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Sample records for contrast agent based

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

    Science.gov (United States)

    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.

  2. Gadolinium-based contrast agents in pediatric magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gale, Eric M.; Caravan, Peter [Massachusetts General Hospital, Harvard Medical School, Department of Radiology, The Martinos Center for Biomedical Imaging, Boston, MA (United States); Rao, Anil G. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); McDonald, Robert J. [College of Medicine, Mayo Clinic, Department of Radiology, Rochester, MN (United States); Winfeld, Matthew [University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (United States); Fleck, Robert J. [Cincinnati Children' s Hospital Medical Center, Department of Pediatric Radiology, Cincinnati, OH (United States); Gee, Michael S. [MassGeneral Hospital for Children, Harvard Medical School, Division of Pediatric Imaging, Department of Radiology, Boston, MA (United States)

    2017-05-15

    Gadolinium-based contrast agents can increase the accuracy and expediency of an MRI examination. However the benefits of a contrast-enhanced scan must be carefully weighed against the well-documented risks associated with administration of exogenous contrast media. The purpose of this review is to discuss commercially available gadolinium-based contrast agents (GBCAs) in the context of pediatric radiology. We discuss the chemistry, regulatory status, safety and clinical applications, with particular emphasis on imaging of the blood vessels, heart, hepatobiliary tree and central nervous system. We also discuss non-GBCA MRI contrast agents that are less frequently used or not commercially available. (orig.)

  3. Novel nanomedicine-based MRI contrast agents for gynecological malignancies.

    Science.gov (United States)

    Mody, Vicky V; Nounou, Mohamed Ismail; Bikram, Malavosklish

    2009-08-10

    Gynecological cancers result in significant morbidity and mortality in women despite advances in treatment and diagnosis. This is due to detection of the disease in the late stages following metastatic spread in which treatment options become limited and may not result in positive outcomes. In addition, traditional contrast agents are not very effective in detecting primary metastatic tumors and cells due to a lack of specificity and sensitivity of the diagnostic tools, which limits their effectiveness. Recently, the field of nanomedicine-based contrast agents offers a great opportunity to develop highly sophisticated devices that can overcome many traditional hurdles of contrast agents including solubility, cell-specific targeting, toxicities, and immunological responses. These nanomedicine-based contrast agents including liposomes, micelles, dendrimers, multifunctional magnetic polymeric nanohybrids, fullerenes, and nanotubes represent improvements over their traditional counterparts, which can significantly advance the field of molecular imaging.

  4. Gd-HOPO Based High Relaxivity MRI Contrast Agents

    Energy Technology Data Exchange (ETDEWEB)

    Datta, Ankona; Raymond, Kenneth

    2008-11-06

    Tris-bidentate HOPO-based ligands developed in our laboratory were designed to complement the coordination preferences of Gd{sup 3+}, especially its oxophilicity. The HOPO ligands provide a hexadentate coordination environment for Gd{sup 3+} in which all he donor atoms are oxygen. Because Gd{sup 3+} favors eight or nine coordination, this design provides two to three open sites for inner-sphere water molecules. These water molecules rapidly exchange with bulk solution, hence affecting the relaxation rates of bulk water olecules. The parameters affecting the efficiency of these contrast agents have been tuned to improve contrast while still maintaining a high thermodynamic stability for Gd{sup 3+} binding. The Gd- HOPO-based contrast agents surpass current commercially available agents ecause of a higher number of inner-sphere water molecules, rapid exchange of inner-sphere water molecules via an associative mechanism, and a long electronic relaxation time. The contrast enhancement provided by these agents is at least twice that of commercial contrast gents, which are based on polyaminocarboxylate ligands.

  5. Macromolecular and dendrimer-based magnetic resonance contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Bumb, Ambika; Brechbiel, Martin W. (Radiation Oncology Branch, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States)), e-mail: pchoyke@mail.nih.gov; Choyke, Peter (Molecular Imaging Program, National Cancer Inst., National Inst. of Health, Bethesda, MD (United States))

    2010-09-15

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20-25 years, a number of gadolinium-based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution, and targeting of dendrimer-based MR contrast agents are also discussed

  6. Nanoparticle-Based Systems for T1-Weighted Magnetic Resonance Imaging Contrast Agents

    Science.gov (United States)

    Zhu, Derong; Liu, Fuyao; Ma, Lina; Liu, Dianjun; Wang, Zhenxin

    2013-01-01

    Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T1-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T1-weighted MRI/computed X-ray tomography (CT) and T1-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality. PMID:23698781

  7. Multifunctional photosensitizer-based contrast agents for photoacoustic imaging.

    Science.gov (United States)

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U S; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-18

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  8. Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging

    Science.gov (United States)

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U. S.; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-06-01

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo.

  9. Characterization of nanoparticle-based contrast agents for molecular magnetic resonance imaging

    Science.gov (United States)

    Shan, Liang; Chopra, Arvind; Leung, Kam; Eckelman, William C.; Menkens, Anne E.

    2012-09-01

    The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, 4,800 newly developed agents have been synthesized and characterized in vitro and in animal models of human disease. Despite this rapid progress, the transfer of these agents to clinical practice is rather slow. To address this issue, the National Institutes of Health launched the Molecular Imaging and Contrast Agents Database (MICAD) in 2005 to provide freely accessible online information regarding molecular imaging probes and contrast agents for the imaging community. While compiling information regarding imaging agents published in peer-reviewed journals, the MICAD editors have observed that some important information regarding the characterization of a contrast agent is not consistently reported. This makes it difficult for investigators to evaluate and meta-analyze data generated from different studies of imaging agents, especially for the agents based on nanoparticles. This article is intended to serve as a guideline for new investigators for the characterization of preclinical studies performed with nanoparticle-based MRI contrast agents. The common characterization parameters are summarized into seven categories: contrast agent designation, physicochemical properties, magnetic properties, in vitro studies, animal studies, MRI studies, and toxicity. Although no single set of parameters is suitable to define the properties of the various types of contrast agents, it is essential to ensure that these agents meet certain quality control parameters at the preclinical stage, so that they can be used without delay for clinical studies.

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  12. Multimodal nanoparticulate bioimaging contrast agents.

    Science.gov (United States)

    Sharma, Parvesh; Singh, Amit; Brown, Scott C; Bengtsson, Niclas; Walter, Glenn A; Grobmyer, Stephen R; Iwakuma, Nobutaka; Santra, Swadeshmukul; Scott, Edward W; Moudgil, Brij M

    2010-01-01

    A wide variety of bioimaging techniques (e.g., ultrasound, computed X-ray tomography, magnetic resonance imaging (MRI), and positron emission tomography) are commonly employed for clinical diagnostics and scientific research. While all of these methods use a characteristic "energy-matter" interaction to provide specific details about biological processes, each modality differs from another in terms of spatial and temporal resolution, anatomical and molecular details, imaging depth, as well as the desirable material properties of contrast agents needed for augmented imaging. On many occasions, it is advantageous to apply multiple complimentary imaging modalities for faster and more accurate prognosis. Since most imaging modalities employ exogenous contrast agents to improve the signal-to-noise ratio, the development and use of multimodal contrast agents is considered to be highly advantageous for obtaining improved imagery from sought-after imaging modalities. Multimodal contrast agents offer improvements in patient care, and at the same time can reduce costs and enhance safety by limiting the number of contrast agent administrations required for imaging purposes. Herein, we describe the synthesis and characterization of nanoparticulate-based multimodal contrast agent for noninvasive bioimaging using MRI, optical, and photoacoustic tomography (PAT)-imaging modalities. The synthesis of these agents is described using microemulsions, which enable facile integration of the desired diversity of contrast agents and material components into a single entity.

  13. Gadolinium-Based Contrast Agents for Vessel Wall Magnetic Resonance Imaging (MRI) of Atherosclerosis.

    Science.gov (United States)

    Calcagno, Claudia; Ramachandran, Sarayu; Millon, Antoine; Robson, Philip M; Mani, Venkatesh; Fayad, Zahi

    2013-02-01

    Cardiovascular disease due to atherosclerosis is the number one killer in the Western world, and threatens to become the major cause of morbidity and mortality worldwide. It is therefore paramount to develop non-invasive methods for the detection of high-risk, asymptomatic individuals before the onset of clinical symptoms or events. In the recent past, great strides have been made in the understanding of the pathological mechanisms involved in the atherosclerotic cascade down to the molecular details. This has allowed the development of contrast agents that can aid in the in vivo characterization of these processes. Gadolinium chelates are among the contrast media most commonly used in MR imaging. Originally used for MR angiography for the detection and quantification of vascular stenosis, more recently they have been applied to improve characterization of atherosclerotic plaques. In this manuscript, we will briefly review gadolinium-chelates (Gd) based contrast agents for non-invasive MR imaging of atherosclerosis. We will first describe Gd-based non-targeted FDA approved agents, used routinely in clinical practice for the evaluation of neovascularization in other diseases. Secondly, we will describe non-specific and specific targeted contrast agents, which have great potential for dissecting specific biological processes in the atherosclerotic cascade. Lastly, we will briefly compare Gd-based agents to others commonly used in MRI and to other imaging modalities.

  14. T(2) relaxation time of hyaline cartilage in presence of different gadolinium-based contrast agents.

    Science.gov (United States)

    Wiener, Edzard; Settles, Marcus; Diederichs, Gerd

    2010-01-01

    The transverse relaxation time, T(2), of native cartilage is used to quantify cartilage degradation. T(2) is frequently measured after contrast administration, assuming that the impact of gadolinium-based contrast agents on cartilage T(2) is negligible. To verify this assumption the depth-dependent variation of T(2) in the presence of gadopentetate dimeglumine, gadobenate dimeglumine and gadoteridol was investigated. Furthermore, the r(2)/r(1) relaxivity ratios were quantified in different cartilage layers to demonstrate differences between T(2) and T(1) relaxation effects. Transverse high-spatial-resolution T(1)- and T(2)-maps were simultaneously acquired on a 1.5 T MR scanner before and after contrast administration in nine bovine patellae using a turbo-mixed sequence. The r(2)/r(1) ratios were calculated for each contrast agent in cartilage. Profiles of T(1), T(2) and r(2)/r(1) across cartilage thickness were generated in the absence and presence of contrast agent. The mean values in different cartilage layers were compared for global variance using the Kruskal-Wallis test and pairwise using the Mann-Whitney U-test. T(2) of unenhanced cartilage was 98 +/- 5 ms at 1 mm and 65 +/- 4 ms at 3 mm depth. Eleven hours after contrast administration significant differences (p cartilage thickness were close to 1.0 (range 0.9-1.3). At 1.5 T, T(2) decreased significantly in the presence of contrast agents, more pronounced in superficial than in deep cartilage. The change in T(2) relaxation rate was similar to the change in T(1). Cartilage T(2) measurements after contrast administration will lead to systematic errors in the quantification of cartilage degradation. 2010 John Wiley & Sons, Ltd.

  15. Characterization of a Novel Hafnium-Based X-ray Contrast Agent.

    Science.gov (United States)

    Frenzel, Thomas; Bauser, Marcus; Berger, Markus; Hilger, Christoph Stephan; Hegele-Hartung, Christa; Jost, Gregor; Neis, Christian; Hegetschweiler, Kaspar; Riefke, Björn; Suelzle, Detlev; Pietsch, Hubertus

    2016-12-01

    Characterization of BAY-576, a new x-ray contrast agent which is not based on iodine, but rather on the heavy metal hafnium. Compared with iodine, hafnium provides better x-ray absorption in the energy range of computed tomography (CT) and allows images of comparable quality to be acquired at a significantly reduced radiation dose. A range of standard methods were used to explore the physicochemistry of BAY-576 as well as its tolerability in in vitro assays, its pharmacokinetics and toxicology in rats, and its performance in CT imaging in rabbits. BAY-576 is an extraordinarily stable chelate with a metal content of 42% (wt/wt) and with excellent water solubility. Formulations of 300 mg Hf/mL exhibited viscosity (3.3-3.6 mPa) and osmolality (860-985 mOsm/kg) in the range of nonionic x-ray agents. No relevant effects on erythrocytes, the coagulation, or complement system or on a panel of 87 potential biological targets were observed. The compound did not bind to plasma proteins of a number of species investigated. After intravenous injection in rats, it was excreted fast and mainly via the kidneys. Its pharmacokinetics was comparable to known extracellular contrast agents. A dose of 6000 mg Hf/kg, approximately 10 to 20 times the expected diagnostic dose, was well tolerated by rats with only moderate adverse effects. Computed tomography imaging in rabbits bearing a tumor in the liver demonstrated excellent image quality when compared with iopromide at the same contrast agent dose in angiography during the arterial phase. At 70% of the radiation dose, BAY-576 provided a contrast-to-noise ratio of the tumor, which was equivalent to iopromide at 100% radiation dose. The profile of BAY-576 indicates its potential as the first compound in a new class of noniodine x-ray contrast agents, which can contribute to the reduction of the radiation burden in contrast-enhanced CT imaging.

  16. Complications from the use of intravenous gadolinium-based contrast agents for magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Elias Junior, Jorge; Santos, Antonio Carlos dos; Nogueira-Barbosa, Marcello Henrique; Muglia, Valdair Francisco; Koenigkam-Santos, Marcel [Universidade de Sao Paulo (USP), Ribeirao Preto, SP (Brazil). Hospital das Clinicas. Centro de Ciencias das Imagens e Fisica Medica]. E-mail: jejunior@fmrp.usp.br

    2008-07-15

    Gadolinium-based contrast agents are much safer than the iodinated ones; however complications may occur and should be recognized for appropriate orientation and management. The total incidence of adverse reactions to contrast agents in magnetic resonance imaging ranges between 2% and 4%. Cases of severe acute reactions to gadolinium, such as laryngospasm and anaphylactic shock, are rare. Chronic complications secondary to the use of gadolinium also can occur and, recently an association between its use and a rare dermatologic disease occurring in patients with renal failure has been reported. Nephrogenic systemic fibrosis was the subject of an official health notification issued by the American Food and Drug Administration. This progressive disease is characterized by hardened skin with fibrotic nodules and plaques which may involve other parts of the body. Patients who have been affected by this disorder presented chronic renal failure, with metabolic acidosis and had been submitted to magnetic resonance angiography, probably involving exposure to large amounts of intravenous paramagnetic contrast. This review is aimed at presenting a succinct description of the gadolinium-based contrast agent types, possible secondary complications, their preventive measures and management. (author)

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

    Science.gov (United States)

    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.

  18. Hafnium-Based Contrast Agents for X-ray Computed Tomography.

    Science.gov (United States)

    Berger, Markus; Bauser, Marcus; Frenzel, Thomas; Hilger, Christoph Stephan; Jost, Gregor; Lauria, Silvia; Morgenstern, Bernd; Neis, Christian; Pietsch, Hubertus; Sülzle, Detlev; Hegetschweiler, Kaspar

    2017-05-15

    Heavy-metal-based contrast agents (CAs) offer enhanced X-ray absorption for X-ray computed tomography (CT) compared to the currently used iodinated CAs. We report the discovery of new lanthanide and hafnium azainositol complexes and their optimization with respect to high water solubility and stability. Our efforts culminated in the synthesis of BAY-576, an uncharged hafnium complex with 3:2 stoichiometry and broken complex symmetry. The superior properties of this asymmetrically substituted hafnium CA were demonstrated by a CT angiography study in rabbits that revealed excellent signal contrast enhancement.

  19. Enhanced relaxivity of Gd3+-based contrast agents geometrically confined within porous nanoconstructs

    OpenAIRE

    Sethi, Richa; Ananta, Jeyarama S.; Karmonik, Christof; Zhong, Meng; Steve H. Fung; Liu, Xuewu; Li, King; Ferrari, Mauro; Wilson, Lon J.; Decuzzi, Paolo

    2012-01-01

    Gadolinium chelates, which are currently approved for clinical MRI use, provide relaxivities well below their theoretical limit, and they also lack tissue specificity. Recently, the geometrical confinement of Gd3+-based contrast agents (CAs) within porous structures has been proposed as a novel, alternative strategy to improve relaxivity without chemical modification of the CA. Here, we have characterized and optimized the performance of MRI nanoconstructs obtained by loading [Gd(DTPA)(H2O)]2...

  20. Synthesis and evaluation of a high relaxivity manganese(II)-based MRI contrast agent.

    Science.gov (United States)

    Troughton, Jeffrey S; Greenfield, Matthew T; Greenwood, Jaclyn M; Dumas, Stéphane; Wiethoff, Andrea J; Wang, Jufeng; Spiller, Marga; McMurry, Thomas J; Caravan, Peter

    2004-10-04

    The manganese(II) ion has many favorable properties that lead to its potential use as an MRI contrast agent: high spin number, long electronic relaxation time, labile water exchange. The present work describes the design, synthesis, and evaluation of a novel Mn(II) complex (MnL1) based on EDTA and also contains a moiety that noncovalently binds the complex to serum albumin, the same moiety used in the gadolinium based contrast agent MS-325. Ultrafiltration albumin binding measurements (0.1 mM, pH 7.4, 37 degrees C) indicated that the complex binds well to plasma proteins (rabbit: 96 +/- 2% bound, human: 93 +/- 2% bound), and most likely to serum albumin (rabbit: 89 +/- 2% bound, human 98 +/- 2% bound). Observed relaxivities (+/- 5%) of the complex were measured (20 MHz, 37 degrees C, 0.1 mM, pH 7.4) in HEPES buffer (r(1) = 5.8 mM(-)(1) s(-)(1)), rabbit plasma (r(1) = 51 mM(-)(1) s(-)(1)), human plasma (r(1) = 46 mM(-)(1) s(-)(1)), 4.5% rabbit serum albumin (r(1) = 47 mM(-)(1) s(-)(1)), and 4.5% human serum albumin (r(1) = 48 mM(-)(1) s(-)(1)). The water exchange rate was near optimal for an MRI contrast agent (k(298) = 2.3 +/- 0.9 x 10(8) s(-)(1)). Variable temperature NMRD profiles indicated that the high relaxivity was due to slow tumbling of the albumin-bound complex and fast exchange of the inner sphere water. The concept of a high relaxivity Mn(II)-based contrast agent was validated by imaging at 1.5 T. In a rabbit model of carotid artery injury, MnL1 clearly delineated both arteries and veins while also distinguishing between healthy tissue and regions of vessel damage.

  1. Experimental system for perfusion imaging and time-intensity processing based on ultrasound contrast agent

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To present a self-developed experimental system for basic studies of blood perfusion imaging and time-intensity evaluating based on ultrasound contrast agent. Methods: The experimental system performed the image reconstruction and time-intensity processing with radio frequency signals. The system was comprised of ultra-high speed hardware data acquisition interface and low computational cost algorithms. The self-made contrast agent ,blood mimic phantom and capillary phantom model were used to validate the experimental system. Results: The images acquired in blood phantoms with linear-array and curve-array transducers were given. The time-intensity curves corresponding to selected region of interested from image sequence were demonstrated. It was also shown the time-intensity based decay curves and a comparison of decay of ultrasound contrast agent under different ultrasound powers. Conclusion: Several experiments resulted from two in vitro phantom models show that the experimental system can be used to basic studies of blood perfusion and further clinical studies of microvasculature perfusion.

  2. Design of water-based ferrofluids as contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Casula, Maria F; Corrias, Anna; Arosio, Paolo; Lascialfari, Alessandro; Sen, Tapas; Floris, Patrizia; Bruce, Ian J

    2011-05-01

    We report the synthesis, characterization and relaxometric study of ferrofluids based on iron oxide, with potential for use as magnetic resonance imaging (MRI) contrast agents (CAs). The effect of different cost-effective, water-based surface modification approaches which can be easily scaled-up for the large scale synthesis of the ferrofluids has been investigated. Surface modification was achieved by silanization, and/or coating with non-toxic commercial dispersants (a lauric polysorbate and a block copolymer with pigment affinic groups, namely Tween 20 and Disperbyk 190) which were added after or during iron oxide nanoparticle synthesis. It was observed that all the materials synthesized functioned as negative contrast agents at physiological temperature and at frequencies covered by clinical imagers. The relaxometric properties of the magnetic nanoparticles were significantly improved after surface coating with stabilizers compared to the original iron oxide nanoparticles, with particular reference to the silica-coated magnetic nanoparticles. The results indicate that the optimization of the preparation of colloidal magnetic ferrofluids by surface modification is effective in the design of novel contrast agents for MRI by enabling better or more effective interaction between the coated iron oxide nanoparticles and protons present in their aqueous environment.

  3. Determination of gadolinium-based MRI contrast agents in biological and environmental samples: A review

    Energy Technology Data Exchange (ETDEWEB)

    Telgmann, Lena [University of Münster, Institute of Inorganic and Analytical Chemistry, Münster (Germany); Sperling, Michael [University of Münster, Institute of Inorganic and Analytical Chemistry, Münster (Germany); European Virtual Institute for Speciation Analysis (EVISA), Münster (Germany); Karst, Uwe, E-mail: uk@uni-muenster.de [University of Münster, Institute of Inorganic and Analytical Chemistry, Münster (Germany)

    2013-02-18

    Highlights: ► All major methods for the analysis of Gd-based MRI contrast agents are discussed. ► Biological and environmental samples are covered. ► Pharmacokinetics and species transformation can be investigated. ► The figures of merit as limit of detection and analysis time are described. -- Abstract: The development of analytical methods and strategies to determine gadolinium and its complexes in biological and environmental matrices is evaluated in this review. Gadolinium (Gd) chelates are employed as contrast agents for magnetic resonance imaging (MRI) since the 1980s. In general they were considered as safe and well-tolerated, when in 2006, the disease nephrogenic systemic fibrosis (NSF) was connected to the administration of MRI contrast agents based on Gd. Pathogenesis and etiology of NSF are yet unclear and called for the development of several analytical methods to obtain elucidation in this field. Determination of Gd complex stability in vitro and in vivo, as well as the quantification of Gd in body fluids like blood and urine was carried out. Separation of the Gd chelates was achieved with high performance liquid chromatography (HPLC) and capillary electrophoresis (CE). For detection, various methods were employed, including UV–vis absorbance and fluorescence spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and inductively coupled plasma mass spectrometry (ICP-MS). A second challenge for analysts was the discovery of high concentrations of anthropogenic Gd in surface waters draining populated areas. The source could soon be determined to be the increasing administration of Gd complexes during MRI examinations. Identification and quantification of the contrast agents was carried out in various surface and groundwater samples to determine the behavior and fate of the Gd chelates in the environment. The improvement of limits of detection (LOD) and limits of quantification (LOQ) was and still is the goal of past and ongoing

  4. Tissue sensitive imaging and tomography without contrast agents for small animals with Timepix based detectors

    Science.gov (United States)

    Trojanova, E.; Schyns, L. E. J. R.; Ludwig, D.; Jakubek, J.; Le Pape, A.; Sefc, L.; Lotte, S.; Sykora, V.; Turecek, D.; Uher, J.; Verhaegen, F.

    2017-01-01

    The tissue type resolving X-ray radiography and tomography can be performed even without contrast agents. The differences between soft tissue types such as kidney, muscles, fat, liver, brain and spleen were measured based on their spectral response. The Timepix based X-ray imaging detector WidePIX2×5 with 300 μm thick silicon sensors was used for most of the measurements presented in this work. These promising results are used for further optimizations of the detector technology and radiographic methods.

  5. Fe3O4-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis

    Science.gov (United States)

    Liu, Jia; Xu, Jie; Zhou, Jun; Zhang, Yu; Guo, Dajing; Wang, Zhigang

    2017-01-01

    Thrombotic disease is a great threat to human health, and early detection is particularly important. Magnetic resonance (MR) molecular imaging provides noninvasive imaging with the potential for early disease diagnosis. In this study, we developed Fe3O4-based poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface-modified with a cyclic Arg-Gly-Asp (cRGD) peptide as an MR contrast agent for the detection of thrombosis. The physical and chemical characteristics, biological toxicity, ability to target thrombi, and biodistribution of the NPs were studied. The Fe3O4-PLGA-cRGD NPs were constructed successfully, and hematologic and pathologic assays indicated no in vivo toxicity of the NPs. In a rat model of FeCl3-induced abdominal aorta thrombosis, the NPs readily and selectively accumulated on the surface of the thrombosis and under vascular endothelial cells ex vivo and in vivo. In the in vivo experiment, the biodistribution of the NPs suggested that the NPs might be internalized by the macrophages of the reticuloendothelial system in the liver and the spleen. The T2 signal decreased at the mural thrombus 10 min after injection and then gradually increased until 50 min. These results suggest that the NPs are suitable for in vivo molecular imaging of thrombosis under high shear stress conditions and represent a very promising MR contrast agent for sensitive and specific detection of thrombosis. PMID:28223802

  6. BR1: A new ultrasonographic contrast agent based on sulfur hexafluoride-filled microbubbles

    Energy Technology Data Exchange (ETDEWEB)

    Scheider, M.; Arditi, M.; Barrau, M.B.

    1995-08-01

    Rationale and objectives. The basic characteristics of BR1, a novel echo contrast agent based on stabilized sulfur hexafluoride (SF{sub 6}) microbubbles have been evaluated. Methods. The authors determined the physicochemical properties (bubble concentration, bubble size distribution, resistance to pressure, and stability) and the acoustic properties (backscatter and attenuation coefficients) of BR1. The diagnostic value of BR1 was evaluated further in minipigs. Left heart images were recorded before and after injection of different doses of BR1. Results. BR1 is formulated as a lyophilized products, which after addition of saline, provides a suspension containing 2 X 10{sup 8} SF{sub 6} microbubbles/mL with a number mean diameter of 2.5 {mu}m. More than 90% of the bubbles are below 8 {mu}m. The use of SF{sub 6} rather than air provides an improved resistance to pressure increases such as the ones occuring in the left heart during systole. After reconstitution, the echogenicity and the bubble characteristics are unchanged for more than 8 hours. The high echogenicity remains almost constant over the entire medical frequency range (1-10 MH{sub Z}). BR1 injections in animals resulted in a homogenous, dose-dependent opacification of the left heart. Conclusions. Considering its high echogenicity, outstanding stability, and resistance to pressure changes, BR1 is a very promising ultrasound contrast agent. 14 refs., 8 figs., 3 tabs.

  7. Removal of gadolinium-based contrast agents: adsorption on activated carbon.

    Science.gov (United States)

    Elizalde-González, María P; García-Díaz, Esmeralda; González-Perea, Mario; Mattusch, Jürgen

    2017-01-31

    Three carbon samples were employed in this work, including commercial (1690 m(2) g(-1)), activated carbon prepared from guava seeds (637 m(2) g(-1)), and activated carbon prepared from avocado kernel (1068 m(2) g(-1)), to study the adsorption of the following gadolinium-based contrast agents (GBCAs): gadoterate meglumine Dotarem®, gadopentetate dimeglumine Magnevist®, and gadoxetate disodium Primovist®. The activation conditions with H3PO4 were optimized using a Taguchi methodology to obtain mesoporous materials. The best removal efficiency by square meter in a batch system in aqueous solution and model urine was achieved by avocado kernel carbon, in which mesoporosity prevails over microporosity. The kinetic adsorption curves were described by a pseudo-second-order equation, and the adsorption isotherms in the concentration range 0.5-6 mM fit the Freundlich equation. The chemical characterization of the surfaces shows that materials with a greater amount of phenolic functional groups adsorb the GBCA better. Adsorption strongly depends on the pH due to the combination of the following factors: contrast agent protonated forms and carbon surface charge. The tested carbon samples were able to adsorb 70-90% of GBCA in aqueous solution and less in model urine. This research proposes a method for the elimination of GBCA from patient urine before its discharge into wastewater.

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

    Science.gov (United States)

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

    2010-09-01

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

  9. Metal-based nanorods as molecule-specific contrast agents for reflectance imaging in 3D tissues

    OpenAIRE

    Javier, David J.; Nitin, Nitin; Roblyer, Darren M.; Richards-Kortum, Rebecca

    2008-01-01

    Anisotropic metal-based nanomaterials have been proposed as potential contrast agents due to their strong surface plasmon resonance. We evaluated the contrast properties of gold, silver, and gold-silver hybrid nanorods for molecular imaging applications in three-dimensional biological samples. We used diffuse reflectance spectroscopy to predict the contrast properties of different types of nanorods embedded in biological model systems of increasing complexity. The predicted contrast propertie...

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

    Science.gov (United States)

    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.

  11. Fe3O4-based PLGA nanoparticles as MR contrast agents for the detection of thrombosis

    Directory of Open Access Journals (Sweden)

    Liu J

    2017-02-01

    Full Text Available Jia Liu,1 Jie Xu,1 Jun Zhou,1 Yu Zhang,1 Dajing Guo,1 Zhigang Wang2 1Department of Radiology, 2Department of Ultrasound, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Yuzhong, Chongqing, People’s Republic of China Abstract: Thrombotic disease is a great threat to human health, and early detection is particularly important. Magnetic resonance (MR molecular imaging provides noninvasive imaging with the potential for early disease diagnosis. In this study, we developed Fe3O4-based poly(lactic-co-glycolic acid (PLGA nanoparticles (NPs surface-modified with a cyclic Arg-Gly-Asp (cRGD peptide as an MR contrast agent for the detection of thrombosis. The physical and chemical characteristics, biological toxicity, ability to target thrombi, and biodistribution of the NPs were studied. The Fe3O4-PLGA-cRGD NPs were constructed successfully, and hematologic and pathologic assays indicated no in vivo toxicity of the NPs. In a rat model of FeCl3-induced abdominal aorta thrombosis, the NPs readily and selectively accumulated on the surface of the thrombosis and under vascular endothelial cells ex vivo and in vivo. In the in vivo experiment, the biodistribution of the NPs suggested that the NPs might be internalized by the macrophages of the reticuloendothelial system in the liver and the spleen. The T2 signal decreased at the mural thrombus 10 min after injection and then gradually increased until 50 min. These results suggest that the NPs are suitable for in vivo molecular imaging of thrombosis under high shear stress conditions and represent a very promising MR contrast agent for sensitive and specific detection of thrombosis. Keywords: iron oxide, poly(lactic-co-glycolic acid, thrombosis, magnetic resonance imaging, cyclic Arg-Gly-Asp peptide

  12. Contrast-enhanced peripheral MRA. Technique and contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Nielsen, Yousef W. [Dept. of Radiology, Copenhagen Univ. Hospital Bispebjerg, Bispebjerg (Denmark)], e-mail: ywnielsen@gmail.com; Thomsen, Henrik S. [Dept. of Diagnostic Radiology, Copenhagen Univ. Hospital Herlev, Herlev (Denmark)

    2012-09-15

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

  13. Molecular MR Imaging of CD44 in Breast Cancer with Hyaluronan-Based Contrast Agents

    Science.gov (United States)

    2009-09-01

    macromolecule as a contrast agent for MR angiography: preparation, properties, and animal studies. Radiology 1993;187(3):701- 706. 6. Frenzel T...Investigative radiology 2008;43(12):817-828. 7. Sieber MA, Lengsfeld P, Frenzel T, Golfier S, Schmitt-Willich H, Siegmund F, Walter J, Weinmann HJ

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

    Directory of Open Access Journals (Sweden)

    Kim Hyo Jeong

    2010-01-01

    Full Text Available Abstract 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.

  15. In vivo dentate nucleus MRI relaxometry correlates with previous administration of Gadolinium-based contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Tedeschi, Enrico; Canna, Antonietta; Cocozza, Sirio; Russo, Carmela; Angelini, Valentina; Brunetti, Arturo [University ' ' Federico II' ' , Neuroradiology, Department of Advanced Biomedical Sciences, Naples (Italy); Palma, Giuseppe; Quarantelli, Mario [National Research Council, Institute of Biostructure and Bioimaging, Naples (Italy); Borrelli, Pasquale; Salvatore, Marco [IRCCS SDN, Naples (Italy); Lanzillo, Roberta; Postiglione, Emanuela; Morra, Vincenzo Brescia [University ' ' Federico II' ' , Department of Neurosciences, Reproductive and Odontostomatological Sciences, Naples (Italy)

    2016-12-15

    To evaluate changes in T1 and T2* relaxometry of dentate nuclei (DN) with respect to the number of previous administrations of Gadolinium-based contrast agents (GBCA). In 74 relapsing-remitting multiple sclerosis (RR-MS) patients with variable disease duration (9.8±6.8 years) and severity (Expanded Disability Status Scale scores:3.1±0.9), the DN R1 (1/T1) and R2* (1/T2*) relaxation rates were measured using two unenhanced 3D Dual-Echo spoiled Gradient-Echo sequences with different flip angles. Correlations of the number of previous GBCA administrations with DN R1 and R2* relaxation rates were tested, including gender and age effect, in a multivariate regression analysis. The DN R1 (normalized by brainstem) significantly correlated with the number of GBCA administrations (p<0.001), maintaining the same significance even when including MS-related factors. Instead, the DN R2* values correlated only with age (p=0.003), and not with GBCA administrations (p=0.67). In a subgroup of 35 patients for whom the administered GBCA subtype was known, the effect of GBCA on DN R1 appeared mainly related to linear GBCA. In RR-MS patients, the number of previous GBCA administrations correlates with R1 relaxation rates of DN, while R2* values remain unaffected, suggesting that T1-shortening in these patients is related to the amount of Gadolinium given. (orig.)

  16. Subharmonic imaging of contrast agents.

    Science.gov (United States)

    Forsberg, F; Shi, W T; Goldberg, B B

    2000-03-01

    Ultrasound contrast agents promise to improve the sensitivity and specificity of diagnostic ultrasound imaging. It is of great importance to adapt ultrasound equipment for optimal use with contrast agents e.g., by exploiting the nonlinear properties of the contrast microbubbles. Harmonic imaging is one technique that has been extensively studied and is commercially available. However, harmonic imaging is associated with problems, due to second harmonic generation and accumulation within the tissue itself. Given the lack of subharmonic generation in tissue, one alternative is the creation of subharmonic images by transmitting at the fundamental frequency (fo) and receiving at the subharmonic (fo/2). Subharmonic imaging should have a much better lateral resolution and may be suitable for scanning deep-lying structures owing to the higher transmit frequency and the much smaller attenuation of scattered subharmonic signals. In this paper, we will review different aspects of subharmonic imaging including implementation, in-vitro gray-scale imaging and subharmonic aided pressure estimation.

  17. Chitosan oligosaccharide based Gd-DTPA complex as a potential bimodal magnetic resonance imaging contrast agent.

    Science.gov (United States)

    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.

  18. Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent.

    Science.gov (United States)

    Ge, Pingju; Sheng, Fugeng; Jin, Yiguang; Tong, Li; Du, Lina; Zhang, Lei; Tian, Ning; Li, Gongjie

    2016-12-01

    Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd2-diethylenetriaminepentaacetate-bis(alendronate) (Gd2-DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pKa, complex constant, and T1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd2-DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd2-DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r1) of 7.613mM(-1)s(-1) (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd2-DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd2-DTPA-BA. The signal intensity of Gd2-DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd2-DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd2-DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  19. Design of a modular protein-based MRI contrast agent for targeted application.

    Directory of Open Access Journals (Sweden)

    Daniel Grum

    Full Text Available Magnetic resonance imaging (MRI offers a non-radioactive alternative for the non-invasive detection of tumours. Low molecular weight MRI contrast agents currently in clinical use suffer either from a lack of specificity for tumour tissue or from low relaxivity and thus low contrast amplification. In this study, we present the newly designed two domain fusion protein Zarvin, which is able to bind to therapeutic IgG antibodies suitable for targeting, while facilitating contrast enhancement through high affinity binding sites for Gd(3+. We show that the Zarvin fold is stable under serum conditions, specifically targets a cancer cell-line when bound to the Cetuximab IgG, and allows for imaging with high relaxivity, a property that would be advantageous for the detection of small tumours and metastases at 1.5 or 3 T.

  20. Peptide-based MRI contrast agent and near-infrared fluorescent probe for intratumoral legumain detection.

    Science.gov (United States)

    Chen, Yu-Jen; Wu, Shou-Cheng; Chen, Chung-Yung; Tzou, Shey-Cherng; Cheng, Tian-Lu; Huang, Ying-Fang; Yuan, Shyng-Shiou; Wang, Yun-Ming

    2014-01-01

    Recent studies suggest that intratumoral legumain promotes tumorigenesis. To monitor legumain activity in tumors, we developed a new MRI contrast agent ([Gd-NBCB-TTDA-Leg(L)]) and a NIR fluorescence probe (CyTE777-Leg(L)-CyTE807). The MRI contrast agent was prepared by introduction of cyclobutyl and benzyl group residues to TTDA (3,6,10-tri(carboxymethyl)-3,6,10-triaza-dodecanedioic acid), followed by the attachment of a legumain-specific substrate peptide (Leg(L)). The NIR fluorescence probe was designed by conjugating two NIR fluorochromes (CyTE777 and CyTE807) with Leg(L). Peptide cleavage of the MRI contrast agent by legumain can increase its hydrophobicity and promote rotational correlation time (τ(R)). Peptide cleavage of the NIR probes by the legumain relieves the self quench of the probe. Peptide cleavage of the MRI contrast agent and the NIR fluorescence probe by legumain were confirmed by T1 relaxometric studies and by fluorescence studies, respectively. In vivo MR images showed that [Gd-NBCB-TTDA-Leg(L)] attained 55.3 fold (254.2% versus 4.6%, at 2.0 h post-injection) higher imaging enhancement, as compared with control contrast agent bearing a noncleaveable peptide ([Gd-NBCB-TTDA-Leg(D)], in the CT-26 (legumain(+)) tumors. Similarly, optical imaging probe CyTE777-Leg(L)-CyTE807 attained 15.2 fold (3.34 × 10(9) photons/min versus 0.22 × 10(9) photons/min, at 24.0 h post-injection) higher imaging enhancement in the CT-26 (legumain(+)) tumors, compared to a NIR control probe (CyTE777-Leg(D)-CyTE807). These data indicate that the [Gd-NBCB-TTDA-Leg(L)] and the CyTE777-Leg(L)-CyTE807 probes may be promising tools to image the legumain-expressing cancers for diagnoses and targeted treatments.

  1. Imaging liver metastases with a new oral manganese-based contrast agent.

    NARCIS (Netherlands)

    Chabanova, E.; Logager, V.; Moller, J.M.; Dekker, H.M.; Barentsz, J.O.; Thomsen, H.S.

    2006-01-01

    RATIONALE AND OBJECTIVES: The purpose of the study was a preliminary evaluation of a new oral, manganese-based, liver-specific contrast medium (CMC-001; CMC Contrast AB, Malmoe, Sweden) for magnetic resonance imaging (MRI) in patients with liver metastases. MATERIALS AND METHODS: The study included

  2. Imaging liver metastases with a new oral manganese-based contrast agent.

    NARCIS (Netherlands)

    Chabanova, E.; Logager, V.; Moller, J.M.; Dekker, H.M.; Barentsz, J.O.; Thomsen, H.S.

    2006-01-01

    RATIONALE AND OBJECTIVES: The purpose of the study was a preliminary evaluation of a new oral, manganese-based, liver-specific contrast medium (CMC-001; CMC Contrast AB, Malmoe, Sweden) for magnetic resonance imaging (MRI) in patients with liver metastases. MATERIALS AND METHODS: The study included

  3. Technique: imaging earliest tooth development in 3D using a silver-based tissue contrast agent.

    Science.gov (United States)

    Raj, Muhammad T; Prusinkiewicz, Martin; Cooper, David M L; George, Belev; Webb, M Adam; Boughner, Julia C

    2014-02-01

    Looking in microscopic detail at the 3D organization of initiating teeth within the embryonic jaw has long-proved technologically challenging because of the radio-translucency of these tiny un-mineralized oral tissues. Yet 3D image data showing changes in the physical relationships among developing tooth and jaw tissues are vital to understand the coordinated morphogenesis of vertebrate teeth and jaws as an animal grows and as species evolve. Here, we present a new synchrotron-based scanning solution to image odontogenesis in 3D and in histological detail using a silver-based contrast agent. We stained fixed, intact wild-type mice aged embryonic (E) day 10 to birth with 1% Protargol-S at 37°C for 12-32 hr. Specimens were scanned at 4-10 µm pixel size at 28 keV, just above the silver K-edge, using micro-computed tomography (µCT) at the Canadian Light Source synchrotron. Synchrotron µCT scans of silver-stained embryos showed even the earliest visible stages of tooth initiation, as well as many other tissue types and structures, in histological detail. Silver stain penetration was optimal for imaging structures in intact embryos E15 and younger. This silver stain method offers a powerful yet straightforward approach to visualize at high-resolution and in 3D the earliest stages of odontogenesis in situ, and demonstrates the important of studying the tooth organ in all three planes of view. Copyright © 2013 Wiley Periodicals, Inc.

  4. Quantitative MRI for Analysis of Active Multiple Sclerosis Lesions without Gadolinium-Based Contrast Agent.

    Science.gov (United States)

    Blystad, I; Håkansson, I; Tisell, A; Ernerudh, J; Smedby, Ö; Lundberg, P; Larsson, E-M

    2016-01-01

    Contrast-enhancing MS lesions are important markers of active inflammation in the diagnostic work-up of MS and in disease monitoring with MR imaging. Because intravenous contrast agents involve an expense and a potential risk of adverse events, it would be desirable to identify active lesions without using a contrast agent. The purpose of this study was to evaluate whether pre-contrast injection tissue-relaxation rates and proton density of MS lesions, by using a new quantitative MR imaging sequence, can identify active lesions. Forty-four patients with a clinical suspicion of MS were studied. MR imaging with a standard clinical MS protocol and a quantitative MR imaging sequence was performed at inclusion (baseline) and after 1 year. ROIs were placed in MS lesions, classified as nonenhancing or enhancing. Longitudinal and transverse relaxation rates, as well as proton density were obtained from the quantitative MR imaging sequence. Statistical analyses of ROI values were performed by using a mixed linear model, logistic regression, and receiver operating characteristic analysis. Enhancing lesions had a significantly (P relaxation rate (1.22 ± 0.36 versus 0.89 ± 0.24), a higher mean transverse relaxation rate (9.8 ± 2.6 versus 7.4 ± 1.9), and a lower mean proton density (77 ± 11.2 versus 90 ± 8.4) than nonenhancing lesions. An area under the receiver operating characteristic curve value of 0.832 was obtained. Contrast-enhancing MS lesions often have proton density and relaxation times that differ from those in nonenhancing lesions, with lower proton density and shorter relaxation times in enhancing lesions compared with nonenhancing lesions. © 2016 by American Journal of Neuroradiology.

  5. Optically tunable nanoparticle contrast agents for early cancer detection: model-based analysis of gold nanoshells.

    Science.gov (United States)

    Lin, Alex W H; Lewinski, Nastassja A; West, Jennifer L; Halas, Naomi J; Drezek, Rebekah A

    2005-01-01

    Many optical diagnostic approaches rely on changes in scattering and absorption properties to generate optical contrast between normal and diseased tissue. Recently, there has been increasing interest in using exogenous agents to enhance this intrinsic contrast with particular emphasis on the development for targeting specific molecular features of disease. Gold nanoshells are a class of core-shell nanoparticles with an extremely tunable peak optical resonance ranging from the near-UV to the mid-IR wavelengths. Using current chemistries, nanoshells of a wide variety of core and shell sizes can easily be fabricated to scatter and/or absorb light with optical cross sections often several times larger than the geometric cross section. Using gold nanoshells of different size and optical parameters, we employ Monte Carlo models to predict the effect of varying concentrations of nanoshells on tissue reflectance. The models demonstrate the importance of absorption from the nanoshells on remitted signals even when the optical extinction is dominated by scattering. Furthermore, because of the strong optical response of nanoshells, a considerable change in reflectance is observed with only a very small concentration of nanoshells. Characterizing the optical behavior of gold nanoshells in tissue will aid in developing nanoshells as contrast agents for optical diagnostics.

  6. New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging

    Science.gov (United States)

    Yu, Shuai; Cheng, Bingbing; Yao, Tingfeng; Xu, Cancan; Nguyen, Kytai T.; Hong, Yi; Yuan, Baohong

    2016-10-01

    Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging.

  7. New generation ICG-based contrast agents for ultrasound-switchable fluorescence imaging

    Science.gov (United States)

    Yu, Shuai; Cheng, Bingbing; Yao, Tingfeng; Xu, Cancan; Nguyen, Kytai T.; Hong, Yi; Yuan, Baohong

    2016-01-01

    Recently, we developed a new technology, ultrasound-switchable fluorescence (USF), for high-resolution imaging in centimeter-deep tissues via fluorescence contrast. The success of USF imaging highly relies on excellent contrast agents. ICG-encapsulated poly(N-isopropylacrylamide) nanoparticles (ICG-NPs) are one of the families of the most successful near-infrared (NIR) USF contrast agents. However, the first-generation ICG-NPs have a short shelf life (6 months). In addition, we have conjugated hydroxyl or carboxyl function groups on the ICG-NPs for future molecular targeting. Finally, we have demonstrated the effect of temperature-switching threshold (Tth) and the background temperature (TBG) on the quality of USF images. We estimated that the Tth of the ICG-NPs should be controlled at ~38–40 °C (slightly above the body temperature of 37 °C) for future in vivo USF imaging. Addressing these challenges further reduces the application barriers of USF imaging. PMID:27775014

  8. Nephrogenic systemic fibrosis associated with gadolinium based contrast agents: A summary of the medical literature reporting

    Energy Technology Data Exchange (ETDEWEB)

    Broome, Dale R. [Department of Radiology, Loma Loma University Medical Center, 11234 Anderson Street, Room 2606, Loma Linda, CA 92354 (United States)], E-mail: dbroome@ahs.llumc.edu

    2008-05-15

    Nephrogenic systemic fibrosis (NSF) is a systemic fibrosing disorder that principally affects the skin, but can involve virtually any tissue in the human body and result in significant disability and even death. Since 2006 numerous retrospective case reports and case series have reported a very strong association of this disease with exposure to gadolinium-based contrast agents (Gd-CA) for MR imaging in the setting of severe or end-stage renal disease. The purpose of this report is to summarize the medical literature reporting of biopsy-proven NSF cases in which the authors specifically investigated patient exposure to Gd-CA. A Pub Med MEDLINE search was performed using the key words-nephrogenic systemic fibrosis and nephrogenic fibrosing dermopathy. All case reports and case series of NSF were reviewed to determine if patients had a preceding exposure to Gd-CA and which specific Gd-CA was involved. If the original reports did not clarify the specific Gd-CA, I reviewed follow-up letters to the editors or contacted the authors to clarify which specific Gd-CA were linked to the NSF cases. If several reports originated from the same institution, clarification was also obtained to avoid redundant reporting. As of February 1, 2008 there have been 190 biopsy-proven cases of NSF published in the peer-reviewed literature with the following associations: 157 gadodiamide (Omniscan, GE Healthcare), 8 gadopentetate (Magnevist, Bayer Healthcare), 3 gadoversetamide (OptiMARK, Covidien), and 18 unspecified Gd-CA, and 4 confounded cases with more than one Gd-CA. Five cases of NSF were unassociated with Gd-CA.

  9. Synthetic Approaches to Heterocyclic Ligands for Gd-Based MRI Contrast Agents

    Directory of Open Access Journals (Sweden)

    Paloma Ballesteros

    2007-08-01

    Full Text Available Magnetic Resonance Imaging (MRI methods are currently used in the clinic for the non invasive detection and characterization of a wide variety of pathologies. Increases in the diagnostic efficiency of MRI have been helped by both the design of dedicated MR sequences revealing specific aspects of the pathology and by the development of more sensitive and selective Contrast Agents (CAs, capable of more precisely delineating the borderline regions. In the present review we focus on the synthetic strategies used to obtain MRI CAs containing heterocyclic rings.

  10. Fabrication and evaluation of tumor-targeted positive MRI contrast agent based on ultrasmall MnO nanoparticles.

    Science.gov (United States)

    Huang, Haitao; Yue, Tao; Xu, Ke; Golzarian, Jafar; Yu, Jiahui; Huang, Jin

    2015-07-01

    Gd(III) chelate is currently used as positive magnetic resonance imaging (MRI) contrast agent in clinical diagnosis, but generally induces the risk of nephrogenic systemic fibrosis (NSF) due to the dissociated Gd(3+) from Gd(III) chelates. To develop a novel positive MRI contrast agent with low toxicity and high sensitivity, ultrasmall MnO nanoparticles were PEGylated via catechol-Mn chelation and conjugated with cRGD as active targeting function to tumor. Particularly, the MnO nanoparticles with a size of ca. 5nm were modified by α,β-poly(aspartic acid)-based graft polymer containing PEG and DOPA moieties and, meanwhile, conjugated with cRGD to produce the contrast agent with a size of ca. 100nm and a longitudinal relaxivity (r1) of 10.2mM(-1)S(-1). Such nanoscaled contrast agent integrated passive- and active-targeting function to tumor, and its efficient accumulation behavior in tumor was verified by in vivo distribution study. At the same time, the PEG moiety played a role of hydrophilic coating to improve the biocompatibility and stability under storing and physiological conditions, and especially might guarantee enough circulation time in blood. Moreover, in vivo MRI revealed a good and long-term effect of enhancing MRI signal for as-fabricated contrast agent while cell viability assay proved its acceptable cytotoxicity for MRI application. On the whole, the as-fabricated PEGylated and cRGD-functionalized contrast agent based on ultrasmall MnO nanoparticles showed a great potential to the T1-weighted MRI diagnosis of tumor.

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

    Science.gov (United States)

    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.

  12. An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis.

    Directory of Open Access Journals (Sweden)

    Bin Zhang

    Full Text Available Nephrogenic systemic fibrosis (NSF is a rare but serious disorder disease affecting patients with advanced renal disease. Although multiple studies have indicated an association between gadolinium-based contrast agents (GBCAs and NSF, some studies published after 2007 found no association. We therefore performed a meta-analysis to evaluate the association and analyze related (cofactors.Studies for analysis were identified by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 2014. Pooled odds ratios (OR with 95% confidence intervals (CI were calculated using the fixed-effects model. Statistical heterogeneity was assessed by Q statistics and the I2 test. Publication bias was evaluated using Begg's test, Egger's test, funnel plot, and classic fail-safe N. Study quality was assessed using the Newcastle-Ottawa Scale. We also conducted sensitivity analyses, subgroup analyses and a cumulative meta-analysis. All statistical analyses were performed using Comprehensive Meta-Analysis 2.0.A total of 14 studies (6,398 patients met the inclusion criteria, but 3 were excluded since they reported no NSF events. Meta-analysis of controlled trials indicated a significant association between GBCAs and NSF development (OR = 16.504; 95% CI: 7.455-36.533; P < 0.001 and between gadodiamide and NSF (OR = 20.037; 95% CI: 3.725-107.784; P < 0.001. No statistical heterogeneity was observed across studies (P = 0.819, I2 = 0%; P = 0.874, I2 = 0%, respectively. Cumulative analysis demonstrated that the pooled ORs for association between GBCAs and NSF decreased post-2007 compared to pre-2007 (OR = 26.708; 95% CI: 10.273-69.436; P<0.001.Although this updated meta-analysis found a significant association between GBCAs and the incidence of NSF in patients with advanced renal disease, the association decreased after 2007. More studies, especially randomized controlled trials, are warranted to examine the potential association

  13. An Updated Study to Determine Association between Gadolinium-Based Contrast Agents and Nephrogenic Systemic Fibrosis

    Science.gov (United States)

    Zhang, Bin; Liang, Long; Chen, Wenbo; Liang, Changhong; Zhang, Shuixing

    2015-01-01

    Background Nephrogenic systemic fibrosis (NSF) is a rare but serious disorder disease affecting patients with advanced renal disease. Although multiple studies have indicated an association between gadolinium-based contrast agents (GBCAs) and NSF, some studies published after 2007 found no association. We therefore performed a meta-analysis to evaluate the association and analyze related (co)factors. Methods Studies for analysis were identified by searching PubMed, Embase, and the Cochrane Central Register of Controlled Trials through December 2014. Pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed-effects model. Statistical heterogeneity was assessed by Q statistics and the I2 test. Publication bias was evaluated using Begg’s test, Egger’s test, funnel plot, and classic fail-safe N. Study quality was assessed using the Newcastle-Ottawa Scale. We also conducted sensitivity analyses, subgroup analyses and a cumulative meta-analysis. All statistical analyses were performed using Comprehensive Meta-Analysis 2.0. Results A total of 14 studies (6,398 patients) met the inclusion criteria, but 3 were excluded since they reported no NSF events. Meta-analysis of controlled trials indicated a significant association between GBCAs and NSF development (OR = 16.504; 95% CI: 7.455–36.533; P < 0.001) and between gadodiamide and NSF (OR = 20.037; 95% CI: 3.725–107.784; P < 0.001). No statistical heterogeneity was observed across studies (P = 0.819, I2 = 0%; P = 0.874, I2 = 0%, respectively). Cumulative analysis demonstrated that the pooled ORs for association between GBCAs and NSF decreased post-2007 compared to pre-2007 (OR = 26.708; 95% CI: 10.273–69.436; P<0.001). Conclusions Although this updated meta-analysis found a significant association between GBCAs and the incidence of NSF in patients with advanced renal disease, the association decreased after 2007. More studies, especially randomized controlled trials, are warranted

  14. Time-domain imaging with quench-based fluorescent contrast agents

    Science.gov (United States)

    Akers, Walter J.; Solomon, Metasebya; Sudlow, Gail P.; Berezin, Mikhail; Achilefu, Samuel

    2012-03-01

    Quench-based probes utilize unique characteristics of fluorescence resonance energy transfer (FRET) to enhance contrast upon de-quenching. This mechanism has been used in a variety of molecular probes for imaging of cancer related enzyme activity such as matrix metalloproteinases, cathepsins and caspases. While non-fluorescent upon administration, fluorescence can be restored by separation of donor and acceptor, resulting in higher intensity in the presence of activator. Along with decreased quantum yield, FRET also results in altered fluorescence lifetime. Time-domain imaging can further enhance contrast and information yield from quench-based probes. We present in vivo time-domain imaging for detecting activation of quench-based probes. Quench-based probes utilize unique characteristics of fluorescence resonance energy transfer (FRET) to enhance contrast upon de-quenching. This mechanism has been used in a variety of molecular probes for imaging of cancer related enzyme activity such as matrix metalloproteinases, cathepsins and caspases. While non-fluorescent upon administration, fluorescence can be restored by separation of donor and acceptor, resulting in higher intensity in the presence of activator. Along with decreased quantum yield, FRET also results in altered fluorescence lifetime. Time-domain imaging can further enhance contrast and information yield from quench-based probes. We present in vivo time-domain imaging for detecting activation of quench-based probes. Time-domain diffuse optical imaging was performed to assess the FRET and quenching in living mice with orthotopic breast cancer. Tumor contrast enhancement was accompanied by increased fluorescence lifetime after administration of quenched probes selective for matrix metalloproteinases while no significant change was observed for non-quenched probes for integrin receptors. These results demonstrate the utility of timedomain imaging for detection of cancer-related enzyme activity in vivo.

  15. Use of intravital microscopy to study the microvascular behavior of microbubble-based ultrasound contrast agents.

    Science.gov (United States)

    Schneider, Michel; Broillet, Anne; Tardy, Isabelle; Pochon, Sibylle; Bussat, Philippe; Bettinger, Thierry; Helbert, Alexandre; Costa, Maria; Tranquart, François

    2012-04-01

    The study describes the use of intravital microscopy (IVM) to assess the behavior of ultrasound contrast agents (UCAs), including targeted UCAs, in the microcirculation of rodents. IVM was performed on various exteriorized organs: hamster cheek pouch, rat mesentery, liver, spinotrapezius muscle, and mouse cremaster muscle. A dorsal skin-fold chamber with MatBIII tumor cells was also implanted in rats. Nontargeted UCAs (SonoVue(®) and BR14) and targeted UCAs (BR55 and P-selectin targeted microbubbles) were tested. IVM was used to measure microbubble size, determine their persistence, and observe their behavior in the blood circulation. Intravenous and intra-arterial injections of high doses of UCAs did not modify the local microvascular hemodynamics. No microbubble coalescence and no increased size were observed. Adhesion of some microbubbles to leukocytes was observed in various microcirculation models. Microbubbles are captured by Kupffer cells in the liver. Targeted microbubbles were shown to adhere specifically to endothelial receptors without compromising local blood flow. These results support the safety of both targeted and nontargeted UCAs as no microvascular flow alteration or plugging of microvessels were observed. They confirm that binding observed with targeted microbubbles are due to the binding of these microbubbles to specific endothelial receptors. © 2012 John Wiley & Sons Ltd.

  16. [Method for Extracting Vascular Perfusion Region Based on Ultrasound Contrast Agent].

    Science.gov (United States)

    Shan, Xin; Wen, Yingang; Lin, Tao; Zhu, Xinjian

    2015-10-01

    Vascular perfusion distribution in fibroids contrast-enhanced ultrasound images provides useful pathological and physiological information, because the extraction of the vascular perfusion area can be helpful to quantitative evaluation of uterine fibroids blood supply. The pixel gray scale in vascular perfusion area of fibroids contrast-enhanced ultrasound image sequences is different from that in other regions, and, based on this, we proposed a method of extracting vascular perfusion area of fibroids. Firstly, we denoised the image sequence, and then we used Brox optical flow method to estimate motion of two adjacent frames, based on the results of the displacement field for motion correction. Finally, we extracted vascular perfusion region from the surrounding background based on the differences in gray scale for the magnitude of the rich blood supply area and lack of blood supply area in ultrasound images sequence. The experimental results showed that the algorithm could accurately extract the vascular perfusion area, reach the precision of identification of clinical perfusion area, and only small amount of calculation was needed and the process was fairly simple.

  17. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    Science.gov (United States)

    Sinharay, Sanhita; Pagel, Mark D.

    2016-06-01

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

  18. A new manganese-based oral contrast agent (CMC-001) for liver MRI. Pharmacological and pharmaceutical aspects

    Energy Technology Data Exchange (ETDEWEB)

    Joergensen, Jan Troest [Research and Development, CMC Contrast AB, Scion DTU, Lyngby (Denmark)], email: jtj@cmc-contrast.dk; Rief, Matthias; Wagner, Moritz [Dept. of Radiology, Charite - Universitaetsmedizin Berlin, Berlin (Germany); Brismar, Torkel B.; Albiin, Nils [Dept. of Radiology, Karolinska Inst., Karolinska Univ. Hospital, Stockholm (Sweden)

    2012-09-15

    Manganese is one of the most abundant metals on earth and is found as a component of more than 100 different minerals. Besides being an essential trace element in relation to the metabolic processes in the body, manganese is also a paramagnetic metal that possesses similar characteristics to gadolinium with regards to T1-weighted (T1-w) magnetic resonance imaging (MRI). Manganese, in the form of manganese (II) chloride tetrahydrate, is the active substance in a new targeted oral contrast agent, currently known as CMC-001, indicated for hepatobiliary MRI. Under physiological circumstances manganese is poorly absorbed from the intestine after oral intake, but by the use of specific absorption promoters, L-alanine and vitamin D3, it is possible to obtain a sufficiently high concentration in the liver in order to achieve a significant signal enhancing effect. In the liver manganese is exposed to a very high first-pass effect, up to 98 %, which prevents the metal from reaching the systemic circulation, thereby reducing the number of systemic side-effects. Manganese is one of the least toxic trace elements, and due to its favorable safety profile it may be an attractive alternative to gadolinium-based contrast agents for patients undergoing an MRI evaluation for liver metastases in the future. In this review the basic pharmacological and pharmaceutical aspects of this new targeted oral hepatobiliary specific contrast agent will be discussed.

  19. A new manganese-based oral contrast agent (CMC-001) for liver MRI: pharmacological and pharmaceutical aspects.

    Science.gov (United States)

    Jørgensen, Jan Trøst; Rief, Matthias; Brismar, Torkel B; Wagner, Moritz; Albiin, Nils

    2012-09-01

    Manganese is one of the most abundant metals on earth and is found as a component of more than 100 different minerals. Besides being an essential trace element in relation to the metabolic processes in the body, manganese is also a paramagnetic metal that possesses similar characteristics to gadolinium with regards to T1-weighted (T1-w) magnetic resonance imaging (MRI). Manganese, in the form of manganese (II) chloride tetrahydrate, is the active substance in a new targeted oral contrast agent, currently known as CMC-001, indicated for hepatobiliary MRI. Under physiological circumstances manganese is poorly absorbed from the intestine after oral intake, but by the use of specific absorption promoters, L-alanine and vitamin D(3), it is possible to obtain a sufficiently high concentration in the liver in order to achieve a significant signal enhancing effect. In the liver manganese is exposed to a very high first-pass effect, up to 98%, which prevents the metal from reaching the systemic circulation, thereby reducing the number of systemic side-effects. Manganese is one of the least toxic trace elements, and due to its favorable safety profile it may be an attractive alternative to gadolinium-based contrast agents for patients undergoing an MRI evaluation for liver metastases in the future. In this review the basic pharmacological and pharmaceutical aspects of this new targeted oral hepatobiliary specific contrast agent will be discussed.

  20. Intra-individual comparison of different gadolinium-based contrast agents in the quantitative evaluation of C6 glioma with dynamic contrast-enhanced magnetic resonance imaging.

    Science.gov (United States)

    Li, Ying; Liu, Gang; Lou, Xin; Chen, Zhiye; Ma, Lin

    2017-01-01

    This experiment aimed to compare the ionic (Gadodiamide, Gd-DTPA-BMA) and non-ionic (Gadopentetate dimeglumine, Gd-DTPA) gadolinium-based contrast agents (GBCA) in the quantitative evaluation of C6 glioma with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). A C6 glioma model was established in 12 Wistar rats, and magnetic resonance (MR) scans were performed six days after tumor implantation. Imaging was performed using a 3.0-T MR scanner with a 7-inch handmade circular coil. Pre-contrast T1 mapping and dynamic contrast-enhanced T1WI after a bolus injection (0.2 mL s(-1)) of GBCA at 0.4 mmol kg(-1) were performed. Each rat received two DCE-MRI scans, 24 h apart. The first and second scans were performed using Gd-DTPA-BMA and Gd-DTPA, respectively. Image data were processed using the Patlak model. Both K (trans) and V p maps were generated. Tumors were manually segmented on all 3D K (trans) and V p maps. Pixel counts and mean values were recorded for use in a paired t-test. Three radiologists independently performed the tumor segmentation and value calculation. The agreements from different observers were subjective to the intra-class correlation coefficient (ICC). Readers demonstrated that the pixel counts of tumors in K (trans) maps were higher with Gd-DTPA-BMA than with Gd-DTPA (P0.05, all readers). The pixel counts of tumors in V p maps, as well as V p values, showed no obvious difference between the two agents (P>0.05, all readers). Excellent interobserver measurement reproducibility and reliability were demonstrated in the ICC tests. The Gd-DTPA-BMA contrast agent had significantly higher pixel counts of glioma in the K (trans) maps, and an increased tendency for average K (trans) values, indicating that DCE-MRI with Gd-DTPA-BMA may be more suitable and sensitive for the evaluation of glioma.

  1. HyperCEST detection of a 129Xe-based contrast agent composed of cryptophane-A molecular cages on a bacteriophage scaffold.

