membrane, is presented. Magnetoliposomes were prepared by reacting lauric acid coated gadolinium oxide nanoparticles with dimyristoylphosphatidylcholine liposomes prepared using a direct injection method. The gadolinium oxide magnetoliposomes were characterized using transmission electron microscopy imaging, x-ray diffraction, and fluorescence. The magnetic properties of the magnetoliposomes were investigated with a superconducting quantum interference device magnetometer and nuclear magnetic resonance (NMR) spectrometry. Our results indicate that the magnetoliposomes contain approximately spherical nanoparticles averaging 20 nm in diameter. The occurrence of a phospholipid bilayer surrounding the magnetic particles is confirmed both by transmission electron micrographs of samples negatively stained with uranyl acetate and by digital fluorescence imaging microscopy measurements of magnetoliposomes labeled with fluorescein. The particles are paramagnetic at room temperature. NMR measurements show that the ratio between the relaxivities of the particles depends largely on their preparation.

  15. Hyperintense Dentate Nuclei on T1-Weighted MRI: Relation to Repeat Gadolinium Administration

    PubMed Central

    Adin, M.E.; Kleinberg, L.; Vaidya, D.; Zan, E.; Mirbagheri, S.; Yousem, D.M.

    2016-01-01

    BACKGROUND AND PURPOSE A hyperintense appearance of the dentate nucleus on T1-weighted MR images has been related to various clinical conditions, but the etiology remains indeterminate. We aimed to investigate the possible associations between a hyperintense appearance of the dentate nucleus on T1-weighted MR images in patients exposed to radiation and factors including, but not limited to, the cumulative number of contrast-enhanced MR images, amount of gadolinium administration, dosage of ionizing radiation, and patient demographics. MATERIALS AND METHODS The medical records of 706 consecutive patients who were treated with brain irradiation at The Johns Hopkins Medical Institutions between 1995 and 2010 were blindly reviewed by 2 readers. RESULTS One hundred eighty-four subjects were included for dentate nuclei analysis. Among the 184 subjects who cumulatively underwent 2677 MR imaging studies following intravenous gadolinium administration, 103 patients had hyperintense dentate nuclei on precontrast T1-weighted MR images. The average number of gadolinium-enhanced MR imaging studies performed in the group with normal dentate nuclei was significantly lower than that of the group with hyperintense dentate nuclei. The average follow-up time was 62.5 months. No significant difference was observed between hyperintense and normal dentate nuclei groups in terms of exposed radiation dose, serum creatinine and calcium/phosphate levels, patient demographics, history of chemotherapy, and strength of the scanner. No dentate nuclei abnormalities were found on the corresponding CT scans of patients with hyperintense dentate nuclei (n = 44). No dentate nuclei abnormalities were found in 53 healthy volunteers. CONCLUSIONS Repeat performance of gadolinium-enhanced studies likely contributes to a long-standing hyperintense appearance of dentate nuclei on precontrast T1-weighted-MR images. PMID:26294649

  16. Gadolinium-DTPA enhancement of lung radiation fibrosis

    SciTech Connect

    Werthmuller, W.C.; Schiebler, M.L.; Whaley, R.A.; Mauro, M.A.; McCartney, W.H. )

    1989-11-01

    Gadolinium-diethylenetriamine pentaacetic acid (DTPA) enhancement of radiation-induced apical pulmonary fibrosis was observed in two patients previously treated for breast cancer. In one case the fibrosis was biopsied twice, with no change in its CT appearance over 3 years. Gadolinium-DTPA may enhance benign apical fibrosis after radiation therapy and should not, in and of itself, be used as evidence of recurrent malignancy.

  17. Drosophila modifier screens to identify novel neuropsychiatric drugs including aminergic agents for the possible treatment of Parkinson’s disease and depression

    PubMed Central

    Lawal, Hakeem O.; Terrell, Ashley; Lam, Hoa A.; Djapri, Christine; Jang, Jennifer; Hadi, Richard; Roberts, Logan; Shahi, Varun; Chou, Man-Ting; Biedermann, Traci; Huang, Brian; Lawless, George M.; Maidment, Nigel T.; Krantz, David E.

    2012-01-01

    Small molecules that increase the presynaptic function of aminergic cells may provide neuroprotection in Parkinson’s disease as well as treatments for attention deficit hyperactivity disorder (ADHD) and depression. Model genetic organisms such as Drosophila melanogaster may enhance the detection of new drugs via modifier or “enhancer/suppressor” screens, but this technique has not been applied to processes relevant to psychiatry. To identify new aminergic drugs in vivo, we used a mutation in the Drosophila vesicular monoamine transporter (dVMAT) as a sensitized genetic background, and performed a suppressor screen. We fed dVMAT mutant larvae ~1000 known drugs and quantitated rescue (suppression) of an amine-dependent locomotor deficit in the larva. To determine which drugs might specifically potentiate neurotransmitter release, we performed an additional secondary screen for drugs that require presynaptic amine storage to rescue larval locomotion. Using additional larval locomotion and adult fertility assays, we validated that at least one compound previously used clinically as an antineoplastic agent potentiates the presynaptic function of aminergic circuits. We suggest that structurally similar agents might be used to development treatments for Parkinson’s disease, depression and ADHD and that modifier screens in Drosophila provide a new strategy to screen for neuropsychiatric drugs. More generally, our findings demonstrate the power of physiologically based screens for identifying bioactive agents for select neurotransmitter systems. PMID:23229049

  18. Multifunctional layered gadolinium hydroxide nanoplates for ultrahigh field magnetic resonance imaging, computed tomography and fluorescence bioimaging.

    PubMed

    Wu, Min; Li, Lei; Yu, Xuefeng; Zhang, Daquan; Sun, Tianying; Li, Xue; Sun, Ling; Lui, Su; Huang, Xiaoqi; Bi, Feng; Wang, Huaiyu; Zhu, Hongyan; Gong, Qiyong

    2014-12-01

    The commonly used clinical magnetic resonance imaging (MRI) contrast agents are generally suitable for MR systems with a magnetic field less than 3.0 T. However, these agents show low contrast efficacy for MR systems with ultrahigh fields ≥ 7.0 T, which is the direction that next-generation MRI scanners are heading. A new contrast agent consisting of layered gadolinium hydroxide nanoplates doped with Ce and Tb (LGdH:Ce,Tb NPs) is presented herein. This material exhibits excellent negative (T2) contrast agent efficacy for 7.0 T MRI with a high r2/r1 ratio of 48.80, whereas it exhibits a lower r2/r1 ratio of 30.60 for 3.0 T MRI. Its performance as a T2 contrast agent in ultrahigh field MRI of subcutaneous liver tumor-bearing nude mice is investigated, demonstrating its ability to be used as a negative target T2 contrast agent to distinguish hepatic carcinoma from healthy tissues. Furthermore, the multifunctionality of the LGdH:Ce,Tb NPs as a contrast agent in X-ray computed tomography (CT) and fluorescence bioimaging is also presented, suggesting the possibility of integrating these imaging technologies for in-depth exploration of bioimaging. PMID:26000375

  19. Sensitive and transportable gadolinium-core plastic scintillator sphere for neutron detection and counting

    NASA Astrophysics Data System (ADS)

    Dumazert, Jonathan; Coulon, Romain; Carrel, Frédérick; Corre, Gwenolé; Normand, Stéphane; Méchin, Laurence; Hamel, Matthieu

    2016-08-01

    Neutron detection forms a critical branch of nuclear-related issues, currently driven by the search for competitive alternative technologies to neutron counters based on the helium-3 isotope. The deployment of plastic scintillators shows a high potential for efficient detectors, safer and more reliable than liquids, more easily scalable and cost-effective than inorganic. In the meantime, natural gadolinium, through its 155 and mostly 157 isotopes, presents an exceptionally high interaction probability with thermal neutrons. This paper introduces a dual system including a metal gadolinium core inserted at the center of a high-scale plastic scintillator sphere. Incident fast neutrons are thermalized by the scintillator shell and then may be captured with a significant probability by gadolinium 155 and 157 nuclei in the core. The deposition of a sufficient fraction of the capture high-energy prompt gamma signature inside the scintillator shell will then allow discrimination from background radiations by energy threshold, and therefore neutron detection. The scaling of the system with the Monte Carlo MCNPX2.7 code was carried out according to a tradeoff between the moderation of incident fast neutrons and the probability of slow neutron capture by a moderate-cost metal gadolinium core. Based on the parameters extracted from simulation, a first laboratory prototype for the assessment of the detection method principle has been synthetized. The robustness and sensitivity of the neutron detection principle are then assessed by counting measurement experiments. Experimental results confirm the potential for a stable, highly sensitive, transportable and cost-efficient neutron detector and orientate future investigation toward promising axes.

  20. Gadolinium enhancement patterns of tumefactive demyelinating lesions: correlations with brain biopsy findings and pathophysiology.

    PubMed

    Kobayashi, Masaki; Shimizu, Yuko; Shibata, Noriyuki; Uchiyama, Shinichiro

    2014-10-01

    Tumefactive demyelinating lesions (TDLs) can mimic brain tumors on radiological images. TDLs are often referred to as tumefactive multiple sclerosis (TMS), but the heterogeneous nature and monophasic course of TDLs do not fulfill clinical and magnetic resonance imaging (MRI) criteria for multiple sclerosis. Redefining TDLs, TMS and other inflammatory brain lesions is essential for the accurate clinical diagnosis of extensive demyelinating brain lesions. We retrospectively analyzed MRI from nine TDL cases that underwent brain biopsy. Patterns of gadolinium enhancement on MRI were categorized as homogenous, inhomogeneous, patchy and diffuse, open ring or irregular rim, and were compared with pathological hallmarks including demyelination, central necrosis, macrophage infiltration, angiogenesis and perivascular lymphocytic cuffing. All cases had coexistence of demyelinating features and axonal loss. Open-ring and irregular rim patterns of gadolinium enhancement were associated with macrophage infiltrations and angiogenesis at the inflammatory border. An inhomogeneous pattern of gadolinium enhancement was associated with perivascular lymphocytic cuffing. Central necrosis was seen in cases of severe multiple sclerosis and hemorrhagic leukoencephalopathy. These results suggest that the radiological features of TDLs may be related to different pathological processes, and indicate that MRI may be useful in understanding their pathophysiology. Further investigation is needed to determine the precise disease entity of these inflammatory demyelinating brain lesions.

  1. Electric and magnetic properties of contrast agents for thermoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Ogunlade, Olumide; Beard, Paul

    2014-03-01

    The endogenous contrast in thermoacoustic imaging is due to the water and ionic content in tissue. This results in poor tissue speci city between high water content tissues. As a result, exogenous contrast agents have been employed to improve tissue speci city and also increase the SNR. An investigation into the sources of contrast produced by several exogenous contrast agents is described. These include three gadolinium based MRI contrast agents, iron oxide particles, single wall carbon nanotubes, saline and sucrose solutions. Both the dielectric and magnetic properties of contrast agents at 3GHz have been measured using microwave resonant cavities. The DC conductivity of the contrast agents were also measured. It is shown that the measured increase in dielectric contrast, relative to water, is due to dipole rotational loss of polar non electrolytes, ionic loss of electrolytes or a combination of both. It is shown that for the same dielectric contrast, electrolytes make better thermoacoustic contrast agents than non-electrolytes, for thermoacoustic imaging.

  2. Designing tripodal and triangular gadolinium oxide nanoplates and self-assembled nanofibrils as potential multimodal bioimaging probes.

    PubMed

    Paik, Taejong; Gordon, Thomas R; Prantner, Andrew M; Yun, Hongseok; Murray, Christopher B

    2013-03-26

    Here, we report the shape-controlled synthesis of tripodal and triangular gadolinium oxide (Gd2O3) nanoplates. In the presence of lithium ions, the shape of the nanocrystals is readily controlled by tailoring reaction parameters such as temperature and time. We observe that the morphology transforms from an initial tripodal shape to a triangular shape with increasing reaction time or elevated temperatures. Highly uniform Gd2O3 nanoplates are self-assembled into nanofibril-like liquid-crystalline superlattices with long-range orientational and positional order. In addition, shape-directed self-assemblies are investigated by tailoring the aspect ratio of the arms of the Gd2O3 nanoplates. Due to a strong paramagnetic response, Gd2O3 nanocrystals are excellent candidates for MRI contrast agents and also can be doped with rare-earth ions to form nanophosphors, pointing to their potential in multimodal imaging. In this work, we investigate the MR relaxometry at high magnetic fields (9.4 and 14.1 T) and the optical properties including near-IR to visible upconversion luminescence and X-ray excited optical luminescence of doped Gd2O3 nanoplates. The complex shape of Gd2O3 nanoplates, coupled with their magnetic properties and their ability to phosphoresce under NIR or X-ray excitation which penetrate deep into tissue, makes these nanoplates a promising platform for multimodal imaging in biomedical applications.

  3. Designing Tripodal and Triangular Gadolinium Oxide Nanoplates and Self-Assembled Nanofibrils as Potential Multimodal Bioimaging Probes

    SciTech Connect

    Paik, T; Gordon, TR; Prantner, AM; Yun, H; Murray, CB

    2013-03-01

    Here, we report the shape-controlled synthesis of tripodal and triangular gadolinium oxide (Gd2O3) nanoplates. In the presence of lithium ions, the shape of the nanocrystals is readily controlled by tailoring reaction parameters such as temperature and time. We observe that the morphology transforms from an initial tripodal shape to a triangular shape with increasing reaction time or elevated temperatures. Highly uniform Gd2O3 nanoplates are self-assembled into nanofibril-like liquid-crystalline superlattices with long-range orientational and positional order. In addition, shape-directed self-assemblies are investigated by tailoring the aspect ratio of the arms of the Gd2O3 nanoplates. Due to a strong paramagnetic response, Gd2O3 nanocrystals are excellent candidates for MRI contrast agents and also can be doped with rare-earth ions to form nanophosphors, pointing to their potential in multimodal imaging. In this work, we investigate the MR relaxometry at high magnetic fields (9,4 and 14.1 T) and the optical properties including near-IR to visible upconversion luminescence and X-ray excited optical luminescence of doped Gd2O3 nanoplates. The complex shape of Gd2O3 nanoplates, coupled with their magnetic properties and their ability to phosphoresce under NIR or X-ray excitation which penetrate deep into tissue, makes these nanoplates a promising platform for multimodal imaging in biomedical applications.

  4. Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection.

    PubMed

    Sancey, Lucie; Kotb, Shady; Truillet, Charles; Appaix, Florence; Marais, Arthur; Thomas, Eloïse; van der Sanden, Boudewijn; Klein, Jean-Philippe; Laurent, Blandine; Cottier, Michèle; Antoine, Rodolphe; Dugourd, Philippe; Panczer, Gérard; Lux, François; Perriat, Pascal; Motto-Ros, Vincent; Tillement, Olivier

    2015-03-24

    We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs.

  5. Long-term in vivo clearance of gadolinium-based AGuIX nanoparticles and their biocompatibility after systemic injection.

    PubMed

    Sancey, Lucie; Kotb, Shady; Truillet, Charles; Appaix, Florence; Marais, Arthur; Thomas, Eloïse; van der Sanden, Boudewijn; Klein, Jean-Philippe; Laurent, Blandine; Cottier, Michèle; Antoine, Rodolphe; Dugourd, Philippe; Panczer, Gérard; Lux, François; Perriat, Pascal; Motto-Ros, Vincent; Tillement, Olivier

    2015-03-24

    We previously reported the synthesis of gadolinium-based nanoparticles (NPs) denoted AGuIX (activation and guiding of irradiation by X-ray) NPs and demonstrated their potential as an MRI contrast agent and their efficacy as radiosensitizing particles during X-ray cancer treatment. Here we focus on the elimination kinetics of AGuIX NPs from the subcellular to whole-organ scale using original and complementary methods such as laser-induced breakdown spectroscopy (LIBS), intravital two-photon microscopy, inductively coupled plasma optical emission spectrometry (ICP-OES), transmission electron microscopy (TEM), and electrospray ionization mass spectrometry (ESI-MS). This combination of techniques allows the exact mechanism of AGuIX NPs elimination to be elucidated, including their retention in proximal tubules and their excretion as degraded or native NPs. Finally, we demonstrated that systemic AGuIX NP administration induced moderate and transient effects on renal function. These results provide useful and promising preclinical information concerning the safety of theranostic AGuIX NPs. PMID:25703068

  6. MRI relaxation properties of water-soluble apoferritin-encapsulated gadolinium oxide-hydroxide nanoparticles.

    PubMed

    Sánchez, Purificación; Valero, Elsa; Gálvez, Natividad; Domínguez-Vera, José M; Marinone, Massimo; Poletti, Giulio; Corti, Maurizio; Lascialfari, Alessandro

    2009-02-01

    We have prepared water-soluble gadolinium oxide nanoparticles that show potential as MRI contrast agents. The particles were built into the apoferritin cavity and have an average size of 5 nm. After seven days a loss of 5% of Gd was detected compared with the as-prepared samples; after that the Gd remained constant and stabilized inside the apoferritin, indicating that the apoferritin capsid acts as a Gd store, avoiding metal delivery and consequent toxicity. The NMR longitudinal and transverse relaxivities resulted about 10 and 70 times higher than the ones of clinically approved paramagnetic Gd-chelates, thus indicating the possible route for synthesizing a novel class of MRI contrast agents.

  7. Gadolinium-loaded nanoparticles engineered from microemulsion templates.

    PubMed

    Oyewumi, Moses O; Mumper, Russell J

    2002-03-01

    Microemulsions (oil-in-water) have been used as templates to engineer stable emulsifying wax and Brij 72 (polyoxyl 2 stearyl ether) nanoparticles. The technique is simple, reproducible, and amenable to large-scale production of stable nanoparticles having diameters below 100 nm. Investigation of the process variables showed that the amount of surfactant used in the preparation of microemulsion templates had the greatest influence on the microemulsion window, as well as the properties and stability of the cured nanoparticles. Emulsifying wax and Brij 72 nanoparticles (2 mg/mL) made with 3 mM polyoxyl 20 stearyl ether and 2.3mM polysorbate 80, respectively, were the most stable based on retention of nanoparticle size over time. Gadolinium acetylacetonate (GdAcAc), a potential anticancer agent for neutron capture therapy (NCT), was entrapped in stable nanoparticles. The apparent water solubility of GdAcAc was increased more than 2000-fold by entrapment into nanoparticles. The entrapment efficiency of GdAcAc was about 100% for emulsifying wax nanoparticles and 86% for Brij 72 nanoparticles, as determined by gel permeation chromatography (GPC). Elution profiles were obtained with light scattering (counts per second) to detect nanoparticles and ultraviolet (UV) absorption of GdAcAc at 288 nm. Challenges of these cured nanoparticles in biologically relevant media such as 10% fetal bovine serum, 10 mM phosphate-buffered saline, 150 mM NaCl, and 10% lactose at 37 degrees C for 60 min demonstrated that these nanoparticles are stable. The ease of preparation of these very small and stable nanoparticles, and the ability to entrap lipophilic drugs such as GdAcAc with high efficiency, suggested that these systems may have potential in cell targeting, especially for specific delivery to tumor cells for NCT. PMID:12026224

  8. Gadolinium-loaded nanoparticles engineered from microemulsion templates.

    PubMed

    Oyewumi, Moses O; Mumper, Russell J

    2002-03-01

    Microemulsions (oil-in-water) have been used as templates to engineer stable emulsifying wax and Brij 72 (polyoxyl 2 stearyl ether) nanoparticles. The technique is simple, reproducible, and amenable to large-scale production of stable nanoparticles having diameters below 100 nm. Investigation of the process variables showed that the amount of surfactant used in the preparation of microemulsion templates had the greatest influence on the microemulsion window, as well as the properties and stability of the cured nanoparticles. Emulsifying wax and Brij 72 nanoparticles (2 mg/mL) made with 3 mM polyoxyl 20 stearyl ether and 2.3mM polysorbate 80, respectively, were the most stable based on retention of nanoparticle size over time. Gadolinium acetylacetonate (GdAcAc), a potential anticancer agent for neutron capture therapy (NCT), was entrapped in stable nanoparticles. The apparent water solubility of GdAcAc was increased more than 2000-fold by entrapment into nanoparticles. The entrapment efficiency of GdAcAc was about 100% for emulsifying wax nanoparticles and 86% for Brij 72 nanoparticles, as determined by gel permeation chromatography (GPC). Elution profiles were obtained with light scattering (counts per second) to detect nanoparticles and ultraviolet (UV) absorption of GdAcAc at 288 nm. Challenges of these cured nanoparticles in biologically relevant media such as 10% fetal bovine serum, 10 mM phosphate-buffered saline, 150 mM NaCl, and 10% lactose at 37 degrees C for 60 min demonstrated that these nanoparticles are stable. The ease of preparation of these very small and stable nanoparticles, and the ability to entrap lipophilic drugs such as GdAcAc with high efficiency, suggested that these systems may have potential in cell targeting, especially for specific delivery to tumor cells for NCT.

  9. Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes.

    PubMed

    Abrikossova, Natalia; Skoglund, Caroline; Ahrén, Maria; Bengtsson, Torbjörn; Uvdal, Kajsa

    2012-07-11

    We have previously shown that gadolinium oxide (Gd(2)O(3)) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd(2)O(3) nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd(2)O(3) nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd(2)O(3) nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd(2)O(3) nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.

  10. Effects of gadolinium oxide nanoparticles on the oxidative burst from human neutrophil granulocytes

    NASA Astrophysics Data System (ADS)

    Abrikossova, Natalia; Skoglund, Caroline; Ahrén, Maria; Bengtsson, Torbjörn; Uvdal, Kajsa

    2012-07-01

    We have previously shown that gadolinium oxide (Gd2O3) nanoparticles are promising candidates to be used as contrast agents in magnetic resonance (MR) imaging applications. In this study, these nanoparticles were investigated in a cellular system, as possible probes for visualization and targeting intended for bioimaging applications. We evaluated the impact of the presence of Gd2O3 nanoparticles on the production of reactive oxygen species (ROS) from human neutrophils, by means of luminol-dependent chemiluminescence. Three sets of Gd2O3 nanoparticles were studied, i.e. as synthesized, dialyzed and both PEG-functionalized and dialyzed Gd2O3 nanoparticles. In addition, neutrophil morphology was evaluated by fluorescent staining of the actin cytoskeleton and fluorescence microscopy. We show that surface modification of these nanoparticles with polyethylene glycol (PEG) is essential in order to increase their biocompatibility. We observed that the as synthesized nanoparticles markedly decreased the ROS production from neutrophils challenged with prey (opsonized yeast particles) compared to controls without nanoparticles. After functionalization and dialysis, more moderate inhibitory effects were observed at a corresponding concentration of gadolinium. At lower gadolinium concentration the response was similar to that of the control cells. We suggest that the diethylene glycol (DEG) present in the as synthesized nanoparticle preparation is responsible for the inhibitory effects on the neutrophil oxidative burst. Indeed, in the present study we also show that even a low concentration of DEG, 0.3%, severely inhibits neutrophil function. In summary, the low cellular response upon PEG-functionalized Gd2O3 nanoparticle exposure indicates that these nanoparticles are promising candidates for MR-imaging purposes.

  11. Gd-based macromolecules and nanoparticles as magnetic resonance contrast agents for molecular imaging

    PubMed Central

    Huang, Ching-Hui; Tsourkas, Andrew

    2013-01-01

    As we move towards an era of personalized medicine, molecular imaging contrast agents are likely to see an increasing presence in routine clinical practice. Magnetic resonance (MR) imaging has garnered particular interest as a platform for molecular imaging applications due its ability to monitor anatomical changes concomitant with physiologic and molecular changes. One promising new direction in the development of MR contrast agents involves the labeling and/or loading of nanoparticles with gadolinium (Gd). These nanoplatforms are capable of carrying large payloads of Gd, thus providing the requisite sensitivity to detect molecular signatures within disease pathologies. In this review, we discuss some of the progress that has recently been made in the development of Gd-based macromolecules and nanoparticles and outline some of the physical and chemical properties that will be important to incorporate into the next generation of contrast agents, including high Gd chelate stability, high “relaxivity per particle” and “relaxivity density”, and biodegradability. PMID:23432004

  12. PARTITIONING OF GADOLINIUM IN THE CHEMICAL PROCESSING CELL

    SciTech Connect

    Reboul, S.; Best, D.; Stone, M.; Click, D.

    2011-04-27

    A combination of short-term beaker tests and longer-duration Sludge Receipt and Adjustment Tank (SRAT) simulations were performed to investigate the relative partitioning behaviors of gadolinium and iron under conditions applicable to the Chemical Processing Cell (CPC). The testing was performed utilizing non-radioactive simple Fe-Gd slurries, non-radioactive Sludge Batch 6 simulant slurries, and a radioactive real-waste slurry representative of Sludge Batch 7 material. The testing focused on the following range of conditions: (a) Fe:Gd ratios of 25-100; (b) pH values of 2-6; (c) acidification via addition of nitric, formic, and glycolic acids; (d) temperatures of {approx}93 C and {approx}22 C; and (e) oxalate concentrations of <100 mg/kg and {approx}10,000 mg/kg. The purpose of the testing was to provide data for assessing the potential use of gadolinium as a supplemental neutron poison when dispositioning excess plutonium. Understanding of the partitioning behavior of gadolinium in the CPC was the first step in assessing gadolinium's potential applicability. Significant fractions of gadolinium partitioned to the liquid-phase at pH values of 4.0 and below, regardless of the Fe:Gd ratio. In SRAT simulations targeting nitric and formic acid additions of 150% acid stoichiometry, the pH dropped to a minimum of 3.5-4.0, and the maximum fractions of gadolinium and iron partitioning to solution were both {approx}20%. In contrast, in a SRAT simulation utilizing a nitric and formic acid addition under atypical conditions (due to an anomalously low insoluble solids content), the pH dropped to a minimum of 3.7, and the maximum fractions of gadolinium and iron partitioning to solution were {approx}60% and {approx}70%, respectively. When glycolic acid was used in combination with nitric and formic acids at 100% acid stoichiometry, the pH dropped to a minimum of 3.6-4.0, and the maximum fractions of gadolinium and iron partitioning to solution were 60-80% and 3-5%, respectively

  13. Getting Acquainted: An Induction Training Guide for First-Year Extension Agents. Suggestions for Completing Certain Learning Experiences Included in the Induction Training Guide; a Supplement to "Getting Acquainted."

    ERIC Educational Resources Information Center

    Collings, Mary Louise; Gassie, Edward W.

    An induction guide to help the extension agent get acquainted with his role and suggestions for completing learning experiences that are included in the guide comprise this two-part publication. The training guide learning experiences, a total of 25, are made up of: Objectives of the New Worker; When Completed; Learning Experiences; Person(s)…

  14. Susceptibility-Based Analysis Of Dynamic Gadolinium Bolus Perfusion MRI

    PubMed Central

    Bonekamp, David; Barker, Peter B.; Leigh, Richard; van Zijl, Peter C.M.; Li, Xu

    2014-01-01

    Purpose An algorithm is developed for the reconstruction of dynamic, gadolinium (Gd) bolus MR perfusion images of the human brain, based on quantitative susceptibility mapping (QSM). Methods The method is evaluated in 5 perfusion scans obtained from 4 different patients scanned at 3T, and compared to the conventional analysis based on changes in the transverse relaxation rate ΔR2* and to theoretical predictions. QSM images were referenced to ventricular CSF for each dynamic of the perfusion sequence. Results Images of cerebral blood flow and blood volume were successfully reconstructed from the QSM-analysis, and were comparable to those reconstructed using ΔR2*. The magnitudes of the Gd-associated susceptibility effects in gray and white matter were consistent with theoretical predictions. Conclusion QSM-based analysis may have some theoretical advantages compared to ΔR2*, including a simpler relationship between signal change and Gd concentration. However, disadvantages are its much lower contrast-to-noise ratio, artifacts due to respiration and other effects, and more complicated reconstruction methods. More work is required to optimize data acquisition protocols for QSM-based perfusion imaging. PMID:24604343

  15. Gadolinium metallo nanocongregates as potential magnetosensors for detecting early stage cancers

    SciTech Connect

    Dutta, Ranu; Pandey, Avinash C.

    2015-04-27

    Gadolinium chelates and gadolinium based inorganic nanoparticles have been extensively studied, because of the high magnetic moment of gadolinium. Here, metallic gadolinium nanocongregates have been developed. Upon injecting these nanoparticles in the mice, they initially circulate in the blood stream and are localized at the cancer site, which could be visualized upon application of magnetic field hence acting as small magnetic nanosensors searching for even small cancers, detecting cancers at a very early stage.

  16. High longitudinal relaxivity of ultra-small gadolinium oxide prepared by microsecond laser ablation in diethylene glycol

    NASA Astrophysics Data System (ADS)

    Luo, Ningqi; Tian, Xiumei; Xiao, Jun; Hu, Wenyong; Yang, Chuan; Li, Li; Chen, Dihu

    2013-04-01

    Ultra-small gadolinium oxide (Gd2O3) can be used as T1-weighted Magnetic Resonance Imaging (MRI) contrast agent own to its high longitudinal relaxivity (r1) and has attracted intensive attention in these years. In this paper, ultra-small Gd2O3 nanoparticles of 3.8 nm in diameter have been successfully synthesized by a microsecond laser ablating a gadolinium (Gd) target in diethylene glycol (DEG). The growth inhibition effect induced by the large viscosity of DEG makes it possible to synthesize ultra-small Gd2O3 by laser ablation in DEG. The r1 value and T1-weighted MR images are measured by a 3.0 T MRI spectroscope. The results show these nanoparticles with a high r1 value of 9.76 s-1 mM-1 to be good MRI contrast agents. We propose an explanation for the high r1 value of ultra-small Gd2O3 by considering the decreasing factor (surface to volume ratio of the nanoparticles, S/V) and the increasing factor (water hydration number of the Gd3+ on Gd2O3 surface, q), which offer a new look into the relaxivity studies of MRI contrast agents. Our research provides a new approach to preparing ultra-small Gd2O3 of high r1 value by laser ablation in DEG and develops the understanding of high relaxivity of ultra-small Gd2O3 MRI contrast agents.

  17. Human aortic endothelial cell labeling with positive contrast gadolinium oxide nanoparticles for cellular magnetic resonance imaging at 7 Tesla.

    PubMed

    Loai, Yasir; Sakib, Nurus; Janik, Rafal; Foltz, Warren D; Cheng, Hai-Ling Margaret

    2012-04-01

    Positive T₁ contrast using gadolinium (Gd) contrast agents can potentially improve detection of labeled cells on magnetic resonance imaging (MRI). Recently, gadolinium oxide (Gd₂O₃) nanoparticles have shown promise as a sensitive T₁ agent for cell labeling at clinical field strengths compared to conventional Gd chelates. The objective of this study was to investigate Gado CELLTrack, a commercially available Gd₂O₃ nanoparticle, for cell labeling and MRI at 7 T. Relaxivity measurements yielded r1  =  4.7 s⁻¹ mM⁻¹ and r₂/r₁  =  6.2. Human aortic endothelial cells were labeled with Gd₂O₃ at various concentrations and underwent MRI from 1 to 7 days postlabeling. The magnetic resonance relaxation times T₁ and T₂ of labeled cell pellets were measured. Cellular contrast agent uptake was quantified by inductively coupled plasma-atomic emission spectroscopy, which showed very high uptake compared to conventional Gd compounds. MRI demonstrated significant positive T₁ contrast and stable labeling on cells. Enhancement was optimal at low Gd concentrations, attained in the 0.02 to 0.1 mM incubation concentration range (corresponding cell uptake was 7.26 to 34.1 pg Gd/cell). Cell viability and proliferation were unaffected at the concentrations tested and up to at least 3 days postlabeling. Gd₂O₃ is a promising sensitive and stable positive contrast agent for cellular MRI at 7 T.

  18. Differential passage of gadolinium through the mouse inner ear barriers evaluated with 4.7T MRI.

    PubMed

    Zou, Jing; Zhang, Weikai; Poe, Dennis; Zhang, Ya; Ramadan, Usama Abo; Pyykkö, Ilmari

    2010-01-01

    Magnetic resonance imaging (MRI), supplemented by contrast agents, is a powerful tool that can be used to visualise the structures of the inner ear in vivo and assess some aspects of physiology, such as the permeability of agents through membranes. The mouse is an excellent animal species for investigating human diseases, including hearing loss but detailed MRI studies with contrast have not been reported. In this work, we aimed to demonstrate the limits of MR imaging resolution of the fine inner ear structures in the mouse and to explore the permeability of the intracochlear barriers to gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) administered by intravenous injection (IV) or intratympanic (IT) routes. Twenty-three female FVB mice were imaged with a 4.7-T MR scanner using both 2D and high resolution 3D sequences. Inner ear region of interest (ROI) signal intensities and perilymph volumes were evaluated. Finer structures were studied using 3D acquisition and reconstruction techniques and comparisons were made to similarly oriented histological sections that were examined by light microscopy. Gd-DOTA enhancement occurred in the perilymphatic compartment and highlighted the contiguous inner ear structures, but enhancement did not appear within the endolymph. The dynamic uptake of Gd-DOTA in the perilymphatic compartments reached an initial plateau 80min after IV administration and continued to slightly increase to a maximum level by 100min. The perilymph volume demonstrated by Gd-DOTA uptake was statistically significantly larger in the IV group (1.72mm(3)) than in the IT group (1.28mm(3)) (p<0.05).

  19. Relaxivity enhancement of aquated Tris(β-diketonate)gadolinium(III) chelates by confinement within ultrashort single-walled carbon nanotubes.

    PubMed

    Law, Justin J; Guven, Adem; Wilson, Lon J

    2014-01-01

    Ultrashort single-walled carbon nanotubes loaded with gadolinium ions (gadonanotubes) have been previously shown to exhibit extremely high T1 -weighted relaxivities (>100 mm(-1) s(-1) ). To further examine the effect of nanoconfinement on the relaxivity of gadolinium-based contrast agents for magnetic resonance imaging, a series of ultrashort single-walled carbon nanotube (US-tube) materials internally loaded with gadolinium chelates have been prepared and studied. US-tubes were loaded with Gd(acac)3  · 2H2 O, Gd(hfac)3  · 2H2 O, and Gd(thd)3 (acac = acetylacetone, hfac = hexafluoroacetylacetone, thd = tetramethylheptanedione). The longitudinal relaxivities of the prepared materials determined at 25°C in a 1.5 T field were 103 mm(-1) s(-1) for Gd(acac)3  · 2H2 O@US-tubes, 105 mm(-1) s(-1) for Gd(hfac)3  · 2H2 O@US-tubes and 26 mm(-1) s(-1) for Gd(thd)3 @US-tubes. Compared with the relaxivities obtained for the unloaded chelates (<10 mm(-1) s(-1) ) as well as accounting for the T1 reduction observed for the empty US-tubes, the boost in relaxivity for chelate-loaded US-tubes is attributed to confinement within the nanotube and depends on the number of coordinated water molecules.

  20. Growth of bulk gadolinium pyrosilicate single crystals for scintillators

    NASA Astrophysics Data System (ADS)

    Gerasymov, I.; Sidletskiy, O.; Neicheva, S.; Grinyov, B.; Baumer, V.; Galenin, E.; Katrunov, K.; Tkachenko, S.; Voloshina, O.; Zhukov, A.

    2011-03-01

    Ce, Pr, and La-doped gadolinium pyrosilicate Gd2Si2O7 (GPS) single crystals were grown by the Czochralski and Top Seeded Solution Growth (TSSG) techniques for the first time. Formation conditions of different pyrosilicate phases were determined. X-ray luminescence integral intensity of Ce-doped GPS is about one order of magnitude higher in comparison with gadolinium oxyorthosilicate Gd2SiO5:Ce (GSO:Ce). All samples demonstrate temperature stability of luminescence yield up to 400 K.

  1. MRI Contrast Agents: Evolution of Clinical Practice and Dose Optimization.

    PubMed

    Khan, Rihan

    2016-08-01

    Accurate detection of lesions throughout the body is of paramount importance in contrast-enhanced magnetic resonance imaging (MRI). Optimal contrast agent performance is therefore of great importance and given the number of MRI contrast agent options today, this topic is of much ongoing study. The goal of this review article is to bring the read up to date on pertinent articles that relate to the evolution of radiological clinical practice and dose optimization pertaining to gadolinium contrast agents. PMID:27367313

  2. A feasibility study to determine the potential of in vivo detection of gadolinium by x-ray fluorescence (XRF) following gadolinium-based contrast-enhanced MRI.

    PubMed

    Mostafaei, F; McNeill, F E; Chettle, D R; Noseworthy, M D

    2015-01-01

    The feasibility of using a (109)Cd γ-ray induced K x-ray fluorescence (K-XRF) system for the in vivo detection of gadolinium (Gd) in bone has been investigated. The K-XRF bone measurement system employs an array of four detectors, and is normally used for the non-invasive study of bone lead levels. The system was used to measure bone simulating phantoms doped with varying levels of gadolinium and fixed amounts of sodium (Na), chlorine (Cl) and calcium (Ca). The detection limits for bare bone phantoms, using a source of activity 0.17 GBq, were determined to be 3.9 ppm and 6.5 ppm (µg Gd per gram phantom) for the Kα1 and Kα2 Gd x-ray peaks, respectively. This leads to an overall detection limit of 3.3 ppm (µg Gd per gram phantom). Layers of plastic were used to simulate overlying soft tissue and this permitted prediction of a detection limit, using the current strength of our radioisotope source, of 6.1 ppm to 8.6 ppm (µg Gd per gram phantom) for fingers with 2-4 mm of overlying tissue. With a new source of activity 5 GBq, we predict that this system could achieve a detection limit of 4-5.6 µg Gd g(-1) Ca. This is within the range of levels (2-30 µg Gd g(-1) Ca) previously found in the bone of patients receiving Gd based contrast imaging agents. The technique is promising and warrants further investigation.

  3. Enhancements in hepatobiliary imaging: the spectrum of gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid usages in hepatobiliary magnetic resonance imaging.

    PubMed

    Channual, Stephanie; Pahwa, Anokh; Lu, David S; Raman, Steven S

    2016-09-01

    Gadolinium-ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA) is a unique hepatocyte-specific contrast agent approved for clinical use in the United States in 2008. Gd-EOB-DTPA-enhanced MR has shown to improve detection and characterization of hepatic lesions. Gd-EOB-DTPA is now being routinely used in daily clinical practice worldwide. Therefore, it is important for radiologists to be familiar with the potential uses and pitfalls of Gd-EOB-DTPA, which extends beyond the assessment of focal hepatic lesions. The purpose of this article is to review the various usages of Gd-EOB-DTPA in hepatobiliary MR imaging. PMID:27225503

  4. Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

    SciTech Connect

    Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; Vohra, Yogesh K.

    2014-11-07

    High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperature of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.

  5. Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

    DOE PAGESBeta

    Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; Vohra, Yogesh K.

    2014-11-07

    High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Smtype→ dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GP and a temperaturemore » of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Furthermore, our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.« less

  6. Structural and magnetic phase transitions in gadolinium under high pressures and low temperatures

    NASA Astrophysics Data System (ADS)

    Samudrala, Gopi K.; Tsoi, Georgiy M.; Weir, Samuel T.; Vohra, Yogesh K.

    2014-10-01

    High pressure structural transition studies have been carried out on rare earth metal gadolinium in a diamond anvil cell at room temperature to 169 GPa. Gadolinium has been compressed to 38% of its initial volume at this pressure. With increasing pressure, a crystal structure sequence of hcp → Sm-type → dhcp → fcc → dfcc → monoclinic has been observed in our studies on gadolinium. The measured equation of state of gadolinium is presented to 169 GPa at ambient temperature. Magnetic ordering temperature of gadolinium has been studied using designer diamond anvils to a pressure of 25 GPa and a temperature of 10 K. The magnetic ordering temperature has been determined from the four-point electrical resistivity measurements carried out on gadolinium. Our experiments show that the magnetic transition temperature decreases with increasing pressure to 19 GPa and then increases when gadolinium is subjected to higher pressures.

  7. Purification of cerium, neodymium and gadolinium for low background experiments

    NASA Astrophysics Data System (ADS)

    Boiko, R. S.; Barabash, A. S.; Belli, P.; Bernabei, R.; Cappella, F.; Cerulli, R.; Danevich, F. A.; Incicchitti, A.; Laubenstein, M.; Mokina, V. M.; Nisi, S.; Poda, D. V.; Polischuk, O. G.; Tretyak, V. I.

    2014-01-01

    Cerium, neodymium and gadolinium contain double beta active isotopes. The most interesting are 150Nd and 160Gd (promising for 0ν2β search), 136Ce (2β+ candidate with one of the highest Q2β). The main problem of compounds containing lanthanide elements is their high radioactive contamination by uranium, radium, actinium and thorium. The new generation 2β experiments require development of methods for a deep purification of lanthanides from the radioactive elements. A combination of physical and chemical methods was applied to purify cerium, neodymium and gadolinium. Liquid-liquid extraction technique was used to remove traces of Th and U from neodymium, gadolinium and for purification of cerium from Th, U, Ra and K. Co-precipitation and recrystallization methods were utilized for further reduction of the impurities. The radioactive contamination of the samples before and after the purification was tested by using ultra-low-background HPGe gamma spectrometry. As a result of the purification procedure the radioactive contamination of gadolinium oxide (a similar purification efficiency was reached also with cerium and neodymium oxides) was decreased from 0.12 Bq/kg to 0.007 Bq/kg in 228Th, from 0.04 Bq/kg to <0.006 Bq/kg in 226Ra, and from 0.9 Bq/kg to 0.04 Bq/kg in 40K. The purification methods are much less efficient for chemically very similar radioactive elements like actinium, lanthanum and lutetium.

  8. Development of gadolinium based nanoparticles having an affinity towards melanin

    NASA Astrophysics Data System (ADS)

    Morlieras, Jessica; Chezal, Jean-Michel; Miot-Noirault, Elisabeth; Roux, Amandine; Heinrich-Balard, Laurence; Cohen, Richard; Tarrit, Sébastien; Truillet, Charles; Mignot, Anna; Hachani, Roxanne; Kryza, David; Antoine, Rodolphe; Dugourd, Philippe; Perriat, Pascal; Janier, Marc; Sancey, Lucie; Lux, François; Tillement, Olivier

    2013-01-01

    Small Rigid Platforms (SRPs) are sub-5 nanometre gadolinium based nanoparticles that have been developed for multimodal imaging and theranostic applications. They are composed of a polysiloxane network surrounded by gadolinium chelates. A covalent coupling with quinoxaline derivatives has been performed. Such derivatives have proven their affinity for melanin frequently expressed in primary melanoma cases. Three different quinoxaline derivatives have been synthesised and coupled to the nanoparticles. The affinity of the grafted nanoparticles for melanin has then been shown in vitro by surface plasmon resonance on a homemade melanin grafted gold chip.Small Rigid Platforms (SRPs) are sub-5 nanometre gadolinium based nanoparticles that have been developed for multimodal imaging and theranostic applications. They are composed of a polysiloxane network surrounded by gadolinium chelates. A covalent coupling with quinoxaline derivatives has been performed. Such derivatives have proven their affinity for melanin frequently expressed in primary melanoma cases. Three different quinoxaline derivatives have been synthesised and coupled to the nanoparticles. The affinity of the grafted nanoparticles for melanin has then been shown in vitro by surface plasmon resonance on a homemade melanin grafted gold chip. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr33457g

  9. Gadolinium chloride pretreatment ameliorates acute cadmium-induced hepatotoxicity.

    PubMed

    Kyriakou, Loukas G; Tzirogiannis, Konstantinos N; Demonakou, Maria D; Kourentzi, Kalliopi T; Mykoniatis, Michael G; Panoutsopoulos, Georgios I

    2013-08-01

    Cadmium is a known industrial and environmental pollutant. It causes hepatotoxicity upon acute administration. Features of cadmium-induced acute hepatoxicity encompass necrosis, apoptosis, peliosis and inflammatory infiltration. Gadolinium chloride (GdCl3) may prevent cadmium-induced hepatotoxicity by suppressing Kupffer cells. The effect of GdCl3 pretreatment on a model of acute cadmium-induced liver injury was investigated. Male Wistar rats 4-5 months old were injected intraperitoneally with normal saline followed by cadmium chloride (CdCl2; 6.5 mg/kg) or GdCl3 (10 mg/kg) followed by CdCl2 (6.5 mg/kg; groups I and II, respectively). Rats of both the groups were killed at 9, 12, 16, 24, 48 and 60 h after cadmium intoxication. Liver sections were analyzed for necrosis, apoptosis, peliosis and mitoses. Liver regeneration was also evaluated by tritiated thymidine incorporation into hepatic DNA. Serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were also determined. Hepatic necrosis, hepatocyte and nonparenchymal cell apoptosis and macroscopic and microscopic types of peliosis hepatis were minimized by gadolinium pretreatment. Serum levels of AST and ALT were also greatly diminished in rats of group II. Tritiated thymidine incorporation into hepatic DNA was increased in gadolinium pretreatment rats. Kupffer cell activation was minimal in both the groups of rats. Gadolinium pretreatment attenuates acute cadmium-induced liver injury in young Wistar rats, with mechanisms other than Kupffer cell elimination.

