WorldWideScience

Sample records for scattering contrast agents

  1. Microbubbles as x-ray scattering contrast agents using analyzer-based imaging

    Energy Technology Data Exchange (ETDEWEB)

    Arfelli, F [Department of Physics, University of Trieste, Via Valerio 2, 34127 Trieste (Italy); Rigon, L [Istituto Nazionale di Fisica Nucleare-Sezione di Trieste, Via Valerio 2, 34127 Trieste (Italy); Menk, R H [Sincrotrone Trieste S.C.p.A., Strada Statale 14-km 163.5 in AREA Science Park, 34012 Basovizza, Trieste (Italy)

    2010-03-21

    Conventional contrast agents utilized in diagnostic radiology are based on x-ray absorption properties; alternative physical principles capable of providing a contrast enhancement in radiographs have never been applied. This study exploits the possibility of using a novel type of contrast media based on x-ray scattering. The contrast agents consist of microbubble echo-enhancing agents, usually applied in ultrasound examinations, which are invisible with conventional x-ray absorption techniques. The experiment was carried out at the medical beamline of the synchrotron radiation laboratory ELETTRA in Trieste, Italy. A flat silicon analyzer crystal typically used for diffraction-enhanced imaging was utilized as a tool for detecting the scattering properties of the contrast agents. In analyzer-based imaging, it is possible to detect the scattering properties of the sample by shifting the analyzer crystal to selected positions of its reflectivity curve. In particular, when the sample consists of a large number of micro-particles an overall effect can be observed. Phantoms containing contrast agents based on microbubbles were imaged at different angular positions of the analyzer crystal. High visibility of the details was demonstrated, and a strong contrast enhancement was measured compared to normal x-ray absorption techniques.

  2. Object reconstruction in scattering medium using multiple elliptical polarized speckle contrast projections and optical clearing agents

    Science.gov (United States)

    Moshe, Tomer; Firer, Michael A.; Abookasis, David

    2015-05-01

    In this paper, we present a hybrid method for improving the imaging quality of objects obscured within a scattering environment by combining multiple elliptical polarized speckle contrast projections with the use of optical clearing agents (OCAs). Elliptically polarized light enables the probing of subsurface volumes, where OCAs decrease light scattering while increasing photons' penetration depth through the medium. Experiments were conducted on object sample and prostate cancer cells embedded within ex vivo biological samples (chicken breasts) in reflection configuration. After immersion with OCAs, the medium was irradiated with an elliptically polarized laser beam and multiple polarized speckled images obtained from a lens array were first converted to speckled contrast images and then processed using a self-deconvolution shift-and-add algorithm. The conversion to contrast images and multiple perspectives acquisition was found to emphasize contrast. Analysis of image quality indicated improvement in object visualization by the combination of elliptical polarization and OCAs. This enhanced imaging strategy may advance the development of improved methods in biomedicine field, specifically biomedical tomography.

  3. Surface modes and acoustic scattering of microspheres and ultrasound contrast agents.

    Science.gov (United States)

    Falou, Omar; Jafari Sojahrood, Amin; Kumaradas, J Carl; Kolios, Michael C

    2012-09-01

    Surface modes of spherical objects subject to ultrasound excitation have been recently proposed to explain experimental measurements of scattering from microspheres and ultrasound contrast agents (UCAs). In this work, the relationship between surface modes and resonance frequencies of microspheres and UCAs is investigated. A finite-element model, built upon the fundamentals of wave propagation and structural mechanics, was introduced and validated against analytical solutions (error <5%). Numerical results showed the existence of a systematic relationship between resonance frequencies and surface modes of a 30 μm microsphere driven at 1-70 MHz. On the contrary, for a 100 nm shelled, 4 μm diameter UCA, no clear relationship between the resonance frequencies and the surface modes was found in the frequency range examined. Instead, the UCA exhibited a collection of complex oscillations, which appear to be a combination of various surface modes and displacements. A study of the effects of varying the shell properties on the backscatter showed the presence of peaks in the backscatter of thick-shelled UCAs, which are not predicted by previous models. In summary, this work presents a systematic effort to examine scattering and surface modes from ultrasound contrast agents using finite-element models.

  4. Influence of Guided Waves in Tibia on Non-linear Scattering of Contrast Agents.

    Science.gov (United States)

    Wang, Diya; Zhong, Hui; Zhai, Yu; Hu, Hong; Jin, Bowen; Wan, Mingxi

    2016-02-01

    The aim of this study was to elucidate the linear and non-linear responses of ultrasound contrast agent (UCA) to frequency-dispersive guided waves from the tibia cortex, particularly two individual modes, S0 (1.23 MHz) and A1 (2.06 MHz). The UCA responses to guided waves were illustrated through the Marmottant model derived from measured guided waves, and then verified by continuous infusion experiments in a vessel-tibia flow phantom. These UCA responses were further evaluated by the enhanced ratio of peak values and the resolutions of UCA backscattered echoes. Because of the individual modes S0 and A1 in the tibia, the peak values of the UCA backscattered echoes were enhanced by 83.57 ± 7.35% (p wave disturbances, respectively. Even though the resolution was partly degenerated, the subharmonic detection sensitivity of UCA was improved by the guided waves. Thus, UCA responses to the double-frequency guided waves should be further explored to benefit the detection of capillary perfusion in tissue layers near the bone cortex, particularly for perfusion imaging in the free flaps and skeletal muscles. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  5. Optical Imaging of Cells with Gold Nanoparticle Clusters as Light Scattering Contrast Agents

    DEFF Research Database (Denmark)

    Tanev, Stoyan

    2011-01-01

    This chapter has two main objectives. First, to review a number of examples illustrating the application of the FDTD approach to the modeling of some typical light scattering configurations that could be associated with flow cytometry. Second, to provide a thorough discussion of these new...... developments in advanced cytometry research by pointing out potential new research directions. A brief description of the FDTD method focusing on the features associated with its application to modeling of light scattering and OPCM cell imaging experiments is provided. The examples include light scattering...

  6. Discriminating between absorption and scattering coefficients in optical characterisation measurements on gold nanoparticle based photoacoustic contrast agents

    NARCIS (Netherlands)

    Ungureanu, C.; Manohar, Srirang; van Leeuwen, Ton; Amelink, A.; Sterenborg, Henricus J.C.M.; Oraevsky, Alexander A.; Wang, Lihong V.

    2009-01-01

    Plasmon resonant nanoparticles such as gold nanoshells and gold nanorods can be tuned to possess sharp interaction peaks in the near-infrared wavelength regions. These have great importance as contrast agents in photoacoustic imaging and as photothermal agents for therapeutic applications due to

  7. Ultrasound contrast agents : dynamics of coated bubbles

    NARCIS (Netherlands)

    Overvelde, M.L.J.

    2010-01-01

    Contrast-enhanced ultrasound imaging relies on the nonlinear scattering of microbubbles suspended in an ultrasound contrast agent. The bubble dynamics is described by a Rayleigh-Plesset-type equation, and the success of harmonic imaging using contrast agents has always been attributed to the

  8. Flow cytometry with gold nanoparticles and their clusters as scattering contrast agents: FDTD simulation of light-cell interaction.

    Science.gov (United States)

    Tanev, Stoyan; Sun, Wenbo; Pond, James; Tuchin, Valery V; Zharov, Vladimir P

    2009-09-01

    The formulation of the finite-difference time-domain (FDTD) approach is presented in the framework of its potential applications to in-vivo flow cytometry based on light scattering. The consideration is focused on comparison of light scattering by a single biological cell alone in controlled refractive-index matching conditions and by cells labeled by gold nanoparticles. The optical schematics including phase contrast (OPCM) microscopy as a prospective modality for in-vivo flow cytometry is also analyzed. The validation of the FDTD approach for the simulation of flow cytometry may open up a new avenue in the development of advanced cytometric techniques based on scattering effects from nanoscale targets. 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

  9. Flow cytometry with gold nanoparticlesand their clusters as scattering contrast agents: FDTD simulation of light-cell interaction

    DEFF Research Database (Denmark)

    Tanev, Stoyan; Sun, Wenbo; Pond, James

    2009-01-01

    The formulation of the Finite-Difference Time-Domain (FDTD) approach is presented in the framework of its potential applications to in vivo flow cytometry based on light scattering. The consideration is focused on comparison of light scattering by a single biological cell alone in controlled refr...

  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. Nuclear magnetic resonance contrast agents

    Science.gov (United States)

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

    1997-12-30

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

  12. Ultrasound Contrast Agent Microbubble Dynamics

    NARCIS (Netherlands)

    Overvelde, M.L.J.; Vos, Henk; de Jong, N.; Versluis, Andreas Michel; Paradossi, Gaio; Pellegretti, Paolo; Trucco, Andrea

    2010-01-01

    Ultrasound contrast agents are traditionally used in ultrasound-assisted organ perfusion imaging. Recently the use of coated microbubbles has been proposed for molecular imaging applications where the bubbles are covered with a layer of targeting ligands to bind specifically to their target cells.

  13. Ultrasound contrast agents: An overview

    Energy Technology Data Exchange (ETDEWEB)

    Cosgrove, David [Imaging Sciences Department, Imperial College, Hammersmith Hospital, London (United Kingdom)]. E-mail: d.cosgrove@csc.mrc.ac.uk

    2006-12-15

    With the introduction of microbubble contrast agents, diagnostic ultrasound has entered a new era that allows the dynamic detection of tissue flow of both the macro and microvasculature. Underpinning this development is the fact that gases are compressible, and thus the microbubbles expand and contract in the alternating pressure waves of the ultrasound beam, while tissue is almost incompressible. Special software using multiple pulse sequences separates these signals from those of tissue and displays them as an overlay or on a split screen. This can be done at low acoustic pressures (MI < 0.3) so that the microbubbles are not destroyed and scanning can continue in real time. The clinical roles of contrast enhanced ultrasound scanning are expanding rapidly. They are established in echocardiography to improve endocardial border detection and are being developed for myocardial perfusion. In radiology, the most important application is the liver, especially for focal disease. The approach parallels that of dynamic CT or MRI but ultrasound has the advantages of high spatial and temporal resolution. Thus, small lesions that can be indeterminate on CT can often be studied with ultrasound, and situations where the flow is very rapid (e.g., focal nodular hyperplasia where the first few seconds of arterial perfusion may be critical to making the diagnosis) are readily studied. Microbubbles linger in the extensive sinusoidal space of normal liver for several minutes whereas they wash out rapidly from metastases, which have a low vascular volume and thus appear as filling defects. The method has been shown to be as sensitive as three-phase CT. Microbubbles have clinical uses in many other applications where knowledge of the microcirculation is important (the macrocirculation can usually be assessed adequately using conventional Doppler though there are a few important situations where the signal boost given by microbubbles is useful, e.g., transcranial Doppler for evaluating

  14. MRI contrast agents: Classification and application (Review).

    Science.gov (United States)

    Xiao, Yu-Dong; Paudel, Ramchandra; Liu, Jun; Ma, Cong; Zhang, Zi-Shu; Zhou, Shun-Ke

    2016-11-01

    Magnetic resonance imaging (MRI) contrast agents are categorised according to the following specific features: chemical composition including the presence or absence of metal atoms, route of administration, magnetic properties, effect on the magnetic resonance image, biodistribution and imaging applications. The majority of these agents are either paramagnetic ion complexes or superparamagnetic magnetite particles and contain lanthanide elements such as gadolinium (Gd3+) or transition metal manganese (Mn2+). These elements shorten the T1 or T2 relaxation time, thereby causing increased signal intensity on T1-weighted images or reduced signal intensity on T2-weighted images. Most paramagnetic contrast agents are positive agents. These agents shorten the T1, so the enhanced parts appear bright on T1-weighted images. Dysprosium, superparamagnetic agents and ferromagnetic agents are negative contrast agents. The enhanced parts appear darker on T2-weighted images. MRI contrast agents incorporating chelating agents reduces storage in the human body, enhances excretion and reduces toxicity. MRI contrast agents may be administered orally or intravenously. According to biodistribution and applications, MRI contrast agents may be categorised into three types: extracellular fluid, blood pool and target/organ-specific agents. A number of contrast agents have been developed to selectively distinguish liver pathologies. Some agents are also capable of targeting other organs, inflammation as well as specific tumors.

  15. 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

  16. New ultrasound contrast agents and technological innovations.

    Science.gov (United States)

    de Jong, N; Ten Cate, F J

    1996-06-01

    Further development of clinical diagnostic procedures, as well as new diagnostic techniques, requires ultrasound specific contrast agents as well as technological innovations. This paper reviews contrast agents developed in the last decade, which are all based on free gas or encapsulated gas bubbles.

  17. Contrast Agent in Magnetic Resonance Imaging

    DEFF Research Database (Denmark)

    Vu-Quang, Hieu

    2015-01-01

    Nanoparticles have been employed as contrast agent in magnetic resonance imaging (MRI) in order to improve sensitivity and accuracy in diagnosis. In addition, these contrast agents are potentially combined with other therapeutic compounds or near infrared bio-imaging (NIR) fluorophores to obtain...... theranostic or dual imaging purposes, respectively. There were two main types of MRI contrast agent that were synthesized during this PhD project including fluorine containing nanoparticles and magnetic nanoparticles. In regard of fluorine containing nanoparticles, there were two types contrast agent...... that were synthesized in project I and II. In project I, Poly (lactic-co-glycolic acid)-block-poly (ethylene glycol)-Folate Pefluorooctyl Bromide/Indocyanine green/ Doxorubicin (PLGA-PEG-Folate PFOB/ICG/Dox) has been formulated for the dual imaging NIR and 19F MRI as well as in the combination of Dox...

  18. Historical Perspective of Imaging Contrast Agents.

    Science.gov (United States)

    Zamora, Carlos A; Castillo, Mauricio

    2017-11-01

    Contrast agents were introduced early in the history of medical imaging. Iodine-based intravascular agents became the radiographic compounds of choice and refinements of their chemical structures led to the highly tolerated low-osmolarity agents in use today. Gadolinium became the most popular compound for MR imaging; however, recognition of nephrogenic systemic fibrosis and in vivo dechelation intensified research on their safety profile. Ultrasonography contrast media evolved from manual injections of air through agitated saline solutions to microbubbles with different gases. Research has concentrated on bubble stabilization and development of small but sufficiently echogenic particles. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Dendrimers as high relaxivity MR contrast agents.

    Science.gov (United States)

    Longmire, Michelle R; Ogawa, Mikako; Choyke, Peter L; Kobayashi, Hisataka

    2014-01-01

    Dendrimers are versatile macromolecules with tremendous potential as magnetic resonance imaging (MRI) contrast agents. Dendrimer-based agents provide distinct advantages over low-molecular-weight gadolinium chelates, including enhanced r1 relaxivity due to slow rotational dynamics, tunable pharmacokinetics that can be adapted for blood pool, liver, kidney, and lymphatic imaging, the ability to be a drug carrier, and flexibility for labeling due to their inherent multivalency. Clinical applications are increasingly being developed, particularly in lymphatic imaging. Herein we present a broad overview of dendrimer-based MRI contrast agents with attention to the unique chemistry and physical properties as well as emerging clinical applications. © 2013 Wiley Periodicals, Inc.

  20. High Framerate Imaging of Ultrasound Contrast Agents

    OpenAIRE

    Viti, Jacopo

    2016-01-01

    markdownabstractUltrasound contrast agents (UCAs) consists of a suspension of tiny gas bubbles that is injected into a patient's bloodstream to enhance the visualization of blood in ultrasound images. As UCAs respond differently to ultrasound pulses compared to the surrounding soft tissues and blood, it is possible to employ specialized techniques to identify and isolate UCAs in an ultrasound image. This is commonly referred to as Ultrasound Contrast Imaging. This PhD thesis evaluates several...

  1. High Framerate Imaging of Ultrasound Contrast Agents

    NARCIS (Netherlands)

    J. Viti (Jacopo)

    2016-01-01

    markdownabstractUltrasound contrast agents (UCAs) consists of a suspension of tiny gas bubbles that is injected into a patient's bloodstream to enhance the visualization of blood in ultrasound images. As UCAs respond differently to ultrasound pulses compared to the surrounding soft tissues and

  2. Thoracic duct lymphography by subcutaneous contrast agent ...

    African Journals Online (AJOL)

    A 4-year-old male Japanese Shiba Inu presented with recurrent chylothorax. The thoracic duct was successfully imaged using computed tomography after the injection of an iodine contrast agent into the subcutaneous tissue surrounding the anus. The thoracic duct was successfully ligated and pericardectomy performed via ...

  3. 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...

  4. Contrast in coherent raman scattering microscopy

    NARCIS (Netherlands)

    Garbacik, E.T.

    2014-01-01

    Coherent anti-Stokes Raman scattering (CARS) microscopy is becoming a widely used technique for sub-micron, chemically-selective imaging at high rates of speed In this thesis I discuss three methods for increasing the specificity and selectivity of coherent Raman experiments. The first method is the

  5. 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

  6. 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. .

  7. Magnetic Resonance Imaging (MRI Contrast Agents for Tumor Diagnosis

    Directory of Open Access Journals (Sweden)

    Weiren Cheng

    2013-01-01

    Full Text Available This review focuses on MRI contrast agents for tumor diagnosis. Several types of low molecular weight Gd3+-based complexes and dextran-coated superparamagnetic iron oxide (SPIO nanoparticles have been used for clinical tumor diagnosis as longitudinal relaxation time (T1 and transverse relaxation time (T2 MRI contrast agents, respectively. To further improve the sensitivity of MRI, new types of chelates for T1 MRI contrast agents and combination of low molecular weight T1 MRI contrast agents with different types of carriers have been investigated. Different types of materials for forming secure coating layers of SPIO and novel superparamagnetic particles with higher relaxivity values have been explored. Various types of ligands were applied to improve the capability to target tumor for both T1 and T2 contrast agents. Furthermore, MRI contrast agents for detection of tumor metabolism were also pursued.

  8. Ultrasound contrast agents: bubbles, drops and particles

    NARCIS (Netherlands)

    Lajoinie, Guillaume Pierre Rene

    2015-01-01

    The research on the medical use of microbubbles has coontinuously provided fascinating results for half a century. Investigating new agents or new uses of existing agents requires both innovative physics and ideas and extensive testing in-vitro and in vivo. The translation from the lab to the clinic

  9. Blood-pool contrast agent for pre-clinical computed tomography

    Science.gov (United States)

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

    2017-03-01

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

  10. 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.)

  11. Investigation of the effect of scattering agent and scattering albedo on modulated light propagation in water.

    Science.gov (United States)

    Mullen, Linda; Alley, Derek; Cochenour, Brandon

    2011-04-01

    A recent paper described experiments completed to study the effect of scattering on the propagation of modulated light in laboratory tank water [Appl. Opt.48, 2607 (2009)APOPAI0003-693510.1364/AO.48.002607]. Those measurements were limited to a specific scattering agent (Maalox antacid) with a fixed scattering albedo (0.95). The purpose of this paper is to study the effects of different scattering agents and scattering albedos on modulated light propagation in water. The results show that the scattering albedo affects the number of attenuation lengths that the modulated optical signal propagates without distortion, while the type of scattering agent affects the degree to which the modulation is distorted with increasing attenuation length. © 2011 Optical Society of America

  12. Contrast agents and renal cell apoptosis

    OpenAIRE

    Romano, Giulia

    2008-01-01

    Contrast media (CM) induce a direct toxic effect on renal tubular cells. This toxic effect may have a role in the pathophysiology of contrast nephropathy. I evaluated: (i) the cytotoxicity of CM [both low-osmolality (LOCM) and iso-osmolality (IOCM)], of iodine alone,and of an hyperosmolar solution (mannitol 8%) on human embryonic kidney (HEK 293), porcine proximal renal tubular (LLC-PK1), and canine Madin–Darby distal tubular renal (MDCK) cells; and (ii) the effectiveness of vario...

  13. 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.

  14. Detection of Contrast Agents: Plane Wave Versus Focused Transmission

    NARCIS (Netherlands)

    J. Viti (Jacopo); H.J. Vos (Rik); N. de Jong (Nico); F. Guidi (Francesco); P. Tortoli (Piero)

    2016-01-01

    textabstractUltrasound contrast agent (UCA) imaging provides a cost-effective diagnostic tool to assess tissue perfusion and vascular pathologies. However, excessive transmission (TX) levels may negatively impact both uniform diffusion and survival rates of contrast agents, limiting their density

  15. Inadvertent intrathecal use of ionic contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Leede, H. van der; Jorens, P.G. [Department of Intensive Care Medicine, University Hospital of Antwerp, Wilrijkstraat 10, 2650 Edegem (Belgium); Parizel, P. [Department of Radiology, University Hospital of Antwerp, Wilrijkstraat 10, 2650 Edegem (Belgium); Cras, P. [Department of Neurology, University Hospital of Antwerp, Wilrijkstraat 10, 2650 Edegem (Belgium)

    2002-07-01

    Intrathecal administration of ionic contrast media may cause severe and fatal neurotoxic reactions due to their hyperosmolarity and ionic nature. They are therefore strictly contraindicated for all radiologic applications involving the central nervous system (e.g., myelography). We present a case in which ioxitalamate was accidentally injected intrathecally. The patient recovered completely due to a combination of the different therapeutic options reported in the literature, including early mechanical ventilation and neuromuscular paralysis, aggressive control of seizures, elevation of head and trunk to prevent cephalad migration of contrast, steroids, cerebrospinal fluid drainage and lavage and prophylactic antibiotics. (orig.)

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

    Science.gov (United States)

    Ogunlade, Olumide; Beard, Paul

    2014-03-01

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

  17. 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.

  18. Microbubble spectroscopy of ultrasound contrast agents (A)

    NARCIS (Netherlands)

    van der Meer, S.M.; Dollet, B.; Chin, Chien T.; Bouakaz, Ayache; Voormolen, Marco; de Jong, N.; Versluis, Andreas Michel; Lohse, Detlef

    2006-01-01

    We present a new optical characterization of the behavior of single ultrasound contrast bubbles. The method consists of insonifying individual bubbles several times successively sweeping the applied frequency and recording movies of the bubble response up to 25 million frames per second with an

  19. Microbubble spectroscopy of ultrasound contrast agents

    NARCIS (Netherlands)

    van der Meer, S.M.; Dollet, B.; Voormolen, Marco M.; Chin, Chien T.; Bouakaz, Ayache; de Jong, N.; Versluis, Michel; Lohse, Detlef

    2007-01-01

    A new optical characterization of the behavior of single ultrasound contrast bubbles is presented. The method consists of insonifying individual bubbles several times successively sweeping the applied frequency, and to record movies of the bubble response up to 25 million frames/s with an ultrahigh

  20. Effect of static scatterers in laser speckle contrast imaging: an experimental study on correlation and contrast.

    Science.gov (United States)

    Vaz, Pedro Guilherme; Humeau-Heurtier, Anne; Figueiras, Edite; Correia, Carlos; Cardoso, Joao M R

    2017-12-05

    Laser speckle contrast imaging (LSCI) is a non-invasive microvascular blood flow assessment technique with good temporal and spatial resolutions. Most LSCI systems, including commercials devices, can only perform qualitative blood flow evaluation which is a major limitation of this technique. There are several factors that prevent LSCI to be a quantitative technique. Among these factors we can highlight the effect of static scatterers. The goal of this work was to study the influence of different static and dynamic scatterers concentrations on laser speckle correlation and contrast. In order to achieve this, a laser speckle prototype was developed and tested using an optical phantom with different concentrations of static and dynamic scatterers. It has been found that the laser speckle correlation can be used to estimate the relative concentration of static/dynamic scatterers within a sample. Moreover, the speckle correlation proved to be independent of the dynamic scatterers velocity which is a fundamental characteristic to be used as contrast correction method. Creative Commons Attribution license.

  1. Contrast agents and renal cell apoptosis.

    Science.gov (United States)

    Romano, Giulia; Briguori, Carlo; Quintavalle, Cristina; Zanca, Ciro; Rivera, Natalia V; Colombo, Antonio; Condorelli, Gerolama

    2008-10-01

    Contrast media (CM) induce a direct toxic effect on renal tubular cells. This toxic effect may have a role in the pathophysiology of contrast nephropathy. We evaluated (i) the cytotoxicity of CM [both low-osmolality (LOCM) and iso-osmolality (IOCM)], of iodine alone, and of an hyperosmolar solution (mannitol 8%) on human embryonic kidney (HEK 293), porcine proximal renal tubular (LLC-PK1), and canine Madin-Darby distal tubular renal (MDCK) cells; and (ii) the effectiveness of various antioxidant compounds [n-acetylcysteine (NAC), ascorbic acid and sodium bicarbonate] in preventing CM cytotoxicity. The cytotoxicity of CM was assessed at different time points, with different methods: cell viability, DNA laddering, flow cytometry, and caspase activation. Both LOCM and IOCM produced a concentration- and time-dependent increase in cell death as assessed by the different methods. On the contrary, iodine alone and hyperosmolar solution did not induce any significant cytotoxic effect. There was not any significant difference in the cytotoxic effect between LOCM and IOCM. Furthermore, both LOCM and IOCM caused a marked increase in caspase-3 and -9 activities and poly(ADP-ribose) fragmentation, while no effect on caspase-8/-10 was observed, thus indicating that the CM activated apoptosis mainly through the intrinsic pathway. Both CM induced an increase in protein expression levels of pro-apoptotic members of the Bcl2 family (Bim and Bad). NAC and ascorbic acid but not sodium bicarbonate had a dose-dependent protective effect on renal cells after 3 h incubation with high dose (200 mg iodine/mL) of both LOCM and IOCM. Both LOCM and IOCM induce a dose-dependent renal cell apoptosis. NAC and ascorbic acid but not sodium bicarbonate prevent this contrast-induced apoptosis.

  2. Hyperpolarized noble gases as contrast agents.

    Science.gov (United States)

    Zhou, Xin

    2011-01-01

    Hyperpolarized noble gases ((3)He and (129)Xe) can provide NMR signal enhancements of 10,000 to 100,000 times that of thermally polarized gases and have shown great potential for applications in lung magnetic resonance imaging (MRI) by greatly enhancing the sensitivity and contrast. These gases obtain a highly polarized state by employing a spin exchange optical pumping technique. In this chapter, the underlying physics of spin exchange optical pumping for production of hyperpolarized noble gases is explained and the basic components and procedures for building a polarizer are described. The storage and delivery strategies of hyperpolarized gases for in vivo imaging are discussed. Many of the problems that are likely to be encountered in practical experiments and the corresponding detailed approaches to overcome them are also discussed.

  3. Synthesis of ultrasound contrast agents: characteristics and size distribution analysis (secondary publication)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hak Jong [Program in Nano Science and Technology, Dept. of Transdisciplinary Studies, Seoul National University Graduate School of Convergence Science and Technology, Seoul (Korea, Republic of); Yoon, Tae Jong [Dept. of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam (Korea, Republic of); Yoon, Young Il [Dept. of Applied Bioscience, CHA University, Pocheon (Korea, Republic of)

    2017-10-15

    The purpose of this study was to establish a method for ultrasound (US) contrast agent synthesis and to evaluate the characteristics of the synthesized US contrast agent. A US contrast agent, composed of liposome and sulfur hexafluoride (SF6), was synthesized by dissolving 21 μmol 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine (DPPC, C40H80NO8P), 9 μmol cholesterol, and 1.9 μmol of dihexadecylphosphate (DCP, [CH3(CH2)15O]2P(O)OH) in chloroform. After evaporation in a warm water bath and drying for 12-24 hours, the contrast agent was synthesized using the sonication process by the addition of a buffer and SF6 gas. The size distribution of the bubbles was analyzed using dynamic light scattering measurement methods. The degradation curve was evaluated by assessing the change in the number of contrast agent bubbles using light microscopy immediately, 12, 24, 36, 48, 60, 72, and 84 hours after synthesis. The echogenicity of the synthesized microbubbles was compared with commercially available microbubbles (SonoVue, Bracco). contrast agent was synthesized successfully using an evaporation-drying-sonication method. Most bubbles had a mean diameter of 154.2 nm and showed marked degradation 24 hours after synthesis. Although no statistically significant differences were observed between SonoVue and the synthesized contrast agent, a difference in echogenicity was observed between the synthesized contrast agent and saline (P<0.01). We successfully synthesized a US contrast agent using an evaporation-dryingsonication method. These results may help future research in the fields of anticancer drug delivery, gene delivery, targeted molecular imaging, and targeted therapy.

  4. Perfusion Imaging with a Freely Diffusible Hyperpolarized Contrast Agent

    OpenAIRE

    Grant, Aaron K.; Vinogradov, Elena; Wang, Xiaoen; Lenkinski, Robert E.; Alsop, David C.

    2011-01-01

    Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized 13C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic 13C images acquired in rat brain with a balanced steady-state free precession (bSSFP) sequence following ...

  5. Biomedical applications of photoacoustic imaging with exogenous contrast agents.

    Science.gov (United States)

    Luke, Geoffrey P; Yeager, Doug; Emelianov, Stanislav Y

    2012-02-01

    Photoacoustic imaging is a biomedical imaging modality that provides functional information, and, with the help of exogenous contrast agents, cellular and molecular signatures of tissue. In this article, we review the biomedical applications of photoacoustic imaging assisted with exogenous contrast agents. Dyes, noble metal nanoparticles, and other constructs are contrast agents which absorb strongly in the near-infrared band of the optical spectrum and generate strong photoacoustic response. These contrast agents, which can be specifically targeted to molecules or cells, have been coupled with photoacoustic imaging for preclinical and clinical applications ranging from detection of cancer cells, sentinel lymph nodes, and micrometastasis to angiogenesis to characterization of atherosclerotic plaques. Multi-functional agents have also been developed, which can carry drugs or simultaneously provide contrast in multiple imaging modalities. Furthermore, contrast agents were used to guide and monitor the therapeutic procedures. Overall, photoacoustic imaging shows significant promise in its ability to assist in diagnosis, therapy planning, and monitoring of treatment outcome for cancer, cardiovascular disease, and other pathologies.

  6. Contrast agent enhanced pQCT of articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Kallioniemi, A S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Jurvelin, J S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Nieminen, M T [Department of Diagnostic Radiology, POB 50, 90029 OYS, Oulu University Hospital, Oulu (Finland); Lammi, M J [Department of Anatomy, Institute of Biomedicine, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Toeyraes, J [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland)

    2007-02-21

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T{sub 1,Gd} and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  7. Characterizing optical properties of nano contrast agents by using cross-referencing OCT imaging.

    Science.gov (United States)

    Xi, Jiefeng; Chen, Yongping; Li, Xingde

    2013-06-01

    We report a cross-referencing method to quickly and accurately characterize the optical properties of nanoparticles including the extinction, scattering, absorption and backscattering cross sections by using an OCT system alone. Among other applications, such a method is particularly useful for developing nanoparticle-based OCT imaging contrast agents. The method involves comparing two depth-dependent OCT intensity signals collected from two samples (with one having and the other not having the nanoparticles), to extract the extinction and backscattering coefficient, from which the absorption coefficient can be further deduced (with the help of the established scattering theories for predicting the ratio of the backscattering to total scattering cross section). The method has been experimentally validated using test nanoparticles and was then applied to characterizing gold nanocages. With the aid of this method, we were able to successfully synthesize scattering dominant gold nanocages for the first time and demonstrated the highest contrast enhancement ever achieved by the gold nanocages (and by any nanoparticles of a similar size and concentration) in an in vivo mouse tumor model. This method also enables quantitative analysis of contrast enhancement and provides a general guideline on choosing the optimal concentration and optical properties for the nanoparticle-based OCT contrast agents.

  8. Diethylenetriaminepentaacetic acid-gadolinium (DTPA-Gd)-conjugated polysuccinimide derivatives as magnetic resonance imaging contrast agents.

    Science.gov (United States)

    Lee, Ha Young; Jee, Hye Won; Seo, Sung Mi; Kwak, Byung Kook; Khang, Gilson; Cho, Sun Hang

    2006-01-01

    Biocompatible polysuccinimide (PSI) derivatives conjugated with diethylenetriaminepentaacetic acid gadolinium (DTPA-Gd) were prepared as magnetic resonance imaging (MRI) contrast agents. In this study, we synthesized PSI derivatives incorporating methoxy-poly(ethylene glycol) (mPEG) as hydrophilic ligand, hexadecylamine as hydrophobic ligand, and DTPA-Gd as contrast agent. PSI was synthesized by the polycondensation polymerization of aspartic acid. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Critical micellization concentrations were determined using fluorescent probes (pyrene). Micelle size and shape were measured by electro-photometer light scattering (ELS) and atomic force microscopy (AFM). The formed micelle size ranged from 100 to 300 nm. The T1-weighted MR images of the phantom prepared with PSI-mPEG-C16-(DTPA-Gd) were obtained in a 3.0 T clinical MR imager, and the conjugates showed a great potential as MRI contrast agents.

  9. Exogenous contrast agents for thermoacoustic imaging: an investigation into the underlying sources of contrast.

    OpenAIRE

    Ogunlade, O.; Beard, P

    2015-01-01

    Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the und...

  10. Functionalized multiwalled carbon nanotubes as ultrasound contrast agents

    Science.gov (United States)

    Delogu, Lucia Gemma; Vidili, Gianpaolo; Venturelli, Enrica; Ménard-Moyon, Cécilia; Zoroddu, Maria Antonietta; Pilo, Giovannantonio; Nicolussi, Paola; Ligios, Ciriaco; Bedognetti, Davide; Sgarrella, Francesco; Manetti, Roberto; Bianco, Alberto

    2012-01-01

    Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5–10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities. PMID:23012426

  11. Dendrimer-based contrast agents for molecular imaging.

    Science.gov (United States)

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

    2008-01-01

    The extensive adaptability of dendrimer-based contrast agents is ideal for the molecular imaging of organs and other target-specific locations. The ability of literally atom-by-atom modification on cores, interiors, and surface groups, permits the rational manipulation of dendrimer-based agents in order to optimize their physical characteristics, biodistribution, receptor-mediated targeting, and controlled release of the payload. Such modifications enable agents to localize preferentially to areas or organs of interest for facilitating target-specific imaging as well as assume excretion pathways that do not interfere with desired applications. Recent innovations in dendrimer research have increased agent directibility and new synthetic chemistry approaches have increased efficiency of production as well as led to the creation of novel dendrimer-based contrast agents. In addition, by taking advantage of the numerous attachment sites available on the surface of a single dendrimer molecule, new synthetic chemistry techniques have led to the development of multi-modality magnetic resonance, radionuclide, and fluorescence imaging agents for molecular imaging. Herein we discuss advances in dendrimer-based contrast agents for molecular imaging focusing mainly on the chemical design as applied to optical, magnetic resonance, computer tomography, radionuclide, and multi-modality imaging.

  12. Advanced design and experimental validation of MRI contrast agents for fluid pressure mapping using microbubbles

    OpenAIRE

    Morris, RH

    2009-01-01

    This work is related to monitoring fluid pressure using Magnetic Resonance Imaging or MRI and includes numerical simulations and experimental MRI. The nature of this study is such that techniques other than MRI have been extensively used to assess the contrast agent for its physical behaviour. These techniques include rheometry, light scattering, optical and scanning electron microscopy. Six MRI experiments in total were performed: The first two experiments use standard spin echo imaging tech...

  13. Feasibility of concurrent dual contrast enhancement using CEST contrast agents and superparamagnetic iron oxide particles.

    NARCIS (Netherlands)

    Gilad, A.A.; Laarhoven, H.W.M. van; McMahon, M.T.; Walczak, P.; Heerschap, A.; Neeman, M.; Zijl, P.C. van; Bulte, J.W.

    2009-01-01

    A major challenge for cellular and molecular MRI is to study interactions between two different cell populations or biological processes. We studied the possibility to simultaneously image contrast agents based on two different MRI contrast mechanisms: chemical exchange saturation transfer (CEST)

  14. Feasibility of concurrent dual contrast enhancement using CEST contrast agents and superparamagnetic iron oxide particles

    NARCIS (Netherlands)

    Gilad, Assaf A.; van Laarhoven, Hanneke W. M.; McMahon, Michael T.; Walczak, Piotr; Heerschap, Arend; Neeman, Michal; van Zijl, Peter C. M.; Bulte, Jeff W. M.

    2009-01-01

    A major challenge for cellular and molecular MRI is to study interactions between two different cell populations or biological processes. We studied the possibility to simultaneously image contrast agents based on two different MRI contrast mechanisms: chemical exchange saturation transfer (CEST)

  15. Contrast enhancement by lipid-based MRI contrast agents in mouse atherosclerotic plaques; a longitudinal study

    NARCIS (Netherlands)

    den Adel, Brigit; van der Graaf, Linda M.; Que, Ivo; Strijkers, Gustav J.; Löwik, Clemens W.; Poelmann, Robert E.; van der Weerd, Louise

    2013-01-01

    The use of contrast-enhanced MRI to enable in vivo specific characterization of atherosclerotic plaques is increasing. In this study the intrinsic ability of two differently sized gadolinium-based contrast agents to enhance atherosclerotic plaques in ApoE(-/-) mice was evaluated with MRI. We

  16. Exogenous contrast agents for thermoacoustic imaging: an investigation into the underlying sources of contrast.

    Science.gov (United States)

    Ogunlade, Olumide; Beard, Paul

    2015-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Ogunlade, Olumide, E-mail: o.ogunlade@ucl.ac.uk; Beard, Paul [Department of Medical Physics and Biomedical Engineering, University College London, London WC1E 6BT (United Kingdom)

    2015-01-15

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

  18. 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.

  19. 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.

  20. Harmonic chirp imaging method for ultrasound contrast agent

    NARCIS (Netherlands)

    Borsboom, Jerome M.G.; Chin, Chien Ting; Bouakaz, Ayache; Versluis, Michel; de Jong, N.

    2005-01-01

    Coded excitation is currently used in medical ultrasound to increase signal-to-noise ratio (SNR) and penetration depth. We propose a chirp excitation method for contrast agents using the second harmonic component of the response. This method is based on a compression filter that selectively

  1. Performance of two neutral oral contrast agents in CT enterography.

    Science.gov (United States)

    Wong, Jessica; Roger, Mark; Moore, Helen

    2015-02-01

    This study compares the performance of two neutral oral contrast agents in CT enterography (CTE). Mannitol 2.5%, an oral osmotic agent, is compared with psyllium fibre (Metamucil). Both these agents are commonly used, but to our knowledge, they have not been compared in CTE. CTE data were collected from 25 consecutive studies for both mannitol and psyllium fibre between 2011 and 2013. All images were reviewed by two radiologists and one registrar blinded to the oral contrast used. Each quadrant was assessed for maximum distension, proportion of bowel loops distended, presence of inhomogeneous content and bowel wall visibility. Overall subjective quality and whether the contrast agent reached the caecum were also assessed. Patients were invited to answer a questionnaire regarding tolerability of the preparations. Wall visibility was rated good in 100% of the mannitol studies, compared with 71% of the psyllium fibre studies, in the right lower quadrant (P = 0.01). No statistically significant difference between groups was observed in either maximal distension or proportion of loops distended in any quadrant. Inhomogeneous material was observed in 12% of the mannitol cases and 86% of the psyllium fibre cases (P psyllium fibre cases (P psyllium fibre studies (P = 0.03). Mannitol achieves studies of better quality and is now the preferred oral contrast for CTE studies at Auckland City Hospital. © 2014 The Royal Australian and New Zealand College of Radiologists.

  2. 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

    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.

  3. Time-resolved nanoseconds dynamics of ultrasound contrast agent microbubbles

    NARCIS (Netherlands)

    Garbin, V.; Garbin, Valeria; Cojoc, Dan; Ferrari, Enrico; Di Fabrizio, Enzo; Overvelde, M.L.J.; Versluis, Michel; van der Meer, S.M.; de Jong, N.; Lohse, Detlef; Dholakia, Kishan; Spalding, Gabriel C.

    2006-01-01

    Optical tweezers enable non-destructive, contact-free manipulation of ultrasound contrast agent (UCA) microbubbles, which are used in medical imaging for enhancing the echogenicity of the blood pool and to quantify organ perfusion. The understanding of the fundamental dynamics of ultrasound-driven

  4. Gold Nanoparticle-Based Fluorescent Contrast Agent with Enhanced Sensitivity.

    Science.gov (United States)

    Kang, Kyung Aih; Nguyen, Mai-Dung

    2017-01-01

    Gold nanoparticle (GNP) based contrast agents that are highly specific and sensitive for both optical and X-ray/CT imaging modalities are being developed for detecting the cancer expressing nucleolin and matrix metallo-proteinase 14 (MMP-14) on the cell membrane: Nucleolin is normally present in the nucleus. For many cancer cells, however, it is over-expressed on the cell membrane, having it to be a good cancer marker. Aptamer AS1411 is known to be an excellent target for nucleolin and also known to treat several cancer types; and MMP-14 in cancer is involved in tumor angiogenesis, blood vessel re-organization, and metastasis. In the proposed agent, AS1411 is selected as the cancer targeting molecule; and the unique property of GNPs of modulating fluorescence are utilized to allow the agent to trigger its fluorescence upon reacting with MMP-14, at an enhanced fluorescence level. GNPs are also natural X-ray/CT contrast agent. Here, as a part of on-going development of the dual-modality contrast agent, we report that conjugating a safe, NIR fluorophore Cypate at a precisely determined distance from the GNP enhanced the Cypate fluorescence up to two times. In addition, successful conjugation of the nucleolin target AS1411 onto the GNP was confirmed and among the GNPs size range 5-30 nm tested, 10 nm GNPs showed the highest X-ray/CT enhancement.

  5. 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.

  6. 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

  7. 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. © 2015 Wiley Periodicals, Inc.

  8. 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}.

  9. Analytical interference by contrast agents in biochemical assays

    DEFF Research Database (Denmark)

    Otnes, Sigrid; Fogh-Andersen, Niels; Rømsing, Janne

    2017-01-01

    Objective. To provide a clinically relevant overview of the analytical interference by contrast agents (CA) in laboratory blood test measurements. Materials and Methods. The effects of five CAs, gadobutrol, gadoterate meglumine, gadoxetate disodium, iodixanol, and iomeprol, were studied on the 29...... most frequently performed biochemical assays. One-day-old plasma, serum, and whole blood were spiked with doses of each agent such that the gadolinium agents and the iodine agents reached concentrations of 0.5mMand 12mg iodine/mL, respectively. Subsequently, 12 assays were reexamined using 1/2 and 1....../4 of these CA concentrations. The results were assessed statistically by a paired Student’s t-test. Results. Iodixanol produced a negative interference on the bicarbonate (p = 0.011), lactate dehydrogenase (p

  10. The advantage of high relaxivity contrast agents in brain perfusion

    Energy Technology Data Exchange (ETDEWEB)

    Cotton, F. [MRI Center, Centre Hospitalier Lyon Sud, Pierre Benite (France); CREATIS, INSA-502, Villeurbanne (France); Lab. d' Anatomie, UFR Laennec, Lyon (France); Hermier, M. [CREATIS, INSA-502, Villeurbanne (France); MRI Center, Neurologic Hospital, Lyon (France)

    2006-01-10

    Accurate MRI characterization of brain lesions is critical for planning therapeutic strategy, assessing prognosis and monitoring response to therapy. Conventional MRI with gadolinium-based contrast agents is useful for the evaluation of brain lesions, but this approach primarily depicts areas of disruption of the blood-brain barrier (BBB) rather than tissue perfusion. Advanced MR imaging techniques such as dynamic contrast agent-enhanced perfusion MRI provide physiological information that complements the anatomic data available from conventional MRI. We evaluated brain perfusion imaging with gadobenate dimeglumine (Gd-BOPTA, MultiHance; Bracco Imaging, Milan, Italy). The contrast-enhanced perfusion technique was performed on a Philips Intera 1.5-T MR system. The technique used to obtain perfusion images was dynamic susceptibility contrast-enhanced MRI, which is highly sensitive to T2* changes. Combined with PRESTO perfusion imaging, SENSE is applied to double the temporal resolution, thereby improving the signal intensity curve fit and, accordingly, the accuracy of the derived parametric images. MultiHance is the first gadolinium MR contrast agent with significantly higher T1 and T2 relaxivities than conventional MR contrast agents. The higher T1 relaxivity, and therefore better contrast-enhanced T1-weighted imaging, leads to significantly improved detection of BBB breakdown and hence improved brain tumor conspicuity and delineation. The higher T2 relaxivity allows high-quality T2*-weighted perfusion MRI and the derivation of good quality relative cerebral blood volume (rCBV) maps. We determined the value of MultiHance for enhanced T2*-weighted perfusion imaging of histologically proven (by surgery or stereotaxic biopsy) intraaxial brain tumors (n=80), multiple sclerosis lesions (n=10), abscesses (n=4), neurolupus (n=15) and stroke (n=16). All the procedures carried out were safe and no adverse events occurred. The acquired perfusion images were of good quality in

  11. Advanced Contrast Agents for Multimodal Biomedical Imaging Based on Nanotechnology.

    Science.gov (United States)

    Calle, Daniel; Ballesteros, Paloma; Cerdán, Sebastián

    2018-01-01

    Clinical imaging modalities have reached a prominent role in medical diagnosis and patient management in the last decades. Different image methodologies as Positron Emission Tomography, Single Photon Emission Tomography, X-Rays, or Magnetic Resonance Imaging are in continuous evolution to satisfy the increasing demands of current medical diagnosis. Progress in these methodologies has been favored by the parallel development of increasingly more powerful contrast agents. These are molecules that enhance the intrinsic contrast of the images in the tissues where they accumulate, revealing noninvasively the presence of characteristic molecular targets or differential physiopathological microenvironments. The contrast agent field is currently moving to improve the performance of these molecules by incorporating the advantages that modern nanotechnology offers. These include, mainly, the possibilities to combine imaging and therapeutic capabilities over the same theranostic platform or improve the targeting efficiency in vivo by molecular engineering of the nanostructures. In this review, we provide an introduction to multimodal imaging methods in biomedicine, the sub-nanometric imaging agents previously used and the development of advanced multimodal and theranostic imaging agents based in nanotechnology. We conclude providing some illustrative examples from our own laboratories, including recent progress in theranostic formulations of magnetoliposomes containing ω-3 poly-unsaturated fatty acids to treat inflammatory diseases, or the use of stealth liposomes engineered with a pH-sensitive nanovalve to release their cargo specifically in the acidic extracellular pH microenvironment of tumors.

  12. Safety of gadolinium contrast agent in hemodialysis patients

    Energy Technology Data Exchange (ETDEWEB)

    Okada, S. [Nippon Medical School, Chiba-Hokuso Hospital (Japan). Dept. of Radiology; Katagiri, K.; Kumazaki, T. [Nippon Medical School, Tokyo (Japan). Dept. of Radiology; Yokoyama, H. [Ishinkai Clinic, Chiba (Japan). Dept. of Urology

    2001-05-01

    Purpose: We evaluated the safety of a gadolinium (Gd) contrast agent in hemodialysis patients. Material and Methods: Seventy hemodialysis patients underwent contrast-enhanced MR examination. After the examination, the patients were hemodialyzed on a usual schedule, i.e., 3 times per week at 4 h each session. The hemodialysis was performed on the same day in 16 patients, the next day in 34, 2 days later in 14 and 3 days later in 6 patients. Serum Gd concentrations before and after the first to fourth hemodialysis sessions were analyzed in 11 patients. Cardiovascular, cutaneous, respiratory, psycho-neurological and digestive side effects were evaluated in all patients. Changes in liver and kidney functions, blood counts, and electrolytes were also checked. Results and Conclusion: Neither side effects nor blood changes were noted in any of the patients. Average excretory rates were 78.2%, 95.6%, 98.7% and 99.5% in the first to fourth hemodialysis sessions, respectively. These results suggest that Gd contrast agents can be used in hemodialysis patients if hemodialysis is carried out promptly after the examination. Key words: Renal failure, hemodialysis; contrast agent, gadolinium.

  13. 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.

  14. Phase-change contrast agents for imaging and therapy.

    Science.gov (United States)

    Sheeran, Paul S; Dayton, Paul A

    2012-01-01

    Phase-change contrast agents (PCCAs) for ultrasound-based applications have resulted in novel ways of approaching diagnostic and therapeutic techniques beyond what is possible with microbubble contrast agents and liquid emulsions. When subjected to sufficient pressures delivered by an ultrasound transducer, stabilized droplets undergo a phase-transition to the gaseous state and a volumetric expansion occurs. This phenomenon, termed acoustic droplet vaporization, has been proposed as a means to address a number of in vivo applications at the microscale and nanoscale. In this review, the history of PCCAs, physical mechanisms involved, and proposed applications are discussed with a summary of studies demonstrated in vivo. Factors that influence the design of PCCAs are discussed, as well as the need for future studies to characterize potential bioeffects for administration in humans and optimization of ultrasound parameters.

  15. Biocompatible astaxanthin as novel contrast agent for biomedical imaging.

    Science.gov (United States)

    Nguyen, Van Phuc; Park, Suhyun; Oh, Junghwan; Wook Kang, Hyun

    2017-08-01

    Photoacoustic imaging (PAI) is a hybrid imaging modality with high resolution and sensitivity that can be beneficial for cancer staging. Due to insufficient endogenous photoacoustic (PA) contrast, the development of exogenous agents is critical in targeting cancerous tumors. The current study demonstrates the feasibility of marine-oriented material, astaxanthin, as a biocompatible PA contrast agent. Both silicon tubing phantoms and ex vivo bladder tissues are tested at various concentrations (up to 5 mg/ml) of astaxanthin to quantitatively explore variations in PA responses. A Q-switched Nd : YAG laser (λ = 532 nm) in conjunction with a 5 MHz ultrasound transducer is employed to generate and acquire PA signals from the samples. The phantom results presented that the PA signal amplitudes increase linearly with the astaxanthin concentrations (threshold detection = 0.31 mg/ml). The tissue injected with astaxanthin yields up to 16-fold higher PA signals, compared with that with saline. Due to distribution of the injected astaxanthin, PAI can image the margin of astaxanthin boles as well as quantify their volume in 3D reconstruction. Further investigations on selective tumor targeting are required to validate astaxanthin as a potential biocompatible contrast agent for PAI-assisted bladder cancer detection. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Tumor Vessel Compression Hinders Perfusion of Ultrasonographic Contrast Agents1

    Science.gov (United States)

    Galiè, Mirco; D'Onofrio, Mirko; Montani, Maura; Amici, Augusto; Calderan, Laura; Marzola, Pasquina; Benati, Donatella; Merigo, Flavia; Marchini, Cristina; Sbarbati, Andrea

    2005-01-01

    Abstract 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. PMID:15967105

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. Nanomaterials incorporated ultrasound contrast agents for cancer theranostics

    Science.gov (United States)

    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) 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. PMID:27807499

  2. Development of microbubble contrast agents for high frequency ultrasound microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Se Jung; Kim, Eun A; Park, Sung Hoon; Lee, Hye Jin; Jun, Hong Young; Byun, Seung Jae; Yoon, Kwon Ha [Wonkwang University School of Medicine, Iksan (Korea, Republic of)

    2007-05-15

    To develop optimal microbubble contrast agents (MBCAs) for performing ultrasound microscopy when examining small animals. We prepared three types of MBCAs. First, a mixture of three parts of 40% dextran and one part of 5% human serum albumin were sonicated with perfluorocarbon (PFC) (MB{sub 1}-D40A5P). Second, three parts of 40% dextran and one part of 1% human serum albumin were sonicated with PFC (MB{sub 2}-D40A1P). Third, all parts of 1% bovine serum albumin were sonicated with PFC (MB{sub 3}-A1P). We measured the microbubbles' sizes and concentrations with using image analysis software. The acoustic properties of the microbubbles were assessed both in vitro and in vivo. The majority of the MB{sub 1}-D40A5Ps had a diameter of 2-5 {mu} m, the mean diameter of the MB{sub 2}-D40A1Ps was 2.5 {mu} m, and the mean diameter of the MB{sub 3}-A1Ps was less than 2.0 {mu} m. Among the microbubbles, the MB{sub 1}-D40A5Ps and MB{sub 2}-D40A1Ps showed increased echogenicity in the abdominal vessels, but the duration of their contrast effect was less than 30 sec. On the contrary, the MB3-A1Ps exhibited strong enhancement in the vessels and their duration was greater than 120 sec. A microbubble contrast agent consisting of all parts of 1% serum albumin sonicated with PFC is an effective contrast agent for ultrasound microscopy.

  3. Perfusion imaging with a freely diffusible hyperpolarized contrast agent.

    Science.gov (United States)

    Grant, Aaron K; Vinogradov, Elena; Wang, Xiaoen; Lenkinski, Robert E; Alsop, David C

    2011-09-01

    Contrast agents that can diffuse freely into or within tissue have numerous attractive features for perfusion imaging. Here we present preliminary data illustrating the suitability of hyperpolarized (13)C labeled 2-methylpropan-2-ol (also known as dimethylethanol, tertiary butyl alcohol and tert-butanol) as a freely diffusible contrast agent for magnetic resonance perfusion imaging. Dynamic (13)C images acquired in rat brain with a balanced steady-state free precession sequence following administration of hyperpolarized 2-methylpropan-2-ol show that this agent can be imaged with 2-4 s temporal resolution, 2 mm slice thickness, and 700 μm in-plane resolution while retaining adequate signal-to-noise ratio. (13)C relaxation measurements on 2-methylpropan-2-ol in blood at 9.4 T yield T(1) = 46 ± 4s and T(2) = 0.55 ± 0.03 s. In the rat brain at 4.7 T, analysis of the temporal dynamics of the balanced steady-state free precession image intensity in tissue and venous blood indicate that 2-methylpropan-2-ol has a T(2) of roughly 2-4s and a T(1) of 43 ± 24 s. In addition, the images indicate that 2-methylpropan-2-ol is freely diffusible in brain and hence has a long residence time in tissue; this in turn makes it possible to image the agent continuously for tens of seconds. These characteristics show that 2-methylpropan-2-ol is a promising agent for robust and quantitative perfusion imaging in the brain and body. Copyright © 2011 Wiley-Liss, Inc.

  4. 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.