    Science.gov (United States)

    Stevens, Todd K; Palaniappan, Krishnan K; Ramirez, R Matthew; Francis, Matthew B; Wemmer, David E; Pines, Alex

    2013-05-01

    A hyperpolarized 129Xe contrast agent composed of many cryptophane-A molecular cages assembled on an M13 bacteriophage has been demonstrated. Saturation of xenon bound in the large number of cryptophane cages is transferred to the pool of aqueous-solvated xenon via chemical exchange, resulting in efficient generation of hyperCEST contrast. No significant loss of contrast per cryptophane cage was observed for the multivalent phage when compared with unscaffolded cryptophane. Detection of this phage-based hyperCEST agent is reported at concentrations as low as 230 fM, representing the current lower limit for NMR/MRI-based contrast agents.

  2. Study on gadolinium complexes based on polysaccharide derivatives as a contrast agent for MRI

    Energy Technology Data Exchange (ETDEWEB)

    Hashiguchi, Yuji; Seri, Shigemi; Kubomura, Kan; Abe, Yukiko; Kamimura, Kenji; Fujimoto, Chieko; Iguchi, Toshio; Iwai, Kumiko (Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba (Japan))

    1993-05-01

    The authors report new gadolinium compounds, polysaccharide-gadolinium chelate, that have the enhancement property in magnetic resonance imaging (MRI) as well as a longer half-life time in blood. Dialdehyde starch (DAS ; mol. wt. 7 x 10[sup 3]) and dialdehyde amylose (DAA ; mol. wt. 3 x 10[sup 3]) were synthesized to increase the half-life time in blood. The binding of gadolinium to DAS or DAA was facilitated by the newly synthesized bifunctional chelating agents N-[2-bis(carboxymethyl)aminoethyl] -N-[2-bis(carboxymethyl)amino -2(p-benzyl)ethyl]glycine (ABDTPA) and 10-[N-(2-aminoethyl)carbamoyl]methyl-[alpha], [alpha]', [alpha]''-trimethyl-1,4,7,10 -tetraazacyclododecane-1,4,7-triacetic acid (DO 3 MA). The enhancement properties of resulting gadolinium compounds were evaluated for biodistribution, relaxivity and enhancement effect. Biodistribution was examined by use of [sup 111]In labelled complex. Relaxivity was measured at 0.5T and 1.5T. Enhancement effect was examined in vivo by using rats that have brain occlusions. Gadolinium(Gd) complexes with DAS or DAA were found to be staying in the blood vessel for a longer period of time than other existing enhancers. The half-life time of DAS-ABDTPA-Gd is 2h, while as DAA-ABDTPA-Gd is 55 min, eighty to ninety percent of gadolinium complexes bound to DAS or DAA were excreted in urine 24 h after administration. Relaxivities of the above gadolinium complexes were 1.2[approx]2 times as high as those of ABDTPA-Gd or DO 3 MA-Gd. These results demonstrate that gadolinium complexes based on polysaccharide derivatives are promising compounds for future use as MRI enhancers. (author).

  3. Facile Preparation of a New Gadofullerene-Based Magnetic Resonance Imaging Contrast Agent with High 1H Relaxivity

    OpenAIRE

    Shu, Chunying; Corwin, Frank D.; Zhang, Jianfei; Chen, Zhijian; Reid, Jonathan E.; Sun, Minghao; Xu, Wei; Sim, Jae Hyun; Wang, Chunru; Fatouros, Panos P.; Alan R Esker; Gibson, Harry W.; Dorn, Harry C.

    2009-01-01

    A new magnetic resonance imaging (MRI) contrast agent based on the trimetallic nitride templated (TNT) metallofullerene, Gd3N@C80, was synthesized by a facile method in high yield. The observed longitudinal and transverse relaxivities, r1 and r2, for water hydrogens in the presence of the water-soluble gadofullerene 2, Gd3N@C80(OH)~26(CH2CH2COOM)~16 (M = Na or H), are 207 and 282 mM-1s-1 (per C80 cage) at 2.4 T, respectively; these values are 50 times larger than those of Gd3+ poly(aminocarbo...

  4. Quantifying activation of perfluorocarbon-based phase-change contrast agents using simultaneous acoustic and optical observation.

    Science.gov (United States)

    Li, Sinan; Lin, Shengtao; Cheng, Yi; Matsunaga, Terry O; Eckersley, Robert J; Tang, Meng-Xing

    2015-05-01

    Phase-change contrast agents in the form of nanoscale droplets can be activated into microbubbles by ultrasound, extending the contrast beyond the vasculature. This article describes simultaneous optical and acoustical measurements for quantifying the ultrasound activation of phase-change contrast agents over a range of concentrations. In experiments, decafluorobutane-based nanodroplets of different dilutions were sonicated with a high-pressure activation pulse and two low-pressure interrogation pulses immediately before and after the activation pulse. The differences between the pre- and post-interrogation signals were calculated to quantify the acoustic power scattered by the microbubbles activated over a range of droplet concentrations. Optical observation occurred simultaneously with the acoustic measurement, and the pre- and post-microscopy images were processed to generate an independent quantitative indicator of the activated microbubble concentration. Both optical and acoustic measurements revealed linear relationships to the droplet concentration at a low concentration range <10(8)/mL when measured at body temperature. Further increases in droplet concentration resulted in saturation of the acoustic interrogation signal. Compared with body temperature, room temperature was found to produce much fewer and larger bubbles after ultrasound droplet activation.

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

    Science.gov (United States)

    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.

  6. Nano/microparticles and ultrasound contrast agents

    Institute of Scientific and Technical Information of China (English)

    Shu-Guang; Zheng; Hui-Xiong; Xu; Hang-Rong; Chen

    2013-01-01

    Microbubbles have been used for many years now in clinical practice as contrast agents in ultrasound imaging.Recently,their therapeutic applications have also attracted more attention.However,the short circulation time(minutes)and relatively large size(two to ten micrometers)of currently used commercial microbubbles do not allow effective extravasation into tumor tissue,preventing efficient tumor targeting.Fortunately,more multifunctional and theranostic nanoparticles with some special advantages over the traditional microbubbles have been widely investigated and explored for biomedical applications.The way to synthesize an ideal ultrasound contrast agent based on nanoparticles in order to achieve an expected effect on contrast imaging is a key technique.Currently a number of nanomaterials,including liposomes,polymers,micelles,dendrimers,emulsions,quantum dots,solid nanoparticles etc.,have already been applied to pre or clinical trials.Multifunctional and theranostic nanoparticles with some special advantages,such as the tumor-targeted(passive or active),multi-mode contrast agents(magnetic resonance imaging,ultrasonography or fluorescence),carrier or enhancer of drug delivery,and combined chemo or thermal therapy etc.,are rapidly gaining popularity and have shown a promising application in the field of cancer treatment.In this mini review,the trends and the advances of multifunctional and theranostic nanoparticles are briefly discussed.

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

    Science.gov (United States)

    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.

  8. Subharmonic and ultraharmonic emissions based on the nonlinear oscillation of encapsulated microbubbles in ultrasound contrast agents

    Institute of Scientific and Technical Information of China (English)

    GONG Yanjun; ZHANG Dong; GONG Xiufen

    2005-01-01

    Subharmonics or ultraharmonics provides better contrast-to-tissue ratio (CTR) than the fundamental or the second harmonics, having prospective application in medical diagnosis. In this paper, subharmonic and ultraharmonic emissions are theoretically studied through nonlinear oscillation of encapsulated bubbles. The optimized frequencies for emissions of the subharmonics and ultraharmonics are discussed. In addition, sound pressure dependences of the subharmonics and ultraharmonics are studied in theory as well as in measurement. Results reveal that the developments of both subharmonics and ultraharmonics have the same trend, i.e. occurrence, growth and saturation, but the generation of ultraharmonic is a little earlier than that of subharmonic.

  9. Facile Preparation of a New Gadofullerene-Based Magnetic Resonance Imaging Contrast Agent with High 1H Relaxivity

    Science.gov (United States)

    Shu, Chunying; Corwin, Frank D.; Zhang, Jianfei; Chen, Zhijian; Reid, Jonathan E.; Sun, Minghao; Xu, Wei; Sim, Jae Hyun; Wang, Chunru; Fatouros, Panos P.; Esker, Alan R.; Gibson, Harry W.; Dorn, Harry C.

    2009-01-01

    A new magnetic resonance imaging (MRI) contrast agent based on the trimetallic nitride templated (TNT) metallofullerene, Gd3N@C80, was synthesized by a facile method in high yield. The observed longitudinal and transverse relaxivities, r1 and r2, for water hydrogens in the presence of the water-soluble gadofullerene 2, Gd3N@C80(OH)~26(CH2CH2COOM)~16 (M = Na or H), are 207 and 282 mM-1s-1 (per C80 cage) at 2.4 T, respectively; these values are 50 times larger than those of Gd3+ poly(aminocarboxylate) complexes, such as commercial Omniscan® and Magnevist®. This high 1H relaxivity for this new hydroxylated and carboxylated gadofullerene derivative provides high signal enhancement at significantly lower Gd concentration as demonstrated by in vitro and in vivo MRI studies. Dynamic light scattering data reveal a unimodal size distribution with an average hydrodynamic radius of ca. 78 nm in pure water (pH = 7), which is significantly different from other hydroxylated or carboxylated fullerene and metallofullerene derivatives reported to date. Agarose gel infusion results indicate that the gadofullerene 2 displayed diffusion properties different from that of commercial Omniscan® and those of PEG5000 modified Gd3N@C80. The reactive carboxyl functionality present on this highly efficient contrast agent may also serve as a precursor for biomarker tissue-targeting purposes. PMID:19445504

  10. Implementation of a phase detection algorithm for dynamic cardiac computed tomography analysis based on time dependent contrast agent distribution.

    Directory of Open Access Journals (Sweden)

    Carsten Kendziorra

    Full Text Available This paper presents a phase detection algorithm for four-dimensional (4D cardiac computed tomography (CT analysis. The algorithm detects a phase, i.e. a specific three-dimensional (3D image out of several time-distributed 3D images, with high contrast in the left ventricle and low contrast in the right ventricle. The purpose is to use the automatically detected phase in an existing algorithm that automatically aligns the images along the heart axis. Decision making is based on the contrast agent distribution over time. It was implemented in KardioPerfusion--a software framework currently being developed for 4D CT myocardial perfusion analysis. Agreement of the phase detection algorithm with two reference readers was 97% (95% CI: 82-100%. Mean duration for detection was 0.020 s (95% CI: 0.018-0.022 s, which was 800 times less than the readers needed (16±7 s, p<03001. Thus, this algorithm is an accurate and fast tool that can improve work flow of clinical examinations.

  11. The in vivo radiosensitizing effect of gold nanoparticles based MRI contrast agents.

    Science.gov (United States)

    Miladi, Imen; Alric, Christophe; Dufort, Sandrine; Mowat, Pierre; Dutour, Aurélie; Mandon, Céline; Laurent, Gautier; Bräuer-Krisch, Elke; Herath, Nirmitha; Coll, Jean-Luc; Dutreix, Marie; Lux, François; Bazzi, Rana; Billotey, Claire; Janier, Marc; Perriat, Pascal; Le Duc, Géraldine; Roux, Stéphane; Tillement, Olivier

    2014-03-26

    Owing to the high atomic number (Z) of gold element, the gold nanoparticles appear as very promising radiosensitizing agents. This character can be exploited for improving the selectivity of radiotherapy. However, such an improvement is possible only if irradiation is performed when the gold content is high in the tumor and low in the surrounding healthy tissue. As a result, the beneficial action of irradiation (the eradication of the tumor) should occur while the deleterious side effects of radiotherapy should be limited by sparing the healthy tissue. The location of the radiosensitizers is therefore required to initiate the radiotherapy. Designing gold nanoparticles for monitoring their distribution by magnetic resonance imaging (MRI) is an asset due to the high resolution of MRI which permits the accurate location of particles and therefore the determination of the optimal time for the irradiation. We recently demonstrated that ultrasmall gold nanoparticles coated by gadolinium chelates (Au@DTDTPA-Gd) can be followed up by MRI after intravenous injection. Herein, Au@DTDTPA and Au@DTDTPA-Gd were prepared in order to evaluate their potential for radiosensitization. Comet assays and in vivo experiments suggest that these particles appear well suited for improving the selectivity of the radiotherapy. The dose which is used for inducing similar levels of DNA alteration is divided by two when cells are incubated with the gold nanoparticles prior to the irradiation. Moreover, the increase in the lifespan of tumor bearing rats is more important when the irradiation is performed after the injection of the gold nanoparticles. In the case of treatment of rats with a brain tumor (9L gliosarcoma, a radio-resistant tumor in a radiosensitive organ), the delay between the intravenous injection and the irradiation was determined by MRI.

  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].

    Science.gov (United States)

    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. Manganese-based contrast agents for MRI%锰对比剂在MRI中的应用

    Institute of Scientific and Technical Information of China (English)

    曾庆斌; 郭茜旎; 罗晴; 吴光耀; 周欣

    2014-01-01

    It is always a challenge to keep improving the contrast of MRI (magnetic resonance imaging) for different tissues and organs in order to detect diseases. Contrast agents, which can enhance the relaxation of protons in water, are usually used to overcome such issue. Gadolinium-based complexes are the most predominantly used contrast agents owing to its good enhancement effect on the relaxation time, but they may be caused a serious disease called nephrogenic systemic ifbrosis (NSF), so they have a limited use in vivo. Manganese is a non-lanthanide paramagnetic metal, and possess a good enhancement effect on the relaxation due to ifve unpaired electrons of bivalent manganese. Manganese-based contrast agents include manganese salts, small organic chelates, macromolecule chelates, oxide nanopaticles and so on. Manganese has also play essential roles in cell biology and very low toxic in vivo, which enables the usage with a large dose in MRI. This paper reviews the recent applications and comments the future outlook of manganese-based contrast agents for MRI.%MRI所面临的一个主要问题是如何提高信号对比度,进而区分病灶与正常的组织和器官,从而达到医学诊断的目的,为了解决这个问题往往就要用到可以加快水质子弛豫的试剂。一般常用的MRI弛豫增强试剂都是含钆类的化合物,因为钆具有很强的顺磁弛豫增强能力。但是钆类对比剂有可能引起肾源性系统性纤维化,因此钆类对比剂的使用也具有一定的局限性。锰也是一种顺磁性金属,其毒性非常低,是生物体内一种必须的元素,二价的锰有5个未成对电子,也具有较强的弛豫增强效果;另外锰对比剂的存在形式比较多样化,比如锰盐、小分子有机螯合物、大分子螯合物、氧化物纳米粒子等,并且锰对比剂毒性相对较低,因此在使用时可以较大剂量的使用。正因如此,锰的对比剂在MRI中也占有一定

  14. Physical characterization methods for iron oxide contrast agents encapsulated within a targeted liposome-based delivery system

    Energy Technology Data Exchange (ETDEWEB)

    Dagata, J A; Farkas, N; Dennis, C L; Shull, R D; Hackley, V A [National Institute of Standards and Technology, Gaithersburg, MD 20899 (United States); Yang, C; Pirollo, K F; Chang, E H [Department of Oncology, Georgetown University Medical Center, 2700 Reservoir Road, Washington, DC 20017 (United States)], E-mail: john.dagata@nist.gov

    2008-07-30

    Intact liposome-based targeted nanoparticle delivery systems (NDS) are immobilized by non-selective binding and characterized by scanning probe microscopy (SPM) in a fluid imaging environment. The size, size distribution, functionality, and stability of an NDS with a payload consisting of a super-paramagnetic iron oxide contrast agent for magnetic resonance imaging are determined. SPM results are combined with information obtained by more familiar techniques such as superconducting quantum interference device (SQUID) magnetometry, dynamic light scattering, and electron microscopy. By integrating the methods presented in this work into the NDS formulation and manufacturing process, size-dependent statistical properties of the complex can be obtained and the structure-function relationship of individual, multi-component nanoscale entities can be assessed in a reliable and reproducible manner.

  15. In vivo detection of copper ions by magnetic resonance imaging using a prion-based contrast agent.

    Science.gov (United States)

    Makino, Satoshi; Umemoto, Tomohiro; Yamada, Hiroshi; Yezdimer, Eric M; Tooyama, Ikuo

    2012-10-01

    Abnormal distributions of transition metals inside the body are potential diagnostic markers for several diseases, including Alzheimer's disease, Parkinson's disease, Wilson's disease, and cancer. In this article, we demonstrate that P57/Gd, a novel prion-based contrast agent, can selectively image tissues with excessive copper accumulation using magnetic resonance imaging (MRI). P57/Gd selectivity binds copper(II) over other physiologically relevant cations such as zinc, iron, manganese, and calcium. To simulate a metabolic copper disorder, we treated mice with an intraperitoneal injection of a CuSO(4) solution to induce a renal copper overload. The MRI signal intensities from the renal cortex and medulla of copper spiked animals that were administered P57/Gd were found to correlate with the ex vivo copper concentrations determined by inductively coupled plasma mass spectrometry.

  16. Gadolinium deposition within the dentate nucleus and globus pallidus after repeated administrations of gadolinium-based contrast agents - current status

    Energy Technology Data Exchange (ETDEWEB)

    Stojanov, Dragan [University of Nis, Faculty of Medicine, Nis (Serbia); Center for Radiology, Nis (Serbia); Aracki-Trenkic, Aleksandra [Center for Radiology, Nis (Serbia); Benedeto-Stojanov, Daniela [University of Nis, Faculty of Medicine, Nis (Serbia)

    2016-05-15

    Gadolinium-based contrast agents (GBCAs) have been used clinically since 1988 for contrast-enhanced magnetic resonance imaging (CE-MRI). Generally, GBCAs are considered to have an excellent safety profile. However, GBCA administration has been associated with increased occurrence of nephrogenic systemic fibrosis (NSF) in patients with severely compromised renal function, and several studies have shown evidence of gadolinium deposition in specific brain structures, the globus pallidus and dentate nucleus, in patients with normal renal function. Gadolinium deposition in the brain following repeated CE-MRI scans has been demonstrated in patients using T1-weighted unenhanced MRI and inductively coupled plasma mass spectroscopy. Additionally, rodent studies with controlled GBCA administration also resulted in neural gadolinium deposits. Repeated GBCA use is associated with gadolinium deposition in the brain. This is especially true with the use of less-stable, linear GBCAs. In spite of increasing evidence of gadolinium deposits in the brains of patients after multiple GBCA administrations, the clinical significance of these deposits continues to be unclear. Here, we discuss the current state of scientific evidence surrounding gadolinium deposition in the brain following GBCA use, and the potential clinical significance of gadolinium deposition. There is considerable need for further research, both to understand the mechanism by which gadolinium deposition in the brain occurs and how it affects the patients in which it occurs. (orig.)

  17. Is the transport of a gadolinium-based contrast agent decreased in a degenerated or aged disc? A post contrast MRI study.

    Directory of Open Access Journals (Sweden)

    Marta Tibiletti

    Full Text Available 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.

  18. High-speed optical observations of contrast agent destruction

    NARCIS (Netherlands)

    Bouakaz, Ayache; Versluis, Michel; Jong, de Nico

    2005-01-01

    Ultrasound contrast agents are now available since a few years and used for diagnostic purposes. Improved diagnostic decisions have been made possible with new imaging methods that are mainly based on the nonlinear properties of gas microbubbles. Since it is well known that contrast agents are destr

  19. Magnetic Resonance Imaging Contrast Agents: A Review of Literature

    Directory of Open Access Journals (Sweden)

    Zahra Sahraei

    2015-10-01

    Full Text Available  Magnetic Resonance Imaging (MRI contrast agents most commonly agents used in diagnosing different diseases. Several agents have been ever introduced with different peculiar characteristics. They vary in potency, adverse reaction and other specification, so it is important to select the proper agent in different situations. We conducted a systematic literature search in MEDLINE/PUBMED, Web of Science (ISI, Scopus,Google Scholar by using keywords "gadolinium" and "MRI contrast Medias", "Gadofosvest", "Gadobenate" and "Gadoxetate". The most frequent contrast media agents made based on gadolinium (Gd. These are divided into two categories based on the structure of their chelating parts, linear agents and macrocyclic agents. All characteristics of contrast media factors, including efficiency, kinetic properties, stability, side effects and the rate of resolution are directly related to the structure of chelating part of that formulation.In vitro data has shown that the macrocyclic compounds are the most stable Gd-CA as they do not bind to serum proteins, they all possess similar and relatively low relaxivity and the prevalence of Nephrogenic Systemic Fibrosis (NSF has decreased by increasing the use of macrocyclic agents in recent years. No cases of NSF have been recorded after the administration of any of the high-relaxivity protein interacting agents, the vascular imaging agent gadofosveset trisodium (Ablavar, the hepatic imaging agent gadoxetate meglumine (Eovist, and the multipurpose agent gadobenate dimeglumine (MultiHance. In pregnancy and lactating women, stable macrocyclic agent is recommended.

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

    Science.gov (United States)

    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.

  1. Exploring a new SPION-based MRI contrast agent with excellent water-dispersibility, high specificity to cancer cells and strong MR imaging efficacy.

    Science.gov (United States)

    Ma, Xuehua; Gong, An; Chen, Bin; Zheng, Jianjun; Chen, Tianxiang; Shen, Zheyu; Wu, Aiguo

    2015-02-01

    Advances in contrast agents have greatly enhanced the sensitivity of magnetic resonance imaging (MRI) technique for early diagnosis of cancer. However, the commercial superparamagnetic iron oxide nanoparticles (SPION)-based contrast agents synthesized by co-precipitation method are not monodisperse with irregular morphologies and ununiform sizes. Other reported SPION-based contrast agents synthesized by solvothermal method or thermal decomposition method are limited by the bad water-dispersibility and low specificity to cancer cells. Herein, we propose a new strategy for exploring SPION-based MRI contrast agents with excellent water-dispersibility and high specificity to cancer cells. The SPION was synthesized by a polyol method and then entrapped into albumin nanospheres (AN). After that, a ligand folic acid (FA) was conjugated onto the surface of the AN to construct a SPION-AN-FA composite. The transmission electron microscope (TEM) and dynamic light scattering (DLS) results indicate that the SPION-AN-FA has a spherical shape, a uniform size and an excellent water-dispersibility (polydispersity index (PDI) contrast agent.

  2. Definition of contrast enhancement phases of the liver using a perfluoro-based microbubble agent, perflubutane microbubbles.

    Science.gov (United States)

    Shunichi, Sasaki; Hiroko, Iijima; Fuminori, Moriyasu; Waki, Hidehiko

    2009-11-01

    To define the contrast enhancement phases in the liver with perflubutane microbubbles, the liver enhancement time-intensity curves were investigated in 14 healthy volunteers. The agent was injected intravenously as a bolus and the liver was imaged with an ultrasound scanner as long as 4h after the injection. Time-intensity curves from the hepatic artery, the intrahepatic portal vein, the hepatic vein and the parenchyma of the liver were obtained from the liver ultrasound images. The arrival of the agent in the hepatic artery, the portal vein and the hepatic vein were visually distinguishable and the mean arrival times were 19.2, 24.3 and 32.2 s after the injection, respectively. The signal intensity in these vessels increased rapidly after the arrival of the contrast and gradually reverted to baseline after the peak. In contrast, within 5 min after the injection, the intensity in the parenchyma increased and reached a plateau, which persisted for at least 2h. The contrast enhancement phases in the liver with perflubutane microbubbles could be defined as two major phases-a vascular phase, in which the vessels are enhanced between 15 s and 10 min after injection, and a Kupffer phase, in which the parenchyma is enhanced 10 min after injection. The vascular phase is divided into three subphases: the arterial phase (15 to 45 s after injection); the portal phase (45 s to 1 min after injection); and the vasculo-Kupffer phase (1 to 10 min after injection).

  3. Basic MR relaxation mechanisms and contrast agent design.

    Science.gov (United States)

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

    2015-09-01

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

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

    Science.gov (United States)

    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.

  5. Process for preparation of MR contrast agents

    DEFF Research Database (Denmark)

    2002-01-01

    The present invention provides a process for the preparation of an MR contrast agent, said process comprising: i) obtaining a solution in a solvent of a hydrogenatable, unsaturated substrate compound and a catalyst for the hydrogenation of said substrate compound; ii) introducing said solution...... in droplet form into a chamber containing hydrogen gas (H2) enriched in para-hydrogen (p-1H2) and/or ortho-deuterium (o-2H2) whereby to hydrogenate said substrate to form a hydrogenated imaging agent; iii) optionally subjecting said hydrogenated imaging agent to a magnetic field having a field strength below...

  6. GADOLINIUM(Gd)-BASED and Ion Oxide Nanoparticle Contrast Agents for Pre-Clinical and Clinical Magnetic Resonance Imaging (mri) Research

    Science.gov (United States)

    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.

  7. 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

    OpenAIRE

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

    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 o...

  8. Nonspherical Oscillations of Ultrasound Contrast Agent Microbubbles

    NARCIS (Netherlands)

    Dollet, Benjamin; Meer, van der Sander M.; Garbin, Valeria; Jong, de Nico; Lohse, Detlef; Versluis, Michel

    2008-01-01

    The occurrence of nonspherical oscillations (or surface modes) of coated microbubbles, used as ultrasound contrast agents in medical imaging, is investigated using ultra–high-speed optical imaging. Optical tweezers designed to micromanipulate single bubbles in 3-D are used to trap the bubbles far fr

  9. Superhydrophobic silica nanoparticles as ultrasound contrast agents.

    Science.gov (United States)

    Jin, Qiaofeng; Lin, Chih-Yu; Kang, Shih-Tsung; Chang, Yuan-Chih; Zheng, Hairong; Yang, Chia-Min; Yeh, Chih-Kuang

    2017-05-01

    Microbubbles have been widely studied as ultrasound contrast agents for diagnosis and as drug/gene carriers for therapy. However, their size and stability (lifetime of 5-12min) limited their applications. The development of stable nanoscale ultrasound contrast agents would therefore benefit both. Generating bubbles persistently in situ would be one of the promising solutions to the problem of short lifetime. We hypothesized that bubbles could be generated in situ by providing stable air nuclei since it has been found that the interfacial nanobubbles on a hydrophobic surface have a much longer lifetime (orders of days). Mesoporous silica nanoparticles (MSNs) with large surface areas and different levels of hydrophobicity were prepared to test our hypothesis. It is clear that the superhydrophobic and porous nanoparticles exhibited a significant and strong contrast intensity compared with other nanoparticles. The bubbles generated from superhydrophobic nanoparticles sustained for at least 30min at a MI of 1.0, while lipid microbubble lasted for about 5min at the same settings. In summary MSNs have been transformed into reliable bubble precursors by making simple superhydrophobic modification, and made into a promising contrast agent with the potentials to serve as theranostic agents that are sensitive to ultrasound stimulation. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Ultrasonic characterization of ultrasound contrast agents

    NARCIS (Netherlands)

    N. de Jong (Nico); M. Emmer (Marcia); A. van Wamel (Annemieke); M. Versluis (Michel)

    2009-01-01

    textabstractThe main constituent of an ultrasound contrast agent (UCA) is gas-filled microbubbles. An average UCA contains billions per ml. These microbubbles are excellent ultrasound scatterers due to their high compressibility. In an ultrasound field they act as resonant systems, resulting in

  11. Acoustic properties of ultrasound contrast agents

    NARCIS (Netherlands)

    N. de Jong (Nico)

    1993-01-01

    textabstractSafety of contrast agents is reported in the years after. Both the intracoronary use of sonicated Renografin as well as intravenous use of commercial product as Albunex and Lechovist has been investigated. Thereafter more pathophysiologic studies were performed. Ten Cate described the po

  12. Advanced detection strategies for ultrasound contrast agents

    NARCIS (Netherlands)

    J.M.G. Borsboom (Jerome)

    2005-01-01

    markdownabstract__Abstract__ Ultrasound contrast agent was discovered serendipitously by Gramiak and Shah in I968 when they injected indocyanine green dye into the heart and observed increased echogenicity of the blood containing the dye. Small cavitation bubbles that were formed upon injection of

  13. In vivo long-term magnetic resonance imaging activity of ferritin-based magnetic nanoparticles versus a standard contrast agent.

    Science.gov (United States)

    Valero, Elsa; Fiorini, Silvia; Tambalo, Stefano; Busquier, Heriberto; Callejas-Fernández, José; Marzola, Pasquina; Gálvez, Natividad; Domínguez-Vera, José M

    2014-07-10

    New long-circulating maghemite nanoparticles of 4 and 6 nm, coated with an apoferritin protein capsid, exhibit useful properties to act as magnetic resonance imaging (MRI) contrast agents. A full in vivo study of the so-called apomaghemites reveals that their long-term MRI properties are better than those of a standard superparamagnetic iron oxide (SPIO) widely used in biomedical applications. The biodistribution of apomaghemites and standard SPIO was investigated by MRI in mice at two different concentrations, 6 and 2.5 mg of Fe·kg(-1), over 60 days. Significant differences are found at low dose (2.5 mg of Fe·kg(-1)). Thus, whereas apomaghemites are active for MR bioimaging of liver for 45 days, standard SPIO is not effective beyond 7 days. On the basis of our data, we may concluded that apomaghemites can act as new long-term MRI liver contrast agents, allowing first the diagnosis of a liver pathology and then monitoring after treatment without the need for a second injection.

  14. BR55: a lipopeptide-based VEGFR2-targeted ultrasound contrast agent for molecular imaging of angiogenesis.

    Science.gov (United States)

    Pochon, Sibylle; Tardy, Isabelle; Bussat, Philippe; Bettinger, Thierry; Brochot, Jean; von Wronski, Mathew; Passantino, Lisa; Schneider, Michel

    2010-02-01

    BR55, an ultrasound contrast agent functionalized with a heterodimer peptide targeting the vascular endothelial growth factor receptor 2 (VEGFR2), was evaluated in vitro and in vivo, demonstrating its potential for specific tumor detection. The targeted contrast agent was prepared by incorporation of a biospecific lipopeptide into the microbubble membrane. Experiments were performed in vitro to demonstrate the binding capacities of BR55 microbubbles on immobilized receptor proteins and on various endothelial or transfected cells expressing VEGFR2. The performance of BR55 microbubbles was compared with that of streptavidin-conjugated microbubbles targeted to the same receptor by coupling them to a biotinylated antibody. The specificity of BR55 binding to human and mouse endothelial cells was determined in competition experiments with the free lipopeptide, vascular endothelial growth factor (VEGF), or a VEGFR2-specific antibody. Molecular ultrasound imaging of VEGFR2 was performed in an orthotopic breast tumor model in rats using a nondestructive, contrast-specific imaging mode. BR55 was shown to bind specifically to the immobilized recombinant VEGFR2 under flow (dynamic conditions). BR55 accumulation on the target over time was similar to that of microbubbles bearing a specific antibody. BR55 avidly bound to cells expressing VEGFR2, and the pattern of microbubble distribution was correlated with the pattern of receptor expression determined by immunocytochemistry. The binding of targeted microbubbles on cells was competed off by an excess of free lipopeptide, the natural ligand (VEGF) and by a VEGFR2-specific antibody (P < 0.001). Although selected for the human receptor, the VEGFR2-binding lipopeptide was also shown to recognize the rodent receptor. Tumor perfusion was assessed during the vascular phase of BR55, and then the malignant lesion was highlighted by specific accumulation of the targeted microbubbles on tumoral endothelium. The presence of VEGFR2 was

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

    Science.gov (United States)

    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.

  16. An accurate homogenized tissue phantom for broad spectrum autofluorescence studies: a tool for optimizing quantum dot-based contrast agents

    Science.gov (United States)

    Roy, Mathieu; Wilson, Brian C.

    2008-02-01

    We are investigating the use of ZnS-capped CdSe quantum dot (QD) bioconjugates combined with fluorescence endoscopy for improved early cancer detection in the esophagus, colon and lung. A major challenge in using fluorescent contrast agents in vivo is to extract the relevant signal from the tissue autofluorescence (AF). The present studies are aimed at maximizing the QD signal to AF background ratio (SBR) to facilitate detection. These contrast optimization studies require optical phantoms that simulate tissue autofluorescence, absorption and scattering over the entire visible spectrum, while allowing us to control the optical thickness. We present an optical phantom made of fresh homogenized tissue diluted in water. The homogenized tissue is poured into a clear polymer tank designed to hold a QD-loaded silica capillary in its center. Because of the non-linear effects of absorption and scattering on measured autofluorescence, direct comparison between results obtained using tissue phantoms of different concentration is not possible. We introduce mathematical models that make it possible to perform measurements on diluted tissue homogenates and subsequently extrapolate the results to intact (non-diluted) tissue. Finally, we present preliminary QD contrast data showing that the 380-420 nm spectral window is optimal for surface QD imaging.

  17. Biodistribution of newly synthesized PHEA-based polymer-coated SPION in Sprague Dawley rats as magnetic resonance contrast agent

    Directory of Open Access Journals (Sweden)

    Park J

    2013-10-01

    polymer was metabolized by the kidney and excreted mainly in the urine; [59Fe] was recycled for erythrocyte production in the spleen and excreted mainly in the feces. The MR image of the liver after intravenous injection demonstrated that [Fe] effectively accumulated in the liver and exhibited high-contrast enhancement on T2-weighted images. Conclusion: This newly synthesized, polymer-coated SPION appears to be a promising candidate for use as a liver-targeted, biocompatible iron oxide MR imaging agent. Keywords: SPION, radiolabeled, polyhydroxyethylaspartamide, pharmacokinetic, liver

  18. Liver-targeting macromolecular MRI contrast agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Macromolecular ligands with liver-targeting group (pyridoxamine, PM) PHEA-DTPA-PM and PAEA-DTPA-PM were prepared by the incorporation of different amount of diethylenetriaminepentaacetic acid monopyridoxamine group (DTPA-PM) into poly-a, b-[N-(2-hydroxyethyl)-L- aspartamide] (PHEA) and poly-a, b-[N-(2-aminoethyl)-L-aspartamide] (PAEA). The macromolecular ligands thus obtained were further complexed with gadolinium chloride to give macromolecular MRI contrast agents with different Gd(Ⅲ) contents. These macromolecular ligands and their gadolinium complexes were characterized by 1H NMR, IR, UV and elementary analysis. Relaxivity studies showed that these polyaspartamide gadolinium complexes possess higher relaxation effectiveness than that of the clinically used Gd-DTPA. Magnetic resonance imaging of the liver in rats and experimental data of biodistribution in mice indicate that these macromolecular MRI contrast agents containing pyridoxamine exhibit liver-targeting property.

  19. Gadobutrol: an alternative contrast agent for digital subtraction dacryocystography

    Energy Technology Data Exchange (ETDEWEB)

    Priebe, M.; Mohr, A.; Brossmann, J.; Heller, M.; Frahm, C. [Department of Diagnostic Radiology, Christian-Albrechts-University of Kiel, Arnold-Heller-Strasse 9, 24105 Kiel (Germany)

    2002-08-01

    We report the application of gadobutrol as a contrast medium for digital subtraction dacryocystography (DS-DCG) in patients with known allergy to iodinated contrast agent. Gadobutrol has the double gadolinium concentration (1.0 mmol/ml) of other gadolinium-based contrast agents. Quality of the DS-DCG images obtained with gadobutrol was comparable to DS-DCG images obtained with iodinated contrast medium. Radiodensity measurements using a micro-CT scanner confirmed a high radiodensity of gadobutrol which was comparable to the radiodensity of iopentol with a iodine concentration of 250 mg/ml and only approximately 20% lower than the radiodensity of iopentol with a concentration of 300 mg/l. Gadobutrol is a well-suited substitute for DS-DCG in patients with allergy to iodinated contrast agents. (orig.)

  20. Ultrasound contrast agents for ultrasound molecular imaging.

    Science.gov (United States)

    Tranquart, F; Arditi, M; Bettinger, T; Frinking, P; Hyvelin, J M; Nunn, A; Pochon, S; Tardy, I

    2014-11-01

    Ultrasound is a real-time imaging technique which is widely used in many clinical applications for its capacity to provide anatomic information with high spatial and temporal resolution. The advent of ultrasound contrast agents in combination with contrast-specific imaging modes has given access to perfusion assessments at an organ level, leading to an improved diagnostic accuracy. More recently, the development of biologically-targeted ultrasound contrast agents has expanded the role of ultrasound even further into molecular imaging applications. Ultrasound molecular imaging can be used to visualize the expression of intravascular markers, and to assess their local presence over time and/or during therapeutic treatment. Major applications are in the field of inflammation and neoangiogenesis due to the strictly intravascular presence of microbubbles. Various technologies have been investigated for attaching the targeting moiety to the shell from simple biotin-avidin constructs to more elaborated insertion within the shell through attachment to PEG residues. This important improvement has allowed a clinical translation of initial pre-clinical investigations, opening the way for an early detection and an accurate characterization of lesions in patients. The combination of anatomic, functional and molecular information/data provided by contrast ultrasound is a powerful tool which is still in its infancy due to the lack of agents suitable for clinical use. The advantages of ultrasound techniques combined with the molecular signature of lesions will represent a significant advance in imaging in the field of personalized medicine. © Georg Thieme Verlag KG Stuttgart · New York.

  1. Nephrogenic systemic fibrosis after application of gadolinium-based contrast agents - a status paper; Nephrogene systemische Fibrose nach Anwendung gadoliniumhaltiger Kontrastmittel - ein Statuspapier zum aktuellen Stand des Wissens

    Energy Technology Data Exchange (ETDEWEB)

    Heinrich, M.; Uder, M. [Erlangen-Nuernberg Univ., Erlangen (Germany). Inst. fuer Radiologie

    2007-06-15

    Recently the association of a rare disease named ''nephrogenic systemic fibrosis'' (NSF) with the administration of gadolinium-containing contrast media, especially gadodiamide (Omniscan, GE-Healthcare), was described. NSF is a scleroderma-like disease characterised by widespread tissue fibrosis. Until now, NSF cases were observed only in patients with kidney disease. Almost all patients were suffering from chronic renal insufficiency, 90 % of them required renal replacement therapy. The true incidence of the disease is unknown. First retrospective analyses of selected collectives of patients with end-stage renal disease showed 2 - 5 % cases of NSF after administration of Gadolinium-containing contrast agents with an odds ratio of 20 - 50 in comparison to non-exposed controls. NSF is a serious adverse reaction, which may result in severe disabilities and even death. Therefore all radiologists applying gadolinium-based contrast agents should be informed about this disease and the recent recommendations for its prevention. On the basis of the published data, Omniscan should not be used in patients with severe renal impairment (GFR < 30 ml/min/1.73 m{sup 2}) and those who have had or are undergoing liver transplantation. In neonates and infants up to 1 year of age, Omniscan should only be used after careful consideration. Also the other gadolinium-based contrast agents should be used in high-risk patients only after careful consideration using the lowest dose possible.

  2. Experimental approbation of a new ultrosound contrast agent based on sulfur geksafluoride in diagnostics of focal liver lesions of inflammatory genesis

    Directory of Open Access Journals (Sweden)

    S. V. Fomina

    2017-01-01

    Full Text Available Purpose of the study. Experimental approbation of a new domestic ultrasound contrast agent (UCA based on sulfur hexafluoride in the diagnosis of focal liver lesions of inflammatory genesis.Materials and methods. The investigated ultrasound contrast agent (UCA was a heterogeneous gas-liquid system consisting of micro bubbles of a sparingly soluble gas of sulfur hexafluoride (SF6 surrounded by a flexible mobile membrane of surfactants. Experimental work was carried out on rabbits. The study group included rabbits of males and females with focal liver lesion of inflammatory genesis (n = 12 weighing 1500- 1700 g. UCA was administered to animals in the ear vein. Focal lesions of the liver in animals were created in the experimental laboratory conditions. 14 days after the operation, all animals were subjected to ultrasound examination of the surgical intervention zones by using the Toshiba Aplio 400 scanners (Japan with a 3,5–8 MHz convection sensor. In a natural study, the size, structure and echogenicity of the focus were assessed, the degree of vascularization, the evenness and clarity of the contours were determined. When performing post contrast ultrasound, the time of the onset of contrast enhancement, the total duration of contrast, the changes in the contrast enhancement of the focus in different phases of the study were measured, the dimensions of the focus were measured, and the evenness and acuity of contours were measured. For histological examination, liver fragments and lungs were used. 

  3. Use of gadolinium-based magnetic resonance imaging contrast agents and awareness of brain gadolinium deposition among pediatric providers in North America

    Energy Technology Data Exchange (ETDEWEB)

    Mithal, Leena B. [Northwestern University, Feinberg School of Medicine, Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Patel, Payal S. [University of Arizona College of Medicine, Department of Pediatrics, Phoenix, AZ (United States); Mithal, Divakar [Northwestern University, Feinberg School of Medicine, Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Pediatric Neurology, Chicago, IL (United States); Palac, Hannah L. [Northwestern University, Biostatistics, Feinberg School of Medicine, Ann and Robert H. Lurie Children' s Hospital of Chicago, Chicago, IL (United States); Rozenfeld, Michael N. [University of Arizona College of Medicine, Department of Radiology, Phoenix, AZ (United States)

    2017-05-15

    Numerous recent articles have reported brain gadolinium deposition when using linear but not macrocyclic gadolinium-based contrast agents (GBCAs). To determine the current landscape of gadolinium use among pediatric institutions and the knowledge base of radiologists and referring providers with regard to GBCAs and brain gadolinium deposition. We e-mailed voluntary closed surveys to 5,390 physicians in various pediatric professional societies between January 2016 and March 2016. We used chi-square and Fisher exact tests to compare response distributions among specialties. We found that 80% of surveyed pediatric hospitals use macrocyclic contrast agents. In the last year, 58% switched their agent, most commonly to gadoterate meglumine, with the most common reason being brain gadolinium deposition. Furthermore, surveys indicated that 23% of hospitals are considering switching, and, of these, 83% would switch to gadoterate meglumine; the most common reasons were brain gadolinium deposition and safety. Radiologists were more aware of brain gadolinium deposition than non-radiologist physicians (87% vs. 26%; P<0.0001). Radiologists and referring providers expressed similar levels of concern (95% and 89%). Twelve percent of radiologists and 2% of referring providers reported patients asking about brain gadolinium deposition. Radiologists were significantly more comfortable addressing patient inquiries than referring pediatric physicians (48% vs. 6%; P<0.0001). The number of MRIs requested by referring pediatric physicians correlated with their knowledge of brain gadolinium deposition, contrast agent used by their hospital, and comfort discussing brain gadolinium deposition with patients (P<0.0001). Since the discovery of brain gadolinium deposition, many pediatric hospitals have switched to or plan to switch to a more stable macrocyclic MR contrast agent, most commonly gadoterate meglumine. Despite this, there is need for substantial further education of radiologists and

  4. Multiwalled carbon nanotube hybrids as MRI contrast agents

    Directory of Open Access Journals (Sweden)

    Nikodem Kuźnik

    2016-07-01

    Full Text Available 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.

  5. Acoustic Nonlinear Behaviour of Microbubble Contrast Agent

    Institute of Scientific and Technical Information of China (English)

    俞金飞; 陆荣荣; 龚秀芬; 石涛

    2002-01-01

    We have investigated the nonlinear characteristics of a microbubble contrast agent Sonazoid R (Nycomed,Norway), including the second, third, 1/2-order, 3/2-order and 5/2-order harmonics. We have measured the 1/2-order subharmonic response to different transmission sound pressures. We have found that subharmonic signals cannot be generated until the acoustic pressure reaches a certain value, which is the most different subharmonic from high harmonics. This result is favourable for the further study of the subharmonic in the bubbly liquid.The 3/2-order ultraharmonic response to acoustic pressure was also measured.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  7. Photoacoustic cell for ultrasound contrast agent characterization

    Science.gov (United States)

    Alippi, A.; Bettucci, A.; Biagioni, A.; D'Orazio, A.; Germano, M.; Passeri, D.

    2010-10-01

    Photoacoustics has emerged as a tool for the study of liquid gel suspension behavior and has been recently employed in a number of new biomedical applications. In this paper, a photoacoustic sensor is presented which was designed and realized for analyzing photothermal signals from solutions filled with microbubbles, commonly used as ultrasound contrast agents in echographic imaging techniques. It is a closed cell device, where photothermal volume variation of an aqueous solution produces the periodic deflection of a thin membrane closing the cell at the end of a short pipe. The cell then acts as a Helmholtz resonator, where the displacement of the membrane is measured through a laser probe interferometer, whereas photoacoustic signal is generated by a laser chopped light beam impinging onto the solution through a glass window. Particularly, the microbubble shell has been modeled through an effective surface tension parameter, which has been then evaluated from experimental data through the shift of the resonance frequencies of the photoacoustic sensor. This shift of the resonance frequencies of the photoacoustic sensor caused by microbubble solutions is high enough for making such a cell a reliable tool for testing ultrasound contrast agent, particularly for bubble shell characterization.

  8. Methods for blood flow measurements using ultrasound contrast agents

    Science.gov (United States)

    Fowlkes, J. Brian

    2003-10-01

    Blood flow measurements using ultrasound contrast agents are being investigated for myocardial perfusion and more recently in other organ systems. The methods are based largely on the relative increase in echogenicity due to the concentration of bubbles present in the ultrasound beam. In the simplest form, regional differences in blood volume can be inferred but the possibility exists to extract perfusion from the transit of contrast agent through tissue. Perfusion measurements rely on determining the flux of blood through a tissue volume and as such require knowledge of the fractional blood volume (FBV), i.e., ml blood/g tissue and the rate of exchange, commonly measured as the mean transit time (MTT). This presentation will discuss methods of determining each of these values and their combination to estimate tissue perfusion. Underlying principles of indicator-dilution theory will be provided in the context of ultrasound contrast agents. Current methods for determining MTT will include imaging of the intravenous bolus, in-plane contrast disruption with interval and real-time contrast recovery imaging, and control of contrast agent flow using arterial disruption (contrast interruption). The advantages and limitations of the methods will be examined along with current applications. [Work supported in part by NIH.

  9. Hybrid material as contrast agent in magnetic resonance images

    OpenAIRE

    Botella Asunción, Pablo; Cabrera García, Alejandro

    2015-01-01

    [EN] The invention relates to a contrast agent of magnetic resonance based on a hybrid material formed by an organo-metallic core derived from Prussian blue and a silica cover, and optionally, molecules of a poly(ethylene glycol), a fluorescent agent, a radio nucleus and/or a substance that directs to specific receptors, cells or tissues, joined by covalent bonding to the surface of the inorganic cover.

  10. Hybrid material as contrast agent in magnetic resonance images

    OpenAIRE

    Botella Asunción, Pablo; Cabrera García, Alejandro

    2015-01-01

    [EN] The invention relates to a contrast agent of magnetic resonance based on a hybrid material formed by an organo-metallic core derived from Prussian blue and a silica cover, and optionally, molecules of a poly(ethylene glycol), a fluorescent agent, a radio nucleus and/or a substance that directs to specific receptors, cells or tissues, joined by covalent bonding to the surface of the inorganic cover.

  11. TAILORING X-RAY BEAM ENERGY SPECTRUM TO ENHANCE IMAGE QUALITY OF NEW RADIOGRAPHY CONTRAST AGENTS BASED ON GD OR OTHER LANTHANIDES.

    Energy Technology Data Exchange (ETDEWEB)

    DILMANIAN,F.A.; WEINMANN,H.J.; ZHONG,Z.; BACARIAN,T.; RIGON,L.; BUTTON,T.M.; REN,B.; WU,X.Y.; ZHONG,N.; ATKINS,H.L.

    2001-02-17

    Gadovist, a 1.0-molar Gd contrast agent from Schering AG, Berlin Germany, in use in clinical MPI in Europe, was evaluated as a radiography contrast agent. In a collaboration with Brookhaven National Laboratory (BNL), Schering AG is developing several such lanthanide-based contrast agents, while BNL evaluates them using different x-my beam energy spectra. These energy spectra include a ''truly'' monochromatic beam (0.2 keV energy bandwidth) from the National Synchrotron Light Source (NSLS), BNL, tuned above the Gd K-edge, and x-ray-tube beams from different kVp settings and beam filtrations. Radiographs of rabbits' kidneys were obtained with Gadovist at the NSLS. Furthermore, a clinical radiography system was used for imaging rabbits' kidneys comparing Gadovist and Conray, an iodinated contrast agent. The study, using 74 kVp and standard Al beam filter for Conray and 66 kVp and an additional 1.5 mm Cu beam filter for Gadovist, produced comparable images for Gadovist and Conray; the injection volumes were the same, while the radiation absorbed dose for Gadovist was slightly smaller. A bent-crystal silicon monochromator operating in the Laue diffraction mode was developed and tested with a conventional x-ray tube beam; it narrows the energy spectrum to about 4 keV around the anode tungsten's Ku line. Preliminary beam-flux results indicate that the method could be implemented in clinical CT if x-ray tubes with {approximately} twice higher output become available.

  12. 钆类造影剂用于肿瘤靶向性成像%Gadolinium-Based Contrast Agents for Tumor Targeting Imaging

    Institute of Scientific and Technical Information of China (English)

    沈爱军; 董海青; 温惠云; 徐梦; 李永勇; 王培军

    2011-01-01

    Magnetic resonance imaging (MRI) is an important technique of medical imaging for the tumor diagnosis, due to its high spatial and temporal resolutions and excellent soft tissue contrast, especially after the usage of various contrast agents. However, the current contrast agents for MRI, such as Gd-DTPA-BMA, Gd-DOTA etc. ,are all small molecules, which are associated with the intrinsic drawbacks such as nonspecificity for the interesting tissue,rapid excretion in vivo. To address the above questions, the novel specific MRI contrast agents with high efficiency and low toxicity are thus becoming research hot spots in both material and medical fields. In this review, particular attention is paid on the recent progress of gadolinium-based MRI contrast agents for tumor targeting imaging by summarizing the relevant research papers. Both passive and active approach for tumor targeting imaging are involved in this review. The synthesis, principle and determined factors of MRI contrast agents for tumor targeting imaging and their in vitro or in vivo effects on the interesting tissue are discussed.%核磁共振成像(MRI)是肿瘤诊断的重要手段,特别是各种造影剂的使用加速了临床应用范围.目前临床MRI检查所用各类造影剂如Gd-DTPA-BMA、Gd-DOTA等均为小分子造影剂,存在组织特异性低、体内停留时间短等缺点.构建具有组织特异性的新一代高效、低毒MRI造影剂成为材料界、医学界的研究热点之一.本文在综合最新文献的研究基础之上,重点关注含钆类造影剂在肿瘤靶向成像中的应用及发展.

  13. MRI contrast agents from molecules to particles

    CERN Document Server

    Laurent, Sophie; Stanicki, Dimitri; Boutry, Sébastien; Lipani, Estelle; Belaid, Sarah; Muller, Robert N; Vander Elst, Luce

    2017-01-01

    This book describes the multiple aspects of (i) preparation of the magnetic core, (ii) the stabilization with different coatings, (iii) the physico-chemical characterization and (iv) the vectorization to obtain specific nanosystems. Several bio-applications are also presented in this book. In the early days of Magnetic Resonance Imaging (MRI), paramagnetic ions were proposed as contrast agents to enhance the diagnostic quality of MR images. Since then, academic and industrial efforts have been devoted to the development of new and more efficient molecular, supramolecular and nanoparticular systems. Old concepts and theories, like paramagnetic relaxation, were revisited and exploited, leading to new scientific tracks. With their high relaxivity payload, the superparamagnetic nanoparticles are very appealing in the context of molecular imaging but challenges are still numerous: absence of toxicity, specificity, ability to cross the biological barriers, etc. .

  14. Research progress of magnetic resonance imaging contrast agents

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Magnetic resonance imaging (MRI) is a clinical diagnostic modality, which has become popular in hospitals around the world. Approximately 30% of MRI exams include the use of contrast agents. The research progress of the paramagnetic resonance imaging contrast agents was described briefly. Three important approaches in the soluble paramagnetic resonance imaging contrast agents design including nonionic, tissue-specific and macromolecular contrast agents were investigated. In addition, the problems in the research and development in future were discussed.

  15. Synthesis of Laboratory Ultrasound Contrast Agents

    Directory of Open Access Journals (Sweden)

    Jaemin Oh

    2013-10-01

    Full Text Available Ultrasound Contrast Agents (UCAs were developed to maximize reflection contrast so that organs can be seen clearly in ultrasound imaging. UCAs increase the signal to noise ratio (SNR by linear and non-linear mechanisms and thus help more accurately visualize the internal organs and blood vessels. However, the UCAs on the market are not only expensive, but are also not optimized for use in various therapeutic research applications such as ultrasound-aided drug delivery. The UCAs fabricated in this study utilize conventional lipid and albumin for shell formation and perfluorobutane as the internal gas. The shape and density of the UCA bubbles were verified by optical microscopy and Cryo SEM, and compared to those of the commercially available UCAs, Definity® and Sonovue®. The size distribution and characteristics of the reflected signal were also analyzed using a particle size analyzer and ultrasound imaging equipment. Our experiments indicate that UCAs composed of spherical microbubbles, the majority of which were smaller than 1 um, were successfully synthesized. Microbubbles 10 um or larger were also identified when different shell characteristics and filters were used. These laboratory UCAs can be used for research in both diagnoses and therapies.

  16. X-ray fluorescence microscopy demonstrates preferential accumulation of a vanadium-based magnetic resonance imaging contrast agent in murine colonic tumors.

    Science.gov (United States)

    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.

  17. Synthesis, Characterization, In Vitro Phantom Imaging, and Cytotoxicity of A Novel Graphene-Based Multimodal Magnetic Resonance Imaging - X-Ray Computed Tomography Contrast Agent.

    Science.gov (United States)

    Lalwani, Gaurav; Sundararaj, Joe Livingston; Schaefer, Kenneth; Button, Terry; Sitharaman, Balaji

    2014-06-14

    Graphene nanoplatelets (GNPs), synthesized using potassium permanganate-based oxidation and exfoliation followed by reduction with hydroiodic acid (rGNP-HI), have intercalated manganese ions within the graphene sheets, and upon functionalization with iodine, show excellent potential as biomodal contrast agents for magnetic resonance imaging (MRI) and computed tomography (CT). Structural characterization of rGNP-HI nanoparticles with low- and high-resolution transmission electron microscope (TEM) showed disc-shaped nanoparticles (average diameter, 200 nm, average thickness, 3 nm). Energy dispersive X-ray spectroscopy (EDX) analysis confirmed the presence of intercalated manganese. Raman spectroscopy and X-ray diffraction (XRD) analysis of rGNP-HI confirmed the reduction of oxidized GNPs (O-GNPs), absence of molecular and physically adsorbed iodine, and the functionalization of graphene with iodine as polyiodide complexes (I3(-) and I5(-)). Manganese and iodine content were quantified as 5.1 ± 0.5 and 10.54 ± 0.87 wt% by inductively-coupled plasma optical emission spectroscopy and ion-selective electrode measurements, respectively. In vitro cytotoxicity analysis, using absorbance (LDH assay) and fluorescence (calcein AM) based assays, performed on NIH3T3 mouse fibroblasts and A498 human kidney epithelial cells, showed CD50 values of rGNP-HI between 179-301 µg/ml, depending on the cell line and the cytotoxicity assay. CT and MRI phantom imaging of rGNP-HI showed high CT (approximately 3200% greater than HI at equimolar iodine concentration) and MRI (approximately 59% greater than equimolar Mn(2+) solution) contrast. These results open avenues for further in vivo safety and efficacy studies towards the development of carbon nanostructure-based multimodal MRI-CT contrast agents.

  18. Design of Gd(III)-based magnetic resonance imaging contrast agents: static and transient zero-field splitting contributions to the electronic relaxation and their impact on relaxivity.

    Science.gov (United States)

    Benmelouka, Meriem; Borel, Alain; Moriggi, Loick; Helm, Lothar; Merbach, André E

    2007-02-01

    A multiple-frequency (9.4-325 GHz) and variable-temperature (276-320 K) electron paramagnetic resonance (EPR) study on low molecular weight gadolinium(III) complexes for potential use as magnetic resonance imaging (MRI) contrast agents has been performed. Peak-to-peak linewidths Delta Hpp and central magnetic fields have been analyzed within the Redfield approximation taking into account the static zero-field splitting (ZFS) up to the sixth order and the transient ZFS up to the second order. Longitudinal electronic relaxation is dominated by the static ZFS contribution at low magnetic fields (B 1.5 T). Whereas the static ZFS clearly depends on the nature of the chelating ligand, the transient ZFS does not. For the relatively fast rotating molecules studied water proton relaxivity is mainly limited by the fast rotation and electronic relaxation has only a marked influence at frequencies below 30 MHz. From our EPR results we can conclude that electronic relaxation will have no influence on the efficiency of Gd(III)-based MRI contrast agents designed for studies at very high magnetic fields (B > 3T).

  19. Towards MRI T2 contrast agents of increased efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Branca, Marlène [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Université de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Marciello, Marzia, E-mail: marziamarciello@icmm.csic.es [Instituto de Ciencia de Materiales de Madrid (ICMM-CSIC), Sor Juana Inés de la Cruz, 3, Cantoblanco, 28049 Madrid (Spain); Ciuculescu-Pradines, Diana [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Université de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France); Respaud, Marc [LPCNO, INSA, 135 Avenue de Rangueil, 31077 Toulouse Cedex 4 (France); Morales, Maria del Puerto [Instituto de Ciencia de Materiales de Madrid (ICMM-CSIC), Sor Juana Inés de la Cruz, 3, Cantoblanco, 28049 Madrid (Spain); Serra, Raphael; Casanove, Marie-José [CNRS, CEMES (Centre d' Elaboration des Matériaux et d' Etudes Structurales) (France); Amiens, Catherine, E-mail: catherine.amiens@lcc-toulouse.fr [CNRS, LCC (Laboratoire de Chimie de Coordination), 205, route de Narbonne, F-31077 Toulouse (France); Université de Toulouse, UPS, INPT, LCC, F-31077 Toulouse (France)

    2015-03-01

    Magnetic nanoparticles can be efficient contrast agents for T2 weighted magnetic resonance imaging (MRI) after tuning of some key parameters such as size, surface state, colloidal stability and magnetization, thus motivating the development of new synthetic pathways. In this paper we report the effects of surface coating on the efficiency of two different types of iron based nanoparticles (NPs) as MRI contrast agents. Starting from well-defined hydrophobic iron oxide nanospheres and iron nanocubes of 13 nm size, we have used three methods to increase their hydrophilicity and transfer them into water: surface ligand modification, ligand exchange or encapsulation. The NPs obtained have been characterized by dynamic light scattering and transmission electron microscopy, and the relaxivities of their stable colloidal solutions in water have been determined. Among all samples prepared, iron nanocubes coated by silica display the highest relaxivity (r{sub 2}) value: 628 s{sup −1} mM{sup −1}. - Highlights: • Surface coating effect on the efficiency of iron based nanoparticles (NPs) as MRI contrast agents. • Synthesis of 2 different types of hydrophobic iron based NPs: iron oxide nanospheres and iron nanocubes (13 nm). • Development of three different procedures to stabilize iron based NPs in water. • Iron nanocubes coated by silica displayed the highest r{sub 2} value (628 s{sup −1} mM{sup −1})

  20. Magnetic nanobeads as potential contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Pablico-Lansigan, Michele H; Hickling, William J; Japp, Emily A; Rodriguez, Olga C; Ghosh, Anup; Albanese, Chris; Nishida, Maki; Van Keuren, Edward; Fricke, Stanley; Dollahon, Norman; Stoll, Sarah L

    2013-10-22

    Metal-oxo clusters have been used as building blocks to form hybrid nanomaterials and evaluated as potential MRI contrast agents. We have synthesized a biocompatible copolymer based on a water stable, nontoxic, mixed-metal-oxo cluster, Mn8Fe4O12(L)16(H2O)4, where L is acetate or vinyl benzoic acid, and styrene. The cluster alone was screened by NMR for relaxivity and was found to be a promising T2 contrast agent, with r1 = 2.3 mM(-1) s(-1) and r2 = 29.5 mM(-1) s(-1). Initial cell studies on two human prostate cancer cell lines, DU-145 and LNCap, reveal that the cluster has low cytotoxicity and may be potentially used in vivo. The metal-oxo cluster Mn8Fe4(VBA)16 (VBA = vinyl benzoic acid) can be copolymerized with styrene under miniemulsion conditions. Miniemulsion allows for the formation of nanometer-sized paramagnetic beads (~80 nm diameter), which were also evaluated as a contrast agent for MRI. These highly monodispersed, hybrid nanoparticles have enhanced properties, with the option for surface functionalization, making them a promising tool for biomedicine. Interestingly, both relaxivity measurements and MRI studies show that embedding the Mn8Fe4 core within a polymer matrix decreases r2 effects with little effect on r1, resulting in a positive T1 contrast enhancement.

  1. Dual-frequency transducer for nonlinear contrast agent imaging.

    Science.gov (United States)

    Guiroy, Axel; Novell, Anthony; Ringgaard, Erling; Lou-Moeller, Rasmus; Grégoire, Jean-Marc; Abellard, André-Pierre; Zawada, Tomasz; Bouakaz, Ayache; Levassort, Franck

    2013-12-01

    Detection of high-order nonlinear components issued from microbubbles has emerged as a sensitive method for contrast agent imaging. Nevertheless, the detection of these high-frequency components, including the third, fourth, and fifth harmonics, remains challenging because of the lack of transducer sensitivity and bandwidth. In this context, we propose a new design of imaging transducer based on a simple fabrication process for high-frequency nonlinear imaging. The transducer is composed of two elements: the outer low-frequency (LF) element was centered at 4 MHz and used in transmit mode, whereas the inner high-frequency (HF) element centered at 14 MHz was used in receive mode. The center element was pad-printed using a lead zirconate titanate (PZT) paste. The outer element was molded using a commercial PZT, and curved porous unpoled PZT was used as backing. Each piezoelectric element was characterized to determine the electromechanical performance with thickness coupling factor around 45%. After the assembly of the two transducer elements, hydrophone measurements (electroacoustic responses and radiation patterns) were carried out and demonstrated a large bandwidth (70% at -3 dB) of the HF transducer. Finally, the transducer was evaluated for contrast agent imaging using contrast agent microbubbles. The results showed that harmonic components (up to the sixth harmonic) of the microbubbles were successfully detected. Moreover, images from a flow phantom were acquired and demonstrated the potential of the transducer for high-frequency nonlinear contrast imaging.

  2. Towards An Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals.

    Science.gov (United States)

    Kanakia, Shruti; Toussaint, Jimmy; Hoang, Dung Minh; Mullick Chowdhury, Sayan; Lee, Stephen; Shroyer, Kenneth R; Moore, William; Wadghiri, Youssef Z; Sitharaman, Balaji

    2015-12-02

    Current clinical Gd(3+)-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn(2+)) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn(2+)/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn(2+) concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe.

  3. Objective evaluation of acute adverse events and image quality of gadolinium-based contrast agents (gadobutrol and gadobenate dimeglumine) by blinded evaluation. Pilot study.