  10. Fluorescent single-stranded DNA-based assay for detecting unchelated Gadolinium(III) ions in aqueous solution.

    PubMed

    Edogun, Osafanmwen; Nguyen, Nghia Huu; Halim, Marlin

    2016-06-01

    The main concern pertaining to the safety of Gadolinium(III)-based contrast agents (GBCAs) is the toxicity caused by the unchelated ion, which may be inadvertently present in the solution due most commonly to excess unreacted starting material or dissociation of the complexes. Detecting the aqueous free ion during the synthesis and preparation of GBCA solutions is therefore instrumental in ensuring the safety of the agents. This paper reports the development of a sensitive fluorogenic sensor for aqueous unchelated Gadolinium(III) (Gd(III)). Our design utilizes single-stranded oligodeoxynucleotides with a specific sequence of 44 bases as the targeting moiety. The fluorescence-based assay may be run at ambient pH with very small amounts of samples in 384-well plates. The sensor is able to detect nanomolar concentration of Gd(III), and is relatively unresponsive toward a range of biologically relevant ions and the chelated Gd(III). Although some cross-reactivity with other trivalent lanthanide ions, such as Europium(III) and Terbium(III), is observed, these are not commonly found in biological systems and contrast agents. This convenient and rapid method may be useful in ascertaining a high purity of GBCA solutions. Graphical abstract Fluorescent aptamer-based assay for detecting unchelated Ln(III) ions in aqueous solution. PMID:27071762

  11. Atherosclerotic neovasculature MR imaging with mixed manganese-gadolinium nanocolloids in hyperlipidemic rabbits.

    PubMed

    Wang, Kezheng; Pan, Dipanjan; Schmieder, Anne H; Senpan, Angana; Caruthers, Shelton D; Cui, Grace; Allen, John S; Zhang, Huiying; Shen, Baozhong; Lanza, Gregory M

    2015-04-01

    A high r1 relaxivity manganese-gadolinium nanocolloid (αvβ3-MnOL-Gd NC) was developed and effectively detected atherosclerotic angiogenesis in rabbits fed cholesterol-rich diets for 12 months using a clinical MRI scanner (3T). 3D mapping of neovasculature signal intensity revealed the spatial coherence and intensity of plaque angiogenic expansion, which may, with other high risk MR bioindicators, help identify high-risk patients with moderate (40% to 60%) vascular stenosis. Microscopy confirmed the predominant media and plaque distribution of fluorescent αvβ3-MnOL-Gd NC, mirroring the MR data. An expected close spatial association of αvβ3-integrin neovasculature and macrophages was noted, particularly within plaque shoulder regions. Manganese oleate bioelimination occurred via the biliary system into feces. Gd-DOTA was eliminated through the bile-fecal and renal excretion routes. αvβ3-MnOL-Gd NC offers an effective vehicle for T1w neovascular imaging in atherosclerosis. From the clinical editor: Cerebrovascular accidents are a leading cause of mortality and morbidity worldwide. The acute formation of thrombus following atherosclerotic plaque rupture has been well recognized as the etiology of stroke. The authors studied microanatomical features of vulnerable atherosclerotic plaque in this article, in an attempt to identify those with high risk of rupture. Gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) was developed as a novel contrast agent for MRI. They show that this agent is effective in providing neovascular imaging.

  12. Progressive increase of T1 signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast.

    PubMed

    Roberts, Donna R; Holden, Kenton R

    2016-03-01

    Recently, there have been reports of gadolinium accumulation in the brain and bone of adult patients with normal renal function who have undergone multiple gadolinium contrast administrations. This case report gives the first description of a pediatric patient who, following multiple contrasted MRI exams, demonstrated abnormal signal on unenhanced T1-weighted imaging involving the dentate nucleus and globus pallidus, a finding which has previously been shown to represent gadolinium deposition in adults. The patient presented here had no history of intracranial pathology which would alter the blood brain barrier or abnormal renal function. The clinical significance of gadolinium accumulation in the human body is currently unknown but is of concern, particularly in pediatric patients who have a lifetime to manifest any potential adverse consequences. Therefore, research is needed to address the clinical significance, if any, of gadolinium deposition in the developing pediatric brain. Given these current uncertainties, clinicians should continue to use prudence in selecting pediatric patients to undergo contrasted MRI and in selecting the appropriate contrast agents to use. PMID:26345358

  13. Progressive increase of T1 signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in the pediatric brain exposed to multiple doses of gadolinium contrast.

    PubMed

    Roberts, Donna R; Holden, Kenton R

    2016-03-01

    Recently, there have been reports of gadolinium accumulation in the brain and bone of adult patients with normal renal function who have undergone multiple gadolinium contrast administrations. This case report gives the first description of a pediatric patient who, following multiple contrasted MRI exams, demonstrated abnormal signal on unenhanced T1-weighted imaging involving the dentate nucleus and globus pallidus, a finding which has previously been shown to represent gadolinium deposition in adults. The patient presented here had no history of intracranial pathology which would alter the blood brain barrier or abnormal renal function. The clinical significance of gadolinium accumulation in the human body is currently unknown but is of concern, particularly in pediatric patients who have a lifetime to manifest any potential adverse consequences. Therefore, research is needed to address the clinical significance, if any, of gadolinium deposition in the developing pediatric brain. Given these current uncertainties, clinicians should continue to use prudence in selecting pediatric patients to undergo contrasted MRI and in selecting the appropriate contrast agents to use.

  14. Gadolinium oxide nanoplates with high longitudinal relaxivity for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Cho, Minjung; Sethi, Richa; Ananta Narayanan, Jeyarama Subramanian; Lee, Seung Soo; Benoit, Denise N.; Taheri, Nasim; Decuzzi, Paolo; Colvin, Vicki L.

    2014-10-01

    Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values moderately reduce as the size of the Gd2O3 nanoplates increases, and are always larger for the PAA-OA coating. Cytotoxicity studies on human dermal fibroblast cells documented no significant toxicity, with 100% cell viability preserved up to 250 μM for the PAA-OA coated Gd2O3 nanoplates. Given the 10 times increase in longitudinal relaxivity over the commercially available Gd-based molecular agents and the favorable toxicity profile, the 2 nm PAA-OA coated Gd2O3 nanoplates could represent a new class of highly effective T1 MRI contrast agents.Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)-1 were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values

  15. Magnetic Resonance Imaging of Therapy-Induced Necrosis Using Gadolinium-Chelated Polyglutamic Acids

    SciTech Connect

    Jackson, Edward F.; Esparza-Coss, Emilio; Wen Xiaoxia; Ng, Chaan S.; Daniel, Sherita L.; Price, Roger E.; Rivera, Belinda; Charnsangavej, Chusilp; Gelovani, Juri G.; Li Chun . E-mail: cli@di.mdacc.tmc.edu

    2007-07-01

    Purpose: Necrosis is the most common morphologic alteration found in tumors and surrounding normal tissues after radiation therapy or chemotherapy. Accurate measurement of necrosis may provide an early indication of treatment efficacy or associated toxicity. The purpose of this report is to evaluate the selective accumulation of polymeric paramagnetic magnetic resonance (MR) contrast agents-gadolinium p-aminobenzyl-diethylenetriaminepentaacetic acid-poly(glutamic acid) (L-PG-DTPA-Gd and D-PG-DTPA-Gd)-in necrotic tissue. Methods and Materials: Two different solid tumor models, human Colo-205 xenograft and syngeneic murine OCA-1 ovarian tumors, were used in this study. Necrotic response was induced by treatment with poly(L-glutamic acid)-paclitaxel conjugate (PG-TXL). T{sub 1}-weighted spin-echo images were obtained immediately and up to 4 days after contrast injection and compared with corresponding histologic specimens. Two low-molecular-weight contrast agents, DTPA-Gd and oligomeric(L-glutamic acid)-DTPA-Gd, were used as nonspecific controls. Results: Initially, there was minimal tumor enhancement after injection of either L-PG-DTPA-Gd or D-PG-DTPA-Gd, but rapid enhancement after injection of low-molecular-weight agents. However, polymeric contrast agents, but not low-molecular-weight contrast agents, caused sustained enhancement in regions of tumor necrosis in both tumors treated with PG-TXL and untreated tumors. These data indicate that high molecular weight, rather than in vivo biodegradation, is necessary for the specific localization of polymeric MR contrast agents to necrotic tissue. Moreover, biotinylated L-PG-DTPA-Gd colocalized with macrophages in the tumor necrotic areas, suggesting that selective accumulation of L- and D-PG-DTPA-Gd in necrotic tissue was mediated through residing macrophages. Conclusions: Our data suggest that MR imaging with PG-DTPA-Gd may be a useful technique for noninvasive characterization of treatment-induced necrosis.

  16. The study of in vivo x-ray fluorescence (XRF) technique for gadolinium (Gd) measurements in human bone

    NASA Astrophysics Data System (ADS)

    Mostafaei, F.; Nie, L. H.

    2016-08-01

    An in vivo K x-ray fluorescence system, based on 109Cd source, for the detection of gadolinium has been investigated. Gd is of interest because of the extensive use of Gd-based contrast agents in MR imaging. A human simulating bone phantom set has been developed. The phantoms were doped with seven concentrations of Gd. Additional elements important for in vivo x-ray fluorescence, Na, Cl and Ca, were also included to create an overall elemental composition consistent with the Reference Man. A new 5 GBq 109Cd source was purchased to improve the source activity in comparison to the previous study (0.17 GBq). The previously published minimum detection limit (MDL) for Gd phantom measurements using KXRF system was 3.3 ppm. In this study the minimum detection limit for bare bone phantoms was found to reduce the MDL to 0.8, a factor of 4.1. The previous published data used only three layers of plastic as soft tissue equivalent materials and found the MDL of 4–4.8 ppm. In this study we have used the plastic with more realistic thicknesses to simulate a soft tissue at tibia. The detection limits for phantoms with Lucite as a tissue equivalent, using a new source, was determined to be 1.81 to 3.47 ppm (μg Gd per gram phantom). Our next study would be testing an in vivo K x-ray fluorescence system, based on 109Cd source on human volunteers who went through MR imaging and were injected by Gd.

  17. The study of in vivo x-ray fluorescence (XRF) technique for gadolinium (Gd) measurements in human bone

    NASA Astrophysics Data System (ADS)

    Mostafaei, F.; Nie, L. H.

    2016-08-01

    An in vivo K x-ray fluorescence system, based on 109Cd source, for the detection of gadolinium has been investigated. Gd is of interest because of the extensive use of Gd-based contrast agents in MR imaging. A human simulating bone phantom set has been developed. The phantoms were doped with seven concentrations of Gd. Additional elements important for in vivo x-ray fluorescence, Na, Cl and Ca, were also included to create an overall elemental composition consistent with the Reference Man. A new 5 GBq 109Cd source was purchased to improve the source activity in comparison to the previous study (0.17 GBq). The previously published minimum detection limit (MDL) for Gd phantom measurements using KXRF system was 3.3 ppm. In this study the minimum detection limit for bare bone phantoms was found to reduce the MDL to 0.8, a factor of 4.1. The previous published data used only three layers of plastic as soft tissue equivalent materials and found the MDL of 4-4.8 ppm. In this study we have used the plastic with more realistic thicknesses to simulate a soft tissue at tibia. The detection limits for phantoms with Lucite as a tissue equivalent, using a new source, was determined to be 1.81 to 3.47 ppm (μg Gd per gram phantom). Our next study would be testing an in vivo K x-ray fluorescence system, based on 109Cd source on human volunteers who went through MR imaging and were injected by Gd.

  18. Gadolinium oxide nanoplates with high longitudinal relaxivity for magnetic resonance imaging.

    PubMed

    Cho, Minjung; Sethi, Richa; Narayanan, Jeyarama Subramanian Ananta; Lee, Seung Soo; Benoit, Denise N; Taheri, Nasim; Decuzzi, Paolo; Colvin, Vicki L

    2014-11-21

    Molecular-based contrast agents for magnetic resonance imaging (MRI) are often characterized by insufficient relaxivity, thus requiring the systemic injection of high doses to induce sufficient contrast enhancement at the target site. In this work, gadolinium oxide (Gd2O3) nanoplates are produced via a thermal decomposition method. The nanoplates have a core diameter varying from 2 to 22 nm, a thickness of 1 to 2 nm and are coated with either an oleic acid bilayer or an octylamine modified poly(acrylic acid) (PAA-OA) polymer layer. For the smaller nanoplates, longitudinal relaxivities (r1) of 7.96 and 47.2 (mM s)(-1) were measured at 1.41 T for the oleic acid bilayer and PAA-OA coating, respectively. These values moderately reduce as the size of the Gd2O3 nanoplates increases, and are always larger for the PAA-OA coating. Cytotoxicity studies on human dermal fibroblast cells documented no significant toxicity, with 100% cell viability preserved up to 250 μM for the PAA-OA coated Gd2O3 nanoplates. Given the 10 times increase in longitudinal relaxivity over the commercially available Gd-based molecular agents and the favorable toxicity profile, the 2 nm PAA-OA coated Gd2O3 nanoplates could represent a new class of highly effective T1 MRI contrast agents.

  19. Hepatocellular carcinoma: conventional MRI findings including gadolinium-enhanced dynamic imaging.

    PubMed

    Ito, Katsuyoshi

    2006-05-01

    A great variety of MR pulse sequences for hepatocellular carcinomas (HCCs) are now available. In this article, we reviewed the current MR imaging techniques that are routinely used for hepatic imaging, and described the optimization of these sequences as well as the utility and characteristics of each sequence for the accurate diagnosis of HCCs. Then, we reviewed various MR imaging findings of advanced and early HCCs with emphasis on signal intensity and hemodynamic patterns. Finally, we described the value of multi-arterial-phase contrast-enhanced dynamic MR imaging of the whole liver with excellent temporal resolution for evaluating transitional hemodynamics of hepatic lesions during the six arterial phases.

  20. Anti-inflammatory effects of praseodymium, gadolinium and ytterbium chlorides.

    PubMed

    Basile, A C; Hanada, S; Sertié, J A; Oga, S

    1984-02-01

    Anti-inflammatory effects of chloride salts of praseodymium, gadolinium and ytterbium were investigated, using various experimental inflammatory models in rats. The lanthanide salts administered by oral route showed no significant effect, but when injected intraperitoneally they significantly inhibited the carrageenin-induced oedema, proportional to their doses ranging from 15 to 75 mg/kg. They also reduced nystatin-induced oedema and vascular permeability response to histamine and serotonin. Pronounced inhibitory effect of lanthanide salts at the dose of 50 mg/kg, i.p., was observed in histamine- and serotonin-induced changes in vascular permeability. Repeated administration of lanthanide salts in the dose of 20 mg/kg for 13 d significantly inhibited arthritis development. The same dose of these salts for a 6-d period similarly reduced granuloma formation. However, praseodymium, gadolinium and ytterbium chlorides showed no significant difference among themselves and their anti-inflammatory effects were smaller than those from phenylbutazone.

  1. About a Gadolinium-doped Water Cherenkov LAGUNA Detector

    SciTech Connect

    Labarga, Luis

    2010-11-24

    Water Cherenkov (wC) detectors are extremely powerful apparatuses for scientific research. Nevertheless they lack of neutron tagging capabilities, which translates, mainly, into an inability to identify the anti-matter nature of the reacting incoming anti-neutrino particles. A solution was proposed by R. Beacon and M. Vagins back in 2004: by dissolving in the water a compound with nucleus with very large cross section for neutron capture like the Gadolinium, with a corresponding emission of photons of enough energy to be detected, they can tag thermal neutrons with an efficiency larger than 80%. In this talk we detail the technique and its implications in the measurement capabilities and, as well, the new backgrounds induced. We discuss the improvement on their physics program, also for the case of LAGUNA type detectors. We comment shortly the status of the pioneering R and D program of the Super-Kamiokande Collaboration towards dissolving a Gadolinium compound in its water.

  2. Gadolinium-enhanced magnetic resonance angiography in brain death

    NASA Astrophysics Data System (ADS)

    Luchtmann, M.; Beuing, O.; Skalej, M.; Kohl, J.; Serowy, S.; Bernarding, J.; Firsching, R.

    2014-01-01

    Confirmatory tests for the diagnosis of brain death in addition to clinical findings may shorten observation time required in some countries and may add certainty to the diagnosis under specific circumstances. The practicability of Gadolinium-enhanced magnetic resonance angiography to confirm cerebral circulatory arrest was assessed after the diagnosis of brain death in 15 patients using a 1.5 Tesla MRI scanner. In all 15 patients extracranial blood flow distal to the external carotid arteries was undisturbed. In 14 patients no contrast medium was noted within intracerebral vessels above the proximal level of the intracerebral arteries. In one patient more distal segments of the anterior and middle cerebral arteries (A3 and M3) were filled with contrast medium. Gadolinium-enhanced MRA may be considered conclusive evidence of cerebral circulatory arrest, when major intracranial vessels fail to fill with contrast medium while extracranial vessels show normal blood flow.

  3. Solid-state gadolinium{endash}magnesium hydride optical switch

    SciTech Connect

    Armitage, R.; Rubin, M.; Richardson, T.; OBrien, N.; Chen, Y.

    1999-09-01

    The optical switching properties of gadolinium{endash}magnesium hydride have been demonstrated in a solid-state electrochromic device. With positive polarization of the hydride electrode, the visible reflectance approaches 35{percent} with virtually zero transmission, while with negative polarization, the visible transmission exceeds 25{percent} at 650 nm. The switching is reversible, with intermediate optical properties between the transparent and reflecting states. {copyright} {ital 1999 American Institute of Physics.}

  4. Magnons as a Bose-Einstein Condensate in Nanocrystalline Gadolinium

    SciTech Connect

    Kaul, S. N.; Mathew, S. P.

    2011-06-17

    The recent observation [S. P. Mathew et al., J. Phys. Conf. Ser. 200, 072047 (2010)] of the anomalous softening of spin-wave modes at low temperatures in nanocrystalline gadolinium is interpreted as a Bose-Einstein condensation (BEC) of magnons. A self-consistent calculation, based on the BEC picture, is shown to closely reproduce the observed temperature variations of magnetization and specific heat at constant magnetic fields.

  5. Late Gadolinium Enhancement Among Survivors of Sudden Cardiac Arrest

    PubMed Central

    Neilan, Tomas G.; Farhad, Hoshang; Mayrhofer, Thomas; Shah, Ravi V.; Dodson, John A.; Abbasi, Siddique A.; Danik, Stephan B.; Verdini, Daniel J.; Tokuda, Michifumi; Tedrow, Usha B.; Jerosch-Herold, Michael; Hoffmann, Udo; Ghoshhajra, Brian B.; Stevenson, William G.; Kwong, Raymond Y.

    2016-01-01

    OBJECTIVES The aim of this study was to describe the role of contrast-enhanced cardiac magnetic resonance (CMR) in the workup of patients with aborted sudden cardiac arrest (SCA) and in the prediction of long-term outcomes. BACKGROUND Myocardial fibrosis is a key substrate for SCA, and late gadolinium enhancement (LGE) on a CMR study is a robust technique for imaging of myocardial fibrosis. METHODS We performed a retrospective review of all survivors of SCA who were referred for CMR studies and performed follow-up for the subsequent occurrence of an adverse event (death and appropriate defibrillator therapy). RESULTS After a workup that included a clinical history, electrocardiogram, echocardiography, and coronary angiogram, 137 patients underwent CMR for workup of aborted SCA (66% male; mean age 56 ± 11 years; left ventricular ejection fraction 43 ± 12%). The presenting arrhythmias were ventricular fibrillation (n = 105 [77%]) and ventricular tachycardia (n = 32 [23%]). Overall, LGE was found in 98 patients (71%), with an average extent of 9.9 ± 5% of the left ventricular myocardium. CMR imaging provided a diagnosis or an arrhythmic substrate in 104 patients (76%), including the presence of an infarct-pattern LGE in 60 patients (44%), noninfarct LGE in 21 (15%), active myocarditis in 14 (10%), hypertrophic cardiomyopathy in 3 (2%), sarcoidosis in 3, and arrhythmogenic cardiomyopathy in 3. In a median follow-up of 29 months (range 18 to 43 months), there were 63 events. In a multivariable analysis, the strongest predictors of recurrent events were the presence of LGE (adjusted hazard ratio: 6.7; 95% CI: 2.38 to 18.85; p < 0.001) and the extent of LGE (hazard ratio: 1.15; 95% CI: 1.11 to 1.19; p < 0.001). CONCLUSIONS Among patients with SCA, CMR with contrast identified LGE in 71% and provided a potential arrhythmic substrate in 76%. In follow-up, both the presence and extent of LGE identified a group at markedly increased risk of future adverse events. PMID

  6. Synthesis of nanocrystals of gadolinium carbonate by reaction crystallization.

    PubMed

    He, Xin-Kuai; Shin, Dongmin; Kim, Woo-Sik

    2012-03-01

    The formation of nano-sized crystals of gadolinium carbonate via reaction crystallization was studied in a semi-batch crystallizer using gadolinium chloride and ammonium hydrogen carbonate as the reactants. The gadolinium carbonate crystals were formed by the aggregation of primary particles sized about 5 nm. Thereby, the crystallization parameters acting directly on the aggregation of the primary particles, such as the reactant concentrations, non-stoichiometry of the reactants, solution pH, acoustic energy, and agitation speed, were mechanistically investigated. As such, increasing the reactant concentrations enhanced the crystal size due to higher nucleation of the primary particles for the aggregation. Non-stoichiometric reactant concentrations resulted in a significant reduction of the crystal size, due to the adsorption of the excess species on the primary particles. Similarly, the surface charge of the primary particles depended on the solution pH. Thus, the crystal size was reduced when the pH deviated from the neutral point. The acoustic cavitation of the ultrasound was much more effective than the turbulent fluid motion of the agitation in inhibiting the primary particle aggregation. Thus, the crystal size was remarkably reduced, even at a low acoustic energy of 6 watts.

  7. High-resolution cellular MRI: gadolinium and iron oxide nanoparticles for in-depth dual-cell imaging of engineered tissue constructs.

    PubMed

    Di Corato, Riccardo; Gazeau, Florence; Le Visage, Catherine; Fayol, Delphine; Levitz, Pierre; Lux, François; Letourneur, Didier; Luciani, Nathalie; Tillement, Olivier; Wilhelm, Claire

    2013-09-24

    Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components.

  8. High-resolution cellular MRI: gadolinium and iron oxide nanoparticles for in-depth dual-cell imaging of engineered tissue constructs.

    PubMed

    Di Corato, Riccardo; Gazeau, Florence; Le Visage, Catherine; Fayol, Delphine; Levitz, Pierre; Lux, François; Letourneur, Didier; Luciani, Nathalie; Tillement, Olivier; Wilhelm, Claire

    2013-09-24

    Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components. PMID:23924160

  9. Air- and water-stable gold-coated gadolinium metal nanocrystals.

    PubMed

    Yan, Chao; Wagner, Michael J

    2013-06-12

    Gold-coated gadolinium nanocrystals, with an average diameter of 3.20 ± 0.35 nm, have been synthesized at ambient temperature by alkalide reduction. Whereas uncoated gadolinium nanoparticles react violently with air and water, the gold-coated gadolinium nanocrystals reported here show no reaction even upon long-term exposure. This is the first example of air- and water-stable lanthanide metal nanocrystals, which may allow for the development of magnetic and biomedical applications of gadolinium and other lanthanide metal and alloy nanocrystals.

  10. Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys

    NASA Astrophysics Data System (ADS)

    Maltsev, Dmitry S.; Volkovich, Vladimir A.; Yamshchikov, Leonid F.; Chukin, Andrey V.

    2016-09-01

    Thermodynamic properties of gadolinium in Ga-Sn and Ga-Zn eutectic based alloys were studied. Temperature dependences of gadolinium activity in the studied alloys were determined at 573-1073 K employing the EMF method. Solubility of gadolinium in the Ga-Sn and Ga-Zn alloys was measured at 462-1073 K using IMCs sedimentation method. Activity coefficients as well as partial and excess thermodynamic functions of gadolinium in the studied alloys were calculated on the basis of the obtained experimental data.

  11. Various ligand-coated ultrasmall gadolinium-oxide nanoparticles: Water proton relaxivity and in-vivo T1 MR image

    NASA Astrophysics Data System (ADS)

    Park, Ja Young; Kim, Sung June; Lee, Gang Ho; Jin, Seonguk; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok

    2015-04-01

    Surface coating of nanoparticles with ligands is essential in magnetic resonance imaging (MRI) because of solubility in water and biocompatibility. In this study, five organic molecules were used for surface coating of ultrasmall gadolinium-oxide (Gd2O3) nanoparticles (d avg = 2.0 nm). All of the samples showed large longitudinal (r1) and transverse (r2) water proton relaxivities with r2/r1 ratios that were close to one, corresponding to ideal conditions for T1 MRI contrast agents. Finally, in-vivo T1 MR images were acquired to prove the effectiveness of the surface-coated ultrasmall Gd2O3 nanoparticles as a T1 MRI contrast agent.

  12. The level of intracellular glutathione is a key regulator for the induction of stress-activated signal transduction pathways including Jun N-terminal protein kinases and p38 kinase by alkylating agents.

    PubMed Central

    Wilhelm, D; Bender, K; Knebel, A; Angel, P

    1997-01-01

    Monofunctional alkylating agents like methyl methanesulfonate (MMS) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) are potent inducers of cellular stress leading to chromosomal aberrations, point mutations, and cell killing. We show that these agents induce a specific cellular stress response program which includes the activation of Jun N-terminal kinases/stress-activated protein kinases (JNK/SAPKs), p38 mitogen-activated protein kinase, and the upstream kinase SEK1/MKK4 and which depends on the reaction mechanism of the alkylating agent in question. Similar to another inducer of cellular stress, UV irradiation, damage of nuclear DNA by alkylation is not involved in the MMS-induced response. However, in contrast to UV and other inducers of the JNK/SAPKs and p38 pathways, activation of growth factor and G-protein-coupled receptors does not play a role in the MMS response. We identified the intracellular glutathione (GSH) level as critical for JNK/SAPK activation by MMS: enhancing the GSH level by pretreatment of the cells with GSH or N-acetylcysteine inhibits, whereas depletion of the cellular GSH pool causes hyperinduction of JNK/SAPK activity by MMS. In light of the JNK/SAPK-dependent induction of c-jun and c-fos transcription, and the Jun/Fos-induced transcription of xenobiotic-metabolizing enzymes, these data provide a potential critical role of JNK/SAPK and p38 in the induction of a cellular defense program against cytotoxic xenobiotics such as MMS. PMID:9234735

  13. Synergistic enhancement of iron oxide nanoparticle and gadolinium for dual-contrast MRI

    SciTech Connect

    Zhang, Fan; Huang, Xinglu; Qian, Chunqi; Zhu, Lei; Hida, Naoki; Niu, Gang; Chen, Xiaoyuan

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer MR contrast agents exert influence on T{sub 1} or T{sub 2} relaxation time of the surrounding tissue. Black-Right-Pointing-Pointer Combined use of iron oxide and Gd-DTPA can improve the sensitivity/specificity of lesion detection. Black-Right-Pointing-Pointer Dual contrast MRI enhances the delineation of tumor borders and small lesions. Black-Right-Pointing-Pointer The effect of DC-MRI can come from the high paramagnetic susceptibility of Gd{sup 3+}. Black-Right-Pointing-Pointer The effect of DC-MRI can also come from the distinct pharmacokinetic distribution of SPIO and Gd-DTPA. -- Abstract: Purpose: The use of MR contrast agents allows accurate diagnosis by exerting an influence on the longitudinal (T{sub 1}) or transverse (T{sub 2}) relaxation time of the surrounding tissue. In this study, we combined the use of iron oxide (IO) particles and nonspecific extracellular gadolinium chelate (Gd) in order to further improve the sensitivity and specificity of lesion detection. Procedures: With a 7-Tesla scanner, pre-contrasted, IO-enhanced and dual contrast agent enhanced MRIs were performed in phantom, normal animals, and animal models of lymph node tumor metastases and orthotopic brain tumor. For the dual-contrast (DC) MRI, we focused on the evaluation of T{sub 2} weighted DC MRI with IO administered first, then followed by the injection of a bolus of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Results: Based on the C/N ratios and MRI relaxometry, the synergistic effect of coordinated administration of Gd-DTPA and IO was observed and confirmed in phantom, normal liver and tumor models. At 30 min after administration of Feridex, Gd-DTPA further decreased T{sub 2} relaxation in liver immediately after the injection. Additional administration of Gd-DTPA also immediately increased the signal contrast between tumor and brain parenchyma and maximized the C/N ratio to -4.12 {+-} 0.71. Dual contrast MRI also enhanced the

  14. High longitudinal relaxivity of ultra-small gadolinium oxide prepared by microsecond laser ablation in diethylene glycol

    SciTech Connect

    Luo Ningqi; Xiao Jun; Hu Wenyong; Chen Dihu; Tian Xiumei; Yang Chuan; Li Li

    2013-04-28

    Ultra-small gadolinium oxide (Gd{sub 2}O{sub 3}) can be used as T{sub 1}-weighted Magnetic Resonance Imaging (MRI) contrast agent own to its high longitudinal relaxivity (r{sub 1}) and has attracted intensive attention in these years. In this paper, ultra-small Gd{sub 2}O{sub 3} nanoparticles of 3.8 nm in diameter have been successfully synthesized by a microsecond laser ablating a gadolinium (Gd) target in diethylene glycol (DEG). The growth inhibition effect induced by the large viscosity of DEG makes it possible to synthesize ultra-small Gd{sub 2}O{sub 3} by laser ablation in DEG. The r{sub 1} value and T{sub 1}-weighted MR images are measured by a 3.0 T MRI spectroscope. The results show these nanoparticles with a high r{sub 1} value of 9.76 s{sup -1} mM{sup -1} to be good MRI contrast agents. We propose an explanation for the high r{sub 1} value of ultra-small Gd{sub 2}O{sub 3} by considering the decreasing factor (surface to volume ratio of the nanoparticles, S/V) and the increasing factor (water hydration number of the Gd{sup 3+} on Gd{sub 2}O{sub 3} surface, q), which offer a new look into the relaxivity studies of MRI contrast agents. Our research provides a new approach to preparing ultra-small Gd{sub 2}O{sub 3} of high r{sub 1} value by laser ablation in DEG and develops the understanding of high relaxivity of ultra-small Gd{sub 2}O{sub 3} MRI contrast agents.

  15. Diagnostic Magnetic Resonance Imaging of Atherosclerosis in Apolipoprotein E Knockout Mouse Model Using Macrophage-Targeted Gadolinium-Containing Synthetic Lipopeptide Nanoparticles

    PubMed Central

    Shen, Zu T.; Zheng, Shaokuan; Gounis, Matthew J.; Sigalov, Alexander B.

    2015-01-01

    Cardiovascular disease is the leading cause of death in Western cultures. The vast majority of cardiovascular events, including stroke and myocardial infarction, result from the rupture of vulnerable atherosclerotic plaques, which are characterized by high and active macrophage content. Current imaging modalities including magnetic resonance imaging (MRI) aim to characterize anatomic and structural features of plaques rather than their content. Previously, we reported that macrophage-targeted delivery of gadolinium (Gd)-based contrast agent (GBCA-HDL) using high density lipoproteins (HDL)-like particles significantly enhances the detection of plaques in an apolipoprotein (apo) E knockout (KO) mouse model, with an atherosclerotic wall/muscle normalized enhancement ratio (NER) of 120% achieved. These particles are comprised of lipids and synthetic peptide fragments of the major protein of HDL, apo A-I, that contain a naturally occurring modification which targets the particles to macrophages. Targeted delivery minimizes the Gd dose and thus reduces the adverse effects of Gd. The aims of the current study were to test whether varying the GBCA-HDL particle shape and composition can further enhance atherosclerotic plaque MRI and control organ clearance of these agents. We show that the optimized GBCA-HDL particles are efficiently delivered intracellularly to and uptaken by both J774 macrophages in vitro and more importantly, by intraplaque macrophages in vivo, as evidenced by NER up to 160% and higher. This suggests high diagnostic power of our GBCA-HDL particles in the detection of vulnerable atherosclerotic plaques. Further, in contrast to discoidal, spherical GBCA-HDL exhibit hepatic clearance, which could further diminish adverse renal effects of Gd. Finally, activated macrophages are reliable indicators of any inflamed tissues and are implicated in other areas of unmet clinical need such as rheumatoid arthritis, sepsis and cancer, suggesting the expanded diagnostic

  16. Left Ventricular Function Evaluation on a 3T MR Scanner with Parallel RF Transmission Technique: Prospective Comparison of Cine Sequences Acquired before and after Gadolinium Injection

    PubMed Central

    Caspar, Thibault; Schultz, Anthony; Schaeffer, Mickaël; Labani, Aïssam; Jeung, Mi-Young; Jurgens, Paul Thomas; El Ghannudi, Soraya; Roy, Catherine; Ohana, Mickaël

    2016-01-01

    Objectives To compare cine MR b-TFE sequences acquired before and after gadolinium injection, on a 3T scanner with a parallel RF transmission technique in order to potentially improve scanning time efficiency when evaluating LV function. Methods 25 consecutive patients scheduled for a cardiac MRI were prospectively included and had their b-TFE cine sequences acquired before and right after gadobutrol injection. Images were assessed qualitatively (overall image quality, LV edge sharpness, artifacts and LV wall motion) and quantitatively with measurement of LVEF, LV mass, and telediastolic volume and contrast-to-noise ratio (CNR) between the myocardium and the cardiac chamber. Statistical analysis was conducted using a Bayesian paradigm. Results No difference was found before or after injection for the LVEF, LV mass and telediastolic volume evaluations. Overall image quality and CNR were significantly lower after injection (estimated coefficient cine after > cine before gadolinium: -1.75 CI = [-3.78;-0.0305], prob(coef>0) = 0% and -0.23 CI = [-0.49;0.04], prob(coef>0) = 4%) respectively), but this decrease did not affect the visual assessment of LV wall motion (cine after > cine before gadolinium: -1.46 CI = [-4.72;1.13], prob(coef>0) = 15%). Conclusions In 3T cardiac MRI acquired with parallel RF transmission technique, qualitative and quantitative assessment of LV function can reliably be performed with cine sequences acquired after gadolinium injection, despite a significant decrease in the CNR and the overall image quality. PMID:27669571

  17. Poly(lactic-co-glycolic acid) encapsulated gadolinium oxide nanoparticles for MRI-based cell tracking.

    PubMed

    Bennewitz, Margaret F; Williams, Simone S; Nkansah, Michael K; Shapiro, Erik M

    2013-06-01

    Superparamagnetic iron oxide particles have proven useful for cell tracking applications by monitoring cell transplantation and migration in living organisms. However, one perceived drawback is that these particles cause dark contrast in MRI, sometimes yielding confusion with other biological phenomena, which also yield dark contrast. To that end, researchers have investigated the use of gadolinium oxide (Gd2O3) based contrast agents for MRI-based cell tracking, as Gd2O3 has favorable r1 molar relaxivity. We synthesized Gd2O3 nanocrystals and encapsulated them within PLGA matrices to form approximatley to 150 nm nanoparticles. r1 was 1.9 mM(-1) sec(-1) and r2 was 8.4 mM(-1) sec(-1). Cell labeling with particles was well tolerated by cells except at very high doses. MRI of labeled cells showed that labeled cells could achieve both R1 and R2 enhancements due to the internalized particles. R2 enhancements were approximately to twice that of R1 enhancements suggesting the use of very short echo times when using Gd2O3 based contrast agents for MRI-based cell tracking.

  18. Concurrent dual contrast for cellular magnetic resonance imaging using gadolinium oxide and iron oxide nanoparticles.

    PubMed

    Loai, Yasir; Ganesh, Tameshwar; Cheng, Hai-Ling Margaret

    2012-01-01

    Rationale and Objectives. Concurrent visualization of differential targets in cellular and molecular imaging is valuable for resolving processes spatially and temporally, as in monitoring different cell subtypes. The purpose of this study was to demonstrate concurrent, dual (positive and negative) contrast visualization on magnetic resonance imaging (MRI) of two colocalized cell populations labeled with Gadolinium "Gd" oxide and iron "Fe" oxide nanoparticles. Materials and Methods. Human aortic endothelial cells (EC) and smooth muscle cells (SMC) were labeled with various concentrations of Gd oxide and Fe oxide, respectively. MRI on single- or mixed-cell samples was performed at 7 tesla. Proper cell phenotype expressions, cell uptake of contrast agents, and the effect of labeling on cell viability and proliferation were also determined. Results. Both contrast agents were efficiently taken up by cells, with viability and proliferation largely unaffected. On MRI, the positive contrast associated with Gd oxide-labeled EC and negative contrast associated with Fe oxide-labeled SMC discriminated the presence of each cell type, whether it existed alone or colocalized in a mixed-cell sample. Conclusion. It is feasible to use Gd oxide and Fe oxide for dual contrast and concurrent discrimination of two colocalized cell populations on MRI at 7 tesla.

  19. The effect of motexafin gadolinium on ALA photodynamic therapy in glioma spheroids

    NASA Astrophysics Data System (ADS)

    Mathews, Marlon S.; Sanchez, Rogelio; Sun, Chung-Ho; Madsen, Steen J.; Hirschberg, Henry

    2008-02-01

    Following surgical removal of malignant brain tumors 80% of all cases develop tumor recurrence within 2 cm of the resected margin. The aim of postoperative therapy is therefore elimination of nests of tumor cells remaining in the margins of the resection cavity. Light attenuation in tissue makes it difficult for adequate light fluences to reach depths of 1-2 cm in the resection margin making it difficult for standard intraoperative photodynamic therapy (PDT) to accomplish this goal. Thus additional agents are required that either increase the efficacy of low fluence PDT or inhibit cellular repair, to enhance effectiveness of PDT in the tumor resection cavity. Motexafin gadolinium (MGd) is one such agent previously reported to enhance the cytotoxic potential of radiation therapy, as well as several chemotherapeutic agents by causing redox stress to cancerous cells. MGd is well tolerated with tumor specific uptake in clinical studies. The authors evaluated MGd as a potential PDT enhancing agent at low light fluences using an in vitro model. Multicellular Glioma spheroids (MGS) of approximately 300 micron diameter, obtained from ACBT cell lines were subjected to acute PDT treatments at 6J, 12J, and 18J light fluences. Growth was determined by measuring diameters in two axes. At four weeks a dose dependent inhibition of spheroid growth was seen in 33%, 55%, and 83% of the MGS at 6J, 12J, and 18J respectively, while inhibition followed by a partial reversal of growth was seen in 17%, 33%, and 17% respectively. This study provides a rationale for the use of this drug as a PDT enhancer in the management of brain tumors.

  20. Antidiabetic Agents.

    ERIC Educational Resources Information Center

    Plummer, Nancy; Michael, Nancy, Ed.

    This module on antidiabetic agents is intended for use in inservice or continuing education programs for persons who administer medications in long-term care facilities. Instructor information, including teaching suggestions, and a listing of recommended audiovisual materials and their sources appear first. The module goal and objectives are then…

  1. Use of Gadolinium as a Primary Criticality Control in Disposing Waste Containing Plutonium at SRS

    SciTech Connect

    Andrew, Vincent

    2005-01-04

    Use of gadolinium as a neutron poison has been proposed for disposing of several metric tons of excess plutonium at the Savannah River Site (SRS). The plutonium will first be dissolved in nitric acid in small batches. Gadolinium nitrate will then be added to the plutonium nitrate solution. The Gd-poisoned plutonium solution will be neutralized and transferred to large under-ground tanks. The pH of small batches of neutralized plutonium solution will be adjusted prior to addition of the glass frit for eventual production as glass logs. The use of gadolinium as the neutron poison would minimize the number of glass logs generated from this disposition. The primary criticality safety concerns regarding the disposal process are: (1) maintaining neutron moderation under all processing conditions since gadolinium has a very large absorption cross section for thermal neutrons, (2) characteristics of plutonium and gadolinium precipitation during the neutralization process, (3) mixing characteristics of the precipitate to ensure that plutonium would remain homogeneously mixed with gadolinium, and (4) potential separation of plutonium and gadolinium during nitric and formic acids addition. A number of experiments were conducted at the Savannah River National Laboratory to study the behavior of plutonium and gadolinium at various stages of the disposition process.

  2. Reversible Low-Light Induced Photoswitching of Crowned Spiropyran-DO3A Complexed with Gadolinium(III) Ions

    PubMed Central

    Kruttwig, Klaus; Yankelevich, Diego R.; Brueggemann, Chantal; Tu, Chuqiao; L’Etoile, Noelle; Knoesen, André; Louie, Angelique Y.

    2016-01-01

    Photoswitchable spiropyran has been conjugated to the crowned ring system DO3A, which improves its solubility in dipolar and polar media and stabilizes the merocyanine isomer. Adding the lanthanide ion gadolinium(III) to the macrocyclic ring system leads to a photoresponsive magnetic resonance imaging contrast agent that displays an increased spin-lattice relaxation time (T1) upon visible light stimulation. In this work, the photoresponse of this photochromic molecule to weak light illumination using blue and green light emitting diodes was investigated, simulating the emission spectra from bioluminescent enzymes. Photon emission rate of the light emitting diodes was changed, from 1.75 × 1016 photons·s−1 to 2.37 × 1012 photons·s−1. We observed a consistent visible light-induced isomerization of the merocyanine to the spiropyran form with photon fluxes as low as 2.37 × 1012 photons·s−1 resulting in a relaxivity change of the compound. This demonstrates the potential for use of the described imaging probes in low light level applications such as sensing bioluminescence enzyme activity. The isomerization behavior of gadolinium(III)-ion complexed and non-complexed spiropyran-DO3A was analyzed in water and ethanol solution in response to low light illumination and compared to the emitted photon emission rate from over-expressed Gaussia princeps luciferase. PMID:22728357

  3. Monte Carlo Study of Radiation Dose Enhancement by Gadolinium in Megavoltage and High Dose Rate Radiotherapy

    PubMed Central

    Zhang, Daniel G.; Feygelman, Vladimir; Moros, Eduardo G.; Latifi, Kujtim; Zhang, Geoffrey G.

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed. PMID:25275550

  4. Monte Carlo study of radiation dose enhancement by gadolinium in megavoltage and high dose rate radiotherapy.

    PubMed

    Zhang, Daniel G; Feygelman, Vladimir; Moros, Eduardo G; Latifi, Kujtim; Zhang, Geoffrey G

    2014-01-01

    MRI is often used in tumor localization for radiotherapy treatment planning, with gadolinium (Gd)-containing materials often introduced as a contrast agent. Motexafin gadolinium is a novel radiosensitizer currently being studied in clinical trials. The nanoparticle technologies can target tumors with high concentration of high-Z materials. This Monte Carlo study is the first detailed quantitative investigation of high-Z material Gd-induced dose enhancement in megavoltage external beam photon therapy. BEAMnrc, a radiotherapy Monte Carlo simulation package, was used to calculate dose enhancement as a function of Gd concentration. Published phase space files for the TrueBeam flattening filter free (FFF) and conventional flattened 6MV photon beams were used. High dose rate (HDR) brachytherapy with Ir-192 source was also investigated as a reference. The energy spectra difference caused a dose enhancement difference between the two beams. Since the Ir-192 photons have lower energy yet, the photoelectric effect in the presence of Gd leads to even higher dose enhancement in HDR. At depth of 1.8 cm, the percent mean dose enhancement for the FFF beam was 0.38±0.12, 1.39±0.21, 2.51±0.34, 3.59±0.26, and 4.59±0.34 for Gd concentrations of 1, 5, 10, 15, and 20 mg/mL, respectively. The corresponding values for the flattened beam were 0.09±0.14, 0.50±0.28, 1.19±0.29, 1.68±0.39, and 2.34±0.24. For Ir-192 with direct contact, the enhanced were 0.50±0.14, 2.79±0.17, 5.49±0.12, 8.19±0.14, and 10.80±0.13. Gd-containing materials used in MRI as contrast agents can also potentially serve as radiosensitizers in radiotherapy. This study demonstrates that Gd can be used to enhance radiation dose in target volumes not only in HDR brachytherapy, but also in 6 MV FFF external beam radiotherapy, but higher than the currently used clinical concentration (>5 mg/mL) would be needed.

  5. Updates for Gadolinium neutron capture measurements at DANCE

    NASA Astrophysics Data System (ADS)

    Dashdorj, Dugersuren; Mitchell, G. E.; Baramsai, B.; Chankova, R.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Wu, C. Y.; Bredeweg, T.; Couture, A.; Haight, R.; Jandel, M.; O'Donnell, J.; Rundberg, R.; Wouters, J.; Ullmann, J.; Vieira, D.; Becvar, F.; Krticka, M.

    2007-10-01

    Neutron capture reactions for several isotopes of Gadolinium have been measured at DANCE array in Los Alamos Neutron Science Center. Progress on the analysis is discussed. The detector response function of DANCE array is presented in connection with the statistical gamma-ray decay cascade simulation. In the region of separated neutron resonances, the statistical gamma-ray decay cascade is simulated using the DICEBOX code. Various models for the photon strength function and level density are used as input. The output of simulations is compared with DANCE data.

  6. Magnetoresistance of polycrystalline gadolinium with varying grain size

    SciTech Connect

    Chakravorty, Manotosh Raychaudhuri, A. K.

    2015-01-21

    In this paper, we report a study of evolution of low field magnetoresistance (MR) of Gadolinium as the grain size in the sample is changed from few microns (∼4 μm) to the nanoscopic regime (∼35 nm). The low field MR has a clear effect on varying grain size. In large grain sample (few μm), the magnetic domains are controlled by local anisotropy field determined mainly by the magnetocrystalline anisotropy. The low field MR clearly reflects the temperature dependence of the magnetocrystalline anisotropy. For decreasing gain size, the contribution of spin disorder at the grain boundary increases and enhances the local anisotropy field.

  7. Dual-Energy X-Radiography With Gadolinium Filter

    NASA Technical Reports Server (NTRS)

    Rutt, Brian

    1987-01-01

    Image resolution increased, and cost reduced. Proposed dual-energy x-ray imaging system, continuous bremsstrahlung spectrum from x-ray tube filtered by foil of nonradioactive gadolinium or another rare-earth metal to form two-peaked energy spectrum. After passing through patient or object under examination, filtered radiation detected by array of energy-discriminating, photon-counting detectors. Detector outputs processed to form x-ray image for each peak and possibly enhanced image based on data taken at both peaks.

  8. Electrical and optical properties of gadolinium doped bismuth ferrite nanoparticles

    SciTech Connect

    Mukherjee, A. Banerjee, M. Basu, S.; Pal, M.

    2014-04-24

    Multiferroic bismuth ferrite (BFO) and gadolinium (Gd) doped bismuth ferrite had been synthesized by a sol-gel method. Particle size had been estimated by Transmission electron microscopy (TEM) and found to decrease with Gd doping. We studied the temperature and frequency dependence of impedance and electric modulus and calculated the grain and grain boundary resistance and capacitance of the investigated samples. We observed that electrical activation energy increases for all the doped samples. Optical band gap also increases for the doped samples which can be used in photocatalytic application of BFO.

  9. Gadolinium Thin Foils in a Plasma Panel Sensor as an Alternative to 3He

    SciTech Connect

    Varner Jr, Robert L; Beene, James R; Friedman, Dr. Peter S.