  5. Nanoparticle Loaded Polymeric Microbubbles as Contrast Agents for Multimodal Imaging.

    Science.gov (United States)

    Teraphongphom, Nutte; Chhour, Peter; Eisenbrey, John R; Naha, Pratap C; Witschey, Walter R T; Opasanont, Borirak; Jablonowski, Lauren; Cormode, David P; Wheatley, Margaret A

    2015-11-03

    Ultrasound contrast agents are typically microbubbles (MB) with a gas core that is stabilized by a shell made of lipids, proteins, or polymers. The high impedance mismatch between the gas core and an aqueous environment produces strong contrast in ultrasound (US). Poly(lactic acid) (PLA) MB, previously developed in our laboratory, have been shown to be highly echogenic both in vitro and in vivo. Combining US with other imaging modalities such as fluorescence, magnetic resonance imaging (MRI), or computerized tomography (CT) could improve the accuracy of many US applications and provide more comprehensive diagnostic information. Furthermore, our MB have the capacity to house a drug in the PLA shell and create drug-loaded nanoparticles in situ when passing through an ultrasound beam. To create multimodal contrast agents, we hypothesized that the polymer shell of our PLA MB platform could accommodate additional payloads. In this study, we therefore modified our current MB by encapsulating nanoparticles including aqueous or organic quantum dots (QD), magnetic iron oxide nanoparticles (MNP), or gold nanoparticles (AuNP) to create bimodality platforms in a manner that minimally compromised the performance of each individual imaging technique.

  6. Effects of microchannel confinement on acoustic vaporisation of ultrasound phase change contrast agents

    Science.gov (United States)

    Lin, Shengtao; Zhang, Ge; Hau Leow, Chee; Tang, Meng-Xing

    2017-09-01

    The sub-micron phase change contrast agent (PCCA) composed of a perfluorocarbon liquid core can be activated into gaseous state and form stable echogenic microbubbles for contrast-enhanced ultrasound imaging. It has shown great promise in imaging microvasculature, tumour microenvironment, and cancer cells. Although PCCAs have been extensively studied for different diagnostic and therapeutic applications, the effect of biologically geometrical confinement on the acoustic vaporisation of PCCAs is still not clear. We have investigated the difference in PCCA-produced ultrasound contrast enhancement after acoustic activation with and without a microvessel confinement on a microchannel phantom. The experimental results indicated more than one-order of magnitude less acoustic vaporisation in a microchannel than that in a free environment taking into account the attenuation effect of the vessel on the microbubble scattering. This may provide an improved understanding in the applications of PCCAs in vivo.

  7. Effects of microchannel confinement on acoustic vaporisation of ultrasound phase change contrast agents.

    Science.gov (United States)

    Lin, Shengtao; Zhang, Ge; Leow, Chee Hau; Tang, Meng-Xing

    2017-08-07

    The sub-micron phase change contrast agent (PCCA) composed of a perfluorocarbon liquid core can be activated into gaseous state and form stable echogenic microbubbles for contrast-enhanced ultrasound imaging. It has shown great promise in imaging microvasculature, tumour microenvironment, and cancer cells. Although PCCAs have been extensively studied for different diagnostic and therapeutic applications, the effect of biologically geometrical confinement on the acoustic vaporisation of PCCAs is still not clear. We have investigated the difference in PCCA-produced ultrasound contrast enhancement after acoustic activation with and without a microvessel confinement on a microchannel phantom. The experimental results indicated more than one-order of magnitude less acoustic vaporisation in a microchannel than that in a free environment taking into account the attenuation effect of the vessel on the microbubble scattering. This may provide an improved understanding in the applications of PCCAs in vivo.

  8. MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

    Science.gov (United States)

    Rasaneh, Samira; Rajabi, Hossein; Babaei, Mohammad Hossein; Akhlaghpoor, Shahram

    2011-06-01

    In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 ± 2.5 and 41 ± 15 nm (size range: 15-87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1-3.5. TMNs were non-toxic to the cells below the 30 μg (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.

  9. MRI contrast agent for molecular imaging of the HER2/neu receptor using targeted magnetic nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira; Rajabi, Hossein, E-mail: hrajabi@modares.ac.ir [Tarbiat Modares University, Department of Medical Physics (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Science and Technology Research Institute, Department of Radioisotope (Iran, Islamic Republic of); Akhlaghpoor, Shahram [Sina Hospital, Tehran Medical University, Noor Medical Imaging Center (Iran, Islamic Republic of)

    2011-06-15

    In this study, Trastuzumab modified Magnetic Nanoparticles (TMNs) were prepared as a new contrast agent for detecting HER2 (Human epidermal growth factor receptor-2) expression tumors by magnetic resonance imaging (MRI). TMNs were prepared based on iron oxide nanoparticles core and Trastuzumab modified dextran coating. The TMNs core and hydrodynamic size were determined by transmission electron microscopy and dynamic light scattering. TMNs stability and cytotoxicity were investigated. The ability of TMNs for HER2 detection were evaluated in breast carcinoma cell lines (SKBr3 and MCF7 cells) and tumor-bearing mice by MRI and iron uptake determination. The particles core and hydrodynamic size were 9 {+-} 2.5 and 41 {+-} 15 nm (size range: 15-87 nm), respectively. The molar antibody/nanoparticle ratio was 3.1-3.5. TMNs were non-toxic to the cells below the 30 {mu}g (Fe)/mL concentration and good stable up to 8 weeks in PBS buffer. TMNs could detect HER2 oncogenes in the cells surface with imagable contrast by MRI. The invivo study in mice bearing tumors indicated that TMNs possessed a good diagnostic ability as HER2 specific contrast agent by MRI. TMNs were demonstrated to be able to selectively accumulate in the tumor cells, with a proper signal enhancement in MRI T2 images. So, the complex may be considered for further investigations as an MRI contrast agent for detection of HER2 expression tumors in human.

  10. 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.

  11. 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.

  12. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging

    Directory of Open Access Journals (Sweden)

    Katja Haedicke

    2017-06-01

    Full Text Available Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher® (BHQ dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to αvβ3-integrin expressing glioblastoma cell spheroids in vitro. The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo. Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  13. Sonophore labeled RGD: a targeted contrast agent for optoacoustic imaging.

    Science.gov (United States)

    Haedicke, Katja; Brand, Christian; Omar, Murad; Ntziachristos, Vasilis; Reiner, Thomas; Grimm, Jan

    2017-06-01

    Optoacoustic imaging is a rapidly expanding field for the diagnosis, characterization, and treatment evaluation of cancer. However, the availability of tumor specific exogenous contrast agents is still limited. Here, we report on a small targeted contrast agent for optoacoustic imaging using a black hole quencher ® (BHQ) dye. The sonophore BHQ-1 exhibited strong, concentration-dependent, optoacoustic signals in phantoms, demonstrating its ideal suitability for optoacoustic imaging. After labeling BHQ-1 with cyclic RGD-peptide, BHQ-1-cRGD specifically bound to α v β 3 -integrin expressing glioblastoma cell spheroids in vitro . The excellent optoacoustic properties of BHQ-1-cRGD could furthermore be proven in vivo . Together with this emerging imaging modality, our sonophore labeled small peptide probe offers new possibilities for non-invasive detection of molecular structures with high resolution in vivo and furthers the specificity of optoacoustic imaging. Ultimately, the discovery of tailor-made sonophores might offer new avenues for various molecular optoacoustic imaging applications, similar to what we see with fluorescence imaging.

  14. 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.

  15. Quinone-fused porphyrins as contrast agents for photoacoustic imaging

    KAUST Repository

    Banala, Srinivas

    2017-06-27

    Photoacoustic (PA) imaging is an emerging non-invasive diagnostic modality with many potential clinical applications in oncology, rheumatology and the cardiovascular field. For this purpose, there is a high demand for exogenous contrast agents with high absorption coefficients in the optical window for tissue imaging, i.e. the near infrared (NIR) range between 680 and 950 nm. We herein report the photoacoustic properties of quinone-fused porphyrins inserted with different transition metals as new highly promising candidates. These dyes exhibit intense NIR absorption, a lack of fluorescence emission, and PA sensitivity in concentrations below 3 nmol mL. In this context, the highest PA signal was obtained with a Zn(ii) inserted dye. Furthermore, this dye was stable in blood serum and free thiol solution and exhibited negligible cell toxicity. Additionally, the Zn(ii) probe could be detected with an up to 3.2 fold higher PA intensity compared to the clinically most commonly used PA agent, ICG. Thus, further exploration of the \\'quinone-fusing\\' approach to other chromophores may be an efficient way to generate highly potent PA agents that do not fluoresce and shift their absorption into the NIR range.

  16. 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.

  17. Biological in situ characterization of polymeric microbubble contrast agents.

    Science.gov (United States)

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

    2016-06-01

    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. Due to their buoyancy, the commonly available approaches to study their behaviour in complex media are not easily applicable and their use in modern medicine requires such behaviour to be fully elucidated. Here we have used for the first time flow cytometry as a new high throughput approach that allows characterisation of the MB dispersion, prior to and after exposure in different biological media and we have additionally developed a method that allows characterisation of the strongly bound proteins adsorbed on the MBs, to fully predict their biological behaviour in biological milieu. Copyright © 2016. Published by Elsevier Ltd.

  18. 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.

  19. The use of contrast agent for imaging biological samples

    Science.gov (United States)

    Dammer, J.; Weyda, F.; Sopko, V.; Jakubek, J.

    2011-01-01

    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 1μm, 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.

  20. Nano-Sized Ultrasound Contrast Agent: Salting-Out Method

    Directory of Open Access Journals (Sweden)

    Margaret A. Wheatley

    2010-03-01

    Full Text Available Tumor imaging by ultrasound is greatly enhanced by the use of ultrasound contrast agents (UCAs, stabilized, gas-filled bodies. They are generally less than 7 μm to pass freely through the capillary bed. Development of a nano-sized agent would enable them to extravasate through the leaky pores of angiogenic vessels. We describe the development of an echogenic, nano-sized polylactic acid UCA by adaptation of a salting-out method. The viscosity of the initial colloidal suspension (concentration and molecular weight of protective colloid [polyvinyl alcohol (PVA] and concentration of polymer was key in determining particle size and polydispersity (increasing viscosity increased both. Addition of the porogens ammonium carbonate and camphor, required to produce hollow echogenic capsules, also increased the size (eg, 5 wt% PVA, mean solid nanocapsule size 386 ± 25 nm, polydispersity index 0.367 ± 0.14, and mean UCA size 640 ± 18 nm, polydispersity index 0.308 ± 0.027. Viscosity had the opposite effect on echogenicity of the resultant nano-UCA, which ranged from 21.69 ± 0.78 dB for 2% PVA to 12.1 ± 0.8 dB for 10% PVA. The UCA prepared with 10% PVA, however, had a longer half-life in the ultrasound beam (t½ > 15 minutes vs t½ < 10 minutes, suggesting a thicker shell. Optimization will require compromise among size, echogenicity, and stability.

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

    Science.gov (United States)

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

    2009-01-01

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

  2. Magnetic nano-particles, contrast agent for NMR imaging; Nanoparticules magnetiques, agents de contraste pour l'imagerie par resonance magnetique

    Energy Technology Data Exchange (ETDEWEB)

    Gazeau, F.; Wilhelm, C.; Bacri, J.C. [Universite Paris 6 / associe a Paris 7, Lab. Milieux Desordonnes et Heterogenes (LMDH), 75 - Paris (France); Clement, O. [Hopital Necker-Enfants-Malades, Lab. Recherche en Imagerie, 75 - Paris (France)

    2004-08-01

    The purpose of contrast media in NMR (nuclear magnetic resonance) imaging is to disturb the magnetization of surrounding protons by generating a local magnetic field. There are 2 types of contrast agents: paramagnetic molecular complexes and ferromagnetic nano-particles. Paramagnetic molecular complexes contain paramagnetic ions such as Gd{sup 3+}, Fe{sup 3+} or Mn{sup 2+}. Ferromagnetic nano-particles are monocrystals of iron oxide whose diameters have a magnitude of about ten nanometers, each particle acts as a little magnet of 10{sup 4} Bohr magnetons. These nano-particles have to be put in colloidal suspension in a bio-compatible solvent in order to be injected into the body. The effect of nano-particles on surrounding protons is far more important than that of paramagnetic complexes because their magnetic moment is increased by a factor 1000. Paramagnetic complexes (like gadolinium chelate) do not aggregate to plasma proteins and as a consequence they go easily through capillary blood vessels, and scatter quickly in the aqueous extra-cellular compartments, they are eliminated through kidneys in a matter of hours. Magnetic nano-particles have a different kinetics inside the body that depends strongly on their sizes and the nature of their surface. Clinical uses of magnetic nano-particles involve pathology in which liver, spleen, or bone marrow are concerned, or lymphography or the visualization of the piling-up of macrophages in any inflammatory zones. (A.C.)

  3. 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.

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

    Science.gov (United States)

    Bader, Kenneth B; Holland, Christy K

    2015-01-01

    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 ICAV = Pr/f (where Pr 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. PMID:23221109

  5. Multivalent, high-relaxivity MRI contrast agents using rigid cysteine-reactive gadolinium complexes.

    Science.gov (United States)

    Garimella, Praveena D; Datta, Ankona; Romanini, Dante W; Raymond, Kenneth N; Francis, Matthew B

    2011-09-21

    MRI contrast agents providing very high relaxivity values can be obtained through the attachment of multiple gadolinium(III) complexes to the interior surfaces of genome-free viral capsids. In previous studies, the contrast enhancement was predicted to depend on the rigidity of the linker attaching the MRI agents to the protein surface. To test this hypothesis, a new set of Gd-hydroxypyridonate based MRI agents was prepared and attached to genetically introduced cysteine residues through flexible and rigid linkers. Greater contrast enhancements were seen for MRI agents that were attached via rigid linkers, validating the design concept and outlining a path for future improvements of nanoscale MRI contrast agents.

  6. Enhancement of ultrasound reflectivity depends on the specific perfluorocarbons utilized to formulate nanoparticle emulsion contrast agents

    Science.gov (United States)

    Marsh, Jon N.; Hall, Christopher S.; Scott, Michael J.; Fuhrhop, Ralph J.; Gaffney, Patrick J.; Wickline, Samuel A.; Lanza, Gregory M.

    2000-04-01

    A nongaseous, ligand-targeted perfluorocarbon nanoparticle emulsion has been developed which can acoustically enhance the presence of molecular epitopes on tissue surfaces. We demonstrate the impact of incorporating perfluorocarbons with specific phase velocities into the emulsions on the acoustic reflectivity of plasma clots targeted using these nanoparticles. Porcine plasma clots were targeted in vitro with specific perfluorocarbon emulsions using anti-fibrin antibody solution (NIB 5F3). Five perfluorocarbons were investigated: perfluorohexane, perfluorooctyl-bromide, perfluorooctane, perfluorodichlorooctane, and perfluorodecalin. Ultrasonic backscatter (17 - 35 MHz) was measured at the front surface of the clots. Backscatter enhancement was determined by comparison with untreated clots. The magnitude of enhancement depended on the perfluorocarbon emulsion used. Perfluorohexane and perfluorooctane exhibited the greatest enhancement relative to untreated clots (23 dB) and perfluorodecalin the least (18 dB), consistent with predictions from a simple acoustic transmission-line model. We conclude that targeted, nongaseous perfluorocarbon contrast agents can significantly increase the sensitivity of ultrasonic detection of low-scattering biological media, and that further optimization of these contrast agents can be realized by judicious choice of the emulsified perfluorocarbon.

  7. Complex interfaces in "phase-change" contrast agents.

    Science.gov (United States)

    Capece, Sabrina; Domenici, Fabio; Brasili, Francesco; Oddo, Letizia; Cerroni, Barbara; Bedini, Angelico; Bordi, Federico; Chiessi, Ester; Paradossi, Gaio

    2016-03-28

    In this paper we report on the study of the interface of hybrid shell droplets encapsulating decafluoropentane (DFP), which exhibit interesting potentialities for ultrasound (US) imaging. The fabrication of the droplets is based on the deposition of a dextran methacrylate layer onto the surface of surfactants. The droplets have been stabilized against coalescence by UV curing, introducing crosslinks in the polymer layer and transforming the shell into an elastomeric membrane with a thickness of about 300 nm with viscoelastic behaviour. US irradiation induces the evaporation of the DFP core of the droplets transforming the particles into microbubbles (MBs). The presence of a robust crosslinked polymer shell introduces an unusual stability of the droplets also during the core phase transition and allows the recovery of the initial droplet state after a few minutes from switching off US. The interfacial tension of the droplets has been investigated by two approaches, the pendant drop method and an indirect method, based on the determination of the liquid ↔ gas transition point of DFP confined in the droplet core. The re-condensation process has been followed by capturing images of single MBs by confocal microscopy. The time evolution of MB relaxation to droplets was analysed in terms of a modified Church model to account for the structural complexity of the MB shell, i.e. a crosslinked polymer layer over a layer of surfactants. In this way the microrheology parameters of the shell were determined. In a previous paper (Chem. Commun., 2013, 49, 5763-5765) we showed that these systems could be used as ultrasound contrast agents (UCAs). In this work we substantiate this view assessing some key features offered by the viscoelastic nature of the droplet shell.

  8. New dextrin nanomagnetogels as contrast agents for magnetic resonance imaging

    OpenAIRE

    Gonçalves, C; Lalatonne, Y.; Melro, L.; Badino, G; M. F. M. Ferreira; David, L.; Geraldes, C. F. G. C.; Motte, L.; Martins, J. A.; Gama, F. M.

    2013-01-01

    This study aims at the production and characterization of a “nanomagnetogel” consisting of superparamagnetic iron oxide nanoparticles (g-Fe2O3) stabilized within a hydrophobized-dextrin nanogel. The nanomagnetogel obtained was extensively characterized with respect to physico-chemical (transmission electron microscopy, cryo-scanning electron microscopy, dynamic light scattering, small angle X-ray scattering), magnetic (relaxometry, MIAplex) and biocompatibility (interaction with c...

  9. Blood Pool Agent Contrast-Enhanced MRA: Level-Set Based Artery-Vein Separation

    NARCIS (Netherlands)

    van Bemmel, C.M.; Spreeuwers, Lieuwe Jan; Verdonck, B.; Viergever, M.A.; Niessen, W.J.

    2002-01-01

    Blood pool agents (BPAs) for contrast-enhanced magnetic resonance angiography (CE-MRA) allow prolonged imaging times for higher contrast and resolution by imaging during the steady state when the contrast agent is distributed through the complete vascular system. However, simultaneous arterial and

  10. Imaging microscopic distribution of antifungal agents in dandruff treatments with stimulated Raman scattering microscopy

    Science.gov (United States)

    Garrett, Natalie L.; Singh, Bhumika; Jones, Andrew; Moger, Julian

    2017-06-01

    Treatment of dandruff condition usually involves use of antidandruff shampoos containing antifungal agents. Different antifungal agents show variable clinical efficacy based on their cutaneous distribution and bioavailability. Using stimulated Raman scattering (SRS), we mapped the distribution of unlabeled low-molecular weight antifungal compounds zinc pyrithione (ZnPT) and climbazole (CBZ) on the surface of intact porcine skin with cellular precision. SRS has sufficient chemical selectivity and sensitivity to detect the agents on the skin surface based on their unique chemical motifs that do not occur naturally in biological tissues. Moreover, SRS is able to correlate the distribution of the agents with the morphological features of the skin using the CH2 stretch mode, which is abundant in skin lipids. This is a significant strength of the technique since it allows the microscopic accumulation of the agents to be correlated with physiological features and their chemical environment without the use of counter stains. Our findings show that due to its lower solubility, ZnPT coats the surface of the skin with a sparse layer of crystals in the size range of 1 to 4 μm. This is consistent with the current understanding of the mode of action of ZnPT. In contrast, CBZ being more soluble and hydrophobic resulted in diffuse homogeneous distribution. It predominantly resided in microscopic lipid-rich crevasses and penetrated up to 60 μm into the infundibular spaces surrounding the hair shaft. The ability of the SRS to selectively map the distribution of agents on the skin's surface has the potential to provide insight into the mechanisms underpinning the topical application of antifungal or skin-active agents that could lead to the rational engineering of enhanced formulations.

  11. Ultrasound imaging and contrast agents: a safe alternative to MRI?

    NARCIS (Netherlands)

    Wink, Margot H.; Wijkstra, Hessel; de La Rosette, Jean J. M. C. H.; Grimbergen, Cornelis A.

    2006-01-01

    Microbubble contrast media are used to enhance ultrasound images. Because ultrasound is a real-time investigation, contrast-enhanced ultrasound offers possibilities for perfusion imaging. This review is conducted to evaluate the safety of contrast-enhanced ultrasound and its possible role in medical

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

    Energy Technology Data Exchange (ETDEWEB)

    Shan, Liang, E-mail: shanli@mail.nih.gov; Chopra, Arvind; Leung, Kam; Eckelman, William C. [National Institutes of Health, Molecular Imaging and Contrast Agent Database, National Center for Biotechnology Information, National Library of Medicine (United States); Menkens, Anne E. [National Institutes of Health, National Cancer Institute (United States)

    2012-09-15

    The development of molecular imaging agents is currently undergoing a dramatic expansion. As of October 2011, {approx}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.

  13. 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

  14. 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)....

  15. Measurement of dynamic scattering beneath stationary layers using multiple-exposure laser speckle contrast analysis

    Science.gov (United States)

    Hirst, Evan; Thompson, Oliver; Andrews, Mike

    2013-02-01

    The retina/choroid structure is an example of a complex biological target featuring highly perfused tissues and vessel flows both near the surface and at some depth. Laser speckle imaging can be used to image blood flows but static scattering paths present a problem for extracting quantifiable data. The speckle contrast is artificially increased by any residual specular reflection and light paths where no moving scatterers are encountered. Here we present results from phantom experiments demonstrating that the static and dynamic contributions to laser speckle contrast can be separated when camera exposures of varying duration are used. The stationary contrast parameter follows the thickness and strength of the overlying scatterer while the dynamic proportion of the scatter resulting from vessel flows and Brownian motion is unchanged. The importance of separating the two scatter components is illustrated by in vivo measurements from a scarred human retina, where the effect of the un-perfused scar tissue can be decoupled from the dynamic speckle from the intact tissue beneath it.

  16. Contrast enhancement for portal images by combination of subtraction and reprojection processes for Compton scattering.

    Science.gov (United States)

    Hariu, Masatsugu; Suda, Yuhi; Chang, Weishan; Myojoyama, Atsushi; Saitoh, Hidetoshi

    2017-11-01

    For patient setup of the IGRT technique, various imaging systems are currently available. MV portal imaging is performed in identical geometry with the treatment beam so that the portal image provides accurate geometric information. However, MV imaging suffers from poor image contrast due to larger Compton scatter photons. In this work, an original image processing algorithm is proposed to improve and enhance the image contrast without increasing the imaging dose. Scatter estimation was performed in detail by MC simulation based on patient CT data. In the image processing, scatter photons were eliminated and then they were reprojected as primary photons on the assumption that Compton interaction did not take place. To improve the processing efficiency, the dose spread function within the EPID was investigated and implemented on the developed code. Portal images with and without the proposed image processing were evaluated by the image contrast profile. By the subtraction process, the image contrast was improved but the EPID signal was weakened because 15.2% of the signal was eliminated due to the contribution of scatter photons. Hence, these scatter photons were reprojected in the reprojection process. As a result, the tumor, bronchi, mediastinal space and ribs were observed more clearly than in the original image. It was clarified that image processing with the dose spread functions provides stronger contrast enhancement while maintaining a sufficient signal-to-noise ratio. This work shows the feasibility of improving and enhancing the contrast of portal images. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  17. Intravenous carbon dioxide as an echocardiographic contrast agent

    NARCIS (Netherlands)

    R.S. Meltzer (Richard); P.W.J.C. Serruys (Patrick); P.G. Hugenholtz (Paul); J.R.T.C. Roelandt (Jos)

    1981-01-01

    textabstractIntravenous carbon dioxide (CO2) was employed to cause echocardiographic contrast in 40 patients. One to 3 cc of medically pure CO2 were agitated with 5 to 8 cc of 5% dextrose in water and rapidly injected into an upper extremity vein. Contrast was obtained in all patients. In 33

  18. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition

    National Research Council Canada - National Science Library

    Aime, Silvio; Caravan, Peter

    2009-01-01

    .... In patients with impaired renal function and nephrogenic systemic fibrosis (NSF), the agents gadodiamide, gadoversetamide, and gadopentetate dimeglumine have been shown to result in Gd deposition in the skin...

  19. Local scattering property scales flow speed estimation in laser speckle contrast imaging

    Science.gov (United States)

    Miao, Peng; Chao, Zhen; Feng, Shihan; Yu, Hang; Ji, Yuanyuan; Li, Nan; Thakor, Nitish V.

    2015-07-01

    Laser speckle contrast imaging (LSCI) has been widely used in in vivo blood flow imaging. However, the effect of local scattering property (scattering coefficient µ s ) on blood flow speed estimation has not been well investigated. In this study, such an effect was quantified and involved in relation between speckle autocorrelation time τ c and flow speed v based on simulation flow experiments. For in vivo blood flow imaging, an improved estimation strategy was developed to eliminate the estimation bias due to the inhomogeneous distribution of the scattering property. Compared to traditional LSCI, a new estimation method significantly suppressed the imaging noise and improves the imaging contrast of vasculatures. Furthermore, the new method successfully captured the blood flow changes and vascular constriction patterns in rats’ cerebral cortex from normothermia to mild and moderate hypothermia.

  20. Inorganic nanocrystals as contrast agents in MRI: synthesis, coating and introduction of multifunctionality

    NARCIS (Netherlands)

    Cormode, David P.; Sanchez-Gaytan, Brenda L.; Mieszawska, Aneta J.; Fayad, Zahi A.; Mulder, Willem J. M.

    2013-01-01

    Inorganic nanocrystals have myriad applications in medicine, including their use as drug or gene delivery complexes, therapeutic hyperthermia agents, in diagnostic systems and as contrast agents in a wide range of medical imaging techniques. In MRI, nanocrystals can produce contrast themselves, with

  1. 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)....

  2. 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

  3. Oral magnetic resonance imaging contrast agent based on Ilex paraguayensis herbal extract

    National Research Council Canada - National Science Library

    Nestle, Nikolaus; Pauls, Sandra; Wunderlich, Arthur

    2006-01-01

    ... ) as an oral contrast agent for MRI. At typical drinking concentrations, yerba mate acts as a “biphasic” contrast agent with T 1 weighting at short echo times and T 2 weighting at echo times greater than about 40 ms...

  4. 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 solute. These findings may help in developing clinical methods of contrast agent-based imaging to detect cartilage injury.

  5. Contrast Agents for Quantitative MicroCT of Lung Tumors in Mice

    Science.gov (United States)

    Lalwani, Kush; Giddabasappa, Anand; Li, Danan; Olson, Peter; Simmons, Brett; Shojaei, Farbod; Arsdale, Todd Van; Christensen, James; Jackson-Fisher, Amy; Wong, Anthony; Lappin, Patrick B; Eswaraka, Jeetendra

    2013-01-01

    The identification and quantitative evaluation of lung tumors in mouse models is challenging and an unmet need in preclinical arena. In this study, we developed a noninvasive contrast-enhanced microCT (μCT) method to longitudinally evaluate and quantitate lung tumors in mice. Commercially available μCT contrast agents were compared to determine the optimal agent for visualization of thoracic blood vessels and lung tumors in naïve mice and in non-small-cell lung cancer models. Compared with the saline control, iopamidol and iodinated lipid agents provided only marginal increases in contrast resolution. The inorganic nanoparticulate agent provided the best contrast and visualization of thoracic vascular structures; the density contrast was highest at 15 min after injection and was stable for more than 4 h. Differential contrast of the tumors, vascular structures, and thoracic air space by the nanoparticulate agent enabled identification of tumor margins and accurate quantification. μCT data correlated closely with traditional histologic measurements (Pearson correlation coefficient, 0.995). Treatment of ELM4–ALK mice with crizotinib yielded 65% reduction in tumor size and thus demonstrated the utility of quantitative μCT in longitudinal preclinical trials. Overall and among the 3 agents we tested, the inorganic nanoparticulate product was the best commercially available contrast agent for visualization of thoracic blood vessels and lung tumors. Contrast-enhanced μCT imaging is an excellent noninvasive method for longitudinal evaluation during preclinical lung tumor studies. PMID:24326223

  6. Relative Conspicuity of Gadolinium-Based Contrast Agents in Interventional Pain Procedures.

    Science.gov (United States)

    Maus, Timothy P; Schueler, Beth A; Magnuson, Dixon J; Magnuson, Dayne

    2017-04-01

    To assess the relative radiographic conspicuity of gadolinium-based contrast agents (GBCAs) that may be used in spinal injection procedures when iodine-based contrast agents are contraindicated. Eight GBCAs and three iodinated agents of varying iodine concentrations were radiographed under conditions representative of lumbar spinal injections at four kilovoltage peak (kVp) values. Radiographic contrast of each agent was measured as the percent pixel value difference with respect to background. Gadobutrol (Gadovist, 1 mM/mL) had the highest radiographic contrast among the gadolinium agents tested. Measured radiographic contrast correlated with the molar concentration of gadolinium. Gadobutrol radiographic contrast lies between the contrast of iohexol concentrations of 240 and 140 mgI/mL. All agents have decreasing contrast as kVp increases, but GBCAs decrease less than iodine-based agents. Gadobutrol is the GBCA with the greatest conspicuity for use in spinal injection procedures. It also has the highest molar concentration of gadolinium, and potential neural toxicity from intrathecal delivery must be considered.

  7. Intravenous ultrasound contrast agents versus other imaging methods in pediatric patients with neoplastic diseases - a comparison.

    Science.gov (United States)

    Piskunowicz, Maciej; Kosiak, Wojciech; Batko, Tomasz; Adamkiewicz-Drożyńska, Elżbieta; Szarmach, Arkadiusz

    2013-12-01

    The lack of registration of ultrasound contrast agents for use in patients below the age of 18 is a significant limitation of their usage. Despite this, examinations with the use of contrast agents are conducted in numerous centers, mainly as part of the diagnostic process of vesicoureteral reflux. Examinations after an intravenous administration of contrast agents are conducted rarely. The reason for this is not only the lack of registration, but also the lack of studies on their safety profile in paediatric patients or no guidelines concerning the dosage. It seems that imaging with the use of such agents could help solve certain clinical problems when other diagnostic methods fail. The paper presents selected cases of pediatric patients treated in oncological departments, in whom the examination with the use of ultrasound contrast agents had a considerable influence on the diagnostic and therapeutic process.

  8. 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 MnCl 2 as well as clinical contrast agents. Following intravenous administration, nanodiamond-manganese complexes outperformed current clinical contrast agents in an orthotopic liver cancer mouse model while also reducing blood serum concentration of toxic free Mn 2+ ions. Thus, nanodiamond-manganese complexes may serve as more effective dual mode MRI contrast agent, particularly in cancer. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Design and Optimization of Gadolinium Based Contrast Agents for Magnetic Resonance Imaging

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, G.A.; Geraldes, C.F.G.C. [University of Coimbra (Portugal). Faculty of Science and Technology; University of Coimbra (Portugal). Center of Neurosciences and Cell Biology. Dept. of Biochemistry; E-mail: geraldes@bioq.uc.pt

    2007-07-01

    The role of Gd{sup 3+} chelates as contrast agents in Magnetic Resonance Imaging is discussed. The theory describing the different contributions to paramagnetic relaxation relevant to the understanding of the molecular parameters determining the relativity of those Gd{sup 3+} chelates, is presented. The experimental techniques used to obtain those parameters are also described. Then, the various approaches taken to optimize those parameters, leading to maximum relativity (efficiency) of the contrast agents, are also illustrated with relevant examples taken from the literature. The various types of Gd{sup 3+}-based agents, besides non-specific and hepatobiliary agents, are also discussed, namely blood pool, targeting, responsive and paramagnetic chemical shift saturation transfer (PARACEST) agents. Finally, a perspective is presented of some of the challenges lying ahead in the optimization of MRI contrast agents to be useful in Molecular Imaging. (author)

  10. 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.)

  11. Iron Oxide as an Mri Contrast Agent for Cell Tracking: Supplementary Issue

    Directory of Open Access Journals (Sweden)

    Daniel J. Korchinski

    2015-01-01

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

  12. [Preparation and evaluation of microbubble ultrasound contrast agent with N-carboxymethyl chitosan].

    Science.gov (United States)

    Lü, Feng; Chen, Su-Xia; Liu, Tian-Jun; Sun, Hong-Fan

    2006-08-01

    To prepare microbubble, made of N-carboxymethyl chitosan, as ultrasound contrast agent and evaluate its characteristics and acoustic effects in vivo. Oil-Water-Oil multiple emulsion/solvent evaporation method was used to prepare the microbubble contrast agent. Both optical micrography and scanning electron micrography were performed to determine the bubble size and morphology. The acoustic effect of the N-carboxymethyl chitosan echo contrast agent was evaluated in vivo in rabbit. Liver echo images were recorded with ultrasound machine before and after intravenous bolus injecting 0.5 ml of the agent. The novel N-carboxymethyl chitosan echo contrast agent was formulated as lyophilized product, with a mean diameter of 2-3 microm and a shell thickness of 250-300 nm. Its size is relatively uniform. The imaging effect was remarkably enhanced with the ultrasonic contrast agent when applied in rabbit livers. It is feasible to prepare excellent microbubble ultrasound contrast agent with N-carboxymethyl chitosan as membrane components.

  13. Comparison of Folate Receptor Targeted Optical Contrast Agents for Intraoperative Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Elizabeth De Jesus

    2015-01-01

    Full Text Available Background. Intraoperative imaging can identify cancer cells in order to improve resection; thus fluorescent contrast agents have emerged. Our objective was to do a preclinical comparison of two fluorescent dyes, EC17 and OTL38, which both target folate receptor but have different fluorochromes. Materials. HeLa and KB cells lines were used for in vitro and in vivo comparisons of EC17 and OTL38 brightness, sensitivity, pharmacokinetics, and biodistribution. In vivo experiments were then performed in mice. Results. The peak excitation and emission wavelengths of EC17 and OTL38 were 470/520 nm and 774/794 nm, respectively. In vitro, OTL38 required increased incubation time compared to EC17 for maximum fluorescence; however, peak signal-to-background ratio (SBR was 1.4-fold higher compared to EC17 within 60 minutes (p<0.001. Additionally, the SBR for detecting smaller quantity of cells was improved with OTL38. In vivo, the mean improvement in SBR of tumors visualized using OTL38 compared to EC17 was 3.3 fold (range 1.48–5.43. Neither dye caused noticeable toxicity in animal studies. Conclusions. In preclinical testing, OTL38 appears to have superior sensitivity and brightness compared to EC17. This coincides with the accepted belief that near infrared (NIR dyes tend to have less autofluorescence and scattering issues than visible wavelength fluorochromes.

  14. Silver nanoparticles (AgNPs) as a contrast agent for imaging of animal tissue using swept-source optical coherence tomography (SSOCT)

    Science.gov (United States)

    Mondal, Indranil; Raj, Shipra; Roy, Poulomi; Poddar, Raju

    2018-01-01

    We present noninvasive three-dimensional depth-resolved imaging of animal tissue with a swept-source optical coherence tomography system at 1064 nm center wavelength and silver nanoparticles (AgNPs) as a potential contrast agent. A swept-source laser light source is used to enable an imaging rate of 100 kHz (100 000 A-scans s‑1). Swept-source optical coherence tomography is a new variant of the optical coherence tomography (OCT) technique, offering unique advantages in terms of sensitivity, reduction of motion artifacts, etc. To enhance the contrast of an OCT image, AgNPs are utilized as an exogeneous contrast agent. AgNPs are synthesized using a modified Tollens method and characterization is done by UV–vis spectroscopy, dynamic light scattering, scanning electron microscopy and energy dispersive x-ray spectroscopy. In vitro imaging of chicken breast tissue, with and without the application of AgNPs, is performed. The effect of AgNPs is studied with different exposure times. A mathematical model is also built to calculate changes in the local scattering coefficient of tissue from OCT images. A quantitative estimation of scattering coefficient and contrast is performed for tissues with and without application of AgNPs. Significant improvement in contrast and increase in scattering coefficient with time is observed.

  15. Iron oxide nanoparticles stabilized with dendritic polyglycerols as selective MRI contrast agents

    Science.gov (United States)

    Nordmeyer, Daniel; Stumpf, Patrick; Gröger, Dominic; Hofmann, Andreas; Enders, Sven; Riese, Sebastian B.; Dernedde, Jens; Taupitz, Matthias; Rauch, Ursula; Haag, Rainer; Rühl, Eckart; Graf, Christina

    2014-07-01

    Monodisperse small iron oxide nanoparticles functionalized with dendritic polyglycerol (dPG) or dendritic polyglycerol sulfate (dPGS) are prepared. They are highly stable in aqueous solutions as well as physiological media. In particular, oleic acid capped iron oxide particles (core diameter = 11 +/- 1 nm) were modified by a ligand exchange process in a one pot synthesis with dPG and dPGS bearing phosphonate as anchor groups. Dynamic light scattering measurements performed in water and different biological media demonstrate that the hydrodynamic diameter of the particles is only slightly increased by the ligand exchange process resulting in a final diameter of less than 30 nm and that the particles are stable in these media. It is also revealed by magnetic resonance studies that their magnetic relaxivity is reduced by the surface modification but it is still sufficient for high contrast magnetic resonance imaging (MRI). Additionally, incubation of dPGS functionalized iron oxide nanoparticles with human umbilical vein endothelial cells showed a 50% survival at 85 nM (concentration of nanoparticles). Surface plasmon resonance (SPR) studies demonstrate that the dPGS functionalized iron oxide nanoparticles inhibit L-selectin ligand binding whereas the particles containing only dPG do not show this effect. Experiments in a flow chamber with human myelogenous leukemia cells confirmed L-selectin inhibition of the dPGS functionalized iron oxide nanoparticles and with that the L-selectin mediated leukocyte adhesion. These results indicate that dPGS functionalized iron oxide nanoparticles are a promising contrast agent for inflamed tissue probed by MRI.Monodisperse small iron oxide nanoparticles functionalized with dendritic polyglycerol (dPG) or dendritic polyglycerol sulfate (dPGS) are prepared. They are highly stable in aqueous solutions as well as physiological media. In particular, oleic acid capped iron oxide particles (core diameter = 11 +/- 1 nm) were modified by a

  16. Transthoracic contrast echocardiography using vitamin B6 and sodium bicarbonate as contrast agents for the diagnosis of patent foramen ovale.

    Science.gov (United States)

    He, Jiang-Chun; Zheng, Jian-Yong; Li, Xin; Yang, Ye; Zhang, Bo-Yang; Chen, Yu; Li, Xian-Feng; Liu, Ying-Ming; Cao, Yi; Zhao, Li; Li, Tian-Chang

    2017-08-01

    To evaluate the utility of transthoracic contrast echocardiography (cTTE) using vitamin B6 and sodium bicarbonate as contrast agents for diagnosing right-to-left shunt (RLS) caused by patent foramen ovale (PFO) compared to that of transesophageal echocardiography (TEE). We investigated 125 patients admitted to our neurology department with unexplained cerebral infarction and migraine. All patients underwent cTTE using vitamin B6 and sodium bicarbonate as contrast agents, after which they underwent transthoracic echocardiography. The Doppler signal was recorded during the Valsalva maneuver, and TEE examinations were performed. The feasibility, diagnostic sensitivity, and safety of cTTE and TEE for PFO recognition were compared. Evidence of PFO was found in 49 (39.20%) patients with cTTE, more than were detected with TEE (39, 31.20%) (χ 2 =5.0625, P=0.0244). cTTE had a sensitivity of 92.31% and a specificity of 84.88% for diagnosing PFO, showing high concordance with TEE for PFO recognition (κ=0.72). Further, results of a semi-quantitative evaluation of PFO-RLS by cTTE were better than those with TEE (Z=-2.011, P=0.044). No significant adverse reaction was discovered during cTTE examination. cTTE using vitamin B6 and sodium bicarbonate as contrast agents has relatively good sensitivity and specificity for diagnosing RLS caused by PFO when compared with those for TEE. Using vitamin B6 and sodium bicarbonate as contrast agents to perform cTTE is recommended for detecting and diagnosing the PFO due to its simplicity, non-invasive character, low cost, and high feasibility.

  17. 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.

  18. Nanoparticles as magnetic resonance imaging contrast agents for vascular and cardiac diseases

    NARCIS (Netherlands)

    Chen, Wei; Cormode, David P.; Fayad, Zahi A.; Mulder, Willem J. M.

    2011-01-01

    Advances in nanoparticle contrast agents for molecular imaging have made magnetic resonance imaging a promising modality for noninvasive visualization and assessment of vascular and cardiac disease processes. This review provides a description of the various nanoparticles exploited for imaging

  19. Contrast agent derived determination of the total circulating blood volume using magnetic resonance.

    Science.gov (United States)

    Pannek, Kerstin; Fidler, Florian; Kartäusch, Ralf; Jakob, Peter M; Hiller, Karl-Heinz

    2012-06-01

    Knowledge of the total circulating blood volume (TCBV) is essential for the treatment of a variety of medical conditions and blood disorders. To date, blood volume analysis is rarely carried out due to the disadvantages of available methods. Our aim was to develop a widely available, simple, fast, yet accurate method for the determination of the total circulating blood volume. Magnetic resonance (MR) is a well-established, non-invasive technique. In this article, we present a method that uses MR contrast agents for the determination of the blood volume. The dependence of MR relaxation times on the concentration of MR contrast agents allows the calculation of the volume the contrast agent has been diluted in. In phantom and in vivo experiments we could demonstrate that TCBV can be determined with high accuracy and precision. This work introduces a novel method for the determination of the total circulating blood volume using magnetic resonance contrast agents as tracers.

  20. Gas Sensor for Volatile Anesthetic Agents Based on Raman Scattering

    Science.gov (United States)

    Schlüter, Sebastian; Popovska-Leipertz, Nadejda; Seeger, Thomas; Leipertz, Alfred

    Continuous monitoring of respiratory and anesthetic gases during a surgery is of vital importance for the patient safety. Commonly the gas composition is determined by gas chromatography or a combination of IR-spectroscopy and electrochemical sensors. This study presents a concept for an optical sensor based on spontaneous Raman scattering which offers several advantages compared to established systems. All essential components can be detected simultaneously, no sample preparation is necessary and it provides fast response times. To reach the performance of a commonly used gas monitor signal gain has to be increased e.g. by using a multi pass setup.

  1. 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. Copyright 2009 John Wiley & Sons, Ltd.

  2. Dynamic manipulation of magnetic contrast agents in photoacoustic imaging

    Science.gov (United States)

    Jia, Congxian; Xia, Jinjun; Pelivanov, Ivan M.; Seo, Chi Hyung; Hu, Xiaoge; Jin, Yongdong; Gao, Xiaohu; O'Donnell, Matthew

    2011-03-01

    Magnetic nanoparticles (MNPs) have been used extensively ex vivo for cellular and molecular separations. We recently showed that a coupled nanoparticle combining a superparamagnetic core with a thin, isolated gold shell providing strong absorption in the near infrared can be used for magnetomotive photoacoustic imaging (mmPA), a new technique in which magnetic manipulation of the particle during PA imaging greatly enhances molecular contrast specificity. This particle can also be biologically targeted for in vivo applications, where mmPA imaging provides a spatially localized readout of magnetic manipulations. As an initial test of potential in vivo molecular assays and integrated molecular therapeutics using magnetic manipulation of nanoparticles, we present experiments demonstrating PA readout of trapped magnetic particles in a flow field. An aqueous solution containing a concentration of 0.05-mg/ml 10-μM superparamagnetic iron oxide particles flowed in a 1.65-mm diameter Zeus PTFE (Teflon) sublite wall tubing at three velocities of 0.8, 1.5 and 3.0-mm/s. Opposed permanent magnets separated by 40-mm were positioned on both sides of the tube. As expected, the targeted objects can be magnetically captured and accumulated locally. By translating the magnets, a dynamic magnetic field (0.1-0.3-T) was alternately generated on the side of the tube closest to one of the magnets and created a synchronous PA motion from accumulated targeted objects. This synchronized motion can be used to differentiate the stationary background or other PA sources moving asynchronously with magnetic manipulations (e.g., moving blood) from targeted cells moving synchronously with the magnetic field. This technology can potentially provide sensitive molecular assays of cellular targets travelling in the vasculature (e.g., metastatic tumor cells).

  3. Evaluation of hepatic contrast enhancement with a hepatocyte-specific magnetic resonance imaging contrast agent (gadoxetic acid) in healthy dogs.

    Science.gov (United States)

    Bratton, Alexandra K; Nykamp, Stephanie G; Gibson, Thomas W G; Cruz-Arámbulo, Robert; Kruth, Stephen A

    2015-03-01

    To determine, by means of MRI, the time to maximal contrast enhancement in T1-weighted images following IV administration of gadoxetic acid in healthy dogs and assess the impact of gadoxetic acid on the signal intensity of T2-weighted images. 7 healthy dogs. No hepatic abnormalities were detected during ultrasonographic examination. Each dog was anesthetized and positioned in dorsal recumbency for MRI. Transverse T1- and T2-weighted images of the liver were acquired prior to and following (at 5-minute intervals) IV injection of 0.1 mL of gadoxetic acid/kg. Signal intensity of the liver parenchyma was measured in 3 regions of interest in the T1- and T2-weighted images before and at various times point after contrast agent administration. Time versus signal-to-noise ratio curves were plotted to determine time to maximal contrast enhancement and contrast agent-related changes in signal intensity in T2-weighted images. Analysis of T1-weighted images revealed that mean ± SD time to maximal enhancement after gadoxetic acid injection was 10.5 ± 3.99 minutes. Signal intensity of T2-weighted images was not significantly affected by gadoxetic acid administration. No injection-related adverse effects were observed in any dog. Results indicated that gadoxetic acid can be used for hepatic MRI in healthy dogs and the resultant hepatic enhancement patterns are similar to those described for humans. Maximal contrast enhancement occurred between 10 and 15 minutes after contrast agent injection; thus, T2-weighted images may be obtained in the interval between injection and maximal enhancement for a more time-efficient clinical protocol.

  4. 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

  5. The histopathologic reaction of rabbit lungs after intrabronchial application of contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Hyo Soon; Kim, Jae Kyu; Shen, Yu Lan; Oh, Jeong Won; Chang, Nam Kyu; Shin, Sang Soo; Park, Jin Gyoon; Kang, Heoung Keun [Chonnam National University Hospital, Gwangju (Korea, Republic of)

    2006-05-15

    The aim of this study was to determine a safe gastrointestinal contrast agent that could be used in various clinical situations where there is a risk of aspiration using a rabbit model. 30 healthy white rabbits were used. The rabbits were divided into 5 groups containing six animals each, one control group (anesthesia only) and 4 groups receiving various contrast agents [Solotop (Barium sulphate suspension), Gastrografin (sodium and meglumine amidotrizoate), and Telebrix (Meglumine ioxitalamate), Visipaque (Iodixanol)]. The contrast agents were injected selectively into a main bronchus via a catheter inserted under fluoroscopy guidance. The rabbits were sacrificed either 1 day or 7 days after injecting the contrast agents, and the tissue reaction of the bronchi and lungs were examined both macro-and microscopically. The level of alveolar septal thickening, peribronchiolar lymphocytic infiltration, pulmonary congestion and edema, inflammatory exudate in the alveoli or bronchiolar lumina, microabscess formation, necrosis, pigmentation of materials injected, and fibropurulent pleurisy were evaluated and graded according to the severity as follows: no change, mild, moderate, marked in degree. The common microscopic findings were alveolar septal thickening and peribronchiolar lymphocytic infiltration. Pulmonary congestion and edema, inflammatory exudate in the alveoli of bronchiolar lumina were observed in 21 out of 24 rabbits receiving the contrast agents. Pigmentation of the materials injected was observed only in the group receiving Solotop. An inflammatory exudate in the alveoli and bronchiolar/bronchial lumina, microabscess formation, and necrosis were noted in most groups, but was more frequent and severe in the group receiving Gastrografin. The histopathological reactions of the rabbit lungs after the intrabronchial application of a contrast agent showed variable degrees of inflammatory reaction. Gastrografin produced most severe and extensive reaction, Solotop

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

    OpenAIRE

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

    2014-01-01

    Characterizing the nonlinear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this paper, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized nonlinear emissions from Targestar-P® microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 minutes, at 10 MHz excitation frequency. The results revealed a considerable increas...

  7. The MRI Contrast Agent Gadoteridol Enhances Distribution of rAAV1 in the Rat Hippocampus

    OpenAIRE

    Hullinger, Rikki; Ugalde, Jeanet; Purón-Sierra, Liliana; Osting, Sue; Burger, Corinna

    2013-01-01

    Contrast agents are commonly used in combination with magnetic resonance imaging (MRI) to monitor the distribution of molecules in the brain. Recent experiments conducted in our laboratory have shown that co-infusion of recombinant Adeno-associated virus serotype 5 (rAAV5) and the MRI contrast agent gadoteridol (Gd) enhances vector transduction of in the rat striatum. The goal of this study was to determine whether gadoteridol may also be used as a tool to enhance transduction efficiency of r...

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

    Science.gov (United States)

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

    2015-12-01

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

  9. A liposomal Gd contrast agent does not cross the mouse placental barrier.

    Science.gov (United States)

    Shetty, Anil N; Pautler, Robia; Ghagahda, Ketan; Rendon, David; Gao, Haijun; Starosolski, Zbigniew; Bhavane, Rohan; Patel, Chandreshkumar; Annapragada, Ananth; Yallampalli, Chandrasekhar; Lee, Wesley

    2016-06-14

    The trans-placental permeability of liposomal Gadolinium (Gd) nanoparticle contrast agents was evaluated in a pregnant mouse model. Pregnant Balb/c mice at 16.5 (±1) days of gestation were imaged using a 3D Spoiled Gradient Echo method at 9.4 T using two contrast agents: a clinically approved Gd chelate, Multihance(®) (gadobenate dimeglumine), and a novel experimental liposomal Gd agent. A Dynamic Contrast Enhancement (DCE) protocol was used to capture the dynamics of contrast entry and distribution in the placenta, and clearance from circulation. A blinded clinical radiologist evaluated both sets of images. A reference region model was used to measure the placental flow and physiological parameters; volume transfer constant (K(trans)), efflux rate constant (K(ep)). The Gd content of excised placentae and fetuses was measured, using inductively coupled plasma mass spectrometry (ICP-MS). MRI images of pregnant mice and ICP-MS analyses of placental and fetal tissue demonstrated undetectably low transplacental permeation of the liposomal Gd agent, while the clinical agent (Multihance) avidly permeated the placental barrier. Image interpretation and diagnostic quality was equivalent between the two contrast agents. Additional testing to determine both maternal and fetal safety of liposomal Gd is suggested.

  10. Myelography: From Lipid-Based to Gadolinium-Based Contrast Agents.

    Science.gov (United States)

    Price, Donald B; Ortiz, A Orlando

    2017-11-01

    Myelographic contrast media of various types have been used over the past 100 years. Many of the early contrast agents had significant toxicities. Gas myelography was tried, but the contrast between gas and soft tissue is poor. Pantopaque, an oil-based iodinated medium was successfully used for decades, but was not compatible with computed tomography (CT) scanning because it was viscous, insoluble, and caused streak artifact. The development of water-soluble agents allowed even distribution in the subarachnoid space and excellent depiction of spinal anatomy on post-myelographic CT scanning. Although invasive, myelography will remain a useful tool for the foreseeable future. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Light comfort zones of mesopelagic acoustic scattering layers in two contrasting optical environments

    KAUST Repository

    Røstad, Anders

    2016-03-31

    We make a comparison of the mesopelagic sound scattering layers (SLs) in two contrasting optical environments; the clear Red Sea and in murkier coastal waters of Norway (Masfjorden). The depth distributions of the SL in Masfjorden are shallower and narrower than those of the Red Sea. This difference in depth distribution is consistent with the hypothesis that the organisms of the SL distribute according to similar light comfort zones (LCZ) in the two environments. Our study suggest that surface and underwater light measurements ranging more than10 orders of magnitude is required to assess the controlling effects of light on SL structure and dynamics.

  12. CO2 and gadopentetate dimeglumine as alternative contrast agents for malfunctioning dialysis grafts and fistulas.

    Science.gov (United States)

    Spinosa, D J; Angle, J F; Hagspiel, K D; Schenk, W G; Matsumoto, A H

    1998-09-01

    Hemodialysis grafts and native fistulas are frequently evaluated angiographically utilizing iodinated contrast material to determine the cause of malfunction. Occasionally, patients are not able to receive iodinated contrast material due to a history of previous severe allergic reaction or concern that iodinated contrast material could worsen renal function requiring premature initiation of permanent dialysis. We set out to test the feasibility of gadopentetate dimeglumine as an alternative contrast agent in conjunction with carbon dioxide (CO2) angiography in the evaluation and treatment of hemodialysis grafts and native fistulas in patients who have a contraindication to iodinated contrast material. Six patients with a malfunctioning hemodialysis graft and native fistula were evaluated. Four patients were successfully evaluated using carbon dioxide and gadopentetate dimeglumine. Two additional patients underwent balloon angioplasty using gadopentetate dimeglumine alone as the alternative contrast agent. All six patients successfully were evaluated and treated using gadopentetate dimeglumine either alone or as a supplement to CO2 angiography. Five of these patients had lesions successfully treated using gadopentetate dimeglumine alone or in combination with CO2 as the angiographic contrast agents. One patient underwent a successful diagnostic angiogram using gadopentetate dimeglumine and CO2 as alternative contrast agents and was subsequently treated with surgical revision. The gadopentetate dimeglumine angiograms identified the arterial anastomosis and more clearly identified stenotic lesions and venous outflow anatomy compared to carbon dioxide angiograms. Gadopentetate dimeglumine is useful as an alternative contrast agent in conjunction with CO2 in patients with malfunctioning hemodialysis grafts and fistulas, who have a contraindication to the administration of iodinated contrast material.