    Science.gov (United States)

    Semelka, Richard C; Hernandes, Mateus de A; Stallings, Clifton G; Castillo, Mauricio

    2013-01-01

    The purpose was to objectively evaluate a recently FDA-approved gadolinium-based contrast agent (GBCA) in comparison to our standard GBCA for acute adverse events and image quality by blinded evaluation. Evaluation was made of a recently FDA-approved GBCA, gadobutrol (Gadavist; Bayer), in comparison to our standard GBCA, gadobenate dimeglumine (MultiHance; Bracco), in an IRB- and HIPAA-compliant study. Both the imaging technologist and patient were not aware of the brand of the GBCA used. A total of 59 magnetic resonance studies were evaluated (59 patients, 31 men, 28 women, age range of 5-85 years, mean age of 52 years). Twenty-nine studies were performed with gadobutrol (22 abdominal and 7 brain studies), and 30 studies were performed with gadobenate dimeglumine (22 abdominal and 8 brain studies). Assessment was made of acute adverse events focusing on objective observations of vomiting, hives, and moderate and severe reactions. Adequacy of enhancement was rated as poor, fair and good by one of two experienced radiologists who were blinded to the type of agent evaluated. No patient experienced acute adverse events with either agent. The target minor adverse events of vomiting or hives, and moderate and severe reactions were not observed in any patient. Adequacy of enhancement was rated as good for both agents in all patients. Objective, blinded evaluation is feasible and readily performable for the evaluation of GBCAs. This proof-of-concept study showed that both GBCAs evaluated exhibited consistent good image quality and no noteworthy adverse events. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. The influence of collagen network integrity on the accumulation of gadolinium-based MR contrast agents in articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Wiener, Edzard; Schmidt, C.; Diederichs, G. [Charite - Universitaetsmedizin Berlin (Germany). Inst. fuer Radiologie; Settles, M. [Klinikum rechts der Isar, Muenchen (Germany). Inst. fuer Roentgendiagnostik; Weirich, G. [Klinikum Rechts der Isar, Muenchen (Germany). Inst. fuer Pathologie und Pathologische Anatomie

    2011-03-15

    Delayed gadolinium-enhanced MR imaging of cartilage is used to quantify the proteoglycan loss in early osteoarthritis. It is assumed that T 1 after Gd-DTPA administration in the near equilibrium state reflects selective proteoglycan loss from cartilage. To investigate the influence of the collagen network integrity on contrast accumulation, the relaxation rates {delta}R1 and {delta}R2 were compared after Gd-DTPA administration in a well established model of osteoarthritis. Collagen or proteoglycan depletion was induced by the proteolytic enzymes papain and collagenase in healthy bovine patellar cartilage. Using a dedicated MRI sequence, T{sub 1} and T{sub 2} maps were simultaneously acquired before and 11 h after Gd-DTPA administration. Depth-dependent profiles of {delta}R1 and {delta}R2 were calculated in healthy, proteoglycan and collagen-depleted articular cartilage and the mean values of different cartilage layers were compared using the Mann-Whitney-U test. In superficial layers (1 mm) there was no significant difference (p > 0.05) in either {delta}R1 or {delta}R2 between proteoglycan-depleted (16.6 {+-} 1.2 s{sup -1}, 15.9 {+-} 1.0 s{sup -1}) and collagen-depleted articular cartilage (15.3 {+-} 0.9 s{sup -1}, 15.5 {+-} 0.9 s{sup -1}). In deep layers (3 mm) both parameters were significantly higher (p = 0.005, 0.03) in proteoglycan-depleted articular cartilage (12.3 {+-} 1.1 s{sup -1}, 9.8 {+-} 0.8 s{sup -1}) than in collagen-depleted articular cartilage (9.1 {+-} 1.1 s{sup -1}, 8.7 {+-} 0.7 s{sup -1}). Both proteoglycan loss and alterations in the collagen network influence the accumulation of Gd-DTPA in articular cartilage with significant differences between superficial and deep cartilage layers. (orig.)

  5. Gadolinium-based contrast agents and nephrogenic systemic fibrosis%含钆对比剂与肾源性系统性纤维化

    Institute of Scientific and Technical Information of China (English)

    高华; 曾新伟; 李冬梅

    2011-01-01

    @@ 含钆(gadolinium,Gd)对比剂(gadolinium-based contrast agents,GBCA) 是临床上应用最多的MRI对比剂,全世界范围内已经使用超过2亿次.但随着对肾源性系统性纤维化(nephrogenic systemic fibrosis,NSF) 的不断报道,越来越多的证据表明NSF的发病与GBCA 的使用有着密切联系,在肾功能不全患者如何使用GBCA已受到越来越多地关注.虽然国内对NSF的病例报道较少,但仍需要密切关注相关研究进展,从而可合理选择医学影像检查方式,尽量减少NSF的发生.

  6. 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

    Directory of Open Access Journals (Sweden)

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

    2010-01-01

    Full Text Available 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.

  7. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation of hepatocellular carcinoma by three-dimensional sonography with a perflubutane-based contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Numata, Kazushi, E-mail: kz-numa@urahp.yokohama-cu.ac.j [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Fukuda, Hiroyuki; Ohto, Masao; Itou, Ryu [Department of Internal Medicine, Naruto General Hospital, 167 Naruto, Sanbu, Chiba 289-1326 (Japan); Nozaki, Akito; Kondou, Masaaki; Morimoto, Manabu [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan); Karasawa, Eii [Department of Gastroenterology, International University of Health and Welfare Atami Hospital, 13-1 Higashi Kaigan-cho, Atami, Shizuoka 413-0012 (Japan); Tanaka, Katsuaki [Gastroenterological Center, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama, Kanagawa 232-0024 (Japan)

    2010-08-15

    Objective: We performed contrast-enhanced three-dimensional sonography (CE 3D US) with a perflubutane-based contrast agent to immediately evaluate the completeness of ablation of small hepatocellular carcinoma (HCC) lesions by extracorporeal high-intensity focused ultrasound (HIFU). Subjects and methods: Twenty-one HCC lesions were treated by a single ultrasound-guided HIFU ablation session, and CE 3D US was performed before, immediately after, and 1 week, and 1 month after HIFU, and contrast-enhanced CT (CE CT) or contrast-enhanced MRI (CE MRI) was performed before HIFU, 1 week and 1 month after HIFU, and during the follow-up period. Results: Immediately and 1 month after HIFU, 17 lesions were evaluated as adequately ablated by CE 3D US, and the other 4 lesions as residual tumors. One month after HIFU, 18 were evaluated as adequately ablated by CE CT or CE MRI, and the other 3 as residual tumors. The evaluation by CE 3D US immediately after HIFU and by CE CT or CE MRI 1 month after HIFU was concordant with 20 lesions. The kappa value for agreement between the findings of CE 3D US and other modalities by two blinded observers was 0.83. When the 1-month CE CT or CE MRI findings were used as the reference standard, the sensitivity, specificity, and accuracy of CE 3D US immediately after HIFU for the diagnosis of the adequate ablation were 100%, 75%, and 95%, respectively. Conclusion: CE 3D US appears to be a useful method for immediate evaluation of therapeutic efficacy of HIFU ablation of HCC lesions.

  8. Computational Fluid Dynamics Simulations of Contrast Agent Bolus Dispersion in a Coronary Bifurcation: Impact on MRI-Based Quantification of Myocardial Perfusion

    OpenAIRE

    Regine Schmidt; Dirk Graafen; Stefan Weber; Schreiber, Laura M.

    2013-01-01

    Contrast-enhanced first-pass magnetic resonance imaging (MRI) in combination with a tracer kinetic model, for example, MMID4, can be used to determine myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). Typically, the arterial input function (AIF) required for this methodology is estimated from the left ventricle (LV). Dispersion of the contrast agent bolus might occur between the LV and the myocardial tissue. Negligence of bolus dispersion could cause an error in MBF determin...

  9. Separation of Gd-humic complexes and Gd-based magnetic resonance imaging contrast agent in river water with QAE-Sephadex A-25 for the fractionation analysis.

    Science.gov (United States)

    Matsumiya, Hiroaki; Inoue, Hiroto; Hiraide, Masataka

    2014-10-01

    Gadolinium complexed with naturally occurring, negatively charged humic substances (humic and fulvic acids) was collected from 500 mL of sample solution onto a column packed with 150 mg of a strongly basic anion-exchanger (QAE-Sephadex A-25). A Gd-based magnetic resonance imaging contrast agent (diethylenetriamine-N,N,N',N″,N″-pentaacetato aquo gadolinium(III), Gd-DTPA(2-)) was simultaneously collected on the same column. The Gd-DTPA complex was desorbed by anion-exchange with 50mM tetramethylammonium sulfate, leaving the Gd-humic complexes on the column. The Gd-humic complexes were subsequently dissociated with 1M nitric acid to desorb the humic fraction of Gd. The two-step desorption with small volumes of the eluting agents allowed the 100-fold preconcentration for the fractionation analysis of Gd at low ng L(-1) levels by inductively coupled plasma-mass spectrometry (ICP-MS). On the other hand, Gd(III) neither complexed with humic substances nor DTPA, i.e., free species, was not sorbed on the column. The free Gd in the effluent was preconcentrated 100-fold by a conventional solid-phase extraction with an iminodiacetic acid-type chelating resin and determined by ICP-MS. The proposed analytical fractionation method was applied to river water samples.

  10. Iopamidol as a gastrointestinal contrast agent. Lack of peritoneal reactivity.

    Science.gov (United States)

    Ferrante, S L; Schreiman, J S; Rouse, J W; Rysavy, J A; Cheng, S C; Frick, M P

    1990-02-01

    The ideal contrast agent in patients suspected of having gastrointestinal perforation is an iso-osmolar, or nearly iso-osmolar substance, that causes no peritoneal reaction. Iopamidol is a nonionic water-soluble contrast medium that may be considered in such situations. Intraperitoneal injections of ionic and nonionic contrast agents were compared in rats to study potentially harmful peritoneal inflammation. Only intraperitoneal barium injection produced any significant tissue reaction, such as adhesions and ascites. There was no difference between iopamidol and the other water-soluble contrast agents. Iopamidol may satisfy the need for nonreactive and nearly iso-osmolar contrast agents for evaluating patients with possible bowel perforation. However, the high cost of this agent may make its clinical application impractical.

  11. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2005-05-01

    Full Text Available Contrast-enhanced ultrasound (CEUS is an advanced approach to in vivo assessment of tumor vascularity and is being increasingly adopted in clinical oncology. It is based on 1- to 10 μm-sized gas microbubbles, which can cross the capillary beds of the lungs and are effective echo enhancers. It is known that high cell density, high transendothelial fluid exchange, and poorly functioning lymphatic circulation all provoke solid stress, which compresses vessels and drastically reduces tumor blood flow. Given their size, we supposed that the perfusion of microbubbles is affected by anatomic features of tumor vessels more than are contrast agents traditionally used in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI. Here, we compared dynamic information obtained from CEUS and DCE-MRI on two experimental tumor models exhibiting notable differences in vessel anatomy. We found that tumors with small, flattened vessels show a much higher resistance to microbubble perfusion than to MRI contrast agents, and appear scarcely vascularized at CEUS examination, despite vessel volume adequate for normal function. Thus, whereas CEUS alone could induce incorrect diagnosis when tumors have small or collapsed vessels, integrated analysis using CEUS and DCE-MRI allows in vivo identification of tumors with a vascular profile frequently associated with malignant phenotypes.

  12. Functional imaging with MR T1 contrast: a feasibility study with blood-pool contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Majos, Agata; Stefanczyk, Ludomir [Medical University of Lodz, Radiology Department, Lodz (Poland); Bogorodzki, Piotr; Piatkowska-Janko, Ewa; Kurjata, Robert [Warsaw University of Technology, Institute of Radioelectronics, Warsaw (Poland); Wolak, Tomasz [Institute of Physiology and Pathology of Hearing, Warsaw (Poland)

    2009-04-15

    The aim of this study was to prove the concept of using a long intravenous half-life blood-pool T1 contrast agent as a new functional imaging method. For each of ten healthy subjects, two dynamic magnetic resonance (MR) protocols were carried out: (1) a reference run with a typical T2* echo-planar imaging (EPI) sequence based on the blood oxygenation level-dependent (BOLD) effect and (2) a run with a T1-sensitive three-dimensional (3D) gradient-echo (GRE) sequence using cerebral blood volume (CBV) contrast after intravenous administration of a contrast agent containing a chelate of gadolinium diethylene-triamine-pentaacetate with a phosphono-oxymethyl substituent. All sequences were performed during the execution of a block-type finger-tapping paradigm. SPM5 software was used for statistical analysis. For both runs maximum activations (peak Z-score = 5.5, cluster size 3,449 voxels) were localized in the left postcentral gyrus. Visual inspection of respective signal amplitudes suggests the T1 contrast to be substantially smaller than EPI (0.5% vs 1%). A new functional imaging method with potentially smaller image artefacts due to the nature of CBV contrast and characteristics of the T1 sequence was proposed and verified. (orig.)

  13. Preclinical Studies of a Kidney Safe Iodinated Contrast Agent

    OpenAIRE

    Rowe, Elizabeth S.; Rowe, Vernon D.; Biswas, Sangita; Mosher, Gerold; Insisienmay, Lovella; Ozias, Marlies K.; Gralinski, Michael R.; Hunter, John; Barnett, James S.

    2016-01-01

    ABSTRACT BACKGROUND AND PURPOSE Contrast‐induced acute kidney injury (CI‐AKI) is a serious complication of the use of iodinated contrast agents. This problem is particularly acute in interventional neurology and interventional cardiology, probably due to the intra‐arterial route of injection, high contrast volumes, and preexisting risk factors of these patients. In an attempt to develop a contrast agent that is less damaging to the kidneys, we have studied the effects of adding a small amount...

  14. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics.

    Science.gov (United States)

    Fu, Lei; Ke, Heng-Te

    2016-09-01

    Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs) an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles (SPIOs), CuS nanoparticles, DNA, siRNA, gold nanoparticles (GNPs), gold nanorods (GNRs), gold nanoshell (GNS), graphene oxides (GOs), polypyrrole (PPy) nanocapsules, Prussian blue (PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics.

  15. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    Institute of Scientific and Technical Information of China (English)

    Lei Fu; Heng-Te Ke

    2016-01-01

    Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs) an ideal platform for construction of cancer theranostic agents. This review focuses on the development of nanomaterials incorporated multifunctional UCAs serving as theranostic agents for cancer diagnostics and therapeutics, via conjugation of superparamagnetic iron oxide nanoparticles (SPIOs), CuS nanoparticles, DNA, siRNA, gold nanoparticles (GNPs), gold nanorods (GNRs), gold nanoshell (GNS), graphene oxides (GOs), polypyrrole (PPy) nanocapsules, Prussian blue (PB) nanoparticles and so on to different types of UCAs. The cancer treatment could be more effectively and accurately carried out under the guidance and monitoring with the help of the achieved theranostic agents. Furthermore, nanomaterials incorporated theranostic agents based on UCAs can be designed and constructed by demand for personalized and accurate treatment of cancer, demonstrating their great potential to address the challenges of cancer heterogeneity and adaptation, which can provide alternative strategies for cancer diagnosis and therapeutics.

  16. Complicações do uso intravenoso de agentes de contraste à base de gadolínio para ressonância magnética Complications from the use of intravenous gadolinium-based contrast agents for magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Jorge Elias Junior

    2008-08-01

    Full Text Available Os agentes de contraste à base de gadolínio são muito mais seguros que o contraste iodado, no entanto, existem complicações que devem ser reconhecidas, para orientação e tratamento adequados. A incidência total de reações adversas aos meios de contraste em ressonância magnética varia entre 2% e 4%. Casos de reações adversas agudas maiores ao gadolínio, como laringoespasmo e choque anafilático, são raros. As complicações crônicas com o uso do gadolínio também existem e, recentemente, foi descrita associação entre seu uso e uma doença dermatológica rara que ocorre em pacientes com insuficiência renal. A fibrose nefrogênica sistêmica foi tema de anúncio público oficial pela agência americana de regulação de drogas, a Food and Drug Administration. Esta doença progressiva caracteriza-se pelo espessamento e endurecimento da pele e fibrose, que podem acometer outras partes do corpo. Os pacientes que desenvolveram esta complicação apresentavam insuficiência renal crônica, estavam em acidose metabólica e foram submetidos a angiografia por ressonância magnética, provavelmente com injeção de grande volume de contraste paramagnético. Esta revisão tem o objetivo de apresentar uma descrição sucinta dos tipos de meios de contraste à base de gadolínio, possíveis complicações e medidas para prevenção e tratamento destas.Gadolinium-based contrast agents are much safer than the iodinated ones; however complications may occur and should be recognized for appropriate orientation and management. The total incidence of adverse reactions to contrast agents in magnetic resonance imaging ranges between 2% and 4%. Cases of severe acute reactions to gadolinium, such as laryngospasm and anaphylactic shock, are rare. Chronic complications secondary to the use of gadolinium also can occur and, recently an association between its use and a rare dermatologic disease occurring in patients with renal failure has been reported

  17. Characterization of Cysteine Coated Magnetite Nanoparticles as MRI Contrast Agent

    Institute of Scientific and Technical Information of China (English)

    Reza Ahmadi; Ning Gu; Hamid Reza Madaah Hosseini

    2012-01-01

    In this work, a kind of stabilized ferrofluid based on magnetite nanoparticles (mean core and its coating size about 21.9 and 1.6 nm, respectively) was synthesized via coprecipitation method. Cysteine was used as surfactant due to its proper conjunction to the surface of magnetite nanoparticles. Coating density and synthesized ferrofluids were characterized by using transmission electron microscope, thermogravimetry analysis, dynamic light scattering and fourier transform infrared spectroscopy techniques. Magnetic resonance imaging studies show that the synthesized ferrofluid can be used as a potential contrast enhancement agent especially for imaging lymphatic system.

  18. Survey of gadolinium-based contrast agent utilization among the members of the Society for Pediatric Radiology: a Quality and Safety Committee report

    Energy Technology Data Exchange (ETDEWEB)

    Blumfield, Einat [Jacobi Medical Center, Department of Radiology, Albert Einstein College of Medicine, South Bronx, NY (United States); Moore, Michael M. [The Pennsylvania State University College of Medicine, Department of Radiology, Penn State Hershey Children' s Hospital, Hershey, PA (United States); Drake, Mary K. [University of Nebraska Medical Center, Department of Radiology, Children' s Hospital and Medical Center, Omaha, NE (United States); Goodman, Thomas R. [Yale School of Medicine, Department of Radiology and Biomedical Imaging, New Haven, CT (United States); Lewis, Kristopher N. [Augusta University, Department of Radiology, Children' s Hospital of Georgia, Augusta, GA (United States); Meyer, Laura T. [Wake Radiology, Raleigh, NC (United States); Ngo, Thang D. [Nemours Children' s Hospital, Department of Medical Imaging, Orlando, FL (United States); Sammet, Christina [Ann and Robert H. Lurie Children' s Hospital of Chicago, Department of Radiology, Chicago, IL (United States); Stanescu, Arta Luana; Iyer, Ramesh S. [Seattle Children' s Hospital, University of Washington School of Medicine, Department of Radiology, Seattle, WA (United States); Swenson, David W. [Warren Alpert Medical School of Brown University, Department of Diagnostic Imaging, Providence, RI (United States); Slovis, Thomas L. [Children' s Hospital of Michigan, Wayne State University School of Medicine, Department of Radiology, Detroit, MI (United States)

    2017-05-15

    Gadolinium-based contrast agents (GBCAs) have been used for magnetic resonance (MR) imaging over the last three decades. Recent reports demonstrated gadolinium retention in patients' brains following intravenous administration. Since gadolinium is a highly toxic heavy metal, there is a potential for adverse effects from prolonged retention or deposition, particularly in children. For this reason, the Society (SPR) for Pediatric Radiology Quality and Safety committee conducted a survey to evaluate the current status of GBCAs usage among pediatric radiologists. To assess the usage of GBCAs among SPR members. An online 15-question survey was distributed to SPR members. Survey questions pertained to the type of GBCAs used, protocoling workflow, requirement of renal function or pregnancy tests, and various clinical indications for contrast-enhanced MRI examinations. A total of 163 survey responses were compiled (11.1% of survey invitations), the majority of these from academic institutions in the United States. Ninety-four percent reported that MR studies are always or usually protocoled by pediatric radiologists. The most common GBCA utilized by survey respondents were Eovist (60.7%), Ablavar (45.4%), Gadovist (38.7%), Magnevist (34.4%) and Dotarem (32.5%). For several clinical indications, survey responses regarding GBCA administration were concordant with American College of Radiology (ACR) Appropriateness Criteria, including seizures, headache and osteomyelitis. For other indications, including growth hormone deficiency and suspected vascular ring, survey responses revealed potential overutilization of GBCAs when compared to ACR recommendations. Survey results demonstrate that GBCAs are administered judiciously in children, yet there is an opportunity to improve their utilization with the goal of reducing potential future adverse effects. (orig.)

  19. In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Langer, R.D., E-mail: rlanger@uaeu.ac.ae [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Lorke, D.E. [Florida International University, Miami, FL (United States); Neidl van Gorkom, K.F. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Petroianu, G. [Florida International University, Miami, FL (United States); Azimullah, S.; Nurulain, S.M.; Singh, S. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Fuchsjäger, M. [Al Ain Hospital, MUV-VAMED, Al Ain (United Arab Emirates)

    2012-10-15

    Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA.

  20. Micro-radiography of biological samples with medical contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Dammer, J., E-mail: jiri.dammer@lf1.cuni.cz [Charles University in Prague, First Faculty of Medicine, Salmovská 1, 120 00 Prague 2 (Czech Republic); Hospital Na Bulovce, Department of Radiological Physics, Budinova 2, 180 81 Prague 8 (Czech Republic); Institute of Experimental and Applied Physics, Czech Technical University in Prague, Horska 3a/22, 128 00 Prague 2 (Czech Republic); Weyda, F. [Faculty of Science, University of South Bohemia, Branisovska 31, 370 05 Ceske Budejovice (Czech Republic); Benes, J. [Charles University in Prague, First Faculty of Medicine, Salmovská 1, 120 00 Prague 2 (Czech Republic); Sopko, V. [Hospital Na Bulovce, Department of Radiological Physics, Budinova 2, 180 81 Prague 8 (Czech Republic); Institute of Experimental and Applied Physics, Czech Technical University in Prague, Horska 3a/22, 128 00 Prague 2 (Czech Republic); Gelbic, I. [Biology Centre, AS CR, Institute of Entomology, Department of Biochemistry and Physiology, Branisovska 31, CZ-37005 Ceske Budejovice (Czech Republic)

    2013-12-01

    Micro-radiography is an imaging technique that uses X-rays to study the internal structures of objects. This fast and easy imaging tool is based on differential X-ray attenuation by various tissues and structures within biological samples. The experimental setup described is based on the semiconductor pixel X-ray detector Medipix2 and X-ray micro-focus tube. Our micro-radiographic system has been recently used not only for the examination of internal structures of various arthropods and other biological objects but also for tracing some processes in selected model species (we used living larvae of mosquito Culex quinquefasciatus). Low concentrations of iodine, lanthanum or gold particles were used as a tracer (contrast agent). Such contrast agents increase the absorption of X-rays and allow a better visibility of internal structures of model organisms (especially the various cavities, pores, etc.). In addition, the movement of tracers in selected timing experiments demonstrates some physiological functions of digestive and excretory system.

  1. Effects of gadolinium-based contrast agents on thyroid hormone receptor action and thyroid hormone-induced cerebellar Purkinje cell morphogenesis

    Directory of Open Access Journals (Sweden)

    Noriyuki Koibuchi

    2016-08-01

    Full Text Available 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 to 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 thyroid hormone-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. In 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 (10−8–10−6 M augmented TR-mediated transcription, but the transcription was suppressed at higher dose (10−5 – 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

  2. Design, synthesis and evaluation of a new Mn - Contrast agent for MR imaging of myocardium based on the DTPA-phenylpentadecanoic acid complex

    Science.gov (United States)

    Belyanin, Maxim L.; Stepanova, Elena V.; Valiev, Rashid R.; Filimonov, Victor D.; Usov, Vladimir Y.; Borodin, Oleg Y.; Ågren, Hans

    2016-11-01

    In the present paper we describe the first synthesis and evaluation of a novel Mn (II) complex (DTPA-PPDA Mn (II)) which contains a C-15 fatty acid moiety that has high affinity to the heart muscle. The complexation energy of DTPA-PPDA Mn (II) evaluated by quantum chemistry methodology indicates that it essentially exceeds the corresponding value for the known DTPA Mn (II) complex. Molecular docking revealed that the affinity of the designed complex to the heart-type transport protein H-FABP well exceeds that of lauric acid. Phantom experiments in low-field MRI the designed contrast agent provides MR imaging comparable to gadopentetic acid.

  3. Contrast Agents for Photoacoustic and Thermoacoustic Imaging: A Review

    Directory of Open Access Journals (Sweden)

    Dan Wu

    2014-12-01

    Full Text Available Photoacoustic imaging (PAI and thermoacoustic imaging (TAI are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

  4. Contrast agents for photoacoustic and thermoacoustic imaging: a review.

    Science.gov (United States)

    Wu, Dan; Huang, Lin; Jiang, Max S; Jiang, Huabei

    2014-12-18

    Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

  5. Cellulose nanoparticles: photoacoustic contrast agents that biodegrade to simple sugars

    Science.gov (United States)

    Jokerst, Jesse V.; Bohndiek, Sarah E.; Gambhir, Sanjiv S.

    2014-03-01

    In photoacoustic imaging, nanoparticle contrast agents offer strong signal intensity and long-term stability, but are limited by poor biodistribution and clearance profiles. Conversely, small molecules offer renal clearance, but relatively low photoacoustic signal. Here we describe a cellulose-based nanoparticle with photoacoustic signal superior to gold nanorods, but that undergoes enzymatic cleavage into constituent glucose molecules for renal clearance. Cellulose nanoparticles (CNPs) were synthesized through acidic cleavage of cellulose linters and purified with centrifugation. TEM indicated that the nanoparticles were 132 +/- 46 nm; the polydispersity index was 0.138. Ex vivo characterization showed a photoacoustic limit of detection of 0.02 mg/mL CNPs, and the photoacoustic signal of CNPs was 1.5- to 3.0-fold higher than gold nanorods (also at 700 nm resonance) on a particle-to-particle basis. Cell toxicity assays suggested that overnight doses below 0.31 mg/mL CNPs produced no significant (p>0.05) impact on cell metabolism. Intravenous doses up to 0.24 mg were tolerated well in nude mice. Subcutaneous and orthotopic tumor xenografts of the OV2008 ovarian cancer cell line were then created in nude mice. Data was collected with a Nexus128 scanner from Endra LifeSciences. Spectral data used a LAZR system from Visualsonics both at 700 nm excitation. We injected CNPs (0.024 mg, 0.048 mg, and 0.80 mg) via tail vein and showed that the tumor photoacoustic signal reached maximum increase between 10 and 20 minutes. All injected concentrations were statistically (p0.96 suggesting quantitative signal. CNP biodegradation was demonstrated ex vivo with a glucose assay. CNPs in the presence of cellulase were reduced to free glucose in under than four hours. The glucose concentration before addition of cellulase was not detectable, but increased to 92.1 μg/mL in four hours. CNPs in the absence of cellulase did not produce glucose. Small fragments of nanoparticle in the

  6. Targeting of ICAM-1 on vascular endothelium under static and shear stress conditions using a liposomal Gd-based MRI contrast agent

    Directory of Open Access Journals (Sweden)

    Paulis Leonie EM

    2012-06-01

    Full Text Available Abstract Background The upregulation of intercellular adhesion molecule-1 (ICAM-1 on the endothelium of blood vessels in response to pro-inflammatory stimuli is of major importance for the regulation of local inflammation in cardiovascular diseases such as atherosclerosis, myocardial infarction and stroke. In vivo molecular imaging of ICAM-1 will improve diagnosis and follow-up of patients by non-invasive monitoring of the progression of inflammation. Results A paramagnetic liposomal contrast agent functionalized with anti-ICAM-1 antibodies for multimodal magnetic resonance imaging (MRI and fluorescence imaging of endothelial ICAM-1 expression is presented. The ICAM-1-targeted liposomes were extensively characterized in terms of size, morphology, relaxivity and the ability for binding to ICAM-1-expressing endothelial cells in vitro. ICAM-1-targeted liposomes exhibited strong binding to endothelial cells that depended on both the ICAM-1 expression level and the concentration of liposomes. The liposomes had a high longitudinal and transversal relaxivity, which enabled differentiation between basal and upregulated levels of ICAM-1 expression by MRI. The liposome affinity for ICAM-1 was preserved in the competing presence of leukocytes and under physiological flow conditions. Conclusion This liposomal contrast agent displays great potential for in vivo MRI of inflammation-related ICAM-1 expression.

  7. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    Directory of Open Access Journals (Sweden)

    Donghee Park

    Full Text Available Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with

  8. Bubble sorting in pinched microchannels for ultrasound contrast agent enrichment

    NARCIS (Netherlands)

    Kok, M.P.; Segers, T.J.; Versluis, M.

    2015-01-01

    Ultrasound contrast agent (UCA) suspensions contain encapsulated microbubbles with a wide size distribution, with radii between 1 and 10 μm. Medical transducers generally operate at a narrow frequency bandwidth, severely limiting the fraction of bubbles that resonates to the driving ultrasound. Thus

  9. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    OpenAIRE

    FU, LEI; Ke, Heng-Te

    2016-01-01

    Nanotechnology provides various nanomaterials with tremendous functionalities for cancer diagnostics and therapeutics. Recently, theranostics has been developed as an alternative strategy for efficient cancer treatment through combination of imaging diagnosis and therapeutic interventions under the guidance of diagnostic results. Ultrasound (US) imaging shows unique advantages with excellent features of real-time imaging, low cost, high safety and portability, making US contrast agents (UCAs)...

  10. Biological in situ characterization of polymeric microbubble contrast agents

    NARCIS (Netherlands)

    Wan, Sha; Egri, Gabriella; Oddo, Letizia; Cerroni, Barbara; Dähne, Lars; Paradossi, Gaio; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A; Monopoli, Marco P

    2016-01-01

    Polymeric microbubbles (MBs) are gas filled particles composed of a thin stabilized polymer shell that have been recently developed as valid contrast agents for the combined use of ultrasonography (US), magnetic resonance imaging (MRI) and single photon emission computer tomography (SPECT) imaging.

  11. Acoustic characterization of single ultrasound contrast agent microbubbles

    NARCIS (Netherlands)

    Sijl, Jeroen; Gaud, Emmanuel; Frinking, Peter J.A.; Arditi, Marcel; Jong, de Nico; Lohse, Detlef; Versluis, Michel

    2008-01-01

    Individual ultrasound contrast agent microbubbles (BR14) were characterized acoustically. The bubbles were excited at a frequency of 2 MHz and at peak-negative pressure amplitudes of 60 and 100 kPa. By measuring the transmit and receive transfer functions of both the transmit and receive transduce

  12. Contrast agents for functional and cellular MRI of the kidney

    Energy Technology Data Exchange (ETDEWEB)

    Grenier, Nicolas [ERT CNRS ' Imagerie Moleculaire et Fonctionnelle' , Universite Victor Segalen-Bordeaux 2, Bordeaux (France) and Service d' Imagerie Diagnostique et Interventionnelle de l' Adulte, Groupe Hospitalier Pellegrin, Place Amelie Raba-Leon, 33076 Bordeaux Cedex (France)]. E-mail: nicolas.grenier@chu-bordeaux.fr; Pedersen, Michael [MR Research Center, Aarhus University Hospital, Aarhus (Denmark); Hauger, Olivier [ERT CNRS ' Imagerie Moleculaire et Fonctionnelle' , Universite Victor Segalen-Bordeaux 2, Bordeaux (France); Service d' Imagerie Diagnostique et Interventionnelle de l' Adulte, Groupe Hospitalier Pellegrin, Place Amelie Raba-Leon, 33076 Bordeaux Cedex (France)

    2006-12-15

    Low-molecular-weight gadolinium (Gd) chelates are glomerular tracers but their role in evaluation of renal function with magnetic resonance (MR) imaging is still marginal. Because of their small size, they diffuse freely into the interstitium and the relationship between measured signal intensity and concentration is complex. New categories of contrast agents, such as large Gd-chelates or iron oxide particules, with different pharmacokinetic and magnetic properties have been developed. These large molecules could be useful for both functional (quantification of perfusion, quantification of glomerular filtration rate, estimation of tubular function) and cellular imaging (intrarenal phagocytosis in inflammatory renal diseases). Continuous development of new contrast agents remains worthwhile to get the best adequacy between the physiological phenomenon of interest and the pharmacokinetic of the agent.

  13. 磁共振钆造影剂纳米制剂的研究进展%Progress in research of nanomedicine-based gadolinium contrast agents for magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    柳盈盈; 范田园

    2013-01-01

    Magnetic resonance imaging (MRI) is a powerful and non-invasive imaging technique that provides very high resolution. It shows both physiological and anatomical details to a certain extent and has no ionizing radiation. However, its resolution cannot meet the clinical needs in some cases, so contrast agents should be used to achieve higher resolution MR images. Data show that about 30% of MRI exams need the use of contrast agents. Gadolinium chelates is one of the most common clinical MRI contrast agents. Traditional gadolinium contrast agents lack specific targeting property, have short half-life and low relaxivity, and cause side effects when large doses of them are used. Recently, the field of nanomedicine-based contrast agents holds great promise for overcoming many traditional hurdles of contrast agents including specific targeting property, half-life, relaxivity, and toxicities. These nanomedicine-based contrast agents mainly include liposomes, dendrimers, micelles, nanoparticles, nanotubes and fullerenes.%磁共振成像作为一种有效的非侵入性的成像技术,具有较高的分辨率,在一定程度上可以显示生理学和解剖学细节,且没有电离辐射.但是磁共振成像的分辨率在某些情况下还不能满足临床需要,所以在某些磁共振检查中需要使用磁共振造影剂以达到增强造影的目的.据文献报道大约30%的磁共振检查需要使用造影剂.钆螯合物是临床上常用的一种磁共振造影剂.传统的钆造影剂缺乏靶向性、半衰期较短、弛豫效能较低且大量使用可导致毒副作用等.目前,已有较多文献报道将钆造影剂制备成纳米制剂后可以使其具有靶向性,延长血中滞留时间,提高弛豫效能,减少总剂量从而降低毒副作用等.钆造影剂纳米制剂主要包括:脂质体、树形分子、胶束、纳米粒、碳纳米管和富勒烯等.

  14. Ultrasound imaging beyond the vasculature with new generation contrast agents.

    Science.gov (United States)

    Perera, Reshani H; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan; Exner, Agata A

    2015-01-01

    Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 µm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer.

  15. Computational Fluid Dynamics Simulations of Contrast Agent Bolus Dispersion in a Coronary Bifurcation: Impact on MRI-Based Quantification of Myocardial Perfusion

    Directory of Open Access Journals (Sweden)

    Regine Schmidt

    2013-01-01

    Full Text Available Contrast-enhanced first-pass magnetic resonance imaging (MRI in combination with a tracer kinetic model, for example, MMID4, can be used to determine myocardial blood flow (MBF and myocardial perfusion reserve (MPR. Typically, the arterial input function (AIF required for this methodology is estimated from the left ventricle (LV. Dispersion of the contrast agent bolus might occur between the LV and the myocardial tissue. Negligence of bolus dispersion could cause an error in MBF determination. The aim of this study was to investigate the influence of bolus dispersion in a simplified coronary bifurcation geometry including one healthy and one stenotic branch on the quantification of MBF and MPR. Computational fluid dynamics (CFD simulations were combined with MMID4. Different inlet boundary conditions describing pulsatile and constant flows for rest and hyperemia and differing outflow conditions have been investigated. In the bifurcation region, the increase of the dispersion was smaller than inside the straight vessels. A systematic underestimation of MBF values up to −16.1% for pulsatile flow and an overestimation of MPR up to 7.5% were found. It was shown that, under the conditions considered in this study, bolus dispersion can significantly influence the results of quantitative myocardial MR-perfusion measurements.

  16. Contrast enhanced cartilage imaging: Comparison of ionic and non-ionic contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Wiener, Edzard [Department of Radiology, Technical University Munich, Ismaninger Str. 22, D-81675 Munich (Germany)]. E-mail: ewiener@roe.med.tu-muenchen.de; Woertler, Klaus [Department of Radiology, Technical University Munich, Ismaninger Str. 22, D-81675 Munich (Germany); Weirich, Gregor [Institute of Pathology, Technical University Munich, Troger Str. 18, D-81675 Munich (Germany); Rummeny, Ernst J. [Department of Radiology, Technical University Munich, Ismaninger Str. 22, D-81675 Munich (Germany); Settles, Marcus [Department of Radiology, Technical University Munich, Ismaninger Str. 22, D-81675 Munich (Germany)

    2007-07-15

    Our objective was to compare relaxation effects, dynamics and spatial distributions of ionic and non-ionic contrast agents in articular cartilage at concentrations typically used for direct MR arthrography at 1.5 T. Dynamic MR-studies over 11 h were performed in 15 bovine patella specimens. For each of the contrast agents gadopentetate dimeglumine, gadobenate dimeglumine, gadoteridol and mangafodipir trinatrium three patellae were placed in 2.5 mmol/L contrast solution. Simultaneous measurements of T {sub 1} and T {sub 2} were performed every 30 min using a high-spatial-resolution 'MIX'-sequence. T {sub 1}, T {sub 2} and {delta}R {sub 1}, {delta}R {sub 2} profile plots across cartilage thickness were calculated to demonstrate the spatial and temporal distributions. The charge is one of the main factors which controls the amount of the contrast media diffusing into intact cartilage, but independent of the charge, the spatial distribution across cartilage thickness remains highly inhomogeneous even after 11 h of diffusion. The absolute {delta}R {sub 2}-effect in cartilage is at least as large as the {delta}R {sub 1}-effect for all contrast agents. Maximum changes were 5-12 s{sup -1} for {delta}R {sub 1} and 8-15 s{sup -1} for {delta}R {sub 2}. This study indicates that for morphologically intact cartilage only the amount of contrast agents within cartilage is determined by the charge but not the spatial distribution across cartilage thickness. In addition, {delta}R {sub 2} can be considered for quantification of contrast agent concentrations, since it is of the same magnitude and less time consuming to measure than {delta}R {sub 1}.

  17. A Nanocomplex System as Targeted Contrast Agent Delivery Vehicle for MRI Dynamic Contrast Enhancement Study

    OpenAIRE

    Korotcov, Alexandru; Shan, Liang; Meng, Huan; Wang, Tongxin; Sridhar, Rajagopalan; Zhao, Yuliang; Liang, Xing-Jie; Wang, Paul C.

    2010-01-01

    We have developed and tested a liposomal nanocomplex system, which contains Gd-DTPA as a payload and transferrin on the surface, as a tumor specific targeting MRI contrast agent for studying prostate cancer tumors in mice. In vivo, the probe significantly enhanced the MRI signal. The image contrast between the peripheral region of the tumor and the non-involved muscle was nearly 50% higher two hours after administration of the nanocomplex. The liposomal nanocomplex increased the amount of Gd ...

  18. Effects of ultrasound and ultrasound contrast agent on vascular tissue

    Directory of Open Access Journals (Sweden)

    Wood Steven C

    2012-07-01

    Full Text Available Abstract Background Ultrasound (US imaging can be enhanced using gas-filled microbubble contrast agents. Strong echo signals are induced at the tissue-gas interface following microbubble collapse. Applications include assessment of ventricular function and virtual histology. Aim While ultrasound and US contrast agents are widely used, their impact on the physiological response of vascular tissue to vasoactive agents has not been investigated in detail. Methods and results In the present study, rat dorsal aortas were treated with US via a clinical imaging transducer in the presence or absence of the US contrast agent, Optison. Aortas treated with both US and Optison were unable to contract in response to phenylephrine or to relax in the presence of acetylcholine. Histology of the arteries was unremarkable. When the treated aortas were stained for endothelial markers, a distinct loss of endothelium was observed. Importantly, terminal deoxynucleotidyl transferase mediated dUTP nick-end-labeling (TUNEL staining of treated aortas demonstrated incipient apoptosis in the endothelium. Conclusions Taken together, these ex vivo results suggest that the combination of US and Optison may alter arterial integrity and promote vascular injury; however, the in vivo interaction of Optison and ultrasound remains an open question.

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

    Science.gov (United States)

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

    2017-04-01

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

  20. Agent-Based Optimization

    CERN Document Server

    Jędrzejowicz, Piotr; Kacprzyk, Janusz

    2013-01-01

    This volume presents a collection of original research works by leading specialists focusing on novel and promising approaches in which the multi-agent system paradigm is used to support, enhance or replace traditional approaches to solving difficult optimization problems. The editors have invited several well-known specialists to present their solutions, tools, and models falling under the common denominator of the agent-based optimization. The book consists of eight chapters covering examples of application of the multi-agent paradigm and respective customized tools to solve  difficult optimization problems arising in different areas such as machine learning, scheduling, transportation and, more generally, distributed and cooperative problem solving.

  1. Carbon nanoparticles as a multimodal thermoacoustic and photoacoustic contrast agent

    Science.gov (United States)

    Cai, Xin; Wu, Lina; Xing, Wenxin; Xia, Jun; Nie, Liming; Zhang, Ruiying; Lanza, Gregory M.; Shen, Baozhong; Pan, Dipanjan; Wang, Lihong V.

    2013-03-01

    We demonstrated the potential of carbon nanoparticles (CNPs) as exogenous contrast agents for both thermoacoustic (TA) tomography (TAT) and photoacoustic (PA) tomography (PAT). In comparison to deionized water, the CNPs provided a four times stronger signal in TAT at 3 GHz. In comparison to blood, The CNPs provided a much stronger signal in PAT over a broad wavelength range of 450-850 nm. Specifically, the maximum signal enhancement in PAT was 9.4 times stronger in the near-infrared window of 635-670 nm. In vivo blood-vessel PA imaging was performed non-invasively on a mouse femoral area. The images, captured after the tail vein injection of CNPs, show a gradual enhancement of the optical absorption in the vessels by up to 230%. The results indicate that CNPs can be potentially used as contrast agents for TAT and PAT to monitor the intravascular or extravascular pathways in clinical applications.

  2. Classification and basic properties of contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Geraldes, Carlos F G C; Laurent, Sophie

    2009-01-01

    A comprehensive classification of contrast agents currently used or under development for magnetic resonance imaging (MRI) is presented. Agents based on small chelates, macromolecular systems, iron oxides and other nanosystems, as well as responsive, chemical exchange saturation transfer (CEST) and hyperpolarization agents are covered in order to discuss the various possibilities of using MRI as a molecular imaging technique. The classification includes composition, magnetic properties, biodistribution and imaging applications. Chemical compositions of various classes of MRI contrast agents are tabulated, and their magnetic status including diamagnetic, paramagnetic and superparamagnetic are outlined. Classification according to biodistribution covers all types of MRI contrast agents including, among others, extracellular, blood pool, polymeric, particulate, responsive, oral, and organ specific (hepatobiliary, RES, lymph nodes, bone marrow and brain). Various targeting strategies of molecular, macromolecular and particulate carriers are also illustrated.

  3. Agents described in the Molecular Imaging and Contrast Agent Database for imaging carbonic anhydrase IX expression.

    Science.gov (United States)

    Sneddon, Deborah; Poulsen, Sally-Ann

    2014-10-01

    Carbonic anhydrase IX (CA IX) is selectively expressed in a range of hypoxic tumours and is a validated endogenous hypoxia marker with prognostic significance; hence, CA IX is of great interest as a molecular imaging target in oncology. In this review, we present an overview of the different imaging agents and imaging modalities that have been applied for the in vivo detection of CA IX. The imaging agents reviewed are all entries in the Molecular Imaging and Contrast Agent Database (MICAD) and comprise antibody, antibody fragments and small molecule imaging agents. The effectiveness of these agents for imaging CA IX in vivo gave variable performance; however, a number of agents proved very capable. As molecular imaging has become indispensable in current medical practice we anticipate that the clinical significance of CA IX will see continued development and improvements in imaging agents for targeting this enzyme.

  4. Multifunctional ultrasound contrast agents for imaging guided photothermal therapy.

    Science.gov (United States)

    Guo, Caixin; Jin, Yushen; Dai, Zhifei

    2014-05-21

    Among all the imaging techniques, ultrasound imaging has a unique advantage due to its features of real-time, low cost, high safety, and portability. Ultrasound contrast agents (UCAs) have been widely used to enhance ultrasonic signals. One of the most exciting features of UCAs for use in biomedicine is the possibility of easily putting new combinations of functional molecules into microbubbles (MBs), which are the most routinely used UCAs. Various therapeutic agents and medical nanoparticles (quantum dots, gold, Fe3O4, etc.) can be loaded into ultrasound-responsive MBs. Hence, UCAs can be developed as multifunctional agents that integrate capabilities for early detection and diagnosis and for imaging guided therapy of various diseases. The current review will focus on such state-of-the-art UCA platforms that have been exploited for multimodal imaging and for imaging guided photothermal therapy.

  5. Advances in Ultrasound Mediated Gene Therapy Using Microbubble Contrast Agents

    Directory of Open Access Journals (Sweden)

    Shashank R. Sirsi, Mark A. Borden

    2012-01-01

    Full Text Available Microbubble ultrasound contrast agents have the potential to dramatically improve gene therapy treatments by enhancing the delivery of therapeutic DNA to malignant tissue. The physical response of microbubbles in an ultrasound field can mechanically perturb blood vessel walls and cell membranes, enhancing drug permeability into malignant tissue. In this review, we discuss literature that provided evidence of specific mechanisms that enhance in vivo gene delivery utilizing microbubble contrast agents, namely their ability to 1 improving cell membrane permeability, 2 modulate vascular permeability, and 3 enhance endocytotic uptake in cells. Additionally, we review novel microbubble vectors that are being developed in order to exploit these mechanisms and deliver higher gene payloads with greater target specificity. Finally, we discuss some future considerations that should be addressed in the development of next-generation microbubbles in order to improve in vivo microbubble gene delivery. Overall, microbubbles are rapidly gaining popularity as efficient gene carriers, and combined with their functionality as imaging contrast agents, they represent powerful theranostic tools for image guided gene therapy applications.

  6. Advances in ultrasound mediated gene therapy using microbubble contrast agents.

    Science.gov (United States)

    Sirsi, Shashank R; Borden, Mark A

    2012-01-01

    Microbubble ultrasound contrast agents have the potential to dramatically improve gene therapy treatments by enhancing the delivery of therapeutic DNA to malignant tissue. The physical response of microbubbles in an ultrasound field can mechanically perturb blood vessel walls and cell membranes, enhancing drug permeability into malignant tissue. In this review, we discuss literature that provided evidence of specific mechanisms that enhance in vivo gene delivery utilizing microbubble contrast agents, namely their ability to 1) improving cell membrane permeability, 2) modulate vascular permeability, and 3) enhance endocytotic uptake in cells. Additionally, we review novel microbubble vectors that are being developed in order to exploit these mechanisms and deliver higher gene payloads with greater target specificity. Finally, we discuss some future considerations that should be addressed in the development of next-generation microbubbles in order to improve in vivo microbubble gene delivery. Overall, microbubbles are rapidly gaining popularity as efficient gene carriers, and combined with their functionality as imaging contrast agents, they represent powerful theranostic tools for image guided gene therapy applications.

  7. Site-specific tumor-targeted fluorescent contrast agents

    Science.gov (United States)

    Achilefu, Samuel I.; Bugaj, Joseph E.; Dorshow, Richard B.; Jimenez, Hermo N.; Rajagopalan, Raghavan; Wilhelm, R. Randy; Webb, Elizabeth G.; Erion, Jack L.

    2001-01-01

    Site-specific delivery of drugs and contrast agents to tumors protects normal tissues from the cytotoxic effect of drugs, and enhances the contrast between normal and diseased tissues. In optical medicine, biocompatible dyes can be used as photo therapeutics or as contrast agents. Previous studies have shown that the use of covalent or non-covalent dye conjugates of carries such as antibodies, liposomes, and polysaccharides improves the delivery of such molecules to tumors. However, large biomolecules can elicit adverse immunogenic reactions and also result in prolonged blood circulation times, delaying visualization of target tissues. A viable alternative to this strategy is to use small bioactive molecule-dye conjugates. These molecules have several advantages over large biomolecules, including ease of synthesis of a variety of high purity compounds for combinatorial screening of new targets, enhanced diffusivity to solid tumors, and the ability to affect the pharmocokinetics of the conjugates by minor structural changes. Thus, we conjugated a near IR light absorbing dye to bioactive peptides that specifically target over expressed tumor receptors in established rat tumor lines. High tumor uptake of the conjugates was obtained without loss of either the peptide receptor affinity or the dye fluorescence. These findings demonstrate the efficacy of a small peptide-dye conjugate strategy for in vivo tumor imaging. Site-specific delivery of photodynamic therapy agents may also benefit form this approach.

  8. Consecutive acquisition of time-resolved contrast-enhanced MR angiography and perfusion MR imaging with added dose of gadolinium-based contrast agent aids diagnosis of suspected brain metastasis.

    Science.gov (United States)

    Tsuchiya, Kazuhiro; Aoki, Shigeki; Shimoji, Keigo; Mori, Harushi; Kunimatsu, Akira

    2013-01-01

    Time-resolved contrast-enhanced magnetic resonance (MR) angiography (TCMRA) and perfusion MR imaging (PWI) have been used to assess the hemodynamics of brain tumors. We assessed the feasibility and value of consecutive performance of these techniques to evaluate suspected brain metastasis following supplementary injection of gadolinium-based contrast medium. In 69 patients with suspected brain metastasis, we obtained precontrast MR images followed by TCMRA and postcontrast T1-weighted images after administration of 0.1 mmol/kg gadoteridol. When findings were negative or equivocal, we injected an additional 0.1-mmol/kg dose of gadoteridol and obtained PWI and second postcontrast T1-weighted images. We used a 3-point scale to grade perfusion maps and TCMRA and assessed whether these techniques added information to conventional MR imaging in the differential diagnosis. We also evaluated whether the second contrast injection improved the conspicuity and/or number of enhancing lesions and used a 4-point scoring system to quantitatively analyze diagnostic yield of TCMRA and PWI. We could assess tumor hemodynamics on PWI maps and TCMRA images in all 69 patients. In 14 cases (20%), PWI and/or TCMRA added information to conventional MR findings. After second injection of contrast medium, lesion conspicuity improved in 58 of the 69 cases (84%), and the number of detected lesions increased in 11 of 31 cases diagnosed with metastatic disease (36%). Quantitative analysis revealed TCMRA and PWI provided significant additional diagnostic information (Kruskal-Wallis test, P<0.0001). Consecutive acquisition of TCMRA and PWI using supplementary contrast injection can facilitate differential diagnosis of suspected brain metastasis and improve the number and conspicuity of detected lesions.

  9. Mn porphyrins as novel molecular magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Mouraviev, Vladimir; Venkatraman, Talaignair N; Tovmasyan, Artak; Kimura, Masaki; Tsivian, Matvey; Mouravieva, Vladimira; Polascik, Tom J; Wang, Haichen; Amrhein, Timothy J; Batinic-Haberle, Ines; Lascola, Christopher

    2012-11-01

    In this study, we investigated the potential of a new class of therapeutic Mn porphyrins as molecular MRI probes for prostate cancer imaging. Two compounds of different bioavailibility were investigated: Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) and Mn(III) meso-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5+)). These compounds have previously been shown to have adjunctive antineoplastic activity through their actions as powerful superoxide dismutase mimics, peroxynitrite scavengers, and modulators of cellular redox-based signaling pathways. Strong paramagnetic MRI contrast properties and affinity for cancer cells suggest their potential application as novel diagnostic imaging agents. MRI experiments were performed at 7.0T on a Bruker Biospec horizontal bore scanner. All in-vivo experiments were performed on 12 C57 black mice implanted with RM-9 prostate cancer cells on the hind limb. Two mg/kg of MnTnHex-2-PyP(5+) (n=6) and 8 mg/kg MnTE-2-PyP(5+) (n=6) were administered intraperitoneally 90 minutes before imaging. All the images were collected using a volume coil and processed using Paravision 4.0. Phantom studies reveal remarkably high T1 relaxivity changes for both metalloporphyrins, which are twofold to threefold higher than commercially available gadolinium chelates. Observable detection limits using conventional T1-weighted MRI are in the low micromolar range for both compounds. In vivo, MR relaxation changes in prostate tumor xenografts were readily observed after a single injection of either MnTE-2-PyP(5+)or MnTnHex-2-PyP(5+), with tumor contrast to background ratio greatest after MnTE-2-PyP(5+) administration. After a single dose of MnTE-2-PyP(5+), contrast changes in prostate tumors are up to sixfold greater than in surrounding, noncancerous tissues, suggesting the potential use of this metalloporphyrin as a novel diagnostic probe for detecting prostate malignancy using MRI.

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

    Science.gov (United States)

    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

  11. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    Science.gov (United States)

    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.

  12. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    Directory of Open Access Journals (Sweden)

    Yu Dexin

    2009-01-01

    Full Text Available Abstract 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

  13. Relating Doses of Contrast Agent Administered to TIC and Semi-Quantitative Parameters on DCE-MRI: Based on a Murine Breast Tumor Model.

    Directory of Open Access Journals (Sweden)

    Menglin Wu

    Full Text Available To explore the changes in the time-signal intensity curve(TIC type and semi-quantitative parameters of dynamic contrast-enhanced(DCEimaging in relation to variations in the contrast agent(CA dosage in the Walker 256 murine breast tumor model, and to determine the appropriate parameters for the evaluation ofneoadjuvantchemotherapy(NACresponse.Walker 256 breast tumor models were established in 21 rats, which were randomly divided into three groups of7rats each. Routine scanning and DCE-magnetic resonance imaging (MRI of the rats were performed using a 7T MR scanner. The three groups of rats were administered different dosages of the CA0.2mmol/kg, 0.3mmol/kg, and 0.5mmol/kg, respectively; and the corresponding TICs the semi-quantitative parameters were calculated and compared among the three groups.The TICs were not influenced by the CA dosage and presented a washout pattern in all of the tumors evaluated and weren't influenced by the CA dose. The values of the initial enhancement percentage(Efirst, initial enhancement velocity(Vfirst, maximum signal(Smax, maximum enhancement percentage(Emax, washout percentage(Ewash, and signal enhancement ratio(SER showed statistically significant differences among the three groups (F = 16.952, p = 0.001; F = 69.483, p<0.001; F = 54.838, p<0.001; F = 12.510, p = 0.003; F = 5.248, p = 0.031; F = 9.733, p = 0.006, respectively. However, the values of the time to peak(Tpeak, maximum enhancement velocity(Vmax, and washout velocity(Vwashdid not differ significantly among the three dosage groups (F = 0.065, p = 0.937; F = 1.505, p = 0.273; χ2 = 1.423, p = 0.319, respectively; the washout slope(Slopewash, too, was uninfluenced by the dosage(F = 1.654, p = 0.244.The CA dosage didn't affect the TIC type, Tpeak, Vmax, Vwash or Slopewash. These dose-independent parameters as well as the TIC type might be more useful for monitoring the NAC response because they allow the comparisons of the DCE data obtained using different

  14. New dual mode gadolinium nanoparticle contrast agent for magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Ketan B Ghaghada

    Full Text Available BACKGROUND: Liposomal-based gadolinium (Gd nanoparticles have elicited significant interest for use as blood pool and molecular magnetic resonance imaging (MRI contrast agents. Previous generations of liposomal MR agents contained gadolinium-chelates either within the interior of liposomes (core-encapsulated gadolinium liposomes or presented on the surface of liposomes (surface-conjugated gadolinium liposomes. We hypothesized that a liposomal agent that contained both core-encapsulated gadolinium and surface-conjugated gadolinium, defined herein as dual-mode gadolinium (Dual-Gd liposomes, would result in a significant improvement in nanoparticle-based T1 relaxivity over the previous generations of liposomal agents. In this study, we have developed and tested, both in vitro and in vivo, such a dual-mode liposomal-based gadolinium contrast agent. METHODOLOGY/PRINCIPAL FINDINGS: THREE TYPES OF LIPOSOMAL AGENTS WERE FABRICATED: core-encapsulated, surface-conjugated and dual-mode gadolinium liposomes. In vitro physico-chemical characterizations of the agents were performed to determine particle size and elemental composition. Gadolinium-based and nanoparticle-based T1 relaxivities of various agents were determined in bovine plasma. Subsequently, the agents were tested in vivo for contrast-enhanced magnetic resonance angiography (CE-MRA studies. Characterization of the agents demonstrated the highest gadolinium atoms per nanoparticle for Dual-Gd liposomes. In vitro, surface-conjugated gadolinium liposomes demonstrated the highest T1 relaxivity on a gadolinium-basis. However, Dual-Gd liposomes demonstrated the highest T1 relaxivity on a nanoparticle-basis. In vivo, Dual-Gd liposomes resulted in the highest signal-to-noise ratio (SNR and contrast-to-noise ratio in CE-MRA studies. CONCLUSIONS/SIGNIFICANCE: The dual-mode gadolinium liposomal contrast agent demonstrated higher particle-based T1 relaxivity, both in vitro and in vivo, compared to either the

  15. Impact of dispersants on relaxivities of magnetite contrast agents

    Science.gov (United States)

    Ma, Ji; Cheng, Lingchao; Chen, Kezheng

    2015-04-01

    Particle size is normally thought to be a major factor to evaluate MRI performance of contrast agents in biological systems. In this regard, three size-relevant regimes, including motional averaging regime, static dephasing regime, and echo-limited regime, have been well developed. In this study, we find the dispersant, which is often used as the subordinate additive in MRI measurements, is another key factor that determines the application of these three regimes in real systems. Our results show that the identically sized particle systems can separately exhibit static dephasing and echo-limited behaviors merely by altering the dispersants in aqueous solution.

  16. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    Science.gov (United States)

    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.

  17. Quantitative Imaging of Cell-Permeable Magnetic Resonance Contrast Agents Using X-Ray Fluorescence

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    Paul J. Endres

    2006-10-01

    Full Text Available The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III chelator with a cellular transduction moiety. Specifically, we coupled Gd(III–diethylenetriaminepentaacetic acid DTPA and Gd(III–1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8–amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-(N,N-dimethylaminostilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF. Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 103 better than 153Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T1 analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination.

  18. Modified Gadonanotubes as a Promising Novel MRI Contrasting Agent

    Directory of Open Access Journals (Sweden)

    Rouzbeh Jahanbakhsh

    2013-07-01

    Full Text Available 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.

  19. Assessment of tumor angiogenesis using fluorescence contrast agents

    Science.gov (United States)

    Chen, Yu; Liu, Qian; Huang, Ping; Hyman, Shay; Intes, Xavier; Lee, William; Chance, Britton

    2003-12-01

    Angiogenesis is an important factor for further tumor growth and thus could be an attractive therapeutic target. Optical imaging can provide a non-invasive way to measure the permeability of tumor blood vessels and assess the tumor vasculature. We have developed a dual-channel near-infrared fluorescence system for simultaneous measurement of the pharmacokinetics of tumorous and normal tissues with exogenous contrast agents. This frequency-domain system consists of the light source (780 nm laser diode), fiber optics, interference filter (830 nm) and the detector (PMT). The fluorescent contrast agent used in this study is Indocyanine Green (ICG), and the normal dosage is 100 μl at a concentration of 5 μM. In vivo animal study is performed on the K1735 melanoma-bearing mouse. The fluorescence signals both tumorous and normal tissues after the bolus injection of ICG through the tail vein are continuously recorded as a function of time. The data is fitted by a double-exponential model to reveal the wash-in and wash-out parameters of different tissues. We observed an elongated wash-out from the tumor compared with normal tissue (leg). The effect of radiation therapy on the tumor vasculature is also discussed.

  20. Agent-Based Cloud Computing

    OpenAIRE

    Sim, Kwang Mong

    2012-01-01

    Agent-based cloud computing is concerned with the design and development of software agents for bolstering cloud service\\ud discovery, service negotiation, and service composition. The significance of this work is introducing an agent-based paradigm for\\ud constructing software tools and testbeds for cloud resource management. The novel contributions of this work include: 1) developing\\ud Cloudle: an agent-based search engine for cloud service discovery, 2) showing that agent-based negotiatio...

  1. The delayed onset of subharmonic and ultraharmonic emissions from a phospholipid-shelled microbubble contrast agent.

    Science.gov (United States)

    Shekhar, Himanshu; Awuor, Ivy; Thomas, Keri; Rychak, Joshua J; Doyley, Marvin M

    2014-04-01

    Characterizing the non-linear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this article, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized non-linear emissions from Targestar-p microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 min, at 10 MHz excitation frequency. The results revealed a considerable increase in the subharmonic and ultraharmonic response (nearly 12-15 and 5-8 dB) after 5-10 min of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 min, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2-5 dB. The temporal changes in the non-linear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, non-linear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving non-linear imaging by careful design of ultrasound contrast agents.

  2. A model for ultrasound contrast agent in a phantom vessel

    KAUST Repository

    Qamar, Adnan

    2014-02-01

    A theoretical framework to model the dynamics of Ultrasound Contrast Agent (UCA) inside a phantom vessel is presented. The model is derived from the reduced Navier-Stokes equation and is coupled with the evolving flow field solution inside the vessel by a similarity transformation approach. The results are computed, and compared with experiments available in literature, for the initial UCA radius of Ro=1.5 μm and 2 μm for the vessel diameter of D=12 μm and 200 μm with the acoustic parameters as utilized in the experiments. When compared to other models, better agreement on smaller vessel diameter is obtained with the proposed coupled model. The model also predicts, quite accurately, bubble fragmentation in terms of acoustic and geometric parameters. © 2014 IEEE.

  3. HIFU Hemostasis of Liver Injuries Enhanced by Ultrasound Contrast Agents

    Science.gov (United States)

    Zderic, Vesna; Vaezy, Shahram; Brayman, Andrew A.; Matula, Thomas J.; O'Keefe, Grant E.; Crum, Lawrence A.

    2005-03-01

    Our objective was to investigate whether High-Intensity Focused Ultrasound (HIFU) hemostasis can be achieved faster in the presence of ultrasound contrast agents (UCA). Incisions (3 cm long and 0.5 cm deep) were made in surgically exposed rabbit liver. Optison at a concentration of 0.18 ml/kg was injected into the mesenteric vein, immediately before the incision was made. The HIFU applicator (frequency of 5.5 MHz, and intensity of 3,700 W/cm2) was scanned manually over the incision (at an approximate rate of 1 mm/s) until hemostasis was achieved. The times to complete hemostasis were measured and normalized with the initial blood loss. The hemostasis times were 59±23 s in the presence of Optison and 70±23 s without Optison. The presence of Optison produced a 37% reduction in the normalized hemostasis times (phemostasis of internal organ injuries.