    2010-01-01

    Gadolinium has long been investigated as a detector for neutrons. It has a thermal neutron capture cross-section that is unparalleled among stable elements, because of the isotopes $^{155,157}$Gd. As a replacement for $^3$He, gadolinium has a significant defect, it produces many gamma-rays with an energy sum of 8 MeV. It also produces conversion electrons, mostly 29 keV in energy. The key to replacing $^3$He with gadolinium is using a gamma-blind electron detector to detect the conversion electrons. We suggest that coupling a layer of gadolinium to a Plasma Panel Sensor (PPS) can provide highly efficient, nearly gamma-blind detection of the conversion. The PPS is a proposed detector under development as a dense array of avalanche counters based on plasma display technology. We will present simulations of the response of prototypes of this detector and considerations of the use of gadolinium in the PPS.

  10. Influence of morphological transformation on luminescence properties of europium-doped gadolinium oxide nanostructures

    NASA Astrophysics Data System (ADS)

    Zhang, Kai; Dondapati, Hareesh; Holloway, Terence; Cao, Wei; Kar, Arik; Patra, Amitava; Pradhan, Aswini K.

    2010-09-01

    Low dimensional europium (Eu3+)-doped gadolinium oxide (Gd2O3) lanthanide nanostructures are synthesized by an effective and simple coprecipitation process followed by subsequent heat treatments. Transmission electron microscope (TEM) images indicate Eu3+-doped Gd2O3 nanostructures undergo significant morphological changes from nanorods to nanoparticles during thermal treatments. Nanostructures with different morphology, including nanotubes, strongly influence the photoluminescence properties. The dependence of luminescence lifetime on morphological nature of the nanostructures demonstrates that the one dimensional nanostructures such as nanorods and nanotubes have higher emission intensity with shorter lifetime. Our analysis suggests that the morphological transformation of the nanostructures plays the most important role in the behavior of radiative and nonradiative relaxation mechanisms, resulting in the overall photoluminescence properties.

  11. Strongest Ferromagnetic Coupling in Designed Gadolinium(III)-Nitroxide Coordination Compounds.

    PubMed

    Kanetomo, Takuya; Yoshitake, Toru; Ishida, Takayuki

    2016-08-15

    Three novel gadolinium(III)-radical complexes [Gd(III)(hfac)3(H2O)(L)] [Gd-L; L = tert-butyl phenyl nitroxide (phNO) and its derivatives (tert-butyl 3-tolyl nitroxide and tert-butyl 4-tert-butylphenyl nitroxide)] were synthesized, and all compounds showed ferromagnetic coupling, obeying the empirical relation: out-of-plane coordination of the Gd ion from the radical π system favors ferromagnetic coupling. In particular, Gd-phNO has a considerably large torsion angle around Gd-O-N-Csp(2) (69.8(9)° on average) and the largest ferromagnetic coupling parameter (2J/kB = +18.0(4) K) in Gd-nitroxide compounds ever known. The validity of our molecular design was assessed on the basis of the magneto-structure relation analysis with many literature data including various paramagnetic ligating groups. PMID:27482940

  12. The preparation of organic infrared semiconductor phthalocyanine gadolinium (III) and its optical and structural characterizations

    NASA Astrophysics Data System (ADS)

    Tang, Li-bin; Ji, Rong-bin; Song, Li-yuan; Chen, Xue-mei; Ma, Yu; Wang, Yi-feng; Qian, Ming; Song, Lei; Su, Hai-ying; Zhuang, Ji-sheng; Yang, Rui-yu

    2009-07-01

    In order to increase the species of organic infrared semiconductor, we synthesized organic infrared semiconductor phthalocyanine gadolinium by using o-phthalodinitrile and GdCl3 as reactants, ammonium molybdate as catalyzer. Under light and dark field modes of microscope, the translucency emerald-like powder of phthalocyanine gadolinium has been observed, the size of the small grain for the sample is around 5μm in diameter, the size of larger grain may reach to several tens of microns. The main vibrational peaks in FT-IR spectrum and Raman spectrum have been assigned. Elementary analysis shows that the experimental data of phthalocyanine gadolinium in the main agree with those of calculated data. The UV-Vis absorption spectrum of the sample indicates the sandwich-like structure of phthalocyanine gadolinium. The organic infrared semiconductor phthalocyanine gadolinium thin film on quartz substrate has been prepared with our synthesized powdered sample by using solution method. The characterizations of XRD and UV-Vis-NIR absorption have been carried out for the phthalocyanine gadolinium thin film on quartz substrate, XRD shows that phthalocyanine gadolinium diffractions occur at 2θ=6.851,8.290 and 8.820 degrees, the corresponding plane spacings (d) for the diffraction peaks are 12.8921, 10.6570, and 10.0176Å.The diffraction peaks locate at low diffraction angle, suggesting that the molecular size of the phthalocyanine gadolinium is big that causes the large spacing of crystal planes. The UV-Vis-NIR absorption of phthalocyanine gadolinium thin film on quartz substrate implies that within near infrared band there is a absorption in the 1.3~2.0μm wavelength range peaked at ca. 1.75μm, indicating the important potential application value of phthalocyanine gadolinium in the field of organic infrared optoelectronics.

  13. Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers.

    PubMed

    Wang, Kezheng; Pan, Dipanjan; Schmieder, Anne H; Senpan, Angana; Hourcade, Dennis E; Pham, Christine T N; Mitchell, Lynne M; Caruthers, Shelton D; Cui, Grace; Wickline, Samuel A; Shen, Baozhong; Lanza, Gregory M

    2015-04-01

    High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138±10 (Dav)/nm; PDI: 0.06; zeta: -27±2 mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5 nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10 nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk. From the clinical editor: The authors developed a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) in this study. These were used as a high-relaxivity paramagnetic MR molecular imaging agent in experimental models. It was shown that MnOL-Gd NC could provide high T1w MR contrast for targeted imaging. As the level of gadolinium used was reduced, there was also reduced risk of systemic side effects from complement activation.

  14. Low field magnetoresistance of gadolinium nanowire

    SciTech Connect

    Chakravorty, Manotosh Raychaudhuri, A. K.

    2014-02-07

    We report low field (μ{sub 0}H < 0.2 T) magnetoresistance (MR) studies on a single Gd nanowire patterned from a nano-structured film (average grain size ∼ 35 nm) by focused ion beam. For comparison, we did similar MR measurements on a polycrystalline sample with large crystallographic grains (∼4 μm). It is observed that in the low field region where the MR is due to motion of magnetic domains, the MR in the large grained sample shows a close relation to the characteristic temperature dependent magnetocrystalline anisotropy including a sharp rise in MR at the spin reorientation transition at 235 K. In stark contrast, in the nanowire, the MR shows complete suppression of the above behaviours and it shows predominance of the grain boundary and spin disorder controlling the domain response.

  15. Enhancement of the normal pancreas: comparison of manganese-DPDP and gadolinium chelate.

    PubMed

    Kettritz, U; Warshauer, D M; Brown, E D; Schlund, J F; Eisenberg, L B; Semelka, R C

    1996-01-01

    The purpose of this paper was to compare manganese-DPDP (Mn-DPDP) and gadolinium chelate (Gd-DTPA) contrast agents for enhancement of the normal pancreas. A total of 14 patients with focal liver disease underwent Mn-DPDP- and Gd-DTPA-enhanced 1.5 T MR examinations using spoiled gradient-echo (FLASH) technique at two separate times. Contrast agents were injected according to the currently recommended practices; Gd-DTPA was injected as a rapid bolus injection in a dosage of 0.1 mmol/kg, and Mn-DPDP was injected as a slow IV injection in a dosage of 5 mumol/kg. Quantitative region of interest measurements were made in 11 patients, and percent contrast enhancement of the pancreas and pancreas-fat signal-to-noise ratios (SNR) were determined for each agent. Images were also evaluated qualitatively by consensus reading of two investigators and overall scan quality was rated on a scale from 1 (poor) to 4 (very good). Enhancement of the pancreas immediately post Gd-DTPA was significantly higher than 15 min post Mn-DPDP (73.3 vs 36.3%; p = 0.003). On postcontrast images the pancreas-fat SNR measurements were 7.7 (i.e., pancreas higher in signal than fat) and -6.1 for Gd-DTPA and Mn-DPDP, respectively, which was significantly different (p < 0.001). Image quality was rated as 3.1 and 2.5 for Gd-DTPA- and Mn-DPDP-enhanced images, respectively. The normal pancreas enhances significantly more with Gd-DTPA than with Mn-DPDP administered under the conditions of this study. Overall image quality is also greater on the Gd-DTPA-enhanced images.

  16. Magnetic Surfactants and Polymers with Gadolinium Counterions for Protein Separations.

    PubMed

    Brown, Paul; Bromberg, Lev; Rial-Hermida, M Isabel; Wasbrough, Matthew; Hatton, T Alan; Alvarez-Lorenzo, Carmen

    2016-01-26

    New magnetic surfactants, (cationic hexadecyltrimethlyammonium bromotrichlorogadolinate (CTAG), decyltrimethylammonium bromotrichlorogadolinate (DTAG), and a magnetic polymer (poly(3-acrylamidopropyl)trimethylammonium tetrachlorogadolinate (APTAG)) have been synthesized by the simple mixing of the corresponding surfactants and polymer with gadolinium metal ions. A magnetic anionic surfactant, gadolinium tri(1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate) (Gd(AOT)3), was synthesized via metathesis. Both routes enable facile preparation of magnetically responsive magnetic polymers and surfactants without the need to rely on nanocomposites or organic frameworks with polyradicals. Electrical conductivity, surface tensiometry, SQUID magnetometry, and small-angle neutron scattering (SANS) demonstrate surface activity and self-aggregation behavior of the magnetic surfactants similar to their magnetically inert parent analogues but with added magnetic properties. The binding of the magnetic surfactants to proteins enables efficient separations under low-strength (0.33 T) magnetic fields in a new, nanoparticle-free approach to magnetophoretic protein separations and extractions. Importantly, the toxicity of the magnetic surfactants and polymers is, in some cases, lower than that of their halide analogues.

  17. Dielectric and magnetic properties of some gadolinium silica nanoceramics

    SciTech Connect

    Coroiu, I. Pascuta, P. Bosca, M. Culea, E.

    2013-11-13

    Some nanostructure gadolinium silica glass-ceramics were obtained undergoing a sol gel method and a heat-treatment at 1000°C about two hours. The magnetic and dielectric properties of these samples were studied. The magnetic properties were evidenced performing susceptibility measurements in the 80-300K temperature range. A Curie-Weiss behavior has acquired. The values estimated for paramagnetic Curie temperature being small and positive suggest the presence of weak ferromagnetic interactions between Gd{sup 3+} ions. The dielectric properties were evaluated from dielectric permittivity (ε{sub r}) and dielectric loss (tanδ) measurements at the frequency 1 kHz, 10 kHz and 100 kHz, in the 25-225°C temperature range and dielectric dispersion at room temperature for 79.5 kHz - 1GHz frequency area. The dielectric properties suggest that the main polarization mechanism corresponds to interfacial polarization, characteristic for polycrystalline-structured dielectrics. The polycrystalline structure of the samples is due to the polymorphous transformations of the nanostructure silica crystallites in the presence of gadolinium oxide. They were highlighted by SEM micrographs.

  18. Gadolinium-hydrogen ion exchange of zirconium phosphate

    NASA Technical Reports Server (NTRS)

    Liu, D. C.; Power, J. L.

    1972-01-01

    The Gd(+3)/H(+) ion exchange on a commercial zirconium phosphate ion exchanger was investigated in chloride, sulfate, and phosphate solutions of Gd(+3) at gadolinium concentrations of 0.001 to 1 millimole per cc and in the pH range of 0 to 3.5. Relatively low Gd(+3) capacities, in the range of 0.01 to 0.1 millimole per g of ion exchanger were found at room temperature. A significant difference in Gd(+3) sorption was observed, depending on whether the ion exchanger was converted from initial conditions of greater or lesser Gd(+3) sorption than the specific final conditions. Correlations were found between decrease in Gd(+3) capacity and loss of exchanger phosphate groups due to hydrolysis during washing and between increase in capacity and treatment with H3PO4. Fitting of the experimental data to ideal ion exchange equilibrium expressions indicated that each Gd(+3) ion is sorbed on only one site of the ion exchanger. The selectivity quotient was determined to be 2.5 + or - 0.4 at room temperature on gadolinium desorption in chloride solutions.

  19. Properties evaluation of a new MRI contrast agent based on Gd-loaded nanoparticles.

    PubMed

    Riyahi-Alam, Nader; Behrouzkia, Zhaleh; Seifalian, Alexander; Haghgoo Jahromi, Soheila

    2010-12-01

    Nanosized materials of gadolinium oxide can provide high-contrast enhancement in magnetic resonance imaging (MRI). The aim of this research was to characterize a novel emulsion composed of a silicon-based nanocomposite polymer (NCP) and gadolinium (III) oxide (Gd₂O₃) nanoparticles. The size and morphological structure of this nanoparticle are determined by particle size analysis device (zeta sizer) and transmission electronic microscope. We determined composition of Gd₂O₃ nanoparticles with energy dispersive X-ray analysis (EDXA) and magnetic resonance signal by T₁-weighted MRI. Cytotoxicity of Gd₂O₃ nanoparticles in SK-MEL-3 cancer cells was evaluated. Zeta sizer showed Gd₂O₃ nanoparticles to be 75 nm in size. EDXA indicated the two main chemical components of gadolinium-nanocomposite polymer emulsion: gadolinium and silicon and MRI also showed a significantly higher incremental relaxivity for Gd₂O₃ nanoparticles compared to Magnevist (conventional contrast agent). In such concentrations, the slope of R₁ relaxivity (1/T₁) vs. concentration curve of Magnevist and Gd₂O₃ were 4.33, 7.98 s⁻¹ mM⁻¹. The slope of R₂ relaxivity (1/T₂) vs. concentration curve of Magnevist and Gd₂O₃ were 5.06, 13.75 s⁻¹ mM⁻¹. No appreciable toxicity was observed with Gd₂O₃ nanoparticles. Gadolinium-nanocomposite polymer emulsion is well characterized and has potential as a useful contrast agent for magnetic resonance molecular imaging.

  20. Antiparasitic agents.

    PubMed

    Rosenblatt, J E

    1992-03-01

    In recent years, introduction of new and more effective agents has improved the overall therapy for parasitic infections. This field, however, is still plagued by numerous problems, including the development of resistance to antimicrobial agents (especially with malaria), unavailability of agents in the United States or lack of approval by the Food and Drug Administration, and major toxicities or lack of experience in pregnant women and children, which limits use in these groups of patients. Widespread resistance of Plasmodium falciparum to chloroquine and other agents has complicated the treatment and prophylaxis of this type of malaria. A combination of quinine and Fansidar is usually effective oral therapy for falciparum malaria; quinidine may be administered if intravenous therapy is needed. Mefloquine, which is currently recommended for prophylaxis against chloroquine-resistant P. falciparum, is also effective for single-dose oral treatment, although this regimen has not yet been approved by the Food and Drug Administration. Metronidazole has been widely used for treatment of gastroenteritis due to Entamoeba histolytica and Giardia lamblia (not approved by the Food and Drug Administration for the latter) and is considered safe and effective. A new macrolide, azithromycin, has been reported to be effective for cryptosporidiosis in experimental animals; currently, no effective therapy is available for human infections. Combinations of sulfonamides with other antifolates, trimethoprim or pyrimethamine, are recommended therapy for Pneumocystis carinii pneumonia or toxoplasmosis, respectively. Therapies for the various types of leishmaniasis and trypanosomiasis are complex, often toxic, and often of limited efficacy. The benzimidazoles are effective for roundworm infections, although thiabendazole has severe toxic effects. The recent introduction of ivermectin has revolutionized the treatment and control of onchocerciasis. Another relatively new agent, praziquantel

  1. Aqueous stability of gadolinium in surface waters receiving sewage treatment plant effluent Boulder Creek, Colorado

    USGS Publications Warehouse

    Verplanck, P.L.; Taylor, H.E.; Nordstrom, D.K.; Barber, L.B.

    2005-01-01

    In many surface waters, sewage treatment plant (STP) effluent is a substantial source of both regulated and unregulated contaminants, including a suite of complex organic compounds derived from household chemicals, pharmaceutical, and industrial and medical byproducts. In addition, STP effluents in some urban areas have also been shown to have a positive gadolinium (Gd) anomaly in the rare earth element (REE) pattern, with the Gd derived from its use in medical facilities. REE concentrations are relatively easy to measure compared to many organic wastewater compounds and may provide a more widely utilized tracer of STP effluents. To evaluate whether sewage treatment plant-associated Gd is a useful tracer of treatment plant effluent, an investigation of the occurrence, fate, and transport of rare earth elements was undertaken. The rare earth element patterns of four of five STP effluents sampled display positive Gd anomalies. The one site that did not have a Gd anomaly serves a small community, population 1200, with no medical facilities. Biosolids from a large metropolitan STP are not enriched in Gd even though the effluent is, suggesting that a substantial fraction of Gd remains in the aqueous phase through routine treatment plant operation. To evaluate whether STP-derived Gd persists in the fluvial environment, a 14-km study reach downstream of an STP was sampled. Gadolinium anomalies were present at all five downstream sites, but the magnitude of the anomaly decreased. Effluent from STPs is a complex mixture of organic and inorganic constituents, and to better understand the chemical interactions and their effect on REEs, the aqueous speciation was modeled using comprehensive chemical analyses of water samples collected downstream of STP input. These calculations suggest that the REEs will likely remain dissolved because phosphate and carbonate complexes dominate over free REE ions. This study supports the application of Gd anomalies as a useful tracer of urban

  2. Renal safety of intravenous gadolinium-enhanced magnetic resonance imaging in patients awaiting liver transplantation.

    PubMed

    Shaffer, Katherine M; Parikh, Mehul R; Runge, Thomas M; Perez, Sebastian D; Sakaria, Sonali S; Subramanian, Ram M

    2015-11-01

    Renal dysfunction in cirrhosis carries a high morbidity and mortality. Given the potential risk of contrast-induced nephropathy associated with iodinated intravenous contrast used in computed tomography (CT), alternate contrast modalities for abdominal imaging in liver transplant candidates need to be examined. The purpose of this study was to examine the renal safety of magnetic resonance imaging (MRI) with gadolinium in patients awaiting liver transplantation. The study involved a retrospective analysis of 352 patients of abdominal MRI with low-dose gadobenate dimeglumine (MultiHance) (0.05 mmol/kg) in patients with cirrhosis and without renal replacement therapy at a single center during the period from 2007 to 2013. For each case, serum creatinine before and within a few days after the MRI were compared. In addition, the patients were analyzed for the development of nephrogenic systemic fibrosis (NSF), a reported complication of gadolinium in chronic kidney disease. The pre-MRI serum creatinine values ranged from 0.36 to 4.86 mg/dL, with 70 patients (20%) having values ≥ 1.5 mg/dL. A comparison of the pre- and post-MRI serum creatinine values did not demonstrate a clinically significant difference (mean change = 0.017 mg/dL; P = 0.38), including those patients with a pre-MRI serum creatinine ≥ 1.5 mg/dL. In addition, no cases of NSF were noted. In conclusion, our findings suggest that MRI with low-dose gadobenate dimeglumine (MultiHance) is a nonnephrotoxic imaging modality in liver transplant candidates, and its use can be cautiously expanded to liver transplant candidates with concomitant renal insufficiency.

  3. Ligand-size dependent water proton relaxivities in ultrasmall gadolinium oxide nanoparticles and in vivo T1 MR images in a 1.5 T MR field.

    PubMed

    Kim, Cho Rong; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Lee, Gang Ho

    2014-10-01

    The dependence of longitudinal (r1) and transverse (r2) water proton relaxivities of ultrasmall gadolinium oxide (Gd2O3) nanoparticles on the surface coating ligand-size was investigated. Both r1 and r2 values decreased with increasing ligand-size. We attributed this to the ligand-size effect. In addition the effectiveness of d-glucuronic acid-coated ultrasmall Gd2O3 nanoparticles as T1 magnetic resonance imaging (MRI) contrast agents was confirmed by measuring the in vitro cytotoxicity and using in vivo T1 MR images in a mouse in a 1.5 T MR field.

  4. Microwave-assisted polyol synthesis of gadolinium-doped green luminescent carbon dots as a bimodal nanoprobe.

    PubMed

    Gong, Ningqiang; Wang, Hao; Li, Shuai; Deng, Yunlong; Chen, Xiao'ai; Ye, Ling; Gu, Wei

    2014-09-16

    The development of multimodal nanoprobes is highly desired in medical imaging because it integrates the advantages of multiple imaging modes. In this study, the gadolinium-doped green luminescent carbon dots (Gd-CDs) were prepared by the simple one-step microwave-assisted polyol method. The obtained Gd-CDs emitted a unique green photoluminescence with a quantum yield of 5.4%. The Gd-CDs exhibited a low cytotoxicity and could optically label the C6 glioma cells. Meanwhile, the r1 relaxivity of Gd-CDs was measured to be 11.356 mM(-1) s(-1). This high r1 value together with the r2/r1 ratio close to 1 nominates Gd-CDs as an excellent T1 contrast agent for magnetic resonance imaging. These Gd-CDs combining two complementary imaging modalities are therefore a promising bimodal nanoprobe in medical imaging for a better diagnosis. PMID:25157595

  5. Microwave-assisted polyol synthesis of gadolinium-doped green luminescent carbon dots as a bimodal nanoprobe.

    PubMed

    Gong, Ningqiang; Wang, Hao; Li, Shuai; Deng, Yunlong; Chen, Xiao'ai; Ye, Ling; Gu, Wei

    2014-09-16

    The development of multimodal nanoprobes is highly desired in medical imaging because it integrates the advantages of multiple imaging modes. In this study, the gadolinium-doped green luminescent carbon dots (Gd-CDs) were prepared by the simple one-step microwave-assisted polyol method. The obtained Gd-CDs emitted a unique green photoluminescence with a quantum yield of 5.4%. The Gd-CDs exhibited a low cytotoxicity and could optically label the C6 glioma cells. Meanwhile, the r1 relaxivity of Gd-CDs was measured to be 11.356 mM(-1) s(-1). This high r1 value together with the r2/r1 ratio close to 1 nominates Gd-CDs as an excellent T1 contrast agent for magnetic resonance imaging. These Gd-CDs combining two complementary imaging modalities are therefore a promising bimodal nanoprobe in medical imaging for a better diagnosis.

  6. Mesoporous silica nanoparticles as a delivery system of gadolinium for effective human stem cell tracking.

    PubMed

    Hsiao, Jong-Kai; Tsai, Chih-Pin; Chung, Tsai-Hua; Hung, Yann; Yao, Ming; Liu, Hon-Man; Mou, Chung-Yuan; Yang, Chung-Shi; Chen, Yao-Chang; Huang, Dong-Ming

    2008-09-01

    The progress of using gadolinium (Gd)-based nanoparticles in cellular tracking lags behind that of superparamagnetic iron oxide (SPIO) nanoparticles in magnetic resonance imaging (MRI). Here, dual functional Gd-fluorescein isothiocyanate mesoporous silica nanoparticles (Gd-Dye@MSN) that possess green fluorescence and paramagnetism are developed in order to evaluate their potential as effective T1-enhancing trackers for human mesenchymal stem cells (hMSCs). hMSCs are labeled efficiently with Gd-Dye@MSN via endocytosis. Labeled hMSCs are unaffected in their viability, proliferation, and differentiation capacities into adipocytes, osteocytes, and chondrocytes, which can still be readily MRI detected. Imaging, with a clinical 1.5-T MRI system and a low incubation dosage of Gd, low detection cell numbers, and short incubation times is demonstrated on both loaded cells and hMSC-injected mouse brains. This study shows that the advantages of biocompatibility, durability, high internalizing efficiency, and pore architecture make MSNs an ideal vector of T1-agent for stem-cell tracking with MRI.

  7. Impact of agglomeration on the relaxometric properties of paramagnetic ultra-small gadolinium oxide nanoparticles.

    PubMed

    Faucher, Luc; Gossuin, Yves; Hocq, Aline; Fortin, Marc-André

    2011-07-22

    Ultra-small gadolinium oxide nanoparticles (US-Gd(2)O(3)) are used to provide 'positive' contrast effects in magnetic resonance imaging (MRI), and are being considered for molecular and cellular imaging applications. However, these nanoparticles can aggregate over time in aqueous medium, as well as when internalized into cells. This study is aimed at measuring in vitro, in aqueous medium, the impact of aggregation on the relaxometric properties of paramagnetic US-Gd(2)O(3) particles. First, the nanoparticle core size as well as aggregation behaviour was assessed by HRTEM. DLS (hydrodynamic diameter) was used to measure the hydrodynamic diameter of nanoparticles and nanoaggregates. The relaxometric properties were measured by NMRD profiling, as well as with (1)H NMR relaxometers. Then, the positive contrast enhancement effect was assessed by using magnetic resonance scanners (at 1.5 and 7 T). At every magnetic field, the longitudinal relaxivity (r(1)) decreased upon agglomeration, while remaining high enough to provide positive contrast. On the other hand, the transverse relaxivity (r(2)) slightly decreased at 0.47 and 1.41 T, but it was enhanced at higher fields (7 and 11.7 T) upon agglomeration. All NMRD profiles revealed a characteristic relaxivity peak in the range 60-100 MHz, suggesting the possibility to use US-Gd(2)O(3) as an efficient 'positive-T(1)' contrast agent at clinical magnetic fields (1-3 T), in spite of aggregation.

  8. Impact of agglomeration on the relaxometric properties of paramagnetic ultra-small gadolinium oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Faucher, Luc; Gossuin, Yves; Hocq, Aline; Fortin, Marc-André

    2011-07-01

    Ultra-small gadolinium oxide nanoparticles (US-Gd2O3) are used to provide 'positive' contrast effects in magnetic resonance imaging (MRI), and are being considered for molecular and cellular imaging applications. However, these nanoparticles can aggregate over time in aqueous medium, as well as when internalized into cells. This study is aimed at measuring in vitro, in aqueous medium, the impact of aggregation on the relaxometric properties of paramagnetic US-Gd2O3 particles. First, the nanoparticle core size as well as aggregation behaviour was assessed by HRTEM. DLS (hydrodynamic diameter) was used to measure the hydrodynamic diameter of nanoparticles and nanoaggregates. The relaxometric properties were measured by NMRD profiling, as well as with 1H NMR relaxometers. Then, the positive contrast enhancement effect was assessed by using magnetic resonance scanners (at 1.5 and 7 T). At every magnetic field, the longitudinal relaxivity (r1) decreased upon agglomeration, while remaining high enough to provide positive contrast. On the other hand, the transverse relaxivity (r2) slightly decreased at 0.47 and 1.41 T, but it was enhanced at higher fields (7 and 11.7 T) upon agglomeration. All NMRD profiles revealed a characteristic relaxivity peak in the range 60-100 MHz, suggesting the possibility to use US-Gd2O3 as an efficient 'positive-T1' contrast agent at clinical magnetic fields (1-3 T), in spite of aggregation.

  9. [Studies of three-dimensional cardiac late gadolinium enhancement MRI at 3.0 Tesla].

    PubMed

    Ishimoto, Takeshi; Ishihara, Masaru; Ikeda, Takayuki; Kawakami, Momoe

    2008-12-20

    Cardiac late Gadolinium enhancement MR imaging has been shown to allow assessment of myocardial viability in patients with ischemic heart disease. The current standard approach is a 3D inversion recovery sequence at 1.5 Tesla. The aims of this study were to evaluate the technique feasibility and clinical utility of MR viability imaging at 3.0 Tesla in patients with myocardial infarction and cardiomyopathy. In phantom and volunteer studies, the inversion time required to suppress the signal of interests and tissues was prolonged at 3.0 Tesla. In the clinical study, the average inversion time to suppress the signal of myocardium at 3.0 Tesla with respect to MR viability imaging at 1.5 Tesla was at 15 min after the administration of contrast agent (304.0+/-29.2 at 3.0 Tesla vs. 283.9+/-20.9 at 1.5 Tesla). The contrast between infarction and viable myocardium was equal at both field strengths (4.06+/-1.30 at 3.0 Tesla vs. 4.42+/-1.85 at 1.5 Tesla). Even at this early stage, MR viability imaging at 3.0 Tesla provides high quality images in patients with myocardial infarction. The inversion time is significantly prolonged at 3.0 Tesla. The contrast between infarction and viable myocardium at 3.0 Tesla are equal to 1.5 Tesla. Further investigation is needed for this technical improvement, for clinical evaluation, and for limitations.

  10. Intravascular contrast agents suitable for magnetic resonance imaging. [Dogs

    SciTech Connect

    Runge, V.M.; Clanton, J.A.; Herzer, W.A.; Gibbs, S.J.; Price, A.C.; Partain, C.L.; James, A.E. Jr.

    1984-10-01

    Two paramagnetic chelates, chromium EDTA and gadolinium DTPA, were evaluated as potential intravenous contrast agents for magnetic resonance imaging. After evaluating both agents in vitro, in vivo studies were conducted in dogs to document changes in renal appearance produced by contrast injection. Acute splenic and renal infarction were diagnosed with contrast-enhanced MR and confirmed by gamma camera imaging following administration of Tc-99m-labeled DMSA and sulfur colloid. The authors conclude that intravenous paramagnetic contrast agents presently offer the best mechanism for assessment of tissue function and changes in perfusion with MR.

  11. Graphene Oxide and Gadolinium-Chelate Functionalized Poly(lactic acid) Nanocapsules Encapsulating Perfluorooctylbromide for Ultrasound/Magnetic Resonance Bimodal Imaging Guided Photothermal Ablation of Cancer.

    PubMed

    Li, Zhenglin; Ke, Hengte; Wang, Jinrui; Miao, Zhaohua; Yue, Xiuli

    2016-03-01

    This paper successfully fabricated a novel multifunctional theranostic agent (PFOB@PLA/GO/Gd-DTPA NCs) by loading perfluorooctylbromide (PFOB) into poly(lactic acid) (PLA) nanocapsules (NCs) followed by surface functionalization with graphene oxide (GO) and gadolinium-chelate (Gd-DTPA). It was found that the resulting nanoagent could serve as a contrast agent simultaneously to enhance ultrasound (US) and magnetic resonance imaging (MRI). Benefiting from the strong absorption in the near infrared (NIR) region, the nanocapsules could efficiently kill cancer cells under NIR laser irradiation. Thus, such a single theranostic agent with the combination of realtime US imaging and high-resolution MR imaging could achieve great therapeutic effectiveness without systemic damage to the body. In addition, the cytotoxicity assay on HUVEC cells revealed a good biocompatibility of PFOB@PLA/GO/Gd-DTPA NCs, showing that the versatile nanocapsule system may hold great potential as an effective nanoplatform for contrast enhanced imaging guided photothermal therapy.

  12. The structural response of gadolinium phosphate to pressure

    DOE PAGESBeta

    Heffernan, Karina M.; Ross, Nancy L.; Spencer, Elinor C.; Boatner, Lynn A.

    2016-06-16

    In this study, accurate elastic constants for gadolinium phosphate (GdPO4) have been measured by single-crystal high-pressure diffraction methods. The bulk modulus of GdPO4 determined under hydrostatic conditions, 128.1(8) GPa (K'=5.8(2)), is markedly different from that obtained with GdPO4 under non-hydrostatic conditions (160(2) GPa), which indicates the importance of shear stresses on the elastic response of this phosphate. Finally, high pressure Raman and diffraction analysis indicate that the PO4 tetrahedra behave as rigid units in response to pressure and that contraction of the GdPO4 structure is facilitated by bending/twisting of the Gd–O–P links that result in increased distortion in the GdO9more » polyhedra.« less

  13. The structural response of gadolinium phosphate to pressure

    NASA Astrophysics Data System (ADS)

    Heffernan, Karina M.; Ross, Nancy L.; Spencer, Elinor C.; Boatner, Lynn A.

    2016-09-01

    Accurate elastic constants for gadolinium phosphate (GdPO4) have been measured by single-crystal high-pressure diffraction methods. The bulk modulus of GdPO4 determined under hydrostatic conditions, 128.1(8) GPa (Kʹ=5.8(2)), is markedly different from that obtained with GdPO4 under non-hydrostatic conditions (160(2) GPa), which indicates the importance of shear stresses on the elastic response of this phosphate. High pressure Raman and diffraction analysis indicate that the PO4 tetrahedra behave as rigid units in response to pressure and that contraction of the GdPO4 structure is facilitated by bending/twisting of the Gd-O-P links that result in increased distortion in the GdO9 polyhedra.

  14. Defect induced mobility enhancement: Gadolinium oxide (100) on Si(100)

    SciTech Connect

    Sitaputra, W.; Tsu, R.

    2012-11-26

    Growth of predominantly single crystal (100)-oriented gadolinium oxide (Gd{sub 2}O{sub 3}) on a p-type Si(100) and growth of a polycrystal with a predominant Gd{sub 2}O{sub 3}(100) crystallite on a n-type Si(100) was performed using molecular beam epitaxy. Despite a poorer crystal structure than Gd{sub 2}O{sub 3}(110), an enhancement in carrier mobility can be found only from the Gd{sub 2}O{sub 3}(100)/n-type Si(100) interface. The mobility of 1715-1780 cm{sup 2}/V {center_dot} s was observed at room temperature, for carrier concentration >10{sup 20} cm{sup -3}. This accumulation of the electrons and the mobility enhancement may arise from the two-dimensional confinement due to charge transfer across the interface similar to transfer doping.

  15. Interplay of disorder and geometrical frustration in Gadolinium Gallium Garnet

    NASA Astrophysics Data System (ADS)

    Woo, Nayoon; Silevitch, D. M.; Rosenbaum, T. F.

    2015-03-01

    We study the effects of disorder on the geometrically frustrated Heisenberg antiferromagnet Gadolinium Gallium Garnet (GGG) using neodymium doping (0.1 to 1%) in combination with linear and nonlinear ac magnetic susceptibility. The Nd doping actually alleviates the effects of disorder due to excess Gd ions occupying Ga sites. The linear, frequency-dependent susceptibility reveals that 1% Nd doping suppresses the appearance of any long-range order from approximately 80mK to below 30mK. The dynamics of isolated, correlated spin clusters were studied as a function of doping level using nonlinear susceptometry. In this regime, both the aggregate moment of the clustered spins and the activation field required to excite a nonlinear response were inversely correlated with the dopant density.

  16. Magnetocaloric effect at cryogenic temperature in gadolinium oxide nanotubes

    NASA Astrophysics Data System (ADS)

    Paul, Rima; Paramanik, Tapas; Das, Kalipada; Sen, Pintu; Satpati, B.; Das, I.

    2016-11-01

    We have synthesized fascinating nano-structure of Gadolinium oxide (Gd2O3) using controlled template-assisted electrochemical deposition technique which showed interesting anisotropic magnetic behavior. The nanotubes of Gd2O3 with average diameter 200 nm, length 10 μm and wall thickness 20 nm are constituted of nanoclusters with average diameter 7.5 nm. The tubes are aligned and are almost uniform throughout their length. Detailed magnetic measurements of aligned Gd2O3 nanotubes have been performed for both parallel and perpendicular magnetic field orientations with respect to the axis of the Gd2O3 nanotube array. Significant differences in magnetization values have been observed between the parallel and perpendicular orientations. Experimental results indicate the superparamagnetic nature of the nanomaterial. Large magnetocaloric effect, associated with the sharp change in magnetization of the Gd2O3 nanotubes, has been observed in the cryogenic temperature regime that shows anisotropic behavior.

  17. Motexafin gadolinium modulates levels of phosphorylated Akt and synergizes with inhibitors of Akt phosphorylation.

    PubMed

    Ramos, Jason; Sirisawad, Mint; Miller, Richard; Naumovski, Louie

    2006-05-01

    Motexafin gadolinium (MGd, Xcytrin) is a tumor-selective expanded porphyrin that targets oxidative stress-related proteins. MGd treatment of the follicular lymphoma-derived cell line HF-1 resulted in growth suppression and apoptosis whereas MGd treatment of the Burkitt's lymphoma-derived cell line Ramos resulted in growth suppression but not apoptosis. Because phosphorylation status of Akt/protein kinase B is regulated by oxidative stress, we monitored total and phosphorylated Akt (pAkt) in MGd-treated HF-1 and Ramos cells. Levels of pAkt increased within 30 minutes after MGd treatment of HF-1 but after 4 hours began to show a progressive decline to below baseline levels before cells underwent apoptosis. In MGd-treated Ramos cells, pAkt increased approximately 2-fold within 4 hours and remained persistently elevated. Because pAkt activates survival pathways, we determined if MGd-induced cell death could be enhanced by inhibiting phosphorylation of Akt. The addition of specific inhibitors of Akt phosphorylation (Akt inhibitor 1 or SH-5) reduced pAkt levels in MGd-treated HF-1 and Ramos cells and synergistically enhanced MGd-induced cell death. MGd was also evaluated in combination with celecoxib, an inhibitor of Akt phosphorylation, or docetaxel, a microtubule inhibitor that can decrease Akt phosphorylation. The combination of MGd/celecoxib or MGd/docetaxel resulted in decreased Akt phosphorylation and in synergistic cytotoxicity compared with either agent alone. These data point to a potential protective role for pAkt in MGd-induced apoptosis and suggest that MGd activity may be enhanced by combining it with agents that inhibit Akt phosphorylation.

  18. Surface modification of gadolinium oxide thin films and nanoparticles using poly(ethylene glycol)-phosphate.

    PubMed

    Guay-Bégin, Andrée-Anne; Chevallier, Pascale; Faucher, Luc; Turgeon, Stéphane; Fortin, Marc-André

    2012-01-10

    The performance of nanomaterials for biomedical applications is highly dependent on the nature and the quality of surface coatings. In particular, the development of functionalized nanoparticles for magnetic resonance imaging (MRI) requires the grafting of hydrophilic, nonimmunogenic, and biocompatible polymers such as poly(ethylene glycol) (PEG). Attached at the surface of nanoparticles, this polymer enhances the steric repulsion and therefore the stability of the colloids. In this study, phosphate molecules were used as an alternative to silanes or carboxylic acids, to graft PEG at the surface of ultrasmall gadolinium oxide nanoparticles (US-Gd(2)O(3), 2-3 nm diameter). This emerging, high-sensitivity "positive" contrast agent is used for signal enhancement in T(1)-weighted molecular and cellular MRI. Comparative grafting assays were performed on Gd(2)O(3) thin films, which demonstrated the strong reaction of phosphate with Gd(2)O(3) compared to silane and carboxyl groups. Therefore, PEG-phosphate was preferentially used to coat US-Gd(2)O(3) nanoparticles. The grafting of this polymer on the particles was confirmed by XPS and FTIR. These analyses also demonstrated the strong attachment of PEG-phosphate at the surface of Gd(2)O(3), forming a protective layer on the nanoparticles. The stability in aqueous solution, the relaxometric properties, and the MRI signal of PEG-phosphate-covered Gd(2)O(3) particles were also better than those from non-PEGylated nanoparticles. As a result, reacting PEG-phosphate with Gd(2)O(3) particles is a promising, rapid, one-step procedure to PEGylate US-Gd(2)O(3) nanoparticles, an emerging "positive" contrast agent for preclinical molecular and cellular applications.

  19. The magnetic, relaxometric, and optical properties of gadolinium-catalyzed single walled carbon nanotubes

    PubMed Central

    Sitharaman, Balaji; Jacobson, Barry D.; Wadghiri, Youssef Z.; Bryant, Henry; Frank, Joseph

    2013-01-01

    We report the magnetic behavior, relaxometry, phantom magnetic resonance imaging (MRI), and near-infrared (NIR) photoluminescence spectroscopy of gadolinium (Gd) catalyzed single-walled carbon nanotubes (Gd-SWCNTs). Gd-SWCNTs are paramagnetic with an effective magnetic moment of 7.29 μB. Gd-SWCNT solutions show high r1 and r2 relaxivities at very low (0.01 MHz) to clinically relevant (61 MHz) magnetic fields (r1 ≥ 130 mM−1 s−1, r2 ≥ 160 mM−1 s−1). Analysis of nuclear magnetic resonance dispersion profiles using Solomon, Bloembergen, and Morgan equations suggests that multiple structural and dynamic parameters such as rotational correlation time τR, rate of water exchange τM, and the number of fast-exchanging water molecules within the inner sphere q may be responsible for the increase in r1 and r2 relaxivity. The T1 weighted MRI signal intensity (gradient echo sequence; repetition time (TR) = 66 ms, echo time (TE) = 3 ms, flop angle = 108°) of Gd-SWCNT phantom solution is 14 times greater than the Gd-based clinical MRI contrast agent Magnevist. Additionally, these nanotubes exhibit near infrared fluorescence with distinct E11 transitions of several semiconducting SWCNTs. Taken together, these results demonstrate that Gd-SWCNTs have potential as a novel, highly efficacious, multimodal MRI-NIR optical imaging contrast agent. PMID:23653487

  20. Prognostic Value of Late Gadolinium Enhancement in Nonischemic Cardiomyopathy.

    PubMed

    Gaztanaga, Juan; Paruchuri, Vijayapraveena; Elias, Elliott; Wilner, Jonathan; Islam, Shahidul; Sawit, Simonette; Viles-Gonzalez, Juan; Sanz, Javier; Garcia, Mario J

    2016-10-01

    The purpose of this study was to determine the prognostic value of late gadolinium enhancement seen on cardiac magnetic resonance (CMR) imaging in patients with nonischemic cardiomyopathy (NICMP). Patients with NICMP are at increased risk for cardiovascular events and death. The presence of late gadolinium enhancement (LGE) in CMR may be associated with a poor prognosis, but its significance is still under investigation. We retrospectively studied 105 consecutive patients with NICMP and left ventricular ejection fraction (LVEF) ≤40% referred for CMR. The cohort was analyzed for the presence of LGE and left and right ventricular functional parameters. Patients were followed for the composite end point of hospitalization for congestive heart failure, appropriate implantable cardioverter-defibrillator therapy, or all-cause mortality. LGE was observed in 68% (n = 71) of the cohort. Both groups were similar in age, LVEF and LV end-diastolic volume. The LGE+ patients were more often men and had larger right ventricular volumes. At a mean follow-up of 806 ± 582 days, there were 26 patients (23 in the LGE+ group) who reached the primary end point. Event-free survival was significantly worse for the LGE+ patients. After adjusting for traditional risk factors (age, gender, and LVEF), patients with LGE had an increased risk of experiencing the primary end point (hazard ratio 4.47, 95% CIs 1.27 to 15.74, p = 0.02). The presence of LGE in patients with NICMP strongly predicts the occurrence of adverse events. In conclusion, this may be important in risk stratification and management. PMID:27614850

  1. The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model.

    PubMed Central

    Crathorne, Louise; Huxley, Nicola; Haasova, Marcela; Snowsill, Tristan; Jones-Hughes, Tracey; Hoyle, Martin; Briscoe, Simon; Coelho, Helen; Long, Linda; Medina-Lara, Antonieta; Mujica-Mota, Ruben; Napier, Mark; Hyde, Chris

    2016-01-01

    BACKGROUND Anaemia is a common side effect of cancer treatments and can lead to a reduction in quality of life. Erythropoiesis-stimulating agents (ESAs) are licensed for use in conjunction with red blood cell transfusions to improve cancer treatment-induced anaemia (CIA). OBJECTIVE To investigate the effectiveness and cost-effectiveness of ESAs in anaemia associated with cancer treatment (specifically chemotherapy). DATA SOURCES The following databases were searched from 2004 to 2013: The Cochrane Library, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Web of Science, Cumulative Index to Nursing and Allied Health Literature, British Nursing Index, Health Management Information Consortium, Current Controlled Trials and ClinicalTrials.gov. The US Food and Drug Administration and European Medicines Agency websites were also searched. Bibliographies of included papers were scrutinised for further potentially includable studies. REVIEW METHODS The clinical effectiveness review followed principles published by the NHS Centre for Reviews and Dissemination. Randomised controlled trials (RCTs), or systematic reviews of RCTs, of ESAs (epoetin or darbepoetin) for treating people with CIA were eligible for inclusion in the review. Comparators were best supportive care, placebo or other ESAs. Anaemia- and malignancy-related outcomes, health-related quality of life (HRQoL) and adverse events (AEs) were evaluated. When appropriate, data were pooled using meta-analysis. An empirical health economic model was developed comparing ESA treatment with no ESA treatment. The model comprised two components: one evaluating short-term costs and quality-adjusted life-years (QALYs) (while patients are anaemic) and one evaluating long-term QALYs. Costs and benefits were discounted at 3.5% per annum. Probabilistic and univariate deterministic sensitivity analyses were performed. RESULTS Of 1457 titles and abstracts screened, 23 studies assessing ESAs within their licensed

  2. Hydroxypyridonate chelating agents

    DOEpatents

    Raymond, Kenneth N.; Scarrow, Robert C.; White, David L.

    1987-01-01

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided.

  3. Theoretical study of structure and stability of small gadolinium carboxylate complexes in liquid scintillator solvents.

    PubMed

    Huang, Pin-Wen

    2014-09-01

    The structural properties of three small gadolinium carboxylate complexes in three liquid scintillator solvents (pseudocumene, linear alkylbenzene, and phenyl xylylethane) were theoretically investigated using density functional theory (B3LYP/LC-RECP) and polarizable continuum model (PCM). The average interaction energy between gadolinium atom and carboxylate ligand (E(int)) and the energy difference of the highest singly occupied molecular orbital and lowest unoccupied molecular orbital (Δ(SL)) were calculated to evaluate and compare the relative stability of these complexes in solvents. The calculation results show that the larger (with a longer alkyl chain) gadolinium carboxylate complex has greater stability than the smaller one, while these gadolinium carboxylates in linear alkylbenzene were found to have greater stability than those in the other two solvents.

  4. Agent Orange

    MedlinePlus

    ... Index Agent Orange Agent Orange Home Facts about Herbicides Veterans' Diseases Birth Defects Benefits Exposure Locations Provider ... millions of gallons of Agent Orange and other herbicides on trees and vegetation during the Vietnam War. ...