  13. Elemental imaging of MRI contrast agents: benchmarking of LA-ICP-MS to MRI

    Energy Technology Data Exchange (ETDEWEB)

    Pugh, J.A.T. [University of Sheffield, Centre for Analytical Sciences, Sheffield (United Kingdom); University of Sheffield, Department of Chemical and Biological Engineering, Sheffield (United Kingdom); Cox, A.G.; McLeod, C.W. [University of Sheffield, Centre for Analytical Sciences, Sheffield (United Kingdom); Bunch, J. [University of Birmingham, School of Chemistry, Birmingham (United Kingdom); Writer, M.J.; Hart, S.L. [UCL Institute of Child Health, Wolfson Centre for Gene Therapy of Childhood Disease, London (United Kingdom); Bienemann, A.; White, E. [University of Bristol, School of Clinical Sciences, Southmead Hospital, Bristol (United Kingdom); Bell, J. [Hammersmith Hospital, Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College London, London (United Kingdom)

    2012-06-15

    Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) has been used to map the spatial distribution of magnetic resonance imaging (MRI) contrast agents (Gd-based) in histological sections in order to explore synergies with in vivo MRI. Images from respective techniques are presented for two separate studies namely (1) convection enhanced delivery of a Gd nanocomplex (developmental therapeutic) into rat brain and (2) convection enhanced delivery, with co-infusion of Magnevist (commercial Gd contrast agent) and Carboplatin (chemotherapy drug), into pig brain. The LA technique was shown to be a powerful compliment to MRI not only in offering improved sensitivity, spatial resolution and signal quantitation but also in giving added value regarding the fate of administered agents (Gd and Pt agents). Furthermore simultaneous measurement of Fe enabled assignment of an anomalous contrast enhancement region in rat brain to haemorrhage at the infusion site. (orig.)

  14. Superparamagnetic Bifunctional Bisphosphonates Nanoparticles: A Potential MRI Contrast Agent for Osteoporosis Therapy and Diagnostic

    Directory of Open Access Journals (Sweden)

    Y. Lalatonne

    2010-01-01

    Full Text Available A bone targeting nanosystem is reported here which combined magnetic contrast agent for Magnetic Resonance Imaging (MRI and a therapeutic agent (bisphosphonates into one drug delivery system. This new targeting nanoplatform consists of superparamagnetic γFe2O3 nanoparticles conjugated to 1,5-dihydroxy-1,5,5-tris-phosphono-pentyl-phosphonic acid (di-HMBPs molecules with a bisphosphonate function at the outer of the nanoparticle surface for bone targeting. The as-synthesized nanoparticles were evaluated as a specific MRI contrast agent by adsorption study onto hydroxyapatite and MRI measurment. The strong adsorption of the bisphosphonates nanoparticles to hydroxyapatite and their use as MRI T2∗ contrast agent were demonstrated. Cellular tests performed on human osteosarcoma cells (MG63 show that γFe2O3@di-HMBP hybrid nanomaterial has no citoxity effect in cell viability and may act as a diagnostic and therapeutic system.

  15. Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging

    Directory of Open Access Journals (Sweden)

    Justin J. Tse

    2017-01-01

    Full Text Available Micro-computed tomography (micro-CT facilitates the visualization and quantification of contrast-enhanced microvessels within intact tissue specimens, but conventional preclinical vascular contrast agents may be inadequate near dense tissue (such as bone. Typical lead-based contrast agents do not exhibit optimal X-ray absorption properties when used with X-ray tube potentials below 90 kilo-electron volts (keV. We have developed a high-atomic number lanthanide (erbium contrast agent, with a K-edge at 57.5 keV. This approach optimizes X-ray absorption in the output spectral band of conventional microfocal spot X-ray tubes. Erbium oxide nanoparticles (nominal diameter 4000 Hounsfield units, and perfusion of vessels < 10 μm in diameter was demonstrated in kidney glomeruli. The described new contrast agent facilitated the visualization and quantification of vessel density and microarchitecture, even adjacent to dense bone. Erbium’s K-edge makes this contrast agent ideally suited for both single- and dual-energy micro-CT, expanding potential preclinical research applications in models of musculoskeletal, oncological, cardiovascular, and neurovascular diseases.

  16. 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...... than 1 μT in water at room temperature. The longitudinal electron spin relaxation rate is calculated from the DNP enhancement curves. The oxygen broadening in water is about 50 μT/mM O2at 37°C. These agents have good properties for oximetry with OMRI....

  17. Galactosylated iodine-based small molecule I.V. CT contrast agent for bile duct imaging.

    Science.gov (United States)

    Jung, Yeonjin; Hwang, Hee Sook; Na, Kun

    2018-04-01

    Computed tomography (CT) with contrast plays an important role as a clinical diagnostic tool but still has a limited diagnostic range. In this work, we developed a novel injectable iodine-based small molecule CT contrast agent, even can be used for bile duct diagnostics. The bile duct diagnosable CT contrast agent (BDICA) is synthesized with 5-amino-2,4,6-triiodoisophthaloyl dichloride (ATIPC), tromethamine and lactobionic acid (LBA) for asialoglycoprotein receptor (ASGPR) targeted delivery via receptor-mediated endocytosis and transport to the bile canaliculi. Specific binding to the ASGPRs was confirmed by in vitro cellular uptake in HepG2 cells (ASGPR positive) and HCT 116 cells (ASGPR negative). Compared to iohexol, BDICA has equal in vivo distribution and a 13-fold iodine increase in content was observed in bile juice after BDICA injection. The radiopaque contrast effect in the bile duct has been clearly shown in in vivo CT scans. Furthermore, within 36 h, 91.3% of the BDICA was eliminated without organ damage, which verified the overall safety of the contrast agent. BDICA not only provides sufficient contrast images similar to iohexol, but also provides superior images of the bile duct. Based on recent studies, it has been shown that BDICA is a promising, safe and effective contrast agent for CT imaging of the organs and soft tissues, including the bile duct. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. 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. Copyright © 2015. Published by Elsevier Inc.

  19. A fast screening protocol for carotid plaques imaging using 3D multi-contrast MRI without contrast agent.

    Science.gov (United States)

    Zhang, Na; Zhang, Lei; Yang, Qi; Pei, Anqi; Tong, Xiaoxin; Chung, Yiu-Cho; Liu, Xin

    2017-06-01

    To implement a fast (~15min) MRI protocol for carotid plaque screening using 3D multi-contrast MRI sequences without contrast agent on a 3Tesla MRI scanner. 7 healthy volunteers and 25 patients with clinically confirmed transient ischemic attack or suspected cerebrovascular ischemia were included in this study. The proposed protocol, including 3D T1-weighted and T2-weighted SPACE (variable-flip-angle 3D turbo spin echo), and T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) was performed first and was followed by 2D T1-weighted and T2-weighted turbo spin echo, and post-contrast T1-weighted SPACE sequences. Image quality, number of plaques, and vessel wall thicknesses measured at the intersection of the plaques were evaluated and compared between sequences. Average examination time of the proposed protocol was 14.6min. The average image quality scores of 3D T1-weighted, T2-weighted SPACE, and T1-weighted magnetization prepared rapid acquisition gradient echo were 3.69, 3.75, and 3.48, respectively. There was no significant difference in detecting the number of plaques and vulnerable plaques using pre-contrast 3D images with or without post-contrast T1-weighted SPACE. The 3D SPACE and 2D turbo spin echo sequences had excellent agreement (R=0.96 for T1-weighted and 0.98 for T2-weighted, pagent. Copyright © 2016. Published by Elsevier Inc.

  20. Evolution of contrast agents for ultrasound imaging and ultrasound-mediated drug delivery

    Directory of Open Access Journals (Sweden)

    Vera ePaefgen

    2015-09-01

    Full Text Available Ultrasound is one of the most frequently used diagnostic methods. It is a non-invasive, comparably inexpensive imaging method with a broad spectrum of applications, which can be increased even more by using bubbles as contrast agents. There are various different types of bubbles: filled with different gases, composed of soft- or hard-shell materials, and ranging in size from nano- to micrometers. These intravascular contrast agents enable functional analyses, e.g. to acquire organ perfusion in real-time. Molecular analyses are achieved by coupling specific ligands to the bubbles’ shell, which bind to marker molecules in the area of interest. Bubbles can also be loaded with or attached to drugs, peptides or genes and can be destroyed by ultrasound pulses to locally release the entrapped agent. Recent studies show that ultrasound contrast agents are also valuable tools in hyperthermia-induced ablation therapy of tumors, or can increase cellular uptake of locally released drugs by enhancing membrane permeability. This review summarizes important steps in the development of ultrasound contrast agents and introduces the current clinical applications of contrast-enhanced ultrasound. Additionally, an overview of the recent developments in ultrasound probe design for functional and molecular diagnosis as well as for drug delivery is given.

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

    Directory of Open Access Journals (Sweden)

    Steven C Dinger

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

  2. Improved double emulsion technology for fabricating autofluorescent microcapsules as novel ultrasonic/fluorescent dual-modality contrast agents.

    Science.gov (United States)

    Gong, An; Ma, Xuehua; Xiang, Lingchao; Ren, Wenzhi; Shen, Zheyu; Wu, Aiguo

    2014-04-01

    The aim of this study is to explore an improved double emulsion technology with in situ reaction of lysine (Lys) and glutaraldehyde (GA) for fabricating autofluorescent Lys-poly(lactic-co-glycolic acid)-GA (Lys-PLGA-GA) microcapsules as novel ultrasonic/fluorescent dual-modality contrast agents. Scanning electron microscope (SEM) and static light scattering (SLS) results show that 80% of the Lys-PLGA-GA microcapsules are larger than 1.0 μm and 90% of them are smaller than 8.9 μm. SEM and laser confocal scanning microscope (LCSM) data demonstrate that the structure of our Lys-PLGA-GA microcapsules is hollow. Compared with the FT-IR spectrum of PLGA microcapsules, a new peak at 1,644 cm(-1) in that of Lys-PLGA-GA microcapsules confirms the formed Schiff base in Lys-PLGA-GA microcapsules. LCSM images and fluorescence spectra show that our Lys-PLGA-GA microcapsules exhibit bright and stable autofluorescence without conjugation to any fluorescent agent, which can be ascribed to the n-π transitions of the CN bonds in the formed Schiff base. Our autofluorescent Lys-PLGA-GA microcapsules might have more wide applications than traditional fluorescent dyes because their excitation and emission spectra are both broad. The fluorescence intensity can also be tuned by the feeding amount of Lys and GA. The MTT assays reveal that the autofluorescent microcapsules are biocompatible. The results of fluorescent imaging in cells and in vitro ultrasonic imaging demonstrate the feasibility of our autofluorescent Lys-PLGA-GA microcapsules as ultrasonic/fluorescent dual-modality contrast agents. This novel ultrasonic/fluorescent dual-modality contrast agent might have potential for a variety of biological and medical applications. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Contrast-agent-enhanced magnetic resonance imaging: early detection of neoplastic lesions of the CNS

    Science.gov (United States)

    Carvlin, Mark J.; Rosa, Louis; Rajan, Sunder S.; Francisco, John

    1991-06-01

    Even though the intrinsic soft tissue contrast sensitivity of magnetic resonance imaging (MRI) affords excellent visualization of anatomic detail, certain pathologic processes may be diagnosed earlier with the administration of a contrast-enhancing agent. At present there is one agent, gadopentetate dimeglumine, GdDTPA, that has received FDA approval for use in the MR scanning of the brain and spine in human patients. This paramagnetic chelate distributes throughout the extracellular fluid space as dictated by capillary permeability so that abnormal vascularity and sites of blood-CNS barrier breakdown are highlighted. Primary neoplastic disease, metastases, meningeal extension, residual and recurrent tumor have been found to be better distinguished in MR images acquired after administration of GdDTPA. Routine administration of GdDTPA for cranial imaging has resulted in the discovery of otherwise occult lesions in approximately 3 of patients. Although the clinical utility and high therapeutic safety index of the first approved magnetic resonance contrast agent, GdDTPA, have been well established, other contrast agents, having different physical, chemical and biological properties, may offer improved sensitivity and bio-specificity. Agents currently being evaluated in vivo include: low osmolal paramagnetic chelates, superparamagnetic particles, metalloporphyrins, liposome encapsulated agents, perfluorocarbons, intravascular macromolecular chelate complexes and labeled monoclonal antibodies. Concurrent with advances in the development of new compounds, innovations in scanning hardware, pulse sequence design and image post-processing are helping to extend the efficacy of contrast media. Additional clinical experience will indicate which contrast agents and which MR techniques can best facilitate the early detection of specific neoplastic lesions.

  4. Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

    Science.gov (United States)

    Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

    2016-01-01

    Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. Copyright © 2015 John Wiley & Sons, Ltd.

  5. Towards a nanoscale mammographic contrast agent: development of a modular pre-clinical dual optical/x-ray agent

    Science.gov (United States)

    Hill, Melissa L.; Gorelikov, Ivan; Niroui, Farnaz; Levitin, Ronald B.; Mainprize, James G.; Yaffe, Martin J.; Rowlands, J. A.; Matsuura, Naomi

    2013-08-01

    Contrast-enhanced digital mammography (CEDM) can provide improved breast cancer detection and characterization compared to conventional mammography by imaging the effects of tumour angiogenesis. Current small-molecule contrast agents used for CEDM are limited by a short plasma half-life and rapid extravasation into tissue interstitial space. To address these limitations, nanoscale agents that can remain intravascular except at sites of tumour angiogenesis can be used. For CEDM, this agent must be both biocompatible and strongly attenuate mammographic energy x-rays. Nanoscale perfluorooctylbromide (PFOB) droplets have good x-ray attenuation and have been used in patients for other applications. However, the macroscopic scale of x-ray imaging (50-100 µm) is inadequate for direct verification that PFOB droplets localize at sites of breast tumour angiogenesis. For efficient pre-clinical optimization for CEDM, we integrated an optical marker into PFOB droplets for microscopic assessment (≪50 µm). To develop PFOB droplets as a new nanoscale mammographic contrast agent, PFOB droplets were labelled with fluorescent quantum dots (QDs). The droplets had mean diameters of 160 nm, fluoresced at 635 nm and attenuated x-ray spectra at 30.5 keV mean energy with a relative attenuation of 5.6 ± 0.3 Hounsfield units (HU) mg-1 mL-1 QD-PFOB. With the agent loaded into tissue phantoms, good correlation between x-ray attenuation and optical fluorescence was found (R2 = 0.96), confirming co-localization of the QDs with PFOB for quantitative assessment using x-ray or optical methods. Furthermore, the QDs can be removed from the PFOB agent without affecting its x-ray attenuation or structural properties for expedited translation of optimized PFOB droplet formulations into patients.

  6. Characterization of D-maltose as a T2-exchange contrast agent for dynamic contrast-enhanced MRI.

    Science.gov (United States)

    Goldenberg, Joshua M; Pagel, Mark D; Cárdenas-Rodríguez, Julio

    2018-01-25

    We sought to investigate the potential of D-maltose, D-sorbitol, and D-mannitol as T 2 exchange magnetic resonance imaging (MRI) contrast agents. We also sought to compare the in vivo pharmacokinetics of D-maltose with D-glucose with dynamic contrast enhancement (DCE) MRI. T 1 and T 2 relaxation time constants of the saccharides were measured using eight pH values and nine concentrations. The effect of echo spacing in a multiecho acquisition sequence used for the T 2 measurement was evaluated for all samples. Finally, performances of D-maltose and D-glucose during T 2 -weighted DCE-MRI were compared in vivo. Estimated T 2 relaxivities (r 2 ) of D-glucose and D-maltose were highly and nonlinearly dependent on pH and echo spacing, reaching their maximum at pH = 7.0 (∼0.08 mM -1 s -1 ). The r 2 values of D-sorbitol and D-mannitol were estimated to be ∼0.02 mM -1 s -1 and were invariant to pH and echo spacing for pH ≤7.0. The change in T 2 in tumor and muscle tissues remained constant after administration of D-maltose, whereas the change in T 2 decreased in tumor and muscle after administration of D-glucose. Therefore, D-maltose has a longer time window for T 2 -weighted DCE-MRI in tumors. We have demonstrated that D-maltose can be used as a T 2 exchange MRI contrast agent. The larger, sustained T 2 -weighted contrast from D-maltose relative to D-glucose has practical advantages for tumor diagnoses during T 2 -weighted DCE-MRI. Magn Reson Med, 2018. © 2018 International Society for Magnetic Resonance in Medicine. © 2018 International Society for Magnetic Resonance in Medicine.

  7. Quantitative evaluation of contrast agent uptake in standard fat-suppressed dynamic contrast-enhanced MRI examinations of the breast.

    Science.gov (United States)

    Kousi, Evanthia; Smith, Joely; Ledger, Araminta E; Scurr, Erica; Allen, Steven; Wilson, Robin M; O'Flynn, Elizabeth; Pope, Romney J E; Leach, Martin O; Schmidt, Maria A

    2018-01-01

    To propose a method to quantify T 1 and contrast agent uptake in breast dynamic contrast-enhanced (DCE) examinations undertaken with standard clinical fat-suppressed MRI sequences and to demonstrate the proposed approach by comparing the enhancement characteristics of lobular and ductal carcinomas. A standard fat-suppressed DCE of the breast was performed at 1.5 T (Siemens Aera), followed by the acquisition of a proton density (PD)-weighted sequence, also fat suppressed. Both sequences were characterized with test objects (T 1 ranging from 30 ms to 2,400 ms) and calibration curves were obtained to enable T 1 calculation. The reproducibility and accuracy of the calibration curves were also investigated. Healthy volunteers and patients were scanned with Ethics Committee approval. The effect of B 0 field inhomogeneity was assessed in test objects and healthy volunteers. The T 1 of breast tumors was calculated at different time points (pre-, peak-, and post-contrast agent administration) for 20 patients, pre-treatment (10 lobular and 10 ductal carcinomas) and the two cancer types were compared (Wilcoxon rank-sum test). The calibration curves proved to be highly reproducible (coefficient of variation under 10%). T 1 measurements were affected by B 0 field inhomogeneity, but frequency shifts below 50 Hz introduced only 3% change to fat-suppressed T 1 measurements of breast parenchyma in volunteers. The values of T 1 measured pre-, peak-, and post-contrast agent administration demonstrated that the dynamic range of the DCE sequence was correct, that is, image intensity is approximately directly proportional to 1/T 1 for that range. Significant differences were identified in the width of the distributions of the post-contrast T 1 values between lobular and ductal carcinomas (P work has demonstrated the feasibility of fat-suppressed T 1 measurements as a tool for clinical studies. The proposed quantitative approach is practical, enabled the detection of differences between

  8. Numerical Modeling of 3-D Dynamics of Ultrasound Contrast Agent Microbubbles Using the Boundary Integral Method

    Science.gov (United States)

    Calvisi, Michael; Manmi, Kawa; Wang, Qianxi

    2014-11-01

    Ultrasound contrast agents (UCAs) are microbubbles stabilized with a shell typically of lipid, polymer, or protein and are emerging as a unique tool for noninvasive therapies ranging from gene delivery to tumor ablation. The nonspherical dynamics of contrast agents are thought to play an important role in both diagnostic and therapeutic applications, for example, causing the emission of subharmonic frequency components and enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces. A three-dimensional model for nonspherical contrast agent dynamics based on the boundary integral method is presented. The effects of the encapsulating shell are approximated by adapting Hoff's model for thin-shell, spherical contrast agents to the nonspherical case. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. Numerical analyses for the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The results show that the presence of a coating significantly reduces the oscillation amplitude and period, increases the ultrasound pressure amplitude required to incite jetting, and reduces the jet width and velocity.

  9. MRI based on iron oxide nanoparticles contrast agents: effect of oxidation state and architecture

    Science.gov (United States)

    Javed, Yasir; Akhtar, Kanwal; Anwar, Hafeez; Jamil, Yasir

    2017-11-01

    Iron oxide nanoparticles (IONPs) extensively employed beyond regenerative medicines to imaging disciplines because of their great constituents for magneto-responsive nano-systems. The unique superparamagnetic behavior makes IONPs very suitable for hyperthermia and imaging applications. From the last decade, versatile functionalization with surface capabilities, efficient contrast properties and biocompatibilities make IONPs an essential imaging contrast agent for magnetic resonance imaging (MRI). IONPs have shown signals for both longitudinal relaxation and transverse relaxation; therefore, negative contrast as well as dual contrast can be used for imaging in MRI. In the current review, we have focused on different oxidation state of iron oxides, i.e., magnetite, maghemite and hematite for their T1 and T2 contrast enhancement properties. We have also discussed different factors (synthesis protocols, biocompatibility, toxicity, architecture, etc.) that can affect the contrast properties of the IONPs. [Figure not available: see fulltext.

  10. Influence of ultrasound contrast agents on spectral Doppler analysis in recipients of liver transplantation

    OpenAIRE

    Young Seo Cho; Kyoung Won Kim; Hye Young Jang; Bo Hyun Kim; Jeongjin Lee; Gi Won Song; Sung Gyu Lee; Dagvasumberel Munkhbaatar

    2017-01-01

    Background/Aims Clinical validation is required to determine whether Doppler measurements are comparable before and after administering ultrasound contrast agent (USCA). The purpose of this study is to explore whether the use of USCA affects spectral Doppler analysis in recipients of liver transplantation (LT). Methods For this study, 36 patients were examined using Doppler ultrasonography (US) along with a contrast-enhanced US for surveillance of vascular complications after LT. The followin...

  11. Iron oxide nanoparticles for use in contrast agents in magnetic resonance imaging; Nanoparticulas de oxido de ferro para uso como agentes de contraste em imagens por ressonancia magnetica

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Elisa M.N. de; Rocha, Maximiliano S. da; Caimi, Priscila de A.; Basso, Nara R. de S.; Zanini, Mara L.; Papaleo, Ricardo M., E-mail: elisa.oliveira@acad.pucrs.br [Pontificia Universidade Catolica do Rio Grande do Sul (PUC-RS), Porto Alegre, RS (Brazil)

    2015-07-01

    In this work were carried out synthesis of iron oxide nanoparticles coated with dextran, comparing the results of using different concentrations of dextran, iron salts, temperature and reaction time. The compounds were analyzed by DLS, XRD, TGA, TEM, FTIR, Zeta Potential and relaxivity. Nanoparticles with dispersion around 10-15 nm and average hydrodynamic diameters of 16-50 nm, with superparamagnetic behavior were obtained. The ratio of the relaxivities (r2/r1) in aqueous solutions was 5.30, close to value of the commercially available iron oxide contrast agents. (author)

  12. Characterization of novel molecular photoacoustic contrast agents for in vivo photoacoustic tomography

    Science.gov (United States)

    Laoui, Samir

    Photoacoustic tomography is a hybrid imaging modality that takes advantage of the high contrast of pure optical imaging and the high intrinsic resolution of ultrasound without the necessity of ionizing radiation. Photoacoustic imaging (PM) is neither purely optical nor purely acoustical in nature, but a combination of the two. It is fundamentally based on light excitation and ultrasonic detection. Photoacoustic imaging has been successful without the introduction of exogenous contrast agents; however, to image deeper regions of biological tissue, a contrast agent is necessary. Several types of photoacoustic contrast agents have been made available for diagnostic purposes; however, the majority of literature has focused on gold nanoparticle systems for which the surface-plasmon resonance effect is important. The only option currently available for molecular PM contrast agents is to choose an existing near infrared absorbing fluorescent probes with the hope that they may generate a substantial photoacoustic (PA) response. However, these dyes have been designed with an optimized fluorescence emission response and are not anticipated to generate an adequate photoacoustic response. This dissertation addresses this lack of precedence in the literature for understanding the mechanism of a photoacoustic signal generation from strongly absorbing dye molecules including BODIPY, cyanine and curcumin systems. This work represents preliminary efforts in bringing novel molecular photoacoustic contrast agents (MPACs) into the photoacoustic imaging arena. To this end, photoacoustic and optical Z-scan experiments, and quenching studies were employed to demonstrate correlation of photoacoustic emission enhancement with excited state absorption mechanisms. To investigate further the photoacoustic emission in a practical imaging setting, MPACs were imaged using a recently developed photoacoustic imaging tomography system which was constructed exclusively for the purpose of this study.

  13. 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.

  14. The Impact of Gadolinium-based Contrast Agent for Carbon Ion Radiotherapy.

    Science.gov (United States)

    Mogi, Nao; Sakai, Makoto; Okada, Ryosuke; Itabashi, Yusuke; Fukushima, Yasuhiro; Kubota, Yoshiki; Sutou, Takayuki; Nakano, Takashi; Ohno, Tatsuya

    2016-01-01

    The contrast agent used in the diagnostic department has high atomic numbers and might influence dose deposition in the particle therapy. In particular, the influence of gadolinium-based (Gd) contrast agent on range in carbon ion radiotherapy has not yet been evaluated. For this reason, we avoid carbon treatment and planning computed tomography (CT) acquisition on days when the contrast-enhanced magnetic resonance image (MRI) is performed. In this study, we evaluated the time required for this beam range effect to vanish by evaluating the temporal changes in the CT values after an enhanced MRI as well as the stopping power of Gd solution. Two types of diluted solutions with Gd contrast agent were used for comparing their transferred stopping power (TSP) and measured stopping power (MSP). The TSP was calculated with a CT value to stopping power ratio table that was created previously. Additionally, to evaluate in vivo attenuation, we measured the CT values in the renal pelvis from the CT images with and without contrast agent for 73 patients. The maximum difference between the TSP and MSP was 85%. The difference between the TSP after 4 hours and the TSP with non-enhanced cases was less than 1%. Moreover, the difference between the MSP after 1 hour and the MSP with non-enhanced cases was less than 0.1%. It was found that the impact of Gd contrast agent can be neglected 1 hour after administration for carbon beam irradiation and 4 hours after for planning the CT image acquisition.

  15. Spectral fractionation detection of gold nanorod contrast agents using optical coherence tomography

    Science.gov (United States)

    Jia, Yali; Liu, Gangjun; Gordon, Andrew Y.; Gao, Simon S.; Pechauer, Alex D.; Stoddard, Jonathan; McGill, Trevor J.; Jayagopal, Ashwath; Huang, David

    2015-01-01

    We demonstrate the proof of concept of a novel Fourier-domain optical coherence tomography contrast mechanism using gold nanorod contrast agents and a spectral fractionation processing technique. The methodology detects the spectral shift of the backscattered light from the nanorods by comparing the ratio between the short and long wavelength halves of the optical coherence tomography signal intensity. Spectral fractionation further divides the halves into sub-bands to improve spectral contrast and suppress speckle noise. Herein, we show that this technique can detect gold nanorods in intralipid tissue phantoms. Furthermore, cellular labeling by gold nanorods was demonstrated using retinal pigment epithelial cells in vitro. PMID:25836459

  16. Development of silica-encapsulated silver nanoparticles as contrast agents intended for dual-energy mammography.

    Science.gov (United States)

    Karunamuni, Roshan; Naha, Pratap C; Lau, Kristen C; Al-Zaki, Ajlan; Popov, Anatoliy V; Delikatny, Edward J; Tsourkas, Andrew; Cormode, David P; Maidment, Andrew D A

    2016-09-01

    Dual-energy (DE) mammography has recently entered the clinic. Previous theoretical and phantom studies demonstrated that silver provides greater contrast than iodine for this technique. Our objective was to characterize and evaluate in vivo a prototype silver contrast agent ultimately intended for DE mammography. The prototype silver contrast agent was synthesized using a three-step process: synthesis of a silver core, silica encapsulation and PEG coating. The nanoparticles were then injected into mice to determine their accumulation in various organs, blood half-life and dual-energy contrast. All animal procedures were approved by the institutional animal care and use committee. The final diameter of the nanoparticles was measured to be 102 (±9) nm. The particles were removed from the vascular circulation with a half-life of 15 min, and accumulated in macrophage-rich organs such as the liver, spleen and lymph nodes. Dual-energy subtraction techniques increased the signal difference-to-noise ratio of the particles by as much as a factor of 15.2 compared to the single-energy images. These nanoparticles produced no adverse effects in mice. Silver nanoparticles are an effective contrast agent for dual-energy x-ray imaging. With further design improvements, silver nanoparticles may prove valuable in breast cancer screening and diagnosis. • Silver has potential as a contrast agent for DE mammography. • Silica-coated silver nanoparticles are biocompatible and suited for in vivo use. • Silver nanoparticles produce strong contrast in vivo using DE mammography imaging systems.

  17. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Comparison and evaluation of indicator dilution models for bolus of ultrasound contrast agents

    Czech Academy of Sciences Publication Activity Database

    Harabis, V.; Kolář, R.; Mézl, M.; Jiřík, Radovan

    2013-01-01

    Roč. 34, č. 2 (2013), s. 151-162 ISSN 0967-3334 R&D Projects: GA ČR GAP102/12/2380 Institutional support: RVO:68081731 Keywords : perfusion model * ultrasound * contrast agent * intravascular perfusion * tissue phantom Subject RIV: FS - Medical Facilities ; Equipment Impact factor: 1.617, year: 2013

  19. Three-dimensional magnetic resonance coronary angiography using a new blood pool contrast agent : Initial experience

    NARCIS (Netherlands)

    Bedaux, WLF; Hofman, MBM; Wielopolski, PA; de Cock, CC; Hoffmann, [No Value; Oudkerk, M; de Feyter, PJ; van Rossum, AC

    2002-01-01

    Objective: The aim of this feasibility study was to assess the effect of a new blood pool contrast agent on magnetic resonance coronary angiography (MRCA) in patients suspected of having coronary artery disease. Methods: Nine patients referred for diagnostic x-ray coronary, angiography in the

  20. Clusters of magnetic nanoparticles as contrast agents for MRI: effect of aggregation on transverse relaxivity

    Czech Academy of Sciences Publication Activity Database

    Dědourková, T.; Kaman, Ondřej; Veverka, Pavel; Koktan, Jakub; Veverka, Miroslav; Kuličková, Jarmila; Jirák, Zdeněk; Herynek, V.

    2015-01-01

    Roč. 51, č. 11 (2015), s. 5300804 ISSN 0018-9464 R&D Projects: GA ČR GA15-10088S; GA MPO FR-TI3/521 Institutional support: RVO:68378271 Keywords : contrast agents * magnetic resonance imaging * magnetic nanoparticles * manganites * transverse relaxivity Subject RIV: BM - Solid Matter Physics ; Magnetism Impact factor: 1.277, year: 2015

  1. Some contrast agents in oil well logging and in medical MRI.

    Science.gov (United States)

    Brown, R J

    1993-04-01

    Magnetite particles and paramagnetic ion chelates are used as contrast agents in both nuclear magnetism logging of oil wells and in medical MRI. An analytic expression for reduction of T2 for free precession signal decay (or gradient echoes) by magnetite particles does not depend on diffusion and agrees with published Monte Carlo computations.

  2. Effect of self-demodulation on the subharmonic response of contrast agent microbubbles

    NARCIS (Netherlands)

    V. Daeichin (Verya); T. Faez (Telli); G. Renaud (G.); J.G. Bosch (Hans); A.F.W. van der Steen (Ton); N. de Jong (Nico)

    2012-01-01

    textabstractSubharmonic (SH) emission from the ultrasound contrast agent (UCA) is of interest since it is produced only by the UCA and not by tissue, opposite to harmonic imaging modes where both tissue and microbubble show harmonics. In this work, the use of the self-demodulation (S-D) signal as a

  3. Melanin-Based Contrast Agents for Biomedical Optoacoustic Imaging and Theranostic Applications.

    Science.gov (United States)

    Longo, Dario Livio; Stefania, Rachele; Aime, Silvio; Oraevsky, Alexander

    2017-08-07

    Optoacoustic imaging emerged in early 1990s as a new biomedical imaging technology that generates images by illuminating tissues with short laser pulses and detecting resulting ultrasound waves. This technique takes advantage of the spectroscopic approach to molecular imaging, and delivers high-resolution images in the depth of tissue. Resolution of the optoacoustic imaging is scalable, so that biomedical systems from cellular organelles to large organs can be visualized and, more importantly, characterized based on their optical absorption coefficient, which is proportional to the concentration of absorbing chromophores. Optoacoustic imaging was shown to be useful in both preclinical research using small animal models and in clinical applications. Applications in the field of molecular imaging offer abundant opportunities for the development of highly specific and effective contrast agents for quantitative optoacoustic imaging. Recent efforts are being made in the direction of nontoxic biodegradable contrast agents (such as nanoparticles made of melanin) that are potentially applicable in clinical optoacoustic imaging. In order to increase the efficiency and specificity of contrast agents and probes, they need to be made smart and capable of controlled accumulation in the target cells. This review was written in recognition of the potential breakthroughs in medical optoacoustic imaging that can be enabled by efficient and nontoxic melanin-based optoacoustic contrast agents.

  4. Dynamic assessment of the focal hepatic lesion in rats using ultrasonic contrast agent.

    Science.gov (United States)

    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.

  5. Contrast Agents for Micro-Computed Tomography of Microdamage in Bone

    National Research Council Canada - National Science Library

    Roeder, Ryan K

    2008-01-01

    ...) and contrast agents with higher x-ray attenuation than bone. The ability to detect the presence and to a limited extent the morphology of microdamage in cortical and trabecular bone using micro-CT was demonstrated using a barium sulfate (BaSO4) stain...

  6. 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...

  7. Manganese ferrite nanoparticle micellar nanocomposites as MRI contrast agent for liver imaging.

    Science.gov (United States)

    Lu, Jian; Ma, Shuli; Sun, Jiayu; Xia, Chunchao; Liu, Chen; Wang, Zhiyong; Zhao, Xuna; Gao, Fabao; Gong, Qiyong; Song, Bin; Shuai, Xintao; Ai, Hua; Gu, Zhongwei

    2009-05-01

    Iron oxide nanoparticles are effective contrast agents for enhancement of magnetic resonance imaging at tissue, cellular or even molecular levels. In this study, manganese doped superparamagnetic iron oxide (Mn-SPIO) nanoparticles were used to form ultrasensitive MRI contrast agents for liver imaging. Hydrophobic Mn-SPIO nanoparticles are synthesized in organic phase and then transferred into water with the help of block copolymer mPEG-b-PCL. These Mn-SPIO nanoparticles are self-assembled into small clusters (mean diameter approximately 80nm) inside micelles as revealed by transmission electron microscopy. Mn-SPIO nanoparticles inside micelles decrease PCL crystallization temperatures, as verified from differential scanning calorimetry and Fourier transform infrared spectroscopy. The Mn-SPIO based nanocomposites are superparamagnetic at room temperature. At the magnetic field of 1.5T, Mn-SPIO nanoparticle clustering micelles have a T(2) relaxivity of 270 (Mn+Fe)mM(-1)s(-1), which is much higher than single Mn-SPIO nanoparticle containing lipid-PEG micelles. This clustered nanocomposite has brought significant liver contrast with signal intensity changes of -80% at 5min after intravenous administration. The time window for enhanced-MRI can last about 36h with obvious contrast on liver images. This sensitive MRI contrast agent may find applications in identification of small liver lesions, evaluation of the degree of liver cirrhosis, and differential diagnosis of other liver diseases.

  8. Development of silica-encapsulated silver nanoparticle as contrast agents intended for dual-energy mammography

    Science.gov (United States)

    Karunamuni, Roshan; Naha, Pratap C.; Lau, Kristen C.; Al-Zaki, Ajlan; Popov, Anatoliy V.; Cormode, David P.; Delikatny, Edward J.; Tsourkas, Andrew; Maidment, Andrew D.A.

    2016-01-01

    Objective Dual-energy (DE) mammography has recently entered the clinic. Previous theoretical and phantom studies demonstrated that silver provides greater contrast than iodine for this technique. Our objective was to characterize and evaluate in vivo a prototype silver contrast agent ultimately intended for DE mammography. Methods The prototype silver contrast agent was synthesized using a three-step process: synthesis of a silver core, silica encapsulation, and PEG coating. The nanoparticles were then injected into mice to determine their accumulation in various organs, blood half-life, and dual-energy contrast. All animal procedures were approved by the Institutional Animal Care and Use Committee. Results The final diameter of the nanoparticles was measured to be 102 (± 9) nm. The particles were removed from the vascular circulation with a half-life of 15 minutes, and accumulated in macrophage-rich organs such as the liver, spleen, and lymph nodes. Dual-energy subtraction techniques increased the signal difference-to-noise ratio of the particles by as much as a factor of 15.2 compared to the single-energy images. These nanoparticles produced no adverse effects in mice. Conclusion Silver nanoparticles are an effective contrast agent for dual-energy x-ray imaging. With further design improvements, silver nanoparticles may prove valuable in breast cancer screening and diagnosis. PMID:26910906

  9. Ultrasound Contrast Agents in the Study of Kidney Function in Health and Disease

    Science.gov (United States)

    Kalantarinia, Kambiz; Okusa, Mark D.

    2008-01-01

    Ultrasound contrast agents are gas filled microbubbles that enhance the ultrasound image. They behave similarly to red blood cells and cross all capillary beds; making contrast enhanced ultrasonography (CEU) a suitable technique to study vasculature and tissue blood flow. Ultrasound contrast agents have been found to be safe after intravenous injection. CEU has been used extensively in the field of cardiology. Currently, study of renal vasculature and renal blood flow requires complicated, time consuming and expensive techniques, which are not commonly used in clinical settings. CEU potentially may serve as a relatively noninvasive and safe technique for studying renal hemodynamics in health and disease. In this article we have reviewed the literature on the use of CEU in the study of kidney disease. PMID:19112526

  10. Fatal anaphylactic reaction to intravenous gadobutrol, a gadolinium-based MRI contrast agent

    Directory of Open Access Journals (Sweden)

    Sabine Franckenberg, MD

    2018-02-01

    Full Text Available We present the rare case of a fatal anaphylactic reaction to gadobutrol, a magnetic resonance imaging contrast agent, in a 42-year-old man. The patient underwent elective magnetic resonance imaging for diagnostic clarification of a suspicious finding in the abdomen. The patient had undergone contrast-enhanced computed tomography previously without the occurrence of any adverse effects. Adverse drug reactions in gadobutrol have a very low prevalence of 0.32%-3.5%, with serious adverse drug reactions in <0.1%. There are only a few cases of fatal anaphylactoid reactions to gadolinium-based contrast agents in general. However, if an anaphylactoid reaction occurs, it can present itself with a fulminant course within minutes.

  11. Tuning phenols with Intra-Molecular bond Shifted HYdrogens as diaCEST MRI contrast agents

    Science.gov (United States)

    Yang, Xing; Yadav, Nirbhay N.; Song, Xiaolei; Banerjee, Sangeeta Ray; Edelman, Hannah; Minn, Il; van Zijl, Peter C. M.; Pomper, Martin G.; McMahon, Michael T.

    2014-01-01

    We characterize what the optimal exchange properties are for CEST contrast agents on 3T clinical scanners using CW saturation transfer, and demonstrate that the exchangeable protons in phenols can be tuned to reach these criteria through proper ring substitution. Systematic modification allows the chemical shift of the exchangeable protons to be positioned between 4.8 ppm to 12 ppm from water and enables adjustment of the proton exchange rate to maximize CEST contrast at these shifts. In particular, 44 hydrogen-bonded phenols are investigated for their potential as CEST MRI contrast agents and the stereoelectronic effects on their CEST properties summarized. Furthermore, we identify a pair of compounds, 2,5-dihydroxyterephthalic acid (42) and 4,6-dihydroxyisophthalic acid (43), which produce the highest sensitivity through incorporating two exchangeable protons per ring. PMID:25302635

  12. 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.

  13. Noninvasive Ambient Pressure Estimation using Ultrasound Contrast Agents -- Invoking Subharmonics for Cardiac and Hepatic Applications

    Science.gov (United States)

    Dave, Jaydev K.

    Ultrasound contrast agents (UCAs) are encapsulated microbubbles that provide a source for acoustic impedance mismatch with the blood, due to difference in compressibility between the gas contained within these microbubbles and the blood. When insonified by an ultrasound beam, these UCAs act as nonlinear scatterers and enhance the echoes of the incident pulse, resulting in scattering of the incident ultrasound beam and emission of fundamental (f0), subharmonic (f0/2), harmonic (n*f0; n ∈ N) and ultraharmonic (((2n-1)/2)*f0; n ∈ N & n > 1) components in the echo response. A promising approach to monitor in vivo pressures revolves around the fact that the ultrasound transmit and receive parameters can be selected to induce an ambient pressure amplitude dependent subharmonic signal. This subharmonic signal may be used to estimate ambient pressure amplitude; such technique of estimating ambient pressure amplitude is referred to as subharmonic aided pressure estimation or SHAPE. This project develops and evaluates the feasibility of SHAPE to noninvasively monitor cardiac and hepatic pressures (using commercially available ultrasound scanners and UCAs) because invasive catheter based pressure measurements are used currently for these applications. Invasive catheter based pressure measurements pose risk of introducing infection while the catheter is guided towards the region of interest in the body through a percutaneous incision, pose risk of death due to structural or mechanical failure of the catheter (which has also triggered product recalls by the USA Food and Drug Administration) and may potentially modulate the pressures that are being measured. Also, catheterization procedures require fluoroscopic guidance to advance the catheter to the site of pressure measurements and such catheterization procedures are not performed in all clinical centers. Thus, a noninvasive technique to obtain ambient pressure values without the catheterization process is clinically

  14. 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.

  15. 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)

  16. 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.

  17. Comparison of synthetic HDL contrast agents for MR imaging of atherosclerosis

    Science.gov (United States)

    Cormode, David P.; Chandrasekar, Rohith; Delshad, Amanda; Briley-Saebo, Karen C.; Calcagno, Claudia; Barazza, Alessandra; Mulder, Willem J. M.

    2009-01-01

    Determining arterial macrophage expression is an important goal in the molecular imaging of atherosclerosis. Here we compare the efficacy of two synthetic, HDL-based contrast agents for magnetic resonance imaging (MRI) of macrophage burden. Each form of HDL was labeled with gadolinium and rhodamine to allow MRI and fluorescence microscopy. Either the 37 or 18 amino acid peptide replaced the apolipoprotein A-I in these agents, which were termed 37pA-Gd or 18A-Gd. The diameters of 37pA-Gd and 18A-Gd are 7.6 nm and 8.0 nm, respectively, while the longitudinal relaxivities are 9.8 and 10.0 (mMs)-1. 37pA has better lipid binding properties. In vitro tests with J774A.1 macrophages proved the particles possessed the functionality of HDL by eliciting cholesterol efflux and were taken up in a receptor-like fashion by the cells. Both agents produced enhancements in atherosclerotic plaques of apolipoprotein E knockout mice of ~90% (n=7 per agent) and are macrophage specific as evidenced by confocal microscopy on aortic sections. The half-lives of 37pA-Gd and 18A-Gd are 2.6 and 2.1 hours, respectively. Despite the more favorable lipid interactions of 37pA, both agents gave similar, excellent contrast for the detection of atherosclerotic macrophages using MRI. PMID:19378935

  18. Comparison of synthetic high density lipoprotein (HDL) contrast agents for MR imaging of atherosclerosis.

    Science.gov (United States)

    Cormode, David P; Chandrasekar, Rohith; Delshad, Amanda; Briley-Saebo, Karen C; Calcagno, Claudia; Barazza, Alessandra; Mulder, Willem J M; Fisher, Edward A; Fayad, Zahi A

    2009-05-20

    Determining arterial macrophage expression is an important goal in the molecular imaging of atherosclerosis. Here, we compare the efficacy of two synthetic, high density lipoprotein (HDL) based contrast agents for magnetic resonance imaging (MRI) of macrophage burden. Each form of HDL was labeled with gadolinium and rhodamine to allow MRI and fluorescence microscopy. Either the 37 or 18 amino acid peptide replaced the apolipoprotein A-I in these agents, which were termed 37pA-Gd or 18A-Gd. The diameters of 37pA-Gd and 18A-Gd are 7.6 and 8.0 nm, respectively, while the longitudinal relaxivities are 9.8 and 10.0 (mM s)(-1). 37pA has better lipid binding properties. In vitro tests with J774A.1 macrophages proved the particles possessed the functionality of HDL by eliciting cholesterol efflux and were taken up in a receptor-like fashion by the cells. Both agents produced enhancements in atherosclerotic plaques of apolipoprotein E knockout mice of approximately 90% (n = 7 per agent) and are macrophage specific as evidenced by confocal microscopy on aortic sections. The half-lives of 37pA-Gd and 18A-Gd are 2.6 and 2.1 h, respectively. Despite the more favorable lipid interactions of 37pA, both agents gave similar, excellent contrast for the detection of atherosclerotic macrophages using MRI.

  19. 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.)

  20. Development of a targeted CT contrast agent: assessment of cellular interactions using novel integrated optical labels

    Science.gov (United States)

    Matsuura, Naomi; Hill, Melissa L.; Gorelikov, Ivan; Zhu, Siqi; Wan, Kelvin; Mainprize, James G.; Yaffe, Martin J.; Rowlands, J. A.

    2009-02-01

    Computed tomography (CT) enables high resolution, whole-body imaging with excellent depth penetration. The development of new targeted radiopaque CT contrast agents can provide the required sensitivity and localization for the successful detection and diagnosis of smaller lesions representing earlier disease. Nanoscale, perfluorooctylbromide (C8F17Br, PFOB) droplets have previously been used as untargeted contrast agents in X-ray imaging, and form the basis of a promising new group of agents that can be developed for targeted CT imaging. For successful targeting to disease sites, new PFOB droplet formulations tailored for ideal in vivo performance (e.g., biodistribution, toxicity, and pharmacokinetics) must be developed. However, the direct assessment of PFOB agents in biological environments early in their development is difficult using CT, as its sensitivity is not adequate for identification of single probes in vitro or in vivo. In order to allow single droplet interactions with cells to be directly assessed using standard cellular imaging tools, we integrate an optical marker within the PFOB agent. In this work, a new method to label a PFOB agent with fluorescent quantum dot (QD) nanoparticles is presented. These composite PFOB-QD droplets loaded into macrophage cells result in fluorescence on a cellular level that correlates well to the strong CT contrast exhibited in corresponding tissue-mimicking cell pellets. QD loading within the PFOB droplet core allows optical labeling without influencing the surface-dependent properties of the PFOB droplets in vivo, and may be used to follow PFOB localization from in vitro cell studies to histopathology.

  1. Cross-Linked and Biodegradable Polymeric System as a Safe Magnetic Resonance Imaging Contrast Agent.

    Science.gov (United States)

    Luo, Qiang; Xiao, Xueyang; Dai, Xinghang; Duan, Zhenyu; Pan, Dayi; Zhu, Hongyan; Li, Xue; Sun, Ling; Luo, Kui; Gong, Qiyong

    2018-01-17

    Owing to the low efficacy of clinically used small-molecule gadolinium (Gd)-based magnetic resonance imaging (MRI) agents, we designed and explored biodegradable macromolecular conjugates as MRI contrast agents. The linear polymeric structure and core-cross-linked formulation possessed different characteristics and features, so we prepared and comparatively studied the two kinds of Gd-based N-(2-hydroxypropyl) methacrylamide (HPMA) polymeric systems (the core-cross-linked pHPMA-DOTA-Gd and the linear one) using the clinical agent diethylene-triamine pentaacetic acid-Gd(III) (DTPA-Gd) as a control. This study was aimed to find the optimal polymeric formulation as a biocompatible and efficient MRI contrast agent. The high molecular weight (MW, 181 kDa) and core-cross-linked copolymer was obtained via the cross-linked block linear copolymer and could be degraded to low-MW segments (29 kDa) in the presence of glutathione (GSH) and cleaned from the body. Both core-cross-linked and linear pHPMA-DOTA-Gd copolymers displayed 2-3-fold increased relaxivity (r1 value) than that of DTPA-Gd. Animal studies demonstrated that two kinds of macromolecular systems led to much longer blood circulation time, higher tumor accumulation, and much higher signal intensity compared with the linear and clinical ones. Finally, in vivo and in vitro toxicity studies indicated that the two macromolecular agents had great biocompatibility. Therefore, we performed preliminary but important studies on the Gd-based HPMA polymeric systems as biocompatible and efficient MRI contrast agents and found that the biodegradable core-cross-linked pHPMA-DOTA-Gd copolymer might have greater benefits for the foreground.

  2. Increased transverse relaxivity in ultrasmall superparamagnetic iron oxide nanoparticles used as MRI contrast agent for biomedical imaging.

    Science.gov (United States)

    Mishra, Sushanta Kumar; Kumar, B S Hemanth; Khushu, Subash; Tripathi, Rajendra P; Gangenahalli, Gurudutta

    2016-09-01

    Synthesis of a contrast agent for biomedical imaging is of great interest where magnetic nanoparticles are concerned, because of the strong influence of particle size on transverse relaxivity. In the present study, biocompatible magnetic iron oxide nanoparticles were synthesized by co-precipitation of Fe 2+ and Fe 3+ salts, followed by surface adsorption with reduced dextran. The synthesized nanoparticles were spherical in shape, and 12 ± 2 nm in size as measured using transmission electron microscopy; this was corroborated with results from X-ray diffraction and dynamic light scattering studies. The nanoparticles exhibited superparamagnetic behavior, superior T 2 relaxation rate and high relaxivities (r 1  = 18.4 ± 0.3, r 2  = 90.5 ± 0.8 s -1 mM -1 , at 7 T). MR image analysis of animals before and after magnetic nanoparticle administration revealed that the signal intensity of tumor imaging, specific organ imaging and whole body imaging can be clearly distinguished, due to the strong relaxation properties of these nanoparticles. Very low concentrations (3.0 mg Fe/kg body weight) of iron oxides are sufficient for early detection of tumors, and also have a clear distinction in pre- and post-enhancement of contrast in organs and body imaging. Many investigators have demonstrated high relaxivities of magnetic nanoparticles at superparamagnetic iron oxide level above 50 nm, but this investigation presents a satisfactory, ultrasmall, superparamagnetic and high transverse relaxivity negative contrast agent for diagnosis in pre-clinical studies. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  3. Balancing stealth and echogenic properties in an ultrasound contrast agent with drug delivery potential.

    Science.gov (United States)

    Jablonowski, Lauren J; Alfego, David; Andorko, James I; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

    2016-10-01

    Contrast agents are currently being modified to combine diagnostic and therapeutic capabilities. For ultrasound (US) imaging with polymeric contrast agents, it is necessary to modify the shell to create "stealth" microbubbles but without these modifications sacrificing the agent's ability to interact with the focused US beam. We hypothesize that addition of the classic immune shielding molecule polyethylene glycol (PEG) to a polylactide (PLA) microbubble shell will affect the acoustic and physical properties of the resulting agents. In an effort to determine the best formulation to achieve a balance between stealth and acoustic activity, we compared two PEGylation techniques; addition of increasing amounts of PEG-PLA copolymer and employing incorporation of a PEG lipid (LipidPEG) into the shell. Loss of acoustic enhancement occurred in a dose-dependent manner for both types of PEGylated agents (loss of signal occurred at >5 wt% PEG-PLA and >1 wt% LipidPEG), while immune activation was also reduced in a dose-dependent manner for the PEG-PLA agents. This study shows that the balance between acoustic behavior and improved immune avoidance was scalable and successful to different degrees with both PEGylation methods, and was best achieved using for PEG-PLA at 5 wt% and for LipidPEG at 1 wt%. Studies are ongoing to evaluate the best method for the targeting and drug delivery capabilities of these agents for applications in cancer treatment. This study represents the basis for understanding the consequences of making modifications to the native polymeric shell. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Epi-detection of vibrational phase contrast coherent anti-Stokes Raman scattering

    NARCIS (Netherlands)

    Garbacik, E.T.; Korterik, Jeroen P.; Otto, Cornelis; Herek, Jennifer Lynn; Offerhaus, Herman L.

    2014-01-01

    We demonstrate a system for the phase-resolved epi-detection of coherent anti-Stokes Raman scattering (CARS) signals in highly scattering and/or thick samples. With this setup, we measure the complex vibrational responses of multiple components in a thick, highly-scattering pharmaceutical tablet in

  5. 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.

  6. 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.

  7. Magnetic resonance imaging with liver-specific contrast agent in primary amyloidosis and intrahepatic cholestasis

    Energy Technology Data Exchange (ETDEWEB)

    Moeller, J.M.; Santoni-Rugiu, E.; Chabanova, E.; Logager, V.; Hansen, A.B.; Thomsen, H.S. [Depts. of Radiology and Pathology, Copenhagen Univ. Hospital, Herlev (Denmark)

    2007-02-15

    Magnetic resonance imaging (MRI) findings in hepatic amyloidosis are not well defined. Here, we report on a patient with renal failure caused by primary amyloidosis (AL type) who developed jaundice. Ultrasound and computed tomography were normal except for some ascites. MRI with oral manganese-containing contrast agent revealed several focal areas without contrast uptake in the hepatocytes and no bile secretion after 8 hours. No extrahepatic bile obstructions were found. Liver biopsy showed severe intraportal, vascular, and parenchymal amyloidosis causing severe cholestasis and atrophy of hepatocytes.

  8. 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.

  9. Molecular imaging of atherosclerosis with nanoparticle-based fluorinated MRI contrast agents.

    Science.gov (United States)

    Palekar, Rohun U; Jallouk, Andrew P; Lanza, Gregory M; Pan, Hua; Wickline, Samuel A

    2015-01-01

    As atherosclerosis remains one of the most prevalent causes of patient mortality, the ability to diagnose early signs of plaque rupture and thrombosis represents a significant clinical need. With recent advances in nanotechnology, it is now possible to image specific molecular processes noninvasively with MRI, using various types of nanoparticles as contrast agents. In the context of cardiovascular disease, it is possible to specifically deliver contrast agents to an epitope of interest for detecting vascular inflammatory processes, which serve as predecessors to atherosclerotic plaque development. Herein, we review various applications of nanotechnology in detecting atherosclerosis using MRI, with an emphasis on perfluorocarbon nanoparticles and fluorine imaging, along with theranostic prospects of nanotechnology in cardiovascular disease.

  10. An analytical study of photoacoustic and thermoacoustic generation efficiency towards contrast agent and film design optimization

    Directory of Open Access Journals (Sweden)

    Fei Gao

    2017-09-01

    Full Text Available Photoacoustic (PA and thermoacoustic (TA effects have been explored in many applications, such as bio-imaging, laser-induced ultrasound generator, and sensitive electromagnetic (EM wave film sensor. In this paper, we propose a compact analytical PA/TA generation model to incorporate EM, thermal and mechanical parameters, etc. From the derived analytical model, both intuitive predictions and quantitative simulations are performed. It shows that beyond the EM absorption improvement, there are many other physical parameters that deserve careful consideration when designing contrast agents or film composites, followed by simulation study. Lastly, several sets of experimental results are presented to prove the feasibility of the proposed analytical model. Overall, the proposed compact model could work as a clear guidance and predication for improved PA/TA contrast agents and film generator/sensor designs in the domain area.