  4. The use of contrast agent for imaging biological samples

    Energy Technology Data Exchange (ETDEWEB)

    Dammer, J; Sopko, V; Jakubek, J [Institute of Experimental and Applied Physics, Czech Technical University in Prague, Horska 3a/22, CZ 12800 Prague 2 (Czech Republic); Weyda, F, E-mail: jiri.dammer@utef.cvut.cz [Biological center of the Academy of Sciences of the Czech Republic, Institute of Entomology, Branisovska 31, CZ-37005 Ceske Budejovice (Czech Republic)

    2011-01-15

    The technique of X-ray transmission imaging has been available for over a century and is still among the fastest and easiest approaches to the studies of internal structure of biological samples. Recent advances in semiconductor technology have led to the development of new types of X-ray detectors with direct conversion of interacting X-ray photon to an electric signal. Semiconductor pixel detectors seem to be specially promising; compared to the film technique, they provide single-quantum and real-time digital information about the objects being studied. We describe the recently developed radiographic apparatus, equipped with Medipix2 semiconductor pixel detector. The detector is used as an imager that counts individual photons of ionizing radiation, emitted by an X-ray tube (micro- or nano-focus FeinFocus). Thanks to the wide dynamic range of the Medipix2 detector and its high spatial resolution better than 1{mu}m, the setup is particularly suitable for radiographic imaging of small biological samples, including in-vivo observations with contrast agent (Optiray). Along with the description of the apparatus we provide examples of the use iodine contrast agent as a tracer in various insects as model organisms. The motivation of our work is to develop our imaging techniques as non-destructive and non-invasive. Microradiographic imaging helps detect organisms living in a not visible environment, visualize the internal biological processes and also to resolve the details of their body (morphology). Tiny live insects are an ideal object for our studies.

  5. Stable and transient subharmonic emissions from isolated contrast agent microbubbles.

    Science.gov (United States)

    Biagi, Elena; Breschi, Luca; Vannacci, Enrico; Masotti, Leonardo

    2007-03-01

    Ultrasound contrast agents (UCAs) have been widely studied in recent years in order to improve and develop new, sophisticated imaging techniques for clinical applications. In order to improve the understanding of microbubble-ultrasound interactions, an acoustic dynamic characterization of UCA microbubble behavior was performed in this work using a high frame-rate acquiring and processing system. This equipment is connected to a commercial scanner that provides RF beam-formed data with a frame-rate of 30 Hz. Acquired RF sequences allows us to follow the dynamics of cavitation mechanisms in its temporal evolution during different insonifying conditions. The experimental setup allowed us to keep the bubbles free in a spatial region of the supporting medium, thus avoiding boundary effects that can alter the ultrasound field and the scattered echo from bubbles. The work focuses on the study of subharmonic emission from an isolated bubble of contrast agent. In particular, the acoustic pressure threshold for a subharmonic stable emission was evaluated for a subset of 50 microbubbles at 3.3 MHz and at 5 MHz of insonation frequencies. An unexpected second pressure threshold, which caused the stand still of the subharmonic emission, was detected at 3.3 MHz and 5 MHz excitation frequencies. A transient subharmonic emission, which is hypothesized as being related to the formation of new free gas bubbles, was detected during the ultrasound-induced destruction of microbubbles. An experimental procedure was devised in order to investigate these behaviors and several sequences of RF echo signals and the related spectra, acquired from an isolated bubble in different insonation conditions, are presented and discussed in this paper.

  6. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    NARCIS (Netherlands)

    Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M.D.; De Jong, N.; Vos, H.J.

    2015-01-01

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher

  7. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    NARCIS (Netherlands)

    Peruzzini, D.; J. Viti (Jacopo); P. Tortoli (Piero); M.D. Verweij (Martin D.); N. de Jong (Nico); H.J. Vos (Rik)

    2015-01-01

    textabstractCurrently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the

  8. Modeling contrast agent flow in cerebral aneurysms: comparison of CFD with medical imaging

    Science.gov (United States)

    Rayz, Vitaliy; Vali, Alireza; Sigovan, Monica; Lawton, Michael; Saloner, David; Boussel, Loic

    2016-11-01

    PURPOSE: The flow in cerebral aneurysms is routinely assessed with X-ray angiography, an imaging technique based on a contrast agent injection. In addition to requiring a patient's catheterization and radiation exposure, the X-ray angiography may inaccurately estimate the flow residence time, as the injection alters the native blood flow patterns. Numerical modeling of the contrast transport based on MRI imaging, provides a non-invasive alternative for the flow diagnostics. METHODS: The flow in 3 cerebral aneurysms was measured in vivo with 4D PC-MRI, which provides time-resolved, 3D velocity field. The measured velocities were used to simulate a contrast agent transport by solving the advection-diffusion equation. In addition, the flow in the same patient-specific geometries was simulated with CFD and the velocities obtained from the Navier-Stokes solution were used to model the transport of a virtual contrast. RESULTS: Contrast filling and washout patterns obtained in simulations based on MRI-measured velocities were in agreement with those obtained using the Navier-Stokes solution. Some discrepancies were observed in comparison to the X-ray angiography data, as numerical modeling of the contrast transport is based on the native blood flow unaffected by the contrast injection. NIH HL115267.

  9. MO-F-CAMPUS-J-01: Effect of Iodine Contrast Agent Concentration On Cerebrovascular Dose for Synchrotron Radiation Microangiography Based On a Simple Mouse Head Model and a Voxel Mouse Head Phantom

    Energy Technology Data Exchange (ETDEWEB)

    Lin, H; Jing, J; Xie, C [Hefei University of Technology, Hefei (China); Lu, Y [Shanghai Jiao Tong University, Shanghai (China)

    2015-06-15

    Purpose: To find effective setting methods to mitigate the irradiation injure in synchrotron radiation microangiography(SRA) by Monte Carlo simulation. Methods: A mouse 1-D head model and a segmented voxel mouse head phantom were simulated by EGSnrc/Dosxyznrc code to investigate the dose enhancement effect of the iodine contrast agent irradiated by a monochromatic synchrotron radiation(SR) source. The influence of, like iodine concentration (IC), vessel width and depth, with and without skull layer protection and the various incident X ray energies, were simulated. The dose enhancement effect and the absolute dose based on the segmented voxel mouse head phantom were evaluated. Results: The dose enhancement ratio depends little on the irradiation depth, but strongly on the IC, which is linearly increases with IC. The skull layer protection cannot be ignored in SRA, the 700µm thick skull could decrease 10% of the dose. The incident X-ray energy can significantly affact the dose. E.g. compared to the dose of 33.2keV for 50mgI/ml, the 32.7keV dose decreases 38%, whereas the dose of 33.7 keV increases 69.2%, and the variation will strengthen more with enhanced IC. The segmented voxel mouse head phantom also showed that the average dose enhancement effect and the maximal voxel dose per photon depends little on the iodine voxel volume ratio, but strongly on IC. Conclusion: To decrease dose damage in SRA, the high-Z contrast agent should be used as little as possible, and try to avoid radiating locally the injected position immediately after the contrast agent injection. The fragile vessel containing iodine should avoid closely irradiating. Avoiding irradiating through the no or thin skull region, or appending thin equivalent material from outside to protect is also a better method. As long as SRA image quality is ensured, using incident X-ray energy as low as possible.

  10. Mechanically Tunable Hollow Silica Ultrathin Nanoshells for Ultrasound Contrast Agents

    Science.gov (United States)

    Liberman, A.; Wang, J.; Lu, N.; Viveros, R.D.; Allen, C. A.; Mattrey, R.F.; Blair, S.L.; Trogler, W.C.; Kim, M. J.; Kummel, A.C.

    2015-01-01

    Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4–3.8 nm and diameters from 2–23 nm. PMID:26955300

  11. Ultrasound contrast agents for bleeding detection and acoustic hemostasis

    Science.gov (United States)

    Zderic, Vesna; Luo, Wenbo; Brayman, Andrew; Crum, Lawrence; Vaezy, Shahram

    2005-04-01

    Objective: To investigate the application of ultrasound contrast agents (UCA) in improving both therapeutic and diagnostic aspects of ultrasound-guided High Intensity Focused Ultrasound (HIFU) therapy. Methods: Incisions (3 cm long, 0.5 cm deep) were made in rabbit livers (in anterior surface for HIFU treatment, or posterior surface for bleeding detection). UCA Optison (~0.1 ml/kg) was injected into mesenteric vein or ear vein. A HIFU applicator (5.5 MHz, 6400 W/cm2) was scanned manually over the incision until hemostasis was achieved. Occult bleeding was monitored with Doppler ultrasound. Results: The presence of Optison produced 37% reduction in hemostasis times normalized to initial bleeding rates. Gross and histological observations showed similar appearance of HIFU lesions produced in the presence of Optison and control HIFU lesions. The temperature reached 100°C in both HIFU only and HIFU+UCA treatments. Tension strength of hemostatic liver incisions was 0.9+/-0.5 N. Almost no bleeding could be detected before Optison injection. First appearance of contrast enhancement localized at the bleeding site was 15 s after Optison injection, and lasted for ~50 s. Conclusion: The presence of UCA during HIFU treatment of liver incisions resulted in shortening of HIFU application times and better visualization of bleeding sites.

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

    Directory of Open Access Journals (Sweden)

    Estelrich J

    2015-03-01

    Full Text Available Joan Estelrich,1,2 María Jesús Sánchez-Martín,1 Maria Antònia Busquets1,2 1Departament de Fisicoquímica, Facultat de Farmàcia, Universitat de Barcelona, Barcelona, Catalonia, Spain; 2Institut de Nanociència I Nanotecnologia (IN2UB, Barcelona, Catalonia, SpainAbstract: 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

  13. Critical Questions Regarding Gadolinium Deposition in the Brain and Body After Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA's Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents.

    Science.gov (United States)

    Runge, Val M

    2017-06-01

    For magnetic resonance, the established class of intravenous contrast media is the gadolinium-based contrast agents. In the 3 decades since initial approval, these have proven in general to be very safe for human administration. However, in 2006, a devastating late adverse reaction to administration of the less stable gadolinium-based contrast agents was identified, nephrogenic systemic fibrosis. The result of actions taken by the European Medicines Agency and the US Food and Drug Administration, stratifying the agents by risk and contraindicating specific agents in severe renal dysfunction, has led to no new cases being identified in North America or Europe. Subsequently, in 2014, long-term deposition in the brain of gadolinium was first shown, after administration of 2 nonionic linear chelates, gadodiamide, and gadopentetate dimeglumine. This has led to an intense focus on the question of in vivo distribution, possible dechelation, and subsequent deposition of gadolinium, together with substantial clarification of the phenomenon as well as stratification of the agents on this basis. This review focuses on 8 critical questions regarding gadolinium deposition in the brain and body, with the answers and discussion therein important for future regulatory decisions and clinical practice. It is now clear that dechelation of gadolinium occurs in vivo with the linear agents and is responsible for this phenomenon, with key experts in the field recommending, except where there is no suitable alternative, a shift in clinical practice from the linear to macrocyclic agents. In addition, on March 10, 2017, the Pharmacovigilance and Risk Assessment Committee of the European Medicines Agency recommended suspension of the marketing authorization for 4 linear gadolinium contrast agents-specifically Omniscan, Optimark, Magnevist, and MultiHance (gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadobenate dimeglumine)-for intravenous injection. Cited in the report was

  14. Counterbalancing the use of ultrasound contrast agents by a cavitation-regulated system.

    Science.gov (United States)

    Desjouy, C; Fouqueray, M; Lo, C W; Muleki Seya, P; Lee, J L; Bera, J C; Chen, W S; Inserra, C

    2015-09-01

    The stochastic behavior of cavitation can lead to major problems of initiation and maintenance of cavitation during sonication, responsible of poor reproducibility of US-induced bioeffects in the context of sonoporation for instance. To overcome these disadvantages, the injection of ultrasound contrast agents as cavitation nuclei ensures fast initiation and lower acoustic intensities required for cavitation activity. More recently, regulated-cavitation devices based on the real-time modulation of the applied acoustic intensity have shown their potential to maintain a stable cavitation state during an ultrasonic shot, in continuous or pulsed wave conditions. In this paper is investigated the interest, in terms of cavitation activity, of using such regulated-cavitation device or injecting ultrasound contrast agents in the sonicated medium. When using fixed applied acoustic intensity, results showed that introducing ultrasound contrast agents increases reproducibility of cavitation activity (coefficient of variation 62% and 22% without and with UCA, respectively). Moreover, the use of the regulated-cavitation device ensures a given cavitation activity (coefficient of variation less 0.4% in presence of UCAs or not). This highlights the interest of controlling cavitation over time to free cavitation-based application from the use of UCAs. Interestingly, during a one minute sonication, while ultrasound contrast agents progressively disappear, the regulated-cavitation device counterbalance their destruction to sustain a stable inertial cavitation activity.

  15. Optical contrast agents to visualize molecular expression in breast cancer

    Science.gov (United States)

    Langsner, Robert James

    Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care. The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence. This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxyglucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation. To image these contrast agents in cancerous

  16. Gauging the likelihood of stable cavitation from ultrasound contrast agents.

    Science.gov (United States)

    Bader, Kenneth B; Holland, Christy K

    2013-01-07

    The mechanical index (MI) was formulated to gauge the likelihood of adverse bioeffects from inertial cavitation. However, the MI formulation did not consider bubble activity from stable cavitation. This type of bubble activity can be readily nucleated from ultrasound contrast agents (UCAs) and has the potential to promote beneficial bioeffects. Here, the presence of stable cavitation is determined numerically by tracking the onset of subharmonic oscillations within a population of bubbles for frequencies up to 7 MHz and peak rarefactional pressures up to 3 MPa. In addition, the acoustic pressure rupture threshold of an UCA population was determined using the Marmottant model. The threshold for subharmonic emissions of optimally sized bubbles was found to be lower than the inertial cavitation threshold for all frequencies studied. The rupture thresholds of optimally sized UCAs were found to be lower than the threshold for subharmonic emissions for either single cycle or steady state acoustic excitations. Because the thresholds of both subharmonic emissions and UCA rupture are linearly dependent on frequency, an index of the form I(CAV) = P(r)/f (where P(r) is the peak rarefactional pressure in MPa and f is the frequency in MHz) was derived to gauge the likelihood of subharmonic emissions due to stable cavitation activity nucleated from UCAs.

  17. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    Science.gov (United States)

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G.-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-06-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.

  18. Comparison of the optoacoustic signal generation efficiency of different nanoparticular contrast agents.

    Science.gov (United States)

    Bost, Wolfgang; Lemor, Robert; Fournelle, Marc

    2012-11-20

    Optoacoustic imaging represents a new modality that allows noninvasive in vivo molecular imaging with optical contrast and acoustical resolution. Whereas structural or functional imaging applications such as imaging of vasculature do not require contrast enhancing agents, nanoprobes with defined biochemical binding behavior are needed for molecular imaging tasks. Since the contrast of this modality is based on the local optical absorption coefficient, all particle or molecule types that show significant absorption cross sections in the spectral range of the laser wavelength used for signal generation are suitable contrast agents. Currently, several particle types such as gold nanospheres, nanoshells, nanorods, or polymer particles are used as optoacoustic contrast agents. These particles have specific advantages with respect to their absorption properties, or in terms of biologically relevant features (biodegradability, binding to molecular markers). In the present study, a comparative analysis of the signal generation efficiency of gold nanorods, polymeric particles, and magnetite particles using a 1064 nm Nd:YAG laser for signal generation is described.

  19. Pineapple juice as a negative oral contrast agent in magnetic resonance cholangiopancreatography: a preliminary evaluation.

    Science.gov (United States)

    Riordan, R D; Khonsari, M; Jeffries, J; Maskell, G F; Cook, P G

    2004-12-01

    The quality of magnetic resonance cholangiopancreatography (MRCP) images is frequently degraded by high signal from the gastrointestinal tract. The aim of this study is to evaluate pineapple juice (PJ) as an oral negative contrast agent in MRCP. Preliminary in vitro evaluation demonstrated that PJ shortened T(2) relaxation time and hence decreased T(2) signal intensity on a standard MRCP sequence to a similar degree to a commercially available negative contrast agent (ferumoxsil). Electrothermal atomic absorption spectrometry assay demonstrated a high manganese concentration in PJ of 2.76 mg dl(-1), which is likely to be responsible for its T(2) imaging properties. MRCP was subsequently performed in 10 healthy volunteers, before and at 15 min and 30 min following ingestion of 400 ml of PJ. Images were assessed blindly by two Consultant Radiologists using a standard grading technique based on contrast effect (degree of suppression of bowel signal), and image effect (diagnostic quality). There were statistically significant improvements in contrast and image effect between pre and post PJ images. There was particularly significant improvement in visualization of the pancreatic duct, but no significant difference between 15 min and 30 min post PJ images. Visualization of the ampulla, common bile duct, common hepatic and central intrahepatic ducts were also significantly improved at 15 min following PJ. Our results demonstrate that PJ, may be used as an alternative to commercially available negative oral contrast agent in MRCP.

  20. Effect of iodine contrast agent concentration on cerebrovascular dose for synchrotron radiation microangiography based on a simple mouse head model and a voxel mouse head phantom by Monte Carlo simulation.

    Science.gov (United States)

    Lin, Hui; Jing, Jia; Lu, Yi-Fan; Xie, Cong; Lin, Xiao-Jie; Yang, Guo-Yuan

    2016-01-01

    Effective setting strategies using Monte Carlo simulation are presented to mitigate the irradiation damage in synchrotron radiation microangiography (SRA). A one-dimensional mouse head model and a segmented voxel phantom mouse head were simulated using the EGSnrc/DOSXYZnrc code to investigate the dose enhancement effect of an iodine contrast agent irradiated by a monochromatic synchrotron radiation source. The influence of the iodine concentration, vessel width and depth, protection with and without the skull layer, and various incident X-ray energies were all simulated. The dose enhancement effect and the absolute dose based on the segmented voxel mouse head phantom were evaluated. The dose enhancement ratio depended little on the irradiation depth, but strongly and linearly increasing on iodine concentration. The protection given by the skull layer cannot be ignored in SRA because a 700 µm-thick skull can decrease the dose by 10%. The incident X-ray energy can affect the dose significantly. Compared with a dose of 33.2 keV for 50 mgI ml(-1), a dose of 32.7 keV decreased by 38%, whereas a dose of 33.7 keV increased by 69.2% and the variation strengthened more with enhanced iodine concentration. The segmented voxel mouse head phantom also showed that the average dose enhancement effect and the maximal voxel dose per photon depended little on the iodine voxel volume ratio but strongly on the iodine concentration. To decrease the damage caused by the dose in SRA, a high-Z contrast agent should be used as little as possible and irradiation of the injection site of the contrast agent should be avoided immediately after the injection. The fragile vessel containing iodine should avoid being closely irradiated. Avoiding irradiating through a thin (or no) skull region, or attaching a thin equivalent material on the outside for protection are better methods. An incident X-ray energy as low as possible should be used as long as the SRA image quality is ensured

  1. Econophysics of agent-based models

    CERN Document Server

    Aoyama, Hideaki; Chakrabarti, Bikas; Chakraborti, Anirban; Ghosh, Asim

    2014-01-01

    The primary goal of this book is to present the research findings and conclusions of physicists, economists, mathematicians and financial engineers working in the field of "Econophysics" who have undertaken agent-based modelling, comparison with empirical studies and related investigations. Most standard economic models assume the existence of the representative agent, who is “perfectly rational” and applies the utility maximization principle when taking action. One reason for this is the desire to keep models mathematically tractable: no tools are available to economists for solving non-linear models of heterogeneous adaptive agents without explicit optimization. In contrast, multi-agent models, which originated from statistical physics considerations, allow us to go beyond the prototype theories of traditional economics involving the representative agent. This book is based on the Econophys-Kolkata VII Workshop, at which many such modelling efforts were presented. In the book, leading researchers in the...

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

    Science.gov (United States)

    Daryaei, Iman; Pagel, Mark D

    2015-01-01

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

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

    Science.gov (United States)

    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.

  4. Ultrasonic microbubble contrast agents and the transplant kidney

    Energy Technology Data Exchange (ETDEWEB)

    Kay, D.H., E-mail: davidhkay@doctors.org.u [Department of Radiology, Western Infirmary, Glasgow (United Kingdom); Mazonakis, M.; Geddes, C. [Department of Renal Medicine, Western Infirmary, Glasgow (United Kingdom); Baxter, G. [Department of Radiology, Western Infirmary, Glasgow (United Kingdom)

    2009-11-15

    Aim: To evaluate the potential application of microbubble agents in the immediate post-transplant period, by studying contrast uptake and washout, and to correlate these values with clinical indices, and thus, assess the potential prognostic value of this technique. Materials and methods: The study group comprised 20 consecutive renal transplant patients within 7 days of transplantation. Sonovue was administered as an intravenous bolus with continuous imaging of the transplant kidney at low mechanical index (MI) for 1 min post-injection. These data were analysed off-line by two observers, and time intensity curves (TIC) for the upper, mid, and lower poles constructed. Within each pole, a region of interest (5 mm square) was placed over the cortex, medullary pyramid, and interlobar artery, resulting in a total of nine TIC for each patient. TIC parameters included the arrival time (AT), time to peak (TTP), peak intensity (Max), gradient of the slope (M), and the area under curve (AUC). Results: For both observers there was good agreement for all values measured from the cortex and medulla, but poor interobserver correlation for the vascular values. In addition, there was only agreement for these values in the upper and mid-pole of the transplant with poor agreement for the lower pole values. The mid-pole of the transplant kidney was chosen as the point of measurement for subsequent studies. Mid-pole values were correlated with clinical data and outcome over the 3-month post-transplant period. Renal microbubble perfusion correlated with the transplant estimated glomerular filtration rate (eGFR) at 3 months post-transplantation (p = 0.016). Discussion: In conclusion, this is the first study to confirm reproducibility of the Sonovue TIC data in transplant patients and to quantify regional variation and perfusion. The statistically significant estimates of transplant perfusion may be of future benefit to transplant recipients and potentially utilized as a prognostic tool

  5. High frequency nonlinear scattering from a micrometer to submicrometer sized lipid encapsulated contrast agent

    NARCIS (Netherlands)

    Goertz, David E.; Frijlink, Martijn E.; de Jong, N.; van der Steen, A.F.W.

    2006-01-01

    An experimental lipid encapsulated contrast agent comprised substantially of micrometer to submicrometer diameter bubbles was evaluated for its capacity to produce nonlinear scattering in response to high transmit frequencies. Agent characterization experiments were conducted at transmit frequencies

  6. Thermal dependence of ultrasound contrast agents scattering efficiency for echographic imaging techniques

    Science.gov (United States)

    Biagioni, Angelo; Bettucci, Andrea; Passeri, Daniele; Alippi, Adriano

    2015-06-01

    Ultrasound contrast agents are used in echographic imaging techniques to enhance image contrast. In addition, they may represent an interesting solution to the problem of non-invasive temperature monitoring inside the human body, based on some thermal variations of their physical properties. Contrast agents, indeed, are inserted into blood circulation and they reach the most important organs inside the human body; consequently, any thermometric property that they may possess, could be exploited for realizing a non-invasive thermometer. They essentially are a suspension of microbubbles containing a gas enclosed in a phospholipid membrane; temperature variations induce structural modifications of the microbubble phospholipid shell, thus causing thermal dependence of contrast agent's elastic characteristics. In this paper, the acoustic scattering efficiency of a bulk suspension of of SonoVue® (Bracco SpA Milan, Italy) has been studied using a pulse-echo technique in the frequency range 1-17 MHz, as it depends upon temperatures between 25 and 65°C. Experimental data confirm that the ultrasonic attenuation coefficient of SonoVue® depends on temperature between 25 and 60°C. Chemical composition of the bubble shell seem to support the hypothesis that a phase transition in the microstructure of lipid-coated microbubbles could play a key role in explaining such effect.

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

    Science.gov (United States)

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

    2010-03-01

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

  8. Ultrasound contrast-agent improves imaging of lower limb occlusive disease

    DEFF Research Database (Denmark)

    Eiberg, J P; Hansen, M A; Jensen, F

    2003-01-01

    to evaluate if ultrasound contrast-agent infusion could improve duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the agreement with digital subtraction arteriography (DSA)....

  9. Methodology and imaging contrast agent in the arthography of the shoulder

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, M.; Taenzer, V.; Wenzel-Hora, B.I.

    1987-11-01

    Arthrography of the shoulder using an isotonic non-ionic contrast medium is performed at a markedly reduced complication rate compared with contrast agents used previously. Diagnostic gain is considerable.

  10. Hydroxy double salts intercalated with Mn(II) complexes as potential contrast agents

    Science.gov (United States)

    Jin, Miao; Li, Wanjing; Spillane, Dominic E. M.; Geraldes, Carlos F. G. C.; Williams, Gareth R.; Bligh, S. W. Annie

    2016-03-01

    A series of Mn(II) aminophosphonate complexes were successfully synthesized and intercalated into the hydroxy double salt [Zn5(OH)8]Cl2·yH2O. Complex incorporation led to an increase in the interlayer spacing from 7.8 to 10-12 Å. Infrared spectroscopy showed the presence of the characteristic vibration peaks of the Mn(II) complexes in the intercalates' spectra, indicating successful incorporation. The complex-loaded composites had somewhat lower proton relaxivities than the pure complexes. Nevertheless, these intercalates may have use as MRI contrast agents for patients with poor kidney function, where traditional Gd(III)-based contrast agents cause severe renal failure.

  11. Small animal optoacoustic tomography system for molecular imaging of contrast agents

    Science.gov (United States)

    Su, Richard; Liopo, Anton; Ermilov, Sergey A.; Oraevsky, Alexander A.

    2016-03-01

    We developed a new and improved Laser Optoacoustic Imaging System, LOIS-3D for preclinical research applications in small animal models. The advancements include (i) a new stabilized imaging module with a more homogeneous illumination of the mouse yielding a better spatial resolution (research applications, such as imaging vascularization and measuring hemoglobin / oxyhemoglobin distribution in the organs as well as imaging exogenous or endogenous optoacoustic contrast agents. As examples, we present in vivo experiments using phantoms and mice with and without tumor injected with contrast agents with indocyanine green (ICG). LOIS-3D was capable of detecting ~1-2 pmole of the ICG, in tissues with relatively low blood content. With its high sensitivity and excellent spatial resolution LOIS-3D is an advanced alternative to fluorescence and bioluminescence based modalities for molecular imaging in live mice.

  12. X-ray Scatter Imaging of Hepatocellular Carcinoma in a Mouse Model Using Nanoparticle Contrast Agents

    Science.gov (United States)

    Rand, Danielle; Derdak, Zoltan; Carlson, Rolf; Wands, Jack R.; Rose-Petruck, Christoph

    2015-10-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide and is almost uniformly fatal. Current methods of detection include ultrasound examination and imaging by CT scan or MRI; however, these techniques are problematic in terms of sensitivity and specificity, and the detection of early tumors (contrast agents can be detected using SFHI. We also demonstrate that directed targeting and SFHI of HCC tumors in a mouse model is possible through the use of HCC-specific antibodies. The enhanced sensitivity of SFHI relative to currently available techniques enables the x-ray imaging of tumors that are just a few millimeters in diameter and substantially reduces the amount of nanoparticle contrast agent required for intravenous injection relative to absorption-based x-ray imaging.

  13. Subharmonic behavior of phospholipid-coated ultrasound contrast agent microbubbles

    NARCIS (Netherlands)

    Sijl, Jeroen; Dollet, Benjamin; Overvelde, Marlies; Garbin, Valeria; Rozendal, Timo; Jong, de Nico; Lohse, Detlef; Versluis, Michel

    2010-01-01

    Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subh

  14. Study on the uptake and distribution of gadolinium based contrast agents in biological samples using laser ablation with inductively coupled plasma mass spectroscopy; Untersuchungen zur Aufnahme und Verteilung von gadoliniumbasierten Kontrastmitteln in biologischen Proben mittels Laserablation mit induktiv gekoppelter Plasma-Massenspektrometrie

    Energy Technology Data Exchange (ETDEWEB)

    Lingott, Jana

    2016-01-05

    Gadolinium based contrast agents are used for magnetic resonance imaging. After their excretion by medicated patients they reach surface water passing waste water treatment plants where they are not removed sufficiently. The behavior of the contrast agents in the environment and the interaction with organisms was investigated in this work due to the toxicity of the free Gd{sup 3+} ion and the associated risks, such as accumulation in the human food chain. In this work, the two elemental analytical imaging methods laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) and synchrotron radiation X-ray fluorescence analysis (SRXRF) have been used to investigate the uptake, distribution, and excretion of Gd-based contrast agents by various biological systems. Both methods were analytically characterized and compared for this application. The detection limits of gadolinium were determined under optimized conditions by LA-ICP-MS and SRXRF. With calibration by remains of dried elemental standard droplets detection limits of 0.78 pg absolute amount of gadolinium (LA-ICP-MS), respectively 89 pg (SRXRF) were reached. Based on filamentous algae as water plants the uptake and the excretion of Gd-based contrast agents were revealed. The dependence on concentration of the contrast agent in the exposition solution and the independence of temporal uptake within one to seven days were studied for duckweed. By LA-ICP-MS gadolinium was quantified in a leaf of cress plant. The verification of the results was performed by SRXRF and ICP-MS after digestion. Furthermore, the uptake and distribution of Gd-based contrast agents in higher organisms (water flea) were observed. The exact location of gadolinium was resolved by three-dimensional μ-computed tomography by the comparison of an exposed with a Gd-free water flea. In all studies, gadolinium was detected in the investigated exposed model organisms. It can be concluded that the contrast agents were taken from the

  15. Identification of chronic myocardial infarction with extracellular or intravascular contrast agents in magnetic resonance imaging

    Institute of Scientific and Technical Information of China (English)

    Jian WANG; Hong-yu LIU; Hang L(U); Bo XIANG; Marco GRUWEL; Boguslaw TOMANEK; Roxanne DESLAURIERS; Gang-hong TIAN

    2008-01-01

    Aim: To determine whether extracellular or intravascular contrast agents could detect chronic scarred myocardium in magnetic resonance imaging (MRI). Methods: Eighteen pigs underwent a 4 week ligation of 1 or 2 diagonal coronary arteries to induce chronic myocardial infarction. The hearts were then removed and perfused in a Langendorff apparatus. Eighteen hearts were divided into 2 groups. The hearts in groups Ⅰ (n=9) and Ⅱ (n=9) 收稿日期the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA, 0.05 mmol/kg) and ga-dolinium-based macromolecular agent (P792, 15 μmol/kg), respectively. First pass T2* MRI was acquired using a FLASH sequence. Delayed enhancement T1 MRI was acquired with an inversion recovery prepared TurboFLASH sequence.Results: Wash-in of both agents resulted in a sharp and dramatic T2* signal loss of scarred myocardium similar to that of normal myocardium. The magnitude and velocity of T2* signal recovery caused by wash-out of extracellular agents in normal myocardium was significantly less than that in scarred myocardium. Conversely, the T2* signal of scarred and normal myocardium recovered to plateau rapidly and simultaneously due to wash-out of intravascular agents. At the fol-lowing equilibrium, extracellular agent-enhanced T1 signal intensity was signifi-cantly greater in scarred myocardium than in normal myocardium, whereas there was no significantly statistical difference in intravascular agent-enhanced T1 sig-nal intensity between scarred and normal myocardium. Conclusion: After admin-istration of extracellular agents, wash-out T2* first-pass and delayed enhanced T1 MRI could identify scarred myocardium as a hyperenhanced region. Conversely, scarred myocardium was indistinguishable from normal myocardium during first-pass and the steady state of intravascular agents.

  16. High performance MRI Contrast Agents Based on Functionalized Carbon Nanotubes%基于碳纳米管的高性能核磁共振造影剂研究进展

    Institute of Scientific and Technical Information of China (English)

    柳月; 邱介山

    2015-01-01

    碳纳米管是一种具有独特结构和性能的一维纳米材料,已在生物医药和基因传输及生物医学成像等方面显示出重要的应用前景。本文介绍由钆及磁性氧化铁纳米颗粒修饰的新型碳纳米管造影剂的制备及应用,其中,钆螯合物、钆催化生长的碳纳米管及钆纳米管作为T1权重核磁共振造影剂,而铁催化生长的碳纳米管和超顺磁性氧化铁纳米颗粒修饰的碳纳米管作为T2权重核磁共振造影剂。这二种类型的造影剂均具有良好的生物相容性,在体外和体内MRI测试中显示出较高的成像对比度。%Carbon nanotubes (CNTs) are one of the most promising 1D nanomaterials with unique morphology and properties, and hold great promise in biomedicine for drug/gene delivery and biomedical imaging. The use of CNTs as potential magnetic resonance imaging (MRI) contrast agents has drawn much attention in the past decades. In this review, the progress in novel magnetic resonance imaging (MRI) contrast agents composed of CNTs decorated with gadolinium or magnetic iron oxide nanoparticles are summarized. The concerned MRI contrast agents are focused on two types of MRI contrast agents, i.e. Gadolinium chelate, Gd catalyzed CNTs and Gadonanotubes as T1-weighted MRI contrast agents, and Fe catalyzed CNTs and superparamagnetic iron oxide modiifed CNTs as T2-weighted MRI contrast agents. Both are hydrophilic, biocompatible, and show a high performance as a MRI contrast in in vitro and in vivo tests.

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

    Science.gov (United States)

    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.

  18. Ultrasmall Nanoplatforms as Calcium-Responsive Contrast Agents for Magnetic Resonance Imaging.

    Science.gov (United States)

    Moussaron, Albert; Vibhute, Sandip; Bianchi, Andrea; Gündüz, Serhat; Kotb, Shady; Sancey, Lucie; Motto-Ros, Vincent; Rizzitelli, Silvia; Crémillieux, Yannick; Lux, Francois; Logothetis, Nikos K; Tillement, Olivier; Angelovski, Goran

    2015-10-07

    The preparation of ultrasmall and rigid platforms (USRPs) that are covalently coupled to macrocycle-based, calcium-responsive/smart contrast agents (SCAs), and the initial in vitro and in vivo validation of the resulting nanosized probes (SCA-USRPs) by means of magnetic resonance imaging (MRI) is reported. The synthetic procedure is robust, allowing preparation of the SCA-USRPs on a multigram scale. The resulting platforms display the desired MRI activity—i.e., longitudinal relaxivity increases almost twice at 7 T magnetic field strength upon saturation with Ca(2+). Cell viability is probed with the MTT assay using HEK-293 cells, which show good tolerance for lower contrast agent concentrations over longer periods of time. On intravenous administration of SCA-USRPs in living mice, MRI studies indicate their rapid accumulation in the renal pelvis and parenchyma. Importantly, the MRI signal increases in both kidney compartments when CaCl2 is also administrated. Laser-induced breakdown spectroscopy experiments confirm accumulation of SCA-USRPs in the renal cortex. To the best of our knowledge, these are the first studies which demonstrate calcium-sensitive MRI signal changes in vivo. Continuing contrast agent and MRI protocol optimizations should lead to wider application of these responsive probes and development of superior functional methods for monitoring calcium-dependent physiological and pathological processes in a dynamic manner.

  19. A human cell model for dynamic testing of MR contrast agents.

    Science.gov (United States)

    Aulanier, Anne-Lise; Doiron, Amber L; Shepherd, Robert D; Rinker, Kristina D; Frayne, Richard; Andersen, Linda B

    2011-02-01

    To determine the initial feasibility of using magnetic resonance (MR) imaging to detect early atherosclerosis, we investigated inflammatory cells labeled with a positive contrast agent in an endothelial cell-based testing system. The human monocytic cell line THP-1 was labeled by overnight incubation with a gadolinium colloid (Gado CELLTrack) prior to determination of the in vitro release profile from T1-weighted MR images. Next, MR signals arising from both a synthetic model of THP-1/human umbilical vein endothelial cell (HUVEC) accumulation and the dynamic adhesion of THP-1 cells to activated HUVECs under flow were obtained. THP-1 cells were found to be successfully--but not optimally--labeled with gadolinium colloid, and MR images demonstrated increased signal from labeled cells in both the synthetic and dynamic THP-1/HUVEC models. The observed THP-1 contrast release profile was rapid, suggesting the need for an agent that is optimized for retention in the target cells for use in further studies. Detection of labeled THP-1 cells was accomplished with no signal enhancement from unlabeled cells. These achievements demonstrate the feasibility of targeting early atherosclerosis with MR imaging, and suggest that using an in vitro system like the one described provides a rapid, efficient, and cost-effective way to support the development and evaluation of novel MR contrast agents.

  20. Agent Based Individual Traffic Guidance

    DEFF Research Database (Denmark)

    Wanscher, Jørgen

    This thesis investigates the possibilities in applying Operations Research (OR) to autonomous vehicular traffic. The explicit difference to most other research today is that we presume that an agent is present in every vehicle - hence Agent Based Individual Traffic guidance (ABIT). The next...

  1. An in vitro study of a microbubble contrast agent using a clinical ultrasound imaging system

    Science.gov (United States)

    Sboros, V.; Moran, C. M.; Pye, S. D.; McDicken, W. N.

    2004-01-01

    Optimal insonation settings for contrast imaging are yet to be specified, mainly due to the lack of good understanding of the behaviour of the microbubbles. A satisfactory model that explains the behaviour of individual contrast agent scatterers has not yet been reported in the literature. An in vitro system based on a commercial scanner (ATL HDI3000) has been developed to investigate the backscatter of such agents. Suspensions of Definity® were introduced in an anechoic tank. The frequency of transmitted ultrasound varied from 1 to 5 MHz, pulse period from 2 to 10 periods and peak negative acoustic pressure from 0.08 to 1.7 MPa. The backscatter at the fundamental and second harmonic frequency windows from the agent was normalized in terms of the corresponding components of backscatter from a blood mimicking fluid suspension. The agent provided a dominant resonance effect at 1.6 MHz transmit frequency. Second harmonic normalized backscatter averaged around 9 dB higher than the fundamental. The normalized fundamental backscatter intensity was linear with peak negative pressure. The second harmonic at resonance peaked at 0.5 MPa suggestive of bubble disruption above such pressure. The system proved capable of illustrating the ultrasonic behaviour of Definity® in vitro, and the investigation suggested particular insonation conditions for optimal image enhancement using Definity®.

  2. Novel nano-sized MR contrast agent mediates strong tumor contrast enhancement in an oncogene-driven breast cancer model.

    Directory of Open Access Journals (Sweden)

    Per-Olof Eriksson

    Full Text Available The current study was carried out to test the potential of a new nanomaterial (Spago Pix as a macromolecular magnetic MR contrast agent for tumor detection and to verify the presence of nanomaterial in tumor tissue. Spago Pix, synthesized by Spago Nanomedical AB, is a nanomaterial with a globular shape, an average hydrodynamic diameter of 5 nm, and a relaxivity (r1 of approximately 30 (mM Mn-1 s-1 (60 MHz. The material consists of an organophosphosilane hydrogel with strongly chelated manganese (II ions and a covalently attached PEG surface layer. In vivo MRI of the MMTV-PyMT breast cancer model was performed on a 3 T clinical scanner. Tissues were thereafter analyzed for manganese and silicon content using inductively coupled plasma-atomic emission spectroscopy (ICP-AES. The presence of nanomaterial in tumor and muscle tissue was assessed using an anti-PEG monoclonal antibody. MR imaging of tumor-bearing mice (n = 7 showed a contrast enhancement factor of 1.8 (tumor versus muscle at 30 minutes post-administration. Contrast was retained and further increased 2-4 hours after administration. ICP-AES and immunohistochemistry confirmed selective accumulation of nanomaterial in tumor tissue. A blood pharmacokinetics analysis showed that the concentration of Spago Pix gradually decreased over the first hour, which was in good agreement with the time frame in which the accumulation in tumor occurred. In summary, we demonstrate that Spago Pix selectively enhances MR tumor contrast in a clinically relevant animal model. Based on the generally higher vascular leakiness in malignant compared to benign tissue lesions, Spago Pix has the potential to significantly improve cancer diagnosis and characterization by MRI.

  3. Contrast-enhanced US-guided Interventions: Improving Success Rate and Avoiding Complications Using US Contrast Agents.

    Science.gov (United States)

    Huang, Dean Y; Yusuf, Gibran T; Daneshi, Mohammad; Husainy, Mohammad Ali; Ramnarine, Raymond; Sellars, Maria E K; Sidhu, Paul S

    2017-01-01

    Ultrasonography (US) is an established modality for intervention. The introduction of microbubble US contrast agents (UCAs) has the potential to further improve US imaging for intervention. According to licensing, UCAs are currently approved for clinical use in restricted situations, but many additional indications have become accepted as having clinical value. The use of UCAs has been shown to be safe, and there is no risk of renal toxic effects, unlike with iodinated or gadolinium contrast medium. Broadly speaking, UCAs can be injected into the bloodstream (intravascular use) or instilled into almost any accessible body cavity (endocavitary use), either in isolation or synchronously. In microvascular applications, contrast-enhanced US (CEUS) enhances delineation of necrotic areas and the vascularized target to improve real-time targeting. The ability of CEUS to allow true assessment of vascularity has also been used in follow-up of devascularizing intervention. In macrovascular applications, real-time angiographic images can be obtained with CEUS without nephrotoxic effects or radiation. In endocavitary applications, CEUS can achieve imaging similar to that of iodinated contrast medium-based fluoroscopy; follow-up to intervention (eg, tubography and nephrostography) can be performed at the bedside, which may be advantageous. The use of UCAs is a natural progression in US-guided intervention. The aim of this article is to describe the indications, contraindications, and techniques of using UCAs as an adjunctive tool for US-guided interventional procedures to facilitate effective treatment, improve complication management, and increase the overall success of interventional procedures. Online supplemental material is available for this article. (©)RSNA, 2016.

  4. Ultrasound contrast-agent improves imaging of lower limb occlusive disease

    DEFF Research Database (Denmark)

    Eiberg, J P; Hansen, M A; Jensen, F

    2003-01-01

    to evaluate if ultrasound contrast-agent infusion could improve duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the agreement with digital subtraction arteriography (DSA).......to evaluate if ultrasound contrast-agent infusion could improve duplex-ultrasound imaging of peripheral arterial disease (PAD) and increase the agreement with digital subtraction arteriography (DSA)....

  5. OUR APPROACH TOWARDS DEVELOPING A SPECIFIC TUMOR-TARGETED MRI CONTRAST AGENT FOR THE BRAIN

    NARCIS (Netherlands)

    GO, KG; BULTE, JWM; DELEY, L; THE, TH; KAMMAN, RL; HULSTAERT, CE; BLAAUW, EH; MA, LD

    1993-01-01

    This review presents various aspects of the technological development, and their assessment in the design of a contrast agent for MRI, tailored to visualise tumours in the brain. First, it was demonstrated that magnetite as a contrast agent exhibited a much stronger relaxivity than gadolinium. The p

  6. Congenital heart disease: cardiovascular MR imaging by using an intravascular blood pool contrast agent.

    NARCIS (Netherlands)

    Makowski, M.R.; Wiethoff, A.J.; Uribe, S.; Parish, V.; Botnar, R.M.; Bell, A.; Kiesewetter, C.; Beerbaum, P.B.J.; Jansen, C.H.; Razavi, R.; Schaeffter, T.; Greil, G.F.

    2011-01-01

    PURPOSE: To compare the image quality and diagnostic performance of a contrast agent-specific inversion-recovery (IR) steady-state free precession (SSFP) magnetic resonance (MR) imaging sequence performed by using an intravascular contrast agent (gadofosveset trisodium) with those of a commonly used

  7. Dextran coated bismuth-iron oxide nanohybrid contrast agents for computed tomography and magnetic resonance imaging.

    Science.gov (United States)

    Naha, Pratap C; Zaki, Ajlan Al; Hecht, Elizabeth; Chorny, Michael; Chhour, Peter; Blankemeyer, Eric; Yates, Douglas M; Witschey, Walter R T; Litt, Harold I; Tsourkas, Andrew; Cormode, David P

    2014-12-14

    Bismuth nanoparticles have been proposed as a novel CT contrast agent, however few syntheses of biocompatible bismuth nanoparticles have been achieved. We herein report the synthesis of composite bismuth-iron oxide nanoparticles (BION) that are based on a clinically approved, dextran-coated iron oxide formulation; the particles have the advantage of acting as contrast agents for both CT and MRI. BION were synthesized and characterized using various analytical methods. BION CT phantom images revealed that the X-ray attenuation of the different formulations was dependent upon the amount of bismuth present in the nanoparticle, while T2-weighted MRI contrast decreased with increasing bismuth content. No cytotoxicity was observed in Hep G2 and BJ5ta cells after 24 hours incubation with BION. The above properties, as well as the yield of synthesis and bismuth inclusion efficiency, led us to select the Bi-30 formulation for in vivo experiments, performed in mice using a micro-CT and a 9.4 T MRI system. X-ray contrast was observed in the heart and blood vessels over a 2 hour period, indicating that Bi-30 has a prolonged circulation half-life. Considerable signal loss in T2-weighted MR images was observed in the liver compared to pre-injection scans. Evaluation of the biodistribution of Bi-30 revealed that bismuth is excreted via the urine, with significant concentrations found in the kidneys and urine. In vitro experiments confirmed the degradability of Bi-30. In summary, dextran coated BION are biocompatible, biodegradable, possess strong X-ray attenuation properties and also can be used as T2-weighted MR contrast agents.

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

    Science.gov (United States)

    Ma, J.; Chen, K.

    2016-04-01

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

  9. Effects of gadolinium-based contrast agent concentrations (0.5 M or 1.0 M) on the diagnostic performance of magnetic resonance imaging examinations: systematic review of the literature.

    Science.gov (United States)

    Lancelot, Eric; Froehlich, John; Heine, Oliver; Desché, Pierre

    2016-11-01

    Background To date there is no agreement as to what is the optimal concentration for gadolinium-based contrast agents (GBCAs). Purpose To assess whether diagnostic performance differences exist between 0.5 M and 1.0 M GBCAs used for magnetic resonance imaging (MRI). Material and Methods A PubMed literature search identified 21 clinical studies published between 2005 and 2013 which evaluated the diagnostic efficacy of both types of GBCAs. Study design, type of procedure, GBCA administration mode, imaging performances, impact on patient management, study limitations, and biases were analyzed. No statistical test was performed on pooled data. Results Sixteen comparative and five non-comparative studies were analyzed, involving 2183 patients who underwent MRI procedures for various indications. In 67% of the studies, 0.5 M and 1.0 M GBCAs were injected at equimolar gadolinium amounts per kg body weight. Only 33% applied the same molar flow rate for delivery of the GBCAs. No significant differences between GBCAs were reported for 23 out of 27 qualitative endpoints (mainly image quality, lesion, and vessel visualization) and 29 out of 40 quantitative endpoints. Three out of four studies with non-equimolar delivery rates showed better contrast-to-noise and signal-to-noise ratios for 1.0 M gadobutrol, without showing an impact on diagnostic performance. Methodological biases were identified in several studies impairing the interpretation of comparisons. Conclusion Imaging differences between 0.5 M and 1.0 M GBCAs were essentially observed under non-equimolar delivery rates. However, they did not result into greater diagnostic efficacy when performed under equimolar conditions.

  10. Metal-oxo containing polymer nanobeads as potential contrast agents for magnetic resonance imaging

    Science.gov (United States)

    Pablico, Michele Huelar

    Magnetic resonance imaging (MRI) has greatly revolutionized the way diseases are detected and treated, as it is a non-invasive imaging modality solely based on the interaction of radiowaves and hydrogen nuclei in the presence of an external magnetic field. It is widely used today for the diagnosis of diseases as it offers an efficient method of mapping structure and function of soft tissues in the body. Most MRI examinations utilize paramagnetic materials known as contrast agents, which enhance the MR signal by decreasing the longitudinal (T1) and transverse (T2) relaxation times of the surrounding water protons in biological systems. This results into increased signal intensity differences thereby allowing better interpretation and analysis of pathological tissues. Contrast agents function by lowering the T1 or lowering the T2, resulting into bright and dark contrasts, respectively. The most common MRI contrast agents that are in clinical use today are gadolinium chelates and superparamagnetic iron oxide nanoparticles, both of which have their own advantages in terms of contrast enhancement properties. In the past few years, however, there has been interest in utilizing metal-containing clusters for MRI contrast enhancement as these materials bridge the gap between the constrained structure and magnetic properties of the gadolinium chelates with the superparamagnetic behavior of the iron oxide nanoparticles. Recently, metallic clusters containing Mn and Fe metal centers have received increased attention mainly because of their potential for high spin states and benign nature. In the quest to further develop novel imaging agents, this research has focused on investigating the use of metal-oxo clusters as potential contrast agents for MRI. The primary goal of this project is to identify clusters that meet the following criteria: high paramagnetic susceptibility, water-soluble, stable, cheap, contain environmentally benign metals, and easily derivatized. This work is

  11. Agent Based Multiviews Requirements Model

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Based on the current researches of viewpoints oriented requirements engineering and intelligent agent, we present the concept of viewpoint agent and its abstract model based on a meta-language for multiviews requirements engineering. It provided a basis for consistency checking and integration of different viewpoint requirements, at the same time, these checking and integration works can automatically realized in virtue of intelligent agent's autonomy, proactiveness and social ability. Finally, we introduce the practical application of the model by the case study of data flow diagram.

  12. Catechin tuned magnetism of Gd-doped orthovanadate through morphology as T1-T2 MRI contrast agents

    Science.gov (United States)

    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

  13. Regional contrast agent quantification in a mouse model of myocardial infarction using 3D cardiac T1 mapping

    Directory of Open Access Journals (Sweden)

    Nicolay Klaas

    2011-10-01

    Full Text Available Abstract Background Quantitative relaxation time measurements by cardiovascular magnetic resonance (CMR are of paramount importance in contrast-enhanced studies of experimental myocardial infarction. First, compared to qualitative measurements based on signal intensity changes, they are less sensitive to specific parameter choices, thereby allowing for better comparison between different studies or during longitudinal studies. Secondly, T1 measurements may allow for quantification of local contrast agent concentrations. In this study, a recently developed 3D T1 mapping technique was applied in a mouse model of myocardial infarction to measure differences in myocardial T1 before and after injection of a liposomal contrast agent. This was then used to assess the concentration of accumulated contrast agent. Materials and methods Myocardial ischemia/reperfusion injury was induced in 8 mice by transient ligation of the LAD coronary artery. Baseline quantitative T1 maps were made at day 1 after surgery, followed by injection of a Gd-based liposomal contrast agent. Five mice served as control group, which followed the same protocol without initial surgery. Twenty-four hours post-injection, a second T1 measurement was performed. Local ΔR1 values were compared with regional wall thickening determined by functional cine CMR and correlated to ex vivo Gd concentrations determined by ICP-MS. Results Compared to control values, pre-contrast T1 of infarcted myocardium was slightly elevated, whereas T1 of remote myocardium did not significantly differ. Twenty-four hours post-contrast injection, high ΔR1 values were found in regions with low wall thickening values. However, compared to remote tissue (wall thickening > 45%, ΔR1 was only significantly higher in severe infarcted tissue (wall thickening r = 0.81 was found between CMR-based ΔR1 values and Gd concentrations from ex vivo ICP-MS measurements. Furthermore, regression analysis revealed that the

  14. Extracellular gadolinium-based contrast media: An overview

    Energy Technology Data Exchange (ETDEWEB)

    Bellin, Marie-France [University Paris-Sud 11, Department of Radiology, University Hospital Paul-Brousse, AP-HP, 12, Avenue Paul Vaillant-Couturier, 94804 Villejuif Cedex (France)], E-mail: marie-france.bellin@pbr.aphp.fr; Van Der Molen, Aart J. [University Paris-Sud 11, Department of Radiology, University Hospital Paul-Brousse, AP-HP, 12, Avenue Paul Vaillant-Couturier, 94804 Villejuif Cedex (France)

    2008-05-15

    Increasing use is made of extracellular MRI contrast agents that alter the image contrast following intravenous administration; they predominantly shorten the T1 relaxation time of tissues. The degree and location of these changes provide substantial diagnostic information. However gadolinium-based contrast agents (Gd-CA) are not inert drugs. They may cause acute non-renal adverse reactions (e.g. anaphylactoid reactions), acute renal adverse reactions (e.g. contrast induced nephropathy), delayed adverse reactions (nephrogenic systemic fibrosis) and problems at the site of injection (e.g. local necrosis). This review describes the current status of Gd-CA, their mechanism of action, chemical structure, pharmacokinetics, dosage, elimination, nephrotoxicity and adverse events.

  15. Biodegradable Polysilsesquioxane Nanoparticles as Efficient Contrast Agents for Magnetic Resonance Imaging

    Science.gov (United States)

    Vivero-Escoto, Juan L.; Rieter, William J.; Lau, Honam; Huxford-Phillips, Rachel C.

    2013-01-01

    Polysilsesquioxane (PSQ) nanoparticles are crosslinked homopolymers formed by condensation of functionalized trialkoxysilanes, and provide an interesting platform for developing biologically and biomedically relevant nanomaterials. In this work, the design and synthesis of biodegradable PSQ particles with extremely high payloads of paramagnetic Gd(III) centers is explored, for use as efficient contrast agents for magnetic resonance imaging (MRI). Two new bis(trialkoxysilyl) derivatives of Gd(III) diethylenetriamine pentaacetate (Gd-DTPA) containing disulfide linkages are synthesized and used to form biodegradable Gd-PSQ particles by base-catalyzed condensation reactions in reverse microemulsions. The Gd-PSQ particles, PSQ-1 and PSQ-2, carry 53.8 wt% and 49.3 wt% of Gd-DTPA derivatives, respectively. In addition, the surface carboxy groups on the PSQ-2 particles can be modified with polyethylene glycol (PEG) and the anisamide (AA) ligand to enhance biocompatibility and cell uptake, respectively. The Gd-PSQ particles are readily degradable to release the constituent Gd(III) chelates in the presence of endogenous reducing agents such as cysteine and glutathione. The MR relaxivities of the Gd-PSQ particles are determined using a 3T MR scanner, with r1 values ranging from 5.9 to 17.8 mMs−1 on a per-Gd basis. Finally, the high sensitivity of the Gd-PSQ particles as T1-weighted MR contrast agents is demonstrated with in vitro MR imaging of human lung and pancreatic cancer cells. The enhanced efficiency of the anisamide-functionalized PSQ-2 particles as a contrast agent is corroborated by both confocal laser scanning microscopy imaging and ICP-MS analysis of Gd content in vitro. PMID:23613450

  16. Iopamidol: a non-ionic contrast agent for peripheral arteriography.

    Science.gov (United States)

    Widrich, W C; Robbins, A H; Rommel, A J; Andrews, R

    1982-10-01

    Ten patients undergoing peripheral arteriography with iopamidol were evaluated in a carefully controlled Phase I study using a variety of objective and subjective tests of discomfort. There was minimal objective evidence of pain, and the patients reported that they perceived minor discomfort and a warm sensation during the contrast injections. Five patients who had previously undergone arteriography using 2 mg of lidocaine per ml of methylglucamine diatrizoate noted a marked decrease in discomfort when iopamidol was used. Opacification of peripheral arteries was excellent. Multiple physical examinations, chemical tests, electrocardiograms, and intra-arterial pressure recordings showed that iopamidol is safe.

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

    Science.gov (United States)

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

    2017-04-01

    Contrast agent-enhanced magnetic resonance (MR) imaging is critical for the diagnosis and monitoring of a number of diseases, including cancer. Certain clinical applications, including the detection of liver tumors, rely on both T1 and T2-weighted images even though contrast agent-enhanced MR imaging is not always reliable. Thus, there is a need for improved dual mode contrast agents with enhanced sensitivity. We report the development of a nanodiamond-manganese dual mode contrast agent that enhanced both T1 and T2-weighted MR imaging. Conjugation of manganese to nanodiamonds resulted in improved longitudinal and transverse relaxivity efficacy over unmodified MnCl2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn(2+) ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage

    Science.gov (United States)

    Silvast, Tuomo S.; Kokkonen, Harri T.; Jurvelin, Jukka S.; Quinn, Thomas M.; Nieminen, Miika T.; Töyräs, Juha

    2009-11-01

    Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks (Ø = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist®, gadodiamide: Omniscan™, ioxaglate: Hexabrix™ or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity.

  19. Phthalocyanine photosensitizers as contrast agents for in vivo photoacoustic tumor imaging.

    Science.gov (United States)

    Attia, Amalina Bte Ebrahim; Balasundaram, Ghayathri; Driessen, Wouter; Ntziachristos, Vasilis; Olivo, Malini

    2015-02-01

    There is a need for contrast agents for non-invasive diagnostic imaging of tumors. Herein, Multispectral Optoacoustic Tomography (MSOT) was employed to evaluate phthalocyanines commonly used in photodynamic therapy as photoacoustic contrast agents. We studied the photoacoustic activity of three water-soluble phthalocyanine photosensitizers: phthalocyanine tetrasulfonic acid (PcS4), Zn(II) phthalocyanine tetrasulfonic acid (ZnPcS4) and Al(III) phthalocyanine chloride tetrasulfonic acid (AlPcS4) in phantom and in tumor-bearing mice to investigate the biodistribution and fate of the phthalocyanines in the biological tissues. PcS4 was observed to grant good contrast between the different reticuloendothelial organs and accumulate in the tumor within an hour of post-administration. ZnPcS4 and AlPcS4 offered little contrast in photoacoustic signals between the organs. PcS4 is a promising photoacoustic contrast agent and can be exploited as a photodiagnostic agent.

  20. Subharmonic behavior of phospholipid-coated ultrasound contrast agent microbubbles.

    Science.gov (United States)

    Sijl, Jeroen; Dollet, Benjamin; Overvelde, Marlies; Garbin, Valeria; Rozendal, Timo; de Jong, Nico; Lohse, Detlef; Versluis, Michel

    2010-11-01

    Coated microbubbles, unlike tissue are able to scatter sound subharmonically. Therefore, the subharmonic behavior of coated microbubbles can be used to enhance the contrast in ultrasound contrast imaging. Theoretically, a threshold amplitude of the driving pressure can be calculated above which subharmonic oscillations of microbubbles are initiated. Interestingly, earlier experimental studies on coated microbubbles demonstrated that the threshold for these bubbles is much lower than predicted by the traditional linear viscoelastic shell models. This paper presents an experimental study on the subharmonic behavior of differently sized individual phospholipid coated microbubbles. The radial subharmonic response of the microbubbles was recorded with the Brandaris ultra high-speed camera as a function of both the amplitude and the frequency of the driving pulse. Threshold pressures for subharmonic generation as low as 5 kPa were found near a driving frequency equal to twice the resonance frequency of the bubble. An explanation for this low threshold pressure is provided by the shell buckling model proposed by Marmottant et al. [J. Acoust. Soc. Am. 118, 3499-3505 (2005)]. It is shown that the change in the elasticity of the bubble shell as a function of bubble radius as proposed in this model, enhances the subharmonic behavior of the microbubbles.

  1. Gd-Si Oxide Nanoparticles as Contrast Agents in Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Alejandro Cabrera-García

    2016-06-01

    Full Text Available We describe the synthesis, characterization and application as contrast agents in magnetic resonance imaging of a novel type of magnetic nanoparticle based on Gd-Si oxide, which presents high Gd3+ atom density. For this purpose, we have used a Prussian Blue analogue as the sacrificial template by reacting with soluble silicate, obtaining particles with nanorod morphology and of small size (75 nm. These nanoparticles present good biocompatibility and higher longitudinal and transversal relaxivity values than commercial Gd3+ solutions, which significantly improves the sensitivity of in vivo magnetic resonance images.

  2. Combined blood pool and extracellular contrast agents for pediatric and young adult cardiovascular magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Joyce T. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Robinson, Joshua D. [Ann and Robert Lurie Children' s Hospital of Chicago, Division of Pediatric Cardiology, 225 E. Chicago Ave., Box 21, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Deng, Jie [Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States); Rigsby, Cynthia K. [Ann and Robert Lurie Children' s Hospital of Chicago, Department of Pediatrics, Chicago, IL (United States); Northwestern University, Department of Radiology, Feinberg School of Medicine, Chicago, IL (United States); Ann and Robert Lurie Children' s Hospital of Chicago, Department of Medical Imaging, Chicago, IL (United States)

    2016-12-15

    A comprehensive cardiac magnetic resonance (cardiac MR) study including both late gadolinium enhancement (LGE) and MR angiography may be indicated for patients with a history of acquired or congenital heart disease. To study the novel use of an extracellular agent for assessment of LGE combined with a blood pool contrast agent for detailed MR angiography evaluation to yield a comprehensive cardiac MR study in these patients. We reviewed clinical cardiac MR studies utilizing extracellular and blood pool contrast agents and noted demographics, clinical data and adverse events. We rated LGE image quality and MR angiography image quality for each vascular segment and calculated inter-rater variability. We also quantified contrast-to-noise ratio (CNR). Thirty-three patients (mean age 13.9 ± 3 years) received an extracellular contrast agent (10 gadobenate dimeglumine, 23 gadopentetate dimeglumine) and blood pool contrast agent (33 gadofosveset trisodium). No adverse events were reported. MRI indications included Kawasaki disease (8), cardiomyopathy and coronary anatomy (15), repaired congenital heart disease (8), and other (2). Mean LGE quality was 2.6 ± 0.6 with 97% diagnostic imaging. LGE quality did not vary by type of contrast agent given (P = 0.07). Mean MR angiography quality score was 4.7 ± 0.6, with high inter-rater agreement (k = 0.6-0.8, P < 0.002). MR angiography quality did not vary by type of contrast agent used (P = 0.6). Cardiac MR studies utilizing both extracellular and blood pool contrast agents are feasible and safe and provide excellent-quality LGE and MR angiography images. The use of two contrast agents allows for a comprehensive assessment of both myocardial viability and vascular anatomy during the same exam. (orig.)

  3. A functional form for injected MRI Gd-chelate contrast agent concentration incorporating recirculation, extravasation and excretion

    Energy Technology Data Exchange (ETDEWEB)

    Horsfield, Mark A [Department of Cardiovascular Sciences, Leicester Royal Infirmary, University of Leicester, Leicester LE1 5WW (United Kingdom); Thornton, John S; Jager, H Rolf [Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London WC1N 3BG (United Kingdom); Gill, Andrew; Priest, Andrew N [Department of Radiology, Addenbrooke' s Hospital, Hills Rd, Cambridge CB2 2QQ (United Kingdom); Morgan, Bruno [Department of Cancer Studies, Leicester Royal Infirmary, University of Leicester, Leicester LE1 5WW (United Kingdom)], E-mail: mah5@le.ac.uk

    2009-05-07

    A functional form for the vascular concentration of MRI contrast agent after intravenous bolus injection was developed that can be used to model the concentration at any vascular site at which contrast concentration can be measured. The form is based on previous models of blood circulation, and is consistent with previously measured data at long post-injection times, when the contrast agent is fully and evenly dispersed in the blood. It allows the first-pass and recirculation peaks of contrast agent to be modelled, and measurement of the absolute concentration of contrast agent at a single time point allows the whole time course to be rescaled to give absolute contrast agent concentration values. This measure of absolute concentration could be performed at a long post-injection time using either MRI or blood-sampling methods. In order to provide a model that is consistent with measured data, it was necessary to include both rapid and slow extravasation, together with excretion via the kidneys. The model was tested on T{sub 1}-weighted data from the descending aorta and hepatic portal vein, and on T*{sub 2}-weighted data from the cerebral arteries. Fitting of the model was successful for all datasets, but there was a considerable variation in fit parameters between subjects, which suggests that the formation of a meaningful population-averaged vascular concentration function is precluded.