  5. Density of Gadolinium Nitrate Solutions for the High Flux Isotope Reactor

    SciTech Connect

    Taylor, Paul Allen; Lee, Denise L

    2009-05-01

    In late 1992, the High Flux Isotope Reactor (HFIR) was planning to switch the solution contained in the poison injection tank from cadmium nitrate to gadolinium nitrate. The poison injection system is an emergency system used to shut down the reactor by adding a neutron poison to the cooling water. This system must be able to supply a minimum of 69 pounds of gadolinium to the reactor coolant system in order to guarantee that the reactor would become subcritical. A graph of the density of gadolinium nitrate solutions over a concentration range of 5 to 30 wt% and a temperature range of 15 to 40{sup o}C was prepared. Routine density measurements of the solution in the poison injection tank are made by HFIR personnel, and an adaptation of the original graph is used to determine the gadolinium nitrate concentration. In late 2008, HFIR personnel decided that the heat tracing that was present on the piping for the poison injection system could be removed without any danger of freezing the solution; however, the gadolinium nitrate solution might get as cold as 5{sup o}C. This was outside the range of the current density-concentration correlation, so the range needed to be expanded. This report supplies a new density-concentration correlation that covers the extended temperature range. The correlation is given in new units, which greatly simplifies the calculation that is required to determine the pounds of gadolinium in the tank solution. The procedure for calculating the amount of gadolinium in the HFIR poison injection system is as follows: (1) Calculate the usable volume in the system; (2) Measure the density of the solution; (3) Calculate the gadolinium concentration using the following equation: Gd(lb/ft{sup 3}) = measured density (g/mL) x 34.681 - 34.785; (4) Calculate the amount of gadolinium in the system using the following equation: Amount of Gd(lb) = Gd concentration (lb/ft{sup 3}) x usable volume (ft{sup 3}). The equation in step 3 is exact for a temperature of

  6. Gadolinium Use in Spine Pain Management Procedures for Patients with Contrast Allergies: Results in 527 Procedures

    SciTech Connect

    Safriel, Yair Ang, Roberto; Ali, Muhammed

    2008-03-15

    Introduction. To review the safety and efficacy of gadolinium in spine pain management procedures in patients at high risk for a contrast reaction and who are not suitable candidates for the use of standard non-ionic contrast. Methods. We reviewed records over a 61-month period of all image-guided spinal pain management procedures where patients had allergies making them unsuitable candidates for standard non-ionic contrast and where gadolinium was used to confirm needle tip placement prior to injection of medication. Results. Three hundred and four outpatients underwent 527 procedures. A spinal needle was used in all but 41 procedures. Gadolinium was visualized using portable C-arm fluoroscopy in vivo allowing for confirmation of needle tip location. The gadolinium dose ranged from 0.2 to 10 ml per level. The highest dose received by one patient was 15.83 ml intradiscally during a three-level discogram. Three hundred and one patients were discharged without complication or known delayed complications. One patient had documented intrathecal injection but without sequelae and 2 patients who underwent cervical procedures experienced seizures requiring admission to the intensive care unit. Both the latter patients were discharged without any further complications. Conclusion. Based on our experience we recommend using gadolinium judiciously for needle tip confirmation. We feel more confident using gadolinium in the lumbar spine and in cervical nerve blocks. Gadolinium should probably not be used as an injectate volume expander. The indications for gadolinium use in cervical needle-guided spine procedures are less clear and use of a blunt-tipped needle should be considered.

  7. [Subclavian artery stenting using gadolinium contrast medium in a case with iodine allergy].

    PubMed

    Miyamoto, Michiyuki; Asano, Takeshi; Osanai, Toshiya; Endo, Shogo; Nakayama, Naoki; Kuroda, Satoshi; Houkin, Kiyohiro

    2012-05-01

    The authors reported a subclavian artery stenting (SAS) using gadolinium contrast medium. The patient was a 65-year-old female who presented dizziness and right upper extremity pain with movement. Digital subtraction angiography revealed right subclavian artery occlusion with subclavian steal phenomenon. We tried to treat this lesion using SAS. However, iodinated contrast medium caused the allergy in this patient and the treatment was discontinued. Therefore, SAS was performed with gadolinium contrast medium. Using gadolinium contrast medium, it is possible to confirm large arteries like innominate artery and subclavian artery. The stenting procedure was performed without complication. The usage of gadolinium contrast medium has the limit and some strategies are important to reduce the usage of gadolinium contrast medium in SAS. First, PercuSurge GuardWire® was placed in the right internal carotid artery to confirm the anatomy, to decide working angle, and to treat the common carotid artery in case of dissection. Second, a "U" shaped guide wire was placed in the distal end from the brachial artery. Guide wire from femoral side was able to pass the lesion at midpoint of the "U" shaped one. SAS using gadolinium contrast medium may be an alternative treatment if a patient with subclavian artery stenosis or occlusion is allergic to iodinated contrast medium.

  8. Stimuli-responsive poly(N-isopropyl acrylamide)-co-tyrosine@gadolinium: Iron oxide nanoparticle-based nanotheranostic for cancer diagnosis and treatment.

    PubMed

    Roy, Ekta; Patra, Santanu; Madhuri, Rashmi; Sharma, Prashant K

    2016-06-01

    In this paper, we have prepared a stimuli-responsive polymer modified gadolinium doped iron oxide nanoparticle (poly@Gd-MNPs) as cancer theranostic agent. The responsive polymer is composed of the poly(N-isopropyl acrylamide)-co-tyrosine unit, which shows excellent loading for the anti-cancer drug (methotrexate) and stimuli dependent release (change in pH and temperature). The in vitro experiment revealed that the poly@Gd-MNPs exhibited T1-weighted MRI capability (r1=11.314mM(-1)s(-1)) with good in-vitro hyperthermia response. The prepared poly@Gd-MNPs has generated quick heating (45°C in 2min) upon exposure to an alternating magnetic field and able to travel a distance of 35cm in 1min in the presence of an external magnet. The poly@Gd-MNPs shows 86% of drug loading capacity with 70% drug release in first 2h. The cytotoxic assay (MTT) demonstrated that the nanoparticle did not affect the viability of normal human fibroblast and efficiently kill the MCF7 cancer cells in the presence of an external magnetic field. To explore the uptake of poly@Gd-MNPs in the cells, bright field cell imaging study was also performed. This study provides a valuable approach for the design of highly sensitive polymer modified gadolinium doped iron oxide-based T1 contrast agents for cancer theranostics. PMID:26962761

  9. Metallofullerenes: a new class of MRI agents and more?

    PubMed

    Fatouros, Panos P; Shultz, Michael D

    2013-11-01

    Metallofullerenes have incited research endeavors across many disciplines owing to their wide range of properties obtainable by altering the metal component inside the fullerene cage or by a variety of surface functionalities. With a metal component of gadolinium, gadofullerenes have particularly shown promise in MRI applications owing to their high proton relaxivity and isolation of the metal from the biological environment. This article aims to give a perspective on the development of metallofullerenes as MRI contrast agents and further applications that distinguish them as a new class of imaging agent.

  10. Synthesis, Characterization, and Thermal Kinetics of Mixed Gadolinium: Calcium Heptamolybdate System

    PubMed Central

    Koul, R. K.; Suri, Shivani; Singh, Vishal; Bamzai, K. K.

    2014-01-01

    Synthesis of mixed gadolinium calcium heptamolybdate (GdCaHM) system in silica gel medium using single gel single tube technique has been successfully achieved. The grown crystal exhibits various morphologies, which includes spherulites, multifaceted, and square platelets. The nature of the grown material was established by X-ray diffraction (XRD) studies. Fourier transform infrared spectroscopy (FTIR) study signifies the presence of heptamolybdate (Mo7O24) and water symmetry structure, whereas energy dispersive X-ray analysis (EDAX) establishes the stoichiometric of the grown crystal as GdCaMo7O24·8H2O. The thermal behaviour was studied using the thermoanalytical techniques, which include thermogravimetry (TG), differential thermal analysis (DTA), and differential scanning calorimetry (DSC). Results obtained on the application of TG based models, namely, Horowitz-Metzger, Coats-Redfern, and Piloyan-Novikova, suggest the contracting cylindrical model as the relevant model for the thermal decomposition of the material. The kinetic parameters, namely, the order of reaction (n), activation energy (Ea), frequency factor (Z), and entropy (ΔS∗), were also calculated using these three models. PMID:27350973

  11. 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

  12. Activatable molecular MRI nanoprobe for tumor cell imaging based on gadolinium oxide and iron oxide nanoparticle.

    PubMed

    Li, Jingjing; Wang, Shan; Wu, Chen; Dai, Yue; Hou, Pingfu; Han, Cuiping; Xu, Kai

    2016-12-15

    Activatable molecular MRI nanoprobe for intracellular GSH sensing was designed. As an alternative to "always on" nanoprobe, activatable imaging nanoprobes which are designed to amplify or boost imaging signals only in response to the targets have attracted more and more attention. In this paper, we designed a novel activatable molecular magnetic resonance imaging (MRI) nanoprobe for tumor cell recognization based on a MRI signal variation induced by the distance change between T1 and T2 contrast agents (CAs) in the presence of glutathione (GSH). To achieve this aim, carboxyl group functionalized iron oxide nanoparticles (Fe3O4 NPs) and polyethylene glycol-coated gadolinium oxide (PEG-Gd2O3) NPs as T2 and T1 MRI CA were connected by cystamine which contains a disulfide linkage. Transmission electron microscopic (TEM), X-ray photoelectron spectroscopy (XPS), energy dispersive spectrometer (EDS), fourier transform infrared spectroscopy (FT-IR), mass spectra and (1)H nuclear magnetic resonance spectroscopy ((1)H NMR) were introduced for their characterizations. The formation of Fe3O4-cystamine-Gd2O3 (Fe3O4-SS-Gd2O3) nanocomplex resulted in a quenched T1 signal due to the near proximity of PEG-Gd2O3 NPs to Fe3O4 NPs and a "light-up" T1 signal with the cleavage of disulfide bond in the presence of GSH. These results provide not only an easy way to realize MRI of tumor cells based on the overexpressed intracellular GSH level, but also a new insight for the design of activatable MRI nanoprobe. PMID:27501342

  13. Functionalization of gadolinium metallofullerenes for detecting atherosclerotic plaque lesions by cardiovascular magnetic resonance

    PubMed Central

    2013-01-01

    Background The hallmark of atherosclerosis is the accumulation of plaque in vessel walls. This process is initiated when monocytic cells differentiate into macrophage foam cells under conditions with high levels of atherogenic lipoproteins. Vulnerable plaque can dislodge, enter the blood stream, and result in acute myocardial infarction and stroke. Imaging techniques such as cardiovascular magnetic resonance (CMR) provides one strategy to identify patients with plaque accumulation. Methods We synthesized an atherosclerotic-targeting contrast agent (ATCA) in which gadolinium (Gd)-containing endohedrals were functionalized and formulated into liposomes with CD36 ligands intercalated into the lipid bilayer. In vitro assays were used to assess the specificity of the ATCA for foam cells. The ability of ATCA to detect atherosclerotic plaque lesions in vivo was assessed using CMR. Results The ATCA was able to detect scavenger receptor (CD36)-expressing foam cells in vitro and were specifically internalized via the CD36 receptor as determined by focused ion beam/scanning electron microscopy (FIB-SEM) and Western blotting analysis of CD36 receptor-specific signaling pathways. The ATCA exhibited time-dependent accumulation in atherosclerotic plaque lesions of ApoE −/− mice as determined using CMR. No ATCA accumulation was observed in vessels of wild type (C57/b6) controls. Non-targeted control compounds, without the plaque-targeting moieties, were not taken up by foam cells in vitro and did not bind plaque in vivo. Importantly, the ATCA injection was well tolerated, did not demonstrate toxicity in vitro or in vivo, and no accumulation was observed in the major organs. Conclusions The ATCA is specifically internalized by CD36 receptors on atherosclerotic plaque providing enhanced visualization of lesions under physiological conditions. These ATCA may provide new tools for physicians to non-invasively detect atherosclerotic disease. PMID:23324435

  14. Convection-enhanced Delivery of Free Gadolinium with the Recombinant Immunotoxin MR1-1

    PubMed Central

    Ding, Dale; Kanaly, Charles W; Bigner, Darrell D; Cummings, Thomas J; Herndon, James E; Pastan, Ira; Raghavan, Raghu

    2011-01-01

    Purpose A major obstacle in glioblastoma (GBM) therapy is the restrictive nature of the blood-brain barrier (BBB). Convection-enhanced delivery (CED) is a novel method of drug administration which allows direct parenchymal infusion of therapeutics, bypassing the BBB. MR1-1 is a novel recombinant immunotoxin that targets the GBM tumor-specific antigen EGFRvIII and can be delivered via CED infusion. However, drug distribution via CED varies dramatically, which necessitates active monitoring. Gadolinium conjugated to diethylenetriamine penta-acetic acid (Gd-DTPA) is a commonly used MRI contrast agent which can be co-infused with therapies using CED and may be useful in monitoring infusion leak and early distribution. Experimental design Forty immunocompetent rats were implanted with intracerebral cannulas that were connected to osmotic pumps and subsequently randomized into four groups that each received 0.2% human serum albumin (HSA) mixed with a different experimental infusion: 1) 25 ng/mL MR1-1; 2) 7 μmol/mL Gd-DTPA; 3) 25 ng/mL MR1-1 and 7 μmol/mL Gd-DTPA; 4) 250 ng/mL MR1-1 and 7μmol/mL Gd-DTPA. The rats were monitored clinically for six weeks then necropsied and histologically assessed for CNS toxicity. Results All rats survived the entirety of the study without clinical or histological toxicity attributable to the study drugs. There was no statistically significant difference in weight change over time among groups (p>0.999). Conclusion MR1-1 co-infused with Gd-DTPA via CED is safe in the long-term setting in a pre-clinical animal model. Our data supports the use of Gd-DTPA, as a surrogate tracer, co-infused with MR1-1 for drug distribution monitoring in patients with GBM. PMID:19898744

  15. Gadolinium-uptake by aquatic and terrestrial organisms-distribution determined by laser ablation inductively coupled plasma mass spectrometry.

    PubMed

    Lingott, Jana; Lindner, Uwe; Telgmann, Lena; Esteban-Fernández, Diego; Jakubowski, Norbert; Panne, Ulrich

    2016-02-01

    Gadolinium (Gd) based contrast agents (CA) are used to enhance magnetic resonance imaging. As a consequence of excretion by patients and insufficient elimination in wastewater treatment plants they are detected in high concentrations in surface water. At present, little is known about the uptake of these species by living organisms in aquatic systems. Therefore the uptake of gadolinium containing chelates by plants and animals grown in exposed water or on soil irrigated with exposed water was investigated. For this purpose two types of plants were treated with two different contrast agents. The uptake of the Gd contrast agents was studied by monitoring the elemental distribution with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This technique allows the multi-elemental analysis of solid samples with high resolution and little sample preparation. The analysis of L. minor showed that the uptake of Gd correlated with the concentration of gadodiamide in the water. The higher the concentration in the exposed water, the larger the Gd signal in the LA-ICP-MS acquired image. Exposure time experiments showed saturation within one day. The L. minor had contact with the CAs through roots and fronds, whereas the L. sativum only showed uptake through the roots. These results show that an external absorption of the CA through the leaves of L. sativum was impossible. All the analyzed parts of the plant showed Gd signal from the CA; the highest being at the main vein of the leaf. It is shown that the CAs can be taken up from plants. Furthermore, the uptake and distribution of Gd in Daphnia magna were shown. The exposure via cultivation medium is followed by Gd signals on the skin and in the area of the intestine, while the uptake via exposed nutrition algae causes the significantly highest Gd intensities in the area of the intestine. Because there are hints of negative effects for human organism these findings are important as they show that Gd based

  16. Gadolinium-uptake by aquatic and terrestrial organisms-distribution determined by laser ablation inductively coupled plasma mass spectrometry.

    PubMed

    Lingott, Jana; Lindner, Uwe; Telgmann, Lena; Esteban-Fernández, Diego; Jakubowski, Norbert; Panne, Ulrich

    2016-02-01

    Gadolinium (Gd) based contrast agents (CA) are used to enhance magnetic resonance imaging. As a consequence of excretion by patients and insufficient elimination in wastewater treatment plants they are detected in high concentrations in surface water. At present, little is known about the uptake of these species by living organisms in aquatic systems. Therefore the uptake of gadolinium containing chelates by plants and animals grown in exposed water or on soil irrigated with exposed water was investigated. For this purpose two types of plants were treated with two different contrast agents. The uptake of the Gd contrast agents was studied by monitoring the elemental distribution with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This technique allows the multi-elemental analysis of solid samples with high resolution and little sample preparation. The analysis of L. minor showed that the uptake of Gd correlated with the concentration of gadodiamide in the water. The higher the concentration in the exposed water, the larger the Gd signal in the LA-ICP-MS acquired image. Exposure time experiments showed saturation within one day. The L. minor had contact with the CAs through roots and fronds, whereas the L. sativum only showed uptake through the roots. These results show that an external absorption of the CA through the leaves of L. sativum was impossible. All the analyzed parts of the plant showed Gd signal from the CA; the highest being at the main vein of the leaf. It is shown that the CAs can be taken up from plants. Furthermore, the uptake and distribution of Gd in Daphnia magna were shown. The exposure via cultivation medium is followed by Gd signals on the skin and in the area of the intestine, while the uptake via exposed nutrition algae causes the significantly highest Gd intensities in the area of the intestine. Because there are hints of negative effects for human organism these findings are important as they show that Gd based

  17. Impedance spectroscopic characterization of gadolinium substituted cobalt ferrite ceramics

    SciTech Connect

    Rahman, Md. T. Ramana, C. V.

    2014-10-28

    Gadolinium (Gd) substituted cobalt ferrites (CoFe{sub 2−x}Gd{sub x}O{sub 4}, referred to CFGO) with variable Gd content (x = 0.0–0.4) have been synthesized by solid state ceramic method. The crystal structure and impedance properties of CFGO compounds have been evaluated. X-ray diffraction measurements indicate that CFGO crystallize in the inverse spinel phase. The CFGO compounds exhibit lattice expansion due to substitution of larger Gd ions into the crystal lattice. Impedance spectroscopy analysis was performed under a wide range of frequency (f = 20 Hz–1 MHz) and temperature (T = 303–573 K). Electrical properties of Gd incorporated Co ferrite ceramics are enhanced compared to pure CoFe{sub 2}O{sub 4} due to the lattice distortion. Impedance spectroscopic analysis illustrates the variation of bulk grain and grain-boundary contributions towards the electrical resistance and capacitance of CFGO materials with temperature. A two-layer heterogeneous model consisting of moderately conducting grain interior (ferrite-phase) regions separated by insulating grain boundaries (resistive-phase) accurately account for the observed temperature and frequency dependent electrical characteristic of CFGO ceramics.

  18. Magnetism of Gadolinium: A First-Principles Perspective.

    PubMed

    Oroszlány, L; Deák, A; Simon, E; Khmelevskyi, S; Szunyogh, L

    2015-08-28

    By calculating the spectral density of states in the ferromagnetic ground state and in the high temperature paramagnetic phase we provide the first concise study of finite temperature effects on the electronic structure of the bulk and the surface of gadolinium metal. The variation of calculated spectral properties of the Fermi surface and the density of states in the bulk and at the surface are in good agreement with recent photoemission experiments performed in both ferromagnetic and paramagnetic phases. In the paramagnetic state we find vanishing spin splitting of the conduction band, but finite local spin moments both in bulk and at the surface. We clearly demonstrate that the formation of these local spin moments in the conduction band is due to the asymmetry of the density of states in the two spin channels, suggesting a complex, non-Stoner behavior. We, therefore, suggest that the vanishing or nearly vanishing spin splitting of spectral features cannot be used as an indicator for Stoner-like magnetism. PMID:26371666

  19. Late Gadolinium Enhancement in Patients with Nonischemic Dilated Cardiomyopathy.

    PubMed

    Memon, Sarfaraz; Ganga, Harsha V; Kluger, Jeffrey

    2016-07-01

    One-third of all patients with heart failure have nonischemic dilated cardiomyopathy (NIDM). Five-year mortality from NIDM is as high as 20% with sudden cardiac death (SCD) as the cause in 30% of the deaths. Currently, the left ventricular ejection fraction (LVEF) is used as the main criteria to risk stratify patients requiring an implantable cardioverter defibrillator (ICD) to prevent SCD. However, LVEF does not necessarily reflect myocardial propensity for electrical instability leading to ventricular tachycardia (VT) or ventricular fibrillation (VF). Due to the differential risk in various subgroups of patients for arrhythmic death, it is important to identify appropriate patients for ICD implantation so that we can optimize healthcare resources and avoid the complications of ICDs in individuals who are unlikely to benefit. We performed a systematic search and review of clinical trials of NIDM and the use of ICDs and cardiac magnetic resonance imaging with late gadolinium enhancement (LGE) for risk stratification. LGE identifies patients with NIDM who are at high risk for SCD and enables optimized patient selection for ICD placement, while the absence of LGE may reduce the need for ICD implantation in patients with NIDM who are at low risk for future VF/VT or SCD. PMID:27071516

  20. Design and development of a Gadolinium-doped water Cherenkov detector

    NASA Astrophysics Data System (ADS)

    Poudyal, Nabin

    This thesis describes a research and development project for neutron capture and detection in Gadolinium doped water. The Sanford Underground Research Facility (SURF) is exploring rare event physics, such as neutrinoless double beta decay (MAJORANA Project) and dark-matter detection (LUX experiment). The success of these experiments requires a careful study and understanding of background radiation, including flux and energy spectrum. The background radiation from surface contamination, radioactive decays of U-238, Th-232, Rn-222 in the surrounding rocks and muon induced neutrons have a large impact on the success of rare-event physics. The main objective of this R&D project is to measure the neutron flux contributing to ongoing experiments at SURF and suppress it by identification and capture method. For this purpose, we first modeled and designed a detector with Geant4 software. The approximate dimension of the detector is determined. The neutron capture percentage of the detector is estimated using Monte Carlo. The energy response of the detector is simulated. Next, we constructed the experimental detector, an acrylic rectangular tank (60cm x 30cm x 30cm), filled with Gadolinium-doped deionized water. The tank is coated with high efficient reflector and then taped with black electrical tape to make it opaque. The voltage dividers attached to PMTs are covered with mu-metal. Two 5-inch Hamamatsu Photomultiplier tubes were attached on both sides facing the tank to collect the Cherenkov light produced in the water. The detector utilizes the principle of Cherenkov light emission by a charged particle moving through a water at a speed higher than the speed of light in the water, hence it has an inherent energy threshold of Cherenkov photon production. This property reduces the lower energy backgrounds. Event data are obtained using the Data Acquisition hardware, Flash Analog to digital converter, along with Multi Instance Data Acquisition software. Post

  1. High-Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

    SciTech Connect

    Werner, Eric J.; Datta, Ankona; Jocher, Christoph J.; Raymond, Kenneth N.

    2008-01-15

    The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.

  2. CHARACTERIZATION OF AN ADVANCED GADOLINIUM NEUTRON ABSORBER ALLOY BY MEANS OF NEUTRON TRANSMISSION

    SciTech Connect

    Gregg W. Wachs

    2007-09-01

    Neutron transmission experiments were performed on samples of an advanced nickel-chromium-molybdenum-gadolinium (Ni-Cr-Mo-Gd) neutron absorber alloy. The primary purpose of the experiments was to demonstrate the thermal neutron absorbing capability of the alloy at specific gadolinium dopant levels. The new alloy is to be deployed for criticality control of highly enriched DOE SNF. For the transmission experiments, alloy test samples were fabricated with 0.0, 1.58 and 2.1 wt% natural gadolinium dispersed in a Ni-Cr-Mo base alloy. The transmission experiments were successfully carried out at the Los Alamos Neutron Science Center (LANSCE). Measured data from the neutron transmission experiments were compared to calculated results derived from a simple exponential transmission formula using only radiative capture cross sections. Excellent agreement between the measured and calculated results demonstrated the expected strong thermal absorption capability of the gadolinium poison and in addition, verified the measured elemental composition of the alloy test samples. The good agreement also indirectly confirmed that the gadolinium was dispersed fairly uniformly in the alloy and the ENDF VII radiative capture cross section data were accurate.

  3. Extraction of gadolinium from high flux isotope reactor control plates. [Alternative method

    SciTech Connect

    Kohring, M.W.

    1987-04-01

    Gadolinium-153 is an important radioisotope used in the diagnosis of various bone disorders. Recent medical and technical developments in the detection and cure of osteoporosis, a bone disease affecting an estimated 50 million people, have greatly increased the demand for this isotope. The Oak Ridge National Laboratory (ORNL) has produced /sup 153/Gd since 1980 primarily through the irradiation of a natural europium-oxide powder followed by the chemical separation of the gadolinium fraction from the europium material. Due to the higher demand for /sup 153/Gd, an alternative production method to supplement this process has been investigated. This process involves the extraction of gadolinium from the europium-bearing region of highly radioactive, spent control plates used at the High Flux Isotope Reactor (HFIR) with a subsequent re-irradiation of the extracted material for the production of the /sup 153/Gd. Based on the results of experimental and calculational analyses, up to 25 grams of valuable gadolinium (greater than or equal to60% enriched in /sup 152/Gd) resides in the europium-bearing region of the HFIR control components of which 70% is recoverable. At a specific activity yield of 40 curies of /sup 153/Gd for each gram of gadolinium re-irradiated, 700 one-curie sources can be produced from each control plate assayed.

  4. Saline as the Sole Contrast Agent for Successful MRI-guided Epidural Injections

    SciTech Connect

    Deli, Martin; Mateiescu, Serban Busch, Martin; Becker, Jan Garmer, Marietta Groenemeyer, Dietrich

    2013-06-15

    Purpose. To assess the performance of sterile saline solution as the sole contrast agent for percutaneous magnetic resonance imaging (MRI)-guided epidural injections at 1.5 T. Methods. A retrospective analysis of two different techniques of MRI-guided epidural injections was performed with either gadolinium-enhanced saline solution or sterile saline solution for documentation of the epidural location of the needle tip. T1-weighted spoiled gradient echo (FLASH) images or T2-weighted single-shot turbo spin echo (HASTE) images visualized the test injectants. Methods were compared by technical success rate, image quality, table time, and rate of complications. Results. 105 MRI-guided epidural injections (12 of 105 with gadolinium-enhanced saline solution and 93 of 105 with sterile saline solution) were performed successfully and without complications. Visualization of sterile saline solution and gadolinium-enhanced saline solution was sufficient, good, or excellent in all 105 interventions. For either test injectant, quantitative image analysis demonstrated comparable high contrast-to-noise ratios of test injectants to adjacent body substances with reliable statistical significance levels (p < 0.001). The mean table time was 22 {+-} 9 min in the gadolinium-enhanced saline solution group and 22 {+-} 8 min in the saline solution group (p = 0.75). Conclusion. Sterile saline is suitable as the sole contrast agent for successful and safe percutaneous MRI-guided epidural drug delivery at 1.5 T.

  5. Acute Respiratory Distress Syndrome after the Use of Gadolinium Contrast Media.

    PubMed

    Park, Jihye; Byun, Il Hwan; Park, Kyung Hee; Lee, Jae-Hyun; Nam, Eun Ji; Park, Jung-Won

    2015-07-01

    Acute respiratory distress syndrome (ARDS) is a medical emergency that threatens life. To this day, ARDS is very rarely reported by iodine contrast media, and there is no reported case of ARDS induced by gadolinium contrast media. Here, we present a case with ARDS after the use of gadobutrol (Gadovist) as a magnetic resonance imaging (MRI) contrast medium. A 26 years old female without any medical history, including allergic diseases and without current use of drugs, visited the emergency room for abdominal pain. Her abdominopelvic computed tomography with iodine contrast media showed a right ovarian cyst and possible infective colitis. Eighty-three hours later, she underwent pelvis MRI after injection of 7.5 mL (0.1 mL/kg body weight) of gadobutrol (Gadovist) to evaluate the ovarian cyst. She soon presented respiratory difficulty, edema of the lips, nausea, and vomiting, and we could hear wheezing upon auscultation. She was treated with dexamethasone, epinephrine, and norepinephrine. Her chest X-ray showed bilateral central bat-wing consolidative appearance. Managed with mechanical ventilation, she was extubated 3 days later and discharged without complications.

  6. Gadolinium-induced nephrogenic systemic fibrosis: the rise and fall of an iatrogenic disease

    PubMed Central

    Qureshi, Zaina P.; Sartor, A. Oliver; Norris, LeAnn B.; Murday, Alanna; Xirasagar, Sudha; Thomsen, Henrik S.

    2012-01-01

    Background. In 2006, nephrologists in Denmark unexpectedly identified chronic kidney disease (CKD) patients with a new syndrome, nephrogenic systemic fibrosis (NSF). Subsequently, 1603 NSF patients were reported to the Food and Drug Administration. Sixty hospitals in the USA account for 93% of these cases, and two hospitals in Denmark account for 4% of these reports. We review Denmark’s identification and subsequent rapid eradication of NSF. Methods. NSF reports from clinicians, the Danish Medicines Agency (DMA) and gadolinium-based contrast agents (GBCAs) manufacturers were reviewed (2002–11). Results. In 1994, the DMA approved a non-ionic linear GBCA, gadodiamide (0.1 mmol/kg), for magnetic resonance imagings (MRIs), with a renal insufficiency contraindication. In 1996, 0.3 mmol/kg dosing received DMA approval. In 1998, the DMA removed renal contraindications. In 1997 and 2002, radiologists at Skejby Hospital and Herlev Hospital, respectively, began performing gadodiamide-enhanced magnetic resonance angiography scans (0.3 mmol/kg) of CKD patients. In 2005, Herlev clinicians requested assistance in evaluating etiological causes of NSF occurring among 10 CKD patients who had developed NSF. This investigation, focusing on infectious agents, was inconclusive. In 2006, Herlev clinicians reported that of 108 CKD patients who had received gadodiamide-enhanced MRI, 20 had developed probable NSF. Herlev radiologists voluntarily discontinued administering gadodiamide to all patients and no new NSF cases at Herlev Hospital developed subsequently. After meeting with Herlev radiologists, Skejby radiologists also discontinued administering gadodiamide to all patients. In 2007, the European Medicines Agency and the DMA contraindicated gadodiamide administration to CKD patients. In 2008, in response to these advisories, radiologists at the other 36 Danish hospitals discontinued administering gadodiamide to all patients, following on practices adopted at Skejby and Herlev

  7. GADOLINIUM OXALATE SOLUBILITY MEASUREMENTS IN NITRIC ACID SOLUTIONS

    SciTech Connect

    Pierce, R. A.

    2012-03-12

    HB-Line will begin processing Pu solutions during FY2012 that will involve the recovery of Pu using oxalate precipitation and filtration. After the precipitation and filtration processes, the filtrate solution will be transferred from HB-Line to H-Canyon. The presence of excess oxalate and unfiltered Pu oxalate solids in these solutions create a criticality safety issue if they are sent to H-Canyon without controls in H-Canyon. One approach involves H-Canyon receiving the filtrate solution into a tank that is poisoned with soluble gadolinium (Gd). Decomposition of the oxalate will occur within a subsequent H-Canyon vessel. The receipt of excess oxalate into the H-Canyon receipt tanks has the potential to precipitate a portion of the Gd poison in the receipt tanks. Because the amount of Gd in solution determines the maximum amount of Pu solids that H-Canyon can receive, H-Canyon Engineering requested that SRNL determine the solubility of Gd in aqueous solutions of 4-10 M nitric acid (HNO{sub 3}), 4-12 g/L Gd, and 0.15-0.25 M oxalic acid (H{sub 2}C{sub 2}O{sub 4}) at 25 °C. The target soluble Gd concentration is 6 g/L. The data indicate that the target can be achieved above 6 M HNO{sub 3} and below 0.25 M H{sub 2}C{sub 2}O{sub 4}. At 25 °C, for 6 M HNO{sub 3}, 11 g/L and 7 g/L Gd are soluble in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. In 4 M HNO{sub 3}, the Gd solubility drops significantly to 2.5 g/L and 0.8 g/L in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. The solubility of Gd at 8-10 M HNO{sub 3} exceeds the solubility at 6 M HNO{sub 3}. The data for 4 M HNO{sub 3} showed good agreement with data in the literature. To achieve a target of 6 g/L soluble Gd in solution in the presence of 0.15-0.25 M oxalate, the HNO{sub 3} concentration must be maintained at or above 6 M HNO{sub 3}. The solubility of Gd in 4 M HNO{sub 3} with 0.15 M oxalate at 10 °C is about 1.5 g/L. For 6 M HNO{sub 3} with 0.15 M oxalate, the solubility of Gd at 10

  8. Patterns of late gadolinium enhancement in Duchenne muscular dystrophy carriers

    PubMed Central

    2014-01-01

    Background This study was designed to assess whether cardiovascular magnetic resonance imaging (CMR) in Duchenne muscular dystrophy carriers (DMDc) may index any cell milieu elements of LV dysfunction and whether this cardiac phenotype may be related to genotype. The null hypothesis was that myocardial fibrosis, assessed by late gadolinium enhancement (LGE), might be similarly accounted for in DMDc and gender and age-matched controls. Methods Thirty DMDc patients had CMR and genotyping with 37 gender and age-matched controls. Systolic and diastolic LV function was assessed by 2D-echocardiography. Results Absolute and percent LGE were higher in muscular symptomatic (sym) than asymptomatic (asy) DMDc (1.77 ± 0.27 vs 0.76 ± 0.17 ml; F = 19.6, p < 0.0001 and 1.86 ± 0.26% vs 0.68 ± 0.17%, F = 22.1, p < 0.0001, respectively). There was no correlation between LGE and age. LGE was seen most frequently in segments 5 and 6; segment 5 was involved in all asy-DMDc. Subepicardial LGE predominated, compared to the mid-myocardial one (11 out of 14 DMDc). LGE was absent in the subendocardium. No correlations were seen between genotyping (type of mutation, gene region and protein domain), confined to the exon’s study, and cardiac phenotype. Conclusions A typical myocardial LGE-pattern location (LV segments 5 and 6) was a common finding in DMDc. LGE was more frequently subepicardial plus midmyocardial in sym-DMDc, with normal LV systolic and diastolic function. No genotype-phenothype correlation was found. PMID:25008475

  9. Structural and optical properties of Nd{sup 3+} doped gadolinium oxide 1D nanorods

    SciTech Connect

    Boopathi, G. Mohan, R.; Raj, S. Gokul; Kumar, G. Ramesh

    2014-04-24

    Neodymium doped gadolinium hydroxide [Nd:Gd(OH)3] nanorods were successfully synthesized at 60 °C through co-precipitation method. The dopant percentage was maintained at 5% and calcination was done at 750 °C temperature for 1 hour to form the respective neodymium doped gadolinium oxide [Nd:Gd{sub 2}O{sub 3}] nanorods. The as-formed and annealed products were investigated in detail by using powder X-ray diffraction (XRD) pattern, scanning electron microscopy (SEM) with an energy dispersive X-ray spectrum (EDX), high-resolution transmission electron microscopy (HRTEM) and photoluminescence (PL) spectrophotometry.

  10. Structural, morphological and optical investigations on Sm{sup 3+} doped gadolinium oxide nanorods

    SciTech Connect

    Boopathi, G.; Mohan, R.; Raj, S. Gokul; Kumar, G. Ramesh

    2014-04-24

    One dimensional uniform Sm{sup 3+} doped gadolinium hydroxide nanorods have been prepared via simple co– precipitation technique at 60 °C temperature for 1 hour. The samples were calcinated at 750 °C to obtain Sm{sup 3+} doped gadolinium oxide nanorods. The 1D nanorods were then subjected to different characterization techniques to ascertain its structural stability and its morphology were investigated using high–resolution transmission electron microscopy. Photoluminescence (PL) spectrophotometry was investigated and the obtained results were discussed in detail.

  11. Significance of Late Gadolinium Enhancement at Right Ventricular Attachment to Ventricular Septum in Patients With Hypertrophic Cardiomyopathy.

    PubMed

    Chan, Raymond H; Maron, Barry J; Olivotto, Iacopo; Assenza, Gabriele E; Haas, Tammy S; Lesser, John R; Gruner, Christiane; Crean, Andrew M; Rakowski, Harry; Rowin, Ethan; Udelson, James; Lombardi, Massimo; Tomberli, Benedetta; Spirito, Paolo; Formisano, Francesco; Marra, Martina P; Biagini, Elena; Autore, Camillo; Manning, Warren J; Appelbaum, Evan; Roberts, William C; Basso, Cristina; Maron, Martin S

    2015-08-01

    Cardiovascular magnetic resonance (CMR) with extensive late gadolinium enhancement (LGE) is a novel marker for increased risk for sudden death (SD) in patients with hypertrophic cardiomyopathy (HC). Small focal areas of LGE confined to the region of right ventricular (RV) insertion to ventricular septum (VS) have emerged as a frequent and highly visible CMR imaging pattern of uncertain significance. The aim of this study was to evaluate the prognostic significance of LGE confined to the RV insertion area in patients with HC. CMR was performed in 1,293 consecutive patients with HC from 7 HC centers, followed for 3.4 ± 1.7 years. Of 1,293 patients (47 ± 14 years), 134 (10%) had LGE present only in the anterior and/or inferior areas of the RV insertion to VS, occupying 3.7 ± 2.9% of left ventricular myocardium. Neither the presence nor extent of LGE in these isolated areas was a predictor of adverse HC-related risk, including SD (adjusted hazard ratio 0.82, 95% confidence interval 0.45 to 1.50, p = 0.53; adjusted hazard ratio 1.16/10% increase in LGE, 95% confidence interval 0.29 to 4.65, p = 0.83, respectively). Histopathology in 20 HC hearts show the insertion areas of RV attachment to be composed of a greatly expanded extracellular space characterized predominantly by interstitial-type fibrosis and interspersed disorganized myocyte patterns and architecture. In conclusion, LGE confined to the insertion areas of RV to VS was associated with low risk of adverse events (including SD). Gadolinium pooling in this region of the left ventricle does not reflect myocyte death and repair with replacement fibrosis or scarring.

  12. Syntheses, structures, magnetism, and optical properties of gadolinium scandium chalcogenides

    SciTech Connect

    Jin Gengbang; Choi, Eun Sang; Albrecht-Schmitt, Thomas E.

    2009-05-15

    Three gadolinium scandium chalcogenides have been synthesized using Sb{sub 2}Q{sub 3} (Q=S, Se) fluxes at 975 deg. C. Gd{sub 3.04}Sc{sub 0.96}S{sub 6}, GdScS{sub 3}, and Gd{sub 1.05}Sc{sub 0.95}Se{sub 3} are crystallized in U{sub 3}ScS{sub 6} type, GdFeO{sub 3} type, and UFeS{sub 3} type structures, respectively. The magnetic susceptibilities for these compounds follow the Curie-Weiss law above their transition temperatures. The effective magnetic moments are close to calculated values for free Gd{sup 3+} ions. The Weiss constants for Gd{sub 3.04}Sc{sub 0.96}S{sub 6}, GdScS{sub 3}, and Gd{sub 1.05}Sc{sub 0.95}Se{sub 3} are determined to be -3.3(1), -4.5(4), and 1.5(1) K, respectively. Gd{sub 3.04}Sc{sub 0.96}S{sub 6} orders antiferromagnetically below 9 K. GdScS{sub 3} exhibits an antiferromagnetic ordering below 3 K with a weak ferromagnetism. Gd{sub 1.05}Sc{sub 0.95}Se{sub 3} undergoes a ferromagnetic transition around 5 K. The optical band gaps for Gd{sub 3.04}Sc{sub 0.96}S{sub 6}, GdScS{sub 3}, and Gd{sub 1.05}Sc{sub 0.95}Se{sub 3} are 1.5, 2.1, and 1.2 eV, respectively. - Graphical abstract: A view of the three-dimensional structure of Gd{sub 3.04}Sc{sub 0.96}S{sub 6} along the c axis.

  13. GADOLINIUM OXALATE SOLUBILITY MEASUREMENTS IN NITRIC ACID SOLUTIONS

    SciTech Connect

    Pierce, R.

    2012-02-22

    HB-Line will begin processing Pu solutions during FY2012 that will involve the recovery of Pu using oxalate precipitation and filtration. After the precipitation and filtration processes, the filtrate solution will be transferred from HB-Line to H-Canyon. The presence of excess oxalate and unfiltered Pu oxalate solids in these solutions create a criticality safety issue if they are sent to H-Canyon without controls in H-Canyon. One approach involves H-Canyon receiving the filtrate solution into a tank that is poisoned with soluble gadolinium (Gd). Decomposition of the oxalate will occur within a subsequent H-Canyon vessel. The receipt of excess oxalate into the H-Canyon receipt tanks has the potential to precipitate a portion of the Gd poison in the receipt tanks. Because the amount of Gd in solution determines the maximum amount of Pu solids that H-Canyon can receive, H-Canyon Engineering requested that SRNL determine the solubility of Gd in aqueous solutions of 4-10 M nitric acid (HNO{sub 3}), 4-12 g/L Gd, and 0.15-0.25 M oxalic acid (H{sub 2}C{sub 2}O{sub 4}) at 25 C. The target soluble Gd concentration is 6 g/L. The data indicate that the target can be achieved above 6 M HNO{sub 3} and below 0.25 M H{sub 2}C{sub 2}O{sub 4}. For 6 M HNO{sub 3}, 10.5 g/L and 7 g/L Gd are soluble in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. In 4 M HNO{sub 3}, the Gd solubility drops significantly to 2 g/L and 0.25 g/L in 0.15 M and 0.25 M H{sub 2}C{sub 2}O{sub 4}, respectively. The solubility of Gd at 8-10 M HNO{sub 3} exceeds the solubility at 6 M HNO{sub 3}. The data for 4 M HNO{sub 3} showed good agreement with data in the literature. To achieve a target of 6 g/L soluble Gd in solution in the presence of 0.15-0.25 M oxalate, the HNO{sub 3} concentration must be maintained at or above 6 M HNO{sub 3}.

  14. Inorganic nanocrystals as contrast agents in MRI:synthesis, coating and introducing multifunctionality

    PubMed Central

    Sanchez-Gaytan, Brenda L.; Mieszawska, Aneta J.; Fayad, Zahi A.

    2013-01-01

    Inorganic nanocrystals have myriad applications in medicine, which includes their use as drug or gene delivery complexes, therapeutic hyperthermia agents, in diagnostic systems and as contrast agents in a wide range of medical imaging techniques. For MRI, nanocrystals can produce contrast themselves, of which iron oxides have been most extensively explored, or be given a coating that generates MR contrast, for example gold nanoparticles coated with gadolinium chelates. These MR-active nanocrystals can be used in imaging of the vasculature, liver and other organs, as well as molecular imaging, cell tracking and theranostics. Due to these exciting applications, synthesizing and rendering these nanocrystals water-soluble and biocompatible is therefore highly desirable. We will discuss aqueous phase and organic phase methods for synthesizing inorganic nanocrystals such as gold, iron oxides and quantum dots. The pros and cons of the various methods will be highlighted. We explore various methods for making nanocrystals biocompatible, i.e. directly synthesizing nanocrystals coated with biocompatible coatings, ligand substitution, amphiphile coating and embedding in carrier matrices that can be made biocompatible. Various examples will be highlighted and their applications explained. These examples signify that synthesizing biocompatible nanocrystals with controlled properties has been achieved by numerous research groups and can be applied for a wide range of applications. Therefore we expect to see reports of preclinical applications of ever more complex MRI-active nanoparticles and their wider exploitation, as well as in novel clinical settings. PMID:23303729

  15. In vitro radiosensitizing effects of ultrasmall gadolinium based particles on tumour cells.

    PubMed

    Mowat, P; Mignot, A; Rima, W; Lux, F; Tillement, O; Roulin, C; Dutreix, M; Bechet, D; Huger, S; Humbert, L; Barberi-Heyob, M; Aloy, M T; Armandy, E; Rodriguez-Lafrasse, C; Le Duc, G; Roux, S; Perriat, P

    2011-09-01

    Since radiotherapy is widely used in cancer treatment, it is essential to develop strategies which lower the irradiation burden while increasing efficacy and become efficient even in radio resistant tumors. Our new strategy is relying on the development of solid hybrid nanoparticles based on rare-earth such as gadolinium. In this paper, we then evidenced that gadolinium-based particles can be designed to enter efficiently into the human glioblastoma cell line U87 in quantities that can be tuned by modifying the incubation conditions. These sub-5 nm particles consist in a core of gadolinium oxide, a shell of polysiloxane and are functionalized by diethylenetriaminepentaacetic acid (DTPA). Although photoelectric effect is maximal in the [10-100 keV] range, such particles were found to possess efficient in-vitro radiosensitizing properties at an energy of 660 keV by using the "single-cell gel electrophoresis comet assay," an assay that measures the number of DNA damage that occurs during irradiation. Even more interesting, the particles have been evidenced by MTT assays to be also efficient radiosensitizers at an energy of 6 MeV for doses comprised between 2 and 8 Gy. The properties of the gadolinium-based particles give promising opening to a particle-assisted radio-therapy by using irradiation systems already installed in the majority of hospitals.

  16. Indirect MR lymphangiography of the head and neck using conventional gadolinium contrast: A pilot study in humans

    SciTech Connect

    Loo, Billy W. . E-mail: BWLoo@Stanford.edu; Draney, Mary T.; Sivanandan, Ranjiv; Ruehm, Stefan G.; Pawlicki, Todd; Xing Lei; Herfkens, Robert J.; Le, Quynh-Thu

    2006-10-01

    Purpose: To evaluate indirect magnetic resonance lymphangiography (MR-LAG) using interstitial injection of conventional gadolinium contrast (gadoteridol and gadopentetate dimeglumine) for delineating the primary lymphatic drainage of head-and-neck sites. Methods and Materials: We performed head-and-neck MR-LAG in 5 healthy volunteers, with injection of dermal and mucosal sites. We evaluated the safety of the procedure, the patterns of enhancement categorized by injection site and nodal level, the time course of enhancement, the optimal concentration and volume of contrast, and the optimal imaging sequence. Results: The worst side effects of interstitial contrast injection were brief, mild pain and swelling at the injected sites that were self-limited. MR-LAG resulted in consistent visualization of the primary lymphatic drainage pattern specific to each injected site, which was reproducible on repeated examinations. The best enhancement was obtained with injection of small volumes (0.3-0.5 mL) of either agent diluted, imaging within 5-15 min of injection, and a three-dimensional fast spoiled gradient echo sequence with magnetization transfer. Conclusions: We found head-and-neck MR-LAG to be a safe, convenient imaging method that provides functional information about the lymphatic drainage of injected sites. Applied to head-and-neck cancer, it has the potential to identify sites at highest risk of occult metastatic spread for radiotherapy or surgical planning, and possibly to visualize micrometastases.

  17. Anthropogenic gadolinium anomalies and rare earth elements in the water of Atibaia River and Anhumas Creek, Southeast Brazil.