  11. Optimizing Acoustic Activation of Phase Change Contrast Agents with the Activation Pressure Matching Method: A Review.

    Science.gov (United States)

    Rojas, Juan D; Dayton, Paul A

    2016-10-12

    Sub-micron phase-change contrast agents consist of a liquid perfluorocarbon core that can be vaporized by ultrasound (acoustic droplet vaporization) to generate contrast with excellent spatial and temporal control. When these agents, commonly referred to as nanodroplets, are formulated with cores of low boiling-point perfluorocarbons such as decafluorobutane and octafluoropropane, they can be activated with lowmechanical index imaging pulses for diagnostic applications. Since the utilization of minimum mechanical index is often desirable to avoid unnecessary biological effects, enabling consistent activation of these agents in an acoustic field is a challenge because the energy that must be delivered to achieve the vaporization threshold increases with depth due to attenuation. A novel vaporization approach called Activation Pressure Matching has been developed to deliver the same pressure throughout a field of view in order to produce uniform nanodroplet vaporization and to limit the amount of energy that is delivered. In this manuscript, we discuss the application of this method with a Versasonics V1 Research Ultrasound System to modulate the output pressure from an ATL L11-5 transducer. Vaporization-pulse spacing optimization can be used in addition to matching the activation pressure through depth, and we demonstrate the feasibility of this approach both in vivo and in vitro. The use of optimized vaporization parameters increases the amount of time a single bolus of nanodroplets can generate useful contrast and provides consistent image enhancement in vivo. Therefore, APM is a useful technique for those wishing to maximize the efficacy of phase change contrast agent while minimizing delivered acoustic energy.

  12. Performance characteristics of magnetic resonance imaging without contrast agents or sedation in pediatric appendicitis

    Energy Technology Data Exchange (ETDEWEB)

    Didier, Ryne A.; Hopkins, Katharine L.; Coakley, Fergus V.; Foster, Bryan R. [Oregon Health and Science University, Department of Diagnostic Radiology, Portland, OR (United States); Krishnaswami, Sanjay [Oregon Health and Science University, Department of Surgery, Portland, OR (United States); Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States); Spiro, David M. [Oregon Health and Science University, Department of Pediatrics, Portland, OR (United States)

    2017-09-15

    Magnetic resonance imaging (MRI) has emerged as a promising modality for evaluating pediatric appendicitis. However optimal imaging protocols, including roles of contrast agents and sedation, have not been established and diagnostic criteria have not been fully evaluated. To investigate performance characteristics of rapid MRI without contrast agents or sedation in the diagnosis of pediatric appendicitis. We included patients ages 4-18 years with suspicion of appendicitis who underwent rapid MRI between October 2013 and March 2015 without contrast agent or sedation. After two-radiologist review, we determined performance characteristics of individual diagnostic criteria and aggregate diagnostic criteria by comparing MRI results to clinical outcomes. We used receiver operating characteristic (ROC) curves to determine cut-points for appendiceal diameter and wall thickness for optimization of predictive power, and we calculated area under the curve (AUC) as a measure of test accuracy. Ninety-eight MRI examinations were performed in 97 subjects. Overall, MRI had a 94% sensitivity, 95% specificity, 91% positive predictive value and 97% negative predictive value. Optimal cut-points for appendiceal diameter and wall thickness were ≥7 mm and ≥2 mm, respectively. Independently, those cut-points produced sensitivities of 91% and 84% and specificities of 84% and 43%. Presence of intraluminal fluid (30/33) or localized periappendiceal fluid (32/33) showed a significant association with acute appendicitis (P<0.01), with sensitivities of 91% and 97% and specificities of 60% and 50%. For examinations in which the appendix was not identified by one or both reviewers (23/98), the clinical outcome was negative. Rapid MRI without contrast agents or sedation is accurate for diagnosis of pediatric appendicitis when multiple diagnostic criteria are considered in aggregate. Individual diagnostic criteria including optimized cut-points of ≥7 mm for diameter and ≥2 mm for wall

  13. 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.)

  14. 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)

  15. 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.

  16. 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.)

  17. Application of an exogenous hyperoxic contrast agent in MR mammography: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, Dorothee R.; Reichenbach, Juergen R.; Rauscher, Alexander; Sedlacik, Jan; Kaiser, Werner A. [Friedrich Schiller University Jena, Institute of Diagnostic and Interventional Radiology, Jena (Germany)

    2005-04-01

    There is interest in applying novel methods to dynamic MR mammography (MRM). One such possibility is to administer an exogenous hyperoxic contrast agent, such as carbogen (95-98% O{sub 2} and 2-5% CO{sub 2}) or pure oxygen (100% O{sub 2}). We report our first experiences with these agents in a patient with an invasive lobular carcinoma. Fourteen dynamic series were acquired with an rf-spoiled 2D multislice gradient echo sequence, including three measurements while breathing air, four measurements with 100% oxygen, three measurements with air and four measurements with carbogen. Afterwards, 0.1 mmol/kg bw of Gd-DTPA was administered to obtain dynamic T1-weighted double-echo 3D axial gradient echo images (TR/TE{sub 1}/TE{sub 2}/{alpha}=7.8 ms/2 ms/4.76 ms/15 ) every 90 s up to 4.5 min after injection. The lesion was well delineated on the contrast-enhanced images, contrary to magnitude images reconstructed from the raw data sets acquired during air/oxygen/carbogen breathing. A ROI-based median-filtered signal-time course revealed a tumor signal increase of roughly 15% between scans acquired during air and oxygen breathing. Though preliminary, these first results are encouraging concerning the exploration of these alternative contrast agents in MRM in greater detail. (orig.)

  18. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Pengfei [State Key Laboratory Breeding Base of Nonferrous Metals and Specific Materials Processing, School of Materials Science and Engineering, Guilin University of Technology, Jian Gan Road 12, Guilin 541004 (China); Shen, Zhiwei [Second Affiliated Hospital of Shantou University Medical College, Dong Xia North Road, Shantou 515041,China (China); Zhang, Baolin, E-mail: baolinzhang@ymail.com [State Key Laboratory Breeding Base of Nonferrous Metals and Specific Materials Processing, School of Materials Science and Engineering, Guilin University of Technology, Jian Gan Road 12, Guilin 541004 (China); Wang, Jun [State Key Laboratory Breeding Base of Nonferrous Metals and Specific Materials Processing, School of Materials Science and Engineering, Guilin University of Technology, Jian Gan Road 12, Guilin 541004 (China); Wu, Renhua, E-mail: rhwu@stu.edu.cn [Second Affiliated Hospital of Shantou University Medical College, Dong Xia North Road, Shantou 515041,China (China)

    2016-12-15

    Highlights: • SPIONs were conjugated with EGTA by EDC/sulfo-NHS method. • The presence of Ca{sup 2+} induced the aggregation of EGTA-SPIONs. • The aggregation of EGTA-SPIONs increased the T2 relaxation time. • EGTA-SPIONs can be used for the calcium imaging with MRI. - Abstract: Superparamagnetic iron oxide nanoparticles (SPIONs) as T2 contrast agents have great potential to sense calcium ion (Ca{sup 2+}) 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 Ca{sup 2+}. 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 Ca{sup 2+}. The T2 values decreased 25% when Ca{sup 2+} 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 Ca{sup 2+}-sensitive MRI.

  20. Insonation frequency selection may assist detection and therapeutic delivery of targeted ultrasound contrast agents.

    Science.gov (United States)

    Payne, Edward; Ooi, Andrew; Manasseh, Richard

    2011-02-01

    Ultrasound-targeted drug delivery relies on the unique nature of ultrasound contrast agents--they are microbubbles that respond strongly to ultrasound. Intravenously injected microbubbles are smaller than a blood cell. By increasing the ultrasound power, the bubbles can be ruptured at the targeted endothelial wall, locally releasing any molecules in the bubble shell. Furthermore, ultrasound-activated microbubbles are known to cause sonoporation--the process by which ultrasound drives molecules through cellular membranes. However, techniques are required to selectively detect and rupture only those microbubbles on target walls. Experiments are presented on the behaviour of microbubbles on walls. For accuracy, imaging measurements are made on model microbubbles larger than contrast agents. Bubble size was varied and the resonant frequency peak determined. Microbubbles on walls have a shifted frequency in good agreement with theory: a 20-25% downshift from the frequency when far from walls. Effects other than the presence of the wall account for less than 5% of the shift. Theory predicts the frequency downshift should be sustained for actual contrast-agent sized bubbles. The effect of real, compliant cell walls requires investigation. An appropriate downshift in the applied ultrasound frequency could selectively tune gene or drug delivery. To make this feasible, it may be necessary to manufacture monodispersed microbubbles.

  1. Transient analysis of electromagnetic wave interactions on high-contrast scatterers using volume electric field integral equation

    KAUST Repository

    Sayed, Sadeed Bin

    2014-07-01

    A marching on-in-time (MOT)-based time domain volume electric field integral equation (TD-VEFIE) solver is proposed for accurate and stable analysis of electromagnetic wave interactions on high-contrast scatterers. The stability is achieved using band-limited but two-sided (non-causal) temporal interpolation functions and an extrapolation scheme to cast the time marching into a causal form. The extrapolation scheme is designed to be highly accurate for oscillating and exponentially decaying fields, hence it accurately captures the physical behavior of the resonant modes that are excited inside the dielectric scatterer. Numerical results demonstrate that the resulting MOT scheme maintains its stability as the number of resonant modes increases with the contrast of the scatterer.

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

    Science.gov (United States)

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

    2016-01-01

    Objectives The aim of this study was to evaluate Gd retention in the deep cerebellar nuclei (DCN) of linear gadolinium-based contrast agents (GBCAs) compared with a macrocyclic contrast agent. Materials and Methods The brain tissue retention of Gd of 3 linear GBCAs (gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide) and a macrocyclic GBCA (gadoterate meglumine) was compared in healthy rats (n = 8 per group) that received 20 intravenous injections of 0.6 mmol Gd/kg (4 injections per week for 5 weeks). An additional control group with saline was included. T1-weighted magnetic resonance imaging was performed before injection and once a week during the 5 weeks of injections and for another 4 additional weeks after contrast period. Total gadolinium concentration was measured with inductively coupled plasma mass spectrometry. Blinded qualitative and quantitative evaluations of the T1 signal intensity in DCN were performed, as well as a statistical analysis on quantitative data. Results At completion of the injection period, all the linear contrast agents (gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide) induced a significant increase in signal intensity in DCN, unlike the macrocyclic GBCA (gadoterate meglumine) or saline. The T1 hypersignal enhancement kinetic was fast for gadodiamide. Total Gd concentrations for the 3 linear GBCAs groups at week 10 were significantly higher in the cerebellum (1.21 ± 0.48, 1.67 ± 0.17, and 3.75 ± 0.18 nmol/g for gadobenate dimeglumine, gadopentetate dimeglumine, and gadodiamide, respectively) than with the gadoterate meglumine (0.27 ± 0.16 nmol/g, P dimeglumine, and gadopentetate dimeglumine to healthy rats were associated with progressive and significant T1 signal hyperintensity in the DCN, along with Gd deposition in the cerebellum. This is in contrast with the macrocyclic GBCA gadoterate meglumine for which no effect was observed. PMID:26606549

  3. 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.

  4. 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.

  5. 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.

  6. Bismuth@US-tubes as a Potential Contrast Agent for X-ray Imaging Applications

    Science.gov (United States)

    Rivera, Eladio J.; Tran, Lesa A.; Hernández-Rivera, Mayra; Yoon, Diana; Mikos, Antonios G.; Rusakova, Irene A.; Cheong, Benjamin Y.; Cabreira-Hansen, Maria da Graça; Willerson, James T.; Perin, Emerson C.; Wilson, Lon J.

    2013-01-01

    The encapsulation of bismuth as BiOCl/Bi2O3 within ultra-short (ca. 50 nm) single-walled carbon nanocapsules (US-tubes) has been achieved. The Bi@US-tubes have been characterized by high-resolution transmission electron microscopy (HR-TEM), energy-dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Bi@US-tubes have been used for intracellular labeling of pig bone marrow-derived mesenchymal stem cells (MSCs) to show high X-ray contrast in computed tomography (CT) cellular imaging for the first time. The relatively high contrast is achieved with low bismuth loading (2.66% by weight) within the US-tubes and without compromising cell viability. X-ray CT imaging of Bi@US-tubes-labeled MSCs showed a nearly two-fold increase in contrast enhancement when compared to unlabeled MSCs in a 100 kV CT clinical scanner. The CT signal enhancement from the Bi@US-tubes is 500 times greater than polymer-coated Bi2S3 nanoparticles and several-fold that of any clinical iodinated contrast agent (CA) at the same concentration. Our findings suggest that the Bi@US-tubes can be used as a potential new class of X-ray CT agent for stem cell labeling and possibly in vivo tracking. PMID:24288589

  7. 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.

  8. Quantification and localization of contrast agents using delta relaxation enhanced magnetic resonance at 1.5 T.

    Science.gov (United States)

    Hoelscher, Uvo Christoph; Lother, Steffen; Fidler, Florian; Blaimer, Martin; Jakob, Peter

    2012-06-01

    Delta relaxation enhanced magnetic resonance (dreMR) is a new imaging technique based on the idea of cycling the magnetic field B (0) during an imaging sequence. The method determines the field dependency of the relaxation rate (relaxation dispersion dR (1)/dB). This quantity is of particular interest in contrast agent imaging because the parameter can be used to determine contrast agent concentrations and increases the ability to localize the contrast agent. In this paper dreMR imaging was implemented on a clinical 1.5 T MR scanner combining conventional MR imaging with fast field-cycling. Two improvements to dreMR theory are presented describing the quantification of contrast agent concentrations from dreMR data and a correction for field-cycling with finite ramp times. Experiments demonstrate the use of the extended theory and show the measurement of contrast agent concentrations with the dreMR method. A second experiment performs localization of a contrast agent with a significant improvement in comparison to conventional imaging. dreMR imaging has been extended by a method to quantify contrast agent concentrations and improved for field-cycling with finite ramp times. Robust localization of contrast agents using dreMR imaging has been performed in a sample where conventional imaging delivers inconclusive results.

  9. A theoretical study on phase-contrast mammography with Thomson-scattering x-ray sources

    Energy Technology Data Exchange (ETDEWEB)

    De Caro, Liberato; Giannini, Cinzia; Bellotti, Roberto; Tangaro, Sabina [Istituto di Cristallografia-Consiglio Nazionale delle Ricerche (IC-CNR), via Amendola 122/O, I-70125 Bari, Italy and Istituto Nazionale Fisica Nucleare, Sezione di Bari, via Amendola 173, 70126 Bari (Italy); Istituto Nazionale Fisica Nucleare, Sezione di Bari, via Amendola 173, 70126 Bari, Italy and Dipartimento Interateneo di Fisica-M. Merlin, Universita degli Studi di Bari, via Amendola 173, 70126 Bari (Italy); Istituto Nazionale Fisica Nucleare, Sezione di Bari, via Amendola 173, 70126 Bari (Italy)

    2009-10-15

    Purpose: The x-ray transmitted beam from any material/tissue depends on the complex refractive index (n=1-{delta}+i{beta}), where {delta} is responsible for the phase shift and {beta} is for the beam attenuation. Although for human tissues, the {delta} cross section is about 1000 times greater than the {beta} ones in the x-ray energy range from 10 to 150 keV, the gain in breast tumor visualization of phase-contrast mammography (PCM) with respect to absorption contact imaging (AI) is limited by the maximum dose that can be delivered to the patient. Moreover, in-line PC imaging (PCI) is the simplest experimental mode among all available x-ray PCI techniques since no optics are needed. The latter is a fundamental requirement in order to transfer the results of laboratory research into hospitals. Alternative to synchrotron radiation sources, the implementation of relativistic Thomson-scattering (TS) x-ray sources is particularly suitable for hospital use because of their high peak brightness within a relatively compact and affordable system. In this work, the possibility to realize PCM using a TS source in a hospital environment is studied, accounting for the effect of a finite deliverable dose on the PC visibility enhancement with respect to AI. Methods: The contrast-to-noise ratio of tumor-tissue lesions in PCM has been studied on the bases of a recent theoretical model, describing image contrast formation by means of both wave-optical theory and the mutual coherence formalism. The latter is used to describe the evolution, during wave propagation, of the coherence of the wave field emitted by a TS source. The contrast-to-noise ratio for both PCI and AI has been analyzed in terms of tumor size, beam energy, detector, and source distances, studying optimal conditions for performing PCM. Regarding other relevant factors which could influence ''tumor'' visibility, the authors have assumed simplified conditions such as a spherical shape description of

  10. 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.

  11. 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.

  12. 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

  13. Colloidal amphiphile self-assembly particles composed of gadolinium oleate and myverol: evaluation as contrast agents for magnetic resonance imaging.

    Science.gov (United States)

    Liu, Guozhen; Conn, Charlotte E; Waddington, Lynne J; Mudie, Stephen T; Drummond, Calum J

    2010-02-16

    Gadolinium oleate has been added at various concentrations to a Myverol inverse bicontinuous cubic phase forming system, and the potential of these systems as magnetic resonance imaging (MRI) contrast agents has been investigated. Differential scanning calorimetry (DSC), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM) measurements on the Gd oleate/Myverol systems indicate that Gd oleate is at least partially incorporated within the cubic phase of Myverol. However, at Gd oleate concentrations greater than 1 wt %, partial phase separation of the system may occur with the formation of a Gd-oleate-rich lamellar phase as well as the cubic phase. Bulk Gd oleate/Myverol mixtures can be dispersed into stable colloidal dispersions. SAXS and cryo-TEM measurements on these dispersions indicate that the presence of Gd oleate in the Myverol system prevents the formation of cubosomes from the bulk cubic phase. Instead, the dispersion consists of putative Gd-oleate-rich nonswelling lamellar nanoparticles as well as colloidal particles lacking ordered internal structure. In vitro studies on these dispersions demonstrated that the relaxivity of select Gd oleate/Myverol systems is much higher than that of pure Gd oleate, exemplifying the promise of this system type for magnetic resonance imaging. The highest water proton relaxivities (r(1) = 34.2 mM(-1) s(-1) and r(2) = 27.3 mM(-1) s(-1) at 20 MHz and room temperature) were obtained at a Gd oleate loading concentration of 1 wt %, with a subsequent decrease in relaxivity with increasing Gd oleate concentration. These maximum relaxivities compare favorably with the relaxivities for the commercial contrast agent, Magnevist (r(1) = 4.91 mM(-1) s(-1) and r(2) = 6.26 mM(-1) s(-1) at 20 MHz and room temperature).

  14. 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.

  15. Porcine In Vivo Validation of a Virtual Contrast Model: The Influence of Contrast Agent Properties and Vessel Flow Rates.

    Science.gov (United States)

    Peach, T W; Ventikos, Y; Byrne, J V; You, Z

    2016-12-01

    Accurately and efficiently modeling the transport of angiographic contrast currently offers the best method of verifying computational fluid dynamics simulations and, with it, progress toward the lofty goal of prediction of aneurysm treatment outcome a priori. This study specifically examines the influence of estimated flow rate and contrast properties on such in silico predictions of aneurysm contrast residence and decay. Four experimental sidewall aneurysms were created in swine, with aneurysm contrast flow patterns and decay rates observed under angiography. A simplified computational fluid dynamics model of the experimental aneurysm was constructed from 3D angiography and contrast residence predicted a priori. The relative influence of a number of estimated model parameters (contrast viscosity, contrast density, and blood flow rate) on contrast residence was then investigated with further simulations. Contrast infiltration and washout pattern were accurately predicted by the a priori computational fluid dynamics model; however, the contrast decay rate was underestimated by ∼25%. This error was attributed to the estimated parent vessel flow rate alone, and the effects of contrast viscosity and density on the decay rate were found to be inconsequential. A linear correlation between the parent vessel flow rate and the corresponding contrast decay rate was observed. In experimental sidewall aneurysms, contrast fluid properties (viscosity and density) were shown to have a negligible effect on variation in the modeled contrast decay rate. A strong linear correlation was observed between parent vessel flow rate and contrast decay over a physiologically reasonable range of flow rates. © 2016 by American Journal of Neuroradiology.

  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. Copper sulfide nanodisk as photoacoustic contrast agent for ovarian tumor detection

    Science.gov (United States)

    Wang, Junxin; Hsu, Su-Wen; Tao, Andrea R.; Jokerst, Jesse V.

    2017-03-01

    Ultrasound is broadly used in the clinics yet is limited in early cancer detection because of its poor contrast between healthy and diseased tissues. Photoacoustic imaging can improve this limitation and has been extensively studied in pre-clinical models. Contrast agents can help improve the accuracy of diagnosis. We recently reported a novel copper sulfide (CuS) nanodisk with strong directionally-localized surface plasmon resonance in the near infrared region. This plasmonic resonance of nanodisks is tunable by changing the size and aspect ratio of CuS nanodisk. Here, we demonstrate this CuS nanodisk is a strong photoacoustic contrast agent. We prepared CuS nanodisks via a solvent-based synthesis followed by surface modification of poly(ethylene glycol) methyl ether thiol for in vivo applications. These CuS nanodisks can be detected at a concentration as low as 26 pM at 920 nm. Their nanosize and strong photoacoustic response make this novel CuS nanodisk a strong candidate for photoacoustic cancer imaging.

  18. 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.

  19. Inorganic nanocrystals as contrast agents in MRI:synthesis, coating and introducing multifunctionality

    Science.gov (United States)

    Sanchez-Gaytan, Brenda L.; Mieszawska, Aneta J.; Fayad, Zahi A.

    2013-01-01

    Inorganic nanocrystals have myriad applications in medicine, which includes their use as drug or gene delivery complexes, therapeutic hyperthermia agents, in diagnostic systems and as contrast agents in a wide range of medical imaging techniques. For MRI, nanocrystals can produce contrast themselves, of which iron oxides have been most extensively explored, or be given a coating that generates MR contrast, for example gold nanoparticles coated with gadolinium chelates. These MR-active nanocrystals can be used in imaging of the vasculature, liver and other organs, as well as molecular imaging, cell tracking and theranostics. Due to these exciting applications, synthesizing and rendering these nanocrystals water-soluble and biocompatible is therefore highly desirable. We will discuss aqueous phase and organic phase methods for synthesizing inorganic nanocrystals such as gold, iron oxides and quantum dots. The pros and cons of the various methods will be highlighted. We explore various methods for making nanocrystals biocompatible, i.e. directly synthesizing nanocrystals coated with biocompatible coatings, ligand substitution, amphiphile coating and embedding in carrier matrices that can be made biocompatible. Various examples will be highlighted and their applications explained. These examples signify that synthesizing biocompatible nanocrystals with controlled properties has been achieved by numerous research groups and can be applied for a wide range of applications. Therefore we expect to see reports of preclinical applications of ever more complex MRI-active nanoparticles and their wider exploitation, as well as in novel clinical settings. PMID:23303729

  20. Inorganic nanocrystals as contrast agents in MRI: synthesis, coating and introduction of multifunctionality.

    Science.gov (United States)

    Cormode, David P; Sanchez-Gaytan, Brenda L; Mieszawska, Aneta J; Fayad, Zahi A; Mulder, Willem J M

    2013-07-01

    Inorganic nanocrystals have myriad applications in medicine, including their use as drug or gene delivery complexes, therapeutic hyperthermia agents, in diagnostic systems and as contrast agents in a wide range of medical imaging techniques. In MRI, nanocrystals can produce contrast themselves, with iron oxides having been the most extensively explored, or can be given a coating that generates MR contrast, for example gold nanoparticles coated with gadolinium chelates. These MR-active nanocrystals can be used for imaging of the vasculature, liver and other organs, as well as molecular imaging, cell tracking and theranostics. As a result of these exciting applications, the synthesis and rendering of these nanocrystals as water soluble and biocompatible are therefore highly desirable. We discuss aqueous phase and organic phase methods for the synthesis of inorganic nanocrystals, such as gold, iron oxides and quantum dots. The pros and cons of the various methods are highlighted. We explore various methods for making nanocrystals biocompatible, i.e. direct synthesis of nanocrystals coated with biocompatible coatings, ligand substitution, amphiphile coating and embedding in carrier matrices that can be made biocompatible. Various examples are highlighted and their applications explained. These examples signify that the synthesis of biocompatible nanocrystals with controlled properties has been achieved by numerous research groups and can be applied to a wide range of applications. Therefore, we expect to see reports of preclinical applications of ever more complex MRI-active nanoparticles and their wider exploitation, as well as in novel clinical settings. Copyright © 2013 John Wiley & Sons, Ltd.

  1. A molecular receptor targeted, hydroxyapatite nanocrystal based multi-modal contrast agent.

    Science.gov (United States)

    Ashokan, Anusha; Menon, Deepthy; Nair, Shantikumar; Koyakutty, Manzoor

    2010-03-01

    Multi-modal molecular imaging can significantly improve the potential of non-invasive medical diagnosis by combining basic anatomical descriptions with in-depth phenotypic characteristics of disease. Contrast agents with multifunctional properties that can sense and enhance the signature of specific molecular markers, together with high biocompatibility are essential for combinatorial molecular imaging approaches. Here, we report a multi-modal contrast agent based on hydroxyapatite nanocrystals (nHAp), which is engineered to show simultaneous contrast enhancement for three major molecular imaging techniques such as magnetic resonance imaging (MRI), X-ray imaging and near-infrared (NIR) fluorescence imaging. Monodispersed nHAp crystals of average size approximately 30 nm and hexagonal crystal structure were in situ doped with multiple rare-earth impurities by a surfactant-free, aqueous wet-chemical method at 100 degrees C. Doping of nHAp with Eu(3+) (3 at%) resulted bright near-infrared fluorescence (700 nm) due to efficient (5)D(0)-(7)F(4) electronic transition and co-doping with Gd(3+) resulted enhanced paramagnetic longitudinal relaxivity (r(1) approximately 12 mM(-1) s(-1)) suitable for T(1) weighted MR imaging together with approximately 80% X-ray attenuation suitable for X-ray contrast imaging. Capability of MF-nHAp to specifically target and enhance the signature of molecular receptors (folate) in cancer cells was realized by carbodiimide grafting of cell-membrane receptor ligand folic acid (FA) on MF-nHAp surface aminized with dendrigraft polymer, polyethyleneimine (PEI). The FA-PEI-MF-nHAp conjugates showed specific aggregation on FR(+ve) cells while leaving the negative control cells untouched. Nanotoxicity evaluation of this multifunctional nHAp carried out on primary human endothelial cells (HUVEC), normal mouse lung fibroblast cell line (L929), human nasopharyngeal carcinoma (KB) and human lung cancer cell line (A549) revealed no apparent toxicity even

  2. Chitosan coated tungsten trioxide nanoparticles as a contrast agent for X-ray computed tomography.

    Science.gov (United States)

    Firouzi, Mehdi; Poursalehi, Reza; Delavari H, Hamid; Saba, Fakhredin; Oghabian, Mohammad A

    2017-05-01

    Recent advances have shown that inorganic nanoparticles (NPs) based on heavy elements are highly appropriate for X-ray computed tomography (CT). In this contribution, tungsten trioxide NPs are prepared by the electrical arc discharge (EAD) method in DI water. The effect of chitosan (CTS) and glutaraldehyde (GTA) as coating and cross-linking agent, respectively, on the hydrodynamic size and zeta potential of prepared tungsten trioxide NPs is investigated. It is found that zeta potential increases by increasing the amounts of CTS. Meanwhile, by increasing the volume of glutaraldehyde (GTA), the final particle size increases whereas the zeta potential deceases. Chitosan coated tungsten trioxide demonstrated no significant cytotoxicity at concentration up to 5mg/mL after 24h. Finally, the X-ray attenuation of prepared chitosan coated tungsten trioxide NPs are higher than Iohexol as the commercially available iodinated contrasting agent at the same concentrations. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. On the application of ultrasonic contrast agents for blood flowmetry and assessment of cardiac perfusion.

    Science.gov (United States)

    Bleeker, H; Shung, K; Barnhart, J

    1990-08-01

    The stability, size, and ultrasonic properties of several ultrasonic microbubble contrast agents such as Albunex, SHU-454, 1% hydrogen peroxide, and sonicated solutions such as 70% and 50% dextrose, 70% sorbitol, 5% albumin, Renografin-76, and others were evaluated. Albunex was the only tested agent that was sufficiently stable over an extended period of time for in vitro ultrasonic characterization. The attenuation and backscatter coefficients of Albunex at 5 and 7.5 MHz were found to be linearly proportional to microsphere concentration at low concentrations (less than 0.01% for attenuation and less than 0.002% for backscatter). Also, Albunex was found to be more echogenic than soft tissues at 5 MHz even after being diluted to 0.0003% of the original concentration. Next, the feasibility of using this acoustic information for contrast blood flowmetry was investigated. In vitro flow estimates in a mock flow loop were made using only the ultrasonic properties of the contrast agent. Bolus injections of Albunex and indicator-dilution curves inferred from ultrasonic measurements were used to estimate calibrated flow rate ranging from 400 to 5000 mL/min. The flow estimates from attenuation measurements showed a good correlation with those from an independent method (r = 0.97), but the results from backscatter studies did not correlate well. These results demonstrate that attenuation measurement may be a feasible alternative for in vivo blood flow measurement in conjunction with the indicator dilution principle or estimation of tissue perfusion such as myocardial perfusion using a time-activity approach.

  4. Influence of spatial resolution and contrast agent dosage on myocardial T1 relaxation times.

    Science.gov (United States)

    Blaszczyk, Edyta; Töpper, Agnieszka; Schmacht, Luisa; Wanke, Felix; Greiser, Andreas; Schulz-Menger, Jeanette; von Knobelsdorff-Brenkenhoff, Florian

    2017-02-01

    Our aim was to study the influence of small variations in spatial resolution and contrast agent dosage on myocardial T1 relaxation time. Twenty-nine healthy volunteers underwent cardiovascular magnetic resonance at 3T twice, including a modified look-locker inversion recovery (MOLLI) technique-3(3)3(3)5-for T1 mapping. Native T1 was assessed in three spatial resolutions (voxel size 1.4 × 1.4 × 6, 1.6 × 1.6 × 6, 1.7 × 1.7 × 6 mm(3)), and postcontrast T1 after 0.1 and 0.2 mmol/kg gadobutrol. Partition coefficient was calculated based on myocardial and blood T1. T1 analysis was done per segment, per slice, and for the whole heart. Native T1 values did not differ with varying spatial resolution per segment (p = 0.116-0.980), per slice (basal: p = 0.772; middle: p = 0.639; apex: p = 0.276), and globally (p = 0.191). Postcontrast T1 values were significantly lower with higher contrast agent dosage (p 3T, very small variations in spatial resolution (voxel sizes between 1.4 × 1.4 × 6 and 1.7 × 1.7 × 6 mm(3)) remained without effect on the native T1 relaxation times. Postcontrast T1 values were naturally shorter with higher contrast agent dosage while the partition coefficient remained constant. Further studies are necessary to test whether these conclusions hold true for larger matrix sizes and in larger cohorts.

  5. Intravenous ultrasound contrast agents versus other imaging methods in pediatric patients with neoplastic diseases – a comparison

    Directory of Open Access Journals (Sweden)

    Maciej Piskunowicz

    2013-12-01

    Full Text Available The lack of registration of ultrasound contrast agents for use in patients below the age of 18 is a significant limitation of their usage. Despite this, examinations with the use of contrast agents are conducted in numerous centers, mainly as part of the diagnostic process of vesicoureteral reflux. Examinations after an intravenous administration of contrast agents are conducted rarely. The reason for this is not only the lack of registration, but also the lack of studies on their safety profile in paediatric patients or no guidelines concerning the dosage. It seems that imaging with the use of such agents could help solve certain clinical problems when other diagnostic methods fail. The paper presents selected cases of pediatric patients treated in oncological departments, in whom the examination with the use of ultrasound contrast agents had a considerable influence on the diagnostic and therapeutic process.

  6. 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....

  7. Site-targeted acoustic contrast agent detects molecular expression of tissue factor after balloon angioplasty

    Science.gov (United States)

    Hall, Christopher S.; Abendschein, Dana R.; Scherrer, David E.; Scott, Michael J.; Marsh, Jon N.; Wickline, Samuel A.; Lanza, Gregory M.

    2000-04-01

    Complex molecular signaling heralds the early stages of pathologies such as angiogenesis, inflammation, and cellular responses to mechanically damaged coronary arteries after balloon angioplasty. In previous studies, we have demonstrated acoustic enhancement of blood clot morphology with the use of a nongaseous, ligand-targeted acoustic nanoparticle emulsion delivered to areas of thrombosis both in vitro and in vivo. In this paper, we characterize the early expression of tissue factor which contributes to subsequent arterial restenosis. Tissue factor is a 42kd glycoprotein responsible for blood coagulation but also plays a well-described role in cancer metastasis, angiogenesis, and vascular restenosis. This study was designed to determine whether the targeted contrast agent could localize tissue factor expressed within the wall of balloon-injured arteries. Both carotid arteries of five pigs (20 kg) were injured using an 8 X 20 mm angioplasty balloon. The carotids were treated in situ with a perfluorocarbon nanoparticle emulsion covalently complexed to either specific anti-tissue factor polyclonal F(ab) fragments (treatment) or non-specific IgG F(ab) fragments (control). Intravascular ultrasound (30 MHz) images of the arteries were obtained before and after exposure to the emulsions. Tissue- factor targeted ultrasonic contrast agent acoustically enhanced the subintima and media at the site of balloon- induced injury compared with control contrast arteries (p less than 0.05). Immunohistochemical staining confirmed the presence of increased tissue factor at the sites of acoustic enhancement. Binding of the targeted agents was demonstrated in vitro by scanning electron microscope images of cultured smooth muscle cells that constitutively express tissue factor. This study demonstrates the concept of molecular imaging and localization of carotid arteries' tissue factor in vivo using a new, nanoparticulate emulsion. Enhancement of the visualization of the molecular

  8. 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.

  9. Contrast agent free detection of bowel perforation using chlorophyll derivatives from food plants

    Science.gov (United States)

    Han, Jung Hyun; Jo, Young Goun; Kim, Jung Chul; Lee, Jee-Bum; Kim, Yong-Chul; Kang, Hoonsoo; Hwang, In-Wook

    2016-01-01

    Chlorophylls occur abundantly in food plants and show bright emission bands at long-wavelength regions (∼675 and ∼720 nm) compared to the autofluorescence of animal organs and peritoneal fluids. The use of these emissions as biomarkers for monitoring bowel perforation with a modality that does not involve synthetic contrast agents seems promising. To validate this, we measured the fluorescence spectra of rat organs, human peritoneal and intestinal fluids, and human intestinal fluids diluted with physiological saline. The developed technique showed a high detection sensitivity (∼50 ppm) under irrigation for abdominal surgery, highlighting the potential of this tool in the surgical setting.

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

    Science.gov (United States)

    Cabrera-García, Alejandro; Vidal-Moya, Alejandro; Bernabeu, Ángela; Pacheco-Torres, Jesús; Checa-Chavarria, Elisa; Fernández, Eduardo; Botella, Pablo

    2016-06-08

    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.

  11. 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.)

  12. Responsive magnetic resonance imaging contrast agents as chemical sensors for metals in biology and medicine.

    Science.gov (United States)

    Que, Emily L; Chang, Christopher J

    2010-01-01

    This tutorial review highlights progress in the development of responsive magnetic resonance imaging (MRI) contrast agents for detecting and sensing biologically relevant metal ions. Molecular imaging with bioactivatable MRI indicators offers a potentially powerful methodology for studying the physiology and pathology of metals by capturing dynamic three-dimensional images of living systems for research and clinical applications. This emerging area at the interface of inorganic chemistry and the life sciences offers a broad palette of opportunities for researchers with interests ranging from coordination chemistry and spectroscopy to supramolecular chemistry and molecular recognition to metals in biology and medicine.

  13. Simultaneous imaging of multiple contrast agents using full-spectrum micro-CT

    Science.gov (United States)

    Clark, D. P.; Touch, M.; Barber, W.; Badea, C. T.

    2015-03-01

    One of the major challenges for in vivo, micro-computed tomography (CT) imaging is poor soft tissue contrast. To increase contrast, exogenous contrast agents can be used as imaging probes. Combining these probes with a photon counting x-ray detector (PCXD) allows energy-sensitive CT and probe material decomposition from a series of images associated with different x-ray energies. We have implemented full-spectrum micro-CT using a PCXD and 2 keV energy sampling. We then decomposed multiple k-edge contrast materials present in an object (iodine, barium, and gadolinium) from water. Since the energy bins were quite narrow, the projection data was very noisy. This noise and further spectral distortions amplify errors in post-reconstruction material decompositions. Here, we propose and demonstrate a novel post-reconstruction denoising scheme which jointly enforces local and global gradient sparsity constraints, improving the contrast-to-noise ratio in full-spectrum micro-CT data and resultant material decompositions. We performed experiments using both calibration phantoms and ex vivo mouse data. Denoising increased the material contrast-to-noise ratio by an average of 13 times relative to filtered backprojection reconstructions. The relative decomposition error after denoising was 21%. To further improve material decomposition accuracy in future work, we also developed a model of the spectral distortions caused by PCXD imaging using known spectra from radioactive isotopes (109Cd, 133Ba). In future work, we plan to combine this model with the proposed denoising algorithm, enabling material decomposition with higher sensitivity and accuracy.

  14. Lanthanide oleates: chelation, self-assembly, and exemplification of ordered nanostructured colloidal contrast agents for medical imaging.

    Science.gov (United States)

    Liu, Guozhen; Conn, Charlotte E; Drummond, Calum J

    2009-12-10

    Eight lanthanide(III) oleates have been prepared and characterized. The chelation and self-assembly structures of these rare-earth oleates have been studied by elemental analysis, Fourier transfer infrared spectroscopy (FTIR), and X-ray powder diffraction (XRD) analysis. Elemental analysis and FTIR results indicate that three oleate anions are complexed with one lanthanide cation and, with the exception of anhydrous cerium(III) oleate, form either a mono- or a hemihydrate. The X-ray analysis showed that the neat lanthanide soaps have a lamellar bilayer structure at room temperature. The thermal behavior has been investigated by cross-polarized optical microscopy (POM), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). POM scans showed that all the lanthanide oleates form a lamellar phase in the presence of excess water. Small-angle X-ray scattering (SAXS) and XRD were used to investigate the internal structure of the bulk lanthanide oleates in excess water, and these X-ray results confirmed that the lanthanide oleates do not swell in water. Select lanthanide oleates were dispersed in water to form nonswelling lamellar submicrometer particles, confirmed by dynamic light scattering (DLS) and synchrotron SAXS measurements. NMR results indicated that colloidal dispersions of lanthanide oleates containing paramagnetic ions, such as gadolinium(III), terbium(III), and dysprosium(III), have a significant effect on the longitudinal (T(1)) and transverse (T(2)) relaxation times of protons in water. Time-resolved fluorescence measurements have demonstrated that colloidal dispersions of europium(III) oleate exhibit strong luminescence. The rare earth metal soaps exemplify the potential of self-assembled chelating amphiphiles as contrast agents in medical imaging modalities such as magnetic resonance imaging (MRI) and fluorescence imaging.

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

    Science.gov (United States)

    Coolen, Bram F; Geelen, Tessa; Paulis, Leonie E M; Nicolay, Klaas; Strijkers, Gustav J

    2011-10-05

    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. 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. 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 T1 mapping by CMR can be used to monitor the accumulation of contrast agents in contrast-enhanced studies of murine myocardial infarction. The contrast agent relaxivity was decreased under in vivo conditions compared to in vitro

  16. 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

    2017-03-01

    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 H 3 PO 4 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.

  17. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. The performance of PEGylated nanocapsules of perfluorooctyl bromide as an ultrasound contrast agent.

    Science.gov (United States)

    Díaz-López, Raquel; Tsapis, Nicolas; Santin, Mathieu; Bridal, Sharon Lori; Nicolas, Valérie; Jaillard, Danielle; Libong, Danielle; Chaminade, Pierre; Marsaud, Véronique; Vauthier, Christine; Fattal, Elias

    2010-03-01

    The surface of polymeric nanocapsules used as ultrasound contrast agents (UCAs) was modified with PEGylated phospholipids in order to escape recognition and clearance by the mononuclear phagocyte system and achieve passive tumor targeting. Nanocapsules consisted of a shell of poly(lactide-co-glycolide) (PLGA) encapsulating a liquid core of perfluorooctyl bromide (PFOB). They were decorated with poly(ethylene glycol-2000)-grafted distearoylphosphatidylethanolamine (DSPE-PEG) incorporated in the organic phase before the solvent emulsification-evaporation process. The influence of DSPE-PEG concentration on nanocapsule size, surface charge, morphology, hydrophobicity and complement activation was evaluated. Zeta potential measurements, Hydrophobic interaction chromatography and complement activation provide evidence of DSPE-PEG presence at nanocapsule surface. Electronic microscopy reveals that the core/shell structure is preserved up to 2.64 mg of DSPE-PEG for 100 mg PLGA. In vivo ultrasound imaging was performed in mice bearing xenograft tumor with MIA PaCa-2 cells, either after an intra-tumoral or intravenous injection of nanocapsules. Tumor was observed only after the intra-tumoral injection. Despite the absence of echogenic signal in the tumor after intravenous injection of nanocapsules, histological analysis reveals their accumulation within the tumor tissue demonstrating that tissue distribution is not the unique property required for ultrasound contrast agents to be efficient. (c) 2009 Elsevier Ltd. All rights reserved.

  19. Use of carbon dioxide as negative contrast agent for magnetic resonance cholangiopancreatography.

    Science.gov (United States)

    Chen, Ching-Wen; Liu, Yi-Sheng; Chen, Chiung-Yu; Tsai, Hong-Ming; Chen, Shu-Chen; Chuang, Ming-Tsung

    2011-02-28

    To evaluate the effects of using CO(2) as negative contrast agent in decreasing the overlapping on the pancreaticobiliary system from intestinal fluids. We evaluated the magnetic resonance cholangiopancreatography (MRCP) images in 117 patients divided into two groups (group 1, without taking gas producing crystals to produce CO(2), n = 64; group 2, with CO(2), n = 53) in a 1.5T unit using MRCP sequence. Anatomic locations of intestinal fluids distribution, overlapping with common bile duct (CBD) and pancreatic duct (PD), were evaluated. In the group with CO(2), the decrease in distribution of intestinal fluids was significant in the gastric antrum (P = 0.001) and duodenal bulb (P < 0.001), but not in the gastric fundus and body and in the second portion of the duodenum (P = 1.000, P = 0.171, and P = 0.584 respectively). In the group with CO(2), the decrease in overlapping with CBD was significant (P < 0.001), but the decrease in overlapping with PD was not (P = 0.106). MRCP with carbon dioxide as negative contrast agent would decrease intestinal fluids in the gastric antrum and duodenal bulb, thereby decreasing overlapping with the CBD.

  20. 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.

  1. Targeted binding of PEG-lipid modified polymer ultrasound contrast agents with tiered surface architecture.

    Science.gov (United States)

    Duncanson, Wynter J; Oum, Kelleny; Eisenbrey, John R; Cleveland, Robin O; Wheatley, Margaret A; Wong, Joyce Y

    2010-06-15

    In order for site-directed polymer ultrasound contrast agents (UCAs) to provide acoustic enhancement at disease sites to distinguish normal tissue from diseased tissue, the surface of these agents must be functionalized with mixtures of grafted polymers. Here a combination of longer liganded polyethylene glycol (PEG)-lipids and shorter unliganded PEG-lipids were introduced into the oil phase of a modified solvent evaporation double emulsion method for preparing UCAs. UCAs with different lengths of both liganded and unliganded lipids were imaged under 7.5 MHz ultrasound. The B-mode image brightness of the mixed PEG-lipid UCAs was within 1 dB the brightness of the unliganded surface. After 15 min of continuous insonation, 70% of the contrast signal remained. The peptide arginine-glycine-aspartic acid (RGD) was added to the surface of these UCAs through a biotin-avidin linkage and binding was assessed under static and shear conditions. Binding was significant after 30 min of static incubation and the adherence of the UCA increased under shear flow from 3 UCA/cell (static) to 5 UCA/cell (shear). 2010 Wiley Periodicals, Inc.

  2. 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.

  3. The MRI Contrast Agent Gadoteridol Enhances Distribution of rAAV1 in the Rat Hippocampus

    Science.gov (United States)

    Hullinger, Rikki; Ugalde, Jeanet; Purón-Sierra, Liliana; Osting, Sue; Burger, Corinna

    2013-01-01

    Contrast agents are commonly used in combination with magnetic resonance imaging (MRI) to monitor the distribution of molecules in the brain. Recent experiments conducted in our laboratory have shown that co-infusion of recombinant Adeno-associated virus serotype 5 (rAAV5) and the MRI contrast agent gadoteridol (Gd) enhances vector transduction of in the rat striatum. The goal of this study was to determine whether gadoteridol may also be used as a tool to enhance transduction efficiency of rAAV1 and rAAV5 within the rat hippocampus. We show that Gd/rAAV1-GFP but not Gd/rAAV5-GFP co-infusion results in significantly higher distribution of the transgene both in the injected hemisphere as well as in the contralateral side and adjacent areas of cortex along the injection track. We also show that Gd/rAAV1-GFP co-infusion has no deleterious effect on hippocampal function as assessed by two tests of spatial memory formation. This work indicates that gadoteridol can be exploited as a method to increase transduction efficiency of AAV1 in the hippocampus for animal studies. PMID:24048419

  4. The MRI contrast agent gadoteridol enhances distribution of rAAV1 in the rat hippocampus.

    Science.gov (United States)

    Hullinger, R; Ugalde, J; Purón-Sierra, L; Osting, S; Burger, C

    2013-12-01

    Contrast agents are commonly used in combination with magnetic resonance imaging (MRI) to monitor the distribution of molecules in the brain. Recent experiments conducted in our laboratory have shown that co-infusion of recombinant Adeno-associated virus serotype 5 (rAAV5) and the MRI contrast agent gadoteridol (Gd) enhances vector transduction in the rat striatum. The goal of this study was to determine whether gadoteridol may also be used as a tool to enhance transduction efficiency of rAAV1 and rAAV5 within the rat hippocampus. We show that Gd/rAAV1-GFP but not Gd/rAAV5-GFP co-infusion results in significantly higher distribution of the transgene both in the injected hemisphere as well as in the contralateral side and adjacent areas of cortex along the injection track. We also show that Gd/rAAV1-GFP co-infusion has no deleterious effect on hippocampal function as assessed by two tests of spatial memory formation. This work indicates that Gd can be exploited as a method to increase transduction efficiency of AAV1 in the hippocampus for animal studies.

  5. Metal-organic-frameworks for biomedical applications in drug delivery, and as MRI contrast agents.

    Science.gov (United States)

    Chowdhury, Mohammad A

    2017-04-01

    The metal-organic-frameworks (MOFs) materials are increasingly gaining attraction to utilise into biomedical applications. MOFs are playing a major role to harnessing dual or multiple modalities in therapeutics and diagnostics. MOFs are mostly devised for particular biomedical application by post-synthetic functionalization or modification using variety of polymers, bio-ligands, and silica coating processes. This article presents a brief overview of two particular areas of biomedical applications where a broad range of MOFs have been used: (1) variety of drug delivery including intracellular drug delivery systems using the MOFs-based carriers; and, (2) development of MOFs-based contrast agents for magnetic resonance image enhancement. Biocompatibility, bio-toxicity, tissue responses, cell viability, cellular uptakes, and, how the effects of size, shape, structural, and morphological properties of the MOFs impact on the utilities in drug delivery and as MRI contrast agents, are discussed. Perspectives, insights and critical reflections into a range of aspects, and future outlook are illustrated. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1184-1194, 2017. © 2017 Wiley Periodicals, Inc.

  6. 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. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. 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

    2014-01-20

    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.

  8. 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.

  9. Ultrasonic Contrast Agent Shell Rupture Detected by Inertial Cavitation and Rebound Signals

    Science.gov (United States)

    Ammi, Azzdine Y.; Cleveland, Robin O.; Mamou, Jonathan; Wang, Grace I.; Bridal, S. Lori; O’Brien, William D.

    2007-01-01

    Determining the rupture pressure threshold of ultrasound contrast agent microbubbles has significant applications for contrast imaging, development of therapeutic agents, and evaluation of potential bioeffects. Using a passive cavitation detector, this work evaluates rupture based on acoustic emissions from single, encapsulated, gas-filled microbubbles. Sinusoidal ultrasound pulses were transmitted into weak solutions of OptisonTM at different center frequencies (0.9, 2.8, and 4.6 MHz), pulse durations (three, five, and seven cycles of the center frequencies), and peak rarefactional pressures (0.07 to 5.39 MPa). Pulse repetition frequency was 10 Hz. Signals detected with a 13-MHz, center-frequency transducer revealed postexcitation acoustic emissions (between 1 and 5 μs after excitation) with broadband spectral content. The observed acoustic emissions were consistent with the acoustic signature that would be anticipated from inertial collapse followed by “rebounds” when a microbubble ruptures and thus generates daughter/free bubbles that grow and collapse. The peak rarefactional pressure threshold for detection of these emissions increased with frequency (e.g., 0.53, 0.87, and 0.99 MPa for 0.9, 2.8, and 4.6 MHz, respectively; five-cycle pulse duration) and decreased with pulse duration. The emissions identified in this work were separated from the excitation in time and spectral content, and provide a novel determination of microbubble shell rupture. PMID:16471439

  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. Method and application for imaging breast cancer using a contrast agent

    Science.gov (United States)

    Huang, Ping; Intes, Xavier; Nioka, Shoko; Kitai, Toshiyuki; Chance, Britton

    2002-04-01

    Diffuse Optical Tomography (DOT) in the Near Infrared Spectral window (NIR) offers new possibilities for medical imaging. And using DOT, Indocyanine green (ICG) is found to be a useful blood pooling contrast agent for optical tumor detection. Here we introduce our efforts on study of breast cancer image reconstruction using ICG as a contrast agent. To improve the signal-to-noise ratio, we developed an effective method to analyze and process the raw data acquired from a CWS (Continuous Wave Spectroscopy) system. Differential absorption images of breast cancers are reconstructed by using ART (Algebraic Reconstruction Technique) which uses the diffusion equation within the Rytov approximation. The experiment device is a combination of sixteen light sources (tungsten bulb) and sixteen light detectors (silicon photodiodes). These sources and detectors are located on a circular holder where the human breasts are placed, each other at equal distance (11 angle apart). It takes a few seconds to acquire data since one source is on, while all the detectors simultaneously detect the photons. So an image includes 16*16 data points. Results from clinical trial in Japan and China show that there is a high concentration of ICG in the location of a cancer, suggesting high blood volume pooling and the usefulness of ICG detecting optically breast cancers.

  12. 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.

  13. Sentinel Lymph Node Characterization with a Dual-Targeted Molecular Ultrasound Contrast Agent.

    Science.gov (United States)

    Nam, Kibo; Stanczak, Maria; Forsberg, Flemming; Liu, Ji-Bin; Eisenbrey, John R; Solomides, Charalambos C; Lyshchik, Andrej

    2017-07-31

    The purpose of this study was to assess the performance of molecular ultrasound with dual-targeted microbubbles to detect metastatic disease in the sentinel lymph nodes (SLNs) in swine model of naturally occurring melanoma. The SLN is the first lymph node in the lymphatic chain draining primary tumor, and early detection of metastatic SLN involvement is critical in the appropriate management of melanoma. Nine Sinclair swine (weight 3-7 kg; Sinclair BioResources, Columbia, MO, USA) with naturally occurring melanoma were examined. Siemens S3000 scanner with a 9L4 probe was used for imaging (Siemens Healthineers, Mountain View, CA). Dual-targeted contrast agent was created using Targestar SA microbubbles (Targeson, San Diego, CA, USA) labeled with ανβ3-integrin and P-selectin antibodies. Targestar SA microbubbles labeled with IgG-labeled were used as control. First, peritumoral injection of Sonazoid contrast agent (GE Healthcare, Oslo, Norway) was performed to detect SLNs. After that, dual-targeted and IGG control Targestar SA microbubbles were injected intravenously with a 30-min interval between injections. Labeled Targestar SA microbubbles were allowed to circulate for 4 min to enable binding. After that, two sets of image clips were acquired several seconds before and after a high-power destruction sequence. The mean intensity difference pre- to post-bubble destruction within the region of interest placed over SLN was calculated as a relative measure of targeted microbubble contrast agent retention. This process was repeated for non-SLNs as controls. All lymph nodes evaluated on imaging were surgically removed and histologically examined for presence of metastatic involvement. A total of 43 lymph nodes (25 SLNs and 18 non-SLNs) were included in the analysis with 18 SLNs demonstrating metastatic involvement greater than 5 % on histology. All non-SLNs were benign. The mean intensity (± SD) of the dual-targeted microbubbles for metastatic SLNs was

  14. 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.

  15. 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.

  16. 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.

  17. Ex vivo confocal imaging with contrast agents for the detection of oral potentially malignant lesions.

    Science.gov (United States)

    El Hallani, S; Poh, C F; Macaulay, C E; Follen, M; Guillaud, M; Lane, P

    2013-06-01

    We investigated the potential use of real-time confocal microscopy in the non-invasive detection of occult oral potentially malignant lesions. Our objectives were to select the best fluorescence contrast agent for cellular morphology enhancement, to build an atlas of confocal microscopic images of normal human oral mucosa, and to determine the accuracy of confocal microscopy to recognize oral high-grade dysplasia lesions on live human tissue. Five clinically used fluorescent contrast agents were tested in vitro on cultured human cells and validated ex vivo on human oral mucosa. Images acquired ex vivo from normal and diseased human oral biopsies with bench-top fluorescent confocal microscope were compared to conventional histology. Image analyzer software was used as an adjunct tool to objectively compare high-grade dysplasia versus low-grade dysplasia and normal epithelium. Acriflavine Hydrochloride provided the best cellular contrast by preferentially staining the nuclei of the epithelium. Using topical application of Acriflavine Hydrochloride followed by confocal microscopy, we could define morphological characteristics of each cellular layer of the normal human oral mucosa, building an atlas of histology-like images. Applying this technique to diseased oral tissue specimen, we were also able to accurately diagnose the presence of high-grade dysplasia through the increased cellularity and changes in nuclear morphological features. Objective measurement of cellular density by quantitative image analysis was a strong discriminant to differentiate between high-grade dysplasia and low-grade dysplasia lesions. Pending clinical investigation, real-time confocal microscopy may become a useful adjunct to detect precancerous lesions that are at high risk of cancer progression, direct biopsy and delineate excision margins. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Tyrosinase-catalyzed melanin as a contrast agent for photoacoustic tomography

    Science.gov (United States)

    Krumholz, Arie; Chavez, Sarah; Yao, Junjie; Fleming, Timothy; Gillanders, William E.; Wang, Lihong V.