  4. Detection of ultrasound contrast agent microbubble with constructed bubble wavelet

    Institute of Scientific and Technical Information of China (English)

    LI Bin; WAN Mingxi

    2005-01-01

    To detect the echo irradiated by microbubble out from the signal reflected by surrounding tissues, a mother wavelet named bubble wavelet according to the modified Herring oscillation equation was constructed and then applied to the original ultrasound radio frequency signal to perform the wavelet transformation. The transformed wavelet coefficients were extracted by selected threshold values to differentiate the echo of microbubble from signal of surround tissues. The effect of bubble wavelet was compared with other three commonly used mother wavelets by computer simulation and phantom experiment. The results demonstrated that there existed a highly correlation between the bubble wavelet and the experimental echo irradiated by microbubble because bubble wavelet had represented the dynamics of microbubble in advance. Furthermore, the wavelet transform results showed a better signal-noise-ratio and a sharper contrast between the echo of microbubble and the signal of surrounding tissues. Finally,constructing an overall mother wavelet library can improve the applicability and robustness of this detection method.

  5. Lumazine Synthase Protein Nanoparticle-Gd(III)-DOTA Conjugate as a T1 contrast agent for high-field MRI.

    Science.gov (United States)

    Song, YoungKyu; Kang, Young Ji; Jung, Hoesu; Kim, Hansol; Kang, Sebyung; Cho, HyungJoon

    2015-10-23

    With the applications of magnetic resonance imaging (MRI) at higher magnetic fields increasing, there is demand for MRI contrast agents with improved relaxivity at higher magnetic fields. Macromolecule-based contrast agents, such as protein-based ones, are known to yield significantly higher r1 relaxivity at low fields, but tend to lose this merit when used as T1 contrast agents (r1/r2 = 0.5 ~ 1), with their r1 decreasing and r2 increasing as magnetic field strength increases. Here, we developed and characterized an in vivo applicable magnetic resonance (MR) positive contrast agent by conjugating Gd(III)-chelating agent complexes to lumazine synthase isolated from Aquifex aeolicus (AaLS). The r1 relaxivity of Gd(III)-DOTA-AaLS-R108C was 16.49 mM(-1)s(-1) and its r1/r2 ratio was 0.52 at the magnetic field strength of 7 T. The results of 3D MR angiography demonstrated the feasibility of vasculature imaging within 2 h of intravenous injection of the agent and a significant reduction in T1 values were observed in the tumor region 7 h post-injection in the SCC-7 flank tumor model. Our findings suggest that Gd(III)-DOTA-AaLS-R108C could serve as a potential theranostic nanoplatform at high magnetic field strength.

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

    Science.gov (United States)

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

    2013-12-01

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

  7. Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

    Science.gov (United States)

    Shan, Liang; Gu, Xinbin; Wang, Paul

    2013-09-01

    Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, books/NBK5330/">), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

  8. An experimental phantom study of the effect of gadolinium-based MR contrast agents on PET attenuation coefficients and PET quantification in PET-MR imaging: application to cardiac studies.

    Science.gov (United States)

    O' Doherty, Jim; Schleyer, Paul

    2017-12-01

    Simultaneous cardiac perfusion studies are an increasing trend in PET-MR imaging. During dynamic PET imaging, the introduction of gadolinium-based MR contrast agents (GBCA) at high concentrations during a dual injection of GBCA and PET radiotracer may cause increased attenuation effects of the PET signal, and thus errors in quantification of PET images. We thus aimed to calculate the change in linear attenuation coefficient (LAC) of a mixture of PET radiotracer and increasing concentrations of GBCA in solution and furthermore, to investigate if this change in LAC produced a measurable effect on the image-based PET activity concentration when attenuation corrected by three different AC strategies. We performed simultaneous PET-MR imaging of a phantom in a static scenario using a fixed activity of 40 MBq [18 F]-NaF, water, and an increasing GBCA concentration from 0 to 66 mM (based on an assumed maximum possible concentration of GBCA in the left ventricle in a clinical study). This simulated a range of clinical concentrations of GBCA. We investigated two methods to calculate the LAC of the solution mixture at 511 keV: (1) a mathematical mixture rule and (2) CT imaging of each concentration step and subsequent conversion to LAC at 511 keV. This comparison showed that the ranges of LAC produced by both methods are equivalent with an increase in LAC of the mixed solution of approximately 2% over the range of 0-66 mM. We then employed three different attenuation correction methods to the PET data: (1) each PET scan at a specific millimolar concentration of GBCA corrected by its corresponding CT scan, (2) each PET scan corrected by a CT scan with no GBCA present (i.e., at 0 mM GBCA), and (3) a manually generated attenuation map, whereby all CT voxels in the phantom at 0 mM were replaced by LAC = 0.1 cm(-1). All attenuation correction methods (1-3) were accurate to the true measured activity concentration within 5%, and there were no trends in image-based

  9. Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents.

    Science.gov (United States)

    Xiao, Wangchuan; Lin, Jiang; Li, Mingli; Ma, Yongjie; Chen, Yuxin; Zhang, Chunfu; Li, Dan; Gu, Hongchen

    2012-01-01

    Long circulation time is critical for blood pool contrast agents used in high-resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long-circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3-(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N-(3-dimethylaminopropyl)-N'-ethylcarbo-diimide hydrochloride/N-hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time.

  10. Synthesis and characterization of ethosomal contrast agents containing iodine for computed tomography (CT) imaging applications.

    Science.gov (United States)

    Shin, Hanjin; Cho, Young-Min; Lee, Kangtaek; Lee, Chang-Ha; Choi, Byoung Wook; Kim, Bumsang

    2014-06-01

    As a first step in the development of novel liver-specific contrast agents using ethosomes for computed tomography (CT) imaging applications, we entrapped iodine within ethosomes, which are phospholipid vesicular carriers containing relatively high alcohol concentrations, synthesized using several types of alcohol, such as methanol, ethanol, and propanol. The iodine containing ethosomes that were prepared using methanol showed the smallest vesicle size (392 nm) and the highest CT density (1107 HU). The incorporation of cholesterol into the ethosomal contrast agents improved the stability of the ethosomes but made the vesicle size large. The ethosomal contrast agents were taken up well by macrophage cells and showed no cellular toxicity. The results demonstrated that ethosomes containing iodine, as prepared in this study, have potential as contrast agents for applications in CT imaging.

  11. Contrast Agent-Enhanced Computed Tomography of Articular Cartilage: Association with Tissue Composition and Properties

    Energy Technology Data Exchange (ETDEWEB)

    Silvast, T.S.; Jurvelin, J.S.; Aula, A.S.; Lammi, M.J.; Toeyraes, J. (Dept. of Clinical Neurophysiology, Kuopio Univ. Hospital, Kuopio (Finland))

    2009-01-15

    Background: Contrast agent-enhanced computed tomography may enable the noninvasive quantification of glycosaminoglycan (GAG) content of articular cartilage. It has been reported that penetration of the negatively charged contrast agent ioxaglate (Hexabrix) increases significantly after enzymatic degradation of GAGs. However, it is not known whether spontaneous degradation of articular cartilage can be quantitatively detected with this technique. Purpose: To investigate the diagnostic potential of contrast agent-enhanced cartilage tomography (CECT) in quantification of GAG concentration in normal and spontaneously degenerated articular cartilage by means of clinical peripheral quantitative computed tomography (pQCT). Material and Methods: In this in vitro study, normal and spontaneously degenerated adult bovine cartilage (n=32) was used. Bovine patellar cartilage samples were immersed in 21 mM contrast agent (Hexabrix) solution for 24 hours at room temperature. After immersion, the samples were scanned with a clinical pQCT instrument. From pQCT images, the contrast agent concentration in superficial as well as in full-thickness cartilage was calculated. Histological and functional integrity of the samples was quantified with histochemical and mechanical reference measurements extracted from our earlier study. Results: Full diffusion of contrast agent into the deep cartilage was found to take over 8 hours. As compared to normal cartilage, a significant increase (11%, P<0.05) in contrast agent concentration was seen in the superficial layer of spontaneously degenerated samples. Significant negative correlations were revealed between the contrast agent concentration and the superficial or full-thickness GAG content of tissue (|R|>0.5, P<0.01). Further, pQCT could be used to measure the thickness of patellar cartilage. Conclusion: The present results suggest that CECT can be used to diagnose proteoglycan depletion in spontaneously degenerated articular cartilage with a

  12. Characterisation of contrast agent microbubbles for ultrasound imaging and therapy research

    OpenAIRE

    2016-01-01

    The high efficiency with which gas microbubbles can scatter ultrasound compared to the surrounding blood pool or tissues has led to their widespread employment as contrast agents in ultrasound imaging. In recent years their applications have been extended to include super-resolution imaging and the stimulation of localized bio-effects for therapy. The growing exploitation of contrast agents in ultrasound, and in particular these recent developments, have amplified the need to characterize and...

  13. In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

    Science.gov (United States)

    2015-09-01

    AD______________ AWARD NUMBER: W81XWH-14-1-0242 TITLE: In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent...2015 4. TITLE AND SUBTITLE In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent 5a. CONTRACT NUMBER W81XWH-14-1-0242 5b...men with false positive PSA elevation and to ensure successful biopsy for those with small cancers. Photoacoustic imaging is an emerging functional

  14. Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications

    OpenAIRE

    Appis, Andrew W; Tracy, Melissa J; Feinstein, Steven B.

    2015-01-01

    Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that ...

  15. Derivation of attenuation map for attenuation correction of PET data in the presence of nanoparticulate contrast agents using spectral CT imaging

    NARCIS (Netherlands)

    Ghadiri, Hossein; Shiran, Mohammad Bagher; Soltanian-Zadeh, Hamid; Rahmim, Arman; Zaidi, Habib; Ay, Mohammad Reza

    2014-01-01

    Uptake value in quantitative PET imaging is biased due to the presence of CT contrast agents when using CT-based attenuation correction. Our aim was to examine spectral CT imaging to suppress inaccuracy of 511 keV attenuation map in the presence of multiple nanoparticulate contrast agents. Using a s

  16. Radioprotection and contrast agent use in pediatrics: what, how, and when.

    Science.gov (United States)

    Lancharro Zapata, Á M; Rodríguez, C Marín

    2016-05-01

    It is essential to minimize exposure to ionizing radiation in children for various reasons. The risk of developing a tumor from exposure to a given dose of radiation is greater in childhood. Various strategies can be used to reduce exposure to ionizing radiation. It is fundamental to avoid unnecessary tests and tests that are not indicated, to choose an alternative test that does not use ionizing radiation, and/or to take a series of measures that minimize the dose of radiation that the patient receives, such as avoiding having to repeat tests, using the appropriate projections, using shields, adjusting the protocol (mAs, Kv, or pitch) to the patient's body volume, etc… When contrast agents are necessary, intracavitary ultrasound agents can be used, although the use of ultrasound agents is also being extended to include intravenous administration. In fluoroscopy, contrast agents with low osmolarity must be used, as in CT where we must adjust the dose and speed of injection to the patient's weight and to the caliber of the peripheral line, respectively. In MRI, only three types of contrast agents have been approved for pediatric use. It is sometimes necessary to use double doses or organ-specific contrast agents in certain clinical situations; the safety of contrast agents for these indications has not been proven, so they must be used off label.

  17. EPR and DNP Properties of Certain Novel Single Electron Contrast Agents Intended for Oximetric Imaging

    DEFF Research Database (Denmark)

    Ardenkjær-Larsen, J. H.; Laursen, I; Leunbach, I.;

    1998-01-01

    Parameters of relevance to oximetry with Overhauser magnetic resonance imaging (OMRI) have been measured for three single electron contrast agents of the triphenylmethyl type. The single electron contrast agents are stable and water soluble. Magnetic resonance properties of the agents have been...... examined with electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), and dynamic nuclear polarization (DNP) at 9.5 mT in water, isotonic saline, plasma, and blood at 23 and 37°C. The relaxivities of the agents are about 0.2–0.4 mM−1s−1and the DNP enhancements extrapolate close...... to the dipolar limit. The agents have a single, narrow EPR line, which is analyzed as a Voigt function. The linewidth is measured as a function of the agent concentration and the oxygen concentration. The concentration broadenings are about 1–3 μT/mM and the Lorentzian linewidths at infinite dilution are less...

  18. Detection of Sulfatase Enzyme Activity with a CatalyCEST MRI Contrast Agent.

    Science.gov (United States)

    Sinharay, Sanhita; Fernández-Cuervo, Gabriela; Acfalle, Jasmine P; Pagel, Mark D

    2016-05-01

    A chemical exchange saturation transfer (CEST) MRI contrast agent has been developed that detects sulfatase enzyme activity. The agent produces a CEST signal at δ=5.0 ppm before enzyme activity, and a second CEST signal appears at δ=9.0 ppm after the enzyme cleaves a sulfate group from the agent. The comparison of the two signals improved detection of sulfatase activity.

  19. A new contrast agent for radiological and dissection studies of the arterial network of anatomic specimens.

    Science.gov (United States)

    Bulla, A; Casoli, C; Farace, F; Mazzarello, V; De Luca, L; Rubino, C; Montella, A

    2014-01-01

    The aim of the present study is to propose a new contrast agent that can be easily applied both to CT and dissection studies to replace lead oxide based formulas for comparative anatomical analyses of the vascularisation of cadaveric specimens. The infusion material was an epoxy resin, especially modified by the addition of barium sulphate to enhance its radiopacity. The final copolymer was toxicologically safe. To test the properties of the new material, several cadaveric limb injections were performed. The injected specimens were both CT scanned to perform 3D vascular reconstructions and dissected by anatomical planes. There was a perfect correspondence between the image studies and the dissections: even the smallest arteries on CT scan can be identified on the specimen and vice versa. The properties of the epoxy allowed an easy dissection of the vessels. The new imaging techniques available today, such as CT scan, can evaluate the vascular anatomy in high detail and 3D. This new contrast agent may help realising detailed vascular studies comparing CT scan results with anatomical dissections. Moreover, it may be useful for teaching surgical skills in the field of plastic surgery.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  1. Sudden death after intravenous administration of a perflutren contrast agent: a case of pseudocomplication?

    Science.gov (United States)

    Mahjoub, Haïfa; Roméo, Philippe; Leung, Tack-Ki; Burelle, Denis; Cartier, Raymond; Basmadjian, Arsène J

    2009-06-01

    Perflutren cardiac ultrasound agents improve diagnostic accuracy in patients whose imaging is technically difficult. This report describes a case of sudden death approximately 5 minutes after the intravenous administration of 0.5 mL of perflutren contrast agent (Definity) during transthoracic echocardiography with suboptimal baseline images performed 10 days after coronary artery bypass graft surgery because of hypotension and tachycardia in a 73-year-old patient with severe left ventricular systolic dysfunction. Autopsy did not reveal a clear direct relationship between perflutren and death. This is the first reported case of death related temporally to an echocardiographic contrast agent occurring in Canada and could represent a case of pseudocomplication.

  2. Non-invasive estimation of blood pressure using ultrasound contrast agents

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2009-01-01

    Local blood pressure measurements provide important information on the state of health of organs in the body and can be used to diagnose diseases in the heart, lungs, and kidneys. This paper presents an experimental setup for investigating the ambient pressure sensitivity of a contrast agent using...... measurement series at 485 kPa showed a sensitivity of 0.41 dB/kPa with a correlation coefficient of 0.89. Based on the measurements at 500 kPa, this acoustic driving pressure was concluded to be too high causing the bubbles to be destroyed. The pressure sensitivity for these two measurement series were 0...... diagnostic ultrasound. The setup resembles a realistic clinical setup utilizing a single array transducer for transmit and receive. The ambient pressure sensitivity of SonoVue (Bracco, Milano, Italy) was measured twice using two different acoustic driving pressures, which were selected based on a preliminary...

  3. Impact of acoustic pressure on ambient pressure estimation using ultrasound contrast agent

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2010-01-01

    Local blood pressure measurements provide important information on the state of health of organs in the body and can be used to diagnose diseases in the heart, lungs, and kidneys. This paper presents an approach for investigating the ambient pressure sensitivity of a contrast agent using diagnostic.......94. The second measurement series at 485 kPa showed a sensitivity of 0.41 dB/kPa with a correlation coefficient of 0.89. Based on the measurements at 500 kPa, this acoustic driving pressure was concluded to be too high causing the bubbles to be destroyed. The pressure sensitivity for these two measurement series...... ultrasound. The experimental setup resembles a realistic clinical setup utilizing a single array transducer for transmit and receive. The ambient pressure sensitivity of SonoVue (Bracco, Milano, Italy) was measured twice using two different acoustic driving pressures, which were selected based...

  4. Intraosseous injection of iodinated computed tomography contrast agent in an adult blunt trauma patient.

    Science.gov (United States)

    Knuth, Thomas E; Paxton, James H; Myers, Daniel

    2011-04-01

    Intraosseous venous access can be life-saving in trauma patients when traditional methods for obtaining venous access are difficult or impossible. Because many blunt trauma patients require expeditious evaluation by computed tomography (CT) scans with intravenous contrast, it is important to evaluate whether intraosseous catheters can be used for administering CT contrast agents in lieu of waiting until secure peripheral intravenous or central venous catheter access can be established. Previous case reports have demonstrated that tibial intraosseous catheters can be used to safely administer CT contrast in the pediatric patient population. Here we report a case in which intraosseous access was the only means of administering intravenous contrast agent in an adult blunt trauma patient. An intraosseous catheter was placed in the standard manner in the right proximal humerus. Intravenous contrast agent was administered through the intraosseous catheter, using the standard blunt trauma protocol at our institution. CT scans were evaluated by a staff radiologist and assessed for the adequacy of diagnosis for blunt traumatic injuries. CT scans of the thorax, abdomen, and pelvis were considered to be adequate for diagnostic purposes and subjectively equivalent to those of studies using traditional central venous access. The intraosseous catheter was discontinued the following day. No complications of intraosseous placement or of contrast administration were identified. Intraosseous catheterization appears to be a feasible and effective alternative to traditional methods of venous access in the administration of iodinated contrast agents for CT evaluation in adult blunt trauma patients. Further study is warranted.

  5. High-Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. Highly stable polymer coated nano-clustered silver plates: a multimodal optical contrast agent for biomedical imaging.

    Science.gov (United States)

    Ray, Aniruddha; Mukundan, Ananya; Xie, Zhixing; Karamchand, Leshern; Wang, Xueding; Kopelman, Raoul

    2014-11-07

    Here, we present a new optical contrast agent based on silver nanoplate clusters embedded inside of a polymer nano matrix. Unlike nanosphere clusters, which have been well studied, nanoplate clusters have unique properties due to the different possible orientations of interaction between the individual plates, resulting in a significant broadening of the absorption spectra. These nanoclusters were immobilized inside of a polymer cladding so as to maintain their stability and optical properties under in vivo conditions. The polymer-coated silver nanoplate clusters show a lower toxicity compared to the uncoated nanoparticles. At high nanoparticle concentrations, cell death occurs mostly due to apoptosis. These nanoparticles were used for targeted fluorescence imaging in a rat glioma cell line by incorporating a fluorescent dye into the matrix, followed by conjugation of a tumor targeting an F3 peptide. We further used these nanoparticles as photoacoustic contrast agents in vivo to enhance the contrast of the vasculature structures in a rat ear model. We observed a contrast enhancement of over 90% following the nanoparticle injection. It is also shown that these NPs can serve as efficient contrast agents, with specific targeting abilities for broadband multimodal imaging that are usable for diagnostic applications and that extend into use as therapeutic agents as well.

  7. Highly stable polymer coated nano-clustered silver plates: a multimodal optical contrast agent for biomedical imaging

    Science.gov (United States)

    Ray, Aniruddha; Mukundan, Ananya; Xie, Zhixing; Karamchand, Leshern; Wang, Xueding; Kopelman, Raoul

    2014-11-01

    Here, we present a new optical contrast agent based on silver nanoplate clusters embedded inside of a polymer nano matrix. Unlike nanosphere clusters, which have been well studied, nanoplate clusters have unique properties due to the different possible orientations of interaction between the individual plates, resulting in a significant broadening of the absorption spectra. These nanoclusters were immobilized inside of a polymer cladding so as to maintain their stability and optical properties under in vivo conditions. The polymer-coated silver nanoplate clusters show a lower toxicity compared to the uncoated nanoparticles. At high nanoparticle concentrations, cell death occurs mostly due to apoptosis. These nanoparticles were used for targeted fluorescence imaging in a rat glioma cell line by incorporating a fluorescent dye into the matrix, followed by conjugation of a tumor targeting an F3 peptide. We further used these nanoparticles as photoacoustic contrast agents in vivo to enhance the contrast of the vasculature structures in a rat ear model. We observed a contrast enhancement of over 90% following the nanoparticle injection. It is also shown that these NPs can serve as efficient contrast agents, with specific targeting abilities for broadband multimodal imaging that are usable for diagnostic applications and that extend into use as therapeutic agents as well.

  8. Preliminary Results on Different Impedance Contrast Agents for Pulmonary Perfusion Imaging with Electrical Impedance Tomography

    Science.gov (United States)

    Nguyen, D. T.; Kosobrodov, R.; Barry, M. A.; Chik, W.; Pouliopoulos, J.; Oh, T. I.; Thiagalingam, A.; McEwan, A.

    2013-04-01

    Recent studies in animal models suggest that the use of small volume boluses of NaCl as an impedance contrast agent can significantly improve pulmonary perfusion imaging by Electrical Impedance Tomography (EIT). However, these studies used highly concentrated NaCl solution (20%) which may have adverse effects on the patients. In a pilot experiment, we address this problem by comparing a number of different Impedance Contrast Boluses (ICBs). Conductivity changes in the lungs of a sheep after the injection of four different ICBs were compared, including three NaCl-based ICBs and one glucose-based ICB. The following procedure was followed for each ICB. Firstly, ventilation was turned off to provide an apneic window of approximately 40s to image the conductivity changes due to the ICB. Each ICB was then injected through a pig-tail catheter directly into the right atrium. EIT images were acquired throughout the apnea to capture the conductivity change. For each ICB, the experiment was repeated three times. The three NaCl-based ICB exhibited similar behaviour in which following the injection of each of these ICBs, the conductivity of each lung predictably increased. The effect of the ICB of 5% glucose solution was inconclusive. A small decrease in conductivity in the left lung was observed in two out of three cases and none was discernible in the right lung.

  9. Empirically Based, Agent-based models

    Directory of Open Access Journals (Sweden)

    Elinor Ostrom

    2006-12-01

    Full Text Available There is an increasing drive to combine agent-based models with empirical methods. An overview is provided of the various empirical methods that are used for different kinds of questions. Four categories of empirical approaches are identified in which agent-based models have been empirically tested: case studies, stylized facts, role-playing games, and laboratory experiments. We discuss how these different types of empirical studies can be combined. The various ways empirical techniques are used illustrate the main challenges of contemporary social sciences: (1 how to develop models that are generalizable and still applicable in specific cases, and (2 how to scale up the processes of interactions of a few agents to interactions among many agents.

  10. The Subharmonic Behavior and Thresholds of High Frequency Ultrasound Contrast Agents

    Science.gov (United States)

    Allen, John

    2016-11-01

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

  11. Poly(Lactic-co-Glycolic) Acid as a Carrier for Imaging Contrast Agents

    Science.gov (United States)

    Doiron, Amber L.; Homan, Kimberly A.; Emelianov, Stanislav; Brannon-Peppas, Lisa

    2010-01-01

    Purpose With the broadening field of nanomedicine poised for future molecular level therapeutics, nano-and microparticles intended for the augmentation of either single- or multimodal imaging are created with PLGA as the chief constituent and carrier. Methods Emulsion techniques were used to encapsulate hydrophilic and hydrophobic imaging contrast agents in PLGA particles. The imaging contrast properties of these PLGA particles were further enhanced by reducing silver onto the PLGA surface, creating a silver cage around the polymeric core. Results The MRI contrast agent Gd-DTPA and the exogenous dye rhodamine 6G were both encapsulated in PLGA and shown to enhance MR and fluorescence contrast, respectively. The silver nanocage built around PLGA nanoparticles exhibited strong near infrared light absorbance properties, making it a suitable contrast agent for optical imaging strategies such as photoacoustic imaging. Conclusions The biodegradable polymer PLGA is an extremely versatile nano- and micro-carrier for several imaging contrast agents with the possibility of targeting diseased states at a molecular level. PMID:19034628

  12. Luminescence study of Eu(III) analogues of esterase-activated magnetic resonance contrast agents.

    Science.gov (United States)

    Giardiello, Marco; Lowe, Mark P

    2009-09-07

    A model for an accumulation and enzyme-activation strategy of a magnetic resonance contrast agent was investigated via the luminescence of Eu(III) analogues. Neutral q = 2 Eu(III) ethyl and acetoxymethyl ester LnaDO3A-based complexes showed increased emission intensity in the presence of serum concentrations of carbonate because of inner-sphere water molecule displacement by the anion. The affinity for carbonate is suppressed by the introduction of negative charge to the complex following enzymatic hydrolysis of the ester groups, resulting in quenching of Eu(III) luminescence and changes in spectral form. The conversion of neutral, carboxylic ester-containing complexes into free acid forms by enzymatic hydrolysis using pig liver esterase was demonstrated by luminescence (Eu) and (1)H NMR spectroscopic investigations (Y). These studies demonstrated that the concept of inhibition of anion binding as a result of enzyme activation is feasible.

  13. USPIO: New MR Contrast Agent for Evaluation of Metastatic Lymph Nodes

    Directory of Open Access Journals (Sweden)

    Mahrooz Malek

    2010-05-01

    Full Text Available accurate detection and characterization of lymph node metastases is crucial for planning therapy and determining prognosis in patients with various un-derlying primary tumors such as the breast, prostate, head and neck, urogenital, melanoma and other cancers. CT and MR imaging are of limited value because they primarily rely on the tumor size for differentiating benign from malignant lymph nodes. Ultrasmall super paramagnetic iron oxide (USPIO (Combidex or Ferumoxtran-10; Advanced Magnetics, Sinerem; Guerbet is an MR contrast agent that has shown improved accuracy in the staging of lymph nodes in cancer patients. Animal and recent human studies have shown that USPIO particles allow MR differentiation of benign from malignant lymph nodes based on enhancement patterns."nThis lecture is a review about new imaging methods in oncological imaging, especially for the lymphatic system.

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

    Science.gov (United States)

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

    2016-12-01

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

  15. High-resolution wide-field imaging of perfused capillaries without the use of contrast agent

    Directory of Open Access Journals (Sweden)

    Nelson DA

    2011-08-01

    Full Text Available Darin A Nelson1, Zvia Burgansky-Eliash1,2, Hila Barash1, Anat Loewenstein3, Adiel Barak4, Elisha Bartov2, Tali Rock2, Amiram Grinvald51Optical Imaging Ltd, Rehovot, Israel; 2Department of Ophthalmology, Edith Wolfson Medical Center, Holon, Israel; 3Department of Ophthalmology, Tel Aviv Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Israel; 4Department of Ophthalmology, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; 5Department of Neurobiology, The Weizmann Institute of Science, Rehovot, IsraelPurpose: Assessment of capillary abnormalities facilitates early diagnosis, treatment, and follow-up of common retinal pathologies. Injected contrast agents like fluorescein are widely used to image retinal capillaries, but this highly effective procedure has a few disadvantages, such as untoward side effects, inconvenience of injection, and brevity of the time window for clear visualization. The retinal function imager (RFI is a tool for monitoring retinal functions, such as blood velocity and oximetry, based on intrinsic signals. Here we describe the clinical use of hemoglobin in red blood cells (RBCs as an intrinsic motion-contrast agent in the generation of detailed noninvasive capillary-perfusion maps (nCPMs.Patients and methods: Multiple series of nCPM images were acquired from 130 patients with diabetic retinopathy, vein occlusion, central serous retinopathy, age-related macular degeneration, or metabolic syndrome, as well as from 37 healthy subjects. After registration, pixel value distribution parameters were analyzed to locate RBC motion.Results: The RFI yielded nCPMs demonstrating microvascular morphology including capillaries in exquisite detail. Maps from the same subject were highly reproducible in repeated measurements, in as much detail and often better than that revealed by the very best fluorescein angiography. In patients, neovascularization and capillary nonperfusion areas were clearly observed. Foveal avascular

  16. An Agent Based Classification Model

    CERN Document Server

    Gu, Feng; Greensmith, Julie

    2009-01-01

    The major function of this model is to access the UCI Wisconsin Breast Can- cer data-set[1] and classify the data items into two categories, which are normal and anomalous. This kind of classifi cation can be referred as anomaly detection, which discriminates anomalous behaviour from normal behaviour in computer systems. One popular solution for anomaly detection is Artifi cial Immune Sys- tems (AIS). AIS are adaptive systems inspired by theoretical immunology and observed immune functions, principles and models which are applied to prob- lem solving. The Dendritic Cell Algorithm (DCA)[2] is an AIS algorithm that is developed specifi cally for anomaly detection. It has been successfully applied to intrusion detection in computer security. It is believed that agent-based mod- elling is an ideal approach for implementing AIS, as intelligent agents could be the perfect representations of immune entities in AIS. This model evaluates the feasibility of re-implementing the DCA in an agent-based simulation environ- ...

  17. Forearm Compartment Syndrome of a Newborn Associated with Extravasation of Contrast Agent

    Directory of Open Access Journals (Sweden)

    Egemen Altan

    2013-01-01

    Full Text Available Extravasation of contrast agents is a possible complication of imaging studies. Although extravasations typically cause minimal swelling or erythema, they can lead to compartment syndrome when the volume of extravasation is high. In this article, we will present an exceptional case where an insignificant amount of contrast agent extravasation led to a forearm compartment syndrome in a newborn, who was treated with an extended fasciotomy. We would like to emphasize the preventive techniques and treatment options of this iatrogenic complication in newborns. Close followup of the patient by the nurses, awareness of the parents and the personnel in the radiology department are the most important preventive measures in this extremity-threatening complication. Forearm compartment syndrome due to contrast agent extravasation may progress more rapidly in newborns even with smaller amounts of extravasation and prompt recognition of the pathology and immediate intervention are unevitable.

  18. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    Energy Technology Data Exchange (ETDEWEB)

    Peruzzini, D.; Viti, J. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Tortoli, P. [MSD lab, Department of Information Engineering, Univ of Florence, Via S.Marta, 3, 50139 Firenze (Italy); Verweij, M. D. [Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands); Jong, N. de; Vos, H. J., E-mail: h.vos@erasmusmc.nl [Erasmus MC, ’s-Gravendijkwal 230, Faculty Building, Ee 2302, 3015 CE Rotterdam (Netherlands); Acoustical Wavefield Imaging, ImPhys, Delft Univ Technology, van der Waalsweg 8, 2628 CH Delft (Netherlands)

    2015-10-28

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. “superharmonic” imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which ‘signal’ denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

  19. Ultrasound contrast agent imaging: Real-time imaging of the superharmonics

    Science.gov (United States)

    Peruzzini, D.; Viti, J.; Tortoli, P.; Verweij, M. D.; de Jong, N.; Vos, H. J.

    2015-10-01

    Currently, in medical ultrasound contrast agent (UCA) imaging the second harmonic scattering of the microbubbles is regularly used. This scattering is in competition with the signal that is caused by nonlinear wave propagation in tissue. It was reported that UCA imaging based on the third or higher harmonics, i.e. "superharmonic" imaging, shows better contrast. However, the superharmonic scattering has a lower signal level compared to e.g. second harmonic signals. This study investigates the contrast-to-tissue ratio (CTR) and signal to noise ratio (SNR) of superharmonic UCA scattering in a tissue/vessel mimicking phantom using a real-time clinical scanner. Numerical simulations were performed to estimate the level of harmonics generated by the microbubbles. Data were acquired with a custom built dual-frequency cardiac phased array probe. Fundamental real-time images were produced while beam formed radiofrequency (RF) data was stored for further offline processing. The phantom consisted of a cavity filled with UCA surrounded by tissue mimicking material. The acoustic pressure in the cavity of the phantom was 110 kPa (MI = 0.11) ensuring non-destructivity of UCA. After processing of the acquired data from the phantom, the UCA-filled cavity could be clearly observed in the images, while tissue signals were suppressed at or below the noise floor. The measured CTR values were 36 dB, >38 dB, and >32 dB, for the second, third, and fourth harmonic respectively, which were in agreement with those reported earlier for preliminary contrast superharmonic imaging. The single frame SNR values (in which `signal' denotes the signal level from the UCA area) were 23 dB, 18 dB, and 11 dB, respectively. This indicates that noise, and not the tissue signal, is the limiting factor for the UCA detection when using the superharmonics in nondestructive mode.

  20. Global contrast based salient region detection

    KAUST Repository

    Cheng, Ming-Ming

    2011-08-25

    Reliable estimation of visual saliency allows appropriate processing of images without prior knowledge of their contents, and thus remains an important step in many computer vision tasks including image segmentation, object recognition, and adaptive compression. We propose a regional contrast based saliency extraction algorithm, which simultaneously evaluates global contrast differences and spatial coherence. The proposed algorithm is simple, efficient, and yields full resolution saliency maps. Our algorithm consistently outperformed existing saliency detection methods, yielding higher precision and better recall rates, when evaluated using one of the largest publicly available data sets. We also demonstrate how the extracted saliency map can be used to create high quality segmentation masks for subsequent image processing.

  1. Clinical superiority of a new nonionic contrast agent (iopamidol) for cardiac angiography.

    Science.gov (United States)

    Gertz, E W; Wisneski, J A; Chiu, D; Akin, J R; Hu, C

    1985-02-01

    The hemodynamic and electrophysiologic alterations induced by ionic contrast agents during cardiac angiography are well described. Recently nonionic contrast agents have become available for cardiac angiography. To evaluate the safety of these new agents, a double-blind randomized study was performed comparing a new nonionic agent (iopamidol) with a commonly used ionic contrast agent (Renografin-76). Eighty-one patients undergoing left ventriculography and coronary angiography were included; 41 received iopamidol and 40 received sodium meglumine diatrizoate (Renografin-76). After left ventriculography, there was a decrease in the arterial pressure with both contrast agents. However, the severity and the duration of hypotension were both significantly greater with Renografin-76 compared with the new nonionic agent (p less than 0.001). After selective injections of the coronary arteries, electrocardiographic analysis demonstrated that the increase in the QT interval (p less than 0.0002) and the changes in both the ST segment and T wave amplitude (p less than 0.001) were significantly greater in the Renografin-76 group compared with the iopamidol group. During coronary angiography, 8 of the 40 patients receiving Renografin-76 required temporary pacing for sinus pauses of 2.5 seconds or more, and 2 of the 40 also developed ventricular fibrillation. None of the 41 patients receiving iopamidol had these complications. This report demonstrates that the electrocardiographic changes, the severity and duration of hypotension and the incidence of serious arrhythmias are significantly greater with Renografin-76 than with iopamidol. Thus, this new nonionic agent appears to enhance the safety of cardiac angiography.

  2. Investigation of a potential macromolecular MRI contrast agent prepared from PPI (G = 2, polypropyleneimine, generation 2) dendrimer bifunctional chelates

    Science.gov (United States)

    Wang, Jianxin Steven

    The long-term objective is to develop magnetic resonance (MR) contrast agents that actively and passively target tumors for diagnosis and therapy. Many diagnostic imaging techniques for cancer lack specificity. A dendrimer based magnetic resonance imaging contrast agent has been developed with large proton relaxation enhancements and high molecular relaxivities. A new type of linear dendrimer based MRI contrast agent that is built from the polypropyleneimine and polyamidoamine dendrimers in which free amines have been conjugated to the chelate DTPA, which further formed the complex with Gadolinium (Gd) was studied. The specific research goals were to test the hypothesis that a linear chelate with macromolecular agents can be used in vitro and in vivo. This work successfully examined the adequacy and viability of the application for this agent in vitro and in vivo. A small animal whole body counter was designed and constructed to allow us to monitor biodistribution and kinetic mechanisms using a radioisotope labeled complex. The procedures of metal labeling, separation and purification have been established from this work. A biodistribution study has been performed using radioisotope induced organ/tissue counting and gamma camera imaging. The ratio of percentage of injected dose per gram organ/tissue for kidney and liver is 3.71 from whole body counter and 3.77 from the gamma camera. The results suggested that retention of Gd (III) is too high and a more kinetically stable chelate should be developed. The pharmacokinetic was evaluated in the whole animal model with the whole body clearance, and a kinetics model was developed. The pharmacokinetic results showed a bi-exponential decay in the animal model with two component excretion constants 1.43e(-5) and 0.0038511, which give half-lives of 3 hours and 33.6 days, respectively. Magnetic resonance imaging of this complex resulted in a 52% contrast enhancement in the rat kidney following the agents' administration in

  3. Size effect of Au/PAMAM contrast agent on CT imaging of reticuloendothelial system and tumor tissue

    Science.gov (United States)

    Wang, Wei; Li, Jian; Liu, Ransheng; Zhang, Aixu; Yuan, Zhiyong

    2016-09-01

    Polyamidoamine (PAMAM)-entrapped Au nanoparticles were synthesized with distinct sizes to figure out the size effect of Au-based contrast agent on CT imaging of passively targeted tissues. Au/PAMAM nanoparticles were first synthesized with narrow distribution of particles size of 22.2 ± 3.1, 54.2 ± 3.7, and 104.9 ± 4.7 nm in diameters. Size effect leads no significant difference on X-ray attenuation when Au/PAMAM was ≤0.05 mol/L. For CT imaging of a tumor model, small Au/PAMAM were more easily internalized via endocytosis in the liver, leading to more obviously enhanced contrast. Similarly, contrast agents with small sizes were more effective in tumor imaging because of the enhanced permeability and retention effect. Overall, the particle size of Au/PAMAM heavily affected the efficiency of CT enhancement in imaging RES and tumors.

  4. Iodinated contrast agents in patients with myasthenia gravis: a retrospective cohort study

    OpenAIRE

    Rath, Jakob; Mauritz, Matthias; Zulehner, Gudrun; Hilger, Eva; Cetin, Hakan; Kasprian, Gregor; Auff, Eduard; Zimprich, Fritz

    2017-01-01

    Currently, it has not been satisfactorily established, whether modern low-osmolality iodinated contrast agents (ICAs) used in computed tomography (CT) studies are a risk factor for exacerbation of myasthenic symptoms. The rate of acute adverse events as well as delayed clinical worsening up to 30?days were analyzed in 73 patients with confirmed myasthenia gravis (MG) who underwent contrast-enhanced CT studies and compared to 52 patients who underwent unenhanced CT studies. One acute adverse e...

  5. Comparison of voiding cystourethrography and urosonography with second-generation contrast agents in simultaneous prospective study

    Science.gov (United States)

    Świętoń, Dominik; Rybczyńska, Dorota; Czarniak, Piotr; Szarmach, Arkadiusz; Kaszubowski, Mariusz; Szurowska, Edyta

    2016-01-01

    Background The invasiveness and exposure to radiation in voiding cystourethrography led to the introduction of alternative methods of diagnosis of vesicoureteral reflux, including contrast enhanced voiding urosonography. While there is a limited number of studies comparing these methods using new generation ultrasound contrast agents, none of them compared both methods simultaneously. This study is aimed at assessing agreement between contrast enhanced voiding urosonography with second-generation ultrasound contrast agents and voiding cystourethrography. Methods From April 2013 to May 2014, 83 children (37 female and 46 male), mean age 3.5 years, age range from 1 month to 17.5 years, underwent prospective simultaneous assessment by contrast enhanced voiding urosonography and voiding cystourethrography, with a total of 166 uretero-renal units evaluated. Results The sensitivity of voiding cystourethrography and contrast enhanced voiding urosonography were comparable, amounting to 88%, however, neither reached 100% for the entire studied population. The negative predictive value of voiding urosonography and voiding cystourethrography was 97%, and there was no difference between both methods. Conclusion Voiding cystourethrography and contrast enhanced voiding urosonography are comparable methods in diagnosis of vesicoureteral reflux, and can be performed alternatively. However, some limitations of contrast enhanced voiding urosonography must be remembered.

  6. Immunological evaluation of the new stable ultrasound contrast agent LK565: a phase one clinical trial

    Directory of Open Access Journals (Sweden)

    Wild P

    2004-09-01

    Full Text Available Abstract Background Ultrasound contrast agents (UCAs allow the enhancement of vascular definition, thereby providing more diagnostic information. LK565 is a new second-generation UCA based on synthetic polymers of aspartic acid which is eliminated from the blood stream via phagocytosis. LK565 forms very stable air-filled microspheres and is capable of repeated passage through the pulmonary capillary bed after peripheral intravenous injection. This characteristic allows examination of the cardiac function or extracardiac vessel abnormalities up to 15 minutes. Methods A phase one clinical study was conducted on 15 healthy volunteers to identify the development of an undesirable immune response. Phagocytosis capacity, TNF-α secretion, and MHC class II upregulation of monocytes was monitored, as well as microsphere specific antibody development (IgM, IgG. Furthermore, the kinetics of the activation surface markers CD69, CD25, CD71, and CD11b on leukocytes were analyzed. Results Due to LK565-metabolism the administration of the UCA led to saturation of phagocytes which was reversible after 24 hrs. Compared to positive controls neither significant TNF-α elevation, neither MHC class II and activation surface markers upregulation, nor specific antibody development was detectable. Conclusion The administration of LK565 provides a comfortable duration of signal enhancement, esp. in echocardiography, without causing a major activation cascade or triggering an adaptive immune response. To minimize the risk of undesirable adverse events such as anaphylactoid reactions, immunological studies should be included in clinical trials for new UCAs. The use of LK565 as another new ultrasound contrast agent should be encouraged as a safe means to provide additional diagnostic information.

  7. Zero echo time magnetic resonance imaging of contrast-agent-enhanced calcium phosphate bone defect fillers.

    Science.gov (United States)

    Sun, Yi; Ventura, Manuela; Oosterwijk, Egbert; Jansen, John A; Walboomers, X Frank; Heerschap, Arend

    2013-04-01

    Calcium phosphate cements (CPCs) are widely used bone substitutes. However, CPCs have similar radiopacity as natural bone, rendering them difficult to be differentiated in classical X-ray and computed tomography imaging. As conventional magnetic resonance imaging (MRI) of bone is cumbersome, due to low water content and very short T(2) relaxation time, ultra-short echo time (UTE) and zero echo time (ZTE) MRI have been explored for bone visualization. This study examined the possibility to differentiate bone and CPC by MRI. T(1) and T(2)* values determined with UTE MRI showed little difference between bone and CPC; hence, these materials were difficult to separate based on T(1) or T(2) alone. Incorporation of ultra-small particles of iron oxide and gadopentetatedimeglumine (Gd-DTPA; 1 weight percentage [wt%] and 5 wt% respectively) into CPC resulted in visualization of CPC with decreased intensity on ZTE images in in vitro and ex vivo experiments. However, these additions had unfavorable effects on the solidification time and/or mechanical properties of the CPC, with the exception of 1% Gd-DTPA alone. Therefore, we tested this material in an in vivo experiment. The contrast of CPC was enhanced at an early stage postimplantation, and was significantly reduced in the 8 weeks thereafter. This indicates that ZTE imaging with Gd-DTPA as a contrast agent could be a valid radiation-free method to visualize CPC degradation and bone regeneration in preclinical experiments.

  8. New calcium-selective smart contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Verma, Kirti Dhingra; Forgács, Attila; Uh, Hyounsoo; Beyerlein, Michael; Maier, Martin E; Petoud, Stéphane; Botta, Mauro; Logothetis, Nikos K

    2013-12-23

    Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca(2+) levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca(2+) in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca(2+) -sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca(2+) in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd(3+)-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca(2+) chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca(2+) present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca(2+) falls in the range required to sense and report changes in extracellular Ca(2+) levels followed by an increase in neural activity. In buffer, with the addition of Ca(2+) the increase in relaxivity ranged from 100-157%, the highest ever known for any T1-based Ca(2+)-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb(3+) analogues, nuclear magnetic relaxation dispersion (NMRD), and (17)O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca(2+) addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration.

  9. Immobilized contrast-enhanced MRI: Gadolinium-based long-term MR contrast enhancement of the vein graft vessel wall.

    Science.gov (United States)

    Mitsouras, Dimitris; Vemula, Praveen Kumar; Yu, Peng; Tao, Ming; Nguyen, Binh T; Campagna, Christina M; Karp, Jeffrey M; Mulkern, Robert V; Ozaki, C Keith; Rybicki, Frank J

    2011-01-01

    An implantable MR contrast agent that can be covalently immobilized on tissue during surgery has been developed. The rationale is that a durable increase in tissue contrast using an implantable contrast agent can enhance postsurgical tissue differentiation using MRI. For small-vessel (e.g., vein graft) MRI, the direct benefit of such permanent "labeling" of the vessel wall by modification of its relaxation properties is to achieve more efficient imaging. This efficiency can be realized as either increased contrast leading to more accurate delineation of vessel wall and lesion tissue boundaries, or, faster imaging without penalizing contrast-to-noise ratio, or a combination thereof. We demonstrate, for the first time, stable long-term MRI enhancement using such an exogenous contrast mechanism based on immobilizing a modified diethylenetriaminepentaacetic acid gadolinium(3+) dihydrogen complex on a human vein using a covalent amide bond. Signal enhancement due to the covalently immobilized contrast agent is demonstrated for excised human vein specimens imaged at 3 T, and its long-term stability is demonstrated during a 4-month incubation period.

  10. Non-invasive ambient pressure estimation using non-linear ultrasound contrast agents

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup

    Many attempts to find a non-invasive procedure to measure the blood pressure locally in the body have been made. This dissertation focuses on the approaches which utilize highly compressible ultrasound contrast agents as ambient pressure sensors. The literature within the topic has been reviewed...

  11. Relaxivity of blood pool contrast agent depends on the host tissue as suggested by semianalytical simulations

    DEFF Research Database (Denmark)

    Jensen, Birgitte Fuglsang; Østergaard, Leif; Kiselev, Valerij G

    Concentration of MRI contrast agents (CA) is commonly determined indirectly using their relaxation effect. In quantitative perfusion studies, the change in the relaxation following a bolus passage is converted into concentrations assuming identical relaxivities for tissue and blood. Simulations...... can be applied to quantitation of perfusion, functional MRI and vessel size imaging...

  12. Unbinding of targeted ultrasound contrast agent microbubbles by secondary acoustic forces

    NARCIS (Netherlands)

    V. Garbin (Valeria); M. Overvelde (Marlies); B. Dollet (Benjamin); N. de Jong (Nico); D. Lohse (Detlef); M. Versluis (Michel)

    2011-01-01

    textabstractTargeted molecular imaging with ultrasound contrast agent microbubbles is achieved by incorporating targeting ligands on the bubble coating and allows for specific imaging of tissues affected by diseases. Improved understanding of the interplay between the acoustic forces acting on the b

  13. Dynamic Assessment of the Focal Hepatic Lesion in Rats Using Ultrasonic Contrast Agent

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chao; DENG Youbin; HUANG Daozhong; ZHANG Qingping

    2006-01-01

    The focal hepatic lesion caused by local injection of absolute alcohol in rats was evaluated with ultrasonic contrast agent and pathologic examination. Twenty adult Wistar rats weighing about 200 g were injected with absolute alcohol (0.05-0.1 mL each one) on the exterior left lobe of the liver under the monitoring of ultrasound. Pulse inversion harmonic imaging was used to evaluate the focal lesion after bolus injection of ultrasonic contrast agent (0.05 mL/200 g) through caudal vein.Seven days later, the focal lesion was studied again as before. The exterior left lobe of liver with focal lesion was incised and underwent pathologic examination. The results showed that all of the focal lesions could be defined clearly after bolus injection of the ultrasonic contrast agent under the mode of pulse inversion harmonic imaging. There was good correlation between the size of the focal lesion measured by ultrasound on the 7th day after the "ablation" under the mode of pulse inversion harmonic imaging and that gotten by pathologic examination (P=0.39). The focus size measured by ultrasound right after the ablation was larger than that gotten by pathologic examination (P= 0.002). It was concluded that ultrasonic contrast agent plus pulse inversion harmonic imaging could be used to assess the size of the focal hepatic lesion caused by local injection of absolute alcohol in rats.

  14. Can focused US with a diagnostic US contrast agent favorably affect renal function?

    Science.gov (United States)

    Sica, Domenic A

    2009-12-01

    Focused ultrasonography (US) with simultaneous administration of a US microbubble contrast agent was used to transiently increase the glomerular filtration rate while altering the sieving properties of glomeruli in normal rabbits. In its current form, this process has very limited application potential to states of abnormal renal function.

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

    Science.gov (United States)

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

    2015-03-01

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

  16. Parametric imaging using subharmonic signals from ultrasound contrast agents in patients with breast lesions.

    Science.gov (United States)

    Eisenbrey, John R; Dave, Jaydev K; Merton, Daniel A; Palazzo, Juan P; Hall, Anne L; Forsberg, Flemming

    2011-01-01

    Parametric maps showing perfusion of contrast media can be useful tools for characterizing lesions in breast tissue. In this study we show the feasibility of parametric subharmonic imaging (SHI), which allows imaging of a vascular marker (the ultrasound contrast agent) while providing near complete tissue suppression. Digital SHI clips of 16 breast lesions from 14 women were acquired. Patients were scanned using a modified LOGIQ 9 scanner (GE Healthcare, Waukesha, WI) transmitting/receiving at 4.4/2.2 MHz. Using motion-compensated cumulative maximum intensity (CMI) sequences, parametric maps were generated for each lesion showing the time to peak (TTP), estimated perfusion (EP), and area under the time-intensity curve (AUC). Findings were grouped and compared according to biopsy results as benign lesions (n = 12, including 5 fibroadenomas and 3 cysts) and carcinomas (n = 4). For each lesion CMI, TTP, EP, and AUC parametric images were generated. No significant variations were detected with CMI (P = .80), TTP (P = .35), or AUC (P = .65). A statistically significant variation was detected for the average pixel EP (P = .002). Especially, differences were seen between carcinoma and benign lesions (mean ± SD, 0.10 ± 0.03 versus 0.05 ± 0.02 intensity units [IU]/s; P = .0014) and between carcinoma and fibroadenoma (0.10 ± 0.03 versus 0.04 ± 0.01 IU/s; P = .0044), whereas differences between carcinomas and cysts were found to be nonsignificant. In conclusion, a parametric imaging method for characterization of breast lesions using the high contrast to tissue signal provided by SHI has been developed. While the preliminary sample size was limited, results show potential for breast lesion characterization based on perfusion flow parameters.

  17. Liposomes loaded with hydrophilic magnetite nanoparticles: Preparation and application as contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    German, S V; Navolokin, N A; Kuznetsova, N R; Zuev, V V; Inozemtseva, O A; Anis'kov, A A; Volkova, E K; Bucharskaya, A B; Maslyakova, G N; Fakhrullin, R F; Terentyuk, G S; Vodovozova, E L; Gorin, D A

    2015-11-01

    Magnetic fluid-loaded liposomes (MFLs) were fabricated using magnetite nanoparticles (MNPs) and natural phospholipids via the thin film hydration method followed by extrusion. The size distribution and composition of MFLs were studied using dynamic light scattering and spectrophotometry. The effective ranges of magnetite concentration in MNPs hydrosol and MFLs for contrasting at both T2 and T1 relaxation were determined. On T2 weighted images, the MFLs effectively increased the contrast if compared with MNPs hydrosol, while on T1 weighted images, MNPs hydrosol contrasting was more efficient than that of MFLs. In vivo magnetic resonance imaging (MRI) contrasting properties of MFLs and their effects on tumor and normal tissues morphology, were investigated in rats with transplanted renal cell carcinoma upon intratumoral administration of MFLs. No significant morphological changes in rat internal organs upon intratumoral injection of MFLs were detected, suggesting that the liposomes are relatively safe and can be used as the potential contrasting agents for MRI.

  18. Near-infrared dye-loaded magnetic nanoparticles as photoacoustic contrast agent for enhanced tumor imaging

    Institute of Scientific and Technical Information of China (English)

    Chuang Gao; Zhi-Fei Dai; Chang-Hui Li; Xiao-Long Liang; Zi-Jian Deng; Dong Peng; Yu-Shen Jin; Yan Ma; Yan-Yan Li; Yu-Kun Zhu; Jian-Zhong Xi; Jie Tian

    2016-01-01

    Objective: Photoacoustic (PA) tomography (PAT) has attracted extensive interest because of its optical absorption contrast and ultrasonic detection. This study aims to develop a biocompatible and biodegradable PA contrast agent particularly promising for clinical applications in human body. Methods: In this study, we presented a PA contrast agent: 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy (polyethylene glycol)] (DSPE-PEG)-coated superparamagnetic iron oxide (SPIO) nanoparticles (NPs) loaded with indocyanine green (ICG). We used ICG and SPIO NPs because both drugs are approved by the U.S. Food and Drug Administration. Given the strong absorption of near-infrared laser pulses, SPIO@DSPE-PEG/ICG NPs with a uniform diameter of ~28 nm could significantly enhance PA signals. Results: We demonstrated the contrast enhancement of these NPs in phantom and animal experiments, in which thein vivo circulation time of SPIO@DSPE-PEG/ICG NPs was considerably longer than that of free ICG. These novel NPs also displayed a high efficiency of tumor targeting. Conclusions: SPIO@DSPE-PEG/ICG NPs are promising PAT contrast agents for clinical applications.

  19. Effect of mechanical convection on the partitioning of an anionic iodinated contrast agent in intact patellar cartilage.

    Science.gov (United States)

    Entezari, Vahid; Bansal, Prashant N; Stewart, Rachel C; Lakin, Benjamin A; Grinstaff, Mark W; Snyder, Brian D

    2014-10-01

    To determine if mechanical convection accelerates partitioning of an anionic contrast agent into cartilage while maintaining its ability to reflect the glycosaminoglycan (GAG) content in contrast-enhanced computed tomography (CECT) of cartilage. Bovine patellae (N = 4) were immersed in iothalamate and serially imaged over 24 h of passive diffusion at 34°C. Following saline washing for 14 h, each patella was serially imaged over 2.5 h of mechanical convection by cyclic compressive loading (120N, 1 Hz) while immersed in iothalamate at 34°C. After similar saline washing, each patella was sectioned into 15 blocks (n = 60) and contrast concentration per time point as well as GAG content were determined for each cartilage block. Mechanical convection produced 70.6%, 34.4%, and 16.4% higher contrast concentration at 30, 60, and 90 min, respectively, compared to passive diffusion (p correlation between contrast concentration and GAG content was significant at all time points and correlation coefficients improved with time, reaching R(2)  = 0.60 after 180 min of passive diffusion and 22.5 min of mechanical convection. Mechanical convection significantly accelerated partitioning of a contrast agent into healthy cartilage while maintaining strong correlations with GAG content, providing an evidence-based rationale for adopting walking regimens in CECT imaging protocols.

  20. Stimuli-Responsive Biodegradable Hyperbranched Polymer-Gadolinium Conjugates as Efficient and Biocompatible Nanoscale Magnetic Resonance Imaging Contrast Agents.

    Science.gov (United States)

    Sun, Ling; Li, Xue; Wei, Xiaoli; Luo, Qiang; Guan, Pujun; Wu, Min; Zhu, Hongyan; Luo, Kui; Gong, Qiyong

    2016-04-27

    The efficacy and biocompatibility of nanoscale magnetic resonance imaging (MRI) contrast agents depend on optimal molecular structures and compositions. Gadolinium [Gd(III)] based dendritic macromolecules with well-defined and tunable nanoscale sizes are excellent candidates as multivalent MRI contrast agents. Here, we propose a novel alternate preparation of biodegradable hyperbranched polymer-gadolinium conjugates via a simple strategy and report potentially efficient and biocompatible nanoscale MRI contrast agents for cancer diagnosis. The enzyme-responsive hyperbranched poly(oligo-(ethylene glycol) methacrylate)-gadolinium conjugate (HB-POEGMA-Gd) was prepared via one-step reversible addition-fragmentation chain transfer (RAFT) polymerization and Gd(III) chelating, and the cRGDyK functionalized polymer (HB-POEGMA-cRGD-Gd) was obtained via click chemistry. By using an enzyme similar to lysosomal cathepsin B, hyperbranched conjugates of high molecular weights (MW) (180 and 210 kDa) and nanoscale sizes (38 and 42 nm) were degraded into low MW (25 and 30 kDa) and smaller products (4.8 and 5.2 nm) below the renal threshold. Conjugate-based nanoscale systems had three-fold more T1 relaxivity compared to clinical agent diethylenediaminepentaacetic acid (DTPA)-Gd. Animal studies with the nanoscale system offered greater tumor accumulation and enhanced signal intensity (SI) in mouse U87 tumors of which the greatest activity was conferred by the cRGDyK moiety functionalized hyperbranched conjugate. In vitro cytotoxicity, hemocompatibility and in vivo toxicity studies confirmed no adverse events. This design strategy for multifunctional Gd(III)-labeled biodegradable dendritic macromolecules may have significant potential as future efficient, biocompatible polymeric nanoscale MRI diagnostic contrast agents for cancer.

  1. Development and characterization of hollow polymeric microcapsules for use as contrast agents for diagnostic ultrasound

    Science.gov (United States)

    Narayan, Padma Jyothi

    1999-09-01

    This thesis concerns the development and characterization of a new type of rigid-shelled ultrasound contrast agent. A novel method was devised for producing hollow, gas- filled, polymer microcapsules, sized to less than 10 μm in diameter for contrast imaging. This method involved the encapsulation of a solid, volatile core material, and its subsequent evacuation by sublimation. The biodegradable polymer, 50/50 poly(D,L-lactide-co- glycolide), was the main focus of this study. Polymer- based contrast agents have many advantages, such as their applicability for concomitant imaging and drug delivery. Three encapsulation techniques were evaluated: solvent evaporation, coacervation, and spray drying. The polymer molecular weight and polydispersity in the solvent evaporation and coacervation techniques strongly affected microcapsule size and morphology. Efficient mechanical agitation and shear were crucial for obtaining high yields in the desired size range (less than 6 μm). In spray drying, a factorial design approach was used to optimize conditions to produce microcapsules. The main factors affecting spray drying were found to be the temperature driving force for drying and initial polymer concentration. The smallest microcapsule mean diameters were produced by spray drying (3-4 μm) and solvent evaporation (5-6 μm). Zeta potential (ζ) studies for all microcapsule types indicated that the encapsulation technique affected their surface properties due to the orientation of the polymer chains within nascent polymer droplets. Microcapsules with the most hydrophilic tendency were produced with solvent evaporation (ζ ~ -50 mV). In vitro acoustic testing revealed that the 20-41 μm size fractions of coacervate microcapsules were the most echogenic. In vivo ultrasound studies with both solvent evaporation and coacervate microcapsules showed visible enhancement of the color Doppler image in the rabbit kidney for the samples less than 10 μm in diameter. A mathematical

  2. Long-Lasting and Efficient Tumor Imaging Using a High Relaxivity Polysaccharide Nanogel Magnetic Resonance Imaging Contrast Agent.

    Science.gov (United States)

    Chan, Minnie; Lux, Jacques; Nishimura, Tomoki; Akiyoshi, Kazunari; Almutairi, Adah

    2015-09-14

    Clinically approved small-molecule magnetic resonance imaging (MRI) contrast agents are all rapidly cleared from the body and offer weak signal enhancement. To avoid repeated administration of contrast agent and improve signal-to-noise ratios, agents with stronger signal enhancement and better retention in tumors are needed. Therefore, we focused on hydrogels because of their excellent water accessibility and biodegradability. Gadolinium (Gd)-chelating cross-linkers were incorporated into self-assembled pullulan nanogels to both impart magnetic properties and to stabilize this material that has been extensively studied for medical applications. We show that these Gd-chelating pullulan nanogels (Gd-CHPOA) have the highest reported relaxivity for any hydrogel-based particles and accumulate in the 4T1 tumors in mice at high levels 4 h after injection. This combination offers high signal enhancement and lasts up to 7 days to delineate the tumor clearly for longer imaging time scales. Importantly, this long-term accumulation does not cause any damage or toxicity in major organs up to three months after injection. Our work highlights the clinical potential of Gd-CHPOA as a tumor-imaging MRI contrast agent, permitting tumor identification and assessment with a high signal-to-background ratio.

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Fang Wang

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

  5. Preparation and initial characterization of biodegradable particles containing gadolinium-DTPA contrast agent for enhanced MRI

    Science.gov (United States)

    Doiron, Amber L.; Chu, Kevin; Ali, Adeel; Brannon-Peppas, Lisa

    2008-01-01

    Accurate imaging of atherosclerosis is a growing necessity for timely treatment of the disease. Magnetic resonance imaging (MRI) is a promising technique for plaque imaging. The goal of this study was to create polymeric particles of a small size with high loading of diethylenetriaminepentaacetic acid gadolinium (III) (Gd-DTPA) and demonstrate their usefulness for MRI. A water-in-oil-in-oil double emulsion solvent evaporation technique was used to encapsulate the MRI agent in a poly(lactide-co-glycolide) (PLGA) or polylactide-poly(ethylene glycol) (PLA-PEG) particle for the purpose of concentrating the agent at an imaging site. PLGA particles with two separate average sizes of 1.83 μm and 920 nm, and PLA-PEG particles with a mean diameter of 952 nm were created. Loading of up to 30 wt % Gd-DTPA was achieved, and in vitro release occurred over 5 h. PLGA particles had highly negative zeta potentials, whereas the particles incorporating PEG had zeta potentials closer to neutral. Cytotoxicity of the particles on human umbilical vein endothelial cells (HUVEC) was shown to be minimal. The ability of the polymeric contrast agent formulation to create contrast was similar to that of Gd-DTPA alone. These results demonstrate the possible utility of the contrast agent-loaded polymeric particles for plaque detection with MRI. PMID:18796605

  6. Liposomes with conjugates of a calix[4]arene and a Gd-DOTA derivative on the outside surface: An efficient potential contrast agent for MRI

    NARCIS (Netherlands)

    Schühle, D.T.; Van Rijn, P.; Laurent, S.; Van der Elst, L.; Muller, R.N.; Stuart, M.C.A.; Schatz, J.; Peters, J.A.