    PubMed

    de Campos, Francisco Ferreira; Enzweiler, Jacinta

    2016-05-01

    The concentrations of rare earth elements (REE), measured in water samples from Atibaia River and its tributary Anhumas Creek, Brazil, present excess of dissolved gadolinium. Such anthropogenic anomalies of Gd in water, already described in other parts of the world, result from the use of stable and soluble Gd chelates as contrast agents in magnetic resonance imaging. Atibaia River constitutes the main water supply of Campinas Metropolitan area, and its basin receives wastewater effluents. The REE concentrations in water samples were determined in 0.22-μm pore size filtered samples, without and after preconcentration by solid-phase extraction with bis-(2-ethyl-hexyl)-phosphate. This preconcentration method was unable to retain the anthropogenic Gd quantitatively. The probable reason is that the Gd chelates dissociate slowly in acidic media to produce the free ion that is retained by the phosphate ester. Strong correlations between Gd and constituents or parameters associated with effluents confirmed the source of most Gd in water samples as anthropogenic. The shale-normalized REE patterns of Atibaia River and Anhumas Creek water samples showed light and heavy REE enrichment trends, respectively. Also, positive Ce anomalies in many Atibaia River samples, as well as the strong correlations of the REE (except Gd) with terrigenous elements, imply that inorganic colloidal particles contributed to the REE measured values. PMID:27068533

  18. Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations

    PubMed Central

    Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo

    2016-01-01

    Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives.

  19. Anthropogenic gadolinium anomalies and rare earth elements in the water of Atibaia River and Anhumas Creek, Southeast Brazil.

    PubMed

    de Campos, Francisco Ferreira; Enzweiler, Jacinta

    2016-05-01

    The concentrations of rare earth elements (REE), measured in water samples from Atibaia River and its tributary Anhumas Creek, Brazil, present excess of dissolved gadolinium. Such anthropogenic anomalies of Gd in water, already described in other parts of the world, result from the use of stable and soluble Gd chelates as contrast agents in magnetic resonance imaging. Atibaia River constitutes the main water supply of Campinas Metropolitan area, and its basin receives wastewater effluents. The REE concentrations in water samples were determined in 0.22-μm pore size filtered samples, without and after preconcentration by solid-phase extraction with bis-(2-ethyl-hexyl)-phosphate. This preconcentration method was unable to retain the anthropogenic Gd quantitatively. The probable reason is that the Gd chelates dissociate slowly in acidic media to produce the free ion that is retained by the phosphate ester. Strong correlations between Gd and constituents or parameters associated with effluents confirmed the source of most Gd in water samples as anthropogenic. The shale-normalized REE patterns of Atibaia River and Anhumas Creek water samples showed light and heavy REE enrichment trends, respectively. Also, positive Ce anomalies in many Atibaia River samples, as well as the strong correlations of the REE (except Gd) with terrigenous elements, imply that inorganic colloidal particles contributed to the REE measured values.

  20. Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations.

    PubMed

    Granata, Vincenza; Cascella, Marco; Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo; Petrillo, Antonella

    2016-01-01

    Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives. PMID:27652261

  1. Gadolinium(III)-Chelated Silica Nanospheres Integrating Chemotherapy and Photothermal Therapy for Cancer Treatment and Magnetic Resonance Imaging.

    PubMed

    Cao, Mingjing; Wang, Pengyang; Kou, Yu; Wang, Jing; Liu, Jing; Li, Yanhui; Li, Jiayang; Wang, Liming; Chen, Chunying

    2015-11-18

    The combination of therapy and diagnosis has been emerging as a promising strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and magnetic resonance imaging (MRI) in one system, we have synthesized a new magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX), indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres (Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC coating serves as a polymer layer to protect from quick release of drugs from the nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG-PDC depends on pH and temperature. The process will be accelerated in the acidic condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the photothermal effects promote DOX release and improve the therapeutic efficacy compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can thus act as a promising theranostic platform for multimodal cancer treatment.

  2. Immediate Adverse Reactions to Gadolinium-Based MR Contrast Media: A Retrospective Analysis on 10,608 Examinations

    PubMed Central

    Fusco, Roberta; dell'Aprovitola, Nicoletta; Catalano, Orlando; Filice, Salvatore; Schiavone, Vincenzo; Izzo, Francesco; Cuomo, Arturo

    2016-01-01

    Background and Purpose. Contrast media (CM) for magnetic resonance imaging (MRI) may determine the development of acute adverse reactions. Objective was to retrospectively assess the frequency and severity of adverse reactions associated with gadolinium-based contrast agents (GBCAs) injection in patients who underwent MRI. Material and Methods. At our center 10608 MRI examinations with CM were performed using five different GBCAs: Gd-BOPTA (MultiHance), Gd-DTPA (Magnevist), Gd-EOBDTPA (Primovist), Gd-DOTA (Dotarem), and Gd-BTDO3A (Gadovist). Results. 32 acute adverse reactions occurred, accounting for 0.3% of all administration. Twelve reactions were associated with Gd-DOTA injection (0.11%), 9 with Gd-BOPTA injection (0.08%), 6 with Gd-BTDO3A (0.056%), 3 with Gd-EOB-DTPA (0.028%), and 2 with Gd-DTPA (0.018%). Twenty-four reactions (75.0%) were mild, four (12.5%) moderate, and four (12.5%) severe. The most severe reactions were seen associated with use of Gd-BOPTA, with 3 severe reactions in 32 total reactions. Conclusion. Acute adverse reactions are generally rare with the overall adverse reaction rate of 0.3%. The most common adverse reactions were not severe, consisting in skin rash and hives. PMID:27652261

  3. Encapsulated gadolinium and dysprosium ions within ultra-short carbon nanotubes for MR microscopy at 11.75 and 21.1 T.

    PubMed

    Rosenberg, Jens T; Cisneros, Brandon T; Matson, Michael; Sokoll, Michelle; Sachi-Kocher, Afi; Bejarano, Fabian Calixto; Wilson, Lon J; Grant, Samuel C

    2014-01-01

    Single-walled carbon nanotubes (SWNTs) have gained interest for their biocompatibility and multifunctional properties. Ultra-short SWNTs (US-tubes) have demonstrated high proton relaxivity when encapsulating gadolinium ions (Gd(3+)) at clinical field strengths. At higher field strengths, however, Gd(3+) ions demonstrate decreased proton relaxation properties while chemically similar dysprosium ions (Dy(3+)) improve relaxation properties. This report investigates the first use of Gd(3+) and Dy(3+) ions within US-tubes (GNTs and DNTs, respectively) at ultra-high magnetic field (21.1 T). Both agents are compared in solution and as an intracellular contrast agent labeling a murine microglia cell line (Bv2) immobilized in a tissue-mimicking agarose phantom using two high magnetic fields: 21.1 and 11.75 T. In solution at 21.1 T, results show excellent transverse relaxation; DNTs outperformed GNTs as a T(2) agent with measured r(2)/r(1) ratios of 247 and 47, respectively. Additionally, intracellular DNTs were shown to be a better T(2) agent than GNTs with higher contrast percentages and contrast-to-noise ratios. As such, this study demonstrates the potential of DNTs at high magnetic fields for cellular labeling and future in vivo, MRI-based cell tracking.

  4. Criticality experiments with low enriched UO/sub 2/ fuel rods in water containing dissolved gadolinium

    SciTech Connect

    Bierman, S.R.; Murphy, E.S.; Clayton, E.D.; Keay, R.T.

    1984-02-01

    The results obtained in a criticality experiments program performed for British Nuclear Fuels, Ltd. (BNFL) under contract with the United States Department of Energy (USDOE) are presented in this report along with a complete description of the experiments. The experiments involved low enriched UO/sub 2/ and PuO/sub 2/-UO/sub 2/ fuel rods in water containing dissolved gadolinium, and are in direct support of BNFL plans to use soluble compounds of the neutron poison gadolinium as a primary criticality safeguard in the reprocessing of low enriched nuclear fuels. The experiments were designed primarily to provide data for validating a calculation method being developed for BNFL design and safety assessments, and to obtain data for the use of gadolinium as a neutron poison in nuclear chemical plant operations - particularly fuel dissolution. The experiments program covers a wide range of neutron moderation (near optimum to very under-moderated) and a wide range of gadolinium concentration (zero to about 2.5 g Gd/l). The measurements provide critical and subcritical k/sub eff/ data (1 greater than or equal to k/sub eff/ greater than or equal to 0.87) on fuel-water assemblies of UO/sub 2/ rods at two enrichments (2.35 wt % and 4.31 wt % /sup 235/U) and on mixed fuel-water assemblies of UO/sub 2/ and PuO/sub 2/-UO/sub 2/ rods containing 4.31 wt % /sup 235/U and 2 wt % PuO/sub 2/ in natural UO/sub 2/ respectively. Critical size of the lattices was determined with water containing no gadolinium and with water containing dissolved gadolinium nitrate. Pulsed neutron source measurements were performed to determine subcritical k/sub eff/ values as additional amounts of gadolinium were successively dissolved in the water of each critical assembly. Fission rate measurements in /sup 235/U using solid state track recorders were made in each of the three unpoisoned critical assemblies, and in the near-optimum moderated and the close-packed poisoned assemblies of this fuel.

  5. A new method for the determination of Gadolinium in ppq levels

    NASA Astrophysics Data System (ADS)

    Brünjes, Robert; Bichler, Andrea; Hofmann, Thilo

    2015-04-01

    The use of Gadolinium (Gd) complexes as a contrast agent in Magnetic Resonance Imaging (MRI) results in an enhanced Gd input in the aquatic environment. Gd-complexes are excreted by humans unmetabolized within 12h after application. Passing the sewage systems with almost no degradation taking place, they successively reach surface waters, which make Gd a capable tracer for surface water/groundwater (SW/GW) interactions. The natural background concentration of Gd and other rare earth elements (REE) occur at ultratrace levels [low ng/L]. Crust-normalized REE patterns show positive Gd-anomalies in surface water, groundwater, and recently also in tap water. The difference between the total concentration and its natural background concentration estimated by the REE pattern is the anthropogenic Gd. Not only densely populated areas are affected by the presence of anthropogenic Gd. Studies have shown that even in rural areas without MRI facilities, anthropogenic Gd can be detected, since people are sent home after treatment. However, low input concentrations and mixing with natural waters lead to a decrease of Gd concentration below the current limit of quantification (LOQ) [1-5ng/L]. Often anthropogenic Gd cannot be calculated, although it is present, because natural background concentration cannot be determined with current methods, in particular in areas with low waste water load (e.g. headwater catchments). A new method using an on-line preconcentration system "SeaFAST" (Elemental Scientific Inc., USA), in combination with a desolvation system "Apex Q" (Elemental Scientific Inc., USA) and a QQQ-ICP-MS instrument (Agilent Technologies, Japan) does lower the LOQ for REE by a factor of 10 to 20. The SeaFAST-system uses a resin with ethylenediaminetriacetic acid and iminodiacetic acid functional groups to preconcentrate specifically REE as they are exclusively trivalent while anions, alkali and alkaline earth cations are washed out. The Apex Q interface is also supposed to

  6. Nickel-based Gadolinium Alloy for Neutron Adsorption Application in Ram Packages

    SciTech Connect

    Gregg Wachs; James Sterbentz; William Hurt; P. E. McConnell; C. V. Robino; F. Tovesson; T. S. Hill

    2007-10-01

    Neutron transmission experiments were performed on samples of an advanced nickel-chromium-molybdenum-gadolinium (Ni-Cr-Mo-Gd) neutron absorber alloy and chromium-nickel (Cr-Ni) stainless steel, modified by the addition of boron. The primary purpose of the experiments was to demonstrate the thermal neutron absorbing capability of the materials at specific gadolinium and boron dopant levels. The Ni-Cr-Mo-Gd alloy is envisioned to be deployed for criticality control of highly enriched U.S. Department of Energy (DOE)-owned spent nuclear fuel (SNF). For these transmission experiments, test samples were fabricated with 0.0, 1.58 and 2.1 wt% natural gadolinium dispersed in a Ni-Cr-Mo base alloy and 1.16 wt% boron in stainless steel. The transmission experiments were successfully carried out at the Los Alamos Neutron Science Center (LANSCE). Measured data from the neutron transmission experiments were compared to calculated results derived from a simple exponential transmission formula using total neutron cross sections. Excellent agreement between the measured and calculated results demonstrated the expected strong thermal absorption capability of the gadolinium and boron elements and in addition, verified the measured elemental composition of the Ni-Cr-Mo-Gd alloy and borated stainless steel test samples. The good agreement also indirectly confirmed that the size and distribution of the gadolinium in both the hot-top (as-cast) and Ni-Cr-Mo-Gd converted to plate was not a discriminator related to neutron absorption. Moreover, the Evaluated Nuclear Data File (ENDF VII) total neutron cross section data were accurate.

  7. Agent oriented programming

    NASA Technical Reports Server (NTRS)

    Shoham, Yoav

    1994-01-01

    The goal of our research is a methodology for creating robust software in distributed and dynamic environments. The approach taken is to endow software objects with explicit information about one another, to have them interact through a commitment mechanism, and to equip them with a speech-acty communication language. System-level applications include software interoperation and compositionality. A government application of specific interest is an infrastructure for coordination among multiple planners. Daily activity applications include personal software assistants, such as programmable email, scheduling, and new group agents. Research topics include definition of mental state of agents, design of agent languages as well as interpreters for those languages, and mechanisms for coordination within agent societies such as artificial social laws and conventions.

  8. A phantom-based feasibility study for detection of gadolinium in bone in-vivo using X-ray fluorescence.

    PubMed

    Lord, M L; McNeill, F E; Gräfe, J L; Noseworthy, M D; Chettle, D R

    2016-06-01

    Gadolinium (Gd) based contrast agents have been commonly used over the past three decades to improve contrast in magnetic resonance imaging. These complexes, originally thought to be stable and clear from the body shortly after administration, have been shown to dissociate to a small extent and deposit in organs such as bone. A safe and non-invasive method for measuring Gd in bone is necessary for further exploring Gd retention in the body following the administration of a contrast agent. A feasibility study using a K x-ray fluorescence (K-XRF) system to measure Gd in human tibias was investigated. Bone phantoms mimicking human tibia were created with Gd concentrations ranging from 0 to 120ppm. The minimum detection limit (MDL) was calculated from 20-hour and 7-hour phantom measurements with a source activity of 0.11GBq. All MDL values were scaled to a more realistic measurement time of 30-minutes with a stronger source. Scaling arguments were based on activity ratio, measurement time, and system dead time. The MDL for a 1GBq source was estimated to be 3.60-3.64ppm, for an average range of tissue thicknesses overlaying a human tibia. For a stronger source of 5GBq and a four detector cloverleaf system, the MDL was estimated to be 1.49-1.52ppm. Determined and predicted MDLs are within the range of previous in-vitro Gd measurement data. The K-XRF system shows promising results for detecting Gd in bone and should be seriously considered for in-vivo measurements. PMID:27019028

  9. Gadolinium-functionalized nanographene oxide for combined drug and microRNA delivery and magnetic resonance imaging.

    PubMed

    Yang, Hung-Wei; Huang, Chiung-Yin; Lin, Chih-Wen; Liu, Hao-Li; Huang, Chia-Wen; Liao, Shih-Sheng; Chen, Pin-Yuan; Lu, Yu-Jen; Wei, Kuo-Chen; Ma, Chen-Chi M

    2014-08-01

    The delivery of anti-cancer therapeutics to tumors at clinically effective concentrations, while avoiding nonspecific toxicity, remains a major challenge for cancer treatment. Here we present nanoparticles of poly(amidoamine) dendrimer-grafted gadolinium-functionalized nanographene oxide (Gd-NGO) as effective carriers to deliver both chemotherapeutic drugs and highly specific gene-targeting agents such as microRNAs (miRNAs) to cancer cells. The positively charged surface of Gd-NGO was capable of simultaneous adsorption of the anti-cancer drug epirubicin (EPI) and interaction with negatively charged Let-7g miRNA. Using human glioblastoma (U87) cells as a model, we found that this conjugate of Let-7g and EPI (Gd-NGO/Let-7g/EPI) not only exhibited considerably higher transfection efficiency, but also induced better inhibition of cancer cell growth than Gd-NGO/Let-7g or Gd-NGO/EPI. The concentration of Gd-NGO/Let-7g/EPI required for 50% inhibition of cellular growth (IC50) was significantly reduced (to the equivalent of 1.3 μg/mL EPI) compared to Gd-NGO/EPI (3.4 μg/mL EPI). In addition, Gd-NGO/Let-7g/EPI could be used as a contrast agent for magnetic resonance imaging to identify the location and extent of blood-brain barrier opening and quantitate drug delivery to tumor tissues. These results suggest that Gd-NGO/Let-7g/EPI may be a promising non-viral vector for chemogene therapy and molecular imaging diagnosis in future clinical applications.

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

    SciTech Connect

    Ogunlade, Olumide 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 substance 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

  11. The investigation of gadolinium oxide porous structure and refinement of the pore size distribution based on the NLDFT-models

    NASA Astrophysics Data System (ADS)

    Mashkovtsev, Maxim A.; Botalov, Maxim S.; Smyshlyaev, Denis V.; Kasimova, Renata E.; Bereskina, Polina A.; Vereshchagin, Artem O.

    2016-09-01

    The study focuses on the characterization of gadolinium oxide surface by the method of low-temperature adsorption/desorption of nitrogen. The specific surface area of gadolinium oxide, the average pore diameter and fractal dimensions were determined. The refinement of the pore distribution was performed on the basis of the NLDFT model. It was shown that there were three kinds of pores with average sizes of 150, 300 and 600 Å.

  12. Sunscreening Agents

    PubMed Central

    Martis, Jacintha; Shobha, V; Sham Shinde, Rutuja; Bangera, Sudhakar; Krishnankutty, Binny; Bellary, Shantala; Varughese, Sunoj; Rao, Prabhakar; Naveen Kumar, B.R.

    2013-01-01

    The increasing incidence of skin cancers and photodamaging effects caused by ultraviolet radiation has increased the use of sunscreening agents, which have shown beneficial effects in reducing the symptoms and reoccurrence of these problems. Many sunscreen compounds are in use, but their safety and efficacy are still in question. Efficacy is measured through indices, such as sun protection factor, persistent pigment darkening protection factor, and COLIPA guidelines. The United States Food and Drug Administration and European Union have incorporated changes in their guidelines to help consumers select products based on their sun protection factor and protection against ultraviolet radiation, whereas the Indian regulatory agency has not yet issued any special guidance on sunscreening agents, as they are classified under cosmetics. In this article, the authors discuss the pharmacological actions of sunscreening agents as well as the available formulations, their benefits, possible health hazards, safety, challenges, and proper application technique. New technologies and scope for the development of sunscreening agents are also discussed as well as the role of the physician in patient education about the use of these agents. PMID:23320122

  13. Safety assessment of nanoparamagnetic contrast agents with different coatings for molecular MRI

    NASA Astrophysics Data System (ADS)

    Azizian, Gholamreza; Riyahi-Alam, Nader; Haghgoo, Soheila; Saffari, Mojtaba; Zohdiaghdam, Reza; Gorji, Ensieh

    2013-04-01

    Despite the wide application of gadolinium as a contrast agent for magnetic resonance imaging (MRI), there is a serious lack of information on its toxicity. Gadolinium and gadolinium oxide (Gd-oxide) are used as contrast agents for magnetic resonance imaging (MRI). There are methods for reducing toxicity of these materials, such as core nanoparticles coating or conjugating. Therefore, for toxicity evaluation, we compared the viability of commercial contrast agents in MRI (Gd-DTPA) and three nanoparticles with the same core Gd2O3 and small particulate gadolinium oxide or SPGO (< 40 nm) but different coatings of diethyleneglycol (DEG) as Gd2O3-DEG and methoxy polyethylene glycol-silane (mPEG-silane: 550 and 2000 Dalton) as SPGO-mPEG-silane550 and SPGO-mPEG-silane2000, respectively, in the SK-MEL3 cell line, by light microscopy, MTT assay using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide, and the LDH assay detecting lactate dehydrogenase activity. The viability values were not statistically different between the three nanoparticles and Gd-DTPA. The MTT and LDH assay results showed that Gd2O3-DEG nanoparticles were more toxic than Gd-DTPA and other nanoparticles. Also, SPGO-mPEG-silane2000 was more biocompatible than other nanoparticles. The obtained results did not show any significant increase in cytotoxicity of the nanoparticles and Gd-DTPA, neither dose-dependent nor time-dependent. Therefore, DEG and PEG, due to their considerable properties and irregular sizes (different molecular weights), were selected as the useful surface covering materials of nanomagnetic particles that could reveal noticeable relaxivity and biocompatibility characteristics.

  14. First measurements with new high-resolution gadolinium-GEM neutron detectors

    NASA Astrophysics Data System (ADS)

    Pfeiffer, D.; Resnati, F.; Birch, J.; Etxegarai, M.; Hall-Wilton, R.; Höglund, C.; Hultman, L.; Llamas-Jansa, I.; Oliveri, E.; Oksanen, E.; Robinson, L.; Ropelewski, L.; Schmidt, S.; Streli, C.; Thuiner, P.

    2016-05-01

    European Spallation Source instruments like the macromolecular diffractometer (NMX) require an excellent neutron detection efficiency, high-rate capabilities, time resolution, and an unprecedented spatial resolution in the order of a few hundred micrometers over a wide angular range of the incoming neutrons. For these instruments solid converters in combination with Micro Pattern Gaseous Detectors (MPGDs) are a promising option. A GEM detector with gadolinium converter was tested on a cold neutron beam at the IFE research reactor in Norway. The μTPC analysis, proven to improve the spatial resolution in the case of 10B converters, is extended to gadolinium based detectors. For the first time, a Gd-GEM was successfully operated to detect neutrons with a measured efficiency of 11.8% at a wavelength of 2 Åand a position resolution better than 250 μm.

  15. Frontiers of X-ray spectromicroscopy in biology and medicine: Gadolinium in brain cancer

    NASA Astrophysics Data System (ADS)

    De Stasio, Gelsomina; Gilbert, B.; Perfetti, P.; Margaritondo, G.; Mercanti, D.; Ciotti, M. T.; Casalbore, P.; Larocca, L. M.; Rinelli, A.; Pallini, R.

    2000-02-01

    We present the first feasibility test of spectromicroscopy on the microlocalization of gadolinium in brain cancer tissue. A gadolinium compound was injected to the patients before the brain tumor was extracted with surgery, and we looked for Gd in the tumor tissue. The goal of the experiment was to understand if Gd Neutron Capture Therapy (GdNCT) is viable for clinical tests, i.e. if there is enough Gd, and it is localized near the nuclei of tumor cells. The experiments were performed using the MEPHISTO X-ray PhotoElectron Emission Microscope (X-PEEM) at the Wisconsin Synchrotron Radiation Center. The present results demonstrate the feasibility of the experiment, and suggest how to improve the sample preparation and data acquisition to achieve the goal.

  16. Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

    PubMed

    Canga, Ana; Kislikova, Maria; Martínez-Gálvez, María; Arias, Mercedes; Fraga-Rivas, Patricia; Poyatos, Cecilio; de Francisco, Angel L M

    2014-01-01

    Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

  17. Interplay of disorder and geometrical frustration in doped gadolinium gallium garnet.

    PubMed

    Woo, N; Silevitch, D M; Ferri, C; Ghosh, S; Rosenbaum, T F

    2015-07-29

    The geometrically frustrated triangular antiferromagnet Gadolinium Gallium Garnet (Gd3Ga5O12 or GGG) exhibits a rich mix of short-range order and isolated quantum states. We investigate the effects of up to 1% neodymium substitution for gallium on the ac magnetic response at temperatures below 1 K in both the linear and nonlinear regimes. Substitutional disorder actually drives the system toward a more perfectly frustrated state, apparently compensating for the effects of imperfect gadolinium/gallium stoichiometry, while at the same time more closely demarcating the boundaries of isolated, coherent clusters composed of hundreds of spins. Optical measurements of the local Nd environment substantiate the picture of an increased frustration index with doping. PMID:26154501

  18. Interplay of disorder and geometrical frustration in doped gadolinium gallium garnet

    NASA Astrophysics Data System (ADS)

    Woo, N.; Silevitch, D. M.; Ferri, C.; Ghosh, S.; Rosenbaum, T. F.

    2015-07-01

    The geometrically frustrated triangular antiferromagnet Gadolinium Gallium Garnet (Gd3Ga5O12 or GGG) exhibits a rich mix of short-range order and isolated quantum states. We investigate the effects of up to 1% neodymium substitution for gallium on the ac magnetic response at temperatures below 1 K in both the linear and nonlinear regimes. Substitutional disorder actually drives the system toward a more perfectly frustrated state, apparently compensating for the effects of imperfect gadolinium/gallium stoichiometry, while at the same time more closely demarcating the boundaries of isolated, coherent clusters composed of hundreds of spins. Optical measurements of the local Nd environment substantiate the picture of an increased frustration index with doping.

  19. Thermal Magnetic Hysteresis in a Copper-Gadolinium-Radical Chain Compound.

    PubMed

    Zhu, Mei; Li, Cun; Wang, Xiufeng; Li, Licun; Sutter, Jean-Pascal

    2016-03-21

    Magnetic bistability spanning over a temperature domain of 40 K can result from a small structural deformation of the gadolinium aminoxyl coordination. This is illustrated for a nitronyl nitroxide 3d-4f chain, [Ln(hfac)3Cu(hfac)2(NIT-Pyrim)2] (Ln(III) = Gd, Dy), which is the first example of a bistable lanthanide-based complex. PMID:26915061

  20. Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy

    SciTech Connect

    Enger, Shirin A.; Rezaei, Arash; Munck af Rosenschoeld, Per; Lundqvist, Hans

    2006-01-15

    Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.

  1. Gadolinium uptake by brain cancer cells: Quantitative analysis with X-PEEM spectromicroscopy for cancer therapy

    NASA Astrophysics Data System (ADS)

    De Stasio, Gelsomina; Gilbert, B.; Perfetti, P.; Margaritondo, G.; Mercanti, D.; Ciotti, M. T.; Casalbore, P.; Larocca, L. M.; Rinelli, A.; Pallini, R.

    2000-05-01

    We present the first X-PEEM spectromicroscopy semi-quantitative data, acquired on Gd in glioblastoma cell cultures from human brain cancer. The cells were treated with a Gd compound for the optimization of GdNCT (Gadolinium Neutron Capture Therapy). We analyzed the kinetics of Gd uptake as a function of exposure time, and verified that a quantitative analytical technique gives the same results as our MEPHISTO X-PEEM, demonstrating the feasibility of semi-quantitative spectromicroscopy.

  2. Proposed experiment to measure {gamma}-rays from the thermal neutron capture of gadolinium

    SciTech Connect

    Yano, Takatomi; Ou, I.; Izumi, T.; Yamaguchi, R.; Mori, T.; Sakuda, M.

    2012-11-12

    Gadolinium-157 ({sup 157}Gd) has the largest thermal neutron capture cross section among any stable nuclei. The thermal neutron capture yields {gamma}-ray cascade with total energy of about 8 MeV. Because of these characteristics, Gd is applied for the recent neutrino detectors. Here, we propose an experiment to measure the multiplicity and the angular correlation of {gamma}-rays from the Gd neutron capture. With these information, we expect the improved identification of the Gd neutron capture.

  3. Optical absorption of Ni2+ and Ni3+ ions in gadolinium gallium garnet epitaxial films

    NASA Astrophysics Data System (ADS)

    Vasileva, N. V.; Gerus, P. A.; Sokolov, V. O.; Plotnichenko, V. G.

    2012-12-01

    Single-crystal Ni-doped gadolinium gallium garnet films were grown for the first time from supercooled Bi2O3-B2O3-based melt solutions by liquid-phase epitaxy. Optical absorption bands due to Ni2+, Ni3+ and Bi3+ ions were observed in those films. Interpretation and tabulation of all absorption bands of nickel ions occupying octahedral and tetrahedral sites in the garnet lattice are presented.

  4. Multi-Agent Information Classification Using Dynamic Acquaintance Lists.

    ERIC Educational Resources Information Center

    Mukhopadhyay, Snehasis; Peng, Shengquan; Raje, Rajeev; Palakal, Mathew; Mostafa, Javed

    2003-01-01

    Discussion of automated information services focuses on information classification and collaborative agents, i.e. intelligent computer programs. Highlights include multi-agent systems; distributed artificial intelligence; thesauri; document representation and classification; agent modeling; acquaintances, or remote agents discovered through…

  5. Large Scale Testing and Development of Gadolinium Trichloride for Use in Neutron Detection in Large Water

    SciTech Connect

    Mark Vagine

    2007-09-18

    Water Cherenkov detectors have been used for many years as inexpensive, effective detectors for neutrino interactions and nucleon decay searches. While many important measurements have been made with these detectors a major drawback has been their inability to detect the absorption of thermal neutrons. We believe an inexpensive, effective technique could be developed to overcome this situation via the addition to water of a solute with a large neutron cross section and energetic gamma daughters which would make neutrons detectable. Gadolinium seems an excellent candidate especially since in recent years it has become very inexpensive, now less than $8 per kilogram in the form of commercially-available gadolinium trichloride, GdCl{sub 3}. This non-toxic, non-reactive substance is highly soluble in water. Neutron capture on gadolinium yields a gamma cascade which would be easily seen in detectors like Super-Kamiokande. We have begun to investigate the use of GdCl{sub 3} as a possible upgrade for the Super-Kamiokande detector with a view toward improving its performance as a detector for atmospheric neutrinos, supernova neutrinos, wrong-sign solar neutrinos, reactor neutrinos, proton decay, and also as a target for the coming T2K long-baseline neutrino experiment. This large-scale investigation, conducted in the one kiloton water Cherenkov detector built for the K2K long-baseline experiment, follows up on highly promising benchtop-scale work previously carried out with the assistance of a 2003 Advanced Detector Research Program grant.

  6. Physico-chemical and NMR relaxometric characterization of gadolinium hydroxide and dysprosium oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Gossuin, Yves; Hocq, Aline; Vuong, Quoc Lam; Disch, Sabrina; Hermann, Raphaël P.; Gillis, Pierre

    2008-11-01

    Gadolinium hydroxide and dysprosium oxide nanoparticles, which constitute a new interesting class of magnetic nanoparticles, are characterized by different methods, using x-ray diffraction, magnetometry and NMR relaxometry at multiple fields. The rod-like particles are first shown to have a simple paramagnetic behavior, like the bulk compound, without any influence of the nanometric size of the particles. Because of their paramagnetic moment, these particles considerably shorten water relaxation times, especially the transverse relaxation time at high fields. The relaxation induced by gadolinium hydroxide particles is due to a proton exchange between the particle surface and bulk water, while the transverse relaxation caused by dysprosium oxide particles is governed by the diffusion of water protons around the magnetized particles. 1/T2 increases linearly with the magnetic field for gadolinium hydroxide particles while a quadratic increase is observed for dysprosium oxide nanoparticles. The relaxation results are compared with those from previous studies and interpreted using different theories for the relaxation induced by magnetic particles.

  7. Gadolinium-chelate nanoparticle entrapped human mesenchymal stem cell via photochemical internalization for cancer diagnosis.

    PubMed

    Kim, Kyoung Sub; Park, Wooram; Na, Kun

    2015-01-01

    To improve the gadolinium (Gd) internalization efficiency in stem cells, gadolinium-chelate nanoparticles were prepared from a pullulan derivative (pullulan-deoxycholic acid (DOCA)-diethylene triamine pentaacetic (DTPA)-Gd conjugate; PDDG) and then the PDDG was entrapped into human mesenchymal stem cells (hMSCs) by the photochemical-internalization (PCI) method for cancer diagnosis via the cancer homing property of hMSCs. The internalization efficiency of Gd in hMSCs was significantly increased to 98 ± 4 pg Gd/cell from 32 ± 2 pg Gd/cell via the PCI method. Moreover, the Gd-entrapped hMSCs revealed a low exocytosis ratio of gadolinium-chelate nanoparticles during cell division in vitro and a high cellular labeling efficiency for at least 21 days in vivo. The cancer-targeting and diagnosis effect of the Gd-entrapped hMSCs were confirmed in a small CT26 tumor-bearing mice model. The stem cells detected an early tumor (∼3 mm(3)) within 2 h using 4.7-T MR and optical imaging. The results demonstrated that the PCI-mediated internalization of Gd-incorporated nanoparticles into hMSCs is a promising protocol for efficient cell labeling and tracking.

  8. Study of the Photon Strength Functions for Gadolinium Isotopes with the DANCE Array

    SciTech Connect

    Dashdorj, D.; Mitchell, G. E.; Baramsai, B.; Chankova, R.; Chyzh, A.; Walker, C.; Agvaanluvsan, U.; Becker, J. A.; Parker, W.; Sleaford, B.; Wu, C. Y.; Bredeweg, T. A.; Couture, A.; Haight, R. C.; Jandel, M.; Rundberg, R. S.; Ullmann, J. L.; Vieira, D. J.; Wouters, J. M.; Krticka, M.

    2009-03-10

    The gadolinium isotopes are interesting for reactor applications as well as for medicine and astrophysics. The gadolinium isotopes have some of the largest neutron capture cross sections. As a consequence they are used in the control rod in reactor fuel assembly. From the basic science point of view, there are seven stable isotopes of gadolinium with varying degrees of deformation. Therefore they provide a good testing ground for the study of deformation dependent structure such as the scissors mode. Decay gamma rays following neutron capture on Gd isotopes are detected by the DANCE array, which is located at flight path 14 at the Lujan Neutron Scattering Center at Los Alamos National Laboratory. The high segmentation and close packing of the detector array enable gamma-ray multiplicity measurements. The calorimetric properties of the DANCE array coupled with the neutron time-of-flight technique enables one to gate on a specific resonance of a specific isotope in the time-of-flight spectrum and obtain the summed energy spectrum for that isotope. The singles gamma-ray spectrum for each multiplicity can be separated by their DANCE cluster multiplicity. Various photon strength function models are used for comparison with experimentally measured DANCE data and provide insight for understanding the statistical decay properties of deformed nuclei.

  9. Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

    PubMed Central

    2014-01-01

    Background Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. Methods All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. Results The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Conclusion Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma. PMID:25287952

  10. Selective Filtration of Gadolinium Trichloride for Use in Neutron Detection in Large Water Cherenkov Detectors

    SciTech Connect

    Vagins, Mark R.

    2013-04-10

    Water Cherenkov detectors have been used for many years as inexpensive, effective detectors for neutrino interactions and nucleon decay searches. While many important measurements have been made with these detectors a major drawback has been their inability to detect the absorption of thermal neutrons. We believe an inexpensive, effective technique could be developed to overcome this situation via the addition to water of a solute with a large neutron cross section and energetic gamma daughters which would make neutrons detectable. Gadolinium seems an excellent candidate especially since in recent years it has become very inexpensive, now less than $8 per kilogram in the form of commercially-available gadolinium trichloride, GdCl{sub 3}. This non-toxic, non-reactive substance is highly soluble in water. Neutron capture on gadolinium yields a gamma cascade which would be easily seen in detectors like Super-Kamiokande. We have been investigating the use of GdCl{sub 3} as a possible upgrade for the Super-Kamiokande detector with a view toward improving its performance as a detector for atmospheric neutrinos, supernova neutrinos, wrong-sign solar neutrinos, reactor neutrinos, proton decay, and also as a target for the coming T2K long-baseline neutrino experiment. This focused study of selective water filtration and GdCl{sub 3} extraction techniques, conducted at UC Irvine, followed up on highly promising benchtop-scale and kiloton-scale work previously carried out with the assistance of 2003 and 2005 Advanced Detector Research Program grants.

  11. Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments

    PubMed Central

    Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew

    2013-01-01

    Neoplastic lesions can create a hostile tumor microenvironment with low extracellular pH. It is commonly believed that these conditions can contribute to tumor progression and resistance to therapy. We report the development and characterization of a pH-responsive magnetic resonance imaging contrast agent, for imaging the acidic tumor microenvironment. The preparation included conjugation of 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid 1-(2,5-dioxo-1-pyrrolidinyl) ester (DOTA-NHS) to the surface of a water soluble glycol chitosan (GC) polymer, which contains pH titrable primary amines, followed by gadolinium complexation (GC-NH2-GdDOTA). GC-NH2-GdDOTA had a chelate to polymer ratio of approximately1:24 and a molar relaxivity of 9.1 mM−1s−1. GC-NH2-GdDOTA demonstrated pH-dependent cellular association in vitro compared to the control. It also generated a 2.4-fold enhancement in signal in tumor bearing mice 2 h post-injection. These findings suggest that glycol chitosan coupled with contrast agents can provide important diagnostic information about the tumor microenvironment. PMID:24044414

  12. Ultrasmall superparamagnetic iron oxides (USPIOs): a future alternative magnetic resonance (MR) contrast agent for patients at risk for nephrogenic systemic fibrosis (NSF)?

    PubMed

    Neuwelt, Edward A; Hamilton, Bronwyn E; Varallyay, Csanad G; Rooney, William R; Edelman, Robert D; Jacobs, Paula M; Watnick, Suzanne G

    2009-03-01

    Gadolinium (Gd) based contrast agents (GBCAs) in magnetic resonance imaging (MRI) are used in daily clinical practice and appear safe in most patients; however, nephrogenic systemic fibrosis (NSF) is a recently recognized severe complication associated with GBCAs. It affects primarily patients with renal disease, such as stage 4 or 5 chronic kidney disease (CKD; glomerular filtration rate <30 ml/min per 1.73 m(2)), acute kidney injury, or kidney and liver transplant recipients with kidney dysfunction. Contrast-enhanced MRI and computed tomography (CT) scans provide important clinical information and influence patient management. An alternative contrast agent is needed to obtain adequate imaging results while avoiding the risk of NSF in this vulnerable patient group. One potential alternative is ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, which provide enhancement characteristics similar to GBCAs. We review our experience in approximately 150 patients on the potential benefits of the USPIOs ferumoxtran-10 and ferumoxytol. We focus on central nervous system (CNS) MRI but also review imaging of other vascular beds. Safety studies, including USPIO administration (ferumoxytol) as iron supplement therapy in CKD patients on and not on dialysis, suggest that decreased kidney function does not alter the safety profile. We conclude that for both CNS MR imaging and MR angiography, USPIO agents like ferumoxytol are a viable option for patients at risk for NSF.

  13. Modified Gadonanotubes as a promising novel MRI contrasting agent

    PubMed Central

    2013-01-01

    Background and purpose of the study Carbon nanotubes (CNTs) are emerging drug and imaging carrier systems which show significant versatility. One of the extraordinary characteristics of CNTs as Magnetic Resonance Imaging (MRI) contrasting agent is the extremely large proton relaxivities when loaded with gadolinium ion (Gdn3+) clusters. Methods In this study equated Gdn3+ clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs. The amount of loaded gadolinium ion into the MWCNTs was quantified by inductively coupled plasma (ICP) method. To improve water solubility and biocompatibility of the system, the complexes were functionalized using diamine-terminated oligomeric poly (ethylene glycol) via a thermal reaction method. Results Gdn3+ loaded PEGylated oxidized CNTs (Gdn3+@CNTs-PEG) is freely soluble in water and stable in phosphate buffer saline having particle size of about 200 nm. Transmission electron microscopy (TEM) images clearly showed formation of PEGylated CNTs. MRI analysis showed that the prepared solution represents 10% more signal intensity even in half concentration of Gd3+ in comparison with commerciality available contrasting agent Magnevist®. In addition hydrophilic layer of PEG at the surface of CNTs could prepare stealth nanoparticles to escape RES. Conclusion It was shown that Gdn3+@CNTs-PEG was capable to accumulate in tumors through enhanced permeability and retention effect. Moreover this system has a potential for early detection of diseases or tumors at the initial stages. PMID:23815852

  14. Incorporation of Integral Fuel Burnable Absorbers Boron and Gadolinium into Zirconium-Alloy Fuel Clad Material

    SciTech Connect

    Sridharan, K.; Renk, T.J.; Lahoda, E.J.; Corradini, M.L

    2004-12-14

    Long-lived fuels require the use of higher enrichments of 235U or other fissile materials. Such high levels of fissile material lead to excessive fuel activity at the beginning of life. To counteract this excessive activity, integral fuel burnable absorbers (IFBA) are added to some rods in the fuel assembly. The two commonly used IFBA elements are gadolinium, which is added as gadolinium-oxide to the UO2 powder, and boron, which is applied as a zirconium-diboride coating on the UO2 pellets using plasma spraying or chemical vapor deposition techniques. The incorporation of IFBA into the fuel has to be performed in a nuclear-regulated facility that is physically separated from the main plant. These operations tend to be very costly because of their small volume and can add from 20 to 30% to the manufacturing cost of the fuel. Other manufacturing issues that impact cost and performance are maintaining the correct levels of dosing, the reduction in fuel melting point due to gadolinium-oxide additions, and parasitic neutron absorption at fuel's end-of-life. The goal of the proposed research is to develop an alternative approach that involves incorporation of boron or gadolinium into the outer surface of the fuel cladding material rather than as an additive to the fuel pellets. This paradigm shift will allow for the introduction of the IFBA in a non-nuclear regulated environment and will obviate the necessity of additional handling and processing of the fuel pellets. This could represent significant cost savings and potentially lead to greater reproducibility and control of the burnable fuel in the early stages of the reactor operation. The surface alloying is being performed using the IBEST (Ion Beam Surface Treatment) process developed at Sandia National Laboratories. IBEST involves the delivery of energetic ion beam pulses onto the surface of a material, near-surface melting, and rapid solidification. The non-equilibrium nature of such processing allows for surface

  15. Mesoporous Silica Nanoparticles with Co-Condensed Gadolinium Chelates for Multimodal Imaging

    PubMed Central

    Taylor-Pashow, Kathryn M. L.; Della Rocca, Joseph; Lin, Wenbin

    2013-01-01

    Several mesoporous silica nanoparticle (MSN) contrast agents have been synthesized using a co-condensation method to incorporate two different Gd3+ complexes at very high loadings (15.5–28.8 wt %). These MSN contrast agents, with an MCM-41 type pore structure, were characterized using a variety of methods including SEM and TEM, nitrogen adsorption measurements, thermogravimetric analysis (TGA), direct current plasma (DCP) spectroscopy, and powder X-ray diffraction (PXRD). The magnetic resonance (MR) relaxivities of these contrast agents were determined using a 3 T MR scanner. The r1 relaxivities of these nanoparticles range from 4.1 to 8.4 mM−1s−1 on a per Gd basis. Additionally, the MSN particles were functionalized with an organic fluorophore and cancer cell targeting peptide to allow for demonstration of both the optical and MR contrast enhancing capabilities in vitro. PMID:24527205

  16. 34 CFR 303.15 - Include; including.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false Include; including. 303.15 Section 303.15 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION EARLY INTERVENTION PROGRAM FOR INFANTS AND TODDLERS...

  17. Acceleration of Natural-Abundance Solid-State MAS NMR Measurements on Bone by Paramagnetic Relaxation from Gadolinium-DTPA

    PubMed Central

    Mroue, Kamal H.; Zhang, Rongchun; Zhu, Peizhi; McNerny, Erin; Kohn, David H.; Morris, Michael D.; Ramamoorthy, Ayyalusamy

    2014-01-01

    Reducing the data collection time without affecting the signal intensity and spectral resolution is one of the major challenges for the widespread application of multidimensional nuclear magnetic resonance (NMR) spectroscopy, especially in experiments conducted on complex heterogeneous biological systems such as bone. In most of these experiments, the NMR data collection time is ultimately governed by the proton spin-lattice relaxation times (T1). For over two decades, gadolinium(III)-DTPA (Gd-DTPA, DTPA = Diethylenetriamine pentaacetic acid) has been one of the most widely used contrast-enhancement agents in magnetic resonance imaging (MRI). In this study, we demonstrate that Gd-DTPA can also be effectively used to enhance the longitudinal relaxation rates of protons in solid-state NMR experiments conducted on bone without significant line-broadening and chemical-shift-perturbation side effects. Using bovine cortical bone samples incubated in different concentrations of Gd-DTPA complex, the 1H T1 values were calculated from data collected by 1H spin-inversion recovery method detected in natural-abundance 13C cross-polarization magic angle spinning (CPMAS) NMR experiments. Our results reveal that the 1H T1 values can be successfully reduced by a factor of 3.5 using as low as 10 mM Gd-DTPA without reducing the spectral resolution and thus enabling faster data acquisition of the 13C CPMAS spectra. These results obtained from 13C-detected CPMAS experiments were further confirmed using 1H-detected ultrafast MAS experiments on Gd-DTPA doped bone samples. This approach considerably improves the signal-to-noise ratio per unit time of NMR experiments applied to bone samples by reducing the experimental time required to acquire the same number of scans. PMID:24881032

  18. Enhanced production of reactive oxygen species by gadolinium oxide nanoparticles under core-inner-shell excitation by proton or monochromatic X-ray irradiation: implication of the contribution from the interatomic de-excitation-mediated nanoradiator effect to dose enhancement.

    PubMed

    Seo, Seung-Jun; Han, Sung-Mi; Cho, Jae-Hoon; Hyodo, Kazuyuki; Zaboronok, Alexander; You, He; Peach, Ken; Hill, Mark A; Kim, Jong-Ki

    2015-11-01

    Core-inner-valence ionization of high-Z nanoparticle atomic clusters can de-excite electrons through various interatomic de-excitation processes, thereby leading to the ionization of both directly exposed atoms and adjacent neutral atoms within the nanoparticles, and to an enhancement in photon-electron emission, which is termed the nanoradiator effect. To investigate the nanoradiator-mediated dose enhancement in the radio-sensitizing of high-Z nanoparticles, the production of reactive oxygen species (ROS) was measured in a gadolinium oxide nanoparticle (Gd-oxide NP) solution under core-inner-valence excitation of Gd with either 50 keV monochromatic synchrotron X-rays or 45 MeV protons. This measurement was compared with either a radiation-only control or a gadolinium-chelate magnetic resonance imaging contrast agent solution containing equal amounts of gadolinium as the separate atomic species in which Gd-Gd interatomic de-excitations are absent. Ionization excitations followed by ROS measurements were performed on nanoparticle-loaded cells or aqueous solutions. Both photoexcitation and proton impact produced a dose-dependent enhancement in the production of ROS by a range of factors from 1.6 to 1.94 compared with the radiation-only control. Enhanced production of ROS, by a factor of 1.83, was observed from Gd-oxide NP atomic clusters compared with the Gd-chelate molecule, with a Gd concentration of 48 μg/mL in the core-level photon excitation, or by a factor of 1.82 under a Gd concentration of 12 μg/mL for the proton impact at 10 Gy (p < 0.02). The enhanced production of ROS in the irradiated nanoparticles suggests the potential for additional therapeutic dose enhancements in radiation treatment via the potent Gd-Gd interatomic de-excitation-driven nanoradiator effect. PMID:26242374

  19. Enhanced production of reactive oxygen species by gadolinium oxide nanoparticles under core-inner-shell excitation by proton or monochromatic X-ray irradiation: implication of the contribution from the interatomic de-excitation-mediated nanoradiator effect to dose enhancement.