    2011-03-01

    It is difficult to distinguish between tumor cells and surrounding cells without staining as is done in histology. We developed tyrosinase-catalyzed melanin as a reporter gene for photoacoustic tomography. Tyrosinase is the primary enzyme responsible for the production of melanin and alone is sufficient to produce melanin in non-melanogenic cells. Two cell lines were created: a stably transfected HeLa line and a transiently transfected 293 line. A phantom experiment was performed with the 293 transfected cells 48 hours post transfection and the results compared with oxygenated whole blood, B16 melanoma and 293 control cells. An in vivo experiment was performed using the transfected HeLa cells xenografted into a nude mouse ear, and then imaged. The results show strong contrast for tyrosinase-catalyzed melanin in both the 293 cells in the tube phantom as well as the in vivo result showing melanin in a nude mouse ear. Transfection increased expression in 293 cells 159 fold and image contrast compared to blood by as much as 50 fold. Due to the strong signal obtained at longer wavelengths and the decrease of blood signal at the same wavelengths, tyrosinase catalyzed melanin is a good candidate as a molecular imaging contrast agent for photoacoustic tomography.

  19. In vivo comparison of tantalum, tungsten, and bismuth enteric contrast agents to complement intravenous iodine for double-contrast dual-energy CT of the bowel.

    Science.gov (United States)

    Rathnayake, Samira; Mongan, John; Torres, Andrew S; Colborn, Robert; Gao, Dong-Wei; Yeh, Benjamin M; Fu, Yanjun

    2016-07-01

    To assess the ability of dual-energy CT (DECT) to separate intravenous contrast of bowel wall from intraluminal contrast, we scanned 16 rabbits on a clinical DECT scanner: n = 3 using only iodinated intravenous contrast, and n = 13 double-contrast enhanced scans using iodinated intravenous contrast and experimental enteric non-iodinated contrast agents in the bowel lumen (five bismuth, four tungsten, and four tantalum based). Representative image pairs from conventional CT images and DECT iodine density maps of small bowel (116 pairs from 232 images) were viewed by four abdominal imaging attending radiologists to independently score each comparison pair on a visual analog scale (-100 to +100%) for (1) preference in small bowel wall visualization and (2) preference in completeness of intraluminal enteric contrast subtraction. Median small bowel wall visualization was scored 39 and 42 percentage points (95% CI 30-44% and 36-45%, both p tantalum contrast, respectively. Median small bowel wall visualization for double-contrast DECT was scored 29 and 35 percentage points (95% CI 20-35% and 33-39%, both p tantalum, respectively, than with bismuth contrast. Median completeness of intraluminal enteric contrast subtraction in double-contrast DECT iodine density maps was scored 28 and 29 percentage points (95% CI 15-31% and 28-33%, both p tantalum, respectively, than with bismuth contrast. Results suggest that in vivo double-contrast DECT with iodinated intravenous and either tantalum- or tungsten-based enteric contrast provides better visualization of small bowel than conventional CT. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  20. Assessing the Efficacy of Nano- and Micro-Sized Magnetic Particles as Contrast Agents for MRI Cell Tracking

    OpenAIRE

    Arthur Taylor; Anne Herrmann; Diana Moss; Violaine Sée; Karen Davies; Williams, Steve R.; Patricia Murray

    2014-01-01

    Iron-oxide based contrast agents play an important role in magnetic resonance imaging (MRI) of labelled cells in vivo. Currently, a wide range of such contrast agents is available with sizes varying from several nanometers up to a few micrometers and consisting of single or multiple magnetic cores. Here, we evaluate the effectiveness of these different particles for labelling and imaging stem cells, using a mouse mesenchymal stem cell line to investigate intracellular uptake, retention and pr...

  1. Biofilm imaging in porous media by laboratory X-Ray tomography: Combining a non-destructive contrast agent with propagation-based phase-contrast imaging tools.

    Directory of Open Access Journals (Sweden)

    Maxence Carrel

    Full Text Available X-ray tomography is a powerful tool giving access to the morphology of biofilms, in 3D porous media, at the mesoscale. Due to the high water content of biofilms, the attenuation coefficient of biofilms and water are very close, hindering the distinction between biofilms and water without the use of contrast agents. Until now, the use of contrast agents such as barium sulfate, silver-coated micro-particles or 1-chloronaphtalene added to the liquid phase allowed imaging the biofilm 3D morphology. However, these contrast agents are not passive and potentially interact with the biofilm when injected into the sample. Here, we use a natural inorganic compound, namely iron sulfate, as a contrast agent progressively bounded in dilute or colloidal form into the EPS matrix during biofilm growth. By combining a very long source-to-detector distance on a X-ray laboratory source with a Lorentzian filter implemented prior to tomographic reconstruction, we substantially increase the contrast between the biofilm and the surrounding liquid, which allows revealing the 3D biofilm morphology. A comparison of this new method with the method proposed by Davit et al (Davit et al., 2011, which uses barium sulfate as a contrast agent to mark the liquid phase was performed. Quantitative evaluations between the methods revealed substantial differences for the volumetric fractions obtained from both methods. Namely, contrast agent-biofilm interactions (e.g. biofilm detachment occurring during barium sulfate injection caused a reduction of the biofilm volumetric fraction of more than 50% and displacement of biofilm patches elsewhere in the column. Two key advantages of the newly proposed method are that passive addition of iron sulfate maintains the integrity of the biofilm prior to imaging, and that the biofilm itself is marked by the contrast agent, rather than the liquid phase as in other available methods. The iron sulfate method presented can be applied to understand

  2. Cranial nerve contrast using nerve-specific fluorophores improved by paired-agent imaging with indocyanine green as a control agent

    Science.gov (United States)

    Torres, Veronica C.; Vuong, Victoria D.; Wilson, Todd; Wewel, Joshua; Byrne, Richard W.; Tichauer, Kenneth M.

    2017-09-01

    Nerve preservation during surgery is critical because damage can result in significant morbidity. This remains a challenge especially for skull base surgeries where cranial nerves (CNs) are involved because visualization and access are particularly poor in that location. We present a paired-agent imaging method to enhance identification of CNs using nerve-specific fluorophores. Two myelin-targeting imaging agents were evaluated, Oxazine 4 and Rhodamine 800, and coadministered with a control agent, indocyanine green, either intravenously or topically in rats. Fluorescence imaging was performed on excised brains ex vivo, and nerve contrast was evaluated via paired-agent ratiometric data analysis. Although contrast was improved among all experimental groups using paired-agent imaging compared to conventional, solely targeted imaging, Oxazine 4 applied directly exhibited the greatest enhancement, with a minimum 3 times improvement in CNs delineation. This work highlights the importance of accounting for nonspecific signal of targeted agents, and demonstrates that paired-agent imaging is one method capable of doing so. Although staining, rinsing, and imaging protocols need to be optimized, these findings serve as a demonstration for the potential use of paired-agent imaging to improve contrast of CNs, and consequently, surgical outcome.

  3. 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.

  4. Magnetic iodixanol - a novel contrast agent and its early characterization.

    Science.gov (United States)

    Arokiaraj, M C; Menesson, E; Feltin, N

    2018-02-01

    Contrast-induced nephropathy is a commonly encountered problem in clinical practice. The purpose of the study was to design and develop a novel contrast agent, which could be used to prevent contrast-induced nephropathy in the future. In total, 20-220nm magnetic nanoparticles were conjugated with iodixanol, and their radio-opacity and magnetic properties were assessed thereafter. Scanning electron microscopy pictures were acquired. Thereafter, the nanoparticles conjugate was tested in cell culture (HUVEC cells), and Quantibody ® assay was studied after cell treatment in 1:5 dilutions for 48h, compared with control. The conjugate preparation had an adequate radio-opacity. A 4mm magnetic bubble was attached to a bar magnet and the properties were studied. The magnetic bubble maintained its structural integrity in all angles including antigravity position. Scanning electron microscopy showed magnetic nanoparticles in all pictures and the particles are of 100-400nm agglomerates with primary particle sizes of roughly 20nm. 1:5 diluted particles had no effect on secretion of IL-1a, IL-1b, IL-4, IL-10, IL-13 and TNFa. Particles increased secretion of IL-8 from 24h and 48h. Secretion of IFNg was also increased when particles were added to the cells as early as 1h. Likewise, IL-6 was strongly secreted by HUVEC treated with particles from 24h incubation time. In contrast, the secretion of MCP-1 was slightly reduced on HUVEC treated with particles. There is potential for a novel iodixanol-magnetic nanoparticle conjugate to be used in cineradiography. Further investigations need to be performed to study its performance in vitro and in vivo. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Vibrational Phase Contrast Microscopy by Use of Coherent Anti-Stokes Raman Scattering

    NARCIS (Netherlands)

    Jurna, M.; Korterik, Jeroen P.; Otto, Cornelis; Herek, Jennifer Lynn; Offerhaus, Herman L.

    2009-01-01

    In biological samples the resonant coherent anti-Stokes Raman scattering signal of less abundant constituents can be overwhelmed by the nonresonant background, preventing detection of those molecules. We demonstrate a method to obtain the phase of the oscillators in the focal volume that allows

  6. Severe reactions to iodinated contrast agents: is anaphylaxis responsible?; Reactions severes avec les produits de contraste iodes: l'anaphylaxie est-elle responsable?

    Energy Technology Data Exchange (ETDEWEB)

    Dewachter, P.; Mouton-Faivre, C. [Hopital Central, Service Anesthesie-Reanimation Chirurgicale, 54 - Nancy (France)

    2001-09-01

    The etiology of severe reactions following injection of iodinated contrast agent is the subject of controversy. No consensus has been established regarding the management of patients at risk, risk factors and pre-medication because in most cases published no diagnostic exploration has been carried out on patients who have experienced a severe reaction. Diagnosis of drug anaphylaxis is based on clinical history, proof of mediator release and drug specific IgE antibodies (when the technique is available) or cutaneous tests (when direct technique is not available). This approach has been adopted for etiologic diagnosis of 5 clinical cases of severe anaphylactoid reactions (including one death) following the injection of ionic and non ionic contrast agents. Clinical symptoms, biology and cutaneous tests are consistent with anaphylaxis. Any patient who has had a severe anaphylactoid reaction following injection of a contrast agent should undergo an allergology assessment to confirm the diagnosis and identify the culprit contrast agent. Indeed, no pre-medication has proved efficient for the prevention of subsequent allergic reactions. (author)

  7. Influence of different contributions of scatter and attenuation on the threshold values in contrast-based algorithms for volume segmentation.

    Science.gov (United States)

    Matheoud, Roberta; Della Monica, Patrizia; Secco, Chiara; Loi, Gianfranco; Krengli, Marco; Inglese, Eugenio; Brambilla, Marco

    2011-01-01

    The aim of this work is to evaluate the role of different amount of attenuation and scatter on FDG-PET image volume segmentation using a contrast-oriented method based on the target-to-background (TB) ratio and target dimensions. A phantom study was designed employing 3 phantom sets, which provided a clinical range of attenuation and scatter conditions, equipped with 6 spheres of different volumes (0.5-26.5 ml). The phantoms were: (1) the Hoffman 3-dimensional brain phantom, (2) a modified International Electro technical Commission (IEC) phantom with an annular ring of water bags of 3 cm thickness fit over the IEC phantom, and (3) a modified IEC phantom with an annular ring of water bags of 9 cm. The phantoms cavities were filled with a solution of FDG at 5.4 kBq/ml activity concentration, and the spheres with activity concentration ratios of about 16, 8, and 4 times the background activity concentration. Images were acquired with a Biograph 16 HI-REZ PET/CT scanner. Thresholds (TS) were determined as a percentage of the maximum intensity in the cross section area of the spheres. To reduce statistical fluctuations a nominal maximum value is calculated as the mean from all voxel > 95%. To find the TS value that yielded an area A best matching the true value, the cross section were auto-contoured in the attenuation corrected slices varying TS in step of 1%, until the area so determined differed by less than 10 mm² versus its known physical value. Multiple regression methods were used to derive an adaptive thresholding algorithm and to test its dependence on different conditions of attenuation and scatter. The errors of scatter and attenuation correction increased with increasing amount of attenuation and scatter in the phantoms. Despite these increasing inaccuracies, PET threshold segmentation algorithms resulted not influenced by the different condition of attenuation and scatter. The test of the hypothesis of coincident regression lines for the three phantoms used

  8. More Than Bubbles: Creating Phase-Shift Droplets from Commercially Available Ultrasound Contrast Agents.

    Science.gov (United States)

    Sheeran, Paul S; Yoo, Kimoon; Williams, Ross; Yin, Melissa; Foster, F Stuart; Burns, Peter N

    2017-02-01

    Phase-shift perfluorocarbon droplets have been investigated for over 20 years as pre-clinical ultrasound contrast agents with distinctive advantages in imaging and therapy. A number of formulation strategies exist, each with inherent advantages and limitations. In this note, we demonstrate a unique opportunity: that phase-shift droplets can be generated directly from commercially available microbubbles. This may facilitate pre-clinical and translational development by reducing the in-house synthesis expertise and resources required to generate high concentration droplet emulsions. Proof-of-principle in vitro and in vivo is given using droplets created from Definity and MicroMarker. The results demonstrate the role of perfluorocarbon choice in the trade-off between thermal stability and vaporization threshold, and suggest that commercial microbubbles with decafluorobutane cores may be ideal for this approach. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  9. 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

    on a preliminary experiment. To compensate for variations in bubble response and to make the estimates more robust, the relation between the energy of the subharmonic and the fundamental component was chosen as a measure over the subharmonic peak amplitude. The preliminary study revealed the growth stage.......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......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...

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

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2009-01-01

    experiment. To compensate for variations in bubble response and to make the estimates more robust, the relation between the energy of the subharmonic and the fundamental component was chosen as a measure over the subharmonic peak amplitude. The preliminary study revealed the growth stage of the subharmonic...... 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......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...

  11. Silica-coated gold nanoplates as stable photoacoustic contrast agents for sentinel lymph node imaging

    Science.gov (United States)

    Luke, Geoffrey P.; Bashyam, Ashvin; Homan, Kimberly A.; Makhija, Suraj; Chen, Yun-Sheng; Emelianov, Stanislav Y.

    2013-11-01

    A biopsy of the first lymph node to which a tumor drains—the sentinel lymph node (SLN)—is commonly performed to identify micrometastases. Image guidance of the SLN biopsy procedure has the potential to improve its accuracy and decrease its morbidity. We have developed a new stable contrast agent for photoacoustic image-guided SLN biopsy: silica-coated gold nanoplates (Si-AuNPs). The Si-AuNPs exhibit high photothermal stability when exposed to pulsed and continuous wave laser irradiation. This makes them well suited for in vivo photoacoustic imaging. Furthermore, Si-AuNPs are shown to have low cytotoxicity. We tested the Si-AuNPs for SLN mapping in a mouse model where they exhibited a strong, sustained photoacoustic signal. Real-time ultrasound and photoacoustic imaging revealed that the Si-AuNPs quickly drain to the SLN, gradually spreading throughout a large portion of the node.

  12. 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.

  13. Investigation of sandwiched gadolinium (III) complexes with tungstosilicates as potential MRI contrast agents.

    Science.gov (United States)

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

    2004-04-01

    Two gadolinium-sandwiched complexes with tungstosilicates, K(13)[Gd(SiW(11)O(39))(2)] (Gd(SiW(11))(2)) and K(11)H(6)[Gd(3)O(3)(SiW(9)O(34))(2)] (Gd(3)(SiW(9))(2)), have been investigated by in vitro and in vivo experiments as potential contrast agents for magnetic resonance imaging (MRI). T(1)-relaxivity of Gd(SiW(11))(2)was 6.59 mM(-1).s(-1) in aqueous solution and 6.85 mM(-1).s(-1) in 0.725 mmol.L(-1) bovine serum albumin solution at 25 degrees C and 9.39 T, respectively. The corresponding T(1)-relaxivity of Gd(3)(SiW(9))(2) was 12.6 and 19.3 mM(-1).s(-1) per Gd, respectively. MRI for Sprague-Dawley rats showed longer and more remarkable enhancement in rat liver after i.v. injection of these two complexes: 39.4 +/- 3.9% and 57.4 +/- 11.6% within the first 30 min after injection, 31.2 +/- 2.6% and 39.9 +/- 7.6% in the next 60 min for Gd(SiW(11))(2) and Gd(3)(SiW(9))(2) at doses of 0.081 and 0.084 mmol Gd/kg, respectively. Our preliminary in vitro and in vivo study indicates that Gd(SiW(11))(2) and Gd(3)(SiW(9))(2) are favorable candidates for hepatic contrast agents for MRI. However, the two complexes exhibit higher acute toxicity and need to be modified and studied further before clinical use.

  14. Quantitative functional lung imaging with synchrotron radiation using inhaled xenon as contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Bayat, S. [TIMC-PRETA, UMR CNRS 5525, Laboratoire de Physiologie, Universite Joseph Fourier, Faculte de Medecine, Domaine de la Merci, Grenoble (France)]. E-mail: sam.bayat@imag.fr; Le Duc, G.; Berruyer, G.; Nemoz, C.; Monfraix, S.; Fiedler, S.; Thomlinson, W. [European Synchrotron Radiation Facility, BP 220, Grenoble (France); Porra, L.; Suortti, P. [Department of Physics, University of Helsinki, Helsinki (Finland); Standertskjoeld-Nordenstam, C.G. [Department of Radiology, University of Helsinki Central Hospital, Helsinki (Finland); Sovijaervi, A.R.A. [Department of Clinical Physiology and Nuclear Medicine, Helsinki University Central Hospital, Helsinki (Finland)

    2001-12-01

    Small airways play a key role in the distribution of ventilation and in the matching of ventilation to perfusion. The purpose of this study was to introduce an imaging method that allows measurement of regional lung ventilation and evaluation of the function of airways with a small diameter. The experiments were performed at the Medical Beamline of the European Synchrotron Radiation Facility. Monochromatic synchrotron radiation beams were used to obtain quantitative respiration-gated images of lungs and airways in two anaesthetized and mechanically ventilated rabbits using inhaled stable xenon (Xe) gas as a contrast agent. Two simultaneous images were acquired at two different energies, above and below the K-edge of Xe. Logarithmic subtraction of the two images yields absolute Xe concentrations. This technique is known as K-edge subtraction (KES) radiography. Two-dimensional planar and CT images were obtained showing spatial distribution of Xe concentrations within the airspaces, as well as the dynamics of filling with Xe. Bronchi down to 1 mm in diameter were visible both in the subtraction radiographs and in tomographic images. Absolute concentrations of Xe gas were calculated within the tube carrying the inhaled gas mixture, small and large bronchi, and lung tissue. Local time constants of ventilation with Xe were obtained by following the evolution of gas concentration in sequential computed tomography images. The results of this first animal study indicate that KES imaging of lungs with Xe gas as a contrast agent has great potential in studies of the distribution of ventilation within the lungs and of airway function, including airways with a small diameter. (author)

  15. Collagen based magnetic nanobiocomposite as MRI contrast agent and for targeted delivery in cancer therapy.

    Science.gov (United States)

    Mandal, A; Sekar, S; Kanagavel, M; Chandrasekaran, N; Mukherjee, A; Sastry, T P

    2013-10-01

    In this study, an attempt has been made with the advent of technology to prepare a multifunctional nanobiocomposite (NBC) for targeted drug delivery in cancer therapy. Collagen (C) was fabricated as nanofibers with multifunctional moieties viz. CFeAb*D by incorporating iron oxide nanoparticles (Fe), coupling with fluorescein isothiocyanate (FITC) labeled antibody (Ab*) and loading an anticancer gemcitabine drug (D). This NBC was characterized by conventional methods and evaluated for its biological activities. The UV-vis and FTIR spectroscopic studies revealed the fluorescein to protein ratio and revealed the presence of iron oxide nanoparticles and their interaction with the collagen molecules, respectively. While SDS-PAGE showed the proteinaceous nature of collagen, VSM and TEM studies revealed magnetic saturation as 54.97emu/g and a magnetic nanoparticle with a diameter in the range of 10-30nm and the dimension of nanofiber ranging from 97 to 270nm. A MRI scan has shown a super paramagnetic effect, which reveals that the prepared NBC can be used as a MRI contrast agent. The MTT assay has shown biocompatibility and an apoptotic effect while phase contrast microscopy exhibited receptor mediated uptake of endocytosis. The novelty in the prepared NBC lies in the collagen nanofibers, which have a higher penetrating property without causing much cell damage, biocompatibility and multifunctional properties and is able to carry multifunctional agents. The study has demonstrated the possible use of CFeAb*D as a multifunctional NBC for biomedical applications. Copyright © 2013 Elsevier B.V. All rights reserved.

  16. Preservation of imaging capability in sensitive ultrasound contrast agents after indirect plasma sterilization.

    Science.gov (United States)

    Albala, Lorenzo; Ercan, Utku K; Joshi, Suresh G; Eisenbrey, John R; Teraphongphom, Nutte; Wheatley, Margaret A

    2015-10-15

    Many injectables are not amenable to standard sterilization methods, which destroy sensitive materials. This is particularly true for ultrasound contrast agents (UCA) consisting of gas bubbles stabilized by a surfactant or polymer shell. We investigated a new method to achieve safe and effective sterilization in production by introducing dielectric-barrier discharge non-thermal plasma. A dielectric-barrier discharge was generated to first produce plasma-treated phosphate-buffered saline (PTPBS), which was used as a sterilant solution for our UCA SE61, avoiding direct heat, pressure, chemicals, or radiation. Treated samples were tested for acoustic properties in vitro and in a flow phantom, and for sterility by standard methods. Three minutes plasma treatment of phosphate-buffered saline (PBS) proved effective. The samples showed significant inactivation of inoculated bacteria upon PTPBS treatment as compared to un-treated-PBS (p=0.0022). The treated and untreated samples showed no statistical significance (p>0.05) in acoustic response or bubble diameter (mean±SEM: 2.52±0.31 μm). Nile Red was used to model intercalation of drug in the hydrophobic shell, intercalated successfully into SE61, and was unaffected by plasma treatment. The PTPBS completely sterilized suspensions of UCA, and it did not compromise the acoustic properties of the agent or its ability to retain a hydrophobic compound. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. 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. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Plasma sterilization of poly lactic acid ultrasound contrast agents: surface modification and implications for drug delivery.

    Science.gov (United States)

    Eisenbrey, John R; Hsu, Jennifer; Wheatley, Margaret A

    2009-11-01

    Poly lactic acid (PLA) ultrasound contrast agents (CA) have been developed previously in our laboratory for ultrasound (US) imaging, as well as surface coated with doxorubicin to create a potential targeted platform of chemotherapeutic delivery using focused US. However, we have previously found it impossible to sterilize these agents while at the same time maintaining their acoustic properties, a task that would probably require fabrication within a clean facility. The purpose of this paper is to investigate the feasibility of using plasma to sterilize these CA while maintaining maximum echogenicity, a step that would greatly facilitate in vivo investigations. Effects of plasma exposure time (1, 3 and 6 min) and intensity (low-10 mA, 6.8 W; medium-15 mA, 10.5 W; and high-25 mA, 18 W) on the CAs' acoustic properties, surface morphology, zeta potential, capacity to carry chemotherapeutics and overall sterility are described. Both increases in plasma intensity and exposure time increased CA zeta potential and also significantly increased drug payload. High-intensity plasma exposure for 3 min was found to be an optimal sterilization protocol for maximal (100%) preservation of CA echogenicity. Plasma exposure resulted in sterile samples and maintained original CA enhancement of 20 dB and acoustic half-life over 75 min, while increasing CA zeta potential by 11 mV and doxorubicin loading efficiency by 10%. This study not only shows how a highly temperature- and pressure-sensitive agent can be sterilized using plasma, but also that surface modification can be used to increase surface binding of the drug.

  19. Using light scattering to measure the response of individual ultrasound contrast microbubbles subjected to pulsed ultrasound in vitro

    Science.gov (United States)

    Guan, Jingfeng; Matula, Thomas J.

    2004-11-01

    Light scattering was used to measure the radial pulsations of individual ultrasound contrast microbubbles subjected to pulsed ultrasound. Highly diluted Optison® or Sonazoid® microbubbles were injected into either a water bath or an aqueous solution containing small quantities of xanthan gum. Individual microbubbles were insonified by ultrasound pulses from either a commercial diagnostic ultrasound machine or a single element transducer. The instantaneous response curves of the microbubbles were measured. Linear and nonlinear microbubble oscillations were observed. Good agreement was obtained by fitting a bubble dynamics model to the data. The pulse-to-pulse evolution of individual microbubbles was investigated, the results of which suggest that the shell can be semipermeable, and possibly weaken with subsequent pulses. There is a high potential that light scattering can be used to optimize diagnostic ultrasound techniques, understand microbubble evolution, and obtain specific information about shell parameters. .

  20. A Novel Polyacrylamide Magnetic Nanoparticle Contrast Agent for Molecular Imaging using MRI

    Directory of Open Access Journals (Sweden)

    Bradford A. Moffat

    2003-10-01

    Full Text Available A novel Polyacrylamide superparamagnetic iron oxide nanoparticle platform is described which has been synthetically prepared such that multiple crystals of iron oxide are encapsulated within a single Polyacrylamide matrix (PolyAcrylamide Magnetic [PAM] nanoparticles. This formulation provides for an extremely large T2 and T2* relaxivity of between 620 and 1140 sec−1 mM−1. Administration of PAM nanoparticles into rats bearing orthotopic 9L gliomas allowed quantitative pharmacokinetic analysis of the uptake of nanoparticles in the vasculature, brain, and glioma. Addition of polyethylene glycol of varying sizes (0.6, 2, and 10 kDa to the surface of the PAM nanoparticles resulted in an increase in plasma half-life and affected tumor uptake and retention of the nanoparticles as quantified by changes in tissue contrast using MRI. The flexible formulation of these nanoparticles suggests that future modifications could be accomplished allowing for their use as a targeted molecular imaging contrast agent and/or therapeutic platform for multiple indications.

  1. In situ gold nanoparticles formation: contrast agent for dental optical coherence tomography

    Science.gov (United States)

    Braz, Ana K. S.; Araujo, Renato E. de; Ohulchanskyy, Tymish Y.; Shukla, Shoba; Bergey, Earl J.; Gomes, Anderson S. L.; Prasad, Paras N.

    2012-06-01

    In this work we demonstrate the potential use of gold nanoparticles as contrast agents for the optical coherence tomography (OCT) imaging technique in dentistry. Here, a new in situ photothermal reduction procedure was developed, producing spherical gold nanoparticles inside dentinal layers and tubules. Gold ions were dispersed in the primer of commercially available dental bonding systems. After the application and permeation in dentin by the modified adhesive systems, the dental bonding materials were photopolymerized concurrently with the formation of gold nanoparticles. The gold nanoparticles were visualized by scanning electron microscopy (SEM). The SEM images show the presence of gold nanospheres in the hybrid layer and dentinal tubules. The diameter of the gold nanoparticles was determined to be in the range of 40 to 120 nm. Optical coherence tomography images were obtained in two- and three-dimensions. The distribution of nanoparticles was analyzed and the extended depth of nanosphere production was determined. The results show that the OCT technique, using in situ formed gold nanoparticles as contrast enhancers, can be used to visualize dentin structures in a non-invasive and non-destructive way.

  2. Discrete nanomolecular polyhedral borane scaffold supporting multiple gadolinium(III) complexes as a high performance MRI contrast agent.

    Science.gov (United States)

    Goswami, Lalit N; Ma, Lixin; Chakravarty, Shatadru; Cai, Quanyu; Jalisatgi, Satish S; Hawthorne, M Frederick

    2013-02-18

    An icosahedral closo-B(12)(2-) scaffold supports 12 copies of Gd(3+)-chelate held in close proximity with each other by suitable linkers which employ azide-alkyne click chemistry. This design is the first member of a new class of polyfunctional MRI contrast agents carrying a high payload of Gd(3+)-chelate in a sterically constrained configuration. The resulting contrast agent shows higher relaxivity values at high magnetic fields. MRI contrast agents currently in use are not as effective in this regard, presumably due to a lack of steric constraint of gadolinium centers and lower water exchange rates. In vivo MRI studies in mice show excellent contrast enhancement even at one-seventh of the safe clinical dose (0.04 mmol Gd/kg) for up to a 1 h exposure.

  3. Applying tattoo dye as a third-harmonic generation contrast agent for in vivo optical virtual biopsy of human skin

    Science.gov (United States)

    Tsai, Ming-Rung; Lin, Chen-Yu; Liao, Yi-Hua; Sun, Chi-Kuang

    2013-02-01

    Third-harmonic generation (THG) microscopy has been reported to provide intrinsic contrast in elastic fibers, cytoplasmic membrane, nucleus, actin filaments, lipid bodies, hemoglobin, and melanin in human skin. For advanced molecular imaging, exogenous contrast agents are developed for a higher structural or molecular specificity. We demonstrate the potential of the commonly adopted tattoo dye as a THG contrast agent for in vivo optical biopsy of human skin. Spectroscopy and microscopy experiments were performed on cultured cells with tattoo dyes, in tattooed mouse skin, and in tattooed human skin to demonstrate the THG enhancement effect. Compared with other absorbing dyes or nanoparticles used as exogenous THG contrast agents, tattoo dyes are widely adopted in human skin so that future clinical biocompatibility evaluation is relatively achievable. Combined with the demonstrated THG enhancement effect, tattoo dyes show their promise for future clinical imaging applications.

  4. Grey scale enhancement of rabbit liver and kidney by intravenous injection of a new lipid-coated ultrasound contrast agent

    Science.gov (United States)

    Liu, Ping; Gao, Yun-Hua; Tan, Kai-Bin; Liu, Zheng; Zuo, Song

    2004-01-01

    AIM: To assess the grey scale enhancement of a new lipid-coated ultrasound contrast agent in solid abdominal organs as liver and kidney. METHODS: Size distribution and concentration of the lipid-coated contrast microbubbles were analyzed by a Coulter counter. Two-dimensional (2D) second harmonic imaging of the hepatic parenchyma, the inferior vena cava and the right kidney of the rabbits were acquired before and after contrast agent injection. Images were further quantified by histogram in Adobe Photoshop 6.0. Time-intensity curves of hepatic parenchyma, inferior vena cava and renal cortex were generated from the original grey scale. RESULTS: The 2D images of hepatic parenchyma and cortex of the kidney were greatly enhanced after injection and the peak time could last more than 50 min. CONCLUSION: This new lipid ultrasound contrast agent could significantly enhance the grey scale imaging of the hepatic parenchyma and the renal cortex for more than 50 min. PMID:15285021

  5. 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.

  6. [Renal enhancement and excretion of the hepatobiliary contrast agent Gd-EOB-DTPA].

    Science.gov (United States)

    Zangos, S; Hammerstingl, R; Mack, M G; Straub, R; Engelmann, K; Eichler, K; Balzer, T; Vogl, T J

    2001-11-01

    To evaluate the clinical value of the renal clearance using MR imaging with different doses of gadolinium ethoxybenzyl-DTPA (Gd-EOB-DTPA) in comparison to gadolinium DTPA (Gd-DTPA). In a double-blind and randomized clinical phase II study. MR imaging at 1.5 T was performed in 61 patients with five different doses of Gd-EOB-DTPA (3, 6, 12.5, 25 and 50 micromol/kg b. w. as a bolus injection). The study protocol comprised T(1)- and T(2)-weighted spin-echo magnetic resonance and two-dimensional fast low-angle shot imaging before and at increasing intervals for up to 45 min after injection of Gd-EOB-DTPA. These images were compared with Gd-DTPA-enhanced imaging (0.1 mmol/kg b. w. as a bolus injection). After bolus injection of the hepatobiliary MR contrast agent Gd-EOB-DTPA a renal elimination was observed. Immediately after the injection of Gd-EOB-DTPA until the eighth minute a corticomedullary enhancement of the kidney was conspicuous. After the fourth minute a contrast enhancement could be seen in the renal pelvis. The best enhancement was noted after 20 minutes in the FLASH GRE and T(1)-weighted images with good pelvicaliceal contrast. After 45 minutes an outflow of Gd-EOB-DTPA into the ureter could be observed. In addition to the hepatobiliary secretion Gd-EOB-DTPA appears useful for the evaluation of renal structures and renal function on account of the renal excretion without diuretic preparation of the patients.

  7. 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

  8. Wide-field color imaging of scatter-based tissue contrast using both high spatial frequency illumination and cross-polarization gating.

    Science.gov (United States)

    Carlson, Mackenzie L; McClatchy, David M; Gunn, Jason R; Elliott, Jonathan T; Paulsen, Keith D; Kanick, Stephen C; Pogue, Brian W

    2017-08-11

    This study characterizes the scatter-specific tissue contrast that can be obtained by high spatial frequency (HSF) domain imaging and cross-polarization (CP) imaging, using a standard color imaging system, and how combining them may be beneficial. Both HSF and CP approaches are known to modulate the sensitivity of epi-illumination reflectance images between diffuse multiply scattered and superficially backscattered photons, providing enhanced contrast from microstructure and composition than what is achieved by standard wide-field imaging. Measurements in tissue-simulating optical phantoms show that CP imaging returns localized assessments of both scattering and absorption effects, while HSF has uniquely specific sensitivity to scatter-only contrast, with a strong suppression of visible contrast from blood. The combination of CP and HSF imaging provided an expanded sensitivity to scatter compared with CP imaging, while rejecting specular reflections detected by HSF imaging. ex vivo imaging of an atlas of dissected rodent organs/tissues demonstrated the scatter-based contrast achieved with HSF, CP and HSF-CP imaging, with the white light spectral signal returned by each approach translated to a color image for intuitive encoding of scatter-based contrast within images of tissue. The results suggest that visible CP-HSF imaging could have the potential to aid diagnostic imaging of lesions in skin or mucosal tissues and organs, where just CP is currently the standard practice imaging modality. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Quantitative Molecular Imaging with a Single Gd-Based Contrast Agent Reveals Specific Tumor Binding and Retention in Vivo.

    Science.gov (United States)

    Johansen, Mette L; Gao, Ying; Hutnick, Melanie A; Craig, Sonya E L; Pokorski, Jonathan K; Flask, Chris A; Brady-Kalnay, Susann M

    2017-06-06

    Magnetic resonance imaging (MRI) has become an indispensable tool in the diagnosis and treatment of many diseases, especially cancer. However, the poor sensitivity of MRI relative to other imaging modalities, such as PET, has hindered the development and clinical use of molecular MRI contrast agents that could provide vital diagnostic information by specifically locating a molecular target altered in the disease process. This work describes the specific and sustained in vivo binding and retention of a protein tyrosine phosphatase mu (PTPμ)-targeted, molecular magnetic resonance (MR) contrast agent with a single gadolinium (Gd) chelate using a quantitative MRI T 1 mapping technique in glioma xenografts. Quantitative T 1 mapping is an imaging method used to measure the longitudinal relaxation time, the T 1 relaxation time, of protons in a magnetic field after excitation by a radiofrequency pulse. T 1 relaxation times can in turn be used to calculate the concentration of a gadolinium-containing contrast agent in a region of interest, thereby allowing the retention or clearance of an agent to be quantified. In this context, retention is a measure of molecular contrast agent binding. Using conventional peptide chemistry, a PTPμ-targeted peptide was linked to a chelator that had been conjugated to a lysine residue. Following complexation with Gd, this PTPμ-targeted molecular contrast agent containing a single Gd ion showed significant tumor enhancement and a sustained increase in Gd concentration in both heterotopic and orthotopic tumors using dynamic quantitative MRI. This single Gd-containing PTPμ agent was more effective than our previous version with three Gd ions. Differences between nonspecific and specific agents, due to specific tumor binding, can be determined within the first 30 min after agent administration by examining clearance rates. This more facile chemistry, when combined with quantitative MR techniques, allows for widespread adoption by academic

  10. Diagnosis of a biliary cystadenoma demonstrating communication with the biliary system by MRI using a hepatocyte-specific contrast agent.

    Science.gov (United States)

    Billington, P D; Prescott, R J; Lapsia, S

    2012-02-01

    Biliary cystadenomas are predominately benign tumours that have a low malignant potential. We present a case of a 30-year-old female with a histopathological confirmation of a biliary cystadenoma following resection. The diagnosis was made pre-operatively by MRI using the hepatocyte-specific contrast agent gadobenate dimeglumine (Gd-BOPTA) (MultiHance; Bracco Diagnostics Inc., Princeton, NJ). At the biliary excretory phase, delayed phase images demonstrated communication between the multilocular cystic mass and the biliary tree, which helped to confirm the diagnosis of biliary cystadenoma. This highlights the beneficial use of hepatocyte-specific agents for their dual function as an extracellular agent and a hepatobiliary agent.

  11. Highly accelerated first-pass contrast-enhanced magnetic resonance angiography of the peripheral vasculature: comparison of gadofosveset trisodium with gadopentetate dimeglumine contrast agents.

    Science.gov (United States)

    Maki, Jeffrey H; Wang, Maisie; Wilson, Gregory J; Shutske, Matthew G; Leiner, Tim

    2009-11-01

    To investigate the blood pool agent gadofosveset trisodium for first-pass, dynamic peripheral contrast-enhanced magnetic resonance angiography (pMRA), and compare the results with a conventional gadolinium contrast agent. A total of 16 patients were imaged at 1.5T using a prototype peripheral vascular coil with high SENSE acceleration. Five received gadopentetate dimeglumine ( approximately 0.25 mmol/kg), and 11 received gadofosveset trisodium (five standard-dose 0.03 mmol/kg, six high-dose 0.05 mmol/kg). Quantitative contrast-enhancement and qualitative image quality evaluation was compared between agents and doses. High-quality diagnostic images were uniformly obtained. The contrast ratio did not significantly differ between gadopentetate dimeglumine and high-dose gadofosveset trisodium, both of which were greater than standard-dose gadofosveset trisodium. High-dose gadofosveset trisodium was equivalent to gadopentetate dimeglumine in image quality and subjective vessel-to-background ratio, but significantly better for depicting small muscular arteries. Standard-dose gadofosveset trisodium showed equivalent image quality and small artery depiction with a slight but significant decrease in vessel-to-background ratio as compared to gadopentatate dimeglumine. Both gadofosveset trisodium doses trended toward more venous enhancement, but this was not a diagnostic problem. First-pass peripheral CE-MRA using gadofosveset trisodium is feasible, yielding image quality comparable to double to triple-dose gadopentetate dimeglumine. Increasing the gadofosveset trisodium dose to 0.05 mmol/kg yields further improvements.

  12. A Proposed Computed Tomography Contrast Agent Using Carboxybetaine Zwitterionic Tantalum Oxide Nanoparticles: Imaging, Biological, and Physicochemical Performance.

    Science.gov (United States)

    FitzGerald, Paul F; Butts, Matthew D; Roberts, Jeannette C; Colborn, Robert E; Torres, Andrew S; Lee, Brian D; Yeh, Benjamin M; Bonitatibus, Peter J

    2016-12-01

    The aim of this study was to produce and evaluate a proposed computed tomography (CT) contrast agent based on carboxybetaine zwitterionic (CZ)-coated soluble tantalum oxide (TaO) nanoparticles (NPs). We chose tantalum to provide superior imaging performance compared with current iodine-based clinical CT contrast agents. We developed the CZ coating to provide biological and physical performance similar to that of current iodinated contrast agents. In addition, the aim of this study was to evaluate the imaging, biological, and physicochemical performance of this proposed contrast agent compared with clinically used iodinated agents. We evaluated CT imaging performance of our CZ-TaO NPs compared with that of an iodinated agent in live rats, imaged centrally located within a tissue-equivalent plastic phantom that simulated a large patient. To evaluate vascular contrast enhancement, we scanned the rats' great vessels at high temporal resolution during and after contrast agent injection. We performed several in vivo CZ-TaO NP studies in healthy rats to evaluate tolerability. These studies included injecting the agent at the anticipated clinical dose (ACD) and at 3 times and 6 times the ACD, followed by longitudinal hematology to assess impact to blood cells and organ function (from 4 hours to 1 week). Kidney histological analysis was performed 48 hours after injection at 3 times the ACD. We measured the elimination half-life of CZ-TaO NPs from blood, and we monitored acute kidney injury biomarkers with a kidney injury assay using urine collected from 4 hours to 1 week. We measured tantalum retention in individual organs and in the whole carcass 48 hours after injection at ACD. Carboxybetaine zwitterionic TaO NPs were synthesized and analyzed in detail. We used multidimensional nuclear magnetic resonance to determine surface functionality of the NPs. We measured NP size and solution properties (osmolality and viscosity) of the agent over a range of tantalum concentrations

  13. Assessing the efficacy of nano- and micro-sized magnetic particles as contrast agents for MRI cell tracking.

    Science.gov (United States)

    Taylor, Arthur; Herrmann, Anne; Moss, Diana; Sée, Violaine; Davies, Karen; Williams, Steve R; Murray, Patricia

    2014-01-01

    Iron-oxide based contrast agents play an important role in magnetic resonance imaging (MRI) of labelled cells in vivo. Currently, a wide range of such contrast agents is available with sizes varying from several nanometers up to a few micrometers and consisting of single or multiple magnetic cores. Here, we evaluate the effectiveness of these different particles for labelling and imaging stem cells, using a mouse mesenchymal stem cell line to investigate intracellular uptake, retention and processing of nano- and microsized contrast agents. The effect of intracellular confinement on transverse relaxivity was measured by MRI at 7 T and in compliance with the principles of the '3Rs', the suitability of the contrast agents for MR-based cell tracking in vivo was tested using a chick embryo model. We show that for all particles tested, relaxivity was markedly reduced following cellular internalisation, indicating that contrast agent relaxivity in colloidal suspension does not accurately predict performance in MR-based cell tracking studies. Using a bimodal imaging approach comprising fluorescence and MRI, we demonstrate that labelled MSC remain viable following in vivo transplantation and can be tracked effectively using MRI. Importantly, our data suggest that larger particles might confer advantages for longer-term imaging.

  14. Assessing the efficacy of nano- and micro-sized magnetic particles as contrast agents for MRI cell tracking.

    Directory of Open Access Journals (Sweden)

    Arthur Taylor

    Full Text Available Iron-oxide based contrast agents play an important role in magnetic resonance imaging (MRI of labelled cells in vivo. Currently, a wide range of such contrast agents is available with sizes varying from several nanometers up to a few micrometers and consisting of single or multiple magnetic cores. Here, we evaluate the effectiveness of these different particles for labelling and imaging stem cells, using a mouse mesenchymal stem cell line to investigate intracellular uptake, retention and processing of nano- and microsized contrast agents. The effect of intracellular confinement on transverse relaxivity was measured by MRI at 7 T and in compliance with the principles of the '3Rs', the suitability of the contrast agents for MR-based cell tracking in vivo was tested using a chick embryo model. We show that for all particles tested, relaxivity was markedly reduced following cellular internalisation, indicating that contrast agent relaxivity in colloidal suspension does not accurately predict performance in MR-based cell tracking studies. Using a bimodal imaging approach comprising fluorescence and MRI, we demonstrate that labelled MSC remain viable following in vivo transplantation and can be tracked effectively using MRI. Importantly, our data suggest that larger particles might confer advantages for longer-term imaging.

  15. MR angiography of collateral arteries in a hind limb ischemia model: comparison between blood pool agent Gadomer and small contrast agent Gd-DTPA.

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    Karolien Jaspers

    Full Text Available The objective of this study was to compare the blood pool agent Gadomer with a small contrast agent for the visualization of ultra-small, collateral arteries (diameter0.10. Inter-observer variation was 24% and 18% for Gadomer and Gd-DTPA, respectively. In conclusion, blood pool agent Gadomer improved vessel conspicuity compared to Gd-DTPA. Steady-state MRA can be considered as an excellent non-invasive alternative to intra-arterial XRA for the visualization of ultra-small collateral arteries.

  16. Pathological mechanism for delayed hyperenhancement of chronic scarred myocardium in contrast agent enhanced magnetic resonance imaging.

    Science.gov (United States)

    Wang, Jian; Xiang, Bo; Lin, Hung-Yu; Liu, Hongyu; Freed, Darren; Arora, Rakesh C; Tian, Ganghong

    2014-01-01

    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. 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. 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. Collateral circulation formation and residual vessel effectively delivered CA into scarred myocardium. However, residual vessel without abnormal hyperpermeability allowed Gd-DTPA rather than P792 to penetrate into extravascular compartment

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

    Science.gov (United States)

    Nakatsuka, Matthew Allan Masao

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

  18. Influence of ultrasound contrast agents on spectral Doppler analysis in recipients of liver transplantation

    Directory of Open Access Journals (Sweden)

    Young Seo Cho

    2017-09-01

    Full Text Available Background/Aims Clinical validation is required to determine whether Doppler measurements are comparable before and after administering ultrasound contrast agent (USCA. The purpose of this study is to explore whether the use of USCA affects spectral Doppler analysis in recipients of liver transplantation (LT. Methods For this study, 36 patients were examined using Doppler ultrasonography (US along with a contrast-enhanced US for surveillance of vascular complications after LT. The following spectral Doppler US parameters were measured before and after administration of USCA: peak systolic velocity, end-diastolic velocity, resistive index, and systolic acceleration time of the graft hepatic artery; peak flow velocity of the graft portal vein; and peak flow velocity and venous pulsatility index of the graft hepatic vein. Results The mean peak systolic and end-diastolic velocities of the hepatic artery and the peak flow velocity of the portal and hepatic veins were increased after intravenously administration of the USCA, ranging from 10% to 13%. However, the changes were not statistically significant (P=0.097, 0.103, 0.128, and 0.190, respectively. There were no significant differences in other measured parameters, including the resistive index (P=0.205 and systolic acceleration time (P=0.489 of the hepatic artery and venous pulsatility index (P=0.494 of the hepatic vein. Conclusions The measured velocities of graft hepatic vessels tended to increase after administration of USCA, but without statistical significance. The comparison of serial Doppler parameters with or without injection of USCA is valid during Doppler surveillance in recipients of LT.

  19. Gold nanoparticle contrast agents in advanced X-ray imaging technologies.

    Science.gov (United States)

    Ahn, Sungsook; Jung, Sung Yong; Lee, Sang Joon

    2013-05-17

    Recently, there has been significant progress in the field of soft- and hard-X-ray imaging for a wide range of applications, both technically and scientifically, via developments in sources, optics and imaging methodologies. While one community is pursuing extensive applications of available X-ray tools, others are investigating improvements in techniques, including new optics, higher spatial resolutions and brighter compact sources. For increased image quality and more exquisite investigation on characteristic biological phenomena, contrast agents have been employed extensively in imaging technologies. Heavy metal nanoparticles are excellent absorbers of X-rays and can offer excellent improvements in medical diagnosis and X-ray imaging. In this context, the role of gold (Au) is important for advanced X-ray imaging applications. Au has a long-history in a wide range of medical applications and exhibits characteristic interactions with X-rays. Therefore, Au can offer a particular advantage as a tracer and a contrast enhancer in X-ray imaging technologies by sensing the variation in X-ray attenuation in a given sample volume. This review summarizes basic understanding on X-ray imaging from device set-up to technologies. Then this review covers recent studies in the development of X-ray imaging techniques utilizing gold nanoparticles (AuNPs) and their relevant applications, including two- and three-dimensional biological imaging, dynamical processes in a living system, single cell-based imaging and quantitative analysis of circulatory systems and so on. In addition to conventional medical applications, various novel research areas have been developed and are expected to be further developed through AuNP-based X-ray imaging technologies.

  20. Gold Nanoparticle Contrast Agents in Advanced X-ray Imaging Technologies

    Directory of Open Access Journals (Sweden)

    Sungsook Ahn

    2013-05-01

    Full Text Available Recently, there has been significant progress in the field of soft- and hard-X-ray imaging for a wide range of applications, both technically and scientifically, via developments in sources, optics and imaging methodologies. While one community is pursuing extensive applications of available X-ray tools, others are investigating improvements in techniques, including new optics, higher spatial resolutions and brighter compact sources. For increased image quality and more exquisite investigation on characteristic biological phenomena, contrast agents have been employed extensively in imaging technologies. Heavy metal nanoparticles are excellent absorbers of X-rays and can offer excellent improvements in medical diagnosis and X-ray imaging. In this context, the role of gold (Au is important for advanced X-ray imaging applications. Au has a long-history in a wide range of medical applications and exhibits characteristic interactions with X-rays. Therefore, Au can offer a particular advantage as a tracer and a contrast enhancer in X-ray imaging technologies by sensing the variation in X-ray attenuation in a given sample volume. This review summarizes basic understanding on X-ray imaging from device set-up to technologies. Then this review covers recent studies in the development of X-ray imaging techniques utilizing gold nanoparticles (AuNPs and their relevant applications, including two- and three-dimensional biological imaging, dynamical processes in a living system, single cell-based imaging and quantitative analysis of circulatory systems and so on. In addition to conventional medical applications, various novel research areas have been developed and are expected to be further developed through AuNP-based X-ray imaging technologies.

  1. Influence of ultrasound contrast agents on spectral Doppler analysis in recipients of liver transplantation.

    Science.gov (United States)

    Cho, Young Seo; Kim, Kyoung Won; Jang, Hye Young; Kim, Bo Hyun; Lee, Jeongjin; Song, Gi Won; Lee, Sung Gyu; Munkhbaatar, Dagvasumberel

    2017-09-01

    Clinical validation is required to determine whether Doppler measurements are comparable before and after administering ultrasound contrast agent (USCA). The purpose of this study is to explore whether the use of USCA affects spectral Doppler analysis in recipients of liver transplantation (LT). For this study, 36 patients were examined using Doppler ultrasonography (US) along with a contrast-enhanced US for surveillance of vascular complications after LT. The following spectral Doppler US parameters were measured before and after administration of USCA: peak systolic velocity, end-diastolic velocity, resistive index, and systolic acceleration time of the graft hepatic artery; peak flow velocity of the graft portal vein; and peak flow velocity and venous pulsatility index of the graft hepatic vein. The mean peak systolic and end-diastolic velocities of the hepatic artery and the peak flow velocity of the portal and hepatic veins were increased after intravenously administration of the USCA, ranging from 10% to 13%. However, the changes were not statistically significant ( P =0.097, 0.103, 0.128, and 0.190, respectively). There were no significant differences in other measured parameters, including the resistive index ( P =0.205) and systolic acceleration time ( P =0.489) of the hepatic artery and venous pulsatility index ( P =0.494) of the hepatic vein. The measured velocities of graft hepatic vessels tended to increase after administration of USCA, but without statistical significance. The comparison of serial Doppler parameters with or without injection of USCA is valid during Doppler surveillance in recipients of LT.

  2. Diagnostic utility of an echo-contrast agent in patients with synovitis using power Doppler ultrasound: a preliminary study with comparison to contrast-enhanced MRI

    Energy Technology Data Exchange (ETDEWEB)

    Magarelli, N.; Tartaro, A.; Bonomo, L. [Istituto di Radiologia, Universita di Chieti (Italy); Guglielmi, G. [Istituto di Radiologia, IRCCS, San Giovanni Rotondo (Italy); Di Matteo, L. [Istituto di Reumatologia, Pescara (Italy); Mattei, P.A. [Facolta di Medicina, Universita Chieti (Italy)

    2001-06-01

    The purpose of this study was to first evaluate Levovist (Schering, Berlin, Germany), an echo-contrast agent, during power Doppler sonography (PDS) in patients with synovitis using asymptomatic joints as controls. Then we evaluated the accuracy of this technique against contrast-enhanced MRI. Forty patients (19 men and 21 women; mean age 40 years) were enrolled on the basis of clinical signs, laboratory tests, and radiographic findings positive for articular inflammatory disease. They were examined with conventional ultrasonography (US) and PDS techniques before and after intravenous contrast medium injection. Fourteen patients then underwent MRI with and without contrast medium 8-14 days after PDS studies. Three expert readers independently evaluated each examination. After contrast medium, synovium in inflammatory arthritis enhanced on PDS compared with normal joints in the same patient. Power Doppler sonography after contrast medium and MRI were concordant in all cases. Power Doppler sonography with contrast medium showed a qualitative increase in signal from synovial vessels, the first sign of synovial changes in inflammatory diseases. (orig.)

  3. Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging

    Directory of Open Access Journals (Sweden)

    Shengtao Lin

    2017-06-01

    Full Text Available We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1 photoacoustic imaging contrast, 2 ultrasound contrast with optical activation, and 3 ultrasound contrast with acoustic activation. This agent, which we name ‘Cy-droplet’, has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a ‘microbubble condensation’ method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ. Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical ‘triggerability’ can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release.

  4. Optically and acoustically triggerable sub-micron phase-change contrast agents for enhanced photoacoustic and ultrasound imaging.

    Science.gov (United States)

    Lin, Shengtao; Shah, Anant; Hernández-Gil, Javier; Stanziola, Antonio; Harriss, Bethany I; Matsunaga, Terry O; Long, Nicholas; Bamber, Jeffrey; Tang, Meng-Xing

    2017-06-01

    We demonstrate a versatile phase-change sub-micron contrast agent providing three modes of contrast enhancement: 1) photoacoustic imaging contrast, 2) ultrasound contrast with optical activation, and 3) ultrasound contrast with acoustic activation. This agent, which we name 'Cy-droplet', has the following novel features. It comprises a highly volatile perfluorocarbon for easy versatile activation, and a near-infrared optically absorbing dye chosen to absorb light at a wavelength with good tissue penetration. It is manufactured via a 'microbubble condensation' method. The phase-transition of Cy-droplets can be optically triggered by pulsed-laser illumination, inducing photoacoustic signal and forming stable gas bubbles that are visible with echo-ultrasound in situ . Alternatively, Cy-droplets can be converted to microbubble contrast agents upon acoustic activation with clinical ultrasound. Potentially all modes offer extravascular contrast enhancement because of the sub-micron initial size. Such versatility of acoustic and optical 'triggerability' can potentially improve multi-modality imaging, molecularly targeted imaging and controlled drug release.