    2010-01-01

    Paramagnetic liposomes used as contrast agents in magnetic resonance imaging (MRI) often suffer from low efficacies because of slow water diffusion through the membrane. We present an approach to overcome this limitation by incorporation of a calix[4]arene based agent that expresses the chelates tow

  7. Colloidal dispersions of maghemite nanoparticles produced by laser pyrolysis with application as NMR contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Veintemillas-Verdaguer, Sabino [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Morales, Maria del Puerto [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Bomati-Miguel, Oscar [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Bautista, Carmen [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Zhao, Xinqing [Instituto de Ciencia de Materiales de Madrid, CSIC, Cantoblanco, 28049 Madrid (Spain); Bonville, Pierre [CEA, CE Saclay, DSM/DRECAM/SPEC, 91191 Gif-Sur-Yvette (France); Alejo, Rigoberto Perez de [Universidad Complutense de Madrid, Unidad de RMN, Paseo Juan XXIII, 1, 28040 Madrid (Spain); Ruiz-Cabello, Jesus [Universidad Complutense de Madrid, Unidad de RMN, Paseo Juan XXIII, 1, 28040 Madrid (Spain); Santos, Martin [Hospital Universitario Puerta de Hierro, Servicio de Cirugia Experimental. C/San Martin de Porres 4, 28035 Madrid (Spain); Tendillo-Cortijo, Francisco J [Hospital Universitario Puerta de Hierro, Servicio de Cirugia Experimental. C/San Martin de Porres 4, 28035 Madrid (Spain); Ferreiros, Joaquin [Hospital Clinico de Madrid ' San Carlos' , Ciudad Universitaria, 28040 Madrid (Spain)

    2004-08-07

    Biocompatible magnetic dispersions have been prepared from {gamma}-Fe{sub 2}O{sub 3} nanoparticles (5 nm) synthesized by continuous laser pyrolysis of Fe(CO){sub 5} vapours. The feasibility of using these dispersions as magnetic resonance imaging (MRI) contrast agents has been analysed in terms of chemical structure, magnetic properties, {sup 1}H NMR relaxation times and biokinetics. The magnetic nanoparticles were dispersed in a strong alkaline solution in the presence of dextran, yielding stable colloids in a single step. The dispersions consist of particle-aggregates 25 nm in diameter measured using transmission electron microscope and a hydrodynamic diameter of 42 nm measured using photon correlation spectroscopy. The magnetic and relaxometric properties of the dispersions were of the same order of magnitude as those of commercial contrast agents produced using coprecipitation. However, these dispersions, when injected intravenously in rats at standard doses showed a mono-exponential blood clearance instead of a biexponential one, with a blood half-life of 7 {+-} 1 min. Furthermore, an important enhancement of the image contrast was observed after the injection, mainly located at the liver and the spleen of the rat. In conclusion, the laser pyrolysis technique seems to be a good alternative to the coprecipitation method for producing MRI contrast agents, with the advantage of being a continuous synthesis method that leads to very uniform particles capable of being dispersed and therefore transformed in a biocompatible magnetic liquid.

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

    Science.gov (United States)

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

    2012-04-01

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

  9. Magnetic resonance angiography with blood-pool contrast agents: future applications

    Energy Technology Data Exchange (ETDEWEB)

    Fink, C. [Univ. Hospitals, Grosshadern, Munich (Germany); Goyen, M. [Univ. Medical Center, Hamburg-Eppendorf, Hamburg (Germany); Lotz, J. [Hannover Medical School, Hannover (Germany)

    2007-03-15

    Blood pool agents remain in the intravascular space for a longer time period. Therefore the optimal imaging window for vascular structures is widened to about 30 minutes. Gadofosveset trisodium (Vasovist, Bayer Schering Pharma AG, Berlin, Germany) is the first blood-pool contrast agent approved in Europe for contrast-enhanced magnetic resonance angiography (MRA) of vessels in the abdomen, pelvis and lower extremity in adults. Other possible applications of blood-pool agents are now being considered, such as assessment of venous thromboembolism, coronary artery disease or sinus venous thrombosis. Perfusion MR imaging holds promise for detecting lung perfusion defects with higher spatial resolution and reduced scan time compared with radionuclide scintigraphy. In coronary artery disease, blood-pool agents enable a substantial increase in the quality of coronary artery imaging. Quantitative myocardial perfusion and myocardial viability seem to be possible, although modifications in protocols and sequence design are necessary for optimal results. Other novel applications of blood-pool agents include monitoring of inflammatory changes in systemic lupus erythematosus and evaluation of tumour invasion into lymph nodes and more reliable assessment of cerebral venous and sinus thrombosis. (orig.)

  10. Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast agents for magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Jahanbin, Tania [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Sauriat-Dorizon, Hélène [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France); Spearman, Peter [Faculty of Science, Engineering and Computing, University of Kingston, Penrhyn Road Kingston upon Thames Surrey KT1 2EE, London (United Kingdom); Benderbous, Soraya, E-mail: soraya.benderbous@univ-tlse3.fr [Université Paul Sabatier, Toulouse III, INSERM U825, CHU Purpan, 31059 Toulouse Cedex 9 (France); Korri-Youssoufi, Hafsa, E-mail: hafsa.korri-youssoufi@u-psud.fr [Institut de Chimie Moléculaire et des Matériaux d' Orsay, UMR CNRS 8182, ECBB, Université Paris-Sud, 91405 Orsay (France)

    2015-07-01

    A novel magnetic resonance imaging (MRI) contrast agent based on gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] conjugated with chitosan nanoparticles has been developed. The chitosan nanoparticles were synthesized following an ionic gelation method and the conditions optimized to generate small nanoparticles (CNs) with a narrow size distribution of 35–65 nm. The gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] was loaded into chitosan nanoparticles by passive adsorption. The interaction of chitosan with Gd(TPyP) has been examined by UV–visible, Fourier transform infrared spectroscopies (FT-IR) and inductively coupled plasma mass spectrometry (ICP-MS), which indicate the successful association of Gd(TPyP) without any structural distortion throughout the chitosan nanoparticles. The potential of Gd(TPyP)-CNs as MRI contrast agent has been investigated by magnetic resonance imaging (MRI) in-vitro. Relaxivities of Gd(TPyP)-CNs obtained from T{sub 1}-weighted images, increased with Gd concentration and attained an optimum r{sub 1} of 38.35 mM{sup −1} s{sup −1}, which is 12-fold higher compared to commercial Gd-DOTA (~ 4 mM{sup −1} s{sup −1} at 3T). The combination of such strong MRI contrast with the known properties of porphyrins in photodynamic therapy and biocompatibility of chitosan, presents a new perspective in using these compounds in cancer theranostics. - Highlights: • Synthesis of chitosan nanoparticles with small size • Study of loading properties with gadolinium porphyrins • In vitro properties of the conjugated complex as contrast agent for MRI imaging • Comparison of MRI properties with commercial contrast agent Gd-DOTA.

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

    Science.gov (United States)

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

    2014-04-18

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

  12. Poly-ε-caprolactone tungsten oxide nanoparticles as a contrast agent for X-ray computed tomography.

    Science.gov (United States)

    Jakhmola, Anshuman; Anton, Nicolas; Anton, Halina; Messaddeq, Nadia; Hallouard, François; Klymchenko, Andrey; Mely, Yves; Vandamme, Thierry F

    2014-03-01

    Inorganic nanomaterials based on heavy elements represent a new class of contrast agents for X-ray computed tomography (CT). Recent advances have shown that these materials are highly suited for CT imaging due to their high density and X-ray absorption capabilities. In this contribution, we demonstrated that tungsten oxide (WO3) nanoparticles coated by poly-ε-caprolactone (PCL) can be used as efficient contrast agent for CT imaging. The obtained particles were characterized by electron microscopy (TEM and SEM), and dynamic light scattering (DLS). We also validated their use for enhanced in vivo imaging, since these nanoparticles were observed to display high X-ray attenuation properties and circulation time (up to 3 h), permitting blood pool imaging.

  13. Agent-based enterprise integration

    Energy Technology Data Exchange (ETDEWEB)

    N. M. Berry; C. M. Pancerella

    1998-12-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  14. Agent-based enterprise integration

    Energy Technology Data Exchange (ETDEWEB)

    N. M. Berry; C. M. Pancerella

    1998-12-01

    The authors are developing and deploying software agents in an enterprise information architecture such that the agents manage enterprise resources and facilitate user interaction with these resources. The enterprise agents are built on top of a robust software architecture for data exchange and tool integration across heterogeneous hardware and software. The resulting distributed multi-agent system serves as a method of enhancing enterprises in the following ways: providing users with knowledge about enterprise resources and applications; accessing the dynamically changing enterprise; locating enterprise applications and services; and improving search capabilities for applications and data. Furthermore, agents can access non-agents (i.e., databases and tools) through the enterprise framework. The ultimate target of the effort is the user; they are attempting to increase user productivity in the enterprise. This paper describes their design and early implementation and discusses the planned future work.

  15. Synthesis and evaluation of nanoglobule-cystamine-(Gd-DO3A, a biodegradable nanosized magnetic resonance contrast agent for dynamic contrast-enhanced magnetic resonance urography

    Directory of Open Access Journals (Sweden)

    Rongzuo Xu

    2010-09-01

    Full Text Available Rongzuo Xu1, Todd Lyle Kaneshiro1, Eun-Kee Jeong2, Dennis L Parker2, Zheng-Rong Lu31Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, USA; 2Department of Radiology, University of Utah, Salt Lake City, UT, USA; 3Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH, USAAbstract: Dynamic contrast-enhanced magnetic resonance imaging has been recently shown to be effective for diagnostic urography. High-resolution urographic images can be acquired with T1 contrast agents for the kidney and urinary tract with minimal noise in the abdomen. Currently, clinical contrast agents are low molecular weight agents and can rapidly extravasate from blood circulation, leading to slow contrast agent elimination through kidney and consequently providing limited contrast enhancement in urinary tract. In this study, a new biodegradable macromolecular contrast agent, nanoglobule-G4-cystamine-(Gd-DO3A, was prepared by conjugating Gd-DO3A chelates on the surface of a generation 4 nanoglobule, poly-l-lysine octa(3-aminopropylsilsesquioxane dendrimer, via a disulfide spacer, where the carrier had a precisely defined nanosize that is far smaller than the renal filtration threshold. The in vivo contrast enhancement and dynamic imaging of the urinary tract of the agent was evaluated in nude mice using a low molecular weight agent Gd(DTPA-BMA as a control. The agent eliminated rapidly from blood circulation and accumulated more abundantly in urinary tract than Gd(DTPA-BMA. The fast elimination kinetics is ideal for functional evaluation of the kidneys. The morphology of the kidneys and urinary tract was better visualized by the biodegradable nanoglobular contrast agent than Gd(DTPA-BMA. The agent also resulted in low liver contrast enhancement, indicating low nonspecific tissue deposition. These features render the G4 nanoglobule-cystamine-(Gd-DO3A conjugate a promising contrast agent for magnetic

  16. Whole tissue AC susceptibility after superparamagnetic iron oxide contrast agent administration in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Lazaro, Francisco Jose [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, 50018 Zaragoza (Spain) and Instituto de Nanociencia de Aragon, Universidad de Zaragoza, 50009 Zaragoza (Spain)]. E-mail: osoro@unizar.es; Gutierrez, Lucia [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, 50018 Zaragoza (Spain); Rosa Abadia, Ana [Dept. Farmacologia y Fisiologia, Universidad de Zaragoza, 50013 Zaragoza (Spain); Soledad Romero, Maria [Dept. Medicina y Psiquiatria, Universidad de Zaragoza, 50009 Zaragoza (Spain); Lopez, Antonio [CNAM - Zaragoza, 50009 Zaragoza (Spain); Jesus Munoz, Maria [Dept. Farmacologia y Fisiologia, Universidad de Zaragoza, 50013 Zaragoza (Spain)

    2007-04-15

    A magnetic AC susceptibility characterisation of rat tissues after intravenous administration of superparamagnetic iron oxide (Endorem{sup (R)}), at the same dose as established for Magnetic Resonance Imaging (MRI) contrast enhancement in humans, has been carried out. The measurements reveal the presence of the contrast agent as well as that of physiological ferritin in liver and spleen while no traces have been magnetically detected in heart and kidney. This preliminary work opens suggestive possibilities for future biodistribution studies of any type of magnetic carriers.

  17. Relaxivity of blood pool contrast agent depends on the host tissue as suggested by semianalytical simulations

    DEFF Research Database (Denmark)

    Kjølby, Birgitte Fuglsang; Østergaard, Leif; Kiselev, Valerij

    Concentration of magnetic resonance imaging (MRI) contrast agents (CA) cannot be measured directly and is commonly determined indirectly using their relaxation effect. This requires knowledge of the relaxivity of the used CA. Quantitative perfusion studies involve measurement of CA concentration...... studies (3,4) as demonstrated in (5). It was previously found (6) that the perfusion measurements using dynamic susceptibility contrast inherently overestimate cerebral blood flow and volume. In view of the present result, this is attributed to the significant difference in the relaxivity of the CA...

  18. Model Based Testing for Agent Systems

    Science.gov (United States)

    Zhang, Zhiyong; Thangarajah, John; Padgham, Lin

    Although agent technology is gaining world wide popularity, a hindrance to its uptake is the lack of proper testing mechanisms for agent based systems. While many traditional software testing methods can be generalized to agent systems, there are many aspects that are different and which require an understanding of the underlying agent paradigm. In this paper we present certain aspects of a testing framework that we have developed for agent based systems. The testing framework is a model based approach using the design models of the Prometheus agent development methodology. In this paper we focus on model based unit testing and identify the appropriate units, present mechanisms for generating suitable test cases and for determining the order in which the units are to be tested, present a brief overview of the unit testing process and an example. Although we use the design artefacts from Prometheus the approach is suitable for any plan and event based agent system.

  19. Synthesis of functionalized magnetite nanoparticles to use as liver targeting MRI contrast agent

    Science.gov (United States)

    Yazdani, Farshad; Fattahi, Bahare; Azizi, Najmodin

    2016-05-01

    The aim of this research was the preparation of functionalized magnetite nanoparticles to use as a liver targeting contrast agent in magnetic resonance imaging (MRI). For this purpose, Fe3O4 nanoparticles were synthesized via the co-precipitation method. The synthesized nanoparticles were coated with silica via the Stober method and finally the coated nanoparticles were functionalized with mebrofenin. Formation of crystalline magnetite particles was confirmed by X-ray diffraction (XRD) analysis. The Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray analyzer (EDX) of the final product showed that silica had been effectively bonded onto the surface of the magnetite nanoparticles and the coated nanoparticles functionalized with mebrofenin. The magnetic resonance imaging of the functional nanoparticles showed that the Fe3O4-SiO2-mebrofenin composite is an effective MRI contrast agent for liver targeting.

  20. Synthesis of cytocompatible Fe3O4@ZSM-5 nanocomposite as magnetic resonance imaging contrast agent

    Science.gov (United States)

    Atashi, Zahra; Divband, Baharak; Keshtkar, Ahmad; Khatamian, Maasoumeh; Farahmand-Zahed, Farzane; Nazarlo, Ali Kiani; Gharehaghaji, Nahideh

    2017-09-01

    In this study, ZSM-5 nano zeolite was used as a support material for iron oxide nanoparticles and the potential ability of the nanocomposite for magnetic resonance imaging (MRI) contrast agent was investigated. The nanocomposite was synthesized by hydrothermal method and characterized using X-ray diffraction and scanning electron microscopy. MRI was carried out by use of a 1.5 Tesla clinical scanner. The T2 weighted images were prepared and the r2 relaxivity was calculated. The sizes of Fe3O4 nanoparticles and related nanocomposite were 13-24 nm and 80-150 nm, respectively. Results of MTT assay confirmed that the prepared nanocomposite is cytocompatible. The r2 relaxivity of the Fe3O4@ZSM-5 nanocomposite was 457.1 mM-1 s-1. This study suggests that the Fe3O4@ZSM-5 nanocomposite has potential to use as an MRI T2 contrast agent.

  1. Novel ultrasound contrast agents--Biodegradable poly(lactic acid) microcapsules

    Institute of Scientific and Technical Information of China (English)

    王身国; 崔文瑾; 李光明; 蔡晴; 智光; 赵玉英; 杨波; 徐勇

    2003-01-01

    As a novel ultrasound diagnostic contrast agent, the preparation, characterization and ultrasound imaging in the body of dog about poly(lactic acid) (PLLA) microcapsules have been studied. The behavior of this kind of contrast agent in the microcirculation was also investigated. Prepared by (water/oil/water) emulsion-solvent evaporation protocol, the PLLA microcapsules with hollow structure can enhance the ultrasound image both in vitro and in vivo, and the enduring time can last as long as 3 h. The microcirculation examination shows that the PLLA microcapsules with a diameter ranging from 2 to 8 μm could pass through the pulmonary capillaries without retention. All the results prove the PLLA microcapsules for potential use for the clinical application.

  2. Preparation and Characterization of Ion-Irradiated Nanodiamonds as Photoacoustic Contrast Agents.

    Science.gov (United States)

    Fang, Chia-Yi; Chang, Cheng-Chun; Mou, Chung-Yuan; Chang, Huan-Cheng

    2015-02-01

    Highly radiation-damaged or irradiated nanodiamonds (INDs) are a new type of nanomaterial developed recently as a potential photoacoustic (PA) contrast agent for deep-tissue imaging. This work characterized in detail the photophysical properties of these materials prepared by ion irradiation of natural diamond powders using various spectroscopic methods. For 40-nm NDs irradiated with 40-keV He+ at a dose of 3 x 10(15) ions/cm2, an average molar extinction coefficient of 4.2 M-1 cm-1 per carbon atom was measured at 1064 nm. Compared with gold nanorods of similar dimensions (10 nm x 67 nm), the INDs have a substantially smaller (by > 4 orders of magnitude) molar extinction coefficient per particle. However, the deficit is readily compensated by the much higher thermal stability, stronger hydrophilic interaction with water, and a lower nanobubble formation threshold (~30 mJ/cm2) of the sp3-carbon-based nanomaterial. No sign of photodamage was detected after high-energy (>100 mJ/cm2) illumination of the INDs for hours. Cell viability assays at the IND concentration of up to 100 µg/mL showed that the nanomaterial is non-cytotoxic and potentially useful for long-term PA bioimaging applications.

  3. PREPARATION OF POLYELECTROLYTE MULTILAYER COATED MICROBUBBLES FOR USE AS ULTRASOUND CONTRAST AGENT

    Institute of Scientific and Technical Information of China (English)

    Zhan-wen Xing; Heng-te Ke; Shao-qin Liu; Zhi-fei Dai; Jin-rui Wang; Ji-bin Liu

    2008-01-01

    Objective To prepare and characterize polyelectrolyte multilayer film coated microbubbles for use as ultrasound contrast agent (UCA) and evaluate its effects in ultrasonic imaging on normal rabbit's fiver parenchyma.Methoda Pcrfluorocarbon (PFC)-containing microbubbles (ST68-PFC) were prepared by sonication based on surfactant ( Span 60 and Tween 80). Subsequently, the resulting ST68-PFC microbnbbles were coated using oppositely charged polyclectrolytes by microbubble-templated layer-by-layer self-assembly technique via electrostatic interaction.The enhancement effects in ultrasonic imaging on normal rabbit's liver parenchyma were assessed.Results The obtained microbubbles exhibited a narrow size distribution. The polyelectrolytes were successfully assembled onto the surface of ST68-PFC microbubbles. In vivo experiment showed that polyelectrolyte multilayer film coated UCA effectively enhanced the imaging of rabbit's liver parenchyma.Conclnsions The novel microbubbles UCA coated with polyelectrolyte multilayer, when enabled more function,has no obvious difference in enhancement effects compared with the pre-modified microbnbbles. The polymers with chemically active groups ( such as amino group and carboxyl group) can be used as the outermost layer for attachment of targeting ligands onto microbubbles, allowing selective targeting of the microbubbles to combine with desired sites.

  4. Yeast Cell Trapping In Ultrasonic Wave Field Using Ultrasonic Contrast Agent

    Science.gov (United States)

    Yamakoshi, Yoshiki; Koitabashi, Yusuke; Nakajima, Naritsugu; Miwa, Takashi

    2006-05-01

    Microobject manipulation using ultrasonic waves is expected to play important roles in constructing future drug or gene delivery systems. The acoustic radiation force, which is applied to microobjects, traps the objects at the desired position. A microjet, which is produced by bubble explosion under high-intensity ultrasonic waves, creates microholes through the cell membrane (sonoporation), which is considered as a sophisticated method of improving the doses of drugs or genes injected into a tissue. Aiming at increasing the trapping force in micro bubble manipulation using ultrasonic waves, we have proposed a novel method based on the self-organization of microbubbles. This method uses seed bubbles in order to trap the target bubbles. In this study, the proposed method is applied to yeast cell trapping using ultrasonic waves. An ultrasonic wave contrast agent (Levovist; Shering A.G., Germany) is used as a seed bubble. It is shown that the number of trapped yeast cells depends on the preparation of the yeast cells. In order to evaluate the result, two additional experiments are carried out by changing the internal gas of the seed bubbles and by using bubbles with a polymer shell.

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

    Science.gov (United States)

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

    2011-04-01

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

  6. Self-Assembled Polyelectrolyte Nanoparticles as Fluorophore-Free Contrast Agents for Multicolor Optical Imaging

    Directory of Open Access Journals (Sweden)

    Da Hye Shin

    2015-03-01

    Full Text Available In this work, we describe the fabrication of self-assembled polyelectrolyte nanoparticles that provide a multicolor optical imaging modality. Poly(γ-glutamic acid(γ-PGA formed self-assembled nanoparticles through electrostatic interactions with two different cationic polymers: poly(L-lysine(PLL and chitosan. The self-assembled γ-PGA/PLL and γ-PGA/chitosan nanoparticles were crosslinked by glutaraldehyde. Crosslinking of the ionic self-assembled nanoparticles with glutaraldehyde not only stabilized the nanoparticles but also generated a strong autofluorescence signal. Fluorescent Schiff base bonds (C=N and double bonds (C=C were generated simultaneously by crosslinking of the amine moiety of the cationic polyelectrolytes with monomeric glutaraldehyde or with polymeric glutaraldehyde. The unique optical properties of the nanoparticles that resulted from the crosslinking by glutaraldehyde were analyzed using UV/Vis and fluorescence spectroscopy. We observed that the fluorescence intensity of the nanoparticles could be regulated by adjusting the crosslinker concentration and the reaction time. The nanoparticles also exhibited high performance in the labeling and monitoring of therapeutic immune cells (macrophages and dendritic cells. These self-assembled nanoparticles are expected to be a promising multicolor optical imaging contrast agent for the labeling, detection, and monitoring of cells.

  7. A contrast study on different gasifying agents of underground coal gasification at Huating Coal Mine

    Institute of Scientific and Technical Information of China (English)

    WANG Zuo-tang; HUANG Wen-gang; ZHANG Peng; XIN Lin

    2011-01-01

    To optimize the technological parameter of underground coal gasification (UCG), the experimental results of air gasification, air-steam gasification, oxygen-enrichment steam gasification, pure oxygen steam gasification and two-stage gasification were studied contrastively based on field trial at the Huating UCG project. The results indicate that the average low heat value of gas from air experiment is the lowest (4.1 MJ/Nm3) and the water gas from two-stage gasification experiment is the highest (10.72 MJ/Nm3). The gas productivity of air gasification is the highest and the pure oxygen steam gasification is the lowest. The gasification efficiency of air gasification, air-steam gasification, oxygen-enriched steam gasification, pure oxygen steam gasification and two-stage gasification is listed in ascending order, ranging from 69.88% to 84.81%. Described a contract study on results of a field test using steam and various levels of oxygen enrichment of 21%, 32%, 42% and 100%. The results show that, with the increasing of O2 content in gasifying agents, the gas caloricity rises, and the optimal O2 concentration range to increase the gas caloricity is 30%~40%. Meanwhile, the consumption of O2 and steam increase, and the air consumption and steam decomposition efficiency fall.

  8. A Gadolinium-containing Magnetic Resonance Image Contrast Agent Promotes Fibrocyte Differentiation

    OpenAIRE

    Vakil, Varsha; Sung, Joanna J.; Piecychna, Marta; Crawford, Jeffrey R.; Kuo, Philip; Abu-Alfa, Ali K.; Cowper, Shawn E.; Bucala, Richard; Gomer, Richard H.

    2009-01-01

    Gadolinium-containing magnetic resonance imaging contrast agents such as Omniscan are associated with Nephrogenic Systemic Fibrosis (NSF). To determine if Omniscan can affect the differentiation of monocytes into fibroblast-like cells called fibrocytes that are found in the fibrotic lesions of NSF, peripheral blood mononuclear cells (PBMCs) from NSF patients, hemodialysis patients without NSF, and healthy, renally sufficient controls were exposed to Omniscan in a standardized in vitro fibrocy...

  9. Ultrasound in Biomedical Engineering: Ultrasound Microbubble Contrast Agents Promote Transdermal Permeation of Drugs

    Directory of Open Access Journals (Sweden)

    Ai-Ho Liao

    2016-09-01

    Full Text Available This report discusses a new development in the use of ultrasound microbubble contrast agents on transdermal drug delivery. The medium surrounding the microbubbles at the optimum concentration from liquid to gel can be modified and it can still achieve the same enhancement for transdermal drug permeation as liquid medium. It was also found that under the same ultrasound power density, microbubbles of larger particle sizes can extend the penetration depths of dye at the phantom surface.

  10. CATS-based Agents That Err

    Science.gov (United States)

    Callantine, Todd J.

    2002-01-01

    This report describes preliminary research on intelligent agents that make errors. Such agents are crucial to the development of novel agent-based techniques for assessing system safety. The agents extend an agent architecture derived from the Crew Activity Tracking System that has been used as the basis for air traffic controller agents. The report first reviews several error taxonomies. Next, it presents an overview of the air traffic controller agents, then details several mechanisms for causing the agents to err in realistic ways. The report presents a performance assessment of the error-generating agents, and identifies directions for further research. The research was supported by the System-Wide Accident Prevention element of the FAA/NASA Aviation Safety Program.

  11. Current status of superparamagnetic iron oxide contrast agents for liver magnetic resonance imaging.

    Science.gov (United States)

    Wang, Yi-Xiang J

    2015-12-21

    Five types of superparamagnetic iron oxide (SPIO), i.e. Ferumoxides (Feridex(®) IV, Berlex Laboratories), Ferucarbotran (Resovist(®), Bayer Healthcare), Ferumoxtran-10 (AMI-227 or Code-7227, Combidex(®), AMAG Pharma; Sinerem(®), Guerbet), NC100150 (Clariscan(®), Nycomed,) and (VSOP C184, Ferropharm) have been designed and clinically tested as magnetic resonance contrast agents. However, until now Resovist(®) is current available in only a few countries. The other four agents have been stopped for further development or withdrawn from the market. Another SPIO agent Ferumoxytol (Feraheme(®)) is approved for the treatment of iron deficiency in adult chronic kidney disease patients. Ferumoxytol is comprised of iron oxide particles surrounded by a carbohydrate coat, and it is being explored as a potential imaging approach for evaluating lymph nodes and certain liver tumors.

  12. The fabrication of novel nanobubble ultrasound contrast agent for potential tumor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Xing Zhanwen; Ke Hengte; Yue Xiuli; Dai Zhifei [Nanobiotechnology Division, State Key Laboratory of Urban Water Resources and Environment, School of Sciences, Harbin Institute of Technology, Harbin 150080 (China); Wang Jinrui; Zhao Bo [Department of Ultrasonography, Peking University Third Hospital, Beijing 100083 (China); Liu Jibin, E-mail: zhifei.dai@hit.edu.cn, E-mail: ji-bin.liu@jefferson.edu [Ultrasound Research and Education Institute, Thomas Jefferson University, Philadelphia, PA 19107 (United States)

    2010-04-09

    Novel biocompatible nanobubbles were fabricated by ultrasonication of a mixture of Span 60 and polyoxyethylene 40 stearate (PEG40S) followed by differential centrifugation to isolate the relevant subpopulation from the parent suspensions. Particle sizing analysis and optical microscopy inspection indicated that the freshly generated micro/nanobubble suspension was polydisperse and the size distribution was bimodal with large amounts of nanobubbles. To develop a nano-sized contrast agent that is small enough to leak through tumor pores, a fractionation to extract smaller bubbles by variation in the time of centrifugation at 20g (relative centrifuge field, RCF) was suggested. The results showed that the population of nanobubbles with a precisely controlled mean diameter could be sorted from the initial polydisperse suspensions to meet the specified requirements. The isolated bubbles were stable over two weeks under the protection of perfluoropropane gas. The acoustic behavior of the nano-sized contrast agent was evaluated using power Doppler imaging in a normal rabbit model. An excellent power Doppler enhancement was found in vivo renal imaging after intravenous injection of the obtained nanobubbles. Given the broad spectrum of potential clinical applications, the nano-sized contrast agent may provide a versatile adjunct for ultrasonic imaging enhancement and/or treatment of tumors.

  13. Neurosurgical confocal endomicroscopy: A review of contrast agents, confocal systems, and future imaging modalities

    Directory of Open Access Journals (Sweden)

    Aqib H Zehri

    2014-01-01

    Full Text Available Background: The clinical application of fluorescent contrast agents (fluorescein, indocyanine green, and aminolevulinic acid with intraoperative microscopy has led to advances in intraoperative brain tumor imaging. Their properties, mechanism of action, history of use, and safety are analyzed in this report along with a review of current laser scanning confocal endomicroscopy systems. Additional imaging modalities with potential neurosurgical utility are also analyzed. Methods: A comprehensive literature search was performed utilizing PubMed and key words: In vivo confocal microscopy, confocal endomicroscopy, fluorescence imaging, in vivo diagnostics/neoplasm, in vivo molecular imaging, and optical imaging. Articles were reviewed that discussed clinically available fluorophores in neurosurgery, confocal endomicroscopy instrumentation, confocal microscopy systems, and intraoperative cancer diagnostics. Results: Current clinically available fluorescent contrast agents have specific properties that provide microscopic delineation of tumors when imaged with laser scanning confocal endomicroscopes. Other imaging modalities such as coherent anti-Stokes Raman scattering (CARS microscopy, confocal reflectance microscopy, fluorescent lifetime imaging (FLIM, two-photon microscopy, and second harmonic generation may also have potential in neurosurgical applications. Conclusion: In addition to guiding tumor resection, intraoperative fluorescence and microscopy have the potential to facilitate tumor identification and complement frozen section analysis during surgery by providing real-time histological assessment. Further research, including clinical trials, is necessary to test the efficacy of fluorescent contrast agents and optical imaging instrumentation in order to establish their role in neurosurgery.

  14. Chitosan-coated nickel-ferrite nanoparticles as contrast agents in magnetic resonance imaging

    Science.gov (United States)

    Ahmad, Tanveer; Bae, Hongsub; Iqbal, Yousaf; Rhee, Ilsu; Hong, Sungwook; Chang, Yongmin; Lee, Jaejun; Sohn, Derac

    2015-05-01

    We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe2O4) nanoparticles as both T1 and T2 contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T1 and T2 relaxivities were 0.858±0.04 and 1.71±0.03 mM-1 s-1, respectively. In animal experimentation, both a 25% signal enhancement in the T1-weighted mage and a 71% signal loss in the T2-weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T1 and T2 contrast agents in MRI. We note that the applicability of our nanoparticles as both T1 and T2 contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles.

  15. Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging.

    Science.gov (United States)

    Xue, Shenghui; Yang, Hua; Qiao, Jingjuan; Pu, Fan; Jiang, Jie; Hubbard, Kendra; Hekmatyar, Khan; Langley, Jason; Salarian, Mani; Long, Robert C; Bryant, Robert G; Hu, Xiaoping Philip; Grossniklaus, Hans E; Liu, Zhi-Ren; Yang, Jenny J

    2015-05-26

    With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd(3+) toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd(3+) and a 10(11)-fold greater selectivity for Gd(3+) over Zn(2+) compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol(-1)⋅s(-1)/89.2 mmol(-1)⋅s(-1) per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10-20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

  16. ESGAR consensus statement on liver MR imaging and clinical use of liver-specific contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Neri, E.; Boraschi, P.; Bartolozzi, C. [University of Pisa, Department of Diagnostic and Interventional Radiology, Pisa (Italy); Bali, M.A.; Matos, C. [Hopital Erasme, MRI Clinics, Department of Radiology, Bruxelles (Belgium); Ba-Ssalamah, A. [The General Hospital of the Medical University of Vienna, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Brancatelli, G. [University of Palermo, Department of Radiology, Palermo (Italy); Alves, F.C. [University Hospital of Coimbra, Medical Imaging Department and Faculty of Medicine, Coimbra (Portugal); Grazioli, L. [Spedali Civili di Brescia, Department of Radiology, Brescia (Italy); Helmberger, T. [Academic Teaching Hospital of the Technical University, Department of Diagnostic and Interventional Radiology and Nuclear Medicine, Klinikum Bogenhausen, Munich (Germany); Lee, J.M. [Seoul National University College of Medicine, Division of Abdominal Imaging, Department of Radiology, Seoul (Korea, Republic of); Manfredi, R. [University of Verona, Department of Radiology, Verona (Italy); Marti-Bonmati, L. [Hospital Universitario y Politecnico La Fe, Area Clinica de Imagen Medica, Valencia (Spain); Merkle, E.M. [Universitaetsspital Basel, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland); Op De Beeck, B. [Antwerp University Hospital, Department of Radiology, Edegem (Belgium); Schima, W. [KH Goettlicher Heiland, Krankenhaus der Barmherzigen Schwestern and Sankt Josef-Krankenhaus, Department of Diagnostic and Interventional Radiology, Vienna (Austria); Skehan, S. [St Vincent' s University Hospital, Department of Radiology, Dublin (Ireland); Vilgrain, V. [Assistance Publique-Hopitaux de Paris, APHP, Hopital Beaujon, Radiology Department, Clichy, Paris (France); Zech, C. [Universitaetsspital Basel, Abteilungsleiter Interventionelle Radiologie, Klinik fuer Radiologie und Nuklearmedizin, Basel (Switzerland)

    2016-04-15

    To develop a consensus and provide updated recommendations on liver MR imaging and the clinical use of liver-specific contrast agents. The European Society of Gastrointestinal and Abdominal Radiology (ESGAR) formed a multinational European panel of experts, selected on the basis of a literature review and their leadership in the field of liver MR imaging. A modified Delphi process was adopted to draft a list of statements. Descriptive and Cronbach's statistics were used to rate levels of agreement and internal reliability of the consensus. Three Delphi rounds were conducted and 76 statements composed on MR technique (n = 17), clinical application of liver-specific contrast agents in benign, focal liver lesions (n = 7), malignant liver lesions in non-cirrhotic (n = 9) and in cirrhotic patients (n = 18), diffuse and vascular liver diseases (n = 12), and bile ducts (n = 13). The overall mean score of agreement was 4.84 (SD ±0.17). Full consensus was reached in 22 % of all statements in all working groups, with no full consensus reached on diffuse and vascular diseases. The consensus provided updated recommendations on the methodology, and clinical indications, of MRI with liver specific contrast agents in the study of liver diseases. (orig.)

  17. Open-Source Automated Parahydrogen Hyperpolarizer for Molecular Imaging Using (13)C Metabolic Contrast Agents.

    Science.gov (United States)

    Coffey, Aaron M; Shchepin, Roman V; Truong, Milton L; Wilkens, Ken; Pham, Wellington; Chekmenev, Eduard Y

    2016-08-16

    An open-source hyperpolarizer producing (13)C hyperpolarized contrast agents using parahydrogen induced polarization (PHIP) for biomedical and other applications is presented. This PHIP hyperpolarizer utilizes an Arduino microcontroller in conjunction with a readily modified graphical user interface written in the open-source processing software environment to completely control the PHIP hyperpolarization process including remotely triggering an NMR spectrometer for efficient production of payloads of hyperpolarized contrast agent and in situ quality assurance of the produced hyperpolarization. Key advantages of this hyperpolarizer include: (i) use of open-source software and hardware seamlessly allowing for replication and further improvement as well as readily customizable integration with other NMR spectrometers or MRI scanners (i.e., this is a multiplatform design), (ii) relatively low cost and robustness, and (iii) in situ detection capability and complete automation. The device performance is demonstrated by production of a dose (∼2-3 mL) of hyperpolarized (13)C-succinate with %P13C ∼ 28% and 30 mM concentration and (13)C-phospholactate at %P13C ∼ 15% and 25 mM concentration in aqueous medium. These contrast agents are used for ultrafast molecular imaging and spectroscopy at 4.7 and 0.0475 T. In particular, the conversion of hyperpolarized (13)C-phospholactate to (13)C-lactate in vivo is used here to demonstrate the feasibility of ultrafast multislice (13)C MRI after tail vein injection of hyperpolarized (13)C-phospholactate in mice.

  18. Synthesis of functionalized magnetite nanoparticles to use as liver targeting MRI contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Yazdani, Farshad, E-mail: fyazdani@ccerci.ac.ir; Fattahi, Bahare; Azizi, Najmodin

    2016-05-15

    The aim of this research was the preparation of functionalized magnetite nanoparticles to use as a liver targeting contrast agent in magnetic resonance imaging (MRI). For this purpose, Fe{sub 3}O{sub 4} nanoparticles were synthesized via the co-precipitation method. The synthesized nanoparticles were coated with silica via the Stober method and finally the coated nanoparticles were functionalized with mebrofenin. Formation of crystalline magnetite particles was confirmed by X-ray diffraction (XRD) analysis. The Fourier transform infrared spectroscopy (FTIR) and energy dispersive X-ray analyzer (EDX) of the final product showed that silica had been effectively bonded onto the surface of the magnetite nanoparticles and the coated nanoparticles functionalized with mebrofenin. The magnetic resonance imaging of the functional nanoparticles showed that the Fe{sub 3}O{sub 4}–SiO{sub 2}-mebrofenin composite is an effective MRI contrast agent for liver targeting. - Highlights: • Superparamagnetic magnetite nanoparticles have been synthesized by simple and economical method. • Preperation of functional MNPs as a MRI contrast agent for liver targeting. • Gaining a good r{sub 2} relaxivity of the coated functional nanoparticles.

  19. Hyperintense acute reperfusion marker is associated with higher contrast agent dosage in acute ischaemic stroke

    Energy Technology Data Exchange (ETDEWEB)

    Ostwaldt, Ann-Christin; Schaefer, Tabea; Villringer, Kersten; Fiebach, Jochen B. [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Rozanski, Michal; Ebinger, Martin [Charite Universitaetsmedizin Berlin, Academic Neuroradiology, Center for Stroke Research Berlin (CSB), Berlin (Germany); Charite Universitaetsmedizin, Department of Neurology, Berlin (Germany); Jungehuelsing, Gerhard J. [Stiftung des Buergerlichen Rechts, Juedisches Krankenhaus Berlin, Berlin (Germany)

    2015-11-15

    The hyperintense acute reperfusion marker (HARM) on fluid-attenuated inversion recovery (FLAIR) images is associated with blood-brain barrier (BBB) permeability changes. The aim of this study was to examine the influence of contrast agent dosage on HARM incidence in acute ischaemic stroke patients. We prospectively included 529 acute ischaemic stroke patients (204 females, median age 71 years). Patients underwent a first stroke-MRI within 24 hours from symptom onset and had a follow-up on day 2. The contrast agent Gadobutrol was administered to the patients for perfusion imaging or MR angiography. The total dosage was calculated as ml/kg body weight and ranged between 0.04 and 0.31 mmol/kg on the first examination. The incidence of HARM was evaluated on day 2 FLAIR images. HARM was detected in 97 patients (18.3 %). HARM incidence increased significantly with increasing dosages of Gadobutrol. Also, HARM positive patients were significantly older. HARM was not an independent predictor of worse clinical outcome, and we did not find an association with increase risk of haemorrhagic transformation. A higher dosage of Gadobutrol in acute stroke patients on initial MRI is associated with increased HARM incidence on follow-up. MRI studies on BBB should therefore standardize contrast agent dosages. (orig.)

  20. Computed tomography enterography: a comparison of different neutral oral contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    D' Ippolito, Giuseppe, E-mail: giuseppe_dr@uol.com.br [Department of Imaging Diagnosis, Universidade Federal de Sao Paulo (UNIFESP), Sao Paulo, SP (Brazil); Braga, Fernanda Angeli; Resende, Marcelo Cardoso; Bretas, Elisa Almeida Sathler; Nunes, Thiago Franchi; Rosas, George de Queiroz; Tiferes, Dario Arie [Abdominal Imaging Section, Department of Imaging Diagnosis - Universidade Federal de Sao Paulo (Unifesp), Sao Paulo, SP (Brazil)

    2012-05-15

    Objective: The purpose of this study was to assess the performance of neutral oral contrast agents, comparing intestinal distension, distinction of intestinal wall, acceptance and side effects. Materials and Methods: Prospective, randomized, and double-blinded study involving 30 patients who underwent computed tomography of abdomen and pelvis with administration of neutral oral contrast agents, divided into three groups according the contrast agent type: milk, water, and polyethylene glycol. The images were consensually analyzed by two observers, considering the degree of bowel distension and intestinal wall distinction. The patients responded to a questionnaire regarding the taste of the ingested solution and on their side effects. Kruskal-Wallis and chi-square tests were employed for statistical analysis. Results: Among 40 studied intestinal segments, appropriate bowel distension (intestinal loop diameter > 2 cm) was observed in 14 segments (35%) in the milk group, 10 segments (25%) in the water group and 23 segments (57%) in the polyethylene glycol group (p = 0.01). Preparation with polyethylene glycol resulted in the best bowel distension, but it presented the worst taste and highest incidence of diarrhea as reported by patients. Conclusion: Bowel preparation with oral polyethylene glycol results in higher degree of bowel distension than with water or milk, but presents worst acceptance related to its taste and frequency of diarrhea as a side effect. (author)

  1. Synthesis and characterization of superparamagnetic iron oxide nanoparticles as calcium-responsive MRI contrast agents

    Science.gov (United States)

    Xu, Pengfei; Shen, Zhiwei; Zhang, Baolin; Wang, Jun; Wu, Renhua

    2016-12-01

    Superparamagnetic iron oxide nanoparticles (SPIONs) as T2 contrast agents have great potential to sense calcium ion (Ca2+) using magnetic resonance imaging (MRI). Here we prepared calcium-responsive SPIONs for MRI, formed by combining poly(ethylene glycol) (PEG) and polyethylenimine (PEI) coated iron oxide nanoparticle (PEI/PEG-SPIONs) contrast agents with the straightforward calcium-sensing compound EGTA (ethylene glycol tetraacetic acid). EGTA was conjugated onto PEI/PEG-SPIONs using EDC/sulfo-NHS method. EGTA-SPIONs were characterized using TEM, XPS, DSL, TGA and SQUIID. DSL results show that the SPIONs aggregate in the presence of Ca2+. MRI analyses indicate that the water proton T2 relaxation rates in HEPES suspensions of the EGTA-SPIONs significantly increase with the calcium concentration because the SPIONs aggregate in the presence of Ca2+. The T2 values decreased 25% when Ca2+ concentration decreased from 1.2 to 0.8 mM. The aggregation of EGTA-SPIONs could be reversed by EDTA. EGTA-SPIONs have potential as smart contrast agents for Ca2+-sensitive MRI.

  2. Intravenous, contrast-enhanced MR colonography using air as endoluminal contrast agent: Impact on colorectal polyp detection.

    LENUS (Irish Health Repository)

    Keeling, Aoife N

    2012-02-01

    PURPOSE: To compare diagnostic accuracy and patient tolerance of MR colonography with intravenous contrast and luminal air (MRC) to conventional colonoscopy (CC). MATERIALS AND METHODS: IRB approval and written informed consent were obtained. Forty-six patients, both screening and symptomatic, underwent MRC followed by CC. The MRC technique employed 3D T1W spoiled gradient echo sequences performed after the administration of gadopenetate dimeglumine, with parallel imaging. The diagnostic accuracy and tolerance of patients for MRC was compared to CC. RESULTS: Twenty-four polyps were detected in eighteen patients with CC (5 polyps >\\/=10mm, 4 polyps 6-9mm, 15 polyps <\\/=5mm). MRC was 66.7% (12\\/18) sensitive and 96.4% (27\\/28) specific for polyp detection on a per-patient basis. When analyzed by polyp size, sensitivity and specificity of MRC was 100% (5\\/5) and 100% (19\\/19), respectively, for lesions greater than 10mm, 100% (4\\/4) and 100% (20\\/20) for lesions 6-9mm, and sensitivity of 20% (3\\/15) lesions less than 5mm. The sensitivity and specificity of MRC for detecting significant lesions (>6mm) was 100% (9\\/9) and 100% (15\\/15), respectively. Regarding tolerance of the exams, there were no significant differences between MRC and CC. Thirty-five percent (n=16) of patients preferred MRC as a future screening test compared to 33% (n=15) for CC. CONCLUSION: MRC using air as an intraluminal contrast agent is a feasible and well-tolerated technique for detecting colonic polyps >\\/=6mm in size. Further studies are warranted.

  3. Intravenous, contrast-enhanced MR colonography using air as endoluminal contrast agent: Impact on colorectal polyp detection.

    LENUS (Irish Health Repository)

    Keeling, Aoife N

    2010-12-03

    PURPOSE: To compare diagnostic accuracy and patient tolerance of MR colonography with intravenous contrast and luminal air (MRC) to conventional colonoscopy (CC). MATERIALS AND METHODS: IRB approval and written informed consent were obtained. Forty-six patients, both screening and symptomatic, underwent MRC followed by CC. The MRC technique employed 3D T1W spoiled gradient echo sequences performed after the administration of gadopenetate dimeglumine, with parallel imaging. The diagnostic accuracy and tolerance of patients for MRC was compared to CC. RESULTS: Twenty-four polyps were detected in eighteen patients with CC (5 polyps ≥10mm, 4 polyps 6-9mm, 15 polyps ≤5mm). MRC was 66.7% (12\\/18) sensitive and 96.4% (27\\/28) specific for polyp detection on a per-patient basis. When analyzed by polyp size, sensitivity and specificity of MRC was 100% (5\\/5) and 100% (19\\/19), respectively, for lesions greater than 10mm, 100% (4\\/4) and 100% (20\\/20) for lesions 6-9mm, and sensitivity of 20% (3\\/15) lesions less than 5mm. The sensitivity and specificity of MRC for detecting significant lesions (>6mm) was 100% (9\\/9) and 100% (15\\/15), respectively. Regarding tolerance of the exams, there were no significant differences between MRC and CC. Thirty-five percent (n=16) of patients preferred MRC as a future screening test compared to 33% (n=15) for CC. CONCLUSION: MRC using air as an intraluminal contrast agent is a feasible and well-tolerated technique for detecting colonic polyps ≥6mm in size. Further studies are warranted.

  4. Fluorescent and scattering contrast agents in a mouse model of colorectal cancer

    Science.gov (United States)

    Winkler, Amy M.; Rice, Photini F. S.; Troutman, Timothy S.; Backer, Marina V.; Backer, Joseph M.; Drezek, Rebekah A.; Romanowski, Marek; Barton, Jennifer K.

    2008-02-01

    In previous work we have demonstrated the utility of laser-induced fluorescence (LIF) and optical coherence tomography (OCT) to identify adenoma in mouse models of colorectal cancer with high sensitivity and specificity. However, improved sensitivity to early disease, as well as the ability to distinguish confounders (e.g. fecal contamination, natural variations in mucosal thickness), is desired. In this study, we investigated the signal enhancement of fluorescent and scattering contrast agents in the colons of AOM-treated mice. The fluorescent tracer scVEGF/Cy, targeted to receptors for vascular endothelial growth factor, was visualized on a dual modality OCT/LIF endoscopic system with 1300-nm center wavelength OCT source and 635-nm LIF excitation. Scattering agents were tested with an 890-nm center wavelength endoscopic OCT system. Agents included nanoshells, 120-nm in diameter, and nanorods, 20-nm in diameter by 80-nm in length. Following imaging, colons were excised. Tissue treated with fluorophore was imaged on an epifluorescence microscope. Histological sections were obtained and stained with H&E and silver enhancer to verify disease and identify regions of gold uptake, respectively. Non-specific signal enhancement was observed with the scattering contrast agents. Specificity for adenoma was seen with the scVEGF/Cy dye.

  5. Gadolinium magnetic resonance contrast agents produce analytic interference in multiple serum assays.

    Science.gov (United States)

    Proctor, Kerry A S; Rao, Lokinendi V; Roberts, William L

    2004-02-01

    Gadolinium magnetic resonance contrast agents are known to interfere with some clinical chemistry tests, particularly colorimetric assays for serum calcium. We studied the effects of 4 agents, gadodiamide, gadoversetamide, gadopentetate dimeglumine, and gadoteridol, for interference with multiple serum assays. Gadodiamide and gadoversetamide produced clinically significant negative interference with colorimetric assays for serum angiotensin-converting enzyme, calcium, and zinc. These agents produced clinically significant positive interference in magnesium and total iron binding capacity assays and both positive and negative interference in iron assays. Gadopentetate dimeglumine produced a negative interference with iron assays, and gadopentetate dimeglumine and gadoteridol produced negative interference with a colorimetric zinc assay. Caution should be exercised when using colorimetric assays for angiotensin-converting enzyme, calcium, iron, magnesium, total iron binding capacity, and zinc in serum samples from patients who have recently received magnetic resonance contrast agents. In general, gadodiamide and gadoversetamide are more likely to produce a clinically significant interference than gadopentetate dimeglumine and gadoteridol. Likewise, certain analytic methods are more prone to interference, while others not affected.

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

    Science.gov (United States)

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

    2017-03-01

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

  7. Multispectral photoacoustic decomposition with localized regularization for detecting targeted contrast agent

    Science.gov (United States)

    Tavakoli, Behnoosh; Chen, Ying; Guo, Xiaoyu; Kang, Hyun Jae; Pomper, Martin; Boctor, Emad M.

    2015-03-01

    Targeted contrast agents can improve the sensitivity of imaging systems for cancer detection and monitoring the treatment. In order to accurately detect contrast agent concentration from photoacoustic images, we developed a decomposition algorithm to separate photoacoustic absorption spectrum into components from individual absorbers. In this study, we evaluated novel prostate-specific membrane antigen (PSMA) targeted agents for imaging prostate cancer. Three agents were synthesized through conjugating PSMA-targeting urea with optical dyes ICG, IRDye800CW and ATTO740 respectively. In our preliminary PA study, dyes were injected in a thin wall plastic tube embedded in water tank. The tube was illuminated with pulsed laser light using a tunable Q-switch ND-YAG laser. PA signal along with the B-mode ultrasound images were detected with a diagnostic ultrasound probe in orthogonal mode. PA spectrums of each dye at 0.5 to 20 μM concentrations were estimated using the maximum PA signal extracted from images which are obtained at illumination wavelengths of 700nm-850nm. Subsequently, we developed nonnegative linear least square optimization method along with localized regularization to solve the spectral unmixing. The algorithm was tested by imaging mixture of those dyes. The concentration of each dye was estimated with about 20% error on average from almost all mixtures albeit the small separation between dyes spectrums.

  8. How to Use MR-Contrast Agent in Tumor Induced Epilepsis

    Directory of Open Access Journals (Sweden)

    Aliakbar Ameri

    2010-05-01

    Full Text Available By year of 1990, second MRI revolution has hap-pened in the diagnosis of infection and tumor assessment "first revolution was made by clinical MRI invention in the early 1980's"."nTumor-associated epilepsis is an important contributor to morbidity in patients with brain tumors. Perilesional tissue changes play a vital role in the generation of tumor-associated seizures.Tumor-associated seizure is usually focal with secondary generalization and often resistant to antiepileptic drugs."nFor studying the tumor well and diagnosis, contrast injection is a necessity and T1 pulse is used for demonstration. It needs pre-contrast T1 to compare with post contrast T1. "nContrast agent "Gadolinium" changes the relaxation time of tissue in T1 pulse "shortening the time". Contrast circulation in the body is in a close circuit from vein or artery to the capillary system, interstitial tissue and contrast does not go inside the normal cells except in hepatocytes, pituicytes and damaged cells "broken blood brain barrier"."nFor tumor diagnosis, MRI with and without Gadolinium is used more than x-ray CT techniques."nOther diagnostic techniques for tumor D.D.X and epilepsis are PET, SPECT, EEG, MEG "MSI" and ultrasound. "nTested Double Dose contrasted images "2 x 1mmol/kg" of Gadolinium by 1.5 Tesla machine increased the enhancement rate about 5-10% but needs double money for contrast. Using 3 Tesla machine also increases signal demonstration but today all imaging "95%" is sufficient by 1.5 Tesla and imaging by 3-Tesla is difficult and expensive. "nConclusion: 1/ Please request MRI with and without GD for tumor diagnosis "pre-contrast T1and post contrast T1 is necessary to diagnosis and D.D.X of any hemorrhage inside the tumor versus enhancement". 2/ Please do not request double dose contrast for imaging "it is more expensive and less effective". 3/ Please request your patients imaging by 1.5 Tesla "3 Tesla imaging is difficult and more expensive". 4/Requesting

  9. Nonlinear Imaging of Microbubble Contrast Agent Using the Volterra Filter: In Vivo Results.

    Science.gov (United States)

    Du, Juan; Liu, Dalong; Ebbini, Emad S

    2016-12-01

    A nonlinear filtering approach to imaging the dynamics of microbubble ultrasound contrast agents (UCAs) in microvessels is presented. The approach is based on the adaptive third-order Volterra filter (TVF), which separates the linear, quadratic, and cubic components from beamformed pulse-echo ultrasound data. The TVF captures polynomial nonlinearities utilizing the full spectral components of the echo data and not from prespecified bands, e.g., second or third harmonics. This allows for imaging using broadband pulse transmission to preserve the axial resolution and the SNR. In this paper, we present the results from imaging the UCA activity in a 200- [Formula: see text] cellulose tube embedded in a tissue-mimicking phantom using a linear array diagnostic probe. The contrast enhancement was quantified by computing the contrast-to-tissue ratio (CTR) for the different imaging components, i.e., B-mode, pulse inversion (PI), and the TVF components. The temporal mean and standard deviation of the CTR values were computed for all frames in a given data set. Quadratic and cubic images, referred to as QB-mode and CB-mode, produced higher mean CTR values than B-mode, which showed improved sensitivity. Compared with PI, they produced similar or higher mean CTR values with greater spatial specificity. We also report in vivo results from imaging UCA activity in an implanted LNCaP tumor with heterogeneous perfusion. The temporal means and standard deviations of the echogenicity were evaluated in small regions with different perfusion levels in the presence and absence of UCA. The in vivo measurements behaved consistently with the corresponding calculations obtained under microflow conditions in vitro. Specifically, the nonlinear VF components produced larger increases in the temporal mean and standard deviation values compared with B-mode in regions with low to relatively high perfusion. These results showed that polynomial filters such as the TVF can provide an important tool

  10. Mn-porphyrins as novel molecular magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Mouraviev, Vladimir; Venkatraman, Talaignair N; Tovmasyan, Artak; Kimura, Masaki; Tsivian, Matvey; Mouravieva, Vladimira; Polascik, Tom J; Wang, Haichen; Amrhein, Timothy J; Batinic-Haberle, Ines; Lascola, Christopher

    2011-11-03

    In this study, we investigated the potential of a new class of therapeutic Mn porphyrins as molecular MRI probes for prostate cancer imaging. Two compounds of different bioavailibility were investigated: Mn(III) meso-tetrakis(N-ethylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5 +)) and Mn(III) mesotetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTnHex-2-PyP(5 +)). These compounds have previously been shown to have adjunctive antineoplastic activity through their actions as powerful superoxide dismutase mimics, peroxynitrite scavengers, and modulators of cellular redox-based signaling pathways. Strong paramagnetic MRI contrast properties and affinity for cancer cells suggest their potential application as novel diagnostic imaging agents. MRI experiments were performed at 7.0T on a Bruker Biospec horizontal bore scanner. All in-vivo experiments were performed on 12 C57 black mice implanted with RM-9 prostate cancer cells on the hind limb. Two mg/kg of MnTnHex-2-PyP(5 +) (n = 6) and 8 mg/kg MnTE-2-PyP(5 +) (n = 6) were administered intraperitoneally 90 minutes before imaging. All the images were collected using a volume coil and processed using Paravision 4.0. Phantom studies reveal remarkably high T1 relaxivity changes for both metalloporphyrins, which are twofold to threefold higher than commercially available gadolinium chelates. Observable detection limits using conventional T1-weighted MRI are in the low micromolar range for both compounds. In vivo, MR relaxation changes in prostate tumor xenografts were readily observed after a single injection of either MnTE-2-PyP(5 +) or MnTnHex-2-PyP(5 +), with tumor contrast to background ratio greatest after MnTE-2-PyP(5 +) administration. After a single dose of MnTE-2-PyP(5 +), contrast changes in prostate tumors are up to sixfold greater than in surrounding, noncancerous tissues, suggesting the potential use of this metalloporphyrin as a novel diagnostic probe for detecting prostate malignancy using MRI.

  11. Ultrasound-enhanced gene transfer: Comparison of contrast agents and ultrasound modalities in vitro and in vivo

    Science.gov (United States)

    Pislaru, Sorin V.; Rajiv, Gulati; Pislaru, Cristina; Kinnick, Randall R.; Singh, Ripudamanjit; Greenleaf, James F.; Simari, Robert D.

    2002-11-01

    Ultrasound (US) enhancement of plasmid-based gene transfer is an emerging technique. Our hypothesis was that two contrast agents (Optison and PESDA), and two US exposure modalities (dedicated continuous wave system and diagnostic scanner) may have different effects. Luciferase plasmid with or without contrast agent was added to vascular smooth muscle cells and endothelial cells, followed by US exposure. Luciferase activity was measured 24 h later. US exposure consistently induced higher transfection rates than all controls. PESDA was superior to Optison in both cell lines. In vitro, continuous wave and diagnostic US were not significantly different. In vivo, Lux and PESDA were injected into skeletal muscles of rats (IM or intra-arterial) followed or not by US exposure. In separate animals, adenovirus encoding for luciferase was injected IM and was not followed by US exposure. Gene transfer efficacy was 8-10 fold higher with US and PESDA than with plasmid alone, but 2 fold lower than with adenovirus. However, as opposed to adenovirus, US-enhanced plasmid gene transfer was highly localized to the injected muscle, with no expression at distal sites. Our results support the hypothesis that contrast agents and exposure modalities are not equivalent with regard to gene transfer efficacy.

  12. Effects of acoustic radiation force on the binding efficiency of BR55, a VEGFR2-specific ultrasound contrast agent.

    Science.gov (United States)

    Frinking, Peter J A; Tardy, Isabelle; Théraulaz, Martine; Arditi, Marcel; Powers, Jeffry; Pochon, Sibylle; Tranquart, François

    2012-08-01

    This work describes an in vivo study analyzing the effect of acoustic radiation force (ARF) on the binding of BR55 VEGFR2-specific contrast-agent microbubbles in a model of prostatic adenocarcinoma in rat. A commercial ultrasound system was modified by implementing high duty-cycle 3.5-MHz center frequency ARF bursts in a scanning configuration. This enabled comparing the effects of ARF on binding in tumor and healthy tissue effectively in the same field of view. Bubble binding was established by measuring late-phase enhancement in amplitude modulation (AM) contrast-specific imaging mode (4 MHz, 150 kPa) 10 min after agent injection when the unbound bubbles were cleared from the circulation. Optimal experimental conditions, such as agent concentration (0.4 × 10(8)-1.6 × 10(8) bubbles/kg), acoustic pressure amplitude (26-51 kPa) and duty-cycle (20%-95%) of the ARF bursts, were evaluated in their ability to enhance binding in tumor without significantly increasing binding in healthy tissue. Using the optimal conditions (38 kPa peak-negative pressure, 95% duty cycle), ARF-assisted binding of BR55 improved significantly in tumor (by a factor of 7) at a lower agent dose compared with binding without ARF, and it had an insignificant effect on binding in healthy tissue. Thus, the high binding specificity of BR55 microbubbles for targeting VEGFR2 present at sites of active angiogenesis was confirmed by this study. Therefore, it is believed that based on the results obtained in this work, ultrasound molecular imaging using target-specific contrast-agent microbubbles should preferably be performed in combination with ARF. Copyright © 2012 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  13. Performance analysis of linear bandpass filter and pulse inversion in separating subharmonic frequency of signals from ultrasound contrast agent

    Directory of Open Access Journals (Sweden)

    Chinda Samakee

    2012-12-01

    Full Text Available Recently, many publications reported the generation of subharmonic frequency (f0/2 and its potential use in imagingfrom ultrasound contrast agent (UCA. Subharmonic imaging (SHI has provided better contrast resolution over the secondharmonic signals due to the lack of subharmonic generation in the tissue region. However, subharmonic separation in SHIutilizes linear bandpass filtering only. In this paper, we compare the subharmonic separation capability of linear band filter(LBF, pulse inversion (PI, and their combination (PILBF based on contrast-to-tissue ratio (CTR. Results show that theCTR values from the LBF, the PI, and the PILBF are 20.30, 40.30, and 52.74 dB, respectively. The optimal stopband attenuation and fractional bandwidth for the PILBF method are 50 dB and 10%, respectively. This high CTR value indicates thefeasibility of the PILBF method in creating high quality ultrasound image from subharmonic frequency.

  14. Highly magnetic iron carbide nanoparticles as effective T(2) contrast agents.

    Science.gov (United States)

    Huang, Guoming; Hu, Juan; Zhang, Hui; Zhou, Zijian; Chi, Xiaoqin; Gao, Jinhao

    2014-01-21

    This paper reports that iron carbide nanoparticles with high air-stability and strong saturation magnetization can serve as effective T2 contrast agents for magnetic resonance imaging. Fe5C2 nanoparticles (~20 nm in diameter) exhibit strong contrast enhancement with an r2 value of 283.2 mM(-1) S(-1), which is about twice as high as that of spherical Fe3O4 nanoparticles (~140.9 mM(-1) S(-1)). In vivo experiments demonstrate that Fe5C2 nanoparticles are able to produce much more significant MRI contrast enhancement than conventional Fe3O4 nanoparticles in living subjects, which holds great promise in biomedical applications.

  15. Iodinated contrast agents in patients with myasthenia gravis: a retrospective cohort study.

    Science.gov (United States)

    Rath, Jakob; Mauritz, Matthias; Zulehner, Gudrun; Hilger, Eva; Cetin, Hakan; Kasprian, Gregor; Auff, Eduard; Zimprich, Fritz

    2017-06-01

    Currently, it has not been satisfactorily established, whether modern low-osmolality iodinated contrast agents (ICAs) used in computed tomography (CT) studies are a risk factor for exacerbation of myasthenic symptoms. The rate of acute adverse events as well as delayed clinical worsening up to 30 days were analyzed in 73 patients with confirmed myasthenia gravis (MG) who underwent contrast-enhanced CT studies and compared to 52 patients who underwent unenhanced CT studies. One acute adverse event was documented. 12.3% of MG patients experienced a delayed exacerbation of symptoms after ICA administration. The rate of delayed severe exacerbation was higher in the contrast-enhanced group. Alternative causes for the exacerbation of MG-related symptoms were more likely than ICA administration in all cases. ICA administration for CT studies in MG patients should not be withheld if indicated, but patients particularly those with concomitant acute diseases should be carefully monitored for exacerbation of symptoms.