    PubMed

    Seo, Seung-Jun; Han, Sung-Mi; Cho, Jae-Hoon; Hyodo, Kazuyuki; Zaboronok, Alexander; You, He; Peach, Ken; Hill, Mark A; Kim, Jong-Ki

    2015-11-01

    Core-inner-valence ionization of high-Z nanoparticle atomic clusters can de-excite electrons through various interatomic de-excitation processes, thereby leading to the ionization of both directly exposed atoms and adjacent neutral atoms within the nanoparticles, and to an enhancement in photon-electron emission, which is termed the nanoradiator effect. To investigate the nanoradiator-mediated dose enhancement in the radio-sensitizing of high-Z nanoparticles, the production of reactive oxygen species (ROS) was measured in a gadolinium oxide nanoparticle (Gd-oxide NP) solution under core-inner-valence excitation of Gd with either 50 keV monochromatic synchrotron X-rays or 45 MeV protons. This measurement was compared with either a radiation-only control or a gadolinium-chelate magnetic resonance imaging contrast agent solution containing equal amounts of gadolinium as the separate atomic species in which Gd-Gd interatomic de-excitations are absent. Ionization excitations followed by ROS measurements were performed on nanoparticle-loaded cells or aqueous solutions. Both photoexcitation and proton impact produced a dose-dependent enhancement in the production of ROS by a range of factors from 1.6 to 1.94 compared with the radiation-only control. Enhanced production of ROS, by a factor of 1.83, was observed from Gd-oxide NP atomic clusters compared with the Gd-chelate molecule, with a Gd concentration of 48 μg/mL in the core-level photon excitation, or by a factor of 1.82 under a Gd concentration of 12 μg/mL for the proton impact at 10 Gy (p < 0.02). The enhanced production of ROS in the irradiated nanoparticles suggests the potential for additional therapeutic dose enhancements in radiation treatment via the potent Gd-Gd interatomic de-excitation-driven nanoradiator effect.

  20. Lipid-modified dendrimers as a tool for the design of nanoparticle-based multimodal MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Boni, Adriano; Gemmi, Mauro; Innocenti, Claudia; Bardi, Giuseppe; Bertero, Alice; Signore, Giovanni; Bifone, Angelo

    2014-03-01

    A fast and easy method for water transfer of iron oxide nanoparticle based on the hydrophobic interaction of oleic acid coated nanoparticles with the amphiphilic PAMAM-C12 dendrimer is described. The process may be conveniently performed in water and yields nanoparticles with good size distribution, diameter modulation and high crystallinity. The nanoparticles have been functionalized with gadolinium ions to obtain T1/T2 dual mode contrast agents. Furthermore, the possibility to deliver and release lipophilic drugs was investigated.

  1. MoS2-Gd Chelate Magnetic Nanomaterials with Core-Shell Structure Used as Contrast Agents in in Vivo Magnetic Resonance Imaging.

    PubMed

    Anbazhagan, Rajeshkumar; Su, Yu-An; Tsai, Hsieh-Chih; Jeng, Ru-Jong

    2016-01-27

    Despite their frequent usages as contrast agents for in vivo MRI imaging, paramagnetic molecules continue to suffer from low resolution, physicochemical instability, and high toxicity. Herein, we present a molybdenum disulfide and gadolinium complex, as an alternative core-shell magnetic nanomaterial that exhibits enhanced paramagnetic property; 4.5-times longer water proton spin-lattice relaxation time (T1) when compared to commercial gadolinium contrast agents; as well as lowered toxicity, extended blood circulation time, increased stability, and desirable excretion characteristic. Transmission electron microscopy (TEM) revealed smooth core-shell nanoparticles 100 nm in size with a shell width of approximately 10 nm. These findings suggest that the synthesized nanomaterial possesses high potential as a positive contrast agent for the enhancement of MRI imaging.

  2. Does gadolinium-based contrast material improve diagnostic accuracy of local invasion in rectal cancer MRI? A multireader study.

    PubMed

    Gollub, Marc J; Lakhman, Yulia; McGinty, Katrina; Weiser, Martin R; Sohn, Michael; Zheng, Junting; Shia, Jinru

    2015-02-01

    OBJECTIVE. The purpose of this study was to compare reader accuracy and agreement on rectal MRI with and without gadolinium administration in the detection of T4 rectal cancer. MATERIALS AND METHODS. In this study, two radiologists and one fellow independently interpreted all posttreatment MRI studies for patients with locally advanced or recurrent rectal cancer using unenhanced images alone or combined with contrast-enhanced images, with a minimum interval of 4 weeks. Readers evaluated involvement of surrounding structures on a 5-point scale and were blinded to pathology and disease stage. Sensitivity, specificity, negative predictive value, positive predictive value, and AUC were calculated and kappa statistics were used to describe interreader agreement. RESULTS. Seventy-two patients (38 men and 34 women) with a mean age of 61 years (range, 32-86 years) were evaluated. Fifteen patients had 32 organs invaded. Global AUCs without and with gadolinium administration were 0.79 and 0.77, 0.91 and 0.86, and 0.83 and 0.78 for readers 1, 2, and 3, respectively. AUCs before and after gadolinium administration were similar. Kappa values before and after gadolinium administration for pairs of readers ranged from 0.5 to 0.7. CONCLUSION. On the basis of pathology as a reference standard, the use of gadolinium during rectal MRI did not significantly improve radiologists' agreement or ability to detect T4 disease.

  3. KGB agents

    NASA Astrophysics Data System (ADS)

    Gaina, Alex

    A short story is reported in which the activity of Communist Party of the USSR and secret KGB agents, which were payed by the State, in view of controlling of the conscience of population. The story reffers to the Physics Department of the Moscow University, Planing Institute of the Gosplan of Moldavian S.S.R. and Chishinau Technical University (actually: Technical University of Moldova), where the author has worked during Soviet times. Almost every 6-th citizen in the USSR was engaged in this activity, while actually the former communists rule in the Republic of Moldova.

  4. Possible gadolinium ions leaching and MR sensitivity over-estimation in mesoporous silica-coated upconversion nanocrystals.

    PubMed

    Zhang, Shengjian; Jiang, Zhaoxia; Liu, XiaoHang; Zhou, Liangping; Peng, Weijun

    2013-09-01

    Mesoporous silica (m-SiO2) coated gadolinium (Gd) ions-doped upconversion nanoparticles (UCNPs) are regarded as one of most attractive nano-platforms which hold great potential in future cancer theranostics. The current general synthetic strategy for such promising structures includes the extraction of surfactant molecules in the final step. Here, in this article, we focus our interest on probing the potential influence of hydrochloric acid extraction on lanthanide ions leakage, MR sensitivity over-estimation and the optical intensity weakening of m-SiO2 coated Gd-doped UCNPs. Control experiments provide evidence of inner core damage, Gd(3+) ion release and residual Gd(3+) ions "trapped" within the core@shell structures. Our investigation shows that: (1) the small Gd-doped UCNPs could be fragile and sensitive to the hydrochloric acid-extraction and thermal treatment processes; and (2) the presence of "trapped" Gd(3+) ions not only provokes the concerns of potential cytotoxicity but also interfere with the contrast imaging tests of Gd-doped UCNPs, providing possible erroneous information on the determination of the longitudinal relaxivities of given probes.

  5. Optical spectra, energy levels, and emission intensity calculations of trivalent thulium ions in gadolinium scandium gallium garnet

    NASA Astrophysics Data System (ADS)

    Seltzer, Michael D.; Gruber, John B.; Rosenblatt, Gregg H.; Morrison, Clyde A.; Filer, Elizabeth D.

    1994-01-01

    Absorption spectra of trivalent thulium ions in gadolinium scandium gallium garnet are reported between 1.9 and 0.25 μm at 4 K. Laser-induced fluorescence was observed at 4 K from the 1D2, 1G4, and 3H4 (4 and 300 K) manifolds. Site-selective excitation experiments reveal large fractions of thulium ions in both regular D2 sites and alternate sites. A crystal-field splitting calculation was carried out in which a parameterized Hamiltonian (including Coulombic, spin-orbit, and crystal-field terms in D2 symmetry) was diagonalized for all multiplet manifolds of the Tm3+ (4f12) configuration. The rms deviation between 56 experimental and calculated Stark levels was 10 cm-1. Calculations were carried out to predict branching ratios for emission from the 3H4 manifold to the 3H5, 3F4, and 3H6 manifolds, as well as line-to-line transition probabilities for transitions between the 3H4 manifold and the 3H5 manifold.

  6. Multi-luminescent hybrid gadolinium oxide nanoparticles as potential cell labeling.

    PubMed

    Fizet, J; Rivière, C; Bridot, J L; Charvet, N; Louis, C; Billotey, C; Raccurt, M; Morel, G; Roux, S; Perriat, P; Tillement, O

    2009-10-01

    This manuscript analyses the use of newly developed hybrid gadolinium oxide nanoparticles as cell-labeling tracers. The nanoparticles are core-shell particles composed of a core of gadolinium oxide of [2-4] nm and a protecting shell of polysiloxane [1-3 nm] where different organic dyes (fluoresceine isothiocyanate (FITC) or rhodamine B isothiocyanate (RBITC)) are embedded. They are functionalized with poly(ethylene glycol)bis(carboxymethyl) to ensure their colloidal stability in biological buffers. These particles are potential multi-labeling tracers (magnetic and optical). In this paper, we show by optical imaging that they can be efficiently internalized in cells without cell alteration. The in-vitro uptake of the nanoparticles was followed in two cell lines (human fibroblasts and a human adenocarnima cell lines MCF7 cells). Nanoparticles distribution within cells was analysed by confocal analysis, and gadolinium concentration within cells was quantified by mass spectrometry (ICP-MS analysis). Nanoparticles uptake is found to be fast and efficient for both cell lines, with fluorescent labeling visible after 10 min of incubation whatever the nature of the fluorophore. The fluorescent intensity is mainly found as concentrated dots in the perinuclear region of the cells and decreases with the number of days in culture, but is still easily detectable after 3 days in culture. No significant effect on cell growth was detected. Finally, we show in this study the protective effect of the polysiloxane layer: encapsulation of RBITC within the polysiloxane shell, leads to a better photostability of this low cost dye than Cy3 and even reach a level comparable to Alexa 595. With their high photostability and long-lasting contrast properties, these hybrid luminescent nanoparticles appears thus as a versatile solution to assess multiple cell fate both in in-vitro cell model as well as in-vivo.

  7. Relaxometric studies of gadolinium-functionalized perfluorocarbon nanoparticles for MR imaging.

    PubMed

    de Vries, Anke; Moonen, Rik; Yildirim, Muhammed; Langereis, Sander; Lamerichs, Rolf; Pikkemaat, Jeroen A; Baroni, Simona; Terreno, Enzo; Nicolay, Klaas; Strijkers, Gustav J; Grüll, Holger

    2014-01-01

    Fluorine MRI ((19) F MRI) is receiving an increasing attention as a viable alternative to proton-based MRI ((1) H MRI) for dedicated application in molecular imaging. The (19) F nucleus has a high gyromagnetic ratio, a 100% natural abundance and is furthermore hardly present in human tissues allowing for hot spot MR imaging. The applicability of (19) F MRI as a molecular and cellular imaging technique has been exploited, ranging from cell tracking to detection and imaging of tumors in preclinical studies. In addition to applications, developing new contrast materials with improved relaxation properties has also been a core research topic in the field, since the inherently low longitudinal relaxation rates of perfluorocarbon compounds result in relatively low imaging efficiency. Borrowed from (1) H MRI, the incorporation of lanthanides, specifically Gd(III) complexes, as signal modulating ingredients in the nanoparticle formulation has emerged as a promising approach to improvement of the fluorine signal. Three different perfluorocarbon emulsions were investigated at five different magnetic field strengths. Perfluoro-15-crown-5-ether was used as the core material and Gd(III)DOTA-DSPE, Gd(III)DOTA-C6-DSPE and Gd(III)DTPA-BSA as the relaxation altering components. While Gd(III)DOTA-DSPE and Gd(III)DOTA-C6-DSPE were favorable constructs for (1) H NMR, Gd(III)DTPA-BSA showed the strongest increase in (19F) R(1). These results show the potential of the use of paramagnetic lipids to increase (19F) R(1) at clinical field strengths (1.5-3 T). At higher field strengths (6.3-14 T), gadolinium does not lead to an increase in (19F) R(1) compared with emulsions without gadolinium, but leads to an significant increase in (19F) R(2). Our data therefore suggest that the most favorable situation for fluorine measurements is at high magnetic fields without the inclusion of gadolinium constructs.

  8. Agent independent task planning

    NASA Technical Reports Server (NTRS)

    Davis, William S.

    1990-01-01

    Agent-Independent Planning is a technique that allows the construction of activity plans without regard to the agent that will perform them. Once generated, a plan is then validated and translated into instructions for a particular agent, whether a robot, crewmember, or software-based control system. Because Space Station Freedom (SSF) is planned for orbital operations for approximately thirty years, it will almost certainly experience numerous enhancements and upgrades, including upgrades in robotic manipulators. Agent-Independent Planning provides the capability to construct plans for SSF operations, independent of specific robotic systems, by combining techniques of object oriented modeling, nonlinear planning and temporal logic. Since a plan is validated using the physical and functional models of a particular agent, new robotic systems can be developed and integrated with existing operations in a robust manner. This technique also provides the capability to generate plans for crewmembers with varying skill levels, and later apply these same plans to more sophisticated robotic manipulators made available by evolutions in technology.

  9. Filling agents.

    PubMed

    Glavas, Ioannis P

    2005-06-01

    Injectable fillers have become an important component of minimally invasive facial rejuvenation modalities. Their ease of use, effectiveness, low morbidity, and fast results with minimal downtime are factors that have made them popular among patients. Soft tissue augmentation has evolved to a unique combination of medicine and art. A wide selection of available agents and new products, each one with unique properties, may be used alone or in combination. The physician acquires the tools to rebalance facial characteristics not only by filling wrinkles but also by having the ability to shape the face and restore bony contours and lines. Careful selection of candidates, realistic expectations, and an understanding of the limitations of fillers are crucial for a successful result.

  10. Safety Evaluation and Imaging Properties of Gadolinium-Based Nanoparticles in nonhuman primates

    PubMed Central

    Kotb, Shady; Piraquive, Joao; Lamberton, Franck; Lux, François; Verset, Michael; Di Cataldo, Vanessa; Contamin, Hugues; Tillement, Olivier; Canet-Soulas, Emmanuelle; Sancey, Lucie

    2016-01-01

    In this article, we report the safety evaluation of gadolinium-based nanoparticles in nonhuman primates (NHP) in the context of magnetic resonance imaging (MRI) studies in atherosclerosis bearing animals and healthy controls. In healthy NHP, the pharmacokinetics and toxicity profiles demonstrated the absence of dose, time, and sex-effects, as well as a suitable tolerance of intravenous administration of the nanoparticles. We investigated their imaging properties for arterial plaque imaging in a standard diet or a high cholesterol diet NHP, and compared their characteristics with clinically applied Gd-chelate. This preliminary investigation reports the efficient and safe imaging of atherosclerotic plaques. PMID:27725693

  11. Combustion synthesis and optical properties of ceria doped gadolinium-oxide nanopowder

    NASA Astrophysics Data System (ADS)

    Tamrakar, Raunak Kumar; Bisen, D. P.

    2013-06-01

    The Ceria doped Gadolinium (Gd2O3) nanopowder was synthesized by combustion synthesis by using urea as a fuel. The combustion synthesis method which is reported here is advantageous from the perspectives of small size of the nanoparticle. The structural and photoluminescence (PL) property of sample was studies. Gd2O3:Ce3+ nanoparticles exhibit green emission around 543 nm. The result of XRD show that synthesized sample has cubic structure. The average size of particle is found to be 45 nm. The surface morphology of the films is also presented.

  12. Caustic Precipitation of Plutonium Using Gadolinium as the Neutron Poison for Disposition to High Level Waste

    SciTech Connect

    Bronikowski, M.G.

    2002-06-24

    Nuclear Materials Management Division (NMMD) has proposed that up to 100 kg of the plutonium (Pu) solutions stored in H-Canyon be precipitated with a nuclear poison and dispositioned to H-Area Tank Farm. The use of gadolinium (Gd) as the poison would greatly reduce the number of additional glass logs resulting from this disposition. This report summarizes the characteristics of the precipitation process and addresses criticality concerns in the Nuclear Criticality Safety Evaluation. No problems were found with the nature of the precipitate or the neutralization process.

  13. Size-dependent Strain in Epitaxial (001)Gadolinium-doped Ceria Nanoislands

    SciTech Connect

    V Solovyov; M Gibert; T Puig; X Obradors

    2011-12-31

    We report size-dependent strain in epitaxial gadolinium doped ceria nanoislands, which was determined by synchrotron x-ray diffraction. Reciprocal space sections of symmetric, (004) and asymmetric, (224) reflections are approximated by a model assuming size-dependent strain of the islands using real-space size distribution obtained by atomic force microscopy. We show that the islands smaller than 40 nm are subjected to a high level of lateral tensile strain and normal compression. The lateral to normal strain ratio determined from the reciprocal map analysis suggests that lateral tension is the primary stress generator, possibly due to oxygen vacancy ordering on the island-substrate interface.

  14. Modification of the crystal structure of gadolinium gallium garnet by helium ion irradiation

    SciTech Connect

    Ostafiychuk, B. K.; Yaremiy, I. P. Yaremiy, S. I.; Fedoriv, V. D.; Tomyn, U. O.; Umantsiv, M. M.; Fodchuk, I. M.; Kladko, V. P.

    2013-12-15

    The structure of gadolinium gallium garnet (GGG) single crystals before and after implantation by He{sup +} ions has been investigated using high-resolution X-ray diffraction methods and the generalized dynamic theory of X-ray scattering. The main types of growth defects in GGG single crystals and radiation-induced defects in the ion-implanted layer have been determined. It is established that the concentration of dislocation loops in the GGG surface layer modified by ion implantation increases and their radius decreases with an increase in the implantation dose.

  15. Late gadolinium enhancement imaging in assessment of myocardial viability: techniques and clinical applications.

    PubMed

    Jimenez Juan, Laura; Crean, Andrew M; Wintersperger, Bernd J

    2015-03-01

    Assessment of myocardial viability is of ever-evolving interest in cardiovascular imaging, with major societies having incorporated viability imaging as class I or class IIa indications in their guidelines to better guide patient management. As with late gadolinium enhancement cardiac magnetic resonance (MR), assessment of residual myocardial viability or the extent of myocardial infarction is straightforward and this technique may easily be combined with other cardiac MR modules. In clinical routine functional assessment and myocardial perfusion imaging if often used in conjunction allowing for a comprehensive assessment of ischemic heart disease.

  16. Modification of the crystal structure of gadolinium gallium garnet by helium ion irradiation

    NASA Astrophysics Data System (ADS)

    Ostafiychuk, B. K.; Yaremiy, I. P.; Yaremiy, S. I.; Fedoriv, V. D.; Tomyn, U. O.; Umantsiv, M. M.; Fodchuk, I. M.; Kladko, V. P.

    2013-12-01

    The structure of gadolinium gallium garnet (GGG) single crystals before and after implantation by He+ ions has been investigated using high-resolution X-ray diffraction methods and the generalized dynamic theory of X-ray scattering. The main types of growth defects in GGG single crystals and radiation-induced defects in the ion-implanted layer have been determined. It is established that the concentration of dislocation loops in the GGG surface layer modified by ion implantation increases and their radius decreases with an increase in the implantation dose.

  17. Electromagnetic excitation of ultrasonic oscillations by yttrium iron garnet films on gallium gadolinium garnet substrates

    NASA Astrophysics Data System (ADS)

    Sarnatskii, V. M.; Mavlonazarov, I. O.; Lutsev, L. V.

    2014-07-01

    We have studied the phenomenon of contactless excitation of ultrasonic oscillations by thin yttrium iron garnet (YIG) films on gallium gadolinium garnet (GGG) substrates upon application of the superposition of a constant magnetic bias field and alternating magnetic field. Dimensional resonance effects that cannot be explained in the framework of existing theoretical notions have been discovered, in particular, in dependences of the amplitude of excited longitudinal oscillations on the YIG film thickness, frequency of ultrasound, and degree of homogeneity and strength of the magnetic bias field. It is suggested that the observed phenomenon is caused by resonant participation of the intrinsic oscillations of domain walls in the excitation of ultrasound.

  18. Controlled manipulation of gadolinium-coordinated supramolecules by low-temperature scanning tunneling microscopy.

    PubMed

    Urgel, José I; Ecija, David; Auwärter, Willi; Barth, Johannes V

    2014-03-12

    Coordination bonding between para-quarterphenyl-dicarbonitrile linkers and gadolinium on Ag(111) has been exploited to construct pentameric mononuclear supramolecules, consisting of a rare-earth center surrounded by five molecular linkers. By employing a scanning tunneling microscope tip, a manipulation protocol was developed to position individual pentamers on the surface. In addition, the tip was used to extract and replace individual linkers yielding tetrameric, pentameric, nonameric, and dodecameric metallosupramolecular arrangements. These results open new avenues toward advanced nanofabrication methods and rare-earth nanochemistry by combining the versatility of metal-ligand interactions and atomistic manipulation capabilities.

  19. Quantitative assessment of synovitis in Legg-Calvé-Perthes disease using gadolinium-enhanced MRI.

    PubMed

    Neal, David C; O'Brien, Jack C; Burgess, Jamie; Jo, Chanhee; Kim, Harry K W

    2015-03-01

    A quantitative method to assess hip synovitis in Legg-Calvé-Perthes disease (LCPD) is not currently available. To develop this method, the areas of synovial enhancement on gadolinium-enhanced MRI (Gd-MRI) were measured by two independent observers. The volume of synovial enhancement was significantly increased in the initial and the fragmentation stages of LCPD (Waldenström stages I and II), with a persistence of synovitis into the reossification stage (stage III). The Gd-MRI method had high interobserver and intraobserver agreements and may serve as a useful method to monitor the effect of various treatments on hip synovitis in LCPD. PMID:25305048

  20. Geometric frustration in gadolinium gallium garnet: a Monte Carlo study

    SciTech Connect

    Petrenko, Oleg A.; Paul, Don McK.

    1999-06-15

    We have studied the magnetic properties of the frustrated triangular antiferromagnet Gd{sub 3}Ga{sub 5}O{sub 12} (GGG) by means of classical Monte Carlo simulations. Low-temperature specific heat, magnetization, susceptibility, autocorrelation function and neutron scattering function have been calculated for several models including different types of magnetic interactions and with the presence of an external magnetic field. In order to reproduce the experimentally observed properties of GGG, the simulation model must include nearest neighbor exchange interactions and also dipolar forces. In zero field there is a tendency to form incommensurate short-range magnetic order around positions in reciprocal space where antiferromagnetic Bragg peaks appear in an applied magnetic field.

  1. Gelled Anti-icing Agents

    NASA Technical Reports Server (NTRS)

    Markles, O. F.; Sperber, H. H.

    1983-01-01

    Pectin added to antifreeze/water mixture. Formulations include water with dimethyl sulfoxide (DMSO) as deicer and pectin as gel former. Without gelling agent, deicer runs off vertical surfaces. Without pectin solution will completely evaporate in far less time. Agents developed have wide potential for ice prevention on runways, highways, bridges and sidewalks.

  2. Health care agents

    MedlinePlus

    Durable power of attorney for health care; Health care proxy; End-of-life - health care agent; Life support treatment - ... Respirator - health care agent; Ventilator - health care agent; Power of attorney - health care agent; POA - health care ...

  3. Battlefield agent collaboration

    NASA Astrophysics Data System (ADS)

    Budulas, Peter P.; Young, Stuart H.; Emmerman, Philip J.

    2001-09-01

    Small air and ground physical agents (robots) will be ubiquitous on the battlefield of the 21st century, principally to lower the exposure to harm of our ground forces in urban and open terrain scenarios. Teams of small collaborating physical agents conducting tasks such as Reconnaissance, Surveillance, and Target Acquisition (RSTA), intelligence, chemical and biological agent detection, logistics, decoy, sentry; and communications relay will have advanced sensors, communications, and mobility characteristics. It is anticipated that there will be many levels of individual and team collaboration between the soldier and robot, robot to robot, and robot to mother ship. This paper presents applications and infrastructure components that illustrate each of these levels. As an example, consider the application where a team of twenty small robots must rapidly explore and define a building complex. Local interactions and decisions require peer to peer collaboration. Global direction and information fusion warrant a central team control provided by a mother ship. The mother ship must effectively deliver/retrieve, service, and control these robots as well as fuse the information gathered by these highly mobile robot teams. Any level of collaboration requires robust communications, specifically a mobile ad hoc network. The application of fixed ground sensors and mobile robots is also included in this paper. This paper discusses on going research at the U.S. Army Research Laboratory that supports the development of multi-robot collaboration. This research includes battlefield visualization, intelligent software agents, adaptive communications, sensor and information fusion, and multi-modal human computer interaction.

  4. First-principles study of 2D electride : Gadolinium carbide

    NASA Astrophysics Data System (ADS)

    Nandadasa, Chandani; Kim, Seong-Gon; Kim, Sungho; Kim, Sung Wng

    Electrides are an exclusive class of ionic compounds in which some electrons are occupying crystal voids instead of attaching to specific atoms or bonds. Using first-principles density functional theory calculations, we study structural, electronic and magnetic properties of Gd2C. The theoretically predicted structure of Gd2C is in good agreement with the available experimental data. Energy band diagram of Gd2C shows that they are crossing the Fermi level. Projected electronic density of states plots indicate that the interstitial sites are the main contributor to the density of states at the Fermi level. Charge of individual atoms including interstitial site are obtained using Bader analysis. Magnetic properties of Gd2C is determined from magnetization density plots. Work functions of Gd2C are determined for (001) and (100) surfaces with the technique of macroscopic average of electrostatic potential with the Fermi energy of bulk.

  5. Detecting agents.

    PubMed Central

    Johnson, Susan C

    2003-01-01

    This paper reviews a recent set of behavioural studies that examine the scope and nature of the representational system underlying theory-of-mind development. Studies with typically developing infants, adults and children with autism all converge on the claim that there is a specialized input system that uses not only morphological cues, but also behavioural cues to categorize novel objects as agents. Evidence is reviewed in which 12- to 15-month-old infants treat certain non-human objects as if they have perceptual/attentional abilities, communicative abilities and goal-directed behaviour. They will follow the attentional orientation of an amorphously shaped novel object if it interacts contingently with them or with another person. They also seem to use a novel object's environmentally directed behaviour to determine its perceptual/attentional orientation and object-oriented goals. Results from adults and children with autism are strikingly similar, despite adults' contradictory beliefs about the objects in question and the failure of children with autism to ultimately develop more advanced theory-of-mind reasoning. The implications for a general theory-of-mind development are discussed. PMID:12689380

  6. 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

    -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

  7. Density functional calculations for structural, electronic, and magnetic properties of gadolinium-oxide clusters

    NASA Astrophysics Data System (ADS)

    Yuan, H. K.; Chen, H.; Tian, C. L.; Kuang, A. L.; Wang, J. Z.

    2014-04-01

    Gadolinium-oxide clusters in various sizes and stoichiometries have been systematically studied by employing the density functional theory with the generalized gradient approximation. The clusters in bulk stoichiometry are relatively more stable and their binding energies increase with the increasing size. Stoichiometric (Gd2O3)n clusters of n = 1-3 prefer cage-like structures, whereas the clusters of n = 4-30 prefer compact structures layered by wedge-like units and exhibit a rough feature toward the bulk-like arrangement with small disorders of atomic positions. The polyhedral-cages analogous to carbon-fullerenes are stable isomers yet not the minimum energy configurations. Their stabilities can be improved by embedding one oxygen atom or a suitable cage to form core-shell configurations. The mostly favored antiferromagnetic couplings between adjacent Gd atoms are nearly degenerated in energy with their ferromagnetic couplings, resulting in super-paramagnetic characters of gadolinium-oxide clusters. The Ruderman-Kittel-Kasuya-Yosida (RKKY)-type mechanism together with the superexchange-type mechanism plays cooperation role for the magnetic interactions in clusters. We present, as a function of n, calculated binding energies, ionization potential, electron affinity, and electronic dipole moment.

  8. Silica nanoparticles coencapsulating gadolinium oxide and horseradish peroxidase for imaging and therapeutic applications.

    PubMed

    Gupta, Nikesh; Shrivastava, Anju; Sharma, Rakesh K

    2012-01-01

    Mesoporous silica nanoparticles coencapsulating gadolinium oxide and horseradish peroxidase (HRP) have been synthesized in the aqueous core of sodium bis-(2-ethylhexyl) sulfosuccinate (AOT)-hexane-water reverse micelle. The average diameter of these silica particles is around 25 nm and the particles are spherical and highly monodispersed as depicted using transmission electron microscopy. The entrapment efficiency of HRP was found to be as high as 95%. Practically, the entrapped enzyme shows zero leachability up to 90 days. The enzyme entrapped in these silica nanoparticles follows Michaelis-Menten kinetics. Peroxidase entrapped in silica nanoparticles shows higher stability towards temperature and pH change as compared to free enzymes. The gadolinium oxide-doped silica nanoparticles are paramagnetic as observed from the nuclear magnetic resonance line-broadening effect on the proton spectrum of the surrounding water molecule. The entrapped enzyme, HRP, has been used to convert a benign prodrug, indole-3-acetic acid (IAA), to a toxic oxidized product and its toxic effect has been tested on cancerous cell lines through thiazolyl blue tetrazolium blue (MTT) assay. In vitro studies on different cancerous cell lines show that the enzyme has been entrapped and retains its activity inside the silica nanoparticles. IAA alone has no cytotoxic effect and it becomes active only after oxidative decarboxylation by HRP.

  9. Disparate ultrafast dynamics of itinerant and localized magnetic moments in gadolinium metal

    PubMed Central

    Frietsch, B.; Bowlan, J.; Carley, R.; Teichmann, M.; Wienholdt, S.; Hinzke, D.; Nowak, U.; Carva, K.; Oppeneer, P. M.; Weinelt, M.

    2015-01-01

    The Heisenberg–Dirac intra-atomic exchange coupling is responsible for the formation of the atomic spin moment and thus the strongest interaction in magnetism. Therefore, it is generally assumed that intra-atomic exchange leads to a quasi-instantaneous aligning process in the magnetic moment dynamics of spins in separate, on-site atomic orbitals. Following ultrashort optical excitation of gadolinium metal, we concurrently record in photoemission the 4f magnetic linear dichroism and 5d exchange splitting. Their dynamics differ by one order of magnitude, with decay constants of 14 versus 0.8 ps, respectively. Spin dynamics simulations based on an orbital-resolved Heisenberg Hamiltonian combined with first-principles calculations explain the particular dynamics of 5d and 4f spin moments well, and corroborate that the 5d exchange splitting traces closely the 5d spin-moment dynamics. Thus gadolinium shows disparate dynamics of the localized 4f and the itinerant 5d spin moments, demonstrating a breakdown of their intra-atomic exchange alignment on a picosecond timescale. PMID:26355196

  10. Thermal neutron capture cross section of gadolinium by pile-oscillation measurements in MINERVE

    SciTech Connect

    Leconte, P.; Di-Salvo, J.; Antony, M.; Pepino, A.; Hentati, A.

    2012-07-01

    Natural gadolinium is used as a burnable poison in most LWR to account for the excess of reactivity of fresh fuels. For an accurate prediction of the cycle length, its nuclear data and especially its neutron capture cross section needs to be known with a high precision. Recent microscopic measurements at Rensselaer Polytechnic Inst. (RPI) suggest a 11% smaller value for the thermal capture cross section of {sup 157}Gd, compared with most of evaluated nuclear data libraries. To solve this inconsistency, we have analyzed several pile-oscillation experiments, performed in the MINERVE reactor. They consist in the measurement of the reactivity variation involved by the introduction in the reactor of small-samples, containing different mass amounts of natural gadolinium. The analysis of these experiments is done through the exact perturbation theory, using the PIMS calculation tool, in order to link the reactivity effect to the thermal capture cross section. The measurement of reactivity effects is used to deduce the 2200 m.s-1 capture cross section of {sup nat}Gd which is (49360 {+-} 790) b. This result is in good agreement with the JEFF3.1.1 value (48630 b), within 1.6% uncertainty at 1{sigma}, but is strongly inconsistent with the microscopic measurements at RPI which give (44200 {+-} 500) b. (authors)

  11. Density functional calculations for structural, electronic, and magnetic properties of gadolinium-oxide clusters

    SciTech Connect

    Yuan, H. K.; Chen, H. Tian, C. L.; Kuang, A. L.; Wang, J. Z.

    2014-04-21

    Gadolinium-oxide clusters in various sizes and stoichiometries have been systematically studied by employing the density functional theory with the generalized gradient approximation. The clusters in bulk stoichiometry are relatively more stable and their binding energies increase with the increasing size. Stoichiometric (Gd{sub 2}O{sub 3}){sub n} clusters of n = 1–3 prefer cage-like structures, whereas the clusters of n = 4–30 prefer compact structures layered by wedge-like units and exhibit a rough feature toward the bulk-like arrangement with small disorders of atomic positions. The polyhedral-cages analogous to carbon-fullerenes are stable isomers yet not the minimum energy configurations. Their stabilities can be improved by embedding one oxygen atom or a suitable cage to form core-shell configurations. The mostly favored antiferromagnetic couplings between adjacent Gd atoms are nearly degenerated in energy with their ferromagnetic couplings, resulting in super-paramagnetic characters of gadolinium-oxide clusters. The Ruderman-Kittel-Kasuya-Yosida (RKKY)-type mechanism together with the superexchange-type mechanism plays cooperation role for the magnetic interactions in clusters. We present, as a function of n, calculated binding energies, ionization potential, electron affinity, and electronic dipole moment.

  12. Effect of solid-phase amorphization on the spectral characteristics of europium-doped gadolinium molybdate

    NASA Astrophysics Data System (ADS)

    Shmurak, S. Z.; Kiselev, A. P.; Kurmasheva, D. M.; Red'Kin, B. S.; Sinitsyn, V. V.

    2010-05-01

    A method is proposed for detecting spectral characteristics of optically inactive molybdates of rare-earth elements by their doping with rare-earth ions whose luminescence lies in the transparency region of all structural modifications of the sample. Gadolinium molybdate is chosen as the object of investigations, while europium ions are used as an optically active and structurally sensitive admixture. It is shown that after the action of a high pressure under which gadolinium molybdate passes to the amorphous state, the spectral characteristics of Gd1.99Eu0.01(MoO4)3 (GMO:Eu) change radically; namely, considerable line broadening is observed in the luminescence spectra and the luminescence excitation spectra, while the long-wave threshold of optical absorption is shifted considerably (by approximately 1.1 eV) towards lower energies. It is found that by changing the structural state of GMO:Eu by solid-state amorphization followed by annealing, the spectral characteristics of the sample can be purposefully changed. This is extremely important for solving the urgent problem of designing high-efficiency light-emitting diodes producing “white” light.

  13. Chemical and magnetic structure of uranium/gadolinium multilayers studied by transmission

    SciTech Connect

    Wilkins, S.B.; Springell, R.; Langridge, S.; Wildes, A.; Sanchez-Hanke, C.; Moore, K.T.; Butterfield, M.; Chivall, J.; Ward, R.C.C.; Wells, M.R.; Lander, G.H.

    2010-04-29

    We present a multitechnique approach to study the detailed chemical and magnetic structure of uranium/gadolinium multilayers. At low temperature the saturation magnetization is found to be {approx}60% of that of bulk gadolinium. We address this problem, which is found in many other multilayers and suggest a model that may have wider applications. Transmission electron microscopy images indicate a microstructure, consistent with a columnar growth of Gd with crystallites of the order 20 {yields} 100{angstrom}. Off-specular neutron scattering is most strongly visible at saturation field, indicating that Gd moments are not aligned with the applied field. X-ray resonant magnetic scattering provides proof of coupled in-plane length scales for both the structural and the magnetic roughness. A detailed x-ray scattering study of both the specular and off-specular reflectivities has been used to investigate the in-plane structure of the multilayers. We calculate the roughness and transverse correlation cut-off length, {zeta}{sub x} = 120 {+-} 30{angstrom}, and present a simple model to determine an average column size of 27 {+-} 6{angstrom} and a reduction in the magnetic saturation of {approx}40%.

  14. Development of a gadolinium-loaded liquid scintillator for the Hanaro short baseline prototype detector

    NASA Astrophysics Data System (ADS)

    Yeo, In Sung; Joo, Kyung Kwang; So, Sun Heang; Song, Sook Hyung; Kim, Hong Joo; So, Jung Ho; Park, Kang Soon; Ma, Kyung Ju; Jeon, Eun Ju; Kim, Jin Yu; Kim, Young Duk; Lee, Jason; Lee, Jeong-Yeon; Sun, Gwang-Min

    2014-02-01

    We propose a new experiment on the site of the Korea Atomic Energy Research Institute (KAERI) located at Daejeon, Korea. The Hanaro short baseline (SBL) nuclear reactor with a thermal power output 30 MW is used to investigate a reactor neutrino anomaly. A Hanaro SBL prototype detector having a 60- l volume has been constructed ˜6 m away from the reactor core. A gadolinium (Gd)-loaded liquid scintillator (LS) is used as an active material to trigger events. The selection of the LS is guided by physical and technical requirements, as well as safety considerations. A linear alkyl benzene (LAB) is used as a base solvent of the Hanaro SBL prototype detector. Three g/ l of PPO and 30 mg/ l of bis-MSB are dissolved to formulate the LAB-based LS. Then, a 0.5% gadolinium (Gd) complex with carboxylic acid is loaded into the LAB-based LS by using the liquidliquid extraction method. In this paper, we will summarize all the characteristics of the Gd-loaded LAB-based LS for the Hanaro prototype detector.

  15. Single crystal Processing and magnetic properties of gadolinium nickel

    SciTech Connect

    Shreve, Andrew John

    2012-01-01

    GdNi is a rare earth intermetallic material that exhibits very interesting magnetic properties. Spontaneous magnetostriction occurs in GdNi at T{sub C}, on the order of 8000ppm strain along the c-axis and only until very recently the mechanism causing this giant magnetostriction was not understood. In order to learn more about the electronic and magnetic structure of GdNi, single crystals are required for anisotropic magnetic property measurements. Single crystal processing is quite challenging for GdNi though since the rare-earth transition-metal composition yields a very reactive intermetallic compound. Many crystal growth methods are pursued in this study including crucible free methods, precipitation growths, and specially developed Bridgman crucibles. A plasma-sprayed Gd2O3 W-backed Bridgman crucible was found to be the best means of GdNi single crystal processing. With a source of high-quality single crystals, many magnetization measurements were collected to reveal the magnetic structure of GdNi. Heat capacity and the magnetocaloric effect are also measured on a single crystal sample. The result is a thorough report on high quality single crystal processing and the magnetic properties of GdNi.

  16. A theoretical investigation of gadolinium (III) solvation in molten salts

    NASA Astrophysics Data System (ADS)

    Hazebroucq, Sandrine; Picard, Gérard S.; Adamo, Carlo

    2005-06-01

    The solvation of lanthanides [here Gd(III)] in molten LiCl and KCl has been studied using a classical solvation approach, based on clusters of increasing size. In particular, density-functional calculations have been carried out on charged and neutral clusters, containing up to 35 chlorine halide molecules. A number of properties have been then evaluated and analyzed, including structural, vibrational, and thermochemical data. Special attention has also been devoted to the analysis of the local structure of the solvent surrounding the Gd3+ cation, a problem deeply investigated by experimentalists. Our results show that the charged clusters are not suitable to model the first solvation shell in such species, since their structures are strongly affected by the large electrostatic contribution. In contrast, more reliable simulations are obtained using the neutral clusters. In the latter, the coordination of Gd(III) in molten salts is computed to be 8 or 6, according to the salt LiCl or KCl. Furthermore, a good agreement is found with the experimental structural data and Raman spectra. Finally, preliminary results of potential interest for the estimation of solvation thermodynamics, a key parameter for exploiting molten salt chemistry, are reported for neutral clusters.

  17. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  18. Lack of increased signal intensity in the dentate nucleus after repeated administration of a macrocyclic contrast agent in multiple sclerosis: An observational study.

    PubMed

    Eisele, Philipp; Alonso, Angelika; Szabo, Kristina; Ebert, Anne; Ong, Melissa; Schoenberg, Stefan O; Gass, Achim

    2016-09-01

    Recently, several studies reported increased signal intensity (SI) in the dentate nucleus (DN) after repeated application of gadolinium-based contrast agents (GBCAs), suggesting a deposition of gadolinium in this location. Patients with relapsing-remitting multiple sclerosis (RRMS) frequently show increased permeability of the blood-brain barrier as part of the inflammatory process in the brain parenchyma, which theoretically might increase the risk of gadolinium deposition. In this retrospective study, we investigated a possible increasing SI in the DN after repeated administrations of the macrocyclic contrast agent gadoterate meglumine.Forty-one RRMS patients (33 women, mean age 38 years) with at least 6 prior gadolinium-enhanced examinations (single dose gadoterate meglumine) were identified. A total of 279 unenhanced T1-weighted examinations were analyzed.SI ratio differences did not differ between the first and last MRI examination, neither for the DN-to-pons ratio (P = 0.594) nor for the DN-to-cerebellum ratio (P = 0.847). There was no correlation between the mean DN-to-pons, or between the mean DN-to-cerebellum SI ratio and the number of MRI examinations (P = 0.848 and 0.891), disease duration (P = 0.676 and 0.985), and expanded disability status scale (EDSS) (P = 0.639 and 0.945).We found no signal increases in the DN after a minimum of 6 injections of the macrocyclic GBCA gadoterate meglumine in RRMS patients. This warrants further investigations in regard to the true pathophysiologic basis of intracerebral gadolinium deposition. PMID:27684794

  19. Boron, Samarium, Gadolinium, Lithium and Hydrogen Abundances in Antarctic Meteorites

    NASA Astrophysics Data System (ADS)

    Shaw, D. M.; Smith, P. L. C.; Zhai, M.

    1992-07-01

    The boron concentrations in 13 Antarctic meteorite specimens were published in 1988 (1). Here we report B, Sm, Gd, and some H abundances in 27 additional chondrites and 14 achondrites, all measured by prompt gamma neutron activation analysis: some Li analyses were also made, using AAS. The accuracy and precision of analysis are particularly important for B, Sm, and Gd, whose abundance levels in meteorites can be 1 ppm or less, so multiple analyses of Reference Materials DTS-1, PCC-1, BHVO-1, and JG-1 were made for controls. The results showed good agreement with recommended values for B and H (expressed as H2O); the results were good also for Sm and Gd but at concentrations 10x meteorites. Precision was adequate, averaging 10 to 15% (1 s.d.) of amount present. Stringent precautions against contamination were maintained during handling and analysis. Natural mobilisation of B in the Antarctic weathering environment is however known to take place (1). The summarised results are as follows: B Sm Gd H2O Li ppm ppm ppm % ppm Mean of 6 analyses of 3 C.C. 0.93 0.36 0.39 0.94 4.3 Mean of 42 analyses of 37 CH 0.78 0.35 0.30 0.97 5.8 Mean of 7 eucrites, howardites 2.7 1.1 1.9 0.75 - The principal observations are that (a) B and Li abundances in CH and C.C. resemble earlier estimates, (b) Sm and Gd in CH and C.C. are markedly higher than expected, (c) B, Sm, and Gd are significantly higher in eucrites and howardites than in other meteorites (including aubrites, diogenites, and ureilites) and (d) estimates of H2O on individual meteorites agree quite well with published results by conventional methods. These observations form the basis for further interpretations. (1) D. M. Shaw, M. D. Higgins, R. W. Hinton, M. G. Truscott, and T. A. Middleton (1988) Boron in chondritic meteorites. Geochimica et Cosmochimica Acta 52, 2311-2319.

  20. Fabrication of a silica sphere with fluorescent and MR contrasting GdPO4 nanoparticles from layered gadolinium hydroxide.

    PubMed

    Yoon, Young-su; Lee, Byung-Il; Lee, Kyung Sig; Heo, Hyejung; Lee, Jung Hee; Byeon, Song-Ho; Lee, In Su

    2010-06-01

    The delaminated gadolinium hydroxide layers doped with Eu(3+) ions were assembled on the surface of silica spheres and annealed at high temperatures, resulting in the formation of fluorescent and MR active GdPO(4) : Eu nanoparticles at the surface.

  1. Neutron and Charged-Particle Induced Cross Sections for Radiochemistry in the Region of Samarium, Europium, and Gadolinium

    SciTech Connect

    Hoffman, R D; Kelley, K; Dietrich, F S; Bauer, R; Mustafa, M

    2004-11-30

    We have developed a set of modeled nuclear reaction cross sections for use in radiochemical diagnostics. Systematics for the input parameters required by the Hauser-Feshbach statistical model were developed and used to calculate neutron and proton induced nuclear reaction cross sections in the mass region of samarium, europium and gadolinium (62 {le} Z {le} 64, 82 {le} N {le} 96).

  2. Feasibility of synchrotron radiation computed tomography on rats bearing glioma after iodine or gadolinium injection. Jeune Equipe RSRM-UJF.