  5. Detection of early carious lesions using contrast enhancement with coherent light scattering (speckle imaging)

    Science.gov (United States)

    Deana, A. M.; Jesus, S. H. C.; Koshoji, N. H.; Bussadori, S. K.; Oliveira, M. T.

    2013-07-01

    Currently, dental caries still represent one of the chronic diseases with the highest prevalence and present in most countries. The interaction between light and teeth (absorption, scattering and fluorescence) is intrinsically connected to the constitution of the dental tissue. Decay induced mineral loss introduces a shift in the optical properties of the affected tissue; therefore, study of these properties may produce novel techniques aimed at the early diagnosis of carious lesions. Based on the optical properties of the enamel, we demonstrate the application of first-order spatial statistics in laser speckle imaging, allowing the detection of carious lesions in their early stages. A highlight of this noninvasive, non-destructive, real time and cost effective approach is that it allows a dentist to detect a lesion even in the absence of biofilm or moisture.

  6. Low-Molecular-Weight Iron Chelates May Be an Alternative to Gadolinium-based Contrast Agents for T1-weighted Contrast-enhanced MR Imaging.

    Science.gov (United States)

    Boehm-Sturm, Philipp; Haeckel, Akvile; Hauptmann, Ralf; Mueller, Susanne; Kuhl, Christiane K; Schellenberger, Eyk A

    2017-01-07

    Purpose To synthesize two low-molecular-weight iron chelates and compare their T1 contrast effects with those of a commercial gadolinium-based contrast agent for their applicability in dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging. Materials and Methods The animal experiments were approved by the local ethics committee. Two previously described iron (Fe) chelates of pentetic acid (Fe-DTPA) and of trans-cyclohexane diamine tetraacetic acid (Fe-tCDTA) were synthesized with stability constants several orders of magnitude higher than those of gadolinium-based contrast agents. The T1 contrast effects of the two chelates were compared with those of gadopentetate dimeglumine in blood serum phantoms at 1.5 T, 3 T, and 7 T. For in vivo studies, a human breast cancer cell line (MDA-231) was implanted in five mice per group. The dynamic contrast effects of the chelates were compared by performing DCE MR imaging with intravenous application of Fe-DTPA or Fe-tCDTA on day 1 and DCE MR imaging in the same tumors with gadopentetate dimeglumine on day 2. Quantitative DCE maps were generated with software and were compared by means of a one-tailed Pearson correlation test. Results Relaxivities in serum (0.94 T at room temperature) of Fe-tCDTA (r1 = 2.2 mmol(-1) · sec(-1), r2 = 2.5 mmol(-1) · sec(-1)) and Fe-DTPA (r1 = 0.9 mmol(-1) · sec(-1), r2 = 0.9 mmol(-1) · sec(-1)) were approximately twofold and fivefold lower, respectively, compared with those of gadopentetate dimeglumine (r1 = 4.1 mmol(-1) · sec(-1), r2 = 4.8 mmol(-1) · sec(-1)). Used at moderately higher concentrations, however, iron chelates generated similar contrast effects at T1-weighted MR imaging in vitro in serum, in vivo in blood, and for DCE MR imaging of breast cancer xenografts. The volume transfer constant values for Fe-DTPA and Fe-tCDTA in the same tumors correlated well with those observed for gadopentetate dimeglumine (Fe-tCDTA Pearson R, 0.99; P = .0003; Fe-DTPA Pearson R, 0

  7. Cell-penetrating peptides and peptide nucleic acid-coupled MRI contrast agents: evaluation of cellular delivery and target binding.

    Science.gov (United States)

    Mishra, Ritu; Su, Wu; Pohmann, Rolf; Pfeuffer, Josef; Sauer, Martin G; Ugurbil, Kamil; Engelmann, Jörn

    2009-10-21

    Molecular imaging of cells and cellular processes can be achieved by tagging intracellular targets such as receptors, enzymes, or mRNA. Seeking to visualize the presence of specific mRNAs by magnetic resonance (MR) imaging, we coupled peptide nucleic acids (PNA) with gadolinium-based MR contrast agents using cell-penetrating peptides for intracellular delivery. Antisense to mRNA of DsRed2 protein was used as proof of principle. The conjugates were produced by continuous solid-phase synthesis followed by chelation with gadolinium. Their cellular uptake was confirmed by fluorescence microscopy and spectroscopy as well as by MR imaging of labeled cells. The cell-penetrating peptide D-Tat(57-49) was selected over two other derivatives of HIV-1 Tat peptide, based on its superior intracellular delivery of the gadolinium-based contrast agents. Further improved delivery of conjugates was achieved upon coupling peptide nucleic acids (antisense to mRNA of DsRed2 protein and nonsense with no natural counterpart). Significant enhancement in MR contrast was obtained in cells labeled with concentrations as low as 2.5 μM of these agents. Specific binding of the targeting PNA containing conjugate to its complementary oligonucleotide sequence was proven by in vitro cell-free assay. In contrast, a lack of specific enrichment was observed in transgenic cells containing the target due to nonspecific vesicular entrapment of contrast agents. Preliminary biodistribution studies showed conjugate-related fluorescence in several organs, especially the liver and bladder, indicating high mobility of the agent in spite of its high molecular weight. No conjugate related toxicity was observed. These results are encouraging, as they warrant further molecular optimization and consecutive specificity studies in vivo of this new generation of contrast agents.

  8. Decafluorobutane as a phase-change contrast agent for low-energy extravascular ultrasonic imaging.

    Science.gov (United States)

    Sheeran, Paul S; Wong, Vincent P; Luois, Samantha; McFarland, Ryan J; Ross, William D; Feingold, Steven; Matsunaga, Terry O; Dayton, Paul A

    2011-09-01

    Currently available microbubbles used for ultrasound imaging and therapeutics are limited to intravascular space due to their size distribution in the micron range. Phase-change contrast agents (PCCAs) have been proposed as a means to overcome this limitation, since droplets formed in the hundred nanometer size range might be able to extravasate through leaky microvasculature, after which they could be activated to form larger highly echogenic microbubbles. Existing PCCAs in the sub-micron size range require substantial acoustic energy to be vaporized, increasing the likelihood of unwanted bioeffects. Thus, there exists a need for PCCAs with reduced acoustic activation energies for use in imaging studies. In this article, it is shown that decafluorobutane, which is normally a gas at room temperature, can be incorporated into metastable liquid sub-micron droplets with appropriate encapsulation methods. The resulting droplets are activatable with substantially less energy than other favored PCCA compounds. Decafluorobutane nanodroplets may present a new means to safely extend ultrasound imaging beyond the vascular space. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  9. 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.)

  10. Angiographic CT with intravenous contrast agent application for monitoring of intracranial flow diverting stents

    Energy Technology Data Exchange (ETDEWEB)

    Saake, Marc; Struffert, Tobias; Goelitz, Philipp; Ott, Sabine; Doerfler, Arnd [University of Erlangen-Nuremberg, Department of Neuroradiology, Erlangen (Germany); Seifert, Frank [University of Erlangen-Nuremberg, Department of Neurology, Erlangen (Germany); Ganslandt, Oliver [University of Erlangen-Nuremberg, Department of Neurosurgery, Erlangen (Germany)

    2012-07-15

    Intracranial flow diverting devices are increasingly used to treat cerebral aneurysms. A reliable, non-invasive follow-up modality would be desirable. Our aim was to compare intra-arterial digital subtraction angiography (ia DSA) to angiographic computed tomography with intravenous contrast agent application (iv ACT) in the visualisation of flow diverting devices and aneurysm lumina. Follow-up monitoring by iv ACT (n = 36) and ia DSA (n = 25) in 14 patients treated with flow diverting devices for intracranial aneurysms was evaluated retrospectively. Images were evaluated by two neuroradiologists in anonymous consensus reading regarding the device deployment, wall apposition, neck coverage of the aneurysm, opacification of the vessel and device lumen, as well as the degree of aneurysm occlusion. Corresponding ia DSA and iv ACT images were scored identically in all patients regarding the stent deployment, wall apposition and neck coverage, as well as the degree of aneurysm occlusion and patency status of the device and parent artery. Opacification of the parent vessel lumen and perfused parts of the aneurysm was considered slightly inferior for iv ACT in comparison with ia DSA (seven of 36 cases), without impact on diagnosis. We demonstrated the feasibility and diagnostic value of iv ACT in follow-up imaging of intracranial flow diverting devices. Due to its high spatial resolution and non-invasive character, this novel technique might become a valuable imaging modality in these patients. (orig.)

  11. Investigation of magnetic properties of various complexes prepared as contrast agents for MRI

    Science.gov (United States)

    Yurt, Ayşegül; Kazancı, Nadide

    2008-12-01

    In this study, the relaxivities of various ferri-ferro and superparamagnetic particles in human serum and deionized water were determined by using MRI system operating at 1.5 T. For this purpose, the spin-lattice (1/ T1) and spin-spin (1/ T2) relaxation rates in serum and deionized water were measured versus increasing concentrations of the DyPO 4, 5Fe 2O 33Gd 2O 3 + dextran, 5Fe 2O 33Gd 2O 3 + CMC, 5Fe 2O 33Gd 2O 3. The longitudinal relaxivity ( r1) and transverse relaxivity ( r2) of proton were determined from the slopes of fits between the relaxation rates and concentrations. T1 and T2 times in serum were decreased due to increased concentrations of the ions added to samples. The r2/ r1 values for ions added to serum ranged from 1 to 4, whereas the r2/ r1 for the ions added to water changed between 0.57 and 1 except that for 5Fe 2O 33Gd 2O 3. PRRE (proton relaxation rate enhancement) data reveals that, the ions added to serum are not bound to the proteins. The present results suggest that chemical compounds of iron oxide studied may have a potential that can be used as an alternative superparamagnetic MRI contrast agent.

  12. Acoustic interrogation and optical visualization of ultrasound contrast agents within microcapsules.

    Science.gov (United States)

    Santhiranayagam, P; Thirumalai, S; Memom, F; Shan, Y; Lee, S J; Mobed-Miremadi, M; Keralapura, M

    2012-01-01

    The effectiveness of localized drug delivery as a treatment for breast cancer requires sufficiently high therapeutic dose, as well as an ability to image the drug for proper spatial targeting. To balance treatment potential and imaging capabilities, we have begun to design a novel drug reservoir using microcapsules that are large in size (> 30 µm) but functionalized with microbubbles or ultrasound contrast agents (UCAs). We term these carriers as 'Acoustically Sensitive Microcapsules' (ASMs). In previous work, we have demonstrated preparation of ASM carriers and their structural changes under therapeutic ultrasound by imaging static changes. In this paper, we describe a combined optical-acoustic setup coupled with a microfluidic device to trap these carriers for imaging and sonication. Using the setup, continuous wave ultrasound (180 kPa, 2.25 MHz, 3 s) produced an average displacement of 3.5 µm in UCAs near the ASM boundary, and exhibited displacement as high as 90 µm near the center of the microcapsule. Longer exposure time and higher acoustic pressure increased UCA displacement within an ASM. These two parameters can be carefully optimized in the future to cause these UCAs to travel to the membrane boundary to help in the drug elution process.

  13. Phospholipid decoration of microcapsules containing perfluorooctyl bromide used as ultrasound contrast agents.

    Science.gov (United States)

    Díaz-López, Raquel; Tsapis, Nicolas; Libong, Danielle; Chaminade, Pierre; Connan, Carole; Chehimi, Mohamed M; Berti, Romain; Taulier, Nicolas; Urbach, Wladimir; Nicolas, Valérie; Fattal, Elias

    2009-03-01

    We present here an easy method to modify the surface chemistry of polymeric microcapsules of perfluorooctyl bromide used as ultrasound contrast agents (UCAs). Capsules were obtained by a solvent emulsification-evaporation process with phospholipids incorporated in the organic phase before emulsification. Several phospholipids were reviewed: fluorescent, pegylated and biotinylated phospholipids. The influence of phospholipid concentration on microcapsule size and morphology was evaluated. Only a fraction of the phospholipids is associated to microcapsules, the rest being dissolved with the surfactant in the aqueous phase. Microscopy shows that phospholipids are present within the shell and that the core/shell structure is preserved up to 0.5 mg fluorescent phospholipids, up to about 0.25 mg pegylated phospholipids or biotinylated phospholipids (for 100 mg of polymer, poly(lactide-co-glycolide) (PLGA)). HPLC allows quantifying phospholipids associated to capsules: they correspond to 10% of pegylated phospholipids introduced in the organic phase. The presence of pegylated lipids at the surface of capsules was confirmed by X-ray photon electron spectroscopy (XPS). The pegylation did not modify the echographic signal arising from capsules. Finally biotinylated microcapsules incubated with neutravidin tend to aggregate, which confirms the presence of biotin at the surface. These results are encouraging and future work will consist of nanocapsule surface modification for molecular imaging.

  14. Effects of Needle and Catheter Size on Commercially Available Ultrasound Contrast Agents.

    Science.gov (United States)

    Eisenbrey, John R; Daecher, Annemarie; Kramer, Michael R; Forsberg, Flemming

    2015-11-01

    To investigate effects of needle and catheter size on in vitro ultrasound contrast agent (UCA) enhancement and concentrations using 4 commercially available UCAs. Definity (Lantheus Medical Imaging, North Billerica, MA), Optison (GE Healthcare, Princeton, NJ), SonoVue (Bracco SA, Geneva, Switzerland), and Sonazoid (GE Healthcare, Oslo, Norway) were investigated. The UCA was injected via a 1-mL syringe (BD, Franklin Lakes, NJ) into a 3-way stopcock (Smith Medical, Dublin, OH) and flushed with 10 mL of saline through an 18-cm infusion extension tube connected to either a 16-, 18-, 20-, 22-, or 24-gauge catheter (BD) or an 18-, 20-, 21-, or 25-gauge needle (BD). In vitro enhancement was determined in a flow phantom (ATS Laboratories, Bridgeport, CT), and microbubble concentrations were determined using an LSRII flow cytometer (BD Biosciences, San Jose, CA). Significant decreases in enhancement and microbubble concentrations were observed for all 4 UCAs (P < .001) when administration was performed through a 25-gauge needle. No statistically significant differences in enhancement or concentrations were observed between all catheter sizes and 18- to 21-gauge needles for SonoVue and Sonazoid. Definity and Optison administration through a 24-gauge catheter resulted in a significant loss of enhancement (P < .02), although these differences were not significant on flow cytometry. Administration of commercial UCAs in a clinical scenario is possible with catheters or needles smaller than 20 gauge, although the minimal allowable size appears to be UCA specific. © 2015 by the American Institute of Ultrasound in Medicine.

  15. Streaming flow from ultrasound contrast agents by acoustic waves in a blood vessel model.

    Science.gov (United States)

    Cho, Eunjin; Chung, Sang Kug; Rhee, Kyehan

    2015-09-01

    To elucidate the effects of streaming flow on ultrasound contrast agent (UCA)-assisted drug delivery, streaming velocity fields from sonicated UCA microbubbles were measured using particle image velocimetry (PIV) in a blood vessel model. At the beginning of ultrasound sonication, the UCA bubbles formed clusters and translated in the direction of the ultrasound field. Bubble cluster formation and translation were faster with 2.25MHz sonication, a frequency close to the resonance frequency of the UCA. Translation of bubble clusters induced streaming jet flow that impinged on the vessel wall, forming symmetric vortices. The maximum streaming velocity was about 60mm/s at 2.25MHz and decreased to 15mm/s at 1.0MHz for the same acoustic pressure amplitude. The effect of the ultrasound frequency on wall shear stress was more noticeable. Maximum wall shear stress decreased from 0.84 to 0.1Pa as the ultrasound frequency decreased from 2.25 to 1.0MHz. The maximum spatial gradient of the wall shear stress also decreased from 1.0 to 0.1Pa/mm. This study showed that streaming flow was induced by bubble cluster formation and translation and was stronger upon sonication by an acoustic wave with a frequency near the UCA resonance frequency. Therefore, the secondary radiant force, which is much stronger at the resonance frequency, should play an important role in UCA-assisted drug delivery. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Self-demodulation effect on subharmonic response of ultrasound contrast agent

    Science.gov (United States)

    Daeichin, V.; Faez, T.; Needles, A.; Renaud, G.; Bosch, J. G.; van der Steen, A. F. W.; de Jong, N.

    2012-03-01

    In this work the use of the self-demodulation (S-D) signal as a mean of microbubble excitation at the subharmonic (SH) frequency to enhance the SH emission of ultrasound contrast agent (UCA) is studied. SH emission from the UCA is of interest since it is produced only by the UCA and is free of the artifacts produced in harmonic imaging modes. The S-D wave is a low-frequency signal produced by nonlinear propagation of an ultrasound wave in the medium. Single element transducer experiments and numerical simulations were conducted at 10 MHz to study the effect of the S-D signal on the SH response of the UCA by modifying the envelope of the excitation bursts. For 6 and 20 transmitted cycles, the SH response is increased up to 25 dB and 22 dB because of the S-D stimulation for a burst with a rectangular envelope compared with a Gaussian envelope burst. Such optimized excitations were used in an array-based micro-ultrasound system (Vevo 2100, VisualSonics Inc., Toronto, ON, Canada) at 18 MHz for in vitro validation of SH imaging. This study suggests that a suitable design of the envelope of the transmit excitation to generate a S-D signal at the SH frequency can enhance the SH emission of UCA and real-time SH imaging is feasible with shorter transmit burst (6- cycle) and low acoustic pressure (~150 KPa) at high frequencies (>15 MHz).

  17. 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.

  18. 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, Nguyen Thi Kim

    2016-02-14

    Iron oxide nanoparticles (IONPs) of low polydispersity were obtained through a simple polyol synthesis in high pressure and high temperature conditions. The control of the size and morphology of the nanoparticles was studied by varying the solvent used, the amount of iron precursor and the reaction time. Compared with conventional synthesis methods such as thermal decomposition or co-precipitation, this process yields nanoparticles with a narrow particle size distribution in a simple, reproducible and cost effective manner without the need for an inert atmosphere. For example, IONPs with a diameter of ca. 8 nm could be made in a reproducible manner and with good crystallinity as evidenced by X-ray diffraction analysis and high saturation magnetization value (84.5 emu g(-1)). The surface of the IONPs could be tailored post synthesis with two different ligands which provided functionality and stability in water and phosphate buffer saline (PBS). Their potential as a magnetic resonance imaging (MRI) contrast agent was confirmed as they exhibited high r1 and r2 relaxivities of 7.95 mM(-1) s(-1) and 185.58 mM(-1) s(-1) respectively at 1.4 T. Biocompatibility and viability of IONPs in primary human mesenchymal stem cells (hMSCs) was studied and confirmed.

  19. Technical aspects of MRI signal change quantification after gadolinium-based contrast agents' administration.

    Science.gov (United States)

    Ramalho, Joana; Ramalho, Miguel; AlObaidy, Mamdoh; Semelka, Richard C

    2016-12-01

    Over the last 2years several studies have been published regarding gadolinium deposition in brain structures in patients with normal renal function after repeated administrations of gadolinium-based contrast agents (GBCAs). Most of the publications are magnetic resonance imaging (MRI) based retrospective studies, where gadolinium deposition may be indirectly measured by evaluating changes in T1 signal intensity (SI) in brain tissue, particularly in the dentate nucleus (DN) and/or globus pallidi (GP). The direct correlation between T1 signal changes and gadolinium deposition was validated by human pathology studies. However, the variability of the MR equipment and parameters used across different publications, along with the inherent limitations of MRI to assess gadolinium in human tissues should be acknowledged when interpreting those studies. Nevertheless, MRI studies remain essential regarding gadolinium bio-distribution knowledge. The aim of this paper is to overview current knowledge of technical aspects of T1 signal intensity evaluation by MRI and describe confounding factors, with the intention to achieve higher accuracy and maximize reproducibility. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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.

  1. Identification of ultrasound contrast agent dilution systems for ejection fraction measurements.

    Science.gov (United States)

    Mischi, Massimo; Jansen, Annemieke H M; Kalker, Antonius A C M; Korsten, Hendrikus H M

    2005-03-01

    Left ventricular ejection fraction is an important cardiac-efficiency measure. Standard estimations are based on geometric analysis and modeling; they require time and experienced cardiologists. Alternative methods make use of indicator dilutions, but they are invasive due to the need for catheterization. This study presents a new minimally invasive indicator dilution technique for ejection fraction quantification. It is based on a peripheral injection of an ultrasound contrast agent bolus. Left atrium and left ventricle acoustic intensities are recorded versus time by transthoracic echocardiography. The measured curves are corrected for attenuation distortion and processed by an adaptive Wiener deconvolution algorithm for the estimation of the left ventricle impulse response, which is interpolated by a monocompartment exponential model for the ejection fraction assessment. This technique measures forward ejection fraction, which excludes regurgitant volumes. The feasibility of the method was tested on a group of 20 patients with left ventricular ejection fractions going from 10% to 70%. The results are promising and show a 0.93 correlation coefficient with echographic bi-plane ejection fraction measurements. A more extensive validation as well as an investigation on the method applicability for valve insufficiency and right ventricular ejection fraction quantification will be an object of future study.

  2. Small Bowel Obstruction Following Computed Tomography and Magnetic Resonance Enterography Using Psyllium Seed Husk As an Oral Contrast Agent

    Directory of Open Access Journals (Sweden)

    Yingming Amy Chen

    2014-01-01

    Full Text Available The authors report a case series describing four patients who developed small bowel obstruction following the use of psyllium seed husk as an oral contrast agent for computed tomography or magnetic resonance enterography. Radiologists who oversee computed tomography and magnetic resonance enterography should be aware of this potential complication when using psyllium seed husk and other bulking agents, particularly when imaging patients with known or suspected small bowel strictures or active inflammation.

  3. Small bowel obstruction following computed tomography and magnetic resonance enterography using psyllium seed husk as an oral contrast agent.

    Science.gov (United States)

    Chen, Yingming Amy; Cervini, Patrick; Kirpalani, Anish; Vlachou, Paraskevi A; Grover, Samir C; Colak, Errol

    2014-01-01

    The authors report a case series describing four patients who developed small bowel obstruction following the use of psyllium seed husk as an oral contrast agent for computed tomography or magnetic resonance enterography. Radiologists who oversee computed tomography and magnetic resonance enterography should be aware of this potential complication when using psyllium seed husk and other bulking agents, particularly when imaging patients with known or suspected small bowel strictures or active inflammation.

  4. A monomeric water-soluble NIR-absorbing porphyrin derivative as in vivo photoacoustic tomography contrast agent

    Science.gov (United States)

    Erfanzadeh, Mohsen; Luciano, Michael; Zhou, Feifei; Brückner, Christian; Zhu, Quing

    2017-03-01

    A PEGylated quinoline-annulated porphyrin derivative was synthesized as in vivo photoacoustic tomography contrast agent. It possesses high solubility and stability in water and phosphate-buffered saline. No toxicity sign was observed in BALB/c mice. The dye demonstrates a 4-fold higher photoacoustic signal generation efficiency compared to fresh rat blood. Injection of the dye results in a significant enhancement of in vivo PAT images of murine tumors. Analysis of the mouse urine after injection revealed an unaltered renal filtration of the contrast agent.

  5. Boron nitride nanotubes for boron neutron capture therapy as contrast agents in magnetic resonance imaging at 3 T

    Energy Technology Data Exchange (ETDEWEB)

    Menichetti, L., E-mail: luca.menichetti@ifc.cnr.it [CNR-National Research Council of Italy, Institute of Clinical Physiology, via G. Moruzzi 1, 56124 Pisa (Italy); De Marchi, D. [Fondazione Toscana Gabriele Monasterio per la Ricerca Medica e la Sanita Pubblica, CNR-Regione Toscana, via Trieste 41, 56126 Pisa (Italy); Calucci, L. [CNR-National Research Council of Italy, ICCOM-Institute of OrganoMetallic Chemistry, via G. Moruzzi 1, 56124 Pisa (Italy); Ciofani, G.; Menciassi, A. [Italian Institute of Technology c/o Scuola Superiore Sant' Anna, viale R. Piaggio 34, 56025 Pontedera (Italy); Forte, C. [CNR-National Research Council of Italy, ICCOM-Institute of OrganoMetallic Chemistry, via G. Moruzzi 1, 56124 Pisa (Italy)

    2011-12-15

    The applicability of boron nitride nanotubes (BNNTs) containing Fe paramagnetic impurities as contrast agents in magnetic resonance imaging (MRI) was investigated. The measurement of longitudinal and transverse relaxation times of water protons in homogeneous aqueous dispersions of BNNTs wrapped with poly(L-lysine) at different concentrations allowed longitudinal (r{sub 1}) and transverse (r{sub 2}) relaxivities to be determined at 3 T. The r{sub 2} value was comparable to those of commercial superparamagnetic iron oxide nanoparticles, indicating that Fe-containing BNNTs have the potential to be used as T{sub 2} contrast-enhancement agents in MRI at 3 T.

  6. Gadolinium Contrast Agent is of Limited Value for Magnetic Resonance Imaging Assessment of Synovial Hypertrophy in Hemophiliacs

    Energy Technology Data Exchange (ETDEWEB)

    Lundin, B.; Berntorp, E.; Pettersson, H.; Wirestam, R.; Jonsson, K.; Staahlberg, F.; Ljung, R. [Dept. of Radiology, Univ Hospital of Lund, Lund (Sweden)

    2007-07-15

    Purpose: To examine the influence of different doses of gadolinium contrast agent on synovial enhancement, to compare magnetic resonance imaging (MRI) findings of synovial hypertrophy and radiographic joint changes in hemophiliacs, and to investigate the value of gadolinium in MRI assessment of synovial hypertrophy in hemophiliacs using dynamic MRI and MRI scoring. Material and Methods: Twenty-one hemophiliacs on prophylactic factor treatment without recent bleeds were subjected to radiography and gadolinium contrast-enhanced dynamic and static MRI of the knee using a standard dose of 0.1 mmol/kg b.w. gadoteridol. In 17 of the patients, the MRI procedure was repeated after a triple dose of gadoteridol. Results: MRI findings of synovial hypertrophy were significantly correlated with Pettersson radiographic scores. In 19 of the 21 MRI investigated joints, administration of contrast agent did not alter the result of the evaluation of synovial hypertrophy. Conclusion: The optimal time interval for volume assessment of synovial hypertrophy after injection of gadolinium contrast agent is dose dependent. Hemophiliacs without recent bleeds have minor to abundant synovial hypertrophy in joints with pronounced radiographic changes. Dynamic MRI is not useful for evaluating hemophilic arthropathy, and gadolinium contrast agent is not routinely indicated for MRI scoring of joints in hemophiliacs.

  7. Evaluation of early vascular complications after liver transplantation: Usefulness of power Doppler US with a microbubble contrast agent -Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Dong Kil; Lim, Hyo Keun; Kim, Seung Hoon; Cho, Jae Min; Lee, Ji Yeon; Lee, Won Jae; Lim, Jae Hoon; Pyeujn, Yong Seon; Joh, Jae Won; Kim, Sung Joo [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2001-03-15

    To evaluate the usefulness of power Doppler ultrasonography (PDUS) with a microbubble contrast agent in assessing the early vascular complications after liver transplantation (LT). In 15 patients with orthotopic LT (n=12) and living -related donor LT (n=3), PDUS examinations, before and after intravenous injection of a microbubble contrast agent (Levovist, Schering AG, Berlin, Germany) were performed one day after the LT. We compared the results of unenhanced PDUS with those of contrast-enhanced PDUS in terms of depicting the complications and conspicuity of the lesions. In three (20%) of 15 patients, flow signal of hepatic artery was not detected on unenhanced PDUS, while contrast PDUS showed flow signals of the hepatic artery in all patients. Both unenhanced and contrast-enhanced PDUS showed portal vein thromboses in two (13%) of 15 patients, but conspicuity of portal vein thromboses was better appreciated on contrast- enhanced PDUS. Compared with unenhanced PDUS, contrast-enhanced PDUS showed better detection of hepatic arterial flow and increased conspicuity od portal vein thromboses on day after LT. Our preliminary data suggest that contrast-enhanced PDUS can be a promising noninvasive technique the early vascular complications after LT.

  8. Brain tumours at 7T MRI compared to 3T - contrast effect after half and full standard contrast agent dose: initial results

    Energy Technology Data Exchange (ETDEWEB)

    Noebauer-Huhmann, Iris-Melanie; Weber, M. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Medical University of Vienna, Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Szomolanyi, P.; Juras, V. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Kronnerwetter, C. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Widhalm, G. [Medical University of Vienna, Department of Neurosurgery, Vienna (Austria); Nemec, S.; Prayer, D. [Medical University of Vienna, Division of Neuroradiology and Musculoskeletal Radiology, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ladd, M.E. [University Duisburg-Essen, Erwin L. Hahn Institute for Magnetic Resonance Imaging, Essen (Germany); German Cancer Research Center (DKFZ), Division of Medical Physics in Radiology, Heidelberg (Germany); Trattnig, S. [Medical University of Vienna, High Field MR Centre, Department of Biomedical Imaging and Image-guided Therapy, Vienna (Austria); Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Austrian Cluster for Tissue Regeneration, Vienna (Austria)

    2015-01-15

    To compare the contrast agent effect of a full dose and half the dose of gadobenate dimeglumine in brain tumours at 7 Tesla (7T) MR versus 3 Tesla (3T). Ten patients with primary brain tumours or metastases were examined. Signal intensities were assessed in the lesion and normal brain. Tumour-to-brain contrast and lesion enhancement were calculated. Additionally, two independent readers subjectively graded the image quality and artefacts. The enhanced mean tumour-to-brain contrast and lesion enhancement were significantly higher at 7T than at 3T for both half the dose (91.8 ± 45.8 vs. 43.9 ± 25.3 [p = 0.010], 128.1 ± 53.7 vs. 75.5 ± 32.4 [p = 0.004]) and the full dose (129.2 ± 50.9 vs. 66.6 ± 33.1 [p = 0.002], 165.4 ± 54.2 vs. 102.6 ± 45.4 [p = 0.004]). Differences between dosages at each field strength were also significant. Lesion enhancement was higher with half the dose at 7T than with the full dose at 3T (p =.037), while the tumour-to-brain contrast was not significantly different. Subjectively, contrast enhancement, visibility, and lesion delineation were better at 7T and with the full dose. All parameters were rated as good, at the least. Half the routine contrast agent dose at 7T provided higher lesion enhancement than the full dose at 3T which indicates the possibility of dose reduction at 7T. (orig.)

  9. 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.

  10. 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

  11. Evaluation of bowel distension and mural visualisation using neutral oral contrast agents for multidetector-row computed tomography.

    Science.gov (United States)

    Lim, Bee Kuan; Bux, Shaik Ismail; Rahmat, Kartini; Lam, Sze Yin; Liew, Yew Wai

    2012-11-01

    We compared the effectiveness of different types of non-commercial neutral oral contrast agents for bowel distension and mural visualisation in computed tomographic (CT) enterography. 90 consecutive patients from a group of 108 were randomly assigned to receive water (n = 30), 3.8% milk (n = 30) or 0.1% gastrografin (n = 30) as oral contrast agent. The results were independently reviewed by two radiologists who were blinded to the contrast agents used. The degree of bowel distension was qualitatively scored on a four-point scale. The discrimination of bowel loops, mural visualisation and visualisation of mucosal folds were evaluated on a 'yes' or 'no' basis. Side effects of the various agents were also recorded. 3.8% milk was significantly superior to water for bowel distension (jejunum, ileum and terminal ileum), discrimination of bowel loops (jejunum and ileum), mural visualisation and visualisation of mucosal folds (ileum and terminal ileum). It was also significantly superior to 0.1% gastrografin for bowel distension, discrimination of bowel loops, mural visualisation and visualisation of mucosal folds (jejunum, ileum and terminal ileum). However, 10% of patients who received 3.8% milk reported immediate post-test diarrhoea. No side effects were documented for patients who received water and 0.1% gastrografin. 3.8% milk is an effective and superior neutral oral contrast agent for the assessment of the jejunum, ileum and terminal ileum in CT enterography. However, further studies are needed to explore other suitable oral contrast agents for CT enterography in lactose- or cow's milk-intolerant patients.

  12. The contrast-source stress-velocity integral-equation formulation of three-dimensional time-domain elastodynamic scattering problems : A structured approach using tensor partitioning

    NARCIS (Netherlands)

    De Hoop, A.T.; Abubakar, A.; Habashy, T.M.

    2009-01-01

    The contrast-source stress-velocity integral-equation formulation of three-dimensional time-domain elastodynamic scattering problems is discussed. A novel feature of the formulation is a tensor partitioning of the relevant dynamic stress and the contrast source volume density of deformation rate.

  13. 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

    2014-01-01

    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 on-screen 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

  14. Comparison of 3% sorbitol vs psyllium fibre as oral contrast agents in MR enterography.

    Science.gov (United States)

    Saini, Sidharth; Colak, Errol; Anthwal, Shalini; Vlachou, Paraskevi A; Raikhlin, Antony; Kirpalani, Anish

    2014-10-01

    To compare the degree of small bowel distension achieved by 3% sorbitol, a high osmolarity solution, and a psyllium-based bulk fibre as oral contrast agents (OCAs) in MR enterography (MRE). This retrospective study was approved by our institutional review board. A total of 45 consecutive normal MRE examinations (sorbitol, n = 20; psyllium, n = 25) were reviewed. The patients received either 1.5 l of 3% sorbitol or 2 l of 1.6 g kg(-1) psyllium prior to imaging. Quantitative small bowel distension measurements were taken in five segments: proximal jejunum, distal jejunum, proximal ileum, distal ileum and terminal ileum by two independent radiologists. Distension in these five segments was also qualitatively graded from 0 (very poor) to 4 (excellent) by two additional independent radiologists. Statistical analysis comparing the groups and assessing agreement included intraclass coefficients, Student's t-test and Mann-Whitney U-test. Small bowel distension was not significantly different in any of the five small bowel segments between the use of sorbitol and psyllium as OCAs in both the qualitative (p = 0.338-0.908) and quantitative assessments (p = 0.083-0.856). The mean bowel distension achieved was 20.1 ± 2.2 mm for sorbitol and 19.8 ± 2.5 mm for psyllium (p = 0.722). Visualization of the ileum was good or excellent in 65% of the examinations in both groups. Sorbitol and psyllium are not significantly different at distending the small bowel and both may be used as OCAs for MRE studies. This is the first study to directly compare the degree of distension in MRE between these two common, readily available and inexpensive OCAs.

  15. 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

  16. 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.

  17. Micro-computed tomography of fatigue microdamage in cortical bone using a barium sulfate contrast agent.

    Science.gov (United States)

    Leng, Huijie; Wang, Xiang; Ross, Ryan D; Niebur, Glen L; Roeder, Ryan K

    2008-01-01

    Accumulation of microdamage during fatigue can lead to increased fracture susceptibility in bone. Current techniques for imaging microdamage in bone are inherently destructive and two-dimensional. Therefore, the objective of this study was to image the accumulation of fatigue microdamage in cortical bone using micro-computed tomography (micro-CT) with a barium sulfate (BaSO(4)) contrast agent. Two symmetric notches were machined on the tensile surface of bovine cortical bone beams in order to generate damage ahead of the stress concentrations during four-point bending fatigue. Specimens were loaded to a specified number of cycles or until one notch fractured, such that the other notch exhibited the accumulation of microdamage prior to fracture. Microdamage ahead of the notch was stained in vitro by precipitation of BaSO(4) and imaged using micro-CT. Reconstructed images showed a distinct region of bright voxels around the notch tip or along propagating cracks due to the presence of BaSO(4), which was verified by backscattered electron imaging and energy dispersive spectroscopy. The shape of the stained region ahead of the notch tip was consistent with principal strain contours calculated by finite element analysis. The relative volume of the stained region was correlated with the number of loading cycles by non-linear regression using a power-law. This study demonstrates new methods for the non-destructive and three-dimensional detection of fatigue microdamage accumulation in cortical bone in vitro, which may be useful to gain further understanding into the role of microdamage in bone fragility.

  18. Gold nanorods as a contrast agent for Doppler optical coherence tomography.

    Directory of Open Access Journals (Sweden)

    Bo Wang

    Full Text Available To investigate gold nanorods (GNRs as a contrast agent to enhance Doppler optical coherence tomography (OCT imaging of the intrascleral aqueous humor outflow.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.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.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.

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

    Science.gov (United States)

    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 experimental setup for investigating the ambient pressure sensitivity of a contrast agent using 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 experiment. To compensate for variations in bubble response and to make the estimates more robust, the relation between the energy of the subharmonic and the fundamental component was chosen as a measure over the subharmonic peak amplitude. The preliminary study revealed the growth stage of the subharmonic component to occur at acoustic driving pressures between 300 and 500 kPa. Based on this, the pressure sensitivity was investigated using a driving pressure of 485 and 500 kPa. At 485 kPa, a linear pressure sensitivity of 0.42 dB/kPa was found having a linear correlation coefficient of 0.94. 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 were 0.42 and 0.25 dB/kPa with linear correlation coefficients of 0.98 and 0.93, respectively.

  20. Novel optical contrast agents containing both DFO and multi-RGD peptides

    Science.gov (United States)

    Ye, Yunpeng; Bloch, Sharon; Achilefu, Samuel

    2007-11-01

    A series of novel near-infrared fluorescent compounds containing both desferrioxamine (DFO) and multi-RGD peptides, i.e. DFO-Cypate-(RGD) n-NH II (1), were designed and synthesized based on a dicarboxylic acid-containing near-infrared fluorescent carbocyanine (Cypate) scaffold. The trimeric 1 (n=3) showed the strongest cellular internalization into A549 cells in vitro among the four analogs of 1 (n=1, 2, 3, 4), suggesting that such a linear array of three RGD peptide motifs might be optimal for synergistic effects on cellular internalization. The four analogs showed higher internalization than an integrin α vβ 3-targeting cyclic RGD peptide analog DFO-cypate-[RGDfK(~)] (2) after 1h of incubation, indicating that the linear arrays of multi-RGD peptides might be different from the cyclic RGD peptide analog in the internalization kinetics and mechanism of receptor targeting. Confocal microscopy showed that 1 (n=4) could localize at least in part to the mitochondria. Noteworthy, the two compounds 1 (n=2, 3) resulted in a 1.5 to 2 fold increase in fluorescence of the calcium indicator fluo4 after 30 min of incubation. These results suggest the possible effects of these compounds on the cellular function by internalization. Such a type of near-infrared fluorescent cypate analogs containing both DFO and multi-RGD peptides could provide a platform for discovering and developing novel multifunctional optical contrast agents for integrin receptor targeting as well as related tumor imaging and therapy.

  1. Improved detection and biopsy of solid liver lesions using pulse-inversion ultrasound scanning and contrast agent infusion

    DEFF Research Database (Denmark)

    Skjoldbye, B.; Pedersen, Morten Høgholm; Struckmann, J.

    2002-01-01

    The purpose of this study was to assess the ability of pulse-inversion ultrasound (US) scanning (PIUS), combined with an IV contrast agent, to detect malignant liver lesions and its impact on patient management (resectability). Additionally, to determine the feasibility of US-guided biopsy of new...

  2. Comparison between a linear versus a macrocyclic contrast agent for whole body MR angiography in a clinical routine setting

    Directory of Open Access Journals (Sweden)

    Rittig Kilian

    2008-12-01

    Full Text Available Abstract Background Previous experiences of whole body MR angiography are predominantly available in linear 0.5 M gadolinium-containing contrast agents. The aim of this study was to compare image quality on a four-point scale (range 1–4 and diagnostic accuracy of a 1.0 M macrocyclic contrast agent (gadobutrol, n = 80 patients with a 0.5 M linear contrast agent (gadopentetate dimeglumine, n = 85 patients on a 1.5 T whole body MR system. Digital subtraction angiography served as standard of reference. Results All examinations yielded diagnostic image quality. There was no significant difference in image quality (3.76 ± 0.3 versus 3.78 ± 0.3, p = n.s. and diagnostic accuracy observed. Sensitivity and specificity of the detection of hemodynamically relevant stenoses was 93%/95% in the gadopentetate dimeglumine group and 94%/94% in the gadobutrol group, respectively. Conclusion The high diagnostic accuracy of gadobutrol in the clinical routine setting is of high interest as medical authorities (e.g. the European Agency for the Evaluation of Medicinal Products recommend macrocyclic contrast agents especially to be used in patients with renal failure or dialysis.

  3. Comparison between a linear versus a macrocyclic contrast agent for whole body MR angiography in a clinical routine setting

    Science.gov (United States)

    Seeger, Achim; Kramer, Ulrich; Fenchel, Michael; Grimm, Florian; Bretschneider, Christiane; Döring, Jörg; Klumpp, Bernhard; Tepe, Gunnar; Rittig, Kilian; Seidensticker, Peter R; Claussen, Claus D; Miller, Stephan

    2008-01-01

    Background Previous experiences of whole body MR angiography are predominantly available in linear 0.5 M gadolinium-containing contrast agents. The aim of this study was to compare image quality on a four-point scale (range 1–4) and diagnostic accuracy of a 1.0 M macrocyclic contrast agent (gadobutrol, n = 80 patients) with a 0.5 M linear contrast agent (gadopentetate dimeglumine, n = 85 patients) on a 1.5 T whole body MR system. Digital subtraction angiography served as standard of reference. Results All examinations yielded diagnostic image quality. There was no significant difference in image quality (3.76 ± 0.3 versus 3.78 ± 0.3, p = n.s.) and diagnostic accuracy observed. Sensitivity and specificity of the detection of hemodynamically relevant stenoses was 93%/95% in the gadopentetate dimeglumine group and 94%/94% in the gadobutrol group, respectively. Conclusion The high diagnostic accuracy of gadobutrol in the clinical routine setting is of high interest as medical authorities (e.g. the European Agency for the Evaluation of Medicinal Products) recommend macrocyclic contrast agents especially to be used in patients with renal failure or dialysis. PMID:19116027

  4. Paramagnetic lipid-coated silica nanoparticles with a fluorescent quantum dot core: a new contrast agent platform for multimodality imaging

    NARCIS (Netherlands)

    Koole, R.|info:eu-repo/dai/nl/298205610; van Schooneveld, M.M.|info:eu-repo/dai/nl/315032863; Hilhorst, J.|info:eu-repo/dai/nl/31413106X; Castermans, K.; Cormode, D.P.; Strijkers, G.J.; de Mello Donega, C.|info:eu-repo/dai/nl/125593899; Vanmaekelbergh, D.A.M.|info:eu-repo/dai/nl/304829137; Griffioen, A.W.; Nicolay, K.; Fayad, Z.; Meijerink, A.|info:eu-repo/dai/nl/075044986; Mulder, W.J.M.

    2008-01-01

    Silica particles as a nanoparticulate carrier material for contrast agents have received considerable attention the past few years, since the material holds great promise for biomedical applications. A key feature for successful application of this material in vivo is biocompatibility, which may be

  5. Biological performance of a size-fractionated core-shell tantalum oxide nanoparticle x-ray contrast agent.

    Science.gov (United States)

    Torres, Andrew S; Bonitatibus, Peter J; Colborn, Robert E; Goddard, Gregory D; FitzGerald, Paul F; Lee, Brian D; Marino, Michael E

    2012-10-01

    Metal-containing nanoparticles show great promise as x-ray contrast media and could enable reduced radiation dose, increased contrast, and the visualization of smaller anatomic features. In this study, we report progress toward these goals using a size-fractionated core-shell tantalum oxide nanoparticle contrast agent. A core-shell tantalum oxide nanoparticle contrast agent was synthesized and size fractionated for preclinical investigation of biodistribution, blood half-life, organ retention, and histopathology. Fractionated agent was injected at anticipated clinical dose and at 3 times the anticipated clinical dose to evaluate biological performance. Computed tomography (CT) imaging studies were also performed to evaluate short-term clearance kinetics and new imaging applications. Improved control of 2-diethylphosphatoethylsilane-TaO nanoparticle size resulted in significantly reduced retention of injected tantalum. In vivo and in vitro CT imaging studies demonstrated short-term biodistribution differences in the kidney between small-molecule iodinated contrast media and fractionated 2-diethylphosphatoethylsilane-TaO, as well as preliminary data about new "Ta-only" imaging applications using multienergy CT image acquisition. Size-fractionated core-shell tantalum oxide nanoparticles with a well-defined particle size distribution have several key features required of clinically viable vascular imaging compounds and may be used in developing multienergy CT imaging applications.

  6. Automatic spectral imaging protocol selection and iterative reconstruction in abdominal CT with reduced contrast agent dose: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peijie; Liu, Jie; Chai, Yaru; Yan, Xiaopeng; Gao, Jianbo; Dong, Junqiang [The First Affiliated Hospital of Zhengzhou University, Department of Radiology, Zhengzhou, Henan Province (China)

    2017-01-15

    To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) with reduced contrast agent dose in abdominal multiphase CT. One hundred and sixty patients were randomly divided into two scan protocols (n = 80) each; protocol A, 120 kVp/450 mgI/kg, filtered back projection algorithm (FBP); protocol B, spectral CT imaging with ASIS and 40 to 70 keV monochromatic images generated per 300 mgI/kg, ASIR algorithm. Quantitative parameters (image noise and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (image noise, small structures, organ enhancement, and overall image quality) were compared. Monochromatic images at 50 keV and 60 keV provided similar or lower image noise, but higher contrast and overall image quality as compared with 120-kVp images. Despite the higher image noise, 40-keV images showed similar overall image quality compared to 120-kVp images. Radiation dose did not differ between the two protocols, while contrast agent dose in protocol B was reduced by 33 %. Application of ASIR and ASIS to monochromatic imaging from 40 to 60 keV allowed contrast agent dose reduction with adequate image quality and without increasing radiation dose compared to 120 kVp with FBP. (orig.)

  7. 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.

  8. Design and Synthesis of Gold Nanoparticle Contrast Agents for Atherosclerosis Imaging with Computed tomography

    Science.gov (United States)

    Chhour, Peter

    Cell tracking offers the opportunity to study migration and localization of cells in vivo, allowing investigations of disease mechanisms and drug efficacy. Monocytes play a key role in the progression of atherosclerotic plaques in the coronary arteries. While x-ray computed tomography (CT) is commonly used to clinically assess coronary plaque burden, cell tracking with CT is mostly unexplored. The establishment of monocyte cell tracking tools would allow for the direct investigation of gene and drug therapies aimed at monocyte recruitment in atherosclerosis. In this thesis, we present the design and optimization of gold nanoparticles as CT contrast agents for cell tracking of monocyte recruitment to atherosclerotic plaques. Gold nanoparticle polymer constructs with controlled localization are evaluated as potential monocyte labels. However, cytotoxic effects were observed at concentrations necessary for cell labeling. Therefore, variations in physical and chemical properties of gold nanoparticles were explored as cell labels for monocyte tracking. Each formulation was screened for effects on cell viability, cell function and uptake in monocytes. The uptake in monocytes revealed a complex relationship with nanoparticle size behavior dependent on the surface ligand used. This led to the selection of an optimal size and coating for monocyte labeling, 11-mercaptoundecanoic acid coated 15 nm gold nanoparticles. This formulation was further investigated for cell viability, function, and uptake with isolated primary monocytes. Moreover, primary monocytes labeled with this formulation were used to observe monocyte recruitment in atherosclerotic mice. Mice with early atherosclerotic plaques received intravenously injections of gold labeled monocytes and their recruitment to plaques were observed over 5 days with CT. Increases in CT attenuation in the plaque and transmission electron microscopy of plaque sections indicated the presence of gold labeled monocytes in the plaque

  9. Ultrasound triggered cell death in vitro with doxorubicin loaded poly lactic-acid contrast agents.

    Science.gov (United States)

    Eisenbrey, J R; Huang, P; Hsu, J; Wheatley, M A

    2009-12-01

    Traditional chemotherapy generally results in systemic toxicity, which also limits drug levels at the area of need. Two ultrasound contrast agents (UCA), with diameters between 1-2 microm in diameter and shell thicknesses of 100-200 nm, composed of poly lactic-acid (PLA), one loaded by surface adsorption and the other loaded by drug incorporation in the shell, were compared in vitro for potential use in cancer therapy. These poly lactic-acid (PLA) UCA platforms contain a gas core that in an ultrasound (US) field can cause the UCA to oscillate or rupture. Following a systemic injection of drug loaded UCA with external application of US focused at the area of interest, this platform could potentially increase drug toxicity at the area of need, while protecting healthy tissue through microencapsulation of the drug. In vitro toxicity in MDA-MB-231 breast cancer cells of the surface-adsorbed and shell-incorporated doxorubicin (Dox) loaded UCA were examined at 5 MHz insonation using a pulse repetition frequency of 100 Hz at varying pressure amplitudes. Both platforms resulted in equivalent cell death compared to free Dox and US when insonated at peak positive pressure amplitudes of 1.26 MPa and above. While no significant changes in cell death were seen for surface adsorbed Dox-UCA with or without insonation, cell death using the platform with Dox incorporated within the shell increased from 16.12% to 25.78% (p=0.0272), approaching double the potency of the platform when insonated at peak positive pressure amplitudes of 1.26 MPa and above. This mechanism is believed to be the result of UCA rupture at higher insonation pressure amplitudes, resulting in more exposed drug and shell surface area as well as increased cellular uptake of Dox containing polymer shell fragments. This study has shown that a polymer UCA with drug housed within the shell may be used for US-triggered cell death. US activation can be used to make a carrier significantly more potent once in the area of

  10. Ultrasound Triggered Cell Death in vitro with Doxorubicin Loaded Poly Lactic Acid Contrast Agents

    Science.gov (United States)

    Eisenbrey, J.R.; Huang, P.; Hsu, J.; Wheatley, M.A.

    2009-01-01

    Traditional chemotherapy generally results in systemic toxicity, which also limits drug levels at the area of need. Two ultrasound contrast agents (UCA), with diameters between 1-2 μm in diameter and shell thicknesses of 100-200 nm, composed of poly lactic-acid (PLA), one loaded by surface adsorption and the other loaded by drug incorporation in the shell, were compared in vitro for potential use in cancer therapy. These poly lactic-acid (PLA) UCA platforms contain a gas core that in an ultrasound (US) field can cause the UCA to oscillate or rupture. Following a systemic injection of drug loaded UCA with external application of US focused at the area of interest, this platform could potentially increase drug toxicity at the area of need, while protecting healthy tissue through microencapsulation of the drug. In vitro toxicity in MDA-MB-231 breast cancer cells of the surface-adsorbed and shell-incorporated doxorubicin (Dox) loaded UCA were examined at 5 MHz insonation using a pulse repetition frequency of 100 Hz at varying pressure amplitudes. Both platforms resulted in equivalent cell death compared to free Dox and US when insonated at peak positive pressure amplitudes of 1.26 MPa and above. While no significant changes in cell death were seen for surface adsorbed Dox-UCA with or without insonation, cell death using the platform with Dox incorporated within the shell increased from 16.12 to 25.78% (p = 0.0272), approaching double the potency of the platform when insonated at peak positive pressure amplitudes of 1.26 MPa and above. This mechanism is believed to be the result of UCA rupture at higher insonation pressure amplitudes, resulting in more exposed drug and shell surface area as well as increased cellular uptake of Dox containing polymer shell fragments. This study has shown that a polymer UCA with drug housed within the shell may be used for US triggered cell death. US activation can be used to make a carrier significantly more potent once in the area of

  11. 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 < 0.001) with the least error. The resulting root mean square and mean absolute errors were 8.16 +/- 0.26 mmHg and 6.70 +/- 0.17 mmHg, respectively. Thus, median processing the subharmonic data extracted as the mean value within a 0.2 MHz bandwidth about the theoretical

  12. Simulations of insonated contrast agents: Saturation and transient break-up

    Science.gov (United States)

    Tsigklifis, Kostas; Pelekasis, Nikos A.