  16. Differential structured illumination microendoscopy for in vivo imaging of molecular contrast agents

    Science.gov (United States)

    Keahey, Pelham; Ramalingam, Preetha; Schmeler, Kathleen

    2016-01-01

    Fiber optic microendoscopy has shown promise for visualization of molecular contrast agents used to study disease in vivo. However, fiber optic microendoscopes have limited optical sectioning capability, and image contrast is limited by out-of-focus light generated in highly scattering tissue. Optical sectioning techniques have been used in microendoscopes to remove out-of-focus light but reduce imaging speed or rely on bulky optical elements that prevent in vivo imaging. Here, we present differential structured illumination microendoscopy (DSIMe), a fiber optic system that can perform structured illumination in real time for optical sectioning without any opto-mechanical components attached to the distal tip of the fiber bundle. We demonstrate the use of DSIMe during in vivo fluorescence imaging in patients undergoing surgery for cervical adenocarcinoma in situ. Images acquired using DSIMe show greater contrast than standard microendoscopy, improving the ability to detect cellular atypia associated with neoplasia. PMID:27621464

  17. Generation of a droplet inside a microbubble with the aid of an ultrasound contrast agent: First result

    NARCIS (Netherlands)

    M. Postema (Michiel); F.J. ten Cate (Folkert); G. Schmitz (Gerd); N. de Jong (Nico); A. van Wamel (Annemieke)

    2007-01-01

    textabstractNew ultrasound contrast agents that incorporate a therapeutic compound have become of interest. Such an ultrasound contrast agent particle might act as the vehicle to carry a drug or gene load to a perfused region of interest. The load could be released with the assistance of ultrasound.

  18. Effect of contrast agent administration on consequences of dosimetry and biology in radiotherapy planning

    Energy Technology Data Exchange (ETDEWEB)

    Lo, Ching-Jung [Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Tao-Yuan 333 Taiwan (China); Department of Radiation Oncology, Chang Gung Memorial Hospital, Kwei-Shan, Tao-Yuan 333 Taiwan (China); Yang, Pei-Ying [Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Tao-Yuan 333 Taiwan (China); Chao, Tsi-Chian, E-mail: chaot@mail.cgu.edu.tw [Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Tao-Yuan 333 Taiwan (China); Tu, Shu-Ju, E-mail: sjtu@mail.cgu.edu.tw [Department of Medical Imaging and Radiological Sciences, College of Medicine, Chang Gung University, 259 Wen-Hua 1st Road, Kwei-Shan, Tao-Yuan 333 Taiwan (China)

    2015-06-01

    In the treatment planning of radiation therapy, patients may be administrated with contrast media in CT scanning to assist physicians for accurate delineation of the target or organs. However, contrast media are not used in patients during the treatment delivery. In particular, contrast media contain materials with high atomic numbers and dosimetric variations may occur between scenarios where contrast media are present in treatment planning and absent in treatment delivery. In this study we evaluate the effect of contrast media on the dosimetry and biological consequence. An analytical phantom based on AAPM TG 119 and five sets of CT images from clinical patients are included. Different techniques of treatment planning are considered, including 1-field AP, 2-field AP+PA, 4-field box, 7-field IMRT, and RapidArc. RapidArc is a recent technique of volumetric modulated arc therapy and is used in our study of contrast media in clinical scenarios. The effect of RapidArc on dosimetry and biological consequence for administration of contrast media in radiotherapy is not discussed previously in literature. It is shown that dose difference is reduced as the number of external beams is increased, suggesting RapidArc may be favored to be used in the treatment planning enhanced by contrast media. Linear trend lines are fitted for assessment of percent dose differences in the planning target volume versus concentrations of contrast media between plans where contrast media are present and absent, respectively.

  19. Highly monodisperse low-magnetization magnetite nanocubes as simultaneous T1-T2 MRI contrast agents

    Science.gov (United States)

    Sharma, V. K.; Alipour, A.; Soran-Erdem, Z.; Aykut, Z. G.; Demir, H. V.

    2015-06-01

    We report the first study of highly monodisperse and crystalline iron oxide nanocubes with sub-nm controlled size distribution (9.7 +/- 0.5 nm in size) that achieve simultaneous contrast enhancement in both T1- and T2-weighted magnetic resonance imaging (MRI). Here, we confirmed the magnetite structure of iron oxide nanocubes by X-ray diffraction (XRD), selected area electron diffraction (SAED) pattern, optical absorption and Fourier transformed infrared (FT-IR) spectra. These magnetite nanocubes exhibit superparamagnetic and paramagnetic behavior simultaneously by virtue of their finely controlled shape and size. The magnetic measurements reveal that the magnetic moment values are favorably much lower because of the small size and cubic shape of the nanoparticles, which results in an enhanced spin canting effect. As a proof-of-concept demonstration, we showed their potential as dual contrast agents for both T1- and T2-weighted MRI via phantom studies, in vivo imaging and relaxivity measurements. Therefore, these low-magnetization magnetite nanocubes, while being non-toxic and bio-compatible, hold great promise as excellent dual-mode T1 and T2 contrast agents for MRI.We report the first study of highly monodisperse and crystalline iron oxide nanocubes with sub-nm controlled size distribution (9.7 +/- 0.5 nm in size) that achieve simultaneous contrast enhancement in both T1- and T2-weighted magnetic resonance imaging (MRI). Here, we confirmed the magnetite structure of iron oxide nanocubes by X-ray diffraction (XRD), selected area electron diffraction (SAED) pattern, optical absorption and Fourier transformed infrared (FT-IR) spectra. These magnetite nanocubes exhibit superparamagnetic and paramagnetic behavior simultaneously by virtue of their finely controlled shape and size. The magnetic measurements reveal that the magnetic moment values are favorably much lower because of the small size and cubic shape of the nanoparticles, which results in an enhanced spin

  20. Dendritic iodinated contrast agents with PEG-cores for CT imaging: synthesis and preliminary characterization.

    Science.gov (United States)

    Fu, Yanjun; Nitecki, Danute E; Maltby, David; Simon, Gerhard H; Berejnoi, Kirill; Raatschen, Hans-Juergen; Yeh, Benjamin M; Shames, David M; Brasch, Robert C

    2006-01-01

    The purpose of this study was to design, synthesize, and initially characterize a representative set of novel constructs for large-molecular radiographic/computed tomography (CT) contrast agents, intended for a primarily intravascular distribution. A new assembly of well-known and biocompatible components consists of paired, symmetrical dendritic polylysines initiated from both ends of a poly(ethylene glycol) (PEG) core, yielding an array of multiple free amino groups to which were conjugated highly soluble and stable triiodophthalamide ("triiodo") moieties. An array of six dendritic contrast agents was synthesized originally, using three different PEG cores (3, 6, 12 kDa) with t-Boc lysine-generated dendrimer "amplifiers" (from three to five generations) containing 16 to 64 amino groups for conjugation with reactive triiodo moieties. A clinically used, nonionic, small molecular CT contrast agent, iobitridol, was derivatized via a hydroxyl protection/deprotection strategy, introducing a new carboxyl group available for conjugation to the lysine amino groups of dendrimers. Final products were purified by size exclusion chromatography and characterized by NMR, UV, HPLC, and elemental analysis. Preliminary evaluations were conducted for physicochemical characterization and in vivo CT contrast enhancement in a rat model. All six iodinated PEG-core dendrimer conjugates were synthesized in good yields, with a high degree of size monodispersity, large apparent molecular weight, favored physicochemical properties. A representative compound, PEG12000-carbamate-Gen4-IOB conjugate, 27% (w%) rich in iodine, demonstrated a desirable strong and persistent intravascular enhancement with a monoexponential blood half-life of approximately 35 min assayed by dynamic CT imaging and also showed high water solubility (>550 mg/mL at 25 degrees C), large apparent molecular size (comparable to a 143-kDa protein), high hydrophilicity (butanol-water partition coefficient 0.015), and

  1. Magnetic red blood cells as new contrast agents for MRI applications

    Science.gov (United States)

    Antonelli, Antonella; Sfara, Carla; Manuali, Elisabetta; Salamida, Sonia; Louin, Gaëlle; Magnani, Mauro

    2013-03-01

    Superparamagnetic iron oxide (SPIO) nanoparticles have been produced and used successfully as potent contrast agents for Magnetic Resonance Imaging (MRI). However, a significant challenge associated with the biological application of SPIO-tracer agents is their behavior in vivo since their efficacy is often compromised due to a rapid recognition and clearance by the reticuloendothelial system (RES) which limits the applicability of such compounds in MRI. The advances in nanotechnology and molecular cell biology had lead to improve stability and biocompatibility of these nanoparticles, but despite a number of efforts, the SPIO half-life in blood circulation is very short. In this contest, the potential of red blood cells (RBCs) loaded with SPIO nanoparticles as a tracer material for MRI has been investigated in order to realize a blood pool tracer with longer blood retention time. Previously, we have proposed the encapsulation into RBCs of superparamagnetic iron oxide nanoparticles carboxydextran coated, such as Resovist contrast agent. This approach led to a nanoparticle reduction in uptake by the RES, increasing the blood circulation half-life of nanoparticles. Recently, the loading procedure was applied to a new contrast agent, the P904 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles coated by hydrophilic derivatives of glucose, recently developed by Guerbet Laboratories. The results evidenced that this nanomaterial can be efficiently loaded into human and murine RBCs at concentrations ranging from 1.5 to 12 mM Fe. In vivo experiments performed in mice have showed an increased survival in the mouse vascular system of P904 encapsulated into RBCs respect to free P904 sample intravenously injected at the equivalent amounts.

  2. Agent Based Reasoning in Multilevel Flow Modeling

    DEFF Research Database (Denmark)

    Lind, Morten; Zhang, Xinxin

    2012-01-01

    to launch the MFM Workbench into an agent based environment, which can complement disadvantages of the original software. The agent-based MFM Workbench is centered on a concept called “Blackboard System” and use an event based mechanism to arrange the reasoning tasks. This design will support the new...

  3. Nonspherical dynamics and shape mode stability of ultrasound contrast agent microbubbles

    Science.gov (United States)

    Calvisi, Michael

    2016-11-01

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

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

    Science.gov (United States)

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

    2013-08-01

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

  5. Relationship between cavitation and loss of echogenicity from ultrasound contrast agents.

    Science.gov (United States)

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

    2013-09-21

    Ultrasound contrast agents (UCAs) have the potential to nucleate cavitation and promote both beneficial and deleterious bioeffects in vivo. Previous studies have elucidated the pulse-duration-dependent pressure amplitude threshold for rapid loss of echogenicity due to UCA fragmentation. Previous studies have demonstrated that UCA fragmentation was concomitant with inertial cavitation. The purpose of this study was to evaluate the relationship between stable and inertial cavitation thresholds and loss of echogenicity of UCAs as a function of pulse duration. Determining the relationship between cavitation thresholds and loss of echogenicity of UCAs would enable monitoring of cavitation based upon the onscreen echogenicity in clinical applications. Two lipid-shelled UCAs, echogenic liposomes (ELIP) and Definity®, were insonified by a clinical ultrasound scanner in duplex spectral Doppler mode at four pulse durations ('sample volumes') in both a static system and a flow system. Cavitation emissions from the UCAs insonified by Doppler pulses were recorded using a passive cavitation detection system and stable and inertial cavitation thresholds ascertained. Loss of echogenicity from ELIP and Definity® was assessed within regions of interest on B-mode images. A numerical model based on UCA rupture predicted the functional form of the loss of echogenicity from ELIP and Definity®. Stable and inertial cavitation thresholds were found to have a weak dependence on pulse duration. Stable cavitation thresholds were lower than inertial cavitation thresholds. The power of cavitation emissions was an exponential function of the loss of echogenicity over the investigated range of acoustic pressures. Both ELIP and Definity® lost more than 80% echogenicity before the onset of stable or inertial cavitation. Once this level of echogenicity loss occurred, both stable and inertial cavitation were detected in the physiologic flow phantom. These results imply that stable and inertial

  6. Enhanced conjugation stability and blood circulation time of macromolecular gadolinium-DTPA contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Jenjob, Ratchapol [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of); Kun, Na [Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743 (Korea, Republic of); Ghee, Jung Yeon [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Shen, Zheyu; Wu, Xiaoxia [Division of Functional Materials and Nano-Devices, Ningbo Institute of Materials Technology & Engineering (NIMTE), Chinese Academy of Sciences, 519 Zhuangshi Street, Zhenhai District, Ningbo, Zhejiang 315201 (China); Cho, Steve K., E-mail: scho@gist.ac.kr [Division of Liberal Arts and Science, GIST College, Gwangju Institute of Science and Technology, Gwangju 500-712 (Korea, Republic of); Lee, Don Haeng [Utah-Inha DDS and Advanced Therapeutics, B-403 Meet-You-All Tower, SongdoTechnopark, 7–50, Songdo-dong, Yeonsu-gu, Incheon 406-840 (Korea, Republic of); Department of Internal Medicine, School of Medicine, Inha University Hospital, Incheon 420-751 (Korea, Republic of); Yang, Su-Geun, E-mail: Sugeun.Yang@Inha.ac.kr [Department of New Drug Development, School of Medicine, Inha University, 2F A-dong, Jeongseok Bldg., Sinheung-dong 3-ga, Jung-gu, Incheon 400-712 (Korea, Republic of)

    2016-04-01

    In this study, we prepared macromolecular MR T1 contrast agent: pullulan-conjugated Gd diethylene triamine pentaacetate (Gd-DTPA-Pullulan) and estimated residual free Gd{sup 3+}, chelation stability in competition with metal ions, plasma and tissue pharmacokinetics, and abdominal MR contrast on rats. Residual free Gd{sup 3+} in Gd-DTPA-Pullulan was measured using colorimetric spectroscopy. The transmetalation of Gd{sup 3+} incubated with Ca{sup 2+} was performed by using a dialysis membrane (MWCO 100–500 Da) and investigated by ICP-OES. The plasma concentration profiles of Gd-DTPA-Pullulan were estimated after intravenous injection at a dose 0.1 mmol/kg of Gd. The coronal-plane abdominal images of normal rats were observed by MR imaging. The content of free Gd{sup 3+}, the toxic residual form, was less than 0.01%. Chelation stability of Gd-DTPA-Pullulan was estimated, and only 0.2% and 0.00045% of Gd{sup 3+} were released from Gd-DTPA-Pullulan after 2 h incubation with Ca{sup 2+} and Fe{sup 2+}, respectively. Gd-DTPA-Pullulan displayed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h), much longer than 0.11 h and 0.79 h of Gd-EOB-DTPA. Abdominal MR imaging showed Gd-DTPA-Pullulan maintained initial MR contrast for 30 min. The extended plasma half-life of Gd-DTPA-Pullulan probably allows the prolonged MR acquisition time in clinic with enhanced MR contrast. - Highlights: • Macromolecule (pullulan) conjugated Gd contrast agent (Gd-DTPA-Pullulan) showed the extended plasma half-life (t{sub 1/2,α} = 0.43 h, t{sub 1/2,β} = 2.32 h) in comparison with Gd-EOB-DTPA • Gd-DTPA-pullulan T1 contrast agent exhibited strong chelation stability against Gd. • The extended blood circulation attributed the enhanced and prolonged MR contrast on abdominal region of rats. • The extended blood circulation may provide prolonged MR acquisition time window in clinics.

  7. Facile Synthesis of Gd-Functionalized Gold Nanoclusters as Potential MRI/CT Contrast Agents

    Directory of Open Access Journals (Sweden)

    Wenjun Le

    2016-04-01

    Full Text Available Multi-modal imaging plays a key role in the earlier detection of disease. In this work, a facile bioinspired method was developed to synthesize Gd-functionalized gold nanoclusters (Gd-Au NCs. The Gd-Au NCs exhibit a uniform size, with an average size of 5.6 nm in dynamic light scattering (DLS, which is a bit bigger than gold clusters (3.74 nm, DLS, while the fluorescent properties of Gd-Au NCs are almost the same as that of Au NCs. Moreover, the Gd-Au NCs exhibit a high longitudinal relaxivity value (r1 of 22.111 s−1 per mM of Gd in phosphate-buffered saline (PBS, which is six times higher than that of commercial Magnevist (A complex of gadolinium with a chelating agent, diethylenetriamine penta-acetic acid, Gd-DTPA, r1 = 3.56 mM−1·s−1. Besides, as evaluated by nano single photon emission computed tomography (SPECT and computed tomography (CT the Gd-Au NCs have a potential application as CT contrast agents because of the Au element. Finally, the Gd-Au NCs show little cytotoxicity, even when the Au concentration is up to 250 μM. Thus, the Gd-Au NCs can act as multi-modal imaging contrast agents.

  8. Palladium nanosheets as highly stable and effective contrast agents for in vivo photoacoustic molecular imaging

    Science.gov (United States)

    Nie, Liming; Chen, Mei; Sun, Xiaolian; Rong, Pengfei; Zheng, Nanfeng; Chen, Xiaoyuan

    2014-01-01

    A stable and efficient contrast agent is highly desirable for photoacoustic (PA) imaging applications. Recently gold nanostructures have been widely reported and studied for PA imaging and photothermal therapy. However, the structures of the nonspherical gold nanoparticles are easily destroyed after laser irradiation and thus may fail to complete the intended tasks. In this study, we propose to apply palladium nanosheets (PNSs), with strong optical absorption in the near-infrared (NIR) region, as a new class of exogenous PA contrast agents. PA and ultrasound (US) images were acquired sequentially by a portable and fast photoacoustic tomography (PAT) system with a hand-held transducer. Significant and long-lasting imaging enhancement in SCC7 head and neck squamous cell carcinoma was successfully observed in mice by PAT over time after tail vein administration of PNSs. The morphology and functional perfusion of the tumors were delineated in PA images due to the nanoparticle accumulation. PAT of the main organs was also conducted ex vivo to trace the fate of PNSs, which was further validated by inductively coupled plasma atomic emission spectrometry (ICP-AES). No obvious toxic effect was observed by in vitro MTT assay and ex vivo histological examination 7 days after PNS administration. With the combination of a portable imaging instrument and signal specificity, PNSs might be applied as stable and effective agents for photoacoustic cancer detection, diagnosis and treatment guidance.

  9. An Agent-Based Distributed Manufacturing System

    Institute of Scientific and Technical Information of China (English)

    J.Li; J.Y.H.Fuh; Y.F.Zhang; A.Y.C.Nee

    2006-01-01

    Agent theories have shown their promising capability in solving distributed complex system ever since its development. In this paper, one multi-agent based distributed product design and manufacturing planning system is presented. The objective of the research is to develop a distributed collaborative design environment for supporting cooperation among the existing engineering functions. In the system, the functional agents for design, manufacturability evaluation,process planning and scheduling are efficiently integrated with a facilitator agent. This paper firstly gives an introduction to the system structure, and the definitions for each executive agent are then described and a prototype of the proposed is also included at the end part.

  10. Ferric ammonium citrate as a positive bowel contrast agent for MR imaging of the upper abdomen

    Energy Technology Data Exchange (ETDEWEB)

    Kivelitz, D.; Taupitz, M.; Hamm, B. [Universitaetsklinikum Charite, Berlin (Germany). Inst. fuer Radiologie; Gehl, H.B. [Medizinische Univ. Luebeck (Germany). Inst. fuer Radiologie; Heuck, A. [Muenchen Univ. (Germany). Radiologische Klinik; Krahe, T. [Koeln Univ. (Germany). Inst. fuer Radiologische Diagnostik; Lodemann, K.P. [Bracco-Byk Gulden GmbH, Konstanz (Germany)

    1999-07-01

    Purpose: To evaluate the safety and diagnostic efficacy of two different doses of ferric ammonium citrate as a paramagnetic oral contrast agent for MR imaging of the upper abdomen. Material and methods: Ninety-nine adult patients referred for MR imaging for a known or suspected upper abdominal pathology were included in this randomized multicenter double-blind clinical trial. Imaging was performed with spin-echo (T1- and T2-weighted) and gradient-echo (T1-weighted) techniques before and after administration of either 1200 mg or 2400 mg of ferric ammonium citrate dissolved in 600 ml of water. Safety analysis included monitoring of vital signs, assessment of adverse events, and laboratory testing. Efficacy with regard to organ distension, contrast distribution, bowel enhancement and delineation of adjacent structures was graded qualitatively. Results: No serious adverse events were reported for either of the two concentrations. A total of 31 minor side effects were noted, of which significantly more occurred in the higher dose group (p<0.01). The diagnostic confidence in defining or excluding disease was graded as better after contrast administration for 48% of all images. Marked or moderate enhancement of the upper gastrointestinal tract was achieved at both doses in 69.5% of cases with no evident difference between the two doses. The higher dose tended to show better results in terms of the contrast assessment parameters. Conclusion: Ferric ammonium citrate is a safe and effective oral contrast agent for MR imaging of the upper abdomen at two different dose levels. The higher dose showed a tendency toward better imaging results while the lower dose caused significantly fewer side effects. Therefore, the 1200 mg dose can be recommended in view of the risk-to-benefit ratio. (orig.)

  11. Copper oxide nanoparticles as contrast agents for MRI and ultrasound dual-modality imaging

    Science.gov (United States)

    Perlman, Or; Weitz, Iris S.; Azhari, Haim

    2015-08-01

    Multimodal medical imaging is gaining increased popularity in the clinic. This stems from the fact that data acquired from different physical phenomena may provide complementary information resulting in a more comprehensive picture of the pathological state. In this context, nano-sized contrast agents may augment the potential sensitivity of each imaging modality and allow targeted visualization of physiological points of interest (e.g. tumours). In this study, 7 nm copper oxide nanoparticles (CuO NPs) were synthesized and characterized. Then, in vitro and phantom specimens containing CuO NPs ranging from 2.4 to 320 μg · mL-1 were scanned, using both 9.4 T MRI and through-transmission ultrasonic imaging. The results show that the CuO NPs induce shortening of the magnetic T1 relaxation time on the one hand, and increase the speed of sound and ultrasonic attenuation coefficient on the other. Moreover, these visible changes are NP concentration-dependent. The change in the physical properties resulted in a substantial increase in the contrast-to-noise ratio (3.4-6.8 in ultrasound and 1.2-19.3 in MRI). In conclusion, CuO NPs are excellent candidates for MRI-ultrasound dual imaging contrast agents. They offer radiation-free high spatial resolution scans by MRI, and cost-effective high temporal resolution scans by ultrasound.

  12. Saline as the Sole Contrast Agent for Successful MRI-guided Epidural Injections

    Energy Technology Data Exchange (ETDEWEB)

    Deli, Martin, E-mail: martin.deli@web.de [University of Witten/Herdecke, Department of Radiology and Microtherapy, Groenemeyer Institute for Microtherapy (GIMT) (Germany); Fritz, Jan, E-mail: jfritz9@jhmi.edu [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science (United States); Mateiescu, Serban, E-mail: mateiescu@microtherapy.de; Busch, Martin, E-mail: busch@microtherapy.de [University of Witten/Herdecke, Department of Radiology and Microtherapy, Groenemeyer Institute for Microtherapy (GIMT) (Germany); Carrino, John A., E-mail: jcarrin2@jhmi.edu [Johns Hopkins University School of Medicine, Russell H. Morgan Department of Radiology and Radiological Science (United States); Becker, Jan, E-mail: j.becker@microtherapy.de; Garmer, Marietta, E-mail: garmer@microtherapy.de; Groenemeyer, Dietrich, E-mail: dg@microtherapy.de [University of Witten/Herdecke, Department of Radiology and Microtherapy, Groenemeyer Institute for Microtherapy (GIMT) (Germany)

    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.

  13. Copper oxide nanoparticles as contrast agents for MRI and ultrasound dual-modality imaging.

    Science.gov (United States)

    Perlman, Or; Weitz, Iris S; Azhari, Haim

    2015-08-07

    Multimodal medical imaging is gaining increased popularity in the clinic. This stems from the fact that data acquired from different physical phenomena may provide complementary information resulting in a more comprehensive picture of the pathological state. In this context, nano-sized contrast agents may augment the potential sensitivity of each imaging modality and allow targeted visualization of physiological points of interest (e.g. tumours). In this study, 7 nm copper oxide nanoparticles (CuO NPs) were synthesized and characterized. Then, in vitro and phantom specimens containing CuO NPs ranging from 2.4 to 320 μg · mL(-1) were scanned, using both 9.4 T MRI and through-transmission ultrasonic imaging. The results show that the CuO NPs induce shortening of the magnetic T1 relaxation time on the one hand, and increase the speed of sound and ultrasonic attenuation coefficient on the other. Moreover, these visible changes are NP concentration-dependent. The change in the physical properties resulted in a substantial increase in the contrast-to-noise ratio (3.4-6.8 in ultrasound and 1.2-19.3 in MRI). In conclusion, CuO NPs are excellent candidates for MRI-ultrasound dual imaging contrast agents. They offer radiation-free high spatial resolution scans by MRI, and cost-effective high temporal resolution scans by ultrasound.

  14. Development of New Contrast Agents for Imaging Function and Metabolism by Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Alexandra Carvalho

    2017-07-01

    Full Text Available Liposomes are interesting nanosystems with a wide range of medical application. One particular application is their ability to enhance contrast in magnetic resonance images; when properly loaded with magnetic/superparamagnetic nanoparticles, this means to act as contrast agents. The design of liposomes loaded with magnetic particles, magnetoliposomes, presents a large number of possibilities depending on the application from image function to metabolism. More interesting is its double function application as theranostics (diagnostics and therapy. The synthesis, characterization, and possible medical applications of two types of magnetoliposomes are reviewed. Their performance will be compared, in particular, their efficiency as contrast agents for magnetic resonance imaging, measured by their relaxivities r 1 and r 2 relating to their particular composition. One of the magnetoliposomes had 1,2-diacyl-sn-glycero-3-phosphocholine (soy as the main phospholipid component, with and without cholesterol, varying its phospholipid to cholesterol molar ratios. The other formulation is a long-circulating liposome composed of 1,2-diacyl-sn-glycero-3-phosphocholine (egg, cholesterol, and 1,2-distearoyl-sn-glycerol-3-phosphoethanolamine- N -[methoxy(polyethylene glycol-2000]. Both nanosystems were loaded with superparamagnetic iron oxide nanoparticles with different sizes and coatings.

  15. Silicon nanoparticles as contrast agents in the methods of optical biomedical diagnostics

    Science.gov (United States)

    Zabotnov, S. V.; Kashaev, F. V.; Shuleiko, D. V.; Gongalsky, M. B.; Golovan, L. A.; Kashkarov, P. K.; Loginova, D. A.; Agrba, P. D.; Sergeeva, E. A.; Kirillin, M. Yu

    2017-07-01

    The efficiency of light scattering by nanoparticles formed using the method of picosecond laser ablation of silicon in water and by nanoparticles of mechanically grinded mesoporous silicon is compared. The ensembles of particles of both types possess the scattering coefficients sufficient to use them as contrast agents in optical coherence tomography (OCT), particularly in the range of wavelengths 700-1000 nm, where the absorption of both silicon and most biological and mimicking tissues is small. According to the Mie theory the main contribution to the scattering in this case is made by the particles having a relatively large size (150-300 nm). In the experiments on visualising the agar phantom surface by means of OCT, the contrast of the medium boundary, provided by nanoparticles amounted to 14 dB and 30 dB for the ablated particles and the porous silicon powder, respectively. The numerical simulation of OCT images of skin in the presence of nanoparticles, confirmed the efficiency of using them as a contrast agent.

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

    Science.gov (United States)

    Makuta, T.; Tamakawa, Y.

    2012-04-01

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

  17. Pathological mechanism for delayed hyperenhancement of chronic scarred myocardium in contrast agent enhanced magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Jian Wang

    Full Text Available OBJECTIVES: To evaluate possible mechanism for delayed hyperenhancement of scarred myocardium by investigating the relationship of contrast agent (CA first pass and delayed enhancement patterns with histopathological changes. MATERIALS AND METHODS: Eighteen pigs underwent 4 weeks ligation of 1 or 2 diagonal coronary arteries to induce chronic infarction. The hearts were then removed and perfused in a Langendorff apparatus. The hearts firstly experienced phosphorus 31 MR spectroscopy. The hearts in group I (n = 9 and II (n = 9 then received the bolus injection of Gadolinium diethylenetriamine pentaacetic acid (0.05 mmol/kg and gadolinium-based macromolecular agent (P792, 15 µmol/kg, respectively. First pass T2* MRI was acquired using a gradient echo sequence. Delayed enhanced T1 MRI was acquired with an inversion recovery sequence. Masson's trichrome and anti- von Willebrand Factor (vWF staining were performed for infarct characterization. RESULTS: Wash-in of both kinds of CA caused the sharp and dramatic T2* signal decrease of scarred myocardium similar to that of normal myocardium. Myocardial blood flow and microvessel density were significantly recovered in 4-week-old scar tissue. Steady state distribution volume (ΔR1 relaxation rate of Gd-DTPA was markedly higher in scarred myocardium than in normal myocardium, whereas ΔR1 relaxation rate of P792 did not differ significantly between scarred and normal myocardium. The ratio of extracellular volume to the total water volume was significantly greater in scarred myocardium than in normal myocardium. Scarred myocardium contained massive residual capillaries and dilated vessels. Histological stains indicated the extensively discrete matrix deposition and lack of cellular structure in scarred myocardium. CONCLUSIONS: Collateral circulation formation and residual vessel effectively delivered CA into scarred myocardium. However, residual vessel without abnormal hyperpermeability allowed Gd

  18. CONTRAST

    DEFF Research Database (Denmark)

    Kristensen, Thomas Krogsgaard

    2007-01-01

    Dette er en afrapportering fra den årlige CONTRAST workshop, der i 2007 blev afholdt i Yaoundé, Cameroon.......Dette er en afrapportering fra den årlige CONTRAST workshop, der i 2007 blev afholdt i Yaoundé, Cameroon....

  19. 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.

    Science.gov (United States)

    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.

  20. L-DOPA-Coated Manganese Oxide Nanoparticles as Dual MRI Contrast Agents and Drug-Delivery Vehicles.

    Science.gov (United States)

    McDonagh, Birgitte Hjelmeland; Singh, Gurvinder; Hak, Sjoerd; Bandyopadhyay, Sulalit; Augestad, Ingrid Lovise; Peddis, Davide; Sandvig, Ioanna; Sandvig, Axel; Glomm, Wilhelm Robert

    2016-01-20

    Manganese oxide nanoparticles (MONPs) are capable of time-dependent magnetic resonance imaging contrast switching as well as releasing a surface-bound drug. MONPs give T2/T2* contrast, but dissolve and release T1-active Mn(2+) and L-3,4-dihydroxyphenylalanine. Complementary images are acquired with a single contrast agent, and applications toward Parkinson's disease are suggested.

  1. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent.

    Science.gov (United States)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-21

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  2. Gold nanorods as a contrast agent for Doppler optical coherence tomography.

    Directory of Open Access Journals (Sweden)

    Bo Wang

    Full Text Available PURPOSE: To investigate gold nanorods (GNRs as a contrast agent to enhance Doppler optical coherence tomography (OCT imaging of the intrascleral aqueous humor outflow. METHODS: A serial dilution of GNRs was scanned with a spectral-domain OCT device (Bioptigen, Durham, NC to visualize Doppler signal. Doppler measurements using GNRs were validated using a controlled flow system. To demonstrate an application of GNR enhanced Doppler, porcine eyes were perfused at constant pressure with mock aqueous alone or 1.0×10(12 GNR/mL mixed with mock aqueous. Twelve Doppler and volumetric SD-OCT scans were obtained from the limbus in a radial fashion incremented by 30°, forming a circular scan pattern. Volumetric flow was computed by integrating flow inside non-connected vessels throughout all 12 scans around the limbus. RESULTS: At the GNR concentration of 0.7×10(12 GNRs/mL, Doppler signal was present through the entire depth of the testing tube without substantial attenuation. A well-defined laminar flow profile was observed for Doppler images of GNRs flowing through the glass capillary tube. The Doppler OCT measured flow profile was not statistically different from the expected flow profile based upon an autoregressive moving average model, with an error of -0.025 to 0.037 mm/s (p = 0.6435. Cross-sectional slices demonstrated the ability to view anterior chamber outflow ex-vivo using GNR-enhanced Doppler OCT. Doppler volumetric flow measurements were comparable to flow recorded by the perfusion system. CONCLUSIONS: GNRs created a measureable Doppler signal within otherwise silent flow fields in OCT Doppler scans. Practical application of this technique was confirmed in a constant pressure ex-vivo aqueous humor outflow model in porcine eyes.

  3. Quantitative ultrasound molecular imaging by modeling the binding kinetics of targeted contrast agent

    Science.gov (United States)

    Turco, Simona; Tardy, Isabelle; Frinking, Peter; Wijkstra, Hessel; Mischi, Massimo

    2017-03-01

    Ultrasound molecular imaging (USMI) is an emerging technique to monitor diseases at the molecular level by the use of novel targeted ultrasound contrast agents (tUCA). These consist of microbubbles functionalized with targeting ligands with high-affinity for molecular markers of specific disease processes, such as cancer-related angiogenesis. Among the molecular markers of angiogenesis, the vascular endothelial growth factor receptor 2 (VEGFR2) is recognized to play a major role. In response, the clinical-grade tUCA BR55 was recently developed, consisting of VEGFR2-targeting microbubbles which can flow through the entire circulation and accumulate where VEGFR2 is over-expressed, thus causing selective enhancement in areas of active angiogenesis. Discrimination between bound and free microbubbles is crucial to assess cancer angiogenesis. Currently, this is done non-quantitatively by looking at the late enhancement, about 10 min after injection, or by calculation of the differential targeted enhancement, requiring the application of a high-pressure ultrasound (US) burst to destroy all the microbubbles in the acoustic field and isolate the signal coming only from bound microbubbles. In this work, we propose a novel method based on mathematical modeling of the binding kinetics during the tUCA first pass, thus reducing the acquisition time and with no need for a destructive US burst. Fitting time-intensity curves measured with USMI by the proposed model enables the assessment of cancer angiogenesis at both the vascular and molecular levels. This is achieved by estimation of quantitative parameters related to the microvascular architecture and microbubble binding. The proposed method was tested in 11 prostate-tumor bearing rats by performing USMI after injection of BR55, and showed good agreement with current USMI methods. The novel information provided by the proposed method, possibly combined with the current non-quantitative methods, may bring deeper insight into

  4. Processing of subharmonic signals from ultrasound contrast agents to determine ambient pressures.

    Science.gov (United States)

    Dave, Jaydev K; Halldorsdottir, Valgerdur G; Eisenbrey, John R; Forsberg, Flemming

    2012-04-01

    Subharmonic-aided pressure estimation (SHAPE) is a technique that utilizes the subharmonic emissions, occurring at half the insonation frequency, from ultrasound contrast agents to estimate ambient pressures. The purpose of this work was to compare the performance of different processing techniques for the raw radiofrequency (rf) data acquired for SHAPE. A closed loop flow system was implemented circulating reconstituted Sonazoid (GE Healthcare, Oslo, Norway; 0.2 ml for 750 ml diluent) and the beam-formed unprocessed rf data were obtained from a 4 mm diameter lumen of a Doppler flow phantom (ATS Laboratories, Inc., Bridgeport, CT) using a SonixRP scanner (Ultrasonix, Richmond, BC, Canada). The transmit frequency and incident acoustic pressures were set to 2.5 MHz and 0.22 MPa, respectively, in order to elicit Sonazoid subharmonic emissions that are ambient-pressure sensitive. The time-varying ambient pressures within the flow phantom were recorded by a Millar pressure catheter. Four techniques for extracting the subharmonic amplitude from the rf data were tested along with two noise filtering techniques to process this data. Five filter orders were tested for the noise removing filters. The performance was evaluated based on the least root-mean-square errors reported after linear least-square regression analyses of the subharmonic data and the pressure catheter data and compared using a repeated ANOVA. When the subharmonic amplitudes were extracted as the mean value within a 0.2 MHz bandwidth about 1.25 MHz and when the resulting temporally-varying subharmonic signal was median filtered with an order of 500, the filtered subharmonic signal significantly predicted the ambient pressures (r2 = 0.90; p subharmonic data extracted as the mean value within a 0.2 MHz bandwidth about the theoretical subharmonic frequency turned out to be the best technique to process acoustic data for SHAPE. The implementation of this technique on ultrasound scanners may permit real

  5. T₁ and T₂ dual-mode MRI contrast agent for enhancing accuracy by engineered nanomaterials.

    Science.gov (United States)

    Shin, Tae-Hyun; Choi, Jin-sil; Yun, Seokhwan; Kim, Il-Sun; Song, Ho-Taek; Kim, Youngmee; Park, Kook In; Cheon, Jinwoo

    2014-04-22

    One of the holy grails in biomedical imaging technology is to achieve accurate imaging of biological targets. The development of sophisticated instrumentation and the use of contrast agents have improved the accuracy of biomedical imaging. However, the issue of false imaging remains a problem. Here, we developed a dual-mode artifact filtering nanoparticle imaging agent (AFIA) that comprises a combination of paramagnetic and superparamagnetic nanomaterials. This AFIA has the ability to perform "AND logic gate" algorithm to eliminate false errors (artifacts) from the raw images to enhance accuracy of the MRI. We confirm the artifact filtering capability of AFIA in MRI phantoms and further demonstrate that artifact-free imaging of stem cell migration is possible in vivo.

  6. Tobacco mosaic virus rods and spheres as supramolecular high-relaxivity MRI contrast agents

    Science.gov (United States)

    Bruckman, Michael A.; Hern, Stephen; Jiang, Kai; Flask, Chris A.; Yu, Xin; Steinmetz, Nicole F.

    2013-01-01

    To compensate for the low sensitivity of magnetic resonance imaging (MRI), nanoparticles have been developed to deliver high payloads of contrast agents to sites of disease. Here, we report the development of supramolecular MRI contrast agents using the plant viral nanoparticle tobacco mosaic virus (TMV). Rod-shaped TMV nanoparticles measuring 300×18 nm were loaded with up to 3,500 or 2,000 chelated paramagnetic gadolinium (III) ions selectively at the interior (iGd-TMV) or exterior (eGd-TMV) surface, respectively. Spatial control is achieved through targeting either tyrosine or carboxylic acid side chains on the solvent exposed exterior or interior TMV surface. The ionic T1 relaxivity per Gd ion (at 60 MHz) increases from 4.9 mM−1s−1 for free Gd(DOTA) to 18.4 mM−1s−1 for eGd-TMV and 10.7 mM−1s−1 for iGd-TMV. This equates to T1 values of ~ 30,000 mM−1s−1 and ~ 35,000 mM−1s−1 per eGd-TMV and iGd-TMV nanoparticle. Further, we show that interior-labeled TMV rods can undergo thermal transition to form 170 nm-sized spherical nanoparticles containing ~ 25,000 Gd chelates and a per particle relaxivity of almost 400,000 mM−1s−1 (15.2 mM−1s−1 per Gd). This work lays the foundation for the use of TMV as a contrast agent for MRI. PMID:23589767

  7. Chitosan-coated nickel-ferrite nanoparticles as contrast agents in magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ahmad, Tanveer [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Department of Physics, Abdul Wali Khan University, Mardan (Pakistan); Bae, Hongsub; Iqbal, Yousaf [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Rhee, Ilsu, E-mail: ilrhee@knu.ac.kr [Department of Physics, Kyungpook National University, Daegu 702-701 (Korea, Republic of); Hong, Sungwook [Division of Science Education, Daegu University, Gyeongsan 712-714 (Korea, Republic of); Chang, Yongmin; Lee, Jaejun [Department of Diagnostic Radiology, College of Medicine, Kyungpook National University and Hospital, Daegu 700-721 (Korea, Republic of); Sohn, Derac [Department of Physics, Hannam University, Daejon (Korea, Republic of)

    2015-05-01

    We report evidence for the possible application of chitosan-coated nickel-ferrite (NiFe{sub 2}O{sub 4}) nanoparticles as both T{sub 1} and T{sub 2} contrast agents in magnetic resonance imaging (MRI). The coating of nickel-ferrite nanoparticles with chitosan was performed simultaneously with the synthesis of the nickel-ferrite nanoparticles by a chemical co-precipitation method. The coated nanoparticles were cylindrical in shape with an average length of 17 nm and an average width of 4.4 nm. The bonding of chitosan onto the ferrite nanoparticles was confirmed by Fourier transform infrared spectroscopy. The T{sub 1} and T{sub 2} relaxivities were 0.858±0.04 and 1.71±0.03 mM{sup −1} s{sup −1}, respectively. In animal experimentation, both a 25% signal enhancement in the T{sub 1}-weighted mage and a 71% signal loss in the T{sub 2}-weighted image were observed. This demonstrated that chitosan-coated nickel-ferrite nanoparticles are suitable as both T{sub 1} and T{sub 2} contrast agents in MRI. We note that the applicability of our nanoparticles as both T{sub 1} and T{sub 2} contrast agents is due to their cylindrical shape, which gives rise to both inner and outer sphere processes of nanoparticles. - Highlights: • Chitosan-coated nickel-ferrite (Ni-Fe{sub 2}O{sub 4}) nanoparticles were synthesized in an aqueous system by chemical co-precipitation. • The characterization of bare and chitosan-coated nanoparticles were performed using various analytical tools, such as TEM, FTIR, XRD, and VMS. • We evaluated the coated particles as potential T{sub 1} and T{sub 2} contrast agents for MRI by measuring T{sub 1} and T{sub 2} relaxation times as a function of iron concentration. • Both T{sub 1} and T{sub 2} effects were also observed in animal experimentation.

  8. Hydrogels incorporating GdDOTA: towards highly efficient dual T1/T2 MRI contrast agents.

    Science.gov (United States)

    Courant, Thomas; Roullin, Valérie Gaëlle; Cadiou, Cyril; Callewaert, Maïté; Andry, Marie Christine; Portefaix, Christophe; Hoeffel, Christine; de Goltstein, Marie Christine; Port, Marc; Laurent, Sophie; Elst, Luce Vander; Muller, Robert; Molinari, Michaël; Chuburu, Françoise

    2012-09-03

    Do not tumble dry: Gadolinium-DOTA encapsulated into polysaccharide nanoparticles (GdDOTA NPs) exhibited high relaxivity (r(1) =101.7 s(-1) mM(-1) per Gd(3+) ion at 37 °C and 20 MHz). This high relaxation rate is due to efficient Gd loading, reduced tumbling of the Gd complex, and the hydrogel nature of the nanoparticles. The efficacy of the nanoparticles as a T(1)/T(2) dual-mode contrast agent was studied in C6 cells.

  9. Development and optimization of near-IR contrast agents for immune cell tracking

    Science.gov (United States)

    Joshi, Pratixa P.; Yoon, Soon Joon; Chen, Yun-Sheng; Emelianov, Stanislav; Sokolov, Konstantin V.

    2013-01-01

    Gold nanorods (NRs) are attractive for in vivo imaging due to their high optical cross-sections and tunable absorbance. However, the feasibility of using NRs for cell tracking has not been fully explored. Here, we synthesized dye doped silica-coated NRs as multimodal contrast agents for imaging of macrophages – immune cells which play an important role in cancer and cardiovascular diseases. We showed the importance of silica coating in imaging of NR-labeled cells. Photoacoustic (PA) imaging of NRs labeled macrophages showed high sensitivity. Therefore, these results provide foundation for applications of silica-coated NRs and PA imaging in tracking of immune cells. PMID:24298419

  10. Gaucher disease in the liver on hepatocyte specific contrast agent enhanced MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Ayyala, Rama S. [Morgan Stanley Children' s Hospital, Department of Radiology, Columbia University Medical Center, New York, NY (United States); Teot, Lisa A. [Boston Children' s Hospital, Department of Pathology, Harvard Medical School, Boston, MA (United States); Perez Rossello, Jeanette M. [Boston Children' s Hospital, Department of Radiology, Harvard Medical School, Boston, MA (United States)

    2017-04-15

    Gaucher disease is a hereditary lipid storage disorder that affects the enzyme beta glucocerebrosidase, causing accumulation of glucocerebroside in macrophages of the reticuloendothelial system. Accumulation can occur in the liver and spleen, manifesting as hepatosplenomegaly, as well as within the bone marrow. Hepatic involvement is usually diffuse but can occasionally manifest as focal liver lesions. We present a case of a 2-year-old boy with Gaucher disease and an infiltrating liver lesion detected on imaging, which was pathologically shown to be focal changes related to the disease. Imaging characteristics of this lesion using hepatocyte specific contrast agent enhanced MRI, which have not been previously discussed in the literature, are described. (orig.)

  11. Variability in contrast agent uptake by different but similar stem cell types

    Directory of Open Access Journals (Sweden)

    Ketkar-Atre A

    2013-11-01

    Full Text Available Ashwini Ketkar-Atre,1 Tom Struys,1,2 Stefaan J Soenen,3 Ivo Lambrichts,2 Catherine M Verfaillie,4 Marcel De Cuyper,5 Uwe Himmelreich1 1Biomedical MRI/MoSAIC, Department of Imaging and Pathology, Biomedical Sciences Group, Katholieke Universiteit Leuven, Leuven, Belgium; 2Lab of Histology, Biomedical Research Institute, Hasselt University, Campus Diepenbeek, Agoralaan, Diepenbeek, Belgium; 3Lab for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium; 4Interdepartmental Stem Cell Institute, O&N IV, Katholieke Universiteit Leuven, Leuven, Belgium; 5Laboratory of BioNanoColloids, Interdisciplinary Research Centre, Katholieke Universiteit Leuven, Kortrijk, Belgium Abstract: The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP-specific parameters. Here, we have studied three different types of NPs (Endorem®, magnetoliposomes [MLs], and citrate coated C-200 to label relatively larger, mesenchymal stem cells (MSCs and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs. Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high

  12. Ultrasound molecular imaging contrast agent binding to both E- and P-selectin in different species.

    Science.gov (United States)

    Bettinger, Thierry; Bussat, Philippe; Tardy, Isabelle; Pochon, Sibylle; Hyvelin, Jean-Marc; Emmel, Patricia; Henrioud, Sylvie; Biolluz, Nathalie; Willmann, Jürgen K; Schneider, Michel; Tranquart, François

    2012-09-01

    Ultrasound molecular imaging is increasingly used in preclinical studies to measure the expression of vascular markers during inflammation process. In this context, a new ultrasound contrast agent functionalized with a recombinant P-selectin glycoprotein ligand-1 analogue (rPSGL-Ig) was developed (MBrPSGL-Ig). This agent was assayed in vitro and in vivo to evaluate its binding performance and potential to image expression of inflammatory markers E- and P-selectin. Performance of this newly developed agent was compared with that of antibody (MBAb) or sialyl Lewis X (MBsLe) containing microbubbles and with control microbubbles (MBC). The targeted ultrasound contrast agents were prepared by coupling biotin-conjugated ligands onto streptavidin-functionalized microbubbles. First, in vitro experiments were performed to measure the adhesion efficiency of these microbubble constructs under static or flow conditions (114 sec), on cell monolayer (human umbilical vein endothelial cells and bEnd.5), or coatings of E- or P-selectin of various animal species, respectively. Second, molecular imaging studies were performed in a rat inflammatory model 24 hours after intramuscular injection of lipopolysaccharide in the hind limb. Finally, immunohistochemistry staining of rat inflamed muscle tissue was performed to assess expression of E- and P-selectin. Microbubbles functionalized with rPSGL-Ig (MBrPSGL-Ig) displayed firm in vitro binding on the coating of both recombinant E- or P-selectin, with an efficiency similar to microbubbles comprising antibody specific for E-selectin (MBE) or P-selectin (MBP). In contrast, lower binding capacity was measured with MBsLe. At the surface of inflamed endothelial cells, MBrPSGL-Ig were able to interact specifically with E- and P-selectin. Binding specificity was demonstrated by performing blocking experiments with target-specific antibodies, resulting in an 80% to 95% decrease in binding. Ten minutes after microbubble injection, echo signal

  13. Contrast Agent Ultrasonography before and after HIFU Treatment of Parathyroid Glands

    Science.gov (United States)

    Kovatcheva, Roussanka; Arnaud, Françoise; Lacoste, François

    2010-03-01

    OBJECTIVES: To observe changes in the parathyroid tissue treated by extracorporeal HIFU. MATERIAL AND METHODS: 5 patients were treated for primary hyperparathyroidism by thermally ablating enlarged parathyroid glands using an external HIFU applicator. The treated glands were visualized with B-Mode and contrast enhanced ultrasonography (CEUS) before, 1 week and 4 weeks post HIFU. Serum iPTH, calcium, and phosphorus levels were monitored before and after the treatment. RESULTS: The initial results showed a correlation between contrast agent uptake of treated parathyroid tissue, the reduction of volume of the gland and the decrease of iPTH levels. CONCLUSIONS These results show it is possible to use CEUS to monitor the thermal ablation of parathyroid glands.

  14. Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

    Science.gov (United States)

    Gongalsky, M. B.; Kargina, Yu. V.; Osminkina, L. A.; Perepukhov, A. M.; Gulyaev, M. V.; Vasiliev, A. N.; Pirogov, Yu. A.; Maximychev, A. V.; Timoshenko, V. Yu.

    2015-12-01

    We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T2) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T1) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g.s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

  15. Porous silicon nanoparticles as biocompatible contrast agents for magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Gongalsky, M. B., E-mail: mgongalsky@gmail.com; Kargina, Yu. V.; Osminkina, L. A. [Department of Physics, Lomonosov Moscow State University, 119991 Moscow (Russian Federation); National Research Nuclear University “MEPhI,” 115409 Moscow (Russian Federation); Perepukhov, A. M.; Maximychev, A. V. [Moscow Institute of Physics and Technology, Dolgoprudny, 141700 Moscow Region (Russian Federation); Gulyaev, M. V. [Research Center for MRI and MRS, Lomonosov Moscow State University, 119991 Moscow (Russian Federation); Vasiliev, A. N. [Department of Physics, Lomonosov Moscow State University, 119991 Moscow (Russian Federation); Pirogov, Yu. A. [Department of Physics, Lomonosov Moscow State University, 119991 Moscow (Russian Federation); Research Center for MRI and MRS, Lomonosov Moscow State University, 119991 Moscow (Russian Federation); Timoshenko, V. Yu. [Department of Physics, Lomonosov Moscow State University, 119991 Moscow (Russian Federation); National Research Tomsk State University, 634050 Tomsk (Russian Federation)

    2015-12-07

    We propose porous silicon nanoparticles (PSi NPs) with natural oxide coating as biocompatible and bioresorbable contrast agents for magnetic resonant imaging (MRI). A strong shortening of the transversal proton relaxation time (T{sub 2}) was observed for aqueous suspensions of PSi NPs, whereas the longitudinal relaxation time (T{sub 1}) changed moderately. The longitudinal and transversal relaxivities are estimated to be 0.03 and 0.4 l/(g·s), respectively, which are promising for biomedical studies. The proton relaxation is suggested to undergo via the magnetic dipole-dipole interaction with Si dangling bonds on surfaces of PSi NPs. MRI experiments with phantoms have revealed the remarkable contrasting properties of PSi NPs for medical diagnostics.

  16. Targeted delivery of cancer-specific multimodal contrast agents for intraoperative detection of tumor boundaries and therapeutic margins

    Science.gov (United States)

    Xu, Ronald X.; Xu, Jeff S.; Huang, Jiwei; Tweedle, Michael F.; Schmidt, Carl; Povoski, Stephen P.; Martin, Edward W.

    2010-02-01

    Background: Accurate assessment of tumor boundaries and intraoperative detection of therapeutic margins are important oncologic principles for minimal recurrence rates and improved long-term outcomes. However, many existing cancer imaging tools are based on preoperative image acquisition and do not provide real-time intraoperative information that supports critical decision-making in the operating room. Method: Poly lactic-co-glycolic acid (PLGA) microbubbles (MBs) and nanobubbles (NBs) were synthesized by a modified double emulsion method. The MB and NB surfaces were conjugated with CC49 antibody to target TAG-72 antigen, a human glycoprotein complex expressed in many epithelial-derived cancers. Multiple imaging agents were encapsulated in MBs and NBs for multimodal imaging. Both one-step and multi-step cancer targeting strategies were explored. Active MBs/NBs were also fabricated for therapeutic margin assessment in cancer ablation therapies. Results: The multimodal contrast agents and the cancer-targeting strategies were tested on tissue simulating phantoms, LS174 colon cancer cell cultures, and cancer xenograft nude mice. Concurrent multimodal imaging was demonstrated using fluorescence and ultrasound imaging modalities. Technical feasibility of using active MBs and portable imaging tools such as ultrasound for intraoperative therapeutic margin assessment was demonstrated in a biological tissue model. Conclusion: The cancer-specific multimodal contrast agents described in this paper have the potential for intraoperative detection of tumor boundaries and therapeutic margins.

  17. Development and evaluation of a novel VEGFR2-targeted nanoscale ultrasound contrast agents

    Science.gov (United States)

    Yu, Houqiang; Li, Chunfang; He, Xiaoling; Zhou, Qibing; Ding, Mingyue

    2016-04-01

    Recent literatures have reported that the targeted nanoscale ultrasound contrast agents are becoming more and more important in medical application, like ultrasound imaging, detection of perfusion, drug delivery and molecular imaging and so on. In this study, we fabricated an uniform nanoscale bubbles (257 nm with the polydispersity index of 0.458) by incorporation of antibody targeted to vascular endothelial growth factor receptor 2 (VEGFR2) into the nanobubbles membrane by using avidin-biotin interaction. Some fundamental characterizations such as nanobubble suspension, surface morphology, particle size distribution and zeta potential were investigated. The concentration and time-intensity curves (TICs) were obtained with a self-made ultrasound experimental setup in vitro evaluation. In addition, in order to evaluate the contrast enhancement ability and the potential tumor-targeted ability in vivo, normal Wistar rats and nude female BALB/c mice were intravascular administration of the nanobubbles via tail vein injection, respectively. Significant contrast enhancement of ultrasound imaging within liver and tumor were visualized. These experiments demonstrated that the targeted nanobubbles is efficient in ultrasound molecular imaging by enhancement of the contrast effect and have potential capacity for targeted tumor diagnosis and therapy in the future.

  18. FEASIBILITY STUDY OF AN ULTRASOUND CONTRAST AGENT (LEVOVIST) IN COLOR DOPPLER IMAGING OF LIVER NEOPLASMS

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    @@ The purpose of this study was to determine the efficacy of using an ultrasound contrast agent(levovist)to enhance the color Doppler imaging of liver neoplasms.Thirty patients with hepatic tumors were enrolled in this study.After intravenous administration of levovist,the color Doppler signals of normal hepatic vessels were enhanced.In various hepatic tumors,the different patterns of tumor vascularity were observed,which had not been demonstrated in conventional non-contrast color Doppler imaging.In 11 of 16 patients with hepatocarcinoma,additoal color Doppler signals were observed in the central part of the tumors.On the contrary,3 patients with metastatic liver lesions the enhanced color Doppler signal appear only at the peripheral of tumors.A typical rim-like color enhancement was seen in 2 of the 3 cases.In six patients with hpatic hemangiomas contrast-enhanced color Doppler imaging demonstrated the blood vessels at the margin of the neoplasms.Contrast-enhanced color Doppler imaging improves the visualization of the hepatic neoplasm vascularity.This technique holds great promise for detecting small liver tumors and differentiating hepatic neoplasms.

  19. Development of Gd(III) porphyrin-conjugated chitosan nanoparticles as contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Jahanbin, Tania; Sauriat-Dorizon, Hélène; Spearman, Peter; Benderbous, Soraya; Korri-Youssoufi, Hafsa

    2015-01-01

    A novel magnetic resonance imaging (MRI) contrast agent based on gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] conjugated with chitosan nanoparticles has been developed. The chitosan nanoparticles were synthesized following an ionic gelation method and the conditions optimized to generate small nanoparticles (CNs) with a narrow size distribution of 35-65 nm. The gadolinium meso-tetrakis(4-pyridyl)porphyrin [Gd(TPyP)] was loaded into chitosan nanoparticles by passive adsorption. The interaction of chitosan with Gd(TPyP) has been examined by UV-visible, Fourier transform infrared spectroscopies (FT-IR) and inductively coupled plasma mass spectrometry (ICP-MS), which indicate the successful association of Gd(TPyP) without any structural distortion throughout the chitosan nanoparticles. The potential of Gd(TPyP)-CNs as MRI contrast agent has been investigated by magnetic resonance imaging (MRI) in-vitro. Relaxivities of Gd(TPyP)-CNs obtained from T1-weighted images, increased with Gd concentration and attained an optimum r1 of 38.35 mM(-1) s(-1), which is 12-fold higher compared to commercial Gd-DOTA (~4 mM(-1) s(-1) at 3T). The combination of such strong MRI contrast with the known properties of porphyrins in photodynamic therapy and biocompatibility of chitosan, presents a new perspective in using these compounds in cancer theranostics.

  20. Application of parametric ultrasound contrast agent perfusion studies for differentiation of hyperplastic adrenal nodules from adenomas—Initial study

    Energy Technology Data Exchange (ETDEWEB)

    Slapa, Rafal Z., E-mail: rz.slapa@gmail.com [Diagnostic Imaging Department, Medical University of Warsaw, Second Faculty of Medicine with English and Physiotherapy Divisions, Warsaw (Poland); Kasperlik–Zaluska, Anna A. [Endocrinology Department, Center for Postgraduate Medical Education, Bielanski Hospital, Warsaw (Poland); Migda, Bartosz [Diagnostic Imaging Department, Medical University of Warsaw, Second Faculty of Medicine with English and Physiotherapy Divisions, Warsaw (Poland); Otto, Maciej [Department of General, Vascular and Transplant Surgery, Medical University of Warsaw, First Faculty of Medicine, Warsaw (Poland); Jakubowski, Wiesław S. [Diagnostic Imaging Department, Medical University of Warsaw, Second Faculty of Medicine with English and Physiotherapy Divisions, Warsaw (Poland)

    2015-08-15

    Highlights: • Adrenal masses may differ on parametric perfusion ultrasound. • Hyperplastic nodules present distinctive patterns on CEUS in regard to adenomas. • Adrenal lesions perfusion should be further investigated with different modalities. - Abstract: Objectives: To evaluate the possibilities of differentiation of non-malignant adrenal masses with the application of the new technique for the evaluation of enhancement after administration of an ultrasound contrast agent: parametric imaging. Patients and Methods: 34 non-malignant adrenal masses in 29 patients were evaluated in a dynamic examination after the administration of ultrasound contrast agent with parametric imaging. Patterns on parametric imaging of arrival time were evaluated. The final diagnosis was based on CT, MRI, biochemical studies, follow up and/or histopathology examination. Results: The study included: 12 adenomas, 10 hyperplastic nodules, 7 myelolipomas, 3 pheochromocytomas, hemangioma with hemorrhage and cyst. The pattern of peripheral laminar inflow of Sonovue on parametric images of arrival time of was 100% sensitive for hyperplastic nodules and 83% specific in regard to adenomas. Conclusions: Parametric contrast enhanced ultrasound may accurately differentiate hyperplastic adrenal nodules from adenomas and could be complementary to CT or MRI. Incorporation of perfusion studies to CT or MRI could possibly enable one-shop complete characterization of adrenal masses. This could deliver additional information in diagnostics of patients with Conn Syndrome and warrants further studies in this cohort of patients.

  1. Web-Based Computing Resource Agent Publishing

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Web-based Computing Resource Publishing is a efficient way to provide additional computing capacity for users who need more computing resources than that they themselves could afford by making use of idle computing resources in the Web.Extensibility and reliability are crucial for agent publishing. The parent-child agent framework and primary-slave agent framework were proposed respectively and discussed in detail.

  2. Effect of intravenous contrast agent volume on colorectal cancer vascular parameters as measured by perfusion computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Goh, V. [Paul Strickland Scanner Centre, Mount Vernon Hospital, Northwood, London (United Kingdom); Bartram, C. [Intestinal Imaging Centre, St Mark' s Hospital, Harrow, London (United Kingdom); Halligan, S. [Department of Academic Radiology, University College Hospital, London (United Kingdom)], E-mail: s.halligan@ucl.ac.uk

    2009-04-15

    Aim: To determine the effect of two different contrast agent volumes on quantitative and semi-quantitative vascular parameters as measured by perfusion computed tomography (CT) in colorectal cancer. Materials and methods: Following ethical approval and informed consent, eight prospectively recruited patients with proven colorectal adenocarcinoma underwent two separate perfusion CT studies on the same day after (a) 100 ml and (b) 50 ml of a 340 mg/ml iodinated contrast medium, respectively. Quantitative (blood volume, blood flow, permeability surface area product) and semi-quantitative (peak enhancement, time to peak enhancement) tumour vascular parameters were determined using commercial software based on distributed parameter analysis and compared using t-testing. Results: Tumour blood volume, blood flow, and permeability surface area product were not substantially different following the injection of 100 ml and 50 ml contrast medium: 6.12 versus 6.23 ml/100 g tissue; 73.4 versus 71.3 ml/min/100 g tissue; 15.6 versus 15.3 ml/min/100 g tissue for 100 and 50 ml, respectively; p > 0.05. Tumour peak enhancement and time to peak were significantly greater following the injection of 100 ml versus 50 ml contrast medium: 41.2 versus 28.5 HU; 16.1 versus 11.8 s for 100 ml and 50 ml, respectively; p = 0.002; p = 0.0003. Conclusion: Quantitative parameters do not appear to change substantially with a higher contrast agent volume suggesting a combined diagnostic staging-perfusion CT study following a single injection is feasible for colorectal cancer.

  3. Developments Toward Diagnostic Breast Cancer Imaging Using Near-Infrared Optical Measurements and Fluorescent Contrast Agents1

    Directory of Open Access Journals (Sweden)

    Daniel J. Hawrysz

    2000-09-01

    Full Text Available The use of near-infrared (NIR light to interrogate deep tissues has enormous potential for molecular-based imaging when coupled with NIR excitable dyes. More than a decade has now passed since the initial proposals for NIR optical tomography for breast cancer screening using time-dependent measurements of light propagation in the breast. Much accomplishment in the development of optical mammography has been demonstrated, most recently in the application of time-domain, frequency-domain, and continuous-wave measurements that depend on endogenous contrast owing to angiogenesis and increased hemoglobin absorbance for contrast. Although exciting and promising, the necessity of angiogenesis-mediated absorption contrast for diagnostic optical mammography minimizes the potential for using NIR techniques to assess sentinel lymph node staging, metastatic spread, and multifocality of breast disease, among other applications. In this review, we summarize the progress made in the development of optical mammography, and focus on the emerging work underway in the use of diagnostic contrast agents for the molecular-based, diagnostic imaging of breast.

  4. Material characterization of poly-lactic acid shelled ultrasound contrast agent and their dynamics

    Science.gov (United States)

    Paul, Shirshendu; Russakow, Daniel; Rodgers, Tyler; Sarkar, Kausik; Cochran, Michael; Wheatley, Margaret

    2011-11-01

    Micron-size gas bubbles encapsulated with lipids and proteins are used as contrast enhancing agents for ultrasound imaging. Biodegradable polymer poly-lactic acid (PLA) has recently been suggested as a possible means of encapsulation. Here, we report in vitro measurement of attenuation and scattering of ultrasound through an emulsion of PLA agent as well as theoretical modeling of the encapsulated bubble dynamics. The attenuation measured with three different transducers of central frequencies 2.25, 3.5 and 5 MHz, shows a peak around 2-3 MHz. These bubbles also show themselves to possess excellent scattering characteristics including strong non-linear response that can be used for harmonic and sub-harmonic contrast imaging. Our recently developed interfacial rheological models are applied to describe the dynamics of these bubbles; rheological model properties are estimated using measured attenuation data. The model is then applied to predict nonlinear scattered response, and the prediction is compared against experimental observation. Partially supported by NSF and NIH.

  5. Phase change events of volatile liquid perfluorocarbon contrast agents produce unique acoustic signatures

    Science.gov (United States)

    Sheeran, Paul S.; Matsunaga, Terry O.; Dayton, Paul A.