    PubMed

    Le Duc, G; Corde, S; Elleaume, H; Estève, F; Charvet, A M; Brochard, T; Fiedler, S; Collomb, A; Le Bas, J F

    2000-01-01

    The purpose of this work was to demonstrate the feasibility of a new imaging technique called synchrotron radiation computed tomography (SRCT). This technique leads to a direct assessment of the in vivo concentration of an iodine- or gadolinium-labeled compound. Rats bearing C6 glioma were imaged by MRI prior to the SRCT experiment. The SRCT experiments were performed after a 1.3 g I/kg (n = 5) or a 0.4 g Gd/kg (n = 5) injection. Finally, brains were sampled for histology. The SRCT images exhibited contrast enhancement at the tumor location. Ten minutes after injection, iodine and gadolinium tissular concentrations were equal to 0.80 ( +/- 0.40) mg/cm3 and 0.50 ( +/- 0.10) mg/cm3, respectively in the peripheral area of the tumor (respective background value: 0.20 +/- 0.02 to 0.10 +/- 0.01). Correlation to MRI and histology revealed that the contrast uptake occurred in the most vascularized area of the tumor. The present study summarizes the feasibility of in vivo SRCT to obtain quantitative information about iodine and gadolinium-labeled compounds. Beyond brain tumor pathology, the SRCT appears as a complementary approach to MRI and CT, for studying iodine- and gadolinium-labeled compounds by the direct achievement of the tissular concentration value in the tissue.

  3. Hybrid gold-gadolinium nanoclusters for tumor-targeted NIRF/CT/MRI triple-modal imaging in vivo

    NASA Astrophysics Data System (ADS)

    Hu, De-Hong; Sheng, Zong-Hai; Zhang, Peng-Fei; Yang, Da-Zhi; Liu, Shu-Hui; Gong, Ping; Gao, Du-Yang; Fang, Sheng-Tao; Ma, Yi-Fan; Cai, Lin-Tao

    2013-01-01

    Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, we prepared hybrid gold-gadolinium nanoclusters (NCs), which are ultrasmall, stable, biocompatible, and suitable for triple-modal NIRF/CT/MRI imaging. Upon intravenously injected, the hybrid NCs are effectively accumulated in tumor tissues and quickly clear by renal excretion, indicating their capacity of tumor targeting and low body residues. Notably, the ultrasmall hybrid NCs would penetrate into the solid tumor for capturing its heterostructure and do not induce potential toxicity in vivo. Hence, the well-defined hybrid gold-gadolinium NCs provide a versatile nanoprobe for cancer targeted imaging and diagnosis in vivo.Multimodal imaging is highly desirable for accurate diagnosis because it can provide complementary information from each imaging modality. In this study, we prepared hybrid gold-gadolinium nanoclusters (NCs), which are ultrasmall, stable, biocompatible, and suitable for triple-modal NIRF/CT/MRI imaging. Upon intravenously injected, the hybrid NCs are effectively accumulated in tumor tissues and quickly clear by renal excretion, indicating their capacity of tumor targeting and low body residues. Notably, the ultrasmall hybrid NCs would penetrate into the solid tumor for capturing its heterostructure and do not induce potential toxicity in vivo. Hence, the well-defined hybrid gold-gadolinium NCs provide a versatile nanoprobe for cancer targeted imaging and diagnosis in vivo. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr33543c

  4. Gadolinium oxide nanoparticles and aptamer-functionalized silver nanoclusters-based multimodal molecular imaging nanoprobe for optical/magnetic resonance cancer cell imaging.

    PubMed

    Li, Jingjing; You, Jia; Dai, Yue; Shi, Meilin; Han, Cuiping; Xu, Kai

    2014-11-18

    Multimodal molecular imaging has attracted more and more interest from researchers due to its combination of the strengths of each imaging modality. The development of specific and multifunctional molecular imaging probes is the key for this method. In this study, we fabricated an optical/magnetic resonance (MR) dual-modality molecular imaging nanoprobe, polyethylene glycol-coated ultrasmall gadolinium oxide (PEG-Gd2O3)/aptamer-Ag nanoclusters (NCs), for tracking cancer cells. To achieve this aim, PEG-Gd2O3 nanoparticles (NPs) as magnetic resonance imaging (MRI) contrast agent and aptamer functionalized silver nanoclusters (aptamer-Ag NCs) as fluorescence reporter were first synthesized by a one-pot approach, respectively. They were then conjugated by the covalent coupling reaction between the carboxyl group on the surface of PEG-Gd2O3 NPs and amino group modified on the 5'-end of AS1411 aptamer. With a suitable ratio, the fluorescence intensity of aptamer-Ag NCs and MR signal of PEG-Gd2O3 nanoparticles could both be enhanced after the formation of PEG-Gd2O3/aptamer-Ag NCs nanoprobe, which favored their application for multimodal molecular imaging. With this nanoprobe, MCF-7 tumor cells could be specifically tracked by both fluorescence imaging and magnetic resonance imaging in vitro. PMID:25338209

  5. Gadolinium oxide nanoparticles and aptamer-functionalized silver nanoclusters-based multimodal molecular imaging nanoprobe for optical/magnetic resonance cancer cell imaging.

    PubMed

    Li, Jingjing; You, Jia; Dai, Yue; Shi, Meilin; Han, Cuiping; Xu, Kai

    2014-11-18

    Multimodal molecular imaging has attracted more and more interest from researchers due to its combination of the strengths of each imaging modality. The development of specific and multifunctional molecular imaging probes is the key for this method. In this study, we fabricated an optical/magnetic resonance (MR) dual-modality molecular imaging nanoprobe, polyethylene glycol-coated ultrasmall gadolinium oxide (PEG-Gd2O3)/aptamer-Ag nanoclusters (NCs), for tracking cancer cells. To achieve this aim, PEG-Gd2O3 nanoparticles (NPs) as magnetic resonance imaging (MRI) contrast agent and aptamer functionalized silver nanoclusters (aptamer-Ag NCs) as fluorescence reporter were first synthesized by a one-pot approach, respectively. They were then conjugated by the covalent coupling reaction between the carboxyl group on the surface of PEG-Gd2O3 NPs and amino group modified on the 5'-end of AS1411 aptamer. With a suitable ratio, the fluorescence intensity of aptamer-Ag NCs and MR signal of PEG-Gd2O3 nanoparticles could both be enhanced after the formation of PEG-Gd2O3/aptamer-Ag NCs nanoprobe, which favored their application for multimodal molecular imaging. With this nanoprobe, MCF-7 tumor cells could be specifically tracked by both fluorescence imaging and magnetic resonance imaging in vitro.

  6. In Vivo Tracking of Phagocytic Immune Cells Using a Dual Imaging Probe with Gadolinium-Enhanced MRI and Near-Infrared Fluorescence.

    PubMed

    Kim, Eun-Joong; Bhuniya, Sankarprasad; Lee, Hyunseung; Kim, Hyun Min; Shin, Weon Sup; Kim, Jong Seung; Hong, Kwan Soo

    2016-04-27

    A novel dual imaging probe for in vivo magnetic resonance imaging (MRI) and optical imaging was developed by combining gadolinium (Gd)-chelating MR probe and a near-infrared (NIR) fluorophore, aza-BODIPY (AB; BODIPY = boron-dipyrromethene). This aza-BODIPY-based bimodal contrast agent (AB-BCA) showed a significant fluorescence emission around the NIR range and an enhanced longitudinal relaxivity in MR modality. The probe was easily delivered to phagocytic cells of the innate immune system, together with macrophages and dendritic cells (DCs), and presented high-performance fluorescence and MR imaging without obvious cytotoxicity. For in vivo visualization of AB-BCA using MRI and optical imaging, bone marrow-derived DCs were labeled and injected into the footpad of mice, and labeled DCs were tracked in vivo. We observed the migration of AB-BCA-labeled DCs into the lymph nodes via lymphatic vessels using NIR fluorescence and T1-weighted MR images. This dual-modality imaging probe was used for noninvasive monitoring of DC migration into lymph nodes and could be useful for investigating advanced cellular immunotherapy. PMID:27058603

  7. Gadolinium promoted proliferation in mouse embryo fibroblast NIH3T3 cells through Rac and PI3K/Akt signaling pathways.

    PubMed

    Shen, Liming; Yang, Aochu; Yao, Pengwei; Sun, Xiaohong; Chen, Cheng; Mo, Cuiping; Shi, Lei; Chen, Youjiao; Liu, Qiong

    2014-08-01

    Nephrogenic systemic fibrosis (NSF) is a fibrosing disorder disease developed in patients with underlying renal insufficiency following exposure to gadolinium-based contrast agents (GBCAs). Previous studies have demonstrated that GdCl3 can promote NIH3T3 fibroblast cell proliferation, which provide a new clue to the role of GBCAs in the development of NSF. In the present study, we further clarify the molecular mechanism of Gd-promoted proliferation. The results showed that intervention with the Rac inhibitor NSC23766 abrogated Gd-promoted proliferation. The levels of active Rac1 significantly increased in Gd-treated cells detected by pull-down assays. In addition, the phosphorylation of Akt was significantly elevated in the treatment group, which was blocked by NSC23766. NSC23766 also reduced the migration of NIH3T3 cells enhanced by Gd. Moreover, the F-actin cytoskeleton was strengthened and the mitotic cell numbers was significantly increased after exposure to Gd. These results suggest that Rac and PI3K/Akt signaling pathways, as well as integrin-mediated signal pathway may play important roles in Gd-induced cell proliferation. In addition, under serum-free condition, Gd could decrease ROS accumulation and increase NIH3T3 cell survival.

  8. Surface capping-assisted hydrothermal growth of gadolinium-doped CeO₂ nanocrystals dispersible in aqueous solutions.

    PubMed

    Sato, Kazuyoshi; Arai, Manami; Valmalette, Jean-Christophe; Abe, Hiroya

    2014-10-14

    Nanocrystals of 20 mol % Gd(3+)-doped CeO2 dispersible in basic aqueous solutions were grown via hydrothermal treatment of anionic Ce(IV) and Gd(III) carbonate complexes at 125-150 °C for 6-24 h with N(CH3)4(+) as a capping agent. The nanocrystals were characterized in detail using dynamic light scattering (DLS), ζ-potential measurements, X-ray diffraction (XRD), specific surface area measurements based on the Brunauer-Emmett-Teller theory (SSA(BET)), transmission electron microscopy (TEM), energy dispersive X-ray spectroscopy, and Raman spectroscopy. DLS analysis revealed that the highly transparent product solution consisted of nanocrystals approximately 10-20 nm of hydrodynamic diameter with a very narrow size distribution, while the ζ-potential analysis results strongly suggested that the N(CH3)4(+) capped negatively charged sites on the nanocrystals' surface and provided sufficient repulsive steric effect to prevent agglomeration. Moreover, the crystallite size (d(XRD)) estimated from the XRD patterns and the equivalent particle size (d(BET)) estimated from the SSA(BET) data were in the range between 5-6 and 4-4.5 nm, respectively, and nearly constant independent of reaction time, indicating suppressed Ostwald ripening due to capping. Good agreement between the values obtained from the d(XRD) and d(BET) analyses with the size of the primary nanocrystals observed in the TEM image also confirmed that the primary nanocrystals were single crystals and nearly free from aggregation. Furthermore, the gadolinium content in the as-prepared nanocrystals was determined to be very close to 20 mol % and remained unchanged after HCl treatment, indicating successful doping of stoichiometric amount of Gd(3+) into CeO2 lattices. Finally, the Raman analysis suggested that only a slightly Gd(3+)-rich phase was present in the nanocrystals grown for shorter reaction times. By increasing the reaction time, even at 125 °C, the Gd(3+) was homogeneously distributed into the CeO2

  9. Detection of small hepatocellular carcinoma: comparison of conventional gadolinium-enhanced MRI with gadolinium-enhanced MRI after the administration of ferucarbotran.

    PubMed

    Kim, Y K; Kim, C S; Han, Y M

    2009-06-01

    We compared the diagnostic efficacy of gadolinium (Gd)-enhanced MRI with that of Gd-enhanced MRI after administration of ferucarbotran for revealing small hypervascular hepatocellular carcinomas (HCCs). 24 patients with 34 HCCs (ranging in size from 0.6-2.0 cm) underwent Gd-enhanced three-dimensional dynamic MRI followed, after an interval of 5-11 days (mean, 7 days), by Gd-enhanced three-dimensional dynamic MRI after administration of ferucarbotran. The two Gd-enhanced arterial-phase MRI scans were compared quantitatively by measuring the tumour-liver contrast-to-noise ratio (CNR) and qualitatively by evaluating the tumour-liver contrast using matched-pairs analysis. The tumour-liver CNR with Gd-enhanced arterial-phase imaging after ferucarbotran (250.3 +/- 103.7) was higher than that with Gd-enhanced arterial-phase imaging (221.1 +/- 96.1) (p < 0.001). Matched-pairs analysis indicated that, for three lesions, the relative tumour-liver contrast was slightly better with Gd-enhanced arterial-phase imaging after ferucarbotran than with conventional Gd-enhanced arterial-phase imaging; however, in the case of the remaining 31 lesions, the two images were equivalent. We concluded that, although Gd-enhanced arterial-phase imaging after ferucarbotran results in better tumour-liver CNR than Gd-enhanced arterial-phase imaging, the ability of the two techniques to reveal small hypervascular HCCs is the same.

  10. Synthesis, characterization and effect of low energy Ar ion irradiation on gadolinium oxide nanoparticles

    SciTech Connect

    Paul, N.; Devi, M.; Mohanta, D.

    2011-08-15

    Graphical abstract: . The figure depicts Raman spectra of (A) unirradiated and (B) 80 keV Ar ion irradiated nanoscale gadolinium oxide (Gd{sub 2}O{sub 3}) systems. Intense Raman signals corresponding to two B{sub g} modes at 288 and 384 cm{sup -1} are observed for irradiated sample along with the evolution of a new peak at 202 cm{sup -1} due to surface defects. Highlights: {yields} Gadolinium oxide nanoparticles are synthesized via a selective reduction route. {yields} 80 keV Ar ion-irradiated specimen showed better symmetric emission than pristine. {yields} Irradiation led point defect contribution was studied through spectroscopic means. -- Abstract: In this work, we report on the surfactant assisted synthesis of gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticles and their characterization through various microscopic and spectroscopic tools. Exhibiting a monoclinic phase, the nanoscale Gd{sub 2}O{sub 3} particles are believed to be comprising of crystallites with an average size of {approx}3.2 nm, as revealed from the X-ray diffraction analysis. The transmission electron microscopy has predicted a particle size of {approx}9 nm and an interplanar spacing of {approx}0.28 nm. Fourier transform infrared spectroscopy studies show that Gd-O inplane vibrations at 536.8 and 413.3 cm{sup -1} were more prominent for 80-keV Ar-ion irradiated Gd{sub 2}O{sub 3} nanosystem than unirradiated system. The photoluminescence (PL) spectra of irradiated specimen have revealed an improvement in the symmetry factor owing to significant enhancement of surface-trap emission, compared to the band-edge counterpart. Irradiation induced creation of point defects (oxygen vacancies) were predicted both from PL and electron paramagnetic resonance (EPR) studies. Further, the Raman spectra of the irradiated sample have exhibited notable vibrational features along with the evolution of a new peak at {approx}202 cm{sup -1}. This can be ascribed to an additional Raman active vibrational response

  11. Investigation of Plutonium and Uranium Precipitation Behavior with Gadolinium as a Neutron Poison

    SciTech Connect

    Visser, A.E.

    2003-10-17

    The caustic precipitation of plutonium (Pu)-containing solutions has been investigated to determine whether the presence of 3:1 uranium (U):Pu in solutions stored in the H-Canyon Facility at the U.S. Department of Energy's (DOE) Savannah River Site (SRS) would adversely impact the use of gadolinium nitrate (Gd(NO3)3) as a neutron poison. In the past, this disposition strategy has been successfully used to discard solutions containing approximately 100 kg of Pu to the SRS high level waste (HLW) system. In the current experiments, gadolinium (as Gd(NO3)3) was added to samples of a 3:1 U:Pu solution, a surrogate 3 g/L U solution, and a surrogate 3 g/L U with 1 g/L Pu solution. A series of experiments was then performed to observe and characterize the precipitate at selected pH values. Solids formed at pH 4.5 and were found to contain at least 50 percent of the U and 94 percent of the Pu, but only 6 percent of the Gd. As the pH of the solution increased (e.g., pH greater than 14 with 1.2 or 3.6 M sodium hydroxide (NaOH) excess), the precipitate contained greater than 99 percent of the Pu, U, and Gd. After the pH greater than 14 systems were undisturbed for one week, no significant changes were found in the composition of the solid or supernate for each sample. The solids were characterized by X-ray diffraction (XRD) which found sodium diuranate (Na2U2O7) and gadolinium hydroxide (Gd(OH)3) at pH 14. Thermal gravimetric analysis (TGA) indicated sufficient water molecules were present in the solids to thermalize the neutrons, a requirement for the use of Gd as a neutron poison. Scanning electron microscopy (SEM) was also performed and the accompanying back-scattering electron analysis (BSE) found Pu, U, and Gd compounds in all pH greater than 14 precipitate samples. The rheological properties of the slurries at pH greater than 14 were also investigated by performing precipitate settling rate studies and measuring the viscosity and density of the materials. Based on the

  12. Pump apparatus including deconsolidator

    SciTech Connect

    Sonwane, Chandrashekhar; Saunders, Timothy; Fitzsimmons, Mark Andrew

    2014-10-07

    A pump apparatus includes a particulate pump that defines a passage that extends from an inlet to an outlet. A duct is in flow communication with the outlet. The duct includes a deconsolidator configured to fragment particle agglomerates received from the passage.

  13. Nocturnal Blood Pressure Pattern Affects Left Ventricular Remodeling and Late Gadolinium Enhancement in Patients with Hypertension and Left Ventricular Hypertrophy

    PubMed Central

    Yokota, Hajime; Imai, Yasuko; Tsuboko, Yusuke; Tokumaru, Aya M.; Fujimoto, Hajime; Harada, Kazumasa

    2013-01-01

    Background Left ventricular hypertrophy (LVH) is an independent predictor of cardiac mortality, regardless of its etiology. Previous studies have shown that high nocturnal blood pressure (BP) affects LV geometry in hypertensive patients. It has been suggested that continuous pressure overload affects the development of LVH, but it is unknown whether persistent pressure influences myocardial fibrosis or whether the etiology of LVH is associated with myocardial fibrosis. Comprehensive cardiac magnetic resonance (CMR) including the late gadolinium enhancement (LGE) technique can evaluate both the severity of changes in LV geometry and myocardial fibrosis. We tested the hypothesis that the nocturnal non-dipper BP pattern causes LV remodeling and fibrosis in patients with hypertension and LVH. Methods Forty-seven hypertensive patients with LVH evaluated by echocardiography (29 men, age 73.0±10.4 years) were examined by comprehensive CMR and 24-h ambulatory blood pressure monitoring (ABPM). Results and Conclusions Among the 47 patients, twenty-four had nocturnal non-dipper BP patterns. Patients with nocturnal non-dipper BP patterns had larger LV masses and scar volumes independent of etiologies than those in patients with dipper BP patterns (p = 0.035 and p = 0.015, respectively). There was no significant difference in mean 24-h systolic BP between patients with and without nocturnal dipper BP patterns (p = 0.367). Among hypertensive patients with LVH, the nocturnal non-dipper blood pressure pattern is associated with both LV remodeling and myocardial fibrosis independent of LVH etiology. PMID:23840777

  14. Results of the Phase I Dose-Escalating Study of Motexafin Gadolinium With Standard Radiotherapy in Patients With Glioblastoma Multiforme

    SciTech Connect

    Ford, Judith M. Seiferheld, Wendy; Alger, Jeffrey R.; Wu, Genevieve; Endicott, Thyra J.; Mehta, Minesh; Curran, Walter; Phan, See-Chun

    2007-11-01

    Purpose: Motexafin gadolinium (MGd) is a putative radiation enhancer initially evaluated in patients with brain metastases. This Phase I trial studied the safety and tolerability of a 2-6-week course (10-22 doses) of MGd with radiotherapy for glioblastoma multiforme. Methods and Materials: A total of 33 glioblastoma multiforme patients received one of seven MGd regimens starting at 10 doses of 4 mg/kg/d MGd and escalating to 22 doses of 5.3 mg/kg/d MGd (5 or 10 daily doses then three times per week). The National Cancer Institute Cancer Therapy Evaluation Program toxicity and stopping rules were applied. Results: The maximal tolerated dose was 5.0 mg/kg/d MGd (5 d/wk for 2 weeks, then three times per week) for 22 doses. The dose-limiting toxicity was reversible transaminase elevation. Adverse reactions included rash/pruritus (45%), chills/fever (30%), and self-limiting vesiculobullous rash of the thumb and fingers (42%). The median survival of 17.6 months prompted a case-matched analysis. In the case-matched analysis, the MGd patients had a median survival of 16.1 months (n = 31) compared with the matched Radiation Therapy Oncology Group database patients with a median survival of 11.8 months (hazard ratio, 0.43; 95% confidence interval, 0.20-0.94). Conclusion: The maximal tolerated dose of MGd with radiotherapy for glioblastoma multiforme in this study was 5 mg/kg/d for 22 doses (daily for 2 weeks, then three times weekly). The baseline survival calculations suggest progression to Phase II trials is appropriate, with the addition of MGd to radiotherapy with concurrent and adjuvant temozolomide.

  15. A Novel Approach to Early Detection of Doxorubicin Cardiotoxicity using Gadolinium Enhanced Cardiovascular Magnetic Resonance Imaging in an Experimental Model

    PubMed Central

    Lightfoot, James C.; D'Agostino, Ralph B.; Hamilton, Craig A; Jordan, Jennifer; Torti, Frank M.; Kock, Nancy D.; Jordan, James; Workman, Susan; Hundley, W Gregory

    2011-01-01

    Background To determine if cardiovascular magnetic resonance (CMR) measures of gadolinium (Gd) signal intensity (SI) within the left ventricular (LV) myocardium are associated with future changes in LV ejection fraction (LVEF) after receipt of doxorubicin (DOX). Methods and Results Forty Sprague-Dawley rats were divided into 3 groups scheduled to receive weekly intravenous doses of: normal saline (NS) (n=7), 1.5 mg/kg DOX (n=19), or 2.5 mg/kg DOX (n=14). MR determinations of LVEF and myocardial Gd-SI were performed before and then at 2, 4, 7, and 10 weeks after DOX initiation. During treatment, animals were sacrificed at different time points so that histopathological assessments of the LV myocardium could be obtained. Within group analyses were performed to examine time-dependent relationships between Gd-SI and primary events (a deterioration in LVEF or an unanticipated death). Six of 19 animals receiving 1.5 mg/kg of DOX and 10/14 animals receiving 2.5 mg/kg of DOX experienced a primary event; no NS animals experienced a primary event. In animals with a primary event, histopathological evidence of myocellular vacuolization occurred (p=0.04), and the Gd-SI was elevated relative to baseline at the time of the event (p<0.0001) and during the measurement period prior to the event (p=0.0001). In all animals (including NS) without an event, measures of Gd-SI did not differ from baseline. Conclusions After DOX, low serial measures of Gd-SI predict an absence of a LVEF drop or unanticipated death. An increase in Gd-SI after DOX forecasts a subsequent drop in LVEF as well as histopathologic evidence of intracellular vacuolization consistent with DOX cardiotoxicity. PMID:20622140

  16. Multiwalled carbon nanotube hybrids as MRI contrast agents.

    PubMed

    Kuźnik, Nikodem; Tomczyk, Mateusz Michał

    2016-01-01

    Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories.

  17. Multiwalled carbon nanotube hybrids as MRI contrast agents

    PubMed Central

    Tomczyk, Mateusz Michał

    2016-01-01

    Summary Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories. PMID:27547627

  18. Multiwalled carbon nanotube hybrids as MRI contrast agents.

    PubMed

    Kuźnik, Nikodem; Tomczyk, Mateusz Michał

    2016-01-01

    Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories. PMID:27547627

  19. Agent planning in AgScala

    NASA Astrophysics Data System (ADS)

    Tošić, Saša; Mitrović, Dejan; Ivanović, Mirjana

    2013-10-01

    Agent-oriented programming languages are designed to simplify the development of software agents, especially those that exhibit complex, intelligent behavior. This paper presents recent improvements of AgScala, an agent-oriented programming language based on Scala. AgScala includes declarative constructs for managing beliefs, actions and goals of intelligent agents. Combined with object-oriented and functional programming paradigms offered by Scala, it aims to be an efficient framework for developing both purely reactive, and more complex, deliberate agents. Instead of the Prolog back-end used initially, the new version of AgScala relies on Agent Planning Package, a more advanced system for automated planning and reasoning.

  20. Web Search Agents: "One-Stop Shopping" for Researchers.

    ERIC Educational Resources Information Center

    Perez, Ernest

    2002-01-01

    Explains Web search agents as tools that apply intelligent agent software technology for the purpose of automating, improving, and speeding up online search operations. Topics include intelligent desktop agents; search agent marketplace; comparing Web search agents; subjective evaluations; and use by researchers. (LRW)

  1. Catechin tuned magnetism of Gd-doped orthovanadate through morphology as T1-T2 MRI contrast agents

    PubMed Central

    Vairapperumal, Tamilmani; Saraswathy, Ariya; Ramapurath, Jayasree S.; Kalarical Janardhanan, Sreeram; Balachandran Unni, Nair

    2016-01-01

    Tetragonal (t)-LaVO4 has turned out to be a potential host for luminescent materials. Synthesis of t-LaVO4 till date has been based on chelating effect of EDTA making it not ideal for bioimaging applications. An alternative was proposed by us through the use of catechin. In recent times there is interest for new MRI contrast agents that can through appropriate doping function both as MRI contrast and optical/upconversion materials. It is generally believed that under appropriate doping, t-LaVO4 would be a better upconversion material than monoclinic (m)-LaVO4. Based on these postulations, this work explores the use of gadolinium doped t-LaVO4 as an MRI contrast agent. From literature, gadolinium oxide is a good T1 contrast agent. Through this work, using catechin as a template for the synthesis of Gd doped t-LaVO4, we demonstrate the possible use as a T1 contrast agent. Interestingly, as the catechin concentration changes, morphology changes from nanorods to square nanoplates and spheres. In this process, a switch from T1 to T2 contrast agent was also observed. Under optimal concentration of catechin, with a rod shaped Gd doped t-LaVO4 an r2/r1 value of 21.30 was observed. Similarly, with a spherical shape had an r2/r1 value of 1.48 was observed. PMID:27752038

  2. Optical modulator including grapene

    DOEpatents

    Liu, Ming; Yin, Xiaobo; Zhang, Xiang

    2016-06-07

    The present invention provides for a one or more layer graphene optical modulator. In a first exemplary embodiment the optical modulator includes an optical waveguide, a nanoscale oxide spacer adjacent to a working region of the waveguide, and a monolayer graphene sheet adjacent to the spacer. In a second exemplary embodiment, the optical modulator includes at least one pair of active media, where the pair includes an oxide spacer, a first monolayer graphene sheet adjacent to a first side of the spacer, and a second monolayer graphene sheet adjacent to a second side of the spacer, and at least one optical waveguide adjacent to the pair.

  3. Chitosan oligosaccharide based Gd-DTPA complex as a potential bimodal magnetic resonance imaging contrast agent.

    PubMed

    Huang, Yan; Cao, Juan; Zhang, Qi; Lu, Zheng-rong; Hua, Ming-qing; Zhang, Xiao-yan; Gao, Hu

    2016-01-01

    A new gadolinium diethylenetriamine pentaacetic acid (DTPA) complex (Gd-DTPA-DMABA-CS11) as a potential bimodal magnetic resonance imaging (MRI) contrast agent with fluorescence was synthesized. It was synthesized by the incorporation of 4-dimethylaminobenzaldehyde (DMABA) and chitosan oligosaccharide (CSn; n=11) with low polydispersity index to DTPA anhydride and then chelated with gadolinium chloride. The structure was characterized by Fourier transform infrared (FTIR), (1)H NMR, elemental analysis and size exclusion chromatography (SEC). MRI measurements in vitro were evaluated. The results indicated that Gd-DTPA-DMABA-CS11 provided higher molar longitudinal relaxivity (r1) (12.95mM(-1)·s(-1)) than that of commercial Gd-DTPA (3.63mM(-1)·s(-1)) at 0.5T. Gd-DTPA-DMABA-CS11 also emitted fluorescence, and the intensity was much stronger than that of Gd-DTPA. Therefore, it can be meanwhile used in fluorescent imaging for improving the sensitivity in clinic diagnosis. Gd-DTPA-DMABA-CS11 as a potential contrast agent is preliminarily stable in vitro. The results of thermodynamic action between Gd-DTPA-DMABA-CS11 and bovine serum albumin (BSA) illustrated that the binding process was exothermic and spontaneous, and the main force was van der Waals' interaction and hydrogen bond. The preliminary study suggested that Gd-DTPA-DMABA-CS11 could be used in both magnetic resonance and fluorescent imaging as a promising bimodal contrast agent.

  4. Hydroxypyridonate chelating agents and synthesis thereof

    DOEpatents

    Raymond, K.N.; Scarrow, R.C.; White, D.L.

    1985-11-12

    Chelating agents having 1-hydroxy-2-pyridinone (HOPO) and related moieties incorporated within their structures, including polydentate HOPO-substituted polyamines such as spermidine and spermine, and HOPO-substituted desferrioxamine. The chelating agents are useful in selectively removing certain cations from solution, and are particularly useful as ferric ion and actinide chelators. Novel syntheses of the chelating agents are provided. 4 tabs.

  5. Using Intelligent Agents To Assist Educators.

    ERIC Educational Resources Information Center

    Knode, Steve; Knode, Jon-David W.

    This paper begins with background on intelligent agents (software programs built to perform certain specific tasks for the user). A taxonomy that categorizes intelligent agents by the degree of intelligence embedded in the software is presented. Applications of today's intelligent agents are discussed, including specific examples of the following:…

  6. Preparing Change Agents for Change Agent Roles.

    ERIC Educational Resources Information Center

    Sedlacek, James R.

    Seventy-seven Spanish- and Portuguese-speaking agricultural change agents from developing Central and South American countries responded to a questionnaire which sought perceptions of the roles in which the change agents felt they were involved and the roles for which they felt they were being trained. The agents were participating in training…

  7. X-ray Absorption Improvement of Single Wall Carbon Nanotube through Gadolinium Encapsulation

    NASA Astrophysics Data System (ADS)

    Alimin; Narsito, I.; Kartini; Santosa, S. J.

    2016-02-01

    X-ray absorption improvement of single-wall carbon nanotube (SWCNT) through gadolinium (Gd) encapsulation has been studied. The liquid phase adsorption using ethanol has been performed for the doping treatment. The Gd-doped SWCNT (Gd@SWCNT) was characterized by nitrogen adsorption isotherms, Raman spectroscopy, Transmission electron microscopy (TEM), and thermal gravimetric analysis (TGA) techniques. A relatively high residual weight of Gd@SWCNT compared to non-doped SWCNT (n-SWCNT) indicated that Gd has been doped in the nanotube. Even though Gd nanoparticles could not be observed clearly by TEM image, however, a significant decrease of nitrogen uptakes at low pressure and RBM (Radial Breathing Mode) upshift of Raman spectra of Gd@SWCNT specimen suggest that the metal nanoparticles might be encapsulated in the internal tube spaces of the nanotube. It was found that Gd-doped in the SWCNT increased significantly mass attenuation coefficient of the nanotube.

  8. Magnetic susceptibility measurements of pure and mixed gadolinium-terbium fumarate heptahydrate crystals

    NASA Astrophysics Data System (ADS)

    Want, B.; Shah, M. D.

    2016-03-01

    Magnetic moment and susceptibility measurements of single crystals of pure and mixed rare earth fumarates of gadolinium and terbium were carried out at room temperature. The experimental values of molar susceptibilities for Gd2 (C4H2O4)3·7H2O, Tb2(C4H2O4)3·7H2O and GdTb (C4H2O4)3·7H2O are 2.68×10-2, 3.89×10-2, and 3.18×10-2 (in emu mol-1 Oe-1), respectively. The calculated effective magnetic moments are in good agreement with the theoretical predictions on rare earth ions.

  9. General synthesis route to fabricate uniform upconversion luminescent gadolinium oxide hollow spheres.

    PubMed

    Jia, Guang; Zhang, Cuimiao; Ding, Shiwen; Wang, Liyong

    2011-08-01

    Uniform upconversion luminescent gadolinium oxide hollow spheres were successfully synthesized via a homogeneous precipitation method with carbon spheres as template followed by a calcination process. During the annealing process, the carbon spheres template can be effectively removed and the amorphous precursor has converted to crystalline Gd2O3, which can be confirmed by the XRD and TG-DSC analysis. SEM and TEM images indicate that the Gd2O3 hollow spheres with diameters of 300-400 nm are uniform in size and distribution. The rare earth activator ions Ln3+-doped Gd2O3 hollow spheres exhibit intense upconversion luminescence with different colors under 980 nm light excitation, which may find potential applications in the fields such as drug delivery or biological labeling. Moreover, the upconversion luminescent mechanisms of the hollow spherical phosphors were investigated in detail.

  10. Magnetically induced optical activity and dichroism of gadolinium oxide nanoparticle-based ferrofluids

    NASA Astrophysics Data System (ADS)

    Paul, Nibedita; Devi, Manasi; Mohanta, Dambarudhar; Saha, Abhijit

    2012-02-01

    The present work reports on magnetically induced optical activity (such as Faraday rotation and linear dichroism) of pristine and gamma-irradiated gadolinium oxide (Gd2O3) nanoparticle-based ferrofluids. The ferrofluids were produced by dispersing N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB)-coated ˜9-nm-sized Gd2O3 particles in a carrier fluid of ethanol. The ferrofluids were then irradiated with 1.25 MeV energetic gamma rays (dose: 868 Gy and 2.635 kGy). Irradiation-led formation of a number of point defects was revealed through high resolution electron microscopy. The interaction of light with the ionized point defects is believed to have caused substantial improvement in the magneto-optic response of irradiated magnetic fluids.

  11. Obtaining gadolinium nanoparticles and studying their properties in a helium flow

    NASA Astrophysics Data System (ADS)

    Petinov, V. I.

    2016-07-01

    A method for obtaining Gd nanoparticles with diameters of 89 to 18 nm upon metal evaporation both in a flow of pure helium and with the addition of 0.5% of oxygen is described. It is found that the addition of O2 does not affect the size of the particles, their structure, or the Curie temperature, though the magnetization is reduced. Particles with sizes of 18 nm have cubic lattice symmetry (fcc) and remain paramagnetic below T c; with an increase in the size of nanoparticles, the proportion of the hexagonal (hcp) phase, which coincides with the gadolinium structure, also grows, and below T c such particles become ferromagnetic. Oxygen impurities seem to have no effect on magnetic and structural transitions in nanoparticles.

  12. Temperature dependence of the magnetic and electrical properties of Permalloy/gadolinium/Permalloy thin films

    NASA Astrophysics Data System (ADS)

    Ranchal, R.; Aroca, C.; Maicas, M.; López, E.

    2007-09-01

    The magnetic and electrical properties of Permalloy/gadolinium/Permalloy (Py/Gd/Py) trilayers have been studied as a function of temperature by using vibrating sample magnetometer and transport measurements with current in plane configuration. The observed dependence of the magnetic moment with temperature can be explained by a paramagnetic contribution. Electrical measurements show that this contribution is originated by the formation of Gd1-xNix alloys at the Py/Gd interfaces because of the Ni diffusion. Despite the Ni diffusion, we find no evidence of amorphization from either the Py layer or the Py/Gd interfaces. We also obtain the Curie temperature of the Gd1-xNix alloys by the position of inflexion points in the resistance versus temperature curve.

  13. Synthesis of bulk-size transparent gadolinium oxide–polymer nanocomposites for gamma ray spectroscopy

    PubMed Central

    Cai, Wen; Chen, Qi; Cherepy, Nerine; Dooraghi, Alex; Kishpaugh, David; Chatziioannou, Arion; Payne, Stephen; Xiang, Weidong

    2015-01-01

    Heavy element loaded polymer composites have long been proposed to detect high energy X- and γ-rays upon scintillation. The previously reported bulk composite scintillators have achieved limited success because of the diminished light output resulting from fluorescence quenching and opacity. We demonstrate the synthesis of a transparent nanocomposite comprising gadolinium oxide nanocrystals uniformly dispersed in bulk-size samples at a high loading content. The strategy to avoid luminescence quenching and opacity in the nanocomposite was successfully deployed, which led to the radioluminescence light yield of up to 27 000/MeV, about twice as much as standard commercial plastic scintillators. Nanocomposites monoliths (14 mm diameter by 3 mm thickness) with 31 wt% loading of nanocrystals generated a photoelectric peak for Cs-137 gamma (662 keV) with 11.4% energy resolution. PMID:26478816

  14. Analysis of Blood Gadolinium in an Isotope Geochemist Following Contrast MRI

    NASA Astrophysics Data System (ADS)

    Wasylenki, L. E.

    2011-12-01

    Normal brain tissue does not have blood flowing throughout it; instead oxygen diffuses across a blood-brain barrier in order to oxygenate brain cells. Brain tumors, however, do grow blood supplies, so an abnormal distribution of blood in the brain is a key indicator of abnormal cell growth. But how is the distribution of blood in inside the brain observed? The lanthanide ion gadolinium(III) has unpaired 5f-shell electrons and is thus paramagnetic. As such, the presence of Gd causes the nuclei of nearby atoms to relax more quickly when excited to high-energy spin states by pulses of radio-frequency energy than they would without Gd nearby. The signal in magnetic resonance imaging correlates with this nuclear spin relaxation time, so gadolinium's presence in certain body tissues makes those tissues appear as bright areas on MRI images. Gadolinium is therefore commonly injected intravenously just prior to MRI imaging, so that the distribution of blood in and around the brain can be mapped. Gadolinium as a free ion is toxic, so it is injected in a relatively inert form, often as gadoversetamide, in which Gd is tightly bound in nine-fold coordination with N, C, and O. This compound is removed from the blood by the kidneys at a rate that is fast compared to the rate of breakdown of this compound in the blood, thus preventing release of toxic Gd in the bloodstream. But how quickly can the kidneys of an isotope geochemist remove Gd from blood? In this experiment, a single isotope geochemist's wristwatch was synchronized with that of the MRI technician and then left in a dressing room with all other magnetically susceptible objects until after the MRI. The time of intravenous injection of gadoversetamide into the isotopist was recorded by the technician and later transmitted verbally to the isotopist. Following the MRI session, blood samples were collected by self-fingerprick, in a Class 100 trace metal clean lab, from 47 to 281 minutes after intravenous injection. For each

  15. Magnetically induced optical activity and dichroism of gadolinium oxide nanoparticle-based ferrofluids

    SciTech Connect

    Paul, Nibedita; Devi, Manasi; Mohanta, Dambarudhar; Saha, Abhijit

    2012-02-15

    The present work reports on magnetically induced optical activity (such as Faraday rotation and linear dichroism) of pristine and gamma-irradiated gadolinium oxide (Gd{sub 2}O{sub 3}) nanoparticle-based ferrofluids. The ferrofluids were produced by dispersing N-cetyl-N,N,N-trimethyl ammonium bromide (CTAB)-coated {approx}9-nm-sized Gd{sub 2}O{sub 3} particles in a carrier fluid of ethanol. The ferrofluids were then irradiated with 1.25 MeV energetic gamma rays (dose: 868 Gy and 2.635 kGy). Irradiation-led formation of a number of point defects was revealed through high resolution electron microscopy. The interaction of light with the ionized point defects is believed to have caused substantial improvement in the magneto-optic response of irradiated magnetic fluids.

  16. Site selectivity in praseodymium- and bismuth-substituted gadolinium gallium garnet epilayers

    SciTech Connect

    Klages, C.P.

    1984-05-01

    Praseodymium- and bismuth-substituted gadolinium gallium garnet (GGG) layers have been prepared by liquid-phase epitaxy on (111)- and (110)-oriented GGG substrates. By an investigation of linear dichroism of Pr/sup 3 +/ -transitions, the supercooling dependence of dodecahedral site selectivity in Pr-substituted GGG can be shown to differ considerably for (110)- and (111)-epitaxial layers. An increase insite selectivity with supercooling is found in (111) layers while it is constant in (110) layers. The long-wavelength /sup 1/S /sub 0/ ..-->.. /sup 3/ P/sub 1/-transition of the B/sub 1/ /sup 3 +/ ion has been utilized to detect site selectivity in (110)oriented Bi-substituted GGG layers.

  17. Corrosion of 304L and 316 in gadolinium nitrate neutron poison solutions

    SciTech Connect

    Chandler, G.T.; Anderson, M.H.

    1991-12-31

    Pitting corrosion has occurred on AISI Type 304L stainless steel (304L) conductivity probes used to monitor liquid levels of gadolinium nitrate neutron poison solutions (GPS). An electrochemical and immersion test program has led to a better understanding of the cause of corrosion of 304L probes. Results indicate that the alternating voltage applied to the probes to monitor contact with solution is the primary factor in the corrosion of the probes. A chloride-containing dye and low pH also contribute to the corrosion process, but appear to play a secondary role. AISI Type 316 stainless steel (316) was found to behave similarly to 304L in GPS, while nickel-based alloys such as Hastelloy G30, Hastelloy C22, and Inconel 625 were found to be more susceptible to corrosion as compared to 304L.

  18. Corrosion of 304L and 316 in gadolinium nitrate neutron poison solutions

    SciTech Connect

    Chandler, G.T.; Anderson, M.H.

    1991-01-01

    Pitting corrosion has occurred on AISI Type 304L stainless steel (304L) conductivity probes used to monitor liquid levels of gadolinium nitrate neutron poison solutions (GPS). An electrochemical and immersion test program has led to a better understanding of the cause of corrosion of 304L probes. Results indicate that the alternating voltage applied to the probes to monitor contact with solution is the primary factor in the corrosion of the probes. A chloride-containing dye and low pH also contribute to the corrosion process, but appear to play a secondary role. AISI Type 316 stainless steel (316) was found to behave similarly to 304L in GPS, while nickel-based alloys such as Hastelloy G30, Hastelloy C22, and Inconel 625 were found to be more susceptible to corrosion as compared to 304L.

  19. Controllable Fabrication and Optical Properties of Uniform Gadolinium Oxysulfate Hollow Spheres

    PubMed Central

    Chen, Fashen; Chen, Gen; Liu, Tao; Zhang, Ning; Liu, Xiaohe; Luo, Hongmei; Li, Junhui; Chen, Limiao; Ma, Renzhi; Qiu, Guanzhou

    2015-01-01

    Uniform gadolinium oxysulfate (Gd2O2SO4) hollow spheres were successfully fabricated by calcination of corresponding Gd-organic precursor obtained via a facile hydrothermal process. The Gd2O2SO4 hollow spheres have a mean diameter of approximately 550 nm and shell thickness in the range of 30–70 nm. The sizes and morphologies of as-prepared Gd2O2SO4 hollow spheres could be deliberately controlled by adjusting the experimental parameters. Eu-doped Gd2O2SO4 hollow spheres have also been prepared for the property modification and practical applications. The structure, morphology, and properties of as-prepared products were characterized by XRD, TEM, HRTEM, SEM and fluorescence spectrophotometer. Excited with ultraviolet (UV) pump laser, successful downconversion (DC) could be achieved for Eu-doped Gd2O2SO4 hollow spheres. PMID:26671661

  20. Characterization of PAH matrix with monazite stream containing uranium, gadolinium and iron

    NASA Astrophysics Data System (ADS)

    Pal, Sangita; Meena, Sher Singh; Goswami, D.

    2016-05-01

    Uranium (U) gadolinium(Gd) and iron (Fe) containing alkaline waste simulated effluent (relevant to alkaline effluent of monazite ore) has been treated with a novel amphoteric resin viz, Polyamidehydroxamate (PAH) containing amide and hydroxamic acid groups. The resin has been synthesized in an eco-friendly manner by polymerization nad conversion to functional groups characterized by FT-IR spectra and architectural overview by SEM. Coloration of the loaded matrix and de-coloration after extraction of uranium is the special characteristic of the matrix. Effluent streams have been analyzed by ICP-AES, U loaded PAH has been characterized by FT-IR, EXAFS, Gd and Fe by X-ray energy values of EDXRF at 6.053 Kev and 6.405 Kev respectively. The remarkable change has been observed in Mössbauer spectrum of Fe-loaded PAH samples.

  1. Effect of a magnetic field on the resonant multistep selective photoionization of gadolinium isotopes

    NASA Astrophysics Data System (ADS)

    Le Guyadec, E.; Ravoire, J.; Botter, R.; Lambert, F.; Petit, A.

    1990-04-01

    A multistep photoionization with three resonant polarized photons has been used to separate the odd and even isotopes of gadolinium. Due to their hyperfine structure ( I= {3}/{2}), the 155,157Gd isotopes can be photoionized via a J=2→2→1→0 scheme with three п photons whereas the even isotopes cannot. If a time delay is introduced between the three laser pulses we show that the presence of a low intensity dc magnetic field affects the selectivity. The effect of this weak field on the 156Gd photoionization rate has been calculated independently of the optical pumping and the result is in good agreement with the experiment.

  2. Carbon quantum dot stabilized gadolinium nanoprobe prepared via a one-pot hydrothermal approach for magnetic resonance and fluorescence dual-modality bioimaging.

    PubMed

    Xu, Yang; Jia, Xiao-Hua; Yin, Xue-Bo; He, Xi-Wen; Zhang, Yu-Kui

    2014-12-16

    Magnetic resonance imaging (MRI) is used extensively for clinical diagnoses. It is critical to design and develop highly efficient MR contrast agents with simple preparation procedure, low toxicity, and high biocompatibility. Here, we report a carbon quantum dots (CQDs)-stabilized gadolinium hybrid nanoprobe (Gd-CQDs) prepared via a one-pot hydrothermal treatment of the mixture of citrate acid, ethanediamine, and GdCl3 at 200 °C for 4 h. In vitro and in vivo tests confirmed their low toxicity and high biocompatibility. Gd-CQDs were observed to have a higher MR response than gadopentetic acid dimeglumine (Gd-DTPA) because of their high Gd content and hydrophilicity. Moreover, the fluorescence of CQDs was remained in Gd-CQDs. The in vivo MR and fluorescence dual-modality imaging of Gd-CQDs was confirmed with zebrafish embryo and mice as models. The modification of Gd-CQDs with arginine-glycine-aspartic acid (RGD) tripeptide provided a high affinity to U87 cancer cells for targeted imaging. Whereas the MR response showed a depth penetration and spatial visualization, fluorescence revealed the fine distribution of Gd-CQDs in tissues because of its high resolution and sensitivity. We found that Gd-CQDs distributed in the tissues in a heterogeneous mode: they entered into the tissue cells but were observed less in the extracellular matrix. The MR and fluorescence dual-modality imaging of Gd-CQDs makes them a potential contrast agent for clinic applications because of their simple preparation procedure, ease of functionalization, high contrast efficiency, low toxicity, and high biocompatibility.