    2013-03-01

    Under insonation contrast agents are known to perform nonlinear pulsations and deform statically, in the form of buckling, or dynamically via parametric mode excitation, and often exhibit jetting and break-up like bubbles without coating. Boundary element simulations are performed in the context of axisymmetry in order to establish the nonlinear evolution of these patterns. The viscoelastic stresses that develop on the coating form the dominant force balance tangentially to the shell-liquid interface, whereas the dynamic overpressure across the shell balances viscoelastic stresses in the normal direction. Strain softening and strain hardening behavior is studied in the presence of shape instabilities for various initial conditions. Simulations recover the pattern of static buckling, subharmonic/harmonic excitation, and dynamic buckling predicted by linear stability. Preferential mode excitation during compression is obtained supercritically for strain softening phospholipid shells while the shell regains its sphericity at expansion. It is a result of energy transfer between the emerging unstable modes and the radial mode, eventually leading to saturated oscillations of shape modes accompanied by asymmetric radial pulsations in favor of compression. Strain softening shells are more prone to sustain saturated pulsations due to the mechanical behavior of the shell. As the sound amplitude increases and before the onset of dynamic buckling, both types of shells exhibit transient break-up via unbalanced growth of a number of unstable shape modes. The effect of pre-stress in lowering the amplitude threshold for shape mode excitation is captured numerically and compared against the predictions of linear stability analysis. The amplitude interval for which sustained shape oscillations are obtained is extended, in the presence of pre-stress, by switching from a strain softening constitutive law to a strain hardening one once the shell curvature increases beyond a certain

  13. Efficacy and safety of lanthanoids as X-ray contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Pietsch, Hubertus, E-mail: Hubertus.Pietsch@bayerhealthcare.com [Contrast Media Research, Bayer Schering Pharma AG, 13353 Berlin (Germany); Jost, Gregor, E-mail: Gregor.Jost@bayerhealthcare.com [Contrast Media Research, Bayer Schering Pharma AG, 13353 Berlin (Germany); Frenzel, Thomas, E-mail: Thomas.Frenzel@bayerhealthcare.com [Contrast Media Research, Bayer Schering Pharma AG, 13353 Berlin (Germany); Raschke, Marian, E-mail: Marian.Raschke@bayerhealthcare.com [Nonclinical Drug Safety, Bayer Schering Pharma AG, Berlin (Germany); Walter, Jakob, E-mail: Jakob.Walter@bayerhealthcare.com [Nonclinical Drug Safety, Bayer Schering Pharma AG, Berlin (Germany); Schirmer, Heiko, E-mail: Heiko.Schirmer@bayerhealthcare.com [Medical Chemistry VI, Bayer Schering Pharma AG, Berlin (Germany); Huetter, Joachim, E-mail: Joachim.Hutter@bayerhealthcare.com [Contrast Media Research, Bayer Schering Pharma AG, 13353 Berlin (Germany); Sieber, Martin A., E-mail: martin.sieber@bayerhealthcare.com [Contrast Media Research, Bayer Schering Pharma AG, 13353 Berlin (Germany)

    2011-11-15

    Objective: It has been suggested that elements from the lanthanoid (Ln) series may be well suited for use as absorbing elements in X-ray contrast agents (CA). Because gadolinium, an element of the lanthanoid series, has been identified as being possibly associated with nephrogenic systemic fibrosis (NSF), a rare but potentially severe disease, we sought to determine if other lanthanoids might possess a similar potential. Materials and methods: By computed tomography (CT), we compared the X-ray attenuation of all lanthanoids to that of iodine in vitro. In addition, we injected Han-Wistar rats on five consecutive days with 2.5 mmol Ln/kg bodyweight intravenously to test several Ln-DTPA-BMA complexes (praseodymium, europium, gadolinium, and holmium). Saline solution and a Ca-DTPA-BMA group served as controls. Ln concentrations in the skin and organs were determined by inductively coupled plasma mass spectrometry (ICP-MS). This method measures the total Ln content and cannot differentiate between chelated and unchelated Ln. In addition, serum cytokine levels were measured by Luminex technology. The complex stability of the Ln-DTPA-BMA complexes was also assessed in vitro. Results: Lanthanoids showed up to 50% higher X-ray attenuation than iodine in CT. The highest X-ray attenuation was observed with holmium and erbium. Differences in the in vitro complex stability of Pr-, Eu-, Gd-, and Ho-DTPA-BMA complexes were observed. The complex stability differences were also reflected by differences in the concentrations in tissue of the lanthanoids in vivo. Injections of Ln complexes caused NSF-like skin lesions in rats and a rapid upregulation of pro-fibrotic and inflammatory serum cytokines. The Ca-DTPA-BMA complex did not to induce pro-fibrotic cytokines or skin lesions. Pr-DTPA-BMA appeared to be toxic; all Pr-DTPA-BMA treated animals died within the first four days of the experiment and were therefore excluded from further analyses. Conclusion: Lanthanoids are very well

  14. Successful transfemoral aortic Edwards(®) SAPIEN(®) bioprosthesis implantation without using iodinated contrast media in a woman with severe allergy to contrast agent.

    Science.gov (United States)

    Leroux, Lionel; Dijos, Marina; Dos Santos, Pierre

    2013-12-01

    Severe anaphylactoid reaction after the use of iodinated contrast media are rare but can contraindicate the use of contrast agent. It was the case of a 53-year-old woman suffering from symptomatic severe aortic stenosis, recused for cardiac surgery because of deleterious effects of chest-wall irradiation, with porcelain aorta. We decided to implant a 23-mm Edwards(®) SAPIEN(®) transcatheter aortic valve via a femoral route without using any contrast media. The implantation was successful after surgical approach of the femoral artery, transesophageal echocardiography guiding, and localization of native leaflets and coronary trunk with catheters. Immediate and one month post-interventional follow-up was favorable and echocardiography showed a good functioning of the aortic bioprosthesis. Although conventional angiography is the best way to visualize the good positioning of the valve before deployment, our case suggests that, in special situations, transfemoral implantation of an Edwards(®) SAPIEN(®) aortic bioprosthesis is feasible without any contrast injection. Copyright © 2012 Wiley Periodicals, Inc.

  15. In Vivo 3T Magnetic Resonance Imaging Using a Biologically Specific Contrast Agent for Prostate Cancer: A Nude Mouse Model

    Directory of Open Access Journals (Sweden)

    Christopher Brian Abraham

    2017-01-01

    Full Text Available We characterized in vivo a functional superparamagnetic iron-oxide magnetic resonance contrast agent that shortens the T2 relaxation time in magnetic resonance imaging (MRI of prostate cancer xenografts. The agent was developed by conjugating Molday ION™ carboxyl-6 (MIC6, with a deimmunized mouse monoclonal antibody (muJ591 targeting prostate-specific membrane antigen (PSMA. This functional contrast agent could be used as a noninvasive method to detect prostate cancer cells that are PSMA positive and more readily differentiate them from surrounding tissues for treatment. The functional contrast agent was injected intravenously into mice and its effect was compared to both MIC6 (without conjugated antibody and phosphate-buffered saline (PBS injection controls. MR imaging was performed on a clinical 3T MRI scanner using a multiecho spin echo (MESE sequence to obtain T2 relaxation time values. Inductively coupled plasma atomic emission spectroscopy was used to confirm an increase in elemental iron in injected mice tumours relative to controls. Histological examination of H&E stained tissues showed normal morphology of the tissues collected.

  16. Development and optimization of a doxorubicin loaded poly(lactic acid) contrast agent for ultrasound directed drug delivery.

    Science.gov (United States)

    Eisenbrey, J R; Burstein, O Mualem; Kambhampati, R; Forsberg, F; Liu, J-B; Wheatley, M A

    2010-04-02

    An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly(lactic acid) (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index=0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 microg/ml, with a half life of over 15 min. In vivo, the agent provided ultrasound enhancement of 13.4+/-1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Development and Optimization of a Doxorubicin Loaded Poly Lactic Acid Contrast Agent for Ultrasound Directed Drug Delivery

    Science.gov (United States)

    Eisenbrey, J.R.; Burstein, O. Mualem; Kambhampati, R.; Forsberg, F.; Liu, J-B.; Wheatley, M.A.

    2010-01-01

    An echogenic, intravenous drug delivery platform is proposed in which an encapsulated chemotherapeutic can travel to a desired location and drug delivery can be triggered using external, focused ultrasound at the area of interest. Three methods of loading poly lactic acid (PLA) shelled ultrasound contrast agents (UCA) with doxorubicin are presented. Effects on encapsulation efficiency, in vitro enhancement, stability, particle size, morphology and release during UCA rupture are compared by loading method and drug concentration. An agent containing doxorubicin within the shell was selected as an ideal candidate for future hepatocellular carcinoma studies. The agent achieved a maximal drug load of 6.2 mg Dox/g PLA with an encapsulation efficiency of 20.5%, showed a smooth surface morphology and tight size distribution (poly dispersity index = 0.309) with a peak size of 1865 nm. Acoustically, the agent provided 19 dB of enhancement in vitro at a dosage of 10 µg/ml, with a half life of over 15 mins. In vivo, the agent provided ultrasound enhancement of 13.4 ± 1.6 dB within the ascending aorta of New Zealand rabbits at a dose of 0.15 ml/kg. While the drug-incorporated agent is thought to be well suited for future drug delivery experiments, this study has shown that agent properties can be tailored for specific applications based on choice of drug loading method. PMID:20060024

  18. Accuracy and Repeatability of Automated Injector Versus Manual Administration of an MRI Contrast Agent-Results of a Laboratory Study.

    Science.gov (United States)

    Endrikat, Jan; Barbati, Ron; Scarpa, Marcella; Jost, Gregor; Ned Uber, Arthur E

    2018-01-01

    The aim of this study was to compare flow rates over time and the deviations from the target flow rate of a magnetic resonance imaging contrast agent achieved by an automated injector versus manual injection. In this laboratory study, the magnetic resonance contrast agent gadobutrol was repeatedly injected by an injector and by 10 experienced technologists. Six scenarios with 2 different target flow rates (1 and 5 mL/s), 2 different contrast volumes (10 and 20 mL), and 2 different intravenous (IV) catheters (22 gauge and 20 gauge) were tested. The flow rates over time were recorded. The target variable was the average absolute deviation and average absolute percentage deviation from the target flow rate. The flow rates over time achieved by an injector were almost identical. Slight deviations from the target flow rate occurred during ramp-up and ramp-down only. Those of manual injection showed high variability over the whole course of the injection. In the 1 mL/s scenarios, the injector deviated from the target flow rate by 0.06 mL/s or less (≤6%) and in the 5 mL/s scenarios by 1.02 mL/s or less (magnetic resonance contrast agent minimally deviated from the target flow rate, whereas manual injection varied widely. Injector administration is more accurate and repeatable.

  19. Voiding urosonography including urethrosonography: high-quality examinations with an optimised procedure using a second-generation US contrast agent.

    Science.gov (United States)

    Duran, Carmina; del Riego, Javier; Riera, Luis; Martin, Cesar; Serrano, Carlos; Palaña, Pau

    2012-06-01

    Voiding urosonography (VUS) is established as a technique for detecting vesicoureteral reflux in children. To evaluate the quality of images of the entire urinary tract when using a second-generation US contrast agent and a modified VUS technique. We evaluated 307 VUS examinations performed using SonoVue® in 591 pelvi-ureter units in 295 children of mean age, 27.1 (S.D., 42.5) months, with 154 (50.2%) of the examinations performed in boys; 58 children also underwent VUS using Levovist®. Three criteria were used for quality assessment of the bladder image: (1) progressive incorporation of contrast material in the bladder, (2) homogeneous bladder-filling to maximum capacity, and (3) visualisation of the posterior bladder wall. Criterion 1 was fulfilled in 305 (99.3%), criterion 2 in 304 (99%) and criterion 3 in 304 (99%) studies. In children who underwent VUS with both contrast agents, the concordance between the two techniques was moderate for findings in the bladder (Cohen K = 0.487; P < 0001) and perfect for findings in the male urethra. By a modified technique we obtained high-quality images of the bladder with the second-generation contrast agent.

  20. New strategies to prolong the in vivo life span of iron-based contrast agents for MRI.

    Science.gov (United States)

    Antonelli, Antonella; Sfara, Carla; Battistelli, Serafina; Canonico, Barbara; Arcangeletti, Marcella; Manuali, Elisabetta; Salamida, Sonia; Papa, Stefano; Magnani, Mauro

    2013-01-01

    Superparamagnetic iron oxide (SPIO) and ultra small superparamagnetic iron oxide (USPIO) nanoparticles have been developed as magnetic resonance imaging (MRI) contrast agents. Iron oxide nanoparticles, that become superparamagnetic if the core particle diameter is ~ 30 nm or less, present R1 and R2 relaxivities which are much higher than those of conventional paramagnetic gadolinium chelates. Generally, these magnetic particles are coated with biocompatible polymers that prevent the agglomeration of the colloidal suspension and improve their blood distribution profile. In spite of their potential as MRI blood contrast agents, the biomedical application of iron oxide nanoparticles is still limited because of their intravascular half-life of only few hours; such nanoparticles are rapidly cleared from the bloodstream by macrophages of the reticulo-endothelial system (RES). To increase the life span of these MRI contrast agents in the bloodstream we proposed the encapsulation of SPIO nanoparticles in red blood cells (RBCs) through the transient opening of cell membrane pores. We have recently reported results obtained by applying our loading procedure to several SPIO nanoparticles with different chemical physical characteristics such as size and coating agent. In the current investigation we showed that the life span of iron-based contrast agents in the mice bloodstream was prolonged to 12 days after the intravenous injection of murine SPIO-loaded RBCs. Furthermore, we developed an animal model that implicates the pretreatment of animals with clodronate to induce a transient suppression of tissue macrophages, followed by the injection of human SPIO-loaded RBCs which make it possible to encapsulate nanoparticle concentrations (5.3-16.7 mM Fe) higher than murine SPIO-loaded RBCs (1.4-3.55 mM Fe). The data showed that, when human RBCs are used as more capable SPIO nanoparticle containers combined with a depletion of tissue macrophages, Fe concentration in animal blood is

  1. High-resolution motion compensated MRA in patients with congenital heart disease using extracellular contrast agent at 3 Tesla

    Directory of Open Access Journals (Sweden)

    Dabir Darius

    2012-10-01

    Full Text Available Abstract Background Using first-pass MRA (FP-MRA spatial resolution is limited by breath-hold duration. In addition, image quality may be hampered by respiratory and cardiac motion artefacts. In order to overcome these limitations an ECG- and navigator-gated high-resolution-MRA sequence (HR-MRA with slow infusion of extracellular contrast agent was implemented at 3 Tesla for the assessment of congenital heart disease and compared to standard first-pass-MRA (FP-MRA. Methods 34 patients (median age: 13 years with congenital heart disease (CHD were prospectively examined on a 3 Tesla system. The CMR-protocol comprised functional imaging, FP- and HR-MRA, and viability imaging. After the acquisition of the FP-MRA sequence using a single dose of extracellular contrast agent the motion compensated HR-MRA sequence with isotropic resolution was acquired while injecting the second single dose, utilizing the timeframe before viability imaging. Qualitative scores for image quality (two independent reviewers as well as quantitative measurements of vessel sharpness and relative contrast were compared using the Wilcoxon signed-rank test. Quantitative measurements of vessel diameters were compared using the Bland-Altman test. Results The mean image quality score revealed significantly better image quality of the HR-MRA sequence compared to the FP-MRA sequence in all vessels of interest (ascending aorta (AA, left pulmonary artery (LPA, left superior pulmonary vein (LSPV, coronary sinus (CS, and coronary ostia (CO; all p  Conclusions An ECG- and navigator-gated HR-MRA-protocol with infusion of extracellular contrast agent at 3 Tesla is feasible. HR-MRA delivers significantly better image quality and vessel sharpness compared to FP-MRA. It may be integrated into a standard CMR-protocol for patients with CHD without the need for additional contrast agent injection and without any additional examination time.

  2. Activation of platelets by low-osmolar contrast media: differential effects of ionic and nonionic agents

    NARCIS (Netherlands)

    Hardeman, M. R.; Konijnenberg, A.; Sturk, A.; Reekers, J. A.

    1994-01-01

    To determine the effects of an ionic low-osmolar contrast medium (ioxaglate) and two nonionic low-osmolar contrast media (iohexol and iopamidol) on human platelet activation in vitro. Flow cytometry analysis subsequent to reaction with fluorescence-labeled monoclonal antibodies was used to detect

  3. Optimization of multi-pulse sequences for nonlinear contrast agent imaging using a cMUT array.

    Science.gov (United States)

    Novell, Anthony; Arena, Christopher B; Kasoji, Sandeep; Dayton, Paul A

    2015-04-21

    Capacitive micromachined ultrasonic transducer (cMUT) technology provides advantages such as wide frequency bandwidth, which can be exploited for contrast agent imaging. Nevertheless, the efficiency of traditional multi-pulse imaging schemes, such as pulse inversion (PI), remains limited because of the intrinsic nonlinear character of cMUTs. Recently, a new contrast imaging sequence, called bias voltage modulation sequence (BVM), has been specifically developed for cMUTs to suppress their unwanted nonlinear behavior. In this study, we propose to optimize contrast agent detection by combining the BVM sequence with PI and/or chirp reversal (CR). An aqueous dispersion of lipid encapsulated microbubbles was exposed to several combinations of multi-pulse imaging sequences. Approaches were evaluated in vitro using 9 inter-connected elements of a cMUT linear array (excitation frequency of 4 MHz; peak negative pressure of 100 kPa). For sequences using chirp excitations, a specific compression filter was designed to compress and extract several nonlinear components from the received microbubble responses. A satisfactory cancellation of the nonlinear signal from the source is achieved when BVM is combined with PI and CR. In comparison with PI and CR imaging modes alone, using sequences incorporating BVM increases the contrast-to-tissue ratio by 10.0 dB and 4.6 dB, respectively. Furthermore, the combination of BVM with CR and PI results in a significant increase of the contrast-to-noise ratio (+29 dB). This enhancement is attributed to the use of chirps as excitation signals and the improved preservation of several nonlinear components contained within the contrast agent response.

  4. Synthesis, structural characterization and in vitro testing of dysprosium containing silica particles as potential MRI contrast enhancing agents

    Energy Technology Data Exchange (ETDEWEB)

    Chiriac, L.B.; Trandafir, D.L. [Faculty of Physics & National Magnetic Resonance Center, Babeş-Bolyai University, Cluj-Napoca, RO-400084 (Romania); Interdisciplinary Research Institute on Bio-Nano-Sciences & Faculty of Physics, Babeş-Bolyai University, Cluj-Napoca, RO-400084 (Romania); Turcu, R.V.F. [Faculty of Physics & National Magnetic Resonance Center, Babeş-Bolyai University, Cluj-Napoca, RO-400084 (Romania); Todea, M. [Interdisciplinary Research Institute on Bio-Nano-Sciences & Faculty of Physics, Babeş-Bolyai University, Cluj-Napoca, RO-400084 (Romania); Simon, S., E-mail: simons@phys.ubbcluj.ro [Faculty of Physics & National Magnetic Resonance Center, Babeş-Bolyai University, Cluj-Napoca, RO-400084 (Romania); Interdisciplinary Research Institute on Bio-Nano-Sciences & Faculty of Physics, Babeş-Bolyai University, Cluj-Napoca, RO-400084 (Romania)

    2016-11-01

    Highlights: • Dysprosium containing silica microparticles obtained by freeze and spray drying. • Higher structural units interconnection achieved in freeze vs. spray dried samples. • Dy occurance on the outermost layer of the microparticles evidenced by XPS. • Enhanced MRI contrast observed for freeze dried samples with 5% mol Dy{sub 2}O{sub 3}. - Abstract: The work is focused on synthesis and structural characterization of novel dysprosium-doped silica particles which could be considered as MRI contrast agents. Sol-gel derived silica rich particles obtained via freeze-drying and spray-drying processing methods were structurally characterized by XRD, {sup 29}Si MAS-NMR and XPS methods. The occurrence of dysprosium on the outermost layer of dysprosium containing silica particles was investigated by XPS analysis. The MRI contrast agent characteristics have been tested using RARE-T{sub 1} and RARE-T{sub 2} protocols. The contrast of MRI images delivered by the investigated samples was correlated with their local structure. Dysprosium disposal on microparticles with surface structure characterised by decreased connectivity of the silicate network units favours dark T{sub 2}-weighted MRI contrast properties.

  5. Contrast-Enhanced Ultrasound Imaging and In Vivo Circulatory Kinetics with Low Boiling Point Nanoscale Phase-Change Perfluorocarbon Agents

    Science.gov (United States)

    Sheeran, Paul S.; Rojas, Juan D.; Puett, Connor; Hjelmquist, Jordan; Arena, Christopher B.; Dayton, Paul A.

    2017-01-01

    Many studies have explored phase-change contrast agents (PCCAs) that can be vaporized by an ultrasonic pulse to form microbubbles for ultrasound imaging and therapy. However, few investigations have been published demonstrating the utility and characteristics of PCCAs as contrast agents in vivo. In this study, we examine the properties of low boiling point nanoscale PCCAs evaluated in vivo, and compare data to conventional microbubbles with respect to contrast generation and circulation properties. In order to do this, we develop a custom pulse sequence to vaporize and image PCCAs using the Verasonics research platform and a clinical array transducer. Results show that droplets can produce similar contrast enhancement to microbubbles (7.29 to 18.24 dB over baseline, depending on formulation), and can be designed to circulate for as much as 3.3 times longer than microbubbles. This study also demonstrates for the first time the ability to capture contrast wash-out kinetics of the target organ as a measure of vascular perfusion. PMID:25619781

  6. Deep-tissue photoacoustic imaging at 1064 nm using a contrast agent based on phosphorus phthalocyanine formulation

    Science.gov (United States)

    Wang, Depeng; Zhou, Yang; Zhang, Yumiao; Geng, Jumin; Wang, Yuehang; Zhang, Yuzhen; Cook, Timothy R.; Lovell, Jonathan F.; Xia, Jun

    2017-03-01

    This study demonstrated the performance of photoacoustic imaging at 1064 nm using phosphorus phthalocyanine (P-Pc), a contrast agent with strong absorption at 1064 nm. Due to high maximum permissible exposure of 1064 nm laser light and strong absorbance of P-Pc at 1064 nm, we demonstrated an imaging depth of 11.6 cm in chicken breast tissue. For animal imaging, we used P-Pc to target tumor and to track intestine dynamics. Thus, using a contrast medium with extreme absorption at 1064 nm readily enables high quality photoacoustic imaging at exceptional depths.

  7. MRI-guided breast vacuum biopsy: Localization of the lesion without contrast-agent application using diffusion-weighted imaging.

    Science.gov (United States)

    Berger, Nicole; Varga, Zsuzsanna; Frauenfelder, Thomas; Boss, Andreas

    2017-05-01

    In magnetic resonance-guided breast vacuum biopsies, the contrast agent for targeting suspicious lesions can typically be applied only once during an intervention, due to the slow elimination of the gadolinium chelate from the extracellular fluid space. This study evaluated the feasibility of diffusion-weighted imaging (DWI) for lesion targeting in vacuum assisted magnetic resonance imaging (MRI) biopsies. DWI may be used as an alternative to dynamic contrast-enhanced MRI with the advantage of reproducibility. However, the targeted lesion requires the characteristics of a mass-like lesion, substantial diffusion restriction, and a minimum size of approximately 1cm. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Blunt abdominal trauma: does the use of a second-generation sonographic contrast agent help to detect solid organ injuries?

    Science.gov (United States)

    Poletti, Pierre-Alexandre; Platon, Alexandra; Becker, Christoph D; Mentha, Gilles; Vermeulen, Bernard; Buhler, Léo H; Terrier, François

    2004-11-01

    The objective of our study was to prospectively evaluate whether a second-generation sonography contrast agent (SonoVue) can improve the conspicuity of solid organ injuries (liver; spleen; or kidney, including adrenal glands) in patients with blunt abdominal trauma. Two hundred ten consecutive hemodynamically stable trauma patients underwent both abdominal sonography and CT at admission. The presence of solid organ injuries and the quality of sonography examinations were recorded. Patients with false-negative sonography findings for solid organ injuries in comparison with CT results underwent control sonography. If a solid organ injury was still undetectable, contrast-enhanced sonography was performed. Findings of admission, control, and contrast-enhanced sonograms were compared with CT results for their ability to depict solid organ injuries. Contrast-enhanced sonography was also performed in patients in whom a vascular injury (pseudoaneurysm) was shown on admission or control CT. CT findings were positive for 88 solid organ injuries in 71 (34%) of the 210 patients. Admission, control, and contrast-enhanced sonograms had a detection rate for solid organ injury of 40% (35/88), 57% (50/88), and 80% (70/88), respectively. The improvement in the detection rate between control and contrast-enhanced sonography was statistically significant (p = 0.001). After exclusion of low-quality examinations, contrast-enhanced sonography still missed 18% of solid organ injuries. Five vascular liver (n = 1) and spleen (n = 4) injuries (pseudoaneurysms) were detected on CT; all were visible on contrast-enhanced sonography. Contrast-enhanced sonography misses a large percentage of solid organ injuries and cannot be recommended to replace CT in the triage of hemodynamically stable trauma patients. However, contrast-enhanced sonography could play a role in the detection of pseudoaneurysms.

  9. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  10. Comparison of gadolinium nanoparticles and molecular contrast agents for radiation therapy-enhancement.

    Science.gov (United States)

    Delorme, Rachel; Taupin, Florence; Flaender, Mélanie; Ravanat, Jean-Luc; Champion, Christophe; Agelou, Mathieu; Elleaume, Hélène

    2017-11-01

    Nanoparticles appear as a novel tool to enhance the effectiveness of radiotherapy in cancer treatments. Many parameters influence their efficacy, such as their size, concentration, composition, their cellular localization, as well as the photon source energy. The current Monte Carlo study aims at comparing the dose-enhancement in presence of gadolinium (Gd), either as isolated atoms or atoms clustered in nanoparticles (NPs), by investigating the role played by these physical parameters at the cellular and the nanometer scale. In parallel, in vitro assays were performed in presence of either the gadolinium contrast agent (GdCA) Magnevist(®) or ultrasmall gadolinium NPs (GdNPs, 3 nm) for comparison with the simulations. PENELOPE Monte Carlo Code was used for in silico dose calculations. Monochromatic photon beams were used to calculate dose enhancements in different cell compartments and low-energy secondary electron spectra dependence with energy. Particular attention has been placed on the interplay between the X-ray beam energy, the Gd localization and its distance from cellular targets. Clonogenic assays were used to quantify F98 rat glioma cell survival after irradiation in the presence of GdNPs or GdCA, using monochromatic X-rays with energies in the 30 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. The simulations that correspond to the experimental conditions were compared with the experimental results. In silico, a highly heterogeneous and clustered Gd-atom distribution, a massive production of low energy electrons around GdNPs and an optimal X-ray beam energy, above the Gd K-edge, were key factors found to increase microscopic doses, which could potentially induce cell death. The different Gd localizations studied all resulted in a lower dose enhancement for the nucleus component than for cytoplasm or membrane compartments, with a maximum dose-enhancement factor (DEF) found at 65 keV and 58 keV, respectively

  11. Numerical modeling of the 3D dynamics of ultrasound contrast agent microbubbles using the boundary integral method

    Science.gov (United States)

    Wang, Qianxi; Manmi, Kawa; Calvisi, Michael L.

    2015-02-01

    Ultrasound contrast agents (UCAs) are microbubbles stabilized with a shell typically of lipid, polymer, or protein and are emerging as a unique tool for noninvasive therapies ranging from gene delivery to tumor ablation. While various models have been developed to describe the spherical oscillations of contrast agents, the treatment of nonspherical behavior has received less attention. However, the nonspherical dynamics of contrast agents are thought to play an important role in therapeutic applications, for example, enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces, and causing tissue ablation. In this paper, a model for nonspherical contrast agent dynamics based on the boundary integral method is described. The effects of the encapsulating shell are approximated by adapting Hoff's model for thin-shell, spherical contrast agents. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. The numerical model agrees well with a modified Rayleigh-Plesset equation for encapsulated spherical bubbles. Numerical analyses of the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The oscillation amplitude and period decrease significantly due to the coating. A bubble jet forms when the amplitude of ultrasound is sufficiently large, as occurs for bubbles without a coating; however, the threshold amplitude required to incite jetting increases due to the coating. When a UCA is near a rigid boundary subject to acoustic forcing, the jet is directed towards the wall if the acoustic wave propagates perpendicular to the boundary. When the acoustic wave propagates parallel to the rigid boundary, the jet direction has components both along the wave direction and towards the boundary that depend mainly on the dimensionless standoff distance of the bubble from the boundary. In all cases, the jet

  12. Optimisation of dynamic nuclear polarisation of [1-13C] pyruvate by addition of gadolinium-based contrast agents

    Science.gov (United States)

    Friesen-Waldner, Lanette; Chen, Albert; Mander, Will; Scholl, Timothy J.; McKenzie, Charles A.

    2012-10-01

    Dynamic nuclear polarisation (DNP) of carbon-13 (13C) enriched endogenous compounds provides a novel means for magnetic resonance imaging and spectroscopy of biological processes. Adding small amounts of gadolinium-based contrast agents (GBCAs) to the 13C-enriched substrate matrix increases the amount of hyperpolarisation that can be achieved, but also may decrease the longitudinal relaxation time (T1) of the 13C nucleus in solution. This study examined the effects of five different GBCA at concentrations of 0.5, 1, 2, and 3 mM on [1-13C]-enriched pyruvic acid. It was found that contrast agents with an open chain structure (Gadobenate dimeglumine, Gadopentetate dimeglumine, Gadodiamide) caused the largest enhancement (up to 82%) in solid state polarisation relative to solutions without GBCA. In the liquid state, T1 of pyruvate decreased by as much as 62% and polarisation was much lower (70%) relative to solutions without GBCA added. Conversely, for GBCA with macrocyclic structures (Gadoterate meglumine, Gadoteridol), the solid state polarisation enhancement was only slightly less than the open chain GBCA, but enhanced polarisation was retained much better in the liquid state with minimal decrease in T1 (25% at the highest GBCA concentrations). Near maximum polarisation in the solid state was obtained at a GBCA concentration of 2 mM, with a higher concentration of 3 mM producing minimal improvement. These results indicate that the macrocyclic contrast agents provide the best combination of high solid state and liquid state polarisations with minimal loss of T1 in experiments with hyperpolarised 13C-enriched pyruvate. This suggests that macrocyclic contrast agents should be the GBCA of choice for maximising signal in experiments with hyperpolarised 13C-enriched pyruvate, particularly for in vivo measurements where shortened substrate T1 is especially problematic.

  13. Retrospective analysis of patients for development of nephrogenic systemic fibrosis following conventional angiography using gadolinium-based contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Hoppe, Hanno; Spagnuolo, Sara; Froehlich, Johannes M.; Thoeny, Harriet C. [University Hospital Bern, Institute of Diagnostic, Interventional, and Pediatric Radiology, Inselspital, Bern (Switzerland); Nievergelt, Helga [University Hospital Bern, Clinic of Dermatology, Bern (Switzerland); Dinkel, Hans-Peter [Hospital Landshut, Institute of Diagnostic and Interventional Radiology, Landshut (Germany); Gretener, Silvia [University Hospital of Bern, Division of Vascular Medicine, Swiss Cardiovascular Center, Bern (Switzerland)

    2010-03-15

    The purpose was to retrospectively review the data of 27 patients with renal insufficiency who underwent conventional angiography with gadolinium-based contrast agents (GDBCA) as alternative contrast agents and assess the occurrence of nephrogenic systemic fibrosis (NSF) together with associated potential risk factors. This HIPAA-compliant study had institutional review board approval, and informed consent was waived. Statistical analysis was performed for all available laboratory and clinical data, including dermatology reports. Type and amount of the GDBCA used were recorded for angiography and additional MRI studies, if applicable. Serum creatinine levels (SCr) pre- and post-angiography were recorded, and estimated glomerular filtration rates (eGFR) were calculated. Ten female and 17 male patients who underwent angiography with GDBCA were included. The mean amount of GDBCA administered was 44 {+-} 15.5 ml (range 15-60 ml) or 0.24 + 0.12 mmol/kg (range 0.1-0.53 mmol/kg). At the time of angiography all patients had renal insufficiency (eGFR <60 ml/min/1.73 m{sup 2}). Mean eGFR pre-angiography was 26 ml/min/1.73 m{sup 2} and 33 ml/min/1.73 m{sup 2} post-angiography. The mean follow-up period covers 28 months, range 1-84 months. Additional MRI studies with GDBCA administration were performed in 15 patients. One patient with typical skin lesions had developed biopsy-confirmed NSF. Conventional arterial angiography with GDBCA may play a role in the development of NSF in patients with renal insufficiency. Alternative contrast agents, such as CO{sub 2} angiography or rather the use of low doses of iodinated contrast agents, should be considered in these patients. (orig.)

  14. Anti-biofouling conducting polymer nanoparticles as a label-free optical contrast agent for high resolution subsurface biomedical imaging.

    Science.gov (United States)

    Au, Kin Man; Lu, Zenghai; Matcher, Stephen J; Armes, Steven P

    2013-11-01

    Optical coherence tomography (OCT) is a modern high resolution subsurface medical imaging technique. Herein we describe: (i) the synthesis of a thiophene-functionalized oligo(ethylene glycol) methacrylate (OEGMA)-based statistical copolymer, denoted poly(2TMOI-OEGMA); (ii) the preparation of sterically-stabilized polypyrrole (PPy) nanoparticles of approximately 60 nm diameter; (iii) the evaluation of these nanoparticles as a NIR-absorbing optical contrast agent for high-resolution OCT imaging. We show that poly(2TMOI-OEGMA)-stabilized PPy nanoparticles exhibit similar optical properties to poly(vinyl alcohol) (PVA)-stabilized PPy nanoparticles of comparable size prepared using commercially available PVA. Spectroscopic measurements and Mie calculations indicate that both types of PPy nanoparticles strongly absorb NIR radiation above 1000 nm, suggesting their potential use as OCT contrast agents. In vitro OCT studies indicate that both types of PPy nanoparticles reduce NIR backscattering within homogeneous intralipid tissue phantoms, offering almost identical contrast performance in this medium. However, PVA-stabilized PPy nanoparticles became colloidally unstable when dispersed in physiological buffer and immersed in a solid biotissue phantom and hence failed to generate a strong contrast effect. In contrast, the poly(2TMOI-OEGMA)-stabilized PPy nanoparticles remained well-dispersed and hence exhibited a strong rapid onset contrast effect within the biotissue phantom under identical physiological conditions. Ex vivo studies performed on excised chicken and porcine skin tissue demonstrated that topical administration of a low concentration of poly(2TMOI-OEGMA)-stabilized PPy nanoparticles rapidly enhances OCT image contrast in both cases, allowing key tissue features to be readily identified. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Calcium-Sensitive MRI Contrast Agents Based on Superparamagnetic Iron Oxide Nanoparticles and Calmodulin

    National Research Council Canada - National Science Library

    Tatjana Atanasijevic; Maxim Shusteff; Peter Fam; Alan Jasanoff

    2006-01-01

    We describe a family of calcium indicators for magnetic resonance imaging (MRI), formed by combining a powerful iron oxide nanoparticle-based contrast mechanism with the versatile calciumsensing protein calmodulin and its targets...

  16. Dependence of photoacoustic signal generation characteristics on fluorescence quantum yields of small organic molecule based contrast agents

    Science.gov (United States)

    Hirasawa, Takeshi; Iwatate, Ryu J.; Kamiya, Mako; Okawa, Shinpei; Urano, Yasuteru; Ishihara, Miya

    2017-03-01

    Photoacoustic (PA) imaging is advantageous in contrast agent imaging because of high spatial resolution at depth more than several millimeter inside biological tissues. To detect small tumors specifically, we are developing small organic molecule-based activatable PA probe with mechanism similar to that of the enzyme-activatable fluorescence probe that have successfully used for rapid fluorescence imaging of small tumors. The probe can be imaged also by fluorescence imaging and the fluorescence image can be merged onto the PA images. To extend the imaging depth by increasing PA signal intensity, PA probe that produce PA signals efficiently is required. To select small organic molecules suitable for PA probe, we synthesized small-organic molecule-based contrast agents with various absorption spectra and fluorescence quantum yields and then we exhaustively evaluated their PA signal generation characteristics including PA signal generation efficiencies. To analyze PA signal generation efficiencies precisely, the absolute values of PA signal pressures produced from aqueous solutions of the contrast agents were measured by P(VDF-TrFE) piezoelectric film acoustic sensor. As a result, small organic molecule with low fluorescence quantum yield produced PA signals efficiently. Thus, as opposed to fluorescence probes, PA probes should have low fluorescence quantum yields. By considering the result and other characteristics including excitation wavelengths, we could single out the small organic molecule suitable for PA probe. We synthesized the new activatable PA probe with low fluorescence quantum yield and excitation wavelength longer than 600 nm and its specificity was examined in in vitro experiment.

  17. Micro-Radiography of Living Biological Organisms with MEDIPIX2 Detector and Application of Various Contrast Agents

    Science.gov (United States)

    Dammer, Jiri; Sopko, Vit; Jakubek, Jan; Weyda, Frantisek; Benes, Jiri; Zahorovsky, Julian

    2012-08-01

    We describe a newly developed radiographic system equipped with Medipix2 semiconductor pixel detector and a micro-focus FeinFocus X-ray tube tabletop. The detector is used as an imager that counts individual photons of ionizing radiation, emitted by the X-ray tube. The digital pixel detectors of the Medipix family represent a highly efficient type of imaging devices with high spatial resolution better than 1μm, and unlimited dynamic range allowing single particle of radiation and to determine their energies. The setup is particularly suitable for radiographic imaging of small biological samples, including in vivo observations with various contrast agents (iodine and lanthanum nitrate). Along with the description of the apparatus we provide examples of application of iodine and lanthanum nitrate contrast agents as tracers in various insects as model organisms. The iodine contrast agent increases the absorption of X-rays and this leads to better resolution of internal structures of biological organisms, and especially the various cavities, pores, etc. Micro-radiographic imaging helps to detect organisms living in a not visible environment, visualize internal biological processes and also to resolve the details of their body (morphology). Tiny live insects are an ideal object for our studies.

  18. DCE-MRI using small-molecular and albumin-binding contrast agents in experimental carcinomas with different stromal content

    Energy Technology Data Exchange (ETDEWEB)

    Farace, Paolo; Merigo, Flavia; Fiorini, Silvia; Nicolato, Elena; Tambalo, Stefano; Daducci, Alessandro [Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona (Italy); Degrassi, Anna [Nerviano Medical Sciences Institute, Milan (Italy); Sbarbati, Andrea [Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona (Italy); Rubello, Domenico, E-mail: domenico.rubello@libero.it [Department of Radiology, Nuclear Medicine, Medical Physics, Services of Radiology and Nuclear Medicine, ' S. Maria della Misericordia' Hospital, Viale Tre Martiri 140, 45100 Rovigo (Italy); Marzola, Pasquina [Department of Morphological-Biomedical Sciences, Section of Anatomy and Histology, University of Verona, Verona (Italy)

    2011-04-15

    Objectives: To compare DCE-MRI experiments performed using a standard small-molecular (Gd-DTPA) and an albumin-binding (MS-325) contrast agent in two carcinoma models with different stromal content. Materials and methods: DU-145 or BXPC-3 cancer cells were subcutaneously injected into nude mice. DCE-MRI was performed by a bolus injection of Gd-DTPA or MS-325 about 2 weeks after inoculation. For quantitative analysis a volume of interest was manually drawn over each tumor. To address the heterogeneous enhancement, each tumor volume was then divided into the 20% most-enhancing and the remaining 80% least-enhancing fractions. Mean tumor enhancement was calculated over these selected tumor volumes and compared between tumor groups and contrast agents. Maps of differential enhancement, peak enhancement and time-to-peak were used for visual evaluation. CD31 and VEGF immunohistochemistry were performed in excised tumors. Results: In the 80% least-enhancing volume, at late time points of the dynamic scan, the mean enhancement elicited by MS-325 was higher in BXPC-3 than in DU-145 tumors. In the 20% most-enhancing volume, using either contrast agents, significant difference between the two tumors types were observed only early, while at later time points of the dynamic scan the difference were obscured by the faster washout observed in the BXPC-3 tumors. Enhancement maps confirmed that BXPC-3 tumors were characterized by marked washout rate using either contrast agent, particularly in the higher enhancing peripheral rim. With MS-325 this washout pattern appeared to be specific to the BXPC-3 carcinomas, since it was not observed in the DU-145 tumors. Finally, in both tumor types, MS-325 produced significantly higher enhancement than Gd-DTPA in the late phase of the dynamic scan. Ex vivo analysis confirmed the marked presence of aberrant infiltrative stroma in BXPC-3 tumors, in which tumor vessels were embedded. In all tumors the central portion was less viable and less

  19. A Functional Iron Oxide Nanoparticles Modified with PLA-PEG-DG as Tumor-Targeted MRI Contrast Agent.

    Science.gov (United States)

    Xiong, Fei; Hu, Ke; Yu, Haoli; Zhou, Lijun; Song, Lina; Zhang, Yu; Shan, Xiuhong; Liu, Jianping; Gu, Ning

    2017-08-01

    Tumor targeting could greatly promote the performance of magnetic nanomaterials as MRI (Magnetic Resonance Imaging) agent for tumor diagnosis. Herein, we reported a novel magnetic nanoparticle modified with PLA (poly lactic acid)-PEG (polyethylene glycol)-DG (D-glucosamine) as Tumor-targeted MRI Contrast Agent. In this work, we took use of the D-glucose passive targeting on tumor cells, combining it on PLA-PEG through amide reaction, and then wrapped the PLA-PEG-DG up to the Fe 3 O 4 @OA NPs. The stability and anti phagocytosis of Fe 3 O 4 @OA@PLA-PEG-DG was tested in vitro; the MRI efficiency and toxicity was also detected in vivo. These functional magnetic nanoparticles demonstrated good biocompatibility and stability both in vitro and in vivo. Cell experiments showed that Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles exist good anti phagocytosis and high targetability. In vivo MRI images showed that the contrast effect of Fe 3 O 4 @OA@PLA-PEG-DG nanoparticles prevailed over the commercial non tumor-targeting magnetic nanomaterials MRI agent at a relatively low dose. The DG can validly enhance the tumor-targetting effect of Fe 3 O 4 @OA@PLA-PEG nanoparticle. Maybe MRI agents with DG can hold promise as tumor-targetting development in the future.

  20. X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in PEGylated dendrimer

    Energy Technology Data Exchange (ETDEWEB)

    Kojima, Chie [Nanoscience and Nanotechnology Research Center, Research Organization for the 21st Century, Osaka Prefecture University, 1-2 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8570 (Japan); Umeda, Yasuhito; Harada, Atsushi; Kono, Kenji [Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531 (Japan); Ogawa, Mikako; Magata, Yasuhiro, E-mail: c-kojima@21c.osakafu-u.ac.jp [Photon Medical Research Center, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192 (Japan)

    2010-06-18

    Gold nanoparticles (Au NPs) are a potential x-ray computed tomography (CT) contrast agent. A biocompatible and bioinactive surface is necessary for application of gold nanoparticle to CT imaging. Polyethylene glycol (PEG)-attached dendrimers have been used as a drug carrier with long blood circulation. In this study, the Au NPs were grown in the PEGylated dendrimer to produce a CT contrast agent. The Au NPs were grown by adding gold ions and ascorbic acid at various equivalents to the Au NP-encapsulated dendrimer solution. Both size and surface plasmon absorption of the grown Au NPs increased with adding a large number of gold ions. The x-ray attenuation of the Au NPs also increased after the seeded growth. The Au NPs grown in the PEG-attached dendrimer at the maximum under our conditions exhibited a similar CT value to a commercial iodine agent, iopamidol, in vitro. The Au NP-loaded PEGylated dendrimer and iopamidol were injected into mice and CT images were obtained at different times. The Au NP-loaded PEGylated dendrimer achieved a blood pool imaging, which was greater than a commercial iodine agent. Even though iopamidol was excreted rapidly, the PEGylated dendrimer loading the grown Au NP was accumulated in the liver.

  1. Assessment of errors caused by X-ray scatter and use of contrast medium when using CT-based attenuation correction in PET

    Energy Technology Data Exchange (ETDEWEB)

    Ay, Mohammad R. [Geneva University Hospital, Division of Nuclear Medicine, Geneva (Switzerland); Zaidi, Habib

    2006-11-15

    Quantitative image reconstruction in positron emission tomography (PET) requires an accurate attenuation map of the object under study for the purpose of attenuation correction. Current dual-modality PET/CT systems offer significant advantages over stand-alone PET, including decreased overall scanning time and increased accuracy in lesion localisation and detectability. However, the contamination of CT data with scattered radiation and misclassification of contrast medium with high-density bone in CT-based attenuation correction (CTAC) are known to generate artefacts in the attenuation map and thus the resulting PET images. The purpose of this work was to quantitatively measure the impact of scattered radiation and contrast medium on the accuracy of CTAC. Our recently developed MCNP4C-based Monte Carlo X-ray CT simulator for modelling both fan- and cone-beam CT scanners and the Eidolon dedicated 3D PET Monte Carlo simulator were used to generate realigned PET/CT data sets. The impact of X-ray scattered radiation on the accuracy of CTAC was investigated through simulation of a uniform cylindrical water phantom for both a commercial fan-beam multi-slice and a prototype cone-beam flat panel detector-based CT scanner. The influence of contrast medium was studied by simulation of a cylindrical phantom containing different concentrations of contrast medium. Moreover, an experimental study using an anthropomorphic striatal phantom was conducted for quantitative evaluation of errors arising from the presence of contrast medium by calculating the apparent recovery coefficient (ARC) in the presence of different concentrations of contrast medium. The analysis of attenuation correction factors (ACFs) for the simulated cylindrical water phantom in both fan- and cone-beam CT scanners showed that the contamination of CT data with scattered radiation in the absence of scatter removal causes underestimation of the true ACFs, namely by 7.3% and 28.2% in the centre for the two

  2. A study on the imaging characteristics of Gold nanoparticles as a contrast agent in X-ray computed tomography

    Science.gov (United States)

    Mesbahi, Asghar; Famouri, Fatemeh; Ahar, Mohammad Johari; Ghaffari, Maryam Olade; Ghavami, Seyed Mostafa

    2017-03-01

    Aim: In the current study, some imaging characteristics of AuNPs were quantitatively analyzed and compared with two conventional contrast media (CM) including Iodine and Gadolinium by using of a cylindrical phantom. Methods: AuNPs were synthesized with the mean diameter of 16 nm and were equalized to the concentration of 0.5, 1, 2 and 4 mg/mL in the same volumes. A cylindrical phantom resembling the head and neck was fabricated and drilled to contain small tubes filled with Iodine, Gadolinium, and AuNPs as contrast media. The phantom was scanned in different exposure techniques and CT numbers of three studied contrast media inside test tubes were measured in terms of Hounsfield Unit (HU). The imaging parameters of the noise and contrast to noise ratios (CNR) were calculated for all studied CMs. Results: AuNPs showed 128% and 166% higher CT number in comparison with Iodine and Gadolinium respectively. Also, Iodine had a greater CT number than Gadolinium for the same exposure techniques and concentration. The maximum CT number for AuNPs and studied contrast materials was obtained at the highest mAs and the lowest tube potential. The maximum CT number were 1033±11 (HU) for AuNP, 565±10 (HU) for Iodine, 458±11 for Gadolinium. Moreover, the maximum CNRs of 433±117, 203±53, 145±37 were found for AuNPs, Iodine and Gadolinium respectively. Conclusion: The contrast agent based on AuNPs showed higher imaging quality in terms of contrast and noise relative to other iodine and gadolinium based contrast media in X-ray computed tomography. Application of the AuNPs as a contrast medium in x-ray CT is recommended.

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

    Directory of Open Access Journals (Sweden)

    Paul A. Dayton

    2004-04-01

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

  4. Optimizing contrast agent concentration and spoiled gradient echo pulse sequence parameters for catheter visualization in MR-guided interventional procedures: an analytic solution.

    Science.gov (United States)

    Sussman, Marshall S; Lindner, Uri; Haider, Masoom; Kucharczyk, Walter; Hlasny, Eugen; Trachtenberg, John

    2013-08-01

    A critical requirement of MR-guided interventions is the visualization of an instrument (e.g., catheter, needle) during the procedure. One approach is to fill the instrument with a contrast agent. Previously, the optimization of contrast agent visualization was performed only empirically. In the present study, an analytic optimization of contrast agent SNR efficiency was performed for a spoiled gradient echo pulse sequence. Optimal flip angle, repetition time, echo time, and contrast agent concentration were derived analytically. The solution is valid for any contrast agent, provided the relationship between T1 , T2 , and doping concentration is known. Phantom experiments validated the analytic optimization for Gd- and MnCl2 -based contrast agents. Results showed excellent agreement between experimentally predicted and theoretically observed magnetization behavior. In vivo experiments demonstrated optimized contrast agent visualization in brain, heart, and prostate applications. The results demonstrated the large SNR that can be achieved with analytic optimization. As a practical guideline, an 11% dilution of 500 mMol/L Gd-DTPA solution, repetition time ≈ 4 ms, echo time ≈ 1 ms, and θ ≈ 65° was found to provide a large SNR. This study derived and validated a method for analytically optimizing contrast agent SNR efficiency. This information may be useful for visualizing instruments during MR-guided interventions. © 2013 Wiley Periodicals, Inc.

  5. Improved evaluation of antivascular cancer therapy using constrained tracer-kinetic modeling for multi-agent dynamic contrast-enhanced MRI

    NARCIS (Netherlands)

    Hectors, Stefanie; Jacobs, Igor; Lok, Jasper; Peters, Johannes; Bussink, Johan; Hoeben, Freek J. M.; Keizer, Henk; Janssen, Henk M.; Nicolay, Klaas; Schabel, Matthias; Strijkers, Gustav

    2018-01-01

    Dynamic contrast-enhanced MRI (DCE-MRI) is a promising technique for assessing the response of tumor vasculature to anti-vascular therapies. Multi-agent DCE-MRI employs a combination of low and high molecular weight contrast agents, which potentially improves the accuracy of estimation of tumor

  6. Scientific and industrial challenges of developing nanoparticle-based theranostics and multiple-modality contrast agents for clinical application

    Science.gov (United States)

    Wáng, Yì Xiáng J.; Idée, Jean-Marc; Corot, Claire

    2015-10-01

    Designing of theranostics and dual or multi-modality contrast agents are currently two of the hottest topics in biotechnology and biomaterials science. However, for single entity theranostics, a right ratio of their diagnostic component and their therapeutic component may not always be realized in a composite suitable for clinical application. For dual/multiple modality molecular imaging agents, after in vivo administration, there is an optimal time window for imaging, when an agent is imaged by one modality, the pharmacokinetics of this agent may not allow imaging by another modality. Due to reticuloendothelial system clearance, efficient in vivo delivery of nanoparticles to the lesion site is sometimes difficult. The toxicity of these entities also remains poorly understood. While the medical need of theranostics is admitted, the business model remains to be established. There is an urgent need for a global and internationally harmonized re-evaluation of the approval and marketing processes of theranostics. However, a reasonable expectation exists that, in the near future, the current obstacles will be removed, thus allowing the wide use of these very promising agents.

  7. Imaging in Vivo Extracellular pH with a Single Paramagnetic Chemical Exchange Saturation Transfer Magnetic Resonance Imaging Contrast Agent

    Directory of Open Access Journals (Sweden)

    Guanshu Liu

    2012-01-01

    Full Text Available The measurement of extracellular pH (pHe has potential utility for cancer diagnoses and for assessing the therapeutic effects of pH-dependent therapies. A single magnetic resonance imaging (MRI contrast agent that is detected through paramagnetic chemical exchange saturation transfer (PARACEST was designed to measure tumor pHe throughout the range of physiologic pH and with magnetic resonance saturation powers that are not harmful to a mouse model of cancer. The chemical characterization and modeling of the contrast agent Yb3+-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, 10-o-aminoanilide (Yb-DO3A-oAA suggested that the aryl amine of the agent forms an intramolecular hydrogen bond with a proximal carboxylate ligand, which was essential for generating a practical chemical exchange saturation transfer (CEST effect from an amine. A ratio of CEST effects from the aryl amine and amide was linearly correlated with pH throughout the physiologic pH range. The pH calibration was used to produce a parametric pH map of a subcutaneous flank tumor on a mouse model of MCF-7 mammary carcinoma. Although refinements in the in vivo CEST MRI methodology may improve the accuracy of pHe measurements, this study demonstrated that the PARACEST contrast agent can be used to generate parametric pH maps of in vivo tumors with saturation power levels that are not harmful to a mouse model of cancer.

  8. Computed Tomography Imaging of Solid Tumors Using a Liposomal-Iodine Contrast Agent in Companion Dogs with Naturally Occurring Cancer.

    Directory of Open Access Journals (Sweden)

    Ketan B Ghaghada

    Full Text Available Companion dogs with naturally occurring cancer serve as an important large animal model in translational research because they share strong similarities with human cancers. In this study, we investigated a long circulating liposomal-iodine contrast agent (Liposomal-I for computed tomography (CT imaging of solid tumors in companion dogs with naturally occurring cancer.The institutional animal ethics committees approved the study and written informed consent was obtained from all owners. Thirteen dogs (mean age 10.1 years with a variety of masses including primary and metastatic liver tumors, sarcomas, mammary carcinoma and lung tumors, were enrolled in the study. CT imaging was performed pre-contrast and at 15 minutes and 24 hours after intravenous administration of Liposomal-I (275 mg/kg iodine dose. Conventional contrast-enhanced CT imaging was performed in a subset of dogs, 90 minutes prior to administration of Liposomal-I. Histologic or cytologic diagnosis was obtained for each dog prior to admission into the study.Liposomal-I resulted in significant (p 1 cm demonstrated a heterogeneous pattern of intra-tumoral signal with visibly higher signal enhancement at the post-24 hour time point. Extra-hepatic, extra-splenic tumors, including histiocytic sarcoma, anaplastic sarcoma, mammary carcinoma and lung tumors, were visualized with a heterogeneous enhancement pattern in the post-24 hour scan.The long circulating liposomal-iodine contrast agent enabled prolonged visualization of small and large tumors in companion dogs with naturally occurring cancer. The study warrants future work to assess the sensitivity and specificity of the Liposomal-I agent in various types of naturally occurring canine tumors.

  9. Delivery of encapsulated Doxorubicin by ultrasound-mediated size reduction of drug-loaded polymer contrast agents.

    Science.gov (United States)

    Eisenbrey, J R; Soulen, M C; Wheatley, M A

    2010-01-01

    Low delivery efficiency combined with systemic toxicity of traditional chemotherapy provides a need for improved chemotherapeutic delivery. Within our laboratory, we have developed polymer ultrasound contrast agents (1.2-1.8 mum in diameter) containing doxorubicin (Dox) within the shell (100-150 nm). In vivo this platform is expected to circulate through the vasculature until activated at the tumor site with external focused ultrasound (US). In vitro, the agent is responsive to US and when insonated at peak positive pressure amplitudes of 0.69 MPa and above, shows dramatic size reduction, eventually reaching a mean particle size of 350 nm, presumably due to fragmentation of, or gas release from the agent. The resulting Dox-polymer particles retain the drug and are small enough to pass through the leaky pores (350-400 nm) within the tumor vasculature, providing a sustained intratumoral release of chemotherapeutic as the polymer degrades. In vivo studies using a VX2 liver tumor model have shown that the combination of the agent and US results in nearly 50% less drug delivered to the nontargeted, healthy liver ( p = 0.009) and a 110% increase ( p = 0.004) in Dox delivery to the viable peripheral tissue of the tumor, relative to the uninsonated controls. This study shows how US-mediated destruction of drug-loaded polymer contrast agent can be used to deliver encapsulated drug for potential sustained release. Penetration mechanisms of these resulting particles and their ability to provide a sustained release from the tumor interstia will be explored in the future.

  10. 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.

  11. Aggregates dynamic in contrasting soils with different fertilizations and role of humic carbon as binding agent

    Science.gov (United States)

    Lugato, E.; Simonetti, G.; Nardi, S.; Berti, A.; Giardini, L.; Morari, F.