    2014-01-01

    Phase-change contrast agents (PCCAs) provide a dynamic platform to approach problems in medical ultrasound (US). Upon US-mediated activation, the liquid core vaporizes and expands to produce a gas bubble ideal for US imaging and therapy. In this study, we demonstrate through high-speed video microscopy and US interrogation that PCCAs composed of highly volatile perfluorocarbons (PFCs) exhibit unique acoustic behavior that can be detected and differentiated from standard microbubble contrast agents. Experimental results show that when activated with short pulses PCCAs will over-expand and undergo unforced radial oscillation while settling to a final bubble diameter. The size-dependent oscillation phenomenon generates a unique acoustic signal that can be passively detected in both time and frequency domain using confocal piston transducers with an ‘activate high’ (8 MHz, 2 cycles), ‘listen low’ (1 MHz) scheme. Results show that the magnitude of the acoustic ‘signature’ increases as PFC boiling point decreases. By using a band-limited spectral processing technique, the droplet signals can be isolated from controls and used to build experimental relationships between concentration and vaporization pressure. The techniques shown here may be useful for physical studies as well as development of droplet-specific imaging techniques.

  6. Gadolinium-containing magnetic resonance image contrast agent promotes fibrocyte differentiation.

    Science.gov (United States)

    Vakil, Varsha; Sung, Joanna J; Piecychna, Marta; Crawford, Jeffrey R; Kuo, Phillip; Abu-Alfa, Ali K; Cowper, Shawn E; Bucala, Richard; Gomer, Richard H

    2009-12-01

    Gadolinium-containing magnetic resonance imaging (MRI) contrast agents such as Omniscan are associated with nephrogenic systemic fibrosis (NSF). To determine if Omniscan can affect the differentiation of monocytes into fibroblast-like cells called fibrocytes that are found in the fibrotic lesions of NSF, peripheral blood mononuclear cells (PBMCs) from NSF patients, hemodialysis patients without NSF, and healthy, renally sufficient controls were exposed to Omniscan in a standardized in vitro fibrocyte differentiation protocol. When added to PBMCs, the gadolinium-containing MRI contrast agent Omniscan generally had little effect on fibrocyte differentiation. However, 10(-8) to 10(-3) mg/mL Omniscan reduced the ability of the fibrocyte differentiation inhibitor serum amyloid P (SAP) to decrease fibrocyte differentiation in PBMCs from 15 of 17 healthy controls and one of three NSF patients. Omniscan reduced the ability of SAP to decrease fibrocyte differentiation from purified monocytes, indicating that the Omniscan effect does not require the presence of other cells (such as T cells) in the PBMCs. Omniscan also reduced the ability of a different fibrocyte differentiation inhibitor, interleukin-12, to decrease fibrocyte differentiation. These data suggest that Omniscan interferes with the regulatory action of signals that inhibit the differentiation of monocytes to fibrocytes. J. Magn. Reson. Imaging 2009;30:1284-1288. (c) 2009 Wiley-Liss, Inc.

  7. Optimization of the protocols for the use of contrast agents in PET/CT studies.

    Science.gov (United States)

    Pelegrí Martínez, L; Kohan, A A; Vercher Conejero, J L

    The introduction of PET/CT scanners in clinical practice in 1998 has improved care for oncologic patients throughout the clinical pathway, from the initial diagnosis of disease through the evaluation of the response to treatment to screening for possible recurrence. The CT component of a PET/CT study is used to correct the attenuation of PET studies; CT also provides anatomic information about the distribution of the radiotracer. CT is especially useful in situations where PET alone can lead to false positives and false negatives, and CT thereby improves the diagnostic performance of PET. The use of intravenous or oral contrast agents and optimal CT protocols have improved the detection and characterization of lesions. However, there are circumstances in which the systematic use of contrast agents is not justified. The standard acquisition in PET/CT scanners is the whole body protocol, but this can lead to artifacts due to the position of patients and respiratory movements between the CT and PET acquisitions. This article discusses these aspects from a constructive perspective with the aim of maximizing the diagnostic potential of PET/CT and providing better care for patients.

  8. Porphyrin Nanodroplets: Sub-micrometer Ultrasound and Photoacoustic Contrast Imaging Agents.

    Science.gov (United States)

    Paproski, Robert J; Forbrich, Alexander; Huynh, Elizabeth; Chen, Juan; Lewis, John D; Zheng, Gang; Zemp, Roger J

    2016-01-20

    A novel class of all-organic nanoscale porphyrin nanodroplet agents is presented which is suitable for multimodality ultrasound and photoacoustic molecular imaging. Previous multimodality photoacoustic-ultrasound agents are either not organic, or not yet demonstrated to exhibit enhanced accumulation in leaky tumor vasculature, perhaps because of large diameters. In the current study, porphyrin nanodroplets are created with a mean diameter of 185 nm which is small enough to exhibit the enhanced permeability and retention effect. Porphyrin within the nanodroplet shell has strong optical absorption at 705 nm with an estimated molar extinction coefficient >5 × 10(9) m(-1) cm(-1) , allowing both ultrasound and photoacoustic contrast in the same nanoparticle using all organic materials. The potential of nanodroplets is that they may be phase-changed into microbubbles using high pressure ultrasound, providing ultrasound contrast with single-bubble sensitivity. Multispectral photoacoustic imaging allows visualization of nanodroplets when injected intratumorally in an HT1080 tumor in the chorioallantoic membrane of a chicken embryo. Intravital microscopy imaging of Hep3-GFP and HT1080-GFP tumors in chicken embryos determines that nanodroplets accumulated throughout or at the periphery of tumors, suggesting that porphyrin nanodroplets may be useful for enhancing the visualization of tumors with ultrasound and/or photoacoustic imaging.

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

    Science.gov (United States)

    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.

  10. Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies

    Energy Technology Data Exchange (ETDEWEB)

    Preda, Lorenzo [Division of Radiology, European Institute of Oncology, IRCCS, Milan (Italy); Agazzi, Alberto; Martinelli, Giovanni [Division of Haematology, European Institute of Oncology, IRCCS, Milan (Italy); Raimondi, Sara [Division of Epidemiology and Biostatistics, European Institute of Oncology, IRCCS, Milan (Italy); University of Milan, Department of Occupational Medicin ' ' Clinica del Lavoro Luigi Devoto' ' Section of Medical Statistics and Biometry ' ' GA Maccacaro' ' , Milan (Italy); Lanfranchi, Carla Federica [University of Milan, IRCCS, School of Medicine, Milan (Italy); Passerini, Rita [Unit of Laboratory Medicine, European Institute of Oncology, IRCCS, Milan (Italy); Calvetta, Albania [Nephrology and Dialysis Unit, Istituto Clinico Humanitas, IRCCS, Rozzano, Milan (Italy); Bellomi, Massimo [Division of Radiology, European Institute of Oncology, IRCCS, Milan (Italy); University of Milan, IRCCS, School of Medicine, Milan (Italy)

    2011-01-15

    To assess the safety of the non-ionic iso-osmolar contrast agent iodixanol on renal function in patients with monoclonal gammopathies undergoing CT. We explored the effect of iodixanol on renal function in 30 patients with monoclonal gammopathies and 20 oncological patients with a normal electrophoretic profile (control group). The parameters used to estimate renal function were: serum creatinine, eGFR (determined 24 h before and 48 h after the administration of iodixanol), and urinary excretion of Neutrophil Gelatinase-Associated Lipocalin (NGAL) determined 2 h and 24 h after. Serum creatinine was also determined 1 month after the administration of iodixanol. No significant increase in serum creatinine values were observed in the monoclonal gammopathies group and in 19/20 patients in the control group. Only 1 patient in the control group developed a transient contrast agent-induced nephropathy. We found no statistically significant difference between the two groups regarding the percentage variation from baseline values of serum creatinine, creatinine clearance, NGAL 2 h after, and eGFR. Whereas NGAL at 24 h showed a statistically significant increase in patients with Monoclonal gammopathies. The use of iodixanol appears to be safe in patients with monoclonal gammopathies and an eGFR {>=} 60 ml/min/1.73 mq. (orig.)

  11. Carboxylated magnetic nanoparticles as MRI contrast agents: Relaxation measurements at different field strengths

    Energy Technology Data Exchange (ETDEWEB)

    Jedlovszky-Hajdu, Angela, E-mail: angela.hajdu@net.sote.hu [Laboratory of Nanochemistry, Department of Biophysics and Radiation Biology, Semmelweis University, Nagyvarad Sq 4, H-1089 Budapest (Hungary); Tombacz, Etelka, E-mail: tombacz@chem.u-szeged.hu [Department of Physical Chemistry and Material Science, University of Szeged, Aradi Vt. Sq 1, Szeged 6720 (Hungary); Banyai, Istvan, E-mail: banyai.istvan@science.unideb.hu [Department of Colloid and Environmental Chemistry, University of Debrecen (Hungary); Babos, Magor, E-mail: babosmagor@yahoo.com [Euromedic Diagnostics Szeged Ltd., Semmelweis St 6, Szeged 6720 (Hungary); Palko, Andras, E-mail: palko@radio.szote.u-szeged.hu [Faculty of Medicine, Department of Radiology, University of Szeged (Hungary)

    2012-09-15

    At the moment the biomedical applications of magnetic fluids are the subject of intensive scientific interest. In the present work, magnetite nanoparticles (MNPs) were synthesized and stabilized in aqueous medium with different carboxylic compounds (citric acid (CA), polyacrylic acid (PAA), and sodium oleate (NaOA)), in order to prepare well stabilized magnetic fluids (MFs). The magnetic nanoparticles can be used in the magnetic resonance imaging (MRI) as contrast agents. Magnetic resonance relaxation measurements of the above MFs were performed at different field strengths (i.e., 0.47, 1.5 and 9.4 T) to reveal the field strength dependence of their magnetic responses, and to compare them with that of ferucarbotran, a well-known superparamagnetic contrast agent. The measurements showed characteristic differences between the tested magnetic fluids stabilized by carboxylic compounds and ferucarbotran. It is worthy of note that our magnetic fluids have the highest r2 relaxivities at the field strength of 1.5 T, where the most of the MRI works in worldwide. - Highlights: Black-Right-Pointing-Pointer Magnetic resonance relaxation measurements were done at different field strengths. Black-Right-Pointing-Pointer Results show characteristic differences between the tested carboxylated MFs. Black-Right-Pointing-Pointer r1 and r2 relaxivities depend on the thickness of the protecting layer. Black-Right-Pointing-Pointer MFs have high r2/r1 ratios at each magnetic field.

  12. Application of extracellular gadolinium-based MRI contrast agents and the risk of nephrogenic systemic fibrosis; Anwendung von extrazellulaeren gadoliniumhaltigen MR-Kontrastmitteln und Risiko der Nephrogenen Systemischen Fibrose

    Energy Technology Data Exchange (ETDEWEB)

    Heverhagen, J.T. [Univ. Hospital Bern (Switzerland). Inst. of Diagnostic, Interventional and Pediatric Radiology, Inselspital; Krombach, G.A. [Justus Liebig Univ. Hopsital Giessen (Germany). Diagnostic and Interventional Radiology; Gizewski, E. [Medical Univ. Innsbruck (Austria). Dept. of Neuroradiology

    2014-07-15

    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.

  13. Avascular necrosis (AVN) of the proximal fragment in scaphoid nonunion: Is intravenous contrast agent necessary in MRI?

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, R., E-mail: schmitt.radiologie@herzchirurgie.de [Department of Diagnostic and Interventional Radiology, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Christopoulos, G.; Wagner, M. [Department of Diagnostic and Interventional Radiology, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Krimmer, H. [Department of Hand Surgery, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Fodor, S. [Department of Diagnostic and Interventional Radiology, Cardiovascular Center, Bad Neustadt an der Saale (Germany); Schoonhoven, J. van; Prommersberger, K.J. [Department of Hand Surgery, Cardiovascular Center, Bad Neustadt an der Saale (Germany)

    2011-02-15

    Purpose: The purpose of this prospective study is to assess the diagnostic value of intravenously applied contrast agent for diagnosing osteonecrosis of the proximal fragment in scaphoid nonunion, and to compare the imaging results with intraoperative findings. Materials and methods: In 88 patients (7 women, 81 men) suffering from symptomatic scaphoid nonunion, preoperative MRI was performed (coronal PD-w FSE fs, sagittal-oblique T1-w SE nonenhanced and T1-w SE fs contrast-enhanced, sagittal T2*-w GRE). MRI interpretation was based on the intensity of contrast enhancement: 0 = none, 1 = focal, 2 = diffuse. Intraoperatively, the osseous viability was scored by means of bleeding points on the osteotomy site of the proximal scaphoid fragment: 0 = absent, 1 = moderate, 2 = good. Results: Intraoperatively, 17 necrotic, 29 compromised, and 42 normal proximal fragments were found. In nonenhanced MRI, bone viability was judged necrotic in 1 patient, compromised in 20 patients, and unaffected in 67 patients. Contrast-enhanced MRI revealed 14 necrotic, 21 compromised, and 53 normal proximal fragments. Judging surgical findings as the standard of reference, statistical analysis for nonenhanced MRI was: sensitivity 6.3%, specificity 100%, positive PV 100%, negative PV 82.6%, and accuracy 82.9%; statistics for contrast-enhanced MRI was: sensitivity 76.5%, specificity 98.6%, positive PV 92.9%, negative PV 94.6%, and accuracy 94.3%. Sensitivity for detecting avascular proximal fragments was significantly better (p < 0.001) in contrast-enhanced MRI in comparison to nonenhanced MRI. Conclusion: Viability of the proximal fragment in scaphoid nonunion can be significantly better assessed with the use of contrast-enhanced MRI as compared to nonenhanced MRI. Bone marrow edema is an inferior indicator of osteonecrosis. Application of intravenous gadolinium is recommended for imaging scaphoid nonunion.

  14. In vitro evaluation of alternative oral contrast agents for MRI of the gastrointestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Babos, Magor [University of Szeged, Faculty of Science (Hungary); Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: babosmagor@yahoo.com; Schwarcz, Attila [University of Pecs, Department of Neurosurgery, Pecs Diagnostic Institute, 7624 Pecs, Retu. 2 (Hungary)], E-mail: attila.schwarcz@aok.pte.hu; Randhawa, Manjit Singh [University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: majyaal@hotmail.com; Marton, Balazs [University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: balazsmarton@freemail.hu; Kardos, Lilla [Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: medlis@tiszanet.hu; Palko, Andras [Euromedic Diagnostics Szeged, 6720 Szeged, Semmelweiss u. 6 (Hungary); University of Szeged, Faculty of Medicine, Department of Radiology, 6720 Szeged, Semmelweiss u. 6 (Hungary)], E-mail: palko@radio.szote.u-szeged.hu

    2008-01-15

    Purpose: In vitro evaluation of different materials as potential alternative oral contrast agents for small bowel MRI. Materials and methods: The T1 and T2 relaxation times of rose hip syrup, black currant extract, cocoa, iron-deferoxamine solution and a commonly used oral contrast material (1 mM Gd-DTPA) were determined in vitro at different concentrations on a 1.0 T clinical MR scanner. T1 values were obtained with an inversion prepared spoiled gradient echo sequence. T2 values were obtained using multiple echo sequences. Finally the materials were visualized on T1-, T2- and T2*-weighted MR images. Results: The relaxation times of the undiluted rose hip syrup (T1 = 110 {+-} 5 ms, T2 = 86 {+-} 3 ms), black currant extract (T1 = 55 {+-} 3 ms, T2 = 39 {+-} 2 ms) and 5 mM iron-deferoxamine solution (T1 = 104 {+-} 4 ms, T2 = 87 {+-} 2 ms) were much shorter than for a 1 mM Gd-DTPA solution (T1 = 180 {+-} 8 ms, T2 = 168 {+-} 5 ms). Dilution of black currant extract to 30% or a 3 mM iron-deferoxamine solution conducted to T1 relaxation times which are quite comparable to a 1 mM Gd-DTPA solution. Despite its much lower metal content an aqueous cocoa suspension (100 g/L) produced T2 relaxation times (T1 = 360 {+-} 21 ms, T2 = 81 {+-} 3 ms) more or less in the same range like the 5 mM iron-deferoxamine solution. Imaging of our in vitro model using clinical sequences allowed to anticipate the T1-, T2- and T2*-depiction of all used substances. Cocoa differed from all other materials with its low to moderate signal intensity on T1- and T2-weighted sequences. While all substances presented a linear 1/T1 and 1/T2 relationship towards concentration, rose hip syrup broke ranks with a disproportionately high increase of relaxation at higher concentrations. Conclusions: Rose hip syrup, black currant extract and iron-deferoxamine solution due to their positive T1 enhancement characteristics and drinkability appear to be valuable oral contrast agents for T1-weighted small bowel MRI

  15. Gastric stromal tumor: two-phase dynamic CT findings with water as oral contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Se Hyo; Cho, June Sik; Shin, Kyung Sook; Jeong, Ki Ho; Park, Jin Yong; Yu, Ho Jun; Kim, Young Min; Jeon, Kwang Jin [College of Medicine, Chungnam National University, Taejon (Korea, Republic of)

    2000-01-01

    To evaluate two-phase dynamic CT with water as oral contrast agents in the CT diagnosis of gastric stromal tumors. We retrospectively reviewed the CT findings in 21 patients with pathologically proven gastric stromal tumors. Six were found to be benign, twelve were malignant, and there were three cases of STUMP (stromal tumor uncertain malignant potential). Two-phase dynamic CT scans with water as oral contrast agents were obtained 60-70 secs (portal phase) and 3 mins (equilibrium phase) after the start of IV contrast administration. We determined the size, growth pattern, and enhancement pattern of the tumors and overlying mucosa, the presence or absence of ulceration and necrosis, tumor extent, and lymph nod and distant metastasis. The CT and pathologic findings were correlated. All six benign tumors and three STUMP were less than 5.5 cm in size, and during the portal phase showed round endogastric masses with highly enhanced, intact overlying mucosa. Twelve malignant tumors were 4.5-15.5 cm in size (mean, 11.5 cm); an endogastric mass was seen in three cases, an exogastric mass in one, and a mixed pattern in eight. On portal phase images the tumors were not significantly enhanced, but highly enhanced feeding vessels were noted in five larger tumors (greater than 10 cm). All 12 malignant tumors showed ulceration and necrosis, and interruption of overlying mucosa was clearly seen during the portal phase. We were readily able to evaluate tumor extent during this phase, and in ten malignant tumors there was no invasion of adjacent organs. Seven malignant tumors showed air density within their necrotic portion (p less than 0.05). On equilibrium phase images, all malignant tumors showed heterogeneous enhancement due to necrosis, and poorly enhanced overlying mucosa. Dynamic CT during the portal phase with water as oral contrast agents was useful for depicting the submucosal origin of gastric stromal tumors and for evaluating the extent of malignant stromal tumors. Our

  16. Evaluation of microbubbles as contrast agents for ultrasonography and magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Ling Li

    Full Text Available BACKGROUND: Microbubbles (MBs can serve as an ultrasound contrast agent, and has the potential for magnetic resonance imaging (MRI. Due to the relatively low effect of MBs on MRI, it is necessary to develop new MBs that are more suitable for MRI. In this study, we evaluate the properties of SonoVue® and custom-made Fe(3O(4-nanoparticle-embedded microbubbles (Fe(3O(4-MBs in terms of contrast agents for ultrsonography (US and MRI. METHODOLOGY/PRINCIPAL FINDINGS: A total of 20 HepG2 subcutaneous-tumor-bearing nude mice were randomly assigned to 2 groups (i.e., n = 10 mice each group, one for US test and the other for MRI test. Within each group, two tests were performed for each mouse. The contrast agent for the first test is SonoVue®, and the second is Fe(3O(4-MBs. US was performed using a Technos(MPX US system (Esaote, Italy with a contrast-tuned imaging (CnTI™ mode. MRI was performed using a 7.0T Micro-MRI (PharmaScan, Bruker Biospin GmbH, Germany with an EPI-T(2* sequence. The data of signal-to-noise ratio (SNR from the region-of-interest of each US and MR image was calculated by ImageJ (National Institute of Health, USA. In group 1, enhancement of SonoVue® was significantly higher than Fe(3O(4-MBs on US (P0.05. The SNR analysis of the enhancement process reveals a strong negative correlation in both cases (i.e., SonoVue® r = -0.733, Fe(3O(4-MBs r = -0.903, with P<0.05. CONCLUSIONS: It might be important to change the Fe(3O(4-MBs' shell structure and/or the imagining strategy of US to improve the imaging quality of Fe(3O(4-MBs on US. As an intriguing prospect that can be detected by US and MRI, MBs are worthy of further study.

  17. Agent-based modeling of sustainable behaviors

    CERN Document Server

    Sánchez-Maroño, Noelia; Fontenla-Romero, Oscar; Polhill, J; Craig, Tony; Bajo, Javier; Corchado, Juan

    2017-01-01

    Using the O.D.D. (Overview, Design concepts, Detail) protocol, this title explores the role of agent-based modeling in predicting the feasibility of various approaches to sustainability. The chapters incorporated in this volume consist of real case studies to illustrate the utility of agent-based modeling and complexity theory in discovering a path to more efficient and sustainable lifestyles. The topics covered within include: households' attitudes toward recycling, designing decision trees for representing sustainable behaviors, negotiation-based parking allocation, auction-based traffic signal control, and others. This selection of papers will be of interest to social scientists who wish to learn more about agent-based modeling as well as experts in the field of agent-based modeling.

  18. Agent based computational model of trust

    NARCIS (Netherlands)

    A. Gorobets (Alexander); B. Nooteboom (Bart)

    2004-01-01

    textabstractThis paper employs the methodology of Agent-Based Computational Economics (ACE) to investigate under what conditions trust can be viable in markets. The emergence and breakdown of trust is modeled in a context of multiple buyers and suppliers. Agents adapt their trust in a partner, the w

  19. Impact of Filling Gas on Subharmonic Emissions of Phospholipid Ultrasound Contrast Agents.

    Science.gov (United States)

    Kanbar, Emma; Fouan, Damien; Sennoga, Charles A; Doinikov, Alexander A; Bouakaz, Ayache

    2017-02-14

    Subharmonic signals backscattered from gas-filled lipid-shelled microbubbles have generated significant research interest because they can improve the detection and sensitivity of contrast-enhanced ultrasound imaging. However, the emission of subharmonic signals is strongly characterized by a temporal dependence, the origins of which have not been sufficiently elucidated. The features that influence subharmonic emissions need to be identified not only to better develop next-generation microbubble contrast agents, but also to develop more efficient subharmonic imaging (SHI) modes and therapeutic strategies. We examined the effect of microbubble filling gas on subharmonic emissions. Phospholipid shelled-microbubbles with different gaseous compositions such as sulfur hexafluoride (SF6), octafluoropropane (C3F8) or decafluorobutane (C4F10), nitrogen (N2)/C4F10 or air were insonated using a driving frequency of 10 MHz and peak negative pressure of 450 kPa, and their acoustic responses were tracked by monitoring both second harmonic and subharmonic emissions. Microbubbles were first acoustically characterized with their original gas and then re-characterized after substitution of the original gas with air, SF6 or C4F10. A measureable change in intensity of the subharmonic emissions with a 20- to 40-min delayed onset and increasing subharmonic emissions of the order 12-18 dB was recorded for microbubbles filled with C4F10. Substitution of C4F10 with air eliminated the earlier observed delay in subharmonic emissions. Significantly, substitution of SF6 for C4F10 successfully triggered a delay in the subharmonic emissions of the resultant agents, whereas substitution of C4F10 for SF6 eliminated the earlier observed suppression of subharmonic emissions, clearly suggesting that the type of filling gas contained in the microbubble agent influences subharmonic emissions in a time-dependent manner. Because our agents were dispersed in air-stabilized phosphate-buffered saline

  20. 1.5 Harmonic Imaging Sonography with microbubble contrast agent improves characterization of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kouji Yamamoto; Katsuya Shiraki; Shigeo Nakanishi; Hiroyuki Fuke; Takeshi Nakano; Akira Hashimoto; Atsuya Shimizu; Toshinobu Hamataki

    2005-01-01

    AIM: To investigate the usefulness of 1.5 Harmonic Imaging Sonography with the use of the contrast agent Levovist for the diagnosis of hepatocellular carcinoma (HCC) and for the evaluation of therapeutic response.METHODS: Phantom experiments were performed to compare the contrast effects of 2nd harmonic imaging and 1.5 Harmonic Imaging Sonography. 1.5 Harmonic Imaging Sonography was employed to examine 36 patients with HCC (42 nodules) before and after the treatment and to compare against the findings obtained using other diagnostic imaging modalities. RESULTS: In 1.5 Harmonic Imaging Sonography, the tumor vessels of HCCs were clearly identified during the early phase, and late-phase images clearly demonstrated the differences in contrast enhancement between the tumor and surrounding hepatic parenchyma. Blood flow within the tumor was detected in 36 nodules (85.7%)during the early phase and in all 42 nodules (100%) during the late phase using 1.5 Harmonic Imaging Sonography,in 38 nodules (90.5%) using contrast-enhanced CT, in 34nodules (81.0%) using digital subtraction angiography (DSA), and in 42 nodules (100%) using US CO2angiography.Following transcatheter arterial embolization, 1.5Harmonic Imaging Sonography detected blood flow and contrast enhancement within the tumors that were judged to contain viable tissue in 20 of 42 nodules (47.6%).However, 6 of these 20 cases were not judged in contrastenhanced CT. 1.5 Harmonic Imaging Sonography was compared with the US CO2 angiography findings as the gold standard, and the sensitivity and specificity of these images for discerning viable and nonviable HCC after transcatheter arterial embolization were 100% and 100%,respectively.CONCLUSION: 1.5 Harmonic Imaging Sonography permits the vascular structures of HCCs to be identified and blood flow within the tumor to be clearly demonstrated.Furthermore, 1.5 Harmonic Imaging Sonography is potentially useful for evaluating the therapeutic effects of transcatheter arterial

  1. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

    Directory of Open Access Journals (Sweden)

    D’Hollander A

    2016-08-01

    Full Text Available Antoine D’Hollander,1–3 Evelien Mathieu,1,4 Hilde Jans,1 Greetje Vande Velde,2,3 Tim Stakenborg,1 Pol Van Dorpe,1,4 Uwe Himmelreich,2,3 Liesbet Lagae1,4 1Department of Life Science Technology, Imec, 2Department of Imaging and Pathology, Faculty of Medicine, Biomedical MRI Unit, 3Faculty of Medicine, Molecular Small Animal Imaging Center (MoSAIC, 4Department of Physics, Faculty of Sciences, Laboratory of Solid State Physics and Magnetism, KU Leuven, Leuven, Belgium Abstract: The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS, realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3. Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. Keywords: SERS, gold nanostars, cancer imaging, Raman active

  2. Chemistry of paramagnetic and diamagnetic contrast agents for Magnetic Resonance Imaging and Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Perez-Mayoral, Elena [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Departamento de Quimica Inorganica y Quimica Tecnica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Negri, Viviana; Soler-Padros, Jordi [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain); Cerdan, Sebastian [Laboratorio de Imagen Espectroscopica por Resonancia Magnetica (LIERM), Instituto de Investigaciones Biomedicas ' Alberto Sols' , CSIC/UAM, c/Arturo Duperier 4, E-28029 Madrid (Spain); Ballesteros, Paloma [Laboratorio de Sintesis Organica e Imagen Molecular por Resonancia Magnetica, Facultad de Ciencias, UNED, Paseo Senda del Rey 9, E-28040 Madrid (Spain)], E-mail: pballesteros@ccia.uned.es

    2008-09-15

    We provide a brief overview of the chemistry and most relevant properties of paramagnetic and diamagnetic contrast agents (CAs) for Magnetic Resonance Imaging and Magnetic Resonance Spectroscopic Imaging. Paramagnetic CAs for MRI consist mainly of Gd(III) complexes from linear or macrocyclic polyaminopolycarboxylates. These agents reduce, the relaxation times T{sub 1} and T{sub 2} of the water protons in a concentration dependent manner, increasing selectively MRI contrast in those regions in which they accumulate. In most instances they provide anatomical information on the localization of lesions and in some specific cases they may allow to estimate some physiological properties of tissues including mainly vascular performance. Because of its ability to discriminate easily between normal and diseased tissue, extracellular pH (pH{sub e}) has been added recently, to the battery of variables amenable to MRI investigation. A variety of Gd(III) containing macrocycles sensitive to pH, endogenous or exogenous polypeptides or even liposomes have been investigated for this purpose, using the pH dependence of their relaxivity or magnetization transfer rate constant (chemical exchange saturation transfer, CEST). Many environmental circumstances in addition to pH affect, however, relaxivity or magnetization transfer rate constants of these agents, making the results of pH measurements by MRI difficult to interpret. To overcome these limitations, our laboratory synthesized and developed a novel series of diamagnetic CAs for Magnetic Resonance Spectroscopic Imaging, a new family of monomeric and dimeric imidazolic derivatives able to provide unambiguous measurements of pH{sub e}, independent of water relaxivity, diffusion or exchange.

  3. Update on the safety and efficacy of commercial ultrasound contrast agents in cardiac applications.

    Science.gov (United States)

    Appis, Andrew W; Tracy, Melissa J; Feinstein, Steven B

    2015-06-01

    Ultrasound contrast agents (UCAs) are currently used throughout the world in both clinical and research settings. The concept of contrast-enhanced ultrasound imaging originated in the late 1960s, and the first commercially available agents were initially developed in the 1980s. Today's microbubbles are designed for greater utility and are used for both approved and off-label indications. In October 2007, the US Food and Drug Administration (FDA) imposed additional product label warnings that included serious cardiopulmonary reactions, several new disease-state contraindications, and a mandated 30 min post-procedure monitoring period for the agents Optison and Definity. These additional warnings were prompted by reports of cardiopulmonary reactions that were temporally related but were not clearly attributable to these UCAs. Subsequent published reports over the following months established not only the safety but also the improved efficacy of clinical ultrasound applications with UCAs. The FDA consequently updated the product labeling in June 2008 and reduced contraindications, although it continued to monitor select patients. In addition, a post-marketing program was proposed to the sponsors for a series of safety studies to further assess the risk of UCAs. Then in October 2011, the FDA leadership further downgraded the warnings after hearing the results of the post-marketing data, which revealed continued safety and improved efficacy. The present review focuses on the use of UCAs in today's clinical practice, including the approved indications, a variety of off-label uses, and the most recent data, which affirms the safety and efficacy of UCAs.

  4. Evaluation of Gd-DTPA-monophytanyl and phytantriol nanoassemblies as potential MRI contrast agents.

    Science.gov (United States)

    Gupta, Abhishek; de Campo, Liliana; Rehmanjan, Beenish; Willis, Scott A; Waddington, Lynne J; Stait-Gardner, Tim; Kirby, Nigel; Price, William S; Moghaddam, Minoo J

    2015-02-03

    Supramolecular self-assembling amphiphiles have been widely used in drug delivery and diagnostic imaging. In this report, we present the self-assembly of Gd (III) chelated DTPA-monophytanyl (Gd-DTPA-MP) amphiphiles incorporated within phytantriol (PT), an inverse bicontinuous cubic phase forming matrix at various compositions. The dispersed colloidal nanoassemblies were evaluated as potential MRI contrast agents at various magnetic field strengths. The homogeneous incorporation of Gd-DTPA-MP in PT was confirmed by polarized optical microscopy (POM) and synchrotron small-angle X-ray scattering (SAXS) of the bulk phases of the mixtures. The liquid crystalline nanostructures, morphology, and the size distribution of the nanoassemblies were studied by SAXS, cryogenic transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS). The dispersions with up to 2 mol % of Gd-DTPA-MP in PT retained inverse cubosomal nanoassemblies, whereas the rest of the dispersions transformed to liposomal nanoassemblies. In vitro relaxivity studies were performed on all the dispersions at 0.54, 9.40, and 11.74 T and compared to Magnevist, a commercially available contrast agent. All the dispersions showed much higher relaxivities compared to Magnevist at both low and high magnetic field strengths. Image contrast of the nanoassemblies was also found to be much better than Magnevist at the same Gd concentration at 11.74 T. Moreover, the Gd-DTPA-MP/PT dispersions showed improved relaxivities over the pure Gd-DTPA-MP dispersion at high magnetic fields. These stable colloidal nanoassemblies have high potential to be used as combined delivery matrices for diagnostics and therapeutics.

  5. Hyaluronic acid-functionalized single-walled carbon nanotubes as tumor-targeting MRI contrast agent

    Directory of Open Access Journals (Sweden)

    Hou L

    2015-07-01

    Full Text Available Lin Hou,* Huijuan Zhang,* Yating Wang, Lili Wang, Xiaomin Yang, Zhenzhong ZhangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, People’s Republic of China*These authors contributed equally to this workAbstract: A tumor-targeting carrier, hyaluronic acid (HA-functionalized single-walled carbon nanotubes (SWCNTs, was explored to deliver magnetic resonance imaging (MRI contrast agents (CAs targeting to the tumor cells specifically. In this system, HA surface modification for SWCNTs was simply accomplished by amidation process and could make this nanomaterial highly hydrophilic. Cellular uptake was performed to evaluate the intracellular transport capabilities of HA-SWCNTs for tumor cells and the uptake rank was HA-SWCNTs> SWCNTs owing to the presence of HA, which was also evidenced by flow cytometry. The safety evaluation of this MRI CAs was investigated in vitro and in vivo. It revealed that HA-SWCNTs could stand as a biocompatible nanocarrier and gadolinium (Gd/HA-SWCNTs demonstrated almost no toxicity compared with free GdCl3. Moreover, GdCl3 bearing HA-SWCNTs could significantly increase the circulation time for MRI. Finally, to investigate the MRI contrast enhancing capabilities of Gd/HA-SWCNTs, T1-weighted MR images of tumor-bearing mice were acquired. The results suggested Gd/HA-SWCNTs had the highest tumor-targeting efficiency and T1-relaxivity enhancement, indicating HA-SWCNTs could be developed as a tumor-targeting carrier to deliver the CAs, GdCl3, for the identifiable diagnosis of tumor.Keywords: gadolinium, magnetic resonance, SWCNTs, hyaluronic acid, contrast agent

  6. Stimulus-responsive ultrasound contrast agents for clinical imaging: motivations, demonstrations, and future directions.

    Science.gov (United States)

    Goodwin, Andrew P; Nakatsuka, Matthew A; Mattrey, Robert F

    2015-01-01

    Microbubble ultrasound contrast agents allow imaging of the vasculature with excellent resolution and signal-to-noise ratios. Contrast in microbubbles derives from their interaction with an ultrasound wave to generate signal at harmonic frequencies of the stimulating pulse; subtracting the elastic echo caused by the surrounding tissue can enhance the specificity of these harmonic signals significantly. The nonlinear acoustic emission is caused by pressure-driven microbubble size fluctuations, which in both theoretical descriptions and empirical measurements was found to depend on the mechanical properties of the shell that encapsulates the microbubble as well as stabilizes it against the surrounding aqueous environment. Thus biochemically induced switching between a rigid 'off' state and a flexible 'on' state provides a mechanism for sensing chemical markers for disease. In our research, we coupled DNA oligonucleotides to a stabilizing lipid monolayer to modulate stiffness of the shell and thereby induce stimulus-responsive behavior. In initial proof-of-principle studies, it was found that signal modulation came primarily from DNA crosslinks preventing the microbubble size oscillations rather than merely damping the signal. Next, these microbubbles were redesigned to include an aptamer sequence in the crosslinking strand, which not only allowed the sensing of the clotting enzyme thrombin but also provided a general strategy for sensing other soluble biomarkers in the bloodstream. Finally, the thrombin-sensitive microbubbles were validated in a rabbit model, presenting the first example of an ultrasound contrast agent that could differentiate between active and inactive clots for the diagnosis of deep venous thrombosis. © 2014 Wiley Periodicals, Inc.

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

    Directory of Open Access Journals (Sweden)

    Yvana Lopes Pinheiro da Silva

    2015-04-01

    Full Text Available 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.

  8. Correction: Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents

    Science.gov (United States)

    Hachani, Roxanne; Lowdell, Mark; Birchall, Martin; Hervault, Aziliz; Mertz, Damien; Begin-Colin, Sylvie; Thanh, Nguy&Ecirtil; N. Thi&Cmb. B. Dot; Kim

    2016-02-01

    Correction for `Polyol synthesis, functionalisation, and biocompatibility studies of superparamagnetic iron oxide nanoparticles as potential MRI contrast agents' by Roxanne Hachani et al., Nanoscale, 2015, DOI: 10.1039/c5nr03867g.

  9. Tumor Delivery of Ultrasound Contrast Agents Using Shiga Toxin B Subunit

    Directory of Open Access Journals (Sweden)

    Olivier Couture

    2011-03-01

    Full Text Available The present study demonstrates the targeting of ultrasound contrast agents to human xenograft tumors by exploiting the overexpression of the glycolipid Gb3 in neovasculature. To this end, microbubbles were functionalized with a natural Gb3 ligand, the B subunit of the Shiga toxin (STxB. The targeting of Gb3-expressing tumor cells by STxB microbubbles was first shown by flow cytometry and fluorescence microscopy. A significantly higher proportion of STxB microbubbles were associated with Gb3-expressing tumor cells compared to cells in which Gb3 expression was inhibited. Moreover, ultrasonic imaging of culture plates showed a 12 dB contrast enhancement in average backscattered acoustic intensity on the surface of Gb3-expressing cells compared to Gb3-negative cells. Also, a 18 dB contrast enhancement was found in favor of STxB microbubbles compared to unspecific microbubbles. Microbubble signal intensity in subcutaneous tumors in mice was more than twice as high after the injection of STxB-functionalized microbubbles compared to the injection of unspecific microbubbles. These in vitro and in vivo experiments demonstrated that STxB-functionalized microbubbles bind specifically to cells expressing the Gb3 glycolipid. The cell-binding moieties of toxins thus appear as a new group of ligands for angiogenesis imaging with ultrasound.

  10. TREG coated iron oxide nanoparticles as contrast agent for MRI in-vivo use

    Science.gov (United States)

    Gutierrez-Garcia, Eric; Hidalgo-Tobon, Silvia; Lopez, Ciro; Gonzalez-Rodriguez, Roberto; Coffer, Jeffery; De Celis Alonso, Benito; Dies Suarez, Pilar; Obregon, Manuel; Perez-Pena, Mario; Platas-Neri, Diana; Mendez-Rojas, Miguel

    2014-11-01

    Super-paramagnetic iron oxide nanoparticles (SPIONs) are of interest due to their great potential applications in diverse fields such as biomedicine. In this work we have prepared SPION nanoparticles using the polyol technique and characterized the magnetic properties of them for MRI in-vivo use. Nanoparticle preparation: All reagents were purchased from commercial sources (Sigma-Aldrich, St. Louis, USA) Iron (III) acetylacetonate, [Fe(acac)3], was used as the iron oxide precursor and thermally decomposed at high temperatures in triethyleneglycol (TREG). Nano-sized magnetite particles were prepared by an adaptation of the method proposed by Wei Cai et al[1-3]. A healthy rabbit was scanned on a clinical 1.5 T Philips MR scanner. Images were taken in 2D mode with a mFFE sequence. Relaxation time T2 was obtained from the MR images using a Matlab algorithm where the signal intensity decay was calculated at each image and then adjusted to a mono-exponential curve. Images were obtained before contrast injection, 24 hours and 36 hours following SPIONs administration. Signal decay at different Echo times for the prepared magnetic SPIONs, before and after contrast injection was measured. It was visualized a concentration of the agent contrast in brain and liver and the results were compared with images obtained from histopathology.

  11. Assurance in Agent-Based Systems

    Energy Technology Data Exchange (ETDEWEB)

    Gilliom, Laura R.; Goldsmith, Steven Y.

    1999-05-10

    Our vision of the future of information systems is one that includes engineered collectives of software agents which are situated in an environment over years and which increasingly improve the performance of the overall system of which they are a part. At a minimum, the movement of agent and multi-agent technology into National Security applications, including their use in information assurance, is apparent today. The use of deliberative, autonomous agents in high-consequence/high-security applications will require a commensurate level of protection and confidence in the predictability of system-level behavior. At Sandia National Laboratories, we have defined and are addressing a research agenda that integrates the surety (safety, security, and reliability) into agent-based systems at a deep level. Surety is addressed at multiple levels: The integrity of individual agents must be protected by addressing potential failure modes and vulnerabilities to malevolent threats. Providing for the surety of the collective requires attention to communications surety issues and mechanisms for identifying and working with trusted collaborators. At the highest level, using agent-based collectives within a large-scale distributed system requires the development of principled design methods to deliver the desired emergent performance or surety characteristics. This position paper will outline the research directions underway at Sandia, will discuss relevant work being performed elsewhere, and will report progress to date toward assurance in agent-based systems.

  12. Dynamic contrast-enhanced MRI using a macromolecular MR contrast agent (P792): Evaluation of antivascular drug effect in a rabbit VX2 liver tumor model

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Sun [Dept. of Radiology, Konkuk University School of Medicine, Seoul (Korea, Republic of); Han, Joon Koo; Lee, Jeong Min; Woo, Sung Min; Choi, Byung Ihn [Seoul National University Hospital, Seoul (Korea, Republic of); Kim, Young Il [Dept. of Radiology, Sheikh Khalifa Specialty Hospital, Ras Al Khaimah (United Arab Emirates); Choi, Jin Young [Dept. of Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-10-15

    To evaluate the utility of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using macromolecular contrast agent (P792) for assessment of vascular disrupting drug effect in rabbit VX2 liver tumor models. This study was approved by our Institutional Animal Care and Use Committee. DCE-MRI was performed with 3-T scanner in 13 VX2 liver tumor-bearing rabbits, before, 4 hours after, and 24 hours after administration of vascular disrupting agent (VDA), using gadomelitol (P792, n = 7) or low molecular weight contrast agent (gadoterate meglumine [Gd-DOTA], n = 6). P792 was injected at a of dose 0.05 mmol/kg, while that of Gd-DOTA was 0.2 mmol/kg. DCE-MRI parameters including volume transfer coefficient (Ktrans) and initial area under the gadolinium concentration-time curve until 60 seconds (iAUC) of tumors were compared between the 2 groups at each time point. DCE-MRI parameters were correlated with tumor histopathology. Reproducibility in measurement of DCE-MRI parameters and image quality of source MR were compared between groups. P792 group showed a more prominent decrease in Ktrans and iAUC at 4 hours and 24 hours, as compared to the Gd-DOTA group. Changes in DCE-MRI parameters showed a weak correlation with histologic parameters (necrotic fraction and microvessel density) in both groups. Reproducibility of DCE-MRI parameters and overall image quality was not significantly better in the P792 group, as compared to the Gd-DOTA group. Dynamic contrast-enhanced magnetic resonance imaging using a macromolecular contrast agent shows changes of hepatic perfusion more clearly after administration of the VDA. Gadolinium was required at smaller doses than a low molecular contrast agent.

  13. Agent-based modeling and network dynamics

    CERN Document Server

    Namatame, Akira

    2016-01-01

    The book integrates agent-based modeling and network science. It is divided into three parts, namely, foundations, primary dynamics on and of social networks, and applications. The book begins with the network origin of agent-based models, known as cellular automata, and introduce a number of classic models, such as Schelling’s segregation model and Axelrod’s spatial game. The essence of the foundation part is the network-based agent-based models in which agents follow network-based decision rules. Under the influence of the substantial progress in network science in late 1990s, these models have been extended from using lattices into using small-world networks, scale-free networks, etc. The book also shows that the modern network science mainly driven by game-theorists and sociophysicists has inspired agent-based social scientists to develop alternative formation algorithms, known as agent-based social networks. The book reviews a number of pioneering and representative models in this family. Upon the gi...

  14. Characteristics and Echogenicity of Clinical Ultrasound Contrast Agents: An In Vitro and In Vivo Comparison Study.

    Science.gov (United States)

    Hyvelin, Jean-Marc; Gaud, Emmanuel; Costa, Maria; Helbert, Alexandre; Bussat, Philippe; Bettinger, Thierry; Frinking, Peter

    2017-05-01

    To compare physicochemical characteristics and in vitro and in vivo contrast-enhanced ultrasound imaging performance of 3 commercially available ultrasound contrast agents: SonoVue (Bracco Imaging SpA, Colleretto Giacosa, Italy; also marketed as Lumason in the USA), Definity (Lantheus Medical Imaging, North Billerica, MA) and Optison (GE Healthcare AS, Oslo, Norway). Physicochemical characteristics were measured with a Multisizer Coulter Counter (Beckman Coulter, Fullerton, CA). Two ultrasound systems (Aplio 500; Toshiba Medical Systems Corp, Tochigi-ken, Japan; and Logiq E9; GE Healthcare, Little Chalfont, England) were used with different transducers. Contrast enhancement was measured in vitro by dose-ranging measurements using a custom-built beaker setup; in vivo imaging performances were compared in pigs (heart and liver) and rabbits (liver). Quantitative analyses were performed with VueBox quantification software (Bracco Suisse SA, Plan-les-Ouates, Switzerland). Measured physicochemical characteristics were in agreement with those provided by the manufacturers. In vitro data demonstrated that the performance of SonoVue was similar to or better than that of Definity but superior to Optison (normalized scattered power 2- to 10-fold higher with SonoVue). Similar results were obtained in vivo, although the duration of enhancement in the pig heart was longer for SonoVue compared to Definity, and quantitative analysis revealed higher enhancement for SonoVue (1.5-fold increase). For liver imaging, SonoVue and Definity showed similar contrast enhancement and duration of enhancement, but compared to Optison, both peak enhancement and duration of enhancement were superior for SonoVue (up to 2-fold increase). Imaging performance of SonoVue was similar to or slightly better than that of Definity, but it was superior to Optison for the conditions used in this study. © 2017 by the American Institute of Ultrasound in Medicine.

  15. Agent-oriented commonsense knowledge base

    Institute of Scientific and Technical Information of China (English)

    陆汝钤; 石纯一; 张松懋; 毛希平; 徐晋晖; 杨萍; 范路

    2000-01-01

    Common sense processing has been the key difficulty in Al community. Through analyzing various research methods on common sense, a large-scale agent-oriented commonsense knowledge base is described in this paper. We propose a new type of agent——CBS agent, specify common sense oriented semantic network descriptive language-Csnet, augment Prolog for common sense, analyze the ontology structure, and give the execution mechanism of the knowledge base.

  16. Iron oxide nanorods as high-performance magnetic resonance imaging contrast agents

    Science.gov (United States)

    Mohapatra, Jeotikanta; Mitra, Arijit; Tyagi, Himanshu; Bahadur, D.; Aslam, M.

    2015-05-01

    An efficient magnetic resonance imaging (MRI) contrast agent with a high R2 relaxivity value is achieved by controlling the shape of iron oxide to rod like morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of 70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity value of 608 mM-1 s-1. The enhanced MRI contrast of nanorods is attributed to their higher surface area and anisotropic morphology. The higher surface area induces a stronger magnetic field perturbation over a larger volume more effectively for the outer sphere protons. The shape anisotropy contribution is understood by calculating the local magnetic field of nanorods and spherical nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical geometry, the induced magnetic field of a rod is stronger and hence the stronger magnetic field over a large volume leads to a higher R2 relaxivity of nanorods.An efficient magnetic resonance imaging (MRI) contrast agent with a high R2 relaxivity value is achieved by controlling the shape of iron oxide to rod like morphology with a length of 30-70 nm and diameter of 4-12 nm. Fe3O4 nanorods of 70 nm length, encapsulated with polyethyleneimine show a very high R2 relaxivity value of 608 mM-1 s-1. The enhanced MRI contrast of nanorods is attributed to their higher surface area and anisotropic morphology. The higher surface area induces a stronger magnetic field perturbation over a larger volume more effectively for the outer sphere protons. The shape anisotropy contribution is understood by calculating the local magnetic field of nanorods and spherical nanoparticles under an applied magnetic field (3 Tesla). As compared to spherical geometry, the induced magnetic field of a rod is stronger and hence the stronger magnetic field over a large volume leads to a higher R2 relaxivity of nanorods. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr00055f

  17. Contrast-enhanced MR angiography: does a higher relaxivity MR contrast agent permit a reduction of the dose administered for routine vascular imaging applications?

    Science.gov (United States)

    Xing, Xiaoying; Zeng, Xiangzhu; Li, Xuan; Zhao, Qiang; Kirchin, Miles A; Pirovano, Gianpaolo; Wang, Xiaoying; Li, Yuan; Iezzi, Roberto; De Cobelli, Francesco

    2015-02-01

    The authors prospectively compared single dose (0.1 mmol/kg bodyweight) gadobenate dimeglumine with double dose (0.2 mmol/kg bodyweight) gadopentetate dimeglumine for contrast-enhanced magnetic resonance angiography (CE-MRA) in patients with suspected or known steno-occlusive disease of the carotid, renal or peripheral vasculature using an intra-individual crossover study design. Twenty-eight patients with suspected or known steno-occlusive disease of the carotid (n = 16), renal (n = 5) or peripheral arteries (n = 7) were randomised to receive either 0.1 mmol/kg gadobenate dimeglumine or 0.2 mmol/kg gadopentetate dimeglumine for a first CE-MRA procedure. After 3-5 days all patients underwent a second identical CE-MRA procedure with the other contrast agent. Three blinded readers assessed images for vessel anatomical delineation, disease detection/exclusion, and global preference. Diagnostic performance for detection of ≥51 % stenosis was determined for 20/28 patients who also underwent digital subtraction angiography (DSA). Non-inferiority was assessed using the Wilcoxon signed rank, McNemar and Wald tests. Quantitative (signal-to-noise and contrast-to-noise ratio) enhancement based on 3D maximum intensity projection reconstructions was compared. No differences were noted for any qualitative parameter. Equivalence was reported for all diagnostic preference end-points. Superiority for gadobenate dimeglumine was reported by all readers for sensitivity for disease detection (80.8-86.5 vs. 75.0-82.7 %). Quantitative enhancement was similar for single dose gadobenate dimeglumine and double dose gadopentetate dimeglumine. Under identical examination conditions a single 0.1 mmol/kg body weight dose of gadobenate dimeglumine can fully replace a double 0.2 mmol/kg body weight dose of gadopentetate dimeglumine for routine CE-MRA procedures.

  18. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents

    Science.gov (United States)

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  19. Experimental validation of proton transverse relaxivity models for superparamagnetic nanoparticle MRI contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Carroll, Matthew R J; Woodward, Robert C; House, Michael J; St Pierre, Timothy G [Centre for Strategic Nanofabrication, School of Physics, University of Western Australia, 35 Stirling Highway, Crawley, WA 6009 (Australia); Teoh, Wey Yang; Amal, Rose [ARC Centre of Excellence for Functional Nanomaterials, School of Chemical Engineering and Industrial Chemistry, University of New South Wales, Sydney, NSW 2052 (Australia); Hanley, Tracey L, E-mail: stpierre@physics.uwa.edu.au [Bragg Institute, Australian Nuclear Science and Technology Organization, New Illawarra Road, Lucas Heights, NSW 2234 (Australia)

    2010-01-22

    Analytical models of proton transverse relaxation rate enhancement by magnetic nanoparticles were tested by making measurements on model experimental systems in a field of 1.4 T. Proton relaxivities were measured for five aqueous suspensions of iron oxide (maghemite) nanoparticles with nominal mean particle sizes of 6, 8, 10, 11, and 13 nm. Proton relaxivity increased with mean particle size ranging from 13 s{sup -1} mM Fe{sup -1} for the 6 nm sample, up to 254 s{sup -1} mM Fe{sup -1} for the 13 nm sample. A strong correlation between the measured and predicted values of the relaxivity was observed, with the predicted values being consistently higher than the measured values. The results indicate that the models give a reasonable agreement with experimental results and hence can be used as the basis for the design of new magnetic resonance imaging contrast and labelling agents.

  20. Aptamer-Modified Temperature-Sensitive Liposomal Contrast Agent for Magnetic Resonance Imaging.

    Science.gov (United States)

    Zhang, Kunchi; Liu, Min; Tong, Xiaoyan; Sun, Na; Zhou, Lu; Cao, Yi; Wang, Jine; Zhang, Hailu; Pei, Renjun

    2015-09-14

    A novel aptamer modified thermosensitive liposome was designed as an efficient magnetic resonance imaging probe. In this paper, Gd-DTPA was encapsulated into an optimized thermosensitive liposome (TSL) formulation, followed by conjugation with AS1411 for specific targeting against tumor cells that overexpress nucleolin receptors. The resulting liposomes were extensively characterized in vitro as a contrast agent. As-prepared TSLs-AS1411 had a diameter about 136.1 nm. No obvious cytotoxicity was observed from MTT assay, which illustrated that the liposomes exhibited excellent biocompatibility. Compared to the control incubation at 37 °C, the liposomes modified with AS1411 exhibited much higher T1 relaxivity in MCF-7 cells incubated at 42 °C. These data indicate that the Gd-encapsulated TSLs-AS1411 may be a promising tool in early cancer diagnosis.

  1. Erythrocytes and microbubble contrast agents, improve the therapeutic efficiency of high intensity focused ultrasound

    Science.gov (United States)

    Takegami, Kenji; Kaneko, Yukio; Watanabe, Toshiaki; Maruyama, Toshiyuki; Matsumoto, Yoichiro; Nagawa, Hirokazu

    2005-03-01

    Erythrocytes, an well as Levovist microbubble contrast agent, enhance the heating effect of high intensity focused ultrasound (HIFU) and increase the coagulation volume produced by HIFU irradiation. In vitro experiments used human plasma with various concentrations of human erythrocytes in combination with or without Levovist. In vivo experiments used eight Japan white rabbits with three levels of anaemia. Using a 2.17 MHz transducer, HIFU was applied for 60 seconds, and the temperature rise and the volume of coagulation necrosis was evaluated. There was a significant correlation between the HIFU-induced temperature rise and hematocrit, with a correlation coefficient of 0.998 (p=0.0001). Although the temperature rise was smaller at low hematocrit, it was significantly increased by adding Levovist to the suspension (panaemia group was significantly increased by using Levovist (p<0.01).

  2. Effects of dissolved gases and an echo contrast agent on ultrasound mediated in vitro gene transfection.

    Science.gov (United States)

    Ogawa, Ryohei; Kondo, Takashi; Honda, Hidemi; Zhao, Qing Li; Fukuda, Shigekazu; Riesz, Peter

    2002-09-01

    The effects of acoustic cavitation on in vitro transfection by ultrasound were investigated. HeLa cells were exposed to 1.0 MHz continuous ultrasound in culture media containing the luciferase gene. Transfection efficiency was elevated when an echo contrast agent, Levovist was added or air was dissolved in the medium. When cells were sonicated in medium saturated with Ar, N2 or N2O which have different gamma values (Cp/Cv), or were saturated with He, Ar or Ne with different thermal conductivities, the effectiveness for the dissolved gases in the ultrasound mediated transfection was Ar > N2 > N2O or Ar > Ne > He, respectively. When free radical formation in water by ultrasound was monitored as a measure of inertial cavitation, it was similarly affected by dissolved gases. These results indicate that the efficiency of ultrasound mediated transfection was significantly affected either by occurrence of or by modification of inertial cavitation due to various gases.

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

    Science.gov (United States)

    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.

  4. Dimethyl sulfoxide (DMSO) as a potential contrast agent for brain tumors.

    Science.gov (United States)

    Delgado-Goñi, T; Martín-Sitjar, J; Simões, R V; Acosta, M; Lope-Piedrafita, S; Arús, C

    2013-02-01

    Dimethyl sulfoxide (DMSO) is commonly used in preclinical studies of animal models of high-grade glioma as a solvent for chemotherapeutic agents. A strong DMSO signal was detected by single-voxel MRS in the brain of three C57BL/6 control mice during a pilot study of DMSO tolerance after intragastric administration. This led us to investigate the accumulation and wash-out kinetics of DMSO in both normal brain parenchyma (n=3 control mice) by single-voxel MRS, and in 12 GL261 glioblastomas (GBMs) by single-voxel MRS (n=3) and MRSI (n=9). DMSO accumulated differently in each tissue type, reaching its highest concentration in tumors: 6.18 ± 0.85 µmol/g water, 1.5-fold higher than in control mouse brain (pDMSO changes revealed clear hotspots of differential spatial accumulation in GL261 tumors. Additional MRSI studies with four mice bearing oligodendrogliomas (ODs) revealed similar results as in GBM tumors. The lack of T(1) contrast enhancement post-gadolinium (gadopentetate dimeglumine, Gd-DTPA) in control mouse brain and mice with ODs suggested that DMSO was fully able to cross the intact blood-brain barrier in both normal brain parenchyma and in low-grade tumors. Our results indicate a potential role for DMSO as a contrast agent for brain tumor detection, even in those tumors 'invisible' to standard gadolinium-enhanced MRI, and possibly for monitoring heterogeneities associated with progression or with therapeutic response. Copyright © 2012 John Wiley & Sons, Ltd.

  5. Efficacy of Black Tea as a Negative Oral Contrast Agent for MR Cholangiopancreatography (MRCP

    Directory of Open Access Journals (Sweden)

    Amir Hossein Jalali

    2010-05-01

    Full Text Available Background/Objective: Evaluation of the use of black tea as negative oral contrast agent in MR cholangiopancreatography (MRCP."nPatients and Methods: Thirty-five patients (mean age, 50.3±19.2 years, who were referred for MRCP, entered in this study. MRCP was performed before, after 5 minutes and after 15 minutes following consumption of 300 ml of black tea. Depiction of the gall bladder, cystic duct, proximal and distal parts of the common bile duct (CBD, intra hepatic ducts, ampula of Vater, main pancreatic duct (MPD and signal loss of the stomach and three different segments of the duodenum were investigated according to VAS and Lickert scores."nResults: Regarding visibility of seven different anatomical parts of the pancreatobiliary tree (gall bladder, cystic duct, CBD, common hepatic duct, intrahepatic duct, ampula of Vater and MPD, the post procedure images were better visualized only in the distal part of CBD, ampula of vater and MPD both in Lickert and VAS scoring (all Ps≤0.001."nThere was no significant difference between the images 5 and 15 minutes after tea consumption. Regarding the obliteration of high signal in the stomach and three different parts of the duodenum, all post tea images of the mentioned parts showed significant disappearance of high signal in Lickert and VAS scoring systems (all Ps≤0.001. "nConclusion: Black tea is an affordable, cheap, available, safe, and efficient oral negative contrast agent for MRCP which reduces the signal intensity of fluids in the gastrointestinal tract and is also efficient for better depiction of MPD, distal part of CBD and ampula.

  6. Biodegradable human serum albumin nanoparticles as contrast agents for the detection of hepatocellular carcinoma by magnetic resonance imaging.

    Science.gov (United States)

    Watcharin, Waralee; Schmithals, Christian; Pleli, Thomas; Köberle, Verena; Korkusuz, Hüdayi; Huebner, Frank; Zeuzem, Stefan; Korf, Hans W; Vogl, Thomas J; Rittmeyer, Claudia; Terfort, Andreas; Piiper, Albrecht; Gelperina, Svetlana; Kreuter, Jörg

    2014-05-01

    Tumor visualization by magnetic resonance imaging (MRI) and nanoparticle-based contrast agents may improve the imaging of solid tumors such as hepatocellular carcinoma (HCC). In particular, human serum albumin (HSA) nanoparticles appear to be a suitable carrier due to their safety and feasibility of functionalization. In the present study HSA nanoparticles were conjugated with gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) using carbodiimide chemistry. The nanoparticles had a uniform spherical shape and a diameter of 235±19nm. For better optical visualization in vitro and in vivo, the HSA-Gd nanoparticles were additionally labeled with rhodamine 123. As shown by confocal microscopy and flow cytometry analysis, the fluorescent nanoparticles were readily taken up by Huh-7 hepatocellular carcinoma cells. After 24h incubation in blood serum, less than 5% of the Gd(III) was released from the particles, which suggests that this nanoparticulate system may be stable in vivo and, therefore, may serve as potentially safe T1 MRI contrast agent for MRI of hepatocellular carcinoma.

  7. Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging.

    Science.gov (United States)

    Mouffouk, Fouzi; Simão, Teresa; Dornelles, Daniel F; Lopes, André D; Sau, Pablo; Martins, Jorge; Abu-Salah, Khalid M; Alrokayan, Salman A; Rosa da Costa, Ana M; dos Santos, Nuno R

    2015-01-01

    Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI.

  8. Surface Modification of Gd Nanoparticles with pH-Responsive Block Copolymers for Use As Smart MRI Contrast Agents.

    Science.gov (United States)

    Zhu, Liping; Yang, Yuan; Farquhar, Kirsten; Wang, Jingjing; Tian, Chixia; Ranville, James; Boyes, Stephen G

    2016-02-01

    Despite recent advances in the understanding of fundamental cancer biology, cancer remains the second most common cause of death in the United States. One of the primary factors indicative of high cancer morbidity and mortality and aggressive cancer phenotypes is tumors with a low extracellular pH (pHe). Thus, the ability to measure tumor pHe in vivo using noninvasive and accurate techniques that also provide high spatiotemporal resolution has become increasingly important and is of great interest to researchers and clinicians. In an effort to develop a pH-responsive magnetic resonance imaging (MRI) contrast agent (CA) that has the potential to be used to measure tumor pHe, well-defined pH-responsive polymers, synthesized via reversible addition-fragmentation chain transfer polymerization, were attached to the surface of gadolinium-based nanoparticles (GdNPs) via a "grafting to" method after reduction of the thiocarbonylthio end groups. The successful modification of the GdNPs was verified by transmission electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis and dynamic light scattering. The performance of the pH-responsive polymer modified GdNPs was then evaluated for potential use as smart MRI CAs via monitoring the relaxivity changes with changing environmental pH. The results suggested that the pH-responsive polymers can be used to effectively modify the GdNPs surface to prepare a smart contrast agent for MRI.

  9. Subharmonic analysis using singular-value decomposition of ultrasound contrast agents.

    Science.gov (United States)

    Mamou, Jonathan; Ketterling, Jeffrey A

    2009-06-01

    Ultrasound contrast agents (UCAs) are designed to be used below 10 MHz, but interest is growing in studying the response of agents to high-frequency ultrasound. In this study, the subharmonic response of polymer-shelled UCAs with a mean diameter of 1.1 mum excited with 40-MHz tone-bursts of 1-20 cycles was analyzed. UCAs were diluted in water and streamed through a flow phantom that permitted single-bubble backscatter events to be acquired at peak-negative pressures from 0.75 to 5.0 MPa. At each exposure condition, 1000 single-bubble-backscatter events were digitized. Subharmonic content at 20 MHz was screened using a conventional and a singular-value-decomposition (SVD) method. The conventional method evaluated each event spectrum individually while the SVD method treated the 1000-event data set at one time. A subharmonic score (SHS) indicative of how much subharmonic content a 1000-event data set contained was computed for both methods. Empirical-simulation results indicated that SHSs obtained from the two methods were linearly related. Also, experimental data with both methods indicated that subharmonic likelihood increased with pulse duration and peaked near 2 MPa. The SVD method also yielded quantitative information about subharmonic events not available with the conventional method.