  3. Engineering tumor-targeted gadolinium hexanedione nanoparticles for potential application in neutron capture therapy.

    PubMed

    Oyewumi, Moses O; Mumper, Russell J

    2002-01-01

    Microemulsions (oil-in-water) have been employed as templates to engineer nanoparticles containing high concentrations of gadolinium for potential application in neutron capture therapy of tumors. Gadolinium hexanedione (GdH), synthesized by complexation of Gd(3+) with 2,4-hexanedione, was used as the nanoparticle matrix alone or in combination with either emulsifying wax or PEG-400 monostearate. Solid nanoparticles (<125 nm size) were obtained by simple cooling of the microemulsions prepared at 60 degrees C to room temperature in one vessel. The feasibility of tumor targeting via folate receptors was studied. A folate ligand was synthesized by chemically linking folic acid to distearoylphosphatidylethanolamine (DSPE) via a poly(ethylene glycol) (PEG; MW 3350) spacer. To obtain folate-coated nanoparticles, the folate ligand (0.75% w/w to 15% w/w) was added to either the microemulsion templates at 60 degrees C or nanoparticle suspensions at 25 degrees C. Efficiencies of folate ligand attachment/adsorption to nanoparticle formulations were monitored by gel permeation chromatography. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line), known to overexpress folate receptors. The uptake of folate-coated nanoparticles was about 10-fold higher than uncoated nanoparticles after 30 min at 37 degrees C. The uptake of folate-coated nanoparticles at 4 degrees C was 20-fold lower than the uptake at 37 degrees C and comparable to the uptake of uncoated nanoparticles at 37 degrees C. Folate-mediated endocytosis was further verified by the inhibition of folate-coated nanoparticles uptake by free folic acid. It was observed that folate-coated nanoparticles uptake decreased to approximately 2% of its initial value with the coincubation of 0.001 mM of free folic acid. The results suggested that these tumor-targeted nanoparticles containing high concentrations of Gd may have potential for neutron capture therapy. PMID:12440870

  4. Engineering tumor-targeted gadolinium hexanedione nanoparticles for potential application in neutron capture therapy.

    PubMed

    Oyewumi, Moses O; Mumper, Russell J

    2002-01-01

    Microemulsions (oil-in-water) have been employed as templates to engineer nanoparticles containing high concentrations of gadolinium for potential application in neutron capture therapy of tumors. Gadolinium hexanedione (GdH), synthesized by complexation of Gd(3+) with 2,4-hexanedione, was used as the nanoparticle matrix alone or in combination with either emulsifying wax or PEG-400 monostearate. Solid nanoparticles (<125 nm size) were obtained by simple cooling of the microemulsions prepared at 60 degrees C to room temperature in one vessel. The feasibility of tumor targeting via folate receptors was studied. A folate ligand was synthesized by chemically linking folic acid to distearoylphosphatidylethanolamine (DSPE) via a poly(ethylene glycol) (PEG; MW 3350) spacer. To obtain folate-coated nanoparticles, the folate ligand (0.75% w/w to 15% w/w) was added to either the microemulsion templates at 60 degrees C or nanoparticle suspensions at 25 degrees C. Efficiencies of folate ligand attachment/adsorption to nanoparticle formulations were monitored by gel permeation chromatography. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line), known to overexpress folate receptors. The uptake of folate-coated nanoparticles was about 10-fold higher than uncoated nanoparticles after 30 min at 37 degrees C. The uptake of folate-coated nanoparticles at 4 degrees C was 20-fold lower than the uptake at 37 degrees C and comparable to the uptake of uncoated nanoparticles at 37 degrees C. Folate-mediated endocytosis was further verified by the inhibition of folate-coated nanoparticles uptake by free folic acid. It was observed that folate-coated nanoparticles uptake decreased to approximately 2% of its initial value with the coincubation of 0.001 mM of free folic acid. The results suggested that these tumor-targeted nanoparticles containing high concentrations of Gd may have potential for neutron capture therapy.

  5. Gadolinium chloride reduces cytochrome P450: relevance to chemical-induced hepatotoxicity.

    PubMed

    Badger, D A; Kuester, R K; Sauer, J M; Sipes, I G

    1997-08-15

    The Kupffer cell inhibitor, gadolinium chloride (GdCl3), protects the liver from a number of toxicants that require biotransformation to elicit toxicity (i.e. 1,2-dichlorobenzene and CCl4), as well as compounds that do not (i.e. cadmium chloride and beryllium sulfate). The mechanism of this protection is thought to result from reduced secretion of inflammatory and cytotoxic products from Kupffer cells (KC). However, since other lanthanides have been shown to decrease cytochrome P450 (P450) activity, the following studies were designed to determine if GdCl3 pretreatment alters hepatic P450 levels or activity. The toxicological relevance of GdCl3-mediated alterations in P450 activity was also estimated by determining the effect of GdCl3 pretreatment on the susceptibility of primary cultured hepatocytes to CCl4 and cadmium chloride (CdCl2). Male and female Sprague-Dawley rats were given GdCl3 (i.v., 10 mg/kg). Twenty-four hours later, livers were either processed for preparation of microsomes or for primary cultures of hepatocytes. Gadolinium chloride treatment reduced total hepatic microsomal P450 as well as aniline hydroxylase activity by approximately 30% in males and 20% in females. In hepatocytes isolated from rats pretreated with GdCl3, the toxicity caused by CCl4, but not CdCl2 was reduced. Interestingly, when GdCl3 was administered in vitro to microsomes, there was no effect on either the microsomal P450 difference spectra or p-hydroxylation of aniline. However, when GdCl3 was incubated with isolated hepatocytes, the cytotoxicity of CCl4 (but not CdCl2) was partially attenuated. These results suggest that, in addition to its inhibitory effects on KC, GdCl3 produces other effects which may alter the susceptibility of hepatocytes to toxicity caused by certain chemicals.

  6. Remote Agent Demonstration

    NASA Technical Reports Server (NTRS)

    Dorais, Gregory A.; Kurien, James; Rajan, Kanna

    1999-01-01

    We describe the computer demonstration of the Remote Agent Experiment (RAX). The Remote Agent is a high-level, model-based, autonomous control agent being validated on the NASA Deep Space 1 spacecraft.

  7. Antibacterial agents in the cinema.

    PubMed

    García Sánchez, J E; García Sánchez, E; Merino Marcos, M L

    2006-12-01

    Numerous procedures used as antibacterial therapy are present in many films and include strategies ranging from different antimicrobial drugs to surgery and supporting measures. Films also explore the correct use and misuse of antimicrobial agents. Side effects and other aspects related to antibacterial therapy have also been reflected in some films. This article refers to the presence of antibacterial agents in different popular movies. There are movies in which antibacterial agents form part of the central plot, while in others it is merely an important part of the plot. In still others, its presence is isolated, and in these it plays an ambient or anecdotal role.

  8. Listening to Include

    ERIC Educational Resources Information Center

    Veck, Wayne

    2009-01-01

    This paper attempts to make important connections between listening and inclusive education and the refusal to listen and exclusion. Two lines of argument are advanced. First, if educators and learners are to include each other within their educational institutions as unique individuals, then they will need to listen attentively to each other.…

  9. Antimicrobials for bacterial bioterrorism agents.

    PubMed

    Sarkar-Tyson, Mitali; Atkins, Helen S

    2011-06-01

    The limitations of current antimicrobials for highly virulent pathogens considered as potential bioterrorism agents drives the requirement for new antimicrobials that are suitable for use in populations in the event of a deliberate release. Strategies targeting bacterial virulence offer the potential for new countermeasures to combat bacterial bioterrorism agents, including those active against a broad spectrum of pathogens. Although early in the development of antivirulence approaches, inhibitors of bacterial type III secretion systems and cell division mechanisms show promise for the future.

  10. Nanoengineered multimodal contrast agent for medical image guidance

    NASA Astrophysics Data System (ADS)

    Perkins, Gregory J.; Zheng, Jinzi; Brock, Kristy; Allen, Christine; Jaffray, David A.

    2005-04-01

    Multimodality imaging has gained momentum in radiation therapy planning and image-guided treatment delivery. Specifically, computed tomography (CT) and magnetic resonance (MR) imaging are two complementary imaging modalities often utilized in radiation therapy for visualization of anatomical structures for tumour delineation and accurate registration of image data sets for volumetric dose calculation. The development of a multimodal contrast agent for CT and MR with prolonged in vivo residence time would provide long-lasting spatial and temporal correspondence of the anatomical features of interest, and therefore facilitate multimodal image registration, treatment planning and delivery. The multimodal contrast agent investigated consists of nano-sized stealth liposomes encapsulating conventional iodine and gadolinium-based contrast agents. The average loading achieved was 33.5 +/- 7.1 mg/mL of iodine for iohexol and 9.8 +/- 2.0 mg/mL of gadolinium for gadoteridol. The average liposome diameter was 46.2 +/- 13.5 nm. The system was found to be stable in physiological buffer over a 15-day period, releasing 11.9 +/- 1.1% and 11.2 +/- 0.9% of the total amounts of iohexol and gadoteridol loaded, respectively. 200 minutes following in vivo administration, the contrast agent maintained a relative contrast enhancement of 81.4 +/- 13.05 differential Hounsfield units (ΔHU) in CT (40% decrease from the peak signal value achieved 3 minutes post-injection) and 731.9 +/- 144.2 differential signal intensity (ΔSI) in MR (46% decrease from the peak signal value achieved 3 minutes post-injection) in the blood (aorta), a relative contrast enhancement of 38.0 +/- 5.1 ΔHU (42% decrease from the peak signal value achieved 3 minutes post-injection) and 178.6 +/- 41.4 ΔSI (62% decrease from the peak signal value achieved 3 minutes post-injection) in the liver (parenchyma), a relative contrast enhancement of 9.1 +/- 1.7 ΔHU (94% decrease from the peak signal value achieved 3 minutes

  11. Intelligent Agent Architectures: Reactive Planning Testbed

    NASA Technical Reports Server (NTRS)

    Rosenschein, Stanley J.; Kahn, Philip

    1993-01-01

    An Integrated Agent Architecture (IAA) is a framework or paradigm for constructing intelligent agents. Intelligent agents are collections of sensors, computers, and effectors that interact with their environments in real time in goal-directed ways. Because of the complexity involved in designing intelligent agents, it has been found useful to approach the construction of agents with some organizing principle, theory, or paradigm that gives shape to the agent's components and structures their relationships. Given the wide variety of approaches being taken in the field, the question naturally arises: Is there a way to compare and evaluate these approaches? The purpose of the present work is to develop common benchmark tasks and evaluation metrics to which intelligent agents, including complex robotic agents, constructed using various architectural approaches can be subjected.

  12. A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

    PubMed

    Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

    2016-01-01

    This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging.

  13. Dramatic impact of the giant local magnetic fields on spin-dependent recombination processes in gadolinium based garnets

    SciTech Connect

    Romanov, N. G. Tolmachev, D. O.; Gurin, A. S.; Uspenskaya, Yu. A.; Asatryan, H. R.; Badalyan, A. G.; Baranov, P. G.; Wieczorek, H.; Ronda, C.

    2015-06-29

    A giant magnetic field effect on spin-dependent recombination of the radiation-induced defects has been found in cerium doped gadolinium based garnet crystals and ceramics, promising materials for scintillator applications. A sharp and strong increase in the afterglow intensity stimulated by external magnetic field and an evidence of the magnetic field memory have been discovered. The effect was ascribed to huge Gd-induced internal magnetic fields, which suppress the recombination, and cross-relaxation with Gd{sup 3+} ions leading to reorientation of the spins of the electron and hole centers. Thus, the spin system of radiation-induced defects in gadolinium garnet based scintillator materials was shown to accumulate significant energy which can be released in external magnetic fields.

  14. Steady-state Raman gain coefficients of potassium-gadolinium tungstate at the wavelength of 532 nm

    NASA Astrophysics Data System (ADS)

    Chulkov, R.; Markevich, V.; Orlovich, V.; El-Desouki, M.

    2015-12-01

    Stokes generation has been considered under the Fourier-limited nanosecond pulse excitation to find Raman gain coefficients in potassium-gadolinium tungstate. Data of numerical simulation under spontaneous Stokes initiation, light diffraction, and optical feedback have been compared with experimental results to reveal coefficient values of 14 ± 3 and 11 ± 3 cm/GW for the p[mm]p and p[gg]p sample orientations, respectively, at 532 nm wavelength.

  15. Biological warfare agents.

    PubMed

    Pohanka, Miroslav; Kuca, Kamil

    2010-01-01

    Biological warfare agents are a group of pathogens and toxins of biological origin that can be potentially misused for military or criminal purposes. The present review attempts to summarize necessary knowledge about biological warfare agents. The historical aspects, examples of applications of these agents such as anthrax letters, biological weapons impact, a summary of biological warfare agents and epidemiology of infections are described. The last section tries to estimate future trends in research on biological warfare agents.

  16. Spacecraft sanitation agent development

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The development of an effective sanitizing agent that is compatible with the spacecraft environment and the human occupant is discussed. Experimental results show that two sanitation agents must be used to satisfy mission requirements: one agent for personal hygiene and one for equipment maintenance. It was also recommended that a water rinse be used with the agents for best results, and that consideration be given to using the agents pressure packed or in aerosol formulations.

  17. Polyion complex micelle MRI contrast agents from poly(ethylene glycol)-b-poly(l-lysine) block copolymers having Gd-DOTA; preparations and their control of T(1)-relaxivities and blood circulation characteristics.

    PubMed

    Shiraishi, Kouichi; Kawano, Kumi; Maitani, Yoshie; Yokoyama, Masayuki

    2010-12-01

    The current study synthesized macromolecular magnetic resonance imaging (MRI) contrast agents constituted of the poly(ethylene glycol)-b-poly(L-lysine) block copolymer (PEG-P(Lys)). A chelate group, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), was attached to the primary amino group of the block copolymer in desired contents. Gd-DOTA-based macromolecular contrast agents were prepared from PEG-P(Lys) having DOTA (PEG-P(Lys-DOTA) and Gd(III) ions. All of the PEG-P(Lys) block copolymers having gadolinium ions (PEG-P(Lys-DOTA-Gd)) showed higher T(1) relaxivity (per gadolinium), r(1)=5.6-7.3mM(-1)s(-1), than that of a low-molecular-weight gadolinium-chelate, diethylenetriaminepentaacetic acid-gadolinium(III) (Gd-DTPA) at 9.4T. The study prepared the polyion complex (PIC) micelles from the amino groups of the lysine units and an oppositely charged polyanion, poly(methacrylic acid) or dextran sulfate, in an aqueous medium. In contrast, the fully DOTA-attached PEG-P(Lys-DOTA-Gd) formed a PIC with a polycation. Compared with partially DOTA-attached cationic PEG-P(Lys-DOTA-Gd), this PIC micelle yielded a forty percent decrease of r(1). This r(1) decrease was considered to result from a change in the accessibility of water molecules to gadolinium ions in the micelles' inner core. The r(1) was decreased upon formation of the PIC micelle, and this change proved that our concept worked in vitro. Blood-circulation characteristics of PIC micelles were controlled by means of changing the molecular weight of the counter anion. The PIC micelles accumulated in tumor tissues, and MRI study showed T1W image of axial slice of tumor area was significantly enhanced at 24h after the injection.

  18. High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

    DOE PAGESBeta

    Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.; Vohra, Y. K.

    2016-04-07

    A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8GPa and 600K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high-pressure area on the order of a few tens of seconds. This device is then used to scan the phasemore » diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in this experiment, the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp → αSm transition proceeds in discontinuous steps at points along the expected phase boundary. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0–10GPa and 300–650K« less

  19. High-pressure high-temperature phase diagram of gadolinium studied using a boron-doped heater anvil

    NASA Astrophysics Data System (ADS)

    Montgomery, J. M.; Samudrala, G. K.; Velisavljevic, N.; Vohra, Y. K.

    2016-04-01

    A boron-doped designer heater anvil is used in conjunction with powder x-ray diffraction to collect structural information on a sample of quasi-hydrostatically loaded gadolinium metal up to pressures above 8 GPa and 600 K. The heater anvil consists of a natural diamond anvil that has been surface modified with a homoepitaxially grown chemical-vapor-deposited layer of conducting boron-doped diamond, and is used as a DC heating element. Internally insulating both diamond anvils with sapphire support seats allows for heating and cooling of the high-pressure area on the order of a few tens of seconds. This device is then used to scan the phase diagram of the sample by oscillating the temperature while continuously increasing the externally applied pressure and collecting in situ time-resolved powder diffraction images. In the pressure-temperature range covered in this experiment, the gadolinium sample is observed in its hcp, αSm, and dhcp phases. Under this temperature cycling, the hcp → αSm transition proceeds in discontinuous steps at points along the expected phase boundary. From these measurements (representing only one hour of synchrotron x-ray collection time), a single-experiment equation of state and phase diagram of each phase of gadolinium is presented for the range of 0-10 GPa and 300-650 K.

  20. Neuroprotective effect of gadolinium: a stretch-activated calcium channel blocker in mouse model of ischemia-reperfusion injury.

    PubMed

    Gulati, Puja; Muthuraman, Arunachalam; Jaggi, Amteshwar S; Singh, Nirmal

    2013-03-01

    The present study was designed to investigate the potential of gadolinium, a stretch-activated calcium channel blocker in ischemic reperfusion (I/R)-induced brain injury in mice. Bilateral carotid artery occlusion of 12 min followed by reperfusion for 24 h was given to induce cerebral injury in male Swiss mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was assessed using Morris water maze test and motor incoordination was evaluated using rota-rod, lateral push, and inclined beam walking tests. In addition, total calcium, thiobarbituric acid reactive substance (TBARS), reduced glutathione (GSH), and acetylcholinesterase (AChE) activity were also estimated in brain tissue. I/R injury produced a significant increase in cerebral infarct size. A significant loss of memory along with impairment of motor performance was also noted. Furthermore, I/R injury also produced a significant increase in levels of TBARS, total calcium, AChE activity, and a decrease in GSH levels. Pretreatment of gadolinium significantly attenuated I/R-induced infarct size, behavioral and biochemical changes. On the basis of the present findings, we can suggest that opening of stretch-activated calcium channel may play a critical role in ischemic reperfusion-induced brain injury and that gadolinium has neuroprotective potential in I/R-induced injury.

  1. X-ray fluorescence microscopy demonstrates preferential accumulation of a vanadium-based magnetic resonance imaging contrast agent in murine colonic tumors.

    PubMed

    Mustafi, Devkumar; Ward, Jesse; Dougherty, Urszula; Bissonnette, Marc; Hart, John; Vogt, Stefan; Karczmar, Gregory S

    2015-01-01

    Contrast agents that specifically enhance cancers on magnetic resonance imaging (MRI) will allow earlier detection. Vanadium-based chelates (VCs) selectively enhance rodent cancers on MRI, suggesting selective uptake of VCs by cancers. Here we report x-ray fluorescence microscopy (XFM) of VC uptake by murine colon cancer. Colonic tumors in mice treated with azoxymethane/dextran sulfate sodium were identified by MRI. Then a gadolinium-based contrast agent and a VC were injected intravenously; mice were sacrificed and colons sectioned. VC distribution was sampled at 120 minutes after injection to evaluate the long-term accumulation. Gadolinium distribution was sampled at 10 minutes after injection due to its rapid washout. XFM was performed on 72 regions of normal and cancerous colon from five normal mice and four cancer-bearing mice. XFM showed that all gadolinium was extracellular, with similar concentrations in colon cancers and normal colon. In contrast, the average VC concentration was twofold higher in cancers versus normal tissue (p < .002). Cancers also contained numerous "hot spots" with intracellular VC concentrations sixfold higher than the concentration in normal colon (p < .0001). No hot spots were detected in normal colon. This is the first direct demonstration that VCs selectively accumulate in cancer cells and thus may improve cancer detection.

  2. Lipid-lowering agents.

    PubMed

    Ewang-Emukowhate, Mfon; Wierzbicki, Anthony S

    2013-09-01

    The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented. PMID:23811423

  3. Lipid-lowering agents.

    PubMed

    Ewang-Emukowhate, Mfon; Wierzbicki, Anthony S

    2013-09-01

    The role of lipid lowering in reducing the risk of mortality and morbidity from cardiovascular disease (CVD) is well established. Treatment particularly aimed at decreasing low-density lipoprotein cholesterol (LDL-C) is effective in reducing the risk of death from coronary heart disease and stroke. Statins form the cornerstone of treatment. However, in some individuals with a high risk of CVD who are unable to achieve their target LDL-C due to either intolerance or lack of efficacy, there is the need for alternative therapies. This review provides an overview of the different classes of currently available lipid-lowering medications including statins, fibrates, bile acid sequestrants (resins), and omega-3 fatty acids. Data are presented on their indications, pharmacology, and the relevant end point clinical trial data with these drugs. It also discusses the human trial data on some novel therapeutic agents that are being developed including those for homozygous familial hypercholesterolemia--the antisense oligonucleotide mipomersen and the microsomal transfer protein inhibitor lomitapide. Data are presented on phase II and III trials on agents with potentially wider applications, cholesterol ester transfer protein inhibitors and proprotein convertase subtilisin kexin 9 inhibitors. The data on a licensed gene therapy for lipoprotein lipase deficiency are also presented.

  4. Revisiting an old friend: manganese-based MRI contrast agents

    PubMed Central

    Pan, Dipanjan; Caruthers, Shelton D.; Senpan, Angana; Schmieder, Ann H.; Wickline, Samuel A.; Lanza, Gregory M.

    2011-01-01

    Non-invasive cellular and molecular imaging techniques are emerging as a multidisciplinary field that offers promise in understanding the components, processes, dynamics and therapies of disease at a molecular level. Magnetic resonance imaging (MRI) is an attractive technique due to the absence of radiation and high spatial resolution which makes it advantageous over techniques involving radioisotopes. Typically paramagnetic and superparamagnetic metals are used as contrast materials for MR based techniques. Gadolinium has been the predominant paramagnetic contrast metal until the discovery and association of the metal with nephrogenic systemic fibrosis (NSF) in some patients with severe renal or kidney disease. Manganese was one of the earliest reported examples of paramagnetic contrast material for MRI because of its efficient positive contrast enhancement. In this review manganese based contrast agent approaches will be presented with a particular emphasis on nanoparticulate agents. We have discussed both classically used small molecule based blood pool contrast agents and recently developed innovative nanoparticle-based strategies highlighting a number of successful molecular imaging examples. PMID:20860051

  5. Paramagnetic water-soluble metallofullerenes having the highest relaxivity for MRI contrast agents.

    PubMed

    Mikawa, M; Kato, H; Okumura, M; Narazaki, M; Kanazawa, Y; Miwa, N; Shinohara, H

    2001-01-01

    Water-soluble gadolinium (Gd) endohedral metallofullerenes have been synthesized as polyhydroxyl forms (Gd@C(82)(OH)(n)(), Gd-fullerenols) and their paramagnetic properties were evaluated by in vivo as well as in vitro for the novel magnetic resonance imaging (MRI) contrast agents for next generation. The in vitro water proton relaxivity, R(1) (the effect on 1/T(1)), of Gd-fullerenols is significantly higher (20-folds) than that of the commercial MRI contrast agent, Magnevist (gadolinium-diethylenetriaminepentaacetic acid, Gd-DTPA) at 1.0 T close to the common field of clinical MRI. This unusually high proton relaxivity of Gd-fullerenols leads to the highest signal enhancement at extremely lower Gd concentration in MRI studies. The strong signal was confirmed in vivo MRI at lung, liver, spleen, and kidney of CDF1 mice after i.v. administration of Gd-fullerenols at a dose of 5 micromol Gd/kg, which was 1/20 of the typical clinical dose (100 micromol Gd/kg) of Gd-DTPA.

  6. Labeling of human mesenchymal stem cell: Comparison between paramagnetic and superparamagnetic agents

    NASA Astrophysics Data System (ADS)

    Yang, Chung-Yi; Tai, Ming-Fong; Chen, Shin-Tai; Wang, Yi-Ting; Chen, Ya-Fang; Hsiao, Jong-Kai; Wang, Jaw-Lin; Liu, Hon-Man

    2009-04-01

    Paramagnetic and superparamagnetic substances are used to trace stem cell in living organisms under magnetic resonance imaging (MRI). We compared paramagnetic and superparamagnetic substance for their labeling efficiency by using clinically widely used gadolinium chelates and iron oxide nanoparticles. Without the aid of transfection agent, human mesenchymal stem cells were labeled with each agent separately in different concentration and the optimized concentration was determined by maintaining same cell viability as unlabeled cells. Iron oxide nanoparticle labeling has a detecting threshold of 12 500 cells in vitro, while gadolinium chelates labeling could be detected for at least 50 000 cells. In life animal study, we found there is an eightfold sensitivity in cells labeled with iron oxide superparamagnetic nanoparticles; however, the magnetic susceptibility artifact would obscure the detail of adjacent anatomical structures. We conclude that labeling stem cells with superparamagnetic substance is more efficacious. However, the cells labeled by superparamagnetic nanoparticles might interfere with the interpretation of anatomical structure. These findings would be beneficial to applications of magnetic substances toward stem cell biology and tissue engineering.

  7. Luminescence properties and electronic structure of Ce{sup 3+}-doped gadolinium aluminum garnet

    SciTech Connect

    Dotsenko, V.P.; Berezovskaya, I.V.; Voloshinovskii, A.S.; Zadneprovski, B.I.; Efryushina, N.P.

    2015-04-15

    Highlights: • The luminescence properties of Ce{sup 3+} ions in (Y, Gd){sub 3}Al{sub 5}O{sub 12} are analyzed. • The Gd{sup 3+} → Y{sup 3+} substitution leads to increasing of Ce{sup 3+} noncubic crystal field splitting parameter. • The excitation spectra for the Ce{sup 3+} emission in GdAG contain bands at 6.67, 7.75, and 9.76 eV. • These features are due to the Ce{sup 3+}-bound exciton formation and O 2p → Al 3s, 3p transitions. • Contributions from Al atoms to the conduction-band density of states are quite essential. - Abstract: Yttrium-gadolinium aluminum garnets (YGdAG) doped with Ce{sup 3+} ions have been prepared by co-precipitation method. The luminescent properties of Ce{sup 3+} ions in Gd{sub 3(1−x)}Ce{sub 3x}Al{sub 5}O{sub 12} (x = 0.01) have been studied upon excitation in the 2–20 eV region. The substitution of Gd{sup 3+} for Y{sup 3+} in the garnet structure results in broadening the emission band and shifting its maximum towards the longer wavelengths. It was found that in addition to the 4f → 5d excitation bands of Ce{sup 3+} ions, the excitation spectra for the Ce{sup 3+} emission contain bands at 6.67, 7.75, and 9.76 eV. These bands are attributed to the Ce{sup 3+}-bound exciton formation and O 2p → Al 3s, 3p transitions, respectively. Although gadolinium states dominate near the bottom of the conduction band of Gd{sub 3}Al{sub 5}O{sub 12}, contributions from Al{sub tetr} and Al{sub oct} atoms to the conduction-band density of states are evaluated as quite essential.

  8. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis

    PubMed Central

    Fontana, Marianna; Pica, Silvia; Reant, Patricia; Abdel-Gadir, Amna; Treibel, Thomas A.; Banypersad, Sanjay M.; Maestrini, Viviana; Barcella, William; Rosmini, Stefania; Bulluck, Heerajnarain; Sayed, Rabya H.; Patel, Ketna; Mamhood, Shameem; Bucciarelli-Ducci, Chiara; Whelan, Carol J.; Herrey, Anna S.; Lachmann, Helen J.; Wechalekar, Ashutosh D.; Manisty, Charlotte H.; Schelbert, Eric B.; Kellman, Peter; Gillmore, Julian D.; Hawkins, Philip N.

    2015-01-01

    Background— The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown. Methods and Results— Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance. Subjects were followed up for a mean of 24±13 months. LGE was performed with phase-sensitive inversion recovery (PSIR) and without (magnitude only). These were compared with extracellular volume measured with T1 mapping. PSIR was superior to magnitude-only inversion recovery LGE because PSIR always nulled the tissue (blood or myocardium) with the longest T1 (least gadolinium). LGE was classified into 3 patterns: none, subendocardial, and transmural, which were associated with increasing amyloid burden as defined by extracellular volume (P<0.0001), with transitions from none to subendocardial LGE at an extracellular volume of 0.40 to 0.43 (AL) and 0.39 to 0.40 (ATTR) and to transmural at 0.48 to 0.55 (AL) and 0.47 to 0.59 (ATTR). Sixty-seven patients (27%) died. Transmural LGE predicted death (hazard ratio, 5.4; 95% confidence interval, 2.1–13.7; P<0.0001) and remained independent after adjustment for N-terminal pro-brain natriuretic peptide, ejection fraction, stroke volume index, E/E′, and left ventricular mass index (hazard ratio, 4.1; 95% confidence interval, 1.3–13.1; P<0.05). Conclusions— There is a continuum of cardiac involvement in systemic AL and ATTR amyloidosis. Transmural LGE is determined reliably by PSIR and represents advanced cardiac amyloidosis. The PSIR technique provides incremental information on outcome even after

  9. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    NASA Astrophysics Data System (ADS)

    Chen, Zhijin; Yu, Dexin; Wang, Shaojie; Zhang, Na; Ma, Chunhong; Lu, Zaijun

    2009-07-01

    Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid-polyethylene glycol/gadolinium-diethylenetriamine-pentaacetic acid (PLA-PEG/Gd-DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA-PEG/Gd-DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA-PEG nanoparticles and the commercial contrast agent, Gd-DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA-PEG/Gd-DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was -12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA-PEG/Gd-DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed ( r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd-DTPA. PLA-PEG/Gd-DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA-PEG/Gd-DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

  10. Utility of delayed gadolinium-enhanced MRI (dGEMRIC) for qualitative evaluation of articular cartilage of patellofemoral joint.

    PubMed

    Nojiri, Takehiro; Watanabe, Nobuyoshi; Namura, Takehiko; Narita, Wataru; Ikoma, Kazuya; Suginoshita, Takehiko; Takamiya, Hisatake; Komiyama, Hiroto; Ito, Hirotoshi; Nishimura, Tsunehiko; Kubo, Toshikazu

    2006-08-01

    Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was used for the measurement of relative proteoglycan depletion of articular cartilage in the patellofemoral (PF) joint following a proprietary protocol, which was compared with the X-ray images, proton density weighted MR images (PDWI) and arthroscopic findings. The study examined 30 knees. The ages ranged from 16 to 74 (average 40.3) years. The Gd-DTPA(2-)containing contrast medium was used in a single dose. The subjects were made to exercise the knee joint for 10 min; and MR images were taken 2 h after intravenous injection of contrast medium. T1-calculated images were produced and the region of interest (ROI) was set as follows. (1) ROI1: entire articular cartilage in a slice through the center of the patella. (2) ROI2: low signal region in T1-calculated images, which were set in a blind fashion by two observers. (3) ROI3: articular cartilage on one side that includes ROI2 where low signal region were detected (medial or lateral). ROI3 was set to examine the contrast of ROI2 with surrounding articular cartilage. The average T1 values of ROI1 was 393.5+/-33.6 ms for radiographic grade 0 and 361.3+/-11.1 ms for grade I, which showed a significant difference (P=0.036). The T1 value of ROI2 was 351.6+/-28.2 ms for grade I, 361.9+/-38.3 ms for grade II, 362.1+/-67.7 ms for grade III, and 297.8+/-54.1 ms for grade IV according to arthroscopic Outerbridge classification. All cases, that demonstrated decrease of T1 values on dGEMRIC (ROI2), showed abnormal arthroscopic or direct viewing findings. The ratio (ROI3/ROI2) in cases of only slight damage classified as Outerbridge grade I (6 cases) was an average of 1.04+/-0.02 and was 1.0 or greater in all cases, thereby indicating well-defined contrast with the surrounding cartilage. The diagnosis of damage in articular cartilage was possible in all 16 cases with radiographic K-L grade I on dGEMRIC, while the intensity changes were not found in 10 of 16 cases on PDWI

  11. Targeted dual-contrast T1- and T2-weighted magnetic resonance imaging of tumors using multifunctional gadolinium-labeled superparamagnetic iron oxide nanoparticles.

    PubMed

    Yang, Hong; Zhuang, Yeming; Sun, Yun; Dai, Antao; Shi, Xiangyang; Wu, Dongmei; Li, Fuyou; Hu, He; Yang, Shiping

    2011-07-01

    Development of a multifunctional nanoparticle (NP) system allowing for dual-contrast T(1)- and T(2)-weighted targeted magnetic resonance (MR) imaging of tumors could significantly improve the diagnosis accuracy. In this study, superparamagnetic silica-coated iron oxide core-shell nanoparticles (Fe(3)O(4)@SiO(2) NPs) with a diameter of approximately 21 nm were synthesized via a thermal decomposition approach and were aminated through silanization. The amine-functionalized Fe(3)O(4)@SiO(2) NPs enabled the covalent conjugation of a paramagnetic gadolinium complex (Gd-DTPA, DTPA: diethylenetriamine pentaacetic acid) and an arginine-glycine-aspartic acid (RGD) peptide as a targeting ligand onto their surface. The formed Fe(3)O(4)@SiO(2)(Gd-DTPA)-RGD NPs are water-dispersible, stable, and biocompatible as confirmed by MTT cell viability assay. Relaxivity measurements show that they have a T(1) relaxivity (r(1)) of 4.2 mM(-1) s(-1) and T(2) relaxivity (r(2)) of 17.4 mM(-1) s(-1) at the Gd/Fe molar ratio of 0.3:1, suggesting a possibility to use them as both T(1) positive and T(2) negative contrast agents. In vitro and in vivo MR imaging experiments show that the developed multifunctional Fe(3)O(4)@SiO(2)(Gd-DTPA)-RGD NPs enable targeted dual-contrast T(1)- and T(2)-weighted MR imaging of tumor cells over-expressing high-affinity α(v)β(3) integrin in vitro and in vivo. Our results clearly indicate that the approach to forming multifunctional Fe(3)O(4)@SiO(2)(Gd-DTPA)-RGD NPs could be extended for fabricating other biologically active NPs for T(1)- and T(2)-weighted MR imaging of other biological systems with high accuracy.

  12. Tracking of mesenchymal stem cells labeled with gadolinium diethylenetriamine pentaacetic acid by 7T magnetic resonance imaging in a model of cerebral ischemia

    PubMed Central

    GENG, KUAN; YANG, ZHONG XIAN; HUANG, DEXIAO; YI, MEIZI; JIA, YANLONG; YAN, GEN; CHENG, XIAOFANG; WU, RENHUA

    2015-01-01

    Progress in the development of stem cell and gene therapy requires repeatable and non-invasive techniques to monitor the survival and integration of stem cells in vivo with a high temporal and spatial resolution. The purpose of the present study was to examine the feasibility of using the standard contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) to label rat mesenchymal stem cells (MSCs) for stem cell tracking. MSCs, obtained from the bilateral femora of rats, were cultured and propagated. The non-liposomal lipid transfection reagent effectene was then used to induce the intracellular uptake of Gd-DTPA. Electron microscopy was used to detect the distribution of Gd-DTPA particles in the MSCs. The labeling efficiency of the Gd-DTPA particles in the MSCs was determined using spectrophotometry, and MTT and trypan blue exclusion assays were used to evaluate the viability and proliferation of the labeled MSCs. T1-weighted magnetic resonance imaging (MRI) was used to observe the labeled cells in vitro and in the rat brain. Gd-DTPA particles were detected inside the MSCs using transmission electron microscopy and a high labeling efficiency was observed. No difference was observed in cell viability or proliferation between the labeled and unlabeled MSCs (P>0.05). In the in vitro T1-weighted MRI and in the rat brain, a high signal intensity was observed in the labeled MSCs. The T1-weighted imaging of the labeled cells revealed a significantly higher signal intensity compared with that of the unlabeled cells (P<0.05) and the T1 values were significantly lower. The function of the labeled MSCs demonstrated no change following Gd-DTPA labeling, with no evident adverse effect on cell viability or proliferation. Therefore, a change in MR signal intensity was detected in vitro and in vivo, suggesting Gd-DTPA can be used to label MSCs for MRI tracking. PMID:25352164

  13. Natural products as antimitotic agents.

    PubMed

    Dall'Acqua, Stefano

    2014-01-01

    Natural products still play an important role in the medicinal chemistry, especially in some therapeutic areas. As example more than 60% of currently-used anticancer agents are derives from natural sources including plants, marine organisms or micro-organism. Thus natural products (NP) are an high-impact source of new "lead compounds" or new potential therapeutic agents despite the large development of biotechnology and combinatorial chemistry in the drug discovery and development. Many examples of anticancer drugs as paclitaxel, combretastatin, bryostatin and discodermolide have shown the importance of NP in the anticancer chemotherapy through many years. Many organisms have been studied as sources of drugs namely plants, micro-organisms and marine organisms and the obtained NP can be considered a group of "privileged chemical structures" evolved in nature to interact with other organisms. For this reason NP are a good starting points for pharmaceutical research and also for library design. Tubulin and microtubules are one of the most studied targets for the search of anticancer compounds. Microtubule targeting agents (MTA) also named antimitotic agents are compounds that are able to perturb mitosis but are also able to arrest cell growing during interphase. The anticancer drugs, taxanes and vinca alkaloids have established tubulin as important target in cancer therapy. More recently the vascular disrupting agents (VDA) combretastatin analogues were studied for their antimitotics properties. This review will consider the anti mitotic NP and their potential impact in the development of new therapeutic agents.

  14. Chemical warfare agents.

    PubMed

    Chauhan, S; Chauhan, S; D'Cruz, R; Faruqi, S; Singh, K K; Varma, S; Singh, M; Karthik, V

    2008-09-01

    Chemical warfare agents (CWA's) are defined as any chemical substance whose toxic properties are utilised to kill, injure or incapacitate an enemy in warfare and associated military operations. Chemical agents have been used in war since times immemorial, but their use reached a peak during World War I. During World War II only the Germans used them in the infamous gas chambers. Since then these have been intermittently used both in war and acts of terrorisms. Many countries have stockpiles of these agents. There has been a legislative effort worldwide to ban the use of CWA's under the chemical weapons convention which came into force in 1997. However the manufacture of these agents cannot be completely prohibited as some of them have potential industrial uses. Moreover despite the remedial measures taken so far and worldwide condemnation, the ease of manufacturing these agents and effectiveness during combat or small scale terrorist operations still make them a powerful weapon to reckon with. These agents are classified according to mechanism of toxicity in humans into blister agents, nerve agents, asphyxiants, choking agents and incapacitating/behavior altering agents. Some of these agents can be as devastating as a nuclear bomb. In addition to immediate injuries caused by chemical agents, some of them are associated with long term morbidities and psychological problems. In this review we will discuss briefly about the historical background, properties, manufacture techniques and industrial uses, mechanism of toxicity, clinical features of exposure and pharmacological management of casualties caused by chemical agents. PMID:21783898

  15. Scintillation properties of cerium-doped gadolinium-scandium-aluminum garnets

    NASA Astrophysics Data System (ADS)

    Kling, A.; Kollewe, D.; Mateika, D.

    1994-07-01

    Optical properties and scintillation responses of cerium doped gadolinium-scandium-aluminum garnets (GSAG), pulled by the Czochralski method, were studied with regard to applications in scintillation counters. Scintillation responses were investigated for irradiation with charged particles, γ-rays and neutrons. The observed decay constant ( τ = 120 ns) is shorter than in common inorganic scintillators like NaI(T1) and bismuth germanate (BGO). The attenuation coefficient exceeds the value reported for Nal(T1). GSAG(Ce) shows a higher light yield (30% when compared with NaI(T1)) and better energy resolution (12.5% for 662 keV γ-rays from 137Cs) than BGO. To demonstrate the feasibility for neutron detection, crystals were irradiated with slow neutrons (from 14.7 meV to 120 meV) from a neutron diffraction spectrometer at the Grenoble pile Melusine and fast neutrons (≥ 7.9 MeV) from the Stuttgart Dynamitron accelerator using the 9Be(α, n) 12C reaction.

  16. Thermal-Diffusivity Dependence on Temperature of Gadolinium Calcium Oxoborate Single Crystals

    NASA Astrophysics Data System (ADS)

    Trefon-Radziejewska, D.; Bodzenta, J.; Łukasiewicz, T.

    2013-05-01

    Thermal diffusivities of pure and doped gadolinium calcium oxoborate (GdCOB) single crystals were measured as a function of the temperature along optical indicatrix axes X, Y, and Z. Three GdCOB samples were investigated, chemically pure single crystal, the one doped with 4 at% of Nd and the next one doped with 7 at% of Yb. Measurements were carried out for temperature range 40 °C to 300 °C. Determination of the thermal diffusivity based on an analysis of thermal wave propagation in the sample. For a detection of temperature disturbance propagating in the sample the mirage effect was used. Obtained results show that the thermal diffusivity decreases with the increase of sample temperature for all investigated crystals. The GdCOB single crystals reveal a strong anisotropy. The thermal diffusivity along Y direction has the highest value while values obtained in X and Z axes are much lower. Dopants cause decrease in the thermal diffusivity for all investigated directions.

  17. Gadolinium metallofullerenol nanoparticles inhibit cancer metastasis through matrix metalloproteinase inhibition: imprisoning instead of poisoning cancer cells

    PubMed Central

    Meng, Huan; Xing, Gengmei; Blanco, Elvin; Song, Yan; Zhao, Lina; Sun, Baoyun; Li, Xiaoda; Wang, Paul C.; Korotcov, Alexandru; Li, Wei; Liang, Xing-Jie; Chen, Chunying; Yuan, Hui; Zhao, Feng; Chen, Zhen; Sun, Tong; Chai, Zhifang; Ferrari, Mauro; Zhao, Yuliang

    2012-01-01

    The purpose of this work is to study the antimetastasis activity of gadolinium metallofullerenol nanoparticles (f-NPs) in malignant and invasive human breast cancer models. We demonstrated that f-NPs inhibited the production of matrix metalloproteinase (MMP) enzymes and further interfered with the invasiveness of cancer cells in tissue culture condition. In the tissue invasion animal model, the invasive primary tumor treated with f-NPs showed significantly less metastasis to the ectopic site along with the decreased MMP expression. In the same animal model, we observed the formation of a fibrous cage that may serve as a physical barrier capable of cancer tissue encapsulation that cuts the communication between cancer- and tumor-associated macrophages, which produce MMP enzymes. In another animal model, the blood transfer model, f-NPs potently suppressed the establishment of tumor foci in lung. Based on these data, we conclude that f-NPs have antimetastasis effects and speculate that utilization of f-NPs may provide a new strategy for the treatment of tumor metastasis. PMID:21930111

  18. The influence of gadolinium and yttrium on biomass production and nutrient balance of maize plants.

    PubMed

    Saatz, Jessica; Vetterlein, Doris; Mattusch, Jürgen; Otto, Matthias; Daus, Birgit

    2015-09-01

    Rare earth elements (REE) are expected to become pollutants by enriching in the environment due to their wide applications nowadays. The uptake and distribution of gadolinium and yttrium and its influence on biomass production and nutrient balance was investigated in hydroponic solution experiments with maize plants using increasing application doses of 0.1, 1 and 10 mg L(-1). It could be shown that concentrations of up to 1 mg L(-1) of Gd and Y did not reduce or enhance the plant growth or alter the nutrient balance. 10 mg L(-1) Gd or Y resulted in REE concentrations of up to 1.2 weight-% in the roots and severe phosphate deficiency symptoms. Transfer rates showed that there was only little transport of Gd and Y from roots to shoots. Significant correlations were found between the concentration of Gd and Y in the nutrient solution and the root tissue concentration of Ca, Mg and P.

  19. Lunar prospector measurements of the distribution of incompatible elements gadolinium, samarium and thorium

    SciTech Connect

    Elphic, R.C.; Lawrence, D.J.; Feldman, W.C.; Barraclough, B.L.; Maurice, S.; Binder, A.B.; Lucey, P.G.

    1999-04-01

    Lunar Prospector neutron spectrometer (NS) and gamma ray spectrometer (GRS) observations have been used to map out the distribution of incompatible elements on the lunar surface. Specifically, the GRS data provide maps of the distribution of thorium and potassium while the NS data provide information on the distribution of iron and titanium, and the rare earth elements gadolinium and samarium. Using results of analysis of Celementine spectral reflectance (CSR) data, the Fe- and Ti-contributions to the NS data can be removed, leaving primarily rare earth element contributions from Gd and Sm. The Th and K maps correlate with the inferred Gd and Sm maps (r {approximately} 0.93), but there are regions of significant disagreement. One of these is in the KREEP-rich circum-Imbrium ring. No clear explanation has emerged for this disagreement, though Th, K, Gd and Sm have differing degrees of incompatibility. These results clearly are important to discussions of the geochemistry of the Procellarum-Imbrium Th-rich Terrane and the South-Pole-Aitken Terrane.

  20. Influence of gadolinium doping on the structure and defects of ceria under fuel cell operating temperature

    SciTech Connect

    Acharya, S. A. Gaikwad, V. M.; Sathe, V.; Kulkarni, S. K.

    2014-03-17

    Correlation between atomic positional shift, oxygen vacancy defects, and oxide ion conductivity in doped ceria system has been established in the gadolinium doped ceria system from X-ray diffraction (XRD) and Raman spectroscopy study at operating temperature (300–600 °C) of Intermediate Temperature Solid Oxide Fuel Cell (IT-SOFC). High temperature XRD data are used to quantify atomic positional shift from mean position with temperature. The Raman spectroscopy study shows additional vibration modes related to ordering of defect spaces (Gd{sub Ce}{sup ′}−V{sub o}{sup ••}){sup *} and (2Gd{sub Ce}{sup ′}−V{sub o}{sup ••}){sup x} generated due to association of oxygen vacancies and reduced cerium or dopant cations site (Gd{sup 3+}), which disappear at 450 °C; indicating oxygen vacancies dissociation from the defect complex. The experimental evidences of cation-anion positional shifting and oxygen vacancies dissociation from defect complex in the IT-SOFC operating temperature are discussed to correlate with activation energy for ionic conductivity.