    2009-04-01

    In the last years aggregates fractionation has become a very common approach to study the close linkage between aggregate formation and SOM turnover. According to the hierarchical theory microaggregates are assumed to be stabilized by persisting binding agents whereas macroaggregates by transient or temporary organic materials. Humic substances, considered to be recalcitrant, should likely act as persistent binding agents but their role, also because of their heterogeneity and discussed origin, is still unclear. In a long-term experiment established in the early 1960s in north-eastern Italy, we wet-sieved large macroaggregates to separate three aggregate sizes (2000-250 mm, 250-53 mm and clay, sandy and peaty), fertilized with manure and mineral fertilizers. We analysed organic (OC) and humic (HC) carbon of each aggregate fraction, also investigating the molecular weight of the humic substances extracted (>60 KDa,60-30 KDa, organic matter distribution and investigate the composition and role of HC as binding agent. The results evidenced that the addition of manure significantly increased the proportion of macroaggregates respect to the mineral fertilization but only in the clay soil. Aggregate hierarchy, according to which SOC concentration increase with increasing aggregates size, was generally supported by our data. The HC values followed the same pattern of the OC, with a very high correlation between these parameters (r >0.95). The HC/OC ratio, ranging narrowly among the aggregates fractions, indicated no hierarchical role of HC as persisting binding agents. However HC extracted in the silt-clay fraction showed higher proportion of low molecular weight fraction in peaty and clay soil, respect to HC of larger aggregates.

  12. New strategies to prolong the in vivo life span of iron-based contrast agents for MRI.

    Directory of Open Access Journals (Sweden)

    Antonella Antonelli

    Full Text Available Superparamagnetic iron oxide (SPIO and ultra small superparamagnetic iron oxide (USPIO nanoparticles have been developed as magnetic resonance imaging (MRI contrast agents. Iron oxide nanoparticles, that become superparamagnetic if the core particle diameter is ~ 30 nm or less, present R1 and R2 relaxivities which are much higher than those of conventional paramagnetic gadolinium chelates. Generally, these magnetic particles are coated with biocompatible polymers that prevent the agglomeration of the colloidal suspension and improve their blood distribution profile. In spite of their potential as MRI blood contrast agents, the biomedical application of iron oxide nanoparticles is still limited because of their intravascular half-life of only few hours; such nanoparticles are rapidly cleared from the bloodstream by macrophages of the reticulo-endothelial system (RES. To increase the life span of these MRI contrast agents in the bloodstream we proposed the encapsulation of SPIO nanoparticles in red blood cells (RBCs through the transient opening of cell membrane pores. We have recently reported results obtained by applying our loading procedure to several SPIO nanoparticles with different chemical physical characteristics such as size and coating agent. In the current investigation we showed that the life span of iron-based contrast agents in the mice bloodstream was prolonged to 12 days after the intravenous injection of murine SPIO-loaded RBCs. Furthermore, we developed an animal model that implicates the pretreatment of animals with clodronate to induce a transient suppression of tissue macrophages, followed by the injection of human SPIO-loaded RBCs which make it possible to encapsulate nanoparticle concentrations (5.3-16.7 mM Fe higher than murine SPIO-loaded RBCs (1.4-3.55 mM Fe. The data showed that, when human RBCs are used as more capable SPIO nanoparticle containers combined with a depletion of tissue macrophages, Fe concentration in

  13. Synthesis and Characterization of Chitosan Coated Manganese Zinc Ferrite Nanoparticles as MRI Contrast Agents

    Directory of Open Access Journals (Sweden)

    M. Zahraei

    2015-04-01

    Full Text Available Manganese zinc ferrite nanoparticles (MZF NPs were synthesized by using a direct, efficient and environmental friendly hydrothermal method. To improve the colloidal stability of MZF NPs for biomedical applications, NPs were coated with chitosan by ionic gelation technique using sodium tripolyphosphate (TPP as crosslinker. The synthesized NPs were characterized by X ray diffraction (XRD analysis, inductively coupled plasma optical emission spectrometry (ICP-OES, fourier transform infrared (FTIR spectroscopy, transmission electron microscopy (TEM, vibrating sample magnetometer (VSM and the dynamic light scattering (DLS methods. The results confirmed the spinel ferrite phase formation without any calcination process after synthesis. Mean particle size of bare NPs was around 14 nm. Moreover, certain molar ratio of chitosan to TPP was required for encapsulation of NPs in chitosan. Coated NPs showed hydrodynamic size of 300 nm and polydispersity index about 0.3.

  14. MR imaging of thrombi using EP-2104R, a fibrin-specific contrast agent: initial results in patients

    Energy Technology Data Exchange (ETDEWEB)

    Spuentrup, Elmar [University Hospital, Technical University (RWTH) Aachen, Department of Diagnostic Radiology, Aachen (Germany); University Hospital, University of Cologne, Department of Radiology, Cologne (Germany); Botnar, Rene M. [Technical University Munich, Department of Nuclear Medicine, Munich (Germany); Wiethoff, Andrea J.; Graham, Phil B. [EPIX Pharmaceuticals, Lexington, MA (United States); Ibrahim, Tareq [Technical University Munich, German Heart Center Munich and Medical Clinic 1, Munich (Germany); Kelle, Sebastian; Nagel, Eike [German Heart Institute, Department of Cardiology, Berlin (Germany); Katoh, Marcus [University Hospital, Technical University (RWTH) Aachen, Department of Diagnostic Radiology, Aachen (Germany); University Hospital Saarland, Department of Diagnostic and Interventional Radiology, Homburg (Germany); Oezgun, Murat; Maintz, David [University of Muenster, Department of Clinical Radiology, Muenster (Germany); Vymazal, Josef [Hospital Na Homolce, Praque (Czech Republic); Guenther, Rolf W. [University Hospital, Technical University (RWTH) Aachen, Department of Diagnostic Radiology, Aachen (Germany)

    2008-09-15

    This study was an initial phase II trial in humans of molecular magnetic resonance (MR) imaging for improved visualization of thrombi in vessel territories potentially responsible for stroke using a new fibrin-specific contrast agent (EP-2104R). Eleven patients with thrombus in the left ventricle (n=2), left or right atrium (n=4), thoracic aorta (n=4) or carotid artery (n=1) as verified by an index examination (ultrasound, computed tomography, or conventional MR) were enrolled. All MR imaging was performed on 1.5 T whole-body MR-system using an inversion-recovery black-blood gradient-echo sequence. The same sequence was performed before and 2-6 h after low-dose intravenous administration of 4{mu}mol/kg EP-2104R. Two investigators assessed image quality and signal amplification. Furthermore, contrast-to-noise ratios (CNR) between the clot and the blood pool/surrounding soft tissue before and after administration of the contrast agent were compared using Student's t-test. MR imaging and data analysis were successfully completed in 10 patients. No major adverse effects occurred. On enhanced images, thrombi demonstrated high signal amplification, typically at the clot surface, with a significantly increased contrast in comparison to the surrounding blood pool and soft tissue (CNR for clot vs. blood pool, unenhanced and enhanced: 6{+-}8 and 29{+-}14; CNR for clot vs. soft tissue, unenhanced and enhanced: 0{+-}4 and 21{+-}13; P<0.01 for both comparisons). EP-2104R allows for molecular MR imaging of thrombi potentially responsible for stroke. High contrast between thrombus and surrounding blood and soft tissues can be achieved with enhanced imaging. (orig.)

  15. Toward ultrasound molecular imaging with phase-change contrast agents: an in vitro proof of principle.

    Science.gov (United States)

    Sheeran, Paul S; Streeter, Jason E; Mullin, Lee B; Matsunaga, Terry O; Dayton, Paul A

    2013-05-01

    Phase-change contrast agents (PCCAs), which normally consist of nanoscale or microscale droplets of liquid perfluorocarbons in an encapsulating shell, can be triggered to undergo a phase transition to the highly echogenic gaseous state upon the input of sufficient acoustic energy. As a result of the subsequent volumetric expansion, a number of unique applications have emerged that are not possible with traditional ultrasound microbubble contrast agents. Although many studies have explored the therapeutic aspects of the PCCA platform, few have examined the potential of PCCAs for molecular imaging purposes. In this study, we demonstrate a PCCA-based platform for molecular imaging using α(v)β(3)-targeted nanoscale PCCAs composed of low-boiling-point perfluorocarbons. In vitro, nanoscale PCCAs adhered to target cells, could be activated and imaged with a clinical ultrasound system and produced a six-fold increase in image contrast compared with non-targeted control PCCAs and a greater than fifty-fold increase over baseline. Data suggest that low-boiling-point nanoscale PCCAs could enable future ultrasound-based molecular imaging techniques in both the vascular and extravascular spaces. Copyright © 2013 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  16. 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.

  17. Application of parametric ultrasound contrast agent perfusion studies for differentiation of hyperplastic adrenal nodules from adenomas-Initial study.

    Science.gov (United States)

    Slapa, Rafal Z; Kasperlik-Zaluska, Anna A; Migda, Bartosz; Otto, Maciej; Jakubowski, Wiesław S

    2015-08-01

    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. 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. 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. 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. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. 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.

  19. Targeted delivery of gold nanoparticle contrast agents for reporting gene detection by magnetic resonance imaging.

    Science.gov (United States)

    Vistain, Luke F; Rotz, Matthew W; Rathore, Richa; Preslar, Adam T; Meade, Thomas J

    2016-01-04

    Detection of protein expression by MRI requires a high payload of Gd(III) per protein binding event. Presented here is a targeted AuDNA nanoparticle capable of delivering several hundred Gd(III) chelates to the HaloTag reporter protein. Incubating this particle with HaloTag-expressing cells produced a 9.4 contrast-to-noise ratio compared to non-expressing cells.

  20. High spatial resolution magnetic resonance imaging of experimental cerebral venous thrombosis with a blood pool contrast agent.

    Science.gov (United States)

    Spuentrup, E; Wiethoff, A J; Parsons, E C; Spangenberg, P; Stracke, C P

    2010-06-01

    The purpose of this study was to investigate the feasibility of clot visualization in small sinus and cortical veins with contrast enhanced MRA in a cerebral venous thrombosis animal model using a blood pool contrast agent, Gadofosveset, and high spatial resolution imaging. For induction of cerebral venous thrombosis a recently developed combined interventional and microsurgical model was used. Cerebral sinus and cortical vein thrombosis was induced in six pigs. Two further pigs died during the procedure. Standard structural, time-of-flight- and phase contrast-angiograms were followed by fast time resolved high resolution 3D MRA (4D MRA) and subsequent high spatial resolution 3D MRA in the equilibrium phase with and without addition of parallel imaging. Visualization of the clots using the different sequences was subjectively compared and contrast-to-noise ratio (CNR) was assessed. In the remaining six animals the procedure and MR-imaging protocol including administration of Gadofosveset was successfully completed. The 3D high resolution MRA in the equilibrium phase without the addition of parallel imaging was superior to all the other applied MR measurement techniques in terms of visualization of the clots. Only applying this sequence bridging vein thromboses were also seen as a small filling defect with a high CNR of >18. Only the non-accelerated high spatial resolution 3D MRA in the equilibrium in conjunction with the blood pool agent Gadofosveset allows for high-contrast visualization of very small clots in the cerebral sinus and cortical veins. STATEMENT CLINICAL IMPACT: Detection of cortical vein thrombosis is of high clinical impact. Conventional MRI sequences often fail to visualize the clot. We could demonstrate that, in contrast to conventional sequences, with high spatial resolution 3D MRA in the equilibrium in conjunction with the blood pool agent Gadofosveset very small clots in the cerebral sinus and cortical veins could be successfully visualized. We

  1. Prospects of molybdenum and rhenium octahedral cluster complexes as X-ray contrast agents.

    Science.gov (United States)

    Krasilnikova, Anna A; Shestopalov, Michael A; Brylev, Konstantin A; Kirilova, Irina A; Khripko, Olga P; Zubareva, Kristina E; Khripko, Yuri I; Podorognaya, Valentina T; Shestopalova, Lidiya V; Fedorov, Vladimir E; Mironov, Yuri V

    2015-03-01

    Investigation of new X-ray contrast media for radiography is an important field of science since discovering of X-rays in 1895. Despite the wide diversity of available X-ray contrast media the toxicity, especially nephrotoxicity, is still a big problem to be solved. The octahedral metal-cluster complexes of the general formula [{M6Q8}L6] can be considered as quite promising candidates for the role of new radiocontrast media due to the high local concentration of heavy elements, high tuning ability of ligand environment and low toxicity. To exemplify this, the X-ray computed tomography experiments for the first time were carried out on some octahedral cluster complexes of molybdenum and rhenium. Based on the obtained data it was proposed to investigate the toxicological proprieties of cluster complex Na2H8[{Re6Se8}(P(CH2CH2CONH2)(CH2CH2COO)2)6]. Observed low cytotoxic and acute toxic effects along with rapid renal excretion of the cluster complex evidence its perspective as an X-ray contrast media for radiography. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Non-degradable contrast agent with selective phagocytosis for cellular and hepatic magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Fei-Yan [Nanchang University, College of Chemistry (China); Gu, Zhe-Jia [Nanchang University, Institute for Advanced Study (China); Zhao, Dawen [UT Southwestern Medical Center, Department of Radiology (United States); Tang, Qun, E-mail: tangqun@ncu.edu.cn [Nanchang University, Institute for Advanced Study (China)

    2015-09-15

    Degradation is the long-existing toxic issue of metal-containing inorganic medicine. In this paper, we fully investigated the degradation of dextran-coated KMnF{sub 3} nanocube in the in vitro and in vivo surroundings. Different from the general decomposing and ion releasing events, this special agent is resistant to acidic environment, as well as ion exchange. Non-degradability was proved by simulated and real cellular experiments. Moreover, it can be engulfed in the macrophage cells and kept stable in the lysosome. Due to its stability and highly selective phagocytosis, implanted liver cancer can be clearly visualized after administration.

  3. Non-degradable contrast agent with selective phagocytosis for cellular and hepatic magnetic resonance imaging

    Science.gov (United States)

    Chen, Fei-Yan; Gu, Zhe-Jia; Zhao, Dawen; Tang, Qun

    2015-09-01

    Degradation is the long-existing toxic issue of metal-containing inorganic medicine. In this paper, we fully investigated the degradation of dextran-coated KMnF3 nanocube in the in vitro and in vivo surroundings. Different from the general decomposing and ion releasing events, this special agent is resistant to acidic environment, as well as ion exchange. Non-degradability was proved by simulated and real cellular experiments. Moreover, it can be engulfed in the macrophage cells and kept stable in the lysosome. Due to its stability and highly selective phagocytosis, implanted liver cancer can be clearly visualized after administration.

  4. Soil aggregation and aggregating agents as affected by long term contrasting management of an Anthrosol.

    Science.gov (United States)

    Zhang, Shulan; Wang, Renjie; Yang, Xueyun; Sun, Benhua; Li, Qinghui

    2016-12-13

    Soil aggregation was studied in a 21-year experiment conducted on an Anthrosol. The soil management regimes consisted of cropland abandonment, bare fallow without vegetation and cropping system. The cropping system was combined with the following nutrient management treatments: control (CONTROL, no nutrient input); nitrogen, phosphorus and potassium (NPK); straw plus NPK (SNPK); and manure (M) plus NPK (MNPK). Compared with the CONTROL treatment, the abandonment treatment significantly increased the formation of large soil macroaggregates (>2 mm) and consequently improved the stability of aggregates in the surface soil layer due to enhancement of hyphal length and of soil organic matter content. However, in response to long-term bare fallow treatment aggregate stability was low, as were the levels of aggregating agents. Long term fertilization significantly redistributed macroaggregates; this could be mainly ascribed to soil organic matter contributing to the formation of 0.5-2 mm classes of aggregates and a decrease in the formation of the >2 mm class of aggregates, especially in the MNPK treatment. Overall, hyphae represented a major aggregating agent in both of the systems tested, while soil organic compounds played significantly different roles in stabilizing aggregates in Anthrosol when the cropping system and the soil management regimes were compared.

  5. Soil aggregation and aggregating agents as affected by long term contrasting management of an Anthrosol

    Science.gov (United States)

    Zhang, Shulan; Wang, Renjie; Yang, Xueyun; Sun, Benhua; Li, Qinghui

    2016-12-01

    Soil aggregation was studied in a 21-year experiment conducted on an Anthrosol. The soil management regimes consisted of cropland abandonment, bare fallow without vegetation and cropping system. The cropping system was combined with the following nutrient management treatments: control (CONTROL, no nutrient input); nitrogen, phosphorus and potassium (NPK); straw plus NPK (SNPK); and manure (M) plus NPK (MNPK). Compared with the CONTROL treatment, the abandonment treatment significantly increased the formation of large soil macroaggregates (>2 mm) and consequently improved the stability of aggregates in the surface soil layer due to enhancement of hyphal length and of soil organic matter content. However, in response to long-term bare fallow treatment aggregate stability was low, as were the levels of aggregating agents. Long term fertilization significantly redistributed macroaggregates; this could be mainly ascribed to soil organic matter contributing to the formation of 0.5-2 mm classes of aggregates and a decrease in the formation of the >2 mm class of aggregates, especially in the MNPK treatment. Overall, hyphae represented a major aggregating agent in both of the systems tested, while soil organic compounds played significantly different roles in stabilizing aggregates in Anthrosol when the cropping system and the soil management regimes were compared.

  6. Pushing the sensitivity envelope of lanthanide-based magnetic resonance imaging (MRI) contrast agents for molecular imaging applications.

    Science.gov (United States)

    Aime, Silvio; Castelli, Daniela Delli; Crich, Simonetta Geninatti; Gianolio, Eliana; Terreno, Enzo

    2009-07-21

    Contrast in magnetic resonance imaging (MRI) arises from changes in the intensity of the proton signal of water between voxels (essentially, the 3D counterpart of pixels). Differences in intervoxel intensity can be significantly enhanced with chemicals that alter the nuclear magnetic resonance (NMR) intensity of the imaged spins; this alteration can occur by various mechanisms. Paramagnetic lanthanide(III) complexes are used in two major classes of MRI contrast agent: the well-established class of Gd-based agents and the emerging class of chemical exchange saturation transfer (CEST) agents. A Gd-based complex increases water signal by enhancing the longitudinal relaxation rate of water protons, whereas CEST agents decrease water signal as a consequence of the transfer of saturated magnetization from the exchangeable protons of the agent. In this Account, we survey recent progress in both areas, focusing on how MRI is becoming a more competitive choice among the various molecular imaging methods. Compared with other imaging modalities, MRI is set apart by its superb anatomical resolution; however, its success in molecular imaging suffers because of its intrinsic insensitivity. A relatively high concentration of molecular agents (0.01-0.1 mM) is necessary to produce a local alteration in the water signal intensity. Unfortunately, the most desirable molecules for visualization in molecular imaging are present at much lower concentrations, in the nano- or picomolar range. Therefore, augmenting the sensitivity of MRI agents is key to the development of MR-based molecular imaging applications. In principle, this task can be tackled either by increasing the sensitivity of the reporting units, through the optimization of their structural and dynamic properties, or by setting up proper amplification strategies that allow the accumulation of a huge number of imaging reporters at the site of interest. For Gd-based agents, high sensitivities can be attained by exploiting a

  7. The gadolinium-based contrast agent Omniscan® promotes in vitro fibroblast survival through in situ precipitation.

    Science.gov (United States)

    Feng, Min; Fan, Yun-Zhou; Ma, Xiao-Jie; Li, Jin-Xia; Yang, Xiao-Gai

    2015-07-01

    The current study aims to explore how the gadolinium (Gd)-based contrast agent (GBCA) Omniscan® enhanced cell viability of murine fibroblasts. The results of scanning electron microscopy showed that Omniscan® can precipitate in cell culture media and deposit on cell membranes. Energy-dispersive X-ray analysis and Fourier-transform infrared spectroscopy demonstrated the presence of Gd and phosphates in the agglomerated particles. By filtering the Omniscan®-containing medium through a 220 nm filter, it can be clearly found that the increased cell viability should be mainly attributed to the insoluble species of gadolinium rather than to chelated gadolinium. Moreover, the effects of other gadolinium-based contrast agents, Magnevist® and Dotarem®, were compared with that of Omniscan®. It is noted that the three contrast agents differed in their ability to induce cell viability, which is possibly ascribed to the different chemical stabilities of gadolinium chelates as demonstrated by the attenuation in cell growth upon the addition of excess ligands to the compounds. The results of flow cytometry analysis also showed that Omniscan® can promote cell growth via an increase in the S-phase cell population as evidenced by the elevated levels of cell cycle associated proteins cyclin D, cyclin A and the phosphorylated Rb protein. Furthermore, our results revealed that integrin-mediated signaling may play an important role in both Omniscan® and Magnevist®-enhanced focal adhesion formation since the blockade of integrins decreased the level of ERK phosphorylation induced by the two GBCAs. Taken together, these data suggested that in situ gadolinium phosphate precipitation formation mediated Omniscan®-promoted fibroblast survival, which is similar to that of gadolinium chloride. It was demonstrated that the application of GBCAs with more stable thermodynamic stability may cause less dissociation of the gadolinium ion and thus resulted in less precipitation, finally

  8. Biliary cystadenoma with bile duct communication depicted on liver-specific contrast agent-enhanced MRI in a child

    Energy Technology Data Exchange (ETDEWEB)

    Marrone, Gianluca; Carollo, Vincenzo; Luca, Angelo [Mediterranean Institute of Transplantation and High Specialization Therapy (ISMETT), Diagnostic and Interventional Radiology, Palermo (Italy); Maggiore, Giuseppe [University Hospital S. Chiara, Gastroenterology and Hepatology, Department of Paediatrics, Pisa (Italy); Sonzogni, Aurelio [Riuniti Hospital, Pathology Department, Bergamo (Italy)

    2011-01-15

    Biliary cystadenoma is a benign, but potentially malignant, cystic neoplasm of the biliary ducts occurring most commonly in middle-aged females and very rarely in children. We present a 9-year-old boy with biliary cystadenoma, diagnosed by MRI using a new liver-specific contrast agent (gadoxetic acid) that is eliminated by the biliary system. The images clearly demonstrate the communication between the multiloculated cystic mass and the biliary tree, suggesting the possibility of biliary cystadenoma. Due to the malignant potential of a cystadenoma, the lesion was resected. The resection was complete and the postoperative course was uneventful. (orig.)

  9. Biliary cystadenoma with bile duct communication depicted on liver-specific contrast agent-enhanced MRI in a child.

    Science.gov (United States)

    Marrone, Gianluca; Maggiore, Giuseppe; Carollo, Vincenzo; Sonzogni, Aurelio; Luca, Angelo

    2011-01-01

    Biliary cystadenoma is a benign, but potentially malignant, cystic neoplasm of the biliary ducts occurring most commonly in middle-aged females and very rarely in children. We present a 9-year-old boy with biliary cystadenoma, diagnosed by MRI using a new liver-specific contrast agent (gadoxetic acid) that is eliminated by the biliary system. The images clearly demonstrate the communication between the multiloculated cystic mass and the biliary tree, suggesting the possibility of biliary cystadenoma. Due to the malignant potential of a cystadenoma, the lesion was resected. The resection was complete and the postoperative course was uneventful.

  10. Upper airway obstruction in infants and children: evaluation by tracheobronchography with a non-ionic contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Lee Tain [Dept. of Radiology, Taichung Veterans General Hospital (Taiwan, Province of China); Lee, S.K. [Dept. of Radiology, Taichung Veterans General Hospital (Taiwan, Province of China)

    1997-03-01

    The clinical benefits of tracheobronchograms using nonionic contrast medium were evaluated prospectively in ten infants and children with suspected airway obstruction who could not be weaned from endotracheal intubation and were in incubators. All patients were examined usedated. The contrast agent was injected via the intubation tube, pumped with an Ambu-bag (Manual Resuscitator, Formosa-CJ Health Business Corporation, Taiwan), and then a chest radiograph was obtained immediately in both anteroposterior and lateral views using portable equipment. Imaging results were correct in eight of ten cases as judged from bronchoscopic, surgical, and clinical data. No complications occurred during or after these examinations. This method provides an easy, safe, and helpful technique for diagnosis of the airway in nonsedated infants and children whose condition is critical. (orig.)

  11. Direct synthesis of magnetite nanoparticles from iron(II) carboxymethylcellulose and their performance as NMR contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Gomes da Silva, Delmarcio; Hiroshi Toma, Sergio; Menegatti de Melo, Fernando [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Carvalho, Larissa Vieira C.; Magalhães, Alvicler; Sabadini, Edvaldo [Instituto de Química, Universidade Estadual de Campinas – UNICAMP, Campinas, SP (Brazil); Domingues dos Santos, Antônio [Instituto de Física, Universidade de São Paulo, São Paulo, SP (Brazil); Araki, Koiti [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil); Toma, Henrique E., E-mail: henetoma@iq.usp.br [Instituto de Química, Universidade de São Paulo, São Paulo, SP (Brazil)

    2016-01-01

    Iron(II) carboxymethylcellulose (CMC) has been successfully employed in the synthesis of hydrophylic magnetite nanoparticles stabilized with a biopolymer coating, aiming applications in NMR imaging. The new method encompasses a convenient one-step synthetic procedure, allowing a good size control and yielding particles of about 10 nm (core size). In addition to the biocompatibility, the nanoparticles have promoted a drastic reduction in the transverse relaxation time (T{sub 2}) of the water protons. The relaxivity rates have been investigated as a function of the nanoparticles concentration, showing a better performance in relation to the common NMR contrast agents available in the market. - Highlights: • Stable, hydrophylic magnetic nanoparticles have been obtained. • Direct use of iron(II) carboxymethylcellulose improves the synthesis. • The magnetic nanoparticles exhibit high spin–spin relaxivity. • The particles promote dark contrast by decreasing the T{sub 2} relaxation time.

  12. MDCT appearance of the appendix: how does the low-density barium sulfate oral contrast agent affect it?

    Science.gov (United States)

    Yaghmai, Vahid; Aghaei-Lasboo, Anahita; Brandwein, Warren M; Tochetto, Sandra; Mafi, John N; Miller, Frank H; Nikolaidis, Paul

    2011-01-01

    We compared the effect of low-density barium sulfate neutral oral contrast agent on the diameter of normal appendix and its luminal content versus that of water on multidetector-row CT. CT scans of 24 patients who had been imaged on two separate occasions for the evaluation of pancreatic pathology, once with water and subsequently with low-density barium sulfate as the neutral oral contrast agent were evaluated (total of 48 scans). Studies were randomized and reviewed in consensus on a workstation in the stack mode by two radiologists blinded to the type of oral contrast. The appendix was measured at baseline and 10 days later to obtain an average diameter. Results of the water and low-density barium sulfate groups were compared using paired t test. Contents of the appendiceal lumen were also noted (gas, fluid, mixed, and collapsed appendix). The average diameter of the appendix for scans obtained with water and low-density barium sulfate was 4.09 ± 0.87 mm (median, 4.22 mm; range, 2.50-5.65 mm) and 4.13 ± 0.93 mm (median, 4 mm, range, 2.2-5.65 mm), respectively. This difference was not statistically significant (P = 0.69). There was no statistically significant difference in the appendiceal content when water or low-density barium sulfate were used as oral contrast (χ (2) = 4.25, P = 0.89). Low-density barium sulfate does not affect appendiceal content or diameter and, therefore, should not adversely affect evaluation of the appendix on multidetector row CT.

  13. High resolution myocardial magnetic resonance stress perfusion imaging at 3 T using a 1 M contrast agent

    Energy Technology Data Exchange (ETDEWEB)

    Klumpp, Bernhard D.; Seeger, Achim; Doering, Joerg; Kramer, Ulrich; Fenchel, Michael; Claussen, Claus D.; Miller, Stephan [Eberhard Karls University Tuebingen, Department for Diagnostic Radiology, Tuebingen (Germany); Doesch, Christina; Hoevelborn, Tobias; Gawaz, Meinrad P. [Eberhard Karls University Tuebingen, Department for Cardiology, Tuebingen (Germany)

    2010-03-15

    Stress perfusion magnetic resonance imaging (MSPMRI) is an established technique for the assessment of myocardial perfusion. Shortcomings at 1.5 T are low signal to noise ratio (SNR) and contrast to noise ratio (CNR). One approach to overcome these shortcomings is to increase field strength and contrast concentration. The aim of our study was to investigate the diagnostic capability of high resolution MSPMRI at 3-T field strength using a 1 M contrast agent. Fifty-seven patients (62.3{+-} 11.0 years) with symptoms of coronary artery disease (CAD) were examined at 3 T. MMRSPI was assessed using a 2D saturation recovery gradient echo (SR GRE) sequence in short axis orientation (TR 1.9 ms, TE 1.0 ms, flip 12 , 0.1 mmol gadobutrol/kg body weight (bw), 140{mu}g adenosine/kg bw/min). Perfusion images were assessed visually and semiquantitatively (upslope, peak signal intensity (SI), and myocardial perfusion reserve index (MPRI)). Standard of reference was invasive coronary angiography. Stress-induced hypoperfusion was found in 43 patients. Sensitivity for hemodynamically relevant CAD (stenoses greater than 70%) was 95%/98%, specificity 80%/87%, diagnostic accuracy 91%/95% (reader 1/reader 2). The MPRI was significantly lower in hypoperfused myocardium (1.3 {+-} 0.2) compared with normal myocardium (2.6 {+-} 0.7). High resolution MMRSPI at 3 T using 1 M contrast agent under daily routine conditions provides reliable detection of stress-induced myocardial hypoperfusion with higher diagnostic accuracy than 1.5-T conditions. (orig.)

  14. 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.

  15. Iodinated contrast agent-induced nephropathy; Mit jodhaltigen Kontrastmitteln induzierte Nephropathie

    Energy Technology Data Exchange (ETDEWEB)

    Erley, C. [St. Joseph-Krankenhaus Berlin, Berlin (Germany)

    2007-09-15

    Contrast-induced nephropathy (CIN) is a well-known complication of therapeutic and diagnostic procedures requiring contrast administration and accounts for 10% of acute renal failure in hospitalized patients. Although the incidence of this complication is relatively low, its consequences can be catastrophic. The development of CIN is associated with increased length of hospital stay, an increased requirement for acute dialysis, and an increased risk of death. Preexisting renal dysfunction, age, diabetes, congestive heart failure, and volume of administered contrast are all associated with a risk of developing CIN. Despite a large number of clinical trials that have evaluated prophylaxis strategies for CIN, no uniform strategies have been developed so far. The use of N-acetyl-L-cysteine (NAC) or theophylline in specific subgroups of patients has been shown to reduce dialysis requirement and mortality in patients undergoing angiographic procedures. Hemofiltration has also shown positive results. In this review we will discuss the epidemiology and the risk factors for CIN and the evidence for commonly employed prophylaxis strategies, and we will provide general recommendations with respect to CIN prevention and management. A practicable strategy to prevent CIN includes: correct identification of individuals at greatest risk, thorough evaluation of whether other diagnostic maneuvers could be employed instead (i.e., sonography), application of low-osmolar contrast media at the minimum acceptable dose, stopping potential nephrotoxic drugs (NSAID), hydration with sodium chloride 0.9% 1 ml/kg per h i.v. 12 h before and after CM application, administration of acetylcysteine 600 mg twice the day before and after (in cases of emergency investigation and high-risk patients 1200 mg i.v.), and theophylline (250-350 mg) the day before and the day after CM application (in cases of emergency investigation 5 mg/kg i.v.). (orig.) [German] Die Kontrastmittelnephropathie (contrast

  16. Tumor-specific contrast agent based on ferric oxide superparamagnetic nanoparticles for visualization of gliomas by magnetic resonance tomography.

    Science.gov (United States)

    Abakumov, M A; Grinenko, N F; Baklaushev, V P; Sandalova, T O; Nukolova, N V; Semyonova, A V; Sokol'ski-Papkov, M; Vishvasrao, H; Kabanov, A V; Chekhonin, V P

    2012-05-01

    The aim of this study was to create vector superparamagnetic nanoparticles for tumor cell visualization in vivo by magnetic resonance tomography. A method for obtaining superparamagnetic nanoparticles based on ferric oxide with the magnetic nucleus diameter of 12 ± 3 nm coated with BSA and forming stable water dispersions was developed. The structure and size of the nanoparticles were studied by transmissive electron microscopy, dynamic light scattering, and x-ray phase analysis. Their T2 relaxivity was comparable with that of the available commercial analog. Low cytotoxicity of these nanoparticles was demonstrated by MTT test on primary and immortalized cell cultures. The nanoparticles were vectorized by monoclonal antibodies to connexin 43 (Cx43). Specific binding of vectorized nanoparticles to C6 glioma Cx43-positive cell membranes was demonstrated. Hence, vector biocompatible nanoparticles with high relaxivity, fit for use as MRT contrast for the diagnosis of poorly differentiated gliomas, were created.

  17. Surface tunable polymersomes loaded with magnetic contrast agent and drug for image guided cancer therapy.

    Science.gov (United States)

    Muthiah, Muthunarayanan; Lee, Sang Joon; Moon, Myeongju; Lee, Hyun Jin; Bae, Woo Kyun; Chung, Ik Joo; Jeong, Yong Yeon; Park, In-Kyu

    2013-03-01

    Polymersomes with different surface charges were synthesized from polysuccinimide (p) by introducing positively charged polyethylenimine (PEI-P), neutrally charged polyethylene glycol (PEG-P), and negatively charged glycine (GLY-P) to the polymer backbone polysuccinimide (P). Then, the polymersomes were prepared with super paramagnetic iron nanoparticles (SPIONs) to obtain PEI-P encapsulating SPIONs (PEI-PS), PEG-P encapsulating SPIONs (PEG-PS), and GLY-P encapsulating SPIONs (GLY-PS), respectively. The average particle sizes of GLY-PS, PEG-PS, and PEI-PS were analyzed by dynamic light scattering, and it was around 163.nm, 105 nm, and 285 nm, respectively. The surface charges of GLY-PS, PEG-PS, and PEI-PS was found to be -29.5, -18.9, and +44, respectively. The presence of PEI, PEG, and GLY in the polymer backbone was confirmed with nuclear magnetic resonance (NMR). The GLY-PS, PEG-PS, and PEI-PS were loaded with the anticancer drug paclitaxel during the preparation. The drug release from the PEG-PS was faster compared to GLY-PS and PEI-PS. An in vivo hemi-spleen mouse metastatic liver model was established and imaged with MRI after intravenous administration of GLY-PS, PEG-PS, and PEI-PS. From the T2-weighted imaging, it was evident that PEG-PS accumulated in the spleen and liver more efficiently than the other charged formulations of GLY-PS and PEI-PS. From this study, the nanoparticle-based delivery and imaging of anti-cancer drugs could be effectively demonstrated simultaneously.

  18. Transmission electron microscopy of rabbit liver after high-intensity focused ultrasound ablation combined with ultrasound contrast agents.

    Science.gov (United States)

    Jiang, Ying; Tian, Xue; Luo, Wen; Zhou, Xiaodong

    2007-01-01

    The purpose of this study was to observe sequential changes in rabbit liver under transmission electron microscopy after high-intensity focused ultrasound (HIFU) ablation. Thirty rabbits were randomly divided into 2 groups. The livers of rabbits in group A underwent single HIFU ablation; those in group B were given the ultrasound contrast agent Sonovue 0.2 mL/kg before HIFU exposure. Five rabbits from each of the 2 groups were killed at 0 h, 6 d, and 14 d after HIFU ablation. Tissue samples that included targeted and untargeted tissues were observed under transmission electron microscopy. Electron microscopy showed that most of the cell organs in targeted areas of groups A and B disappeared early after HIFU, but the basic cell structure was seen in group A. On the sixth day after HIFU ablation in the 2 groups, all cells in the targeted areas were disrupted and fibrous bands were detected in the rims of targeted areas. In surrounding areas, cell swelling in group B was more severe than in group A, and a greater number of apoptotic bodies were found in group B. The use of an ultrasound contrast agent can enhance the effects of HIFU ablation on the destruction of cell ultrastructure and can enlarge the region of HIFU ablation; this provides experimental evidence for control of HIFU effects.

  19. Synthesis and characterization of PVP-functionalized superparamagnetic Fe3O4 nanoparticles as an MRI contrast agent

    Directory of Open Access Journals (Sweden)

    2010-06-01

    Full Text Available The magnetite (Fe3O4 nanoparticles (MNPs coated with poly(N-vinyl pyrrolidone (PVP via covalent bonds were prepared as T2 contrast agent for magnetic resonance imaging (MRI. The surface of MNPs was first coated with 3-(trimethoxysilyl propyl methacrylate (silan A by a silanization reaction to introduce reactive vinyl groups onto the surface, then poly(N-vinyl pyrrolidone was grafted onto the surface of modified-MNPs via surface-initiated radical polymerization. The obtained nanoparticles were characterized by FT-IR (Fourier transform infrared spectroscopy, XRD (X-ray diffraction, TEM (transmission electron microscopy, VSM (vibrating sample magnetometer, and TGA (thermogravimetric analysis. The MNPs had an average size of 14 nm and exhibited superparamagnetism and high saturation magnetization at room temperature. T2-weighted MRI images of PVP-grafted MNPs showed that the magnetic resonance signal is enhanced significantly with increasing nanoparticle concentration in water. The r1 and r2 values per millimole Fe, and r2/r1 value of the PVP-grafted MNPs were calculated to be 2.6 , 72.1, and 28.1(mmol/l–1•s–1, respectively. These results indicate that the PVP-grafted MNPs have great potential for application in MRI as a T2 contrast agent.

  20. In vivo imaging of inflammatory responses by photoacoustics using cell-targeted gold nanorods (GNR) as contrast agent

    Science.gov (United States)

    Kim, K.; Agarwal, A.; Mcdonald, A. M.; Moore, R. M.; Myers, D. D., Jr.; Witte, R. S.; Huang, S.-W.; Ashkenazi, S.; Kaplan, M. J.; Wakefield, T. W.; O'Donnell, M.; Kotov, N. A.

    2008-02-01

    Cardiovascular inflammatory activity was imaged in vivo. Inflammation is known to be a major cause of cardiovascular disease. Photoacoustic (PA) imaging was employed using bio-conjugated gold nanorods (GNR) as a contrast agent. A mouse model based on vascular endothelium injury by a photochemical reaction of Rose Bengal (RB) dye to green light laser was used. Following a mid-line laparotomy under an approved animal protocol, anti-ICAM-1 conjugated GNR was injected through the dorsal penile vein followed by RB injection through the same vein. The inferior vena cava immediately distal to the renal veins of a C57BL/6 mouse was exposed to the green light laser for 10 minutes. The peak absorption of GNR was tuned to be 700 nm to minimize possible background absorption by blood and RB. The stability of GNR in the blood plasma was tested in vitro. Photoacoustic images were obtained through an ultrasound gel pouch in the mouse abdomen using a commercial ultrasound probe to evaluate inflammatory changes to the vascular endothelium, confirmed by histology. Preliminary results demonstrate the feasibility of in vivo photoacoustic imaging by a commercial ultrasound scanner of inflammation using GNR as a contrast agent.

  1. Preparation and Characterization of Novel Perfluorooctyl Bromide Nanoparticle as Ultrasound Contrast Agent via Layer-by-Layer Self-Assembly for Folate-Receptor-Mediated Tumor Imaging

    Directory of Open Access Journals (Sweden)

    Yue Hu

    2016-01-01

    Full Text Available A folate-polyethylene glycol-chitosan derivative was synthesized and its structure was characterized. An optimal perfluorooctyl bromide nanocore template was obtained via utilizing the ultrasonic emulsification method combining with orthogonal design. The targeted nanoparticles containing targeted shell of folate-polyethylene glycol-chitosan derivative and perfluorooctyl bromide nanocore template of ultrasound imaging were prepared successfully by exploiting layer-by-layer self-assembly as contrast agent for ultrasound. Properties of the novel perfluorooctyl bromide nanoparticle were extensively studied by Dynamic Light Scattering and Transmission Electron Microscopy. The targeted nanoparticle diameter, polydispersity, and zeta potential are around 229.5 nm, 0.205, and 44.7±0.6 mV, respectively. The study revealed that spherical core-shell morphology was preserved. Excellent stability of targeted nanoparticle is evidenced by two weeks of room temperature stability tests. The results of the cell viability assay and the hemolysis test confirmed that the targeted nanoparticle has an excellent biocompatibility for using in cell studies and ultrasound imaging in vivo. Most importantly, in vitro cell experiments demonstrated that an increased amount of targeted nanoparticles was accumulated in hepatocellular carcinoma cell line Bel7402 relative to hepatoma cell line L02. And targeted nanoparticles had also shown better ultrasound imaging abilities in vitro. The data suggest that the novel targeted nanoparticle may be applicable to ultrasonic molecular imaging of folate-receptor overexpressed tumor.

  2. Temperature-dependent differences in the nonlinear acoustic behavior of ultrasound contrast agents revealed by high-speed imaging and bulk acoustics.

    Science.gov (United States)

    Mulvana, Helen; Stride, Eleanor; Tang, Mengxing; Hajnal, Jo V; Eckersley, Robert

    2011-09-01

    Previous work by the authors has established that increasing the temperature of the suspending liquid from 20°C to body temperature has a significant impact on the bulk acoustic properties and stability of an ultrasound contrast agent suspension (SonoVue, Bracco Suisse SA, Manno, Lugano, Switzerland). In this paper the influence of temperature on the nonlinear behavior of microbubbles is investigated, because this is one of the most important parameters in the context of diagnostic imaging. High-speed imaging showed that raising the temperature significantly influences the dynamic behavior of individual microbubbles. At body temperature, microbubbles exhibit greater radial excursion and oscillate less spherically, with a greater incidence of jetting and gas expulsion, and therefore collapse, than they do at room temperature. Bulk acoustics revealed an associated increase in the harmonic content of the scattered signals. These findings emphasize the importance of conducting laboratory studies at body temperature if the results are to be interpreted for in vivo applications. Copyright © 2011 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  3. Contrast-enhanced MR imaging of postoperative scars and VX2 carcinoma in rabbits: comparison of macromolecular contrast agent and gadopentetate dimeglumine.

    Science.gov (United States)

    Lee, Joon Woo; Moon, Woo Kyung; Weinmann, Hanns-Joachim; Kim, Soo Jeoung; Kim, Jong Hyo; Park, Seong Ho; Kim, Tae Jung; Yoon, Chang Jin; Kim, Young Hoon; Cho, Eun Yoon; Ha, Sung Whan; Kang, Wee-Saing; Chang, Kee Hyun

    2003-10-01

    To compare the magnetic resonance (MR) imaging enhancement patterns of a blood pool contrast agent, SH L 643A, with those of gadopentetate dimeglumine in postoperative scars and VX2 carcinomas in rabbits and to compare these enhancement patterns with microvessel density in pathologic specimens. Eighteen rabbits with experimentally induced postoperative scars (n = 12) or VX2 carcinoma (n = 6) in the thighs underwent sequential MR imaging first with gadopentetate dimeglumine and then, 24 hours later, with SH L 643A. The enhancement ratios (ie, the ratios of postcontrast to precontrast signal intensity) and the microvessel densities of postoperative scars and VX2 carcinomas were assessed. Differences were tested for by using the Mann-Whitney U and Wilcoxon signed rank tests. In postoperative scars, enhancement ratios were consistently lower with injection of SH L 643A than with injection of gadopentetate dimeglumine for up to 30 minutes (P gadopentetate dimeglumine (P gadopentetate dimeglumine at all time points. The mean difference between the enhancement ratios of the VX2 carcinomas and postoperative scars was 0.64 +/- 0.10 (range, 0.50-0.77) with SH L 643A and 0.36 +/- 0.16 (range, 0.17-0.66) with gadopentetate dimeglumine (P gadopentetate dimeglumine. Enhancement ratios at SH L 643A-enhanced MR imaging corresponded well with microvessel density in postoperative scars and VX2 carcinomas. Copyright RSNA, 2003

  4. Surfactant shedding and gas diffusion during pulsed ultrasound through a microbubble contrast agent suspension.

    Science.gov (United States)

    O'Brien, Jean-Pierre; Stride, Eleanor; Ovenden, Nicholas

    2013-08-01

    Interest in coated microbubbles as agents for therapeutic and quantitative imaging applications in biomedical ultrasound has increased the need for their accurate theoretical characterization. Effects such as gas diffusion, variation in the properties of the coating and the resulting changes in bubble behavior under repeated exposure to ultrasound pulses are, however, still not well understood. In this study, a revised equation for microbubble motion is proposed that includes the effects of gas diffusion, as well as adsorption, desorption and shedding of a surfactant from the bubble surface. This is incorporated into a nonlinear wave propagation model to account for these additional time dependent effects in the response of microbubble populations. The results from the model indicate there can be significant changes in both bubble behavior and the propagated pulse over time. This is in agreement with existing experimental data but is not predicted by existing propagation models. The analysis indicates that changes in bubble dynamics are dominated by surfactant shedding on the timescale of a diagnostic ultrasound pulse and gas diffusion over the timescale of the pulse repetition frequency. The implications of these results for the development of more accurate algorithms for quantitative imaging and for therapeutic applications are discussed.

  5. In vivo 3D PIXE-micron-CT imaging of Drosophila melanogaster using a contrast agent

    Science.gov (United States)

    Matsuyama, Shigeo; Hamada, Naoki; Ishii, Keizo; Nozawa, Yuichiro; Ohkura, Satoru; Terakawa, Atsuki; Hatori, Yoshinobu; Fujiki, Kota; Fujiwara, Mitsuhiro; Toyama, Sho

    2015-04-01

    In this study, we developed a three-dimensional (3D) computed tomography (CT) in vivo imaging system for imaging small insects with micrometer resolution. The 3D CT imaging system, referred to as 3D PIXE-micron-CT (PIXEμCT), uses characteristic X-rays produced by ion microbeam bombardment of a metal target. PIXEμCT was used to observe the body organs and internal structure of a living Drosophila melanogaster. Although the organs of the thorax were clearly imaged, the digestive organs in the abdominal cavity could not be clearly discerned initially, with the exception of the rectum and the Malpighian tubule. To enhance the abdominal images, a barium sulfate powder radiocontrast agent was added. For the first time, 3D images of the ventriculus of a living D. melanogaster were obtained. Our results showed that PIXEμCT can provide in vivo 3D-CT images that reflect correctly the structure of individual living organs, which is expected to be very useful in biological research.

  6. A novel approach to contrast-induced nephrotoxicity: the melatonergic agent agomelatine.

    Science.gov (United States)

    Karaman, Adem; Diyarbakir, Busra; Durur-Subasi, Irmak; Kose, Duygu; Özbek-Bilgin, Asli; Topcu, Atilla; Gundogdu, Cemal; Durur-Karakaya, Afak; Bayraktutan, Zafer; Alper, Fatih

    2016-01-01

    To study the potential nephroprotective role of agomelatine in rat renal tissue in cases of contrast-induced nephrotoxicity (CIN). The drug's action on the antioxidant system and proinflammatory cytokines, superoxide dismutase (SOD) activity, levels of glutathione (GSH) and malondialdehyde (MDA) and the gene expression of interleukin-6 (IL-6), tumour necrosis factor (TNF)-α and nuclear factor kappa B (NF-κB) was measured. Tubular necrosis and hyaline and haemorrhagic casts were also histopathologically evaluated. The institutional ethics and local animal care committees approved the study. Eight groups of six rats were put on the following drug regimens: Group 1: healthy controls, Group 2: GLY (glycerol), Group 3: CM (contrast media--iohexol 10 ml kg(-1)), Group 4: GLY+CM, Group 5: CM+AGO20 (agomelatine 20 mg kg(-1)), Group 6: GLY+CM+AGO20, Group 7: CM+AGO40 (agomelatine 40 mg kg(-1)) and Group 8: GLY+CM+AGO40. The groups were evaluated by one-way analysis of variance and Duncan's multiple comparison test. Agomelatine administration significantly improved the serum levels of blood urea nitrogen (BUN) and creatinine, SOD activity, GSH and MDA. The use of agomelatine had substantial downregulatory consequences on TNF-α, NF-κB and IL-6 messenger RNA levels. Mild-to-severe hyaline and haemorrhagic casts and tubular necrosis were observed in all groups, except in the healthy group. The histopathological scores were better in the agomelatine treatment groups. Agomelatine has nephroprotective effects against CIN in rats. This effect can be attributed to its properties of reducing oxidative stress and inhibiting the secretion of proinflammatory cytokines (NF-κB, TNF-α and IL-6). CIN is one of the most important adverse effects of radiological procedures. Renal failure, diabetes, malignancy, old age and non-steroidal anti-inflammatory drug use pose the risk of CIN in patients. Several clinical studies have investigated ways to avoid CIN. Theophylline

  7. Study on multi-density contrast agent fillers of duct casting based on CT three-dimensional reconstruction.

    Science.gov (United States)

    Huang, Hai-Long; Chen, Jin-Jun; Wang, Yu; Chen, Xiao-Yu; Gong, Da-Cong

    2017-04-01

    The three-dimensional visualization model of human body duct is based on virtual anatomical structure reconstruction with duct angiography, which realizes virtual model transferred from two-dimensional, planar and static images into three-dimensional, stereoscopic and dynamic ones repectively. In recent years, the multi-duct segmentation and division of the same specimen (or organ) is the focus of attention shared by surgeons and clinical anatomists. On the basis of 4.22 g/cm(3) body bone density, this study has screened out metal oxide contract agent with different density for infusion and modeling, as well as compared and analyzed the effects of three-dimensional image of CT virtual bronchoscopy (CTVB), three-dimensional image of CT maximum intensity projection and three-dimensional model. This experiment result showed synchronously infusing multi-duct of same specimen (or organ) with contrast agent in different densities could reconstruct three-dimensional models of all ducts once only and adjust threshold to develop single or multiple ducts. It was easier to segment and observe the duct structure, anastomosis, directions and crossing in different parts, which was beyond comparison with three-dimensional image of CTVB. Although the existing three-dimensional duct reconstruction techniques still cannot be applied in living bodies temporarily, this study focused on a creative design of ducts segmentation in different density, which proposed a new experimental idea for developing multi-duct three-dimensional model in living body in the future. It will play a significant role in disease diagnosis and individual design in surgical treatment program. Therefore, this study observes the three-dimensional status of human duct with the application of contrast agent fillers in different density, combined with three-dimensional reconstruction technology. It provides an innovative idea and method for constructing three-dimensional model of digital multi-duct specimen, and

  8. Radio-contrast agent-induced hyperthyroidism: case report and review of the literature

    Energy Technology Data Exchange (ETDEWEB)

    Iakovou, Ioannis, E-mail: iiakovou@auth.gr, E-mail: iiakovou@icloud.com [Nuclear Medicine Department, Papageorgiou Hospital, Thessaloniki (Greece); Zapandiotis, Apostolos; Mpalaris, Vassileios; Goulis, Dimitrios G. [Medical School, Aristotle University of Thessaloniki (Greece)

    2016-11-01

    A 66 year-old woman with a history of a euthyroid multinodular goiter underwent a head and neck computed tomography (CT) scan (total iodine load of 35 g) in order to evaluate the extent of retrosternal expansion. Less than 24 h after the iodine-based contrast media (ICM) administration, she presented with symptoms and laboratory findings typical of thyrotoxicosis. She was treated successfully with antithyroid medications. This is the shortest time reported in the literature and it is of clinical importance, as it may have an impact to the recommendations given by the attending physician. Given the fact that a large number of ICM examinations are performed in everyday practice, physicians should be aware of this possible thyroid-specific effect. Prophylactic drugs could be considered in high-risk populations, such as administration of perchlorate and a thionamide class drug to elderly patients with suppressed TSH and/or palpable goiter, started the day before and continued for two weeks after ICM administration. (author)

  9. Albumin-based nanoparticles as magnetic resonance contrast agents: I. Concept, first syntheses and characterisation.

    Science.gov (United States)

    Stollenwerk, M M; Pashkunova-Martic, I; Kremser, C; Talasz, H; Thurner, G C; Abdelmoez, A A; Wallnöfer, E A; Helbok, A; Neuhauser, E; Klammsteiner, N; Klimaschewski, L; von Guggenberg, E; Fröhlich, E; Keppler, B; Jaschke, W; Debbage, P

    2010-04-01

    To develop a platform for molecular magnetic resonance imaging, we prepared gadolinium-bearing albumin-polylactic acid nanoparticles in the size range 20-40 nm diameter. Iterative cycles of design and testing upscaled the synthesis procedures to gram amounts for physicochemical characterisation and for pharmacokinetic testing. Morphological analyses showed that the nanoparticles were spheroidal with rough surfaces. Particle sizes were measured by direct transmission electron microscopical measurements from negatively contrasted preparations, and by use of photon correlation spectroscopy; the two methods each documented nanoparticle sizes less than 100 nm and generally 10-40 nm diameter, though with significant intrabatch and interbatch variability. The particles' charge sufficed to hold them in suspension. HSA retained its tertiary structure in the particles. The nanoparticles were stable against turbulent flow conditions and against heat, though not against detergents. MRI imaging of liquid columns was possible at nanoparticle concentrations below 10 mg/ml. The particles were non-cytotoxic, non-thrombogenic and non-immunogenic in a range of assay systems developed for toxicity testing of nanoparticles. They were micellar prior to lyophilisation, but loosely structured aggregated masses after lyophilisation and subsequent resuspension. These nanoparticles provide a platform for further development, based on non-toxic materials of low immunogenicity already in clinical use, not expensive, and synthesized using methods which can be upscaled for industrial production.

  10. Multifunctional polyelectrolyte microcapsules as a contrast agent for photoacoustic imaging in blood.

    Science.gov (United States)

    Yashchenok, Alexey M; Jose, Jithin; Trochet, Philippe; Sukhorukov, Gleb B; Gorin, Dmitry A

    2016-08-01

    The polyelectrolyte microcapsules that can be accurate either visualized in biological media or in tissue would enhance their further in vivo application both as a carrier of active payloads and as a specific sensor. The immobilization of active species, for instance fluorescent dyes, quantum dots, metal nanoparticles, in polymeric shell enables visualization of capsules by optical imaging techniques in aqueous solution. However, for visualization of capsules in complex media an instrument with high contrast modality requires. Herein, we show for the first time photoacoustic imaging (PAI) of multifunctional microcapsules in water and in blood. The microcapsules exhibit greater photoacoustic intensity compare to microparticles with the same composition of polymeric shell presumably their higher thermal expansion. Photoacoustic intensity form microcapsules dispersed in blood displays an enhanceme